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 visual 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 perception of light despite treatment. formed when retinal detachments failed to resolve spontaneously. 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 infection. 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 described, 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 cellaT 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 peripheral 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.

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©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 experience 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 anterior 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, no analysis of the extent of scarring was made; in- tained at diagnosis in all patients, who had symptoms for stead, the interval before a response to treatment was ob- a median of 3 weeks (range, 1-12 weeks) (Table 2). served. Pars plana vitrectomy was performed when retinal de- Eleven patients (28%) had unilateral disease; of the re- tachment (RD) failed to resolve spontaneously. maining bilaterally affected patients, all but one had signs For purposes of statistical analysis, Snellen visual acuity (VA) in the fellow eye by the time of initial presentation. Me- values were converted to logMAR equivalents (−log decimal acu- dian VA was 6/120 (range, 6/6 to NLP), including 11 pa- ity) before being reconverted to Snellen acuity for presenta- tients (28%) already experiencing NLP (1 bilaterally). tion in this article. LogMAR equivalents for counting fingers, Fifty-nine (88%) of 67 eyes exhibited active disease; of hand movements, LP, and NLP were estimated at 1.85, 2.30, the remaining 8 eyes, 6 had widespread retinal atrophy 2.70, and 3.00, respectively.14 Data were analyzed with com- mercial software (Excel for Mac, 2011; Microsoft Corp). (the retinas in 5 of these had extensive detachments) and 2 eyes (with VAs of 6/5 and 6/6) had midperipheral retinal scarring without retinal detachment. Multifocal le- RESULTS sions were observed in 23 of 53 eyes (43%) with areas of confluence evident in 52 of 55 eyes (95%) (Figure 1). In total, 67 eyes of 39 patients (38 black, 1 Indian) with Among 65 eyes, less than or equal to 1ϩ anterior cham- a clinical diagnosis of PORN were included. Twelve pa- ber and vitreous cells were observed in 52 (80%) and 37

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Characteristica No. (%) Patient related Unilateral 11 (28) Visual acuity, median (range)b 6/120 (6/6 to NLP) Eye related NLP at presentation 12 (18) Active retinitis 59 (88) Anterior chamber reaction (n = 65) Absent 17 (26) Trace 11 (17) 1ϩ 24 (37) 2ϩ 9 (14) 3ϩ 4 (6) Posterior synechiae (n=65) 1 (2) Keratic precipitates (n=65) 37 (57) Vitritis (n = 65) B Absent 9 (14) 1ϩ 28 (43) 2ϩ 17 (26) 3ϩ 11 (17) Location of retinal involvement (n = 64) Zone 1 4 (6) Zones 1 and 2 7 (11) Zone 2 9 (14) Zones 2 and 3 7 (11) Zone 3 0 Zones 1, 2, and 3 37 (58) Vasculitis (n = 48) 14 (29)

Abbreviation: NLP, no light perception. a Thirty-nine patients, 67 eyes; proportions based on all eyes or patients unless specified otherwise because of insufficient data. b Median calculated from the log of decimal equivalents.

