Response: Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes.

In Reply: We thank Dr Kumari and Dr Dubey for their thoughtful review of our study, and for highlighting some important points that we will address. In assessing glaucomatous progression, the baseline visual field or optical coherence tomography test and next test closest to 12 months after starting anti-VEGF therapy were selected to calculate rate of change in functional and structural parameters. Although subjects underwent perimetry and optical coherence tomography examinations multiple times over the study period, the decision to use just 2 fields or examinations allowed for standardized rates of change that corresponded to the initiation of injections. However, given that patient performance on perimetry fluctuates, we acknowledge that this lowers the reliability and may be weakness of our analysis. Likewise, we recognize that retinal disease could contribute to retinal nerve fiber layer changes, such as with resolution of edema. Patients with a history of laser photocoagulation were not included in the study.1 With regards to the point on asymmetric progression of glaucoma, indeed this may affect comparisons between injected and fellow eyes, even though measurements of baseline characteristics were similar when averaged between groups. However, visual field progression correlates between eyes in patients with chronic open-angle glaucoma,2 and patient-specific factors such as systemic comorbidities and environment are also well controlled for when using the fellow eye to evaluate natural progression. In future studies, the inclusion criteria could be refined to ensure similar baseline severity of glaucoma in both eyes for each individual subject, excluding those with significant asymmetry. Finally, we agree that examining the correlation between number of injections and functional/structural change would be worthwhile and may strengthen the argument that progression was related to injections rather than to preexisting glaucoma. Longitudinal monitoring of disc changes and other clinical measures that are more specific to glaucomatous disease may also help to distinguish the effects of glaucoma from retinal disease and other confounding factors. We appreciate the helpful suggestions by Dr Kumari and Dr Dubey.


Response to: Effects of Intravitreal Anti-VEGF Therapy on Glaucoma-like Progression in Susceptible Eyes
In Reply: We are grateful to Gόmez-Mariscal and her colleagues for their insight and thoughtful comments on our study. We also thank them for bringing our attention to their paper, which appeared as an Epub (June 28, 2019) and was subsequently published (October, 2019) after submission of our manuscript. We note with interest that our 2 studies are consistent in finding retinal nerve fiber layer thinning despite lack of sustained intraocular pressure elevation in the treated and untreated groups.
Greater progression of visual field changes observed in injected eyes may be the result of glaucomatous progression or retinal disease, which is difficult to parse out. To this end, as stated in our paper, we performed post hoc analyses looking at a subpopulation of patients with exudative macular degeneration. Although not reaching statistical significance due to the subgroup's small sample size, there was a trend towards greater visual field progression in injected eyes compared to noninjected controls. 1 Panretinal photocoagulation (PRP) did not influence our findings as none of the patients included had a history of PRP. Structural changes observed in the nonretinal vein occlusion (RVO) subgroups were statistically significant, also parallel to those found in the overall study sample. Although resolution of optic disc swelling could be contributory in the RVO group, our subgroup findings provide evidence that retinal nerve fiber layer changes may occur in both RVO and non-RVO patients after intravitreal anti-vascular endothelial growth factor (VEGF) therapy.
Together, our studies emphasize the importance of monitoring for glaucoma-like progression in eyes receiving multiple anti-VEGF injections. Gόmez-Mariscal et al 2 observed structural changes in their patient sample with substantially fewer RVO cases, which confirms the trend observed in our subgroup analysis. Although structural and functional changes are one way to look at progression, equally relevant and clinically important are the findings in our study of significantly greater need for glaucoma laser and surgery in eyes receiving anti-VEGF injections (27% vs. 7%). The role of glaucoma specialists in comanaging patients with ocular hypertension or baseline glaucoma should be reinforced.
Further surveillance is required to evaluate the impact of repeated intravitreal anti-VEGF therapy in high risk eyes. We are appreciative for the helpful comments and contribution by Gόmez-Mariscal and colleagues.

Considerations and Innovations in the Perioperative Use of Mitomycin C for Glaucoma Filtration Surgery and Bleb Revisions
To the Editor: In response to the article titled "Historical Considerations and Innovations in the perioperative use of mitomycin C for Glaucoma filtration surgery and bleb revisions" published in your esteemed journal, which is a well thought off and written paper, I would like to raise a few points regarding this study. The article showed that the use of mitomycin C has greatly improved the success of filtering procedures. 1 The vascular endothelial growth (VEGF) factor may be present in the aqueous humor of glaucoma patients who have undergone glaucoma surgery. VEGF receptors are present in the fibroblasts of the Tenon capsule and act in the formation of collagen cross-linking and contraction, resulting in scar