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Purpose: To introduce a method to calculate retinal irradiance caused by ophthalmoscopy. This may be used to verify the compliance of an instrument with the radiation limits set by light hazard standards. The proposed method is simpler to use and less prone to error than the methods currently found in the light hazard standards., Methods: The optical properties of the standardised human eye, specified by current light hazard standards, are used to calculate the magnification of an aerial image of the retinal surface by the combination of the optics of eye and the auxiliary lens used for ophthalmoscopy. The magnification of the aerial image is used to transform the spectral irradiance of the instrument illumination source to retinal irradiation values. The spectral irradiance of the instrument illumination source can be measured directly as the aerial image is located in the focal plane of the viewing optics of the ophthalmoscope. These spectral irradiation values are then processed using weightings specified by current light hazard standards to give a weighted irradiance which is converted directly to a retinal irradiance value., Results: A single formula is provided to calculate the retinal irradiance using the processed, measured spectral irradiance values of the illumination source., Conclusion: The new method introduced here is simpler to use, requires fewer physical measurements and is less likely to introduce measurement error than that currently found in light hazard standards. The only physical measurement that needs to be taken is the illumination source spectral irradiance measured in the viewing focal plane of the instrument. These values are weighted using given in the light hazard standards. The combined irradiance value is then converted to retinal irradiance using the formula given in this paper., (© 2024 College of Optometrists.)

Purpose: To evaluate whether providing clinicians with an artificial intelligence (AI)-based vascular severity score (VSS) improves consistency in the diagnosis of plus disease in retinopathy of prematurity (ROP)., Design: Multireader diagnostic accuracy imaging study., Participants: Eleven ROP experts, 9 of whom had been in practice for 10 years or more., Methods: RetCam (Natus Medical Incorporated) fundus images were obtained from premature infants during routine ROP screening as part of the Imaging and Informatics in ROP study between January 2012 and July 2020. From all available examinations, a subset of 150 eye examinations from 110 infants were selected for grading. An AI-based VSS was assigned to each set of images using the i-ROP DL system (Siloam Vision). The clinicians were asked to diagnose plus disease for each examination and to assign an estimated VSS (range, 1-9) at baseline, and then again 1 month later with AI-based VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye examination from the Imaging and Informatics in ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis., Main Outcome Measures: Mean linearly weighted κ value for plus disease diagnosis compared with RSD. Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPR) for labels 1 through 9 compared with RSD for plus disease., Results: Expert agreement improved significantly, from substantial (κ value, 0.69 [0.59, 0.75]) to near perfect (κ value, 0.81 [0.71, 0.86]), when AI-based VSS was integrated. Additionally, a significant improvement in plus disease discrimination was achieved as measured by mean AUC (from 0.94 [95% confidence interval (CI), 0.92-0.96] to 0.98 [95% CI, 0.96-0.99]; difference, 0.04 [95% CI, 0.01-0.06]) and AUPR (from 0.86 [95% CI, 0.81-0.90] to 0.95 [95% CI, 0.91-0.97]; difference, 0.09 [95% CI, 0.03-0.14])., Conclusions: Providing ROP clinicians with an AI-based measurement of vascular severity in ROP was associated with both improved plus disease diagnosis and improved continuous severity labeling as compared with an RSD for plus disease. If implemented in practice, AI-based VSS could reduce interobserver variability and could standardize treatment for infants with ROP., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. All rights reserved.)

Objective: This paper aims at quantifying biomarkers from the segmentation of retinal arteries in adaptive optics ophthalmoscopy images (AOO)., Methods: The segmentation is based on the combination of deep learning and knowledge-driven deformable models to achieve a precise segmentation of the vessel walls, with a specific attention to bifurcations. Biomarkers (junction coefficient, branching coefficient, wall to lumen ratio ( wlr)) are derived from the resulting segmentation., Results: reliable and accurate segmentations ( mse = 1.75 ±1.24 pixel) and measurements are obtained, with high reproducibility with respect to images acquisition and users, and without bias., Significance: In a preliminary clinical study of patients with a genetic small vessel disease, some of them with vascular risk factors, an increased wlr was found in comparison to a control population., Conclusion: The wlr estimated in AOO images with our method (AOV, Adaptive Optics Vessel analysis) seems to be a very robust biomarker as long as the wall is well contrasted.

