Analysis aqueous humor lipid profile of neovascular glaucoma secondary to diabetic retinopathy and lipidomic alteration response to anti-VEGF treatment.

The objective of this study was to examine the lipid spectrum of aqueous humor (AH) in patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy and to investigate the lipid alteration response to anti-vascular endothelial growth factor (anti-VEGF) treatment. Lipidomic analysis using ultra-high performance liquid chromatography-tandem mass spectrometry was conducted to compare the lipid profiles of the AH in NVG patients with those of a control group. Lipid changes in the AH of NVG patients before and after intravitreal conbercept injections were also evaluated. The identification of lipids showing differential expression was accomplished through both multivariate and univariate analyses. This study included 13 NVG patients and 20 control subjects. Based on LipidSearch software, 639 lipid species across 33 lipid classes were detected in the participants' AH. The combination of univariate and multivariate statistical analyses yielded 53 differentially expressed lipids (VIP >1 and P < 0.05). In addition, 9 lipids were found to be differentially expressed before and after the intravitreal conbercept injections in the NVG patients. Significant alterations in the metabolic pathways of glycerophospholipid and glycerolipid exhibited notable changes. Our results highlighted the lipid changes in patients' AH in relation to the progression of NVG, and indicated that the modified lipids could potentially be utilized as therapeutic targets for NVG.

Comparative efficacy and safety of different anti-VEGF agents combined with different delivery methods for neovascular glaucoma: a systematic review and Bayesian network meta-analysis.

OBJECTIVE: To compare the efficacy and safety of different anti-vascular endothelial growth factor (VEGF) agents combined with different delivery methods for neovascular glaucoma (NVG). DESIGN: Systematic review and Bayesian network meta-analysis (NMA). DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, ISRCTN and Chinese databases including the China National Knowledge Infrastructure, China Science Periodical Database (Wanfang Database), VIP Journal Integration Platform and China Biology Medicine Database were searched from inception to 5 September 2022. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that investigated the treatment of NVG using different anti-VEGF agents combined with various methods of drug administration, without any language limitations. All patients included underwent panretinal laser photocoagulation and there were no restrictions on prior glaucoma surgery. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed the risk of bias. Random-effect Bayesian NMA was conducted to compare the efficacy and safety and rank priority of anti-VEGF regimens. The source of heterogeneity and the related factors affecting the stability of the results were also explored. CINeMA (Confidence in Network Meta-Analysis) was used to assess the certainty of evidence. RESULTS: Our analysis included 17 RCTs involving a total of 1311 eyes from 1228 patients. We examined five different treatment regimens, which used three different anti-VEGF drugs. The following treatments showed a significant decrease in intraocular pressure (IOP) compared with the control group at 1 month after glaucoma surgery: simultaneous intravitreal and intracameral injection of conbercept (ICCIVC) (mean difference (MD)=-11.56, 95% credible interval (CrI) -20.8 to -2.24), intravitreal injection of conbercept (MD=-8.88, 95% CrI -13.93 to -3.78), intravitreal injection of ranibizumab (MD=-7.62, 95% CrI -10.91 to -4.33) and intravitreal injection of bevacizumab IVB) (MD=-5.51, 95% CrI -10.79 to -0.35). The surface under the cumulative ranking curve (SUCRA) analysis indicated that ICCIVC (82.0%) may be the most effective regimen in reducing IOP. In terms of safety, there were no statistically significant differences among the interventions. According to the SUCRA analysis, ICCIVC (68.0%) was considered the safest choice with the fewest complications. Subgroup and meta-regression analyses showed that mean age was the main source of heterogeneity. Sensitivity analysis demonstrated the robustness of the study results. CONCLUSION: ICCIVC was more effective and safer than other anti-VEGF regimens for NVG. Simultaneous intravitreal and intracameral injection was found to be the best route of administration, and conbercept was found to be the superior drug selection when compared with ranibizumab and bevacizumab. PROSPERO REGISTRATION NUMBER: CRD42022309676.

Retrospective Analysis of Radiation-Induced Complications of Uveal Melanoma Patients Treated With Brachytherapy in the Era of Anti-VEGF.

