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Purpose: To assess treatment response of Polypoidal choroidal vasculopathy (PCV) in a Caucasian population of British ethnicity with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections alone and with a combination of anti-VEGF injections and photodynamic therapy (PDT)., Setting/venue: Department of Ophthalmology, University Hospital Southampton NHS Foundation Trust, United Kingdom., Methods: Retrospective review of 95 Caucasian patients in a single centre with diagnosis of PCV between 2013 and 2018 were included. Best corrected visual acuity (BCVA), central retinal thickness (CRT), indocyanine green angiography (ICGA) characteristics, numbers and type of treatment were analysed at baseline and at 1 year., Results: One hundred and one eyes included from 95 patients received either anti-VEGF injections (n = 79, 78.2%) alone or combination therapy with anti-VEGF and PDT (n = 6, 6%). A third untreated group was also observed (n = 16, 15.8%). Five eyes were excluded from the study due to structural retinal damage. Mean number of injections was 7.3 in the monotherapy group and 6.5 in the combination group. Both treatment groups showed improvement in BCVA at 1 year and this was statistically significant in the monotherapy group with a mean gain of 8.3 letters (p < 0.001). Mean CRT decreased in all treatment groups at twelve months and this change was significant (p < 0.01). In the observation group, vision and CRT remained stable., Conclusions: This study demonstrates significant improvements in BCVA at one year in our Caucasian cohort of British ethnicity with PCV in the treatment group., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Aims: To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA)., Methods: Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes., Results: A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector., Conclusions: Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features., (© 2024. The Author(s).)

Purpose: To assess the prognostic value of subretinal (SRF) and intraretinal fluid (IRF) localizations in type 1 macular neovascularization (MNV) due to age-related macular degeneration (AMD)., Subjects: Eyes were prospectively treated with anti-vascular epithelial growth factor (anti-VEGF) intravitreal injections (IVT) according to a Pro-Re-Nata (PRN) or Treat and Extend (TAE) regimen during 24 months. A total of 211 eyes with treatment-naïve type 1 MNV secondary to AMD were consecutively included. Eyes were divided between 2 groups according to the fluid localization: presence of SRF alone (SRF group), or presence of IRF associated or not with SRF (IRF ± SRF group)., Results: At baseline the mean BCVA was 66.2 letters. SRF was present in 94.8% of eyes, IRF in 30.8%, and both in 25.6%. Data were available for 201 eyes at 12 months, and 157 eyes at 24 months. The presence of IRF at baseline was associated with lower baseline BCVA and significantly lower BCVA at 12 months (p < 0.001) and 24 months (p < 0.001). Eyes with SRF alone displayed better visual outcomes (BCVA at month 12, SRF = 74.3 letters, IRF ± SRF = 56.9 letters). In the presence of baseline IRF, fibrosis (p = 0.03) and atrophy (p < 0.001) were more frequently found at 24 months. In a multivariate model, the presence of baseline IRF was significantly associated with lower BCVA at month 12 but not at month 24., Conclusion: In type 1 MNV, the presence of baseline IRF was associated with worse visual outcomes compared to SRF alone, and more frequent atrophy and fibrosis., (© 2024. The Author(s).)

Background: Age-related macular degeneration (AMD) remains a primary cause of blindness, with neovascular AMD (nAMD) presenting particular treatment challenges. Despite anti-vascular endothelial growth factor (anti-VEGF) therapies, many patients exhibit a suboptimal response to the previously available anti-vascular endothelial growth factor (anti-VEGF) therapies. This study evaluates the efficacy and treatment interval extension of faricimab in this patient cohort., Methods: In a retrospective single-centre study at University Hospitals of Bristol and Weston, UK, nAMD patients suboptimally responsive to previous anti-VEGF therapies were switched to faricimab. Treatment started with an initiation phase of 4 monthly injections followed by a 'Treat and Extend' protocol. Outcomes included best-recorded visual acuity (BRVA), central subfield thickness (CST), the presence of retinal fluid, and treatment intervals., Results: Among 98 eyes of 79 patients, following faricimab treatment, significant reductions in CST and retinal fluid were noted, indicating decreased disease activity. While BRVA changes were not statistically significant, the anatomical improvements suggest a potential therapeutic benefit. Notably, 40% of patients achieved extended treatment intervals, reducing the treatment burden., Conclusion: Faricimab offers a promising alternative for nAMD patients with suboptimal responses to prior anti-VEGF treatments, demonstrating significant anatomical improvements and the possibility of extended dosing intervals. These findings highlight the need for prospective real-world studies to further assess faricimab's role in nAMD management and its long-term impact on patient outcomes., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objectives: To determine real-life quantitative changes in OCT biomarkers in a large set of treatment naive patients in a real-life setting undergoing anti-VEGF therapy. For this purpose, we devised a novel deep learning based semantic segmentation algorithm providing the first benchmark results for automatic segmentation of 11 OCT features including biomarkers for neovascular age-related macular degeneration (nAMD)., Methods: Training of a Deep U-net based semantic segmentation ensemble algorithm for state-of-the-art semantic segmentation performance which was used to analyze OCT features prior to, after 3 and 12 months of anti-VEGF therapy., Results: High F1 scores of almost 1.0 for neurosensory retina and subretinal fluid on a separate hold-out test set with unseen patients. The algorithm performed worse for subretinal hyperreflective material and fibrovascular PED, on par with drusenoid PED, and better in segmenting fibrosis. In the evaluation of treatment naive OCT scans, significant changes occurred for intraretinal fluid (mean: 0.03 µm 3 to 0.01 µm 3 , p < 0.001), subretinal fluid (0.08 µm 3 to 0.01 µm 3 , p < 0.001), subretinal hyperreflective material (0.02 µm 3 to 0.01 µm 3 , p < 0.001), fibrovascular PED (0.12 µm 3 to 0.09 µm 3 , p = 0.02) and central retinal thickness C0 (225.78 µm 3 to 169.40 µm 3 ). The amounts of intraretinal fluid, fibrovascular PED, and ERM were predictive of poor outcome., Conclusions: The segmentation algorithm allows efficient volumetric analysis of OCT scans. Anti-VEGF provokes most potent changes in the first 3 months while a gradual loss of RPE hints at a progressing decline of visual acuity. Additional research is required to understand how these accurate OCT predictions can be leveraged for a personalized therapy regimen., (© 2024. The Author(s).)

