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Neovascular age-related macular degeneration (nvAMD) is the leading cause of severe vision loss in the elderly in the developed world. While the introduction of therapies targeting vascular endothelial growth factor (VEGF) has provided the first opportunity to significantly improve vision in patients with nvAMD, many patients respond inadequately to current anti-VEGF therapies. It was recently demonstrated that expression of a second angiogenic mediator, angiopoietin-like 4 (ANGPTL4), synergizes with VEGF to promote choroidal neovascularization (CNV) in mice and correlates with reduced response to anti-VEGF therapy in patients with nvAMD. Here, we report that expression of ANGPTL4 in patients with nvAMD increases following treatment with anti-VEGF therapy and that this increase is dependent on accumulation of hypoxia-inducible factor (HIF)-1α in response to inhibition of VEGF/KDR signaling in the retinal pigment epithelium (RPE). We therefore explored HIF-1 inhibition with 32-134D, a recently developed pharmacologic HIF-inhibitor, for the treatment of nvAMD. 32-134D prevented the expression of both VEGF and ANGPTL4 and was at least as effective as aflibercept in treating CNV in mice. Moreover, by preventing the increase in HIF-1α accumulation in the RPE in response to anti-VEGF therapy, combining 32-134D with aflibercept was more effective than either drug alone for the treatment of CNV. Collectively, these results help explain why many patients with nvAMD respond inadequately to anti-VEGF therapy and suggest that the HIF inhibitor 32-134D will be an effective drug-alone or in combination with current anti-VEGF therapies-for the treatment of patients with this blinding disease., Competing Interests: Competing interests statement:G.L.S. and A.S. are co-founders of and hold equity in HIF Therapeutics, Inc. S.S., Y.H., G.L.S., and A.S. are inventors on provisional patent application PCT/US2022/039883. This arrangement has been reviewed and approved by the Johns Hopkins University in accordancewith its conflict of interest policies.

Wet age-related macular degeneration (AMD) is an acquired degeneration of the retina that can lead to central vision impairment. It is primarily treated with intravitreal injections of vascular endothelial growth factor inhibitors. Although vascular endothelial growth factor inhibitors can effectively prevent progression of vision loss in many patients, they require ongoing regular administration and are therefore associated with considerable treatment burden. To gain insights into the impact of wet AMD and its treatment, AMCP convened an expert panel of managed care stakeholders in April 2024 through its Market Insights program. Key issues related to wet AMD identified by participants included cost and affordability, provider-related considerations, biosimilar adoption, measuring and improving quality, and incorporating the patient voice. Suggested payer best practices related to these issues in wet AMD also emerged from the discussion.

Purpose: To report real-world clinical evidence of brolucizumab in treating neovascular age-related macular degeneration (nAMD)., Methods: This study included 37 eyes with nAMD treated with intravitreal injections of brolucizumab. The main outcomes were best corrected visual acuity (BCVA) changes, central retinal thickness (CRT), and serious ocular adverse events. Intraretinal fluid (IRF) and subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci, macular atrophy, and retinal pigment epithelial tears were evaluated., Results: The mean BCVA of all patients showed a post-treatment value of 0.47 ± 0.33 log of minimum angle of resolution (LogMAR), compared to a baseline measure of 0.50 ± 0.28 LogMAR ( P = 0.372). For treatment-naïve patients, a non-statistically significant improvement in BCVA was observed ( P = 0.116). Both treatment-naive patients and the entire patient cohort exhibited a statistically significant improvement in the mean CRT after injections. Majority of patients exhibited improvements in optical coherence tomography findings, specifically in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes experienced ocular adverse events in the form of intraocular inflammation., Conclusion: Brolucizumab did not yield a substantial improvement in BCVA, but it exhibited efficacy in reducing CRT in the entire study population and treatment-naive patients with nAMD. Our study identified intraocular inflammation as a significant adverse event with brolucizumab. Thus, precise patient selection, education, and vigilant inflammation monitoring are crucial for patients undergoing this treatment., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Background/objectives: Some eyes with neovascular age-related macular degeneration (nAMD) and centre-involving diabetic macular oedema (DMO) fail to respond sufficiently or lose response over time to standard of care intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. This paper explores clinical scenarios for switching to dual action angiopoietin-2 (Ang-2)/VEGF-A inhibitor faricimab (Vabysmo, Roche Products Limited) in previously anti-VEGF-treated patients., Methods: A national steering group meeting of UK retina specialists was held in London on 27 October 2023. Clinician practice and experience were reviewed together with pivotal clinical trial data and early findings from real-world settings. Roche Products Limited facilitated and funded the meeting., Results: While there is no standardised protocol for identifying suboptimal response, the authors review relevant clinical biomarkers of disease activity used in routine clinical practice to determine patient response and guide treatment decisions. Common reasons identified for considering a change of treatment were lack of efficacy demonstrated by suboptimal anatomic or visual improvement and insufficient durability of response. The panel outline strategies for switching to faricimab among eligible patients with a prior anti-VEGF treatment history, with initial monthly loading doses or maintaining the previous treatment interval before attempting to extend, that may be integrated into current treat-and-extend (T&E) clinical pathways for treating patients with nAMD and DMO. General considerations for switching between treatments are also reviewed., Conclusion: Clinicians may consider a treatment switch to faricimab in nAMD and DMO patients who have suboptimal disease control or insufficient durability of response on initial anti-VEGF therapy., (© 2024. The Author(s).)

