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Background/aims: To determine the suitability of functional MRI (fMRI) as an objective measure of macular function following therapeutic intervention; conventional psychophysical measures rely heavily on patient compliance., Methods: Twenty patients with neovascular age-related macular degeneration (nAMD) were studied with high-resolution fMRI, visual acuity, reading accuracy and speed, contrast sensitivity (CS) and microperimetry (MP) before and after 3 monthly intravitreal injections of ranibizumab. Population-receptive field retinotopic maps calculated from fMRI data were compared with psychophysical measures and optical coherence tomography., Results: Best-corrected visual acuity (BCVA) responders (≥5 letters) showed an increase of 29.5% in activated brain area, while non-responders showed a decrease of 0.8%. Radial histograms over eccentricity allowed quantification of the absolute number of significant voxels and thus differences before and after treatment. Responders showed increases in foveal (α<0.5°) activation, while non-responders did not. Absence of intraretinal fluid and preservation of outer retinal layers was associated with higher numbers of active V1 voxels and better BCVA. Higher voxel numbers were associated with improved reading performance and, less marked, with BCVA, CS and MP., Conclusion: The data show that retinotopic mapping using fMRI can successfully be applied objectively to evaluate the therapeutic response in nAMD patients treated with anti-vascular endothelial growth factor therapy. This demonstrates the ability of retinotopic mapping to provide an objective assessment of functional recovery at a cortical level; the technique can therefore be applied, in other degenerative macular diseases, to the assessment of potential therapeutic interventions such as gene therapy or cell replacement therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: To assess the anatomic and functional outcomes in eyes with diabetic macular edema (DME) switched from intravitreal aflibercept to faricimab in a real-world setting., Methods: Retrospective, interventional consecutive case series. Patients with DME were switched from aflibercept to faricimab and categorized based on central subfield thickness (CST) 4 weeks after last aflibercept injection into responding DME (rDME, CST reduction >20% or CST ≤ 250 µm) and nonresponding DME (nrDME, CST unchanged or increased). Patients received a loading dose of two monthly faricimab injections followed by a treat-and-extend regimen. Differences in response between rDME and nrDME were analyzed based on injection interval, change in CST, and visual acuity (VA) 12 weeks postswitch., Results: Fifty-two eyes of 40 patients met inclusion criteria (rDME: n = 26, nrDME: n = 26). Baseline and week 12: VA (logMAR) rDME 0.29 ± 0.23 and 0.22 ± 0.28, nrDME 0.42 ± 0.32 and 0.36 ± 0.29; CST (µm) rDME 370 ± 99 and 288 ± 80, nrDME 384 ± 85 and 380 ± 129. After 12 weeks, 54% rDME and 25% nrDME eyes showed a CST decrease of >20% or CST ≤ 250 µm. Forty-six percent rDME and 50% nrDME eyes had a ±20% CST change, 25% of nrDME eyes had a >20% CST increase, and 73% of rDME eyes and 47% of nrDME eyes reached an extended interval of 8 weeks or longer after 12 weeks., Conclusions: Most DME eyes previously responding or not responding to aflibercept experienced a reduction or stabilization of DME after 12 weeks of faricimab treatment. rDME showed a better anatomic response, and treatment intervals could be extended earlier and longer than nrDME.

Objective: To analyze the presence and morphologic characteristics of drusenoid pigment epithelial detachments (DPEDs) in spectral-domain optical coherence tomography (SD-OCT) in Caucasian patients with early and intermediate age-related macular degeneration (AMD) as well as the influence of these characteristics on best-corrected visual acuity (BCVA) and disease progression., Design: Prospective observational cohort study., Participants: 89 eyes of 56 patients with early and intermediate AMD., Methods: Examinations consisted of BCVA, SD-OCT, and indocyanine green angiography. Evaluated parameters included drusen type, mean drusen height and -volume, the presence of DPED, DPED maximum height, -maximum diameter, -volume, topographic location, the rate of DPED collapse, and the development of macular neovascularization (MNV) or geographic atrophy (GA)., Results: DPED maximum height (162.34 µm ± 75.70 μm, p = 0.019) was significantly associated with the development of GA and MNV. For each additional 100 μm in maximum height, the odds of developing any late AMD (GA or MNV) increased by 2.23 (95% CI = 1.14-4.35). The presence of DPED (44 eyes, p = 0.01), its volume (0.20 mm ± 0.20 mm, p = 0.01), maximum diameter (1860.87 μm ± 880.74 μm, p = 0.03), maximum height (p < 0.001) and topographical location in the central millimetre (p = 0.004) of the Early Treatment Diabetic Retinopathy Study (ETDRS)-Grid were significantly correlated with BCVA at the last follow-up (0.15logMAR ± 0.20logMAR; Snellen equivalent approximately 20/28). DPEDs occurred significantly less in the outer quadrants than in the central millimetre and inner quadrants of ETDRS-Grid (all p values < 0.001)., Conclusions: The height of drusen and DPEDs is a biomarker that is significantly associated with the development of late AMD and visual loss. DPEDs affect predominantly the center and inner quadrants of the ETDRS-Grid., Competing Interests: Footnotes and Disclosure G.S.R. has received grant funding from RetInSight and speaker fees from Apellis. U.S.-E is a scientific consultant for Apellis, has received grant funding from Genentech, Kodiak, Novartis, Apellis, and RetInSight and has received patents/royalty from RetInSight. The rest of the authors indicate no financial support or conflicts of interest. All authors attest that they meet the current ICMJE criteria for authorship., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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 efficacy, durability, and safety of the bispecific antibody faricimab, which inhibits both angiopoietin-2 and VEGF-A., Design: TENAYA (ClinicalTrials.gov identifier, NCT03823287) and LUCERNE (ClinicalTrials.gov identifier, NCT03823300) were identically designed, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials., Participants: Treatment-naive patients with neovascular age-related macular degeneration (nAMD) 50 years of age or older., Methods: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg every 8 weeks (Q8W). Faricimab fixed dosing based on protocol-defined disease activity at weeks 20 and 24 up to week 60, followed up to week 108 by a treat-and-extend personalized treatment interval regimen., Main Outcome Measures: Efficacy analyses included change in best-corrected visual acuity (BCVA) from baseline at 2 years (averaged over weeks 104, 108, and 112) and proportion of patients receiving Q16W, every 12 weeks (Q12W), and Q8W dosing at week 112 in the intention-to-treat population. Safety analyses included ocular adverse events (AEs) in the study eye through study end at week 112., Results: Of 1326 patients treated across TENAYA/LUCERNE, 1113 (83.9%) completed treatment (n = 555 faricimab; n = 558 aflibercept). The BCVA change from baseline at 2 years was comparable between faricimab and aflibercept groups in TENAYA (adjusted mean change, +3.7 letters [95% confidence interval (CI), +2.1 to +5.4] and +3.3 letters [95% CI, +1.7 to +4.9], respectively; mean difference, +0.4 letters [95% CI, -1.9 to +2.8]) and LUCERNE (adjusted mean change, +5.0 letters [95% CI, +3.4 to +6.6] and +5.2 letters [95% CI, +3.6 to +6.8], respectively; mean difference, -0.2 letters [95% CI, -2.4 to +2.1]). At week 112 in TENAYA and LUCERNE, 59.0% and 66.9%, respectively, achieved Q16W faricimab dosing, increasing from year 1, and 74.1% and 81.2%, achieved Q12W or longer dosing. Ocular AEs in the study eye were comparable between faricimab and aflibercept groups in TENAYA (55.0% and 56.5% of patients, respectively) and LUCERNE (52.9% and 47.5% of patients, respectively) through week 112., Conclusions: Treat-and-extend faricimab treatment based on nAMD disease activity maintained vision gains through year 2, with most patients achieving extended dosing intervals., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate change in retinal layers 18 months after femtosecond laser-assisted cataract surgery (LCS) and manual cataract surgery (MCS) in a representative age-related cataract population using artificial intelligence (AI)-based automated retinal layer segmentation., Methods: This was a prospective, randomized and intraindividual-controlled study including 60 patients at the Medical University of Vienna, Austria. Bilateral same-day LCS and MCS were performed in a randomized sequence. To provide insight into the development of cystoid macular oedema (CME), retinal layer thickness was measured pre-operatively and up to 18 months post-operatively in the central 1 mm, 3 mm and 6 mm., Results: Fifty-six patients completed all follow-up visits. LCS compared to MCS did not impact any of the investigated retinal layers at any follow-up visit (p > 0.05). For the central 1 mm, a significant increase in total retinal thickness (TRT) was seen after 1 week followed by an elevated plateau thereafter. For the 3 mm and 6 mm, TRT increased only after 3 weeks and 6 weeks and decreased again until 18 months. TRT remained significantly increased compared to pre-operative thickness (p < 0.001). Visual acuity remained unaffected by the macular thickening and no case of CME was observed. Inner nuclear layer (INL) and outer nuclear layer (ONL) were the main causative layers for the total TRT increase. Photoreceptors (PR) declined 1 week after surgery but regained pre-operative values 18 months after surgery., Conclusion: Low-energy femtosecond laser pre-treatment did not influence thickness of the retinal layers in any topographic zone compared to manual high fluidic phacoemulsification. TRT did not return to pre-operative values 18 months after surgery. The causative layers for subclinical development of CME were successfully identified., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

To compare the effectiveness and safety of scleral buckling and pars plana vitrectomy in treating retinal detachment without posterior vitreous detachment. A total of 88 eyes of 83 patients with retinal detachment without prior posterior vitreous detachment were investigated retrospectively. Group A comprised patients who underwent scleral buckling (n = 47) and Group B (n = 36) patients who were treated with pars plana vitrectomy. Anatomical success, postoperative visual acuity, and ocular adverse events were evaluated. The primary and final anatomical success rate showed a nonsignificant difference (p = 0.465 and p = 0.37 respectively). No significant difference was observed in the reoperation rate or development of epiretinal membrane between the groups (p = 0.254 and p = 0.254 respectively). However, scleral buckling resulted in significantly better visual acuity at the last follow-up (0.12 ± 0.23) compared to pars plana vitrectomy (0.37 ± 0.46, p = 0.001). The incidence of cataract progression was also significantly higher in the pars plana vitrectomy group (46%) compared to the scleral buckling group (10%, p < 0.001). Scleral buckling and pars plana vitrectomy show similar success rates in treating retinal detachment without vitreous detachment. However, due to less cataract progression and better visual acuity outcomes, scleral buckling is recommended for these cases. Determining vitreous status before surgery is crucial for optimal outcomes., (© 2024. The Author(s).)

