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Purpose: The aim of this study was to investigate the preoperative and postoperative change in retinal sensitivity in relation to the distance to the retinal detachment (RD) in patients with fovea-on RD., Methods: We prospectively evaluated 13 patients with fovea-on RD and a healthy control eye. Preoperatively, OCT scans of the RD border and the macula were obtained. The RD border was highlighted on the SLO image. Microperimetry was used to assess the retinal sensitivity at the macula, the RD border and the retina around the RD border. At 6 weeks, 3 and 6 months postoperatively, follow-up examinations of OCT and microperimetry were performed in the study eye. Microperimetry was performed once in control eyes. Microperimetry data were overlaid on the SLO image. The shortest distance to the RD border was calculated for each sensitivity measurement. The change in retinal sensitivity was calculated as control-study. The relation between the change in retinal sensitivity and the distance to the RD border was assessed using a locally weighted scatterplot smoothing curve., Results: Preoperatively, the greatest loss in retinal sensitivity was 21 dB at 3° inside the RD which decreased linearly, through the RD border, and reached a plateau of 2 dB at 4°. For 6 weeks and 3 months postoperatively, the greatest retinal sensitivity loss remained at 3° inside the RD but was 4 dB and sensitivity loss decreased linearly to a plateau of 0 dB at 5° outside the RD. At 6 months postoperatively, the greatest sensitivity loss was 2 dB at 3° inside the RD, and decreased linearly to a plateau of 0 dB at 2° outside the RD., Conclusions: Retinal damage extends beyond the detached retina. Retinal sensitivity loss of the attached retina decreased drastically as the distance to the RD increased. Postoperative recovery occurred for both attached and detached retina., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

The early detection of glaucoma is essential in preventing visual impairment. Artificial intelligence (AI) can be used to analyze color fundus photographs (CFPs) in a cost-effective manner, making glaucoma screening more accessible. While AI models for glaucoma screening from CFPs have shown promising results in laboratory settings, their performance decreases significantly in real-world scenarios due to the presence of out-of-distribution and low-quality images. To address this issue, we propose the Artificial Intelligence for Robust Glaucoma Screening (AIROGS) challenge. This challenge includes a large dataset of around 113,000 images from about 60,000 patients and 500 different screening centers, and encourages the development of algorithms that are robust to ungradable and unexpected input data. We evaluated solutions from 14 teams in this paper and found that the best teams performed similarly to a set of 20 expert ophthalmologists and optometrists. The highest-scoring team achieved an area under the receiver operating characteristic curve of 0.99 (95% CI: 0.98-0.99) for detecting ungradable images on-the-fly. Additionally, many of the algorithms showed robust performance when tested on three other publicly available datasets. These results demonstrate the feasibility of robust AI-enabled glaucoma screening.

Prcis: Irregular visual field test frequency at relatively short intervals initially and longer intervals later on in the disease provided acceptable results in detecting glaucoma progression., Purpose: It is challenging to maintain a balance between the frequency of visual field testing and the long-term costs that may result from insufficient treatment of glaucoma patients. This study aims to simulate real-world circumstances of visual field data to determine the optimum follow-up scheme for the timely detection of glaucoma progression using a linear mixed effects model (LMM)., Materials and Methods: An LMM with random intercept and slope was used to simulate the series of mean deviation sensitivities over time. A cohort study including 277 glaucoma eyes that were followed for 9.0±1.2 years was used to derive residuals. Data were generated from patients with early-stage glaucoma having various regular and irregular follow-up scenarios and different rates of visual field loss. For each condition, 10,000 series of eyes were simulated, and one confirmatory test was conducted to identify progression., Results: By doing one confirmatory test, the percentage of incorrect progression detection decreased considerably. The time to detect progression was shorter for eyes with an evenly spaced 4-monthly schedule, particularly in the first 2 years. From then onward, results from twice-a-year testing were similar to results from examinations scheduled 3 times per year., Conclusions: Irregular visual field test frequency at relatively short intervals initially and longer intervals later on in the disease provided acceptable results in detecting glaucoma progression. This approach could be considered for improving glaucoma monitoring. Moreover, simulating data using LMM may provide a better estimate of the disease progression time., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Significant visual impairment due to glaucoma is largely caused by the disease being detected too late., Objective: To build a labeled data set for training artificial intelligence (AI) algorithms for glaucoma screening by fundus photography, to assess the accuracy of the graders, and to characterize the features of all eyes with referable glaucoma (RG)., Design: Cross-sectional study., Subjects: Color fundus photographs (CFPs) of 113 893 eyes of 60 357 individuals were obtained from EyePACS, California, United States, from a population screening program for diabetic retinopathy., Methods: Carefully selected graders (ophthalmologists and optometrists) graded the images. To qualify, they had to pass the European Optic Disc Assessment Trial optic disc assessment with ≥ 85% accuracy and 92% specificity. Of 90 candidates, 30 passed. Each image of the EyePACS set was then scored by varying random pairs of graders as "RG," "no referable glaucoma (NRG)," or "ungradable (UG)." In case of disagreement, a glaucoma specialist made the final grading. Referable glaucoma was scored if visual field damage was expected. In case of RG, graders were instructed to mark up to 10 relevant glaucomatous features., Main Outcome Measures: Qualitative features in eyes with RG., Results: The performance of each grader was monitored; if the sensitivity and specificity dropped below 80% and 95%, respectively (the final grade served as reference), they exited the study and their gradings were redone by other graders. In all, 20 graders qualified; their mean sensitivity and specificity (standard deviation [SD]) were 85.6% (5.7) and 96.1% (2.8), respectively. The 2 graders agreed in 92.45% of the images (Gwet's AC2, expressing the inter-rater reliability, was 0.917). Of all gradings, the sensitivity and specificity (95% confidence interval) were 86.0 (85.2-86.7)% and 96.4 (96.3-96.5)%, respectively. Of all gradable eyes ( n  = 111 183; 97.62%) the prevalence of RG was 4.38%. The most common features of RG were the appearance of the neuroretinal rim (NRR) inferiorly and superiorly., Conclusions: A large data set of CFPs was put together of sufficient quality to develop AI screening solutions for glaucoma. The most common features of RG were the appearance of the NRR inferiorly and superiorly. Disc hemorrhages were a rare feature of RG., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2023 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