Background: To compare the visual outcomes of different anti-vascular endothelial growth factor (VEGF) drugs, including aflibercept, ranibizumab, and bevacizumab, in a real-world setting in Korea., Methods: We collected data from patients who received monotherapy using one of these three anti-VEGF drugs as naïve treatment after being diagnosed with neovascular age-related macular degeneration. The number of injections and visual acuity (VA) outcomes of each cohort were obtained and pairwise comparisons were performed using propensity score matching., Results: A total of 254 aflibercept, 238 ranibizumab, and 282 bevacizumab treatment-naïve eyes were included. The mean VA change at 3 years for all cohorts combined was -1.8 letters, and the mean number of injections was 9.4. In the direct comparison of the three drugs, the mean change in the VA letter score was +2.0 letters for aflibercept and -11.7 letters for bevacizumab (P < 0.001). The number of aflibercept injections was significantly higher than the number of bevacizumab injections (P = 0.002). The visual outcomes for aflibercept and ranibizumab were +4.7 letters and -1.9 letters, respectively, and comparable results were obtained (P = 0.13). The VA outcomes for ranibizumab and bevacizumab were also not significantly different (P = 0.09). The numbers of injections for aflibercept, ranibizumab, and bevacizumab were 10.8, 6.7, and 8.8, respectively. Significant differences were observed between the injection frequencies comparisons of aflibercept and ranibizumab and ranibizumab and bevacizumab (P < 0.001 and P = 0.002, respectively)., Conclusions: In the Korean clinical medical environment, which included various confounding factors, especially socioeconomic ones, the aflibercept VA outcome was significantly better than that of bevacizumab, and aflibercept injections were the most numerous. These real-world data imply that the drug effect as well as the environment in which the drug can be sufficiently used affected patient final VA scores., Competing Interests: NO authors have competing interests, (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s).)

Background: Optical coherence tomography angiography (OCTA) is a relatively new extension of Optical coherence tomography (OCT) that generates non-invasive, depth-resolved images of the retinal microvasculature which allows for the detection of various features of diabetic retinopathy., Objectives: This study aimed to detect biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal ranibizumab (IVR) by means of OCTA., Patients and Methods: This prospective interventional study was undertaken on 111 eyes of 102 naïve participants who had diabetic macular edema; enrolled patients were evaluated by taking a complete ophthalmologic history, examination and investigations by use of a pre-designed checklist involving Optical Coherence Tomography Angiography., Results: Regarding the best corrected visual acuity (BCVA) the Mean ± SD was 0.704 ± 0.158 preoperatively and 0.305 ± 0.131 postoperatively in good responder patients; and was 0.661 ± 0.164 preoperatively and 0.54 ± 0.178 postoperatively in poor responders. The central macular thickness (CMT) was 436.22 ± 54.66 μm preoperatively and 308.12 ± 33.09 μm postoperatively in good responder patients; and was 387.74 ± 44.05 μm preoperatively and 372.09 ± 52.86 μm postoperatively in poor responders. By comparing the pre injection size of the foveal avascular zone area (FAZ-A) in both groups, it found that the mean ± SD of FAZ-A was 0.297 ± 0.038 mm in good responder patients compared to 0.407 ± 0.05 mm in non-responder patients. The preoperative superficial capillary plexus (SCP) foveal vascular density (VD) was 24.02 ± 3.01% in good responder patients versus 17.89 ± 3.19% um in poor responders. The preoperative SCP parafoveal VD was 43.06 ± 2.67% in good responder patients versus 37.96 ± 1.82% um in poor responders. The preoperative deep capillary plexus (DCP) foveal VD was 30.58 ± 2.89% in good responder patients versus 25.45 ± 3.14% in poor responders. The preoperative DCP parafoveal VD was 45.66 ± 2.21% in good responder patients versus 43.26 ± 2.35% um in poor responders, this was statistically significant., Conclusion: OCTA offers an accurate measurement for VD in the macula as well as the FAZ-A which could be used to predict an early anatomical response of anti-VEGF treatment in DME., (© 2024. The Author(s).)

Purpose: To evaluate the impact of home optical coherence tomography (OCT)-guided patient management on treatment burden and visual outcomes., Methods: An interventional trial was conducted to compare frequency of treatment and visual acuity for the neovascular age-related macular degeneration patients before and during use of home optical coherence tomography over a period of 6 months. Patient adherence to regular scanning was measured by the number of scans performed per week. The characteristics of episodes of fluid recurrence and classification of typical fluid volume trajectories were performed., Results: Twenty-seven eyes (21 with diagnosis of neovascular age-related macular degeneration and one converted during the study), of 15 patients were monitored for 6 months, scanning at 6.2 times/week per eye and yielding 4,435 scans of which 91.2% were eligible for artificial intelligence-based fluid volume quantification. Total number of monitoring weeks before and during the study were 1,555 and 509. The mean (SD) number of weeks per injection before and during home OCT management were 8.0 (4.7) and 15.3 (8.5) (P = 0.004), respectively. The mean (SD) visual acuity change before and during home OCT-based management was 3.5 (12.0) letters and 0.0 (9.5) letters (P = 0.45), respectively, showing no significant impact on visual acuity., Conclusion: For the first time, remote patient monitoring with a home OCT allowed personalized management of neovascular age-related macular degeneration. This study showed significant reduction in treatment burden while maintaining stable visual acuity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Importance: While combined treatment of anti-vascular endothelial growth factor (VEGF) injections plus panretinal photocoagulation (PRP) is a common approach for treating proliferative diabetic retinopathy (PDR) in the clinical practice setting, large randomized clinical trials typically use monotherapy. Subsequently, information is limited as to whether the order of treatment when combining PRP and anti-VEGF injections for PDR affects outcomes., Objective: To compare outcomes of patients with PDR treated with PRP and subsequent anti-VEGF injections with outcomes of matched patients treated with anti-VEGF injections and subsequent PRP., Design, Setting, and Participants: This retrospective cohort study used data from January 2003 to January 2024 in the TriNetX aggregated electronic health records network, with data analysis performed in January 2024. Patients with PDR treated with PRP and anti-VEGF injections were eligible for inclusion., Exposures: Patients with new PDR diagnoses stratified by therapy with PRP and subsequent anti-VEGF injections or anti-VEGF injections and subsequent PRP., Main Outcomes and Measures: The primary outcome was the need for pars plana vitrectomy (PPV), defined by Current Procedural Terminology codes 67040 or 67113. The secondary outcome included incidence of PPV, vitreous hemorrhage (VH), or tractional retinal detachment (TRD). Relative risk ratios, relative risk differences, and 95% CIs were all calculated for univariate comparison of the cohorts and the development of primary outcomes after matching., Results: Before propensity score matching (PSM), which controlled for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR treated with PRP first and subsequent anti-VEGF injections and 1549 patients with PDR treated with anti-VEGF injections and subsequent PRP were included. Post-PSM, mean (SD) participant age was 63.0 (13.1) years in cohort 1 (PRP and subsequent anti-VEGF injection) and 63.0 (12.4) years in cohort 2 (anti-VEGF injection and subsequent PRP). Of 1377 total participants in each cohort, 641 patients (46.6%) and 663 patients (48.1%) in cohorts 1 and 2 were female, respectively. Treatment with PRP first and subsequent anti-VEGF injection was associated with higher rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55-2.27; risk difference [RD], 8.93%; 95% CI, 6.31%-11.55%; P < .001), with similar associations at 6 months, 1 year, and 3 years. Treatment with PRP and subsequent anti-VEGF injection was associated with higher rates of VH at 5 years (RR, 1.40; 95% CI, 1.09-1.80; RD, 6.47%; 95% CI, 1.66%-11.29%; P < .001) and TRD at 5 years (RR, 1.85; 95% CI, 1.35-2.53; RD, 4.31%; 95% CI, 2.10%-6.52%; P < .001), with similar findings at 6 months, 1 year, and 3 years compared with patients treated with anti-VEGF injection and subsequent PRP., Conclusions and Relevance: In this retrospective cohort study, findings suggest that patients with PDR treated with PRP first then subsequent anti-VEGF injection are more likely to undergo PPV for VH and TRD compared with matched patients treated with anti-VEGF agents first, then PRP. These findings support the need for further investigations to determine if the order of PRP and anti-VEGF injections should be considered when treating patients with PDR.

