Comment on: Efficacy and safety of posterior subtenon interferon alfa-2B injection in recurrent inflammatory macular edema

Dear Editor, We read with great attention the article by Kawali A et al.,[1] titled “Efficacy and safety of posterior subtenon interferon alfa-2B injection in recurrent inflammatory macular edema,” recently published in the Indian Journal of Ophthalmology. The authors should be commended for exploring an innovative, steroid-sparing therapeutic strategy for recurrent inflammatory macular edema (IME), a condition that continues to pose significant management challenges in routine clinical practice. Macular edema remains a major cause of visual morbidity in uveitis and postoperative inflammatory states. Although corticosteroids remain the mainstay of therapy, their long-term use is limited by ocular and systemic adverse effects, including secondary glaucoma, cataract progression, and infection reactivation.[2] Hence, there is a growing need for alternative anti-inflammatory agents with a favorable safety profile. In this context, interferon alfa-2B has emerged as a promising option due to its anti-inflammatory, immunomodulatory, and anti-angiogenic properties.[3] The authors demonstrate a statistically significant short-term reduction in central macular thickness (CMT) and improvement in best-corrected visual acuity (BCVA) following a single posterior subtenon interferon injection (PSII). The rapid anatomical response noted at 1 week highlights the potential of this route in achieving effective posterior segment drug delivery, overcoming the limitations of topical interferon therapy related to poor penetration and frequent dosing requirements.[4,5] The scleral permeability to large molecules, as highlighted in earlier pharmacokinetic studies, provides a strong rationale for the subtenon route in delivering biologic agents such as interferon.[6] However, Several Issues Merit Emphasis First, the effect of PSII appeared to be transient, with partial rebound of CMT at 1–2 months. This raises important questions regarding optimal dosing frequency and the need for repeat injections to maintain sustained therapeutic benefits. Future prospective studies with predefined reinjection protocols could help clarify this issue. Second, the heterogeneity of etiologies included in the study—ranging from pseudophakic IME to postinfectious and uveitic causes—although reflective of real-world practice, limits definitive conclusions regarding disease-specific efficacy. The occurrence of granulomatous anterior uveitis with vitritis in one patient following PSII is noteworthy. While interferon-associated retinopathy and inflammatory reactions are well documented in systemic therapy,[7] localized periocular administration is generally considered safer. Nonetheless, this adverse event underscores the importance of vigilant postinjection monitoring, particularly in eyes with a prior history of infection or complex inflammatory pathology. Another practical concern highlighted by the authors is the significant pain experienced by several patients during injection. This observation, though not widely reported in previous literature, is clinically relevant and may impact patient acceptance of the procedure. Standardization of analgesic protocols and injection techniques could improve patient comfort and compliance in future applications. Despite these limitations, the study adds valuable evidence supporting interferon alfa-2B as a viable steroid-sparing option in refractory IME. The findings align with earlier reports demonstrating the efficacy of topical and periocular interferon in pseudophakic and uveitic macular edema.[4,5,8] Larger, controlled, prospective trials with longer follow-up are now warranted to better define patient selection criteria, durability of response, safety profile, and cost-effectiveness of PSII. In conclusion, Kawali A et al.[1] have opened an important avenue in the management of recurrent IME. Posterior subtenon interferon alfa-2B injection appears to be a promising adjunct or alternative in selected cases, particularly where steroid-related complications are a concern. Larger, prospective, controlled studies with standardized protocols, stratified etiologies, and longer follow-up are needed before PSII can be widely adopted in routine uveitis and macular edema practice. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.