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AimTo show the characteristics and outcomes of patients with neovascular age-related macular degeneration (nAMD) who had extended remission (ER) while on a pro re nata (PRN) treatment protocol.MethodsThis was a retrospective case-control study of a consecutive series of patients with nAMD treated with a PRN antivascular endothelial growth factor (anti-VEGF) drug regimen. ER was defined as the absence of haemorrhage, intraretinal/subretinal fluid on optical coherence tomography and leakage on fluorescein angiography for 52 weeks after cessation of anti-VEGF therapy. Matching patients with nAMD who did not achieve ER were included as control group. Cox regression analysis was fitted to identify predictors of time to achieve ER and time to recurrence. A logistic regression analysis of baseline characteristics was used to identify predictors of achieving ER.ResultsOf 830 eyes treated with anti-VEGF monotherapy, 77 (9.2%) eyes achieved ER during a median follow-up of 236 weeks (range 70-525 weeks). Cox regression analysis showed that ER was achieved earlier in eyes with isolated intraretinal fluid (HR, 2.05; 95% CI 1.929 to 4.520; p=0.045) at presentation. Logistic regression analysis showed that type 3 choroidal neovascularisation (OR, 0.090; 95% CI 0.021 to 0.382; p=0.001), thinner choroid (OR, 0.993; 95% CI 0.988 to 0.998; p=0.004) and absence of macular atrophy (OR, 0.233; 95% CI 0.065 to 0.839; p=0.026) at baseline increased the likelihood of achieving ER.ConclusionER is achievable in 9.2% of patients under PRN therapy for nAMD. At presentation with nAMD, anatomical features on retinal imaging may predict the likelihood of achieving ER and a shorter time to achieve ER.

AimTo review the longitudinal changes of outer retinal tubulations (ORTs) in wet age-related macular degeneration (AMD) and their response to anti-vascular endothelial growth factor (VEGF) therapy by spectral-domain optical coherence tomography (SD-OCT), and to correlate these observations with disease activity, presence or absence of fluid, and patients' demographics.MethodsRetrospective study of wet AMD eyes treated with anti-VEGF agents and showing ORTs on SD-OCT, and the patients' fellow eye with wet AMD but without ORTs.ResultsFifty-one wet AMD eyes from 31 patients diagnosed and treated for wet AMD were included in the review and analysis of data; 33 eyes showed ORTs at baseline, while 18 fellow eyes had no ORTs. During a median follow-up treatment period of 11 months, 23 eyes had stable ORTs and 10 eyes had ORT changes. Among the 10 eyes with ORTs changes, ORTs collapsed during anti-VEGF treatment in 5 eyes but then reappeared within 12 months after stopping treatment. In two eyes, ORTs increased in size during anti-VEGF treatment, while in two other eyes ORTs collapsed without any treatment. In a single eye, ORTs collapsed within 10 months of no treatment and did not reappear upon recurrence of fluid. Eyes with ORTs tended to have lower visual acuity than eyes with no ORTs due to greater disruption of the external limiting membrane in the fovea.ConclusionsORTs documented by SD-OCT may exhibit multiple types of longitudinal changes, such as collapse, recurrence or enlargement, which could be associated with anti-VEGF treatment or spontaneous. Some ORTs may have a vascular component or may be vascular in nature, considering their response to anti-VEGF treatment, while other ORTs are likely composed only of degenerating photoreceptor cells and may collapse independently from anti-VEGF treatments.

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.)

