PURPOSE. A growing body of evidence points to complement dysregulation in diabetes. Early studies have indicated the presence of complement components inside the eye in patients with diabetic retinopathy, but these data have been confounded by leakage of proteins from the systemic circulation into the vitreous cavity. METHODS. We took samples of plasma and vitreous from patients with and without proliferative diabetic retinopathy (PDR) and measured levels of 16 complement components as well as albumin. We employed a normalized ratio using local and systemic complement and albumin levels to control for vascular leakage into the vitreous cavity. RESULTS. Before normalizing, we found significantly higher levels of 16 complement components we measured in PDR eyes compared to controls. After normalizing, levels of C4, factor B, and C5 were decreased compared to controls, while C3a and Ba levels were elevated compared to controls. We also found higher ratios of C3a/C3, C5a/C5, and Ba/factor B in PDR eyes compared to controls. CONCLUSIONS. We found evidence of local, intraocular activation of C3, C5, and factor B. The normalized data suggest involvement of the alternative complement pathway. By showing activation of specific complement components in PDR, this study identifies targets for diagnostic and therapeutic potential.

Purpose A growing body of evidence suggests complement dysregulation is present in the vitreous of patients with diabetic eye disease. Further translational study could be simplified if aqueous—as opposed to vitreous—were used to sample the intraocular complement environment. Here, we analyze aqueous samples and assess whether a correlation exists between aqueous and vitreous complement levels. Methods We collected aqueous, vitreous, and plasma samples from patients with and without proliferative diabetic retinopathy (PDR) undergoing vitrectomy. We assessed correlation between complement levels in aqueous and vitreous samples after using a normalizing ratio to correct for vascular leakage. Spearman correlation coefficients were used to assess the correlation between complement levels in the aqueous and vitreous. Results Aqueous samples were obtained from 17 cases with PDR and 28 controls. In all patients, aqueous Ba, C3a, and albumin levels were strongly correlated with vitreous levels (Spearman correlation coefficient of 0.8 for Ba and C3a and 0.7 for albumin; all P values < 0.0001). In PDR eyes only, aqueous and vitreous C3a levels were significantly correlated (Spearman correlation coefficient 0.7; P = 0.002), whereas in control eyes, both Ba and C3a (Spearman correlation coefficients of 0.7; P < 0.0001) were significantly correlated. Conclusions A strong correlation exists between aqueous and vitreous complement levels in diabetic eye disease. Translational Relevance The results establish that accurate sampling of the intraocular complement can be done by analyzing aqueous specimens, allowing for the rapid and safe measurement of experimental complement targets and treatment response.

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Purpose. To assess the risk for capsular rupture during routine phacoemulsification in patients with a history of anti-VEGF injections and other possible risk modifiers such as treatment patterns, type of anti-VEGF agent, and experience of the surgeon, among others. Methods. This study reviewed the medical records of 11,129 patients from 7 different hospitals in 5 countries. The study included 939 patients that underwent routine phacoemulsification and had a history of anti-VEGF therapy. We excluded patients with known risk factors for capsular rupture, as well as patients with a history of other retinal procedures. The study extracted data regarding general demographics, the number of previous injections, type of anti-VEGF agent, details of cataract surgery, and anti-VEGF treatment patterns. Results. Overall prevalence of posterior capsular rupture: 7.45% (95% CI: 5.9–9.32%). The mean number of injections per patient was 3.37 ± 2.8. More than 50% of the patients received their last anti-VEGF injection within three months before cataract surgery. The complication rate during intravitreal injections was 1.07%. In the univariate analysis, the experience of the cataract surgeon (inexperience surgeons; OR: 2.93) and the history of prior anti-VEGF therapy (OR: 1.77) were significant risk indicators for PCR ( p < 0.05 ). However, after controlling for age in the multivariate analysis, the trend did not reach a statistical significance. Conclusion. The risk for capsular rupture is higher in patients with a history of intravitreal anti-VEGF injections.