Purpose: To evaluate the postoperative outcome of strabismus surgery performed in children aged 1-6 years by investigating the change of the preoperative angle of deviation (AOD), elevation in adduction, best-corrected visual acuity (BCVA) and refractive error., Methods: Retrospective chart review of 62 children who received strabismus surgery between January 2018 and December 2021 at the Department of Ophthalmology and Optometry of the Medical University of Vienna. Age, sex, type of strabismus, AOD, BCVA, refractive error and visual acuity were evaluated with respect to the postoperative outcome., Results: Mean follow-up was 13.55 ± 11.38 months with a mean age of 3.94 ± 1.97 years (range: 1.0-6.0) at time of surgery. 74.19% of patients (n = 46) had isolated or combined esotropia, 12.90% (n = 8) had isolated or combined exotropia and 12.90% (n = 8) had isolated strabismus sursoadductorius. Mean preoperative AOD of 15.69 ± 16.91°/15.02 ± 14.88° (near/distance) decreased to 4.00 ± 9.18°/4.83 ± 7.32° (near/distance) at final follow-up (p < 0.001). BCVA improved from 0.26 ± 0.26/0.25 ± 0.23 (left/right) to 0.21 ± 0.25/0.20 ± 0.23 (left/right) (p = 0.038). There was no significant change regarding refractive error (p = 0.109) or elevation in adduction (p = 0.212). Success rate which was defined as a residual AOD of less than 10° was 74.19% (n = 46). In 3.23% (n = 2) retreatment was necessary., Conclusion: Strabismus surgery in infants was shown to have a satisfactory outcome with a low retreatment rate. Surgical success rate was not linked to age, sex, type of strabismus or the preoperative parameters AOD, refractive error and visual acuity in this study., (© 2024. The Author(s).)

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

Geographic atrophy (GA) is an advanced and irreversible form of age-related macular degeneration (AMD). Chronic low grade inflammation is thought to act as an initiator of this degenerative process, resulting in loss of photoreceptors (PRs), retinal pigment epithelium (RPE) and the underlying choriocapillaris. This review examined the challenges of clinical trials to date which have sought to treat GA, with particular reference to the successful outcome of C3 complement inhibition. Currently, optical coherence tomography (OCT) seems to be the most suitable method to detect GA and monitor the effect of treatment. In addition, the merits of using novel anatomical endpoints in detecting GA expansion are discussed. Although best-corrected visual acuity is commonly used to monitor disease in GA, other tests to determine visual function are explored. Although not widely available, microperimetry enables quantification of retinal sensitivity (RS) and macular fixation behaviour related to fundus characteristics. There is a spatial correlation between OCT/fundus autofluorescence evaluation of PR damage outside the area of RPE loss and RS on microperimetry, showing important associations with visual function. Standardisation of testing by microperimetry is necessary to enable this modality to detect AMD progression. Artificial intelligence (AI) analysis has shown PR layers integrity precedes and exceeds GA loss. Loss of the ellipsoid zone has been recognised as a primary outcome parameter in therapeutic trials for GA. The integrity of the PR layers imaged by OCT at baseline has been shown to be an important prognostic indicator. AI has the potential to be invaluable in personalising care and justifying treatment intervention., Competing Interests: Competing interests: SV: consultant to AbbVie, Apellis, Bayer, Novartis, Hoffman La Roche and Zeiss. AL: consultant to Allergan, Bayer, Beyeonics, ForSight Labs, Notal Vision, Novartis and Roche. LO’T: consultant to Novartis and Bayer. UMS-E: contract research for Roche, Novartis, Apellis, RetInSight. Scientific consultancy for Boehringer, AbbVie, Novartis, Roche, RetInSight, Heidelberg Engineering and Stealth Bio Therapeutics. DZ: Consultant to AbbVie, Bayer, Novartis and Hoffman La Roche. UC: consultant to Apellis, Boehringer Ingelheim, Iveric and Hoffman La Roche., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate associations between residual subretinal fluid (rSRF) volumes, quantified using artificial intelligence and treatment outcomes in a subretinal fluid (SRF)-tolerant treat-and-extend (T&E) regimen in neovascular age-related macular degeneration., Methods: Patients enrolled in the prospective, multicenter FLUID study randomized in an SRF-tolerant T&E regimen were examined by spectral-domain optical coherence tomography and tested for best-corrected visual acuity (BCVA). Intraretinal fluid and SRF volumes were quantified using artificial intelligence tools. In total, 375 visits of 98 patients were divided into subgroups: extended intervals despite rSRF and extended intervals without fluid. Associations between BCVA change, SRF volume, subgroups, and treatment intervals were estimated using linear mixed models., Results: In extended intervals despite rSRF, increased SRF was associated with reduced BCVA at the next visit in the central 1 mm (-0.138 letters per nL; P = 0.014) and 6 mm (-0.024 letters per nL; P = 0.049). A negative association between increased interval and BCVA change was found for rSRF in 1 mm and 6 mm (-0.250 and -0.233 letter per week interval, respectively; both P < 0.001). Extended intervals despite rSRF had significantly higher SRF volumes in the central 6 mm at the following visit (P = 0.002)., Conclusion: Artificial intelligence-based analysis of extended visits despite rSRF demonstrated increasing SRF volumes associated with BCVA loss at the consecutive visit. This negative association contributes to the understanding of rSRF volumes on treatment outcomes in neovascular age-related macular degeneration.

Purpose: The purpose of this study was to assess density and morphology of cone photoreceptors (PRs) and corresponding retinal sensitivity in ischemic compared to nonischemic retinal capillary areas of diabetic eyes using adaptive optics optical coherence tomography (AO-OCT) and microperimetry (MP)., Methods: In this cross-sectional, observational study five eyes of four patients (2 eyes with proliferative diabetic retinopathy (DR) and 3 eyes moderate nonproliferative DR) were included. PR morphology and density was manually assessed in AO-OCT en face images both at the axial position of the inner-segment outer segment (IS/OS) and cone outer segment tips (COSTs). Retinal sensitivity was determined by fundus-controlled microperimetry in corresponding areas (MP-3, Nidek)., Results: In AO-OCT, areas affected by capillary nonperfusion showed severe alterations of cone PR morphology at IS/OS and COST compared to areas with intact capillary perfusion (84% and 87% vs. 9% and 8% of area affected for IS/OS and COST, respectively). Mean reduction of PR signal density in affected areas compared to those with intact superficial capillary plexus (SCP) and deep capillary plexus (DCP) perfusion of similar eccentricity was -38% at the level of IS/OS (P = 0.01) and -39% at the level of COST (P = 0.01). Mean retinal sensitivity was 10.8 ± 5.4 in areas affected by DCP nonperfusion and 28.2 ± 1.5 outside these areas (P < 0.001)., Conclusions: Cone PR morphology and signal density are severely altered in areas of capillary nonperfusion. These structural changes are accompanied by a severe reduction of retinal sensitivity, indicating the importance of preventing impaired capillary circulation in patients with DR.

Purpose: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD)., Methods: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates., Results: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875)., Conclusion: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.

Purpose: To investigate quantitative differences in fluid volumes between subretinal fluid (SRF)-tolerant and SRF-intolerant treat-and-extend regimens for neovascular age-related macular degeneration and analyze the association with best-corrected visual acuity., Methods: Macular fluid (SRF and intraretinal fluid) was quantified on optical coherence tomography volumetric scans using a trained and validated deep learning algorithm. Fluid volumes and complete resolution was automatically assessed throughout the study. The impact of fluid location and volumes on best-corrected visual acuity was computed using mixed-effects regression models., Results: Baseline fluid quantifications for 348 eyes from 348 patients were balanced (all P > 0.05). No quantitative differences in SRF/intraretinal fluid between the treatment arms was found at any study-specific time point (all P > 0.05). Compared with qualitative assessment, the proportion of eyes without SRF/intraretinal fluid did not differ between the groups at any time point (all P > 0.05). Intraretinal fluid in the central 1 mm and SRF in the 1-mm to 6-mm macular area were negatively associated with best-corrected visual acuity (-2.8 letters/100 nL intraretinal fluid, P = 0.007 and -0.20 letters/100 nL SRF, P = 0.005, respectively)., Conclusion: Automated fluid quantification using artificial intelligence allows objective and precise assessment of macular fluid volume and location. Precise determination of fluid parameters will help improve therapeutic efficacy of treatment in neovascular age-related macular degeneration.

