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A catalogue of neuronal cell types has often been called a 'parts list' of the brain1, and regarded as a prerequisite for understanding brain function2,3. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision4,5. Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi)6-10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with 'boundary types' that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development.

PURPOSE: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients. METHODS: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression. RESULTS: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648. CONCLUSIONS: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma. TRANSLATIONAL RELEVANCE: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.

PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None. SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24 to 2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean ± SD age at first test 12.0 ± 3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (P < .04). Mean ± SD patient-level reliability score was 51.7 ± 38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all P < .02), and number of prior VF tests was not (P = .56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.ResultsThere were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p

Background/aimsTo investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma.MethodsA longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics.ResultsFaster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively).ConclusionsSignificant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma.

AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

PurposeTo compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.MethodsForty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included.ResultsThirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27).ConclusionsIn this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

PurposeTo report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.DesignSingle-center, retrospective chart review.MethodsIn this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.ResultsThree out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.ConclusionsWe observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.Translational relevanceCaution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

PurposeTo assess the feasibility and performance of Vivid Vision Perimetry (VVP), a new virtual reality (VR)-based visual field platform.MethodsChildren 7-18 years of age with visual acuity of 20/80 or better undergoing Humphrey visual field (HVF) testing were recruited to perform VVP, a VR-based test that uses suprathreshold stimuli to test 54 field locations and calculates a fraction seen score. Pearson correlation coefficients were calculated to evaluate correlation between HVF mean sensitivity and VVP mean fraction seen scores. Participants were surveyed regarding their experience.ResultsA total of 37 eyes of 23 participants (average age, 12.9 ± 3.1 years; 48% female) were included. All participants successfully completed VVP testing. Diagnoses included glaucoma (12), glaucoma suspect (7), steroid-induced ocular hypertension (3), and craniopharyngioma (1). Sixteen participants had prior HVF experience, and none had prior VVP experience, although 7 had previously used VR. Of the 23 HVF tests performed, 9 (39%) were unreliable due to fixation losses, false positives, or false negatives. Similarly, 35% of VVP tests were unreliable (as defined by accuracy of blind spot detection). Excluding unreliable HVF tests, the correlation between HVF average mean sensitivity and VVP mean fraction seen score was 0.48 (P = 0.02; 95% CI, 0.09-0.74). When asked about preference for the VVP or HVF examination, all participants favored the VVP, and 70% were "very satisfied" with VVP.ConclusionsIn our cohort of 23 pediatric subjects, VVP proved to be a clinically feasible VR-based visual field testing, which was uniformly preferred over HVF.

This study aimed to investigate the impact of eccentric-vision training on population receptive field (pRF) estimates to provide insights into brain plasticity processes driven by practice. Fifteen participants underwent functional magnetic resonance imaging (fMRI) measurements before and after behavioral training on a visual crowding task, where the relative orientation of the opening (gap position: up/down, left/right) in a Landolt C optotype had to be discriminated in the presence of flanking ring stimuli. Drifting checkerboard bar stimuli were used for pRF size estimation in multiple regions of interest (ROIs): dorsal-V1 (dV1), dorsal-V2 (dV2), ventral-V1 (vV1), and ventral-V2 (vV2), including the visual cortex region corresponding to the trained retinal location. pRF estimates in V1 and V2 were obtained along eccentricities from 0.5° to 9°. Statistical analyses revealed a significant decrease of the crowding anisotropy index (p = 0.009) after training, indicating improvement on crowding task performance following training. Notably, pRF sizes at and near the trained location decreased significantly (p = 0.005). Dorsal and ventral V2 exhibited significant pRF size reductions, especially at eccentricities where the training stimuli were presented (p < 0.001). In contrast, no significant changes in pRF estimates were found in either vV1 (p = 0.181) or dV1 (p = 0.055) voxels. These findings suggest that practice on a crowding task can lead to a reduction of pRF sizes in trained visual cortex, particularly in V2, highlighting the plasticity and adaptability of the adult visual system induced by prolonged training.

Background/aimsTo assess the long-term variability of macular optical coherence tomography (OCT)/OCT angiography (OCTA) and visual field (VF) parameters.MethodsHealthy and glaucoma eyes with ≥1-year follow-up were included. 24-2 VF and macular OCT/OCTA parameters, including VF mean deviation (MD), whole-image vessel density (wiVD) and ganglion cell complex thickness (wiGCC) were analysed. Intraclass correlation coefficient (ICC), root mean squared error (RMSE), within-subject test-retest SD (Sw) and test-retest variability were calculated for stable eye cohort (max follow-up=1.5 years). Rates of change and RMSE were evaluated in the extended cohort including all eyes (unlimited follow-up).ResultsFrom a total of 230 eyes (150 participants; age=67.7 years), 86 eyes (37%, 62 participants) were stable. In stable eyes, OCT parameters showed the highest mean (95%) ICC (wiGCC=0.99 (0.99, 0.99)), followed by VF (VF MD=0.91 (0.88, 0.93)) and OCTA (wiVD=0.82 (0.75, 0.87)). RMSE and Sw for VF MD were 0.92 dB and 0.81 dB, respectively, for wiVD were 1.64% and 1.48%, respectively, and for wiGCC, 0.91 µm and 0.78 µm, respectively. The long-term test-rest variability of VF MD, wiVD and wiGCC was 2.2 dB, 4.1% and 2.2 µm, respectively. In the extended cohort (mean follow-up=3.0 years), all parameters had significant rates of change (p

