Session 243 Diabetic macular edema and anti-VEGF

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Session 243 Diabetic macular edema and anti-VEGF
ARVO 2016 Annual Meeting Abstracts
243 Diabetic macular edema and anti-VEGF
Monday, May 02, 2016 11:00 AM–12:45 PM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 2066–2120/B0298–B0352
Organizing Section: Retina
Program Number: 2066 Poster Board Number: B0298
Presentation Time: 11:00 AM–12:45 PM
Impact of Ranibizumab on visual impairment among patients
with bilateral diabetic macular oedema
Franck Fajnkuchen1, 2, Linda Hrarat2, Anne Laurence Best2,
Salomon Y. Cohen1, Corinne Delahaye-Mazza1, Typhaine Grenet1,
Sylvia Nghiem-buffet1, Gabriel Quentel1, Gilles Chaine2,
Audrey Giocanti2. 1Ophthalmology, Centre d’Imagerie et de Laser,
PARIS, PARIS, France; 2Hôpital Avicenne, Bobigny, France.
Purpose: In case of bilateral retinal disease, there is a strong
relationship between visual impairment and visual acuity on the
better eye. Diabetic macular edema (DME) is often a bilateral
disease. The purpose of this study was to assess the impact of
intravitreal injections (IVT) of Ranibizumab on visual impairment
among patients with simultaneous visual acuity loss due to DME.
Methods: We performed a retrospective study including all patients
with DME and visual loss treated with ranibizumab since November
2011 and with a minimum follow up of 6 months. Patients were
recruited in two sites (Hôpital Avicenne, Bobigny and Centre
d’Imagerie et de Laser, Paris). Patients selected in this study were
those who exhibited a simultaneous visual decrease on both eyes. The
simultaneous decrease was defined as visual loss that requires IVT
of ranibizumab with less than 6 month interval between the right eye
and the left eye. Visual impairment was defined as visual acuity less
than 20/40 in the better eye. A 6 month follow-up was performed.
Results: 138 patients were treated with ranibizumab. Among these
patients 35.5% (49 patients) underwent bilateral IVT. In 63.2% of
cases (31 patients) IVT were performed with an interval of less than
six months between the first and the second affected eye. At baseline
83.9% of patients had a visual acuity of their better eye < 20/40. At
the end of the follow-up 51.6% of patients had a visual acuity of their
better eye < 20/40, i.e a reduction of 38.4% of visual impairment. On
the better eye, mean visual acuity (VA) at baseline was 57.86 ETDRS
letters, 68,51 letters at month 3 and 66 letters at month 6, i.e a +8.68
letters VA gain. Mean VA difference between both eyes was 13.64
letters. On the worse eye, mean baseline VA was at 44.22 letters,
55.69 letters at month 3 and 53.18 letters at month 6, a mean VA gain
of +8.96 letters.
Conclusions: Among patients with bilateral simultaneous occurrence
of DME, intravitreal injections of ranibizumab reduce the frequency
of visual impairment.
Commercial Relationships: Franck Fajnkuchen, Novartis (C),
Bayer (C), Allergan (C); Linda Hrarat, None; Anne Laurence Best,
None; Salomon Y. Cohen, bayer (C), Novartis (C), allergan (C);
Corinne Delahaye-Mazza, None; Typhaine Grenet, Novartis (C),
Bayer (C), Allergan (C); sylvia nghiem-buffet, Novartis (C), Bayer
(C), Allergan (C); gabriel quentel, Novartis (C), Bayer (C), Allergan
(C); Gilles Chaine, None; Audrey Giocanti, None
Program Number: 2067 Poster Board Number: B0299
Presentation Time: 11:00 AM–12:45 PM
Effect of long-term anti-VEGF treatment on the retinal
microarchitecture of patients with diabetic macular edema
Magdalena A. Wirth1, Matthias D. Becker1, 2, Stephan Michels1, 3.
1
Department of ophthalmology, Triemli Hospital, Zurich,
Switzerland; 2Ophthalmology, University Heidelberg, Heidelberg,
Germany; 3Ophthalmology, University Zurich, Zurich, Switzerland.
Purpose: To study the effect of long-term intravitreal ranibizumab on
the retinal microarchitecture in patients with diabetic macular edema
(DME).
Methods: For this retrospective study 31 patients, with a history
of at least 20 intravitreal ranibizumab injections (IVI, n=31), were
selected from our database comprising 383 patients treated for DME.
Spectral domain optical coherence tomography (SD-OCT) images
were evaluated at baseline (BL,prior to first ranibizumab injection)
and after 20 IVI for disorganization of retinal inner layers (DRIL),
retinal atrophy (RA), disruption of retinal pigment epithelium/bruch
complex (RPE/BR) and integrity of external limiting membrane/
ellipsoid zone (ELM/EZ), as well as alterations at the outer plexiform
layer/henle fiber layer junction (OPL/HE). Primary outcome was the
amount of patients with above mentioned alterations at BL versus
after 20 IVI. Best corrected visual acuity (BCVA) and degree of DME
were defined as secondary outcome measures. Patients with further
degenerative or vascular retinal diseases, ischemic maculopathy and
focal laser treatments during the observation period were excluded
from the analysis. Graders were masked as to clinical data and to
the number of injections. Statistical analyses were performed using
SPSS. The Wilcoxon signed ranks test was applied to study statistical
differences.
Results: At BL all included patients showed retinal microstructural
alterations (DRIL 100%, RA 54.9%, RPE/BR 93.6%, ELM/EZ
83.9%, OPL/HE 100%). Between BL and IVI 20 no significant
microstructural retinal changes were encountered (DRIL p=0.19,
RA p=0.13, RPE/BR p=0.26, ELM/EZ p=1.0, OPL/HE p=1.0).
The amount of patients with CME differed significantly (p=0.01).
9 patients (29%) were pretreated with other intravitreal agents, 14
patients (45.2%) underwent focal laser coagulation prior BL. The
treatment period with ranibizumab ranged from 14 to 47 months
(mean=29, SD±7). Mean BCVA at baseline (BL) was 69.3±12.5
letters, after IVI 20 69.9±14.9.
Conclusions: No effect on pre-existing retinal alterations was
encountered following long-term IVI. Thus, intravitreal ranibizumab
appears to represent a “neutral” treatment option with the known
effect on DME, but without impact on the restoration of retinal
layer disruption. Alterations of the retinal microarchitecture may be
causative for the functional outcome in patients with DME.
Commercial Relationships: Magdalena A. Wirth, None;
Matthias D. Becker; Stephan Michels, Pfenex (C), Novartis (C),
Roche (C), Bayer (C), Novartis (F), Clanotech (C), Bayer (F),
Allergan (C)
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to access the versions of record.
ARVO 2016 Annual Meeting Abstracts
Support: Stiftung wissenschaftliche Forschung, Fonds
Ophthalmologie, City Hospital Triemli and Werner H. Spross
Foundation
Program Number: 2068 Poster Board Number: B0300
Presentation Time: 11:00 AM–12:45 PM
Comparison of aqueous concentrations of angiogenic and
inflammatory cytokines based on optical coherence tomography
patterns of diabetic macular edema
Seung Jun Lee. Ophthalmology, Kangwon National University,
Chuncheon, Korea (the Republic of).
Purpose: The purpose was to compare aqueous inflammatory and
angiogenic cytokine levels in diabetic macular edema (DME).
Methods: Aqueous samples were obtained from 50 eyes with DME
and 12 normal eyes (control group). DME was classified according
to the morphologic pattern based on optical coherence tomography:
Diffuse retinal thickening (DRT; n=19), cystoid macular edema
(CME; n=17), or serous retinal detachment (SRD; n=14). Aqueous
samples were collected just before intravitreal injection and at the
beginning of cataract surgery in the control group. Interleukin (IL)6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic
protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and
vascular endothelial growth factor (VEGF) levels were measured by
multiplex bead assay.
Results: The IL-6, IL-8, IP-10, and PDGF-AA levels differed
significantly among the three groups of DME (P=0.014, P=0.038,
P=0.021, and P=0.041, respectively). However, there were no
differences between groups in aqueous concentration levels of MCP1 and VEGF (P=0.205 and P=0.062, respectively). IL-6 (P=0.026)
and IL-8 (P=0.023) correlated positively with central foveal thickness
(CFT) in the CME group. None of the cytokine levels correlated
significantly with CFT in any of the DRT and SRD groups.
Conclusions: Aqueous concentrations of cytokines varied according
to the morphologic pattern of DME, which might explain the
variable response to treatments such as intravitreal bevacizumab or
triamcinolone injection.
Commercial Relationships: Seung Jun Lee, None
Program Number: 2069 Poster Board Number: B0301
Presentation Time: 11:00 AM–12:45 PM
Effects of second-line intravitreal anti-VEGF therapy for
refractory diabetic macular edema
Sachi Abe1, Sakiko Goto1, Katsuhiro Nishi1, Teiko Yamamoto2,
Hidetoshi Yamashita1. 1Department of Ophthalmology and Visual
Sciences, Yamagata University School of Medicine, Yamagata, Japan;
2
Kaname-cho Yamamoto Eye Clinic, Tokyo, Japan.
Purpose: There are several treatment modalities to treat diabetic
macular edema (DME), which have been applied to DME patients in
the real world. According to DRCR net, the topical steroid therapy
has certain effects on DME especially in patients with pseudophacia,
so we have used the topical steroid therapy as the first-line treatment.
In these situations, it is mandatory to change the treatment modalities
in the refractory DME. The aim of this study is to investigate the
effects of intravitreal injection of ranibizumab 0.5mg(IVR) as the
second-line treatment in persistent DME even after the topical steroid
therapy.
Methods: This study was a retrospective non-randomized study,
approved by the Ethics Committee of Yamagata University School of
Medicine.[UMIN 000001432] This study included persistent DME
patients with poor effects of topical steroid therapy, and/or those with
the intolerable increase of intraocular pressure after steroid therapy.
The subjects were examined every month and treated by IVR with
Pro Re Nata regimen. Main outcome measures were best-corrected
visual acuity(BCVA)shown by logMAR and central macular
thickness(CRT) and complications which were investigated at every
monthly visit.
Results: Thirty-three eyes of 24subjects were included this study
(10 male and 14 female subjects). At the baseline the mean BCVA
was 0.577±0.40, and the mean CRT was 548.1±158.9μm. The mean
duration of observation was 4.9 months and the mean number of
IVR applidacion was 2.1 after the treatment changes. The mean
BCVA was significantly improved to 0.429±0.34(p=0.004) after
1month, and was to 0.38±0.33(p=0.043)after 3months. The mean
CRT decreased significantly to 426.9±125.1(p<0.01) after 1 month, to
453.6±165.2(p=0.015) after 3 months. No remarkable complications
were detected.
Conclusions: Intravitreal injections of ranibizumab was effective as
the second-line treatment modality even in the eyes with persistent
diabetic macular edema after steroid therapy.
Commercial Relationships: Sachi Abe; Sakiko Goto,
Senju Pharmaceutical Co.,Ltd. (P); Katsuhiro Nishi, None;
Teiko Yamamoto, Senju Pharmaceutical Co.,Ltd. (P);
Hidetoshi Yamashita, Senju Pharmaceutical Co.,Ltd. (P), Senju
Pharmaceutical Co.,Ltd. (C), Senju Pharmaceutical Co.,Ltd. (F),
Novartis Pharma K.K. (F)
Program Number: 2070 Poster Board Number: B0302
Presentation Time: 11:00 AM–12:45 PM
The efficacy of aflibercept in the management of treatmentresistant diabetic macular edema: a 12-month prospective study
Bobak Bahrami2, 1, Shaun Ewe2, Thomas H. Hong2, Meidong Zhu2, 3,
Andrew A. Chang2, 3. 1University of Sydney, Sydney, NSW, Australia;
2
Sydney Institute of Vision Science, Sydney, NSW, Australia; 3Save
Sight Institute, Sydney, NSW, Australia.
Purpose: Patients with diabetic macular edema (DME) may
demonstrate poor anatomical and visual improvements despite
intensive intravitreal bevacizumab injections. We performed a
prospective, open-label clinical trial to evaluate the efficacy of
switching therapy from bevacizumab to aflibercept in patients with
treatment resistant DME.
Methods: Patients with DME and a central macular thickness
(CMT) >300µm on spectral domain optical coherence tomography
(SD-OCT) despite at least 4 treatments in the prior 6 months with
intravitreal bevacizumab were recruited for this trial. Those with poor
diabetic control, defined as a glycosylated haemoglobin (HbA1C)
>12%, were excluded. All participants were reviewed every 4 weeks
up to 48 weeks. Five initial loading doses of 2mg of intravitreal
aflibercept were administered every 4-weeks until week 20, at which
point the treatment interval was extended to 8-weeks until week 48.
At every visit, ophthalmic examinations included best-corrected
visual acuity (BCVA) measured with Early Treatment of Diabetic
Retinopathy Study charts and CMT measured with SD-OCT. Primary
outcomes were changes in CMT and BCVA at week 48 compared to
baseline.
Results: A total of 22 eyes from 22 patients who have completed 48
weeks of follow-up were included in this analysis. Baseline mean ±
standard deviation (SD) age of these patients was 63.8±10.7 years,
duration of diabetes was 16.7±10.3 years and HbA1C was 7.8±1.7%..
Prior to enrolment, study eyes had 21.6±11.3 intravitreal anti-VEGF
injections over a period of 33.6±25.7 months. Mean CMT reduced
from 415±108µm at baseline to 348±100µm at 48-weeks (67µm
reduction, p=0.03). Mean BCVA improved from 67.8±10.4 letters at
baseline to 71.0±10.6 letters at 48-weeks (3.2 letter gain, p=0.02).
CMT decreased with each successive loading dose until the treatment
interval was extended to 8 weeks, at which point an oscillating
pattern was observed. BCVA was not affected in this manner and
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ARVO 2016 Annual Meeting Abstracts
visual gains were maintained despite extension of the treatment
interval.
Conclusions: Intravitreal aflibercept was effective in improving
anatomical and visual outcomes among these patients poorly
responsive to intravitreal bevacizumab with 12 months of follow up.
Commercial Relationships: Bobak Bahrami, None; Shaun Ewe;
Thomas H. Hong, None; Meidong Zhu, None; Andrew A. Chang,
Novartis (C), Bayer (C), Alcon (C), Bayer (F)
Support: Supported by Bayer Corporation Global (Bayer Healthcare
AG, Leverkusen, Germany). The sponsor had no role in the design or
conduct of this research.
Clinical Trial: ACTRN12614001307695
Program Number: 2071 Poster Board Number: B0303
Presentation Time: 11:00 AM–12:45 PM
Conversion to aflibercept after prior anti-VEGF therapy for
persistent diabetic macular edema
Ehsan Rahimy1, Abtin Shahlaee1, M. Ali Khan1, Gui-Shuang Ying2,
Joseph Maguire1, Allen Ho1, Carl D. Regillo1, Jason Hsu1. 1Wills Eye
Hospital, Philadelphia, PA; 2Scheie Eye Institute, Philadelphia, PA.
Purpose: To evaluate the short-term functional and anatomic
outcomes of patients with persistent diabetic macular edema (DME)
who were converted from bevacizumab and/or ranibizumab to
aflibercept.
Methods: Only eyes treated with at least 4 consecutive injections of
bevacizumab/ranibizumab spaced 4-6 weeks apart prior to conversion
and with at least 2 aflibercept injections afterwards were considered
for inclusion. Pertinent patient demographic, examination, and
treatment data were extracted from clinical charts and tabulated for
anlaysis.
Results: Fifty eyes of 37 patients were included. Eyes received
a mean of 13.7 bevacizumab/ranibizuman injections prior to
conversion, followed by 4.1 aflibercept injections over 4.6 months
or subsequent follow-up. The mean logMAR visual acuity at the
pre-switch visit was 0.60 +/- 0.43 (Snellen equivalent: 20/80). This
improved to 0.55 +/- 0.48 (Snellen equivalent: 20/70) by the second
visit after conversion, corresponding to a mean logMAR change of
-0.05 +/- 0.22 (P=0.12). The average central macular thickness from
the pre-switch spectral-domain optical coherence tomography scan
was 459 +/- 139 microns. This significantly improved to 349 +/- 108
microns by the second visit following conversion, reflecting a mean
decrease of 112 +/- 141 microns (P<0.0001). The mean intraocular
pressure (IOP) recorded at the pre-switch visit was 15.1 +/- 3.3
mmHg. At the second follow-up after converting to aflibercept, the
IOP averaged 14.9 +/- 3.2 mmHg, with a mean decrease of 0.2 +/- 3.0
mmHg (P=0.63).
Conclusions: Conversion to aflibercept for persistent DME resulted
in significant anatomical improvements. While trends towards
improved visual acuity and reduction in IOP were additionally
observed, these were not statistically significant.
Comparison of visual acuity, central macular thickness, and
intraocular pressure before and after conversion to aflibercept for
diabetic macular edema through first 2 post-switch visits (n=50 eyes).
Dashed line indicates where switch to aflibercept occurred.
Anatomical improvement after conversion to aflibercept for diabetic
macular edema (DME). Four representative cases of persistent DME
previously receiving chronic anti-VEGF therapy with corresponding
spectral-domain optical coherence tomography images at the preswitch visit (left column), first visit following conversion (middle
column), and the second visit following conversion (right column).
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/
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ARVO 2016 Annual Meeting Abstracts
Commercial Relationships: Ehsan Rahimy; Abtin Shahlaee,
None; M. Ali Khan, None; Gui-Shuang Ying, None;
Joseph Maguire, Genentech (C), Regeneron (C); Allen Ho,
Genentech (C), Regeneron (F), Regeneron (C), Genentech (F);
Carl D. Regillo, Genentech (C), Regeneron (F), Regeneron (C),
Genentech (F); Jason Hsu, None
Support: J. Arch McNamara fund through Wills Eye Hospital was
used for statistical analysis
Program Number: 2072 Poster Board Number: B0304
Presentation Time: 11:00 AM–12:45 PM
Changes in aqueous concentrations of various cytokines after
intravitreal ranibizumab for diabetic macular edema
Yuichi Toriyama, Takao Hirano, Motoharu Tokimitsu, Dai Chiba,
Toshiyuki Kyomoto, Toshinori Murata. Department of
Ophthalmology, Shinshu university, Matsumoto, Japan.
Purpose: To investigate the changes in aqueous cytokine levels after
intravitreal injection of ranibizumab(IVR) for diabetic macular edema
(DME).
Methods: Aqueous humor samples were collected before and at 4
weeks after IVR from 18 eyes with DME, and concentrations of 27
cytokines were measured using a multiplex bead immunoassay.
Results: The aqueous VEGF concentrations decreased below
the lowest detectable limit in 16 of the 18 eyes at 4 weeks after
IVR (P < 0.001; mean baseline 374.35 pg/ml). IL-10 and IL12 concentrations also showed a significant decrease (IL-10,
4.55→0.32 pg/ml, P < 0.001; IL-12, 37.79→0.81 pg/ml, P <
0.001). Only IP-10 concentrations showed a significant increase
after IVR (717.5→1165.3 pg/ml, P < 0.005). VEGF, IL-10 and
IL-12 concentrations were correlated with the severity of diabetic
retinopathy. There was a significant correlation between the increase
in the IP-10 concentrations after IVR and improvement of retinal
thickness (R = 0.59, P < 0.05).
Conclusions: IVR influence on the aqueous concentrations of IL-10,
IL-12 and IP-10 as well as VEGF.
Commercial Relationships: Yuichi Toriyama, Novartis (F);
Takao Hirano, Novartis (F); Motoharu Tokimitsu; Dai Chiba,
Novartis (F); Toshiyuki Kyomoto, Novartis (F); Toshinori Murata,
Novartis (F)
Clinical Trial: http://www.umin.ac.jp/, UMIN000012549
Program Number: 2073 Poster Board Number: B0305
Presentation Time: 11:00 AM–12:45 PM
Efficacy of intravitreal aflibercept injection in eyes with diabetic
macular edema
Norihiro Shimizu, Toshiyuki Oshitari, Tomoaki Tatsumi, Eiju Sato,
Yoko Takatsuna, Shuichi Yamamoto. Chiba University Hospital,
Funabashi, Japan.
