Anti-vascular Endothelial Growth Factor Agents Research Articles

GCN-assisted attention-guided UNet for automated retinal OCT segmentation

With the increase in the aging population of many countries, the prevalence of neovascular age-related macular degeneration (nAMD) is expected to increase. Morphological parameters such as intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), and pigment epithelium detachment (PED) of spectral-domain optical coherence tomography (SD-OCT) images are vital markers for proper treatment of nAMD, especially to get the information of treatment response to determine the proper treatment interval and switching of anti-vascular endothelial growth factor (VEGF) agents. For the precise evaluation of the change in nAMD lesions and patient-specific treatment, quantitative evaluation of the lesions in the OCT volume scans is necessary. However, manual segmentation requires many resources, and the number of studies of automatic segmentation is increasing rapidly. Improving automated segmentation performance in SD-OCT visual results requires long-range contextual inference of spatial information between retinal lesions and layers. This paper proposes a GAGUNet (graph convolution network (GCN)-assisted attention-guided UNet) model with a novel global reasoning module considering these points. The dataset used in the main experiment of this study underwent rigorous review by a retinal specialist from Konkuk University Hospital in Korea, contributing to both data preprocessing and validation to ensure a qualitative assessment. We conducted experiments on the RETOUCH dataset as well to demonstrate the scalability of the proposed model. Overall, our model demonstrates superior performance over the baseline models in both quantitative and qualitative evaluations.

METHOD OF POVIDONE-IODINE APPLICATION AND ENDOPHTHALMITIS RISK.

To evaluate the proportion of patients developing endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents according to the mode of povidone-iodine (PI) antisepsis. A retrospective review of the anti-vascular endothelial growth factor injections given in a 7-year period at a community-based retinal practice. Endophthalmitis was diagnosed to have occurred if an eye developed intraocular inflammation and was given antibiotics with or without supportive culture identification of an organism. As part of their habitual clinical practice, component physicians used 5% PI as two drops, one drop, or just a dot of PI administered with a cotton-tipped applicator to the site before injection. There were 113,610 intravitreal injections administered and 23 cases were diagnosed with endophthalmitis over the 7-year period, for a rate of 1 case per 4,940 injections. The mode of PI antisepsis showed no significant relation to the rate of endophthalmitis ( P = 0.55, chi-square test). The proportion of endophthalmitis by physician demonstrated no significant difference ( P = 0.39, chi-square test). The use of PI has been associated with decreased incidence of endophthalmitis, but the mode of application has not been standardized. The results of this study suggest that "more is not better" in PI antisepsis in endophthalmitis. Moreover, the toxicity of PI on the ocular surface is known to be dose-related.

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

ObjectiveTo compare the efficacy and safety of different anti-vascular endothelial growth factor (VEGF) agents combined with different delivery methods for neovascular glaucoma (NVG).DesignSystematic review and Bayesian network meta-analysis (NMA).Data sourcesPubMed,...

Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study

Introduction: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. Methods: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. Results: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 μm vs. 780.2 μm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p < 0.001). The mean postoperative VA at 6 months was 0.67 and 0.91 (p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 μm vs. 326.5 μm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p < 0.001, odds ratio [OR] = 11.1) and displacement to arcade or beyond (52.5% vs. 17.5%, p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. Conclusion: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

Topical Dorzolamide as Adjunctive Treatment With Intravitreal Bevacizumab in Bilateral Diabetic Macular Edema.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME. This prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center, Al-Zahra Eye Hospital, Zahedan, Iran, between April 2021 and April 2022. Thisstudy included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first three months. Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P > 0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P > 0.05). The present study showed a decrease in CMT in both study groups (P < 0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs. -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P < 0.001). The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline, but it did not have an additive effect on BCVA improvement compared to IVB monotherapy.

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

PurposeTo compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months.MethodsThis was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F).ResultsA total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = − 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = − 0.53; p < 0.001 and PCV, r = − 0.09; p = 0.58).ConclusionPEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Initial Outcome of Subconjunctival Bevacizumab for Corneal Neovascularization - a Case Series

Introduction : Corneal neovascularization (CNV) has a variety of causes and threatens corneal clarity, thus optimal visual acuity. Conventional medical management includes topical steroids and matrix metalloproteinase inhibitors like doxycycline. Anti-vascular endothelial growth factor (anti-VEGF) agents have demonstrated promise but remain off-label for this indication.&#x0D; Case Illustration : We present three patients with corneal neovascularization varied in etiology who underwent subconjunctival injection of Bevacizumab . Case 1: a-female-69 years old came with blurred vision after had Stephen Johnson Syndrome which affect her cornea. The examination revealed opacification of cornea accompanied by neovascularization at 5 until 9 o’clock position up to edge of pupil in the left. Case 2: a-male-47 years old presented corneal haze with neovascularization almostin all corneal region on background of fungal keratitis. Case 3: a-male-63 years old who underwent penetrating keratoplasty of indication corneal lekoma following an episode of fungal keratitis. There was opacity in all corneal region and neovascularization in 360 degree of limbus. All of these patients showed regression of neovessel after first injection of bevacizumab.&#x0D; Discussion : Corneal neovascularization is a condition caused by disruption homeostasis in which proangiogenic balanced by antiangiogenic, thereby maintaining avascularity. Bevacizumab as VEGF-A-binding proteins could prevent VEGF-A from binding cell surface receptors.&#x0D; Conclusion : Subconjunctival injection of Bevacizumab can be considered as a treatment for corneal neovascularization. It has shown promising effects in recess neovascularization in cornea regardlessthe etiology.