Purpose: This study explores the immune cells' role in anti-VEGF resistance in nAMD patients, and the potential of Zi-Yin-Jiang-Huo-Tang (ZYJHT), a Traditional Chinese Medicine formula, as complementary therapy., Methods: Aqueous humor proteomics data from 10 nAMD patients with anti-VEGF resistance and 10 nAMD patients without anti-VEGF resistance were analyzed, investigating immune cells's role in anti-VEGF resistance and its underlying mechanism. Network pharmacology methods are employed to analyze the active ingredients in ZYJHT that contribute to therapeutic effects and their mechanisms. Real-time PCR (polymerase chain reaction) was used to detect changes in the expression of SOD1 (superoxide dismutase 1) after treatment with compounds targeting SOD1 in ARPE-19 cells., Results: nAMD patients with anti-VEGF resistance showed enhancement of biological processes linked to the positive regulation of immune function, along with decreased cellular resistance to oxidative stress. Infiltration of B cells memory, plasma cells, CD8 + and γδ-T cells were higher in nAMD patients with anti-VEGF resistance. SOD1 was identified as a hub gene in the occurrence of anti-VEGF resistance and a core therapeutic target of ZYJHT, negatively correlated with B and T cell infiltration. Compounds diosgenin, naringenin, and liquiritin in ZYJHT can bind to SOD1 and upregulating SOD1 expression in ARPE-19 cells.

Purpose: To investigate outcomes after Brolucizumab injection in naïve treatment or non-responder patients with exudative age-related macular degeneration (AMD)., Methods: It is a retrospective, comparative, cohort study conducted at the tertiary referral center of the University Hospital Polyclinic of Bari, for 5 years, from November 2017 until May 2022. 41 eyes with wet-AMD (w-AMD) were included, undergoing anti-vascular endothelial growth factor (VEGF) intravitreal injections. The sample was divided into two groups, the Bro-Switch group, and the Bro-Naïve group. The Bro-Switch group previously received a slot of other anti-VEGF intravitreal drugs. The Bro-Naïve group received Brolucizumab (Bro) as the first treatment. The pigment epithelium detachment (PED) and the best-corrected visual acuity (BCVA) outcomes before and after Bro-injection were evaluated., Results: A significant reduction in PED measurement was registered in all eyes treated with Bro-injection ( p  = 0.35). The Bro-Naïve group improved better in PED measurement (mean difference: 297.92 ± 72,32) as compared to the Bro-Switch group (mean difference: 185.06 ± 11.07). On the contrary, no significant reduction in BCVA in the two groups was recorded ( p  = 0.66)., Conclusion: We suggest Bro-injection for w-AMD as effective anatomical outcomes in PED flattening, but not similar in visual results. Although this study evaluated short-term outcomes, the hopeful results can lead to interesting medium-long time effects.

