Purpose To evaluate the efficacy and safety of intrastromal voriconazole (IS-VCZ) and intrastromal amphotericin B (IS-AMB) for fungal keratitis. Methods PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from inception for randomized trials, comparative observational studies, and case series evaluating IS-VCZ or IS-AMB. Random-effects meta-analyses were performed for comparative and single-arm outcomes. Results Thirty-six studies were included: 33 evaluated IS-VCZ (732 eyes) and 7 evaluated IS-AMB (171 eyes), with four contributing to both groups. In uncontrolled single-arm analyses, pooled healing proportions were 79.1% (95% CI, 70.5%–85.7%) for IS-VCZ and 86.4% (95% CI, 71.9%–94.1%) for IS-AMB; these estimates were descriptive and do not establish treatment efficacy. Pooled therapeutic keratoplasty rates were 12.3% (95% CI, 6.7%–21.4%) and 13.2% (95% CI, 4.4%–33.4%), respectively. Compared with non-intrastromal therapies, IS-VCZ demonstrated no significant difference in clinical healing (OR 1.20, 95% CI 0.40–3.56), therapeutic keratoplasty (OR 1.29, 95% CI 0.59–2.82), or final visual acuity (MD 0.22, 95% CI −0.51 to 0.94). Comparative evidence remained limited, with wide confidence intervals across several outcomes. Comparative evidence for IS-AMB was limited and similarly demonstrated no significant differences in healing (OR 2.62, 95% CI 0.68–10.03), therapeutic keratoplasty (OR 0.45, 95% CI 0.02–8.23), or healing time (MD −5.64 days, 95% CI −25.05 to 13.77). Substantial heterogeneity was observed across most pooled outcomes. Conclusions Current comparative evidence is insufficient to establish the efficacy of IS-VCZ or IS-AMB relative to existing antifungal therapies. Uncontrolled studies report favorable healing outcomes, but these findings cannot establish treatment efficacy. Intrastromal antifungal therapy may have a role as adjunctive or salvage treatment, but higher-quality comparative studies with standardized protocols are needed.
Purpose To characterize longitudinal ocular surface outcomes and survival in a contemporary cohort of patients with membranous conjunctivitis (MC) after allogeneic hematopoietic cell transplantation (HCT). Methods Retrospective review of serial ocular assessments performed on patients from baseline through 12-18 months post-HCT as part of the transplant clinical trials at the National Institutes of Health (NIH) Clinical Center. These exams included ocular symptoms, Schirmer's test (ST), conjunctival redness (CR), tear breakup time (TBUT), corneal staining (COS) and fibrosis assessment. Survival was analyzed from HCT and MC diagnosis. Results MC occurred in 32/369 patients (8.6%) and was associated with acute (28.1%) or chronic (65.6%) graft-versus-host disease (GVHD); two patients (6.3%) had isolated MC without systemic GVHD. MC preceded or coincided with systemic GVHD diagnosis in 46.9% of patients. Median time from HCT to MC was 116 days (range 31 to 1126). The most common presenting symptoms were noninfectious mucoid discharge (50%) and foreign body sensation (37.5%). Tear volume declined by 70.2% at MC diagnosis and remained persistently reduced throughout follow-up. CR and COS increased (both P < 0.001), whereas TBUT decreased (P = 0.005) and remained abnormal. Subtarsal fibrosis developed in 72.4% of surviving patients. Two-year survival was 50% from both HCT and MC diagnosis. Conclusion Membranous conjunctivitis is a severe inflammatory ocular GVHD phenotype that occurs in both acute and chronic GVHD and is associated with persistent tear dysfunction and conjunctival fibrosis, underscoring the importance of pre-HCT ophthalmic examination and post-HCT surveillance for early recognition and coordinated multidisciplinary management.