Purpose: To assess if ocular motility impairment, and the ensuing diplopia, after Baerveldt Glaucoma device (BGI) implantation, is related to the presence of a large fluid reservoir (bleb), using Magnetic Resonance Imaging (MRI)., Methods: In a masked observational study (CCMO-registry number: NL65633.058.18), the eyes of 30 glaucoma patients with (n = 12) or without diplopia (n = 18) who had previously undergone BGI implantation were scanned with a 7 Tesla MRI-scanner. The substructures of the BGI-complex, including both blebs and plate, were segmented in 3D. Primary outcomes were a comparison of volume and height of the BGI-complex between patients with and without diplopia. Comparisons were performed by using an unpaired t-test, Fisher's Exact or Mann-Whitney test. Correlations were determined by using Spearman correlation., Results: The median volume and height of the BGI-complex was significantly higher in patients with compared to patients without diplopia (p = 0.007 and p = 0.025, respectively). Six patients had an excessively large total bleb volume (median of 1736.5mm3, interquartile range 1486.3-1933.9mm3), four of whom experienced diplopia (33% of the diplopia patients). Fibrotic strands through the BGI plate, intended to limit the height of the bleb, could be visualized but were not related to diplopia (75% versus 88%; p = 0.28)., Conclusions: With MRI, we show that in a significant number of diplopia cases a large bleb is present in the orbit. Given the large volume of these blebs, they are a likely explanation of the development of diplopia in at least some of the patients with diplopia after BGI implantation. Additionally, the MR-images confirm the presence of fibrotic strands. As these strands are also visible in patients with a large bleb, they are apparently not sufficient to restrict the bleb height., Competing Interests: J.W.B. reports research support from Philips Healthcare during the conduct of the study. All other authors declare that no competing interests exists. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Corneal guttae, which are the abnormal growth of extracellular matrix in the corneal endothelium, are observed in specular images as black droplets that occlude the endothelial cells. To estimate the corneal parameters (endothelial cell density [ECD], coefficient of variation [CV], and hexagonality [HEX]), we propose a new deep learning method that includes a novel attention mechanism (named fNLA), which helps to infer the cell edges in the occluded areas. The approach first derives the cell edges, then infers the well-detected cells, and finally employs a postprocessing method to fix mistakes. This results in a binary segmentation from which the corneal parameters are estimated. We analyzed 1203 images (500 contained guttae) obtained with a Topcon SP-1P microscope. To generate the ground truth, we performed manual segmentation in all images. Several networks were evaluated (UNet, ResUNeXt, DenseUNets, UNet++, etc.) and we found that DenseUNets with fNLA provided the lowest error: a mean absolute error of 23.16 [cells/mm[Formula: see text]] in ECD, 1.28 [%] in CV, and 3.13 [%] in HEX. Compared with Topcon's built-in software, our error was 3-6 times smaller. Overall, our approach handled notably well the cells affected by guttae, detecting cell edges partially occluded by small guttae and discarding large areas covered by extensive guttae., (© 2022. The Author(s).)

Purpose: Accurate assessment of visual field (VF) trend may help clinicians devise the optimum treatment regimen. This study was conducted to investigate the behavior of VF sequences using pointwise and region-wise linear, exponential, and sigmoid regression models., Materials and Methods: In a retrospective cohort study, 277 eyes of 139 patients with glaucoma who had been followed for at least 7 years were investigated. Linear, exponential, and sigmoid regression models were fitted for each VF test location and Glaucoma Hemifield Test (GHT) region to model the trend of VF loss. The model with the lowest root mean square error (RMSE) was selected as the best fit., Results: The mean age (standard deviation [SD]) of the patients was 59.9 years (9.8) with a mean follow-up time of 9.3 (0.7) years. The exponential regression had the best fit based on pointwise and region-wise approaches in 39.3% and 38.1% of eyes, respectively. The results showed a better performance based on sigmoid regression in patients with initial VF sensitivity threshold greater than 22 dB (71.6% in pointwise and 62.2% in region-wise approaches). The overall RMSE of the region-wise regression model was lower than the overall RMSE of the pointwise model., Conclusions: In the current study, nonlinear regression models showed a better fit compared to the linear regression models in tracking VF loss behavior. Moreover, findings suggest region-wise analysis may provide a more appropriate approach for assessing VF deterioration., Translational Relevance: Findings may confirm a nonlinear progression of VF deterioration in patients with glaucoma.

Purpose: To determine the sensitivity of optical coherence tomography (OCT) and standard automated perimetry (SAP) for detecting glaucomatous progression in the superior and inferior hemiretina., Methods: We calculated contrast-to-noise ratios (CNRs) for OCT retinal nerve fiber layer (RNFL) thickness of hemiretinas and for SAP mean total deviation (MTD) of the corresponding hemifields from longitudinal data (205 eyes, 125 participants). The glaucoma stage for each hemiretina was based on the corresponding hemifield's MTD. Contrast was defined as the difference of the parameter between two consecutive glaucoma stages, whereas noise was the measurement variability of the parameter in those stages. The higher the CNR of a parameter, the more sensitive it is to detecting progression in the transition between successive stages., Results: There were no statistically significant differences for the RNFL CNR and MTD CNR between superior and inferior hemiretinas. As the glaucoma stage of the opposite hemiretina worsened, the MTD CNR in the transition from moderate to advanced glaucoma significantly increased. The RNFL CNR in the transition from mild to moderate glaucoma significantly decreased in case of advanced glaucoma in the opposite hemiretina., Conclusions: Similar to full retinas, detecting conversion to glaucoma in hemiretinas is more sensitive with OCT than SAP, whereas with more advanced disease, SAP is more sensitive for detecting progression. More importantly, the sensitivity for detecting progression in one hemiretina with either technique depends on the glaucoma severity in the opposite hemiretina., Translational Relevance: Monitoring glaucomatous progression with either OCT or SAP partly depends on the glaucoma severity in the opposite hemiretina.

