VITREORETINAL ISSUES
| INTRAOCULAR STEROIDS FOR VITREORETINAL DISEASE —J. Michael Jumper, MD, Assistant Clinical Professor,
University of California, San Francisco, School of Medicine, and Chief, Retina Service, California Pacific Medical
Center and West Coast Retina Medical Group, San Francisco
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| Triamcinolone acetonide (eg, Kenalog-40): readily available; inexpensive; intraocular use—early reports of success encouraged
widespread use, despite lack of good evidence; improvements seen immediately, but problems may develop
later; intended use—manufacturer has not sought expanded indication; information in package insert, added in 2006,
states “not for intraocular use”; preservative-free formulations—available at compounding pharmacies, but not uniformly
produced or adequately studied; other formulations also free of preservatives
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 | Kenalog-40: pharmacokinetics—relatively long half-life in vitreous (decreases from 18 to 3 days in vitrectomized eyes);
anti-inflammatory potency 5-times that of endogenous cortisol and one-fifth that of dexamethasone; inactive
ingredients—include preservative (benzyl alcohol, 0.99% weight/volume) and suspension agents (polysorbate 80 and
carboxymethylcellulose); crystals—5 to 32 µm; size may change as product ages
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| Injectable triamcinolone (Triesence): intravitreal injection approved by Food and Drug Administration (FDA) for management
of noninfectious uveitis and for visualization during vitrectomy; preservative-free formulation with same suspension
agents as Kenalog-40 (but lower percentage of weight/volume); crystals more uniform in size (5-7 µm)
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| Other preparations: injectable triamcinolone in hyaluronate-based hydrogel vehicle used in 2 in-progress clinical trials
(Standard Care vs Corticosteroid for Retinal Vein Occlusion [SCORE] and Diabetic Retinopathy Clinical Research
[DRCR] studies); formulation contains relatively uniform crystals and no preservatives
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| Adverse events associated with triamcinolone: elevated intraocular pressure (IOP) occurs in up to 50% of patients; infectious
and sterile endophthalmitis occur in 0.87% and 2.8%, respectively
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| Proposed causes of sterile endophthalmitis: preservatives—unlikely, because preservative-free formulations associated with
similar rates of sterile endophthalmitis; endotoxins—up to 4.4 endotoxin U/mg allowable in triamcinolone acetonide; in
comparison, FDA-approved ocular injections limited to 0.96 endotoxin U/mg (“endotoxin-free” formulations must have
even less); hypothesis that endotoxins responsible for inflammation not supported by evidence; inflammatory response to
microparticles—macrophages engulf crystals then lyse, releasing contents and causing inflammation; hyaluronate suspension
may reduce exposure and foreign-body response
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| Dexamethasone: 4-mg/mL formulation has intravitreal half-life of 3.5 hr; component in combination therapy for age-related
macular degeneration (AMD); micronized dexamethasone delivered by bioerodible implant (breaks down to water
and lactic acid); implant injected into vitreous; bevelled incision important to achieve water-tight seal; half-life, 30 to 35
days; results from clinical trials—beneficial for patients with persistent macular edema (ME); current trial looking at effect
on uveitis in progress
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| Fluocinolone intravitreal implant (Retisert): releases drug over 2.5 yr; procedure—implant positioned in posterior segment
(through incision in pars plana); limited vitrectomy removes prolapsed vitreous; implant sewn in place in vitreous
cavity; good apposition critical for wound healing (decreased by corticosteroids)
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| Macular degeneration: choroidal neovascularization occurs in phases (initiation; active; involution); inhibition of vascular
endothelial growth factor (VEGF) seems to affect initiation phase; corticosteroids and photodynamic therapy (PDT)
affect active stage
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| Therapeutic approaches: combination therapy—PDT plus triamcinolone injections; good initial results; approach abandoned
when new options became available; triple therapy—reduced-fluence PDT, limited vitrectomy, intravitreal
dexamethasone (0.2 mL), plus intravitreal bevacizumab ([Avastin] 0.06 mL [1.5 mg]), completed within 24 hr; results
include modest improvements in vision and retinal thickness; ≈4% of patients require repeat triple therapy; ≈17% of
patients require additional injections of Avastin
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| Retinal vascular occlusion: initial benefit of intravitreal corticosteroids decreases with time; visual improvement seen at 3
mo decreases to baseline by 12 mo; elevated IOP common; DRCR and SCORE studies in progress
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| Use of fluocinolone implant: case—woman with panuveitis and severe cystic edema has visual acuity of 20/200 and
fovea \>1 mm thick; triamcinolone injection results in temporary improvement in vision and foveal thickness, but edema
recurs at ≈3 mo; fluocinolone intravitreal implant placed; central edema resolved, and visual acuity improved to 20/70;
clinical trials—patients who received implants had decreased rates of disease recurrence, improved visual acuity, and
decreased need for systemic immunosuppressive agents
