Diagnostic and therapeutic challenges in acute retinal necrosis; an update

Abstract

Acute retinal necrosis (ARN) is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. ARN may present with a wide spectrum of clinical findings compatible with panuveitis including anterior uveitis, scleritis, vitritis, necrotizing retinitis, occlusive vasculitis, and optic disc edema. The American Uveitis Society introduced clinical criteria in 1994 for the diagnosis of ARN, while more recent criteria have been proposed by the Standardization of Uveitis Nomenclature (SUN) Working Group and the Japanese ARN Study Group. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases, while utilizing retinal imaging and applying AI algorithms in these areas of clinical research could be highly beneficial. Over the last few years, significant progress has been made in achieving timely diagnosis and treatment. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques and flow cytometry used for intraocular fluids. systemic (intravenous or oral) antivirals with adjunctive intravitreal antiviral therapy are recommended as first-line therapy to reduce disease severity, the risk of vision loss, and retinal detachment incidence. Although aciclovir was the first existing antiviral agent, at present many clinicians prefer high-dose valaciclovir orally or intravenous aciclovir combined with intravitreal foscarnet. Despite significant progress in diagnosing and treating ARN, further research is needed to improve visual outcomes in this challenging clinical condition.

Fig. 1. A 63-year-old gentleman with a free ophthalmic and systemic history presented to the eye casualty with gradual worsening of his right eye vision over the last 48 h.

At presentation, the visual acuity of the affected eye did not exceed counting fingers at a 1-metre distance. a Dilated fundoscopy revealed dense vitritis (vitreous haze: 3 + ) (green asterisk) with distinct, multifocal, peripheral, confluent patches of yellowish infiltrates in the deep retina (blue arrows). Retinal haemorrhages can also be observed (yellow arrow). Aqueous humour was obtained with anterior chamber paracentesis and was sent for polymerase chain reaction (PCR) and flow cytometry. Due to the high suspicion of acute retinal necrosis patient was empirically started on antiviral treatment. PCR was positive for varicella-zoster virus. b Signs of occlusive vasculitis (blue arrows) with limited retinal haemorrhages (yellow arrows). c Patient was initially treated with intravenous aciclovir 750 mg three times daily. On the 6th day of this course 16 mg of oral prednisolone was added to the therapeutic regimen. Due to the occlusive vasculitis oral aspirin 100 mg once daily was also administered to the patient. He received an overall of 11 intravitreal ganciclovir injections Fundoscopic image after two months. Best corrected Snellen visual acuity remained stable at 5/10. d Examination of the peripheral retina with evidence of peripheral retinal atrophy.

Fig. 2. Suggested diagnostic and therapeutic algorithm for the management of patients with suspected acute retinal necrosis.

ARN is a rare but severe ophthalmic pathology defined by panuveitis, retinal necrosis, and high rates of retinal detachment. ARN may lead to poor visual outcomes even if promptly diagnosed and treated. The primary goal of treating ARN is to halt the progression of the disease in the affected eye and prevent it from developing to the other eye. Clinicians must always inquire about a possible history of a prior herpetic infection, and request medical assessment from other specialties (e.g., neurology) and neuro-imaging (e.g., in cases with herpes encephalitis) when necessary. The precise identification of the viral cause in suspected ARN cases has been greatly enhanced by the advancements in PCR techniques used for intraocular fluids. AC tap can be obtained and used for PCR testing and flow cytometric analysis to establish a diagnosis of ARN. Systemic treatment can be commenced empirically while waiting for the laboratory results. Further treatments (e.g., intravitreal antiviral agents or oral steroids) can be also added to the therapeutic regimen. Multimodal imaging is a valuable tool in evaluating patients with ARN, particularly in unusual cases. Close follow-up is mandatory to control the inflammatory process and evaluate the risk of potential complications (e.g., CMO, RD). AC anterior chamber, ARN acute retinal necrosis, CMO cystoid macular oedema, HZO herpes zoster ophthalmicus, Hx history, IOP intraocular pressure, PCR polymerase chain reaction, PPV pars plana vitrectomy, RD retinal detachment, VA visual acuity.

Fig. 3. Flow cytometry analysis of aqueous humour.

CD45 marker and side scatter are used to characterize lymphocytes (gated at region R1). In gated lymphocytes, further characterization of lymphocyte sub-populations is made by using CD3/CD19 (T lymphocytes /B lymphocytes) and CD4/CD8 (T cell sub-populations). Percentages of cell populations are presented in the upper right of each quadrant.

Fig. 4. CMV retinitis.

Fundoscopic view (right eye) of a patient with CMV retinitis before (a) and after (b) treatment.