Aims: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV)., Methods: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients., Results: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006)., Conclusion: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To evaluate the efficacy and safety of intravitreal triamcinolone acetonide (TA) injection at the end of emergency surgery for open globe injury (OGI) to suppress traumatic proliferative vitreoretinopathy (TPVR)., Methods: A single-centre, participant-masked, prospective, randomised controlled clinical trial. A total of 68 globe rupture patients with zone III were randomised to the control group (n=34) or the TA group (n=34) in 1:1 allocation ratio. Patients were treated with 0.1 mL TA in the TA group and 0.1 mL balanced salt solution in the control group at the end of emergency surgery. The primary outcome was the assessment of TPVR during vitrectomy 10±3 days later. Secondary outcomes included visual acuity (VA), retinal attachment rate, macular attachment rate, proliferative vitreoretinopathy (PVR) recurrent rate, side effects 6 months after vitrectomy., Results: During vitrectomy, the TPVR grade of the control group was significantly more severe than the TA group (p=0.028). The TPVR score was significantly better in the TA group (9.30±0.82) than in the control group (6.44±1.06) (p=0.036). The final VA improved in 23 eyes (92%) in the TA group and in 14 eyes (63.64%) in the control group (p=0.008). The retinal attachment rates were 88% and 63.64% in the TA and control group, respectively (p=0.049). The two groups showed no significant difference in macular repositioning and PVR recurrent rate (p=0.215, 0.191). Temporary intraocular pressure elevation occurred in one eye in the TA group after emergency surgery., Conclusions: Early intravitreal TA injection for OGI effectively reduces TPVR, increases surgical success and improves visual prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To predict antivascular endothelial growth factor (VEGF) treatment requirements, visual acuity and morphological outcomes in neovascular age-related macular degeneration (nAMD) using fluid quantification by artificial intelligence (AI) in a real-world cohort., Methods: Spectral-domain optical coherence tomography data of 158 treatment-naïve patients with nAMD from the Fight Retinal Blindness! registry in Zurich were processed at baseline, and after initial treatment using intravitreal anti-VEGF to predict subsequent 1-year and 4-year outcomes. Intraretinal and subretinal fluid and pigment epithelial detachment volumes were segmented using a deep learning algorithm (Vienna Fluid Monitor, RetInSight, Vienna, Austria). A predictive machine learning model for future treatment requirements and morphological outcomes was built using the computed set of quantitative features., Results: Two hundred and two eyes from 158 patients were evaluated. 107 eyes had a lower median (≤7) and 95 eyes had an upper median (≥8) number of injections in the first year, with a mean accuracy of prediction of 0.77 (95% CI 0.71 to 0.83) area under the curve (AUC). Best-corrected visual acuity at baseline was the most relevant predictive factor determining final visual outcomes after 1 year. Over 4 years, half of the eyes had progressed to macular atrophy (MA) with the model being able to distinguish MA from non-MA eyes with a mean AUC of 0.70 (95% CI 0.61 to 0.79). Prediction for subretinal fibrosis reached an AUC of 0.74 (95% CI 0.63 to 0.81)., Conclusions: The regulatory approved AI-based fluid monitoring allows clinicians to use automated algorithms in prospectively guided patient treatment in AMD. Furthermore, retinal fluid localisation and quantification can predict long-term morphological outcomes., Competing Interests: Competing interests: UMS-E: Scientific consultancy for Genentech, Novartis, Roche, Heidelberg Engineering, Kodiak, RetInSight, Topcon. HB: Grants from Heidelberg Engineering and Apellis. Speaker fees from Bayer, Roche and Apellis. DB: Scientific consultancy, grants and speaker fees for Bayer and Novartis. GSR: Grant from RetInSight.VM, OL, PF, MBN: No financial support or conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