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| Use of corticosteroids during ocular surgery: therapeutic uses—retained lens material (speaker uses triamcinolone); infectious
endophthalmitis (speaker uses dexamethasone); visualization—during vitrectomy and membrane peeling
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| EVALUATION AND TREATMENT OF IRITIS ASSOCIATED WITH GLAUCOMA —Todd P. Margolis, MD, PhD,
Professor of Ophthalmology and Director, F.I. Proctor Foundation, University of California, San Francisco, School of Medicine
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| Uveitis with elevated IOP: when acute, etiology almost always infectious; chronic disease caused by mixed mechanism
glaucoma (any chronic iritis or uveitis can result in elevated IOP)
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| Herpes simplex virus (HSV) and varicella zoster virus (VZV): clinical features—typical history includes previous or
concurrent viral ocular disease (not always obvious); evidence of previous interstitial keratitis; diffuse pleomorphic
granulomatous keratic precipitates ([KP]; not limited to Arlt’s triangle); abnormal pupillary response or accommodation;
iris atrophy (cells and pigment may occur in anterior chamber); live virus may be present; iris atrophy—patchy,
focal, or diffuse (if diffuse, VZV likely cause); subtle changes in iris sphincter suggest atrophy (retroillumination aids
visualization); diagnostic testing—decreased corneal sensation; polymerase chain reaction (PCR) to detect viral DNA
in aqueous; local immune response in aqueous (Goldmann-Witmer coefficient)
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| Chronic and recurrent VZV: infection may recur clinically or subclinically (even without skin eruptions); mucus plaque may
occur years after episode of zoster ophthalmicus (plaque typically positive for VZV DNA); treatment—systemic antiviral
therapy; small amounts of topical steroids useful once plaque resolves (avoid immunosuppression until virus cleared);
reactivation—may involve only small number of neurons; may cause chronic or recurrent iritis
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| Toxoplasmosis: clinical features—diffuse granulomatous KP; classic vitreoretinal findings (eg, “headlight in fog”); scar
with classic pigmentary changes; diagnosis—seropositivity for Toxoplasma gondii; PCR reveals T gondii DNA in vitreous;
classic presentations easy to recognize, but nonclassic presentations (eg, diffuse uveitis) also occur
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| Fuchs heterochromic cyclitis (FHC): syndrome includes heterochromia and classic KP (somewhat stellate and diffuse; seen
on retroillumination); evidence of viral etiology—rubella virus RNA found in aqueous; local immune response in aqueous
(consistent with viral infection); epidemiologic studies suggest decline in incidence of FHC associated with use of rubella
vaccine; treatment with corticosteroids causes local immunosuppression and may exacerbate FHC
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| Cytomegalovirus (CMV): may cause hypertensive iritis, even in immunocompetent patients (typically, 20-50 yr of age);
clinical features—unilateral; KP may be small and grey or brown; endotheliitis or heterochromia may occur;
diagnosis—viral DNA and local immune response in aqueous; treatment—long-term treatment with valganciclovir or
ganciclovir (but long-term use of ganciclovir may cause suppression of bone marrow); new antiviral agents in phase 3 trials;
case examples—chronic uveitis with classic clinical features; viral transmission through corneal transplantation;
note on diagnostics—PCR more sensitive than cell cultures (also true for other viruses)
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| Posner-Schlossmann syndrome (PSS): patients—20 to 50 yr of age; often atopic; episodes—unilateral; intermittent (every
2 mo to 5 yr); duration hours to weeks; characterized by transient high IOP, with some cells and KP present; heterochromia
present in ≈33% of cases; parasympathetic inhibition—pupils may be unequally dilated; affected eye has
decreased accommodation; effects consistent with VZV infection; etiology—commonly infectious (often, herpesvirus)
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| Sarcoidosis: suggested as cause of uveitis with elevated IOP; evidence—Mycobacterium tuberculosis catalase-peroxidase
present in granulomas; patients have immune response to this and other mycobacterial proteins; pathophysiology—
immune response persists, even after mycobacterial infection clears
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| Syphilis: associated with uveitis with elevated IOP; diagnosis—maculopapular rash may occur on palms; venereal disease
research laboratory (VDRL) test typically insufficient; antibody test especially important in patients with ocular involvement
(more sensitive than VDRL)
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| MANAGEMENT OF POSTERIOR SEGMENT COMPLICATIONS IN PEDIATRIC UVEITI S —Janet L. Davis, MD,
Professor, Bascom Palmer Eye Institute, Miami, FL
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| Complications: ME; epiretinal membrane; subretinal neovascular membrane; scarring; vitreous opacification (eg, strands,
veils, sheets, membranes); retinal traction, holes, and detachment; complications involving optic nerve—edema (possibly
secondary to iridocyclitis); atrophy; neovascularization; perineuritis; peripapillary choroidal neovascularization; complications
involving retina—edema; atrophy; exudative conditions
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| Posterior uveitis: visible lesions posterior to equator; complications common; preventing complications primary goal of treatment;
prolonged inflammatory reaction may cause atrophy of retina (including retinal pigment epithelium [RPE] and macula)