Background/aimsTo evaluate the association of macular vessel density (VD) and ganglion cell complex (GCC) thickness with 10-2 central visual field (CVF) progression in glaucoma.MethodsIn this retrospective cohort study, patients with glaucoma from Diagnostic Innovation in Glaucoma Study with≥five 10-2 visual field (VF) tests and 3-year follow-up before optical coherence tomography (OCT) and OCT angiography (OCTA) imaging were included. Whole-image GCC thickness (wiGCC) and superficial VD (wiVD) were obtained from 6*6 macula scans. The association of wiVD and wiGCC with past rate of 10-2 VF mean deviation worsening, and with past CVF progression (defined using clustered linear regression criteria) was evaluated using linear mixed models after adjusting for confounders.ResultsFrom 238 eyes (141 patients), 25 eyes (11%) of 16 patients were CVF progressors. In the multivariable analysis of the association between OCT/OCTA parameters and past rate of 10-2 CVF worsening, lower wiVD (β=-0.04 (-0.05, -0.02); p

PURPOSE: Predict central 10° global and local visual field (VF) measurements from macular optical coherence tomography (OCT) volume scans with deep learning (DL). METHODS: This study included 1121 OCT volume scans and 10-2 VFs from 289 eyes (257 patients). Macular scans were used to estimate 10-2 VF mean deviation (MD), threshold sensitivities (TS), and total deviation (TD) values at 68 locations. A three-dimensional (3D) convolutional neural network based on the 3D DenseNet121 architecture was used for prediction. We compared DL predictions to those from baseline linear models. We carried out 10-fold stratified cross-validation to optimize generalizability. The performance of the DL and baseline models was compared based on correlations between ground truth and predicted VF measures and mean absolute error (MAE; ground truth - predicted values). RESULTS: Average (SD) MD was -9.3 (7.7) dB. Average (SD) correlations between predicted and ground truth MD and MD MAE were 0.74 (0.09) and 3.5 (0.4) dB, respectively. Estimation accuracy deteriorated with worsening MD. Average (SD) Pearson correlations between predicted and ground truth TS and MAEs for DL and baseline model were 0.71 (0.05) and 0.52 (0.05) (P < 0.001) and 6.5 (0.6) and 7.5 (0.5) dB (P < 0.001), respectively. For TD, correlation (SD) and MAE (SD) for DL and baseline models were 0.69 (0.02) and 0.48 (0.05) (P < 0.001) and 6.1 (0.5) and 7.8 (0.5) dB (P < 0.001), respectively. CONCLUSIONS: Macular OCT volume scans can be used to predict global central VF parameters with clinically relevant accuracy. TRANSLATIONAL RELEVANCE: Macular OCT imaging may be used to confirm and supplement central VF findings using deep learning.

ObjectivesTo investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma.DesignA retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES).SettingThree tertiary glaucoma centres in the USA.Participants825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies.Outcome measuresDevelopment of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time.ResultsVF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years).ConclusionAlcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people.Trial registration numberNCT00221897 and NCT00221923.

Background/aimsTo investigate the factors associated with choroidal microvasculature drop-out (MvD) enlargement detected by optical coherence tomography angiography (OCT-A) in glaucomatous eyes.MethodsNinety-one eyes of 68 primary open-angle glaucoma patients were enrolled. Only eyes with a minimum of four good quality OCT-A and OCT scans of the optic nerve head acquired at least and with a minimum of 2 years follow-up were included. Area and angular circumference of MvD were analysed on en face images. Univariable and multivariable mixed effects models were constructed to identify the factors contributing to MvD area and angular circumference change over time.ResultsPeripapillary MvD was detected in 53 (58.2%) eyes at baseline and in an additional 17 (18.6%) eyes during follow-up, whereas MvD was not detected in 21 (23.0 %) eyes during the entire follow-up period. In multivariable analysis, worse baseline visual field (VF) mean deviation (MD) (ß=0.27, 95% CI 0.10 to 0.44, p=0.002), greater intraocular pressure (IOP) fluctuations (ß=0.86, 95% CI 0.24 to 1.48, p=0.007), higher peak IOP (ß=0.17, 95% CI -0.01 to 0.35, p=0.067) and greater number of IOP lowering medications (ß=1.36, 95% CI 0.67 to 2.05, p

Animal sensory systems are tightly adapted to the demands of their environment. In the visual domain, research has shown that many species have circuits and systems that exploit statistical regularities in natural visual signals. The zebrafish is a popular model animal in visual neuroscience, but relatively little quantitative data is available about the visual properties of the aquatic habitats where zebrafish reside, as compared to terrestrial environments. Improving our understanding of the visual demands of the aquatic habitats of zebrafish can enhance the insights about sensory neuroscience yielded by this model system. We analyzed a video dataset of zebrafish habitats captured by a stationary camera and compared this dataset to videos of terrestrial scenes in the same geographic area. Our analysis of the spatiotemporal structure in these videos suggests that zebrafish habitats are characterized by low visual contrast and strong motion when compared to terrestrial environments. Similar to terrestrial environments, zebrafish habitats tended to be dominated by dark contrasts, particularly in the lower visual field. We discuss how these properties of the visual environment can inform the study of zebrafish visual behavior and neural processing and, by extension, can inform our understanding of the vertebrate brain.

Fixation constraints in visual tasks are ubiquitous in visual and cognitive neuroscience. Despite its widespread use, fixation requires trained subjects, is limited by the accuracy of fixational eye movements, and ignores the role of eye movements in shaping visual input. To overcome these limitations, we developed a suite of hardware and software tools to study vision during natural behavior in untrained subjects. We measured visual receptive fields and tuning properties from multiple cortical areas of marmoset monkeys who freely viewed full-field noise stimuli. The resulting receptive fields and tuning curves from primary visual cortex (V1) and area MT match reported selectivity from the literature which was measured using conventional approaches. We then combined free viewing with high-resolution eye tracking to make the first detailed 2D spatiotemporal measurements of foveal receptive fields in V1. These findings demonstrate the power of free viewing to characterize neural responses in untrained animals while simultaneously studying the dynamics of natural behavior.

