Fluorescein Angiography Basics

AAO 2014
HIV/AIDS and the Eye:
Epidemics, Endemics, and
Syndemics
Lorne Yudcovitch, OD, MS, FAAO
James Kundart OD, MEd, FAAO, FCOVD-A
Disclosure Statement: Nothing to disclose
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HIV Subtypes
What is HIV?
 The Human
Immunodeficiency
Virus (HIV) causes the
disease AIDS (Acquired
Immunodeficiency
Syndrome)
 This retrovirus (that
converts RNA to DNA)
specifically attacks
T cells (CD4+ cells)
http://ipaki.com/content/html/34/102.html
HIV Subtypes
 HIV has high
genetic variability
 HIV-1
 Most common
and pathogenic
strain
 Group M is most
common (90%+)
 Many subtypes
(including
recombinants)
HIV-2
Not as common;
mainly Africa
8 groups; only two
are epidemic (A
and B)
Many tests for HIV-1
can also detect
HIV-2
http://en.wikipedia.org/wiki/HIV
http://www.niaid.nih.gov/topics/hivaids/understanding/biology/Pages/structure.aspx
HIV/AIDS Definition
 Revised Surveillance Case Definition for HIV Infection
— US, Apr 2014
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6303a1.htm?s_cid=rr6303a1_e
HIV/AIDS Stages
If negative HIV test within 6 months of first HIV infection
diagnosis, stage is 0
And remains 0 until 6 months after diagnosis
 Definition primarily for monitoring HIV infection
burden on population
 Not for clinical decisions for individual patients
 Classified in one of five HIV infection stages (0, 1, 2, 3,
or unknown)
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
If “stage-3-defining opportunistic illness” has been diagnosed,
stage is 3
CMV, Toxoplasmosis, HSV, Candida, TB, Kaposi’s, others
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HIV Pandemic in 15-49 Year
Olds Worldwide (2011)
HIV Mortality Worldwide 2013
http://en.wikipedia.org/wiki/AIDS
HIV/AIDS in Cities US vs. Africa
 33.4 million people living
with HIV/AIDS in 2008
(down from 40.3 in 2005)
 2.7 million people newly
infected with HIV (down
from 4.9 million in 2005)
 60% of infections are in
sub-Saharan Africa
 Women ~50% of all
infections worldwide
Source: Wafaa M. El-Sadr, M.D., M.P.H., Kenneth H. Mayer, M.D., and Sally L. Hodder, M.D. AIDS in America — Forgotten but Not Gone
The New England Journal of Medicine. Downloaded from www.nejm.org at VA LIBRARY NETWORK on November 22, 2010.
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
HIV/AIDS in America (2010)
HIV/AIDS by County in US (2011)
 As many as
1,000,000 people
infected
Leading killer of
African-American
males, age 25-44
 7x more than
whites
 2/3 of AIDS cases in
both women and
children were
among AfricanAmericans
 20% are unaware
 56,300 new
infections per year
 Over 18,000 die of
AIDS each year in
the US alone
Source: Wafaa M. El-Sadr, M.D., M.P.H., Kenneth H. Mayer, M.D., and Sally L. Hodder, M.D. AIDS in America — Forgotten but Not Gone
The New England Journal of Medicine. Downloaded from www.nejm.org at VA LIBRARY NETWORK on November 22, 2010.
HIV Transmission
http://weblogs.baltimoresun.com/health/hivaids/
Acute HIV/AIDS Manifestations
1. Allergic
2. Autoimmune
3. Opportunistic
Infections
http://www.nckansil.