Steroidal nanoformulations for the treatment of uveitis: potential, promises and future perspectives.

Intraocular inflammation, commonly referred to as uveitis, is a prevalent ocular disease. The categorization of uveitis may be based on the prevailing anatomical site, which includes anterior, intermediate, and posterior uveitis. There exists a significant body of evidence indicating that T cells play a pivotal role in the pathogenesis of autoimmune uveitis. In addition to the presence of T cells, an elevation in levels of inflammatory cytokines and a reduction in regulatory cytokines were also noted. The primary pharmacological interventions for uveitis comprise of corticosteroids, methotrexate, anti-vascular endothelial growth factor (VEGF) agents, anti-tumor necrosis factor-alpha (TNF-α) antibodies, and sirolimus. These medications offer prompt alleviation for inflammation. Nevertheless, prolonged administration of corticosteroids invariably leads to unfavorable adverse reactions. The traditional topical corticosteroids exhibit certain limitations, including inadequate transcorneal permeation and low corneal retention, leading to reduced ocular bioavailability. Consequently, there is a growing inclination towards the creation of innovative steroid drug delivery systems with the aim of reducing the potential for adverse effects, while simultaneously enhancing the drug's corneal permeation and retention. This review is an attempt to compile all the research work done so far in this field and provides a brief overview of the global efforts to develop innovative nanocarrier-based systems for corticosteroids.

Comparison Between Results of Trabeculectomy With or Without Anti- Vascular Endothelilal Growth Factor in Patients With Neovascular Glaucoma at Undaan Eye Hospital Surabaya, Indonesia

Introduction &amp; ObjectivesNew intraocular medication, Anti-vascular endothelial growth factor (Anti-VEGF) agents has beendeveloped in the management of neovascular glaucoma and in glaucoma surgery. But there are nostudies comparing trabeculectomy with Anti-VEGF to no Anti-VEGF treatment in patients withneovascular glaucoma. This study aims to compare decrease of intraocular pressure (IOP) betweentrabeculectomy with Anti-VEGF and without Anti-VEGF in neovascular glaucoma.&#x0D; MethodsThis observational retrospective study comprised 30 medical records of neovascular glaucoma,divided to 15 medical records of patients with anti-VEGF before trabeculectomy and medical recordsof patients operated with trabeculectomy without anti-VEGF, monitored between January 2021 toDecember 2021. Patients with incomplete medical records were excluded. Data collected are age,gender, risk factor, intraocular pressure pre operative, and during 6 months follow-up IOP postoperative. Data analysis uses an Independent T test.&#x0D; ResultsFrom 30 samples, mean IOP in trabeculectomy with anti-VEGF group generally is 12,26 mmHg.Meanwhile, mean IOP in trabeculectomy without anti-VEGF group generally is 16,74 mmHg. Tindependent test between 2 groups shows that there are significant mean difference between themduring 1-5 months follow-up (1 month: p = 0,022; 2 months: p = 0,007; 3 months: p = 0,007; 4months: p = 0,042; 5 months: p = 0,029).&#x0D; ConclusionTrabeculectomy with prior administration of intravitreal anti-VEGF shows good IOP reduction andcan be implemented in NVG patients.

The Effects of Bevacizumab in Augmenting Trabeculectomy for Glaucoma : Systematic Review and Meta-Analysis

Introduction &amp; Objectives : Anti-vascular endothelial growth factor (VEGF) agents have been used to slow the healing response and postoperative scar tissue formation. To determine the effectiveness of adding Anti VEGF bevacizumab to the results of trabeculectomy in glaucoma.&#x0D; Methods : Searches were conducted in a structured way using keywords across several data sources, including Pubmed, Proquest and Cochrane library. The keywords used for searching were “Bevacizumab”, “Trabeculectomy” and “Glaucoma”. The reviewed articles are Randomized Control Trial in english, conducted on humans in the last 15 years. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.&#x0D; Results : From a total of 353 articles, there were 6 studies with 362 eyes of 352 patients been evaluated for the effectiveness of bevacizumab addition to trabeculectomy. The primary outcome of all articles was the assessment of Intra Ocular Pressure (IOP). No significant difference in IOP was found between the subconjunctival bevacizumab + Mytomycin-c group and mytomycin-c alone group (MD 0.11 ; 95% CI -0.10 to 0.33), as well as subconjunctival comparison with mytomycin-c (MD 0.11 ; 95% CI -0.29 to 0.50). Similar results were also found in the intracameral and placebo groups (MD 0.08 ; -0.22 to 0.38). However, 3 articles reported significant differences in peripheral vascularity of the bleb both by the Moorfields Bleb Grading System and by the Indiana Bleb Appearance System.&#x0D; Conclusion : The addition of bevacizumab to trabeculectomy did not show any benefit in reducing IOP when compared with MMC. But it gives better peripheral vascularity of the bleb.

Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014–2019

ABSTRACT Purpose To characterize trends in use of and expenditure for the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept, ranibizumab, and bevacizumab among the population enrolled in Original Medicare from 2014 to 2019. Methods The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to extract Medicare Part B fee-for-service outpatient injection claims data submitted by ophthalmologists. Multivariable linear regression models were used to evaluate the association between reimbursement, ophthalmologist availability, and agent administration rate. Results Between 2014 and 2019, 17,588,995 intravitreal injection claims were filed by 4218 US ophthalmologists. Medicare costs for anti-VEGF injections increased from 2.51 B USD in 2014 to 4.02 B USD in 2019. Increased state-level ophthalmologist availability and incremental increases in average reimbursement amounts were found to be significantly associated with a 6.8-fold variation in 2019 overall anti-VEGF injection rates across states. Conclusions Medicare injection rates and costs for anti-VEGF injections have both increased between 2014 and 2019, largely driven by increased aflibercept use. There is a significant association between ophthalmologist availability and anti-VEGF injection rate on the state level, suggesting access to care may contribute to the observed state-level disparities in intravitreal injection rates. Further characterization of factors contributing to the state-level variation in injection rates of individual anti-VEGF agents may help inform interventions promoting equitable access to and use of these drugs.

Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration.

Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.

One-year outcome of brolucizumab for neovascular age-related macular degeneration in Japanese patients

A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab. Among these eyes, 30 with treatment-naïve nAMD and 77 treated with other anti-VEGF agents for more than a year were included. All eyes were managed using a treat and extend (TAE) or modified TAE regimen. The last injection intervals at 52 weeks were 12.9 and 12.1 weeks in the treatment-naïve and switch therapy groups, respectively. Among switch therapy group patients whose pre-switch injection intervals were shorter than 120 days (n = 62 eyes), the injection interval was significantly longer after the switch than before, with a mean difference of 2.7 weeks (P < 0.0001). Intraocular inflammation events occurred in 2 and 7 treatment-naïve and switch therapy patients, respectively. In conclusion, brolucizumab might reduce the treatment burden in patients who required the injection of other anti-VEGF agents with a 120-day interval or shorter, despite a relatively high discontinuation rate due to intraocular inflammation.

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota’s influence

The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.

Best Vitelliform Macular Dystrophy Natural History Study Report 1: Clinical Features and Genetic Findings

To analyze the genetic findings, clinical spectrum, and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults. Single-center retrospective, consecutive, observational study. Patients with a clinical diagnosis of BVMD from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene. Data were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed. Molecular genetic test findings and clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiologic parameters. Two hundred twenty-two patients from 141 families were identified harboring 69 BEST1 variants. Mean age at presentation was 26.8 years (range, 1.3-84.8 years) and most patients (61.5%) demonstrated deterioration of central vision. Major funduscopic findings included 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes, and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/47) for the right eye and 0.33 logMAR (Snellen equivalent, 20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 logMAR and 0.009 logMAR, respectively, over a mean follow-up of 9.7 years. Thirty-seven patients (17.3%) received a diagnosis of CNV over a mean follow-up of 8.0 years. Eyes with CNV that received treatment with an anti-vascular endothelial growth factor (VEGF) agent showed better mean BCVA compared with eyes that were not treated with an anti-VEGF agent (0.28 logMAR [Snellen equivalent, 20/38] vs. 0.62 logMAR [Snellen equivalent, 20/83]). Most eyes exhibited a hyperopic refractive error (78.7%), and 13 patients (6.1%) received a diagnosis of amblyopia. Among the 3 most common variants, p.(Ala243Val) was associated with a later age of onset, better age-adjusted BCVA, and less advanced Gass stages compared with p.(Arg218Cys) and p.(Arg218His). BVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Antivascular Endothelial Growth Factor Injection

To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of antivascular endothelial growth factor (VEGF) agents. Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into 2 groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84±45days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR 11.4, P=.008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR 13.8, P=.003), patent ductus arteriosus ligation (OR 10.7, P=.032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR 7.0, P=.018). All anti-VEGF agents carry a risk of ROP reactivation, with the risk being greater with ranibizumab 0.25mg than with bevacizumab 0.625mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.

Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.

To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents. This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED. Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae. In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.