Figure 1. Digitally composited fundal photographs from the same patient. A, (57%), respectively, with 14 of 48 eyes (29%) exhibit- Multifocal and confluent areas of outer retinal necrosis on initial evaluation. B, After 2 weeks of intravitreal ganciclovir injections, with subsequent ing vasculitis. Immune status, when subdivided into pa- scarring (final visual acuity, 6/9). tients with CD4ϩ T-lymphocyte counts of 0 to 24, 25 to 49, 50 to 74, and more than 75/µL, correlated positively with both the degree of vitritis (P=.03, ␹2 test) and pres- Table 3. Intravitreal Ganciclovir Therapy and Response ence of vasculitis (P=.05, ␹2 test). In 50 active eyes with salvageable vision, intravitreal Characteristic No. (%) ganciclovir injections were started immediately (Table 3). a Six treated eyes were excluded from further analysis be- No. treated 50 (72) No. of ganciclovir injections, median (range) 12 (2-36) cause of disciform keratitis precluding useful retinal view Duration of treatment, median (range), wk 12 (0-49) (n=2) and follow-up of 1 week or less (n=4). A median Time to first scarring response, median (range), d 21 (7-42) total of 12 injections (range, 2-36) were given. Local- Endophthalmitis 0 ized scarring (ie, response to treatment) (Figure 2) was observed at a mean interval of 21 days (range, 7-42). Im- a Seventeen eyes did not receive intravitreal injections; 12 had no light provements in visual outcomes trended toward signifi- perception at the initial examination, 2 had light perception but poor light Յ projection, and one 6/6 eye had inactive peripheral scarring. Two other eyes cance in eyes responding early ( 21 days), achieving a of the same patient (active right eye, inactive left eye) were managed median final VA of 6/36 (P=.046, paired t test). This com- conservatively; highly active antiretroviral therapy–mediated disease pares with eyes responding late (Ͼ21 days), finishing with regression was already evident. a median Snellen equivalent of approximately counting fingers at 1 m (2.08 logMAR). Excluding 9 other pa- 0-14.2 months), including 14 that were detached when tients in whom direct macular necrosis or atrophy was the patient was first evaluated (Table 4). The remain- evident at their first visit (ie, prejudicing therapy- ing 4 retinas detached at 26, 35, 42, and 61 weeks. Reti- mediated visual improvement), the benefits of an ear- nas in patients receiving HAART at their first visit were lier response to treatment were more evident with a me- significantly less likely to detach, with an odds ratio of dian final VA of 6/21 (P=.003, paired t test). No patient 0.07 (95% CI, 0.02-0.26; PϽ.001). One patient who de- developed bacterial endophthalmitis during the study pe- veloped a dense cataract following uncontrolled im- riod (547 total injections). mune recovery uveitis underwent vitrectomy for a pre- Of 34 eyes (51%) with RD, 30 retinas (88%) de- sumed RD detected on B-scan ultrasonography, although tached within 7 weeks (median interval, 7 days; range, no RD was found during the operation. For the most part,

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 eyes with RD not undergoing surgery were not considered salvageable; 1 patient declined surgery and another A with VA of 6/18 was lost to follow-up after the previous week’s visit. The retinas of 3 patients with small peripheral detachments overlying or adjacent to thinned atro- phic (ie, inactive) retina spontaneously reattached: a re- duction in fluid was documented after 2 weeks in 2 patients and by 3 weeks in the third patient. Resorption of fluid was complete by 6, 8, and 16 weeks, respectively. Seven patients underwent vitrectomy, with successful anatomic reattachment maintained in 6 at the most recent follow-up. The development of an RD was significantly associated with poorer visual outcome (PϽ.001, paired t test). Excluding eyes with NLP (n=12) at the start of the study period, the median final VA was counting fingers B (range, 6/4 to NLP) (Table 5). Nine eyes lost LP despite treatment at a median of 12 days after diagnosis. Visual acuity at the patient’s first visit significantly correlated with the final VA (PϽ.001, paired t test), with better outcomes evident in patients with good vision at the start of treatment.