Purpose: To determine whether the postoperative corneal endothelial cell density (ECD) differs between glaucoma patients who underwent Baerveldt implant (BGI) surgery and patients who underwent a trabeculectomy (TE) over 5 years ago., Methods: Cross-sectional, observational study including 34 patients who underwent TE and 36 patients who underwent BGI surgery 5-11 years ago, as part of a randomized clinical trial. None of the patients had a history of intraocular surgery prior to their glaucoma surgery. Central and peripheral ECD was measured by using a non-contact specular microscope., Results: Central and peripheral ECD in the TE group was 2285 ± 371 cells/mm 2 (mean ± SD) and 2463 ± 476 cells/mm 2 , respectively. Central and peripheral ECD in the BGI group was 1813 ± 745 cells/mm 2 and 1876 ± 764 cells/mm 2 , respectively. The central and peripheral ECD was statistically significantly higher in the TE group than in the BGI group (p = 0.001 for both). Additional intraocular surgical interventions were more prevalent in the BGI group (23) than in the TE group (5) (p < 0.001). In a subanalysis, without eyes that had undergone additional surgical interventions, only the peripheral ECD was statistically significantly higher in the TE group compared with the BGI group (p = 0.011). For the BGI group, a longer postoperative period resulted in a lower central ECD (r = -0.614, p = 0.004)., Conclusion: Long-term ECD in eyes that underwent a BGI was considerably lower compared with eyes that underwent a TE, mainly in the peripheral cornea. This suggests that BGI causes a larger decrease of ECD than TE. Additionally, the decrease after BGI appears to continue for a longer period than after TE., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To increase insight into the myopic presentation of central serous chorioretinopathy (CSC) by comparing a large group of myopic patients with CSC with reference groups with only one of the diagnoses., Methods: Myopic patients with CSC (spherical equivalent ≤-3D, n = 46), emmetropic patients with CSC (spherical equivalent -0.5 to 0.5 D, n = 83), and myopic, non-CSC patients (n = 50) were included in this multicenter cross-sectional study. Disease characteristics and imaging parameters, such as subfoveal choroidal thickness and indocyanine green angiography patterns, were compared between cases and reference groups., Results: In myopic patients with CSC, median subfoveal choroidal thickness (286 µm [IQR 226-372 µm]) was significantly thicker than subfoveal choroidal thickness in myopic, non-CSC patients (200 µm [IQR 152-228 µm], P < 0.001) but thinner than emmetropic patients with CSC (452 µm [IQR 342-538 µm], P < 0.001). They also had pachyvessels in 70% of the eyes comparable with emmetropic CSC (76%, P = 0.70). Choroidal hyperpermeability was frequently present on indocyanine green angiography in both myopic and emmetropic CSC eyes. Need for treatment, treatment success, and recurrence rate were not significantly different between CSC groups., Conclusion: Myopic CSC presents with similar imaging and clinical characteristics as emmetropic CSC, apart from their thinner choroids. Keeping in mind the structural changes of myopia, other imaging characteristics could aid the diagnostic process., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Purpose: To investigate the effect of two surgical techniques in primary Baerveldt glaucoma implant (BGI) surgery, that is the sutured technique and the unsutured (free) plate technique, on the ocular motility and prevalence of diplopia. We hypothesize that the free plate technique results in a lower diplopia prevalence., Methods: We performed a prospective study of patients who underwent BGI surgery with the free plate technique and compared them with patients from a previous study who had undergone BGI surgery with the sutured technique. Their ductions, ocular alignment and fusion range and the prevalence of diplopia were measured before surgery and at 3 months, 6 months and 1 year postoperatively., Results: We analysed 57 free plate and 51 sutured plate patients. One year postoperatively, we found no statistically significant difference in the prevalence of diplopia between the two techniques. All duction changes between baseline and 1-year follow-up were restrictions and occurred statistically significantly more frequently in the free plate than in the sutured plate group (p = 0.03; 60% versus 34%). About the ocular alignment, in the horizontal direction, a change in exodirection was more common in both groups, while in the vertical direction, a hyperdeviation of the operated eye was more common. The vertical ocular alignment change was smaller in the free plate group than in the sutured plate group (p = 0.04 at near and p = 0.02 at distance)., Conclusions: One year postoperatively, the prevalence of diplopia was not significantly different between patients with the sutured plate and patients with the free plate technique. Both surgical techniques induce diplopia and changes in ocular motility and/or in ocular alignment., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: In eye movement perimetry, peripheral stimuli are confirmed by goal-directed eye movements toward the stimulus. The saccadic reaction time (SRT) is regarded as an index of visual field responsiveness, whereas in standard automated perimetry (SAP), the visual field sensitivity is tested. We investigated the relation between visual field sensitivity and responsiveness in corresponding locations of the visual field in healthy controls and in patients with mild, moderate and advanced glaucoma. Materials and Methods: Thirty-four healthy control subjects and 42 glaucoma patients underwent a 54-point protocol in eye movement perimetry (EMP) and a 24-2 SITA standard protocol in a Humphrey Field Analyzer. The visual field points were stratified by total deviation sensitivity loss in SAP into 6 strata. A generalized linear mixed model was applied to determine the influence of the various factors. Results: The generalized linear mixed model showed that the mean SRT increased with increasing glaucoma severity, from 479 ms in the control eyes to 678 ms in the eyes of patients with advanced glaucoma ( p < 0.001). Mean SRTs significantly increased with increasing SAP sensitivity loss. Even at the locations where no sensitivity loss was detected by SAP (total deviation values greater or equal than 0 dB), we found lengthened SRTs in mild, moderate and advanced glaucoma compared to healthy controls ( p < 0.05) and in moderate and advanced glaucoma compared to mild glaucoma ( p < 0.05). At locations with total deviation values between 0 and -3 dB, -3 and -6 dB and -6 and -12 dB, we found similar differences. Conclusions: The lengthened SRT in areas with normal retinal sensitivities in glaucomatous eyes, i.e., planning and execution of saccades to specific locations, precede altered sensory perception as assessed with SAP. Better understanding of altered sensory processing in glaucoma might allow earlier diagnosis of emerging glaucoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Thepass, Lemij, Vermeer, van der Steen and Pel.)

Purpose: The purpose of this study was to assess the accuracy of artificial neural networks (ANN) in estimating the severity of mean deviation (MD) from peripapillary retinal nerve fiber layer (RNFL) thickness measurements derived from optical coherence tomography (OCT)., Methods: Models were trained using 1796 pairs of visual field and OCT measurements from 1796 eyes to estimate visual field MD from RNFL data. Multivariable linear regression, random forest regressor, support vector regressor, and 1D convolutional neural network (CNN) models with sectoral RNFL thickness measurements were examined. Three independent subsets consisting of 698, 256, and 691 pairs of visual field and OCT measurements were used to validate the models. Estimation errors were visualized to assess model performance subjectively. Mean absolute error (MAE), root mean square error (RMSE), median absolute error, Pearson correlation, and R-squared metrics were used to assess model performance objectively., Results: The MAE and RMSE of the ANN model based on the testing dataset were 4.0 dB (95% confidence interval = 3.8-4.2) and 5.2 dB (95% confidence interval = 5.1-5.4), respectively. The ranges of MAE and RMSE of the ANN model on independent datasets were 3.3-5.9 dB and 4.4-8.4 dB, respectively., Conclusions: The proposed ANN model estimated MD from RNFL measurements better than multivariable linear regression model, random forest, support vector regressor, and 1-D CNN models. The model was generalizable to independent data from different centers and varying races., Translational Relevance: Successful development of ANN models may assist clinicians in assessing visual function in glaucoma based on objective OCT measures with less dependence on subjective visual field tests.