Purpose: We aimed to determine the correlation between optical coherence tomography (OCT)- and demographic features and baseline best corrected visual acuity (BCVA) in treatment-naïve patients with retinal vein occlusion (RVO)., Methods: This was a cross-sectional posthoc analysis of OCT images that included RVO patients from two prospective, open-label, multicentre studies. The morphological grading was done manually, in the standardized setting of a reading centre. Main outcome measure was the estimated difference in Early Treatment Diabetic Retinopathy Study letters associated with each individual biomarker., Results: Included were 381/301 treatment-naïve patients with BRVO/CRVO. For BRVO, statistically significant correlations with BCVA were seen for a 100 µm increase in central subfield thickness (CST; -3.1 letters), intraretinal cysts at centre point (CP; +4.1), subretinal fluid (SRF) at CP (+3.0) and hyperreflective foci (HRF) at the central B-scan (-2.2). In CRVO, a 100 µm increase in CST was associated with a loss of -3.4 letters. In the total cohort, 100 µm increase in CST, SRF at CP and HRF at the central B-scan correlated with a difference of -3.2,+3.2 and -2.0 letters. A 10-year increase in age and female gender yielded a -2.0 and -2.5 letter decrease in the total cohort. Adjusted multiple R 2 for the respective group was 18.3%/26.3%/23.5%., Conclusions: Of all parameters studied, only CST and age were consistently associated with worse BCVA in treatment-naïve RVO patients. Morphology on OCT explained only a modest part of functional loss in this patient cohort., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT)., Methods: In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC)., Results: Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group., Conclusions: We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

Purpose: To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) during the primary response to anti-VEGF therapy using aflibercept., Methods: Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti-VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post-initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi-automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed., Results: Thirty-two consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. Close follow-up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best-corrected visual acuity and quantitative change in lesion size over time, but not baseline size., Conclusions: Using SSOCTA, a morphologic neovascular response pattern can be identified in anti-VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To determine microvascular changes in children with a history of retinopathy of prematurity (ROP) and in a control group of full-term children., Methods: In a cross-sectional study, 30 eyes of 15 children aged 6-8 years with a history of ROP were evaluated with swept-source optical coherence tomography angiography (SS-OCTA). Twenty-eight eyes of 22 age-matched full-term children served as a healthy control group. The foveal avascular zone (FAZ), vessel density (VD) and choroidal vascular flow area (VFA) were evaluated on OCTA and correlated with central retinal thickness (CRT), visual acuity (VA), birth weight (BW), gestational age (GA) and ROP stages., Results: Twenty-two eyes of 14 children with a history of ROP (stage 1-3) and 25 eyes of 19 full-term children were available for evaluation. In the ROP group, the gestational age was 27 ± 2 weeks and birth weight was 781 ± 164 g. In the ROP group, CRT was higher in the central ETDRS segment (mean difference [95% CI]: 32.8 µm [18.7; 47.0], p = 0.0002) compared to the controls. Smaller mean FAZ area (-0.12 [-0.19; -0.04], p = 0.004) and perimeter (-662 [-1228; -96], p = 0.03) was found in comparison to the control group. An oval shape of the FAZ was observed among patients with a history of ROP. The mean central VD of the superficial plexus was 28 ± 8/23 ± 8% and of the deep plexus 7 ± 7/3 ± 5% (ROP group/control group; p > 0.05). No statistically significant difference was found regarding the choroidal VFA. Only weak correlation of FAZ and VD with function was observed., Conclusions: Swept-source optical coherence tomography angiography imaging revealed significant microvascular anomalies in children with a history of ROP indicating disturbance of early morphological development of the central retina., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To prospectively evaluate the outcomes of different subtypes of neovascular age-related macular degeneration during intravitreal aflibercept monotherapy., Methods: Forty-four eyes of 44 patients with treatment-naïve polypoidal choroidal vasculopathy (PCV, n = 12), hemorrhagic choroidal neovascularization (hCNV, n = 12), pigment epithelium detachment (PED, n = 11), or retinal angiomatous proliferation (RAP, n = 9) were included and followed for 12 months. All patients received intravitreal aflibercept monotherapy., Results: Mean visual acuity at baseline in PCV was 67 ± 16 Early Treatment Diabetic Retinopathy Study letters (20/50 Snellen equivalent), in hCNV 55 ± 21 (20/80), in RAP lesions 64 ± 11 (20/50), and in PED 74 ± 7 (20/32). At Month 12, visual acuity in PCV was 66 ± 16 (20/50), in hCNV 69 ± 17 (20/40), in RAP 68 ± 12 (20/50), and in PED 69 ± 18 (20/40). At the 12-month follow-up, visual acuity improved or was stable (±5 letters from baseline) in 84% of eyes (37/44 patients), with hCNV showing the greatest mean visual acuity gain. Mean central retinal thickness in patients with PCV was 523 ± 251 µm, in hCNV 497 ± 171, in RAP lesions 573 ± 132, and in PED 541 ± 158 and decreased to 310 ± 91 µm in PCV, 323 ± 75 µm in hCNV, 357 ± 173 µm in RAP lesions, and 422 ± 150 µm in PED. The mean area of atrophy increased from 2.0 ± 3.6 mm2 at baseline to 4.6 ± 8.6 mm2 at Month 12 (mean difference [95% confidence interval] -0.8 [-8.5 to 7.0], P = 0.8), with the greatest atrophy in patients with PED at Month 12., Conclusion: All subtypes of neovascular age-related macular degeneration showed anatomical improvement and stabilization of visual function during intravitreal treatment.

Purpose: To report the 96-week outcomes from HAWK and HARRIER., Design: Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD)., Participants: Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER)., Methods: After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w., Main Outcome Measures: Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w., Results: Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 μm vs. -148.7 μm; 95% confidence interval for treatment difference, -46.2 to -5.9 μm; P = 0.0115) and HARRIER (LS mean, -197.7 μm vs. -155.1 μm; 95% confidence interval for treatment difference, -62.0 to -23.3 μm; P < 0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P < 0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile., Conclusions: Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Large amounts of optical coherence tomographic (OCT) data of diabetic macular edema (DME) are acquired, but many morphologic features have yet to be identified and quantified., Objective: To examine the volumetric change of intraretinal fluid (IRF) and subretinal fluid (SRF) in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms., Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. This analysis was performed from December 7, 2017, to January 15, 2020., Interventions: Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab, or bevacizumab with or without deferred laser., Main Outcomes and Measures: The association of treatment with IRF and SRF volumes and best-corrected visual acuity (BCVA) during 12 months using deep learning algorithms., Results: Among the 570 study participants (302 [53%] male; 369 [65%] white; mean [SD] age, 43.4 [12.6] years), the mean fluid volumes in the central 3 mm were 448.6 nL (95% CI, 412.3-485.0 nL) of IRF and 36.9 nL (95% CI, 27.0-46.7 nL) of SRF at baseline and 161.2 nL (95% CI, 135.1-187.4 nL) of IRF and 4.4 nL (95% CI, 1.7-7.1 nL) of SRF at 12 months. The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) score of 63.2 (95% CI, 60.2-66.1) (approximate Snellen equivalent of 20/63 [95% CI, 20/50-20/63]) in eyes with SRF vs 66.9 (95% CI, 65.7-68.1) (approximate Snellen equivalent, 20/50 [95% CI, 20/40-20/50]) without SRF (P < .001) and a greater gain in ETDRS score (0.5; 95% CI, 0.3-0.8) every 4 weeks during follow-up in eyes with SRF at baseline vs 0.4 (95% CI, 0.3-0.5) in eyes without SRF at baseline (P = .02) when adjusted for baseline BCVA. Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; 95% CI, 5.3-162.5 nL; P < .001) and every 4 weeks thereafter (difference, 10.4 nL; 95% CI, 0.7-20.0 nL; P = .004). Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; 95% CI, 1.4-154.7 nL; P < .001)., Conclusions and Relevance: Automated segmentation of fluid in DME revealed that the presence of SRF was associated with lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. These automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT01627249.

Purpose: To characterize retinal morphology differences among different types of choroidal neovascularization and visual function changes at the onset of exudative age-related macular degeneration., Methods: In a post hoc analysis of a prospective clinical study, 1,097 fellow eyes from subjects with choroidal neovascularization in the study eye enrolled in the HARBOR trial were evaluated. The onset of exudation was diagnosed on monthly optical coherence tomography by two masked graders. At conversion as well as 1 month earlier, pigment epithelial detachment, intraretinal cystoid fluid, subretinal fluid, subretinal hyperreflective material, as well as ellipsoid zone and external limiting membrane loss were quantitatively analyzed. Hyperreflective foci, retinal pigment epithelial defects, haze and vitreoretinal interface status were evaluated qualitatively. Main outcome measures included visual acuity and rates of morphologic features at conversion and 1 month earlier., Results: New-onset exudation was detected in 92 eyes. One month before conversion, hyperreflective foci, pigment epithelial detachment, retinal pigment epithelial defects, and haze were present in the majority of eyes. At the onset of exudation, the volumes of intraretinal cystoid fluid, subretinal fluid, subretinal hyperreflective material and pigment epithelial detachment, and the areas of external limiting membrane and ellipsoid zone loss significantly increased. The mean vision loss was -2.2 letters. Pathognomonic patterns of the different choroidal neovascularization types were already apparent 1 month before conversion., Conclusion: Characteristic choroidal neovascularization-associated morphological changes are preceding disease conversion, while vision loss at the onset of exudation is minimal. Individual lesion types are related to specific changes in optical coherence tomography morphology already before the time of conversion. Our findings may help to elucidate the pathophysiology of neovascular age-related macular degeneration and support the diagnosis of imminent disease conversion.

