Two-year outcomes of intravitreal conbercept therapy for polypoidal choroidal vasculopathy.

BACKGROUND: This study aims to evaluate the two-year outcomes of polypoidal choroidal vasculopathy (PCV) treated with conbercept and to investigate the predictive response factors. METHODS: Consecutive patients with PCV who received three-loading intravitreal conbercept, followed by as-needed reinjections, were studied retrospectively. The best corrected visual acuity (BCVA), central retinal thickness (CRT) and polyps were evaluated. Patients who achieved dry maculae in month 6 were categorised into the dry group, or otherwise, into the non-dry group. The predictive factors for a dry macula were evaluated. RESULTS: A total of 25 eyes from 25 patients (17 males; mean age: 62.8 ± 6.4 years) were included. At month 24, the average BCVA increased significantly from 49.9 ± 15.0 letters to 57.2 ± 16.0 letters (p = 0.040); the average CRT decreased significantly from 430.16 ± 166.55 µm to 278.31 ± 157.34 µm (p = 0.00), and 88% of the eyes achieved dry maculae. The number of polyps changed from 55 to 20 (fading rate: 63.6%; p < 0.001). The mean number of intravitreal injections was 8.6 ± 5.4. The dry group (10 eyes, 40%) was more likely to have higher branching vascular network vessel density (BVN VD; p = 0.021), submacular haemorrhages (p = 0.011) but lack polyp-related serous pigmented epithelial detachment (PED) (p = 0.037). CONCLUSIONS: Conbercept was effective in eyes with PCV at maintaining functional and anatomical improvement. Baseline characteristics, including BVN VD, the presence of polyps with serous PED and submacular haemorrhage, seemed to be related to the response to conbercept.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.

Incidence of intraocular inflammation and its risk factors in patients treated with brolucizumab: a nationwide cohort study.

This study aimed to evaluate the incidence of clinically significant intraocular inflammation (csIOI) after treatment with intravitreal injection (IVI) of brolucizumab and identify csIOI risk factors. We categorized 60,966 South Korean patients from a nationwide population-based cohort into 4 groups: groups 1 (Ranibizumab), 2 (Aflibercept), 3 (Brolucizumab), and 4 (switched to brolucizumab). We used the Kaplan-Meier method to estimate the cumulative incidence of csIOI in each group and calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). We constructed a multivariate model using forward selection methods to identify risk factors for csIOI. The cumulative incidence of csIOI within 180 days of the index date in groups 1, 2, 3, and 4 was 0.36% (67/18,537), 0.49% (186/37,951), 3.47% (38/1,095), and 3.69% (125/3,383), respectively. Multivariate analysis revealed a significant increase in csIOI risk in groups 3 (HR 11.08, 95% CI 7.42-16.53, P < 0.001) and 4 (HR 10.40, 95% CI 7.67-14.09, P < 0.001). History of retinal vascular occlusion (HR 1.56, 95% CI 1.01-2.40, P = 0.043) significantly increased csIOI risk after brolucizumab IVI treatment; female sex (HR 0.78, 95% CI 0.64-0.96, p = 0.020) and diabetes (HR 0.72, 95% CI 0.58-0.90, p = 0.004) decreased the risk. csIOI incidence was higher after brolucizumab IVI treatment than after ranibizumab and aflibercept IVI treatment. Retinal vein occlusion history, female sex, and diabetes are associated with csIOI after brolucizumab IVI treatment.

PD-L1 and VEGF dual blockade enhances anti-tumor effect on brain metastasis in hematogenous metastasis model.

Immunotherapy improves survival outcomes in cancer patients, but there is still an unmet clinical need in the treatment of brain metastases. Here, we used a mouse model to investigate the antitumor effect of programmed death-ligand 1 (PD-L1) and vascular endothelial growth factor (VEGF) dual blockade on metastatic brain tumors and evaluated immune responses during treatment. After establishing hematogenous brain metastasis by transplanting murine bladder carcinoma MBT2 cells stably expressing secNLuc reporter via the internal carotid artery of C3H/HeNCrl mice, we observed the formation of metastases not only in the brain parenchyma but also in the ventricles. The observed pathological areas showed that metastases in the ventricle were histologically larger than that in the brain parenchyma. Regarding the total tumor burden in the whole brain as revealed by Nluc activities, the combination of anti-PD-L1 antibody and anti-VEGF antibody showed a stronger anti-tumor effect than each single agent. Anti-PD-L1 antibody alone enhanced CD8+ T cell priming in regional lymph nodes, increased the proportion of activated CD8+ T cells in whole brain, and increased the density of CD8+ cells in the brain parenchyma. Furthermore, anti-VEGF antibody alone decreased microvessel density (MVD) in ventricular metastases, and the combination treatment increased intratumoral CD8+ cell density in the brain parenchyma and ventricular metastases. These results suggest that PD-L1 blockade enhanced cancer immunity not only in brain metastases lesions but also in the regional lymph nodes of the metastases, and that the addition of VEGF blockade increased the antitumor effect by increasing the infiltration of activated CD8+ T cell and decreasing MVD.