Purpose: Perifoveal exudative vascular anomalous complex (PEVAC) was initially described as an isolated aneurysmal lesion in healthy eyes. Similar aneurysmal abnormalities may occur in association with retinal vascular diseases such as diabetic retinopathy or retinal vein occlusions (PEVAC-resembling). The aim of this study was to compare several imaging characteristics of PEVAC and PEVAC-resembling lesions., Methods: Ten eyes with a PEVAC and 27 eyes with a PEVAC-resembling lesion were included in this cross-sectional study. They were all imaged with optical coherence tomography (OCT), OCT angiography (OCT-A) and colour fundus photography (CFP). Several clinical, morphological and vascular characteristics were assessed and compared between both PEVAC types., Results: All PEVAC lesions were unilateral, while PEVAC-resembling lesions appeared bilateral in 23% of patients (p > 0.05). Unilateral multifocal PEVAC-resembling lesions were more frequently observed (56%) than unilateral multifocal PEVAC lesions (10%, p < 0.01). Furthermore, 90% of the PEVAC lesions were located within 500 µm from the centre of the fovea, while this was only true for 56% of the PEVAC-resembling lesions (p > 0.05). No notable differences were observed in other studied characteristics., Conclusions: The clinical, morphological and vascular features of PEVAC and PEVAC-resembling lesions are similar based on multimodal imaging. Given the bilaterality and multifocality seen in PEVAC-resembling lesions, an underlying retinal vascular disease may stimulate the quantity of aneurysmal abnormalities. Due to the similarities with PEVAC-resembling lesions, PEVAC may also be considered a microangiopathy but with an unknown origin., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Optical properties, such as the attenuation coefficients of multi-layer tissue samples, could be used as a biomarker for diagnosis and disease progression in clinical practice. In this paper, we present a method to estimate the attenuation coefficients in a multi-layer sample by fitting a single scattering model for the OCT signal to the recorded OCT signal. In addition, we employ numerical simulations to obtain the theoretically achievable precision and accuracy of the estimated parameters under various experimental conditions. Finally, the method is applied to two sets of measurements obtained from a multi-layer phantom by two experimental OCT systems: one with a large and one with a small Rayleigh length. Numerical and experimental results show an accurate estimation of the attenuation coefficients when using multiple B-scans., Competing Interests: The authors declare no conflicts of interest., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Purpose: To explore the short-term vascular and structural changes of type 3 neovascularization using optical coherence tomography angiography (OCT-A) when treated with a combination of photodynamic therapy (PDT) and intravitreal bevacizumab (IVB), and to evaluate the course of different sequences of the combined therapies., Methods: Thirty eyes of 29 treatment-naïve patients with a type 3 neovascularization were included in this prospective observational cohort study. They were all treated with PDT and IVB 2 weeks apart, starting either with PDT (PDT-first group) or IVB (IVB-first group). Optical coherence tomography angiography (OCT-A) imaging was performed at week 0, 2, 4 and 18, and best corrected visual acuity (BCVA) at week 0 and 18. Vascular, structural and functional features were graded and analysed over time., Results: In all patients, at all follow-up visits, vascular and structural features were significantly more often decreased or resolved than unchanged or increased. Best corrected visual acuity (BCVA) significantly improved at 18 weeks. Vascular, structural and functional outcomes were all slightly better in the PDT-first group compared to the IVB-first group, although not statistically significant., Conclusion: Combined treatment of PDT and IVB is effective in short-term for type 3 neovascularization based on vascular and structural features. Initial treatment with PDT tended to be more effective than with IVB., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare quantitative optical coherence tomography angiography (OCT-A) measurements of the parafoveal microvasculature in retinal capillary plexuses among Behҫet uveitis (BU) patients, non-ocular Behҫet's disease (NOBD) patients, and healthy volunteers (HVs)., Methods: Sixty-eight subjects were enrolled in this prospective observational cross-sectional study. OCT-A imaging was performed using the Heidelberg Engineering Spectralis OCT. A custom algorithm was developed to calculate the vessel density (VD) in three retinal vascular layers: deep capillary plexus, intermediate capillary plexus, and superficial vascular plexus. The foveal avascular zone (FAZ) and acircularity index were calculated for the whole retinal vascular complex., Results: We analyzed one eye from 21 BU patients (age, 51 ± 10 years), 23 NOBD patients (age, 48 ± 14 years), and 22 HVs (age, 44 ± 13 years). One-way multivariate analysis of covariance showed a statistically significant difference in VD among the three groups when combining the layers after controlling for scan quality (P < 0.001). The VD was lowest in the BU group and highest in the HV group in all layers. The FAZ area was also statistically significant different among the groups (P < 0.005), with the largest FAZ areas in BU patients and smallest FAZ areas in the HV group. However, no statistically significant difference was found for the acircularity index., Conclusions: The parafoveal microvasculature is affected not only in BU patients but also in NOBD patients. Most deviations in the retinal microcirculation in Behҫet patients were found in the deeper layers of the retina by using the quantitative VD measurement.

Purpose: To examine the intra- and intergrader agreement on morphologic characteristics of type 3 neovascularization on optical coherence tomography angiography (OCT-A)., Methods: OCT-A images of 22 eyes from 21 patients with a new-onset, treatment-naive type 3 neovascularization were included in this cross-sectional retrospective agreement study. Each image was graded three times by two independent medical retina specialists to assess intra- and intergrader agreement. The graders scored the presence or absence of the following vascular and structural features: intraretinal neovascularization (IRN), subretinal neovascularization, sub-retinal pigment epithelium (RPE) neovascularization (SRPEN), retinal choroidal anastomosis (RCA), intraretinal cysts, subretinal fluid, and pigment epithelial detachment. Agreement was analyzed for each feature using Gwet's AC 1 , к statistics, and percentage of agreement., Results: The best agreement (AC 1 ) was found for intraretinal neovascularization (within grader1 : 0.94; within grader2 : 0.93 and between: 1.00) and intraretinal cysts (within grader1 , 1.00; within grader2 , 0.97 and between, 1.00). The poorest intragrader agreements were observed for SRPEN (within grader1 , 0.54 and within grader2 , 0.36) and RCA (within grader1 , 0.45 and within grader2 , 0.52), and the poorest intergrader agreement was found for SRPEN, RCA, and pigment epithelial detachment (0.18, 0.37, and 0.15, respectively)., Conclusions: Although the agreement values were high for intraretinal features, considerable grader variability was found for the vascular and structural features in the deeper retina or under the RPE. Clinicians should be careful to base therapeutic decisions on qualitative OCT-A assessment, because even well-trained specialists show a considerable grader variation in their subjective evaluation., Translational Relevance: The clinical value of OCT-A imaging largely depends on the agreement of subjective evaluations by ophthalmologists., Competing Interests: Disclosure: L.M. Smid, None; M.E.J. van Velthoven, None; K.T. Wong, None; J.P. Martinez-Ciriano, None; K.A. Vermeer, None, (Copyright 2021 The Authors.)

Purpose: To report a series of 21 patients with perifoveal exudative vascular anomalous complex (PEVAC) and to investigate the anatomical changes over time., Methods: We conducted a retrospective study. Clinical data of consecutive patients, presenting at the Rotterdam Eye Hospital between 2014 and 2019, were analyzed. The data collected included best-corrected visual acuity, fundus photography, optical coherence tomography (OCT), OCT-angiography, fluorescence angiography, and indocyanine green angiography., Results: We included 21 patients with a PEVAC lesion with a mean follow-up of 24.3 ± 13.8 months (range, 9-46 months). Patients with PEVAC were on average 75.3 ± 11.1 years (range, 53-90 years). The large perifoveal vascular aneurysmal abnormality was associated with small retinal hemorrhages in six patients and hard exudates in three patients. The PEVAC lesion was associated with intraretinal cystic spaces on OCT in 15 patients. Twelve of 21 patients showed no changes in cystic spaces on OCT during follow-up: 9 patients had stable cystic spaces and 3 patients had no cystic spaces. In contrast, in 9 of 21 patients, we observed changes in cystic spaces on OCT during follow-up. In two patients, cystic spaces appeared during follow-up, and in seven patients, there was a spontaneous resolution of cystic spaces. In three of these seven patients, the PEVAC lesion completely disappeared. Two patients, with stable intraretinal cystic spaces on OCT, were treated with intravitreal injections of anti-vascular endothelial growth factor without improvement., Conclusion: Perifoveal exudative vascular anomalous complex is an idiopathic perifoveal retinal vascular abnormality that is associated with intraretinal cystic spaces. These intraretinal cystic spaces associated with a PEVAC lesion, and even the PEVAC lesion itself, can have a spontaneous resolution over time.