PURPOSE: To associate clinical factors and radiation doses delivered by iodine-125 plaque brachytherapy to visual outcomes and development of radiation-induced ocular complications in patients with uveal melanoma in the era of anti-vascular endothelial growth factor (anti-VEGF) injections. DESIGN: Retrospective cohort study. METHODS: A retrospective chart review was performed for 225 patients treated with iodine-125 brachytherapy for uveal melanoma. The effects of radiation doses (focal doses, average dose to the entire eye, and integral dose) on visual outcomes and development of radiation complications (radiation retinopathy, radiation optic neuropathy, vitreous hemorrhage, and neovascular glaucoma) were analyzed using multivariate Cox regression snalysis. RESULTS: Median follow-up was 33.6 months (range, 12-105.6 months). Radiation retinopathy was associated with younger age, tumor distance to optic nerve <6 mm, and maximum radiation dose to fovea. Radiation optic neuropathy was associated with White race, tumor distance to optic nerve <6 mm, and integral radiation dose. Vitreous hemorrhage was associated with White race and integral radiation dose. Incidence of neovascular glaucoma was low in our study, with 2 patients (0.9%) developing the complication. Of the 123 patients who developed radiation retinopathy, 82 patients (66.7% of radiation retinopathy patients, 37.3% of total patients) received anti-VEGF injections. CONCLUSIONS: Our study found multiple associations between radiation doses and complications as well as visual outcomes on multivariate analysis. Given that the majority of our patients who developed radiation retinopathy received anti-VEGF injections, our study helps to illustrate the course and progression of radiation-induced complications in the new era of anti-VEGF.

Trabeculectomy with concurrent intravitreal bevacizumab in neovascular glaucoma.

PURPOSE: To evaluate the clinical efficacy of concurrent intravitreal bevacizumab (IVB) injection with trabeculectomy with mitomycin-C (MMC) in neovascular glaucoma (NVG). METHODS: Patients with NVG who underwent trabeculectomy with concurrent IVB (group 1) and those who underwent IVB sequentially, followed by trabeculectomy with MMC (group 2) in 1-2 weeks between January 2021 and August 2022, were included in this retrospective hospital-based study. The need for medications for intraocular pressure (IOP) control at 6 months in the two groups was the primary outcome measured and compared between the groups. The association of the need for medications postoperatively with clinical variables was assessed using stepwise multivariate regression statistics. RESULTS: We finally included 40 patients ( n = 12 in group 1, n = 28 in group 2) with no significant differences in presenting age between groups. The IOP at 1 day and 1 week were not significantly different between groups though the IOP at 1, 3, and 6 months. IOP was lower in group 1 eyes with the 6-month IOP, being significantly lower in group 1, P = 0.05. Three eyes in group 1 and 11 eyes in group 2 required anti-glaucoma medications in the postoperative period. Multivariate regression identified preoperative IVB >3 (ß =0.7, P < 0.001) and recurrent vitreous hemorrhage (ß = 0.7, P = 0.004) as prognostic factors ( R2 = 40.6%) determining the need for anti-glaucoma medication (AGM) postoperatively in both groups. CONCLUSION: Concurrent IVB with trabeculectomy with mitomycin-C is a feasible alternative in patients with NVG with refractory high-presenting IOP. This may serve to address raised IOP as well as retinal ischemia, thereby improving surgical success rates in the most challenging NVG cases.

Short-Term Outcomes of Trabeculectomy With or Without Anti-VEGF in Patients With Neovascular Glaucoma: A Systematic Review and Meta-Analysis.

Objectives: The aim of this study was to compare the safety and efficacy of trabeculectomy alone or combined with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular glaucoma. Methods: We conducted a systematic review and meta-analysis to compare the effects of trabeculectomy alone or combined with intravitreal injections of anti-VEGF agents for the treatment of neovascular glaucoma. We searched four databases (PubMed, Cochrane Library, Embase, and Web of Science) up to January 2023 and extracted data on three surgical outcomes: postoperative intraocular pressure, success rate and complications. We used a random-effects model to calculate pooled relative risk (RR) or standardized mean difference (SMD) estimates and 95% confidence intervals (CIs). We assessed publication bias using Begg and Egger tests. Results: We included seven studies with 353 eyes. Compared to trabeculectomy alone, trabeculectomy with anti-VEGF had a lower risk of postoperative complications (RR, 0.60; 95% CI, 0.41-0.89) and higher success rate (RR, 1.19; 95% CI, 1.02-1.40). The intraocular pressure reduction was significantly greater in the trabeculectomy with anti-VEGF augmentation group than the trabeculectomy group from 1 week (SMD, -1.36; 95% CI, -2.76 to 0.04) to 6 months (SMD, -0.79; 95% CI, -1.50 to -0.07) after surgery. Conclusions: According to current evidence, adding intravitreal injection of anti-VEGF agents to trabeculectomy may improve the short time outcomes of patients with neovascular glaucoma.