COMMENT

The accumulation of significant numbers of patients with PORN is a reflection of the HIV/AIDS epidemic in southern Africa. As of 2008, South Africa had the largest bur- Figure 2. Digitally composited fundal photographs from the same patient. den of any nation, with an estimated prevalence of 10.6% A, On initial evaluation, extensive posterior pole retinal scarring, arteriole (approximately 5.2 million people). Our hospital is lo- nonperfusion, and well-delineated full-thickness retinal necrosis were evident. B, Two months later, no signs of active retinitis were seen (final cated in the province of KwaZulu-Natal, which has the visual acuity, hand movements). highest overall prevalence (15.8%). Peak prevalence oc- curs in women aged 25 to 29 years (32.7%) and men aged 15 30 to 34 years (25.8%). The availability of HAART in Table 4. RD Characteristics South Africa, long contentious by its absence, received governmental support in March 2007 after initiation of Duration of the National Strategic Plan for HIV/AIDS aiming to en- No. (%) Follow-up, sure that, by 2011, at least 80% of individuals eligible for RD (n = 34) Median (Range), mo antiretroviral treatment have access to it. On presentation 14 (41) 2.6 (0-19.4) Although Engstrom and colleagues’1 original article Subsequent development 20 (59) 12.3 (0-36) set the benchmark for both diagnostic criteria and vi- Interval before RD developed, 4 (1-42) . . . sual outcomes for PORN, the clinical entity was first de- median (range), wk 2 No. undergoing vitrectomy 7 (21) 11 (0-26) scribed and so named in 1990 by Forster et al, and evi- Interval before surgery, median 8 (3-12)a ... dence for VZV involvement was reported by Margolis et (range), wk 16 al the following year. Historically, initial treatments in- Redetachment 1 (14) . . . volved 1 or more systemic antiviral agents, with combination therapy appearing to yield better outcomes: Spaide Abbreviation: RD, retinal detachment. a and colleagues17 demonstrated preservation of 20/100 VA Delays in surgery occurred in 2 patients because of public sector strikes. or better in 6 patients treated with combination systemic antivirals; patients in 2 further studies18,19 main- pared with 60% in the original series of Engstrom et al1 tained 20/80 VA or better in 10% and 22% of eyes, re- (excluding those with NLP on their first evaluation). spectively. In contrast, 5 of 12 eyes (42%) treated with In addition to outcomes, there were differences in fea- both intravenous and intravitreal antivirals achieved the tures at the initial examination in our series compared same final VA of 20/80 or better,6 while a more recent with those described by Engstrom et al. First, fewer of series of 5 eyes receiving intravitreal therapy attained a our patients exhibited absent or minimal inflammation final VA of 20/50 or better.7 Several other publica- when first seen, with 80% and 57% of patients having tions,4,8,10,11,20-24 all but 2 of them single case reports, have 1ϩ anterior chamber or less and vitreous cells, respec- reported mixed outcomes, with limited follow-up. Our tively, compared with 85% and 95% in the study by Eng- article, representing, to our knowledge, the largest pub- strom et al. Second, at the start of the study period, 58% lished series of patients with PORN treated with intra- of our patients had retinal involvement in all 3 zones com- vitreal antiviral therapy, found an improvement in final pared with just 28% among the patients of Engstrom et VA, with only 9 (13%) eyes losing perception of light com- al. These differences may be linked: delays in seeking care,

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Characteristic No. (%) of Eyes Final VA NLP Final VA (%) Follow-up Duration All eyes 67 (100) HM (6/4 to NLP)b 21 (31) 7 mo (0 to 36 mo)b Eyes grouped by VA at initial examination Ն6/60 31 (46) 6/60 (6/4 to NLP) 2 (6) 6 mo (1 wk to 36 mo) LP to 5/60 24 (36) LP (6/6 to NLP) 7 (29) 6 mo (3 d to 36 mo) NLP 12 (18) NLP 12 (100) 3 mo (1 d to 15 mo) P value Ͻ.001c Eyes grouped by scarring response to IVG (n = 44)d Յ21 d 24 (55) 6/36 (−3)e 4 (17) 3 mo (12 d to 36 mo) Ͼ21 d 20 (45) CF at 1 m (−10) 3 (15) 13 mo (18 d to 26 mo) P value .046f Eyes grouped by RD (n = 63)g RD 32 (51) LP (6/12 to NLP) 12 (38) 11 mo (0 to 26 mo) No RD 31 (49) 6/60 (6/4 to NLP) 9 (29) 9 mo (3 d to 25 mo) P value Ͻ.001f

Abbreviations: CF, counting fingers; HM, hand movement; IVG, intravitreal ganciclovir; NLP, no light perception; LP, light perception; RD retinal detachment; VA, visual acuity. a Snellen acuities recalculated from logMAR equivalents used for statistical analysis. b Median (range). c Analysis of variance test. d Six patients were excluded because follow-up was 1 week or less (n = 4) or disciform keratitis precluded useful retinal view (n = 2). e Median relative gain or loss (−) in equivalent logMAR lines compared with the VA at the initial examination. f Paired t test. g Four patients were excluded because follow-up was 1 week or less.

