Search

Optical Coherence Tomography Angiography (OCTA), a functional extension of OCT, has the potential to replace most invasive fluorescein angiography (FA) exams in ophthalmology. So far, OCTA's field of view is however still lacking behind fluorescence fundus photography techniques. This is problematic, because many retinal diseases manifest at an early stage by changes of the peripheral retinal capillary network. It is therefore desirable to expand OCTA's field of view to match that of ultra-widefield fundus cameras. We present a custom developed clinical high-speed swept-source OCT (SS-OCT) system operating at an acquisition rate 8-16 times faster than today's state-of-the-art commercially available OCTA devices. Its speed allows us to capture ultra-wide fields of view of up to 90 degrees with an unprecedented sampling density and hence extraordinary resolution by merging two single shot scans with 60 degrees in diameter. To further enhance the visual appearance of the angiograms, we developed for the first time a three-dimensional deep learning based algorithm for denoising volumetric OCTA data sets. We showcase its imaging performance and clinical usability by presenting images of patients suffering from diabetic retinopathy.

Bruch's membrane (BM) segmentation on optical coherence tomography (OCT) is a pivotal step for the diagnosis and follow-up of age-related macular degeneration (AMD), one of the leading causes of blindness in the developed world. Automated BM segmentation methods exist, but they usually do not account for the anatomical coherence of the results, neither provide feedback on the confidence of the prediction. These factors limit the applicability of these systems in real-world scenarios. With this in mind, we propose an end-to-end deep learning method for automated BM segmentation in AMD patients. An Attention U-Net is trained to output a probability density function of the BM position, while taking into account the natural curvature of the surface. Besides the surface position, the method also estimates an A-scan wise uncertainty measure of the segmentation output. Subsequently, the A-scans with high uncertainty are interpolated using thin plate splines (TPS). We tested our method with ablation studies on an internal dataset with 138 patients covering all three AMD stages, and achieved a mean absolute localization error of 4.10 [Formula: see text]m. In addition, the proposed segmentation method was compared against the state-of-the-art methods and showed a superior performance on an external publicly available dataset from a different patient cohort and OCT device, demonstrating strong generalization ability.

To investigate the therapeutic effect of intravitreal pegcetacoplan on the inhibition of photoreceptor (PR) loss and thinning in geographic atrophy (GA) on conventional spectral-domain OCT (SD-OCT) imaging by deep learning-based automated PR quantification.Post hoc analysis of a prospective, multicenter, randomized, sham (SM)-controlled, masked phase II trial investigating the safety and efficacy of pegcetacoplan for the treatment of GA because of age-related macular degeneration.Study eyes of 246 patients, randomized 1:1:1 to monthly (AM), bimonthly (AEOM), and SM treatment.We performed fully automated, deep learning-based segmentation of retinal pigment epithelium (RPE) loss and PR thickness on SD-OCT volumes acquired at baseline and months 2, 6, and 12. The difference in the change of PR loss area was compared among the treatment arms. Change in PR thickness adjacent to the GA borders and the entire 20° scanning area was compared between treatment arms.Square-root transformed PR loss area in μm or mm, PR thickness in μm, and PR loss/RPE loss ratio.A total of 31 556 B-scans of 644 SD-OCT volumes of 161 study eyes (AM 52, AEOM 54, SM 56) were evaluated from baseline to month 12. Comparison of the mean change in PR loss area revealed statistically significantly less growth in the AM group at months 2, 6, and 12 than in the SM group (-41 μm ± 219 vs. 77 μm ± 126; P = 0.0004; -5 μm ± 221 vs. 156 μm ± 139; P0.0001; 106 μm ± 400 vs. 283 μm ± 226; P = 0.0014). Photoreceptor thinning was significantly reduced under AM treatment compared with SM within the GA junctional zone, as well as throughout the 20° area. A trend toward greater inhibition of PR loss than RPE loss was observed under therapy.Distinct and reliable quantification of PR loss using deep learning-based algorithms offers an essential tool to evaluate therapeutic efficacy in slowing disease progression. Photoreceptor loss and thinning are reduced by intravitreal complement C3 inhibition. Automated quantification of PR loss/maintenance based on OCT images is an ideal approach to reliably monitor disease activity and therapeutic efficacy in GA management in clinical routine and regulatory trials.

To apply an automated deep learning automated fluid algorithm on data from real-world management of patients with neovascular age-related macular degeneration for quantification of intraretinal/subretinal fluid volumes in optical coherence tomography images.Data from the Vienna Imaging Biomarker Eye Study (VIBES, 2007-2018) were analyzed. Databases were filtered for treatment-naive neovascular age-related macular degeneration with a baseline optical coherence tomography and at least one follow-up and 1,127 eyes included. Visual acuity and optical coherence tomography at baseline, Months 1 to 3/Years 1 to 5, age, sex, and treatment number were included. Artificial intelligence and certified manual grading were compared in a subanalysis of 20%. Main outcome measures were fluid volumes.Intraretinal/subretinal fluid volumes were maximum at baseline (intraretinal fluid: 21.5/76.6/107.1 nL; subretinal fluid 13.7/86/262.5 nL in the 1/3/6-mm area). Intraretinal fluid decreased to 5 nL at M1-M3 (1-mm) and increased to 11 nL (Y1) and 16 nL (Y5). Subretinal fluid decreased to a mean of 4 nL at M1-M3 (1-mm) and remained stable below 7 nL until Y5. Intraretinal fluid was the only variable that reflected VA change over time. Comparison with human expert readings confirmed an area under the curve of0.9.The Vienna Fluid Monitor can precisely quantify fluid volumes in optical coherence tomography images from clinical routine over 5 years. Automated tools will introduce precision medicine based on fluid guidance into real-world management of exudative disease, improving clinical outcomes while saving resources.

The fovea centralis is an essential landmark in the retina where the photoreceptor layer is entirely composed of cones responsible for sharp, central vision. The localization of this anatomical landmark in optical coherence tomography (OCT) volumes is important for assessing visual function correlates and treatment guidance in macular disease. In this study, the "PRE U-net" is introduced as a novel approach for a fully automated fovea centralis detection, addressing the localization as a pixel-wise regression task. 2D B-scans are sampled from each image volume and are concatenated with spatial location information to train the deep network. A total of 5586 OCT volumes from 1,541 eyes were used to train, validate and test the deep learning method. The test data is comprised of healthy subjects and patients affected by neovascular age-related macular degeneration (nAMD), diabetic macula edema (DME) and macular edema from retinal vein occlusion (RVO), covering the three major retinal diseases responsible for blindness. Our experiments demonstrate that the PRE U-net significantly outperforms state-of-the-art methods and improves the robustness of automated localization, which is of value for clinical practice.

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening.