Purpose: Efficacy of intravitreal aflibercept injection in eyes with
diabetic macular edema
Methods: The medical records of 46 eyes of 40 patients who were
diagnosed with DME and had received IVA treatment in the Chiba
University Hospital from December in 2014 to October in 2015
were reviewed. The IVA had been injected 3 times within 4 weeks
and since then pro re nata. The CMT and BCVA were measured
at 1, 3, and 6 months after the IVA. Of these 46 eyes, 36 had been
treated with a sub-Tenon’s injection of triamcinolone acetonide
(STTA), 28 eyes with photocoagulation for microaneurysms, 30
eyes had panretinal photocoagulation, and 25 eyes had other types
of anti-VEGF antibody injections (24 had ranibizumab and 1 had
bevacizumab, and 1 had both of them).
Results: The mean age of the patients was 64.5 years, the mean
injection times of IVA were 2.6 times for 6 months. The CMT was
481.5 μm before treatment, 368.6 μm at 1 month, 374.2 μm at 3
months, and 395.5 μm at 6 months after the IVA. The CMT was
still significantly thinner at 6 months after the IVA (P<0.05). The
mean BCVA in logMAR units was 0.39 before IVA, 0.34 at 1 month,
0.36 at 3 months, and 0.34 at 6 months after the IVA. The BCVA
was significantly improved only at 1 and 6 months after the IVA
(P<0.05). The CMT of eyes with serous retinal detachment (SRD)
was still significantly thinner at 1 and 3 months, and the BCVA
was significantly improved at 1 and 6 months after the IVA. In eyes
without SRD, the CMT was significantly thinner throughout the
entire period, and the BCVA was significantly improved at only 1
month after the IVA. In the eyes with previous IVR treatment, the
CMT was significantly thinner during the observation period but
the BCVA was not significantly improved at any time after the IVA.
In the eyes without previous IVR treatment, the CMT was also
significantly thinner during the observation period and the BCVA was
significantly improved at only 6 months after the IVA.
Conclusions: The results indicate that IVA is effective until 6 months
and is effective even in eyes with prior anti-VEGF antibody injection
treatment.
Commercial Relationships: Norihiro Shimizu, None;
Toshiyuki Oshitari; Tomoaki Tatsumi, None; Eiju Sato, None;
Yoko Takatsuna, None; Shuichi Yamamoto, None
Program Number: 2074 Poster Board Number: B0306
Presentation Time: 11:00 AM–12:45 PM
Intravitreal ranibizumab for diabetic macular edema in
vitrectomized versus nonvitrectomized eyes
Yoshito Koyanagi, Shigeo Yoshida, Yoshiyuki Kobayashi, Yuki Kubo,
Muneo Yamaguchi, Takahito Nakama, Shintaro Nakao, Yuji Oshima,
Tatsuro Ishibashi, Koh-hei Sonoda. Department of Ophthalmology,
Graduate School of Medical Sciences, Kyushu University, Fukuoka,
Japan.
Purpose:
There remains limited evidence regarding the effectiveness of
intravitreal anti-vascular endothelial growth factor (VEGF)
treatment on diabetic macular edema (DME) after vitrectomy.
The purpose of this study was to compare the effectiveness of
intravitreal ranibizumab (IVR) for DME in vitrectomized versus
nonvitrectomized eyes.
Methods:
We prospectively evaluated data from the baseline through the
6-month visits for 25 eyes of 20 patients who underwent IVR for
DME between February 2014 and April 2015 at Kyushu University
Hospital. Ten eyes were vitrectomized at least 3 months before IVR
treatments and 15 eyes were nonvitrectomized. The inclusion criteria
were best-corrected visual acuity (BCVA) less than 0.7 (decimal
notation) and/or central macular thickness (CMT) greater than 350
μm measured by optical coherence tomography. Paired t-test and
Student’s t-test were used for statistical analysis. The Institutional
Ethical Committee of Kyushu University Hospital approved the
present study.
Results:
At baseline, there were no significant differences between both
groups with respect to age, sex, glycemic control, logMAR BCVA,
CMT, or number of injections. The mean changes in logMAR
BCVA and CMT were both significant at 6 months compared
to baseline (-0.10 ± 0.04: p<0.05, and -165 ± 41 μm: p<0.01,
respectively) when the nonvitrectomized and vitrectomized
groups were combined. The mean change in logMAR BCVA was
significant in the nonvitrectomized groups (-0.15 ± 0.05, p<0.01),
and was not significant in the vitrectomized groups (-0.04 ± 0.06,
p=0.5). In contrast, the mean CMT change was significant both
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ARVO 2016 Annual Meeting Abstracts
in the nonvitrectomized groups (-152 ± 43 μm, p<0.01) and in
the vitrectomized groups (-185 ± 82 μm, p<0.05). At the 6-month
visit, 73% and 40% of the eyes had greater than 0.1 reductions
from baseline in logMAR BCVA in the nonvitrectomized and
vitrectomized groups, respectively. There were not significant
differences between both groups in the mean change of BCVA and
CMT.
Conclusions:
These results indicate that IVR may be an important treatment option
for vitrectomized DME eyes, although the improvement appeared
slower in vitrectomized eyes.
Commercial Relationships: Yoshito Koyanagi, None;
Shigeo Yoshida, None; Yoshiyuki Kobayashi, None; Yuki Kubo,
None; Muneo Yamaguchi, None; Takahito Nakama, None;
Shintaro Nakao, None; Yuji Oshima, None; Tatsuro Ishibashi,
None; Koh-hei Sonoda, None
Program Number: 2075 Poster Board Number: B0307
Presentation Time: 11:00 AM–12:45 PM
Contrast sensitivity after intravitreal bevacizumab versus
modified grid laser in clinically significant macular edema - a
comparative study
Henna Garg. Ophthalmology, Government Medical College &
Hospital, Chandigarh, Panchkula, India.
Purpose: To compare the effect of intravitreal bevacizumab (IVB)
with modified grid laser on contrast sensitivity, visual acuity, 10-2
automated perimetry and central macular thickness (CMT) in
clinically significant macular edema (CSME).
Methods: Thirty eyes of metabolically stable patients with CMT
equal to or less than 350 microns on OCT were included. The
patients were randomized (1: 1) into two groups, group I was treated
with IVB monotherapy for CSME and followed up on monthly
requirement of IVB while Group II was administered modified grid
laser treatment and supplement laser treatment as and when required
after initial treatment. The follow up was done at 1, 3 and 6 months
for all the patients. BCVA was recorded for all patients using ETDRS
visual acuity chart. Contrast sensitivity and 10-2 automated perimetry
were done at initial and last visits. Fundus examination and OCT
were done in all the patients at each visit.
Results: Outcome parameters were visual acuity, contrast sensitivity,
10-2 automated perimetry and CMT. Mean change in visual acuity
was improvement of 6 letters in group 1 and loss of 0.4 letters in
group 2 which was statistically significant (p=0.001). Increase in
contrast sensitivity was 3.2 % in group 1 and decrease in contrast
sensitivity was 4.1% in group 2 and this change was statistically
significant (p=0.004). Also, final visual acuity directly correlated
with contrast sensitivity (r=-0.849, p=.001). Change in visual field
was an increase of 0.39 db in group 1 and decrease of 0.20 db in
group 2 which was not statistically significant (p = 0.09). Statistically
significant reduction in CMT was seen in both the groups (group 1:
0.022 and group 2 : 0.001) but this change was not significant when
both the groups were compared. Mean number of injections was 3 in
group 1 and supplementary grid laser was required in only 2 patients
(12.5%).
Conclusions: Significant improvement in visual acuity and contrast
sensitivity was achieved with IVB versus laser. Also, visual acuity
had direct correlation with contrast sensitivity, that is, eyes with better
visual acuity had better contrast sensitivity. Improvement in CSME as
measured by CMT was observed in both the treatment modalities but
none of these did significantly better than the other.
Commercial Relationships: Henna Garg, None
Program Number: 2076 Poster Board Number: B0308
Presentation Time: 11:00 AM–12:45 PM
A quantitative approach to predict differential effects of antiVEGF treatment on diffuse and focal leakage in patients with
diabetic macular edema
Michael J. Allingham1, Dibyendu Mukherjee2, Erin Lally1,
Hossein Rabbani3, Priyatham S. Mettu1, Scott W. Cousins1,
Sina Farsiu1, 2. 1Ophthalmology, Duke University Eye Center, Durham,
NC; 2Biomedical Engineering, Duke University, Durham, NC; 3Medical
Image & Signal Processing Research Center, Isfahan University of
Medical Sciences, Isfahan, Iran (the Islamic Republic of).
Purpose: To use semi-automated segmentation of fluorescein
angiography (FA) to determine whether anti-vascular endothelial
growth factor (VEGF) treatment for diabetic macular edema (DME)
differentially affects microaneurysm (MA) associated leakage,
termed focal leakage, versus non-MA associated leakage, termed
diffuse leakage.
Methods: We performed a retrospective study of 14 subjects treated
with at least three consecutive injections of anti-VEGF agents for
DME (mean 5.3 injections, range 3-9) who underwent Heidelberg
FA prior to and following anti-VEGF therapy. Inclusion criteria
were center involving DME and FA of adequate quality for analysis.
Exclusion criteria included macular edema due to cause besides
DME, concurrent treatment for DME besides anti-VEGF, macular
photocoagulation within 1 year. At each time point, total leakage was
automatically segmented using our previously published software
(Rabbani et al. IOVS 2015). Microaneurysms were identified by
an expert grader and leakage within a 100 micron radius of each
MA was classified as focal leakage and automatically segmented.
Remaining leakage was classified as diffuse leakage. The absolute
and percent change in total, diffuse and focal leakage was calculated
for each subject.
Results: Mean pretreatment total leakage was 5.20 mm2 and
decreased by a mean of 24.4% (mean change -1.34 mm2) following
treatment. Diffuse leakage decreased by a mean of 29.5% (mean
absolute change -1.34 mm2) while focal leakage increased by 4.20%
(mean absolute change +0.002 mm2).
Conclusions: Anti-VEGF treatment for DME results in decreased
diffuse leakage but had relatively little effect on focal leakage as
assessed by FA. This suggests that diffuse leakage may be a marker
of VEGF-mediated leakage and that patients with predominantly
diffuse pattern leakage may be more responsive to anti-VEGF
therapy.
Commercial Relationships: Michael J. Allingham, None;
Dibyendu Mukherjee, None; Erin Lally, None; Hossein Rabbani,
None; Priyatham S. Mettu, None; Scott W. Cousins, None;
Sina Farsiu
Support: NIH grant 5K12EY016333-09; NIH grant R01 EY022691
Program Number: 2077 Poster Board Number: B0309
Presentation Time: 11:00 AM–12:45 PM
Conversion to Aflibercept for Diabetic Macular Edema
Unresponsive To Bevacizumab in Chicago Cook County Health
System
Christy Cunningham2, Sakshi Sahni1, Mina Farahani2,
Catherine Thomas1, Susan Anderson-Nelson2, Veena Raiji2, 4,
Dimitra Skondra2, 3. 1Rosalind Franklin University of Medicine
and Science, North Chicago, IL; 2J. Stroger Cook County Hospital,
Chicago, IL; 3Feinberg School of Medicine, Northwestern, Chicago,
IL; 4Ophthalmology, Loyola University, Maywood, IL.
Purpose: Chicago’s Cook County Hospital and Health System
(CCHHS) is one of the largest public county hospitals in the
USA, serving a diabetic patient population with limited access to
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ARVO 2016 Annual Meeting Abstracts
preventative screening and primary care services, thus representing
a unique subset, unrepresentative of the general population.
Consequently, these individuals are more likely to have poorly
controlled diabetes and present later in the course of their disease
with more severe and longstanding diabetic macular edema (DME).
The purpose of this study was to investigate if eyes with DME
not adequately controlled with bevacizumab would benefit from
conversion to aflibercept in our diabetic population.
Methods: This study was a retrospective chart review of eyes
with persistent DME after a series of at least three intravitreal
injections (IVI) with bevacizumab 1.25 mg every 4-6 weeks that
were subsequently converted to IVI of aflibercept 2 mg. Collected
data included visual acuity and central foveal thickness (CFT) on
registered Heidelberg spectral-domain optical coherence tomography
(SD-OCT).
Results: In total, 23 eyes from 17 subjects of mean age of 63.2
years were included. The mean glycosylated hemoglobin (HgbA1c)
was 7.61%. Mean CFT immediately prior to the switch was 428
micrometers and mean visual acuity was 0.480 logMAR. To date,
mean number of afibercept IVI was 1.9 (range 1-3 injections) and
mean follow-up after switching to aflibercept was 2.9 months (range
1-7 months). Anatomical improvement on OCT was shown in 91.3%
of eyes (21 out of 23 eyes) after conversion to afibercept IVI. Mean
CFT after afibercept IVI decreased significantly to 330 micrometers
(P=0.0077). Visual acuity improved in 43.5% of eyes (10 out of 23
eyes) after conversion to afibercept with mean visual acuity of 0.375
logMAR at the end of follow-up (P=0.063).
Conclusions: Eyes with persistent DME unresponsive to
bevacizumab IVI demonstrate anatomical and visual acuity
improvement after conversion to aflibercept in our diabetic
population at CCHHS in Chicago.
Commercial Relationships: Christy Cunningham, None;
Sakshi Sahni, None; Mina Farahani, None; Catherine Thomas,
None; Susan Anderson-Nelson; Veena Raiji, None;
Dimitra Skondra, None
Program Number: 2078 Poster Board Number: B0310
Presentation Time: 11:00 AM–12:45 PM
Effects of anti-VEGF antibodies to the viability, proliferation
and wound healing activity of cultured human retinal pigment
epithelial cells under high glucose stress
Tae Kwann Park, Jong Rok Oh, Young-Hoon Ohn. Ophthalmology,
Soonchunhyang Univ Hospital, Bucheon-si, Korea (the Republic of).
Purpose: To investigate the changes of RPE cell viability,
proliferative potential, and wound healing activity at high glucose
condition and evaluate the effects of anti-VEGF antibodies to the
RPE cells under high glucose level.
Methods: ARPE-19 cells were cultured in DMEM/Ham’s F-12 (1:1)
at different glucose level (5, 25, and 75 mM). Viability was evaluated
in methyl thiazolyl tetrazolium (MTT) assay at 5 days after treatment
with each glucose concentration. Migration ability was measured in a
wound healing assay at 3 days. Cell Death Detection Kit was used to
assess apoptosis at 3 days and 14days. And proliferative potential was
assessed by EdU Imaging kit at 3days. Cultured cells were treated
with anti-VEGF antibodies at clinically relevant concentrations
(bevacizumab 250 µg/mL, ranibizumab 125 µg/mL, aflibercept 500
µg/mL). Then, experiment was repeated at different glucose level.
Significance was evaluated with an unpaired, two-tailed Student t
test. A P-value < 0.05 was considered to indicate significance.
Results: The viability and migration of ARPE-19 cells were
significantly decreased in high glucose levels. (Viability; 87.6±2.6%
at75mM with 5mM set as 100% p<0.05, Migration; 24.5±1.3 %
at 5mM, 25.6±1.2 % at25mM, 13.7±1.3% at 75mM, p<0.05). At
14 days, the percentage of TUNEL positive cell was significantly
increased in 75mM glucose level compared to 5mM (75mM
:152.3±18.8% with 25mM set as 100%). Percentage of EdU positive
cell was also significantly decreasd (75mM : 35.8±10.5 % with 5mM
set as 100%, p<0.05). In 75mM glucose level, the groups treated
with Anti-VEGF, especially showed to decrease of cell viability,
proliferation and increase of apoptosis (p<0.05). However, there was
no significant difference generally between the anti-VEGF groups.
Conclusions: High glucose concentration interfered RPE cell
viability, wound healing activity, and proliferation. Further, antiVEGF antibodies aggravated those functions of RPE cells on high
glucose level. It may be consider that anti-VEGF long-term use
in diabetic retinopathy patients can give a negative effect on RPE
function.
Commercial Relationships: Tae Kwann Park, None; Jong
Rok Oh; Young-Hoon Ohn, None
Support: This work was supported by grants from Basic Science
Research Programthrough the National Research Foundation of
Korea (NRF) funded by the ministry of Education, Science, and
Technology (grant number 2013R1A1A2009899; Seoul, South
Korea).
Program Number: 2079 Poster Board Number: B0311
Presentation Time: 11:00 AM–12:45 PM
Achievement of ≥20/40 vision with ranibizumab in patients with
diabetic macular edema: a post-hoc analysis of the RESTORE
study
Victor Chong1, Jonathan Alsop2, Philippe Margaron3, Paul Mitchell4.
1
Oxford Eye Hospital, Oxford, United Kingdom; 2Numerus Ltd,
Wokingham, United Kingdom; 3Novartis Pharma AG, Basel,
Switzerland; 4Department of Ophthalmology, Centre for Vision
Research, Westmead Millennium Institute, The University of Sydney,
Sydney, NSW, Australia.
Purpose: RESTORE, a Phase III, randomized, multicenter, 12-month
core study and 24-month open-label extension study, assessed the
efficacy and safety of ranibizumab (RBZ) in patients with visual
impairment due to diabetic macular edema (DME). In this post-hoc
analysis, we studied the proportion of patients who achieved ≥20/40
vision at Month 12 and at Month 36, according to whether they had
≥20/40 vision at baseline and Month 12, respectively.
Methods: We analysed the 343 patients who received study treatment
and had at least one post-baseline BCVA measurement during the
core study. Patients were randomized to one of three treatment groups
at baseline: RBZ 0.5 mg (n=115), RBZ 0.5 mg + laser (n=118) and
laser (n=110). The extension study comprised 240 patients, all of
whom were eligible to receive RBZ 0.5 mg pro re nata (PRN) and
laser PRN at the investigator’s discretion. 20/40 vision (or better) was
defined as a best-corrected visual acuity (BCVA) score ≥69 letters
in the study eye. Missing data were imputed using a last observation
carried forward (LOCF) approach.
Results: Between baseline and Month 12, the proportion of patients
achieving ≥20/40 vision increased by 26.9% (from 46.1% to 73.0%)
with RBZ monotherapy, by 23.8% (from 38.1% to 61.9%) with RBZ
+ laser and by 6.3% (from 38.2% to 44.5%) with laser. RBZ was
also superior to laser in the subset of patients with < 20/40 vision
at baseline (n=203), in whom the proportion achieving ≥20/40
vision in the three treatment groups was 54.8%, 39.7% and 27.9%,
respectively. Among patients entering the extension study, the
proportion of patients achieving ≥20/40 vision at Month 36 varied
by initial randomized treatment assignment, being highest with RBZ
monotherapy (78.3%), intermediate with RBZ + laser (67.1%) and
lowest with laser (60.0%). In the subset of patients with <20/40
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ARVO 2016 Annual Meeting Abstracts
vision at Month 12 (n=85), approximately one-third had achieved
≥20/40 vision at Month 36, irrespective of treatment in the core study.
Conclusions: The data suggest that, in comparison with laser
photocoagulation treatment, early RBZ treatment offers the best
chance of achieving ≥20/40 vision. Regardless of initial treatment,
some patients may achieve ≥20/40 vision when switched to RBZ
treatment.
