Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults.

BACKGROUND: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. METHODS: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. RESULTS: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001). CONCLUSION: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.

Enhancing the structure-function relationship in glaucoma using anatomical compensation of retinal nerve fibre layer.

BACKGROUND/AIMS: To investigate whether compensating retinal nerve fibre layer (RNFL) thickness measurements for demographic and anatomical ocular factors can strengthen the structure-function relationship in patients with glaucoma. METHODS: 600 eyes from 412 patients with glaucoma (mean deviation of the visual field (MD VF) -6.53±5.55 dB) were included in this cross-sectional study. Participants underwent standard automated perimetry and spectral-domain optical coherence tomography imaging (Cirrus; Carl Zeiss Meditec). Compensated RNFL thickness was computed considering age, refractive error, optic disc parameters and retinal vessel density. The relationship between MD VF and RNFL thickness measurements, with or without demographic and anatomical compensation, was evaluated sectorally and focally. RESULTS: The superior arcuate sector exhibited the highest correlation between measured RNFL and MD VF, with a correlation of 0.49 (95% CI 0.37 to 0.59). Applying the compensated RNFL data increased the correlation substantially to 0.62 (95% CI 0.52 to 0.70; p<0.001). Only 61% of the VF locations showed a significant relationship (Spearman's correlation of at least 0.30) between structural and functional aspects using measured RNFL data, and this increased to 78% with compensated RNFL measurements. In the 10°-20° VF region, the slope below the breakpoint for compensated RNFL thickness demonstrated a more robust correlation (slope=1.66±0.18 µm/dB; p<0.001) than measured RNFL (slope=0.27±0.67 µm/dB; p=0.688). CONCLUSION: Compensated RNFL data improve the correlation between RNFL measurements and VF parameters. This indicates that creating structure-to-function maps that consider anatomical variances may aid in identifying localised structural and functional loss in glaucoma.

Optical coherence tomography choroidal enhancement using generative deep learning.

Spectral-domain optical coherence tomography (SDOCT) is the gold standard of imaging the eye in clinics. Penetration depth with such devices is, however, limited and visualization of the choroid, which is essential for diagnosing chorioretinal disease, remains limited. Whereas swept-source OCT (SSOCT) devices allow for visualization of the choroid these instruments are expensive and availability in praxis is limited. We present an artificial intelligence (AI)-based solution to enhance the visualization of the choroid in OCT scans and allow for quantitative measurements of choroidal metrics using generative deep learning (DL). Synthetically enhanced SDOCT B-scans with improved choroidal visibility were generated, leveraging matching images to learn deep anatomical features during the training. Using a single-center tertiary eye care institution cohort comprising a total of 362 SDOCT-SSOCT paired subjects, we trained our model with 150,784 images from 410 healthy, 192 glaucoma, and 133 diabetic retinopathy eyes. An independent external test dataset of 37,376 images from 146 eyes was deployed to assess the authenticity and quality of the synthetically enhanced SDOCT images. Experts' ability to differentiate real versus synthetic images was poor (47.5% accuracy). Measurements of choroidal thickness, area, volume, and vascularity index, from the reference SSOCT and synthetically enhanced SDOCT, showed high Pearson's correlations of 0.97 [95% CI: 0.96-0.98], 0.97 [0.95-0.98], 0.95 [0.92-0.98], and 0.87 [0.83-0.91], with intra-class correlation values of 0.99 [0.98-0.99], 0.98 [0.98-0.99], and 0.95 [0.96-0.98], 0.93 [0.91-0.95], respectively. Thus, our DL generative model successfully generated realistic enhanced SDOCT data that is indistinguishable from SSOCT images providing improved visualization of the choroid. This technology enabled accurate measurements of choroidal metrics previously limited by the imaging depth constraints of SDOCT. The findings open new possibilities for utilizing affordable SDOCT devices in studying the choroid in both healthy and pathological conditions.

Retinal Nerve Fiber Layer Damage Assessment in Glaucomatous Eyes Using Retinal Retardance Measured by Polarization-Sensitive Optical Coherence Tomography.

