Abstract
Purpose
To raise awareness of ophthalmologists that Varicella Zoster Virus (VZV) retinitis should be considered in the differential diagnosis of retinitis that presents with features of progressive outer retinal necrosis (PORN) in healthy immunocompetent patients.
Observations
Case 1 is a 39-year-old healthy Caucasian male who presented after one week of decreased vision in the left eye. Patient was found to have optic disc edema and multifocal retinitis primarily localized to the posterior pole with only a few lesions in the periphery and minimal vitritis. Viral PCR of a vitreous tap was positive for 1 million copies of VZV. Patient ultimately progressed to no light perception vision despite multiple intravitreal injections of foscarnet and several days of intravenous acyclovir therapy. Case 2 is another 39-year-old healthy Caucasian male that presented after 2 weeks of decreased vision in the left eye. On initial exam by his primary ophthalmologist, patient was found to have optic disc edema and multifocal retinitis primarily localized to the posterior pole with no peripheral lesions and no vitritis. The patient then presented to our clinic with extensive retinitis throughout the posterior pole and periphery, and he underwent a vitreous tap with viral PCR positive for 3160 copies of VZV. He was treated with intravitreal injections of foscarnet and intravenous acyclovir therapy with subtle progression to the right eye and only minimal improvement of left eye vision to 20/200.
Conclusions and Importance
Progressive outer retinal necrosis (PORN) is a herpetic retinopathy characterized by rapidly progressive necrosis of the outer retina in severely immunocompromised subjects. As demonstrated in this case series, VZV retinitis should be considered as a differential diagnosis in patients with hallmark features of PORN, even in the absence of obvious systemic immunosuppression.
1
Introduction
Acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN) represent two variants of rapidly progressing necrotizing herpetic retinitis, each with distinctly different features. The Executive Committee of the American Uveitis Society characterizes ARN as a peripheral necrotizing retinitis and occlusive retinal arteritis with a prominent inflammatory reaction in the vitreous and anterior chamber. It can occur in both immunocompromised and immunocompetent individuals. By contrast, PORN has been described almost exclusively in immunocompromised persons, such as those infected with HIV/AIDS or otherwise immunosuppressed. The clinical features of PORN that distinguish it from ARN include early involvement of necrotizing lesions in the posterior pole and macula, little to no intraocular inflammation, and minimal vasculopathy. The etiology of both conditions involves a reactivation of a latent herpetic infection, varicella zoster virus (VZV) being the most common cause, followed by herpes simplex virus (HSV) types 1 and 2.
Here we report two unique cases of healthy adults that presented with necrotizing herpetic retinitis with hallmark features of PORN. In each case, there was a delay in care due the atypical presentation in patients without known immunosuppression.
2
Findings
2.1
Case 1
A 39-year-old Caucasian male presented with a one-week history of eye pain and decreased vision in the left eye. The patient was incarcerated at this time and seen by a physician in the federal facility who initiated treatment with artificial tears. The patient’s only known medical history included hypertension. His past ocular history, surgical history and family history were non-contributory. Visual acuity was 20/20 in the right eye, and light perception only in the left eye. There was a positive relative afferent pupillary defect in the left eye. Intraocular pressures by applanation tonometry were 19 mmHg and 50 mmHg in the right and left eye, respectively. Examination of the unaffected right eye was normal. Examination of the left eye revealed a clear cornea and 2+ anterior chamber cells. Dilated fundus exam of the left eye showed trace vitritis, grade-4 disc edema with peripapillary hemorrhages, and multifocal retinitis primarily localized to the macula and posterior pole with only a few lesions in the mid-periphery ( Fig. 1 A). Fluorescein angiogram (FA) of the left eye was consistent with early areas of blocked fluorescence in the macula, followed by late leakage from the disc and minimal leakage from retinal vessels in the inferior arcade ( Fig. 1 B). Indocyanine green angiography (ICG) of the left eye revealed mild blockage in the macula and few areas in the posterior pole and mid-periphery ( Fig. 1 C). Optical coherence tomography (OCT) examination of the macula in the left eye revealed cystoid macular edema ( Fig. 1 D). Right eye FA, ICG and OCT of the macula were non-revealing.
The patient denied recent travel, high-risk sexual behavior, recent tick bites, previous eye surgery or trauma, and intravenous drug use. HIV screen, T spot, and Syphilis IgG were negative, and CD4 count was normal. Viral quantitative polymerase chain reaction of a vitreous tap was positive for 1 million copies of varicella zoster virus (VZV). He received intravitreal foscarnet (2.4mg in 0.1 mL) followed by anterior chamber paracentesis which normalized the intraocular pressure. The patient was started on 2 g of oral valacyclovir four times daily with frequent topical steroid drops. At follow-up 48 hours later, he had progressed to no light perception vision in the left eye, and exam was otherwise stable. At this time the patient received re-injection with foscarnet and admission to the hospital for intravenous acyclovir (15mg/kg every 8 hours). He was also started on atropine drops and dorzolamide-timolol eye drops twice a day for high intraocular pressure. After 48 hours of hospitalization, intravenous solumedrol (250mg every 6 hours) was started and continued for 5 days. The patient completed 7 days of intravenous acyclovir, and was discharged back to the federal facility on 2 g of oral valacyclovir four times a day for 7 days, followed by 2 g three times a day for 30 days.
At one-month follow-up, visual acuity was still 20/20 in the right eye and no light perception in the left eye. Fundus exam of the right eye was unremarkable, and the left eye revealed optic disc pallor with resolving retinitis ( Fig. 1 E). OCT of the macula in the left eye showed resolution of macular edema ( Fig. 1 F). Oral valacyclovir was decreased to 1 g three times a day.
2.2
Case 2
A 39-year-old Caucasian male initially presented to an outside general ophthalmologist with the complaint of decreased vision in the left eye. His exam demonstrated grade-2-disc edema concerning for optic neuritis. Over the next two weeks the patient developed retinal lesions mainly throughout the posterior pole, consistent with retinitis ( Fig. 2 A–B). At this time, the patient was started on topical steroid drops and atropine drops and referred to our clinic for evaluation. Associated medical conditions only included hypertension. His past ocular history, surgical history, and family history were non-contributory. The patient denied recent travel, high-risk sexual behavior, recent tick bites, previous eye surgery or trauma, and intravenous drug use. An HIV screen, Syphilis IgG, and purified protein derivative (PPD) tests were negative. At the time of presentation to our clinic, visual acuity was 20/20 in the right eye and count fingers at 5 feet in the left eye. There was a positive relative afferent pupillary defect in the left eye. Intraocular pressures by applanation tonometry were 19 mmHg and 24 mmHg in the right and left eye, respectively. Examination of the unaffected right eye was normal ( Fig. 2 F). Examination of the left eye revealed 2+ cells in the anterior chamber, minimal vitritis, grade-3 disc edema, and multifocal retinitis throughout posterior pole, periphery and macula with sparing of the fovea ( Fig. 2 C). OCT of the macula in the left eye revealed subretinal fluid superonasal to the fovea. ( Fig. 2 D). OCT of the right eye was normal. A vitreous tap was performed, and the patient received an intravitreal injection of foscarnet (2.4mg in 0.1 mL) and was started on 2 g of oral valacyclovir four times daily with frequent topical steroid drops. Viral quantitative polymerase chain reaction of the vitreous tap was positive for 3160 copies of VZV.
