Acute retinal necrosis and ocular neovascularization caused by cytomegalovirus following intravitreal dexamethasone implant (Ozurdex® ) in an immunocompetent patient.

Abstract

Ocular cytomegalovirus (CMV) infection usually manifests as a haemorrhagic retinitis in severely immunocompromised patients. Previous reports have highlighted that otherwise immunocompetent patients can develop CMV or other types of viral retinitis in the context of subtenonial or intravitreal triamcinolone (Shah et al. 2010; Takakura et al. 2014). Recently, Vannozzi et al. (2016) reported a case of CMV retinitis following the use of a dexamethasone implant (Ozurdex; Allergan Inc., Irvine, CA, USA). However, their patient was also on systemic immunosuppression with mycophenolate mofetil. The authors speculated whether the systemic immunosuppression and/or central retinal vein occlusion in this patient might have contributed to the development of CMV retinitis. Here, we report a case of ocular CMV infection in a 67-year-old immunocompetent patient receiving Ozurdex implants every 3–4 months for 4 years for a chronic, bilateral idiopathic panuveitis. Approximately two weeks after administration of the 14th dexamethasone implant in his right eye, the patient complained of redness, photophobia, floaters and diminished vision. On examination, he was found to have granulomatous keratic precipitates, 3 + cells and flare in the anterior chamber, iris haemorrhages, 2 + cells in the vitreous, occlusive retinal vasculitis and peripheral yellow-white areas of retinal necrosis in 360o. Vitreous samples were taken, and intravenous acyclovir therapy was initiated for a suspected herpes simplex or varicella-zoster-related acute retinal necrosis (ARN). However, quantitative polymerase chain reaction revealed 139 000 CMV units per ml, as well as a small amount of Epstein–Barr virus (EBV) DNA. Serology was CMV and EBV IgG positive and IgM negative. Therapy was changed to intravenous ganciclovir, followed by oral valganciclovir, and the patient's condition gradually improved over the next weeks. Eventually, granular hyperpigmentation occurred in the affected retina (Fig. 1A). Ultra-widefield angle fluorescein angiography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) revealed extensive peripheral retinal non-perfusion (Fig. 1B), likely as a result of his occlusive CMV-related retinal vasculitis. Panretinal photocoagulation was subsequently performed. Three months after the onset of the CMV infection, the patient was found to have florid iris and angle neovascularisation (rubeosis) (Fig. 1C), and a localized superotemporal peripheral retinal detachment. The latter was treated conservatively, with laser retinopexi. The visual prognosis for this patient remains uncertain. Prior to the CMV infection, he had a Snellen best-corrected visual acuity of 0.8 in his right eye, upon diagnosis it had dropped to 0.2, and after 4 months follow-up, the visual acuity remained at 0.2. He also had a concentric scotoma and persistent ocular hypotony, likely as a result of viral damage to the ciliary body. Our case raises three important issues. Firstly, ocular CMV infections can have an atypical course in immunocompetent patients and cause a greater degree of anterior segment inflammation with haemorrhagic iritis and ciliary body damage, occlusive retinal vasculitis and peripheral retinal necrosis similar to ARN (Babiuch et al. 2010; Pathanapitoon et al. 2013; Schneider et al. 2013; Tyagi et al. 2015). Secondly, viral retinitis may represent an underreported and/or unrecognised risk of Ozurdex administration. To our knowledge, there are only four reports, including our own, of viral retinitis following Ozurdex treatment (Ozturk et al. 2014; Kucukevcilioglu et al. 2015; Vannozzi et al. 2016). Conversely, intravitreal triamcinolone has been associated with a 0.41% incidence of viral retinitis in large systematic case series (Shah et al. 2010). Thirdly, the protracted course of CMV retinitis in the context of local corticosteroid treatment may cause more widespread vascular damage and increase the risk of ischaemia-induced ocular neovascularisation, as was seen in both our case and that reported by Vanozzi et al. (2016) These patients might therefore benefit from early photocoagulation if widefield angle angiography reveals large ischaemic areas.