Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study.

INTRODUCTION: The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. METHODS: This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. RESULTS: The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; - 7.4 ± 23.0 versus - 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (- 179.9 vs - 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2-6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). CONCLUSION: At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01846273.

Relationship Between Retinal Layer Thickness and Genetic Susceptibility to Age-Related Macular Degeneration in Asian Populations.

Purpose: For OCT retinal thickness measurements to be used as a prodromal age-related macular degeneration (AMD) risk marker, the 3-dimensional (3D) topographic variation of the relationship between genetic susceptibility to AMD and retinal thickness needs to be assessed. We aimed to evaluate individual retinal layer thickness changes and topography at the macula that are associated with AMD genetic susceptibility. Design: Genetic association study. Participants: A total of 1579 healthy participants (782 Chinese, 353 Malays, and 444 Indians) from the multiethnic Singapore Epidemiology of Eye Diseases study were included. Methods: Spectral-domain OCT and automatic segmentation of individual retinal layers were performed to produce 10 retinal layer thickness measurements at each ETDRS subfield, producing 3D topographic information. Age-related macular degeneration genetic susceptibility was represented via single nucleotide polymorphisms (SNPs) and aggregated via whole genome (overall) and pathway-specific age-related macular degeneration polygenic risk score (PRSAMD). Main Outcome Measures: Associations of individual SNPs, overall PRSAMD, and pathway-specific PRSAMD with retinal thickness were analyzed by individual retinal layer and ETDRS subfield. Results: CFH rs10922109, ARMS2-HTRA1 rs3750846, and LIPC rs2043085 were the top AMD susceptibility SNPs associated with retinal thickness of individual layers (P < 1.67 × 10-3), all at the central subfield. The overall PRSAMD was most associated with thinner L9 (outer segment photoreceptor/retinal pigment epithelium complex) thickness at the central subfield (ß = -0.63 µm; P = 5.45 × 10-9). Pathway-specific PRSAMD for the complement cascade (ß = -0.53 µm; P = 9.42 × 10-7) and lipoprotein metabolism (ß = -0.05 µm; P = 0.0061) were associated with thinner photoreceptor layers (L9 and L7 [photoreceptor inner/outer segments], respectively) at the central subfield. The mean PRSAMD score was larger among Indians compared with that of the Chinese and had the thinnest thickness at the L9 central subfield (ß = -1.00 µm; P = 2.91 × 10-7; R2 = 5.5%). Associations at other retinal layers and ETDRS regions were more heterogeneous. Conclusions: Overall genetic susceptibility to AMD and the aggregate effects of the complement cascade and lipoprotein metabolism pathway are associated most significantly with L7 and L9 photoreceptor thinning at the central macula in healthy individuals. Photoreceptor thinning has potential to be a prodromal AMD risk marker, and topographic variation should be considered. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating the outcome of screening for glaucoma using colour fundus photography-based referral criteria in a teleophthalmology screening programme for diabetic retinopathy.

AIMS: To evaluate the effectiveness of glaucoma screening using glaucoma suspect (GS) referral criteria assessed on colour fundus photographs in Singapore's Integrated Diabetic Retinopathy Programme (SiDRP). METHODS: A case-control study. This study included diabetic subjects who were referred from SiDRP with and without GS between January 2017 and December 2018 and reviewed at Singapore National Eye Centre. The GS referral criteria were based on the presence of a vertical cup-to-disc ratio (VCDR) of ≥0.65 and other GS features. The final glaucoma diagnosis confirmed from electronic medical records was retrospectively matched with GS status. The sensitivity, specificity and positive predictive value (PPV) of the test were evaluated. RESULTS: Of 5023 patients (2625 with GS and 2398 without GS) reviewed for glaucoma, 451 (9.0%, 95% CI 8.2% to 9.8%) were confirmed as glaucoma. The average follow-up time was 21.5±10.2 months. Using our current GS referral criteria, the sensitivity, specificity and PPV were 81.6% (95% CI 77.7% to 85.1%), 50.6% (95% CI 49.2% to 52.1%) and 14.0% (95% CI 13.4% to 14.7%), respectively, resulting in 2257 false positive cases. Increasing the VCDR cut-off for referral to ≥0.80, the specificity increased to 93.9% (95% CI 93.1% to 94.5%) but the sensitivity decreased to 11.3% (95% CI 8.5% to 14.6%), with a PPV of 15.4% (95% CI 12.0% to 19.4%). CONCLUSIONS: Opportunistic screening for glaucoma in a lower VCDR group could result in a high number of unnecessary referrals. If healthcare infrastructures are limited, targeting case findings on a larger VCDR group with high specificity will still be beneficial.

