ANATOMICAL CHANGES ON SEQUENTIAL MULTIMODAL IMAGING IN PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX.

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.

MYOPIC PRESENTATION OF CENTRAL SEROUS CHORIORETINOPATHY.

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.

LONGITUDINAL STUDY OF RPE65-ASSOCIATED INHERITED RETINAL DEGENERATIONS.

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.

Treatment Effects in Retinal Angiomatous Proliferation Imaged with OCT Angiography.

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.

In vivo exploration of retinal nerve fiber layer morphology in Parkinson's disease patients.

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.

Preoperative Posturing of Patients with Macula-On Retinal Detachment Reduces Progression Toward the Fovea.

PURPOSE: Traditionally, preoperative posturing consisting of bed rest and positioning is prescribed to patients with macula-on retinal detachment (RD) to prevent RD progression and detachment of the fovea. Execution of such advice can be cumbersome and expensive. This study aimed to investigate if preoperative posturing affects the progression of RD. DESIGN: Prospective cohort study. PARTICIPANTS: Ninety-eight patients with macula-on RD were included. Inclusion criteria were volume optical coherence tomography (OCT) scans could be obtained with sufficient quality; and the smallest distance from the fovea to the detachment border was 1.25 mm or more. METHODS: Patients were admitted to the ward for bed rest in anticipation of surgery and were positioned on the side where the RD was mainly located. At baseline and before and after each interruption for meals or toilet visits, a 37°×45° OCT volume scan was performed using a wide-angle Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany). The distance between the nearest point of the RD border and fovea was measured using a custom-built measuring tool. MAIN OUTCOME MEASURES: The RD border displacement and the average RD border displacement velocity moving toward (negative) or away (positive) from the fovea were determined for intervals of posturing and interruptions. RESULTS: The median duration of intervals of posturing was 3.0 hours (interquartile range [IQR], 1.8-14.0 hours; n = 202) and of interruptions 0.37 hours (IQR, 0.26-0.50 hours; n = 197). The median RD border displacement was 2 µm (IQR, -65 to +251 µm) during posturing and -61 µm (IQR, -140 to 0 µm) during interruptions, a statistically significant difference (P < 0.001, Mann-Whitney U test). The median RD border displacement velocity was +1 µm/hour (IQR, -21 to +49 µm/hour) during posturing and -149 µm/hour (IQR, -406 to +1 µm/hour) during interruptions, a statistically significant difference (P < 0.001). CONCLUSIONS: By making use of usual interruptions of preoperative posturing we were able to show, in a prospective and ethically acceptable manner, that RD stabilizes during posturing and progresses during interruptions in patients with macula-on RD. Preoperative posturing is effective in reducing progression of RD.

Bayesian hierarchical modeling of longitudinal glaucomatous visual fields using a two-stage approach.

The Bayesian approach has become increasingly popular because it allows to fit quite complex models to data via Markov chain Monte Carlo sampling. However, it is also recognized nowadays that Markov chain Monte Carlo sampling can become computationally prohibitive when applied to a large data set. We encountered serious computational difficulties when fitting an hierarchical model to longitudinal glaucoma data of patients who participate in an ongoing Dutch study. To overcome this problem, we applied and extended a recently proposed two-stage approach to model these data. Glaucoma is one of the leading causes of blindness in the world. In order to detect deterioration at an early stage, a model for predicting visual fields (VFs) in time is needed. Hence, the true underlying VF progression can be determined, and treatment strategies can then be optimized to prevent further VF loss. Because we were unable to fit these data with the classical one-stage approach upon which the current popular Bayesian software is based, we made use of the two-stage Bayesian approach. The considered hierarchical longitudinal model involves estimating a large number of random effects and deals with censoring and high measurement variability. In addition, we extended the approach with tools for model evaluation. Copyright © 2017 John Wiley & Sons, Ltd.

INTRAVITREAL VERSUS SUBRETINAL ADMINISTRATION OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR COMBINED WITH GAS FOR ACUTE SUBMACULAR HEMORRHAGES DUE TO AGE-RELATED MACULAR DEGENERATION: An Exploratory Prospective Study.

PURPOSE: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood. METHODS: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 µm and 1,250 µm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea. RESULTS: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91-99%) in the intravitreal rtPA group and 100% (95-100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56). CONCLUSION: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Parallel line scanning ophthalmoscope for retinal imaging.

A parallel line scanning ophthalmoscope (PLSO) is presented using a digital micromirror device (DMD) for parallel confocal line imaging of the retina. The posterior part of the eye is illuminated using up to seven parallel lines, which were projected at 100 Hz. The DMD offers a high degree of parallelism in illuminating the retina compared to traditional scanning laser ophthalmoscope systems utilizing scanning mirrors. The system operated at the shot-noise limit with a signal-to-noise ratio of 28 for an optical power measured at the cornea of 100 µW. To demonstrate the imaging capabilities of the system, the macula and the optic nerve head of a healthy volunteer were imaged. Confocal images show good contrast and lateral resolution with a 10°×10° field of view.