Background/objectives: Anti-VEGF treatment response in DMO has been measured by changes in the central subfield thickness (CST) and best visual acuity (BVA) outcomes at 3 months after initial treatment, termed early or limited early response (ER/LER). This study correlates LER with 12-month BVA, CST, and retinal fluid volumes quantified by a machine learning algorithm on optical coherence tomography (OCT)., Subjects/methods: The study included treatment naïve DMO patients ≥ 18 years with OCT scans at baseline (M0), M3, M6, and M12. The 220 patients were categorized as limited early responders (LER) if they had ≤ 10% CST reduction and/or < 5 ETDRS letter gain at M3. BVA, CST, and subretinal (SRF), intraretinal (IRF), and total retinal (TRF) fluid volumes quantified by a machine learning algorithm were compared between groups and across time., Results: At M12, the anatomic LER (aLER), defined solely by CST, had significantly worse BVA and CST versus the anatomic ER (aER) group (p < 0.001). Retinal fluid M12 outcomes did not significantly vary between all LER and ER groups. No significant BVA, CST, TRF, and IRF variance across time for LER was found (p > 0.1)., Conclusions: BVA and CST M12 outcomes vary by aLER/aER status indicating that CST may be a strong predictor of treatment outcomes, while retinal fluid volumes were not predicted by LER status., (© 2024. The Author(s).)

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.

To investigate long-term treatment outcomes of polypoidal choroidal vasculopathy (PCV) with classic type leakage and to compare the outcomes with those of PCV without classic type leakage. This retrospective study included 153 patients diagnosed with PCV and treated with anti-vascular endothelial growth factor (VEGF). Patients showing classic type leakage on fluorescein angiography were included in the classic type leakage group (N = 40, 26.1%), and those without classic type leakage were included in the occult group (N = 113, 73.9%). The best-corrected visual acuity (BCVA) at baseline and 24 months, changes in BCVA, incidence of fibrosis, and lesion reactivation after initial loading injections were compared between the two groups. There was no significant difference in the baseline BCVA between the classic type leakage group (mean logarithm of minimal angle of resolution 0.67 ± 0.53[Snellen equivalents = 20/93]) and the occult group (0.55 ± 0.49[20/70])(P = 0.639). In addition, the BCVA at 24 months (0.44 ± 0.53[20/55] vs. 0.38 ± 0.41[20/47])(P = 1.000), changes in BCVA (0.22 ± 0.42 improvement[2.2 lines] vs. 0.16 ± 0.36 improvement[1.6 lines]) (P = 0.366), and lesion reactivation (P = 0.787) did not differ between the two groups. The incidence of fibrosis was higher in the classic type leakage group (37.5%) than in the occult group (14.2%) (P = 0.002). Although the incidence of fibrosis was higher in PCVs with classic type leakage, the overall treatments were not significantly different between PCVs with and without classic type leakage. In addition, substantial visual improvement was noted at 24 months, suggesting that PCVs with classic type leakage can be effectively treated with anti-VEGF therapy., (© 2024. The Author(s).)

Aims: To report the outcomes of patients with neovascular age-related macular degeneration (nAMD) at Palmerston North Eye Clinic (PNEC) during 2020 and 2021, comparing time to treatment initiation based on nurse-injector availability and during COVID-19 restrictions., Methods: Data were recorded from a prospective database for patients with nAMD at PNEC. Each patient's electronic health record was reviewed to ensure the accuracy of the database and to fill in missing data points. Statistics were done using Microsoft Excel and R., Results: One hundred and fifty-six eyes were diagnosed with nAMD during the study. Mean time from referral triage to first injection was 13.08 days across the study period. Time to treatment initiation was not statistically different by level of COVID-19 restriction but there was a significant difference in first specialist appointment to injection interval when three nurse-injectors were available compared to four. The effect seemed most evident in subsequent months after reduced nurse-injector availability began., Conclusions: Despite an increase in nAMD diagnoses each year, PNEC continues to meet national guidelines for interval from referral to treatment initiation through innovations in practice. As demand for intravitreal injections continues to increase, further resourcing and research into newer agents will be required to keep wait times compliant with guidelines., Competing Interests: Nil., (© PMA.)

Background: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance., Methods: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab., Results: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 μm) and NDME (mean maximum diameter = 74.70 ± 2.86 μm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001)., Conclusions: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness., (© 2024. The Author(s).)

Purpose: To investigate the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy on post-vitrectomy macular edema (PVME) and determine the risk factors for PVME recovery., Methods: This retrospective study included 179 eyes of 179 patients who underwent pars plana vitrectomy for proliferative diabetic retinopathy and developed PVME within 3 months after surgery. Eyes were grouped according to postoperative anti-VEGF treatment., Results: Central retinal thickness (CRT) decreased significantly from baseline to 3-month follow-up in groups with (509.9 ± 157.2 μm vs. 401.2 ± 172.1 μm, P < 0.001) or without (406.1 ± 96.1 μm vs. 355.1 ± 126.0 μm, P = 0.008) postoperative anti-VEGF treatment. Best-corrected visual acuity (BCVA) did not differ between the two groups during follow-up. In the group not receiving anti-VEGF therapy, BCVA was significantly improved at 1, 2, and 3 months (P = 0.007, P < 0.001, and P < 0.001, respectively), while in the anti-VEGF group, BCVA was significantly improved at 1 and 3 months (P = 0.03 and P < 0.001). A thicker baseline CRT (β = 0.44; 95% confidence interval, 0.26-0.61; P < 0.001) was significantly associated with decreasing CRT., Conclusion: PVME tends to spontaneously resolve in the early postoperative period. The effect of anti-VEGF therapy in the first 3 months after diagnosis appears to be limited., (© 2024. The Author(s).)