Commercial Relationships: Victor Chong, Novartis International AG,
Basel, Switzerland (F), Allergan, Irvine, CA, (C), Novartis International
AG, Basel, Switzerland (R), Novartis, Basel, Switzerland (C), Quantel,
New York, NY (F), Quantel, New York, NY (C), Heidelberg, Ladenburg,
Germany (R), Bayer HealthCare, Whippany, NJ (C), Bayer HealthCare,
Whippany, NJ (R); Jonathan Alsop, Numerus Ltd, Novartis, Basel,
Switzerland (F); Philippe Margaron, Novartis Pharma AG, Basel,
Switzerland; Paul Mitchell, Alcon (R), Pfizer (C), Bayer (C), Bayer
(R), Alcon (C), Novartis Pharma AG (R), Allergan (R), Novartis
Pharma AG (C), Solvay (Abbott) (C), Pfizer (R), Solvay (Abbott) (R),
Allergan (C)
Clinical Trial: NCT00687804
Program Number: 2080 Poster Board Number: B0312
Presentation Time: 11:00 AM–12:45 PM
OCT Predictors for BCVA Response to Intravitreal anti-VEGF
Treatment in Eyes with Diabetic Macular Edema
Ana Rita Santos1, 2, Christian Schwartz2, Silvia N. Simao1, 2,
Miguel Costa3, Dalila Alves3, Maria Luisa Ribeiro1, Joao Figueira1, 4,
Jose G. Cunha-Vaz5, 6. 1CEC, AIBILI, Coimbra, Portugal; 2CORC,
AIBILI, Coimbra, Portugal; 34C, AIBILI, Coimbra, Portugal;
4
Ophthalmology Department, Coimbra University Hospital, Coimbra,
Portugal; 5AIBILI, Coimbra, Portugal; 6Faculty of Medicine,
University of Coimbra, Coimbra, Portugal.
Purpose: To determine OCT morphological characteristics that can
predict the response to anti-VEGF treatment of Diabetic Macular
Edema (DME).
Methods: Seventy-one patients with DME were enrolled in a
prospective, observational study, following accepted clinical
practice (NCT01947881-CHARTRES). Of these, 67 completed
the study. All patients received monthly intravitreal injections of
anti-VEGF Lucentis in the first 3 months. All patients underwent
BCVA measurements by ETDRS protocol and SD-OCT (Cirrus
HD-OCT 5000, Zeiss Meditec) at baseline, months 1, 2, 3 and 6
and Color Fundus Photography (CFP) and Fluorescein Angiography
(FA) at baseline and months 3 and 6. The treatment response
was characterized in groups according to the increase of BCVA
letters: Good Responders (improvement of ≥ 10 letters), Moderate
Responders (improvement between 5 letters and 10 letters) and Poor
Responders (improvement of < 5 letters or loss of letters). The SDOCT images were analyzed and graded by an independent Reading
Center to obtain a morphological characterization of DME before
and after treatment. Central Retinal Thickness (CRT), extension
of Disorganization of the Retinal Inner Layers (DRIL), size of
intraretinal cystoid spaces and extension of disruption of External
Limitant Membrane (ELM), Ellipsoid Zone (EZ) and Retinal Pigment
Epithelium (RPE), were quantified in the 1 mm area centered on the
fovea.
Results: Twenty-six patients (38.80%) were identified as Good
Responders, 19 (28.35%) as Moderate Responders and 22 (32.83%)
as Poor Responders. No significant differences regarding BCVA
and central retinal thickness (CRT) were found at baseline between
the 3 groups (p=0.176 and p=0.573 respectively). Higher values
of DRIL area and disruption of external retinal layers at baseline,
especially EZ and ELM layers, were significantly correlated with
a poor response to treatment ((0.12; CI: 0.02- 0.59; P=0.009)
(0.24; CI: 0.07- 0.86; P=0.029) and (0.21; CI: 0.04- 1.20; P=0.079,
respectively). A poor response to treatment was also correlated
with the presence of larger cystoid spaces in the 1 mm centered on
fovea (80.95% of larger cysts in poor responders vs 46.15% in good
responders).
Conclusions: Higher values of DRIL area and disruption of external
retinal layers, especially damage of the EZ and ELM are good
predictors for BCVA response to anti-VEGF therapy in DME.
Commercial Relationships: Ana Rita Santos, None;
Christian Schwartz, None; Silvia N. Simao, None; Miguel Costa,
None; Dalila Alves; Maria Luisa Ribeiro, None; Joao Figueira,
None; Jose G. Cunha-Vaz, Novartis (C)
Support: Novartis Grant
Clinical Trial: NCT01947881
Program Number: 2081 Poster Board Number: B0313
Presentation Time: 11:00 AM–12:45 PM
Intravitreal Aflibercept Injection (IAI) for Diabetic Macular
Edema (DME): 148-Week Results from VISTA and VIVID
Diana V. Do. School of Medicine, Truhlsen Eye Institute, U of
Nebraska, Omaha, NE.
Purpose: To compare efficacy and safety of IAI with macular laser
photocoagulation in DME.
Methods: VISTA and VIVID were two similarly designed phase 3 trials
that treated 461 and 404 DME patients, respectively, with IAI 2 mg q4
weeks (2q4), IAI 2 mg q8 weeks following 5 monthly doses (2q8), or
laser control with monthly follow-up through week 148. Starting at week
24, if rescue treatment criteria were met, IAI patients received active
laser, and laser control patients received IAI 2q8. Beginning at week
100, patients in the laser control group who had not already qualified
for IAI rescue treatment received IAI as needed per retreatment criteria.
The primary efficacy endpoint was mean change from baseline in bestcorrected visual acuity (BCVA) at week 52.
Results: At week 52, mean BCVA gains from baseline in the
2q4, 2q8, and laser control groups were 12.5, 10.7, and 0.2 letters
(P<.0001) in VISTA, and 10.5, 10.7, and 1.2 letters (P<.0001) in
VIVID, respectively. At week 100, the corresponding gains were
11.5, 11.1, and 0.9 letters (P<.0001) In VISTA, and 11.4, 9.3, and
0.7 letters (P<.0001) in VIVID, respectively. At week 148, the
corresponding gains were 10.4, 10.5, and 1.4 letters (P<.0001)
in VISTA, and 10.3, 11.7, and 1.6 letters (P<.0001) in VIVID,
respectively. When measurements after rescue treatment was given
were included in the analysis, mean BCVA gains from baseline to
week 148 were 10.5, 11.2, and 8.2 letters (P<.05 for 2q8) in VISTA,
and 11.2 and 12.9, and 7.0 letters (P<.01) in VIVID, respectively.
Over 148 weeks, cataract was the most frequent ocular SAE with
IAI in both studies: VISTA, 1.3%; VIVID, 4.1%. The frequency of
APTC-defined arterial thromboembolic events with IAI was similar
across studies: VISTA, 10.4%; VIVID, 7.0%.
Conclusions: BCVA gains observed with both IAI regimens (over
control) at weeks 52 and 100 were maintained at week 148, with
similar efficacy in the 2q4 and 2q8 groups. Over 148 weeks, the
incidence of adverse events was consistent with the known safety
profile of IAI.
Commercial Relationships: Diana V. Do, Regeneron
Pharmaceuticals, Inc (C)
Clinical Trial: NCT01363440
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2082 Poster Board Number: B0314
Presentation Time: 11:00 AM–12:45 PM
Prognostic factors in the treatment of diabetic macular edema
(DME) using aflibercept, ranibizumab and bevacizumab (DRCR.
net protocol T)
Ursula Schmidt-Erfurth, Hrvoje Bogunovic, Thomas Schlegl,
Amir Sadeghipour, Sebastian M. Waldstein, Bianca Gerendas.
Christian Doppler Laboratory for Ophthalmic Image Analysis,
Department of Ophthalmology, Vienna Reading Center, Vienna,
Austria.
Purpose: Anti-VEGF therapy has been established as the gold
standard in the treatment of diabetic macular edema (DME)
achieving improvement in best corrected visual acuity (BCVA) as
well as reduction of central retinal thickness (CRT). The consecutive
aim is to optimize treatment outcomes and disease management by
identification of prognostic features and substance characteristics.
Advanced analyses of optical coherence tomography (OCT) images
using computational methods allows to deduct prognostic factors.
Methods: Post-hoc analyses were conducted in randomized trial
data from 629 individuals with DME involving the center of the
macula and BCVA from 78 to 24 ETDRS letters. Participants were
randomized 1:1:1 to receive intravitreal therapy with aflibercept (2.0
mg), ranibizumab (0.3 mg) or bevacizumab (1.25 mg) according to a
protocol-specified, as needed regimen. Spectral-domain OCT images
were analyzed using automated algorithms for fluid quantification
and retinal layer segmentation. CRT was measured in µm, intraretinal
cystoid fluid (IRC) and subretinal fluid (SRF) were measured as
volume in mm3 within the central 3 mm of the macula at baseline,
weeks 4,8,12, and 24. Predictive computerized modeling was used
for ranking of the most important predictive features for BCVA.
Results: Baseline CRT and baseline IRC volume showed a moderate
correlation with BCVA at baseline which declined over weeks 24
and 52. Using modeling, IRC in the outer nuclear layer temporal to
the fovea seemed to have the greatest predictive value. SRF had no
relevant prognostic value for BCVA outcomes. The IRC volume at
week 4 was already predictive of BCVA outcomes up to week 52
with a difference of +3 letters. Persistent IRC beyond month 3 was a
poor prognostic factor. Aflibercept was most efficient in reducing IRC
volumes and superior to ranibizumab/bevacizumab from week 24
which translated into superior BCVA gains. These prognostic findings
were identical for the overall group as well as for eyes with a baseline
BCVA < 69 ETDRS letters.
Conclusions: From treatment initiation, IRC volume appears to be
the most relevant predictive factor determining BCVA gains. An antiVEGF substance having an effect on rapid IRC reduction enhances
the benefit. Automated algorithms and predictive modeling offer
promising tools to identify predictive factors.
Commercial Relationships: Ursula Schmidt-Erfurth, Bayer
Healthcare AG (Berlin, Germany) (C), Alcon Laboratories, Inc.
(Fort Worth, TX) (C), Boehringer Ingelheim GmbH (Ingelheim,
Germany) (C), Novartis Pharma AG, (Basel, Switzerland)
(C); Hrvoje Bogunovic, None; Thomas Schlegl, None;
Amir Sadeghipour, None; Sebastian M. Waldstein, Bayer
Healthcare AG (Berlin, Germany) (C), Novartis Pharma AG, (Basel,
Switzerland) (C); Bianca Gerendas
Clinical Trial: NCT01627249
Program Number: 2083 Poster Board Number: B0315
Presentation Time: 11:00 AM–12:45 PM
Long-term diabetic retinopathy and macular edema outcomes
with anti-VEGF treatments in randomized controlled clinical
studies
Marco A. Zarbin1, Ivo Stoilov2, Na Lu2. 1Institute of Ophthalmology
& Visual Science, Rutgers-New Jersey Medical School, Newark, NJ;
2
Genentech, Inc., South San Francisco, CA.
Purpose: To examine the similarities and potential differences in
long-term vision outcomes (≥2 years) across trials of ranibizumab
(RBZ), aflibercept (AFL), and bevacizumab (BVZ) for the treatment
of diabetic retinopathy (DR) and diabetic macular edema (DME).
Methods: Study designs, primary endpoints, inclusion/exclusion
criteria, baseline (BL) characteristics, long-term vision and DR
outcomes, and injection frequencies were compared for the Diabetic
Retinopathy Clinical Research Network Protocol-I, -T, and -S, RISE/
RIDE, VIVID/VISTA and BOLT. DR severity was evaluated on
fundus photographs (FP) graded on the Early Treatment Diabetic
Retinopathy Study DR Severity Scale (DRSS).
Results: BL vision varied across the trials. Protocol-I, -T and S
enrolled patients with BCVA up to 20/32 (Snellen equivalent),
whereas RIDE/RISE and VIVID/VISTA restricted BL BCVA to 20/40
or worse. At BL, 24−34% of eyes in Protocol-I and RIDE/RISE were
graded to have mild/moderate proliferative DR (PDR; DRSS 60−65)
vs. only 1−7% in VIVID/VISTA and BOLT. The majority of patients
in Protocol S had moderate- and high-risk BL PDR. Mean change in
BCVA from BL and percentage of patients with 2-step improvement
on the DRSS are shown in Figures 1 and 2, respectively. Only 1-year
data were available from Protocol T. In most trials, baseline vision
correlated with vision gains suggesting a ceiling effect. Injection
frequencies (less than monthly) were comparable for the 3 antiVEGFs despite different doses and molecular structures.
Conclusions: This cross-trial comparison suggests that intensive
early anti-VEGF treatment can resolve DME and significantly
improve vision. These outcomes were maintained with less
than monthly treatment. In Protocol S, RBZ was effective in the
management of moderate- and high-risk PDR. Although findings
should be interpreted with caution given the limitations of cross-trial
comparisons, there was no additional benefit of aflibercept 2 mg
over ranibizumab 0.3 mg with respect to treatment burden or DR
improvement.
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ARVO 2016 Annual Meeting Abstracts
Commercial Relationships: Marco A. Zarbin, Novartis Pharma
AG (C), Healios, KK (C), Genentech/Roche (C), Ophthotech (C),
Makindus (C); Ivo Stoilov, Genentech, Inc.; Na Lu, Genentech, Inc.
Support: Genentech, Inc., South San Francisco, CA, provided
support for the study and participated in the study design; conducting
the study; and data collection, management, and interpretation.
Clinical Trial: NCT00473382
Program Number: 2084 Poster Board Number: B0316
Presentation Time: 11:00 AM–12:45 PM
Grading OCT characteristics did not clearly predict treatment
outcomes in the RELIGHT study participants
Tunde Peto1, Usha Chakravarthy2, Susanne Lupton3, Kara Gibson3,
James Warburton5, Ian A. Pearce4. 1Ophthalmology, NIHR
BMRC for Ophthalmology at Moorfields Eye Hospital NHS
Foundation Trust and UCL Institute of Ophthalmology, London,
United Kingdom; 2Vision Sciences, Queen’s University Belfast,
Belfast, United Kingdom; 3Novartis Pharmaceutical UK Limited,
Frimlley Park, United Kingdom; 4Ophthalmology, Royal Liverpool
Hospital, Liverpool, United Kingdom; 5Novartis Pharma AG, Basel,
Switzerland.
Purpose: To report on the relationship between severity of diabetic
retinopathy (DR) as measured by the Early Treatment Diabetic
Retinopathy Scale and treatment outcomes in participants of the
Ranibizumab treatment of diabetic macular oEdema with bimonthLy
monItorinG after a pHase of initial Treatment (RELIGHT) Study
Methods: The RELIGHT study enrolled 109 participants who were
treated with ranibizumab monthly for 3 months (loading phase) and
then re-treated on pre-specified criteria. The colour images were
systematically graded for DR severity scores, and spectral domain
tomograms were graded for neuroretinal thickness, disruption of
outer retinal zones and DMO type (cystoid dome shaped, diffuse,
subretinal fluid) and presence of hyperreflective foci. Descriptive
statistics were generated and the relationship between DR severity at
baseline (BL) and responsiveness to treatment at M3, 5 and 12 was
examined using chi-squared tests.
Results: Of the 109 participants enrolled colour and OCT images
were available in 81%. DR severity at M12 was unchanged or
improved in 81.4% of patients. There was no association between
DR severity at BL and response to DMO treatment, as defined by
>10% decrease on OCT thickness (p=0.5). Retinal thickness on OCT
was maximum in the central retinal subfield. Sub-retinal fluid when
present at BL, was resolved in all cases by M12. Both maximum
retinal thickness and foveal centre point thickness reduced between
BL and M12, while choroidal thickness remained unchanged.
There was no difference in the presence of any level of severity of
ellipsoid layer disruption between BL and M12 (91.8% and 87.8%
respectively), but the proportion of eyes with extensively disrupted
layer decreased from 31.8% to 19.5%. Intraretinal hyper-reflective
foci which were found in three-quarters of eyes at BL did not change
over time. None of the OCT characteristics predicted visual acuity
outcomes.
Conclusions: In this study population, no clear pattern emerged
based on OCT and colour imaging characteristics to predict treatment
outcomes at 12-months in DMO and DR. When response was defined
as a reduction of >10% in OCT thickness at any time-point during
the treatment period, 92% of patients showed reduction in DMO with
ranibizumab during some stage of their treatment cycle during the
12-month follow-up.
Commercial Relationships: Tunde Peto, OPTOS (F), Novartis (F);
Usha Chakravarthy; Susanne Lupton, Novartis; Kara Gibson,
Novartis; James Warburton, Novartis; Ian A. Pearce, Novartis (F)
Support: Novartis Pharmaceuticals UK Reading Centre Support
Grant
Clinical Trial: NCT01257815
Program Number: 2085 Poster Board Number: B0317
Presentation Time: 11:00 AM–12:45 PM
OCT retinal thickness response after first intravitreal injection is
a predictor of visual acuity response to anti-VEGF treatment of
DME
Miguel Costa2, Ana Rita Santos4, 5, Sandrina Nunes2, Dalila Alves2,
Christian Schwartz5, Joao Figueira4, 1, Silvia N. Simao4, 5,
Jose G. Cunha-Vaz6, 3. 1Ophthalmology Department, Coimbra
University Hospital, Coimbra, Portugal; 24C, AIBILI, Coimbra,
Portugal; 3Faculty of Medicine, University of Coimbra, Coimbra,
Portugal; 4CEC, AIBILI, Coimbra, Portugal; 5CORC, AIBILI,
Coimbra, Portugal; 6AIBILI, Coimbra, Portugal.
Purpose: Identify early predictors of anti-VEGF treatment response
in patients with diabetic macular edema (DME).
Methods: In a propspective observational study (NCT01947881,
CHARTRES Study) Seventy-one diabetes type II patients with DME
and indication for intravitreal injection (IVT) of Lucentis® were
treated for at least 3 months with monthly IVT of Lucentis® and
followed-up for an additional 3 months. All patients underwent best
corrected visual acuity (BCVA) measurements according to ETDRS
protocol and SD-OCT, and all images were graded by an independent
Reading Centre obtaining a complete morphological characterization
of DME before, during, and after treatment. An exploratory predictor
analysis for the BCVA change after 3 IVTs (3 months) was carried
out with multivariate linear regression for selection of predictors and
ROC curve analysis for determination of predictive performance and
threshold selection.
Results: Sixty-seven patients completed the study and were included
in this analysis.
Central retinal thickness (CRT) decrease after first IVT (1 month) was
found to be an independent predictor of BCVA treatment response
at 6 months on a multivariate regression with baseline BCVA and
baseline CRT as covariates (p=0.014). On a ROC analysis, the 8.7%
CRT decrease was identified as the threshold that distinguished
more accurately patients that recovered more than 5 BCVA letters at
3 months (sensitivity 71.7%, specificity 47.6%, ROC AUC 0.581).
Patients with a decrease of 8.7% or more in CRT after first ITV
injection (65.7 %) experienced a significantly greater improvement
in BCVA letters after 3 months (8.5±7.2 letters) when comparing
with patients with a CRT decrease < 8.7% (4.0±9.7 letters), p=0.038.
BCVA improvement at 1 month was not significantly different
between groups (p=0.102), but there was already a significant overall
increase in BCVA at 1 month (4.0±6.4 letters, p<0.001). Patients with
larger cysts responded better to treatment (Table 1) but the presence
of larger cysts did not improve the predictive capability of CRT
decrease.
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ARVO 2016 Annual Meeting Abstracts
Conclusions: CRT decrease ≥ 8.7% at one month, after the first ITV
anti-VEGF injection for DME predicts a better BCVA recovery at 6
months independently of baseline BCVA or CRT. A more practical
threshold of 10 % can be used with only a slight reduction in
sensitivity.
57.8% of eyes presented non-proliferative DR. In the treatment naïve
eyes (n=459), 50.5% received ranibizumab, 40.5% had monitoring
alone, and 3.9% each received laser and corticosteroids, respectively.
