Transcript GRAND ROUNDS

GRAND
ROUNDS
September 1, 2006
Denise A. John
St. Thomas Hospital
Case
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HPI: 60 y/o ♂ presents for an eye exam.
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ø ocular c/o’s
ROS: (+) L temporal headache
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All other systems unremarkable
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FHX: Diabetes; HTN, stroke
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SHX: Quit ETOH ‘04; ø tobacco/IVDA
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Allergies: NKDA
Ocular Exam
NLP
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VA SC
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Motility: Full OU
CF ‘4ft  20/200
4
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IOP
8
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Pupils: (+) RAPD OD
NO VIEW
B-Scan: Funnel-shaped
retinal detachment
Differential Diagnosis
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Infectious
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Indolent CMV retinitis
Toxoplasma retinitis
Acute retinal necrosis
(ARN)
Progressive outer retinal
necrosis (PORN)
Choroidal pneumocystosis
Cryptococcal choroiditis
Tuberculosis
Candidiasis
Syphilis
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Neoplastic
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Ocular lymphoma
Metastasis
Inflammatory
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Sarcoidosis
Vasculitides
More Info…
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PMHX:
 HIV/AIDS (Dx ’04)
 CD4: 155 cells/mm3 (5/05)
 HIV nephropathy
 Hepatitis C
 Chronic anemia
 HTN
 Chickenpox
POHX:
 S/p steel injury OD
 HZO OS (5/05)
 Conjunctivitis
 Keratitis
 Uveitis
 Post-herpetic Neuralgia
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MEDS:
 Acyclovir 400mg QID; HAART;
lisinopril; atenolol; bactrim;
Refresh PM
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External Exam:
 Left hypo-pigmented scar:
CNV1 distribution
 LUL Entropion & trichiasis
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SLE:
 OD: Shallow AC; 360°
posterior synechiae; white
cataract
 OS: PEE; posterior
synechiae;
ø AC rxn; 2-3+ NSC/3-4+
PSC;
ø vitritis
Epidemiology: HIV
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40 million individuals infected worldwide
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900,000 in the U.S.
70-80% treated for a HIV-related eye disorder
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CD4 count may be used to predict the occurrence of
specific ocular infections
CD4 Count & Ocular
Infections
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< 500 cells/mm3
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Kaposi sarcoma
Tuberculosis
Lymphoma
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< 100 cells/mm3
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Conjunctival/retinal
microvasculopathy
CMV retinitis
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< 250 cells/mm3
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Pneumocystosis
Toxoplasmosis
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VZV retinitis
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Most common
2nd most common
Cryptococcosis
Microsporidiosis
CMV Retinitis
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Occurs in
immunocompromised
 Slow progression
 Starts in periphery
 Spreads along retinal
vasculature towards
posterior pole
 Dense white/granular
opacification (fullretinal thickness)
 Hemorrhage
 Mild vitritis
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Acute Retinal
Necrosis
Occurs in
immunocompetent
 > 1 foci of full-thickness
retinal necrosis with
discrete borders
 Spreads 360°
circumferentially in
peripheral retina
 Posterior pole
involvement is spared
until late
 Vasculitis
 Prominent inflammatory
reaction (AC & vitreous)
Progressive
Outer Retinal
Necrosis
PORN
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Rare form of necrotizing herpetic retinopathy
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First described by Forster et al. (1990)
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2 pts: Fulminant outer retinal necrosis sparing the
inner retina & vasculature
Occurs in the immunocompromised:
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Immunosuppressed organ-transplant recipients
Immune-deficient individuals:
Cancer
 Advanced AIDS
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Pathogenesis
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Varicella-Zoster Virus
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Virus remains latent in sensory ganglia
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Reactivated during times of loss of T-cell regulatory