Introduction: Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the industrialized world. While effective treatment is available for neovascular AMD, no therapy is successful for the non-neovascular form. Herein, the authors report the current knowledge on non-neovascular AMD pathogenesis and the promising research on treatments., Areas Covered: In the present review, the authors summarize the most recent advances in the treatment of non-neovascular AMD and provide an update on current treatment strategies. Evidence available from preclinical and clinical studies and from a selective literature search is reported., Expert Opinion: When investigating AMD, numerous pathological cascades and alterations of physiological processes have been investigated. It is well-known that AMD is a multifactorial disease, with environmental causes and genetics playing a role. Perturbations in multiple pathogenic pathways have been identified and this led to the development of several molecules directed at specific therapeutic targets. However, despite the huge research effort, the only proven approach so far is oral antioxidant supplementation. We believe that, in addition to successful advancement of promising drugs, further research should be directed at tailoring therapy to specific patient groups, eventually employing a combinational therapy strategy.

Purpose : To evaluate the functional and morphological outcomes of patients with SO tamponade due to primary rhegmatogenous retinal detachment (primRD) and recurrent rhegmatogenous detachment (recRD). Methods : Seventy-five eyes were enrolled in this prospective study between January 2009 and December 2016. Patients with primRD and recRD were evaluated in a complete ophthalmic examination including best-corrected visual acuity (BCVA) and OCT before and after silicone oil removal (SOR). Results : The primRD group comprised 35 eyes and the recRD group 40 eyes with a duration of SO tamponade of 9 ± 4/12 ± 11 months in the primRD/recRD groups ( p = .088). The preoperative OCT revealed a high rate of morphological changes such as ERM (primRD: 24%; recRD: 69%) and CME (primRD: 10%; recRD: 55%) in the recRD compared with the primRD group (ERM: p = .18; CME: p = .04). No such difference was observed postoperatively. Disruption of the ellipsoid zone (EZ) was similar in both groups (primRD: 52%; recRD: 72%) before SOR and was restored in 66%/58% (primRD/recRD) after SOR. No difference was found regarding pre- and postoperative VA (0.91 ± 0.54/0.90 ± 0.54logMAR primRD/recRD preoperative; 0.76 ± 0.56/0.71 ± 0.53logMAR primRD/recRD at the last follow-up; p = .96/ p = .70). EZ integrity (0.43 ± 0.31logMAR) was associated with better functional results than an interrupted EZ (0.86 ± 0.43logMAR; p < .001). A significant positive correlation of the duration of SO tamponade and the final VA was found in the primRD (r = 0.396, p = .02) whereas none in the recRD group (r = 0.196; p = .31). Conclusion : Morphological changes including ERM and CME were more pronounced in the recRD group, but only before SOR. Interestingly, the pre- and postoperative BCVA were similar in both groups with EZ integrity being a factor of good functional outcome. The duration of SO tamponade had a statistically significant negative impact on the postoperative VA in the primary detachments.

Purpose: To examine the prevalence of central retinal atrophy in patients treated for diabetic macular edema (DME) in a clinical setting., Methods: Retrospective data analysis of patients with DME, focusing on those who developed central retinal thinning after DME treatment at the Department of Ophthalmology, Medical University Vienna. Patient characteristics and clinical data including best-corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescence angiography images were reviewed and DME treatment strategies analysed using descriptive statistics. The correlation between visual acuity and ocular, systemic or DME treatment factors was calculated using linear regression models and ancovas., Results: A total of 6684 outpatient visits by 1437 patients with diabetes were analysed. Out of 149 patients, who had had a central subfield thickness (CST) below 200 μm, 32 (36 eyes) had previously been diagnosed with a centre involving DME with an average CST of 473 ± 103 μm and average visual acuity of 0.62 ± 0.44 logMAR at first presentation. At the time of central atrophy, 29 (81%) out of 36 eyes had a history of laser treatment, 11 (31%) a vitrectomy, 32 (88%) repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF; mean 5.3 ± 3.8) and 22 (61%) intravitreal corticosteroid injections (mean 2.5 ± 2.7). Visual function (0.67 ± 0.43 logMAR) at the time of atrophy was not significantly correlated to central retinal thickness (191 ± 7 μm) or any other ocular, systemic or treatment factors., Conclusions: Only 4% of patients treated for DME developed central retinal thinning in our observation period. On average, our atrophy patients had higher CST and lower BCVA when they first presented with DME compared to the overall DME cohort, and they received a combination of intravitreal injections and laser for DME treatment. Central retinal atrophy might not be attributed to excessive use of intravitreally applied anti-VEGF or any other DME therapy alone., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare inter- and intraobserver reliability and intermodality agreement on quantification of geographic atrophy, using two routinely available quantification tools, based on blue-light fundus autofluorescence (BAF) and spectral-domain optical coherence tomography (SD-OCT)., Methods: Quantifications of atrophic lesions within the central 5 mm of 30 eyes from 30 patients (mean age: 76.1 years) were independently performed by two clinicians on BAF images using the region finder (RF; Heidelberg Engineering) and on SD-OCT using the advanced retinal pigment epithelium tool (ARPET; Carl Zeiss Meditec) at baseline and follow-up (mean interval: 336 days). Inter- and intraobserver reliability was determined by intraclass correlation coefficients (ICC) and Bland-Altmann plots. Additionally, graders rated the experienced difficulty of each measurement., Results: Intraclass correlation coefficients (ICC) showed excellent inter- and intraobserver reliability with values between 0.994 and 0.998 for RF and slightly higher values for ARPET of 0.997 and 0.999. Bland-Altman plots showed smaller variability for ARPET. Mean interobserver differences (95% CI) for size measurements were -0.11 (-0.27; 0.05) (baseline) and -0.05 mm² (-0.18; 0.08) (follow-up) for RF and -0.04 (-0.14; 0.06) and -0.06 mm² (-0.14; 0.02) for ARPET. Measurements of lesions were on average 0.57 mm² (0.35; 0.79) or 7.6% larger in ARPET. Lesion size between graders did not differ significantly. There was no statistically significant difference in relative enlargement rates between methods. There was poor to moderate agreement between graders when rating the experienced difficulty of each measurement., Conclusion: Semi-automated analysis of geographic atrophy with RF and ARPET is equally reliable and reproducible in clinical settings, despite both algorithms require frequent adjustment by users. The ARPET restricts size measurements to the central 5 mm, which limits its ability to fully track GA progression. Results of both tools are not interchangeable as measurements with ARPET result in larger lesion sizes., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmological Scandinavica Foundation.)

Background: To evaluate the change in peripheral perfusion status in patients with retinal vein occlusion (RVO) during dexamethasone treatment., Methods: Thirty-five eyes of patients with macular oedema due to either branch or central retinal vein occlusion were included. At baseline, patients were treated with an intravitreal dexamethasone implant (Ozurdex ® ) and followed until month 6. Wide-field angiographies were classified as ischaemic and nonischaemic. Peripheral nonperfusion (PNP) was determined manually by calculating the percentage of nonperfusion area in relation to the total visible retina (ischaemic index)., Results: Thirteen eyes showed evidence of >10 disc area of PNP at baseline and were graded as ischaemic RVO. In nonischaemic eyes, the mean area of PNP was 0.3% at baseline, 0.6% after 1 month, 0.6% after 3 months and 0.6% after 6 months, respectively (p > 0.05). In ischaemic RVO, the ischaemic index was calculated to be 18% at baseline. One month after treatment, mean area of PNP was 16% and after 3 months was 19% (p = 0.8; p = 0.6). After retreatment, total PNP area was 18% (month 6; p = 0.9). During treatment, best-corrected visual acuity (BCVA) increased and central retinal thickness (CRT) decreased from baseline to final follow-up with no differences between nonischaemic/ischaemic RVO. A significant negative correlation between the total area of PNP and visual acuity was identified (r = -0.6; p = 0.04)., Conclusion: Using 200° wide-field fluorescein angiography, the ischaemic index was shown to remain stable during dexamethasone treatment. This finding was consistent in ischaemic as well as in nonischaemic conditions., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Importance: Anti-vascular endothelial growth factor treatment is the first-line therapy in the treatment of center-involving diabetic macular edema. Data on capillary perfusion changes under repeated treatment in a possibly compromised vascular network are limited., Objective: To evaluate the association of repeated ranibizumab injections on macular perfusion in patients with diabetic macular edema., Design, Setting, and Participants: This study analyzed prospectively collected data from the 12-month RESTORE core study and the 24-month open label RESTORE extension study, which assessed the efficacy and safety of ranibizumab in patients with visual impairment due to diabetic macular edema. Of 345 patients with center-involving diabetic macular edema who had enrolled in the 12-month RESTORE core study, 240 entered the 24-month RESTORE extension study. Of these, 83 (34.6%) received ranibizumab, 83 (34.6%) received ranibizumab and laser combination therapy, and 74 (30.8%) received laser monotherapy in the first year of the study; 208 completed the 24-month extension study. Fluorescence angiography images were taken from each participant twice each year graded by Vienna Reading Center on severity of capillary loss in the parafoveal area, regularity of the foveal avascular zone outline, and measurement of the size of the foveal avascular zone, following a standardized protocol. Data analysis took place from July 2014 through December 2017., Main Outcomes and Measures: Change in 3 fluorescence angiography perfusion parameters over the course of treatment., Results: Mean (SD) patient age was 62.6 (8.8) years; 124 of 208 (59.2%) were male and 197 of 208 (94.6%) were white. The number of patients with definite altered foveal avascular zone regularity at baseline was 103 of 240 patients (42.9%); another 118 patients (49.2%) had questionably altered regularity at baseline. Definitive capillary loss was found in 65 of 240 patients (27.1%) at baseline. Mean (SD) foveal avascular zone size at baseline was 0.261 (0.232) mm2 in ranibizumab monotherapy, 0.231 (0.219) mm2 in ranibizumab and macular laser combination therapy, and 0.201 (0.13) mm2 in laser monotherapy. No treatment arm experienced significant increase in foveal avascular zone size at any time in the study period. At month 36, ranibizumab monotherapy resulted in a mean increase of 0.073 mm2 (95% CI, 0.005-0.142 mm2) and combination therapy resulted in a mean increase of 0.117 mm2 (95% CI, 0.045-0.188 mm2), but no changes were statistically significant. No changes occurred in foveal avascular zone regularity in any treatment group, and no differences were found in capillary loss around the fovea in the 3 treatment groups; neither element could be correlated with visual acuity or central retinal thickness., Conclusions and Relevance: Repeated ranibizumab treatment was not associated with impaired macular perfusion in our study cohort. Because our data do not suggest a harmful effect of anti-vascular endothelial growth factor therapy on capillary integrity, patients with severe microangiopathy and advanced capillary dropout should not be denied these treatments.