Anti-vascular endothelial growth factor for neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. OBJECTIVES: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more types of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 19 October 2021; metaRegister of Controlled Trials to 19 October 2021; and two additional trial registers to 19 October 2021. We did not use any date or language restrictions in the electronic search for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. MAIN RESULTS: We included five RCTs (356 eyes of 353 participants). Each trial was conducted in a different country: two in China, and one each in Brazil, Egypt, and Japan. All five RCTs included both men and women; the mean age of participants was 55 years or older. Two RCTs compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP alone. One RCT randomized participants to receive an injection of either intravitreal aflibercept or placebo at the first visit, followed by non-randomized treatment according to clinical findings after one week. The remaining two RCTs randomized participants to PRP with and without ranibizumab, one of which had insufficient details for further analysis. We assessed the RCTs to have an unclear risk of bias for most domains due to insufficient information to permit judgment.   Four RCTs examined achieving control of IOP, three of which reported our time points of interest. Only one RCT reported our critical time point at one month; it found that the anti-VEGF group had a 1.3-fold higher chance of achieving control of IOP at one month (RR 1.32, 95% 1.10 to 1.59; 93 participants) than the non-anti-VEGF group (low certainty of evidence). For other time points, one RCT found a three-fold greater achievement in control of IOP in the anti-VEGF group when compared with the non-anti-VEGF group at one year (RR 3.00; 95% CI:1.35 to 6.68; 40 participants). However, another RCT found an inconclusive result at the time period ranging from 1.5 years to three years (RR 1.08; 95% CI: 0.67 to 1.75; 40 participants).  All five RCTs examined mean IOP, but at different time points. Very-low-certainty evidence showed that anti-VEGFs were effective in reducing mean IOP by 6.37 mmHg (95% CI: -10.09 to -2.65; 3 RCTs; 173 participants) at four to six weeks when compared with no anti-VEGFs.  Anti-VEGFs may reduce mean IOP at three months (MD -4.25; 95% CI -12.05 to 3.54; 2 studies; 75 participants), six months (MD -5.93; 95% CI -18.13 to 6.26; 2 studies; 75 participants), one year (MD -5.36; 95% CI -18.50 to 7.77; 2 studies; 75 participants), and more than one year (MD -7.05; 95% CI -16.61 to 2.51; 2 studies; 75 participants) when compared with no anti-VEGFs, but such effects remain uncertain. Two RCTs reported the proportion of participants who achieved an improvement in visual acuity with specified time points. Participants receiving anti-VEGFs had a 2.6 times (95% CI 1.60 to 4.08; 1 study; 93 participants) higher chance of improving visual acuity when compared with those not receiving anti-VEGFs at one month (very low certainty of evidence). Likewise, another RCT found a similar result at 18 months (RR 4.00, 95% CI 1.33 to 12.05; 1 study; 40 participants).  Two RCTs reported the outcome, complete regression of new iris vessels, at our time points of interest. Low-certainty evidence showed that anti-VEGFs had a nearly three times higher chance of complete regression of new iris vessels when compared with no anti-VEGFs (RR 2.63, 95% CI 1.65 to 4.18; 1 study; 93 participants). A similar finding was observed at more than one year in another RCT (RR 3.20, 95% CI 1.45 to 7.05; 1 study; 40 participants).  Regarding adverse events, there was no evidence that the risks of hypotony and tractional retinal detachment were different between the two groups (RR 0.67; 95% CI: 0.12 to 3.57 and RR 0.33; 95% CI: 0.01 to 7.72, respectively; 1 study; 40 participants). No RCTs reported incidents of endophthalmitis, vitreous hemorrhage, no light perception, and serious adverse events. Evidence for the adverse events of anti-VEGFs was low due to limitations in the study design due to insufficient information to permit judgments and imprecision of results due to the small sample size. No trial reported the proportion of participants with relief of pain and resolution of redness at any time point. AUTHORS' CONCLUSIONS: Anti-VEGFs as an adjunct to conventional treatment could help reduce IOP in NVG in the short term (four to six weeks), but there is no evidence that this is likely in the longer term. Currently available evidence regarding the short- and long-term effectiveness and safety of anti-VEGFs in achieving control of IOP, visual acuity, and complete regression of new iris vessels in NVG is insufficient. More research is needed to investigate the effect of these medications compared with, or in addition to, conventional surgical or medical treatment in achieving these outcomes in NVG.