AimTo evaluate the efficacy of a standardised combination therapy for clinically significant diabetic macular oedema using bevacizumab injections followed by navigated laser photocoagulation to stabilise retinal thickness.MethodsIn this pilot study we retrospectively reviewed charts and imaging of 23 eyes treated with the standardised combination regimen. Eyes initially received monthly bevacizumab injections, followed by navigated laser photocoagulation when central retinal thickness (CRT) was

Purpose: Post hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment and to assess SHRM thickness and thickness variability as a potential biomarker of visual outcomes in patients with neovascular age-related macular degeneration (nAMD)., Methods: Optical coherence tomography images from the brolucizumab (n=700) and aflibercept (n=696) arms were analysed for the maximum SHRM thickness across the macula over 96 weeks. In a pooled treatment-agnostic analysis, the effect of week 12 SHRM thickness and SHRM thickness variability on best-corrected visual acuity (BCVA) through week 96 were also assessed., Results: Brolucizumab was associated with numerically higher percentage reductions from baseline in SHRM thickness versus aflibercept in all patients (week 96: 54.4% vs 47.6%, respectively) and also in the matched subgroups with disease activity at week 16 (week 96: 51.6% vs 33.8%, respectively). In eyes with lower SHRM measurements at week 12, mean BCVA gains from baseline were higher at week 96 (<200 µm, +6.47 Early Treatment Diabetic Retinopathy Study letters; ≥200 µm, +3.10 letters). Eyes with the lowest SHRM thickness variability from week 12 to week 96 showed the greatest mean BCVA gains from baseline (week 96: <12 µm, +7.42 letters; >71 µm, -2.95 letters)., Conclusions: In HAWK and HARRIER, greater reductions in maximum SHRM thickness from baseline were observed with brolucizumab compared with aflibercept. Furthermore, the data suggest that SHRM thickness postloading and SHRM thickness variability over time are biomarkers for visual outcomes in patients with nAMD., Competing Interests: Competing interests: SS: Consultant for Novartis, Allergan, Amgen, Apellis, Iveric, Nanoscope, Astellas, Jannsen, Roche/Genentech, Oxurion, Regeneron, 4DMT, Optos, Centervue, Heidelberg, Notal, Biogen, Boehringer Ingelheim. Speaker fees from Optos, Carl Zeiss Meditec, Nidek, Topcon, Novartis. DS: Consultant for Amgen, Bayer, Genentech, Iveric Bio, Novartis, Optovue; Research grants from Amgen, Boehringer, Genentech, Heidelberg, Optovue, Regeneron, Topcon; Speaker fees from Optovue. AMK: Consultant: Abbvie, Adverum, AGTC, Aldebaran Therapeutics, Alimera, Apellis, Arrowhead, Asclepix, Aviceda, Bausch and Lomb, Broadwing Bio, Cholgene, 4DMT, Eyepoint, Frontera Therapeutics, Gemini, Genentech, Graybug, Gyroscope, Iveric Bio, Janssen, Kartos Therapeutics, Kato Pharma, Kodiak, Kriya Therapeutics, Ocular Therapeutix, Oculis, Ocuterra, Opthea, Oxurion, Nanoscope, Novartis, Perfuse, PolyPhotonix, Protagonist, Ray Therapeutics, Recens Medical, Regeneron, Retrotope, Regenxbio, RevOpsis, Roche, Stealth, Thea, Unity Bio, Vanotech, Vial. Research Support: Adverum, Alkahest, Annexon, Apellis, Asclepix, 4DMT, Gemini, Genentech, Inc., Graybug Vision, Gyroscope, Iveric Bio, Kodiak, Neurotech, NGM Bio, Ocular Therapeutix, Oculis, Ocuterra, Opthea, Oxurion, Novartis, Recens Medical, Regenxbio, Roche, Unity Bio. Speaker: Abbvie, Apellis, Bausch and Lomb, Genentech, Novartis. Equity: Aviceda, Recens Medical, Retrotope, RevOpsis, PolyPhotonix. RT: Alcon, Apellis, Bausch and Lomb, FCI, Iveric Bio, Moria, Zeiss, Optovue, Topcon, Alimera, Allergan, Bayer, Novartis, Oculis, Genentech, Roche, Thea. AAC: Consultant: Novartis, Bayer, Roche, Alcon, Apellis; Speaker fees: Novartis, Bayer, Roche, Alcon, Apellis. Nidek; Grant funding: Novartis, Bayer, Roche. IS, KG: Employee of Novartis Pharma AG. DTW: Consultant for Abbvie, Alcon, Apellis, Bayer, Bausch Health, Biogen, Boehringer Ingelheim, Novartis, Ripple Therapeutics, Roche, Topcon, Zeiss. Research grants from Novartis, Roche., (© 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.)

