Authors’ Response: Posterior subtenon interferon alfa-2B injection in inflammatory macular edema

To the Editor, We thank the authors for their thoughtful comments on our article, “Efficacy and safety of posterior subtenon interferon (IFN) alfa-2B injection in recurrent inflammatory macular edema.”[1] We acknowledge that the effect of a single posterior subtenon’s IFN (PSII) injection may not be sustained long-term, as observed during the follow-up in most of our cases. Our study was a real-world, retrospective case series primarily aimed at assessing early anatomical and functional response rather than defining an optimal reinjection protocol. Importantly, IFN does not act as a depot injection, unlike posterior subtenon’s triamcinolone injection; therefore, attenuation of effect after a single periocular dose is expected. The rapid reduction in central macular thickness observed at 1 week supports effective posterior segment delivery via the subtenon’s route, consistent with known scleral permeability to large biologic molecules.[2,3] Prospective studies with predefined reinjection criteria are required to clarify dosing intervals and durability of response. The heterogeneity of etiologies in our cohort reflects routine uveitis practice, where inflammatory macular edema (IME) often arises from diverse but overlapping inflammatory pathways. While this limits disease-specific conclusions, it supports IFN’s role as a broad-acting agent targeting shared inflammatory mechanisms. The patient (Case 4: post-endophthalmitis IME) in our series developed granulomatous anterior uveitis 40 days after PSII[1] but has since completed 10 months of follow-up without recurrence of uveitis. The delayed and isolated episode in an eye recovering from endophthalmitis suggests that the inflammatory event cannot be conclusively attributed to PSII. While interferon-associated inflammatory reactions are well documented with systemic therapy, localized periocular administration has generally demonstrated a favorable safety profile.[1] Nevertheless, vigilant postinjection monitoring remains essential. Pain during the injection was experienced by several patients in our series. Injection-related pain has been well documented with subcutaneous IFN therapy and has also been reported with periocular administration, including subconjunctival and intralesional use.[4,5] Pain during PSII is typically immediate and occurs during drug delivery, likely due to chemical irritation of the richly innervated Tenon’s capsule and acute tissue distension. Although usually transient and self-limiting, this adverse effect underscores the importance of patient counseling and appropriate peri-procedural analgesia. An additional practical observation from our series is that PSII demonstrated efficacy in several eyes with an inadequate or incomplete response to topical IFN therapy as many patients had received it before PSII. This suggests that the posterior subtenon route may overcome limitations related to drug penetration and adherence associated with topical therapy. In conclusion, PSII appears to be a useful steroid-sparing adjunct in IME, particularly in eyes at risk of steroid-related complications such as glaucoma, cataract progression, or infection reactivation, or in those with inadequate response to topical IFN therapy. We concur that larger, controlled, prospective studies with longer follow-up, etiologic stratification, and standardized reinjection protocols are necessary before broader clinical adoption. We thank the authors again for their insightful comments and for advancing the discussion on this emerging therapeutic approach. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.