Purpose: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV)., Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups., Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution., Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: The purpose of this study is to evaluate the role of a polyethylene glycol 400 - propylene glycol - hydroxypropyl guar - hyaluronic acid eye drops in relieving the symptoms of dry eye syndrome after anti-VEGF intravitreal injection., Methods: In this randomized, parallel-group study, patients were randomized to receive standard therapy alone or study eye drops plus standard therapy. Patients enrolled were older than 50 with exudative age-related macular degeneration, who have never had intravitreal injections, and without severe dry eye condition or severe ocular or systemic conditions. Patients had baseline preoperative evaluation (V0), and successively after 15 (V1) and 30 (V2) days. At VO and V1 T-BUT, Schirmer's test, fluorescein staining, DEQ5 and OSDI questionnaires were performed and at V2 (30) the OSDI questionnaire was administered., Results: 80 patients were included in the study, of them 40 received standard therapy plus study eye drops. DEQ5 questionnaire showed an increase in the control group between the values at V0 and V1, while in the study group a decrease was observed. No changes in T-BUT, Schirmer, and fluorescein staining values between V0 and V1 were observed in both groups. OSDI data in the control group showed no statistically significant differences, while in the study group they showed a statistically significant difference., Conclusions: In our study patients undergoing for the first time intravitreal treatment presented dry eye symptoms in the postoperative period: in this group of patients the use of a tears substitute reduces postoperative ocular discomfort., 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.

Purpose: The Observe-and-Plan (O&P) regimen allows for individualised treatment. In this study, we evaluated injection burden and intervals using aflibercept in an O&P regimen for eyes with neovascular age-related macular degeneration (AMD)., Methods: This was a retrospective registry-based study of treatment-naïve eyes with neovascular AMD. Treatment data were compiled for 3 years after commencement of intravitreal aflibercept therapy. We evaluated clinical consequences at the first follow-up after loading dose, the proportion of patients who obtained and kept dry macula after loading dose, number of injections and intervals between injections., Results: Data were obtained for 1103 eyes. After loading dose, 0.4% were lost to follow-up, 7.5% discontinued, 50.9% booked for further injections and 41.3% booked for monthly observations. After loading dose, the macula remained dry in 49.2% at 3 months, 34.0% at 6 months, 23.7% at 12 months and 15.2% at 24 months. For the entire population, median cumulative total number of injections was 7, 12 and 15, after 1, 2 and 3 years, respectively. After the 3rd year, the proportion of eyes in the short 4-6 weeks treatment interval was 51.1%, 8 weeks interval was kept in 14.4% and the extended treatment intervals of 10 and 12 weeks was possible in 34.4%., Conclusion: After loading dose, one in two eyes required further injections. A large proportion required therapy with shorter intervals than the label-recommended 8 weeks. The large majority of those who obtained a dry macula after loading dose turned exudative again, mostly within the first 3 months., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To measure aqueous flare levels in treatment naïve eyes suffering from wet age- related macular degeneration (wAMD) treated with intravitreal brolucizumab., Methods: Patients with treatment naïve wAMD in one eye were prospectively enrolled. Flare levels were measured with laser flare photometry at baseline, 1 day and 1 month after each of the 3 monthly injections during the loading phase., Results: Twenty-two eyes from 22 patients aged 76.7 ± 6.0 years were enrolled. Flare values were 10.6 ± 3.7 photons/msec at baseline and 12.6 ± 5.8 photons/msec at the last follow up visit, 1 month after the third injection ( p  = 0.289, repeated measures ANOVA). The mean change in flare after the first injection was 4.2 ± 3.6. photons/msec, 6.6 ± 8.9 photons/msec after the 2nd and 8.6 ± 20.8 photons/msec after the 3rd injection ( p  = 0.640, repeated measures ANOVA). No patient had clinical signs of intraocular inflammation., Conclusions: Eyes receiving brolucizumab injections for wAMD showed similar flare at baseline, during and 1 month after completion of three-monthly intravitreal injections. There was no evidence of subclinical inflammation during the loading phase of brolucizumab based on laser flare photometry measurements., 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.

Purpose: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics., Design: Prospective cohort study., Methods: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption., Results: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized β = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R² of 0.453., Conclusions: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption., Competing Interests: Conflict of Interest All authors declare no competing interests, financial disclosures, or personal relationships that could potentially influence the objectivity or integrity of this research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Vujosevic is a consultant for Abbvie, Boehringer and Ingelheim, Bayer, Novartis, Roche, Zeiss. C. Astarita and V. Gallinari are AbbVie employee and may own AbbVie stocks/options., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

Purpose: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown., Methods: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group., Results: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population., Conclusion: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

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).)