Aims: To evaluate the effect of an intraoperative dose of intravitreal bevacizumab (Avastin) on surgical success following trabeculectomy with mitomycin-C (MMC) over 12 months., Methods: A single centre, parallel, double-blinded randomised, placebo-controlled trial recruiting patients requiring trabeculectomy for progressing glaucoma. Patients were randomised to intravitreal bevacizumab or placebo., Main Outcome Measure: The primary outcome of treatment success was defined by 'complete success' when intraocular pressure (IOP) remained less than a predefined target IOP without the requirement of topical medication, or 'qualified success' where topical medication was required to meet the predefined target IOP threshold. Secondary outcomes included the need for subsequent IOP-lowering interventions, and structural parameters associated with bleb function., Results: From 131 patients randomised to bevacizumab (n=65) or placebo (n=66), 128 patients completed 12 months of follow-up (98%). At 12 months, success rates were higher in the bevacizumab group (complete success: 94% vs 83%; p=0.015; qualified success: 98% vs 90%; p=0.033). Within the placebo group, the requirement for topical therapy was higher at 6 months (p=0.045) and 12 months (p=0.045), and the requirement for bleb needling was higher at 1 month (p=0.035). Blebs within the bevacizumab group were larger at 1 month (p<0.001) and demonstrated less vessel inflammation (p<0.0001)., Conclusion: Bevacizumab given as a single intravitreal dose during trabeculectomy with MMC resulted in improved surgical success as 12 months. Furthermore, bevacizumab was associated with a significant reduction in the need for additional medication or further surgery to achieve target IOP. Bevacizumab was also associated with larger blebs that were less inflamed and required fewer subsequent interventions., Trial Registration Number: ACTRN12614000375651., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: In experimental studies, intravitreally applied antibodies against epidermal growth factor (EGF), EGF family members (amphiregulin, neuregulin-1, betacellulin, epigen, epiregulin) and against the EGF receptor (EGFR) were associated with a reduction in lens-induced axial elongation and decrease in physiological eye elongation in guinea pigs and in non-human primates. Here, we investigated the intraocular tolerability and safety of a fully human monoclonal IgG2-antibody against EGFR, already in clinical use in oncology, as a potential future therapeutic approach for axial elongation in adult eyes with pathological myopia., Methods: The clinical, monocentre, open-label, multiple-dose, phase-1 study included patients with myopic macular degeneration of stage 4, who received intravitreal injections of panitumumab in various doses and in intervals ranging between 2.1 months and 6.3 months., Results: The study included 11 patients (age:66.8±6.3 years), receiving panitumumab injections in doses of 0.6 mg (4 eyes; 1×1 injection, 3×2 injections), 1.2 mg (4 eyes; 1×1 injection, 2×2 injections, 1×3 injections) and 1.8 mg (3 eyes; 1×1 injection, 2×2 injections), respectively. None of the participants showed treatment-emergent systemic adverse events or intraocular inflammatory reactions. Best-corrected visual acuity (1.62±0.47 logarithm of the minimal angle of resolution (logMAR) vs 1.28±0.59 logMAR; p=0.08) and intraocular pressure (13.8±2.4 mm Hg vs 14.3±2.6 mm Hg; p=0.20) remained unchanged. In nine patients with a follow-up of >3 months (mean:6.7±2.7 months), axial length did not change significantly (30.73±1.03 mm vs 30.77±1.19 mm; p=0.56)., Conclusions: In this open-labelled, phase-1 study with a mean follow-up of 6.7 months, panitumumab repeatedly administered intravitreally up to a dose of 1.8 mg was not associated with intraocular or systemic adverse effects. During the study period, axial length remained unchanged., Trial Registration Number: DRKS00027302., Competing Interests: Competing interests: JBJ and SP-J: Patent holder with Biocompatibles UK (Franham, Surrey, UK) (Jonas JB, Wallrapp C, Geigle P, Panda-Jonas S, Thoemes E): (Title: Treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and / or anti-angiogenic factor; Patent number: 20120263794), and European patent EP 3 271 392, JP 2021-119187, and US 2021 0340237 A1: Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia; Patent application: European patent application: WO 2021/198369 A1; PCT/EP2021/058500: Agents for the use in the therapeutic or prophylactic treatment of retinal pigment epithelium associated diseases., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To evaluate the safety and effectiveness of intravitreal dexamethasone (DEX) implant in patients with active uveitis due to ocular toxocariasis (OT)., Methods: Seventy-eight patients with OT were recruited in this