The attenuation coefficient (AC) is an optical property of tissue that can be estimated from optical coherence tomography (OCT) data. In this paper, we aim to estimate the AC accurately by compensating for the shape of the focused beam. For this, we propose a method to estimate the axial PSF model parameters and AC by fitting a model for an OCT signal in a homogenous sample to the recorded OCT signal. In addition, we employ numerical analysis to obtain the theoretical optimal precision of the estimated parameters for different experimental setups. Finally, the method is applied to OCT B-scans obtained from homogeneous samples. The numerical and experimental results show accurate estimations of the AC and the focus location when the focus is located inside the sample., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Purpose: To associate the change in the foveal avascular zone (FAZ) and vessel density (VD) with final best corrected visual acuity (BCVA) in eyes after macula-off rhegmatogenous retinal detachment surgery, and to investigate the evolution of FAZ and VD during 12 months of follow-up., Methods: We prospectively evaluated 47 patients with macula-off rhegmatogenous retinal detachment and healthy fellow eyes. At 1.5, 3.0, 6.0, and 12.0 months postoperatively, optical coherence tomography angiography scans were obtained from both eyes on a 3.0 × 3.0 mm macula-centered grid. En face images of the superficial vascular plexus, intermediate capillary plexus and deep capillary plexus were used to quantify FAZ and VD. BCVA was assessed with ETDRS-charts (logarithm of the minimal angle of resolution).At 12 months postoperatively, the association between the change in optical coherence tomography angiography parameters and visual function in study eyes was evaluated using the Spearman correlation coefficient. We calculated the BCVA difference and the percentage difference of FAZ and VD between the study and control eye. The evolution of FAZ and VD was investigated with linear mixed-effects models with nested random effects (eyes nested within patients)., Results: At 12 months postoperatively, FAZ difference of the deep capillary plexus and BCVA difference were correlated ( P = 0.0004, r s = 0.5). Furthermore, there was no evidence that FAZ and VD changed during follow-up., Conclusions: Although FAZ and VD remained stable during 12 months after surgery for macula-off rhegmatogenous retinal detachment, a smaller FAZ in the deep capillary plexus is associated with better BCVA., Translational Relevance: Reduction in FAZ area may be caused by angiogenesis to counteract ischemia, therefore therapeutic stimulation of angiogenesis could be beneficial to visual recovery., Competing Interests: Disclosure: H. Ng, None; E.C. La Heij, None; E.-R. Andrinopoulou, None; J.C. van Meurs, None; K.A. Vermeer, None, (Copyright 2020 The Authors.)

Purpose: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers., Methods: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis., Results: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients., Conclusion: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes.

Purpose: To present a fully automatic method to estimate the corneal endothelium parameters from specular microscopy images and to use it to study a one-year follow-up after ultrathin Descemet stripping automated endothelial keratoplasty., Methods: We analyzed 383 post ultrathin Descemet stripping automated endothelial keratoplasty images from 41 eyes acquired with a Topcon SP-1P specular microscope at 1, 3, 6, and 12 months after surgery. The estimated parameters were endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX). Manual segmentation was performed in all images., Results: Our method provided an estimate for ECD, CV, and HEX in 98.4% of the images, whereas Topcon's software had a success rate of 71.5% for ECD/CV and 30.5% for HEX. For the images with estimates, the percentage error in our method was 2.5% for ECD, 5.7% for CV, and 5.7% for HEX, whereas Topcon's software provided an error of 7.5% for ECD, 17.5% for CV, and 18.3% for HEX. Our method was significantly better than Topcon's ( P < 0.0001) and was not statistically significantly different from the manual assessments ( P > 0.05). At month 12, the subjects presented an average ECD = 1377 ± 483 [cells/mm 2 ], CV = 26.1 ± 5.7 [%], and HEX = 58.1 ± 7.1 [%]., Conclusions: The proposed method obtains reliable and accurate estimations even in challenging specular images of pathologic corneas., Translational Relevance: CV and HEX, not currently used in the clinic owing to a lack of reliability in automatic methods, are useful biomarkers to analyze the postoperative healing process. Our accurate estimations allow now for their clinical use., Competing Interests: Disclosure: J.P. Vigueras-Guillén, None; J. van Rooij, None; A. Engel, None; H.G. Lemij, None; L.J. van Vliet, None; K.A. Vermeer, None, (Copyright 2020 The Authors.)

Purpose: To determine the impact of postoperative visual function on the vision-related quality of life (VRQoL) in patients after anatomically successful surgery for macula-off rhegmatogenous retinal detachment (RRD) and to propose a classification to grade the extent of macular detachment using preoperative optical coherence tomography (OCT) scans., Methods: This prospective study evaluated 48 patients. At 12 months after surgery, visual function assessments were as follows: metamorphopsia (M-CHARTS), aniseikonia (New Aniseikonia Test), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS]), low contrast BCVA (10% ETDRS), color vision (Hardy Rand Rittler), and stereopsis (Titmus Fly). VRQoL was assessed by the National Eye Institute Visual Functioning Questionnaire-25 (NEIVFQ-25). Associations between visual function parameters and NEIVFQ-25 scores were evaluated. Preoperative OCT-scans were classified into six stages according to the extent of macular detachment based on an ETDRS-grid: incomplete perifoveal detachment (1), incomplete parafoveal detachment (2), incomplete foveal detachment (3), complete foveal detachment (4), complete parafoveal detachment (5), and complete perifoveal detachment (6)., Results: General vision and driving were the lowest scoring categories. General vision had the strongest correlation with low contrast BCVA (r = -0.41, P = 0.002), while driving had the strongest correlation with stereopsis (r = -0.39, P = 0.008). All macular detachments were graded stage 3 or beyond. Patients with stage 3 macular detachments had the highest visual function values compared to the other stages. The highest percentage of patients with metamorphopsia, aniseikonia and BCVA>0.1 logMAR was found in stages 5 and 6., Conclusions: Macula-off RRD particularly affects general vision and driving. The extent of macular detachment is a potential predictor for visual function and can be graded using the proposed classification.

Objectives: To evaluate the performance of a deep learning based Artificial Intelligence (AI) software for detection of glaucoma from stereoscopic optic disc photographs, and to compare this performance to the performance of a large cohort of ophthalmologists and optometrists., Methods: A retrospective study evaluating the diagnostic performance of an AI software (Pegasus v1.0, Visulytix Ltd., London UK) and comparing it with that of 243 European ophthalmologists and 208 British optometrists, as determined in previous studies, for the detection of glaucomatous optic neuropathy from 94 scanned stereoscopic photographic slides scanned into digital format., Results: Pegasus was able to detect glaucomatous optic neuropathy with an accuracy of 83.4% (95% CI: 77.5-89.2). This is comparable to an average ophthalmologist accuracy of 80.5% (95% CI: 67.2-93.8) and average optometrist accuracy of 80% (95% CI: 67-88) on the same images. In addition, the AI system had an intra-observer agreement (Cohen's Kappa, κ) of 0.74 (95% CI: 0.63-0.85), compared with 0.70 (range: -0.13-1.00; 95% CI: 0.67-0.73) and 0.71 (range: 0.08-1.00) for ophthalmologists and optometrists, respectively. There was no statistically significant difference between the performance of the deep learning system and ophthalmologists or optometrists., Conclusion: The AI system obtained a diagnostic performance and repeatability comparable to that of the ophthalmologists and optometrists. We conclude that deep learning based AI systems, such as Pegasus, demonstrate significant promise in the assisted detection of glaucomatous optic neuropathy.