Contribution of common and rare variants to Asian neovascular age-related macular degeneration subtypes.

Neovascular age-related macular degeneration (nAMD), along with its clinical subtype known as polypoidal choroidal vasculopathy (PCV), are among the leading causes of vision loss in elderly Asians. In a genome-wide association study (GWAS) comprising 3,128 nAMD (1,555 PCV and 1,573 typical nAMD), and 5,493 controls of East Asian ancestry, we identify twelve loci, of which four are novel ([Formula: see text]). Substantial genetic sharing between PCV and typical nAMD is noted (rg = 0.666), whereas collagen extracellular matrix and fibrosis-related pathways are more pronounced for PCV. Whole-exome sequencing in 259 PCV patients revealed functional rare variants burden in collagen type I alpha 1 chain gene (COL1A1; [Formula: see text]) and potential enrichment of functional rare mutations at AMD-associated loci. At the GATA binding protein 5 (GATA5) locus, the most significant GWAS novel loci, the expressions of genes including laminin subunit alpha 5 (Lama5), mitochondrial ribosome associated GTPase 2 (Mtg2), and collagen type IX alpha 3 chain (Col9A3), are significantly induced during retinal angiogenesis and subretinal fibrosis in murine models. Furthermore, retinoic acid increased the expression of LAMA5 and MTG2 in vitro. Taken together, our data provide insights into the genetic basis of AMD pathogenesis in the Asian population.

Clinical utility of ultra-widefield fluorescein angiography and optical coherence tomography angiography for retinal vein occlusions.

Retinal vein occlusions (RVOs) are the second most common retinal vascular disease after diabetic retinopathy, and are a significant cause of visual impairment, especially in the elderly population. RVOs result in visual loss due to macular ischemia, cystoid macular edema (CME), and complications related to neovascularization. Vascular assessment in RVOs traditionally relies on standard fluorescein angiography (FA) for assessment of macular and retinal ischemia, which aids in prognostication and guides intervention. Standard FA has significant limitations-it is time-consuming, requires invasive dye administration, allows for limited assessment of the peripheral retina, and is usually evaluated semi-qualitatively, by ophthalmologists with tertiary expertise. More recently, the introduction of ultra-widefield FA (UWF FA) and optical coherence tomography angiography (OCTA) into clinical practice has changed the tools available for vascular evaluation in RVOs. UWF FA allows for evaluation of peripheral retinal perfusion, and OCTA is non-invasive, rapidly-acquired, and provides more information on capillary perfusion. Both modalities can be used to provide more quantitative parameters related to retinal perfusion. In this article, we review the clinical utility and impact of UWF FA and OCTA in the evaluation and management of patients with RVOs.

Optical Coherence Tomography Angiography in Retinal Vascular Disorders.

Traditionally, abnormalities of the retinal vasculature and perfusion in retinal vascular disorders, such as diabetic retinopathy and retinal vascular occlusions, have been visualized with dye-based fluorescein angiography (FA). Optical coherence tomography angiography (OCTA) is a newer, alternative modality for imaging the retinal vasculature, which has some advantages over FA, such as its dye-free, non-invasive nature, and depth resolution. The depth resolution of OCTA allows for characterization of the retinal microvasculature in distinct anatomic layers, and commercial OCTA platforms also provide automated quantitative vascular and perfusion metrics. Quantitative and qualitative OCTA analysis in various retinal vascular disorders has facilitated the detection of pre-clinical vascular changes, greater understanding of known clinical signs, and the development of imaging biomarkers to prognosticate and guide treatment. With further technological improvements, such as a greater field of view and better image quality processing algorithms, it is likely that OCTA will play an integral role in the study and management of retinal vascular disorders. Artificial intelligence methods-in particular, deep learning-show promise in refining the insights to be gained from the use of OCTA in retinal vascular disorders. This review aims to summarize the current literature on this imaging modality in relation to common retinal vascular disorders.

Review of Retinal Imaging Modalities for Hydroxychloroquine Retinopathy.