BACKGROUND/OBJECTIVES: Tablet-based perimetry could be used to test for glaucomatous visual field defects in settings without easy access to perimeters, although few studies have assessed diagnostic accuracy of tablet-based tests. The goal of this study was to determine the diagnostic accuracy of iPad perimetry using the visualFields Easy application. SUBJECTS/METHODS: This was a prospective, cross-sectional study of patients undergoing their first Humphrey Field Analyser (HFA) visual field test at a glaucoma clinic in India. Participants underwent 24-2 SITA Standard HFA testing and iPad-based perimetry with the visualFields Easy application. Reference standards for both visual field loss and suspected glaucoma were determined by ophthalmologist review of HFA results and optic disc photographs. Receiver operating characteristic curves were constructed to assess diagnostic accuracy at various test thresholds. RESULTS: 203 eyes from 115 participants were included, with 82 eyes classified as moderate or worse glaucoma. iPad perimetry had an area under the receiver operating characteristic (AUROC) curve of 0.64 (95% CI 0.57 to 0.71) for detection of any visual field defect relative to HFA and an AUROC of 0.68 (0.59 to 0.76) for detection of moderate or worse glaucoma relative to ophthalmologist examination. At a set specificity of 90%, the sensitivity of iPad perimetry for detection of moderate or worse glaucoma was 35% (22-48%). CONCLUSIONS: iPad perimetry using the visualFields Easy application had inadequate diagnostic accuracy to be used as a screening tool for glaucoma in this South Indian population.

PurposeTo evaluate disease progression using static perimetry (SP) in patients with USH2A-related retinal degeneration, including Usher syndrome type 2 (USH2) and nonsyndromic autosomal recessive retinitis pigmentosa.DesignProspective, observational cohort study.MethodsA total of 102 patients with biallelic disease-causing sequence variants in USH2A with baseline best-corrected visual acuity (BCVA) letter score ≥54 were recruited from 16 clinical sites in Europe and North America. SP, BCVA, full-field stimulus thresholds, spectral domain optical coherence tomography macular scans, and fundus-guided mesopic microperimetry were performed at baseline and annually. The main outcome measures were total hill of vision (VTOT), hill of vision in the central 30° (V30), VTOT minus V30 (VPERIPH), and mean sensitivity.ResultsThe average decline (95% CI) was 2.05 (1.40, 2.70) decibel-steradian (dB-sr)/y for VTOT, 0.48 (0.32, 0.65) dB-sr/y for V30, 1.53 (0.97, 2.08) dB-sr/y for VPERIPH, and 0.55 (0.40, 0.71) dB/y for mean sensitivity. Average percentage decline per year was 8.3 (5.5, 11.1) for VTOT, 5.2 (3.0, 7.4) for V30, 16.0 (9.5, 22.0) for VPERIPH, and 5.1 (3.5, 6.7) for mean sensitivity. Changes from baseline to year 2 in all SP measures were highly correlated (r's ranging from 0.52 [V30 vs VPERIPH] to 0.98 [VTOT vs VPERIPH]).ConclusionsQuantitative measures of SP declined significantly over 2 years in USH2A-related retinal degeneration. The annual percentage rate of change was greatest for VTOT and VPERIPH, whereas V30 and mean sensitivity changed least, reflecting earlier and more severe peripheral degeneration compared with central loss.

PurposeTo determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care.DesignObservational study.ParticipantsSix hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years.MethodsThis study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye.Main outcome measuresPrevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes).ResultsBased on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively.ConclusionsThis study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Background/aimsTo assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes.MethodsEighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates.ResultsICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities.ConclusionsOCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change.Trial registration numberNCT00221897.

A left visual field (LVF) bias in perceptual judgments, response speed, and discrimination accuracy has been reported in humans. Cognitive factors, such as visual spatial attention, are known to modulate or even eliminate this bias. We investigated this problem by recording pupillometry together with functional magnetic resonance imaging (fMRI) in a cued visual spatial attention task. We observed that (i) the pupil was significantly more dilated following attend-right than attend-left cues, (ii) the task performance (e.g. reaction time [RT]) did not differ between attend-left and attend-right trials, and (iii) the difference in cue-related pupil dilation between attend-left and attend-right trials was inversely related to the corresponding difference in RT. Neuroscientically, correlating the difference in cue-related pupil dilation with the corresponding cue-related fMRI difference yielded activations primarily in the right hemisphere, including the right intraparietal sulcus and the right ventrolateral prefrontal cortex. These results suggest that (i) there is an asymmetry in visual spatial attention control, with the rightward attention control being more effortful than the leftward attention control, (ii) this asymmetry underlies the reduction or the elimination of the LVF bias, and (iii) the components of the attentional control networks in the right hemisphere are likely part of the neural substrate of the observed asymmetry in attentional control.