Purpose: To quantify the long-term impact (24 months) on the visual results and activity of neovascular lesions of COVID-19 confinement in patients with nAMD in our population., Methods: A retrospective observational study of patients with nAMD who attended consultation or were treated during the 3 months before confinement was carried out., Results: 144 patients (168 eyes) with nAMD were included, 51 of them (35.42%) came during confinement, and at 24 months the final cohort was 118 patients (133 eyes). The previous VA of 57.99 ± 23.68 letters decreased, clinically relevant and statistically significant, by an average of 6.87 (±16.84) and 7.89 (±19.58) at 12- and 24-months follow-up. This change differs significantly from the two-year vision change observed in the national database of pretreated patients. The median number of injections and consultations is lower in our group at 12 months, compared to the pre-pandemic national database, and tends to equalize at 24 months. We did not find differences in vision when we compared patients who attended consultations during confinement or in treatment intervals greater than 8 weeks (Tq8w)., Conclusions: The VA of patients with nAMD decreased significantly after confinement, probably due to the lower number of antiangiogenic injections and consultations during the first year, and did not recover during the second year despite the increase in the number of injections and visits close to those reported before confinement., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: To estimate the cost-impact if faricimab were approved for the treatment of neovascular age-related macular degeneration (nAMD) in New Zealand., Methods: A retrospective, single-centre cost-analysis study. Data on intravitreal agent and injection intervals were obtained and statistically compared. Cost estimates were based on internal facility and publicly available data. The current costs of care were compared to two scenarios: one where all eyes receive faricimab, and another where eyes receiving aflibercept switch to faricimab., Results: A total of 352 eyes from 292 patients were analysed. Present values locally over 10 years were estimated at -$6,776,340 for the first scenario and $5,015,922 for the second, releasing 252 and 176 hours of clinical time per year, respectively. Nationally, the savings extrapolated to -$187,925,737 and $139,104,706, respectively. The analysis indicates significant direct cost savings for the health sector and potential reductions in patient harm due to fewer injections., Conclusions: The approval of faricimab for the treatment of nAMD could result in substantial direct cost savings for the health sector. Additional benefits include reducing patient harm and improving ophthalmic health inequalities for Māori and Pacific peoples. Further research in diverse patient populations across multiple centres is needed to estimate the magnitude of cost savings more accurately. This study highlights the potential of faricimab to alleviate the treatment burden and provide a more sustainable healthcare option for nAMD in New Zealand, especially in cases of recalcitrant nAMD, if used in a tailored and patient-specific manner alongside the existing armamentarium of treatments., Competing Interests: The authors declare that they have no conflicts of interest. There has been no financial support for this work that could have influenced its outcome. In particular, there has been no funding or any form of support from any of the manufacturers of the agents described in this paper. All authors contributed equally to the conception, design and analysis of this study., (© PMA.)

Background: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD)., Methods: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI., Results: Forty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6-22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047)., Conclusion: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements., (© 2024. The Author(s).)

Aims: To identify baseline characteristics that best correlate to treatment interval for naive neovascular age-related macular degeneration patients treated with faricimab in the first year (Y1) of the TENAYA and LUCERNE phase 3 trials, and to further understand how these characteristics may impact treatment intervals., Methods: This post-hoc analysis of Y1 data from the TENAYA and LUCERNE trials evaluated ocular baseline characteristics associated with Y1 treatment intervals. Patients were categorised into three subgroups based on their Y1 treatment interval: Q16W, Q12W or Q8W. Baseline characteristics (central subfield thickness (CST), best-corrected visual acuity, presence of subretinal fluid in centre 1 mm, presence of retinal fluid in centre 1 mm, macular neovascularisation (MNV) location and MNV type) were inputted into an R package 'rpart' to create a classification tree model. A data-driven tree model based on CST was fitted, producing CST subgroups of low, middle and high ranges. Within each CST subgroup, the model identified the most impactful variables and associated thresholds., Results: After fitting the data to produce data-driven CST ranges, the model chose MNV location, followed by MNV lesion type as the most impactful baseline characteristics with these factors having a p value <0.05 in a multivariate analysis., Conclusions: Among the selected ocular baseline characteristics from TENAYA and LUCERNE trial, CST, MNV type and MNV location were seen as the most relevant variables to enable extension of treatment intervals during Y1. While this analysis provides insights for treatment intervals during the first year, further analysis incorporating Y2 data from the TENAYA and LUCERNE studies will be needed to assess factors influencing treatment intervals over a longer period., Competing Interests: Competing interests: PS was an employee at Roche at the time of study conduct, but is now a full time specialist senior registrar at Moorfields Eye Hospital (ie, since August 2023). NR and YT are employees at Genentech, PM and AK are employees at 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.)