Objectives To evaluate the quantitative impact of drusen and hyperreflective foci (HRF) volumes on mesopic retinal sensitivity in non-exudative age-related macular degeneration (AMD). Methods In a standardized follow-up scheme of every three months, retinal sensitivity of patients with early or intermediate AMD was assessed by microperimetry using a custom pattern of 45 stimuli (Nidek MP-3, Gamagori, Japan). Eyes were consecutively scanned using Spectralis SD-OCT (20° × 20°, 1024 × 97 × 496). Fundus photographs obtained by the MP-3 allowed to map the stimuli locations onto the corresponding OCT scans. The volume and mean thickness of drusen and HRF within a circle of 240 µm centred at each stimulus point was determined using automated AI-based image segmentation algorithms. Results 8055 individual stimuli from 179 visits from 51 eyes of 35 consecutive patients were matched with the respective OCT images in a point-to-point manner. The patients mean age was 76.85 ± 6.6 years. Mean retinal sensitivity at baseline was 25.7 dB. 73.47% of all MP-spots covered drusen area and 2.02% of MP-spots covered HRF. A negative association between retinal sensitivity and the volume of underlying drusen (p 3) and HRF volume (p = 0.002, Estimate -5.230 db/µm3) was found. During observation time, no eye showed conversion to advanced AMD. Conclusion A direct correlation between drusen and lower sensitivity of the overlying photoreceptors can be observed. For HRF, a small but significant correlation was shown, which is compromised by their small size. Biomarker quantification using AI-methods allows to determine the impact of sub-clinical features in the progression of AMD.

Background /Objectives To compare two suturing techniques in patients undergoing upper eyelid blepharoplasty by using the FACE-Q™ Eye Module questionnaire to assess patient-reported outcomes and by blinded Likert-scale gradings of two experienced surgeons. Methods 90 patients undergoing bilateral blepharoplasty were randomly assigned to a suturing technique (running cutaneous or subcuticular closure) using Prolene 6.0. Patients completed the FACE-Q eye module questionnaire before surgery and 7 days and 3 months after surgery. Further, two trained oculoplastic surgeons assessed the outcome. FACE-Q ratings were RASCH-transformed, and linear models were fitted for appraisal and satisfaction results. Intraclass correlation coefficient (ICC) was calculated to assess the surgeons’ rating agreement. Results There was no statistically significantly difference in patients’ FACE-Q self-assessments regarding satisfaction with eyes and appraisal of upper eyelids between the two suturing techniques investigated, both 7 days and 3 months after blepharoplasty. The more content the patient at baseline, the less the increase in satisfaction after 3 months. There was good agreement between blinded graders in outcome assessment expressed by an ICC of 0.86. Dry-eye symptoms increased after surgery, independent of the suturing technique, patient age or sex. Conclusion In conclusion, this study shows that post operative patient satisfaction is independent of suturing technique, but depends on baseline FACE-Q reports. These findings are valuable in patient communication and selection and are in line with observer-based assessments. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Background/objectives We aim to develop an objective fully automated Artificial intelligence (AI) algorithm for MNV lesion size and leakage area segmentation on fluorescein angiography (FA) in patients with neovascular age-related macular degeneration (nAMD). Subjects/methods Two FA image datasets collected form large prospective multicentre trials consisting of 4710 images from 513 patients and 4558 images from 514 patients were used to develop and evaluate a deep learning-based algorithm to detect CNV lesion size and leakage area automatically. Manual segmentation of was performed by certified FA graders of the Vienna Reading Center. Precision, Recall and F1 score between AI predictions and manual annotations were computed. In addition, two masked retina experts conducted a clinical-applicability evaluation, comparing the quality of AI based and manual segmentations. Results For CNV lesion size and leakage area segmentation, we obtained F1 scores of 0.73 and 0.65, respectively. Expert review resulted in a slight preference for the automated segmentations in both datasets. The quality of automated segmentations was slightly more often judged as good compared to manual annotations. Conclusions CNV lesion size and leakage area can be segmented by our automated model at human-level performance, its output being well-accepted during clinical applicability testing. The results provide proof-of-concept that an automated deep learning approach can improve efficacy of objective biomarker analysis in FA images and will be well-suited for clinical application.

Purpose To assess the characteristics and long-term outcomes of adult patients with dysthyroid optic neuropathy (DON) who underwent orbital decompression surgery and/or received intravenous (IV) methylprednisolone. Methods Retrospective chart review of 98 eyes of 49 patients who were diagnosed and treated with bilateral DON between 2007 and 2018 at the Department of Ophthalmology and Optometry and Oral and Maxillofacial Surgery of the Medical University of Vienna. Results The mean follow-up period was 4.1 ± 2.7 years. The most common presenting symptoms were eyelid and periorbital swelling (45%) representing active inflammation. Upgaze restriction was the most common clinical finding (73%). At time of diagnosis, the mean clinical activity score was 4 ± 1/4 ± 1 (right/left eye, respectively). Sixty-three percent (31/49) of the patients were treated both with IV methylprednisolone and underwent orbital decompression surgery, 22% (11/49) were treated with IV methylprednisolone alone and 14% (7/49) underwent surgical decompression only. Seventy-one percent (30/42) of the patients underwent 3-wall decompression. The mean reduction of proptosis in patients treated with both IV methylprednisolone and orbital decompression surgery was 4/5 mm. Mean of reduction in proptosis in patients receiving IV methylprednisolone only was 1/0 mm and in patients with surgical decompression only was 5/5 mm. Mean VA was 0.1 ± 0.5/0.1 ± 0.5 logMAR at baseline and 0.05 ± 0.7/0.05 ± 0.7 at final follow-up. In 92% (45/49), VA was preserved or improved at final follow-up. Conclusions The majority of patients with DON were treated both with IV corticosteroids and 3-wall decompression surgery. Vision could be successfully preserved in most cases and reduction of proptosis was achieved, especially after orbital decompression surgery.

Summary Background The aim of this study was to profile patients with simple and complex congenital nasolacrimal duct obstruction (CNLDO) and to determine the success rates of interventions at a third-level referral center. Methods In this retrospective and comparative study, medical records of patients with CNLDO were reviewed. Demographic data, types of CNLDO, surgical approach, type of silicone intubation, as well as outcome were recorded up to 3 months after the intervention. Obstruction location was identified by probing and irrigation following the American Academy of Ophthalmology (AAO) approach. Success rates were calculated for treatment approach and age group. Results Based on the outcome of 130 eyes with CNLDO, the overall success rate was 96%. The mean age of patients was 2.5 ± 2.2 months; 73% of cases were simple and 27% were complex CNLDO. Five children had to undergo reoperation; consequently, there was a lower success rate in the complex CNLDO (91%) than in the simple CNLDO subgroup (97%). There was a male predominance (61.5%), which was also present in the simple and complex CNLDO subgroups. The most frequent type of CNLDO was complete nasolacrimal duct obstruction (NLDO, 55.4%), followed by partial (17.7%) and bony NLDO (11.5%). In 87% of eyes, initial probing was performed followed by dacryocystorhinostomy (10%). Mono- or bi-canalicular lacrimal drainage system intubation was used in 86% of eyes. Conclusion The AAO-based diagnostic approach followed by an individualized treatment regimen yielded excellent success rates of 96% in unselected patients with CNLDO. These success rates were independent of patient age or gender.