PrcisWe updated a clinical decision support tool integrating predicted visual field (VF) metrics from an artificial intelligence model and assessed clinician perceptions of the predicted VF metric in this usability study.PurposeTo evaluate clinician perceptions of a prototyped clinical decision support (CDS) tool that integrates visual field (VF) metric predictions from artificial intelligence (AI) models.MethodsTen ophthalmologists and optometrists from the University of California San Diego participated in 6 cases from 6 patients, consisting of 11 eyes, uploaded to a CDS tool ("GLANCE", designed to help clinicians "at a glance"). For each case, clinicians answered questions about management recommendations and attitudes towards GLANCE, particularly regarding the utility and trustworthiness of the AI-predicted VF metrics and willingness to decrease VF testing frequency.Main outcomes and measuresMean counts of management recommendations and mean Likert scale scores were calculated to assess overall management trends and attitudes towards the CDS tool for each case. In addition, system usability scale scores were calculated.ResultsThe mean Likert scores for trust in and utility of the predicted VF metric and clinician willingness to decrease VF testing frequency were 3.27, 3.42, and 2.64, respectively (1=strongly disagree, 5=strongly agree). When stratified by glaucoma severity, all mean Likert scores decreased as severity increased. The system usability scale score across all responders was 66.1±16.0 (43rd percentile).ConclusionsA CDS tool can be designed to present AI model outputs in a useful, trustworthy manner that clinicians are generally willing to integrate into their clinical decision-making. Future work is needed to understand how to best develop explainable and trustworthy CDS tools integrating AI before clinical deployment.

Face mask-wearing practices and their impact on the visual field bear particular importance in the coronavirus disease 2019 (COVID-19) pandemic era. This case series examines 10 participants with no history of ocular impairment or visual field defects who underwent age-corrected visual field testing in both eyes with different types of face masks. Wearing duckbill N95 masks was consistently associated with increased accuracy errors in the inferior altitudinal visual field when compared to wearing surgical masks or no masks. These findings support public health guidance that has previously attributed the risks of falls and accidents to face mask wearing.

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3-5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly's directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

This study compared between TEMPO, a new binocular perimeter, with the Humphrey Field Analyzer (HFA). Patients were tested with both TEMPO 24-2 Ambient Interactive Zippy Estimated by Sequential Testing (AIZE)-Rapid and HFA 24-2 Swedish Interactive Threshold Algorithm (SITA)-Fast in a randomized sequence on the same day. Using a mixed-effects model, visual field (VF) parameters and reliability indices were compared. Retinal nerve fiber layer (RNFL) thickness was measured using Cirrus optical coherence tomography (OCT), and coefficient of determinations for VF and OCT parameters were calculated and compared using Akaike information criteria. 740 eyes (including 68 healthy, 262 glaucoma suspects, and 410 glaucoma) of 370 participants were evaluated. No significant differences were seen in mean deviation and visual field index between the two perimeters (P > 0.05). A stronger association between VF mean sensitivity (dB or 1/L) and circumpapillary RNFL was found for TEMPO (adjusted R2 = 0.25; Akaike information criteria [AIC] = 5235.5 for dB, and adjusted R2 = 0.29; AIC = 5200.8 for 1/L, respectively) compared to HFA (adjusted R2 = 0.22; AIC = 5263.9 for dB, and adjusted R2 = 0.22; AIC = 5262.7 for 1/L, respectively). Measurement time was faster for TEMPO compared to HFA (261 s vs. 429 s, P

PurposeTo investigate the relationship of longitudinal changes in macular vessel density (VD) from OCT angiography and in ganglion cell complex (GCC) from OCT with central visual field (VF) in eyes with early glaucoma.DesignObservational cohort.ParticipantsA total of 95 eyes, 37 preperimetric and 58 with early glaucoma (24-2 VF mean deviation [MD] ≥ -6 decibels), with an average follow-up of 3.8 years and 5.3 visits, were included.MethodsWhole-image VD (wiVD) and whole-image GCC (wiGCC) and parafoveal scans, as well as localized regions of interest (LROIs), hemiretinae of whole images, and superior, inferior, temporal, and nasal sectors of parafoveal maps, were matched with central VF locations. Age-adjusted rates of change of VD, GCC, mean sensitivity of VF locations, and 10-2 VF MD were calculated using linear mixed-effect models. Normalized rates of change were calculated for comparison of change rates in wiVD and wiGCC.Main outcome measuresStructure-function (SF) correlations of VD and GCC with central VF measurement change rates and comparison of different correlations of SF relationships after bootstrapping the difference of the correlation coefficients.ResultsVessel density loss and GCC thinning demonstrated significant correlations with central VF damage, globally and with most LROIs. The SF correlation (r, 95% confidence interval [CI]) between wiVD and 10-2 VF MD change rates was 0.42 [0.24, 0.58], whereas it was 0.27 [0.08, 0.45] between wiGCC and 10-2 VF MD changes rates (all P < 0.05). In contrast to GCC thinning, VD loss in the parafoveal sectors demonstrated significant correlations with central VF damage in inferior and temporal sectors. Differences in the relationship of SF with central VF damage were not significant between VD loss and GCC thinning. The mean (95% CI) normalized change rates of wiVD (-7.40 [-7.71 to 7.09] %/year) was faster than that of wiGCC (-2.39 [-2.94 to 1.84] %/year) (P < 0.05).ConclusionsRates of VD loss and GCC thinning are associated with central VF loss over time. Assessment of both macular VD and GCC thickness should be considered for evaluation of glaucoma progression.