as in this series, would allow for greater spread of the dis- ing retinal pigment epithelium to pump the detachment ease throughout the retina in terms of confluence (95% flat. This may explain 3 RDs in this series that sponta- vs 40%) and in progression from outer to inner retinal neously reattached. layers, both of which might be expected to elicit a greater An explanation for the later, inactive RD group may vitreous response. Absence of a significant inflamma- be found in work by Brar and colleagues,25 who de- tory response is generally a useful means of distinguish- scribed pathologic vitreoretinal interface changes on op- ing presumed herpetic necrotizing retinopathies (ie, PORN tical coherence tomography in patients with healed CMVR vs acute retinal necrosis); however, our data suggest that, scars. They noted several abnormalities, including epireti- in patients with AIDS and PORN, vitritis can occur, with nal membranes and vitreoretinal gliosis, concluding that severity increasing in line with the CD4ϩ T-lymphocyte the associated traction may explain the higher inci- count. dence of retinal elevation, breaks, and detachment in these Analysis of outcomes with and without RD revealed, eyes. We can assume, although not confirm, that such a unsurprisingly, a strongly significant trend to worse VA mechanism applies to this series as well, since both CMVR following detachment despite successful reattachment in and PORN involve viral-mediated full-thickness retini- 6 of 7 cases. Our results also suggest that the retinas in tis with resulting retinal atrophy. We postulate that the patients receiving HAART when first evaluated were sig- later (inactive) RD group may be a sequela of posterior nificantly less likely to detach. However, we caution re- vitreous detachment in areas incorporating these patho- garding interpretation of this, since we were unable to logic vitreoretinal adhesions. confirm in most patients the duration of treatment and The level of immune recovery at which antiviral whether their HIV was resistant to current therapy. Both therapy in PORN may be safely discontinued has not been of these factors may explain the low initial CD4ϩ T- established. More evidence exists in the literature26,27 re- lymphocyte counts, even in patients receiving HAART. lated to the treatment of CMVR, in which most authors The timing of detachment appears to fall into 2 dis- consider CD4ϩ T-lymphocyte counts greater than 100/µL tinct groups, with the vast majority of retinas detaching as a safe level to stop maintenance treatment. Our group’s within the first few weeks (ie, during the active necrotic experience of CMVR concurs with this, having no docu- phase) and a few detaching many months later (ie, dur- mented cases of relapse above this level when patients ing the inactive phase). This bimodal trend is also seen are adherent to HAART (unpublished data), and this same in patients with CMVR-related RD (unpublished data). level was used as a cut-off point in this PORN series. The early group can be explained by full-thickness ne- There are several limitations to this study, princi- crosis, leading to holes though both the inner and outer pally related to the inherent difficulties in developing- retina, as a prelude to rhegmatogenous RD. These holes country health care: delays in seeking care (due to lack are usually large enough to be identified on funduscopy of transport, lack of money for transport, public sector but in a few cases are presumably too small. We pro- strikes, and lack of awareness of visual symptoms) and pose that these latter examples are associated with one a more general lack of hospital resources. It is in light of or more sieve-like holes that can occasionally self-seal these facts that our patients sought care later than would with the ensuing scarring process, allowing a function- be expected in the developed world, by which time 12