Conclusions: The BOREAL DME study findings suggest that, in
real-life practice in France, anti-VEGFs, primarily ranibizumab
0.5 mg, are the primary treatment for VI due to DME, followed by
monitoring alone in 2014. Macular laser is currently rarely used in
the French population.
Treatment response.
Commercial Relationships: Miguel Costa, None; Ana
Rita Santos, None; Sandrina Nunes, None; Dalila Alves, None;
Christian Schwartz, None; Joao Figueira, None; Silvia N. Simao,
None; Jose G. Cunha-Vaz, Novartis (C)
Support: Novartis Grant
Clinical Trial: NCT01947881
Program Number: 2086 Poster Board Number: B0318
Presentation Time: 11:00 AM–12:45 PM
Management of diabetic macular edema with visual impairment
in real-life practice in France: findings from the cross-sectional
BOREAL DME study
Catherine P. Garcher1, Pascale G. Massin2, Frank Fajnkuchen3,
Agnes Glacet-Bernard4, Laurent Kodjikian5,
Jean-François M. GIRMENS6, Cécile Delcourt7,
Pierre-Jean Guillausseau8, Anne Ponthieux9. 1Ophtalmology, CHU
Dijon, Dijon, France; 2Ophtalmology, Hôpital Lariboisiére, Paris,
France; 3Centre Imagerie et Laser, Paris, France; 4Centre Hospitalier
Intercommunal de Créteil, Créteil, France; 5Hospices Civils de Lyon,
Lyon, France; 6Hôpital des Quinze-Vingt, Paris, France; 7ISPEP,
Bordeaux, France; 8Hôpital Lariboisiére, Paris, France; 9Retine,
Novartis Pharma SAS, Rueil-Malmaison, France.
Purpose: Diabetic macular edema (DME) is the leading cause
of visual impairment (VI) in patients with diabetes. With the
introduction of anti-vascular endothelial growth factor (anti-VEGF)
agents, management of DME has evolved. The aim of this study was
to identify the routine practice for the management of patients with
VI due to DME (best-corrected visual acuity [BCVA] ≤20/40) in
France in 2014.
Methods: The cross-sectional, observational BOREAL DME
study was conducted in a real-life practice in France on request
of health authority. The study included patients with Type 1 or 2
diabetes aged ≥18 years who had a reduction in BCVA due to DME
(≤20/40) irrespective of treatment prescribed at inclusion (including
monitoring alone). The following medical data were collected
from patients’ medical files: general patient characteristics, disease
characteristics (including diabetes and DME), previous treatment for
VI due to DME, and treatment prescribed at inclusion.
Results: Of the 1023 screened patients, 918 were included in the
study (Figure 1). The mean age of the patients was 67.0 years with
an average 18.9 years of diabetes; 53.1% were male and 67.3% had
bilateral DME (Table 1). For this analysis we included 1321 eyes
with VI due to DME (BCVA ≤20/40; Figure 1). The majority of eyes
(64.6%) had received prior treatment for reduction in BCVA due
to DME. In the analyzed eyes, anti-VEGF (49.6%) was the most
frequently prescribed treatment at inclusion followed by monitoring
alone (41.1%). 65.9% of eyes with monitoring alone had received
prior treatment. Corticosteroids were prescribed for 6.5% of eyes,
while only 2.2% of eyes received laser. The mean BCVA and central
retinal thickness were 53.5 letters and 415 µm, respectively. Overall,
Figure 1: Patient Disposition
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ARVO 2016 Annual Meeting Abstracts
A cyst is defined in optical coherence tomography (OCT) as central
if it has a central bulge above the tangential line at the interface
vitreomacular plan.
The main outcomes measured were the mean change of bestcorrected visual acuity (BCVA) from baseline to 3rd month, 6th mont
and 12th month. Secondary outcomes were the number of intravitreal
injection and central retinal thickness (CRT) mean change.
Results: Seventy eight eyes (60 patients) were included: 20 eyes in
G1 ans 58 in G2.
The initial average of BCVA was 43,5 letters for G1 and 50,5 for G2.
At baseline, CRT was 550,9μm in G1 and 512μm in G2.
At 3 months, in G1, the average change in BCVA was +13.75 letters,
the average variation of the CRT was -193μm. In G2, the average
change in BCVA was +10,27 letters, the average variation of the CRT
was -142,7μm. There were 2.85 intravitreal injection in G1 and 2.71
in G2.
At 6 months, in G1, the average change in BCVA was +18,25 letters,
the average variation of the CRT was -194μm. In G2, the average
change in BCVA was +12,2 letters, the average variation of the CRT
was -144,3μm. There were 4 intravitreal injection in G1 and 3,86 in
G2.
At 12 months, in G1, the average change in BCVA was +13,45
letters, the average variation of the CRT was -183,3μm. In G2, the
average change in BCVA was +11,53 letters, the average variation of
the CRT was -158,1μm. There were 5,65 intravitreal injection in G1
and 5,22 in G2.
Conclusions: In this study we do not find significant difference in the
gain of BCVA between patients with or without an initial central cyst.
A central cyst in diabetic macular edema do not seem to be a
poor prognostic factor on functional and anatomical efficiency of
ranibizumab intravitreal injection.
Commercial Relationships: Pierre-Antoine REY, None;
Franck Fajnkuchen, None; Linda Hrarat, None; sylvia nghiembuffet, None; Valérie Sarda, None; Audrey Giocanti, None;
Gilles Chaines
Disease characteristics and prior ocular treatment history of evaluable
patients and eligible eyes
Commercial Relationships: Catherine P. Garcher, Novartis
(C), Bayer (C), Alcon (C), Horus (C), Thea (C), Alimera (C),
Baudch and Lomb (C), Zeiss (C), Allergan (C); Pascale G. Massin,
Novartis (C), Bayer (C), Allergan (C); Frank Fajnkuchen, Novartis
(C); Agnes Glacet-Bernard, Novartis (C), Bayer (C), Allergan (C);
Laurent Kodjikian, Novartis (C); Jean-François M. GIRMENS,
Novartis (C), Bayer (C), Allergan (C); Cécile Delcourt, Novartis (C);
Pierre-Jean Guillausseau, Novartis (C); Anne Ponthieux, Novartis
Support: Novartis Pharma SAS
Program Number: 2087 Poster Board Number: B0319
Presentation Time: 11:00 AM–12:45 PM
Impact of central cyst on functional and anatomical outcomes in
diabetic macular edema treated by ranibizumab
Pierre-Antoine REY, Franck Fajnkuchen, Linda Hrarat,
Sylvia Nghiem-buffet, Valérie Sarda, Audrey Giocanti,
Gilles Chaines. Ophtalmology, Avicenne Hospital, Paris, France.
Purpose: The purpose of our study is to evaluate the functional and
anatomical efficiency of ranibizumab intravitreal injection in patient
with diabetic macular edema (DME) with or without central cyst.
Methods: This is a retrospective single-center observational study
from March 2011 to November 2015.
Patients with diabetic macular edema requiring ranibizumab injection
were included. A first group (G1) included patients with a central cyst
and a control group (G2) included patients without central cyst.
Program Number: 2088 Poster Board Number: B0320
Presentation Time: 11:00 AM–12:45 PM
Impact of Baseline Characteristics on Change in Diabetic
Retinopathy Severity Scale (DRSS) Score in the VISTA and
VIVID Studies
Dilsher Dhoot. California Retina Consultants, Santa Barbara, CA.
Purpose: To evaluate the influence of baseline clinical characteristics
and treatment factors on improvement of DRSS scores at week 100
compared with baseline.
Methods: VISTA and VIVID were double-masked, phase 3 trials
randomizing 466 and 406 DME patients, respectively, to receive
intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI
2 mg every 8 weeks following 5 initial monthly doses (2q8), or laser.
Change in DRSS score was an exploratory endpoint at week 100. The
objective of this ad hoc analysis was to determine, using observed
data, what factors influenced ≥2-step improvement in DRSS scores at
week 100. Factors considered were baseline age, gender, race, HbA1c
level, duration of diabetes, best-corrected visual acuity (BCVA),
central retinal thickness (CRT), and baseline DRSS score. Regression
analysis was performed to determine the impact of these factors.
Results: In the integrated VIVID and VISTA studies, 10.2%, 34.7%
(p = .0018), and 38.5% (p < .001) of laser, 2q4, and 2q8 patients,
respectively, experienced a ≥2-step improvement in DRSS score at
week 100 compared with baseline. Baseline DRSS score was the only
factor significantly associated with ≥2-step DRSS score improvement
(p < .0001). Age, gender, race, HbA1c level, duration of diabetes,
BCVA and CRT did not have an impact on the ability to gain ≥2-step
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ARVO 2016 Annual Meeting Abstracts
improvement in DRSS score. The most frequent ocular serious
adverse event from baseline to week 100 was cataract (2.4%, 1.0%,
and 0.3% for the 2q4, 2q8, and laser groups, respectively) in a pooled
analysis of VISTA and VIVID.
Conclusions: Overall, a significant proportion of patients in the
VIVID and VISTA trials experienced at least a 2-step improvement
in DRSS score at week 100. Baseline DRSS score was the most
significant identified factor associated with ≥2-step improvement in
DRSS score at week 100.
Commercial Relationships: Dilsher Dhoot, Regeneron
Pharmaceuticals, LLC (R)
Clinical Trial: NCT01363440
Program Number: 2089 Poster Board Number: B0321
Presentation Time: 11:00 AM–12:45 PM
Visual Outcome of Patients in Ranibizumab for Edema
of the mAcula in Diabetes (READ-3) Study Based on the
Characteristics of Edema on Optical Coherence Tomography
Kanika Aggarwal1, Aniruddha Agarwal2, Rubbia Afridi2,
Mohammad A. Sadiq2, Muhammad Hassan2, Mohamed K. Soliman2, 3,
Salman Sarwar2, Quan Dong Nguyen2, Diana V. Do2, Yasir J. Sepah2.
1
Advanced Eye Center, Department of Ophthalmology, Post Graduate
Institute of Medical Education and Research, Chandigarh, India;
2
Department of Ophthalmology and Visual Sciences, Stanley M.
Truhlsen Eye Institute, University of Nebraska Medical Center,
Omaha, NE; 3Ophthalmology, Assiut University, Assiut, Egypt.
Purpose: The morphologic subtype/location of diabetic macular
edema (DME) may influence the treatment response to ranibizumab
(RBZ). In this study, evaluation of visual outcomes among patients
enrolled in the Ranibizumab for Edema of the mAcula in Diabetes
(READ-3) study based on the location of DME on spectral-domain
optical coherence tomography (SD-OCT) was performed.
Methods: In the READ-3 study, patients received monthly
intravitreal injections of 0.5 or 2.0mg RBZ. Patients with centerinvolving DME and central subfield thickness ≥250µm at baseline
were enrolled. SD-OCT images (Heidelberg Spectralis® were
analyzed at baseline and month 6 (primary endpoint) to identify
the location of edema. DME was classified as (1) center-involving
DME alone (fluid within 1mm central ETDRS circle); (2) non-center
involving DME, and (3) combination of the two. Patients with
subretinal fluid (SRF) at baseline and month 6 were identified. Mean
change in best-corrected visual acuity (BCVA) (ETDRS letters)
among the three groups was compared using one-way ANOVA test.
Results: 152 eyes (152 patients) were randomized. 119 eyes were
included (61 eyes in 2mg arm) in the study. At baseline, 7 eyes had
only center-involving DME (6 eyes in 2mg arm). All the remaining
eyes had combined center + non-center involving DME. At 6 months,
91 eyes (76.47%) had persistent DME (45 eyes in 2mg arm). 14/91
eyes (15.38%) had only center-involving DME (10 eyes in 2mg
arm) and 67/45 eyes (73.63%) (28 eyes in 2mg arm) had combined
center + non-center involving DME. The median (interquartile range)
BCVA gain was 5 (2-12) letters in the center-involved DME group,
12 (6.5-12.75) in the non-center involved group, and 7 (2-13) letters
in combined group (p=0.461). Mean BCVA gain was not significantly
different between the 2mg and 0.5mg arms for any of the 3 groups
(p>0.64). 14 and 19 eyes had SRF on OCT at baseline in 2mg and
0.5mg arms, respectively. At month 6, SRF was observed in 1 eye
in both the groups. Mean BCVA gain in these eyes was 10.48±7.60
compared to 7.24±10.13 in eyes with no SRF at baseline (p=0.042).
Conclusions: Among patients treated with RBZ, location of
intraretinal DME on OCT, and the treatment dose of intravitreal RBZ
does not influence the final BCVA outcome. However, eyes with SRF
at baseline show superior visual gains compared to eyes without SRF.
Commercial Relationships: Kanika Aggarwal, None;
Aniruddha Agarwal, None; Rubbia Afridi, None;
Mohammad A. Sadiq, None; Muhammad Hassan, None;
Mohamed K. Soliman, None; Salman Sarwar, None; Quan
Dong Nguyen; Diana V. Do, Genentech (C), Regeneron (C), Santen
(C), Allergan (F); Yasir J. Sepah, Genentech (C), Optovue (F),
Ziess (F)
Support: Research to prevent Blindness (RPB)
Program Number: 2090 Poster Board Number: B0322
Presentation Time: 11:00 AM–12:45 PM
The predictive features of optical coherent topography in
anatomical response to ranibizumab in patients with diabetic
macular edema
Angela Ding, Samia Fatum, Victor Chong. Ophthalmology, Oxford
Eye Hospital, Oxford, United Kingdom.
Purpose: Anti-vascular endothelial growth factor (VEGF) agents
are now considered to be the first line therapy for patients with
visual loss due to foveal involving diabetic macular edema (DME).
However, in many patients, the response is sub-optimal, and about
25%, there is no anatomical response in the first 6 months. As we
now have other options, such as steroids and surgery, it might be
useful to predict those with poor anatomical response and consider
steroids or surgery as first line therapy.
Methods: A total of 152 consecutive foveal involving DME patients,
who have received ranibizumab 0.5 mg (an anti-VEGF agent)
monthly for 6 months were included in the study. All patients had
spectral-domain optical coherent topography (SD-OCT) using
Heidelberg Spectralis (Heidelberg, Germany) at baseline and at 6
months (1 month after the last injection). We divided the patients into
3 groups based on the reduction of central sub-field thickness (CST),
namely non-responder NR (<10% reduction), partial-responder PR
(>10% reduction but not normal), and good responder GR (normal
central thickness). The baseline SD-OCT were scored based on
the presence or absence of the following features, subretinal fluid,
petalloid appearances, foveal eversion, foval edema, epiretinal
membrane (ERM) and central foveal cyst. Only the NR and the GR
groups were used for statistical analysis using Chi-Square test.
Results: There were 47 (31%) patients in the NR group (average
age 68, 52% female), 35 (23%) in the PR group (average age 67,
30% female), and 70 (46%) in the GR group (average age 67, 40%
female). There were no statistical significant difference in all the
analysed features except the presence of ERM (51.1% in NR vs
27.1% in GR group, p=0.008). The presence of subretinal fluid was
less common in the NR group but did not reach statistical significant
(10.6% in NR vs 20.0 % in GR group, p=0.10).
Conclusions: The presence of ERM statistically increases the risk of
non-anatomical responding in SD-OCT with 6 ranibizimab injections
in DME patients. It is unclear whether the thickness or the location
of the ERM would increase the prediction value. Furthermore, it is
unclear whether steroids would be useful in this group of patients.
Surgical intervention might be needed in some cases.
Commercial Relationships: Angela Ding, None; Samia Fatum,
None; Victor Chong, Pfenex (C), Novartis (C), Bayer (C), Quantel
Medical (C), Allergan (C)
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2091 Poster Board Number: B0323
Presentation Time: 11:00 AM–12:45 PM
Impact of vitrectomy on outcomes of treatment for diabetic
macular oedema with intravitreal ranibizumab
Sheelah Antao1, Mark Fajgenbaum1, Namritha V. Patrao1,
Roger Wong2, Lyndon da Cruz1, James W. Bainbridge1,
Ranjan Rajendram1. 1Moorfields Eye Hospital, London, United
Kingdom; 2St Thomas’ Hospital, London, United Kingdom.
Purpose: There is limited data available on the effect of vitrectomy
on treatment outcomes of intravitreal anti-VEGF therapy for diabetic
macular oedema (DMO). We performed a retrospective study to
determine whether treatment outcomes of intravitreal ranibizumab
for DMO differed in eyes that had undergone vitrectomy prior to
initiation of treatment from those in non-vitrectomised eyes. We also
looked at whether there was a difference in the number of injections
needed over the first 12 months of treatment.
Methods: 235 eyes that underwent at least 3 intravitreal ranibizumab
treatments for centre-involving DMO at a tertiary centre over a
2-year time frame were included. Eyes that had undergone vitrectomy
prior to the intitiation of ranibizumab were identified. Visual
acuity (VA), central subfield thickness (CST) on optical coherence
tomography (OCT) macular volume (MV) on OCT for each were
recorded at the start of treatment and at 12 months. The number of
injections required (based on a treatment regimen of 3 initial monthly
loading doses then PRN injections) were determined for each patient.
The outcomes were compared between the two groups.
Results: 199 eyes had no previous history of vitrectomy and 36 had
undergone vitrectomy prior to the initiation of ranibizumab treatment.
There was a mean gain of 6.1 ETDRS letters in the vitrectomy group
and 7.0 letters in the no-vitrectomy group (p=0.1274). The mean
change in CST was -55.5 microns (SD=134.2) vs -118.3 microns
(SD=174.7) (p=0.0450) and the mean change in MV was -0.202 mm2
(SD=1.368) vs -1.496mm2 (SD=2.096)(p=0.00006) in the vitrectomy
and no-vitrectomy groups respectively. The vitrectomy group
underwent a mean of 6.1 injections over the first 12 months compared
with 7.1 injections in the no-vitrectomy group (p=0.0131).
Conclusions: The 2 groups had a similar gain in ETDRS letters
over the first 12 months of treatment with intravitreal ranibizumab.
The mean decrease in CST and in MV was slightly higher in the
no-vitrectomy group compared with the vitrectomy group. Our
data suggest that whilst the reduction in macular thickness and
volume was slightly greater in non-vitrectomised eyes, the visual
outcome was not affected by previous vitrectomy. Larger studies are
required to further examine the influence of vitrectomy on treatment
outcomes. Continued follow-up of these and similar patients may
provide data on longer-term outcomes.
Commercial Relationships: Sheelah Antao, None;
Mark Fajgenbaum, None; Namritha V. Patrao, None;
Roger Wong; Lyndon da Cruz, None; James W. Bainbridge,
None; Ranjan Rajendram, None
Program Number: 2092 Poster Board Number: B0324
Presentation Time: 11:00 AM–12:45 PM
Ischemic index as a predictor of response to antivegf therapy
Avni Badami, Nisha Warrier, Kate McConnell, Steven Ness. Boston
Medical Center, Boston, MA.
Purpose: Ultra-widefield fluorescein angiography (UWFA)
allows examiners to view up to 200 degrees of the retina in a
single photograph. In diabetic retinopathy, ischemia promotes the
production of vascular endothelial growth factor (VEGF) which can
lead to a breakdown of the blood-retinal barrier and cause diabetic
macular edema through increased vessel permeability. We aim to
determine the relationship of retinal ischemia and responsiveness
to antivegf treatment in patients with diabetic macular edema. We
hypothesize that patients found to have a higher ischemic index
will have a poorer response or smaller decrease in central macular
thickness after a single treatment with antivegf therapy.
Methods: With IRB approval, a retrospective review of 12 eyes
from 9 patients with diabetic macular edema who underwent UWFA
testing and subsequent antivegf treatment were selected. Excluded
patients included those with prior panretinal laser photocoagulation,
antivegf treatment within 6 months prior to UWFA, and patients
with any coexisting ophthalmologic diseases. Areas of ischemia (in
pixels) were graded using ImageJ software and divided by the total
area of the image in pixels to determine an ischemic index. Central
macular thicknesses (CMT) from each patient prior and post antivegf
treatment were determined from optical coherence tomography. The
primary outcome evaluated was the determination of a correlation
between ischemic index and change in CMT pre and post antivegf
treatment.