retrospective study, including 51 patients in DEX group treated with intravitreal DEX implant and 27 patients in control group without intervention. The reduction of vitreous haze scores (VHS), the best-corrected visual acuity (BCVA) changes, intraocular pressure (IOP) and cataract progression and formation were recorded at baseline (V0), 1 (V1), 3 (V3) and 6 months (V6) after treatment in DEX group, and V0 and V6 in control group., Results: There was no change in VHS and BCVA in control group between V0 and V6. Better VHS (p=0.001) and BCVA (p=0.022) was achieved in DEX group; the rate of VHS=0 was 0%, 67.4%, 42.9% and 44.9% at V0, V1, V3 and V6, respectively (p＜0.001), and the mean BCVA was improved from logMAR 1.5±0.9 to 1.2±0.9 at V1, 1.4±1.0 at V3 and 1.4±1.2 at V6. A favourable BCVA at V1 was associated with older age (p=0.038) and uninvolved macula (p=0.000) in DEX group. No significant difference in IOP elevation ≥10 mm Hg, cataract progression and formation between groups. More eyes needed retinal surgery in control group (p<0.001)., Conclusions: This was the first study to investigate use of intravitreal DEX implant in OT patients, which can efficiently reduce ocular inflammation and improve BCVA in macular uninvolved patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes., Methods: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool., Results: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections., Conclusion: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide., Competing Interests: Competing interests: JZ-V is a grant holder for Novartis Pharmaceuticals, Bayer and Allergan, and a consultant for Novartis Pharmaceuticals, Bayer, Allergan, Alcon, Alimera Sciences, Bausch and Lomb, Brill Pharma, DORC, Preceyes, Roche, Topcon, and Zeiss. Laia Gomez-Baldo is an employee of Novartis. SDZ, CC, SApostolopoulos and AM are employees of RetinAI., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe., Methods: The study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOP-lowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation., Results: Six hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seventy-three eyes (64.6% of 113 phakic) required cataract surgery during follow-up. Mean VA increased from a baseline of 52.2 letters to 57.1 letters at month 36, with improvement observed up to month 48. Supplementary therapies were given in 43.7% of eyes. When classified by length of cDMO less than or greater than the median duration those with a shorter history experienced greater VA gains than those with a longer history., Conclusion: This study confirms the favourable, long-term benefit-to-risk profile of the FAc implant in eyes with cDMO, with an additional benefit in patients when this therapy is administered earlier., Competing Interests: Competing interests: RK - Reports grants from Chengdu Kanghong; grants, personal fees, and non-financial support from Alimera, Bayer, Novartis and Roche, personal fees and non-financial support from Allergan outside the submitted work. TP—speaker honoraria and advisory board member from Alimera Sciences, Allergan, Bayer, Novartis, Boehringer-Ingelheim and Roche. FK—reports a commercial relationship with Alimera Sciences. SRT—reports financial relationships with GlaxoSmithKline and Novartis, and speaker honoraria, advisory boards and travel grants from Alimera Sciences, Allergan, Bayer, GlaxoSmithKline, Novartis and Santen. JPCdS—reports financial support from Alcon, Alimera Sciences and Novartis. LH—statistical consultant to Genentech, Recens Medical, Polyphotonix, and Alimera Sciences. CB—advisory board member for Alimera Sciences, Bayer Novartis, Roche, Janssen, Boehringer-Ingelheim. UC—a speaker and advisory board member for Alimera Sciences, an advisory board member for Allergan, Bayer, Novartis and Roche, and has received grants from Bayer, Novartis and Roche., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD)., Methods: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models., Results: Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference -6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference -75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference -41.9 um; p=0.001) and year 2 (difference -43.3 um; p=0.001)., Conclusions: In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones., Trial Registration Number: ClinicalTrials.gov NCT00593450., Competing Interests: Competing interests: ED is a consultant to Novartis International AG. MGM serves on a data and safety monitoring committee for Genentech/Roche. GJ has a consultancy relationship with Alcon/Novartis, Genentech/Roche, Neurotech, EyePoint Pharmaceuticals and Adverum. G-SY is a consultant to Chengdu Kanghong Biotech, Ziemer Ophthalmic Systems AG and Synergy Research., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To describe