Objectives To assess the therapeutic response to brolucizumab and aflibercept by deep learning/OCT-based analysis of macular fluid volumes in neovascular age-related macular degeneration. Methods In this post-hoc analysis of two phase III, randomised, multi-centre studies (HAWK/HARRIER), 1078 and 739 treatment-naive eyes receiving brolucizumab or aflibercept according to protocol-specified criteria in HAWK and HARRIER, respectively, were included. Macular fluid on 41,840 OCT scans was localised and quantified using a validated deep learning-based algorithm. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) for all central macular areas (1, 3 and 6 mm) in nanolitres (nL) and best corrected visual acuity (BCVA) change in ETDRS letters were associated using mixed models for repeated measures. Results Baseline IRF volumes decreased by >92% following the first intravitreal injection and consistently remained low during follow-up. Baseline SRF volumes decreased by >74% following the first injection, while PED volume resolved by 68–79% of its baseline volume. Resolution of SRF and PED was dependent on the substance and regimen used. Larger residual post-loading IRF, SRF and PED volumes were all independently associated with progressive vision loss during maintenance, where the differences in mean BCVA change between high and low fluid volume subgroups for IRF, SRF and PED were 3.4 letters (p p p Conclusions Deep-learning methods allow an accurate assessment of substance and regimen efficacy. Irrespectively, all fluid compartments were found to be important markers of disease activity and were relevant for visual outcomes.

To determine microvascular changes in patients with genetically proven Marfan syndrome.In a cross-sectional study, 32 eyes of 16 patients with genetically proven Marfan syndrome were evaluated using swept-source optical coherence tomography angiography (SS-OCTA). Patients were analyzed regarding lens status and systemic vascular disease. The foveal avascular zone (FAZ) and vessel density (VD) of the superficial and deep vascular plexus and central retinal thickness (CRT) were evaluated on SS-OCTA.44/56% patients presented without/with subluxation of the lens. 69% of patients had presence of mitral valve insufficiency, aortic dilatation or aneurysm of the aortic root. In patients with Marfan syndrome the mean area of the FAZ was 0.2 ± 0.1 mm and the average VD of the superficial/deep vascular plexus was 36 ± 5%/22 ± 7%. In patients with subluxation of the lens FAZ area and perimeter were larger when compared to patients without subluxation of the lens (0.18 ± 0.08/0.28 ± 0.10 mm and 1.7 ± 0.4/2.3 ± 0.8;In patients with Marfan syndrome SS-OCTA imaging revealed microvascular differences in patients with lens subluxation and/or systemic vascular disease.

ZusammenfassungDer Vienna Fluid Monitor ist ein künstlicher Intelligenz(KI)-Algorithmus zur präzisen Lokalisation und Quantifizierung von retinaler Flüssigkeit. Der Algorithmus soll Klinikern und Klinikerinnen helfen, objektive und genaue Behandlungsentscheidungen bei der antivaskulären endothelialen Wachstumsfaktor(Anti-VEGF)-Therapie von Patienten mit neovaskulärer altersbedingter Makuladegeneration zu treffen. Ziel der Implementierung ist die Optimierung der Patientensicherheit, die Erhaltung der Sehleistung und gleichzeitig die Behandlungslast für das Gesundheitssystem und die Patienten zu verringern.

To investigate the functional associations of intraretinal fluid (IRF) and subretinal fluid (SRF) volumes at baseline and after the loading dose as well as fluid change after the first injection with best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) who received an anti-VEGF treatment over 24 months.Post hoc analysis of a phase III, randomized, multicenter trial in which ranibizumab was administered monthly or in a pro re nata regimen (HARBOR).Study eyes of 1094 treatment-naïve patients with nAMD.IRF and SRF volumes were segmented automatically on monthly spectral domain OCT images. Fluid volumes and changes thereof were included as covariates into longitudinal mixed-effects models, which modeled BCVA trajectories.BCVA estimates corresponding to baseline, follow-up, and persistent IRF/SRF volumes after the loading dose; BCVA estimates of change in fluid volumes after the first injection; and marginal and conditional RAnalysis of 22 494 volumetric scans revealed that foveal IRF consistently shows a negative correlation with BCVA at baseline and subsequent visits (-3.23 and -4.32 letters/100 nL, respectively). After the first injection, BCVA increased by +2.13 letters/100 nL decrease in foveal IRF. Persistent IRF was associated with lower baseline BCVA and less improvement. Foveal SRF correlated with better BCVA at baseline and subsequent visits (+6.52 and +1.42 letters/100 nL, respectively). After the first injection, SRF decrease was associated with significant vision gain (+5.88 letters/100 nL). Foveal fluid correlated more with BCVA than parafoveal IRF/SRF.Although IRF consistently correlates with decreased function and recovery throughout therapy, SRF is associated with a more pronounced functional improvement. Moreover, SRF resolution provides increased benefit. Fluid-function correlation represents an essential base for the development of personalized treatment regimens, optimizing functional outcomes, and reducing treatment burden.

Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials.

A panel of imaging experts was assembled to review neovascular age-related macular degeneration optical coherence tomography angiography descriptors published to date, and test agreement on use of these terms, which was found to be low. Optical coherence tomography angiography (OCTA) has been used to identify and characterize macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). 1 , 2 , 3 , 4 Many studies have explored OCTA morphological features of MNV that might serve as biomarkers to assess disease activity and response to treatment. 1 , 2 , 3 , 4 , 5 , 6 The proliferation of studies however has resulted in an OCTA terminology that has been variable and inconsistent. To address inconsistency of nomenclature and allow harmonization, a multidisciplinary panel of retinal imaging experts with a history of relevant research contributions to the field was assembled with the purpose of reviewing published terminology and to recommend a reduced list of key terms pertinent to OCTA. The group was called UNICORN, because of its ultimate goal of generating a UNIfied COmmentary of the committee of inteRnational experts on the nomenclature for Neovascular AMD in OCTA. In this report we describe the first steps, which included a review of OCTA descriptors of neovascular AMD (nAMD) published to date, and an exercise that tested agreement of these terms among retinal imaging experts. Prior to the first UNICORN meeting, a non-systematic review of the literature was performed, using the search terms “optical coherence tomography angiography” or “OCT angiography” or “OCT-A”, AND “neovascular macular degeneration” or “neovascular age-related macular degeneration” or “neovascular AMD” or “nAMD” or “wet age-related macular degeneration” or “wet AMD” or “wet ARMD”. A dictionary of OCTA descriptors relating to the features of MNV in AMD was generated and circulated to the panel.