RISK FACTORS FOR SURGERY OR BLINDNESS IN NEOVASCULAR GLAUCOMA EYES TREATED WITH ANTI-VEGF INJECTIONS BY A RETINA SPECIALIST.

PURPOSE: To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy. METHODS: This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice. RESULTS: Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg ( P < 0.001), two or more topical glaucoma medications ( P = 0.003), worse than 20/100 vision ( P = 0.024), proliferative diabetic retinopathy ( P = 0.001), eye pain or discomfort ( P = 0.010), and new patient status ( P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity ( P = 0.199). CONCLUSION: Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.

A systematic review and meta-analysis of randomised controlled trials in the management of neovascular glaucoma: absence of consensus and variability in practice.

PURPOSE: Neovascular glaucoma (NVG) is characterised by neovascularisation of the angle and therefore elevated intraocular pressure (IOP). This results in progressive optic neuropathy and loss of visual acuity. Treatment aims to reduce IOP in order to prevent optic nerve damage. A systematic review was completed synthesising results from randomised control trials (RCTs) comparing interventions for the management of NVG and their efficacy and safety. METHODS: Data was sourced from Web of Science, Embase and Medline after 1st January 2000. The primary outcome measures were mean IOP at follow-up and success rate. The secondary outcomes included mean IOP lowering medications and total complications. A meta-analysis was completed on comparative studies using Revman (version 5.4). RESULTS: For the two studies comparing Ahmed glaucoma valve (AGV) + pan-retinal photocoagulation (PRP) vs AGV + PRP + intra-vitreal bevacizumab (IVB), there was no difference in mean IOP or odds of success from the meta-analysis. From the 4 studies examining the utilisation of anti-vascular endothelial growth factor (anti-VEGF), one study showed lower mean IOP at 1 (p = 0.002) and 3 months (p = 0.033) for IVB vs sham injection. In the 2 studies studying transcleral diode laser (TDL), there were no significant findings. From the 4 studies looking at trabeculectomy (trab), lower mean IOP at 6 (p = 0.001), 9 (p = 0.01), 12 (p = 0.02) and 18 months (p = 0.004) was shown for intra-vitreal ranibizumab (IVR) + PRP + visco-trabeculectomy vs IVR + PRP + trab, and a significantly lower mean IOP was present in the Baerveldt group vs trab at 6 months (p = 0.03). In the 2 studies investigating the AGV, there was a lower mean IOP at 1 month (p = 0.01) in the AGV + triamcinolone (TCA) group. The risk of bias was low for 4 studies, high for 4 studies and 6 studies had some concerns. CONCLUSION: This is the first meta-analysis of RCTs in the management of neovascular glaucoma. The lack of high-quality evidence contributes to the lack of consensus in managing NVG. Our results highlight modern treatment strategies and the need for better powered RCTs with long-term follow-up in order to establish optimal treatment modalities and true patient outcomes.

Intermediate-term outcomes of the Aurolab aqueous drainage implant in neovascular glaucoma.