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 eyes (18%) had already lost LP. Consequently, several Financial Disclosure: None reported. eyes had confluent areas of full-thickness retinal necro- Funding/Support: This study was supported in part by sis at the patient’s first visit, having presumably pro- subsistence travel grants from the Ellison-Cliffe Travel- gressed beyond the early stages of multifocal outer reti- ling Fellowship of The Royal Society of Medicine (Dr D. nitis. Similar reasons, in addition to the 31% mortality M. Gore) and the Sir William Lister Travel Award and rate, are likely to contribute to the large numbers of pa- Dorey Bequest of the Royal College of Ophthalmolo- tients lost to follow-up. This resulted in considerable varia- gists (Drs D. M. Gore and S. K. Gore). tions in treatment length (eg, range of number of ganciclovir injections, 2-36) and a high proportion of patients REFERENCES being excluded from the final analysis. Additionally, the explicit rationing of hospital finan- 1. Engstrom RE Jr, Holland GN, Margolis TP, et al. The progressive outer retinal cial resources meant that we were unable to perform poly- necrosis syndrome: a variant of necrotizing herpetic retinopathy in patients with merase chain reaction analysis to confirm the etiologic AIDS. Ophthalmology. 1994;101(9):1488-1502. agent. Varicella zoster virus has been confirmed as the 2. Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol. causative agent in the overwhelming majority of PORN 1990;110(4):341-348. 16,19,28-32 cases in the literature ; one notable exception iden- 3. Austin RB. 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Yin PD, Kurup SK, Fischer SH, et al. Progressive outer retinal necrosis in the era 11 PORN exist; an additional study of patients with PORN of highly active antiretroviral therapy: successful management with intravitreal highlighted 8 of 11 patients (73%) with concurrent central injections and monitoring with quantitative PCR. J Clin Virol. 2007;38(3):254- nervous system disease varying from unexplained confu- 259. 9. Blair MP, Goldstein DA, Shapiro MJ. Optical coherence tomography of progres- sionepisodestosevereencephalopathicdisease.Despitethis, sive outer retinal necrosis. Retina. 2007;27(9):1313-1314. the prohibitive costs of oral valganciclovir (induction, 10. Yeh S, Wong WT, Weichel ED, Lew JC, Chew EY, Nussenblatt RB. Fundus au- R19 479 [US $2531]; maintenance: R13 914 [US $1808] per tofluorescence and OCT in the management of progressive outer retinal necro- month) or inpatient intravenous ganciclovir and/or foscar- sis [published online March 9, 2010]. 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Holland GN; Executive Committee of the American Uveitis Society. Standard di- the causes of death were unavailable. agnostic criteria for the acute retinal necrosis syndrome. Am J Ophthalmol. 1994; In summary, despite some patients retaining good vi- 117:663-667. sion, the functional outcomes overall in this series re- 14. Schulze-Bonsel K, Feltgen N, Burau H, Hansen L, Bach M. Visual acuities “hand motion” and “counting fingers” can be quantified with the Freiburg visual acuity main dire, and it is a reminder of the often catastrophic test. Invest Ophthalmol Vis Sci. 2006;47(3):1236-1240. loss of vision that accompanies PORN. By far the most 15. Shisana O, Rehle T, Simbayi LC, et al; SABSSM III Implementation Team. South encouraging result from these data appears to be im- African National HIV Prevalence, Incidence, Behaviour and Communication Sur- proved visual outcomes associated with early response vey 2008: A Turning Tide Among Teenagers? Cape Town, South Africa: HSRC Press; 2008. to intravitreal ganciclovir injections. The best outcomes 16. Margolis TP, Lowder CY, Holland GN, et al. Varicella-zoster virus retinitis in pa- are likely to be seen in patients who begin intravitreal tients with the acquired immunodeficiency syndrome. Am J Ophthalmol. 1991; (and systemic) therapy within a few days of symptom on- 112(2):119-131. set, before macular involvement is apparent. 17. Spaide RF, Martin DF, Teich SA, Katz A, Toth I. Successful treatment of progressive outer retinal necrosis syndrome. Retina. 1996;16(6):479-487. 18. Ciulla TA, Rutledge BK, Morley MG, Duker JS. The progressive outer retinal ne- Submitted for Publication: September 20, 2011; final re- crosis syndrome: successful treatment with combination antiviral therapy. Oph- vision received November 29, 2011; accepted Decem- thalmic Surg Lasers. 1998;29(3):198-206. ber 4, 2011. 19. Moorthy RS, Weinberg DV, Teich SA, et al. Management of varicella zoster virus Correspondence: Daniel M. Gore, MRCOphth, Depart- retinitis in AIDS. Br J Ophthalmol. 1997;81(3):189-194. 20. You YS, Lee SJ, Lee SH, Park CH, Kwon OW. Progressive outer retinal necrosis ment of Ophthalmology, University of KwaZulu-Natal, combined with vitreous hemorrhage in a patient with acquired immunodefi- Private Bag 7, Congella 4013, South Africa (danielmgore ciency syndrome. Korean J Ophthalmol. 2007;21(1):51-54. @gmail.com). 21. Roig-Melo EA, Macky TA, Heredia-Elizondo ML, Alfaro DV III. Progressive outer

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Ophthalmic Images

Dislocation of Dexamethasone Intravitreous Implant Bogomil Voykov, MD, FEBO Karl Ulrich Bartz-Schmidt, MD

A 46-year-old woman had visual acuity impairment in the left eye after riding a bicycle. The pseudophakic left eye (scleral-fixated posterior chamber intraocular lens) had received a dexamethasone intravitreous implant (Ozurdex) 2 weeks earlier. Visual acuity was 20/100 OS and was 2 lines worse on the Early Treatment Diabetic Retinopathy Study chart than before implantation. The right eye was blind due to chronic intermediate uveitis. On examination, distinct corneal edema of the left eye was seen. The implant was dislocated in the anterior chamber with endothelial contact. Intraocular pressure was 10 mm Hg OS. After explantation of the implant, both corneal edema and visual acuity slowly recovered.

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