the clinical impact of external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption and subretinal fluid (SRF) seen on optical coherence tomography (OCT) in eyes with vitreomacular traction (VMT) without macular hole (MH) in the Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole study., Methods: Phase 3b randomised double-blind sham-controlled multicentre study including 144 eyes with VMT without MH. Eyes were randomised to receive a single intravitreal injection of ocriplasmin or sham injection and were followed for 24 months. Eyes were analysed for presence, course and clinical impact of ELM disruption, EZ disruption and SRF on OCT., Results: ELM disruption, EZ disruption and SRF were present in 32.6%, 52.2% and 45.8% of ocriplasmin-treated eyes and 39.6%, 42.6% and 37.5% of sham-treated eyes at baseline. VMT resolution was associated with resolution of ELM and EZ disruption and SRF. A small number of eyes had persistent ELM disruption, EZ disruption and/or SRF at the seventh visit or later (17 months or later) following medical or surgical VMT resolution. Resolution of ELM disruption, EZ disruption and/or SRF was associated with an improvement of visual acuity from baseline. Following VMT resolution, ELM recovery usually preceded EZ recovery and SRF resolution., Conclusions: ELM disruption, EZ disruption and/or SRF are present in a significant percentage of eyes with VMT without MH. Release of VMT is usually associated with outer retinal recovery and an associated improvement in visual acuity. ELM recovery typically precedes EZ recovery and SRF resolution following VMT release., Competing Interests: Competing interests: AST: Alimera Sciences (Consultant), Bausch & Lomb (Consultant), Genentech (Consultant), Knights Templar Foundation (Grant), Zeiss (Consultant). LD: Oxurion NV (Consultant). PK-W: Oxurion NV (Employee). GJ: Neurotech (consultant), Novartis (Consultant), Eyepoint Pharmaceuticals (Consultant), Noveome (Consultant), Iveric (Consultant)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: To assess the long-term safety and efficacy of epimacular brachytherapy (EMB) for chronic, active, neovascular age-related macular degeneration (nAMD)., Methods: This pivotal, randomised, controlled surgical device trial recruited patients with chronic nAMD receiving intravitreal ranibizumab from 24 UK hospitals. Participants were randomised to either pars plana vitrectomy with 24 Gray EMB and pro re nata (PRN) ranibizumab (n=224) or PRN ranibizumab monotherapy (n=119). Although masking was not possible, masked clinicians assessed best-corrected visual acuity (BCVA) and imaging. After month 24, participants reverted to standard care, with either ranibizumab or aflibercept, returning for a month 36 study visit., Results: Of 363 participants, 309 (85.1%) completed month 36. The number of injections was 12.1±8.1 in the EMB group versus 11.4±6.1 in the ranibizumab group (difference 0.7, 95% CI of difference -0.9 to 2.3, p = 0.41) between months 1 and 36, and 3.6±3.3 (n=200) versus 3.9±2.7 (n=102) (difference -0.3, 95% CI of difference -1.0 to 0.4, p=0.43) between months 25 and 36 (standard care). Over 36 months, BCVA change was -19.7±18.5 letters in the EMB group and -4.8±12.5 in the ranibizumab group (difference -14.9, 95% CI of difference -18.5 to -11.2, p < 0.0001). The month 36 BCVA of 20 EMB-treated participants with microvascular abnormalities (MVAs) at month 24 was similar to EMB-treated participants without MVAs (-21.8 vs -19.4 letters, p = 0.65)., Conclusion: EMB does not reduce the number of anti-vascular endothelial growth factor (VEGF) injections, either within or outside of a trial setting, and is associated with worse BCVA than anti-VEGF monotherapy., Trial Registration Number: NCT01006538., Competing Interests: Competing interests: TLJ received conference support and his employer received unrestricted research grant support from NeoVista. NeoVista had no role in data collection, analysis, or in the preparation or review of this manuscript. TLJ’s employer received free use of equipment from Oraya for an investigator-initiated trial of SRT, and his employer received research funding from Novartis for an unrelated project. His employer receives site payments for participants enrolled in various commercial clinical trials of AMD., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care., Methods: A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits., Results: At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits., Conclusions: HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes., Competing Interests: Competing interests: JJA, ILM, HM, P-HG, LO’T and MCG are members of advisory boards for Novartis and Bayer. JJA, HM and MCG are also members of advisory boards for Allergan. PHG is a member of advisory boards for Horus. ARH, MCG and JJA report personal fees and others from Novartis, others from Bayer, outside the submitted work. DB received a research grant from Novartis. MCG and DB are inventors of the software used to collect the data for this analysis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular endothelial growth factors (VEGF) injections., Methods: This is a retrospective cohort study conducted in Hong Kong, China. 