Efficacy and Safety of Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion: A Meta-Analysis.

INTRODUCTION: Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has become the mainstay of treatment in many retinal diseases. The comparative efficacy and safety of newer bispecific anti-VEGF/angiopoietin 2 (Ang2) agents in the treatment paradigm versus widely used monospecific anti-VEGF agents remains unclear. METHODS: A systematic literature search of MEDLINE, Embase, and Cochrane Library was conducted to identify comparative observational studies and randomized controlled trials published from 2015 to Jul 2024. With assessment by three independent reviewers, original English peer-reviewed full-text articles evaluating faricimab versus monospecific anti-VEGF agent(s) in FDA-indicated retinal disease with data on at least one set of efficacy and/or safety outcomes for each treatment arm and a minimum 3-month follow-up period were included. Data were appraised using the Cochrane RoB2 and ROBINS-I tools, PRISMA, and GRADE guidelines. All outcomes were collected at last follow-up. Random effects meta-analyses with 95% confidence intervals (CI) were conducted to calculate weighted mean differences (WMD) and risk ratios (RR). Change in best-corrected visual acuity (BCVA, ETDRS letters), change in central subfield thickness (CSFT, µm), and presence of retinal fluid were primary endpoints; ocular adverse events were secondary endpoints. RESULTS: Across 13 studies, in the context of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), 2226 eyes received anti-VEGF monotherapy and 3022 received faricimab. Final and change in BCVA were similar between treatment groups. Faricimab was associated with a significantly higher reduction in CSFT in DME and RVO eyes but not in nAMD eyes. The incidence of ocular adverse events were similar between groups. CONCLUSION: There was no difference in BCVA between faricimab and anti-VEGF monotherapy in nAMD, DME, and RVO. While faricimab offered superior improvement in central subfield thickness at final follow-up for DME and RVO eyes, this effect was not seen in nAMD eyes. Future studies are needed to establish the long-term safety and efficacy of faricimab for retinal vascular disease.

Scleral Buckling Alone or in Combination with Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment Repair: A Meta-Analysis of 7,212 Eyes.

PURPOSE: The efficacy and safety of scleral buckling (SB) versus combination SB and pars plana vitrectomy (SB + PPV) for rhegmatogenous retinal detachment (RRD) repair remains unclear. METHODS: A systematic review and meta-analysis was conducted to identify comparative studies published from Jan 2000-Jun 2021 that reported on the efficacy and/or safety following SB and SB + PPV for RRD repair. Final best-corrected visual acuity (BCVA) represented the primary endpoint, while reattachment rates and ocular adverse events were secondary endpoints. A random-effects meta-analysis was performed, and 95% confidence intervals were calculated. RESULTS: Across 18 studies, 3912 SB and 3300 SB + PPV eyes were included. Final BCVA was nonsignificantly different between SB and SB + PPV (20/38 vs. 20/66 Snellen; WMD = -0.11 LogMAR; 95% CI: [-0.29, 0.07]; p = 0.23). Primary reattachment rate was similar between procedures (p = 0.74); however, SB alone achieved a significantly higher final reattachment rate (97.40% vs. 93.86%; RR = 1.03; 95% CI: [1.00, 1.06]; p = 0.04). Compared to SB + PPV, SB alone had a significantly lower risk of postoperative macular edema (RR = 0.69; 95% CI: [0.47, 1.00]; p = 0.05) and cataract formation (RR = 0.34; 95% CI: [0.12, 0.96]; p = 0.04). The incidence of macular hole, epiretinal membrane, residual subretinal fluid, proliferative vitreoretinopathy, elevated intraocular pressure, and extraocular muscle dysfunction were similar between SB and SB + PPV. CONCLUSIONS: There was no significant difference in final BCVA between SB + PPV and SB alone in RRD. SB alone offers a slightly higher final reattachment rate along with a reduced risk of macular edema and cataract. Primary reattachment rate and the incidence of other complications were similar between the two procedures.

Subfoveal Choroidal Neovascular Membrane Secondary to Idiopathic Intracranial Hypertension.

Purpose: To present a rare case of subfoveal choroidal neovascular membrane (CNVM) secondary to idiopathic intracranial hypertension. Methods: A case was evaluated. Results: A 21-year-old woman presented with a 2-week history of painless blurred vision in the right eye. She described initial metamorphopsia and intermittent bitemporal headaches lasting 30 minutes. She denied pain with eye movements and a history of trauma. Her body mass index was 49 kg/m2. The visual acuity (VA) was 20/320 OD and 20/20 OS; there was no relative afferent pupillary defect. A dilated fundus examination showed bilateral optic disc edema and a subfoveal CNVM in the right eye. The patient was started on oral acetazolamide 500 mg twice daily and treated with 2 intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Three months later, the VA was 20/30 in the right eye and the disc edema had improved. Conclusions: CNVMs in the setting of idiopathic intracranial hypertension-related papilledema may be subfoveal and have an excellent response to anti-VEGF agents.