Efficacy of ranibizumab and aflibercept on reducing maximum diameter of largest cyst in diabetic cystoid macular edema: MARMASIA study group.

PURPOSE: This study aimed to compare the effect of intravitreal aflibercept (IVA) and ranibizumab (IVR) on the maximal diameter of the largest intraretinal cyst (mdIRC), indicating chronicity in patients with diabetic cystoid macular edema (CME). METHODS: This retrospective, comparative study included a subgroup of patients from the MARMASIA Study with treatment-naïve diabetic CME who had IVA (IVA group) or IVR (IVR group) on a pro re nata regimen after a loading dose of 3-monthly injections and followed-up for 24 months. Best-corrected visual acuity (logMAR), central macular thickness (CMT, µm), and mdIRC (µm) and their changes during the study period in the IVA and IVR groups were compared. RESULTS: A total of 175 eyes (65 [37.1%] in IVA and 110 [62.9%] in IVR group) of 113 patients were included in the study analysis. Both groups had statistically significant improvements in BCVA and CMT during the follow-up (p < 0.05 for all), which were comparable between the groups at each time point. However, the mean reduction in mdIRCs was consistently and significantly higher in the IVA group compared to the IVR group at each follow-up examination (F[1, 3.52] = 6.93, p = 0.009). CONCLUSION: IVA seems to have a greater impact in reducing cyst sizes than IVR in diabetic CME.

Advancements and emerging trends in ophthalmic anti-VEGF therapy: a bibliometric analysis.

INTRODUCTION: Vascular Endothelial Growth Factor (VEGF) is associated with abnormal fundus neovascularization. Consequently, Anti-VEGF agents are vital for ophthalmic treatment. This paper reviews the application of anti-VEGF agents in ophthalmology over the past two decades with the aim of providing insights for further research. METHODS: A meticulous search strategy was employed in the Web of Science Core Collection literature from 2003 to 2023 to gather relevant literature, which was then analyzed using VOSviewer, CiteSpace, and the R package Bibliometrix. RESULTS: The study included 3,602 publications from 83 countries and 3,445 institutions. The United States and China have emerged as leading contributors in terms of the publication volume. Johns Hopkins University, the University of Sydney, and Genentech Inc were identified as frontrunners in this field. "Retina" had the highest publication volume, whereas "Ophthalmology" had the highest citation frequency. Among the 15,918 scholars, Bressler NM, Holz FG, Glassman AR, and Bandello F led in publication volume, while Brown DM was the most cited author. High-frequency keywords included "Endothelial Growth Factor," "Therapy," "Safety," and "Randomized Clinical Trial." CONCLUSION: Anti-VEGF drugs have shown notable success in treating neovascular eye diseases, especially wet age-related macular degeneration and diabetic macular edema, focusing on clinical efficacy, injection regimens, and safety. Future directions include developing new anti-VEGF drugs, drug delivery systems, non-invasive administration, multi-target drugs, leveraging big data and artificial intelligence, and addressing the current treatment limits. Continuous innovation and method improvement in this field promise more breakthroughs, providing effective, safe, and economical options for eye disease treatment.

Factors Affecting Compliance and Visual Outcomes in Patients Receiving Intravitreal Bevacizumab Injections.