Results: Of the included subjects, 12 of 12 eyes (100%) exhibited
at least one area of retinal ischemia on UWFA. The mean ischemic
index was 28.8% (range 12.3-57.8%, SD 14.4%). Central macular
thickness decreased by a mean of 58.8 micrometers (range decrease
of 261-increase of 141 micrometers, SD 114.2 micrometers)
following a single intravitreal antiVEGF injection. Using a linear
regression model, no significant correlation was found between
ischemic index and change in central macular thickness post
antiVEGF injection (r=0, p>0.05, n=12).
Conclusions: While the results of this retrospective review do not
support our hypothesis that patients with a higher ischemic index
would have a smaller decrease in CMT post antivegf treatment,
further studies are needed to determine whether larger areas of retinal
ischemia correlate with a poorer response to antivegf treatment.
Commercial Relationships: Avni Badami, None; Nisha Warrier;
Kate McConnell, None; Steven Ness, None
Program Number: 2093 Poster Board Number: B0325
Presentation Time: 11:00 AM–12:45 PM
Ranibizumab (0.3 MG) For Persistent Diabetic Macular Edema
(DME) After Recent, Frequent, And Chronic Bevacizumab:
1-Year Rotate Trial Results
Amina Farooq, Heather Frazier, Chelsea Fechter, William B. Marcus,
Harinderjit Singh, Dennis M. Marcus. Clinical Trial Research,
Southeast Retina Center, Evans, GA.
Purpose: There is limited prospective data evaluating the safety
and efficacy of 0.3 mg ranibizumab for persistent DME after
bevacizumab. We evaluated the safety and potential efficacy of
0.3 mg intravitreal ranibizumab in eyes with persistent DME after
bevacizumab.
Methods: The ROTATE Trial is an open-label, prospective,
unmasked, randomized study of intravitreally administered 0.3 mg
ranibizumab in 30 eyes with persistent DME after bevacizumab.
Thirty eyes were randomized in a 1:2 ratio to a Sustained group
(12 mandatory monthly injections of 0.3 mg ranibizumab through
1 year) or a PRN group (6 mandatory monthly injections of 0.3 mg
ranibizumab, followed by criteria-based PRN dosing). Subjects were
evaluated monthly for additional ranibizumab or rescue treatment.
Results: Twenty-nine of 30 enrolled eyes have completed 12-month
follow-up. At baseline, mean BCVA was 63(Snellen equivalent
20/63) and 64 (Snellen equivalent 20/50) ETDRS letters, in the
Sustained and PRN groups, respectively Mean baseline CST was 401
um and 453 um in the Sustained and PRN groups, respectively. At
12 months, mean BCVA was 70 (Snellen equivalent 20/40) and 71
(Snellen equivalent 20/40) letters in the sustained and PRN groups,
respectively. Average visual acuity increased 6.7 and 7.1 letters at 12
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ARVO 2016 Annual Meeting Abstracts
months from baseline in the Sustained, and PRN groups respectively,
with 16 of 30 eyes gaining ≥ 5 letters at 6 months. At 12 months,
mean CST was 307 um and 331 um in the Sustained and PRN groups,
respectively. Average OCT central subfield thickness thinned 92 um
and 129 um at 12 months from baseline in the Sustained and PRN
groups, respectively; 22 of 29 eyes decreasing thickness by at least
10% through 6 months. Adverse events included 2 deaths, one patient
with multiple comorbidities (renal failure, cirrhosis, and pulmonary
congestion secondary to right heart failure), myocardial infarction in
one patient, elevated blood pressure (2 patients), and mild posterior
subcapsular cataracts in 2 eyes. No endophthalmitis, retinal tears,
detachments, or vitreous hemorrhage were observed.
Conclusions: Ranibizumab 0.3 mg may provide additional visual
acuity and anatomic benefit for eyes with persistent DME after
recent, chronic and frequent bevacizumab.
Commercial Relationships: Amina Farooq, None;
Heather Frazier, None; Chelsea Fechter, None;
William B. Marcus; Harinderjit Singh, Acucela (F), Regeneron
(F), Pfizer (F), Xcovery (F), Chiltern (F), Allergan (F), Del Mar (F),
Alcon (F), Neurotech (F), Ophthotech (F), Alimera (F), Genentech
(F), Thrombogenics (F); Dennis M. Marcus, Regeneron (F),
Xcovery (F), Chiltern (F), Allergan (F), Del Mar (F), Neurotech (F),
Regeneron (C), Genentech (F), Acucela (F), Pfizer (F), Genentech
(C), Alcon (F), Thrombogenics (C), Alimera (C), Ophthotech (F),
Alimera (F), Thrombogenics (F)
Support: Investigator Initiated Study Supported by Genentech
Clinical Trial: NCT01845844
Program Number: 2094 Poster Board Number: B0326
Presentation Time: 11:00 AM–12:45 PM
Retrospective Review of Snellen Visual Acuity in Patients with
Diabetic Macular Edema, Prior to Initiation of Anti-VEGF
Treatment
Sarah Fishbein, Nathan Steinle, Gina Hong. R&D, California Retina
Consultants, Santa Barbara, CA.
Purpose: DRCR.net Protocol T shows that treatment-naive DME
patients presenting with ETDRS BCVA ≤20/50 showed better
improvement in BCVA when treated with aflibercept compared to
those treated with bevacizumab and ranibizumab. The only evidence
to date that has stratified visual acuity of treatment naïve DME
patients, inclusive of all baseline visual acuities, was in ETDRS
Report No. 19, published in 1995. In a real world practice setting, the
ratio of treatment-naive patients with DME that present with visual
acuity of 20/40 or better to those with 20/50 or worse has not been
investigated.
Methods: In a retrospective random sample chart review, we
recorded the Snellen Visual Acuity (VA) of patients (n=181) just
prior to initial Anti-VEGF treatment for DME. We then calculated
the percentage of patients presenting with Snellen VA of 20/50 or
worse (n=111) and also the percentage of patients that would have
an equivalent BCVA on ETDRS of 20/50 or worse (n = 87) using a
published correction factor between Snellen and ETDRS charts.
Results: Patients with Snellen VA of 20/50 or worse represented
61.3% of the patient population in a clinical setting. When a
published correction factor is applied to convert Snellen to ETDRS
vision, 48.1% of the DME patient population present with ETDRS
BCVA of 20/50 or worse. While DRCR.net Protocol T did not include
patients with visual acuity better than 20/32 or worse than 20/320
in their clinical trial, our analysis included all patients presenting
with anti-VEGF naive DME regardless of VA. This shows a more
representative sample of DME patients that one would find in a
real clinical setting and represents the first published report on this
subject.
Conclusions: In DRCR.net Protocol T, about 50% of the patients
enrolled had baseline ETDRS BCVA of 20/32 to 20/40, and the
remaining 50% had baseline ETDRS BCVA of 20/50 or worse.
When comparing the proportion of patients in Group 1 (20/32 to
20/40) to those in Group 2 (20/50 or worse), between the randomized
prospective DRCR.net trial and this real world retrospective clinical
chart review, we found that the 50:50 ratio of the randomized trial
does accurately represent how patients present in a clinic. The
results of this real world retrospective chart review show that when
a published correction factor is applied, about half (48.1%) of DME
patients present with ETDRS BCVA of 20/50 or worse.
Commercial Relationships: Sarah Fishbein; Nathan Steinle,
None; Gina Hong, None
Program Number: 2095 Poster Board Number: B0327
Presentation Time: 11:00 AM–12:45 PM
Treatment outcomes of intravitreal ranibizumab for diabetic
macular oedema in vitrectomised eyes
Vicky Hsin-Ju Lu1, Sheelah Antao1, Mark Fajgenbaum1, 2,
Roger Wong2, James W. Bainbridge1, Lyndon da Cruz1,
Robin D. Hamilton1, Ranjan Rajendram1. 1Medical Retina,
Moorfields Eye Hospital NHS Trust, London, United Kingdom;
2
Department of Ophthalmology, King’s College London, St Thomas’
Hospital Campus, London, United Kingdom.
Purpose: There is little data looking at the outcomes of anti-vascular
endothelial growth factors (anti-VEGF) treatment in eyes that have
been previously vitrectomised. We performed a retrospective study to
review outcomes after intravitreal ranibizumab therapy for diabetic
macular oedema (DMO).
Methods: Eyes that had undergone vitrectomy prior to the initiation
of treatment for DMO were included. Parameters recorded include
best-corrected visual acuity (BCVA) as measured on standardised
Early Treatment Diabetic Retinopathy Study (ETDRS) visual chart,
central subfield thickness (CST) and macular volume (MV) on
optical coherence tomography (OCT) at recruitment and follow-up.
The average number of injections per month were calculated for the
follow-up period.
Results: Thirty-nine eyes of 35 patients who underwent one or more
injections for DMO were included. Of these, one patient died from
unrelated causes during the follow-up period.
The mean follow-up period was 18 months (range 11.5 - 23.5
months). There was a mean visual gain of 3.5 letters (standard
deviation 14.0) over the follow-up period. The mean change in CST
was -50.2 microns (standard devaition 135.2) and the mean change in
MV was +0.199mm2 (standard deviation 1.339). Subgroup analysis
by diagnosis showed a mean decrease in CST in all groups except
those eyes that underwent vitrectomy for rhegmatogenous retinal
detachment (n=4) or for dropped nucleus during cataract surgery
(n=1).
The subgroups with the largest gains in BCVA were vitrectomy only,
vitrecomy with delamination, and vitrectomy with membrane peel
plus intravitreal steroid injection with gains of 30, 9.3 and 8.0 letters
respectively. The average number of injections given per month was
0.4 (range 0 - 0.8). Of the 38 eyes, three went on to have intravitreal
triamcinolone and a further three underwent Iluvien implants.
Conclusions: Intravitreal anti-VEGF treatment can have favourable
effects on visual acuity and central macular thickness in previously
vitrectomised eyes. The indication for vitrectomy may be linked to
the outcome as it may be a marker of severity of diabetic retinopathy
or other retinal disease. Larger numbers are required to further define
the effects of vitrectomy on outcomes of anti-VEGF therapy in
diabetic macular oedema.
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ARVO 2016 Annual Meeting Abstracts
Commercial Relationships: Vicky Hsin-Ju Lu, None;
Sheelah Antao, None; Mark Fajgenbaum, None; Roger Wong,
None; James W. Bainbridge, None; Lyndon da Cruz, None;
Robin D. Hamilton, None; Ranjan Rajendram
Program Number: 2096 Poster Board Number: B0328
Presentation Time: 11:00 AM–12:45 PM
Initial results of intravitreal Aflibercept (Eylea) in diabetic
macula oedema in North-East Scotland
Pallavi Tyagi, Zain Juma, Loreena Bilal, Cynthia Santiago.
Ophthalmology, NHS Grampian, Aberdeen, United Kingdom.
Purpose: To determine the clinical effectiveness of aflibercept
intravitreal injections (IVI) in treatment of patients with diabetic
macular oedema.
Methods: Single-centre retrospective study over 16 months (July
2014 - November 2015). 17 patients (21 eyes) with clinically
significant diabetic macular oedema (DMO) treated with a minimum
of 5 loading aflibercept injections were identified from Medisoft
software. 1 patient was excluded as he had a concurrent central
retinal vein occlusion. All patients followed the Scottish medical
consortium (SMC) protocol, comprising of initial loading with 5
monthly injections of 0.5ml aflibercept, followed by 2-monthly
injections for the next 3 visits, followed by a treat and extend
regime. Primary outcomes were change in best corrected visual
acuity (BCVA) in ETDRS letters and central retinal thickness (CRT)
measured by optical coherence tomography (OCT).
Results: 16 patients (20 eyes) were included. 15 eyes had previously
received Ranibizumab or Bevacizumab IVI and 5 eyes were
treatment-naive. Mean age at first injection was 70 (53 – 89) years.
Average number of injections was 5.85 (5-12) per eye. Mean followup was 7.9 (5.3-16.6) months. Following loading doses, BCVA
improved in 18 (90%) eyes and worsened in 2 (10%). Patients on
average gained 5.6 ETDRS letters with 20% gaining 1-5 letters, 45%
gaining 6-10 letters and 25% gaining 11-15 letters. 2 eyes lost 1 or 12
letters. Results were sustained at last visit where average letter gain
was 5.8 letters with 20% gaining 1-5 letters, 40% gaining 6-10 letters,
25% gaining 11-15 letters. 3 patients had reduced vision. All eyes had
reduced CRT on OCT. Average CRT reduction was 186 microns after
5th loading injection and 184 microns on last visit.
Conclusions: With the recommended treatment protocol,
aflibercept has shown a good initial response in eyes with DMO
in a small North-East Scotland cohort. Results are consistent with
published one-year data from randomised clinical trials. This study
demonstrates benefit of aflibercept in both treatment-naive and
previously treated eyes.
Commercial Relationships: Pallavi Tyagi; Zain Juma, None;
Loreena Bilal, None; Cynthia Santiago, None
Program Number: 2097 Poster Board Number: B0329
Presentation Time: 11:00 AM–12:45 PM
Adherence to therapy and treatment outcomes in patients
with clinically significant macular edema treated with antiVEGF therapy in an inner city hospital eye clinic: a quality
improvement study
Vikram S. Makhijani, Jonathan Levine, Brandon B. Johnson,
Pearl Rosenbaum. Ophthalmology, Bronx-Lebanon Hospital Center,
Bronx, NY.
Purpose: To measure compliance with follow-up recommendations
in patients receiving anti-VEGF therapy for clinically significant
macular edema (CSME) and to analyze quality of outcomes in
compliant versus noncompliant patients.
Methods: A retrospective chart review of 80 consecutive patients
with CSME seen at the hospital eye clinic between October 2014 and
October 2015 and treated with a course of intravitreal Ranibizumab,
Bevacizumab, or Aflibercept. Treatment choice was at the discretion
of the treatment provider. Exclusion criteria were patients with prior
injection, laser, or surgical treatment other than cataract extraction,
or CSME secondary to non-diabetic etiology. Physician-prescribed
follow-up interval (PFU) was compared to actual patient follow-up
dates (AFU) and any discrepancy between the PFU and AFU or loss
to follow-up was recorded. Patients with a discrepancy between PFU
and AFU of greater than 21 days were considered non-adherent.
Baseline and post-treatment best-corrected visual acuity (BCVA)
were compared between the adherent and non-adherent groups using
Student’s t-test. The following data were also recorded: central
foveal thickness (CFT), age, ethnicity/race, insurance type, degree of
retinopathy, number of treatments, type of treatments, and baseline
and most recent hemoglobin A1c.
Results: 54% of patients were in the adherent group and 46% in
the non-adherent group. Mean (SD) baseline BCVA was LogMAR
0.57 (0.17), and post-treatment 0.41 (0.18) after a mean of 3.6 (1.4)
treatments. Mean delay from PFU for the total group was 23 days.
Patients with a higher discrepancy between PFU and AFU (greater
than 21 days increase) or lost to follow-up had a lower magnitude of
acuity improvement (LogMAR 0.01 [0.24]) than those with higher
compliance (LogMAR 0.33 [0.10]), p=0.01. Overall, 63% of patients
had an improvement in acuity after treatments.
Conclusions: A large percentage of the studied population did not
adhere to prescribed follow-up. This results in treatment outcomes
for patients with CSME worse than in reported studies of compliant
patient populations. Future research may explore and identify
systems, health, or social issues which hinder adequate followup, and take measures to improve patient compliance in order to
maximize visual rehabilitation.
Commercial Relationships: Vikram S. Makhijani, University
of California, Berkeley (P); Jonathan Levine, None;
Brandon B. Johnson, None; Pearl Rosenbaum, None
Program Number: 2098 Poster Board Number: B0330
Presentation Time: 11:00 AM–12:45 PM
Changes in systemic MCP-1 levels in patients with diabetic
maculopathy receiving different intravitreal anti-VEGF agents
Emily H. Shao1, 2, Frederick Tam3, Simon Taylor2, 1. 1Ophthalmology,
University of Surrey, Guildford, United Kingdom; 2Royal Surrey
County Hospital, Guildford, United Kingdom; 3Imperial College
London, London, United Kingdom.
Purpose: Vascular endothelial growth factor (VEGF) has become
a major target for the treatment of retinal disease. However, the
systemic effects of intraocular administration of anti-VEGF drugs
remain controversial and this may be particularly important in
patients with coexistent diabetic maculopathy and nephropathy, as
VEGF is essential for the maintenance of normal renal function.
Monocyte chemoattractant protein 1 (MCP1) is a key chemokine that
regulates migration and infiltration of monocytes/ macrophages. It
also mediates acute ischaemic and toxic kidney injury and is a major
marker of acute kidney injury. In this study we analysed systemic
changes in VEGF and MCP-1 levels in diabetic patients with diabetic
macular oedema who was treated with a course of bevacizumab,
ranibizumab and aflibercept injections for diabetic macular oedema.
Methods: Serum samples were obtained from thirty patients with
diabetic macular oedema, randomised to bevacizumab, ranibizumab
and aflibercept treatment. They were each treated with 3 intravitreal
injections over a period of 3 months. Peripheral venous blood
samples were taken at each visit and centrifuged at 3,000 rpm for
10 minutes followed by being stored at – 70°C until analysis. Serum
VEGF 165 and MCP-1 levels were determined using enzyme-
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ARVO 2016 Annual Meeting Abstracts
linked immunosorbent assay (R&D systems, UK) both pre and post
immunodepletion to remove complexed VEGF.
Results: There were greater suppression of serum VEGF 165
levels was suppressed by intravitreal bevacizumab in comparison
to ranibizumab and aflibercept (p=0.03). Serum MCP-1 levels
conversely increased with intravitreal anti-VEGF therapy, after the
end of the first course of three injections (p=0.04). Patients with
poorer initial renal function had a significantly greater increase in
systemic MCP-1 levels following intravitreal Bevacizumab relative
to patients with normal baseline renal function.
Conclusions: These results suggest that repeated intravitreal antiVEGF therapy lead to a decrease in systemic VEGF levels, with
corresponding increase in MCP-1 levels in diabetic patients. Patients
with poor baseline renal function were the most affected, suggesting
that the systemic decrease in VEGF levels with intravitreal
Bevacizumab may be of particular significance in diabetic patients
with coexistent nephropathy.
Changes in systemic VEGF with anti-VEGF therapy
Systemic MCP-1 changes with anti-VEGF therapy
Commercial Relationships: Emily H. Shao, None; Frederick tam,
None; Simon Taylor, None
Program Number: 2099 Poster Board Number: B0331
Presentation Time: 11:00 AM–12:45 PM
Are the initial treatment results of Ranibizumab for Diabetic
Macular Oedema maintained at 1 year with Pro re nata protocol?
A real life experience
Ajay Kumar K. Kotagiri, Maged Habib, Alex Stubbing -Moore,
Dalvir Bajwa, Deepali Varma, Maria Teresa Sandinha,
Jonathan Smith, David Steel. Ophthalmology, Sunderland Eye
Infirmary, Sunderland, United Kingdom.
Purpose:
Various treatment protocols have been adopted for the use of
Ranibizumab (RBZ) for diabetic macular oedema (DMO) based
on published trial results. The utility of these regimes in real-life
practice has not been reported. This study was conducted to evaluate
the efficacy of RBZ Pro re nata (PRN) protocol at 1 year following a
fixed loading dose and whether earlier visual acuity gains with RBZ
treatment are maintained.
Methods:
Observational study with prospectively collected real-life data using
an electronic database on patients with DMO treated with RBZ. All
patients received RBZ loading dose of fixed four monthly injections
with two further monthly injections if needed. This is followed by
PRN protocol with monthly monitoring visits and deferred laser
treatment if required. Baseline demographic and clinical data were
collected. Best corrected visual acuity (BCVA) together with central
retinal thickness (CRT) was recorded each visit as well as injections
needed.