Fully automatic evaluation of the corneal endothelium from in vivo confocal microscopy.

BACKGROUND: Manual and semi-automatic analyses of images, acquired in vivo by confocal microscopy, are often used to determine the quality of corneal endothelium in the human eye. These procedures are highly time consuming. Here, we present two fully automatic methods to analyze and quantify corneal endothelium imaged by in vivo white light slit-scanning confocal microscopy. METHODS: In the first approach, endothelial cell density is estimated with the help of spatial frequency analysis. We evaluate published methods, and propose a new, parameter-free method. In the second approach, based on the stochastic watershed, cells are automatically segmented and the result is used to estimate cell density, polymegathism (cell size variability) and pleomorphism (cell shape variation). We show how to determine optimal values for the three parameters of this algorithm, and compare its results to a semi-automatic delineation by a trained observer. RESULTS: The frequency analysis method proposed here is more precise than any published method. The segmentation method outperforms the fully automatic method in the NAVIS software (Nidek Technologies Srl, Padova, Italy), which significantly overestimates the number of cells for cell densities below approximately 1200 mm(-2), as well as previously published methods. CONCLUSIONS: The methods presented here provide a significant improvement over the state of the art, and make in vivo, automated assessment of corneal endothelium more accessible. The segmentation method proposed paves the way to many possible new morphometric parameters, which can quickly and precisely be determined from the segmented image.

Retinal damage extends beyond the border of the detached retina in fovea-on retinal detachment.

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.

AIROGS: Artificial Intelligence for Robust Glaucoma Screening Challenge.

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.

Frequency of Visual Fields Needed to Detect Glaucoma Progression: A Computer Simulation Using Linear Mixed Effects Model.

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.

Angiography of the retina and the choroid with phase-resolved OCT using interval-optimized backstitched B-scans.

In conventional phase-resolved OCT blood flow is detected from phase changes between successive A-scans. Especially in high-speed OCT systems this results in a short evaluation time interval. This method is therefore often unable to visualize complete vascular networks since low flow velocities cause insufficient phase changes. This problem was solved by comparing B-scans instead of successive A-scans to enlarge the time interval. In this paper a detailed phase-noise analysis of our OCT system is presented in order to calculate the optimal time intervals for visualization of the vasculature of the human retina and choroid. High-resolution images of the vasculature of a healthy volunteer taken with various time intervals are presented to confirm this analysis. The imaging was performed with a backstitched B-scan in which pairs of small repeated B-scans are stitched together to independently control the time interval and the imaged lateral field size. A time interval of ≥ 2.5 ms was found effective to image the retinal vasculature down to the capillary level. The higher flow velocities of the choroid allowed a time interval of 0.64 ms to reveal its dense vasculature. Finally we analyzed depth-resolved histograms of volumetric phase-difference data to assess changes in amount of blood flow with depth. This analysis indicated different flow regimes in the retina and the choroid.

Contrast-to-Noise Ratios to Evaluate the Detection of Glaucomatous Progression in the Superior and Inferior Hemiretina.

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.

Pointwise and Region-Wise Course of Visual Field Loss in Patients With Glaucoma.

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.

The long-term postoperative effect of the Baerveldt glaucoma drainage device and of a trabeculectomy on the corneal endothelium.

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/mm2 (mean ± SD) and 2463 ± 476 cells/mm2 , respectively. Central and peripheral ECD in the BGI group was 1813 ± 745 cells/mm2 and 1876 ± 764 cells/mm2 , 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.

Magnetic resonance imaging reveals possible cause of diplopia after Baerveldt glaucoma implantation.

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.

DenseUNets with feedback non-local attention for the segmentation of specular microscopy images of the corneal endothelium with guttae.

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.

Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid.

In optical frequency domain imaging (OFDI) the measurement of interference fringes is not exactly reproducible due to small instabilities in the swept-source laser, the interferometer and the data-acquisition hardware. The resulting variation in wavenumber sampling makes phase-resolved detection and the removal of fixed-pattern noise challenging in OFDI. In this paper this problem is solved by a new post-processing method in which interference fringes are resampled to the exact same wavenumber space using a simultaneously recorded calibration signal. This method is implemented in a high-speed (100 kHz) high-resolution (6.5 µm) OFDI system at 1-µm and is used for the removal of fixed-pattern noise artifacts and for phase-resolved blood flow measurements in the human choroid. The system performed close to the shot-noise limit (<1dB) with a sensitivity of 99.1 dB for a 1.7 mW sample arm power. Suppression of fixed-pattern noise artifacts is shown up to 39.0 dB which effectively removes all artifacts from the OFDI-images. The clinical potential of the system is shown by the detection of choroidal blood flow in a healthy volunteer and the detection of tissue reperfusion in a patient after a retinal pigment epithelium and choroid transplantation.