Purpose: To evaluate the evolution of surgical methods over a 7-year period in patients with primary rhegmatogenous retinal detachment (RRD) and its relation to functional outcome and intra- and postoperative complications., Methods: This prospective observational study included 628 patients with primary RRD who underwent surgical repair between January 2009 and December 2015. The main outcome measures were the type of surgical procedure ((scleral buckle (SB), pars plana vitrectomy (PPV), combination of SB and PPV or cryocoagulation (CC)) and intraocular tamponades. In addition, functional outcome and intra/postoperative complications were assessed over the observational period., Results: During the 7-year observation, the percent of SB procedures decreased from 40.5% in 2009 to 2.7% in 2014, while PPV increased from 38% in 2009 to above 90% in 2014. In 2015, the SB procedure was performed in 10.3% and PPV in 85.6% of patients with RRD (p < 0.001). No consistent trend was observed for the use of intraocular gas tamponade. The functional outcome within the 7-year observation ranged from 0.25 ± 0.31logmar in 2012 to 0.42 ± 0.40logmar in 2009 and showed no statistically significant trend (p = 0.28). Intraoperative complications did not change between 2009 and 2015. The rate of cataract surgery and epiretinal membrane development did not change (p = 0.27; p = 0.09). The percent of re-detachment ranged from 6.2 to 16.5% within the observational period (p = 0.14)., Conclusion: A shift toward PPV alone for primary RRD repair was observed during the 7-year observation. No decrease in functional outcome or increase of intra- and postoperative complications or decrease of primary and final anatomic success rate was observed following the change in surgical procedure.

Background/aims: The objective is to identify imaging biomarkers in optical coherence tomography predicting functional/anatomical outcomes in diabetic macular oedema (DMO)., Methods: The presented study is a post hoc analysis of the RESTORE/RESTORE-extension studies. Best-corrected visual acuity (BCVA) was analysed using general estimating equation models using treatment group/morphological features as predictor variables. In addition, linear multiple regression models analysed BCVA gain up to 12 and 36 months with BCVA/morphological baseline characteristics as independent predictor variables. The correlations between central retinal thickness (CRT)/BCVA were calculated as Spearman's/Pearson's correlation coefficients., Results: A weak negative linear correlation between CRT/BCVA was observed in all study arms at baseline (r=-0.34, p<0.001) and at month 36 (r=-0.26, p<0.001). Patients with baseline height of intraretinal cystoid fluid (IRC) ≤380 µm had better baseline BCVA compared with patients with IRC height >380 µm (64.84±10.63 vs 61.66±9.92 letters; p=0.0071, respectively), which was maintained until the end of month 12 (70.5±12.33 vs 67.0±14.09 letters; p=0.0252, respectively). With laser, there was a trend for patients with subretinal fluid (SRF) at baseline to lose BCVA letters at month 12 (-5.38±16.54 vs 2.49±9.72 letters; p=0.1038), whereas ranibizumab patients trended towards higher BCVA gains (10.28±7.14 vs 6.76±7.67; p=0.0563), compared with those without SRF. With combined therapy, all patients had similar BCVA gains regardless of SRF (p=0.3768)., Conclusion: With ranibizumab treatment, the height of IRC spaces at baseline was a better predictor of functional/anatomical improvement than CRT alone. There was also a trend for SRF to show a positive impact on ranibizumab therapy response and a negative impact on laser therapy response., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To evaluate the potential of machine learning to predict best-corrected visual acuity (BCVA) outcomes from structural and functional assessments during the initiation phase in patients receiving standardized ranibizumab therapy for neovascular age-related macular degeneration (AMD)., Design: Post hoc analysis of a randomized, prospective clinical trial., Participants: Data of 614 evaluable patients receiving intravitreal ranibizumab monthly or pro re nata according to protocol-specified criteria in the HARBOR trial., Methods: Monthly spectral-domain (SD) OCT volume scans were processed by validated, fully automated computational image analysis. This system performs spatially resolved 3-dimensional segmentation of retinal layers, intraretinal cystoid fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachments (PED). The extracted quantitative OCT biomarkers and BCVA measurements at baseline and months 1, 2, and 3 were used to predict BCVA at 12 months using random forest machine learning. This approach was also used to correlate OCT morphology to BCVA at baseline (structure-function correlation)., Main Outcome Measures: Accuracy (R 2 ) of the prediction models; ranking of input variables., Results: Computational image analysis enabled fully automated quantitative characterization of neovascular lesions in a large-scale clinical SD-OCT data set. At baseline, OCT features and BCVA were correlated with R 2  = 0.21. The most relevant biomarker for BCVA was the horizontal extension of IRF in the foveal region, whereas SRF and PED ranked low. In predicting functional outcomes, the model's accuracy increased in a linear fashion with each month. If only the baseline visit was considered, the accuracy was R 2  = 0.34. At month 3, final visual acuity outcomes could be predicted with an accuracy of R 2  = 0.70. The strongest predictive factor for functional outcomes at 1 year was consistently the individual BCVA level during the initiation phase., Conclusions: In this large-scale study based on a wide spectrum of morphologic and functional features, baseline BCVA correlated modestly with baseline SD-OCT, whereas functional outcomes were determined by BCVA levels during the initiation phase with a minor influence of fluid-related features. This finding suggests a re-evaluation of current diagnostic imaging features and a search for novel imaging approaches, where machine learning is a promising approach., (Copyright © 2017 American Academy of Ophthalmology. All rights reserved.)

Purpose: We develop a longitudinal statistical model describing best-corrected visual acuity (BCVA) changes in anti-VEGF therapy in relation to imaging data, and predict the future BCVA outcome for individual patients by combining population-wide trends and initial subject-specific time points., Methods: Automatic segmentation algorithms were used to measure intraretinal (IRF) and subretinal (SRF) fluid volume on monthly spectral-domain optical coherence tomography scans of eyes with central retinal vein occlusion (CRVO) receiving standardized anti-VEGF treatment. The trajectory of BCVA over time was modeled as a multivariable repeated-measure mixed-effects regression model including fluid volumes as covariates. Subject-specific BCVA trajectories and final treatment outcomes were predicted using a population-wide model and individual observations from early follow-up., Results: A total of 193 eyes (one per patient, 12-month follow-up, 2420 visits) were analyzed. The population-wide mixed model revealed that the impact of fluid on BCVA is highest for IRF in the central millimeter around the fovea, with -31.17 letters/mm3 (95% confidence interval [CI], -39.70 to -23.32), followed by SRF in the central millimeter, with -17.50 letters/mm3 (-31.17 to -4.60) and by IRF in the parafovea, with -2.87 letters/mm3 (-4.71 to -0.44). The influence of SRF in the parafoveal area was -1.24 letters/mm3 (-3.37-1.05). The conditional R2 of the model, including subject-specific deviations, was 0.887. The marginal R2 considering the population-wide trend and fluid changes was 0.109. BCVA at 1 year could be predicted for an individual patient after three visits with a mean absolute error of six letters and a predicted R2 of 0.658 using imaging information., Conclusions: The mixed-effects model revealed that retinal fluid volumes and population-wide trend only explains a small proportion of the variation in BCVA. Individual BCVA outcomes after 1 year could be predicted from initial BCVA and fluid measurements combined with the population-wide model. Accounting for fluid in the predictive model increased prediction accuracy.