control
Difficult to isolate/grow in-vitro
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Only organism isolated in the retina via culture, PCR &
direct fluorescent antibody assay
PORN
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Engstrom, et al. PORN: A variant of
necrotizing herpetic retinopathy in patients
with AIDS. Ophth 1994. 38 ♂ pts (65 eyes):
CD4 count: 21 cells/mm3 (0-130 cells/mm3)
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Largest study on PORN
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Retrospective chart review
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Median f/u 3 months (0-10 months)
Objective: Characterize the clinical features & course
PORN
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History of cutaneous zoster : 67% (22/33 pts)
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41%: involved CNV1
12 of 15 pts: PORN occurred after a median of 2
months (2 months – 2 years)
3 of 15 pts: PORN occurred concurrently
12 of 38 pts: Taking oral acyclovir at the time
PORN was diagnosed
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50%: Acyclovir 800mg 5x/day
Clinical Features
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Ocular complaints
 vision: Most common (54% eyes)
 Constriction of visual fields (28% eyes)
 Floaters (11% eyes)
 Pain (6% eyes)
7 pts with unilateral symptoms had asymptomatic
disease in the fellow eye
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Clinical Features
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Usually bilateral disease
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28 of 38 pts: Unilateral disease at diagnosis
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2nd eye became affected in 17 pts  median of 10
days after diagnosis (3 days – 4 weeks) in 6 pts
Intraocular inflammation is minimal to absent
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23 of 60 eyes: Anterior segment inflammation
61% mild AC reaction
 11% keratic precipitates (fine, white deposits)
 6% posterior synechiae
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15 of 61 eyes: Vitreous inflammation
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80% mild vitritis
Clinical Features
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Multifocal, discrete lesions of the outer retina 
rapidly progress to confluence & full-thickness
retinal involvement
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Perivenular lucency
Clinical Features
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Characteristic macular
lesion:
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Parafoveal opacification
with a “cherry-red spot”
Ø contiguous with
peripheral lesions
Peripheral lesions +
posterior pole
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Zone 1: 32% eyes
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ø lesions only in zone 1
Zone 2: 72% eyes
Zone 3: 86% eyes
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28% eyes all 3 zones
Clinical Features
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Disease quiescence
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Dense white plaques:
“cracked mud”
appearance
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Atrophic areas + holes
Clinical Features
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Other manifestations:
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11 of 65 eyes: Optic nerve abnormalities
Disc swelling
 Hyperemia
 Atrophy
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11 of 29 pts: Afferent pupillary defect
13 of 61 eyes: Retinal vasculopathy
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Vascular sheathing/occlusion
 Areas within or near retinal necrosis
FA: PORN
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Walton et al. FA in PORN.
Retina 16: 1996
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Early: Microvascular changes
 equatorial & peripheral retina
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Confluent retinal disease: 
retinal vasculature & loss of
capillaries; RPE damage;
choriocapillaris leakage
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Reactivation: Brush-fire
pattern of choroidal leakage at
lesion border
PORN = Retinochoroiditis
Management: PORN
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Exact combination of antivirals & duration of
treatment not known
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Guided by anecdotal information
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Herpes-zoster traditionally treated with acyclovir;
however, may not be effective in pts treated
long-term with the oral form 2° to resistance
Management
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Moorthy et al. Management of VZVR in AIDS.