The dynamic nature of retinal cellular processes necessitates advancements in gene delivery and live monitoring techniques to enhance the understanding and treatment of ocular diseases. This study introduces an optimized adeno-associated virus (AAV) approach, utilizing specific serotypes and promoters to achieve optimal transfection efficiency in targeted retinal cells, including retinal ganglion cells (RGCs) and Müller glia. Leveraging the precision of confocal scanning laser ophthalmoscopy (CSLO), this work presents a non-invasive method for in vivo imaging that captures the longitudinal expression of AAV-mediated green fluorescent protein (GFP). This approach eliminates the need for terminal procedures, preserving the continuity of observation and the well-being of the subject. Furthermore, the GFP signal can be traced in AAV-infected RGCs along the visual pathway to the superior colliculus (SC) and lateral geniculate nucleus (LGN), enabling the potential for direct visual pathway mapping. These findings provide a detailed protocol and demonstrate the application of this powerful tool for real-time studies of retinal cell behavior, disease pathogenesis, and the efficacy of gene therapy interventions, offering valuable insights into the living retina and its connections.

Image based cell-specific biomarkers will play an important role in monitoring treatment outcomes of novel therapies in patients with Stargardt (STGD1) disease and may provide information on the exact mechanism of retinal degeneration. This study reports retinal image features from conventional clinical imaging and from corresponding high-resolution imaging with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) in a heterogenous cohort of patients with Stargardt (STGD1) disease. This is a prospective observational study in which 16 participants with clinically and molecularly confirmed STGD1, and 7 healthy controls underwent clinical assessment and confocal AOSLO imaging. Clinical assessment included short-wavelength and near-infrared fundus autofluorescence, spectral-domain optical coherence tomography, and macular microperimetry. AOSLO images were acquired over a range of retinal eccentricities (0°-20°) and mapped to areas of interest from the clinical images. A regular photoreceptor mosaic was identified in areas of normal or near normal retinal structure on clinical images. Where clinical imaging indicated areas of retinal degeneration, the photoreceptor mosaic was disorganised and lacked unambiguous cones. Discrete hyper-reflective foci were identified in 9 participants with STGD1 within areas of retinal degeneration. A continuous RPE cell mosaic at the fovea was identified in one participant with an optical gap phenotype. The clinical heterogeneity observed in STGD1 is reflected in the findings on confocal AOSLO imaging., (© 2024. The Author(s).)

Adaptive optics ophthalmoscopy has enabled visualization of the in vivo human photoreceptor mosaic in health, disease and its treatment. Despite this, the clinical utility of the imaging technology has been limited by a lack of automated analysis techniques capable of accurately quantifying photoreceptor structure and a lack of an available normative image database. Here, we present a fully automated algorithm for estimating cone spacing and density over a complete adaptive optics montage along with a database of normative images and cone densities. We imaged the cone mosaics surrounding the fovea and along the horizontal and vertical meridians of fifty normal-sighted controls with a custom-built, multimodal adaptive optics scanning light ophthalmoscope. Cone spacing was automatically measured in the frequency domain and spacing measurements were converted to estimates of cone density at all locations across the montage. Consistent with previous reports, cone density measurements were highest near fovea (152,906 ± 53,209 cones/mm 2 ) and decreased exponentially with eccentricity. A 2.5-fold variation was found in cone density estimates at 0.1 mm, this variation decreased to 1.75-fold at 1 mm. We provide all images, mosaic quantifications, and automated software open source. This database will aid investigators in translating adaptive optics ophthalmoscopy to clinical applications., (© 2024. The Author(s).)

Purpose: The purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM)., Methods: Thirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD., Results: Mean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83., Conclusions: CNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.

Purpose: To describe an ophthalmoscopic sign, termed a meniscus micropyon, and its possible association with proliferative vitreoretinopathy/epiretinal membrane (ERM) formation after retinal surgery with gas tamponade., Methods: Patients with intravitreal gas were examined postoperatively by one of six vitreoretinal surgeons from four institutions. A micropyon was defined as a white-yellow, solid-appearing consolidation along the meniscus (i.e., the fluid-gas interface)., Results: A micropyon was visualized and photographed in 49 patients who received intravitreal gas. Preoperatively, retinal breaks were present in all 49 eyes and rhegmatogenous retinal detachment in 45 (92%). Postoperatively, 39 eyes (80%) developed epiretinal proliferation: 16 eyes (33%) developed recurrent rhegmatogenous retinal detachment from proliferative vitreoretinopathy, 6 eyes (12%) re-detached without frank proliferative vitreoretinopathy, 9 eyes (18%) developed postoperative ERM/worsening, and 8 eyes (16%) had postoperative ERM but no preoperative optical coherence tomography to determine if the postoperative ERM was new or worsening. The single-operation anatomical success in eyes with a micropyon was 51%, which was lower than that of a contemporaneous rhegmatogenous retinal detachment control group (91%) in which no micropyon was detected. In two patients, micropyons were biopsied during pars plana vitrectomy and examined histopathologically; they consist predominantly of white blood cells., Conclusion: The meniscus micropyon is an ophthalmoscopic sign that can occur after retinal surgery with gas tamponade. Features that distinguish a micropyon from postvitrectomy fibrin/fibrinoid syndrome include delayed appearance, hyperautofluorescence, absence of translucent strands or sheets in the anterior chamber or vitreous cavity, and the histopathologic identification of white blood cells. A clinically detectable micropyon may be a biomarker of proliferative vitreoretinopathy/ERM formation.