Purpose: To assess differences in choriocapillaris (CC) and macular neovascularization (MNV) optical coherence tomography angiography quantitative parameters between long-term persistently nonexudative MNVs (NE-MNVs) and long-term activated NE-MNVs in age-related macular degeneration., Methods: Age-related macular degeneration patients with treatment-naïve NE-MNVs with >2 years of follow-up and no evidence of exudation within the first 6 months from diagnosis were retrospectively recruited. Two groups were considered according to the occurrence (EX group) or not (NE group) of exudation within the first 2 years of follow-up. Segmentation of the MNV and of the perilesional CC were obtained from enface optical coherence tomography angiography acquisitions at diagnosis and at 6-month follow-up. OCT B-scan images of the MNV were also collected. Fractal ratio was defined as the ratio between MNV fractal dimension (FrD) and CC FrD., Results: Fifty (50) eyes were included (20 EX group and 30 NE group). EX group showed higher flow deficit density and flow deficit number at the 6-month follow-up. It also showed higher MNV FrD, lower CC FrD, and higher fractal ratio at the 6-month follow-up. The fractal ratio significantly increased at 6-month acquisitions in the EX group, showing an area under the ROC curves of 0.887 (95% CI 0.869-0.922)., Conclusion: Fractal ratio at 6 months can predict exudation risk of MNV within 2 years from diagnosis. This suggests increased structural complexity of the NE-MNV accompanied by progressive capillary rarefaction of the perilesional CC as a key driving factor for the development of exudation in NE-MNV.

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.)

Purpose: To correlate baseline spectral-domain optical coherence tomography characteristics with the number of as-needed intravitreal injections of ranibizumab over a 24-month follow-up period in eyes with neovascular age-related macular degeneration., Methods: Two hundred thirty-six eyes of 236 subjects with neovascular age-related macular degeneration treated with ranibizumab 0.5 mg pro re nata in the HARBOR study were enrolled. Baseline spectral-domain optical coherence tomography images were evaluated by certified reading center graders for specific morphologic features of the macular neovascularization lesion and surrounding retina. Baseline optical coherence tomography features and patient demographics correlated with the number of injections over the next 2 years., Results: The mean number of injections in the 0.5 mg pro re nata group was 8.07 (median 8, 3-12) after 12 months and 14.25 (median 14, 3-24) after 24 months of treatment. After multivariate, linear, regression analysis, the only baseline parameter that was independently associated with a higher injection frequency at both 12 and 24 months was a greater baseline subretinal fluid thickness., Conclusion: A greater subretinal fluid thickness at baseline was associated with a higher frequency of pro re nata injections over 12 and 24 months in eyes treated with ranibizumab for neovascular age-related macular degeneration. These findings may be of value in counseling patients who are about to initiate therapy for macular neovascularization.

Purpose: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL])., Method: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics., Results: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL., Conclusion: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To explore changes in reticular pseudodrusen (RPD) number and location after the development of macular neovascularization (MNV) in eyes with prior intermediate age-related macular degeneration, focusing on different retinal regions differently affected by MNV., Methods: This retrospective longitudinal study included intermediate age-related macular degeneration eyes with RPD that developed MNV. Reticular pseudodrusen were assessed at baseline when MNV was diagnosed (MNV stage) and after anti-vascular endothelial growth factor treatment. Three regions of interest were considered: MNV area, subretinal fluid (SRF) area, and a marginal area of 1,000 µm around SRF (marginal zone). Reticular pseudodrusen counts were compared with age- and sex-matched control eyes with RPD that did not develop MNV., Results: Reticular pseudodrusen number exhibited a significant decrease after MNV development in the MNV area (P = 0.048) and in the area with SRF (P = 0.078). A statistically significant decrease was also disclosed in the marginal area around SRF (P = 0.002), associated with larger SRF areas. Control eyes did not show any significant change in the RPD count., Conclusion: Reticular pseudodrusen reduction after MNV development suggests a complex interplay involving the MNV itself, the presence of SRF, and trophic changes. The results of this study highlight the role of MNV in retinal nutritional balance and provide intriguing results in the RPD life cycle.