The lack of reliable biomarkers makes predicting the conversion from intermediate to neovascular age-related macular degeneration (iAMD, nAMD) a challenging task. We develop a Deep Learning (DL) model to predict the future risk of conversion of an eye from iAMD to nAMD from its current OCT scan. Although eye clinics generate vast amounts of longitudinal OCT scans to monitor AMD progression, only a small subset can be manually labeled for supervised DL. To address this issue, we propose Morph-SSL, a novel Self-supervised Learning (SSL) method for longitudinal data. It uses pairs of unlabelled OCT scans from different visits and involves morphing the scan from the previous visit to the next. The Decoder predicts the transformation for morphing and ensures a smooth feature manifold that can generate intermediate scans between visits through linear interpolation. Next, the Morph-SSL trained features are input to a Classifier which is trained in a supervised manner to model the cumulative probability distribution of the time to conversion with a sigmoidal function. Morph-SSL was trained on unlabelled scans of 399 eyes (3570 visits). The Classifier was evaluated with a five-fold cross-validation on 2418 scans from 343 eyes with clinical labels of the conversion date. The Morph-SSL features achieved an AUC of 0.766 in predicting the conversion to nAMD within the next 6 months, outperforming the same network when trained end-to-end from scratch or pre-trained with popular SSL methods. Automated prediction of the future risk of nAMD onset can enable timely treatment and individualized AMD management.

Objectives: To assess the agreement in evaluating optical coherence tomography (OCT) variables in the leading macular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) among OCT-certified graders. Methods: SD-OCT volume scans of 356 eyes were graded by seven graders. The grading included presence of intra- and subretinal fluid (IRF, SRF), pigment epithelial detachment (PED), epiretinal membrane (ERM), conditions of the vitreomacular interface (VMI), central retinal thickness (CRT) at the foveal centerpoint (CP) and central millimeter (CMM), as well as height and location of IRF/SRF/PED. Kappa statistics (κ) and intraclass correlation coefficient (ICC) were used to report categorical grading and measurement agreement. Results: The overall agreement on the presence of IRF/SRF/PED was κ = 0.82/0.85/0.81; κ of VMI condition was 0.77, that of ERM presence 0.37. ICC for CRT measurements at CP and CMM was excellent with an ICC of 1.00. Height measurements of IRF/SRF/PED showed robust consistency with ICC=0.85-0.93. There was substantial to almost perfect agreement in locating IRF/SRF/PED with κ=0.67-0.86. Between diseases, κ of IRF/SRF presence was 0.69/0.80 for nAMD, 0.64/0.83 for DME and 0.86/0.89 for RVO. Conclusion: Even in the optimized setting, featuring certified graders, standardized image acquisition and the use of a professional reading platform, there is a disease dependent variability in biomarker evaluation that is most pronounced for IRF in nAMD as well as DME. Our findings highlight the variability in the performance of human expert OCT grading and the need for AI-based automated feature analyses.

Purpose To report on the morphological characteristics and regional distribution of multifocal macular neovascularization type 3 (mMNV3). Methods Twenty-two consecutive eyes of 21 patients with mMNV3 were included using multimodal imaging. The count and stage of lesions of all MNV types and the existence of exudate and hemorrhage were determined. Also, we addressed the regional distribution of MNV3 lesions between the superior-inferior and the nasal-temporal halves of the macula, and the range of the distance of the lesions from the central fovea. Furthermore, we explored the number of feeding vessels including the cilioretinal artery. Results We found 51 lesions in 22 eyes of 21 patients. They were bifocal in 16 (73%) eyes, trifocal in 5 (23%), and quadrifocal in one (4%). No lesion of MNV1 or 2 was found. Fifteen (68%), 2 (9%), and 16 (73%) eyes were associated with retinal hard exudate, subretinal pigment epithelium exudate, and intraretinal hemorrhage, respectively. Thirty (59%) lesions were located in the temporal half of the macula, whereas 21 (41%) were located nasally (p = 0.07). One (2%) lesion was closer than 500 µm, 49 (96%) between 500 and 1500 µm, and one (2%) between 1500 and 3000 µm. The lesions were supplied by one arteriole in one (4%) eye, two arterioles in 16 (73%) eyes, and 3 arterioles in 5 (23%) eyes. The CRA contributed as a feeding vessel in 5 (23%) eyes. Conclusion The multifocal variant of MNV3 has specific morphological and topographical characteristics. Multimodal imaging allows the understanding of the pathomorphological condition in more detail.

To investigate the impact of qualitatively graded and deep learning quantified imaging biomarkers on growth of geographic atrophy (GA) secondary to age-related macular degeneration.This prospective study included 1062 visits of 181 eyes of 100 patients with GA. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images were acquired at each visit. Hyperreflective foci (HRF) were quantitatively assessed in SD-OCT volumes using a validated deep learning algorithm. FAF images were graded for FAF patterns, subretinal drusenoid deposits (SDD), GA lesion configuration and atrophy enlargement. Linear mixed models were calculated to investigate associations between all parameters and GA progression.FAF patterns were significantly associated with GA progression (p 0.001). SDD was associated with faster GA growth (p = 0.005). Eyes with higher HRF concentrations showed a trend towards faster GA progression (p = 0.072) and revealed a significant impact on GA enlargement in interaction with FAF patterns (p = 0.01). The fellow eye status had no significant effect on lesion enlargement (p 0.05). The diffuse-trickling FAF pattern exhibited significantly higher HRF concentrations than any other pattern (p 0.001).Among a wide range of investigated biomarkers, SDD and FAF patterns, particularly in interaction with HRF, significantly impact GA progression. Fully automated quantification of retinal imaging biomarkers such as HRF is both reliable and merited as HRF are indicators of retinal pigment epithelium dysmorphia, a central pathogenetic mechanism in GA. Identifying disease markers using the combination of FAF and SD-OCT is of high prognostic value and facilitates individualized patient management in a clinical setting.

Background/Objectives: To evaluate the use of encircling scleral buckling for treating retinal detachment (RD) and its complications as well as success rate within the last decade. Subjects/Methods: This retrospective observational study included 163 eyes receiving encircling scleral buckling (ESB) or ESB combined with vitrectomy (SBV) between 2009 and 2018. Main outcome measures include usage rate of ESB and SBV, indications and mean age. Furthermore, intra-/postoperative complications, intraocular tamponades as well as influences on functional outcome (BCVA) and central retinal thickness (CRT) were evaluated. For statistical analysis, patients were divided into five groups of two years each. Results: ESB and SBV surgeries decreased from initially 32% of all RD-operations between 2009-2010 to 9.2% between 2017-2018 (p phakic > aphakic, p ESB, p=0.017) and macula on/off (off > on, p=0.036). Conclusion: After an initial decrease, a rebound in ESB and SBV surgeries was noticed, with a significant reduction in mean age. Indications for surgery shifted over our observational period. No significant differences in functional outcome as well as intra- and postoperative complications were observed.

Given the wide spectrum of unique characteristics of macular neovascularization type 3 (MNV3) compared with types 1 and 2, we suggest regrading the colour photography assessment of the AREDS study to verify the impact of AREDS supplements on eyes with MNV3.