Direct ophthalmoscopy continues to be the "gold standard" method for retinal and optic nerve evaluation despite known challenges for learners to acquire this clinical skill and minimal opportunities for patient-facing practice. Here we review current literature regarding smartphone fundoscopy (SF) as an alternative learning tool that remains underutilized in Canadian medical schools. SF has significant advantages over direct ophthalmoscopy, such as enhanced learner visualization of ocular structure and pathologies, greater learner usability in comparison, and improved fundus assessment during more difficult ocular examinations such as with pediatric patients. Furthermore, SF provides opportunities for instructor exchange and feedback, group learning, increased learner confidence, and most important, an improved patient experience. Yet challenges remain with SF, including patient confidentiality during data capture and sharing and meaningful integration into an already limited and saturated curriculum. Our review finds SF to be a pedagogic tool with the potential to reinvigorate fundoscopy learning to improve competency in this important clinical skill., Competing Interests: Footnotes and Disclosure The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the capabilities and incapabilities of a GPT-4V(ision)-based chatbot in interpreting ocular multimodal images., Methods: We developed a digital ophthalmologist app using GPT-4V and evaluated its performance with a dataset (60 images, 60 ophthalmic conditions, 6 modalities) that included slit-lamp, scanning laser ophthalmoscopy, fundus photography of the posterior pole (FPP), optical coherence tomography, fundus fluorescein angiography and ocular ultrasound images. The chatbot was tested with ten open-ended questions per image, covering examination identification, lesion detection, diagnosis and decision support. The responses were manually assessed for accuracy, usability, safety and diagnosis repeatability. Auto-evaluation was performed using sentence similarity and GPT-4-based auto-evaluation., Results: Out of 600 responses, 30.6% were accurate, 21.5% were highly usable and 55.6% were deemed as no harm. GPT-4V performed best with slit-lamp images, with 42.0%, 38.5% and 68.5% of the responses being accurate, highly usable and no harm, respectively. However, its performance was weaker in FPP images, with only 13.7%, 3.7% and 38.5% in the same categories. GPT-4V correctly identified 95.6% of the imaging modalities and showed varying accuracies in lesion identification (25.6%), diagnosis (16.1%) and decision support (24.0%). The overall repeatability of GPT-4V in diagnosing ocular images was 63.3% (38/60). The overall sentence similarity between responses generated by GPT-4V and human answers is 55.5%, with Spearman correlations of 0.569 for accuracy and 0.576 for usability., Conclusion: GPT-4V currently is not yet suitable for clinical decision-making in ophthalmology. Our study serves as a benchmark for enhancing ophthalmic multimodal models., Competing Interests: Competing interests: None of the authors has a financial or proprietary interest in any material or method mentioned., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Insight into the immune status of the living eye is essential as we seek to understand ocular disease and develop new treatments. The nonhuman primate (NHP) is the gold standard preclinical model for therapeutic development in ophthalmology, owing to the similar visual system and immune landscape in the NHP relative to the human. Here, we demonstrate the utility of phase-contrast adaptive optics scanning light ophthalmoscope (AOSLO) to visualize immune cell dynamics on the cellular scale, label-free in the NHP., Methods: Phase-contrast AOSLO was used to image preselected areas of retinal vasculature in five NHP eyes. Images were registered to correct for eye motion, temporally averaged, and analyzed for immune cell activity. Cell counts, dimensions, velocities, and frequency per vessel were determined manually and compared between retinal arterioles and venules. Based on cell appearance and circularity index, cells were divided into three morphologies: ovoid, semicircular, and flattened., Results: Immune cells were observed migrating along vascular endothelium with and against blood flow. Cell velocity did not significantly differ between morphology or vessel type and was independent of blow flood. Venules had a significantly higher cell frequency than arterioles. A higher proportion of cells resembled "flattened" morphology in arterioles. Based on cell speeds, morphologies, and behaviors, we identified these cells as nonclassical patrolling monocytes (NCPMs)., Conclusions: Phase-contrast AOSLO has the potential to reveal the once hidden behaviors of single immune cells in retinal circulation and can do so without the requirement of added contrast agents that may disrupt immune cell behavior.

