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Progressive Outer Retinal Necrosis Outcomes in the Intravitreal Era

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Progressive Outer Retinal Necrosis Outcomes in the Intravitreal Era CLINICAL SCIENCES Progressive Outer Retinal Necrosis Outcomes in the Intravitreal Era Daniel M. Gore, MRCOphth; Sri K. Gore, MRCOphth; Linda Visser, FCS(Ophth)SA Objective: To describe the functional and anatomic out- with 12 eyes (18%) having already lost perception of light. comes of progressive outer retinal necrosis treated with Intravitreal ganciclovir injections were started immedi- intravitreal ganciclovir sodium injections. ately in all salvageable eyes (n=50). Improvements in vi- sual outcomes trended toward significance in eyes re- Methods: A retrospective, interventional case series of sponding early (Յ21 days), achieving a median final VA all patients fitting established clinical diagnostic criteria of 6/36 (P=.046). Retinal detachment occurred in 34 eyes for progressive outer retinal necrosis was conducted at (51%), predicating a significantly worse visual outcome a single institution in South Africa. Eyes with salvage- (PϽ.001). Excluding eyes with no light perception at the able vision were treated with repeated intravitreal gan- start of the study period, median final VA was hand move- ciclovir injections until regression was achieved or the ments (range, 6/4 to no light perception); 9 eyes lost per- eye lost light perception. Pars plana vitrectomy was per- ception of light despite treatment. formed when retinal detachments failed to resolve spon- taneously. The main outcome measures were visual acu- Conclusions: Progressive outer retinal necrosis re- ity (VA) and response to intravitreal ganciclovir. mains a devastating condition, often with acute and pro- found loss of vision. Intravitreal ganciclovir may offer a Results: Thirty-nine patients (67 eyes), all of whom were HIV-positive (median CD4ϩ T-lymphocyte count, 30/ more targeted approach and, compared with earlier re- µL), were included; 12 patients (31%) died during the ports using systemic therapy alone, may result in better study period. Twenty-eight of 36 patients (78%) had a visual outcomes. recent history of cutaneous varicella zoster virus infec- tion. At the initial evaluation, the mean VA was 6/120, Arch Ophthalmol. 2012;130(6):700-706 O DATE, THE LARGEST AND of immunosuppression have been de- most comprehensive de- scribed, principally iatrogenic (ie, scriptive series of progres- chemotherapy).3 sive outer retinal necrosis Early reports, including that by Eng- (PORN, also known as vari- strom et al,1 documented treatment only Tcella zoster virus [VZV] retinitis or rap- with systemic antiviral therapy. More re- idly progressive herpetic retinal necro- cently, better outcomes appear to have been sis) remains that published by Engstrom achieved with local therapy, including in- and colleagues in 1994,1 crystallizing the travitreal antiviral injections and/or im- devastating nature of the condition in plants.4-11 These publications have for the which disease in two-thirds of eyes pro- most part been single case reports or small gressed to no light perception (NLP) case series. We reviewed our large collec- within 4 weeks of onset. Occurring in pro- tion of patients with PORN treated with in- foundly immunocompromised patients, travitreal antiviral injections on a back- the cardinal features are multifocal le- ground of the South African human sions characterized by deep retinal opaci- immunodeficiency virus (HIV) epidemic. fication without granular borders, some- times including areas of confluent METHODS opacification; lesion location in the pe- ripheral retina, with or without macular Author Affiliations: This study received ethics and institutional Department of Ophthalmology, involvement; extremely rapid progres- board approval from the Biomedical Research Nelson R Mandela School of sion; absence of vascular inflammation; Ethics Administration of the University of Kwa- Medicine, University of and minimal or no intraocular inflamma- Zulu-Natal and Inkosi Albert Luthuli Central KwaZulu-Natal, Durban, South tion.1,2 Although almost exclusively found Hospital. The research adhered to the tenets Africa. in persons with AIDS, other mechanisms of the Declaration of Helsinki. ARCH OPHTHALMOL / VOL 130 (NO. 6), JUNE 2012 WWW.ARCHOPHTHALMOL.COM 700 ©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Hospital records were reviewed for cases of PORN between 2004 and 2011. All diagnoses were made by a single consultant Table 1. Medical and Demographic Data retinal surgeon (L.V.) with, to date, more than 15 years of expe- rience managing retinitis related to HIV/AIDS with intravitreal Characteristica No. (%) therapy. Diagnoses were based on funduscopic findings in a con- Age, median (range), y 39 (27-59) firmed HIV-positive