This review provides an overview of conventional and novel retinal imaging modalities for hydroxychloroquine (HCQ) retinopathy. HCQ retinopathy is a form of toxic retinopathy resulting from HCQ use for a variety of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Each imaging modality detects a different aspect of HCQ retinopathy and shows a unique complement of structural changes. Conventionally, spectral-domain optical coherence tomography (SD-OCT), which shows loss or attenuation of the outer retina and/or retinal pigment epithelium-Bruch's membrane complex, and fundus autofluorescence (FAF), which shows parafoveal or pericentral abnormalities, are used to assess HCQ retinopathy. Additionally, several variations of OCT (retinal and choroidal thickness measurements, choroidal vascularity index, widefield OCT, en face imaging, minimum intensity analysis, and artificial intelligence techniques) and FAF techniques (quantitative FAF, near-infrared FAF, fluorescence lifetime imaging ophthalmoscopy, and widefield FAF) have been applied to assess HCQ retinopathy. Other novel retinal imaging techniques that are being studied for early detection of HCQ retinopathy include OCT angiography, multicolour imaging, adaptive optics, and retromode imaging, although further testing is required for validation.

FIVE-YEAR INCIDENCE OF FELLOW EYE NEOVASCULAR INVOLVEMENT IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY IN AN ASIAN POPULATION.

PURPOSE: To assess 5-year cumulative incidence and risk factors of fellow eye involvement in Asian neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy. METHODS: In a prospective cohort study of Asian nAMD and polypoidal choroidal vasculopathy, the fellow eyes were evaluated for exudation. The 5-year incidence of exudation was compared between nAMD and polypoidal choroidal vasculopathy. RESULTS: A total of 488 patients were studied. The 5-year incidence of exudation in fellow eyes was 16.2% (95% confidence interval: 12.0-20.2). Polypoidal choroidal vasculopathy compared with nAMD in the first eye was associated with lower fellow eye progression (9.8% [95% confidence interval: 5.1-14.3]) vs. 22.9% [95% confidence interval: 15.8-29.3], P < 0.01). Drusen (hazards ratio 2.11 [95% confidence interval: 1.10-4.06]), shallow irregular retinal pigment epithelium elevation (2.86 [1.58-5.18]), and pigment epithelial detachment (3.01 [1.27-7.17]) were associated with greater progression. A combination of soft drusens and subretinal drusenoid deposits, and specific pigment epithelial detachment subtypes (multilobular, and sharp peaked) were associated with progression. Pigment epithelial detachment, shallow irregular retinal pigment epithelium elevation, and new subretinal hyperreflective material occurred at 10.4 ± 4.2 months, 11.1 ± 6.0 months, and 6.9 ± 4.3 months, respectively, before exudation. CONCLUSION: The 5-year incidence of fellow eye involvement in Asian nAMD is lower than among Caucasians because of a higher polypoidal choroidal vasculopathy prevalence. Drusens, shallow irregular retinal pigment epithelium elevation, and pigment epithelial detachment are risk factors for fellow eye progression.

PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE.

PURPOSE: To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness. METHODS: This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness. RESULTS: Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 µm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 µm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 µm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 µm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed. CONCLUSION: Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.

CHOROIDAL VASCULAR ALTERATIONS IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate morphologic alterations in choroidal veins in eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective review of baseline indocyanine green angiography in eyes with typical nAMD and PCV. We evaluated Haller layer veins in the early-phase indocyanine green angiography (before 2 minutes) for 1) macular anastomosis, 2) dilated Haller veins, and 3) focal variation in vessel caliber by at least 50% from the narrowest to largest diameters. RESULTS: We included 70 patients with gradable indocyanine green angiography for the prespecified features in the study eye (36 typical nAMD and 34 PCV) and 59 fellow eyes. The median subfoveal choroidal thickness was 167 µm versus 219 µm, P = 0.08, in the presenting eyes in typical nAMD and PCV, respectively. Macular anastomosis was common in both typical nAMD and PCV (presenting eyes 58.3% vs. 58.8%. P = 0.97; fellow eyes 65.5% vs. 63.3%, P = 0.86). Dilated Haller veins were numerically less common in typical nAMD than PCV (presenting eyes 52.8% vs. 67.6%, P = 0.21; fellow eyes 65.5% vs. 70.0%, P = 0.71), while vascular caliber variation was numerically more common in typical nAMD than PCV (presenting eyes 72.2% vs. 63.8%, P = 0.45; fellow eyes 69.0% vs. 56.7%, P = 0.33). The presence of all three features was more common in the presenting eyes with PCV compared with typical nAMD (35.3% vs. 13.9%, P = 0.03). In a multivariable analysis, every increase of 100 µm of CT conferred a 2.75 risk of having all three features present. CONCLUSION: Choroidal vascular remodeling is common in both tAMD and PCV but may be driven by different stimuli.