PurposeTo investigate the effect of smoking on rates of progressive visual field (VF) damage over time in glaucoma.DesignRetrospective cohort study.ParticipantsFive hundred eleven eyes of 354 patients with glaucoma followed up from multicenter glaucoma registries.MethodsIn this longitudinal study, 354 patients with primary open-angle glaucoma with a minimum of 3 years of follow-up and 5 VF tests were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Univariate and multivariate linear mixed models were used to investigate the effects of smoking on rates of 24-2 VF mean deviation loss. Visual field progression was defined using pointwise linear and significant negative VF mean deviation loss. Logistic regression was used to identify baseline factors and whether different levels of smoking intensity were associated with VF progression. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between smoker and never smoker groups.Main outcome measuresVisual field progression.ResultsFive hundred eleven eyes of 354 patients were included over the median follow-up of 12.5 years. Median baseline age was 64.8 years. Of the 354 patients, 124 (35%) were Black, and 149 (42.1%) and 168 (59.8%) had reported a history of smoking or alcohol consumption, respectively. In a multivariate model, higher smoking intensity was associated with faster VF loss (coefficient, -0.05 decibels (dB)/year per 10 pack-years; 95% confidence interval [CI], -0.08 to -0.01 dB/year per 10 pack-years; P = 0.010). Developing VF progression in eyes of heavy smokers (≥ 20 pack-years) was 2.2 times more than in eyes of patients without smoking history (odds ratio, 2.21; 95% CI, 1.02-4.76; P = 0.044). Statistically significant differences were found between heavy smokers (≥ 20 pack-years) and never smokers by Kaplan-Meier analysis (P = 0.011, log-rank test).ConclusionsHeavy smokers are more likely to sustain VF loss in eyes with glaucoma. The prospective longitudinal design of this study supports the hypothesis that levels of smoking may be a significant predictor for glaucoma progression. Additionally, this information can be used for clinically relevant tobacco prevention and intervention messages.

PrcisThe earlier a person quits smoking the more likely is the optic nerve be spared from damage.PurposeTo investigate the effect of smoking cessation on visual field (VF) progression in glaucoma.MethodsPrimary open angle glaucoma patients with a minimum of 3 years follow-up and 5 VFs were included. Linear mixed models were used to investigate the effects of smoking on the rates of 24-2 VF mean deviation loss after adjusting for confounding factors. Cox proportional hazard regression was used to identify whether different levels of smoking intensity were associated with VF progression with respect to different duration of quitting.ResultsFive hundred eleven eyes of 354 patients were included over the mean follow-up of 12.4 years. Mean baseline age (95% confidence interval) was 62.3 (61.2, 63.4) years. One hundred forty nine (42.1%) patients were smokers. In a multivariable model, smoking intensity was associated with faster VF loss (-0.06, 95% confidence interval (-0.10, -0.01) dB/year per 10 pack-years, P =0.01) among smokers. Heavy smokers (≥20 pack-years) who had quit ˂25 years prior had significantly greater odds of VF progression compared with never smokers (odds ratio=2.49 (1.01, 6.08); P =0.046). There was no significant difference in odds of VF progression in heavy smokers who had quit smoking more than 25 years compared with never smokers ( P =0.43). A significantly higher proportion of VF progression was found in heavy smokers who quit < 25 years compared with heavy smokers who quit ≥25 years by Kaplan-Meier analysis ( P =

PrcisBoth macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma.PurposeThe purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes.MethodsMacular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD)

PrcisDecreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity.PurposeTo investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG.MethodsIn this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density.ResultsA total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041).ConclusionsSmoking intensity is associated with reduced optic nerve vessel density in glaucoma.

PurposeTo evaluate the association between rates of choroidal microvasculature dropout (MvD) change and rates of circumpapillary retinal nerve fiber layer (cpRNFL) loss in primary open-angle glaucoma (POAG) eyes.DesignCohort study from clinical trial data.MethodsA total of 91 eyes of 68 POAG patients with and without localized MvD at baseline with at least 4 visits and 2 years of follow-up with optical coherence tomography angiography (OCT-A) and OCT scans were included. Area and angular circumference of MvD were evaluated on OCT-A en face and B-scan choroidal vessel density images during the follow-up period. Joint longitudinal mixed effects models were used to estimate the rates of change in MvD area or angular circumference and RNFL thickness. Univariable and multivariable regressions were completed to identify the factors contributing to cpRNFL thinning.ResultsMvD was identified in 53 eyes (58.2%) at baseline. Seventeen eyes (18.6%) that did not show MvD at baseline developed it over the follow-up period. Over a mean follow-up of 4.0 years, the mean rates of change in MvD area and angular circumference (95% CI) were 0.05 (0.04, 0.06) mm2 per year and 13.2° (10.7°, 15.8°) per year, respectively. In multivariable models, the rate of cpRNFL thinning was significantly associated with the rates of change in MvD area and angular circumference (P = .008 and P = .009, respectively).ConclusionsRates of MvD area and angular circumference change over time were associated with concurrent rates of cpRNFL loss in POAG eyes.

PurposeTo evaluate the role of corneal hysteresis (CH) as a risk factor of central visual field (VF) progression in a cohort of glaucoma suspect and glaucoma patients.DesignProspective cohort study.MethodsTwo hundred forty-eight eyes of 143 subjects who were followed for an average of 4.8 years with a minimum of 5 visits with 10-2 and 24-2 VF tests were included. Univariable and multivariable linear mixed-effects models were used to identify characteristics associated with the rate of change over time in 10-2 and 24-2 mean deviation (MD). Mixed-effects logistic regression was used to evaluate characteristics associated with an increased likelihood of event-based 10-2 VF progression based on the clustered pointwise linear regression criterion.ResultsCH was significantly associated with 10-2 and 24-2 VF progression in the univariable trend-based analysis. In multivariable trend-based analyses, lower CH was associated with a faster rate of decline in 10-2 MD (0.07 dB/y per 1 mm Hg, P < .001) but not with 24-2 MD (P = .490). In multivariable event-based analysis, lower CH was associated with an increased likelihood of 10-2 VF progression (odds ratio = 1.35 per 1 mm Hg lower, P = .025). Similar results were found in eyes with early glaucomatous damage at the baseline (baseline: 24-2 MD ≥ -6 dB).ConclusionsLower CH was associated with a statistically significant, but relatively small, increased risk of central VF progression on the 10-2 test grid. Given the substantial influence of central VF impairment on the quality of life, clinicians should consider using CH to assess the risk of progression in patients with primary open-angle glaucoma including those with early disease.