PURPOSE: To assess the outcomes of the non-valved Aurolab aqueous drainage implant (AADI) in neovascular glaucoma (NVG). METHODS: Data of consecutive patients with NVG who underwent AADI and had a minimum follow-up of 2 years were included. The primary outcome measure was the cumulative rate of surgical failure defined as intraocular pressure (IOP) >21 mm Hg or reduced <20% below baseline, IOP ≤5 mm Hg, reoperation for glaucoma or a complication, or loss of light perception vision. RESULTS: We included 85 eyes of 85 patients with NVG, with a mean age of 61.2±9.3 years. The most common aetiologies were proliferative diabetic retinopathy (n=43) and central retinal vein occlusion (n=24). The mean IOP decreased from 36.8±12.5 mm Hg at baseline to 15.8±7.5 mm Hg at 2-year follow-up (p<0.001) and the number of IOP-lowering medications reduced from 3.4±0.8 to 1.5±1.1 (p<0.001). The cumulative rate of failure increased from 3.1% (95% CI 1.1% to 11.8%) at 1 year to 33.8% (95% CI 20.4% to 52.5%) at 2 years. Multivariable analysis showed that eyes with open angles had a lower risk of failure (HR 0.17, 95% CI 0.10 to 1.03, p=0.09). The logarithm of minimum angle of resolution visual acuity declined from 0.98±0.7 to 1.8±1.0 at 2 years (p<0.001). CONCLUSION: Approximately one-third of NVG eyes that received the AADI failed after 2 years of follow-up similar to other series. Early AADI implantation at the open angle stage of NVG may yield better results.

The role of Anti-VEGF agents in treatment of neovascular glaucoma.

Aim: The aim of this study was to show the efficacy of intravitreal treatment with Bevacizumab (Avastin) in patients with secondary neovascular glaucoma, in different stages of the disease. Method: A retrospective study was performed on 67 patients with neovascular glaucoma. The main parameters evaluated were the patients' history, slit lamp examination, visual acuity, ocular tonometry, fundus examination, gonioscopy, and visual field. Results: It was observed that the pathology had a preponderance in males of the 6th decade, with frequently unilateral damage. Patients were referred to an ophthalmologist when the diseases reached an advanced stage, usually when the visual acuity had no light perception and the intraocular pressure was over 45 mmHg. However, the treatment with Avastin intravitreal showed a good evolution, with regression of neovessels in the first 4-7 days and maintenance of intraocular pressure within normal limits in about 60% of cases, 3 months after injection. Conclusion: The most effective treatment in secondary neovascular glaucoma is the correct therapy of the main disease. The association of Avastin and laser photocoagulation leads to regression in iris and retinal neovessels. Abbreviations: anti-VEGF = anti-Vascular Endothelial Growth Factor, PDGF = Platelet Derived Growth Factor, bFGF = basic Fibroblast Growth Factor.

[Changes of cytokines in the aqueous humor of neovascular glaucoma at the angle-closure stage].