To identify correlations between the vascular characteristics of macular neovascularization (MNV) obtained by optical coherence tomography angiography (OCTA) and distinct retinal fluid volumes in neovascular age-related macular degeneration (nAMD).In this prospective interventional study, 54 patients with treatment-naïve type 1 or 2 nAMD were included and treated with intravitreal aflibercept. At baseline and month 1, each patient underwent a SD-OCT volume scan and volumetric flow scan using a swept-source OCTA. A deep learning algorithm was used to automatically detect and quantify fluid in OCT scans. Angio Tool, a National Cancer Institute algorithm, was used to skeletonize MNV properties and quantify lesion size (LS), vessel area (VA), vessel density (VD), total number of endpoints (TNE), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL) and mean-e-lacunarity (MEL). Subsequently, linear regression models were used to investigate a correlation between OCTA parameters and fluid quantifications.The median amount of fluid within the central 6-mm EDTRS ring was 173.7 nl at baseline, consisting of 156.6 nl of subretinal fluid (SRF) and 2.3 nl of intraretinal fluid (IRF). Fluid decreased significantly in all compartments to 1.76 nl (SRF) and 0.64 nl (IRF). The investigated MNV parameters did not change significantly after the first treatment. There was no significant correlation between MNV parameters and relative fluid decrease after anti-VEGF treatment. Baseline fluid correlated statistically significant but weakly with TNE (p = 0.002, RMacular neovascularization parameters at baseline and month 1 played only a minor role in the exudation process in nAMD. None of the MNV parameters were correlated with the treatment response.

Age-related macular degeneration (AMD) is one of the main causes of visual impairment and blindness in patients over 60 years in developed countries. Whilst no effective form of therapy is available for the dry form of AMD, intravitreal application of anti-VEGF substances is able to prevent the progression of neovascular AMD (nAMD) in most cases. Aside from the drugs ranibizumab, aflibercept and brolucizumab, other agents such as bevacizumab are often used off-label in order to save expense. The treatment intervals have also been refined, so as to reduce the burden on patients and health care systems. After fixed injection intervals, the pro re nata-regimen has been developed. Each month, it is decided whether the patient receives intravitreal injections based on fixed criteria. In the treat and extend-protocol, patients receive injections on each visit, but the intervals between injections vary due to the clinical outcomes. The observe-and-plan regime allows scheduling of the injection intervals in blocks, for three consecutive injections at a time. However, results of real-world studies were not able to reproduce those obtained in the pivotal studies. A high number of visits and fear of the injection procedure impose a burden on patients, that is mostly accepted due to fear of vision loss. Caregivers also complain of loss of productivity and income from having to provide regular support to patients. Health care systems worldwide are affected by increasing treatment numbers and the costs involved. The treatment of nAMD constitutes an achievement for modern medicine. However, despite the challenges, it must be evaluated and reviewed repeatedly in order to provide the best therapy for patients.Die altersbedingte Makuladegeneration (AMD) ist eine der Hauptursachen für Visusbeeinträchtigung und Erblindung von Menschen über 60 Jahren in entwickelten Ländern. Während für die trockene Spätform derzeit keine effektiven Therapieoptionen existieren, kann ein Fortschreiten der neovaskulären AMD (nAMD) bei einer regulären Behandlung mittels intravitrealer Applikation von Anti-VEGF-Substanzen zumeist verhindert werden. Neben den zugelassenen Wirkstoffen Ranibizumab, Aflibercept und seit Kurzem Brolucizumab werden andere Wirkstoffe wie Bevacizumab häufig Off-Label angewandt, um Kosten einzusparen. Auch das Behandlungsintervall wurde mehrfach weiterentwickelt, um die Frequenz der Injektionen bei Visuserhalt zu reduzieren und somit Kliniken und Patienten zu entlasten. Nach fix vorgegebenen Injektionsabständen etablierte sich das Pro-re-nata-Regime, bei dem anhand von festgelegten Kriterien in monatlichen Abständen entschieden wird, ob eine Injektion verabreicht wird. Bei dem Treat-and-extend-Protokoll erhalten Patienten an jedem Termin eine Injektion und die Abstände zwischen den Injektionen werden abhängig von klinischen Ergebnissen verändert. Das Observe-and-plan-Regime erlaubt als Erweiterung des Treat-and-extend-Protokolls eine blockweise Festlegung der Injektionsabstände für jeweils 3 aufeinanderfolgende Injektionen. Leider konnten die Ergebnisse in Real-World-Studien bei keinem der genannten Behandlungsschemata an die der Zulassungsstudien heranreichen. Hohe Terminanzahl und Angst vor dem Injektionsverfahren stellen Belastungen für Patienten dar. Angehörige beklagen Produktivitäts- und Einkommensverluste durch regelmäßige Betreuung der Patienten. Nicht zuletzt sind Gesundheitssysteme weltweit von den steigenden Behandlungszahlen und dem damit verbundenen Aufwand sowie den Kosten betroffen. Die Therapie der nAMD ist eine Errungenschaft der modernen Medizin, die stetig evaluiert und überarbeitet werden muss, um Patienten trotz Herausforderungen bestmöglich zu therapieren.

Objective: To evaluate changes in intraocular pressure after congenital cataract surgery in a real-world setting. Methods: This retrospective case series included all children aged 0–2 years undergoing lens extraction due to congenital cataract. Development of an elevated intraocular pressure was divided into three groups: secG, suspG and OHT. Further, risk factors for IOP changes, the therapeutic approach and functional outcome were assessed during follow-up. Results: One hundred and sixty-one eyes of 110 patients aged 0–2 years were included, whereof 29 eyes of 17 children developed secondary glaucoma (secG; 11 eyes/8 patients), glaucoma suspect (suspG; three eyes/three patients) or ocular hypertension (OHT; 15 eyes/10 patients). No difference in surgrical procedure ( p = 0.62) was found, but age at cataract surgery differed significantly ( p = 0.048), with the secG group (1.74 ± 1.01 months) being the youngest (suspG: 3.93 ± 1.80 months; OHT group: 5.91 ± 5.36 months). Secondary surgical intervention was significantly higher in the secG (4.64 ± 3.41) followed by the suspG (2.00 ± 2.65) and OHT groups (0.40 ± 0.74; p Conclusion: Initial lensectomy and anterior vitrectomy procedure together with or without IOL implantation seems to have no influence for the development of IOP changes after pediatric cataract surgery. However, children who developed secondary glaucoma had cataract surgery significantly earlier, within the first 2–3 months of life. Glaucoma surgery was required to achieve final IOP control in most eyes. The development of secondary glaucoma was also associated with a significant increase in surgical re-treatments.

Comparison of two ultra-widefield (UWF) color-fundus (CF) imaging devices in diabetic patients for visualization of retinal periphery and detection of early microvascular lesions. The total gradable areas (TGA) seen on non-mydriatic CF-images of two UWF-imaging devices (Optos Daytona P200T; Zeiss Clarus 700) were compared and differences in projected area measured. Retinal periphery outside the 7 standard fields (7SF) was divided into: F3 temporal, F4 superotemporal, F5 inferotemporal, F6 superonasal, F7 inferonasal. DR stage was evaluated in the 7SF and the TGA on images of both devices and compared using Cohens κ. 67 eyes of 67 patients (52.5 ± 15.3 years) were analysed. DR stages in the 7SF were no (n = 36 Optos, n = 35 Clarus), mild (n = 16 Optos, n = 17 Clarus), and moderate DR (n = 15). Optos depicted significantly more area in F3 (median [interquartile range]; 2.41% [1.06–4.11] vs 0% [0–0], P P = 0.002). In 4 eyes DR-stage was higher using Optos due to peripheral lesions not seen on the Clarus. Interrater reliability of DR-stage on both devices was almost perfect in the 7SF (κ = 0.975) and the TGA (κ = 0.855). Reliability in detecting signs of early DR is high on both devices. Clarus allowed for better visualization of the inferonasal field, Optos of the temporal field.