Background Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients. Therefore, this study aims to determine the success rates of intravitreal bevacizumab therapy and the visual outcomes which may be increased by determining the factors affecting patient compliance and raising awareness about DR, neovascular AMD, and RVO among patients and studying the factors responsible for non-compliance to treatment. Methodology This experimental pre-post study was conducted in the ophthalmology department at a tertiary care hospital and research center in western Maharashtra from September 2022 to June 2024. A total of 150 eyes of 150 patients who were diagnosed cases of DR, neovascular AMD, and non-ischemic RVO were included in the study. Written informed consent was obtained from each patient. Data were entered in Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and statistical analysis was done using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). The chi-square test was employed to check the association between categorical variables. Pearson's correlation test was used, and p-values <0.05 were considered significant. Results The compliance rate in our study was 79.3% (113 individuals). In our study, 58% (87 individuals) were male while 42% (63 individuals) were females. Most patients were from urban areas 74.7% (112 individuals). Among the study participants, DR patients constituted 48.6% (73 individuals), while neovascular AMD and RVO were seen in 32% (48 individuals) and 19.4% (29 individuals), with 62% (93 individuals) being diabetic and 64.7% (97 individuals) being hypertensive. In our study, 92% (138 individuals) were willing to take treatment, with 88.7% (133 individuals) worried about their visual outcomes and 66% (99 individuals) afraid of getting injected. Appointments posed a financial burden to 30.7% (46 individuals) of patients, with 55.3% (83 individuals) having transportation issues. Overall, 18.7% (28 individuals) of patients had missed appointments between 14 and 90 days while 30.7% (46 individuals) had missed their appointments by 90 and 365 days. Younger patients with a shorter duration of diabetes had higher compliance rates. Post-injection, there was an overall significant improvement in vision as well as a reduction in the central subfield macular thickness, volume cube, and thickness average cube. Conclusions In the present study, four-fifths of the patients were compliant with treatment, and visual improvement was significant. In addition, there was a significant reduction in the macular thickness after the treatment. One of the factors for non-compliance included in our study was the need for follow-up. Younger patients and those with a shorter duration of diabetes had significantly higher compliance. We recommend further studies should be conducted to compare the effectiveness with the control group in randomized control trials.

[Diagnosis of choroidal nevus following multiple intravitreal anti-VEGF injections (case study)]. / Diagnostika nevusa khorioidei posle mnogokratnykh intravitreal'nykh in"ektsii anti-VEGF-preparata (klinicheskoe nablyudenie).

This article describes a clinical case of a female patient with choroidal nevus, who was previously diagnosed in another clinic with "subretinal neovascular membrane as a result of central serous chorioretinopathy" and subsequently underwent multiple intravitreal anti-VEGF injections. Based on the analysis of OCT angiography images, the macular changes in this case were interpreted as a polypoidal form of neovascularization in a patient with subfoveolar choroidal nevus.

Intraocular drugs: pharmacokinetic strategies and the influence on efficacy and durability.

INTRODUCTION: The modern treatment of chorioretinal vascular diseases follows the recent development and rapid adoption of drugs that inhibit vascular endothelial growth factor (VEGF). All anti-VEGF drugs are delivered intravitreally, with clinical behavior, including efficacy, durability, and safety, largely determined by their pharmacokinetic properties. AREAS COVERED: Properties of these new drugs include additional binding targets (placental growth factor (PlGF) and angiopoietin 2 (Ang 2)), binding affinity, potency, intravitreal half-life, and increased molar dose. A PubMed search for 'pharmacokinetics of anti-VEGF drugs' was performed from 2000 to 2023. Relevant studies were reviewed and referred to in the manuscript. EXPERT OPINION: Early developers concentrated on improving efficacy, but since maximum efficacy with VEGF inhibition has been reached, development has pivoted to extending the duration of action. Durability strategies include inhibiting additional pathways (faricimab), increasing molar dose (abicipar, brolucizumab, faricimab, and aflibercept 8 mg), and prolonging the intravitreal half-life (abicipar and KSI-301). Recent phase 3 trials demonstrated modest improvements in durability, but failures that might be attributed to these strategies (conjugation and manufacturing processes) have occurred. Future drug development focuses on extending duration of action with implantable reservoirs (ranibizumab port delivery system), sustained release devices (tyrosine kinase inhibitors), and gene therapy.

Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies.

Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME.

The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses.

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD.

Inflammation and Vasculitis Related to Brolucizumab.