Review of Fibrosis in Neovascular Age-Related Macular Degeneration.

PURPOSE: To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD). DESIGN: Systematic review and meta-analysis. METHODS: The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included. RESULTS: Identification of fibrosis is challenging. Optical coherence tomography angiography and polarization-sensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (-26.86 letters). CONCLUSIONS: There is a need to identify effective treatment strategies for fibrosis and to closely monitor at-risk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis.

Serum Cholesterol Efflux Capacity in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Purpose: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD). Design: Case-control study. Participants: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants. Methods: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and lipoprotein subfractions measured using nuclear magnetic resonance (Nightingale, Ltd). Associations between cholesterol efflux capacity (measured in percentage) and lipid subfractions were investigated in the patients and control participants. Main Outcome Measures: Cholesterol efflux capacity and lipid subfractions in control, eAMD, and nAMD. Associations between HDL subfractions and cholesterol efflux capacity. Results: Cholesterol efflux capacity was higher in patients with eAMD (68.0 ± 11.3% [mean ± standard deviation]) and nAMD (75.9 ± 27.7%) than in the control participants (56.9 ± 16.7%) after adjusting for age, gender, and use of lipid-lowering drug (P < 0.0001). Nuclear magnetic resonance lipidomics demonstrated that the mean diameter of HDL was larger both in eAMD (9.96 ± 0.27 mm [mean ± standard deviation]) and PCV (9.97 ± 0.23 mm) compared with that of the control participants (9.84 ± 0.24 mm; P = 0.0001 for both). Among the 28 HDL subfractions, most of the small, medium, and large HDLs, but none of the 7 extra large HDLs fractions, were associated moderately with cholesterol efflux capacity in eAMD and PCV (R = 0.149-0.277). Conclusions: Serum cholesterol efflux capacity was increased in eAMD and PCV, but not tAMD, possibly reflecting differential underlying pathophysiologic features of lipid dysregulation in tAMD and PCV. Further studies should be directed toward investigating the diverse biological activities of HDL in AMD, including macular pigment transport, regulation of inflammation, and local cholesterol transport system.

Understanding patient preferences in anti-VEGF treatment options for age-related macular degeneration.

PURPOSE: (1) To investigate the relative importance of convenience (consultation frequency and injection frequency) against treatment outcomes (visual and anatomical outcomes) and out-of-pocket medical costs via a discrete choice experiment (DCE), and (2) to investigate how patient characteristics affect patient treatment preferences. METHODS: Eligibility criteria were: (1) receiving a neovascular age-related macular degeneration (nAMD) diagnosis; (2) receiving anti-VEGF treatment; (3) being ≥21 years old, and (4) being able to speak and understand English/Mandarin. Patients were presented with eight choice tasks and asked to choose between their current treatment and two hypothetical treatments that varied by six attributes: number of clinic visits in a year, number of injections in a year, vision quality, control of swelling in retina, drug labelling and out-of-pocket cost. RESULTS: This analysis involved 180 patients. Based on latent class logistic regressions, vision quality was the most important attribute (34%) followed by cost (24%). The frequency of total clinic visits (15%) was the third most-important attribute, closely followed by labelling (12%) and control of retina swelling (11%). Injection frequency was the least important attribute (4%). CONCLUSIONS: Vision quality was the most important attribute followed by the out-of-pocket costs. Given the same outcomes, patients preferred treatment regimens which require fewer total clinic visits. In comparison, injection frequency alone did not influence patient preferences. With increasing treatment options for nAMD, understanding patients' preferences can help clinicians in selecting agents and treatment regimen most preferred for each patient, which may lead to improved long-term adherence and outcomes.

Three-dimensional modelling of the choroidal angioarchitecture in a multi-ethnic Asian population.