Purpose: To assess the diagnostic performance and structure-function association of retinal retardance (RR), a customized metric measured by a prototype polarization-sensitive optical coherence tomography (PS-OCT), across various stages of glaucoma. Methods: This cross-sectional pilot study analyzed 170 eyes from 49 healthy individuals and 68 patients with glaucoma. The patients underwent PS-OCT imaging and conventional spectral-domain optical coherence tomography (SD-OCT), as well as visual field (VF) tests. Parameters including RR and retinal nerve fiber layer thickness (RNFLT) were extracted from identical circumpapillary regions of the fundus. Glaucomatous eyes were categorized into early, moderate, or severe stages based on VF mean deviation (MD). The diagnostic performance of RR and RNFLT in discriminating glaucoma from controls was assessed using receiver operating characteristic (ROC) curves. Correlations among VF-MD, RR, and RNFLT were evaluated and compared within different groups of disease severity. Results: The diagnostic performance of both RR and RNFLT was comparable for glaucoma detection (RR AUC = 0.98, RNFLT AUC = 0.97; P = 0.553). RR showed better structure-function association with VF-MD than RNFLT (RR VF-MD = 0.68, RNFLT VF-MD = 0.58; z = 1.99; P = 0.047) in glaucoma cases, especially in severe glaucoma, where the correlation between VF-MD and RR (r = 0.73) was significantly stronger than with RNFLT (r = 0.43, z = 1.96, P = 0.050). In eyes with early and moderate glaucoma, the structure-function association was similar when using RNFLT and RR. Conclusions: RR and RNFLT have similar performance in glaucoma diagnosis. However, in patients with glaucoma especially severe glaucoma, RR showed a stronger correlation with VF test results. Further research is needed to validate RR as an indicator for severe glaucoma evaluation and to explore the benefits of using PS-OCT in clinical practice. Translational Relevance: We demonstrated that PS-OCT has the potential to evaluate the status of RNFL structural damage in eyes with severe glaucoma, which is currently challenging in clinics.

Myopia Control: Are We Ready for an Evidence Based Approach?

INTRODUCTION: Myopia and its vision-threatening complications present a significant public health problem. This review aims to provide an updated overview of the multitude of known and emerging interventions to control myopia, including their potential effect, safety, and costs. METHODS: A systematic literature search of three databases was conducted. Interventions were grouped into four categories: environmental/behavioral (outdoor time, near work), pharmacological (e.g., atropine), optical interventions (spectacles and contact lenses), and novel approaches such as red-light (RLRL) therapies. Review articles and original articles on randomized controlled trials (RCT) were selected. RESULTS: From the initial 3224 retrieved records, 18 reviews and 41 original articles reporting results from RCTs were included. While there is more evidence supporting the efficacy of low-dose atropine and certain myopia-controlling contact lenses in slowing myopia progression, the evidence about the efficacy of the newer interventions, such as spectacle lenses (e.g., defocus incorporated multiple segments and highly aspheric lenslets) is more limited. Behavioral interventions, i.e., increased outdoor time, seem effective for preventing the onset of myopia if implemented successfully in schools and homes. While environmental interventions and spectacles are regarded as generally safe, pharmacological interventions, contact lenses, and RLRL may be associated with adverse effects. All interventions, except for behavioral change, are tied to moderate to high expenditures. CONCLUSION: Our review suggests that myopia control interventions are recommended and prescribed on the basis of accessibility and clinical practice patterns, which vary widely around the world. Clinical trials indicate short- to medium-term efficacy in reducing myopia progression for various interventions, but none have demonstrated long-term effectiveness in preventing high myopia and potential complications in adulthood. There is an unmet need for a unified consensus for strategies that balance risk and effectiveness for these methods for personalized myopia management.

Defining the structure-function relationship of specific lesions in early and advanced age-related macular degeneration.