Objective: To evaluate the concentration of cytokines in the aqueous humor of neovascular glaucoma (NVG) patients at the angle-closure stage in different treatment periods and its relationship with recurrence. Methods: A prospective case-control study. Angle-closure stage NVG patients who came to Peking University Third Hospital from September 2018 to September 2019 were enrolled and followed-up for at least 12 months. Patients received triple sequential therapy, including anti-vascular endothelium growth factor (VEGF) injection, trabeculectomy, and panretinal photocoagulation. The aqueous humor before anti-VEGF treatment, before trabeculectomy, and during recurrence was collected. Multiplex bead immunoassay was applied to measure the concentration of 45 cytokines including VEGF, interleukin (IL), and chemokine. The relevant data were compared with the values of 25 proliferative diabetic retinopathy (PDR) patients and 24 age-related cataract patients undergoing phacoemulsification as controls. The concentration of cytokines was presented as M (Q1, Q3). The nonparametric Kruskal-Wallis H test was applied to compare the cytokine concentration between the NVG group and controls. The difference between the recurrence and non-recurrence groups was compared with the Mann-Whitney U test. Results: The average age of NVG patients was (60±11) years, and there were 22 males and 10 females. No significant differences were found in age and gender between the NVG group and the two control groups (both P>0.05). The median concentrations of VEGF in the NVG group before anti-VEGF treatment, before trabeculectomy, and after recurrence were 2 151.3 (1 433.1, 4 280.0) ng/L, 655.4 (287.3, 836.3) ng/L and 2 003.4 (1 603.1, 2 468.9) ng/L respectively. The concentrations of VEGF before anti-VEGF treatment and after recurrence in the NVG group were significantly higher than the PDR group [453.8 (189.9, 595.8) ng/L] and the cataract group [143.5 (112.7, 269.8) ng/L] (all P<0.05). The median concentration of programmed cell death protein ligand 1 (PD-L1) was 38.9 (22.4, 50.6) ng/L before anti-VEGF treatment, higher than that in the PDR group [12.0 (6.3, 20.1) ng/L] and the cataract group [14.6 (11.4, 19.3) ng/L]. The median concentration of fractalkine was 242.7 (189.0, 306.7) ng/L, higher than that in the PDR group [131.1 (119.1, 157.6) ng/L] and the cataract group [116.7 (10.2, 135.9) ng/L]. The median concentration of IL-7 was 18.0 (12.0, 32.7) ng/L, higher than that in the PDR group [7.7 (2.0, 10.8) ng/L] and the cataract group [3.3 (1.9, 6.8) ng/L]. The median concentration of eotaxin was 84.0 (52.4, 122.7) ng/L, higher than that in the PDR group [26.6 (17.1, 72.3) ng/L] and the cataract group [7.1 (5.6, 14.8) ng/L]. The median concentration of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was 3.6 (2.8, 6.4) ng/L, higher than that in the cataract group [1.1 (0.3, 2.3) ng/L]. All the differences were statistically significant (all P<0.05). There were no significant differences between the NVG and control groups in other cytokines or other treatment periods (all P>0.05). Six NVG patients suffered recurrence during the follow-up. The baseline concentration of IL-7 of these patients [10.5 (8.4, 16.0) ng/L] was significantly lower than that in patients who did not have recurred disease [22.7 (15.7, 34.1) ng/L] (Z=-2.74, P<0.01). Conclusions: In the angle-closure stage of NVG patients, the concentrations of VEGF, PD-L1, fractalkine, IL-7, eotaxin, and TRAIL in the aqueous humor significantly increase during the onset of disease. Lower IL-7 may indicate a recurring tendency.

Effect of anti-vascular endothelial growth factor on the surgical outcome of neovascular glaucoma: An overview and meta-analysis.

BACKGROUND: Bevacizumab is known to be very effective in inhibiting ocular neovascularization in neovascular glaucoma (NVG). The purpose of this study is to evaluate the effect of anti-vascular endothelial growth factor on the surgical outcome of Ahmed glaucoma valve implantation (AGVI) in NVG. METHODS: An extensive search of PubMed, EMBASE, and the Cochrane Library was carried out in January 2021 to select relevant studies. The weighted mean difference of the intraocular pressure reduction percentage from baseline to endpoint was used for the primary efficacy estimate. Mantel-Haenszel odds ratios and 95% confidence intervals (CIs) for success rate were employed as secondary efficacy estimates. The number of postoperative interventions and the tolerability estimate for adverse events were also measured using odds ratios. We conducted meta-analyses of fixed effects models using comprehensive meta-analysis software to pool the results of the included studies. Heterogeneity was assessed using Q-value and I2 measures. RESULTS: Nine studies were included in the analysis, encompassing a total of 410 eyes. There was no significant difference in intraocular pressure reduction percentage between the AGVI-only group and the AGVI with adjuvant bevacizumab group (estimate 0.324; 95% CI, -0.278-0.926; P = .244). However, the success rate favored the AGVI with adjuvant bevacizumab group (estimate 0.561; 95% CI, 0.097-1.025, P = .018). CONCLUSIONS: AGVI with adjuvant bevacizumab had no significant effect on lowering IOP in patients with neovascular glaucoma compared with AGVI alone. However, the final success rate was higher for AGVI with adjuvant bevacizumab treatment than with AGVI alone.

Clinical profile and outcomes of neovascular glaucoma in the era of anti-vascular endothelial growth factor.