Purpose: To evaluate whether prolongation of interruptions of preoperative posturing by sitting upright influences retinal detachment (RD) progression. The secondary objective was to find clinical factors to identify patients with a high risk for RD progression., Design: Prospective cohort study., Participants: One hundred ninety-eight patients divided among 3 cohorts of patients with macula-on RD were included. Inclusion criteria were volume OCT scans of sufficient quality and smallest distance from the fovea to the detachment border of at least 1.25 mm. In the second and third cohort, 50 patients with only superior temporal RD were included., Methods: Patients were admitted to the ward in anticipation of surgery. Preoperative bed rest and positioning were prescribed. The position of the RD border was determined based on OCT imaging performed at baseline, before and after the usual interruptions for meals or toilet visits. The duration of interruptions was prolonged with sitting upright for 20 minutes in cohort 2 and for 40 minutes in cohort 3. Various secondary outcome measures were defined, such as the baseline area of subretinal fluid (SRF) as measured on ultrasound images in the third cohort., Main Outcome Measures: The RD border displacement was determined. The worst RD progression from baseline was given by the shortest distance to the fovea in any of the OCT scans during follow-up. The worst relative RD progression from baseline was defined as the worst RD progression from baseline as a percentage of the baseline distance between RD border and fovea., Results: The median duration of interruptions was 22, 41, and 58 minutes in cohorts 1, 2, and 3, respectively. The median RD border displacement during interruptions in patients with superior temporal RD was not significantly different among the cohorts (P = 0.28). The correlation coefficient between the SRF area at baseline and worst relative RD progression from baseline was 0.37 (95% confidence interval, 0.04-0.66; P = 0.009)., Conclusions: We did not find a significant increase in RD progression after prolongation of interruptions by sitting upright. Patients with a larger area of SRF on ultrasound showed more RD progression from baseline., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The morphometric parameters of the corneal endothelium - cell density (ECD), cell size variation (CV), and hexagonality (HEX) - provide clinically relevant information about the cornea. To estimate these parameters, the endothelium is commonly imaged with a non-contact specular microscope and cell segmentation is performed to these images. In previous work, we have developed several methods that, combined, can perform an automated estimation of the parameters: the inference of the cell edges, the detection of the region of interest (ROI), a post-processing method that combines both images (edges and ROI), and a refinement method that removes false edges. In this work, we first explore the possibility of using a CNN-based regressor to directly infer the parameters from the edge images, simplifying the framework. We use a dataset of 738 images coming from a study related to the implantation of a Baerveldt glaucoma device and a standard clinical care regarding DSAEK corneal transplantation, both from the Rotterdam Eye Hospital and both containing images of unhealthy endotheliums. This large dataset allows us to build a large training set that makes this approach feasible. We achieved a mean absolute percentage error (MAPE) of 4.32% for ECD, 7.07% for CV, and 11.74% for HEX. These results, while promising, do not outperform our previous work. In a second experiment, we explore the use of the CNN-based regressor to improve the post-processing method of our previous approach in order to adapt it to the specifics of each image. Our results showed no clear benefit and proved that our previous post-processing is already highly reliable and robust.

Optical coherence tomographic (OCT) images provide valuable information for understanding the changes occurring in the retina due to glaucoma, specifically, related to the retinal nerve fiber layer and the optic nerve head. In this paper, we propose a deep learning approach using Capsule network for glaucoma classification, which directly operates on 3D OCT volumes. The network is trained only on labelled volumes and does not attempt any region/structure segmentation. The proposed network was assessed on 50 volumes and found to achieve 0.97 for the area under the ROC curve (AUC). This is considerably higher than the existing approaches which are majorly based on machine learning or rely on segmentation of the required structures from OCT. Our network also outperforms 3D convolutional neural networks despite the fewer network parameters and fewer epochs needed for training.

Uveitis is characterised as a recurrent inflammation of the eye and an ongoing inflammation can have severe impact on the visual acuity of the patient. The Rotterdam Eye Hospital has been collecting data on every uveitis patient visiting the hospital since 2000. We propose a joint model for the inflammation and visual acuity with the purpose of making dynamic predictions. Dynamic prediction models allow predictions to be updated during the follow-up of the patient based on the patient's disease history. The joint model consists of a submodel for the inflammation, the event history outcome, and one for the visual acuity, the longitudinal outcome. The inflammation process is described with a two-state reversible multistate model, where transition times are interval censored. Correlated log-normal frailties are included in the multistate model to account for the within eye and within patient correlation. A linear mixed model is used for the visual acuity. The joint model is fitted in a two-stage procedure and we illustrate how the model can be used to make dynamic predictions. The performance of the method was investigated in a simulation study. The novelty of the proposed model includes the extension to a multistate outcome, whereas, previously, the standard has been to consider survival or competing risk outcomes. Furthermore, it is usually the case that the longitudinal outcome affects the event history outcome, but in this model, the relation is reversed., (© 2018 John Wiley & Sons, Ltd.)

Purpose: We determine the contrast-to-noise ratios (CNRs) of structural and functional measurements to assess their sensitivity to detect progression in the various stages of glaucoma., Methods: We calculated the CNRs for the mean peripapillary retinal nerve fiber layer (RNFL) thickness measured by spectral domain optical coherence tomography, and the mean deviation (MD) and visual field index (VFI) determined by standard automated perimetry for the transitions between five stages. Longitudinal data from healthy and glaucomatous eyes from a prospective study were used. Contrast was defined as the change in the mean value of the parameter between two successive stages. Noise was defined as the variability of the parameter and calculated from the residuals of linear regression on the data from five subsequent visits per eye., Results: We studied 205 eyes from 125 participants (46% men, 54% women). CNRs for different parameters varied considerably across the range of disease severity (0.8-12.2). The RNFL thickness had a higher CNR in the transition from normal to mild glaucoma (12.2) compared to the CNRs of the functional measures (MD 4.1, VFI 4.5). The CNRs for the functional measures were higher in the transition from moderate to advanced (MD 5.2, VFI 5.8) and advanced to severe glaucoma (MD 7.2, VFI 5.8) compared to the RNFL thickness (CNR 0.8 and 3.2, respectively)., Conclusions: The RNFL thickness is more sensitive for detecting glaucomatous progression at the onset of glaucoma compared to the functional measures, while the latter are more sensitive for detecting progression in the later stages of glaucoma., Translational Relevance: The CNR method can be used to determine which measurement is most sensitive for detecting progression in glaucoma, differentiated for the severity of the disease. Furthermore, it creates a basic toolset for determining the most sensitive measurement in detecting progression not only in glaucoma, but other (ophthalmic) diseases as well.

