Ultra-Early OCT Changes After Intravitreal Injection: Evidence Consistent with Transient Mechanical Compression

(1) Background: Ultra-early optical coherence tomography (OCT) changes following intravitreal injection may reflect transient mechanical compression rather than pharmacologic effects; however, this temporal profile has not been rigorously characterised with appropriate statistical methodology. (2) Methods: In this prospective observational study, 40 eyes of 40 consecutive patients (one per patient) with macular edema secondary to neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or chronic central serous retinopathy (CSR) underwent intravitreal bevacizumab (n = 35) or triamcinolone acetonide (n = 5). Goldmann applanation tonometry and spectral-domain OCT were performed at baseline, 2–5 min, 15 ± 5 min, 24 h, and 48 h post-injection. Repeated-measures ANOVA with Greenhouse–Geisser correction, linear regression, and Spearman rank correlation were applied. (3) Results: Central subfield thickness (CST) decreased markedly at 15 ± 5 min (mean −24.8 ± 11.5%; 95% CI: −28.5% to −21.1%; p < 0.001; partial η2 = 0.70), with near-complete rebound by 48 h (−1.0%; p = 0.400). Peak intraocular pressure (IOP) elevation correlated with CST reduction (Spearman rs = 0.61; 95% CI: 0.39–0.77; p < 0.001), and baseline CST predicted thinning magnitude (R2 = 0.52; p < 0.001). (4) Conclusions: Ultra-early OCT thinning after intravitreal injection is consistent with transient mechanical compression. Retinal thickness measurements within 48 h post-injection should be interpreted with caution when assessing treatment response, as early anatomic reduction may not reflect pharmacologic efficacy.