com/transmissionof-hiv-1021746.html
http://en.wikipedia.org/wiki/AIDS
Anterior Segment
Manifestations of AIDS
1. Allergic Conjunctivitis and
Steven-Johnson Syndrome
in HIV/AIDS
Conjunctival
vascular changes
(75%)
Dry eye (10-15%)
SPK
 Microsporidia (parasitic
protozoan) is cause
 Mild conjunctivitis
 CD4 below 50 cells/ml3
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
http://en.wikipedia.org/wiki/Steve
n-Johnson_syndrome
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2. Reactive Arthritis, Uveitis, and
Retinal Vasculitis in HIV/AIDS
3. Opportunistic Ocular
Infections in HIV/AIDS
 Toxoplasmosis
(shown here)
 Tuberculosis eye
disease
 Aspergillosis
 Molluscum
contagiosum
 Oral candidiasis
 Herpes zoster
http://emedicine.medscape.com/article/1201027-overview
HIV/AIDS Toxoplasmosis:
Retinitis and Dementia
Image from the Pacific University Ocular Disease Digital Collection
TB Eye Disease and Aspergillosis
http://emedicine.medscape.com/arti
cle/1209505-clinical#a0217
Rifabutin (TB med)
CME and Resolution
http://www.dermaamin.com/site/atlas-ofdermatology/1-a/123-aspergillosis-.html
Maculopapular Rash (left) and
Cryptococcal Infection (right)
http://www.biomedsearch.com/nih/Rifabutin-associatedhypopyon-uveitis-retinal/22311604.html
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
Molluscum Contagiosum (left)
and Eosinophillic Folliculitis(right)
Oral Hairy Leukoplakia (left) and
Esophageal Candidiasis (right)
Herpes Zoster Ophthalmicus
and HIV/AIDS
Chronic HIV/AIDS
Ocular Manifestations
 Neoplasia
(Kaposi’s
sarcoma)
 HIV Retinopathy
 TreatmentRelated and
Drug Toxicity
http://en.wikipedia.org/wiki/AIDS
AIDS and Kaposi’s Sarcoma
Kaposi’s Sarcoma
 Rare dermatologic neoplasm in
immunocompromised patients
 Endemic in Africa
 One of the more common cancers in
AIDS
 Sites:
 Lymph nodes 80%
 GI tract 80%
 Pulmonary involvement 10%
 Conjunctival and/or lid involvement in
17%-24% of AIDS patients
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
Kaposi's Sarcoma in a 70-Year-Old
Male Immunocompetent Patient
Kaposi’s Sarcoma Treatment
Radiation
(brachytherapy,
beam irradiation)
Chemotherapy
(antineoplastic
drugs)
Excision/destruction
(cryo/thermal)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128134/
Symptoms of Ocular Infection in
AIDS Patients
Painless decrease in
vision in one or both
eyes
Hazy vision
Floaters/flashes
Metamorphopsia (left;
use Amsler Grid)
VF defect
http://www.myvisiontest.com/about.php
May be asymptomatic
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128134/
Early Signs of HIV/AIDS Retinopathy
 Cotton wool spots (CWS)
may be initial ocular
manifestation of AIDS
 While CWS are present in
2/3 of patients, they are
nonspecific for AIDS
 DDX: Diabetic
retinopathy,
hypertension, severe
anemia, lupus, leukemia
 The presumed cause is
CMV (cytomegalovirus)
infection
Source: Salisa Williams, OD
AIDS and CMV Retinitis
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
AIDS-Related Cytomegalovirus
(CMV) Retinitis
 CMV is infectious for
patients of all ages
 Latent infections are
common, as
between 50 -80% of
US adults are CMV
seropositive
 CMV infection in
AIDS patients is
common, especially
in those without
treatment
Signs of CMV Ocular Infection
in AIDS Patients
 Necrotizing retinitis with
or without hemorrhages
is usual presentation
 Patchy yellow-white
areas with secondary
hemorrhage along the
edges
 This is often described as
brushfire retinitis
CMV Retinopathy in AIDS
 CMV infection
occurs most
commonly through
reactivation of latent
virus
 Prior to treatment of
AIDS, CMV was the
most common
ocular opportunistic
infection (12%-46%),
as well as the
leading cause of
blindness in AIDS
http://imagebank.asrs.org/file/3352/hiv-retinopathy-re
Centrifugal Retinitis
 Occurs most
frequently along the
major vascular
arcades or near the
optic nerve head
 ALL retinal layers
affected  full
thickness retinal
destruction,
spreading directly
from diseased to
healthy retina
http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/CMVRetinitis/index.htm
http://www.pacificu.edu/library/DigitalCollections.cfm
Sequelae of CMV Retinitis
 Vessel attenuation
 Calcifications in
atrophic retina
 Capillary
nonperfusion
 Chorioretinal scarring
 Loss of VA (site
specific)
 Optic atrophy
http://imagebank.asrs.org/file/931/cytomegalovirusretinitis-active-with-papillary-involvement
 Retinal detachment
(24-50%)