Background/objectives: To compare the prevalence of intra-ocular inflammation (IOI) between brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD) after intra-vitreal injections (IVI) and to compare the IOI odds ratios (ORs) of both therapies with the prevalence of septic endophthalmitis after IVI that was previously reported in the literature. Methods: A total of 468 IVI of brolucizumab (117 eyes) were compared with 2884 IVI of aflibercept (305 eyes) regarding IOI and occlusive retinal vasculitis (RV) from December 2021 to June 2023 in this retrospective study. The OR was calculated for both anti-VEGF agents and was compared with the relative risk of septic endophthalmitis after IVI. Results: There were four eyes with unilateral IOI related to brolucizumab (3.42%), one presenting uveitis (0.85%), two vitritis (1.71%) and the last one presenting occlusive RV (0.85%), compared with two eyes presenting unilateral IOI (anterior uveitis, 0.66%) and none with RV from the aflibercept cohort. The incidence of IOI per injection with brolucizumab (0.855%) was significantly higher compared with aflibercept (0.069%, p = 0.004). The OR of IOI related to brolucizumab IVI compared with septic endophthalmitis was 20 times greater (1.49 for aflibercept, p = 0.646, versus 20.15 for brolucizumab, p < 0.001). The OR of RV with brolucizumab compared with septic endophthalmitis was 4.6. Conclusion: Data from our department suggest a much higher risk of IOI and occlusive retinal vasculitis after brolucizumab when compared with aflibercept. The risk of IOI and severe sight-threatening complications related to brolucizumab is greater than the risk of septic endophthalmitis after any IVI.

Impact of Intra-Retinal Fluids on Changes in Retinal Ganglion Cell and Nerve Fiber Layers in Neovascular AMD under Anti-VEGF Therapy.

Purpose: To investigate the influence of intraretinal fluid (IRF) on change in retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (RGCL) and thickness in patients with naive neovascular AMD under anti-VEGF treatment. Design: post hoc analysis. Methods: 97 eyes of 83 patients on continuous therapy with intravitreal anti-vascular endothelial growth factors (anti-VEGF) and a follow-up of 24 months were included. RGCL and RNFL thickness in the perifoveal (-O), parafoveal (PF), and nasal areas and number of injections (IVI) were recorded before the first IVI as well as 1 and 2 years after initiating treatment and compared longitudinally and between groups with and without IRF. Results: The group with IRF at baseline had a higher RNFL thickness at baseline and showed a significant reduction in RNFL-PF between baseline and first and second follow-ups (p < 0.001) but not between first and second follow-ups. The group without IRF showed no significant reduction in RNFL over time. The presence of IRF was not associated with a reduction in RNFL-O or RNFL-nasal. RGCL thickness decreased significantly in both groups with and without IRF after 2 years. Number of IVIs showed no significant correlation to RNFL or RGCL after stratification for the presence of IRF. Conclusions: The presence of IRF has a significant influence on RNFL thickness at baseline as well as on its changes over time during anti-VEGF therapy. The preoperative presence of IRF should be considered when comparing changes in RNFL thickness after IVI.

Interpretation of SD-OCT imaging data in real-life conditions versus standardized reading centre analysis in eyes with diabetic macular oedema or macular oedema secondary to retinal vein occlusion: 24-month follow-up of the ORCA study.

PURPOSE: As part of the prospective, non-interventional OCEAN study, the ORCA module evaluated physicians' spectral domain optical coherence tomography (SD-OCT) image interpretations in the treatment of diabetic macular oedema (DME) or macular oedema (ME) secondary to retinal vein occlusion (RVO). METHODS: Presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) was evaluated independently by physicians and reading centres (RCs) on 1612 SD-OCT scans of 133 patients diagnosed with either DME or ME secondary to RVO. Agreement between physicians and RCs was calculated for both cohorts individually and as a combined ME cohort. Physicians' treatment decisions were analysed related to the results of the OCT-evaluations. RESULTS: For the combined ME cohort, presence of IRF/SRF was recorded by RCs in 792/1612 (49.1%) visits and by physicians in 852/1612 (52.9%) visits, with an agreement regarding presence or absence of foveal fluid in 70.4% of cases. In 64.4% (510/792) of visits with RC-detected foveal IRF and/or SRF no injection was given. In 30.3% of these visits with foveal fluid no reason was identified for a 'watch and wait' approach indicating possible undertreatment. BCVA deterioration was seen in a quarter of these eyes at the following visit. CONCLUSION: Despite good agreement between physicians and RCs to recognize SRF and IRF, our data indicate that omitting injections despite foveal involvement of fluid is frequent in routine clinical practice. This may put patients at risk of undertreatment, which may negatively impact real-life BCVA outcomes. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier NCT02194803.