Purpose: To correlate the area of geographic atrophy (GA) and residual foveal sparing (FS), and to identify the minimum FS and maximum GA area allowing sufficient visual acuity (VA) for daily tasks., Design: Prospective cohort study., Methods: Thirty-six eyes of 25 patients with GA and FS were followed for 18 months using spectral-domain optical coherence tomography and VA tests. Volume scans were imported into software enabling grading of areas in B-scans and computing of planimetric measurements in complete volume scans. Correlation of areas 1 (complete atrophy), 2 (FS in the central millimeter), and 3 (FS in the central 3 mm) with each other and with best-corrected VA (BCVA) were evaluated., Results: Baseline means of areas 1, 2, and 3 were 6.15 mm 2 , 0.49 mm 2 , and 3.08 mm 2 , respectively. At 1 year, area 1 increased by a mean of 1.33 mm 2 , while areas 2 and 3 were decreased by 0.12 mm 2 and 0.65 mm 2 , respectively. From baseline to 18 months and from visit to visit, all areas and BCVA changed progressively (P < .001). Significant thresholds in GA size and FS for achieving a BCVA ≥ 70 ETDRS letters were detected (area 1: ≤6 mm 2 ; area 2: ≥0.48 mm 2 ; and area 3: ≥3.28 mm 2 )., Conclusion: GA and FS changed inversely over time. In general, FS highly correlated with BCVA, while GA progression correlated with the central 3-mm FS regression, but not with BCVA. A threshold in GA and FS area could be determined for BCVA necessary for daily activity., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To suggest a novel classification of neovascular age-related macular degeneration (AMD) based on optical coherence tomography angiography (OCTA) and to correlate morphological characteristics based on optical coherence tomography (OCT)/OCTA with clinical criteria of disease activity., Methods: A total of 88 eyes with neovascular AMD (14 treatment-naïve, 74 eyes following anti-vascular endothelial growth factor treatment (VEGF)) were examined using the AngioVue OCTA system (Optovue, Inc., Fremont, CA, USA) and evaluated based on vascular morphology. Choroidal neovascularization (CNV)-vessel morphology based on OCTA and associations with retinal layers were described and correlated with clinical markers of disease activity., Results: In treatment-naïve CNV, CNV-vessel morphology based on OCTA showed a dense-net configuration (DN) in 12 of 14 eyes, a loose-net configuration (LN) in one of 14 eyes and an unidentifiable CNV pattern in one of 14 eyes, whereas in treated CNV, DN was registered in 43.2% (32/74), LN in 27% (20/74), DN with additional LN (mixed type) in 14.9% (11/74) and an unidentifiable CNV pattern in 14.9% (11/74). Clinical correlations revealed a significantly longer disease duration for LN with a median value of 4.3 years compared to DN with 2.0 years (p = 0.009) and for CNV involving the outer retina with 3.1 years compared to CNV not involving the outer retina with 1.9 years (p = 0.051)., Conclusion: Optical coherence tomography angiography (OCTA) allows identification of distinct CNV-specific vascular patterns at the level of the outer retinal layer and choriocapillaris. Correlation with clinical and functional parameters may be useful to better understand pathophysiological mechanisms and guide efficient therapeutic strategies., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the influence of intravitreal dexamethasone implant on inflammatory and angiogenic cytokine levels in the aqueous of patients with retinal vein occlusion (RVO)., Methods: Forty eyes of 40 consecutive patients with macular oedema (ME) due to branch and central retinal vein occlusion (BRVO/CRVO) were treated with an intravitreal dexamethasone implant (Ozurdex ® ) at baseline and evaluated until month 6. Retreatment was performed in case of recurrent ME earliest 4 months after the baseline treatment. Aqueous humour samples were taken at baseline, months 1, 3, 6 and at the time of each retreatment. Concentrations of 29 different cytokines were measured by Luminex ® bead assays. The control group comprised healthy patients undergoing cataract surgery., Results: At baseline concentrations of interleukin (IL)-8, angiopoietin (ANG)-2 and intercellular adhesion molecule (ICAM)-1 were highly elevated in patients with CRVO compared with controls (p = 0.006; p = 0.02; p = 0.03). Vascular endothelial growth factor (VEGF) concentrations were upregulated in patients with BRVO and CRVO (p = 0.003; p = 0.001). Retreatment with a dexamethasone implant was necessary after 4 months in 14/8 (BRVO/CRVO) patients, 5 months in 5/3 patients and 6 months in one patient (BRVO). After the initial treatment, macrophage chemo-attractant protein (MCP)-1 and IL17-E concentrations decreased in BRVO (p < 0.001; p = 0.01) and MCP-1 and IL1-α in CRVO (p = 0.01; p = 0.003). Vascular endothelial growth factor (VEGF) concentrations did not change during treatment in either group (p = 0.3). A mixed-effect model showed that cytokine concentrations positively correlated with central retinal thickness changes., Conclusions: Intravitreal dexamethasone treatment resulted in alterations in the concentrations of pro-inflammatory cytokines MCP-1 and IL17-E in patients with BRVO and MCP-1 and IL1-α in patients with CRVO. These data highlight the important role of inflammatory mediators involved in ME due to RVO., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for diabetic macular edema (DME) over 3 years., Design: Two similarly designed phase 3 trials: VISTA DME and VIVID DME ., Participants: Patients (eyes; n = 872) with central-involved DME., Methods: Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser control. From week 24, if rescue treatment criteria were met, IAI patients received active laser, and laser control patients received IAI 2q8. From week 100, laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria., Main Outcome Measures: The primary end point was the change from baseline in best-corrected visual acuity (BCVA) at week 52. We report the 148-week results., Results: Mean BCVA gain from baseline to week 148 with IAI 2q4, IAI 2q8, and laser control was 10.4, 10.5, and 1.4 letters (P < 0.0001) in VISTA and 10.3, 11.7, and 1.6 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9%, 35.8%, and 13.6% (P < 0.0001) in VISTA and 41.2%, 42.2%, and 18.9% (P < 0.0001) in VIVID, respectively. Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score in both VISTA (29.9% and 34.4% vs. 20.1% [P = 0.0350, IAI 2q4; P = 0.0052, IAI 2q8]) and VIVID (44.3% and 47.8% vs. 17.4% [P < 0.0001 for both]). In an integrated safety analysis, the most frequent ocular serious adverse event was cataract (3.1%, 2.1%, 0.3% for 2q4, 2q8, and control)., Conclusions: Visual improvements observed with both IAI regimens (over laser control) at weeks 52 and 100 were maintained at week 148, with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups. Treatment with IAI also had positive effects on the DRSS score. Over 148 weeks, the incidence of adverse events was consistent with the known safety profile of IAI., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the efficacy of intravitreal aflibercept and ranibizumab on the exudative activity of neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT) and to correlate morphologic findings with visual acuity (VA) outcomes., Design: Post hoc analysis of the prospective VIEW trials., Participants: Data of 1815 patients randomized to 0.5 mg ranibizumab every 4 weeks (Q4wks), 2 mg aflibercept Q4wks, or 2 mg aflibercept every 8 weeks (Q8wks)., Methods: Standardized OCT evaluation was performed by masked reading centers for the presence of intraretinal cystoid fluid (IRC), subretinal fluid (SRF), and pigment epithelial detachment (PED). Rates of feature resolution were compared between drugs and regimen. Associations between morphologic features and VA were analyzed using multivariate modeling., Main Outcome Measures: Resolution rates of IRC, SRF, and PED, and associations between morphology and VA., Results: At baseline, the proportions of eyes with IRC, SRF, and PED were balanced between the aflibercept and ranibizumab groups. At week 12, IRC resolved in 50% of eyes with both agents. Subretinal fluid resolved in 70% of pooled aflibercept-treated eyes and in 59% of ranibizumab-treated eyes, and PED resolved in 29% and 24% of pooled aflibercept-treated eyes and ranibizumab-treated eyes, respectively. At week 52, IRC resolved in 57% (aflibercept Q4wks), 50% (aflibercept Q8wks), and 52% (ranibizumab) of patients; SRF resolved in 75% (both aflibercept Q4wks/Q8wks) and 66% (ranibizumab) of patients; and PED resolved in 40% (aflibercept Q4wks), 34% (aflibercept Q8wks), and 28% (ranibizumab) of patients. During fixed dosing (weeks 12-52) all exudative features showed synchronized fluctuations after treatment-free visits in the Q8wks aflibercept regimen. During pro re nata dosing (weeks 52-96), greater proportions of patients showed recurrent fluid in all treatment arms. Presence of IRC was generally associated with lower VA at baseline, which translated into poorer final VA outcomes., Conclusions: Fluid resolution in all compartments was consistently greater for aflibercept Q4wks than for aflibercept Q8wks and ranibizumab. At week 52, Q8wks aflibercept-treated eyes were, on average, as dry as or drier than with ranibizumab despite the extended treatment interval. Independent of agent or regimen, preexisting morphologic features of the retina at baseline markedly influenced VA outcomes., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate anatomical and functional outcomes of macula-on and macula-off rhegmatogenous retinal detachment (RRD) after 23-gauge vitrectomy and gas endotamponade, in eyes after successful cataract surgery., Methods: Forty-six pseudophakic eyes of 46 consecutive patients who underwent surgery for RRD repair were included. Based on the severity degree and extension of the RRD, diluted C3F8, SF6 or C2F6 gases were used for endotamponade. Patients were followed 1 month, 3 months, 6 months and 12 months after surgery. Main outcome variables were functional and anatomic outcomes till 12 months after surgery., Results: Proliferative vitreoretinopathy of grade B or C was observed in 43%. C3F8 was used in 59%, SF6 in 28% and C2F6 in 13%. Reattachment after the first intervention was achieved in 89%. Preoperatively, 63% of patients presented with fovea-off retinal detachment. No intraoperative complications were registered. Preoperatively, eyes with macula-on RRD had a logMar BCVA of 0.3 ± 0.6 compared with 1.2 ± 0.7 in the macula-off group (p = 0.01). The mean visual acuity significantly improved to 0.06 ± 0.1 logMar in macula-on eyes and to 0.2 ± 0.3 logMar in macula-off eyes at 12 months (p = 0.01 compared to baseline and p = 0.04 between both the groups). The mean final postoperative CRT was 318 ± 48 µm in the macula-on group compared with 305 ± 71 µm in the macula-off group (p = 0.5)., Conclusions: Even morphological improvement after 23-gauge vitrectomy and gas endotamponade was comparable between macula-on and macula-off eyes, macula-off RRDs showed delayed visual rehabilitation. Both groups showed significant visual acuity improvement until 12 months, however, macula-on RRDs showed significantly more improvement than macula-off RRDs.

