Acute retinal necrosis after Boston type I keratoprosthesis.

A case report of a 68-year-old male who developed acute retinal necrosis (ARN) after Boston type I keratoprosthesis is presented. The procedure was performed for multiple graft failure secondary to herpetic keratitis. Clinical data including visual acuity, color fundus photography, fluorescein angiography, laboratory tests findings, and management are presented. After exclusion of other causes by laboratory workup, the patient was diagnosed with ARN most likely secondary to herpetic infection. Intravenous acyclovir and oral prednisolone were administered to the patient resulting in marked improvement in visual acuity and regression in the size of the retinitis. The patient eventually developed a soft eye and choroidal detachment with light perception vision. In patients with a history of herpetic keratitis or keratouveitis, it is highly advisable to maintain prophylactic systemic antiviral treatment before and after any ocular procedure such as the Boston keratoprosthesis.

INTRODUCTION

The acute retinal necrosis (ARN) syndrome is described as a fulminant retinitis with moderate to severe uveitis that usually occurs in otherwise healthy patients. Mild forms of the disease12 and occurrence in immunocompromised hosts34 have been reported. ARN was firstly described by Urayama and colleagues in 1971 who found the syndrome was due to viral infection of the retina.5 Herpes virus infection was presumed to be the pathogenic agent. Subsequently, varicella–zoster virus (VZV), herpes simplex virus (HSV), and Epstein–Barr virus (EBV) were also associated to the pathogenesis of ARN.26–14

Clinical features of ARN include anterior uveitis and vitritis, patchy or confluent areas of white or cream-colored retinal necrosis initially affecting the peripheral retina and extending posteriorly, and secondary retinal atrophy, which may lead to rhegmatogenous retinal detachment (RD). In the majority of cases, there is an occlusive vasculopathy associated with arteritis and phlebitis involving the retinal and choroidal vasculature. Neovascularization and secondary vitreous hemorrhage may occur. The major causes of poor visual outcome in ARN are RD and optic nerve or macular involvement from ischemic vasculopathy. Less frequently, visual loss can occur due to macular hole, macular pucker, or hypotony.

The Boston keratoprosthesis was first described in 1974 by Dr. Claes Dohlman. However, it did not gain popularity at that time due to complications and suboptimal design. The device was approved by the FDA for use in the United States in 1992. High success rates based on visual acuity outcomes and retention rates of the device have been reported in the literature.15 The Multicenter Boston Type 1 Keratoprosthesis Study, a prospective case series of 141 cases from 17 centers with an average follow-up of 8.5 months, reported retention rates of 95% with visual acuity better than 20/40 in 23% of patients and better than 20/200 in 57% of patients.16 The Boston keratoprosthesis can be beneficial in patients with graft failure due to herpetic keratitis. However, lifelong prophylactic antibiotics and oral antiviral therapy are required in such cases.17

In this case report, we present, to the best of our knowledge, the first case of ARN that occurred 3 weeks after the Boston keratoprosthesis procedure secondary to herpetic infection.

CASE REPORT

A 68-year-old male diabetic presented with corneal scarring due to recurrent corneal microbial and herpetic infection with upper lid entropion secondary to stage IV trachoma in left eye (OS). The patient was blind in the right eye since childhood. The patient had undergone extracapsular cataract extraction in the left eye for an immature cataract, many years prior to presentation. One year postoperatively, the patient developed two episodes of recurrent herpetic keratitis and was managed successfully with topical acyclovir ointment and was instructed to continue a maintenance dose of prophylactic oral acyclovir 500 mg once daily.

Concurrently, the patient developed glaucoma which was controlled with topical antiglaucoma medications. Ten years later the patient underwent penetrating keratoplasty (PKP) secondary to visually significant corneal scaring which failed due to recurrent herpetic keratitis. Once the eye was free of infection for 1 year, PKP combined with trabeculectomy was successfully performed. Three years after combined PKP and trabeculectomy, the graft failed and recurrent herpetic keratitis was successfully treated. The vision was count fingers at one foot with dense corneal scar and deep vascularization. The patient was instructed to start a maintenance dose of prophylactic valacyclovir 500 mg once daily. The eye remained quiet and he discontinued valacyclovir for 4 years.

In April 2009, patient underwent an uneventful Boston Type I keratoprosthesis procedure. His best-corrected visual acuity improved to 20/80 and he was maintained on a megasoft bandage contact lens with topical moxifloxacin four times a day, topical fortified vancomycin 25 mg/ml four times a day, and topical antiglaucoma [Figure 1].