Purpose: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the development and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD)., Design: Retrospective, clinical cohort study., Methods: The study included patients with nAMD with anti-vascular endothelial growth factor (VEGF) injections who underwent uneventful cataract surgery between 2007 and 2018 with follow-up until June 2023. Subsequent MA rates were compared between subjects who received a BLF IOL or a non-BLF IOL. All optical coherence tomography scans were manually reviewed in a masked manner regarding patient baseline variables and IOL status by an experienced research technician. By using Heidelberg software, the area of MA was manually evaluated and calculated (mm 2 ) by the program. The overall risk of developing new-onset MA and the effect of IOL type on disease progression were assessed. Death was included as a censoring event., Results: Included were 373 eyes of 373 patients (mean age, 78.6 ± 6.7 years at surgery; 67.4% were female). BLF IOLs were implanted in 206 eyes, and non-BLF IOLs were implanted in 167 eyes with comparable follow-up times (3164 ± 1420 days vs 3180 ± 1403 days, respectively, P = .908) and other baseline parameters (age, gender, corrected distance visual acuity, macular thickness, cumulative number of anti-VEGF injections). Nine preexisting and 77 new-onset MA cases were detected, with similar distribution between BLF and non-BLF eyes (P = .598 and P = .399, respectively). Both univariate Kaplan-Meier (P = .366) and multivariate Cox regression analyses adjusted for age and gender showed that BLF-IOLs were comparable to non-BLF IOLs regarding hazard for new-onset MA (hazard ratio [HR], 1.236; 95% CI, 0.784-1.949; P = .363). Final MA area at the last visit was 5.14 ± 4.71 mm 2 for BLF IOLs and 8.56 ± 9.17 mm 2 for non-BLF IOLs (P = .028), with the mean annual MA area increase of 0.78 ± 0.84 mm 2 and 1.26 ± 1.32 mm 2 , respectively (P = .042)., Conclusions: BLF IOLs did not show added benefit over non-BLF IOLs in terms of MA-free survival but were associated with less progression over time in a cohort of patients with nAMD., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED)., Methods: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined., Results: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm 2 , OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test)., Conclusions: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD)., Methods: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated., Results: A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension., Conclusion: Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To investigate the effect of macular fluid volumes (subretinal fluid [SRF], intraretinal fluid [IRF], and pigment epithelium detachment [PED]) after initial treatment on functional and structural outcomes in neovascular age-related macular degeneration in a real-world cohort from Fight Retinal Blindness!, Methods: Treatment-naive neovascular age-related macular degeneration patients from Fight Retinal Blindness! (Zürich, Switzerland) were included. Macular fluid on optical coherence tomography was automatically quantified using an approved artificial intelligence algorithm. Follow-up of macular fluid, number of anti-vascular endothelial growth factor treatments, effect of fluid volumes after initial treatment (high, top 25%; low, bottom 75%) on best-corrected visual acuity, and development of macular atrophy and fibrosis was investigated over 48 months., Results: A total of 209 eyes (mean age, 78.3 years) were included. Patients with high IRF volumes after initial treatment differed by -2.6 (p = 0.021) and -7.4 letters (p = 0.007) at months 12 and 48, respectively. Eyes with high IRF received significantly more treatments (+1.6 [p < 0.001] and +5.3 [p = 0.002] at months 12 and 48, respectively). Patients with high SRF or PED had comparable best-corrected visual acuity outcomes but received significantly more treatments for SRF (+2.4 [p < 0.001] and +11.4 [p < 0.001] at months 12 and 48, respectively) and PED (+1.2 [p = 0.001] and +7.8 [p < 0.001] at months 12 and 48, respectively)., Discussion: Patients with high macular fluid after initial treatment are at risk of losing vision that may not be compensable with higher treatment frequency for IRF. Higher treatment frequency for SRF and PED may result in comparable treatment outcomes. Quantification of macular fluid in all compartments is essential to detect eyes at risk of aggressive disease., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with "observe before treat-and-extend (O-TAE)" strategy in the real-world setting., Methods: This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed., Results: A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the first year (p = 0.010) and 0.25 ± 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 ± 74.53 μm at baseline to 269.62 ± 48.12 μm in the first year (p < 0.001) and 279.14 ± 54.64 μm in the second year (p < 0.001). Number of injections were 5.11 ± 1.69 in the first year and 3.84 ± 2.39 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months., Conclusions: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Purpose: To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA)., Methods: In this retrospective study, eyes of treatment-naïve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for ≥ 5 years were classified into the tAMD-SMH ( +), tAMD-SMH (-), PCV-SMH ( +), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed., Results: This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH ( +) group (n = 6), the mean logMAR BCVA significantly deteriorated from 0.59 ± 0.45 at baseline to 0.88 ± 0.47 at the final visit (P = 0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n = 45), PCV-SMH ( +) (n = 12), or PCV-SMH (-) (n = 64) groups (all P > 0.05). The tAMD-SMH ( +) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P = 0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV., Conclusion: The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the effect of four versus three loading aflibercept injections on macular fluid resolution and visual acuity (VA) in exudative neovascular AMD (nAMD)., Methods: Multicentre, retrospective cohort study of treatment naïve nAMD eyes undergoing 3 versus 4 loading doses of aflibercept. Change in VA and fluid resolution on optical coherence tomography (OCT), were evaluated at 8 weeks post loading. The primary outcome was proportion of patients with no intraretinal (IRF) and/or subretinal (SRF) fluid at central 1 mm and whole macula at 8 weeks after loading. Data were summarised with mean ± SD for continuous variables, and n (%) for categorical variables., Results: Data from 995 patients was analysed (355 patients - 4 loading doses and 640-3 loading doses). At 8 weeks post 4 loading doses proportion of eyes with neither IRF nor SRF, no IRF and no SRF were 62.8%, 88.7% and 79.2% at fovea versus 56.1%, 87.9% and 69.9% in the whole macula, respectively. Fluid resolution at both fovea and macula were significantly higher in eyes with 4 loading injections versus 3 (p = 0.0001). The mean VA change was +4.0 (±11.3) and +5.4(±13.3) letters for 3 and 4 loading doses groups (p = 0.09)., Conclusion: Four loading dose injections of aflibercept results in higher proportion of eyes with total fluid resolution in the central subfield and total macular scan when compared to those receiving 3 loading dose injections at 8 weeks post loading phase. However, the better drying effect of 4th loading dose does not translate into better short-term VA outcomes., (© 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.)

