EFFECTS OF INTRAVITREAL BEVACIZUMAB THERAPY ON GLOMERULAR FILTRATION RATES IN PATIENTS TREATED FOR PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To assess whether the repeated use of intravitreal bevacizumab injections in treatment of proliferative diabetic retinopathy is associated with a long-term decline in the glomerular filtration rate (GFR). METHODS: Three hundred charts were retrospectively reviewed, of which 60 patients met the criteria for inclusion. The criteria were as follows: reception of at least one bevacizumab injection, baseline GFR before initial bevacizumab injection, and end GFR 6 to 24 months after baseline. Analysis controlled for time between baseline and end GFR measurements, blood pressure, hemoglobin A1C, race, sex, age, and use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Significance testing was performed with step-wise multiple linear regression. The significance threshold was 5%, and all tests were two-sided. RESULTS: Patients received a range of 1 to 17 injections (average 3.6). The average baseline GFR was 76 ± 38 mL/minute, and the end GFR was 63 ± 39 mL/min. The number of injections patients received was not associated with end GFR ( P = 0.72), GFR reduction ( P = 0.88), or percent GFR reduction ( P = 0.49). CONCLUSION: Increased number of intravitreal bevacizumab injections at therapeutic dosage was not associated with reduced GFR in patients with proliferative diabetic retinopathy. This study supports that intravitreal antivascular endothelial growth factor agents are renally safe.

Tie-2/Angiopoietin pathway modulation as a therapeutic strategy for retinal disease.

Introduction: The Tie-2/Angiopoietin pathway is a therapeutic target for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Activation of Tie-2 receptor via Ang-1 maintains vascular stability to limit exudation. Ang-2, a competitive antagonist to Ang-1, and VE-PTP, an endothelial-specific phosphatase, interfere with the Tie-2-Ang-1 axis, resulting in vascular leakage. Areas covered: Faricimab, a bispecific antibody that inhibits VEGF-A and Ang-2, is in phase 3 trials for nAMD and DME. Nesvacumab is an Ang-2 inhibitor; when coformulated with aflibercept, it failed to show benefit over aflibercept monotherapy in achieving visual gains in phase 2 studies of nAMD and DME. ARP-1536 is an intravitreally administered VE-PTP inhibitor undergoing preclinical studies. AKB-9778 is a subcutaneously administered VE-PTP inhibitor that, when combined with monthly ranibizumab, reduced DME more effectively than ranibizumab monotherapy in a phase 2 study. AKB-9778 monotherapy did not reduce diabetic retinopathy severity score compared to placebo. AXT107, currently in the preclinical phase, promotes conversion of Ang-2 into a Tie-2 agonist and blocks signaling through VEGFR2 and other receptor tyrosine-kinases. Expert opinion: Tie-2/Angiopoietin pathway modulators show promise to reduce treatment burden and improve visual outcomes in nAMD and DME, with potential to treat cases refractory to current treatment modalities.

Glaucoma Surgery Calculator: Limited Additive Effect of Phacoemulsification on Intraocular Pressure in Ab Interno Trabeculectomy.

PURPOSE: To compare intraocular pressure (IOP) reduction and to develop a predictive surgery calculator based on the results between trabectome-mediated ab interno trabeculectomy in pseudophakic patients versus phacoemulsification combined with trabectome-mediated ab interno trabeculectomy in phakic patients. METHODS: This observational surgical cohort study analyzed pseudophakic patients who received trabectome-mediated ab interno trabeculectomy (AIT) or phacoemulsification combined with AIT (phaco-AIT). Follow up for less than 12 months or neovascular glaucoma led to exclusion. Missing data was imputed by generating 5 similar but non-identical datasets. Groups were matched using Coarsened Exact Matching based on age, gender, type of glaucoma, race, preoperative number of glaucoma medications and baseline intraocular pressure (IOP). Linear regression was used to examine the outcome measures consisting of IOP and medications. RESULTS: Of 949 cases, 587 were included consisting of 235 AIT and 352 phaco-AIT. Baseline IOP between groups was statistically significant (p≤0.01) in linear regression models and was minimized after Coarsened Exact Matching. An increment of 1 mmHg in baseline IOP was associated with a 0.73±0.03 mmHg IOP reduction. Phaco-AIT had an IOP reduction that was only 0.73±0.32 mmHg greater than that of AIT. The resulting calculator to determine IOP reduction consisted of the formula -13.54+0.73 × (phacoemulsification yes:1, no:0) + 0.73 × (baseline IOP) + 0.59 × (secondary open angle glaucoma yes:1, no:0) + 0.03 × (age) + 0.09 × (medications). CONCLUSIONS: This predictive calculator for minimally invasive glaucoma surgery can assist clinical decision making. Only a small additional IOP reduction was observed when phacoemulsification was added to AIT. Patients with a higher baseline IOP had a greater IOP reduction.