Figure 1

(a) Left eye with vascularized corneal scaring with graft failure before surgery (b) after keratoprosthesis with a clear graft

Three weeks after the keratoprosthesis procedure, patient presented to the emergency room complaining of painless and gradual decrease in vision over 3 days. The presenting vision was hand motion. Anterior segment examination revealed clear graft and the keratoprosthesis was in place. Fundus examination showed 3+ vitritis and large, demarcated areas of hemorrhagic necrotizing retinitis involving all quadrants, encroaching the optic disc and the macula [Figure 2]. Fluorescein angiography demonstrated a typical peripheral vascular leakage related to vasculitis with evidence of ischemic optic neuritis.

Figure 2

(a) Vitritis and large, demarcated areas of hemorrhagic necrotizing retinitis involving all quadrants and encroaching the optic disc and the macula, (b) fluorescein angiography demonstrated a typical peripheral vascular leakage related to vasculitis with evidence of ischemic optic neuritis

The patient was diagnosed with ARN secondary to herpetic infection. Serology testing indicated high titers of herpes simplex virus type 2 which confirmed the diagnosis. The patient was immediately admitted and started on intravenous acyclovir 10 mg/kg every 8 hours with topical prednisolone acetate 1% four times a day with close monitoring of his renal functions. Forty eight hours after admission the patient was also placed on oral prednisolone 100 mg (1 mg/kg) once daily. After 11 days, intravenous acyclovir was stopped in favor of oral valacyclovir 1 g every 8 hours due to mild to moderate changes in the renal function tests. During this time, there was marked improvement in visual acuity from hand motion to 20/200 and regression in the size of retinitis [Figure 3]. Prophylactic laser retinopexy was performed [Figure 4].

Figure 3

Fundus examination and corresponding fluorescein angiography showed regression in the size of retinitis after the initiation of therapy

Figure 4

Fundus image documenting prophylactic laser retinopexy

Four weeks later, there was a marked reduction in vision to light perception, with a soft eye and choroidal detachment without RD on B-scan ultrasound.

DISCUSSION

ARN is an uncommon but devastating complication of HSV infection that can cause loss of an eye. Systemic acyclovir therapy is recommended in many studies.618–22 Hung and coworkers23 found that oral administration of acyclovir (400 mg five times a day) to normal volunteers can produce mean plasma levels of 8.7 μm and mean aqueous levels of 3.3 μm. Aqueous acyclovir levels of 8.7 to 11.2 μm are achievable using intravenous acyclovir (1500 mg/m2/day), which are sufficient to treat most cases of ARN. Ten days of treatment is generally sufficient because progression of retinal lesions usually stops within several days of initiation of intravenous therapy.1823 In cases that are unresponsive to acyclovir, cultures of a retinal biopsy specimen may indicate an acyclovir-resistant strain of HSV that is sensitive to ganciclovir.2425

The use of systemic steroid (up to 120 mg daily) is recommended as the disease is frequently associated with optic nerve inflammation and occlusion of arteriolar vessels that may cause optic nerve and retinal ischemia.6181925

Our patient presented with severe necrotizing retinitis and optic nerve inflammation that initially responded well to systemic acyclovir and steroid therapy but his condition deteriorated secondary to ciliary body shutdown caused by severe inflammation and ended with a pre-phthisical eye.

After the initial HSV infection, HSV establishes a latent infection in the trigeminal or other sensory ganglia. Recurrent viral shedding can cause infection in one or both eyes. Standard corneal transplantation is traditionally the procedure of choice in the visual restoration of patients with significantly scarred herpetic eyes.17 Studies have documented the benefit of acyclovir therapy in HSV patients who have undergone PKP. Tambasco and colleagues recommended the use of oral acyclovir, 400 mg twice a day, for at least 1 year postoperatively for herpes simplex keratitis due to a significant reduction in recurrent episodes.26

The patient in the current case remained free of infection and prophylactic antiviral medication for 4 years before the keratoprosthesis procedure. The keratoprosthesis did help the patient and improved vision to 20/80; however, he developed a complicated course of ARN that led to the loss of his functional eye.

The Boston keratoprosthesis can be of value in patients with graft failure from herpetic keratitis, but ARN with severe visual loss can occur after this procedure. We highly recommended continued prophylactic systemic antiviral treatment before and after any ocular procedure such as the Boston keratoprosthesis for any patient with history of herpetic keratitis or keratouveitis.