PURPOSE: To report the clinical profile and visual impairment in various stages of neovascular glaucoma (NVG) at a tertiary eye center in East India. METHODS: The electronic medical records of the hospital database of patients with neovascular glaucoma seen between 2013 and 2020 were reviewed. Gonioscopic details were used to stratify patients into nonspecified NVG (Group 1), open-angle NVG (Group 2), and closed-angle NVG (Group 3). The clinical profile, angle features, cause of NVG, systemic associations, visual impairment, and blindness (defined as logarithm of the minimum angle of resolution, LogMar >1.3 at baseline and at final follow-up), and outcomes of medical/surgical interventions were compared between the three groups. RESULTS: Of 846 eyes of 810 patients with NVG (Group 1, n = 564 eyes, Group 2, n = 61 eyes, and Group 3, n = 220 eyes), at baseline, the blindness rates in Groups 3 and 2 were 90 and 75%, respectively. The time from a previous intervention to the onset of NVG ranged from 3 to 5 months, while the median duration of NVG was about 4-4.5 months (0.03-120 months). Multivariate regression identified a longer duration of NVG as the only variable associated with poor final visual acuity. CONCLUSION: Visual morbidity by NVG remains as high as 75-90% in developing countries, even with the availability of anti-VEGFs and after improved management/investigative at all stages.

Comparison of conbercept and ranibizumab combined mitomycin C-augmented trabeculectomy for neovascular glaucoma.

PURPOSE: To compare the efficacy and security of conbercept and ranibizumab combined with trabeculectomy and panretinal photocoagulation for neovascular glaucoma (NVG). METHODS: One hundred and sixty patients with NVG were randomly divided into a conbercept group comprised of 80 patients and a ranibizumab group comprised of 80 patients. The postoperative and preoperative visual acuities, intraocular pressures frequency of anti-glaucoma medications, and surgical complications were recorded. The expressions of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (FLT-1), and placenta-like growth factor (PLGF) in the aqueous humor were determined using an enzyme-linked immunosorbent assay. Examining the fundus and obtaining photographs used indirect ophthalmoscopy. Kaplan-Meier and log-rank analyses estimated the success rates. RESULTS: All patient follow-up periods were at 1 year. The differences observed in IOP and the frequencies of anti-glaucoma medications at various follow-up time points were not statistically significant (all P > 0.05). The differences observed in both the group visual acuities at various follow-up time points were not statistically significant (P > 0.05). Rates of surgery complications were 18.75% and 25.00% in the conbercept group and ranibizumab group, respectively. The expressions of VEGF, FLT-1, and PLGF significantly decreased (all P < 0.05). The recurrence percentages were 30.00% and 36.25% after conbercept and ranibizumab treatment, respectively. CONCLUSION: The conbercept effects were similar with that of ranibizumab. Intravitreal injection of conbercept was effective for NVG treatment, which provides a new therapeutic drug for NVG treatment.

Rapid growth of primary uveal melanoma following intravitreal bevacizumab injection: a case report and review of the literature.

Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents.

Intravitreal Aflibercept in Japanese Patients with Neovascular Glaucoma: The VEGA Randomized Clinical Trial.

INTRODUCTION: Neovascular glaucoma is characterized by neovascularization of the iris and the anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may improve intraocular pressure (IOP) and neovascularization. METHODS: The VEGA trial assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma in a 13-week, randomized, double-masked, sham-controlled, phase 3 study performed at multiple sites in Japan that enrolled patients with anterior segment neovascularization and IOP > 25 mmHg. Patients received background therapy plus IVT-AFL (2 mg) or sham injection at baseline. Patients were re-treated if presenting with IOP > 21 mmHg and incomplete regression of iris neovascularization, receiving additional sham or IVT-AFL injections at week 1 and IVT-AFL injections at weeks 5 and/or 9. Double-masking was maintained throughout. The primary endpoint was change in IOP from baseline to week 1. RESULTS: Fifty-four patients were randomly assigned (full analysis set); the per-protocol set comprised 52 patients. At week 1, the least squares mean change in IOP was -9.9 mmHg for IVT-AFL versus -5.0 mmHg for sham [full analysis set: difference -4.9 mmHg (95% confidence interval -10.2 to 0.3; P = 0.06); per-protocol set: -5.5 mmHg (95% CI -10.8 to -0.2; P = 0.04)]. At week 1, a greater proportion of patients administered IVT-AFL versus sham achieved IOP ≤ 21 mmHg and had improved neovascularization grades. Patients in the sham group who met re-treatment criteria and received IVT-AFL at week 1 [n = 22 (81.5%)] had an additional mean IOP decrease of 9.2 mmHg by week 2, and the proportion with improvement in neovascularization grades increased from 11.5% to 69.2%. Increases in the proportion of patients with improved neovascularization grades and the proportion who achieved IOP control (≤ 21 mmHg) were also observed by week 2 in this group. Overall, 77.8% and 74.1% of patients treated with IVT-AFL and sham/IVT-AFL, respectively, received a single IVT-AFL injection. The most common ocular treatment-emergent adverse event was punctate keratitis (9.3%: 7.4% and 11.1% in the IVT-AFL and sham/IVT-AFL groups, respectively). CONCLUSIONS: IVT-AFL was associated with clinically meaningful improvements in IOP control, indicating that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT02396316.