AimTo assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA).MethodsSingle-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss’ κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated.ResultsFifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-OCTA and UWF-FA was high in the superotemporal (κ=0.98) and inferotemporal (κ=0.94) and weak in the superonasal (κ=0.24) and inferonasal quadrants (κ=0.42). On UWF-FA, 63% of NVEs (n=153) were located in the temporal quadrants with 93% (n=142) of them being detected on WF-OCTA scans.ConclusionThe high reliability of non-invasive WF-OCTA imaging in detecting PDR can improve clinical examination with the potential to replace FA as a single diagnostic tool.

PurposeTo predict visual outcomes and treatment needs in a treat & extend (T&E) regimen in neovascular age-related macular degeneration (nAMD) using a machine learning model based on quantitative optical coherence tomography (OCT) imaging biomarkers.Materials and methodsStudy eyes of 270 treatment-naïve subjects, randomized to receiving ranibizumab therapy in the T&E arm of a randomized clinical trial were considered. OCT volume scans were processed at baseline and at the first follow-up visit 4 weeks later. Automated image segmentation was performed, where intraretinal (IRF), subretinal (SRF) fluid, pigment epithelial detachment (PED), hyperreflective foci, and the photoreceptor layer were delineated using a convolutional neural network (CNN). A set of respective quantitative imaging biomarkers were computed across an Early Treatment Diabetic Retinopathy Study (ETDRS) grid to describe the retinal pathomorphology spatially and its change after the first injection. Lastly, using the computed set of OCT features and available clinical and demographic information, predictive models of outcomes and retreatment intervals were built using machine learning and their performance evaluated with a 10-fold cross-validation.ResultsData of 228 evaluable patients were included, as some had missing scans or were lost to follow-up. Of those patients, 55% reached and maintained long (8, 10, 12 weeks) and another 45% stayed at short (4, 6 weeks) treatment intervals. This provides further evidence for a high disease activity in a major proportion of patients. The model predicted the extendable treatment interval group with an AUROC of 0.71, and the visual outcome with an AUROC of up to 0.87 when utilizing both, clinical and imaging features. The volume of SRF and the volume of IRF, remaining at the first follow-up visit, were found to be the most important predictive markers for treatment intervals and visual outcomes, respectively, supporting the important role of quantitative fluid parameters on OCT.ConclusionThe proposed Artificial intelligence (AI) methodology was able to predict visual outcomes and retreatment intervals of a T&E regimen from a single injection. The result of this study is an urgently needed step toward AI-supported management of patients with active and progressive nAMD.

To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance.Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected.Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%).Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.

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-naive 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 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.

AimTo prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years.MethodsIn this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer.ResultsAmong 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, pConclusionSubclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease.Trial registration number EudraCT20156000239634.

Purpose Anti–vascular endothelial growth factor (VEGF) treatment of neovascular age-related macular degeneration (AMD) is a highly effective advance in the retinal armentarium. OCT offering 3-dimensional imaging of the retina is widely used to guide treatment. Although poor outcomes reported from clinical practice are multifactorial, availability of reliable, reproducible, and quantitative evaluation tools to accurately measure the fluid response, that is, a “VEGF meter,” may be a better means of monitoring and treating than the current purely qualitative evaluation used in clinical practice. Design Post hoc analysis of a phase III, randomized, multicenter study. Participants Study eyes of 1095 treatment-naive subjects receiving pro re nata (PRN) or monthly ranibizumab therapy according to protocol-specified criteria in the HARBOR study. Methods A deep learning method for localization and quantification of fluid in all retinal compartments was applied for automated segmentation of fluid with every voxel classified by a convolutional neural network (CNN). Three-dimensional volumes (nanoliters) for intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were determined in 24 362 volume scans obtained from 1095 patients treated over 24 months in a phase III clinical trial with randomization to 2 drug dosages (0.5 mg and 2.0 mg ranibizumab) and 2 regimens (monthly and PRN). A multivariable mixed-effects regression model was used to test for differences in fluid between the arms and for fluid/function correlation. Main Outcome Measures Fluid volume in nanoliters, structure-function as Pearson’s correlation coefficient, and as a coefficient of determination (R2). Results Fluid volumes were quantified in all visits of all patients. Automated segmentation demonstrated characteristic response patterns for each fluid compartment individually: Intraretinal fluid showed the greatest and most rapid resolution, followed by SRF and PED the least. The loading dose treatment achieved resolution of all fluid types close to the lowest levels attainable. Dosage and regimen parameters correlated directly with resulting fluid volumes. Fluid/function correlation showed a volume-dependent negative impact of IRF on vision and weak positive prognostic effect of SRF. Conclusions Automated quantification of the fluid response may improve therapeutic management of neovascular AMD, avoid discrepancies between clinicians/investigators, and establish structure/function correlations.

To quantitatively measure hyperreflective foci (HRF) during the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using deep learning (DL) and investigate the association with local and global growth of GA.Eyes with GA were prospectively included. Spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence images were acquired every 6 months. A 500-μm-wide junctional zone adjacent to the GA border was delineated and HRF were quantified using a validated DL algorithm. HRF concentrations in progressing and nonprogressing areas, as well as correlations between HRF quantifications and global and local GA progression, were assessed.A total of 491 SDOCT volumes from 87 eyes of 54 patients were assessed with a median follow-up of 28 months. Two-thirds of HRF were localized within a millimeter adjacent to the GA border. HRF concentration was positively correlated with GA progression in unifocal and multifocal GA (all P.001) and de novo GA development (P = .037). Local progression speed correlated positively with local increase of HRF (P value range.001-.004). Global progression speed, however, did not correlate with HRF concentrations (P.05). Changes in HRF over time did not have an impact on the growth in GA (P.05).Advanced artificial intelligence (AI) methods in high-resolution retinal imaging allows to identify, localize, and quantify biomarkers such as HRF. Increased HRF concentrations in the junctional zone and future macular atrophy may represent progressive migration and loss of retinal pigment epithelium. AI-based biomarker monitoring may pave the way into the era of individualized risk assessment and objective decision-making processes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Limited information is available on morphologic and functional regeneration of photoreceptors after retinal detachment (RD) surgery. This observational clinical study compared morphologic and functional changes of cones after vitrectomy for macula-off retinal detachment.Prospective, fellow-eye comparative case series.StudyPopulation: Five eyes after vitrectomy with gas for macula-off retinal detachment (retinal detachment eyes, RDE) and 5 healthy fellow eyes (HFE) of 5 patients (mean age 59.8 years, macula-off duration 0.5 days to 5.5 days). ObservationProcedures: Eyes were examined with adaptive-optics optical coherence tomography (AO-OCT), spectral-domain OCT (SDOCT), and microperimetry (MP) at 6 (baseline, BL) and 56 weeks (follow-up, FUP) after 23 gauge pars plana vitrectomy and SF6 gas tamponade. Eight corresponding regions at foveal eccentricities of 2.5° (ecc 2.5°) and 6.5° (ecc 6.5°) were analyzed in every eye. AO-OCT en face images and SD-OCT B-scans were graded regarding irregularity and loss of photoreceptor signals ranging from none to severe changes. The number of detectable cones at height of the inner-outer segment junction (IS/OS) and cone outer segment tips (COST) was counted manually in AO-OCT images. MP with a custom grid was used to assess retinal sensitivity at these locations. MainOutcomeMeasures: Cone density, cone pattern regularity and signal attenuation, retinal sensitivity.In comparison to HFE, RDE showed highly irregular cone patterns in AO-OCT and irregular outer retinal bands in SDOCT. Despite significant improvement of cone pattern regularity compared to BL (P.001), 63% of AO images showed remaining cone pattern irregularity and 45.5% of SDOCT B-scans showed severe signal reduction at FUP. In HFE, mean cone density retrieved from IS/OS and COST remained around 20,000/mmThe combination of AO-OCT, SDOCT, and microperimetry is a powerful tool to capture cone regeneration after vitreoretinal surgery. Our study shows that cone morphology and function improve within 56 weeks after RD surgery but structural and functional impairment is still present.