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| Retinal vascular disease: Behçet’s syndrome—retinal vascular disease with explosive attacks of retinal inflammation (eg,
small infarctions and exudative infiltrates); left untreated, severe cases result in blindness, closure of retinal vasculature,
and profound retinal atrophy; aggressive immunosuppressive therapy recommended; idiopathic retinal vasculitis, aneurysm,
neuroretinitis (IRVAN) syndrome—relatively rare; diagnosis based on presence of retinal arterial macroaneurysms;
excess exudate forms lipid nodule; poor response to immunosuppressive therapy; large-vessel retinal vascular
occlusions—may occur in patients with peripheral occlusive retinal vasculitis or infection; generally require panretinal
photocoagulation (medical treatment not always necessary)
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| Choroidal vascular disease: imaging—indocyanine green (ICG) angiography better than fluorescein angiography (FA),
but ICG dye no longer available; actively leaking vessels hyperfluoresce on ICG angiography; late effects of occlusion
(eg, damage to choroidal vasculature and choriocapillaris, secondary changes in RPE) also seen
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| Peripapillary fibrosis: caused by deep inflammation in choroid; occurs specifically with panuveitic disorders; results in inflamed
optic disc; exudative reaction forms tight bands of fibrosis around optic nerve head; associated with sympathetic
ophthalmia, Vogt-Koyanagi-Harada (VKH) syndrome, and sarcoidosis; recurrent choroidal neovascularization results in
progressive scarring
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| Inner choroid disease: choroidal neovascularization common; imaging—FA; optical coherence tomography (OCT);
treatment—early stages of disease typically respond better to corticosteroid or immunosuppressive therapy (eg,
VEGF inhibition) than to laser photocoagulation; VEGF inhibition preferred if fluid present (otherwise, oral corticosteroids
often sufficient)
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| Multifocal choroiditis: case—woman with 22-yr history of episodic inflammation; no light perception in one eye; visual acuity
in other eye 20/300; scarring present in fundus; diffuse degenerative process throughout retina, presumably from repeated
attacks of choroidal inflammation; electroretinography (ERG) shows marked impairment with some prolongation
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| Birdshot chorioretinopathy: choroidal disease leads to retinal dysfunction and scarring; thin retina and choroidal hyperreflectivity
seen on OCT; as disease progresses, changes occur in optic nerve head, and retinal function and visual acuity
decrease profoundly; imaging—in early stages, choroidal vessels appear sclerotic on FA; with progression, little choroidal
capillaris remains, and choroidal periphery becomes occluded
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| Intermediate uveitis: no visible lesions posterior to equator; vitreous inflammation predominates; common complications include
ME and peripheral exudation; treatment—sub-Tenon injection of corticosteroid (longer action and fewer risks than
intravitreal injection); imaging—OCT useful for visualizing macular damage and directing management
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| Pars planitis: FA reveals characteristic pattern of vasculitis (preserved vascular tree without large-vessel occlusions; inflammation
in small vessels); peripheral detachment may occur; variant—Coats’ disease-like response; telangiectatic
vessels; yellow subretinal exudate; retinal elevation; peripheral vasoproliferative tumor; associated with early age at
onset (eg, in patients with pars planitis since childhood); treatment—aggressive treatment may spare vision (especially
important in children); angiography useful for assessing leakage; peripheral inflammation—may affect night
vision and visual field; causes loss of function in peripheral retina; treatment intensity—depends on severity of disease;
includes observation, topical corticosteroids, regional therapy, and systemic immunosuppression
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| Retinal detachment: peripheral membrane present, but may be difficult to see because of synechiae; surgery—infusion
cannula placed superiorly (twelve o’clock position safest); high-resolution ultrasonography aids visualization of anterior
segment and presence of membrane over pars plana
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| Comparing complications in adults and children: adults—higher frequency of ME; children—incidence of posterior
complications (including iridocyclitis), 77%; macular complications, 71%; cystoid ME, 34%; higher risk (compared to
adults) of developing peripapillary choroidal neovascular membrane (caused by breaks in Bruch’s membrane or inflammatory
infiltrates)
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| Closing comments: define complications of uveitis structurally (with OCT or angiography) and functionally (with visual
field test and ERG); control inflammation “by whatever means necessary”; managing complications—bevacizumab
([Avastin]; ≈50% response rate among patients with ME); triamcinolone acetonide for uveitis
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Suggested Reading
Batioglu F et al: Two-year results of intravitreal triamcinolone acetonide injection for the treatment of macular edema due
to central retinal vein occlusion. Ann Ophthalmol (Skokie) 39:307, 2007; Buggage RR et al: A double-masked, randomized
study to investigate the safety and efficacy of daclizumab to treat the ocular complications related to Behçet’s disease.
