Acute retinal necrosis (ARN) following chickenpox in a patient of Vogt-Koyanagi-Harada (VKH) syndrome using immunosuppressants

Abstract

A 36-year-old woman presented with diminution of vision and floaters in both the eyes. Both eyes had disc oedema, multiple pockets of neurosensory detachments along with vitritis. Fluorescein angiography and optical coherence tomography showed characteristic features of Vogt-Koyanagi-Harada (VKH) syndrome (figure 1). She was started on corticosteroid pulse therapy and immunosuppressants following which her VKH lesions resolved. However, she developed chickenpox after 2 weeks and after 1 month she developed discrete yellowish white retinitis patches in the periphery of the right eye which were consistent with a diagnosis of acute retinal necrosis. She was started on oral antivirals for the same and immunosuppressants were withheld in view of immunocompromised state potentially acting as a trigger for reactivation of latent virus. Retinitis patches started to resolve and showed a favourable response to the treatment.

Background

Acute retinal necrosis (ARN) is characterised by a rapidly progressive retinal necrosis associated with vitreous inflammation in immunocompetent individuals. However, ARN is also known to occur in an immunocompromised state which was the scenario in the case we encountered. ARN can also occur after chickenpox and in a patient on long-term immunosuppression. Uveitis and anterior chamber inflammation in a patient with a history of chickenpox should lead to suspicion of viral retinitis. Both ARN and Vogt-Koyanagi-Harada (VKH) syndrome are vision-threatening entities and their presentation at the same time in an individual can pose a treatment challenge. This case report highlights the course of management for salvaging vision in such cases.

Case presentation

A 36-year-old woman presented with chief complaints of gradually progressive blurring of vision in both the eyes, floaters and headache for 3 weeks. On examination, her best-corrected visual acuity (BCVA) was 20/200 with ciliary congestion and anterior chamber reaction of cells 2+ in both the eyes. Fundus examination in both eyes revealed disc oedema and multiple pockets of neurosensory detachments (NSD) involving macula (figure 1) and optical coherence tomography (OCT) revealed multiple areas of multiple NSD, retinal pigment epithelium (RPE) undulations and septae-like projections from outer retinal layers (figure 2). There was increased choroidal thickening on ultrasound B scan in both eyes (figure 3).

Figure 1.

Fundus photograph (top row) of the right and left eyes showing multiple pockets of NSDs (arrow). Fluorescein angiography (bottom row) showing pinpoint leaks in the early arteriovenous phase (arrow head). NSD, neurosensory detachment.

Figure 2.

Swept source OCT of the right and left eyes showing multiple NSDs (arrow), RPE undulations (arrowhead) and septae arising from outer retinal layers (asterisk). NSD, neurosensory detachment; OCT, optical coherence tomography; RPE, retinal pigment epithelium.

Figure 3.

Ultrasonography of the right and left eyes showing choroidal thickening (double-headed arrow) and NSDs (arrow). NSD, neurosensory detachment.

Based on clinical examination and investigation findings, a diagnosis of probable VKH was made and the patient was started on corticosteroid pulse therapy (intravenous methylprednisolone 1 g, three doses given on consecutive days) and subsequent systemic corticosteroids (prednisolone 1 mg/kg body weight) and immunosuppressants (azathioprine, 50 mg two times per day). The patient responded to treatment and there was a decrease in anterior chamber reaction and disc oedema along with resolution of NSD. Also, her BCVA improved to 20/20 in both eyes. The patient was shifted to a course of oral steroids (prednisolone 60 mg) and immunosuppressant (azathioprine 50 mg) thereafter.

After 2 months, her right eye developed peripheral confluent yellow-white retinitis patches without any evidence of vitritis (figure 4). She also gave a history of having chickenpox 2 weeks earlier, for which she had taken a course of oral antivirals.

Figure 4.

Montage view of the right eye showing peripheral confluent yellow-white retinitis patches without any evidence of vitritis in mid periphery.

Investigations

Fluorescein angiography showed multiple focal areas of pinpoint hyperfluorescence along with pooling corresponding to pockets of NSD and disc leakage in both eyes (figure 1).

OCT of both eyes showed multiple NSD, RPE undulations and septae-like projections from outer retinal layers (figure 2).