Results:
100 eyes of 73 patients included. Mean baseline BCVA was 60.1
letters (Standard Deviation (SD)13.7), with mean CRT of 472 (SD
107.7). Following maximum of six fixed monthly loading doses,
the mean change in BCVA was 6 letters with a reduction of CRT
reduction of -141.6 microns. However, following PRN dosing at 1
year, BCVA deteriorated by 4.2 letters while CRT was maintained.
There was a mean of 6.6 injections in the first year with an average
follow up intervals of 7.5 weeks.
Conclusions:
The real life experience of RBZ treatment with a PRN protocols
for DMO struggles to reflect phase 3 trials results. BCVA gains by
earlier fixed dosing are not maintained. This could be due to several
factors, including capacity issues to allow monthly monitoring and
timely treatment. In real life, planned fixed dosing or treat and extend
protocols may be better options for delivering more effective care.
Commercial Relationships: Ajay Kumar K. Kotagiri, None;
Maged Habib, None; Alex Stubbing-Moore, None; Dalvir Bajwa,
None; Deepali Varma, None; Maria Teresa Sandinha, None;
Jonathan Smith, None; David Steel, None
Program Number: 2100 Poster Board Number: B0332
Presentation Time: 11:00 AM–12:45 PM
Good real-world outcomes in DME patients with poor baseline
visual acuity at 1 year: results from LUMINOUSTM
Paul Mitchell. Centre for Vision Research, Department of
Ophthalmology and Westmead Millennium Institute, University of
Sydney, Sydney, NSW, Australia.
Purpose: Ranibizumab (RBZ) is approved for the treatment of visual
impairment secondary to diabetic macular edema (DME). However,
there are limited data on its use in DME patients in real-world
settings. LUMINOUSTM (NCT01318941) is an ongoing, 5-year,
global, multicenter, observational, non-interventional, open-label
study designed to evaluate the safety, efficacy, treatment patterns, and
health-related quality of life outcomes associated with RBZ 0.5 mg
treatment in clinical practice. Here we present baseline characteristics
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ARVO 2016 Annual Meeting Abstracts
of 4427 DME patients enrolled before March 2015 and efficacy and
safety results of 1828 DME patients enrolled before March 2014 who
had the potential for 1-year follow-up, from the third interim analysis
(IA) of LUMINOUSTM.
Methods: Consenting adult (≥18 years) DME patients, who were
treatment naïve (T1) or previously treated with RBZ (T2) /other
ocular treatments (T3), were treated according to the local product
label. Data were analyzed by prior treatment status of the primary
treated eye.
Results: Baseline data are available from 4427 patients: mean age,
64.0 years; males, 57.2%; Caucasians, 73.9%; mean HbA1c, 62.7
mmol/mol. T2 had higher baseline visual acuity (VA) (59.1 letters)
and lower central retinal thickness (CRT) (370.4 μm) compared with
other treatment groups (T1, VA: 53.9 letters, CRT: 414.8 μm; T3:
VA: 55.6 letters, CRT: 430.1 μm). All three treatment groups showed
improvement in VA and CRT at 1 year (Table). The VA improvements
in T1 were similar to T3 at 1 year but with a lower mean number of
injections and visits (Table). Treatment-naïve patients with relatively
lower baseline VA (VA <23 letters and ≥23 to <39 letters) showed
greater VA improvements than those with baseline VA ≥39 letters
(Figure). The rate of ocular and non-ocular serious adverse events
reported was 0.38% and 4.86%, respectively.
Conclusions: Prior RBZ-treated patients showed higher baseline VA
and lower CRT versus treatment- naïve patients. One-year follow-up
outcomes from LUMINOUSTM showed VA improvement irrespective
of previous treatment status. Greater VA improvements were
observed in treatment naïve patients with a relatively low baseline VA
(<39 letters). The results from this IA in LUMINOUSTM support the
well-established safety profile of RBZ.
Figure. VA outcomes stratified by baseline VA in treatment-naïve
patients at 1-year
Program Number: 2101 Poster Board Number: B0333
Presentation Time: 11:00 AM–12:45 PM
Differences in anti-vascular endothelial growth factor (antiVEGF) injection frequency and costs for ranibizumab versus
aflibercept in patients with diabetic macular edema (DME)
Carlos Quezada Ruiz1, Yamina Rajput1, Kathleen Wilson2,
Alice Huang2, David M. Smith2, Helen Varker2, Stephen S. Johnston2.
1
Genentech, Inc., South San Francisco, CA; 2Truven Health
Analytics, Bethesda, MD.
Purpose: To compare the frequency and costs of intravitreal antiVEGF injections, in treatment-naïve (TN) or previously-treated
(PT) patients with DME receiving ranibizumab (RBZ) 0.3 mg vs
aflibercept (AFL) 2.0 mg.
Methods: This retrospective study of US Medicare claims data
included patients who initiated treatment with RBZ or AFL (index
date [ID] August 10, 2012 to July 31, 2015) with the following
criteria: aged ≥18 years on ID; 12 months’ continuous eligibility
before ID and for 3–12 months following ID without switching
to a different anti-VEGF agent. Number of injections and related
costs were determined at 3-, 6-, 9-, and 12-month follow-up.
Injection frequency and costs for RBZ vs AFL were compared by
multivariate regression models. All models were adjusted for patient
demographics and clinical characteristics.
Results: In both TN (baseline [BL]: RBZ [N=1,305]; AFL [N=409])
and PT (BL: RBZ [N=756]; AFL [N=575]) patients, there were
no statistically significant differences between treatment groups
in the frequency of injections at months 3, 6, 9, and 12. However,
statistically significant differences in cost, in favor of RBZ, were
seen across all time points in both TN and PT patients. For example,
in TN patients at 6-months’ follow-up, adjusted injection costs were
$3,466 vs $5,979 for RBZ (N=912) and AFL (N=138), respectively;
the adjusted cost ratio was 1.73 (95% CI=1.53–1.94), p<0.0001. The
adjusted cost ratio was also significantly in favor of RBZ at months
3 and 9 (p<0.0001) and month 12 (p=0.04). Similarly, in PT patients
at 6 months, the adjusted injection costs were $3,660 vs $5,759 for
RBZ (N=465) and AFL (N=165), respectively; the adjusted cost ratio
was 1.57 (95% CI=1.35–1.84), p<0.0001. The adjusted cost ratio was
also significantly in favor of RBZ at month 3 (p<0.0001), month 9
(p=0.009) and month 12 (p=0.018).
Conclusions: For each analyzed follow-up period, and for both
TN and PT patients, injection frequency did not differ significantly
between RBZ and AFL treatments. Importantly, substantial and
statistically significant differences (all p<0.05) in the costs of antiVEGF injections were observed between RBZ and AFL treatments.
While the data should be interpreted with caution (decreasing sample
size; need for continued study) RBZ was the less costly treatment for
DME regardless of follow-up time.
Commercial Relationships: Carlos Quezada Ruiz, Genentech,
Inc.; Yamina Rajput, Genentech, Inc.; Kathleen Wilson, Truven
Health Analytics (C); Alice Huang, Truven Health Analytics (C);
David M. Smith, Truven Health Analytics (C); Helen Varker,
Truven Health Analytics (C); Stephen S. Johnston, Truven Health
Analytics (C)
Support: Genentech, Inc., South San Francisco, CA, provided
support for the study and participated in the study design; conducting
the study; and data collection, management, and interpretation.
Table. Efficacy results at 1 year
Commercial Relationships: Paul Mitchell, Roche (R), Novartis
(C), Roche (C), Novartis (R), Bayer (C), Bayer (R), Genentech (R),
Abbott (C), Genentech (C), Allergan (R), Abbott (R), Allergan (C)
Clinical Trial: NCT01318941
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ARVO 2016 Annual Meeting Abstracts
Program Number: 2102 Poster Board Number: B0334
Presentation Time: 11:00 AM–12:45 PM
Dose-response analysis of ranibizumab as-needed regimens
for best-corrected visual acuity improvement in patients with
diabetic macular edema using a modeling approach
Yuan Xiong1, Etienne Pigeolet2, Philippe Margaron2, Amy Racine2.
1
Novartis Pharmaceutical Corporation, East Hanover, NJ; 2Noavartis
Pharma AG, Basel, Switzerland.
Purpose: Ranibizumab (RBZ) 0.5 mg pro re nata (PRN) has a wellestablished efficacy profile and is approved for treatment of diabetic
macular edema (DME) in >100 countries worldwide. The Diabetic
Retinopathy Clinical Research Network (DRCR.net) Protocol T study
compared the efficacy of RBZ 0.3 mg PRN with other anti-vascular
endothelial growth factor agents; this dosing regimen is neither
studied previously nor approved. We assessed the dose responses of
RBZ using a step-wise modeling approach for better understanding of
the Protocol T 12-month efficacy results.
Methods: Summary data from the randomized clinical trials (RCT)
RESOLVE, RESTORE, REVEAL, RESPOND, RETAIN, RISE,
RIDE, Protocol I, and Protocol T with relevant arms were included in
the analyses. An exploratory analysis was performed to verify a doseresponse signal, then a dose-response model was built to describe
the relationship between the average monthly doses of RBZ and the
mean best-corrected visual acuity (BCVA) change from baseline at
Month 12. A similar analysis was performed in a subgroup of patients
with baseline BCVA <69 letters from RESOLVE, RESTORE,
REVEAL, RESPOND, RETAIN, and Protocol T studies.
Results: The pooled exploratory analysis indicated a linear doseresponse a dose range within which the RBZ average monthly dose
from Protocol T falls into (Figure 1). After accounting for inter-study
variability (study design, retreatment algorithms, etc.), the doseresponse model predicted that, in Protocol T, RBZ 0.5 mg PRN may
have provided a median BCVA gain of 13 letters (approximately 2–3
letters more than RBZ 0.3 mg PRN) with a mean of 7–7.5 injections
over 12 months (Figure 2). In the subgroup with baseline BCVA <69
letters, it was predicted that a mean of 9 RBZ 0.5 mg PRN injections
may have led to a median BCVA gain of 19 letters.
Conclusions: The dose-response model suggested that, in Protocol
T, RBZ 0.5 mg PRN may have led to higher BCVA gains compared
with RBZ 0.3 mg PRN. It was predicted that, compared with RBZ
0.3 mg PRN, RBZ 0.5 mg PRN may have led to a BCVA gain of 2–3
letters more in the overall population and 4–5 letters in patients with
baseline BCVA <69 letters.
Commercial Relationships: Yuan Xiong, Novartis Pharmaceutical
Corporation; Etienne Pigeolet, Novartis Pharma AG;
Philippe Margaron, Novartis Pharma AG; Amy Racine, Novartis
Pharma AG
Program Number: 2103 Poster Board Number: B0335
Presentation Time: 11:00 AM–12:45 PM
SHORT-TERM VARIATION OF MACULAR THICKNESS
AFTER INTRAVITREAL BEVACIZUMAB INJECTION FOR
DIABETIC MACULAR EDEMA
Marcia C. Martins, Vanessa C. Storti, Natalia Abujamra,
Erico Pacheco, Nicolau Homar, Rafael A. Leal, Gulherme N. Borges,
Adle Saulo Nogueira, Anna Carolina C. Araujo, Arnaldo F. Bordon.
HOSPITAL OFTALMOLOGICO DE SOROCABA, SOROCABA,
Brazil.
Purpose: To evaluate the short-term variation of central macular
thickness (CMT) after intravitreal bevacizumab injection for diabetic
macular edema.
Methods: A prospective observational clinical study was performed.
Written informed consent was obtained for every patient. Study was
approved by the Ethics Committee number 35463914.2.0000.0088.
Trial was registered at EudraCT number 2015-005516-15.
Assessment for best corrected visual acuity (BCVA) was performed
at baseline and 24 hours, 3 days, 7 days, 14 days, 21 days, and
28 days after intravitreal injection of bevacizumab. Complete
ophthalmic examination including fundus biomicroscopy and optical
coherence tomography central macular thickness using Spectralis
(Heidelberg Engineering) were performed at baseline and 1 hour, 4
hours, 24 hours, 3 days, 7 days, 14 days, 21 days, and 28 days after
intravitreal injection of bevacizumab.
Results: A total of 16 eyes of 12 patients (6 male; mean age, 62 ± 8.7
years; range, 50-74 years) who completed the 28-day follow-up were
included for analysis. Mean CMT at baseline was: 551 ± 219.38μm;
Mean CMT at 1 hour, 4-hour, 24-hour, 3-day, 7 day, 14-day, 21-day,
and 28-day were: 543 ± 217μm, 531 ± 217μm, 505 ± 189μm, 473
± 153μm, 475 ± 150μm, 453 ± 137μm, 466 ± 169μm, and 465 ±
164μm, respectively.
Statistically significant reduction of CMT compared to baseline was
found at the 4-hour follow-up (mean CMT reduction: t=3.6389, p <
0.01), and lasted until the 28-day follow-up (mean CMT reduction:
t=2.1453, p < 0.05). Improvement in mean BCVA was observed in
the 24-hour follow-up and lasted until the 28-day follow-up although
it was not statistically significant.
Conclusions: Bevacizumab produced improvement in CMT as soon
as 4-hour after injection that persists up to 28 days. However, visual
acuity did not reached statistical significance level, probably due to
the sample size.
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ARVO 2016 Annual Meeting Abstracts
Commercial Relationships: Marcia C. Martins; Vanessa C. Storti,
None; Natalia Abujamra, None; Erico Pacheco, None;
Nicolau Homar, None; Rafael A. Leal, None; Gulherme N. Borges,
None; Adle Saulo Nogueira, None; Anna Carolina C. Araujo,
None; Arnaldo F. Bordon, None
Clinical Trial: 2015-005516-15
Program Number: 2104 Poster Board Number: B0336
Presentation Time: 11:00 AM–12:45 PM
Treatment of Diabetic Macular Edema with Aflibercept in Eyes
with Previous Nonresponse to Ranibizumab and/or Bevacizumab
Rachel Sadowsky1, Polly Quiram2. 1University of Minnesota,
Minnetonka, MN; 2VitreoRetinal Surgery, PA, Minneapolis, MN.
Purpose: Diabetic Macular Edema (DME) is a vascular endothelial
growth factor (VEGF) driven process that can be effectively treated
with intravitreal injections of anti-VEGF agents bevacizumab
and ranibizumab. In a subset of patients, DME persists and visual
loss occurs despite active treatment with these anti-VEGF agents.
The Food and Drug Administration recently approved aflibercept,
now a third commonly used intravitreous anti-VEGF agent. This
retrospective chart review identified patients with persistent DME
as “nonresponders,” and tested the hypothesis that treatment with
aflibercept improves functional and structural outcomes in patients
that were otherwise resistant to prior anti-VEGF therapies.
Methods: The design of this study is a single center, retrospective
chart review. Consecutive eyes previously receiving intravitreal
bevacizumab (1.25mg) or ranibizumab (0.3mg) for chronic DME and
later switched to aflibercept (2mg) were identified. Inclusion criteria
included “nonresponding” eyes previously receiving 6 or more
injections of ranibizumab and/or bevacizumab for DME. Exclusion
criteria included eyes receiving less than 6 previous intravitreal
injections of anti-VEGF agents. Eyes with less than 6 month follow
up were excluded. Primary outcomes include mean change in visual
acuity (VA) and mean change in central subfield foveal thickness
(CSFT) by SD-OCT following initiation of aflibercept therapy.
Results: In this study, 58 eyes deemed “nonresponders” were
identified for analysis. Prior to treatment with aflibercept, 53%
of eyes were treated primarily with bevacizumab, and 47% with
ranibizumab. The mean number of total injections before aflibercept
was 16 (range 6-49). Of eyes with chronic DME, 58% previously
received focal laser (mean 2.7; range 1-8). At initiation of aflibercept
therapy, mean VA was 20/60 and CSFT was 417 ±117mm. Following
a single dose of aflibercept, mean VA improved to 20/50 (p=0.015)
and CSFT improved to 351 ± 88mm (p=0.011). Following 3
treatments of aflibercept, mean VA improved to 20/40 (p=0.16) and
CSFT improved to 364 ± 119mm (p=0.03).
Conclusions: This study has identified eyes with chronic DME that
are nonresponsive to intravitreal bevacizumab and ranibizumab. The
novel mechanism of aflibercept appears to benefit eyes with chronic
DME. Additional analysis will determine the long-term (1 year)
benefit of aflibercept in eyes with chronic DME.
Commercial Relationships: Rachel Sadowsky, None;
Polly Quiram, None
Support: 2015 VitreoRetinal Surgery Foundation Research Award
Program Number: 2105 Poster Board Number: B0337
Presentation Time: 11:00 AM–12:45 PM
Effects of Two Different Doses of Ranibizumab on Diabetic
Retinopathy Severity and Progression in the Ranibizumab for
Edema of the Macula in Diabetes (READ-3) Study
Mohammad A. Sadiq1, Muhammad Hassan1, Mohamed K. Soliman1, 2,
Salman Sarwar1, Rubbia Afridi1, Aniruddha Agarwal1, Diana V. Do1,
Quan Dong Nguyen1, Yasir J. Sepah1. 1. University of Nebraska
Medical Center, Truhlsen Eye Institute, Omaha, NE; 2Ophthalmology,
Assiut University, Assiut, Egypt.
Purpose: To evaluate the effects of two different doses of
Ranibizumab (0.5mg and 2.0mg) on severity of diabetic retinopathy
(DR) in patients with diabetic macular edema (DME).
Methods: In the READ-3 study, patients with DME received six
mandatory monthly intravitreal injections of either 0.5 or 2.0mg of
ranibizumab (RBZ) followed by as needed (PRN) injections until
month 24. The main outcome measure of this sub-study was to assess
the effects of two different doses of ranibizumab on the grade of DR
in the study eye. Inclusion criterion included completion of month
24 visits and availability of gradable seven-field fundus photographs
at baseline and month 24 visits. Fundus photographs were analyzed
at the two visits by a central reading center. Diabetic retinopathy
severity scale (DRSS) scores were assessed using the Early Treatment
Diabetic Retinopathy Study (ETDRS) severity scale. Participants
with a history of pan retinal photocoagulation (PRP) were assigned to
a minimum severity level of 60. Frequencies of change in severity of
DR were compared using the chi-square test and the Fisher exact test.
Results: 152 eyes (152 patients) were randomized in the READ-3
study. 70 eyes (70 patients) met above inclusion criteria and were
thus analyzed. There were 43 eyes in the 0.5mg group and 27 eyes
in the 2.0mg group. A total of 28 eyes (40%; 18 in 0.5mg and 10 in
2.0mg) had a history of prior PRP. At 24 months, 33.3% eyes (groups
combined) showed a ≥2-step reduction in the DRSS score. Forty
percent (40%) of eyes in the low dose group (0.5mg) and 23.5 % of
patients in the high dose group (2.0mg) showed a ≥2-step reduction
in the DRSS score. The difference between the two doses was not
significant (p=0.51). None of the patients demonstrated worsening of
DR status or developed any complications of the disease.
Conclusions: Both high-dose and low-dose intravitreal RBZ can lead
to reduction in degree and progression of DR in patients with DME.
High-dose RBZ does not appear to provide additional benefit over 0.5
mg RBZ in improving DR.
Commercial Relationships: Mohammad A. Sadiq, None;
Muhammad Hassan; Mohamed K. Soliman, None;
Salman Sarwar, None; Rubbia Afridi, None; Aniruddha Agarwal,
None; Diana V. Do, Genentech (C), Regeneron (F), Regeneron (C),
Genentech (F), Allergan (C), Santen (C); Quan Dong Nguyen,
Santen (F), Regeneron (F), Bausch and Lomb (C), Santen (C),
MacuSight (F), Ophthotech (F), Genentech (F), L-path (F);
Yasir J. Sepah, None
Support: Unrestricted educational grant from Research to prevent
blindness (RPB)
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to access the versions of record.