PurposeTo develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma.DesignSecondary analysis of VF data from a longitudinal cohort study.ParticipantsOne thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals).MethodsAll participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined.Main outcome measuresThe classification of VF in highly myopic eyes and its associated risk factors.ResultsWe found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were > 89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P < 0.001] and 1.06 [95% CI, 1.04-1.10; P < 0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P < 0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036).ConclusionsWe propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies.

The mouse visual cortex contains interconnected higher visual areas, but their functional specializations are unclear. Here, we used a data-driven approach to examine the representations of complex visual stimuli by L2/3 neurons across mouse higher visual areas, measured using large-field-of-view two-photon calcium imaging. Using specialized stimuli, we found higher fidelity representations of texture in area LM, compared to area AL. Complementarily, we found higher fidelity representations of motion in area AL, compared to area LM. We also observed this segregation of information in response to naturalistic videos. Finally, we explored how receptive field models of visual cortical neurons could produce the segregated representations of texture and motion we observed. These selective representations could aid in behaviors such as visually guided navigation.

PurposeTo compare the rates of visual field (VF) progression between individuals of Black and White race and to investigate whether treatment effects may help explain differences previously reported between racial groups.DesignMulticenter prospective observational cohort study.MethodsParticipants were patients in referral tertiary care glaucoma clinics with open angle glaucoma. Eyes were excluded who had

PurposeTo compare measurements of global and regional circumpapillary capillary density (cpCD) with retinal nerve fiber layer (RNFL) thickness and characterize their relationship with visual function in early primary open-angle glaucoma (POAG).DesignCross-sectional study.ParticipantsEighty healthy eyes, 64 preperimetric eyes, and 184 mild POAG eyes from the Diagnostic Innovations in Glaucoma Study.MethodsGlobal and regional RNFL thickness and cpCD measurements were obtained using OCT and OCT angiography (OCTA). For direct comparison at the individual and diagnostic group level, RNFL thickness and capillary density values were converted to a normalized relative loss scale.Main outcome measuresRetinal nerve fiber layer thickness and cpCD normalized loss at the individual level and diagnostic group. Global and regional areas under the receiver operating characteristic curve (AUROC) for RNFL thickness and cpCD to detect preperimetric glaucoma and glaucoma, R2 for the strength of associations between RNFL thickness function and capillary density function in diagnostic groups.ResultsBoth global and regional RNFL thickness and cpCD decreased progressively with increasing glaucoma severity (P < 0.05, except for temporal RNFL thickness). Global and regional cpCD relative loss values were higher than those of RNFL thickness (P < 0.05) in preperimetric glaucoma (except for the superonasal region) and glaucoma (except for the inferonasal and superonasal regions) eyes. Race, intraocular pressure (IOP), and cpCD were associated with greater cpCD than RNFL thickness loss in early glaucoma at the individual level (P < 0.05). Global measurements of capillary density (whole image capillary density and cpCD) had higher diagnostic accuracies than RNFL thickness in detecting preperimetric glaucoma and glaucoma (P < 0.05; except for cpCD/RNFL thickness comparison in glaucoma [P = 0.059]). Visual function was significantly associated with RNFL thickness and cpCD globally and in all regions (P < 0.05, except for temporal RNFL thickness-function association [P = 0.070]).ConclusionsAssociations between capillary density and visual function were found in the regions known to be at highest risk for damage in preperimetric glaucoma eyes and all regions of mild glaucoma eyes. In early glaucoma, capillary density loss was more pronounced than RNFL thickness loss. Individual characteristics influence the relative magnitudes of capillary density loss compared with RNFL thickness loss. Retinal nerve fiber layer thickness and microvascular assessments are complementary and yield valuable information for the detection of early damages seen in POAG.

PurposeVisual field (VF) results that show more test points outside normal limits on the pattern deviation map than on the total deviation map have been assumed to be evidence of unreliable VF results. We propose the term pattern reversal to describe this VF finding and explore its association with paracentral loss.DesignRetrospective cohort and case-control studies.ParticipantsGlaucoma and glaucoma suspect patients who completed VF testing in Veteran's Affairs ophthalmology or optometry clinics.MethodsIn the cohort study, VF results were included that demonstrated pattern reversal. The area of pattern reversal was categorized as peripheral, paracentral, or mixed (both peripheral and paracentral). In the case-control study, a group of patients with paracentral loss confirmed on 10-2 VF tests were compared with a control group whose VF results were without paracentral loss.Main outcome measuresIn the cohort study, the calculated false-positive (FP) error rates were compared among groups categorized by area of pattern reversal. In the case-control study, the rates of pattern reversal were compared between patients with and without paracentral loss.ResultsTwo hundred seventeen eyes of 145 patients were included in the cohort study. Visual field results with pattern reversal and mixed loss had significantly higher FP rates compared with those with paracentral or peripheral loss only (16.25% vs. 6.26% and 8.15%, respectively; P < 0.001). Fifty-five eyes of 41 patients were included in the case group and 55 eyes of 41 patients were included in the control group. Patients with paracentral loss were more likely to have history of pattern reversal compared with those without paracentral loss (58.2% vs. 29.1%; P = 0.004). Twelve eyes with paracentral loss had 24-2 VF results that showed defects on the pattern deviation map, but not on the total deviation map.ConclusionsPattern reversal may be associated with paracentral VF loss and is not always associated with elevated FP rates.