Purpose: To evaluate the response of type 1 and type 2 macular neovascularization (MNV) components under anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration (AMD) using projection-resolved optical coherence tomography angiography (PR-OCTA)., Methods: This retrospective study included eyes with treatment-naïve exudative AMD treated with anti-VEGF injections under a pro re nata (PRN) protocol over 1 year. Two-dimensional MNV areas and three-dimensional MNV volumes were derived from macular PR-OCTA scans using an automated convolutional neural network. MNV was detected as flow signal within the outer retinal slab. Type 1 components and type 2 components were analyzed separately., Results: Of 17 enrolled eyes, 12 eyes were pure type 1 MNV and five eyes were type 2 MNV. In eyes with pure type 1, the total (sum of type 1 and type 2 components) MNV area and volume did not change from baseline to 6 months or 12 months (P > 0.05). In eyes with type 2 MNV, the total MNV area significantly decreased from the baseline to 6 months (P = 0.0074) and 12 months (P = 0.014). The total type 2 MNV volume also decreased from baseline visit to visits at 6 months and at 12 months, nearing statistical signifiicance (P = 0.061 and P = 0.074). In eyes with type 2 MNV, the type 1 component increased from 0.093 mm2 to 0.30 mm2 (P = 0.058), and the type 2 component decreased from 0.37 mm2 at 6 months to 0 at 12 months (P = 0.0087)., Conclusions: Type 1 and type 2 MNV may have different response under PRN anti-VEGF treatment over 1 year.

Purpose: We evaluated the features predicting visual acuity (VA) after one year in neovascular age-related macular degeneration (nAMD) patients., Methods: A total of 527 eyes of 506 patients were included. Machine learning (ML) models were trained to predict VA deterioration beyond a logarithm of the minimum angle of resolution of 1.0 after 1 year based on the sequential addition of multimodal data. BaseM models used clinical data (age, sex, treatment regimen, and VA), SegM models included fluid volumes from optical coherence tomography (OCT) images, and RawM models used probabilities of visual deterioration (hereafter probability) from deep learning classifiers trained on baseline OCT (OCT0) and OCT after three loading doses (OCT3), fluorescein angiography, and indocyanine green angiography. We applied SHapley Additive exPlanations (SHAP) for machine learning model interpretation., Results: The RawM model based on the probability of OCT0 outperformed the SegM model (area under the receiver operating characteristic curve of 0.95 vs. 0.91). Adding probabilities from OCT3, fluorescein angiography, and indocyanine green angiography to RawM showed minimal performance improvement, highlighting the practicality of using raw OCT0 data for predicting visual outcomes. Applied SHapley Additive exPlanations analysis identified VA after 3 months and OCT3 probability values as the most influential features over quantified fluid segments., Conclusions: Integrating multimodal data to create a visual predictive model yielded accurate, interpretable predictions. This approach allowed the identification of crucial factors for predicting VA in patients with nAMD., Translational Relevance: Interpreting a predictive model for 1-year VA in patients with nAMD from multimodal data allowed us to identify crucial factors for predicting VA.

Purpose: This study was carried out to investigate the effects of retinopathy of prematurity (ROP) and intravitreal antivascular endothelial growth factor (VEGF) injections on the corneal endothelium in the childhood period of patients who have had ROP., Methods: The material of comparative case-control clinical study consisted of patients followed up with ROP between February 2013 and February 2023. The eyes in the study group were divided into two subgroups consisting of those who received intravitreal anti-VEGF injections (subgroup 1) and those who were followed up only (subgroup 2). Central corneal endothelial cell density (ECD), coefficient of variation (CV), central corneal thickness (CCT), and pleomorphism parameters in the childhood period were evaluated by corneal specular microscopy and compared with age-matched healthy control subjects., Results: There were 84 eyes of 42 patients with ROP in the study group and 80 eyes of 40 healthy children in the control group. Mean CCT was significantly higher in subgroup 1 and the control group than in subgroup 2 (p = 0.037), and mean ECD was significantly higher in subgroup 2 than in subgroup 1 and the control group (p < 0.001). There was no significant difference between subgroup 1 and the control group in mean ECD and CCT values (p = 1.000 for both cases)., Conclusions: Considering that ROP patients who received intravitreal anti-VEGF injections had more advanced-stage ROP than ROP patients who were followed up only, these findings suggest that intravitreal anti-VEGF applications in ROP cases may lead to corneal endothelial parameters similar to those of healthy eyes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objective: This study evaluated the efficacy and durability of faricimab in patients with neovascular age-related macular degeneration (nAMD) who were previously treated with anti-vascular endothelial growth factor (anti-VEGF) agents., Patients and Methods: This retrospective case series was conducted at a single tertiary center in the United States. It focused on nAMD patients who transitioned to faricimab after initial anti-VEGF therapy, with a follow-up period of at least 9 months. "Complete dryness" was defined as the absence of intra- and/or subretinal fluid on optical coherence tomography. Durability was gauged by the extension of treatment intervals relative to the injection frequency of the previous agent., Results: Sixty-two eyes from 62 patients were included. Treatment interval ranged from 5 to 10 weeks; 10 (16%) patients were able to be extended by 2 or more weeks compared to their previous regimen. Median (interquartile range [IQR]) central field thickness was 310 μm (254, 376) on initiating faricimab and declined by the ninth month ( P values at 3, 6, and 9 months were 0.01, 0.02, and 0.07, respectively). Median (IQR) visual acuity at initiation of faricimab was 0.4 (0.20, 0.50) and did not change by the ninth month. Complete anatomical dryness was present in 10 (16%) eyes before switching; 90% remained dry at 9 months. Of 52 (84%) incompletely dry eyes before switching, 15% achieved complete dryness by 9 months on faricimab., Conclusions: Faricimab modestly improved the treatment intervals for a small proportion of previously treated patients on anti-VEGF therapy. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:504-509.] .