The objective of this study is to define structure-function relationships of pathological lesions related to age-related macular degeneration (AMD) using microperimetry and multimodal retinal imaging. We conducted a cross-sectional study of 87 patients with AMD (30 eyes with early and intermediate AMD and 110 eyes with advanced AMD), compared to 33 normal controls (66 eyes) recruited from a single tertiary center. All participants had enface and cross-sectional optical coherence tomography (Heidelberg HRA-2), OCT angiography, color and infra-red (IR) fundus and microperimetry (MP) (Nidek MP-3) performed. Multimodal images were graded for specific AMD pathological lesions. A custom marking tool was used to demarcate lesion boundaries on corresponding enface IR images, and subsequently superimposed onto MP color fundus photographs with retinal sensitivity points (RSP). The resulting overlay was used to correlate pathological structural changes to zonal functional changes. Mean age of patients with early/intermediate AMD, advanced AMD and controls were 73(SD = 8.2), 70.8(SD = 8), and 65.4(SD = 7.7) years respectively. Mean retinal sensitivity (MRS) of both early/intermediate (23.1 dB; SD = 5.5) and advanced AMD (18.1 dB; SD = 7.8) eyes were significantly worse than controls (27.8 dB, SD = 4.3) (p < 0.01). Advanced AMD eyes had significantly more unstable fixation (70%; SD = 63.6), larger mean fixation area (3.9 mm2; SD = 3.0), and focal fixation point further away from the fovea (0.7 mm; SD = 0.8), than controls (29%; SD = 43.9; 2.6 mm2; SD = 1.9; 0.4 mm; SD = 0.3) (p ≤ 0.01). Notably, 22 fellow eyes of AMD eyes (25.7 dB; SD = 3.0), with no AMD lesions, still had lower MRS than controls (p = 0.04). For specific AMD-related lesions, end-stage changes such as fibrosis (5.5 dB, SD = 5.4 dB) and atrophy (6.2 dB, SD = 7.0 dB) had the lowest MRS; while drusen and pigment epithelial detachment (17.7 dB, SD = 8.0 dB) had the highest MRS. Peri-lesional areas (20.2 dB, SD = 7.6 dB) and surrounding structurally normal areas (22.2 dB, SD = 6.9 dB) of the retina with no AMD lesions still had lower MRS compared to controls (27.8 dB, SD = 4.3 dB) (p < 0.01). Our detailed topographic structure-function correlation identified specific AMD pathological changes associated with a poorer visual function. This can provide an added value to the assessment of visual function to optimize treatment outcomes to existing and potentially future novel therapies.

Titanium Implants Coated with Hydroxyapatite Used in Orbital Wall Reconstruction-A Literature Review.

With the increasing incidences of orbital wall injuries, effective reconstruction materials and techniques are imperative for optimal clinical outcomes. In this literature review, we delve into the efficacy and potential advantages of using titanium implants coated with nanostructured hydroxyapatite for the reconstruction of the orbital wall. Titanium implants, recognized for their durability and mechanical strength, when combined with the osteoconductive properties of hydroxyapatite, present a potentially synergistic solution. The purpose of this review was to critically analyze the recent literature and present the state of the art in orbital wall reconstruction using titanium implants coated with nanostructured hydroxyapatite. This review offers clinicians detailed insight into the benefits and potential drawbacks of using titanium implants coated with nanostructured hydroxyapatite for orbital wall reconstruction. The highlighted results advocate for its benefits in terms of osseointegration and provide a novel strategy for orbital reconstruction, though further studies are essential to establish long-term efficacy and address concerns.

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients.

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT05650905.

Effect of anti-VEGF on retinal blood flow in diabetic mice using laser speckle flowgraphy.

PURPOSE: To assess intra- (repeatability) and inter-observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. METHODS: 'Mean blur rate (MBR)' was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland-Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 µg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post-injection. Hurvich and Tsai's criterion was used. RESULTS: Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98-0.99) and reproducibility was moderate to excellent (ICC 0.64-0.96). There was a non-significant IOP increase in all Akita eyes at Day 28 (p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 (p < 0.05). CONCLUSION: Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post-injection without significant increase in IOP.

The Impact of Photopigment Bleaching on the Human Rod Photoreceptor Subretinal Space Measured Via Optical Coherence Tomography.