Treatment and Characteristics of Pachychoroid Neovasculopathy Accompanying Recalcitrant Intraretinal Cysts.

PURPOSE: To evaluate the clinical characteristics associated with chronic pachychoroid neovasculopathy (PNV) accompanying recalcitrant intraretinal cysts. METHODS: This is a retrospective, single-center, case-series study involving 20 eyes of 18 patients with PNV who did not respond to bevacizumab or ranibizumab and had to switch to aflibercept. Optical coherence tomography images were assessed before and after switching of intravitreal injection drug. RESULTS: The intraretinal cysts involved the outer nuclear layer and inner nuclear layer in 15 patients (75.0%), and involved only the inner nuclear layer in five patients (25.0%). All participants showed retinal pigment epithelium atrophy and outer retinal layer defect including external limiting membrane defect co-localized to the intraretinal cystic lesion. With the initial injection, bevacizumab and ranibizumab injections did not show a significant decrease in choroidal thickness (CT). Twenty (100.0%) patients showed poor response of intraretinal cyst response (IRCR). After a switch to aflibercept, IRCR was good in 17 (85.0%) patients and poor in three (15.0%) patients. Reduction of CT was great in aflibercept injections (from 229.0 µm to 204.0 µm, median, p < 0.001). Best-corrected visual acuity did not show significant improvement before or after switching drugs. CONCLUSION: Intravitreal aflibercept injections were more effective in the reduction of CT and IRCR than bevacizumab and ranibizumab injections. The primary source of the intraretinal cyst fluid could be from the choroid.

Real-World Efficacy of Intravitreal Faricimab for Diabetic Macular Edema: A Systematic Review.

BACKGROUND: Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. METHODS: We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. RESULTS: We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61-81% of treatment-naïve eyes and 36-78% of previously treated eyes. CONCLUSIONS: Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

BACKGROUND/OBJECTIVES: Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. METHODS: This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. RESULTS: A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 µm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. CONCLUSIONS: In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

Laser Treatment for Diabetic Retinopathy: History, Mechanism, and Novel Technologies.

Background: Diabetic retinopathy (DR), as a complication of diabetes mellitus (DM), remains a significant contributor to preventable vision impairment in the working-age population. Laser photocoagulation is essential in treating DR in conjunction with anti-vascular endothelial growth factor (VEGF) injection, steroids, and vitrectomy. This review summarizes the history of laser photocoagulation and highlights its current role and long-term effectiveness in real-world conditions. Methods: The National Clinical Trial (NCT), PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases were searched utilizing combined or individual keywords, and a total of 121 articles were reviewed by the authors. Results: Several novel laser photocoagulation technologies, such as patterned scanning laser, subthreshold micropulse laser, navigated laser, multimodal imaging-guided laser, and retina rejuvenation therapy, substantially decrease the adverse effects and improve the accuracy and security of laser therapy. Numerous studies have demonstrated the outstanding clinical efficacy of combination therapies with pharmacologic treatments like anti-VEGF in treating DR and diabetic macular edema (DME). A 20-year follow-up retrospective study in our center preliminarily demonstrated the long-term effectiveness of conventional laser photocoagulation. Conclusions: More clinical trials are required to confirm the clinical effectiveness of novel laser technologies. Better treatment protocols for the combination therapy may be detailed. Anti-VEGF treatment has better effects, especially for DME and in a short period. But in real-world conditions, given the long-term effectiveness and economic advantages of conventional laser treatment, it should be prioritized over anti-VEGF injection in certain situations.

Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration.

Background/Objectives: The objective of this study was to determine the treatment effect of foselutoclax in neovascular age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in AMD studies. Methods: A total of five subjects were included in the study who had active choroidal neovascularization and a history of at least two anti-vascular endothelial growth factor (VEGF) injections in the last 6 months. Subjects received a 50 µL intravitreal injection of foselutoclax at the baseline visit and Weeks 4, 24, and 28 of the study period. Results: After foselutoclax treatment, the largest improvement in the mfERG N1-P1 response density occurred at Week 8 as three of five subjects achieved a ≥20% gain. In addition, three of five subjects demonstrated a BCVA improvement of ≥5 ETDRS letters over baseline at Weeks 4, 8, and 24. The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Conclusions: Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment.