Clinical Outcomes After Same-Agent Double-Dose Anti-VEGF Escalation in Eyes with a Suboptimal Response to...

Background/Objectives: A substantial proportion of eyes with exudative macular diseases show a suboptimal response to standard-dose anti-vascular endothelial growth factor (anti-VEGF) therapy, and evidence regarding clinical outcomes after same-agent double-dose escalation remains limited. We evaluated the functional and anatomical outcomes of same-agent double-dose anti-VEGF therapy in such eyes. Methods: In this observational real-world cohort study, we retrospectively reviewed eyes with exudative macular diseases that were switched to same-agent double-dose anti-VEGF therapy because of a suboptimal response to prior standard-dose treatment. Eligibility required clinician-assessed persistent or recurrent exudative activity during the standard-dose treatment course despite at least three prior anti-VEGF injections, based on the longitudinal treatment and imaging history. Insufficient visual response and inadequate durability were considered additional, potentially overlapping features supporting dose escalation. Primary outcomes were functional and anatomical changes after switching. Secondary outcomes included injection interval, time-to-event outcomes, and associated baseline factors. Results: A total of 104 patients (111 eyes) were included. Mixed-effects modeling showed a small longitudinal improvement in BCVA of 0.007 logMAR per month (p = 0.028) and an estimated CST decrease of approximately 2.1% per month (p < 0.001). In visit-specific analyses, BCVA did not differ significantly from baseline at the first three post-switch visits and differed significantly only at the final follow-up (p = 0.004); however, the median BCVA was 0.70 logMAR at both baseline and final follow-up, and the median within-eye change was 0.00 logMAR (IQR, -0.25 to 0.10). CST was significantly lower than baseline at all post-switch visits (all p < 0.01). Among the 73 eyes with calculable paired interval data, injection intervals did not differ significantly between the standard-dose and double-dose phases (p = 0.289). Baseline pigment epithelial detachment was associated with a less favorable BCVA change (p = 0.002), and worse baseline visual acuity was associated with a higher risk of subretinal fibrosis (hazard ratio, 2.854; p = 0.002). Conclusions: In this uncontrolled pre-post cohort, anatomical changes after same-agent double-dose escalation were more consistent than functional changes. The BCVA change was statistically detectable but small in magnitude and of uncertain clinical relevance. No significant interval extension was observed among the 73 eyes with complete paired interval data during the relatively short follow-up.