ARVO 2016 Annual Meeting Abstracts
Program Number: 2106 Poster Board Number: B0338
Presentation Time: 11:00 AM–12:45 PM
Progression of Diabetic Retinopathy in the Bevordex study: a
randomized clinical trial of intravitreal bevacizumab versus
intravitreal dexamethasone for diabetic macular edema
Lyndell L. Lim1, 3, Dania Qatarneh1, Lauren Hodgson1,
Hemal Mehta2, Sanjeewa Wickremasinghe1, 3, Anna Campain2,
Mark C. Gillies2, Samantha Fraser-Bell2. 1Centre for Eye Research
Australia, University of Melbourne, East Melbourne, VIC, Australia;
2
Save Sight Institute, The University of Sydney, Sydney, NSW,
Australia; 3Royal Victorian Eye and Ear Hospital, Melbourne, VIC,
Australia.
Purpose: To compare the effect of bevacizumab (Avastin;
Genentech, South Francisco, CA) with dexamethasone implants
(Ozurdex; Allergan, Inc., Irvine, CA) on the progression of diabetic
retinopathy (DR).
Methods: Post-hoc analysis of 24 month data from a phase 2,
prospective, multicenter, randomized, single-masked clinical trial
(clinicaltrials.gov identifier NCT01298076). Eightly-eight eyes of 61
patients with center-involving diabetic macular edema (DME) were
recruited: 42 eyes were randomized to receive bevacizumab every
4 weeks and 46 eyes were randomized to receive a dexamethasone
implant every 16 weeks, both pro re nata. Main outcome measures
included change in DR severity based on reading center assessment
of color fundus photographs using the modified Airlie House scale,
and development of clinically important events defining high-risk
proliferative diabetic retinopathy (PDR).
Results: Neither treatment showed a statistically significant
propensity toward increasing or decreasing the DR grade at 1 and
2 years, with no significant difference between the two groups
(p=0.71). Despite ongoing treatment, a small number of eyes
developed PDR at 2 years; 1 eye (3%) receiving Bevacizumab and 7
eyes (18.9%) receiving Dexamethasone (p=0.05 Fisher’s exact test).
There was no association between HbA1C, systemic blood pressure
(BP) and progression of DR.
Conclusions: Both bevacizumab and dexamethasone implants have
a similar effect on the progression of DR severity when administered
for DME, with the majority of patients retaining the same grade on
ETDRS photographic assessment after 1 and 2 years of follow up.
Importantly, the development of PDR still occurred in some eyes
undergoing either treatment, reinforcing the need to monitor all
aspects of DR when actively managing DME with either of these
treatments.
Commercial Relationships: Lyndell L. Lim, Allergan (R),
Abbvie (R), Bayer (R), Novartis (F), Bayer (F); Dania Qatarneh,
Bayer (F); Lauren Hodgson, None; Hemal Mehta, None;
Sanjeewa Wickremasinghe, Novartis (S), Bayer (S), Novartis
(R), Bayer (R); Anna Campain, None; Mark C. Gillies;
Samantha Fraser-Bell, Allergan (R), Allergan (F), Bayer (F)
Support: NHMRC Project Grant 2010; Allergan Unrestricted
Educational Grant
Clinical Trial: NCT01298076
Program Number: 2107 Poster Board Number: B0339
Presentation Time: 11:00 AM–12:45 PM
Short-term outcomes of aflibercept therapy for diabetic macular
edema in patients with incomplete response to ranibizumab and/
or bevacizumab
Raphaelle Ores, Elise Philippakis, Pascale G. Massin,
Ramin Tadayoni, Benedicte M. Dupas. Service d’Ophtalmologie,
Hôpital Lariboisière, AP-HP, Paris, France.
Purpose: To investigate the effects of aflibercept 2 mg on diabetic
macular edema in patients with incomplete response to ranibizumab
and/or bevacizumab.
Methods: Retrospective interventional study. Data from 9
consecutive patients with diabetic macular edema (DME) that showed
incomplete response to ranibizumab 0.5 mg, and/or bevacizumab
1.25 mg and who were switched to aflibercept 2mg were collected.
Incomplete response was defined on Spectral Domain-OCT (SDOCT) by a decrease of central subfield foveal thickness (CSFT)<
20% four weeks after at least 3 monthly intravitreal injections
of ranibizumab 0.5 mg, and/or bevacizumab 1.25 mg, and the
persistence of fluid with a CSFT > 315 µm. Anatomic and functional
responses were retrospectively assessed 4 weeks after at least 3
monthly intravitreal injections of aflibercept.
Results: Ten eyes of 9 patients were included (mean follow-up:
8.8±2.8 months). The mean age was 58.8±8.5 years and all patients
had type 2 diabetes (median HbA1C 7.2%). Median duration of DME
was 41 months (range 13-79) and baseline mean CSFT was 597±149
µm. Four weeks after 3 consecutive monthly intravitreal injections of
aflibercept, 7 eyes over 10 (70%) showed an anatomic improvement
(decrease of CSFT >20%) with a decrease in average CSFT from
529μm to 389μm (p=0.0026). No significant visual acuity (VA) gain
was observed (from 0.44±0.2 to 0.39±0.27 LogMAR (p = 0.3)).
Conclusions: Our findings suggest that in patients with DME with
persistent fluid on SD-OCT after at least 3 injections of ranibizumab
0.5 mg and/or bevacizumab 1.25 mg, a switch to intravitreal
injections of aflibercept allowed to obtain an anatomic improvement
in 70% of cases, with no additional VA gain.
Commercial Relationships: Raphaelle Ores, None;
Elise Philippakis, None; Pascale G. Massin, None;
Ramin Tadayoni, None; Benedicte M. Dupas, None
Program Number: 2108 Poster Board Number: B0340
Presentation Time: 11:00 AM–12:45 PM
Effects of antiangiogenic treatment in vitreomacular adhesion in
patients with diabetic macular edema
Alexandros Deligiannidis, Jose Lorenzo Carrero. POVISA hospital,
Vigo, Spain.
Purpose:
To describe the effect of antiangiogenic treatment to the progression
of posterior vitreous detachment in diabetic patients with macular
edema.
Methods:
Retrospective study of all diabetic patients with macular edema who
were treated with antiangiogenic treatment in two institutions during
a 3-year period. Baseline ophthalmic and follow-up examination
included evaluation of the vitreoretinal interface with OCT.
Results:
There were 145 patients with gradable OCT exams: Initially; 35
(24%) patients had no detectable PVD, 39 (26%) patients with broad
VMA, 44 (30%) with focal VMA, 11 (7,5%), with no VMA but
posterior vitreous attachment to the optic disc, and 16 (11%) patients
with complete PVD. During follow-up, there were 47 (32%) patients
who experienced progression of the vitreous detachment. Patients
who experienced progression of the vitreomacular detachment were
likely to have been treated with more injections (mean: 6,15) than
patients who did not progress (mean: 3,32). (unpaired t-test p=0,001).
There were no differences concerning visual outcome and reduction
of the macular thickness.
Conclusions:
Antiangiogenic treatment may induce progression of the posterior
vitreous detachment at the posterior vitreoretinal interface in diabetic
patients with macular edema.
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ARVO 2016 Annual Meeting Abstracts
Commercial Relationships: Alexandros Deligiannidis, None;
Jose Lorenzo Carrero, None
Program Number: 2109 Poster Board Number: B0341
Presentation Time: 11:00 AM–12:45 PM
Effect of selective oral inhibition of CCR2/5 chemokine receptors
compared to intravitreal ranibizumab on diabetic macular edema
(DME)
Brian B. Berger1, Jeremy Gale2, Steven Gilbert2, Sergei Popa4,
Marla Sultan2, Ronald Schachar2, Rob Webster2,
Christelle Perros -Huguet3. 1Retina Research Center, Austin,
TX; 2Pifzer Inc., Cambridge, MA; 3Alexion Pharmaceutical, Inc.,
Cheshire, CT; 4Spitalul Clinic Republican, Chisnau, Moldova (the
Republic of).
Purpose: Chemokine receptor ligands are elevated in the aqueous
and vitreous in diabetics and the MCP-1/CCR2 receptor axis appears
to play an important role in alterations to the blood-retinal barrier
in diabetes. We hypothesized that combined blockade of CCR2 and
CCR5 receptors would improve DME. Hence, the efficacy and safety
of a novel, highly specific and long-acting dual CCR2/5 receptor
antagonist, PF-04634817, on DME was assessed in a multinational,
multicenter, randomized, double-masked, placebo-controlled, parallel
group trial of DME patients with Type 1 and 2 diabetes.
Methods: DME patients with ETDRS BCVA of 24-78 letters and
spectral domain optical coherence tomographic central retinal
thickness (CRT) of >250mm in the study eye at baseline were
randomly assigned to receive for 12 weeks either PF-04634817
200mg orally once daily plus masked sham therapy given monthly
or ranibizumab (0.3 or 0.5mg) intravitreal injection monthly plus
daily oral placebo. Change from baseline at 12 weeks in BCVA, CRT,
fluorescein angiographic (FA) area of leakage and grades of diabetic
retinopathy (DR) were assessed.
Results: 199 subjects, with mean (SD) BCVA in the study eye of
62.3 (+11.43) letters and a mean CRT of 453.1 mm (+159.55) were
randomized. Following 12 weeks of dosing mean BCVA improved
4.4 (+8.21) and 6.4 (+7.83) letters, and mean CRT decreased
24.5mm (+97.74) and 110.4mm (+130.53) in the PF-04634817 and
ranibizumab groups, respectively. The least squares mean difference
in BCVA was 2.41 letters (80% CI: – 3.91 to 0.91) in favor of
ranibizumab. There were 6.9% and 15.4% 3-line gainers, a mean
0.17mm2 (+4.96) and 7.33mm2 (+9.28) decrease in FA leakage area,
and a mean 0.0 (+0.61) and 0.5 (+1.03) reduction in grades of DR
with PF-04634817 and ranibizumab, respectively. Adverse events
(AEs) following PF-04634817 treatment were mostly mild, with the
only treatment-related AE of headache exceeding 1% incidence.
Conclusions: Although there was a mean 4.4 letter improvement
in BCVA following oral treatment with PF-04634817, it was
unaccompanied by anatomical improvements in the retina of the
study or fellow eyes. This suggests that changes in BCVA following
monotherapy of selective inhibition of CCR2/5 for DME should be
interpreted with caution, but further study in combination with other
agents may be of value.
Commercial Relationships: Brian B. Berger, Aciont Inc. (F),
Allegro Ophthalmics (F), GlaxoSmithKline (F), Panoptica (F),
Aerpio Therapeutics (F), Ampio Pharmaceuticals (F), Bausch &
Lomb (F), Daiichi Sankyo (F), Genentech (F), Alcon Laboratories
(C), University of Virginia (F), Pfizer (F), Novartis (F), Diabetic
Retinopathy Clinical Research (F), Santen Inc. (C), Alimera Advisory
Board (C), Tyrogenex Inc (F), StemCells Inc (F), Ophthotech
(F), Allergan (C); Jeremy Gale; Steven Gilbert, Pfizer, Inc.;
Sergei Popa, Eli Lilly and Company (F), J&J Pharmaceuticals (F),
Gilead Sciences (F), Idenix Pharmaceuticals (F), Astellas Pharma
(F), Sanofi (F), Merck Pharmaceuticals (F), UCB Pharma (F), Pfizer,
Inc. (F); Marla Sultan, Pfizer, Inc.; Ronald Schachar, Pfizer, Inc.;
Rob Webster, Pfizer, Inc.; Christelle Perros-Huguet, Alexion
Pharmaceuticals
Clinical Trial: NCT01994291
Program Number: 2110 Poster Board Number: B0342
Presentation Time: 11:00 AM–12:45 PM
Evaluation of En-face OCT Images in Diabetic Macular Edema
with Anti-VEGF Treatment
Shintaro Horie, Mitsunao Ide, Kei Morohoshi, Kyoko Ohno-Matsui.
Ophthalmology, Tokyo Medical and Dental University, Tokyo, Japan.
Purpose: In diabetic macular edema (DME), en-face OCT presents
two-dimensional distribution of microcysts, which intuitively
indicates severity of the disease. In this study, utility of area measured
by en-face OCT was examined comparing with the other factors in
sectional OCT.
Methods: 17 eyes of 14 DME patients in our outpatient clinic (Tokyo
Medical and Dental University Hospital), who were given antiVEGF therapy (either Ranibizumab or Aflibercept) and en-face OCT
examination (RTVueXR Avanti®) from March 2015 to November
2015, were included. Data obtained from clinical records and OCT
images were retrospectively examined. The area of DME was
measured by en-face OCT (3mm square). The central or maximum
retinal thickness was measured by sectional swept-source OCT
(Topcon Atlantis®). Correlation analysis was performed within the
areas of macular edema, central retinal thickness and maximum
retinal thickness.
Results: The area of DME measured by en-face OCT was
significantly correlated with central retinal thickness by sectional
OCT (p<0.0001). When comparing before and after administrations
of the anti VEGF drugs, the alteration of area and that of maximum
retinal thickness were significantly related (p=0.011). In this study,
the comparison between the Ranibizumab treated and the Aflibercept
treated group showed no significant differences in those factors.
Conclusions: En-face OCT is useful for clinical management of
DME not only it give us intuitive two-dimensional pathology but also
it is related to other conventional factors in sectional OCT. Utilizing
en-face OCT in the assessment of therapeutic effects is also hopeful.
Commercial Relationships: Shintaro Horie, None; Mitsunao Ide,
None; Kei Morohoshi, None; Kyoko Ohno-Matsui, None
Support: JSPS KAKENHI Grant number 26861438
Program Number: 2111 Poster Board Number: B0343
Presentation Time: 11:00 AM–12:45 PM
Effects of Two Different Doses of Ranibizumab on the Resolution
and Recurrence of Diabetic Macular Edema in the Ranibizumab
for Edema of the Macula in Diabetes (READ-3) Study
Rubbia Afridi1, Aniruddha Agarwal1, Mohammad A. Sadiq1,
Kanika Aggarwal3, Muhammad Hassan1, Mohamed K. Soliman1, 2,
Salman Sarwar1, Diana V. Do1, Quan Dong Nguyen1, Yasir J. Sepah1.
1
Stanley M.Truhlsen Eye Institute, Omaha, NE; 2Dept. Of
Ophthalmology, Assiut University Hospital, Assiut, Egypt;
3
Advanced Eye Center, Post-Graduate Institute of Medical Education
and Research, Chandigarh, India.
Purpose: To determine the number of intravitreal injections of
ranibizumab (RBZ) required to achieve resolution of diabetic macular
edema (DME) on spectral-domain optical coherence tomography
(SD-OCT), and the time interval for DME to recur
Methods: The READ-3 Study assessed efficacy of two doses
(0.5mg and 2.0mg) of intravitreal RBZ for DME. Study eyes were
randomized to one of two doses to receive monthly injections
starting at baseline, until month 5. Thereafter, patients were followed
monthly and retreated if central retinal thickness was ≥250µm (time-
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ARVO 2016 Annual Meeting Abstracts
domain OCT) and/or fluid was detected on SD-OCT within 200x200
macular scan centered on fovea, until month 24. Two masked graders
determined presence or absence of edema on OCT. Fisher’s exact test
was used to calculate difference between two arms
Results: 152 eyes (152 patients) were randomized in READ-3 study.
107 (70%) eyes (0.5mg=50, 2.0mg=57) had resolution of DME
during the course of the study. 45 (30%) eyes had persistent DME
that did not resolve at any visit during the course of study or until
exit visit. Of the 107 eyes, 58 eyes (0.5mg=23, 2.0mg=35; p=0.123)
received 5-7 injections, 14 eyes (0.5mg=8, 2.0mg=6) received
8-10 injections, 22 eyes (0.5mg = 13, 2.0mg = 9) received 10-15
injections; 13 eyes (0.5mg=6, 2.0mg=7) received 16-23 injections to
achieve resolution of edema. Mean number of injections required to
achieve resolution of DME was 9.21 and 10.26 injections in 2.0 and
0.5mg groups, respectively (p=0.21). DME did not recur in 8 eyes
(0.5mg=4, 2.0mg=4) throughout the study after initial resolution.
Among the remaining eyes which were followed monthly, 62
(0.5mg=32, 2.0mg=30) had recurrence of edema after treatment was
deferred beyond one month, 20 eyes (0.5mg=10, 2.0mg=10) after
treatment was deferred beyond two months while another 10 eyes
(0.5mg=1, 2.0mg=9) had recurrence of edema after treatment was
deferred beyond three months. Mean duration to retreatment was
69 days for both groups (0.5mg=69 days, 2.0mg=68 days; p>0.05).
There was no difference in number of patients requiring more than 6
injections in two treatment arms (p=0.42)
Conclusions: Eyes with DME require continuous treatment with
RBZ despite initial resolution of fluid on OCT. Higher dosage of
RBZ did not exhibit greater efficacy in reducing rate of recurrence of
DME
Commercial Relationships: Rubbia Afridi, None;
Aniruddha Agarwal, None; Mohammad A. Sadiq, None;
Kanika Aggarwal, None; Muhammad Hassan, None;
Mohamed K. Soliman, None; Salman Sarwar, None; Diana V. Do;
Quan Dong Nguyen, Novartis (C), allergan (F), Regeneron
Pharmaceuticals, Inc (C), Santen Pharmaceutical Co., Ltd (F),
AbbVie, Inc (C), Genentech, Inc (C), Bausch & Lomb, Inc. (F);
Yasir J. Sepah, Genentech (C), Optovue (F), Zeiss (F)
Program Number: 2112 Poster Board Number: B0344
Presentation Time: 11:00 AM–12:45 PM
Is HbA1c a predictor of response to ranibizumab therapy in
diabetic macular edema?
Angela Rees, Habib Abubakar, Ranjan Rajendram, Sheelah Antao,
Namritha Patrao, Razia Amin, Zaid Shalchi. Medical Retina,
Moorfields Eye Hospital, London, United Kingdom.
Purpose: Ranibizumab has transformed the treatment of diabetic
macular edema but little is known about how systemic glycaemic
control affects treatment outcome. We wanted to investigate the effect
of glycated haemoglobin (HbA1c) on the efficacy of ranibizumab in
the treatment of diabetic macular edema using a retrospective clinical
case series.
Methods: The Moorfields OpenEyes and diabetes nursing databases
were used to study eyes with diabetic macular edema treated with
ranibizumab from October 2013 to November 2015 at the main City
Road site. Only eyes receiving at least 3 injections and completing
12 months follow-up were included. Where both eyes received
treatment, the first treated eye was included for analysis. When both
eyes received initial treatment simultaneously, random number tables
were used to select the eye for analysis. The primary outcome was
number of injections in year 1. The secondary outcome was gain in
visual acuity ETDRS letters. Good glycaemic control was defined as
HbA1c ≤ 59 mmol/mol (7.5%), with poor control above this figure.
Results: One hundred and nineteen eyes were included in the
analysis. 62 (52.0%) eyes were in patients with poor glycaemic
control. The mean±SD number of injections in year 1 was similar
in both the good and poor control groups (6.66±3.51 vs 6.63±3.61,
p=0.95). The gain in ETDRS letters was also similar in both low and
high HbA1c groups (5.00±7.39 vs 8.06±15.23, p=0.16).
Conclusions: HbA1c is not a predictor of outcome in eyes with
diabetic macular edema receiving ranibizumab therapy.