Impact of eyewear insurance coverage on utilization of eyecare providers in Ontario, Canada.

OBJECTIVE: To obtain prescription eyewear in Ontario, eye exams must be performed by optometrists or ophthalmologists (eye care providers [ECPs]). In 2004, government-insured routine eye exams were delisted for Ontarians aged 20-64 leaving eye exam coverage only for those aged ≤19 and 65+. We assessed whether having eyewear insurance impacts Ontarians' utilization of ECPs. DESIGN: Cross-sectional survey. PARTICIPANTS: Ontarians aged 12+ without diabetes responding to the Canadian Community Health Survey in 2003, 2005, and 2013/2014. METHODS: We compared the utilization of ECPs by eyewear insurance status and eligibility for government-funded eye exams. Individuals with eyewear insurance funded by employers, government or privately were considered to have insurance. RESULTS: ECP utilization was significantly higher in Ontarians with eyewear insurance versus those without, in all survey years and all age groups, including those eligible for government-funded eye exams (e.g., 66.4% vs 59.1% [p < 0.05] for the 65+). This higher level of utilization was particularly evident among Ontarians aged 20-64 in 2013/2014, when this group no longer had government-funded eye exams (34.9% vs 19.9% among 20-39-year-olds, 43.4% vs 32.9% among 40-64-year-olds, p < 0.05 for both). Adjusting for confounding effects, the likelihood of visiting an ECP was greater among Ontarians with eyewear insurance than those without (adjusted prevalence ratio 1.26 for Ontarians aged 12+ and 1.41 for those aged 20-64; p < 0.05 for both). CONCLUSIONS: Lack of eyewear insurance negatively impacts the utilization of ECPs, even among Ontarians eligible for government-funded eye exams, where the cost barrier for eye exams has been removed by the Ontario government.

Safety and Efficacy of a Treat-and-Extend Regimen of Anti-Vascular Endothelial Growth Factor Agents for Diabetic Macular Edema or Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis.

[Box: see text] Background and Objective: This meta-analysis evaluates treat-and-extend regimens relative to monthly and as-needed (prn) regimens using anti-vascular endothelial growth factor agents for diabetic macular edema and macular edema secondary to retinal vein occlusion. MATERIALS AND METHODS: Comparative studies evaluating a treat-and-extend regimen relative to a monthly or prn regimen with anti-vascular endothelial growth factor therapy for diabetic macular edema or macular edema secondary to retinal vein occlusion were included following a systematic literature search. RESULTS: Seven studies of 984 eyes were included. Relative to a monthly regimen, treat-and-extend was similar for change in best-corrected visual acuity at final follow-up (P = .59) and had a lower number of injections (P < .00001). Relative to a prn regimen, treat-and-extend was similar for change in best-corrected visual acuity at final follow-up (P = .84) and was associated with a higher number of injections (P = .02). CONCLUSION: This meta-analysis found that a treat-and extend regimen was nonsignificantly different compared to monthly and prn regimens in efficacy and safety end points. [Ophthalmic Surg Lasers Imaging Retina 2023;54(3):131-138.].

Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis.

Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, µm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&E versus monthly (WMD, -0.62 letters; 95% CI, -2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, -10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, -3.55 to 6.91; P = 0.53; WMD, -18.91 microns; 95% CI, -46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, -2.95 to 5.11; P = 0.60) regimens. T&E was associated with a reduced injection burden versus monthly (WMD, -4.52 injections; 95% CI, -6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&E, bimonthly, monthly, and PRN dosing. T&E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.

Investigating the role of inflammation in keratoconus: A retrospective analysis of 551 eyes.

PURPOSE: Keratoconus (KCN), classically defined as a noninflammatory corneal ectasia, was recently associated with chronic inflammation. This study aimed to further evaluate the association between inflammation and KCN severity by assessing patient tear films. METHODS: Retrospective chart review of consecutive patients (July 2016-February 2020) referred to a tertiary KCN centre. Using tomography Kmax values, the worst-eyes of patients with a diagnosis of KCN and tear film test results were included. Eyes were stratified as matrix metalloproteinase-9 (MMP9) positive or negative and analyzed using independent t and Pearson chi-squared tests. A p-value ≤ 0.05 was considered significant. RESULTS: 551 (51.40%) unilateral eyes were included. Mean age was 30.1 years and 70.1% were male. 55.5% of the eyes were MMP9 positive. Mean corrected distance visual acuity was 20/30<συπ>-3 Snellen and Kmax was 60.1 Diopters. MMP9 positive eyes had a higher Kmax (p = 0.048), and were more likely from patients who were male (p < 0.001), had a paediatric history of asthma (p = 0.042), and used glasses (p = 0.041). MMP9 negative eyes more likely corresponded to soft contact lens users (p = 0.012). No other significant differences were found in risk factors, topography, tomography, and tear film osmolarity. CONCLUSION: MMP9 positive keratoconic eyes had significantly higher Kmax readings which may correlate with increased disease severity, supporting an association between keratoconus and inflammation. Further research is warranted to evaluate the role of targeted therapy and contact lens use on MMP9 levels in keratoconic eyes and whether disease progression is affected.