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
Complications of CMV Retinitis
 HIV retinopathy
(CWS and/or
intraretinal
hemorrhages)
 HZV and HSV retinitis
 Toxo retinochoroiditis
 Infectious multifocal
choroiditis
 PORN (progressive
outer retinal necrosis,
shown here)
http://www.lookfordiagnosis.com
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Other CMV Ocular Complications
• Papillitis, macular
edema, vasculitis, and
uveitis are all possible
• Uveitis can result from
CMV alone
• Immune recovery
uveitis (IRU) – may
occur when patient’s
immune system
recognizes and reacts
to viral antigens in the
retina after successful
HIV therapy
http://www.medscape.org/viewarticle/750394_2
HIV Tests
 Enzyme-Linked Immunosorbent Assay (ELISA)
 Western Blot
 Rapid Antibody Tests
 OraQuick® In-Home HIV Test
 OraSure Technologies
 FDA approved July 3, 2012;
no Rx needed
 Tests fluid sample from mouth
 20-40 minute results
 Medical consult/testing still encouraged due to
potential for false positives/negatives
Bloodwork and HIV/AIDS
CD4 > 400: RTC q 1 year
Solitary IRH and/or CWS
CD4 100-400: RTC q 6 months
Few more IRHs and/or CWSs
CD4 < 100: RTC q 3 months
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
Immune Recovery Uveitis
and Cidofovir (Vistide)
http://www.ehealthme.com/
ds/vistide/uveitis
http://www.ncbi.nlm.nih.gov/pm
c/articles/PMC1722828/
Bloodwork and HIV/AIDS
Always ask about Helper T cell (CD4)
count and HIV viral load when managing
these patients
These monitor the progression of HIV infection
Normal CD4 = 1,000 cells/mm3
Average decline of 85 cells/year
Retinitis develops at ~ 50-75 cells/mm3
Return to clinic based on CD4 count
Bloodwork and HIV/AIDS
Viral load very high (above
100,000) when first infected
As immune system responds,
load lowers to ‘set point’
This ‘set point’ determines
how fast HIV might progress
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Bloodwork and HIV/AIDS
Higher viral loads usually
correspond with lower CD4
Women tend to have lower viral
loads than men
Several assay tests for viral load
(measures HIV RNA)
PCR (polymerase chain reaction)
is common one
Clinical Pearls Regarding
Bloodwork and HIV/AIDS
Bloodwork and HIV/AIDS
Trends of viral load
determines treatment
efficacy
An aim of HIV doctors is to
get viral load down ASAP
Ideally within 6 months of
treatment start
Untreated HIV Time Course
 There is no viral load in non-infected patients
 Zero virus copies are in all non-infected patients
 Infected patients could have ‘undetectable’ (i.e.
20-75 copies, depending on lab) viral load
 Can number in the millions in one blood sample
 The trend of viral load over time is important
 CD4 count is more important than viral load
 US Federal guidelines recommends treatment
when CD4 count drops below 350 cells/mm3
Source: http://aids.gov
HIV Treatment
1. Nucleoside Reverse Transcriptase Inhibitors
(NRTIs)
http://en.wikipedia.org/wiki/HIV
HIV Tx #1. Nucleoside
Reverse Transcriptase
Inhibitors
Zidovudine (ZDV, AZT)
2. Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs)
 Thymidine analog; first
approved for HIV
3. Protease Inhibitors (PIs)
 Incorporate into cell and viral
DNA
4. Antiretroviral Fusion Inhibitor
5. Three or more drugs used concurrently for
best outcomes (usually from two or more
classes), as in HAART
 Useful for AIDS dementia
 Can reduce mother-to-infant
HIV transmission from 25% to 8%
 Myelosuppression can occur
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
Other Nucleoside Reverse
Transcriptase Inhibitors
Didanosine
 Pancreatitis
 Peripheral neuropathy can occur
Zalcitabine
 Peripheral neuropathy can occur
Stavudine
 Peripheral neuropathy can occur
Lamivudine
 No dose-limiting toxic effects
HIV Tx #2: Non-Nucleoside
Reverse Transcriptase Inhibitors
 Binds/inactivates reverse transcriptase
 Inhibits HIV-1 (but not HIV-2 or other retroviruses)
Nevirapine
 Can reduce mother-infant transmission by
40%
Delavirdine
Efavirenz
 Unique neurotoxic effects (abnormal dreams)
Tenofovir
 ‘Newer’ drug – pre-exposure prophylaxis
(PrEP)
HIV Tx #3: Protease Inhibitors
 Binds to viral proteases, preventing viral
assembly; does not require intracellular activation
Saquinavir
 First protease inhibitor (1995); not used much now
HIV Tx #4:
Antiretroviral Fusion Inhibitor
Prevents fusion of HIV with host cell outer
membrane, preventing infection of cells
Ritonavir
Indinavir
Amprenavir
Nelfinavir
Ganciclovir (drug shortage?)