PurposeTo determine the predictors of Bruch membrane opening (BMO) location accuracy and the visibility of the BMO location in glaucoma and healthy individuals with and without axial high myopia.DesignCross-sectional study.MethodsHealthy eyes and eyes with glaucoma from an American study and a Korean clinic population were classified into 2 groups: those with no axial high myopia (axial length [AL]

PurposeTo evaluate the association of macular superficial vessel density (SVD) and projection-resolved deep vessel density (DVD) with past visual field (VF) progression in patients with primary open-angle glaucoma.DesignRetrospective cohort.MethodsIn this longitudinal study, 208 eyes of 147 patients with glaucoma from the Diagnostics Innovations in Glaucoma Study were included. Eligible participants were required to have at least five 24-2 VF tests over a minimum follow-up period of 3 years before macular optical coherence tomography angiography imaging. VF progression was defined based on both event-based pointwise linear regression and trend-based methods. The association of macular SVD and DVD with the probability and rate of past VF progression was evaluated using a linear mixed effects model.ResultsFifty-two (25%) eyes had VF progression based on the pointwise linear regression based criterion at the end of a mean ± standard deviation follow-up duration of 6.9 ± 1.2 years. In the event-based multivariable analysis, a lower baseline SVD was associated with a higher likelihood of past VF progression (odds ratio per 1% lower. 1.28; 95% confidence interval, 1.02-1.59). Similarly, in the trend-based multivariable analysis, lower macular SVD was associated with a faster past rate of mean deviation decline (coefficient = -0.03 dB/year; 95% confidence interval, -0.04 to -0.01). Event-based and trend-based analyses found no significant associations for macular DVD with the likelihood/rate of past VF progression (P > .05).ConclusionsLower macular SVD, and not DVD, was associated with a higher probability of past VF progression. Macular optical coherence tomography angiography imaging shows promise for identifying eyes at risk of VF progression in patients with glaucoma.

PrcisTracking failure frequency (TFF) increases with dry eye symptom severity and in the left eye.PurposeSymptoms of dry eye disease are commonly encountered in glaucoma patients and can be exacerbated by topical glaucoma medications. Dry eye disease may influence the reliability of visual field (VF) tests and impact the accurate interpretation of the results.Patients and methodsPatients at the Veterans Administration Medical Center San Diego completed the 5-item Dry Eye Questionnaire before VF testing between December 2018 and February 2019. VF reliability metrics were recorded for each patient. Standard reliability metrics included fixation losses, false positive, and false negative rates. Gaze tracking (GT) metrics included percent of stimuli with gaze deviations between 1 and 2 degrees, 3 and 5 degrees, 6 degrees or greater, and percent of stimuli with tracking failure (TFF). The use of glaucoma medications and artificial tears was also recorded.ResultsA total of 494 patients completed the 5-item Dry Eye Questionnaire and VF testing. There was no association between dry eye symptom severity and standard reliability metrics or most GT metrics. However, TFF increased as dry eye symptom severity increased (P=0.015). TFF was also greater in the left eye, which was tested second (P=0.012); no other reliability metrics were related to laterality. Patients were more likely to use artificial tears with increased dry eye symptom severity (P

PurposeTo compare convolutional neural network (CNN) analysis of en face vessel density images to gradient boosting classifier (GBC) analysis of instrument-provided, feature-based optical coherence tomography angiography (OCTA) vessel density measurements and OCT retinal nerve fiber layer (RNFL) thickness measurements for classifying healthy and glaucomatous eyes.DesignComparison of diagnostic approaches.MethodsA total of 130 eyes of 80 healthy individuals and 275 eyes of 185 glaucoma patients with optic nerve head (ONH) OCTA and OCT imaging were included. Classification performance of a VGG16 CNN trained and tested on entire en face 4.5 × 4.5-mm radial peripapillary capillary OCTA ONH images was compared to the performance of separate GBC models trained and tested on standard OCTA and OCT measurements. Five-fold cross-validation was used to test predictions for CNNs and GBCs. Areas under the precision recall curves (AUPRC) were calculated to control for training/test set size imbalance and were compared.ResultsAdjusted AUPRCs for GBC models were 0.89 (95% CI = 0.82, 0.92) for whole image vessel density GBC, 0.89 (0.83, 0.92) for whole image capillary density GBC, 0.91 (0.88, 0.93) for combined whole image vessel and whole image capillary density GBC, and 0.93 (0.91, 095) for RNFL thickness GBC. The adjusted AUPRC using CNN analysis of en face vessel density images was 0.97 (0.95, 0.99) resulting in significantly improved classification compared to GBC OCTA-based results and GBC OCT-based results (P ≤ 0.01 for all comparisons).ConclusionDeep learning en face image analysis improves on feature-based GBC models for classifying healthy and glaucoma eyes.