Purpose To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. Design Consensus meeting. Participants An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. Methods During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. Main Outcome Measures A consensus classification of neovascular AMD. Results The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. Conclusions The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Objective: The aim of this study was to evaluate and compare the underlying pathologies, demographic and retinal detachment characteristics in pediatric and early adulthood retinal detachment. Methods: Patients with rhegmatogenous, serous, or tractional retinal detachment aged 0–26 years were retrospectively reviewed. The preschool group (n = 4) comprised children aged 0–6 years, the pediatric group (n = 19) comprised children aged 7–16 years, and the early adulthood group (n = 13) aged 17–26 years. Demographic information and retinal detachment characteristics, type of surgery, and intraocular tamponade were analyzed. Postoperatively, the functional outcome, anatomic success, and ocular adverse events were evaluated. Due to the low patient number in the preschool group, statistical analysis was performed for pediatric group and early adulthood group only. Results: All causes of retinal detachment were present in the pediatric group, but only rhegmatogenous retinal detachment in the early adulthood group. In both groups, the main type of surgical intervention was pars plana vitrectomy (pediatric group: 52%, early adulthood group: 38%; p = 0.36). The type of intraocular tamponade varied statistically significantly between the groups (p = 0.014). Silicone oil was the main intraocular tamponade in the pediatric group (48%), whereas no tamponade (54%) followed by gas tamponade (46%) in the early adulthood group. Final attachment rate was similar in both groups (pediatric group: 89%, early adulthood group: 100%; p = 0.35). Re-detachment occurred significantly sooner in the pediatric group (1.3 ± 0.3 months) than in the early adulthood group (4.3 ± 1.4 months; p = 0.03). Conclusion: In pediatric and early adulthood retinal detachment, pars plana vitrectomy appeared as a successful surgical intervention. Re-attachment rate and re-treatment were similar in both groups with a better functional outcome observed in cases of retinal detachment in early adulthood and poorer results in young children.

PurposeTo report on patients with macular neovascularisation type III (MNV3) arising from cilioretinal arteries (CRAs) (cilioretinal macular neovascularisation type III (cMNV3)).MethodsWe reviewed baseline examinations of patients with neovascular age-related macular degeneration using multimodal imaging. We determined the type and distribution of MNV lesions in each cMNV3 case, the range of distances from the fovea, existence of exudative maculopathy, intraretinal haemorrhage and other morphological characteristics. 50 consecutive eyes with usual MNV3 without CRA were included as a control group.Results102 eyes of 102 patients were identified with MNV3 lesions. Among these, we found 12 eyes (12%) with cMNV3, 84 eyes (82%) with usual MNV3 without CRA and 6 eyes (6%) with usual MNV3 with CRA. Ten cases of cMNV3 had one lesion, and two cases had two lesions. The lesions were distributed equally between the superior and inferior halves of the macula, whereas in the nasal and temporal halves, there were 8 (57%) and 6 (43%) lesions, respectively. All cMNV3 lesions were located between 500 and 1500 µm from the central fovea except one, which was located between 1500 and 3000 µm. None of the lesions had macular neovascularisation type I (MNV1) or macular neovascularisation type II (MNV2) elsewhere in both groups. Exudative maculopathy and intraretinal haemorrhage were found in seven (88%) and five (63%) of the eight pure cMNV3 cases, respectively.ConclusioncMNV3 can be solitary or multiple, isolated or accompanied with usual MNV3 lesions, but not with concurrent MNV1 or MNV2. It is frequently associated with extensive exudative maculopathy, intraretinal haemorrhage and subretinal fluid.

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-naive 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.

To identify disease activity and effects of intravitreal pegcetacoplan treatment on the topographic progression of geographic atrophy (GA) secondary to age-related macular degeneration quantified in spectral-domain OCT (SD-OCT) by automated deep learning assessment.Retrospective analysis of a phase II clinical trial study evaluating pegcetacoplan in GA patients (FILLY, NCT02503332).SD-OCT scans of 57 eyes with monthly treatment, 46 eyes with every-other-month (EOM) treatment, and 53 eyes with sham injection from baseline and 12-month follow-ups were included, in a total of 312 scans.Retinal pigment epithelium loss, photoreceptor (PR) integrity, and hyperreflective foci (HRF) were automatically segmented using validated deep learning algorithms. Local progression rate (LPR) was determined from a growth model measuring the local expansion of GA margins between baseline and 1 year. For each individual margin point, the eccentricity to the foveal center, the progression direction, mean PR thickness, and HRF concentration in the junctional zone were computed. Mean LPR in disease activity and treatment effect conditioned on these properties were estimated by spatial generalized additive mixed-effect models.LPR of GA, PR thickness, and HRF concentration in μm.A total of 31,527 local GA margin locations were analyzed. LPR was higher for areas with low eccentricity to the fovea, thinner PR layer thickness, or higher HRF concentration in the GA junctional zone. When controlling for topographic and structural risk factors, we report on average a significantly lower LPR by -28.0% (95% confidence interval [CI], -42.8 to -9.4; P = 0.0051) and -23.9% (95% CI, -40.2 to -3.0; P = 0.027) for monthly and EOM-treated eyes, respectively, compared with sham.Assessing GA progression on a topographic level is essential to capture the pathognomonic heterogeneity in individual lesion growth and therapeutic response. Pegcetacoplan-treated eyes showed a significantly slower GA lesion progression rate compared with sham, and an even slower growth rate toward the fovea. This study may help to identify patient cohorts with faster progressing lesions, in which pegcetacoplan treatment would be particularly beneficial. Automated artificial intelligence-based tools will provide reliable guidance for the management of GA in clinical practice.