Importance: Robust and sensitive imaging biomarkers for visual function are an unmet medical need in the management of neovascular age-related macular degeneration., Objective: To determine the correlation of 3-dimensionally quantified intraretinal cystoid fluid (IRC) and subretinal fluid (SRF) with best-corrected visual acuity (BCVA) in treatment-naive neovascular age-related macular degeneration and during antiangiogenic therapy., Design, Setting, and Participants: Retrospective cohort study between November 2009 and November 2011 at an institutional referral center and reading center of patients with treatment-naive subfoveal choroidal neovascularization receiving intravitreal ranibizumab or aflibercept over 12 months. All individual IRC and SRF lesions were manually delineated on each of the 128 B-scan sections of spectral-domain optical coherence tomographic volume scans at baseline and months 1, 6, and 12. Correlations were computed between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. A systematic parameter search was conducted to detect annotation-derived variables with best predictive value. An exponential model for BCVA change balancing for the ceiling effect was constructed., Main Outcomes and Measures: Goodness of fit of correlations between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change., Results: Thirty-eight patients were included (25 female, 13 male; mean [SD] age at enrollment, 78.49 [8.23] years; mean [SD] BCVA score at baseline, 54 [16] Early Treatment Diabetic Retinopathy Study letters [Snellen equivalent approximately 20/160], with a gain to 63 [19] letters [Snellen equivalent approximately 20/100] at month 12). A total of 19,456 scans underwent complete quantification of IRC and SRF. The best correlation with BCVA at baseline was achieved using a coverage-based, foveal area-weighted IRC parameter (R2 = 0.59; P < .001). The same baseline parameter also predicted BCVA at 12 months (R2 = 0.21; P = .003). The BCVA gain correlated with IRC decrease in the exponential model (R2 = 0.40; P < .001) and linear model (R2 = 0.25; P = .002). No robust associations were found between SRF and baseline BCVA (R2 = 0.06; P = .14) or BCVA change (R2 = 0.14; P = .02)., Conclusions and Relevance: In this proof-of-principle study, IRC-derived morphometric variables correlated well with treatment-naive BCVA and BCVA outcomes in antiangiogenic therapy. While IRC reduction was associated with BCVA gains, some IRC-mediated neurosensory damage remained permanent.

Purpose: To establish the predictive value of defined retinal morphologic parameters on visual outcomes and re-treatment needs in patients with neovascular age-related macular degeneration (nAMD) receiving ranibizumab treatment., Design: Post hoc analysis of a prospective, 12-month, multicenter, phase IIIb trial., Participants: Three hundred fifty-three treatment-naïve patients with nAMD., Methods: Available data from 319 treatment-naïve patients receiving ranibizumab 0.3 mg monthly (frequent regimen; n = 102) or ranibizumab 0.3 or 0.5 mg quarterly (pooled 0.3/0.5 mg = infrequent regimen; n = 217) were analyzed to assess the correlations between baseline retinal morphologic parameters and best-corrected visual acuity (BCVA) change (structure-function correlations). The BCVA was measured at monthly visits. Optical coherence tomography scans were acquired monthly for quantitative measures of the central retinal thickness and qualitative assessment of retinal morphologic features. Assessed morphologic parameters included intraretinal cystoid fluid (IRC), subretinal fluid (SRF), pigment epithelial detachment, and vitreomacular interface configuration classification comprising vitreomacular adhesion and posterior vitreous detachment (PVD). An analysis of covariance was conducted to evaluate the impact of retinal morphologic features on BCVA change at month 12., Main Outcome Measures: Change in BCVA from baseline to month 12 compared between frequent and infrequent treatment arms., Results: Relevant predictive factors for BCVA change at month 12 were baseline SRF (P = 0.05), PVD (P = 0.03), IRC (P = 0.05), treatment frequency (P < 0.01), and BCVA (P < 0.01). The presence of both SRF and PVD at baseline was associated with similar BCVA gains regardless of treatment frequency (mean difference in BCVA gains at month 12 of +2.6 letters in favor of infrequent treatment). Subretinal fluid was present in 71% of patients, and PVD was present in 64% of patients., Conclusions: In patients with both SRF and PVD at baseline, similar BCVA outcomes were observed regardless of treatment frequency. These patients may require less frequent treatments compared with patients without SRF, without PVD, or without either who may require more frequent injections for maintenance of vision. This finding may have implications in clinical practice by helping to tailor an individualized re-treatment interval in nAMD patients., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare current imaging methods with respect to their ability to detect the condition of the fovea in patients with geographic atrophy (GA)., Methods: The retinas of 176 eyes with GA were imaged using two spectral-domain optical coherence tomography (SD-OCT) systems, Cirrus HD-OCT and Spectralis HRA+OCT, and fundus autofluorescence (FAF) and infrared imaging (IR) was used in the scanning laser ophthalmoscope (SLO) mode. Polarization-sensitive OCT (PS-OCT), which selectively visualizes the RPE in addition to SD-OCT features, was used to image 95 eyes. Geographic atrophy lesions were categorized as fovea spared, involved, or not quantifiable (grades 0, 1, and 2). Morphologic gradings were subsequently correlated with best-corrected visual acuity (BCVA) measurements to independently identify the corresponding functional condition of the fovea. Cohen's κ statistics with a bootstrap method was applied to compare retinal imaging methods., Results: In PS-OCT, 84% of eyes with BCVA greater than or equal to 20/40 were detected, whereas in conventional retinal imaging the rate ranged from 27% in FAF to 45% in the SD-OCT segment. Cohen's κ statistics revealed significant differences between the gradings of PS-OCT and conventional imaging with κ = 0.488 and a global Hotelling's T2 statistic of 17.9 with a P value of P = 0.003. Statistical tests revealed no statistically significant differences between the conventional retinal imaging modalities., Conclusions: Polarization-sensitive OCT can better allow correct grading of the fovea in relation to BCVA and identify foveal sparing than other imaging modalities. The differences in imaging precision should be considered in diagnostic and therapeutic evaluations.