This study aimed to describe the topographic variation of the macula's choroidal angioarchitecture using three-dimensional (3D) choroidal vascularity index (CVI) of healthy eyes from an Asian population and to investigate the associations of CVI. 50 participants were recruited via stratified randomisation based on subfoveal choroidal thickness from the Singapore Epidemiology of Eye Diseases Study. Macular volume scans were acquired using spectral-domain optical coherence tomography with enhanced depth imaging. CVI was assessed based on B-scan binarisation and choroid segmentation. The 3D CVI of the whole, superior, central, and inferior macula were 62.92 ± 1.57%, 62.75 ± 1.93%, 63.35 ± 1.72%, and 62.66 ± 1.70%, respectively, pairwise comparisons P all > 0.05). 3D CVI (Whole Macula) and 2D CVI (Subfoveal) were associated only with each other and not with other ocular and systemic factors. 2D CVI (Subfoveal) had a moderate agreement with 3D CVI (Central Macula) [intraclass corelation coefficient (ICC) = 0.719], and had poorer agreement with 3D CVI of the whole macula, superior, and inferior macula (ICC = 0.591, 0.483, and 0.394, respectively). Scanning volume did not influence 3D CVI measurements. In conclusion, 3D CVI demonstrated no significant topographic variation. CVI was not correlated with demographic or ocular structural features. 2D CVI of the fovea is partially representative of 3D CVI of the macula.

Novel volumetric imaging biomarkers for assessing disease activity in eyes with PCV.

The aim of this study was to evaluate influence of baseline imaging features on visual and anatomical outcomes in eyes with PCV treated with anti-VEGF monotherapy. In this prospective study we enrolled participants with treatment-naïve PCV who followed a treat-and-extend protocol using intravitreal aflibercept (IVA) monotherapy. Baseline clinical features evaluatedincluded best corrected visual acuity (BCVA), traditional features such as lesion size, fluid-related OCT parameters and novel parameters using automated software. This included quantitative and qualitative pigment epithelium detachment (PED) parameters [height, volume]; and choroidal parameters. [choroidal thickness (CT), choroidal volume (CV) and choroidal vascularity index (CVI). We evaluated the predictive value of each parameter on visual and anatomical outcome at month 12. We additionally evaluated initial treatment response after 3 monthly injections with respect to month 12 outcomes. Fifty-two eyes from 52 participants were included in the study. The BCVA increased from 61.1 ± 13.2 to 69.6 ± 13.2 early treatment diabetic retinopathy study (ETDRS) letters (p < 0.01) and CRT reduced from 455.7 ± 182.4 µm to 272.7 ± 86.2 (p < 0.01) from baseline to month 12. The proportion of eyes with PED decreased significant from 100% at baseline to 80% at month 12 (p < 0.01). Reduction in the mean maximum height of PED (from 381.3 ± 236.3 µm to 206.8 vs ± 146.4 µm) and PED volume (from 1322 ± 853 nl to 686 ± 593 nl) (p < 0.01) was also noted from baseline to month12. Baseline features associated with better month 12 BCVA included baseline BCVA (ß = - 0.98, 95%CI - 3.38 to - 1.61, p = 0.02) and baseline CRT (ß = - 0.98, 95%CI - 1.56 to - 0.40, p = 0.04) while the disease activity at month12 was significantly associated with lower baseline CRT (366.0 ± 129.5 vs 612.0 ± 188.0 , p < 0.001), lower baseline PED height (242.0 ± 150.0 vs 542.0 ± 298.0 µm, p < 0.01), lower baseline PED volume (0.6 ± 0.3 mm3 vs 2.2 ± 1.3 mm3 vs, p < 0.01), lower proportion with marked CVH (17.9% vs 46.2%, p = 0.02) and lower mean CVI (61.8 ± 1.4 vs 63.0 ± 1.4, p < 0.02). Additionally, a larger decrease in CRT (per 100 nm) and larger PED volume reduction (per 100 nl) at month 3 from baseline were associated with greater BCVA gain and inactive disease. PED-related volumetric parameters have an additional predictive value to traditional biomarkers of disease activity in eyes with PCV undergoing anti-VEGF monotherapy. With increasingly precise quantification, PEDs can be a crucial biomarker in addition to traditional parameters and may aid in retreatment decisions.