Purpose: This study aimed to investigate the potential of microRNAs (miRNAs) in tears, blood, and aqueous humor as biomarkers for predicting treatment response in wet age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy., Methods: In a single-center prospective cohort study, treatment-naïve wet AMD patients and age-matched controls were enrolled. Clinical data and miRNA levels (miR-199a-3p, miR-365-3p, miR-200b-3p, miR-195-5p, miR-335-5p, and miR-185-5p) in tears, blood, and aqueous humor were collected. Treatment response was categorized into responders and non-responders based on visual acuity and central subfield thickness. MiRNA levels were quantified using reverse-transcription PCR. Statistical analyses were performed, including ROC analysis, to evaluate predictive accuracy., Results: Dysregulated miRNA profiles were observed in wet AMD tears and blood compared to controls. Specifically, miR-199a-3p, miR-195-5p, and miR-185-5p were upregulated, while miR-200b-3p was downregulated in tears. All six miRNAs were elevated in wet AMD blood samples. Notably, responders showed higher tear expression of miR-195-5p and miR-185-5p. Combining these miRNAs yielded the highest predictive power (AUC = 0.878, p = 0.006) for anti-VEGF responders., Conclusions: Dysregulated miRNA profiles in tears and blood suggest their potential as biomarkers for wet AMD. MiR-195-5p and miR-185-5p in tears demonstrate predictive value for anti-VEGF treatment responders. This study underscores the non-invasive prediction potential of miRNA tear analysis in wet AMD treatment responses., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes., Methods: Male KK-A y mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 μg/kg) 24 h before the experiment., Results: Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1β were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca 2+ signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group., Conclusion: Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

Importance: There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy., Objective: To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME)., Design, Setting, and Participants: This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 μm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023., Interventions: Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization., Main Outcomes and Measures: Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate., Results: Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] μm for the control group vs -32 [-48 to 25] μm for the vitrectomy group; difference, 62 μm; 95% CI, -110 to 11; P = .11)., Conclusions and Relevance: Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME., Trial Registration: isrctn.org Identifier: ISRCTN59902040.

Purpose: To assess the onset, treatment frequency, and visual outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment due to secondary choroidal neovascularization (CNV) in patients with pseudoxanthoma elasticum (PXE)., Design: Retrospective cohort study METHODS: One-hundred six eyes of 53 patients with PXE were analyzed. The assessment of CNV activity relied on hemorrhage visible on funduscopy and intra- / subretinal fluid on optical coherence tomography (OCT), individually defining a shortening or extension of treatment interval. Best-corrected visual acuity (BCVA) at baseline, age at anti-VEGF therapy initiation, and BCVA-drop events at exudation onset (worsening of BCVA of 2 or more lines) were documented. Further, we assessed the number of injections during the first year and the total number of injections, the time to treatment initiation of the fellow eye, and BCVA over time., Results: During a median observation period of 77 months (IQR 49; 126) patients received a median number of 28.0 anti-VEGF-injections (IQR 9.8; 43.5). Eight patients received no injection (median age at baseline 38.1 years), 11 patients underwent anti-VEGF treatment in one eye (median age 47.2 years) and 34 patients in both eyes (median age 51.8 years). The median age at the first anti-VEGF treatment was 52.80 years (IQR 47.2-57.6). Applying Cox regression models, the median "survival" time of fellow eye until treatment initiation was 16.8 months. In the group of bilateral treated patients, the median time difference was 9.6 months (IQR 2.1- 32.4, range 0-122) The median number of injections was 5.5 per eye in the first year of treatment (IQR 3-7) and was associated with the total number of injections in the observation period (2.33, CI 1.22-3.44, P < .001). A better BCVA at the last follow-up visit was associated with a better baseline BCVA (P < .001, R 2 = 0.318) and with the absence of a BCVA drop at the onset of exudation (P = 0.035, R 2 = 0.339)., Conclusions: The results of this study indicate that anti-VEGF treatment is required for most PXE patients at a relatively young age. Once treatment in one eye is initiated, the time to fellow eye treatment is relatively short. A BCVA drop before treatment initiation is a risk factor for worse visual outcomes, suggesting that treatment is prudent before exudation affects the central retina. Given the young age of onset and intensive treatment needs, patients with PXE might particularly benefit from longer-acting anti-VEGF therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy., Methods: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis., Results: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018)., Conclusion: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

Purpose of Review: We describe the history, utilization, and series results of panretinal photocoagulation (PRP) and ranibizumab and provide an analysis of PRP and ranibizumab usage before versus after the publication of the 2-year and 5-year results of the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S trial., Recent Findings: Number of ranibizumabs performed began to increase and number of PRPs performed began to decrease in 2016. After publication of the 2-year results, there was significant negative trend in PRP services and significant positive trend in ranibizumab services (both P < 0.001). After publication of the 5-year results, there was significant negative trend in PRP services (P = 0.003). There were significant negative trends (all P < 0.001) in reimbursement factors for PRP from 2013 to 2020: average work RVU (wRVU), nonfacility physical expense RVU, facility PE RVU, malpractice RVU (MP RVU)., Summary: Both PRP and ranibizumab have undergone numerous trials comparing their efficacy to other treatment options or no treatment at all. The publication of the 2-year results of Protocol S was associated with an increase in utilization of ranibizumab and decrease in utilization of PRP, with continued decrease after the publication of the 5-year results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II., Methods: The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated., Results: One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p < 0.05). At 12 mons PMA the ocular parameters also presented no statistical difference between the two treated groups (p > 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p < 0.05) whereas there was no statistical difference revealed between the two treated groups (p > 0.05)., Conclusions: Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment., (© 2024. The Author(s).)

Deep learning techniques were used in ophthalmology to develop artificial intelligence (AI) models for predicting the short-term effectiveness of anti-VEGF therapy in patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME). 180 BRVO-ME patients underwent pre-treatment FFA scans. After 3 months of ranibizumab injections, CMT measurements were taken at baseline and 1-month intervals. Patients were categorized into good and poor prognosis groups based on macular edema at the 4th month follow-up. FFA-Net, a VGG-based classification network, was trained using FFA images from both groups. Class activation heat maps highlighted important locations. Benchmark models (DesNet-201, MobileNet-V3, ResNet-152, MansNet-75) were compared for training results. Performance metrics included accuracy, sensitivity, specificity, F1 score, and ROC curves. FFA-Net predicted BRVO-ME treatment effect with an accuracy of 88.63% and an F1 score of 0.89, with a sensitivity and specificity of 79.40% and 71.34%, respectively.The AUC of the ROC curve for the FFA-Net model was 0.71. The use of FFA based on deep learning technology has feasibility in predicting the treatment effect of BRVO-ME. The FFA-Net model constructed with the VGG model as the main body has good results in predicting the treatment effect of BRVO-ME. The typing of BRVO in FFA may be an important factor affecting the prognosis., (© 2024. The Author(s).)