Ultrasound B scan showed choroidal thickening along with NSDs in both eyes (figure 3).

At the time of presentation of ARN, the patient was investigated for a complete uveitis profile. The complete haemogram was normal. The CD4 count was 673 cells/µL and the patient was non-reactive for HIV by ELISA.

Differential diagnosis

In view of her medical history and the clinical presentation, the differential diagnoses of ARN, progressive outer retinal necrosis (PORN) and CMV retinitis in the right eye were considered. However, her CD4 counts were normal and her tests for HIV were also negative. The peripheral multiple confluent lesions were suggestive of acute retinal necrosis.

Treatment

The patient was started on oral valacyclovir (2 g three times per day), oral steroids were continued and immunosuppressant (azathioprine) was withheld in view of active retinitis. After 1 week of antiviral therapy, retinitis patches were seen to be resolving, retinal infiltration had decreased substantially (figure 5) and her visual acuity improved from 20/125 to 20/60.

Figure 5.

Montage view of the right eye showing resolving retinitis patches with a centripetal pattern of resolution without pigmentation.

Outcome and follow-up

The patient responded well to the treatment with retinitis patches disappearing over a period of time. However, 1 month later, the patient developed a rhegmatogenous retinal detachment in the right eye for which she underwent pars plana vitrectomy with silicone oil injection.

At a 4-month follow-up, she had BCVA of 20/80 in the right eye and 20/30 in the left eye with evidence of grade 1 vitritis in both eyes. At the time of last follow-up (8 months follow-up), the patient was maintaining a BCVA of 20/50 in the right eye and 20/30 in the left eye.

Taking recurrence of VKH into consideration, oral immunosuppressants were started again along with systemic steroids and prophylactic antivirals. The patient has subsequently been kept on long-term antiviral prophylaxis of oral valacyclovir¹ along with immunomodulators for VKH.

Discussion

ARN is a vision-threatening condition characterised by full-thickness retinal necrosis² which coalesces and spreads circumferentially if untreated. ARN is primarily a clinical diagnosis based on the criteria laid down by American Uveitis Society.³ Laboratory investigations and microbial examinations play only a supportive role. Due to the fulminant and rapidly progressive course of ARN, an early and prompt clinical diagnosis is essential to ensure an early intervention and treatment of this condition. The differential diagnosis for these retinitis lesions includes PORN syndrome, which involves posterior pole, to begin with and is usually devoid of vitreous and anterior chamber inflammation.⁴

ARN has been known to occur in both healthy and immunocompromised individuals.⁵ Also, the degree of vitreous inflammation is generally determined by the immune status of the patient.⁶ Immunocompromised status of our patient (on systemic steroids and immunosuppressants) accounted for the absence of vitreous and anterior chamber inflammation. There have been numerous factors documented in the literature which act as a trigger for reactivation of virus leading to ARN.

Chang et al described a case of ARN in a patient who had received intravitreal triamcinolone injection.⁷

Matsuo et al had described a series of ARN as a novel complication of chicken pox in three adults.⁸

ARN has also been known to occur following steroid therapy for herpes zoster-associated dermatitis of the thigh,⁹ in a patient after kidney transplant on immunosuppressants¹⁰ and after penetrating trauma with an intraocular foreign body.¹¹ In all of the above cases, systemic as well as the ocular immune status deviation has been a trigger for reactivation of the virus.

Our case of ARN in a patient undergoing treatment for active VKH highlights the treatment challenges in dealing with such cases. It is important to be aware of ARN in immunocompromised patients and in patients with a history of chickenpox. The presence of inflammation should lead to meticulous retinal evaluation in patients on long-term systemic immunosuppression and these patients usually need long-term prophylaxis with systemic antivirals.

Learning points.

• Meticulous retinal evaluation is needed in patients who have signs of uveitis and a history of chickenpox.

• Patients undergoing treatment for Vogt-Koyanagi-Harada (VKH) syndrome with immunosuppresants can be immunosuppressed and can be at a risk of developing acute retinal necrosis (ARN).

• Prophylactic antivirals are useful in preventing the recurrence of ARN in immunosuppressed patients like those with VKH on long-term immunosuppression.