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Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed., Competing Interests: Competing interests: DZ has received grants from Roche, has served on scientific advisory boards for AbbVie, Allergan, Bayer, Johnson & Johnson, Novartis and Roche, and has served as a speaker for AbbVie, Allergan, Bayer, Novartis and Roche. RG is a consultant and has served on advisory boards for Apellis, Bayer, Belite Bio, Boehringer Ingelheim Pharmaceuticals, Character Biosciences, Novartis, Ocular Therapeutix and Roche/Genentech. J-FK is a consultant for Allergan/AbbVie, Apellis, Bayer, Carl Zeiss Meditec, Janssen, Nano Retina, Roche and Théa, and is a member of the Data and Safety Monitoring Boards for Alexion and Novo Nordisk. LW is a consultant for Bayer, Lumibird Medical, Novartis and Roche. FV is a consultant for Allergan, Bayer, Novartis and Roche, and has received research grants from Allergan, Bayer and Novartis. NE has served on advisory boards for Alcon, Allergan, Apellis, Bayer, Bayer Global, Biogen, Janssen Global, Novartis, Novartis Global, Roche and STADA; has received research grants from Bayer and Novartis; has received lecture fees from Alcon, Allergan, Apellis, Bayer, Bayer Global, Novartis, Novartis Global, Roche and STADA; and has served on steering committees for Genentech and Medscape WebMD. SB is a consultant for Allergan, Bausch & Lomb, Bayer, Horus Pharma, Novartis and Roche. YC is a consultant and lecturer for Bayer, Novartis and Roche. JJA is a consultant and has served on advisory boards for Allergan/AbbVie, Bayer, Novartis, Roche and Apellis., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To investigate the additional prognostic value of quantifying the extent of colour fundus photography (CFP)-defined hyperpigmentary abnormalities (HPAs) compared with their presence alone for predicting progression to late-stage age-related macular degeneration (AMD) and to understand their association with visual sensitivity in individuals with intermediate AMD., Methods: 140 participants with bilateral large drusen underwent multimodal imaging and microperimetry at baseline and then every 6 months for up to 3 years. Baseline CFPs were graded for the presence of HPAs and their extent was quantified. Optical coherence tomography (OCT) scans were used to quantify drusen volume. Predictive models for progression to late AMD (including OCT signs of atrophy) were developed using either HPA presence or extent. The association between HPA extent with mean visual sensitivity (both overall and sector based) was also evaluated. All models were adjusted for the confounders of baseline age and drusen volume., Results: The predictive performance for late AMD development was not significantly different for HPA presence or extent (p=0.92). Increasing HPA extent in each sector, but not its overall extent in an eye, was associated with reduced sector-based visual sensitivity (p<0.001 and p=0.671, respectively)., Conclusion: In a cohort with bilateral large drusen, quantifying HPA extent did not improve the prediction of late AMD development compared with presence alone. HPA extent was associated with more local, rather than generalised, reductions in visual sensitivity. These findings suggest that quantification of HPA extent adds little to the prediction of AMD progression, but that it provides an imaging biomarker of visual dysfunction., Competing Interests: Competing interests: Financial disclosure(s): PVW reports personal fees from Roche/Genentech, Bayer Australia, Novartis and Mylan outside the submitted work. RG reports personal fees from Roche/Genentech, Bayer, Novartis and Apellis outside the submitted work. KLG, HK, XH, MJ, CA, LH, LR, GM and ZW report nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors., Methods: This was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed., Results: The prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA., Conclusions: The risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition., Competing Interests: Competing interests: MCG and DB are inventors of the software used to collect the data for this analysis. MCG and JJA are members of advisory boards for Novartis, Bayer and Allergan. JJA reports personal fees and other from Novartis, other from Bayer, outside the submitted work., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD)., Methods: Database observational study of eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that received ranibizumab for at least 12 months before switching to aflibercept and followed for at least 12 months after the switch. Visual acuity (VA) recorded at 12 months after the switch was analysed using locally weighted scatterplot smoothing curves. Lesion activity was graded according to a prospectively identified definition. Main outcomes were change in VA and treatment intervals 12 months after the treatment switch. Secondary outcomes included change in activity grading, effect of duration of treatment before switching and analysis of eyes that switched back., Results: A total of 384 eyes switched from ranibizumab to aflibercept after a mean duration of 39.8 months on the original treatment. The mean VA did not change from the time of switching treatment (63.4, SD 15.9 logarithm of the minimum angle of resolution letters) to 12 months later (63.3, SD 16.7). While 10% of eyes gained 10 or more letters 12 months after the switch, 13% lost the same amount. The mean number of injections decreased by around one injection in the 12 months after switching (p<0.001), with a decrease in the proportion of choroidal neovascular membrane lesions that were graded as active. Eyes that had been treated for the longest time (49 or more months) before switching had worse vision at the point of switch but neither change in VA nor treatment interval was different between groups. The small proportion (6.9%) of eyes that switched back again to ranibizumab had already lost a mean of 5.2 letters from the first switch to the switch back and continued to lose vision at a similar rate for at least 6 months., Conclusions: The mean VA of eyes that switched treatments from ranibizumab to aflibercept was not different 12 months later. There was a modest increase in treatment intervals and a somewhat greater proportion of eyes that were graded as inactive after the switch., Competing Interests: JJA, RG, APH, ILM and MCG are members of advisory boards for Novartis and Bayer. JJA and MCG are also members of advisory boards for Allergan. MCG, JJA, APH and RG report personal fees and others from Novartis, others from Bayer, outside the submitted work. DB and APH received a research grant from Novartis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)