Ocul Immunol Inflam 15:63, 2007; Chaudhary V et al: Triamcinolone acetonide as adjunctive treatment to verteporfin in
neovascular age-related macular degeneration: a prospective randomized trial. Ophthalmology 114:2183, 2007; de Groot-
Mijnes JD et al: Rubella virus is associated with Fuchs heterochromatic iridocyclitis. Am J Ophthalmol 141:212, 2006;
Jones R 3rd et al: Herpes simplex virus: an important etiology for secondary glaucoma. Int Ophthalmol Clin 47:99, 2007;
Kang SW et al: Triple therapy of vitrectomy, intravitreal triamcinolone, and macular laser photocoagulation for intractable
diabetic macular edema. Am J Ophthalmol 144:878, 2007; Paccola L et al: Intravitreal triamcinolone versus bevacizumab
for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol 92:76, 2008; Romero R et al: Pars
planitis in children: epidemiologic, clinical, and therapeutic characteristics. J Pediatr Ophthalmol Strabismus 44:288, 2007;
Roth DB et al: Short-term complications of intravitreal injection of triamcinolone acetonide. Retina 28:66, 2008; Roth DB
et al: Micropulsed laser photocoagulation and intravitreal triamcinolone acetonide injection for the treatment of retinal angiomatous
proliferation. Retina 27:1201, 2007; van Boxtel LA et al: Cytomegalovirus as a cause of anterior uveitis in immunocompetent
patients. Ophthalmology 114:1358, 2007; Westeneng AC et al: Infectious uveitis in immunocompromised
patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. Am J
Ophthalmol 144:781, 2007; Wu L et al: Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of
the Pan-American Collaborative Retina Study Group (PACORES). Graefes Arch Clin Exp Ophthalmol 246:81, 2008.
Educational Objectives
| The goal of this program is to improve the recognition and management of vitreoretinal disease and uveitis. After hearing and
assimilating this program, the clinician will be better able to:
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| 1. Discuss the role of intravitreal corticosteroids in the management of vitreoretinal disease.
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| 2. Describe the proposed etiologies of sterile endophthalmitis associated with intravitreal injections of triamcinolone
acetonide.
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| 3. List the differential diagnosis for acute uveitis with glaucoma.
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| 4. Recognize the signs and symptoms of viral uveitis, and perform appropriate diagnostic work-up.
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| 5. Summarize the posterior segment complications associated with uveitis in children.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of
interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and
not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Jumper is a
speaker and advisory board member for Genentech; Dr. Davis receives grant support from Lux Bioscience and Genentech
and is a consultant for Lux Bioscience and Novartis. Dr. Margolis and the planning committee reported nothing to disclose.
Acknowledgments
Drs. Jumper and Margolis were recorded at Ophthalmology 2007, presented by the Beckman Vision Center, Department of
Ophthalmology, University of California, San Francisco, and held December 14-15, 2007, in San Francisco; Dr. Davis was
recorded at Vitreoretinal Course Update, presented by the Bascom Palmer Eye Institute, Department of Ophthalmology,
University of Miami Miller School of Medicine, and held May 4-5, 2007, in Miami, FL. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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