Purpose: The aim of this study was to explore the relationship between compliance with preoperative posturing advice and progression of macula-on retinal detachment (RD) and to evaluate whether head positioning or head motility contributes most to RD progression., Methods: Sixteen patients with macula-on RD were enrolled, admitted to the ward, and instructed to posture preoperatively. The primary outcome parameter was compliance, which was defined as the average head orientation deviation from advised positioning. Secondary outcome parameters included the average rotational and linear head acceleration. The head orientation and acceleration were measured with a head-mounted inertial measurement unit (IMU). Optical coherence tomography (OCT) imaging was performed at baseline and during natural interruptions of posturing for meals and toilet visits to measure RD progression toward the fovea., Results: The Spearman correlation coefficient with RD progression was 0.37 ( P = 0.001, r s 2 = 0.13) for compliance, 0.52 ( P < 0.001, r s 2 = 0.27) for rotational acceleration, and 0.49 ( P < 0.001, r s 2 = 0.24) for linear acceleration. The correlation coefficient between RD progression and rotational acceleration was statistically significantly higher than the correlation coefficient between RD progression and compliance ( P = 0.034)., Conclusion: The strength of the correlation between RD progression and compliance was moderate. However, the correlation between RD progression and rotational and linear acceleration was much stronger. Preoperative posturing is effective by reducing head movements rather than enforcing head positioning., Translational Relevance: Monitoring the efficacy of preoperative posturing in macula-on RD using OCT and IMU measurements shows that a new and combined application of these technologies leads to clinically relevant insights.

Background: Corneal endothelium (CE) images provide valuable clinical information regarding the health state of the cornea. Computation of the clinical morphometric parameters requires the segmentation of endothelial cell images. Current techniques to image the endothelium in vivo deliver low quality images, which makes automatic segmentation a complicated task. Here, we present two convolutional neural networks (CNN) to segment CE images: a global fully convolutional approach based on U-net, and a local sliding-window network (SW-net). We propose to use probabilistic labels instead of binary, we evaluate a preprocessing method to enhance the contrast of images, and we introduce a postprocessing method based on Fourier analysis and watershed to convert the CNN output images into the final cell segmentation. Both methods are applied to 50 images acquired with an SP-1P Topcon specular microscope. Estimates are compared against a manual delineation made by a trained observer., Results: U-net (AUC=0.9938) yields slightly sharper, clearer images than SW-net (AUC=0.9921). After postprocessing, U-net obtains a DICE=0.981 and a MHD=0.22 (modified Hausdorff distance), whereas SW-net yields a DICE=0.978 and a MHD=0.30. U-net generates a wrong cell segmentation in only 0.48% of the cells, versus 0.92% for the SW-net. U-net achieves statistically significant better precision and accuracy than both, Topcon and SW-net, for the estimates of three clinical parameters: cell density (ECD), polymegethism (CV), and pleomorphism (HEX). The mean relative error in U-net for the parameters is 0.4% in ECD, 2.8% in CV, and 1.3% in HEX. The computation time to segment an image and estimate the parameters is barely a few seconds., Conclusions: Both methods presented here provide a statistically significant improvement over the state of the art. U-net has reached the smallest error rate. We suggest a segmentation refinement based on our previous work to further improve the performance., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Purpose: This prospective case series is aimed at exploring optical coherence tomographic angiography (OCT-A) as a treatment monitoring tool in patients treated for retinal angiomatous proliferation (RAP)., Methods: Twelve treatment-naïve RAP patients were included, with a median age of 79 years (range 65-90). Patients were imaged with an experimental 1,040-nm swept-source phase-resolved OCT-A instrument before and after treatment. Treatment consisted of either intravitreal bevacizumab or triamcinolone injections with or without photodynamic therapy (PDT). Abnormal blood flow after treatment was graded as increased, unchanged, decreased, or resolved., Results: OCT-A images before and after treatment could be obtained in 9 patients. The median follow-up period was 10 weeks (range 5-19). After various treatments, the RAP lesion resolved in 7 patients, in 1 patient the OCT-A depicted decreased flow in the lesion, and 1 patient showed unchanged abnormal blood flow. Monotherapy with intravitreal bevacizumab injections resolved RAP in 1 out of 2 patients. Combined therapy of bevacizumab with PDT resolved RAP in 6 out of 7 patients., Conclusions: OCT-A visualized resolution of abnormal blood flow in 7 out of 9 RAP patients after various short-term treatment sequences. OCT-A may become an important noninvasive monitoring tool for optimizing treatment strategies in RAP patients., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Corneal endothelium images obtained by in vivo specular microscopy provide important information to assess the health status of the cornea. Estimation of clinical parameters, such as cell density, polymegethism, and pleomorphism, requires accurate cell segmentation. State-of-the-art techniques to automatically segment the endothelium are error-prone when applied to images with low contrast and/or large variation in cell size. Here, we propose an automatic method to segment the endothelium. Starting with an oversegmented image comprised of superpixels obtained from a stochastic watershed segmentation, the proposed method uses intensity and shape information of the superpixels to identify and merge those that constitute a cell, using support vector machines. We evaluated the automatic segmentation on a data set of in vivo specular microscopy images (Topcon SP-1P), obtaining 95.8% correctly merged cells and 2.0% undersegmented cells. We also evaluated the parameter estimation against the results of the vendor's built-in software, obtaining a statistically significant better precision in all parameters and a similar or better accuracy. The parameter estimation was also evaluated on three other data sets from different imaging modalities (confocal microscopy, phase-contrast microscopy, and fluorescence confocal microscopy) and tissue types (ex vivo corneal endothelium and retinal pigment epithelium). In comparison with the estimates of the data sets' authors, we achieved statistically significant better accuracy and precision in all parameters except pleomorphism, where a similar accuracy and precision were obtained.

Purpose: The purpose of this study was to quantify any diplopia and motility changes after the implantation of a Baerveldt glaucoma implant (BGI) or after trabeculectomy (TE)., Methods: We analyzed 51 patients with a BGI and 52 patients with a TE from a prospective cohort study. To quantify any diplopia, we asked patients about the presence of diplopia at 1 year after surgery. To quantify any ocular motility changes, we measured ductions in eight gaze directions, the patients' ocular alignment and their fusion range before and 1 year after surgery., Results: In the BGI group, 14 patients (28%) experienced diplopia compared with one patient (2%) in the TE group ( P < 0.001). Duction changes were more commonly observed in the BGI group (35%) than in the TE group (19%). In the BGI group, ductions were mostly restricted in elevation (13%; P < 0.001), in abduction (13%), in elevation in 25° adduction (13%; P = 0.044), and in elevation in 25° abduction (25%; P < 0.001). In 32% of the patients, their near horizontal ocular alignment shifted, notably in exodirection ( P = 0.04). The fusion range decreased significantly in the horizontal direction (-12.6° ± 10.3°, mean ± standard deviation; P = 0.01)., Conclusions: BGI surgery was significantly associated with postoperative diplopia and impaired eye motility (reduced ductions), mostly present in abduction, elevation, elevation in 25° adduction, and elevation in 25° abduction. Even without impaired ductions, diplopia could come about., Translational Relevance: By studying diplopia across glaucoma patients prospectively with diplopia questionnaires and extensive orthoptic measurements, we gain better insight into its occurrence.