Pars plana vitrectomy versus scleral buckle: A comprehensive meta-analysis of 15,947 eyes.

Pars plana vitrectomy (PPV) and scleral buckling (SB) are two of the most common surgical treatments for rhegmatogenous retinal detachment (RRD). This meta-analysis compares the efficacy and safety of PPV and SB for RRD. A systematic literature review was performed using Ovid MEDLINE, EMBASE and Cochrane CENTRAL from 2000 to June, 2021. Comparative studies, randomized controlled trials and observational studies investigating PPV and SB for RRD repair were included. The primary endpoint was final best- corrected visual acuity (BCVA). Secondary endpoints were reattachment rates, total operation time, and incidence of adverse events. Subgroup analyses including phakic status, presence of PVR-C or greater at baseline, and macular attachment status were conducted. Across 41 studies (8 RCTs, 33 observational studies), 5,401 SB and 10,546 PPV eyes were included. SB achieved a statistically significant, but likely not clinically significant, better final BCVA than PPV (0.38 ± 0.53 vs. 0.33 ± 0.53 logMAR (20/48 vs. 20/43 Snellen); weighted mean difference [WMD]: 0.07; 95% confidence interval: [0.02-0.11]; P = 0.005). SB had a better final BCVA compared to PPV in observational studies (P = 0.007) but not in RCTs (P = 0.21). SB had a lower incidence of post-operative cataract formation (P < 0.00001) and iatrogenic breaks (P < 0.00001), but a higher incidence of choroidal/subretinal hemorrhage (P = 0.007), choroidal detachment (P = 0.004), and residual subretinal fluid (RSRF) (P < 0.00001). Primary (86.5% vs. 84.8%; P = 0.13) and final (96.7% vs. 97.7%; P = 0.12) reattachment rates were similar between PPV and SB. PPV had a significantly higher primary reattachment rate in RCTs (P = 0.02) but not in observational studies (P = 0.30). SB was associated with a better final BCVA than PPV; however, this result was primarily driven by observational studies and phakic patients who developed cataracts. Primary and final reattachment rates were similar between the comparators. SB was associated with a significantly lower incidence of iatrogenic breaks and cataracts, while PPV was associated with a reduced risk of choroidal detachment, subretinal hemorrhage, and RSRF.

Pars Plana Vitrectomy with and without Supplemental Scleral Buckle for the Repair of Rhegmatogenous Retinal Detachment: A Meta-analysis.

TOPIC: It is unclear whether there are differences in safety and efficacy between pars plana vitrectomy (PPV) alone and PPV with a supplemental scleral buckle (SB; PPV-SB) for the treatment of rhegmatogenous retinal detachment. CLINICAL RELEVANCE: This meta-analysis aimed to compare the safety and efficacy of these surgical procedures. METHODS: In this meta-analysis, Ovid MEDLINE, Embase, and Cochrane Library were systematically searched (January 2000-June 2021). The primary outcome was the final best corrected visual acuity (BCVA), whereas the secondary outcomes were reattachment rates and complications. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions tool for nonrandomized studies. RESULTS: This study included 15 661 eyes from 38 studies (32 observational studies and 6 RCTs). The median follow-up duration was 6 months. The final BCVA was similar between PPV and PPV-SB (weighted mean difference [WMD], -0.03 logarithm of the minimum angle of resolution [-0.14 to 0.07]; P = 0.55). There was a significant difference in the single-operation success rate (SOSR) (88.2% versus 86.3%; relative risk [RR], 0.97 [0.95-1.00]; P = 0.03), favoring PPV-SB; however, there was no significant difference in the final reattachment rate (RR, 1.00 [0.99-1.01]; P = 0.56). Pars plana vitrectomy required a significantly higher number of operations to achieve final anatomical reattachment (WMD, 0.13 [0.02-0.24]; P = 0.02). In terms of complications, PPV was significantly less likely to be associated with macular edema (RR, 0.47 [0.25-0.88]; P = 0.02) and epiretinal membrane formation (RR, 0.70 [0.52-0.94]; P = 0.02), but these differences were no longer significant in studies published after 2010 or in RCTs. Significant proliferative vitreoretinopathy, lens status, and macular attachment status did not mediate differences in these effects. CONCLUSIONS: There were no significant differences in the final visual acuity outcomes between PPV and PPV-SB. Pars plana vitrectomy with supplemental SB was associated with a greater SOSR than standalone PPV, although the magnitude of the effect was small, with a high number needed to treat. The final reattachment rate was similar. In recent studies and in RCTs, the risk of complications was similar between the procedures.