Optical coherence tomography angiography (OCTA) is a novel noninvasive imaging modality for visualization of retinal blood flow in the human retina. Using specific OCTA imaging biomarkers for the identification of pathologies, automated image segmentations of the blood vessels can improve subsequent analysis and diagnosis. We present a novel segmentation method for vessel density identification based on frequency representations of the image, in particular, using so-called Gabor filter banks. The algorithm is evaluated qualitatively and quantitatively on an OCTA image in-house data set from $10$ eyes acquired by a Cirrus HD-OCT device. Qualitatively, the segmentation outcomes received very good visual evaluation feedback by experts. Quantitatively, we compared the resulting vessel density values with automated in-built values provided by the device. The results underline the visual evaluation. For the evaluation of the FAZ identification substep, manual annotations of $2$ expert graders were used, showing that our results coincide well in visual and quantitative manners. Lastly, we suggest the computation of adaptive local vessel density maps that allow straightforward analysis of retinal blood flow in a local manner.

To evaluate neuroretinal integrity in different subtypes of optical coherence tomography (OCT)-graded partial-thickness macular holes.Fovea-centred SD-OCT images (Cirrus, Carl Zeiss Meditec AG; Spectralis, Heidelberg Engineering GmbH) and visual acuity (VA) acquired at every visit were analysed by two retina specialists retrospectively in 71 eyes of 65 patients. Partial-thickness macular holes were classified as lamellar macular hole (LMH), epiretinal membrane foveoschisis (ERMF) or macular pseudohole (MPH).Lamellar macular hole, ERMF and MPH were diagnosed in 33 (47%), 31 (43%) and 7 (10%) eyes with a VA of 0.18 ± 0.25, 0.15 ± 0.2, and 0.06 ± 0.08 (p = 0.323), respectively. Median follow-up time was 11 (interquartile range 4-32.5), 10 (interquartile range 5-18) and 19 (interquartile range 8-24) months in LMH, ERMF and MPH. In all subgroups, VA remained stable during the follow-up (p = 0.652, p = 0.915 and p = 1.000). Epiretinal proliferations (EP) were present in 12 LMH and 3 ERMF. At baseline, eyes with EP had significantly worse VA (p 0.001), wider foveal cavities (p = 0.007) and thinner foveal floors (p 0.001) compared with eyes without EP. Twelve out of 15 eyes with EP showed exudative cystoid spaces. Among all 71 eyes, 51 remained morphologically and functionally stable during follow-up.In our study cohort, EP are associated with worse VA and advanced neuroretinal tissue loss presenting with wider foveal cavities and thinner foveal floors. During the follow-up period, VA remained stable in all entities of partial-thickness macular holes.

To develop and validate a deep learning model to automatically segment three structures using an anterior segment optical coherence tomography (AS-OCT): The intraocular lens (IOL), the retrolental space (IOL to the posterior lens capsule) and Berger's space (BS; posterior capsule to the anterior hyaloid membrane).An artificial intelligence (AI) approach based on a deep learning model to automatically segment the IOL, the retrolental space, and BS in AS-OCT, was trained using annotations from an experienced clinician. The training, validation and test set consisted of 92 cross-sectional OCT slices, acquired in 47 visits from 41 eyes. Annotations from a second experienced clinician in the test set were additionally evaluated to conduct an inter-reader variability analysis.The AI model achieved a Precision/Recall/Dice score of 0.97/0.90/0.93 for IOL, 0.54/0.65/0.55 for retrolental space, and 0.72/0.58/0.59 for BS. For inter-reader variability, Precision/Recall/Dice values were 0.98/0.98/0.98 for IOL, 0.74/0.59/0.62 for retrolental space, and 0.58/0.57/0.57 for BS. No statistical differences were observed between the automated algorithm and the inter-reader variability for BS segmentation.The deep learning model allows for fully automatic segmentation of all investigated structures, achieving human-level performance in BS segmentation. We, therefore, expect promising applications of the algorithm with particular interest in BS in automated big data analysis and real-time intra-operative support in ophthalmology, particularly in conjunction with primary posterior capsulotomy in femtosecond laser-assisted cataract surgery.

To perform an optical coherence tomography (OCT)-based analysis of geographic atrophy (GA) progression in patients treated with pegcetacoplan.Post hoc analysis of a phase 2 multicenter, randomized, sham-controlled trial.Manual annotation of retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) loss was performed on OCT volumes from baseline and month 12 from the phase 2 FILLY trial of intravitreal pegcetacoplan for the treatment of GA secondary to age-related macular degeneration.Correlation of GA areas measured on fundus autofluorescence and OCT. Difference in square root transformed growth rates of RPE, EZ, and ELM loss between treatment groups (monthly injection [AM], injection every other month [AEOM], and sham [SM]).OCT volumes from 113 eyes of 113 patients (38 AM, 36 AEOM, and 39 SM) were included, resulting in 11 074 B-scans. The median growth of RPE loss was significantly slower in the AM group (0.158 [0.057-0.296]) than the SM group (0.255 [0.188-0.359], P = .014). Importantly, the growth of EZ loss was also significantly slower in the AM group (0.127 [0.041-0.247]) than the SM group (0.232 [0.130-0.349], P = .017). There was no significant difference in the growth of ELM loss between the treatment groups (P = .114).OCT imaging provided consistent results for GA growth compared with fundus autofluorescence. In addition to slower RPE atrophy progression in patients treated with pegcetacoplan, a significant reduction in EZ impairment was also identified by OCT, suggesting the use of OCT as a potentially more sensitive monitoring tool in GA therapy.

To explore the condition of fellow eyes of patients with macular neovascularization Type 3 (MNV3) and to verify whether the retinal-choroidal anastomosis (RCA) develops equally in all MNV types.The contralateral eyes of 94 patients with MNV3, 96 patients with MNV1, and 96 patients with MNV2 were included. Multimodal imaging was performed. The MNV3 stage including the development of fibrosis and RCA over 24 months was determined.In the contralateral eyes of patients of the solitary (one lesion) MNV3 group, 32 eyes (42.1%) showed early/intermediate age-related macular degeneration, 25 eyes (33%) showed MNV3, and 11 eyes (14.5%) experienced fibrosis, of which 4 eyes (5.2%) had a RCA, 7 eyes (9.2%) had atrophy after resolved MNV3, and 1 eye (1.3%) developed MNV1. In the multifocal (more than one lesion) MNV3 group, 2 eyes (11.1%) showed early/intermediate age-related macular degeneration, 9 eyes (50%) showed 15 MNV3 lesions, and 4 eyes (22.2%) showed fibrosis, of which 2 eyes (11.1%) manifested with a RCA and 3 eyes (16.7%) showed atrophy after resolved MNV3. The number of eyes with a RCA accounted for 40% of all eyes with fibrosis. The count of simultaneous bilateral multifocal MNV3 was 5 (55.6%). In the MNV1 and MNV2 groups, no eye developed a RCA. The incidence of RCAs in the scarred eyes in MNV3 was significantly higher (P0.0001).Retinal-choroidal anastomosis is an exclusive clinical feature of MNV3. The development of the multifocal MNV3 is usually bilateral and simultaneous. The occurrence of fibrosis in MNV3 has decreased dramatically after the introduction of the antiangiogenic therapy.