196 eyes with centre-involving DMO, who received anti-VEGF injections between 1 January 2011 and 30 June 2018 were recruited. Medical records of the participants were retrieved retrospectively, visual acuity (VA) at baseline, 6, 12 and 24 months and SD-OCT before initiation and after completion of anti-VEGF treatment were obtained. The SD-OCT images were evaluated for the morphology of DMO, vitreomacular status, presence of disorganisation of retinal inner layers (DRIL), sizes of intraretinal cysts, visibility of external limiting membrane (ELM), ellipsoid zone (EZ) and cone outer segment tip (COST) and the presence of hyper-reflective foci in retina or the choroid., Results: The presence of baseline DRIL, hyper-reflective foci in retina and disruption of ELM/EZ and COST were associated with worse baseline and subsequent VA up to 24 months after treatment. Improvement in DRIL (p=0.048), ELM/EZ (p=0.001) and COST (p=0.002) disruption after treatment was associated with greater improvement in VA at 12 months. Eyes with cystoid macular oedema (p=0.003, OR=8.18) and serous retinal detachment (p=0.011, OR=4.84) morphology were more likely to achieve at least 20% reduction in central subfield thickness., Conclusion and Relevance: Baseline SD-OCT biomarkers and their subsequent change predict VA and improvement in vision in eyes with DMO treated with anti-VEGF injections. We proposed an SD-OCT-based system that can be readily used in real-life eye clinics to improve decision making in the management of DMO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To analyse the morphological characteristics of eyes with neovascular age-related macular degeneration (AMD) with good long-term visual acuity after anti-VEGF (vascular endothelial growth factor) therapy., Methods: Retrospective, observational study of 175 patients with neovascular AMD with >5 years of follow-up after initiating anti-VEGF therapy. Spectral-domain optical coherence tomography images were assessed for thickness of pigment epithelial detachment (PED), subretinal hyper-reflective material (SHRM), subretinal fluid and subfoveal choroidal, as well as the integrity of the outer retinal bands., Results: The final analysis cohort included 203 eyes (175 patients) followed for a mean of 7.84±1.70 years (range: 5-11). The maximum PED thickness in the foveal central subfield (FCS) was significantly lower (p<0.001) in the poor vision group (13.11 μm) compared with the intermediate (86.25 μm) or good (97.92 μm) vision groups, respectively. In contrast, the maximum thickness of SHRM in the FCS was significantly thicker (p<0.001) in eyes with poor vision (149.46 μm) compared with eyes with intermediate vision (64.37 μm) which in turn were significantly thicker (p<0.001) than eyes with good vision (9.35 μm). The good vision group also had better continuity of all outer retinal bands (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) compared with the other two groups (all p<0.001)., Conclusion: A thicker PED and thinner SHRM were correlated with better vision in eyes with neovascular AMD following long-term anti-VEGF therapy. If replicated in future prospective studies, these findings may have implications for design of optimal anatomic endpoints for neovascular AMD treatment., Competing Interests: Competing interests: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. CW reported receiving grants, personal fees or nonfinancial support from Adverum, Aerie Pharmaceuticals, Aldeyra, Alimera Sciences, Allergan, Apellis, Arctic Vision, Arrowhead, Bausch + Lomb, Bayer, Bionic Vision Technologies, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, EyePoint, Gemini Therapeutics, Genentech, Graybug Vision, Gyroscope, IONIS Pharmaceutical, IVERIC Bio, Kato DSRC, Kodiak Sciences, LMRI, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Novartis, OccuRx, Ocular Therapeutix, ONL Therapeutics, Opthea, Outlook Therapeutics, Oxurion (formerly Thrombogenics), Palatin, Pentavision, PolyPhotonix, RecensMedical, Regeneron, RegenXBio, Roche, SAI MedPartners, SamChunDang Pharm., Santen, Senju, Taiwan Liposome Company, Takeda, Thea Open Innovation, Verana Health, Visgenx, Xbrane BioPharma. DS reported receiving grants, personal fees, or nonfinancial support from Amgen, Genentech, Heidelberg, Optovue, Regeneron, Topcon, Bayer, Iveric Bio, Novartis. SS reported receiving grants, personal fees, or nonfinancial support from Carl Zeiss