Efficacy and Safety of Intravitreal Aflibercept Injection in Japanese Patients with Neovascular Glaucoma: Outcomes from the VENERA Study.

INTRODUCTION: Neovascular glaucoma is characterized by neovascularization of the iris and anterior angle chamber. Intravitreal anti-vascular endothelial growth factor agents may decrease intraocular pressure (IOP) and improve neovascularization. The VENERA study assessed the efficacy and safety of intravitreal aflibercept (IVT-AFL) in patients with neovascular glaucoma. METHODS: This was a 5-week, single-arm, nonrandomized, open-label, phase 3 study performed at 7 study sites in Japan that enrolled Japanese patients with anterior segment neovascularization and IOP > 25 mmHg who had not undergone (within 30 days prior), nor were imminently scheduled to undergo (within 8 days following) intraocular surgeries, including panretinal photocoagulation (PRP). Patients received background therapy plus 2 mg IVT-AFL at baseline. Background therapy with systemic IOP-lowering drugs was prohibited for 3 days before day 1 and until IOP evaluation at week 1. The primary endpoint was the change in IOP from baseline to week 1 and the secondary endpoint was the proportion of patients with an improvement of ≥ 1 grade of neovascularization of the angle (NVA) from baseline to week 1. RESULTS: Sixteen patients received treatment (full analysis set); the per-protocol set comprised 15 patients. The mean IOP decreased from 34.1 mmHg at baseline to 25.8 mmHg at week 1 (mean change, -8.3 mmHg [95% confidence interval; CI -12.2 to -4.4; P = 0.0004]). At week 1, 81.3% of patients had an improvement in the grade of neovascularization of the iris (NVI) and 50.0% of patients had an improvement in NVA grade. The proportion of patients with controlled IOP (≤ 21 mmHg) was 43.8% (95% CI 19.8-70.1) at week 1, and increased to 56.3% at week 2 and 86.7% at week 5. The most common ocular treatment-emergent adverse event was eye pain, which occurred in 4 patients (25.0%). CONCLUSIONS: IVT-AFL was associated with statistically significant and clinically meaningful IOP reductions, without concomitant use of systemic IOP-lowering drugs or PRP. The safety profile was consistent with the known safety profile of IVT-AFL. These findings supplement those from the previous VEGA study, and suggest that IVT-AFL may be a potential treatment option for patients with neovascular glaucoma. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03639675.

Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept.

Purpose: To provide a detailed review on the therapeutic efficacy of conbercept for the management of ocular vasculopathies. Methods: A comprehensive literature search of various electronic databases was performed. Results: Ocular vasculopathy is one of the major causes of visual impairment and blindness which includes a range of disorders. Vascular endothelial growth factor (VEGF) regulates angiogenesis, enhances vascular permeability, and drives the formation of neovascularization. Anti-VEGF therapy has been shown to prevent vision loss or potentially improve vision in patients with exudative or neovascular retinal disease. The most recent anti-VEGF drug in China is conbercept. In the USA and Europe, bevacizumab is the most recently approved anti-VEGF agent. Conclusions: Conbercept serves as another anti-VEGF option for patients with neovascular AMD and other retinal vascular disorders. There have not been many clinical trials that study conbercept as compared with other currently available anti-VEGF drugs. There is a need for large-scale, well-designed, randomized clinical trials to ensure its long-term safety and efficacy and to determine if it has any advantages over other anti-VEGF agents.

Anti-vascular endothelial growth factor for neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. OBJECTIVES: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. MAIN RESULTS: We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up. AUTHORS' CONCLUSIONS: Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.