Background: To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab., Methods: Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA., Result: During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period., Conclusions: Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: We characterised the relationships between monitoring frequency, ranibizumab injection need and vision in patients receiving as-needed (pro re nata; PRN) ranibizumab for macular oedema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in this post-hoc analysis of SHORE and HORIZON., Methods: Patients aged 18 years and older with macular oedema due to BRVO/CRVO were included in this analysis. Injection frequency and best-corrected visual acuity (BCVA) were evaluated by PRN injection frequency in the PRN dosing phase (months (M) 7-15) of SHORE and through 12 months of HORIZON. Prespecified PRN re-treatment criteria for each trial were based on protocol-prespecified BCVA and optical coherence tomography outcomes., Results: After the initial 7 monthly ranibizumab injections, patients in SHORE gained a mean of 18.3 letters from baseline. Patients randomised to PRN, on average, maintained these gains. However, some patients experienced additional mean gains, whereas others suffered losses (range 4.0 (95% CI 0.7 to 7.3) to -4.6 (95% CI -11.8 to 2.6) letters in patients who received 0 and 6-7 PRN injections, respectively). In BRAVO and CRUISE (lead-in trials), patients experienced mean gains from baseline to M6 (monthly dosing) of 19.3 and 15.0 letters, respectively, with gains maintained with PRN from M6 to M12. However, mean BCVA changes from baseline to M12 varied in HORIZON (range -0.4 (95% CI -2.5 to 1.6) to -3.6 (95% CI -6.2 to -1.0) letters in patients who received zero and six injections, respectively, during the preceding PRN phase of BRAVO and CRUISE)., Conclusion: The BRVO/CRVO population is heterogenous with a varied response to ranibizumab treatment., Competing Interests: Competing interests: RBB is a consultant for Rezolute, Ribomic, Unity Bio and Visgenx; receives financial support from Genentech, Inc. and NGM Bio; and holds a patent or personal financial interest in Oculinea. PAC is an advisory board member for Aerpio, Allegro, Applied Genetic Technologies Corporation, Exonate, Merck and Roche/Genentech, Inc.; co-founder of Graybug Vision; consultant for AsclepiX, Bausch + Lomb, CureVac, Graybug Vision, Novartis, Perfuse Therapeutics and Wave Life Sciences; and investigator for Aerpio, Oxford Biomedica, Regeneron, Regenxbio, Roche/Genentech, Inc. and Sanofi Genzyme. SB, CQ-R and ZH are employees of Genentech, Inc. ML indicates no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The study was designed to investigate microvascular and morphological changes in retinal vein occlusion (RVO) using multimodal imaging after intravitreal ranibizumab (IVR) with or without triamcinolone acetonide (IVTA) injections., Methods: This was a retrospective and observational study. Fifty patients (52 eyes) diagnosed with RVO were enrolled. Best corrected visual acuity (BCVA), ophthalmoscopy, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SDOCT), and optical coherence tomography angiography (OCTA) were employed sequentially both before treatment and at the last visit after treatment., Results: The mean logMAR VAs in BRVO eyes decreased significantly after treatment (P = 0.029). OCTA showed there was a significant difference in foveal avascular zone (FAZ) in BRVO eyes (P = 0.024), superificial foveal vessel density in both CRVO (P = 0.0004) and BRVO eyes (P = 0.02155). OCT showed the foveal thickness had significant differences after treatment in both CRVO (P < 0.0001) and BRVO eyes (P = 0.0001). BCVA was associated most commonly with ellipsoid zone integrity (P = 0.022). The BCVA in eyes treated with IVR and IVTA was significantly decreased compared with IVR only in BRVO group (P = 0.021). However, the combination of IVR + IVTA significantly improved intraocular pressure (IOP) compared with IVR only in BRVO group (P = 0.037)., Conclusion: Both IVR and IVR + IVTA can significantly improve the central vision, macular structure, and functions in BRVO group. Simultaneous IVR with IVTA can significantly increase BCVA compared with IVR only in BRVO group., (© 2024. The Author(s).)

To investigate biometric and refractive results in patients with type 1 retinopathy of prematurity (ROP) treated by intravitreal injection (IVI) of ranibizumab (R) and bevacizumab (B) at the corrected age of 6. This is a single-center retrospective study. Infants diagnosed with type 1 ROP and treated with IVI of either R or B as the primary therapy were included. Data on axial length, anterior chamber depth (ACD), and lens thickness (LT) were obtained using A-scan ultrasound. Cycloplegic refraction, keratometry (K), and best-corrected visual acuity were also documented. Additionally, optical coherence tomography angiography was performed to assess the foveal avascular zone and the density of superficial and deep vessels. We analyzed the structural and functional differences between the 2 groups and compared them with findings from a previous study conducted when these children were between the ages of 1 and 3. The study included 60 eyes from 34 patients, with 34 eyes receiving B and 26 eyes receiving R injections for ROP. In biometric outcomes, there was still a deeper ACD (3.36 ± 0.24 mm in the B group; 3.52 ± 0.21 mm in the R group) and thinner LT (3.63 ± 0.16 mm in the B group; 3.53 ± 0.12 mm in the R group) in the R group, as previously reported at the age of 3. In the refractive aspect, the eyes treated with B had higher myopia at the ages of 1 and 3; however, at the age of 6, refractive errors did not differ significantly between the 2 groups. At the corrected age of 6, the eyes treated with IVI of R were associated with deeper ACD and thinner LT. Interestingly, the emmetropization process resulted in a similar incidence of high myopia at the age of 6, which was different from the outcomes observed at younger ages., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: In Medicare Advantage (MA), step therapy for physician-administered drugs is an approach to lowering drug spending. The impact of step therapy in MA on prescribing behavior and the magnitude of any changes has not been analyzed., Objective: To evaluate the impact of step therapy on macular degeneration drug prescribing patterns for 3 large MA insurers., Design, Setting, and Participants: This was a retrospective encounter-based analysis using 20% nationally representative MA outpatient and carrier encounter records for 2017 to 2019. Participants were MA beneficiaries who were 65 years or older and had received a macular degeneration drug administration. Macular degeneration drug administrations for beneficiaries of MA Aetna, Humana, and UnitedHealthcare (UHC) insurers were assessed. Humana implemented macular degeneration step therapy in 2019, setting bevacizumab as the plan-preferred drug, and aflibercept and ranibizumab as the plan-nonpreferred drugs. Aetna and UHC, which did not implement macular degeneration step therapy, served as the control group. Data analyses were performed from May 2024 to December 2024., Exposures: A macular degeneration drug administration subject to a step therapy policy., Main Outcome and Measures: A binary indicator of whether the drug administered was bevacizumab. Linear probability models and a difference-in-differences framework were used to quantify changes in prescribing patterns before and after the introduction of step therapy for MA insurers that did and did not implement step therapy. To empirically measure the impact of step therapy, the first administration of a treatment episode was assessed, followed by switching patterns., Results: A total of 18 331 MA beneficiaries, 21 683 treatment episodes, and 171 985 drug administrations were included across the control and treatment groups. The difference-in-differences regressions found a 7.8% (95% CI, 4.9%-10.7%; P < .001) greater probability of being prescribed bevacizumab for the first administration due to step therapy. The predicted probabilities of preferred-drug administration in the treatment group increased from 0.61 to 0.70 between the periods before and after step therapy implementation for the first administration. Step therapy was not significantly associated with an increased rate of medication switching (hazard ratio, 0.86; 95% CI, 0.71-1.06; P = .15)., Conclusions and Relevance: The findings of this retrospective encounter-based analysis indicate that step therapy is associated with a greater probability of prescribing the plan-preferred drug for the first administration. The analysis failed to find a statistically significant greater rate of medication switching within a treatment episode. Step therapy changed macular degeneration prescribing patterns, but step therapy alone did not transition all administrations to the plan-preferred drug.