Purpose: To relate the functional response to distinct morphological features of the retina during aflibercept treatment for neovascular AMD (nAMD)., Methods: A total of 726 retinal locations in 22 consecutive eyes presenting with treatment-naive nAMD underwent a standardized examination with spectral-domain optical coherence tomography (SD-OCT) and topographic microperimetry (MP) at baseline, after 3 and 12 months of continuous intravitreal aflibercept therapy. The retinal sensitivity at each stimulus location was registered to the corresponding location on SD-OCT morphology. Subsequently, the microperimetric responses were evaluated with respect to the following underlying SD-OCT features: neovascular complex (NVC), subretinal fluid (SRF), intraretinal fluid (IRF), intraretinal cystoid space (IRC), serous pigment epithelium detachment (sPED), and fibrovascular pigment epithelium detachment (fPED)., Results: Baseline sensitivity was reduced to mean values of 1.8 dB in NVC, 2.2 dB in IRC, 2.8 dB in IRF, 2.6 dB in sPED, 3.6 dB in SRF, and 4.6 dB in fPED. Improvements in retinal sensitivity were most pronounced during the initial 3-month interval, when significant recovery was documented for SRF and sPED with +4.0/5.5 dB (P < 0.0001) and to a lesser extent for IRF, IRC, fPED, with +1.1, 1.7, 2.3 dB, respectively. From month 3 to 12, the additional benefit ranged from 0.3 to 1.0 dB (P > 0.05 for each category)., Conclusions: Significant functional benefits following intravitreal aflibercept treatment could be detected over all defined morphological pathologies. The level of improvement varied dependent on the associated feature with the best prognosis for visual improvement in SRF and sPED and least with intraretinal fluid and particularly intraretinal cysts., (Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To quantitatively analyze morphological features in eyes with neovascular AMD (nAMD) at baseline, after 12 months, and after 24 months of intravitreal ranibizumab treatment and to perform a structure/function correlation., Methods: Eyes with treatment-naïve nAMD were treated with intravitreal ranibizumab according to a standardized dosing regimen over 2 years and followed continuously in a prospective study design. The central foveal area of 1000 μm (horizontal)×960 μm (vertical) of spectral-domain optical coherence tomography (SD-OCT) volume scans was evaluated quantitatively (using proprietary software) for the following pathologies: alteration of the external limiting membrane (ELM), alteration of the ellipsoid zone, subretinal fluid, pigment epithelium detachment, drusen, intraretinal cysts, subretinal mass, and subretinal pigment epithelium mass. The total area of each pathology was calculated in mm2 at baseline and after 1 and 2 years of ranibizumab therapy and correlated with BCVA results., Results: In total, 480 central SD-OCT scans of 20 consecutive patients were evaluated. In the multivariate regression analysis, the area of ELM alteration, the area of intraretinal cysts, and foveal retinal thickness were significant variables influencing visual acuity at baseline (R=-0.827; R2=0.684; P<0.001). The area of ELM alteration was the only significant factor to be directly associated with visual acuity at 12 months (R=-0.846; R2=0.716; P<0.001) and 24 months (R=-0.778; R2=0.606; P<0.001)., Conclusions: The integrity of the ELM appears to be the most important feature correlating with visual acuity in native nAMD as well as nAMD treated with intravitreal ranibizumab at each time interval, but not prospectively. In general, no significant predictors for an individual gain or loss in mid- (12 months) or long-term BCVA results (24 months) were found by OCT., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose:   To evaluate the effect of fluid accumulation on local visual function in inflammatory cystoid-macular-edema (ICME)., Methods:   This cross-sectional study applied optical-coherence-tomography over a 12×12 fovea-centered field in 50 patients with ICME and mapped the extent of fluid-filled spaces in various retinal layers, of subretinal-fluid and of diffuse-edema. Regression analysis examined effect of planimetric fluid-distribution on best-corrected-visual-acuity (BCVA) and mean microperimetric-sensitivity., Results:   BCVA decreased with increasing central-neuroretinal-thickness (r= 0.52, p= 0.001), total central-retinal-thickness, including subneuroretinal-fluid (r= 0.41, p= 0.006), total cystoid-and-diffuse edema-area (r= 0.35, p= 0.036) and cystoid inner-nuclear-layer area (r= 0.39, p= 0.02). Mean retinal-sensitivity decreased with increasing diffuse edema-area (r= -0.86, p<0.0001), total cystoid-and-diffuse edema-area (r= -0.54, p= 0.001), cystoid inner-nuclear-layer area (r= -0.46, p= 0.008) and cystoid ganglion-cell-layer area (r= -0.6, p=0.049), central-neuroretinal-thickness (r= -0.42, p= 0.028) and total central-retinal-thickness (r= -0.34, p= 0.039). In multivariate-analyses BCVA was best described by central-neuroretinal-thickness, duration of edema, total cystoid-and-diffuse edema-area and cystoid inner-nuclear-layer area (R(2) = 0.5, p= 0.002). Mean retinal-sensitivity was best described by diffuse edema-area, total cystoid-and-diffuse edema-area and central-neuroretinal-thickness (R(2) = 0.75, p< 0.0001). Subretinal-fluid area and cystoid outer-nuclear/Henle's layer area had no effect on either BCVA or microperimetry., Conclusions:   Thickening of the neurosensory-fovea, not subfoveal-fluid, had major impact on both BCVA and retinal-sensitivity. The extent of edema in inner retinal layers also had major impact on both of these two functional parameters. Visual-impairment seems to differ depending on the layers involved, thus different types of fluid accumulation may potentially be given varying treatment priorities., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To identify the effects of anti-angiogenic therapy in neovascular age-related macular degeneration (AMD) in respect to morphologic type and time course and to identify prognostic factors for visual outcome on the basis of standardized optical coherence tomography (OCT) analysis., Design: Subanalysis of a prospective, 12-month, multicenter, phase IIIb trial (Efficacy and Safety of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration [EXCITE])., Participants: A total of 353 treatment-naïve patients with subfoveal choroidal neovascularization (CNV) receiving quarterly or monthly ranibizumab therapy., Methods: Patients were randomized to receive 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised a loading phase of 3 consecutive monthly injections followed by a 9-month maintenance phase of monthly or quarterly injections. Best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study protocol, and retinal morphology was assessed by Stratus OCT (Carl Zeiss Meditec, Dublin, CA). Imaging data were evaluated by certified examiners of the Vienna Reading Center using a standardized protocol., Main Outcome Measures: The BCVA was measured using ETDRS charts and retinal morphology was assessed by OCT., Results: During the loading phase, there was a significant correlation between a reduction in central retinal thickness and an increase in BCVA (P < 0.001), which decreased during the maintenance phase in all treatment arms. The proportion of patients showing retinal morphologic changes, such as intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachments (PEDs), decreased significantly in all groups (P < 0.001), more intensively in the 0.5 mg quarterly than in both 0.3 mg groups. Intraretinal cysts resolved most rapidly followed by SRF, whereas PED decreased at a slower rate and intensity. Patients with IRC at baseline had lower BCVA levels that remained lower over the entire study period, whereas recurrence of IRC during follow-up showed no additional negative effect on function. Baseline SRF had no effect on visual recovery; however, recurrence of SRF during follow-up showed a tendency for an additional negative effect on function (P = 0.06). Baseline PED showed a negative influence on visual outcome only in combination with IRC and SRF., Conclusions: There is a distinct response pattern and time course of morphologic parameters associated with anti-vascular endothelial growth factor therapy in neovascular AMD. Specific alterations, such as IRC, SRF, and PED, as baseline or follow-up features are significantly influencing the potential for visual gain., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema., Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy., Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 ± 0.28 to 0.39 ± 0.3 (P = 0.018) and 0.71 ± 0.53 to 0.56 ± 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti-vascular endothelial growth factor therapy from 0.59 ± 0.29 to 0.49 ± 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 ± 0.65 to 0.90 ± 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease., Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.

Purpose: To identify neurosensory recovery, testing different functional variables during monthly intravitreal standard anti-vascular endothelial growth factor (VEGF) therapy in neovascular age-related macular degeneration (AMD)., Design: Prospective interventional cohort study., Methods: Sixty-four treatment-naïve neovascular AMD patients with subfoveal lesions were treated and examined monthly for distance visual acuity, reading acuity, maximum reading speed, and contrast sensitivity and with microperimetry evaluating the percentage of absolute and relative scotoma and mean central retinal sensitivity weighted by area. Improvements in reading acuity, distance acuity, reading speed, contrast sensitivity, mean central retinal sensitivity, and scotoma area in dependence of age, lesion type, lesion size, and mean central retinal sensitivity were evaluated by a random-slope and random-intercept model. Recovery pattern of parameters was compared by correlating the individual slopes of each variable., Results: Initially, a rapid short-term effect of anti-VEGF treatment was documented throughout all functional variables. Progressive functional gain over 1 year was observed for distance visual acuity (P = .011), contrast sensitivity (P ≤ .0001), and mean central retinal sensitivity (P ≤ .0001), but not for reading acuity (P = .31) and maximum reading speed (P = .94). Decrease of absolute scotoma area missed statistical significance over time (P = .053) and also fixation stability did not improve (P = .08). However, lesion size influenced the course of absolute scotoma area (P = .0015), while lesion type had no effect on any visual function variable evaluated. The individual slopes of reading acuity and distance visual acuity showed a moderate correlation; however, all other variables showed only a weak or no significant correlation among each other., Conclusion: Visual recovery in anti-VEGF therapy is reflected in a characteristic pattern of functional changes over time, whereas distance visual acuity does not seem to comprehensively reflect overall visual function gain., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the 3-year therapeutic benefit of intravitreal bevacizumab in neovascular related macular degeneration (nAMD) in a standard clinical setting involving 3 initial injections and a pro re nata regimen as recommended in the PRONTO study., Methods: In this interventional clinical study, 181 eyes of 160 consecutive patients with active neovascular related macular degeneration meeting recommended criteria for inclusion and protocol criteria for anti-vascular endothelial growth factor therapy undergoing intravitreal bevacizumab monotherapy were observed. Data of treatment-naive eyes (Group 1, n = 114) were analyzed separately from eyes that had undergone previous photodynamic therapy plus intravitreal triamcinolone (Group 2, n = 67). Re-treatment criteria were based on clinical outcome following the official European label regimen. After 1 year of continuous service at an academic referral center, follow-up was performed in private practices in collaboration with the referral center. Main outcome parameters were best-corrected visual acuity and central retinal thickness., Results: After 3 years, best-corrected visual acuity decreased in the overall population (0.23 ± 0.16 to 0.16 ± 0.21. P = 0.002) and in both groups compared with baseline (0.24 ± 0.21 to 0.17 ± 0.21, Group 1, P = 0.03; 0.22 ± 0.19 to 0.16 ± 0.21, Group 2, P > 0.05), whereas central retinal thickness increased in the overall population (291 ± 92 to 319 ± 110 μm, P = 0.01) and in both groups (291 ± 96 to 325 ± 117 μm, Group 1, P > 0.05; 290 ± 83 to 308 ± 96 μm, Group 2, P > 0.05) because of chronic cystic degeneration changes of the macula. Mean treatment rate was 5.1 ± 3.9 (Group 1) versus 3.7 ± 2.7 (Group 2, P = 0.01). Five cases of severe intraocular inflammation after intravitreal bevacizumab were documented., Discussion: While the functional and morphological benefits persisted for the first year after intravitreal bevacizumab treatment, after this time both functional and morphologic results were disappointing during long-term follow-up with visual acuity loss as the main retreatment criterion. After stabilization of the disease, a monthly follow-up of optical coherence tomography and re-treatment based on morphologic, clinical, and vision outcomes may increase the efficacy in patients with neovascular related macular degeneration under anti-vascular endothelial growth factor treatment.