Purpose: The purpose of this study was to investigate rod photopigment bleaching-driven intrinsic optical signals (IOS) in the human outer retina and its measurement repeatability based on a commercial optical coherence tomography (OCT) platform. Methods: The optical path length of the rod photoreceptor subretinal space (SRS), that is, the distance between signal bands of rod outer segment tips and retinal pigment epithelium, was measured in 15 healthy subjects in ambient light and during a long-duration bleaching white-light exposure. Results: On 2 identical study days (day 1 and day 2 [D1 and D2]), light stimulation resulted in a significant decrease in rod SRS by 21.3 ± 7.6% and 19.8 ± 8.5% (both P < 0.001), respectively. The test-retest reliability of the SRS maximum change of an individual subject was moderate for single measures (intraclass correlation coefficient [ICC] = 0.730, 95% confidence interval [CI] = 0.376, 0.900, P < 0.001) and good for average measures (ICC = 0.844, 95% CI = 0.546, 0.947, P < 0.001). The mean area under the stimulus response curve with values of 14.8 ± 9.4 and 15.5 ± 7.5 µm × minutes (P = 0.782) showed excellent agreement between the stimulus response on D1 and D2. Intermittent dark adaptation of the retina led to an initial increase of the SRS by 6.1% (P = 0.018) and thereafter showed a decrease toward baseline, despite continued dark adaptation. Conclusions: The data indicate the potential of commercial OCT in measuring slow IOS in the outer retina suggesting that the rod SRS could serve as a biomarker for photoreceptor function. The presented approach could provide an easily implementable clinical tool for the early detection of diseases affecting photoreceptor health.

Ocular microvascular complications in diabetic retinopathy: insights from machine learning.

INTRODUCTION: Diabetic retinopathy (DR) is a leading cause of preventable blindness among working-age adults, primarily driven by ocular microvascular complications from chronic hyperglycemia. Comprehending the complex relationship between microvascular changes in the eye and disease progression poses challenges, traditional methods assuming linear or logistical relationships may not adequately capture the intricate interactions between these changes and disease advances. Hence, the aim of this study was to evaluate the microvascular involvement of diabetes mellitus (DM) and non-proliferative DR with the implementation of non-parametric machine learning methods. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study that included optical coherence tomography angiography (OCTA) images collected from a healthy group (196 eyes), a DM no DR group (120 eyes), a mild DR group (71 eyes), and a moderate DR group (66 eyes). We implemented a non-parametric machine learning method for four classification tasks that used parameters extracted from the OCTA images as predictors: DM no DR versus healthy, mild DR versus DM no DR, moderate DR versus mild DR, and any DR versus no DR. SHapley Additive exPlanations values were used to determine the importance of these parameters in the classification. RESULTS: We found large choriocapillaris flow deficits were the most important for healthy versus DM no DR, and became less important in eyes with mild or moderate DR. The superficial microvasculature was important for the healthy versus DM no DR and mild DR versus moderate DR tasks, but not for the DM no DR versus mild DR task-the stage when deep microvasculature plays an important role. Foveal avascular zone metric was in general less affected, but its involvement increased with worsening DR. CONCLUSIONS: The findings from this study provide valuable insights into the microvascular involvement of DM and DR, facilitating the development of early detection methods and intervention strategies.

Are Macula or Optic Nerve Head Structures Better at Diagnosing Glaucoma? An Answer Using Artificial Intelligence and Wide-Field Optical Coherence Tomography.

Purpose: We wanted to develop a deep-learning algorithm to automatically segment optic nerve head (ONH) and macula structures in three-dimensional (3D) wide-field optical coherence tomography (OCT) scans and to assess whether 3D ONH or macula structures (or a combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed using 319 OCT scans of glaucoma eyes and 298 scans of nonglaucoma eyes. Scans were compensated to improve deep-tissue visibility. We developed a deep-learning algorithm to automatically label major tissue structures, trained with 270 manually annotated B-scans. The performance was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D-CNN) was then designed using 500 OCT volumes and corresponding automatically segmented labels. This algorithm was trained and tested on three datasets: cropped scans of macular tissues, those of ONH tissues, and wide-field scans. The classification performance for each dataset was reported using the area under the curve (AUC). Results: Our segmentation algorithm achieved a DC of 0.94 ± 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field scans, followed by ONH scans, and finally macula scans, with AUCs of 0.99 ± 0.01, 0.93 ± 0.06 and 0.91 ± 0.11, respectively. Conclusions: This study showed that wide-field OCT may allow for significantly improved glaucoma diagnosis over typical OCTs of the ONH or macula. Translational Relevance: This could lead to mainstream clinical adoption of 3D wide-field OCT scan technology.

Segregation of neuronal and vascular retinal damage in patients with hypertension and diabetes.