Br J Ophth, 1997. 20 pts (39 eyes); 11 pts
using oral acyclovir at time of diagnosis
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Retrospective chart review
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median f/u 6 months (1-26 months)
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Objective: Investigate visual outcome
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2 week IV treatment:
Acyclovir (10mg/kg Q8h)
 Ganciclovir (5mg/kg Q12h x 2 weeks; then 5mg/kg/day)
 Foscarnet (180mg/kg/day in 2 or 3 divided doses)
 Ganciclovir + foscarnet
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Management
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Results:
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Rates of NLP : acyclovir (9 of 10 eyes) & foscarnet (3
of 5 eyes)
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Ø VA > 20/200
Rates of NLP : combination therapy (5 of 18 eyes) &
ganciclovir (2 of 6 eyes)
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VA > 20/200
Combination therapy: 3 of 18 eyes
 Ganciclovir: 1 of 6 eyes
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Conclusion: Treatment with IV combination therapy
or ganciclovir associated with a better final vA VS
acyclovir or foscarnet alone
Management
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Ciulla, et al. PORN: Successful treatment with
combination antiviral therapy. Ophth Surgery &
Lasers. 1998. 6 pts with AIDS
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Retrospective chart review
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Median f/u 29 weeks (27 -38 weeks)
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Objective: Assess 2-drug combination therapy
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IV Treatment duration: median 29 weeks (27-38
weeks)
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Ganciclovir (5mg/kg Q12h) + acyclovir (500mg/m2 Q8h)
Foscarnet (60mg/kg Q8-12h) + ganciclovir
Foscarnet + acyclovir
Management
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Results:
 All 6 pts had resolution of disease
 1 of 6 pts had recurrence
 At diagnosis 3 of 12 eyes without disease 
remained uninvolved
 10 of 12 eyes developed RD
Conclusion: Prolonged combination therapy
arrested progression of retinitis; maintained
remission & prevented fellow eye involvement; does
not prevent retinal detachment
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Role of ganciclovir intraocular implant & oral agents in
combination therapy is unclear
Management
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Intravitreal injection (ganciclovir & foscarnet);
intravitreal ganciclovir implant
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No protection for fellow eye
Complications
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Retinal necrosis
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Retinal tears/holes
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Rhegmatogenous retinal detachment
Management
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Prophylactic laser retinopexy
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Engstrom et al. 1994
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14 of 54 eyes: Laser ~ 1 week after diagnosis
 93% developed a RD
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Median interval ~ 3 weeks
Ø significant difference: laser VS no laser:
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Zone of involvement of RD
Extent of RD
Interval from diagnosis to RD
Management
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Rhegmatogenous retinal detachment
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Engstrom et al. 1994
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43 of 65 eyes: Median interval 4 weeks
 No relationship to extent of disease or disease activity
 Vitrectomy/endolaser/silicone oil
 16 of 43 eyes: Retinas successfully attached in all
eyes
 Re-detached in 4 eyes
 NLP in 56% (laser) VS 63% (no laser)
Prognosis
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Visual prognosis is poor
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Macular involvement
Ineffectiveness of antiviral agents
Recurrence
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Engstrom, et al. 1994
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At least 10 pts despite being on maintenance therapy
 Characterized by development of new disease foci
 In 6 pts associated with discontinuation/reduction in
maintenance dose; median time to recurrence was
2 weeks (1-6 weeks)
~ 50% of individuals  deceased 5 months after
diagnosis
Back To Our Patient…
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Patient admitted to medicine
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Infectious disease consulted
Received IV foscarnet (40mg/kg Q12 x 14 days)
 ø Progression of lesions
 VA improved to 20/60 (+1.75)
 Discharged on oral acyclovir 800mg 5x day
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Take Home Points…
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Progressive outer retinal necrosis is a
rapidly progressive necrotizing retinitis
occurring in immunocompromised
individuals, esp. AIDS pts
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Management is anecdotal: use of highdose IV anti-virals may be beneficial
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Poor visual prognosis
References
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E-Medicine: Ocular manifestations of HIV
Forster et al. Rapidly PORN in AIDS. Am J Ophth 110: 341. 1990
Moorthy et al. Management of VZV retinitis in AIDS. Br J Ophth,
1997.
Walton et al. Fluorescein angiography in PORN. Retina 16: 1996
Ciulla, et al. The PORN: Successfully treatment with combination
antiviral therapy. Ophth Surgery & Lasers. 1998
BCSC. Retina & Vitreous. AAO. 2004-05
BCSC. Uveitis & Intraocular Inflammation. AAO. 2004-05
Yanoff. Ophthalmology, 2nd Ed. Mosby. 1121-22
Kanski. Clinical Ophthalmology, 5th Ed. Butterworth Heinemann.
288-93. 2003