PurposeTrend analysis of visual field (VF) global indices may underestimate the rate of progression in severe glaucoma because of the influence of test points without detectable sensitivity. To test this hypothesis, we compared the rates of change of VF global indices with and without exclusion of undetectable points at various disease stages.Materials and methodsSix hundred and forty-eight eyes of 366 glaucoma patients with 8 or more reliable 30-2 standard automated perimetry over more than 2 years were enrolled. We calculated targeted mean total deviation (TMTD) by averaging total deviation except points which were consistently undetectable in 3 baseline tests. Eyes were classified as early (≥-6 dB), moderate (-6 dB to -12 dB), advanced (-12 dB to -20 dB), and severe (

PurposeTo measure visual fields using two-color dark-adapted chromatic perimetry in a subset of participants in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A), a study of USH2A-mediated syndromic (USH2) and autosomal recessive nonsyndromic retinitis pigmentosa, determine percentage retaining rod function, and explore relationships between dark-adapted visual fields (DAVF) and rod function from ERG and full-field stimulus thresholds (FST).MethodsFull-field rod mean sensitivity, number of rod loci, maximum sensitivity, DAVF full-field hill of vision (DAVF VTOT), and 30° hill of vision (DAVF V30) were measured in one eye for DAVF ancillary study participants (n = 49). Loci where cyan relative to red sensitivity was more than 5 dB on dark-adapted chromatic perimetry were considered rod mediated. Correlation coefficients between the DAVF measures and standard clinical measures were estimated, as were kappa statistics (κ) for agreement between DAVF and other measures of rod function.ResultsOf 49 participants tested with DAVF, 38 (78%) had evidence of rod function, whereas 15 (31%) had measurable rod ERGs. DAVF maximum sensitivity was highly correlated with FST white thresholds (r = -0.80; P < .001). Although not statistically significant, the number of rod loci and DAVF VTOT were lower in eyes with longer disease duration by 0.82 (95% confidence interval, -1.76, 0.12) loci/year and 0.59 (95% confidence interval, -1.82, 0.64) dB-steradians/year, respectively.ConclusionsRod-mediated function on FST and DAVF is present in many patients with symptomatic USH2A-related retinal degeneration, including some without measurable rod ERGs. RUSH2A longitudinal data will determine how these measures change with disease progression and whether they are useful for longitudinal studies in inherited retinal degenerations.

PurposeTo characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON).DesignProspective, longitudinal study.ParticipantsEight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years.MethodsOCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm1 GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model.Main outcome measuresChange rates of macula GCC thickness and superficial vessel density.ResultsSignificant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 μm/year; P = 0.025) and GON group (-0.79 μm/year; P = 0.058) were faster than those of the healthy group (-0.11 μm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease.ConclusionsWhereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.

PurposeTo evaluate the agreement between Compass New Grid (NG) and 10-2 test protocols for detecting early glaucomatous defects in the central 10 degrees of the visual field (CVFD).DesignCross-sectional study.ParticipantsA total of 123 eyes of 14 healthy individuals, 17 glaucoma suspects, and 32 glaucoma patients were enrolled.MethodsSubjects performed NG and 10-2 Compass automated perimetry testing within 1 week. For both test protocols, total deviation (TD) and pattern deviation (PD) plot CVFDs were defined by 3 contiguous points with probabilities of

PurposeTo compare standard reliability metrics and gaze tracking (GT) metrics on the Humphrey field analyzer (HFA).DesignRetrospective cross-sectional study.MethodsThe study was performed at the VA Medical Center, San Diego, and included 494 glaucoma and glaucoma suspect patients who had an HFA 24-2 SITA Fast visual field (VF) performed in both eyes. Standard reliability metrics (fixation loss [FL], false-positive [FP], and false-negative [FN]) were compared to GT metrics (deviations of 1°-2° [M1], deviations of 3°-5° [M3], deviations >6° [M6], and tracking failure frequency [TFF]). The main outcome measures were Spearman rank-based correlation coefficient and area under the receiver operating characteristic (AUROC) curves between standard and GT reliability metrics.ResultsThe 95th percentile limits for GT metrics were 66.7% for M1, 67.5% for M3, 49.5% for M6, and 79.8% for TFF. There were statistically significant correlations between standard and GT reliability metrics using the 95th percentile as a binary cutoff for GT metrics. However, low Spearman correlation values and AUROC calculations suggest little clinical significance of the associations. FN increased as VF severity worsened (P < .001). M6 was lower in eyes with mild compared to moderate and advanced VF loss (P = .012).ConclusionsGT metrics do not have a clinically significant association with standard reliability metrics. Both FN and M6 are influenced by VF severity. Aggregate GT metrics do not aid in reliability assessment. These findings suggest that GT metrics may provide an alternative or complementary measure of VF reliability.

In higher mammals, thalamic afferents to primary visual cortex (area V1) segregate according to their responses to increases (ON) or decreases (OFF) in luminance. This organization induces columnar, ON/OFF domains postulated to provide a scaffold for the emergence of orientation tuning. To further test this idea, we asked whether ON/OFF domains exist in mouse V1. Here we show that mouse V1 is indeed parceled into ON/OFF domains. Interestingly, fluctuations in the relative density of ON/OFF neurons on the cortical surface mirror fluctuations in the relative density of ON/OFF receptive field centers on the visual field. Moreover, the local diversity of cortical receptive fields is explained by a model in which neurons linearly combine a small number of ON and OFF signals available in their cortical neighborhoods. These findings suggest that ON/OFF domains originate in fluctuations of the balance between ON/OFF responses across the visual field which, in turn, shapes the structure of cortical receptive fields.

PurposeThe purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10.MethodsPatients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected.ResultsSixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1.ConclusionsRetinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS.

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and present challenges to clinical decision-making. We generated a dataset of Optical Coherence Tomography (OCT) based high-resolution circular measurements on NRR phenotypes, along with other clinical covariates, of 3973 healthy eyes as part of an established clinical cohort of Asian Indian participants. We introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, followed by meta-clustering to characterize the clusters using clinical covariates, and presented a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40-49 years with predictive potential for glaucoma. Our dataset also addresses the disparity of representation of this particular population in normative OCT databases.