This study aimed to examine the impact of diabetes and hypertension on retinal nerve fiber layer (RNFL) thickness components. Optical coherence tomography (OCT) measurements do not consider blood vessel contribution, which this study addressed. We hypothesized that diabetes and/or hypertension would lead to thinner RNFL versus controls due to the vascular component. OCT angiography was used to measure the RNFL in 121 controls, 50 diabetes patients, 371 hypertension patients, and 177 diabetes patients with hypertension. A novel technique separated the RNFL thickness into original (vascular component) and corrected (no vascular component) measurements. Diabetes-only (98 ± 1.7 µm; p = 0.002) and diabetes with hypertension (99 ± 0.8 µm; p = 0.001) patients had thinner original RNFL versus controls (102 ± 0.8 µm). No difference was seen between hypertension-only patients (101 ± 0.5 µm; p = 0.083) and controls. After removing the blood vessel component, diabetes/hypertension groups had thinner corrected RNFL versus controls (p = 0.024). Discrepancies in diabetes/hypertension patients were due to thicker retinal blood vessels within the RNFL thickness (p = 0.002). Our findings suggest that diabetes and/or hypertension independently contribute to neurodegenerative thinning of the RNFL, even in the absence of retinopathy. The differentiation of neuronal and vascular components in RNFL thickness measurements provided by the novel technique highlights the importance of considering vascular changes in individuals with these conditions.

Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study.

Importance: Clinical trial results of topical atropine eye drops for childhood myopia control have shown inconsistent outcomes across short-term studies, with little long-term safety or other outcomes reported. Objective: To report the long-term safety and outcomes of topical atropine for childhood myopia control. Design, Setting, and Participants: This prospective, double-masked observational study of the Atropine for the Treatment of Myopia (ATOM) 1 and ATOM2 randomized clinical trials took place at 2 single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs 0.1% vs 0.5%; 2006 through 2012). Main Outcome Measures: Change in cycloplegic spherical equivalent (SE) with axial length (AL); incidence of ocular complications. Results: Among the original 400 participants in each original cohort, the study team evaluated 71 of 400 ATOM1 adult participants (17.8% of original cohort; study age, mean [SD] 30.5 [1.2] years; 40.6% female) and 158 of 400 ATOM2 adult participants (39.5% of original cohort; study age, mean [SD], 24.5 [1.5] years; 42.9% female) whose baseline characteristics (SE and AL) were representative of the original cohort. In this study, evaluating ATOM1 participants, the mean (SD) SE and AL were -5.20 (2.46) diopters (D), 25.87 (1.23) mm and -6.00 (1.63) D, 25.90 (1.21) mm in the 1% atropine-treated and placebo groups, respectively (difference of SE, 0.80 D; 95% CI, -0.25 to 1.85 D; P = .13; difference of AL, -0.03 mm; 95% CI, -0.65 to 0.58 mm; P = .92). In ATOM2 participants, the mean (SD) SE and AL was -6.40 (2.21) D; 26.25 (1.34) mm; -6.81 (1.92) D, 26.28 (0.99) mm; and -7.19 (2.87) D, 26.31 (1.31) mm in the 0.01%, 0.1%, and 0.5% atropine groups, respectively. There was no difference in the 20-year incidence of cataract/lens opacities, myopic macular degeneration, or parapapillary atrophy (ß/γ zone) comparing the 1% atropine-treated group vs the placebo group. Conclusions and Relevance: Among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of 2 to 4 years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.

Relationship Between Retinal Layer Thickness and Genetic Susceptibility to Age-Related Macular Degeneration in Asian Populations.