Meditec, Nidek, Topcon, Heidelberg, Optos, Centervue, Amgen, Allergan, Genentech/Roche, Oxurion, Novartis, Regeneron, Bayer, 4DMT, Merck, Apellis, Astellas., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diabetic macular oedema (DME) is a worldwide major cause of low vision and blindness. Intravitreal antivascular endothelial growth factor (anti-VEGF) constitutes an effective treatment. Clinical practice guidelines (CPGs) are synthesis documents that seek to improve patient care., Objectives: To identify CPGs that make anti-VEGF recommendations for DME and to assess their reporting quality and their considerations when making recommendations., Eligibility Criteria: CPGs published between December 2009 and December 2019 that make explicit anti-VEGF recommendations in DME., Sources of Evidence: Sensitive search strategy in Embase, Google Scholar and hand-searching on 165 websites., Methods: We extracted information from each CPG with a previously piloted sheet. Two independent authors applied theAppraisal of Guidelines, Research and Evaluation tool (AGREE-II) assessment for each CPG., Results: The 21 included CPGs recommend anti-VEGF for DME, but there is a wide variation among the clinical aspects included, such as location of DME, visual acuity required, therapeutical alternatives or discontinuation. Most have a poor quality of reporting based on the AGREE-II tool assessment, especially those developed by ophthalmological societies, those that have an exclusive content about DME, and those where most of their authors disclose conflict of interest (COI) with pharmaceutical industry or where their authors did not report COIs. Pharmaceutical-sponsored CPGs did not use systematic reviews (SRs) to support their recommendations. Very few recommendations consider patient values and preferences, equity, acceptability and feasibility of the intervention., Conclusions: Most of the CPGs that made recommendations of anti-VEGF for DME have poor quality of reporting, do not use SRs and do not consider patients' values and preferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD)., Methods: Setting : Multicentre. Design : Randomised, double-masked, parallel-group, phase III equivalence study. Patient population : ≥50 years old participants with nAMD (n=705), one 'study eye'., Intervention: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures : Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks., Results: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively., Conclusions: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ., Competing Interests: Competing interests: NB reported receiving grants from Samsung Bioepis to Johns Hopkins University during the conduct of the study and receiving grants from Bayer, Biogen, F. Hoffman-LaRoche, Novartis, Regeneron outside the submitted work. JS is a consultant for Bayer and Zeiss and received lecture fee from Bayer. AV received grants from Novartis, Bayer, Opthtotec/Iveric Bio, Samsung Bioepis, Amgen, Qilu, Chengdu Kanghong, Roche, Mylan, Receptos, Shire, Panoptica, Xbrain, Formycon, Genentech, Bioeq, Allergan, Thrombogenics, Regeneron, Alcon and Clearside Biomedical and is a consultant for and an advisory board member of Novartis, Bayer, Allergan, Bausch & Lomb, Medicontour and Zeiss. AP is a consultant for Roche, Bayer and Novartis received travel grants from Novartis and his company has received investigator fees from Samsung Bioepis, Roche, Iveric Bio, Allergan and Chengdu Kanghong. GV is a consultant for Alcon and Novartis, received travel grants from Novartis and Medicontur and his department has been involved in the conduct of several studies sponsored by Samsung Bioepis, Allergan, Chengdu Kanghong, Xbrane Biopharma, Thrombogenics, Amgen, Qilu, F. Hoffmann-La Roche, Bayer, Ophtotec, Novartis and Regeneron. YHY is a consultant for Alcon, Allergan Bayer and Roche, is Board Member of Allergan, Bayer and Roche, received grants from Allergan, Samsung Bioepis, Bayer, Novartis and Roche and received lecture fee from Allergan, Bayer and Roche. TP received travel grants from Alcon, Novartis and Bausch & Lomb and his department has been involved in the conduct of several studies sponsored by Mylan, Samsung Bioepis, Xbrane Biopharma, Kanghong Pharmaceuticals, F. Hoffmann-La Roche, Allergan, Bayer and Ophtotec. SJW is a consultant for Samsung Bioepis, Janssen, Allergan, Novartis, Curacle, Novelty Nobility, Alteogen, Philophos, Panols Bioscience, is equity owner of Retimark and Panolos Bioscience, is Board Member of Novartis and Novelty Nobility, received grants from Samsung Bioepis, Novelty Nobility, Novartis, Abbvie, Alteogen and Curacle and received lecture fee from Novartis, Bayer, Allergan, Abbvie, Alcon and Taejoon. Inkyung Oh, Hansol Jeong and Mercy Yeeun Kim are employees of Samsung Bioepis., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)