Purpose: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative., Methods: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT)., Results: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF)., Conclusions: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches., (© 2024. The Author(s).)

Purpose: To evaluate the effect of intravitreal bevacizumab on aqueous levels of a panel of 12 inflammatory cytokines in patients with neovascular age-related macular degeneration (nAMD) and correlate response to treatment, as measured by change in the central subfovea thickness (CST), with cytokine levels., Methods: Thirty-three treatment-naïve patients with nAMD received a loading dose of intravitreal bevacizumab consisting of three injections at six weekly intervals. The aqueous samples prior to the first (baseline), second (week 6), and third (week 12) injections were analyzed for cytokine levels. Participants were subgrouped based on changes in CST on spectral-domain optical coherence tomography (SD-OCT) at 12 weeks. Group 1 included patients with a decrease in CST (responders; n = 27). Group 2 included patients who had no decrease in CST (poor responders; n = 6)., Results: Aqueous IL-8 was the only cytokine to demonstrate a significant difference in levels between responders and poor responders, with higher interleukin-8 (IL-8) at week 12 in the poor responder group. Aqueous IL-6 and IL-8 levels showed a positive correlation with CST on SD-OCT (Spearman r = 0.45 and 0.55, respectively). There was a temporal increase overall in cytokine concentration accompanying bevacizumab treatment., Conclusions: Aqueous IL-6 and IL-8 may be important markers of treatment response or poor response in nAMD. Future therapeutic strategies may include targeted treatment against both vascular endothelial cell growth factor (VEGF) and IL-6 and/or IL-8 in patients who do not respond to anti-VEGF treatment alone.

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: To examine the changes in aqueous humor cytokine levels and clinical outcomes of switching from aflibercept to faricimab in eyes with neovascular age-related macular degeneration (nAMD)., Methods: Fifty-four eyes of 54 patients with AMD undergoing treatment with aflibercept under a treat-and-extend (TAE) regimen were switched to faricimab and studied prospectively. Best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status were analyzed using optical coherence tomography. Aqueous humor was collected before and after the switch, and angiopoietin-2 (Ang-2), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) A levels were measured., Results: After switching from aflibercept to faricimab, exudative changes improved in 28 eyes (52%), remained stable in eight eyes (15%), and worsened in 18 eyes (33%). BCVA changed from 0.27 ± 0.31 to 0.26 ± 0.29 (P = 0.46), CRT decreased from 306.2 ± 147.5 µm to 278.6 ± 100.4 µm (P = 0.11), and CCT changed from 189.5 ± 92.8 µm to 186.8 ± 93.9 µm (P = 0.21). VEGF-A levels were below the detection sensitivity in many cases throughout the pre- and post-switching periods. Ang-2 significantly decreased from 23.8 ± 23.5 pg/mL to 16.4 ± 21.9 pg/mL (P < 0.001), and PlGF significantly increased from 0.86 ± 0.85 pg/mL to 1.72 ± 1.39 pg/mL (P < 0.001)., Conclusions: Switching from aflibercept to faricimab in patients with nAMD may not only suppress VEGF-A but also Ang-2 and reduce exudative changes.