Purpose: For OCT retinal thickness measurements to be used as a prodromal age-related macular degeneration (AMD) risk marker, the 3-dimensional (3D) topographic variation of the relationship between genetic susceptibility to AMD and retinal thickness needs to be assessed. We aimed to evaluate individual retinal layer thickness changes and topography at the macula that are associated with AMD genetic susceptibility. Design: Genetic association study. Participants: A total of 1579 healthy participants (782 Chinese, 353 Malays, and 444 Indians) from the multiethnic Singapore Epidemiology of Eye Diseases study were included. Methods: Spectral-domain OCT and automatic segmentation of individual retinal layers were performed to produce 10 retinal layer thickness measurements at each ETDRS subfield, producing 3D topographic information. Age-related macular degeneration genetic susceptibility was represented via single nucleotide polymorphisms (SNPs) and aggregated via whole genome (overall) and pathway-specific age-related macular degeneration polygenic risk score (PRSAMD). Main Outcome Measures: Associations of individual SNPs, overall PRSAMD, and pathway-specific PRSAMD with retinal thickness were analyzed by individual retinal layer and ETDRS subfield. Results: CFH rs10922109, ARMS2-HTRA1 rs3750846, and LIPC rs2043085 were the top AMD susceptibility SNPs associated with retinal thickness of individual layers (P < 1.67 × 10-3), all at the central subfield. The overall PRSAMD was most associated with thinner L9 (outer segment photoreceptor/retinal pigment epithelium complex) thickness at the central subfield (ß = -0.63 µm; P = 5.45 × 10-9). Pathway-specific PRSAMD for the complement cascade (ß = -0.53 µm; P = 9.42 × 10-7) and lipoprotein metabolism (ß = -0.05 µm; P = 0.0061) were associated with thinner photoreceptor layers (L9 and L7 [photoreceptor inner/outer segments], respectively) at the central subfield. The mean PRSAMD score was larger among Indians compared with that of the Chinese and had the thinnest thickness at the L9 central subfield (ß = -1.00 µm; P = 2.91 × 10-7; R2 = 5.5%). Associations at other retinal layers and ETDRS regions were more heterogeneous. Conclusions: Overall genetic susceptibility to AMD and the aggregate effects of the complement cascade and lipoprotein metabolism pathway are associated most significantly with L7 and L9 photoreceptor thinning at the central macula in healthy individuals. Photoreceptor thinning has potential to be a prodromal AMD risk marker, and topographic variation should be considered. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics - OMEGA Report 1.

INTRODUCTION: The aim of this study was to describe the design and the participants' baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing. RESULTS: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487). CONCLUSION: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.

Predicting glaucoma progression using deep learning framework guided by generative algorithm.

Glaucoma is a slowly progressing optic neuropathy that may eventually lead to blindness. To help patients receive customized treatment, predicting how quickly the disease will progress is important. Structural assessment using optical coherence tomography (OCT) can be used to visualize glaucomatous optic nerve and retinal damage, while functional visual field (VF) tests can be used to measure the extent of vision loss. However, VF testing is patient-dependent and highly inconsistent, making it difficult to track glaucoma progression. In this work, we developed a multimodal deep learning model comprising a convolutional neural network (CNN) and a long short-term memory (LSTM) network, for glaucoma progression prediction. We used OCT images, VF values, demographic and clinical data of 86 glaucoma patients with five visits over 12 months. The proposed method was used to predict VF changes 12 months after the first visit by combining past multimodal inputs with synthesized future images generated using generative adversarial network (GAN). The patients were classified into two classes based on their VF mean deviation (MD) decline: slow progressors (< 3 dB) and fast progressors (> 3 dB). We showed that our generative model-based novel approach can achieve the best AUC of 0.83 for predicting the progression 6 months earlier. Further, the use of synthetic future images enabled the model to accurately predict the vision loss even earlier (9 months earlier) with an AUC of 0.81, compared to using only structural (AUC = 0.68) or only functional measures (AUC = 0.72). This study provides valuable insights into the potential of using synthetic follow-up OCT images for early detection of glaucoma progression.

Combining retinal structural and vascular measurements improves discriminative power for multiple sclerosis patients.

Data on how retinal structural and vascular parameters jointly influence the diagnostic performance of detection of multiple sclerosis (MS) patients without optic neuritis (MSNON) are lacking. To investigate the diagnostic performance of structural and vascular changes to detect MSNON from controls, we performed a cross-sectional study of 76 eyes from 51 MS participants and 117 eyes from 71 healthy controls. Retinal macular ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the Cirrus AngioPlex. The best structural parameter for detecting MS was compensated RNFL from the optic nerve head (AUC = 0.85), followed by GCC from the macula (AUC = 0.79), while the best vascular parameter was the SCP (AUC = 0.66). Combining structural and vascular parameters improved the diagnostic performance for MS detection (AUC = 0.90; p<0.001). Including both structure and vasculature in the joint model considerably improved the discrimination between MSNON and normal controls compared to each parameter separately (p = 0.027). Combining optical coherence tomography (OCT)-derived structural metrics and vascular measurements from optical coherence tomography angiography (OCTA) improved the detection of MSNON. Further studies may be warranted to evaluate the clinical utility of OCT and OCTA parameters in the prediction of disease progression.