Commercial Relationships: Angela Rees, None; Habib Abubakar,
None; Ranjan Rajendram; Sheelah Antao, None;
Namritha Patrao, None; Razia Amin, None; Zaid Shalchi, None
Program Number: 2113 Poster Board Number: B0345
Presentation Time: 11:00 AM–12:45 PM
Compliance for angiogenesis inhibitor treatment with
ranibizumab in diabetic macular edema. A seven years
experience in Mexican population of the Mexican Institute of
Ophthalmology
Ramirez Neria Paulina1, Renata Garcia Franco1,
Brenda Rodriguez Camacho2, Kristo Aronne Lopez1. 1Retina and
Vitreous, Instituto Mexicano de Oftalmologia I.A.P., Mexico State,
Mexico; 2Instituto Mexicano de Oftalmologia I.A.P., Queretaro,
Mexico.
Purpose: Report adherence to anti-angiogenic therapy in patients
with diabetic macular edema (DDME) in Mexican population treated
with intravitreal ranibizumab (IVR).
Methods: We analized the medical records of the Mexican Institute
of Ophthalmology in patients with diabetic macular edema who had
been treated with intravitreal ranibizumab (2008 -2015).
Results: A total of 47 patients (50 eyes) with diabetic macular
edema that met the inclusion criteria were found. The mean age
of the patients was 61.92 ± 8.85 years. The mean best corrected
visual acuity (BCVA) at diagnosis was 20/160 (0.9 logMAR). About
compliance, 90% of patients received the second IVR, with a mean
BCVA of 20/125 (0.8 logMAR) found at month 3. By month 3, 22%
of patients didn not show up to get the IVR, and by the 6th month,
30% of patients refuse to get treatment. Even when patients refused
to have the IVR, they did show up for follow up visits, with a mean
10.78 months follow up. The mean number of IVB was 4.14 (1-11
range). Central foveal thicknesses (CFT) of all patients at follow-up
were averaged, regardless of the number of injections received, with
a mean CFT of 302.18 μm, this is a 78.100 μm reduction compared
to baseline (380.36 μm).
Conclusions: Our results exhibit a smaller number of monthly IVR
compared to large clinical trails, such as those made by PACORES
in hispanic population. The lack of adherence to treatment negatively
influences the final BCVA and CFT of our patients, that is why,
investigating the causes of this and work on improving adherence to
it, would be beneficial for our population.
Commercial Relationships: Ramirez Neria Paulina, None;
Renata Garcia Franco, None; Brenda Rodriguez Camacho, None;
Kristo Aronne Lopez, None
Program Number: 2114 Poster Board Number: B0346
Presentation Time: 11:00 AM–12:45 PM
Hyperuricemia is associated with anti-VEGF response in patients
with diabetic macular edema
Yun Wen Chen, Wei-Yu Chiang, Jon-Jer Lee. Kaohsiung Chang Gung
Memorial Hospital, Kaohsiung, Taiwan.
Purpose: Hyperuricemia is associated with diabetic nephropathy,
cardiovascular diseases and progression of diabetic retinopathy. The
aim of this study was to explore the role of serum uric acid (SUA)
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ARVO 2016 Annual Meeting Abstracts
in response to intravitreous anti-VEGF treatment in patients with
diabetic macular edema (DME).
Methods: A 24-weeks prospective study of DME patients who
underwent at least 3 monthly intravitreal injection (IVI) of
anti-VEGF was conducted at a medical center. Baseline SUA
concentration and parameters such as visual acuity (VA), central
foveal thickness (CFT), glycemic control (HbA1c) were collected
and analyzed to determine their contribution to the response of antiVEGF treatment.
Results: A total of 27, including 12 females and 15 males with
age between 50 and 75 years old were enrolled. Ten (37%) of
them showed hyperuricemia (SUA > 7.0 mg/dL). No significant
difference was observed in VA, CFT, and HbA1c level at baseline
and additional laser and/or IVI treatment at the end of study. Patients
with hyperuricemia showed better VA improvement (0.55 vs. 0.06
logMAR, p = 0.019) at 12 weeks and thinner CFT (277 vs. 361µM)
at 24 weeks than those without hyperuricemia after treatment.
Hyperuricemia is an independent factor associated with CFT less than
300µM at 24 weeks (p=0.038; 95% confidence interval, 0.01-0.82),
but not associated with recovery of VA.
Conclusions: High concentration of SUA is associated with the
response of anti-VEGF treatment in patient with DME. These
findings provide evidence for studying the role uric acid in retinal
VEGF production in patients with type 2 diabetes mellitus.
Commercial Relationships: Yun Wen Chen, None; WeiYu Chiang; Jon-Jer Lee, None
Program Number: 2115 Poster Board Number: B0347
Presentation Time: 11:00 AM–12:45 PM
Diabetic Macular Oedema and Chronic Kidney Disease:
Response to treatment with anti-vascular endothelial growth
factor (VEGF)
Alice Bruynseels1, 2, Rita Pinto1, Dawn Sim1, Ranjan Rajendram1.
1
Ophthalmology, Moorfields Eye Hospital, Surrey, United Kingdom;
2
Ophthalmology, St George’s Hospital, London, United Kingdom.
Purpose: To establish treatment response of intravitreal anti-vascular
endothelial growth factor (anti-VEGF) therapy for Diabetic Macular
Oedema (DME) in patients with Chronic Kidney Disease (CKD).
Methods: Data were collected retrospectively on patients with Type
1 and 2 Diabetes and CKD who had DME treated with ranibizumab
between 2013 and 2015. Parameters analyzed included Optical
Coherence Tomography (OCT) central retinal thickness (CRT),
macular volume (MV), and visual acuity (VA), in injected and fellow,
non-injected (control) eyes of patients at 4 months and 1 year. Renal
parameters included: CKD stage, estimated glomerular filtration rate
(eGFR) at baseline, 4 months and 1 year. Patients with less than 8
months follow-up, receiving less than 3 intravitreal injections or other
anti-VEGF were excluded.
Results: 19 eyes of 16 patients were included, ethnicites were six
White British, five Black and five South Asian (Indian/Pakistani).
There were seven patients with stage 3 CKD, six stages 4 and 5, and
three patients on haemodialysis (HD). The mean number of injections
was 6 over 11.5 months. The mean change in VA was +10 ETDRS
letters, mean reduction in CRT was -107µm and MV -1.49mm3.
A trend was observed in non-injected (control) eyes, with thicker
maculae in advanced CKD stages. In non-injected CKD stages 3a
and 3b, the CRT was 239µm compared to 346µm in patients on
haemodialysis (p=0.08). No differences were observed in injected
eyes. At 1 year, reduction in CSFT (r=0.48, p=0.045) and MV
(r=0.49, p=0.04) in the injected eye was correlated to the eGFR at 1
year. This relationship was not observed in the fellow non-injected
(control) eyes.
Conclusions: Our data suggests severity of CKD was associated
with severity of DME. We further observed that anti-VEGF injection
therapy was beneficial in reducing macular thickness and volumes in
patients with advancing renal disease (during the course of therapy)
as defined by EGFR levels.
Commercial Relationships: Alice Bruynseels, None; Rita Pinto,
None; Dawn Sim, Allergan European Panel (F), Fight for Sight UK
(F); Ranjan Rajendram
Program Number: 2116 Poster Board Number: B0348
Presentation Time: 11:00 AM–12:45 PM
The response to ranibizumab therapy after three injections
predicts 12-month outcomes in DME in the absence of rescue
laser therapy
Joanna Dilley, Simon Taylor. Royal Surrey County Hospital,
Surbiton, United Kingdom.
Purpose: Intravitreal ranibizumab is the first-line treatment for
diabetic macular oedema (DME) in the UK, but 25-40% of patients
have a partial or no response. Intravitreal corticosteroids are secondline, but guidance on when to switch therapy is incomplete. We
performed a retrospective, observational clinical study to identify
whether 12-month outcomes can be predicted from the response to
the first three injections of ranibizumab.
Methods: We analysed data of 100 patients who had been treated
with intravitreal injections of ranibizumab for DME and who had at
least one year of follow-up. Treatment was given as a loading dose
of 3 injections followed by an as needed (PRN) retreatment regime;
rescue laser treatment was not used. We recorded visual acuity (VA)
and graded a change of 5+ letters as significant. We also recorded
changes in central retinal thickness (CRT) and DME morphology,
partial improvement being >10% reduction in excess CRT and
significant improvement being >90% reduction. These were recorded
at baseline, 3 months and at 12 months.
Results: After 3 injections of ranibizumab, 51% of patients showed
a significant improvement in VA and 84% of this cohort maintained
this improvement at 12-months. Of the 33% who showed no
improvement or a worsening of VA after 3 injections, 82% had
no improvement after 12-months (p-value <0.05). The remaining
16% demonstrated a non-significant improvement in VA, of these
eyes 50% showed a significant improvement at 12-months and
the remainder showed a worsening or stable VA. Similarly, 80%
of patients who had a significant reduction in CRT at 3-months
maintained this at 12-months whereas 82% of patients who did not
have a significant reduction in CRT at 3 months did not improve by
12-months.
Conclusions: The response to three ranibizumab injections is a good
predictor of the 12-month outcome of continued treatment in DME,
when measured by change in visual acuity. Similar predictions can be
made following a 3-month measurement of CRT excess compared to
baseline, in the absence of rescue laser therapy. This may help guide
whether an early switch to alternative therapy such as corticosteroids
is likely to be beneficial.
Commercial Relationships: Joanna Dilley; Simon Taylor, None
Program Number: 2117 Poster Board Number: B0349
Presentation Time: 11:00 AM–12:45 PM
Retinal Vasculature Changes in Patients with Diabetic Macular
Edema treated with Intravitreal Anti-VEGF
Jay Berdia, Jonathan Levine, Brandon B. Johnson. Ophthalmology,
Bronx Lebanon Hospital Center, New York, NY.
Purpose: Recent studies have shown that intravitreal anti-vascular
endothelial growth factor (VEGF) therapy, a common treatment
for diabetic macular edema (DME), can reverse clinical signs of
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ARVO 2016 Annual Meeting Abstracts
diabetic retinopathy. In this retrospective study we used fluorescein
angiography (FA) to characterize microvascular retinal changes after
intravitreal anti-VEGF therapy for macular edema.
Methods: Retrospective case series of 20 patients (20 eyes), with an
average age of 71 (range 57 to 83), who underwent FA before and
after anti-VEGF treatment for DME. To assess changes in the retinal
vasculature, FAs were graded by a single grader using the protocol
described in Early Treatment Diabetic Retinopathy Study (ETDRS)
Report 11. For each patient, early and late phase angiograms were
graded and a separate averaged score was given for macular capillary
loss and fluorescein leakage. The primary outcome measure was
degree of capillary loss and fluorescein leakage before and after
anti-VEGF treatment. Secondary outcome measures were changes in
central retinal thickness (CRT) measured by spectral domain optical
coherence tomography (SD-OCT, Heidelberg) and hemoglobin A1c
(HbA1c) before and after treatment. Patients with prior treatment for
diabetic retinopathy or macular edema were not excluded.
Results: The average number of anti-VEGF injections per subject
was 9. The average score for capillary loss before and after
treatment was 2.1 and 1.5 respectively (p=0.01). The average score
for fluorescein leakage before and after treatment was 1.5 and 1.2
respectively (p=.19). The average CRT before and after treatment was
534µm and 312µm respectively (p<0.01). There was no significant
changes in HbA1c between dates of FA (p=0.27).
Conclusions: The study showed a statistically significant
improvement in capillary dropout for our diabetic patients treated
with intravitreal anti-VEGF therapy for DME. No statistically
significant changes were found in degree of fluorescein leakage. We
found a statistically significant decrease in CRT as demonstrated in
previous studies. This study may provide a clinical-angiographic
correlation of the reversal of diabetic retinopathy seen following antiVEGF treatment.
Commercial Relationships: Jay Berdia, None; Jonathan Levine;
Brandon B. Johnson, None
Program Number: 2118 Poster Board Number: B0350
Presentation Time: 11:00 AM–12:45 PM
Intravitreal Aflibercept reduces the retinal vessel diameter in
patients with diabetic macular edema
Andrea Consigli1, Athanasios Papanastasiou1, Sayon Roy2,
Gabriele Thumann1, Argyrios Chronopoulos1. 1Department of
Ophthalmology, University Hospitals and School of Medicine,
Geneva, Switzerland; 2Departments of Medicine and Ophthalmology,
Boston University School of Medicine, Boston, MA.
Purpose: In the course of diabetic retinopathy (DR) initial
retinal vessels dilation, a biomarker for DR progression, shifts to
constriction, which signifies potential proliferative state. The aim of
this study was to assess retinal vessel diameter changes in relation
to macular edema formation following intravitreal treatment with
aflibercept in patients with diabetic macular edema (DME)
Methods: Seven treatment naive patients (9 eyes) aged 60 ± 11
years with DME were followed one week before and after during the
loading phase of intravitreal treatment with Aflibercept. Static retinal
vessel analysis as well as optical coherence tomography (OCT) scans
were performed at every examination. Further analysis included
systemic blood pressure before each measurement as well as HbA1c
values throughout the time course of the study.
Results: Static retinal vessel analysis demonstrated a reduction in
retinal artery diameter from 95.59±10.68 μm to 93.63±11.77 μm at
end of first month, to 87.6±5 μm at end of third month after initiation
of Aflibercept treatment. The reduction in retinal artery diameter one
week after the the third injection was statistically significant (p <
0.05). Similarly, retinal vein diameter was reduced from 117.14±10.4
μm to 110.2±7 μm at end of first month to 109±7 μm at end of third
month. The reduction in retinal vein diameter one week after the third
injection was statistically significant (p < 0.05). DME, as assessed
by OCT, decreased significantly from 467±96.5 μm (baseline)
to 344±97.3 μm (month 3) (p = 0.0434). Regression analysis
demonstrated a significant correlation between decreased retinal
artery diameter and macular edema reduction (p < 0.001 and p > 0.05
for retinal arteries and veins respectively).
Conclusions: Intravitreal Aflibercept injection in eyes with DME
resulted in significant reduction in the diameter of both retinal arteries
and veins by 3 months. Furthermore the reduction in DME was
significantly correlated with the arterial diameter reduction. These
data seem to indicate a restoration of the normal vessel caliber under
Aflibercept treatment with potential implications in the pathogenesis
and treatment of DME.
Commercial Relationships: Andrea Consigli, None;
Athanasios Papanastasiou, None; Sayon Roy, None;
Gabriele Thumann, None; Argyrios Chronopoulos, None
Program Number: 2119 Poster Board Number: B0351
Presentation Time: 11:00 AM–12:45 PM
Blockade of Angiotensin II retards the progression of diabetic
retinopathy through downregulating Muller cell-derived VEGF
PENG QIN1, Amy C. Lo1, 2, Ian Wong1, 2. 1Ophthalmology, The
University of Hong Kong, Hong Kong, Hong Kong; 2Research
Centre of Heart, Brain, Hormone & Healthy Aging, The University of
Hong Kong, Hong Kong, Hong Kong.
Purpose: The intraocular Angiotensin II (Ang II) has long been
viewed as a pro-inflammatory factor released in response to
hyperglycemia and may contribute to the pathogenesis of diabetic
retinopathy. We aimed to determine if antagonism of diabetesinduced Ang II by its type I receptor blocker, Candesartan, can
normalize the elevated pathogenic Vascular Endothelial Growth
Factor (VEGF) and its associated retinal pathological changes in
experimental diabetic retinopathy.
Methods: Candesartan (0.1ug/g/day or 1.0ug/g/day in drinking
water) was given to Ins2Akita/+ mice, a spontaneous diabetes mouse
model. Vehicle-treated (0.1% DMSO) Ins2Akita/+ mice and their
wildtype littermates, Ins2+/+ mice, were used as controls. Retinal
function was assessed by scotopic ERG. After 12, 22 or 32 weeks
of hyperglycemia with or without Candesartan treatment, vascular
pathologic alterations including the expression of VEGF, Occludin
and ZO-1, leukostasis as well as vascular permeability in the retina
were evaluated. Astrocyte morphology was examined by glial
fibrillary acidic protein (GFAP) immunohistochemistry. Microglia
activation was determined by co-localization of CD68 and ionized
calcium-binding adapter molecule 1 (iba-1). As the cellular origin of
pathogenic VEGF was thought to be Muller cell, we used primary
cultured Muller cell harvested from Ins2+/+ mice to investigate the
effect of Ang II and its inhibition on VEGF expression.
Results: Vehicle-treated Ins2Akita/+ mice showed the following
diabetes induced abnormalities (p<0.05) when compared with
age-matched wildtype littermates: decreased b-wave amplitude
in scotopic ERG, increased VEGF expression, reduced level
and redistribution of Occludin and ZO-1, enhanced leukostasis,
vascular leakage, microglia activation and astrocytic atrophy.
Candesartan-treated Ins2Akita/+ mice (either dose) exhibited
attenuation of the aforementioned pathological alterations (p<0.05)
when compared with vehicle-treated Ins2Akita/+ mice. In in vitro
studies, Ang II upregulated Muller cell-derived VEGF expression
at both transcriptional and translational level (p<0.01), which was
normalized by treatment with Candesartan (p<0.01).
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ARVO 2016 Annual Meeting Abstracts
Conclusions: Treatment with Candesartan ameliorated
hyperglycemia-induced retinal dysfunction, vascular leakage,
inflammation, and glia atrophy, possibly by downregulating
pathogenic Muller cell-derived VEGF.
Commercial Relationships: PENG QIN, None; Amy C. Lo, None;
Ian Wong, None
Support: Seed Funding Programme for Basic Research (project no:
201310159038), The University of Hong Kong
Program Number: 2120 Poster Board Number: B0352
Presentation Time: 11:00 AM–12:45 PM
Diabetic retinopathy: what happens before VEGF?
Samir Jabbour1, Michael G. Quigley1, 2. 1Ophthalmology, Centre
hospitalier de l’Université de Montréal, Montreal, QC, Canada;
2
Bellevue Ophthalmology Clinic, Montreal, QC, Canada.
Purpose: Today, VEGF is recognized as playing an important role
in the genesis and evolution of diabetic retinopathy. Several clinical
conditions including myopia, retinitis pigmentosa (RP) and growth
hormone (GH) deficiency have been associated with protection of the
retina from diabetic retinopathy. A study by Suzuma et al. (Diabetes,
2001) showed that cyclic stretch within retinal capillaries induces the
expression of VEGF and that decreasing this stretch returns VEGF
production to baseline levels. We hypothesize that these previously
mentioned protective conditions result in a decreased hydrostatic
pressure and stretch at the level of capillaries, down regulating
the expression of VEGF and hence mitigating the development of
diabetic retinopathy.
Methods: Using a previously described pressure attenuation index
(PAI) (Quigley et al., Archives of Ophthalmology, 1999), the relative
capillary hydrostatic pressure in normotensives (120/80 mmHg),
hypertensives (150/100 mmHg), and in the above-mentioned
protective conditions was calculated. This index combines the
Murray law and Poisseuille’s principle and shows that pressure in a
given vascular system is attenuated in proportion to its length and
inversely proportional to its diameter.
Results: Hypertensives have a 4mmHg increase in intraluminal
capillary pressure compared to normotensives. An increase in the
eye’s myopia to -6 diopters, which is equivalent to a 15% increase
in retinal vessel length, would result in a 4.4 mmHg decrease in the
capillary pressure over normal. In RP, an arteriolar narrowing of 69%
from normal would decrease capillary pressure by 13 mm Hg over
normal. In GH deficiency, decreased flow due to narrowing of blood
vessels would result in a capillary pressure of 7.5 mm Hg less than
normal.
Conclusions: Protective conditions in diabetic retinopathy lead to
a calculable decreased intraluminal capillary hydrostatic pressure
which would decrease capillary stretch and VEGF production. A
lowering of the end-arteriolar pressure could be a common pathway
to decreasing VEGF production and mitigating the effects of diabetes
on the microvessels, and could be considered as a goal towards which
therapeutic modalities are directed.
Commercial Relationships: Samir Jabbour; Michael G. Quigley,
None
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/
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