patient: well-demarcated, multifocal, co- Female sex 26 (67) alescing, and deep or full-thickness areas of predominantly pos- CD4ϩ T-lymphocytes at diagnosis, median 30 (4-163) terior retinal necrosis. Vitritis and vasculitis were not considered (range), cells/µLb exclusion criteria because of frequently advanced disease in our History of pulmonary tuberculosis (n = 28) 23 (82) patients when first seen. If HIV was not already diagnosed, pa- History of herpes zoster/simplex infection (n = 36) tients were counseled for testing and, where available, highly ac- Total 28 (78) tive antiretroviral therapy (HAART) was started. Information on Varicella (chicken pox) 4 (11) a recent episode of VZV reactivation (shingles) or primary vari- Herpes zoster (shingles) 24 (67) cella (chicken pox) was sought. Laboratory confirmation by poly- Disciform keratitisc 5 (14) merase chain reaction was unfortunately not available because Interval for zoster preceding PORN, median 2.5 (1-24) of financial constraints. Estimation of the extent of retinal in- (range), mo (n = 16) volvement (ie, percentage) was not possible because of inad- Duration of PORN-related visual symptoms, 3 (1-12) equate documentation; instead, we recorded the location accord- median (range), mo ing to a standard zone grading system: zone 1 encompasses an Died during the study 12 (31) area extending 3000 µm from the center of the fovea or 1500 µm Abbreviation: PORN, progressive outer retinal necrosis. from the optic nerve, zone 2 extends from zone 1 to the vortex a 12 Thirty-nine patients unless otherwise noted; proportions based on all veins (equator), and zone 3 extends anterior to the equator. Fun- patients unless specified otherwise because of insufficient data. dus photographs were taken where possible. b All patients had documented human immunodeficiency virus. All but 1 Patients with clinical features consistent with acute retinal patient had a CD4ϩ T-lymphocyte count less than 100/µL. necrosis and cytomegaloviral retinitis (CMVR) were ex- c Five patients had active disciform keratitis in one or both eyes at the cluded. Regarding acute retinal necrosis, diagnostic criteria from initial examination; 3 of these patients also reported a history of cutaneous varicella zoster virus. the American Uveitis Society were used: peripheral, well- delineated foci of retinal necrosis with occlusive vasculopa- thy, circumferential spread and prominent vitritis, and ante- rior chamber inflammation.13 Diagnostic features of CMVR tients (31%) died during the study period (Table 1) and included the following subtypes: fulminant (posterior retinal 18 patients (46%) were lost to follow-up, including 6 who hemorrhage with necrotic retina), granular (peripheral retini- later returned. All patients were HIV positive, including tis, with little or no edema, hemorrhage, or vasculitis), and 6 new diagnoses at their initial visit to the clinic. Of the frosted-branch angiitis (retinal perivasculitis). 33 patients with previously diagnosed HIV, only 12 (36%) Any eye with active retinitis that had potential for vision (ie, were already receiving HAART on their first visit to the light perception [LP] or better with good projection) was treated clinic, including 2 who had been treated for less than 1 with repeated intravitreal ganciclovir injections (2 mg in 0.08 month. mL of normal saline). Injections were administered twice weekly The median CD4ϩ T-lymphocyte count was 30/µL. Of (Tuesdays and Fridays) for 2 weeks (induction phase) and then weekly, with activity and response to treatment monitored as 36 patients for whom a history was documented, cuta- standard at each visit. When no signs of active disease were vis- neous VZV infection occurred in 28 (78%) (24 shingles ible, treatment was tapered to injections every 2 weeks (main- and 4 primary varicella); 5 patients (14%) also had a con- tenance phase), continued until HAART-mediated immune re- current disciform keratitis (4 ipsilaterally), presumed VZV constitution was confirmed by improved CD4ϩ T-lymphocyte in origin. Another patient was initially treated else- counts above 100/µL. Before the availability of HAART, main- where for presumed VZV-meningitis with intravenous tenance injections were continued weekly until the patient died. acyclovir before being referred to our department with Patients with bilateral disease received simultaneous injec- a decrease in vision on day 3 of admission. Twenty- tions. Activity was defined as retinal opacification consistent three of 28 patients (82%) had either active or previous with necrosis. Response to treatment was qualified as the first pulmonary tuberculosis. signs of localized disease control, specifically, retinal scarring. Because serial fundal photographs were not available for most A history of deterioration and/or loss of vision was ob- patients,
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