Background: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration., Methods: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group., Results: In the IVA group, the MH at baseline (215 ± 177 μm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly., Conclusions: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy., (© 2024. The Author(s).)

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.

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.)

Purpose: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD)., Study Design: Retrospective, interventional case series., Methods: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined., Results: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss., Conclusions: Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis., (© 2024. The Author(s).)

Purpose: To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting., Methods: A retrospective monocentric study including 44 eyes treated with an upload of 4 × monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution., Results: 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79 ± 7 years. The total number of previous anti-VEGF before switching to IVF was 32 ± 15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65 ± 0.26 to 0.50 ± 0.23 at 16 W (p < 0.01). CMT (µm) decreased significantly from 422 ± 68 to 362 ± 47 at 16 W (p < 0.01). SFCT did not change significantly at 16 W (p = 0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p = 0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p > 0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed., Conclusion: In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The purpose of this study was to describe the management of a hemorrhagic bacillary layer detachment (BALAD) in a patient with neovascular age-related macular degeneration., Methods: The clinical records and imaging were reviewed., Results: A 74-year-old woman presented with acute-onset hemorrhagic neovascular age-related macular degeneration with a large hemorrhagic BALAD. The intra-BALAD hemorrhage was amenable to displacement with SF 6 pneumatic displacement with subsequent VA recovery., Conclusion: Sulfur hexafluoride (SF 6 ) pneumatic displacement in combination with aflibercept injection is a viable means by which to manage a hemorrhagic BALAD in the context of neovascular age-related macular degeneration. Displacement of large intra-BALAD hemorrhages can result in good visual recovery.

Purpose: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity., Methods: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not., Results: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group., Conclusion: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

Purpose: MNV3 or Retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (nAMD). We present the 5 year long term visual and anatomical outcomes of patients with MNV3 lesions treated with intravitreal Aflibercept., Methods: This is a prospective study of treatment naïve patients with reading centre graded MNV3 lesions. After the loading phase, the patients received intravitreal Aflibercept as per the View study up to year 3, thereafter it was given on a prn basis. At each visit, best corrected visual acuity (BCVA) and optical coherence tomography (OCT) central macular thickness (CMT) was measured., Results: Thirty one patients reached study completion. Mean BCVA of treated eyes had decreased by 0.6 ETDRS letters at the end of year 5 compared with baseline. At study completion, 81% of eyes had stable vision while 19% of eyes had gained 15 letters or more. At study end, 26% of eyes had BCVA of 6/12 or better, while 19% had lost 15 letters or more (all had central foveal photoreceptor loss). There was a maximal mean reduction in CMT of 164 microns (p = <0.0001) while 68% of maculae were fluid free at study completion. Eighty seven percent of treated eyes developed nascent GA, of which in 74% of eyes was involving the fovea., Discussion: Despite initial improvement in mean BCVA, the improvement in BCVA was not maintained despite good overall control of the MNV3 lesions. The loss of BCVA was most likely due to the majority of eyes developing centre involving macular atrophy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept., Methods: Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared., Results: 2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08-4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1-22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p = 0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%)., Conclusions: STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: The aim of the study was to explore factors affecting the progression of neovascular age-related macular degeneration (nAMD) and identify predictive factors that can estimate the duration of intravitreal treatments., Methods: This retrospective real-world study included 421 nAMD patients treated at the Kuopio University Hospital during years 2007-2021. The collected data included background demographics, treatment history, visual acuity and retinal biomarker analysis. Impact of baseline factors on age at diagnosis, treatment duration, received treatment intensity and visual acuity gains were analysed., Results: Heavy smoking and high body mass index (BMI) were associated with an earlier onset, while the use of anticoagulation and anti-aggregation medication were associated with a later onset of nAMD. A low number of injections during the first year of treatment and the presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p = 0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRF) and complete RPE and outer retinal atrophy (cRORA; 20.7% vs. 5%, p = 0.02) were observed in patients with IRF., Conclusions: Our results reveal that heavy smoking and high BMI are accelerating factors for earlier emergence of nAMD, while the presence of IRF results in a fast-progressing disease. More intriguingly, the link between IRF and appearance of subretinal drusenoid deposits, HRF, and increased retinal atrophy was observed., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)