Hypertensive Uveitis After Intravitreal Faricimab Injections: A Response to Clinical and Methodological Considerations

We thank Dr. Qin for his commentary [1] on our case series describing hypertensive intraocular inflammation (IOI) that occurred following intravitreal faricimab injections [2]. We appreciate the opportunity to clarify several points that were raised. First, we agree that the reporting of adverse events warrants careful interpretation. The use of patient-based denominators for reporting IOI incidence is well established, and was adopted in the pivotal TENAYA and LUCERNE trials for faricimab [3], as well as in the meta-analysis by Stevanovic et al. [4], which Dr. Qin has also cited. Although a total of 6865 faricimab injections were administered in our centre during the study period, we have intentionally steered clear of reporting IOI incidence as an event rate per injection. This is because the risk of IOI with subsequent injections is likely cumulative and potentially non-linear, due to immune sensitisation with repeated drug exposure. The use of a denominator based on the total number of injections administered, as suggested by Dr. Qin, assumes that consecutive injections are independent risk events of equal statistical probability, and this may not accurately reflect the immunological pathogenesis of such IOI. Second, with respect to patient #5 in our original paper, we acknowledged the diagnostic dilemma of distinguishing infective endophthalmitis from non-infectious IOI. We are in agreement with Dr. Qin that it is pertinent to exclude infection. As previously mentioned, infectious endophthalmitis typically presents with acute visual loss, eye pain and redness, marked anterior chamber inflammation, often with a hypopyon and significant vitritis. In contrast, patient #5 reported no eye pain or redness; the inflammation was predominantly anterior and there was no deep vitritis. A vitreous tap was offered to exclude low-grade infection, but the patient declined, and a joint decision was made to start topical steroids judiciously. She was monitored the next day, and there was no worsening of inflammation. This case underscores the importance of individualised clinical management. Vitreous sampling is not without risk, and in cases where clinical presentation is not clearly consistent with exogenous endophthalmitis, the probability of infection must be weighed against procedural risks and potential delay in appropriate therapy. Such dilemmas should be actively discussed with patients to allow for a collaborative and informed decision. If steroids are initiated without ocular fluid sampling, we advocate close monitoring with early medical or surgical intervention should inflammation progress. As for the use of multimodal imaging, angiographic vascular leakage is not uncommon in an acutely inflamed eye, regardless of aetiology. Nevertheless, angiography is particularly useful when there are signs of occlusive disease, significant vascular exudation or disproportionate visual loss. Third, among the four patients with elevated intraocular pressure (IOP), two to four topical glaucoma medications were required for acute control. Only one patient (#3) received a short course of oral acetazolamide 250 mg once daily. IOP normalised within 1 week in all except patient #1, who required approximately 3 weeks. All topical agents were successfully tapered over the course of one to 7 months with no discernible glaucomatous sequelae, reflecting timely IOP management. Lastly, we concur that an algorithm for monitoring such cases would be valuable. However, given our small cohort of five patients, we are cautious to propose an overarching framework. Larger datasets are needed before establishing formal surveillance recommendations, as multiple factors can influence management, such as the probability and timing of IOI occurrence, extent of inflammation and IOP elevation, severity of the underlying retinal disease and status of the fellow eye. Theoretically, while more frequent monitoring for all patients receiving faricimab may be ideal, this needs to be balanced against real-world considerations, including clinic capacity, patient burden, and resource constraints. We are grateful to Dr. Qin for the constructive discussion and hope these clarifications address the concerns raised. Thank you. The authors have nothing to report. The authors have nothing to report. The original study has been evaluated by the Singhealth Centralised Institutional Review Board and deemed not to require ethics approval. All patients have previously given consent. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.