Treatment with Subtenon and Intravitreal Triamcinolone Acetonide for Cystoid Macular Edema after Cytomegalovirus Retinitis: A Case Report

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Dear Editor,

Cytomegalovirus (CMV) retinitis is an opportunistic ocular infection in immunocompromised patients, and cystoid macular edema (CME) is one of the complications causing visual impairment [1]. The treatment option encompass intravitreal ganciclovir, intravitreal bevacizumab, topical steroid, or nonsteroidal anti-inflammatory drugs (NSAIDs) [2]. Due to concerns about viral replication, physicians have been reluctant to administer steroids locally in CME with CMV retinitis, and no reports exist on this matter.

Here we describe a case of CME with inactive CMV retinitis treated with repeated subtenon and intravitreal triamcinolone acetonide injections. The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (No. B-2401-878-701). Written informed consent for publication of the study details and clinical images was obtained from the patient.

A 63-year-old man presented with a superior visual field defect in his left eye, persisting for 5 days. His medical history includes liver transplantation for hepatocellular carcinoma 17 years ago, and kidney transplantation for end-stage renal disease 1 year ago. He was receiving immunosuppressants (prednisolone, tacrolimus, mycophenolate sodium) since 1 year ago. The visual acuity in his left eye was 20 / 30, and intraocular pressure was 32 mmHg. The anterior chamber and anterior vitreous showed 2+ cells. Fundus examination revealed multiple, whitish, well-demarcated retinal necrosis with retinal hemorrhages in the left eye mainly at peripheral retina (Fig. 1A, 1B). Anterior chamber polymerase chain reaction confirmed positive for CMV. Oral valganciclovir 450 mg was started twice daily for 10 days, then reduced to 450 mg every other day for 2 months due to kidney problem and discontinued afterwards. Alongside oral valganciclovir, weekly intravitreal ganciclovir (2 mg/0.04 mL) was administered five times. After treatment, CMV retinitis became inactive, and the macula remained flat (Fig. 1C, 1D). Four months later, CME was observed with decreased visual acuity to 20 / 50 without anterior segment inflammation, and the peripheral fundus remained stable (Fig. 1E, 1F). The patient had no retinal vein occlusion or diabetes history which could cause macular edema. Initial treatment involved topical NSAIDs and prednisolone, followed by three weekly ganciclovir injections. However, CME worsened (Fig. 1G, 1H). Suspecting uveitic CME, subtenon triamcinolone acetonide (8 mg/0.2 mL) was cautiously administered. Dexamethasone implant was avoided concerning the risk of retinitis recurrence from prolonged effect. As CME improved without viral reactivation during short-term follow-up, two more subtenon triamcinolone (16 mg/0.4 mL) injections were administered after 3 weeks and 2 months each, resulting in partial resolution of CME (Fig. 1I, 1J). However, 5 weeks after the last subtenon injection, CME worsened (Fig. 1K, 1L). Consequently, intravitreal triamcinolone (4 mg/0.1 mL) injection was delivered, resulting in complete resolution of CME after 5 weeks without recurrence of retinitis (Fig. 1M, 1N). Eleven weeks after the last injection, increased peripheral retinal infiltration appeared, without recurrence of CME (Fig. 1O, 1P). Three weekly intravitreal ganciclovir injections were administered, and the patient remained stable without further CME or retinitis recurrence for 4 months after the final antiviral injection (Fig. 1Q, 1R).

Fig. 1

Wide fundus photography and optical coherence tomography (OCT) of the patient. (A, B) At initial presentation, wide fundus photography shows multiple, whitish, well-demarcated areas of retinal necrosis with retinal hemorrhages at peripheral retina. (C, D) Cytomegalovirus retinitis becomes inactive after administration of oral valganciclovir and five times of weekly intravitreal ganciclovir injections. (E, F) Four months after intravitreal valganciclovir injection, OCT shows newly appeared cystoid macular edema (CME), but peripheral fundus shows no evidence of retinitis reactivation. (G, H) CME worsens despite application of topical nonsteroidal anti-inflammatory drugs and prednisolone acetate along with three times of weekly intravitreal ganciclovir injection. (I, J) After two injections of subtenon triamcinolone acetonide, OCT shows partial regression of CME. (K, L) CME worsened after the third subtenon triamcinolone. (M, N) OCT shows complete resolution of CME without reactivation of retinitis after one intravitreal triamcinolone injection. (O, P) Eleven weeks after the intravitreal triamcinolone injection, fundus shows increased infiltration in the peripheral retina, but OCT shows absence of CME. (Q, R) Four months after three additional intravitreal ganciclovir injections, OCT shows a stable retina without retinitis reactivation and no recurrence of CME.

CME was reported in 37% (25 of 67 eyes) of CMV retinitis cases [2]. Among them, 64.7% (11 of 17 eyes) with active retinitis achieved complete resolution of CME through intravitreal antivirals. However, in inactive retinitis, intravitreal ganciclovir, intravitreal bevacizumab, and topical steroids showed ineffective. The cause of CME in inactive CMV retinitis remains unclear, but previous studies suggested immune restoration or reactive inflammation from residual viral antigen may be the cause, and elevated CD4+ T cell may contribute to intraocular inflammation [2,3].

This hypothesis might suggest potential efficacy of local steroid injections for CME in inactive CMV retinitis. Sorland et al. [4] reported a case of CME in acute retinal necrosis successfully treated with repeated intravitreal dexamethasone implant without retinitis reactivation. In our case, subtenon and intravitreal triamcinolone injections proved to be effective treatment option for CME in inactive CMV retinitis. Our limitation is that recurrence risk might have been reduced with sufficient antiviral coverage during steroid injection. Steroids always require careful consideration of retinitis recurrence; in this case, additional antiviral injections were needed for the retinitis recurrence. Caution must be taken with steroid injections with thorough clinical evaluation, especially in immunocompromised patients. Nevertheless, the recurrence of retinitis does not negate the effectiveness of steroid injections in controlling CME. Further research should focus on identifying biomarkers for safe, effective steroid injection in CME in inactive CMV retinitis.

In conclusion, subtenon or intravitreal steroid injection can be considered for CME in inactive CMV retinitis, with close monitoring.

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