 Intravitreal pellet used for CMV retinitis
HIV Tx #5: Combination
Anti-HIV Therapy
Enfuviritide (T20)
Subcutaneous injection
Trade name: Fuzeon
Combination HIV/AIDS
Medications
 Combination of NRTI with two NNRTIs
 Called “Triple Therapy”, or “Highly
Active Antiretroviral Therapy” (HAART),
better known as “the cocktail”
 Not often well-tolerated,
expensive, can lead to multi-drug
resistance if not used correctly
 Drugs targeting HIV integrase in the
works
http://en.wikipedia.org/wiki/Management_of_HIV/AIDS
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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AAO 2014
HIV/AIDS Pre- and Post-Care
with HAART
 Medical care with HAART
suppresses viral replication,
increases CD4 count
Universal Precautions
 Applies to all patients (not ust HIV/AIDS)
 No evidence to date that HIVcan be contracted
through tears, contact lenses, or routine patient
contact (CDC)
 Pre-HAART (1995-98)
 CMV retinitis in 20-40%
 Survival 1985  12
months
 Hand wash between patients
 Gloves if blood risk (not tears)
 HAART (1998-00)
 CMV retinitis
decreased by 80%
 Survival 2005  30
months
 Mask if airborne risk
 Eye/face shield if splash/spray risk
http://www.natap.org/2006/CROI/CROI_32.htm
 Hazardous waste disposal units
Universal Precautions
Universal Precautions
 Instrument Sterilization
 Minimum 15 min. @ 121°C
 Percent of hep C virus RNA remaining after tonometer disinfection:
 dry gauze wipes  95.65%
 70% isopropyl alcohol 5-second wipes  88.91%
 Instrument disinfection
 10 minute soak in 3% H2O2
 15 minute soak in 1:10
bleachdilution
 cold water wash  4.78%
 povidone iodine 10% 5-second wipes  0.72%
 3% hydrogen peroxide soak with cold water wash  0.07%
 20 minute soak in 2%
glutaraldehyde
 Contact lenses
 isopropyl alcohol soak and cold water wash  0.02%
 RGPs
 H2O2 disinfection
 Soft CLs
 H2O2 disinfection
 Heat disinfection
Keys to Comanagement of
Patients with HIV/AIDS
 Early diagnosis
 Screening exam
every few months:
 With retinal specialist
 With primary care
physician
 With infectious
disease specialist
 With immunologist
 Low vision devices
 Testing to determine
HIV infection
 Consultation/referral
to medical physician
skilled in treating
HIV-infected
patients
 No separate
treatment of the
eyes may be
necessary
JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
Selected References
1.
Wafaa M. El-Sadr, M.D., M.P.H., Kenneth H. Mayer, M.D., and Sally L. Hodder, M.D. “AIDS in America —
Forgotten but Not Gone.” The New England Journal of Medicine. Downloaded from www.nejm.org at VA
LIBRARY NETWORK on November 22, 2010.
Segal WA, Pirnazar JR, Arens M, Pepose JA. Disinfection of Goldmann tonometers after contamination with
hepatitis C virus. American Journal of Ophthalmology Volume 131, Issue 2, Pages 184–187, February 2001
3. Mansour AM, Jampol LM, Logani S, Read J, Henderly D. Cotton-wool spots in acquired immunodeficiency
syndrome compared with diabetes mellitus, systemic hypertension, and central retinal vein occlusion. Arch
Ophthalmol. 1988Aug;106(8):1074-7. PubMed PMID: 3401133.
4. Wafaa M. El-Sadr, M.D., M.P.H., Kenneth H. Mayer, M.D., and Sally L. Hodder, M.D. From AIDS in America —
Forgotten but Not Gone. The New England Journal of Medicine Downloaded from www.nejm.org at VA
LIBRARY NETWORK on November 22, 2010.
5. http://www.hivguidelines.org/clinical-guidelines/adults/ophthalmologic-complications-of-hiv-infection/
6. Revised Surveillance Case Definition for HIV Infection — US, Apr 2014
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6303a1.htm?s_cid=rr6303a1_e
7. Christopher J L Murray et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and
malaria during 1990—2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet, Early
Online Publication, 22 July 2014doi:10.1016/S0140-6736(14)60844-8
8. http://www.cdc.gov/hiv/library/reports/surveillance/index.html
9. For more on HAART, see Retina. Jul-Aug 2005; 25(5):633-49
10. Lightman, S (ed.). HIV and the Eye. London” Imperial College Press, 2000.
11. www.cdc.gov
2.
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JTK LBY - HIV/AIDS and the Eye:
Epidemics, Endemics, and Syndemics
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