Purpose: To identify patterns and rates of visual field (VF) loss in primary open-angle glaucoma (POAG) across different levels of severity., Design: Retrospective, observational case series., Participants: Visual fields of 278 eyes of 139 patients with POAG (9 years of follow-up with ∼17 visits) from the Rotterdam Eye Hospital in The Netherlands were analyzed to identify patterns and rates of VF loss., Main Outcome Measures: Rate of VF decline for the entire VF, each region, and test point. Hemifield asymmetric rate if VF decline for each region and test point., Methods: Total deviation (TD) values were extracted from the Humphrey VF Analyzer (Carl Zeiss Meditec, Dublin, CA). Eyes were stratified into 3 glaucoma stages by means of the mean deviation (MD): better than -6 decibels (dB), worse than -6 dB and better than -12 dB, and worse than -12 dB. Each hemifield was divided into 5 regions according to the Glaucoma Hemifield Test (GHT): central, paracentral, nasal, and peripheral arcuates 1 and 2. Point-wise and region-wise asymmetric patterns of VF loss and rate of VF loss were identified by comparing the values in the superior hemifield and the inferior hemifield at each severity level using a generalized estimating equation., Results: The mean age of the patients was 60.2±10.3 years (mean ± standard deviation [SD]). The rate of MD loss, for all eyes taken together, was -0.11 dB/year. In the cross-sectional analysis, in eyes in the early and moderate stages, central and peripheral arcuate 2 regions in the superior hemifield were worse than their inferior counterpart, whereas in the advanced stage all GHT regions in the superior hemifield were significantly worse than the corresponding regions in the inferior hemifield (P ≤ 0.05). In the longitudinal analysis, there was no significant difference in the rate of VF loss between the GHT regions in the superior and inferior hemifields., Conclusions: Our findings suggest that in POAG, VF damage is worse in the superior hemifield than in the inferior hemifield., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Thinning of the retinal nerve fiber layer (RNFL) is a recently discovered feature of Parkinson's disease (PD). Its exact pathological mechanism is yet unknown. We aimed to determine whether morphological changes of the RNFL are limited to RNFL thinning or also comprise an altered internal structure of this layer. Therefore, we investigated RNFL thickness and applied the RNFL attenuation coefficient (RNFL-AC), a novel method derived from optical coherence tomography, in PD patients and healthy controls (HCs). In this pilot study, we included 20 PD patients and 20 HCs matched for age, sex, and ethnicity. An ophthalmologist investigated all participants thoroughly, and we acquired retinal images from both eyes of each participant with a Spectralis optical coherence tomography system. We obtained both the RNFL-AC and RNFL thickness from peripapillary RNFL scans for the entire RNFL, as well as for each quadrant separately. We found no significant differences in the average RNFL-AC or the RNFL-AC of the separate retinal quadrants between PD patients and the HC group. However, compared to the HC group, PD patients had a significantly thinner RNFL in the temporal retinal quadrant. RNFL thinning was found in the temporal quadrant in PD patients without a corresponding change in the RNFL-AC. These findings suggest a reduction in the number of RNFL axons (atrophy) without other major changes in the structural integrity of the remaining RNFL.

People with diabetes mellitus need annual screening to check for the development of diabetic retinopathy (DR). Tracking small retinal changes due to early diabetic retinopathy lesions in longitudinal fundus image sets is challenging due to intra- and intervisit variability in illumination and image quality, the required high registration accuracy, and the subtle appearance of retinal lesions compared to other retinal features. This paper presents a robust and flexible approach for automated detection of longitudinal retinal changes due to small red lesions by exploiting normalized fundus images that significantly reduce illumination variations and improve the contrast of small retinal features. To detect spatio-temporal retinal changes, the absolute difference between the extremes of the multiscale blobness responses of fundus images from two time points is proposed as a simple and effective blobness measure. DR related changes are then identified based on several intensity and shape features by a support vector machine classifier. The proposed approach was evaluated in the context of a regular diabetic retinopathy screening program involving subjects ranging from healthy (no retinal lesion) to moderate (with clinically relevant retinal lesions) DR levels. Evaluation shows that the system is able to detect retinal changes due to small red lesions with a sensitivity of at an average false positive rate of 1 and 2.5 lesions per eye on small and large fields-of-view of the retina, respectively.

Background: Eye Movement Perimetry (EMP) uses Saccadic Eye Movement (SEM) responses for visual field evaluation. Previous studies have demonstrated significant delay in initiation of SEMs among glaucoma patients in comparison with healthy subjects. The aim of the current study was to develop an EMP-based screening grid to identify glaucomatous visual field defects., Methods: An interactive test consisting of 36 locations and two stimulus contrasts (162 cd/m 2 and 190 cd/m 2 on a background of 140 cd/m 2 ) was evaluated in 54 healthy subjects and 50 primary glaucoma patients. Each subject was presented a central fixation target combined with the random projection of Goldmann size III peripheral targets. Instructions were given to look at each peripheral target on detection and then re-fixate at the central fixation target while the saccades were assessed using an eye tracker. From each seen peripheral target, the Saccadic Reaction Time (SRT) was calculated for contrast level 162 cd/ m 2 . These values were used to plot Receiver Operating Characteristic (ROC) curves for each test locations and the Area Under the Curve (AUC) values were used to identify the locations with highest susceptibility to glaucomatous damage. Each stimulus location with an AUC less than 0.75 along with its mirrored test location around the horizontal axis were eliminated from the grid., Results: The mean age was 48.1 ± 16.6 years and 50.0 ± 14.5 years for healthy subjects and glaucoma patients respectively. A significant increase of SRT values by 76.5% (p < 0.001) was found in glaucoma patients in comparison with the healthy subjects. From the ROC analysis, ten out of 36 locations meeting the cut-off criteria of AUC were eliminated resulting in a new grid containing 26 test locations. SRT values were significantly different (p < 0.05) between the healthy subjects and glaucoma irrespective of the grids used., Conclusions: The present study resulted in a screening grid consisting of 26 locations predominantly testing nasal, superior and inferior areas of the visual field. An internal validation of the modified grid showed 90.4% of screening accuracy which makes it a potential approach for population based glaucoma screening.

Retinal motion detection with an accuracy of 0.77 arcmin corresponding to 3.7 µm on the retina is demonstrated with a novel digital micromirror device based ophthalmoscope. By generating a confocal image as a reference, eye motion could be measured from consecutively measured subsampled frames. The subsampled frames provide 7.7 millisecond snapshots of the retina without motion artifacts between the image points of the subsampled frame, distributed over the full field of view. An ophthalmoscope pattern projection speed of 130 Hz enabled a motion detection bandwidth of 65 Hz. A model eye with a scanning mirror was built to test the performance of the motion detection algorithm. Furthermore, an in vivo motion trace was obtained from a healthy volunteer. The obtained eye motion trace clearly shows the three main types of fixational eye movements. Lastly, the obtained eye motion trace was used to correct for the eye motion in consecutively obtained subsampled frames to produce an averaged confocal image correct for motion artefacts., Competing Interests: JFdB: Heidelberg Engineering, GmBH (F, P, R), KAV: (P).