Importance: Anti-vascular endothelial growth factor (VEGF) intravitreal injections, a mainstay of treatment for many retinal diseases to optimize visual outcomes, have been included in prior authorization (PA) initiatives. However, if clinicians are extremely accurate in their use of anti-VEGF medications, such administrative burdens may need reconsideration., Objective: To quantify PA for anti-VEGF medications (aflibercept, ranibizumab, and bevacizumab) that were approved and determine associated administrative burdens experienced by retina practices., Design, Setting, and Participants: Prospective multicenter quality improvement study conducted from January 2022 through June 2022, and participants were 9 private retina practices across the US., Main Outcomes and Measures: Overall rate of approval of PA requests, reasons for requesting PA, and overall rate of delay of care resulting from PA procedures., Results: In total, 2365 PA requests were recorded, 2225 of which met inclusion criteria. Overall, 2140 (96.2%) requests were approved. The most common reason for requesting PA, at 64% (1423 of 2225 requests), was reauthorization for a previously utilized medication. Of the 2140 approvals, 59.6% (1277) resulted in a delay in care greater than 24 hours, and 40% (863) were given on the date of service. In a granular analysis of a subset of delayed approvals, 23.9% (173 of 725) were approved within 1 day, 15.9% (115 of 725) were approved within 2 to 3 days, 21.5% (156 of 725) were approved within 4 to 7 days, 26.3% (191 of 725) were approved within 8 to 31 days, and 12.4% (90 of 725) were approved within more than 31 days. Overall, PA denial for step therapy was 2.9% (65 of 2225) of requests and uncovered diagnoses was 0.9% (20 of 2225) of requests. The median staff time spent to obtain a single PA was 100 (range, 0-200) minutes., Conclusions and Relevance: In this study, PA requests were almost always approved but led to a delay in patient care in most patients. The current study suggests that the PA process may not be effective for retina specialists if these results can be generalized to other practices in the US and if less burdensome and less costly approaches could result in similar approval rates. Potential short-term solutions may include eliminating the PA process for bevacizumab and reauthorizations for established patients.

Purpose: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements., Methods: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas., Results: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material., Conclusions: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Purpose: To report the treatment response of a case of tubercular choroidal granuloma and subretinal abscess with intravitreal anti-vascular endothelial growth factor (anti-VEGF) and moxifloxacin., Method: Retrospective interventional case report., Results: A 34-year-old man presented with bilateral choroidal granuloma and subretinal abscess in one eye. He was a known case of spinal tuberculosis and was on anti-tubercular therapy. Patient was successfully treated with intravitreal injection of anti-VEGF and moxifloxacin., Conclusion: Intravitreal anti-VEGF and moxifloxacin combination may be beneficial in tubercular choroidal granuloma and subretinal abscess.

Purpose: To explore the long-term effect of diabetic retinopathy on response to anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration-associated type 1 macular neovascularization (MNV) using optical coherence tomography angiography (OCTA)., Methods: A total of 45 eyes with exudative neovascular age-related macular degeneration (nAMD) with type 1 MNV were included in the analysis. Among them, 24 eyes of 24 patients had no history of diabetes mellitus (DM) in their anamnesis and were assigned to the Not Diabetic group; 21 eyes of 21 patients had mild diabetic retinopathy and were included in the Diabetic group. We considered the following outcome measures: (1) best-corrected visual acuity changes; (2) central macular thickness; (3) MNV lesion area; and (4) MNV flow area. The OCTA acquisitions were performed at the following time points: (1) baseline visit, which corresponded to the day before the first injection; (2) post-loading phase (LP), which was scheduled at 1 month after the last LP injection; and (3) 12-month follow-up visit., Results: All morphofunctional parameters showed a significant improvement after the LP and at the 12-month follow-up visit. Specifically, both the Diabetic group and the Not Diabetic group displayed a significant reduction of MNV lesion areas at both the post-LP assessment (P = 0.026 and P = 0.016, respectively) and the 12-month follow-up (P = 0.039 and P = 0.025, respectively). Similarly, the MNV flow area was significantly decreased in both the Diabetic group and the Not Diabetic group at the post-LP assessment (P < 0.001 and P = 0.012, respectively) and at the 12-month follow-up (P = 0.01 and P = 0.035, respectively) compared to baseline. A smaller reduction in the MNV lesion area was observed in the Diabetic group at both the post-LP evaluation (P = 0.015) and the 12-month follow-up (P = 0.032). No other significant differences were found between the groups for the other parameters (P > 0.05)., Conclusions: Our results indicated that the Diabetic group exhibited a smaller reduction in MNV lesion area after 12 months of anti-VEGF treatment. This highlights the importance of considering diabetic retinopathy as a potential modifier of treatment outcomes in nAMD management, with DM serving as a crucial risk factor during anti-angiogenic treatment.

