Intravitreal Antivirals in the Management of Patients With Acquired Immunodeficiency Syndrome With Progressive Outer Retinal Necrosis FREE

Retinal infection with herpes varicella zoster in patients with acquired immunodeficiency syndrome (AIDS) usually produces multifocal outer retinal whitening that rapidly progresses to confluent, full-thickness retinal necrosis. This form of necrotizing herpetic retinopathy, known as progressive outer retinal necrosis, differs from acute retinal necrosis syndrome principally in the lack of prominent intraocular inflammation.¹ Treatment with intravenous antiviral therapy alone has been associated with a disappointing visual prognosis.² We report the visual outcomes associated with the use of combination systemic and intravitreal antivirals in the management of 7 patients with AIDS with progressive outer retinal necrosis.

There were 4 men and 3 women with AIDS (mean age, 34.6 years [range, 27-38 years]) (Table 1). Two of the 7 patients had a history of cutaneous varicella-zoster virus infection and 1 had encephalitis. Six of 7 patients had bilateral involvement at the time of the diagnosis of retinitis, and the remaining patient developed involvement of the fellow eye within a 2-month period. Median follow-up was 10 months, with a range of 4 to 30 months. All 7 patients demonstrated clinical features consistent with progressive outer retinal necrosis.

Median visual acuity at the time of diagnosis was 20/80 (Table 2). The visual acuity in 8 eyes ranged from 20/20 to 20/80 and 6 eyes were hand motions to no light perception. All patients were able to see at least 20/60 in at least 1 eye. Retinal lesions were present in zone 3 in all 14 eyes: only in zone 3 in 3 eyes (21%); only in zones 3 and 2 in 3 eyes (21%); and in all 3 zones in 8 eyes (57%). No patient had lesions confined to only zones 1 or 2. Three of 7 patients (5 eyes) had retinal detachment at diagnosis, and 3 detachments involved the macula. Of the 9 retinas that were not detached at diagnosis, 5 were treated with a prophylactic demarcating laser. One laser-treated retina subsequently detached. All 4 nondetached retinas that were not treated with the demarcating laser subsequently detached.

All patients received intravenous ganciclovir sodium and foscarnet; 1 patient also received intravenous acyclovir. Two patients (4 eyes) received intravitreal injections of ganciclovir sodium (2 mg/0.05 mL) and foscarnet (1.2 mg/0.05 mL). The remaining 5 patients (7 eyes) received intravitreal injections of ganciclovir sodium (2 mg/0.05 mL). A median of 6 injections (range, 3-15 injections) during 14 days (range, 6-88 days) were given per eye. Two eyes with light perception vision were not injected. One eye with hand motion vision and retinal detachment recovered a visual acuity of 20/80 after injections and retinal detachment repair. Three other eyes with hand motions or worse vision were injected and had poor visual outcomes.

Five (45%) of 11 treated eyes achieved a final visual acuity of 20/80 or better, and only 2 (18%) of the 11 treated eyes progressed to no light perception vision. All patients maintained a visual acuity of 20/400 or better in at least 1 eye. No progression of disease occurred during intravitreal treatment. Recurrent disease occurred in only 1 eye and was treated successfully by resumption of both intravenous and intravitreal ganciclovir and foscarnet therapy.

In the original series of 38 patients with progressive outer retinal necrosis treated with intravenous antivirals alone, 42 (67%) of 63 eyes progressed to no light perception within 4 weeks after diagnosis.² A subsequent study of 20 patients with progressive outer retinal necrosis treated with intravenous antivirals reported 19 (49%) of 39 eyes progressing to no light perception within 6 months.³ The outcomes of patients treated with more than 1 intravenous antiviral agent were statistically better than those who received only a single drug, but only 4 (10%) of 39 eyes achieved a visual acuity of 20/80 or better. In a more recent study of 6 patients with progressive outer retinal necrosis treated with combination intravenous antivirals, a final visual acuity of 20/80 or better was achieved in only 2 (22%) of 9 treated eyes.⁴ In contrast, 5 (45%) of the 12 eyes treated with both intravenous and intravitreal antivirals (35% of the 14 total eyes) in the current series had a final visual acuity of 20/80 or better. Five of the 7 eyes with final visual outcomes that were light perception or no light perception had hand motions to no light perception at the time of diagnosis.

Rhegmatogenous retinal detachment also contributes to poor visual outcome and occurred in about 70% of eyes in the prior series,^{2 - 4} in which most retinas detached after treatment was begun. In the current series, there was a similar total rate of detachments, with 35% detached at the time of diagnosis and 35% detaching subsequently. However, in the current series, 1 (20%) of 5 retinas treated with a demarcating laser subsequently detached compared with 4 (100%) of 4 untreated retinas. The more rapid healing from the use of intravitreal antivirals together with the use of a prophylactic demarcating laser may have contributed to the reduced rate of retinal detachment after treatment was begun.

The limitations of comparing results of the current series with results reported in historical controls should be noted. For instance, the original series of patients was reported soon after the recognition of progressive outer retinal necrosis as a syndrome² ; earlier recognition and treatment might have improved the prognosis in these eyes. In addition, most patients in the originally reported series were treated with intravenous acyclovir rather than ganciclovir, foscarnet, or combination systemic antiviral therapy.² Moreover, the current use of highly active antiretroviral therapy (HAART) likely influences the prognosis of progressive outer retinal necrosis as it does with cytomegalovirus retinitis. However, in the current series, only 2 patients were being treated with HAART (either because the patients were initially examined before the widespread use of HAART or because of noncompliance with medical therapy). Finally, although the zones of retinal involvement were known for the patients in the current series, the retrospective nature of this study does not permit precise quantification of the baseline extent of disease, which would be necessary, for instance, to accurately assess the efficacy of laser demarcation in preventing retinal detachment.

Published information on visual outcomes following the use of intravitreal antivirals in the management of progressive outer retinal necrosis is limited, consisting of only 3 reports.^{5 - 7} Three (50%) of 6 involved eyes of the reported 4 patients achieved a final visual acuity of 20/80 or better with intravitreal therapy.

Progressive outer retinal necrosis remains rare enough that it is difficult to define optimal treatment. Our preferred regimen for intravitreal treatment is to inject intravitreous ganciclovir sodium (2 mg/0.05 mL) and foscarnet (1.2 mg/0.05 mL) 3 times weekly for 2 weeks, followed by maintenance therapy of injections once or twice per week as indicated until the retinitis is stabilized. Laser photocoagulation to demarcate necrotizing retinitis is applied whenever possible. Because central nervous system involvement can occur in association with necrotizing herpetic retinitis,⁸ we also use systemic antiviral therapy. Our preferred regimen is intravenous ganciclovir or oral valganciclovir at induction doses for 3 weeks and intravenous foscarnet at induction doses for 2 weeks, followed by maintenance antiviral therapy with oral valganciclovir and intravenous foscarnet until complete healing is achieved. A successful transition to oral valganciclovir or valacyclovir can often be made after several weeks of combination antivirals even if there is no improvement in the immune system.

An appropriate control group with which to compare the poor prognosis of progressive outer retinal necrosis treated with intravenous antivirals alone^{2 - 4} would be necessary to draw definitive conclusions. However, combination systemic and intravitreal antiviral therapy may be associated with improved efficacy in achieving disease resolution, maintaining disease remission, and preserving visual acuity.

This study was supported in part by Research to Prevent Blindness Inc, New York, NY.

Corresponding author and reprints: Janet L. Davis, MD, Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101.