Three-Dimensional Structural Phenotype of the Optic Nerve Head as a Function of Glaucoma Severity.

Importance: The 3-dimensional (3-D) structural phenotype of glaucoma as a function of severity was thoroughly described and analyzed, enhancing understanding of its intricate pathology beyond current clinical knowledge. Objective: To describe the 3-D structural differences in both connective and neural tissues of the optic nerve head (ONH) between different glaucoma stages using traditional and artificial intelligence-driven approaches. Design, Setting, and Participants: This cross-sectional, clinic-based study recruited 541 Chinese individuals receiving standard clinical care at Singapore National Eye Centre, Singapore, and 112 White participants of a prospective observational study at Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. The study was conducted from May 2022 to January 2023. All participants had their ONH imaged using spectral-domain optical coherence tomography and had their visual field assessed by standard automated perimetry. Main Outcomes and Measures: (1) Clinician-defined 3-D structural parameters of the ONH and (2) 3-D structural landmarks identified by geometric deep learning that differentiated ONHs among 4 groups: no glaucoma, mild glaucoma (mean deviation [MD], ≥-6.00 dB), moderate glaucoma (MD, -6.01 to -12.00 dB), and advanced glaucoma (MD, <-12.00 dB). Results: Study participants included 213 individuals without glaucoma (mean age, 63.4 years; 95% CI, 62.5-64.3 years; 126 females [59.2%]; 213 Chinese [100%] and 0 White individuals), 204 with mild glaucoma (mean age, 66.9 years; 95% CI, 66.0-67.8 years; 91 females [44.6%]; 178 Chinese [87.3%] and 26 White [12.7%] individuals), 118 with moderate glaucoma (mean age, 68.1 years; 95% CI, 66.8-69.4 years; 49 females [41.5%]; 97 Chinese [82.2%] and 21 White [17.8%] individuals), and 118 with advanced glaucoma (mean age, 68.5 years; 95% CI, 67.1-69.9 years; 43 females [36.4%]; 53 Chinese [44.9%] and 65 White [55.1%] individuals). The majority of ONH structural differences occurred in the early glaucoma stage, followed by a plateau effect in the later stages. Using a deep neural network, 3-D ONH structural differences were found to be present in both neural and connective tissues. Specifically, a mean of 57.4% (95% CI, 54.9%-59.9%, for no to mild glaucoma), 38.7% (95% CI, 36.9%-40.5%, for mild to moderate glaucoma), and 53.1 (95% CI, 50.8%-55.4%, for moderate to advanced glaucoma) of ONH landmarks that showed major structural differences were located in neural tissues with the remaining located in connective tissues. Conclusions and Relevance: This study uncovered complex 3-D structural differences of the ONH in both neural and connective tissues as a function of glaucoma severity. Future longitudinal studies should seek to establish a connection between specific 3-D ONH structural changes and fast visual field deterioration and aim to improve the early detection of patients with rapid visual field loss in routine clinical care.

Therapeutic Potential of Cannabinoids in Glaucoma.

Glaucoma is a leading cause of irreversible blindness worldwide. To date, intraocular pressure (IOP) is the only modifiable risk factor in glaucoma treatment, but even in treated patients, the disease can progress. Cannabinoids, which have been known to lower IOP since the 1970s, have been shown to have beneficial effects in glaucoma patients beyond their IOP-lowering properties. In addition to the classical cannabinoid receptors CB1 and CB2, knowledge of non-classical cannabinoid receptors and the endocannabinoid system has increased in recent years. In particular, the CB2 receptor has been shown to mediate anti-inflammatory, anti-apoptotic, and neuroprotective properties, which may represent a promising therapeutic target for neuroprotection in glaucoma patients. Due to their vasodilatory effects, cannabinoids improve blood flow to the optic nerve head, which may suggest a vasoprotective potential and counteract the altered blood flow observed in glaucoma patients. The aim of this review was to assess the available evidence on the effects and therapeutic potential of cannabinoids in glaucoma patients. The pharmacological mechanisms underlying the effects of cannabinoids on IOP, neuroprotection, and ocular hemodynamics have been discussed.