Introduction: SB11 (Byooviz™; Samsung Bioepis Co., Ltd.) is a ranibizumab (Lucentis ® ; Genentech, Inc.) biosimilar targeting vascular endothelial growth factor A for the treatment of retinal diseases. The pre-filled syringe (PFS) presentation of SB11 offers an alternative administration method to the vial, with the potential for enhanced safety and efficient syringe preparation. The objective of this study was to assess the ability of healthcare professionals (HCPs) to follow the instructions for use to prepare and administer SB11 PFS intravitreal (IVT) injections to patients with neovascular age-related macular degeneration (nAMD) or macular edema secondary to retinal vein occlusion (RVO)., Methods: This study was an open-label, single-arm, single-dose clinical study to evaluate the usability of the SB11 PFS in patients with nAMD or macular edema secondary to RVO. Four HCPs prepared and administered 0.5 mg SB11 PFS IVT injections to 34 patients. Product use task completion (12 tasks in total) was assessed by independent observers. Safety was assessed up to 7 days after injection of the investigational product., Results: A total of 34 patients were enrolled and completed the study. All 12 tasks were successfully completed in 34 (100%) patients without a use-related failure. Most patients (32 patients, 94.1%) experienced no adverse events (AEs), whereas 2 (5.9%) patients experienced three treatment-emergent AEs (TEAEs) which were mild to moderate in severity. There were no severe or serious TEAEs reported during the study., Conclusions: This study showed that HCPs were able to successfully prepare and administer the SB11 PFS via IVT injection. No unexpected safety issues were identified. The SB11 PFS is a promising alternative for therapeutic administration of SB11 in patients with retinal disease., Trial Registration: ClinicalTrials.gov identifier NCT06176963; EudraCT number 2021-003566-12., (© 2024. The Author(s).)

Purpose: To assess the suitability of machine learning (ML) techniques in predicting the development of fibrosis and atrophy in patients with neovascular age-related macular degeneration (nAMD), receiving anti-VEGF treatment over a 36-month period., Methods: An extensive analysis was conducted on the use of ML to predict fibrosis and atrophy development on nAMD patients at 36 months from start of anti-VEGF treatment, using only data from the first 12 months. We use data collected according to real-world practice, which includes clinical and genetic factors., Results: The ML analysis consistently identified ETDRS as a relevant factor for predicting the development of atrophy and fibrosis, confirming previous statistical analyses. Also, it was shown that genetic variables did not demonstrate statistical relevance in the prediction. Despite the complexity of predicting macular degeneration, our model was able to obtain a balance accuracy of 63% and an AUC of 0.72 when predicting the development of atrophy or fibrosis at 36 months., Conclusion: This study demonstrates the potential of ML techniques in predicting the development of fibrosis and atrophy in nAMD patients receiving long-term anti-VEGF treatment. The findings highlight the importance of clinical factors, particularly ETDRS (early treatment diabetic retinopathy study) visual acuity test, in predicting these outcomes. The lessons learned from this research can guide future ML-based prediction tasks in the field of ophthalmology and contribute to the design of data collection processes., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

This retrospective study aimed to investigate the progression of central retinal vein occlusion (CVO) prior to treatment initiation and its impact on prognosis. Of the 54 studied eyes with acute CVO, the average logMAR visual acuity (VA) at the initial visit was 0.65 ± 0.49 with an average time to treatment of 14.9 ± 14.5 days. VA at the initial treatment was identified as a stronger predictor of VA at the final visit compared to VA at the first visit or other factors. Patients who received treatment more than 28 days after the initial visit experienced a significant decline in VA compared to those treated within 28 days (0.21 ± 0.35 vs. 0.04 ± 0.13, p = 0.006). Additionally, patients who were treated between 15 and 28 days showed a greater decrease in VA compared to those treated within 14 days (0.12 ± 0.46 vs. 0.018 ± 0.02, p = 0.026). These findings from the current retrospective analysis suggesting that there is a possibility of VA decline at the initial treatment associating with worse prognosis even when treatment is administered within a month should be further investigated in the prospective study. Also, it may be crucial to consider frequent monitoring of acute CVO patients for initiating treatment at the optimal timing., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of the subthreshold micropulse laser (SMPL) combined with ranibizumab in treating diabetic macular edema (DME). Methods: This was a prospective randomized controlled study. Patients diagnosed with DME in the Ophthalmology Department of Beijing Hospital were enrolled from January 2020 to December 2022. Patients were randomized in a ratio of 1∶1 using a table of random numbers into the ranibizumab monotherapy group and the SMPL combined with ranibizumab therapy group. We compared the changes of best-corrected visual acuity, central macular thickness measured by optical coherence tomography and optical coherence tomography angiography parameters, including the vessel density of the superficial and deep capillary plexus (DCP), foveal avascular zone size and peripapillary vessel density, at baseline, 6 and 12 months after the treatment. After 12 months of follow-up, fundus fluorescein angiography results, adverse events, and the number of injections or laser therapies were recorded. The Fisher's exact test and group t -test were used for statistical analysis. Results: Seventy-two patients (72 eyes) were enrolled, with a mean age of (61.1±8.2) years. Patients in the combination therapy group included 19 males and 17 females, while patients in the ranibizumab monotherapy group were 17 males and 19 females. There was no statistically significant difference in baseline characteristics between the two groups ( P >0.05). A significant improvement in best-corrected visual acuity was shown in both groups at 6 and 12 months [(58.5±12.9) and (58.2±12.2) ETDRS letters in the combination therapy group, and (63.3±13.1) and (63.8±12.5) ETDRS letters in the ranibizumab monotherapy group]. A significant reduction in central macular thickness was shown in both groups at 6 and 12 months [(451.0±185.5) and (380.4±159.3)μm in the combination therapy group, and (387.5±135.5) and (372.8±146.1)μm in the ranibizumab monotherapy group]. However, there was no significant difference between groups at each timepoint (all P >0.05). At 12 months, the vessel density of the superficial capillary plexus showed no statistical difference compared to the baseline value in each group or between groups (42.6%±5.9% in the ranibizumab monotherapy group and 42.2%±5.5% in the combination therapy group, P >0.05). The vessel density of the DCP in the combination therapy group significantly increased to 47.5%±5.6% at 12 months, significantly different from that in the ranibizumab group (43.4%±5.1%; P <0.05). The foveal avascular zone size in the ranibizumab monotherapy group reduced to (0.32±0.13) mm 2 , significantly different from that in the combination therapy group [(0.34±0.16) mm 2 ] at 12 months ( P <0.05). Patients in the ranibizumab monotherapy group received (7.3±2.5) intravitreal injections, while patients in the combination therapy group received 3 injections. No unfavorable outcomes on fundus fluorescein angiography or systemic or topical severe adverse events were observed during the follow-up. Conclusions: The SMPL combined with intravitreal ranibizumab injections was effective and safe in treating DME patients. The combination treatment significantly reduced the number of injections and improved the vessel density of the DCP and macular ischemia, compared to the ranibizumab monotherapy.

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment., (© 2024. The Author(s).)