Visual floaters can significantly affect quality of vision. Although these opacities are visible on ophthalmoscopy, objectively measuring severity has been difficult. The standard approach has been to monitor individuals for complications rather than treating the floaters. With advances in surgical instrumentation and techniques, ophthalmologists have multiple options for treating visually significant floaters, most commonly pars plana vitrectomy and laser vitreolysis. This article aims to review the literature discussing methods for diagnosing and treating floaters., Competing Interests: Disclosure: No financial disclosures reported. Artificial intelligence was not used in the study, research, preparation, or writing of this manuscript., (Copyright 2024 by the Missouri State Medical Association.)

Purpose: To investigate the sensitivity of fluorescence lifetime imaging ophthalmoscopy (FLIO) to detect retinal laser spots by comparative analysis with other imaging modalities., Methods: A diode laser with a wavelength of 514 nm was applied with pulse durations of 5.2, 12, 20, and 50 µs. The laser pulse energy was increased so that the visibility of the laser spot by slit-lamp fundus examination (SL) under the irradiator's observation covers from the subvisible to visible range immediately after irradiation. The irradiated areas were then examined by fundus color photography (FC), optical coherence tomography (OCT), fundus autofluorescence (AF), FLIO, and fluorescein angiography (FA). The visibility of a total of over 2200 laser spots was evaluated by two independent researchers, and effective dose (ED) 50 laser pulse energy values were calculated for each imaging modality and compared., Results: Among examined modalities, FA showed the lowest mean of ED50 energy value and SL the highest, that is, they had the highest and lowest sensitivity to detect retinal pigment epithalium (RPE)-selective laser spots, respectively. FLIO also detected spots significantly more sensitively than SL at most laser pulse durations and was not significantly inferior to FA. AF was also often more sensitive than SL, but the difference was slightly less significant than FLIO., Conclusion: Considering its high sensitivity in detecting laser spots and previously reported potential of indicating local wound healing and metabolic changes around laser spots, FLIO may be useful as a non-invasive monitoring tool during and after minimally invasive retinal laser treatment., (© 2024. The Author(s).)

Background/objectives: To evaluate the diagnostic performance of B-scan kinetic ultrasonography (USG), standard ultra-widefield (UWF) imaging, and indirect ophthalmoscopy (IDO) in retinal break detection in cataractous eyes., Subjects/methods: We consecutively enrolled 126 cataract patients (including 246 eyes) with no comorbidities that could decrease best corrected visual acuity (BCVA). Three index tests (USG, nonmydriatic UWF, and mydriatic IDO) were performed preoperatively to screen for retinal breaks. One week after cataract extraction, a dilated IDO examination was repeated for the definitive diagnosis of retinal break as the reference standard. The sensitivity, specificity, Youden index (YI), and predictive values of each index test were calculated according to postoperative ophthalmoscopic findings. A deep-learning nomogram was developed to quantify the risk of retinal break presence using patients' baseline data and findings reported from preoperative ophthalmic tests., Results: Fifty-two eyes (21%) were excluded from appropriate preoperative UWF imaging because of massive lens opacity. The BCVA cutoff point with maximum YI indicating UWF applicability was 0.6 logMAR (YI = 0.3; area under curve [AUC] = 0.7). Among all 246 eyes, preoperative IDO, USG, and UWF showed fair interobserver agreement (all κ > 0.2). According to postoperative IDO findings, the index tests with the highest sensitivity and specificity were USG (100%) and preoperative IDO (99%), respectively., Conclusions: For cataractous eyes without vision-impairing comorbidities, a BCVA better than 0.6 logMAR (Snellen acuity, 20/80) allows for appropriate nonmydriatic standard UWF imaging. In a high-volume clinic equipped with skilled ophthalmic examiners, screening with USG followed by directed IDO allows the efficient identification of retinal breaks in cataractous eyes., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Competing Interests: The authors report no conflicts of interest.

Purpose: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics., Methods: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data., Results: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction., Conclusion: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.

Purpose: Retinitis pigmentosa (RP), the most common inherited retinal disease, is characterized by progressive photoreceptor degeneration. It remains unknown to what extent surviving photoreceptors transduce light and support vision in RP. To address this, we correlated structure and functional measures using adaptive optics scanning laser ophthalmoscopy (AOSLO), adaptive optics microperimetry, and adaptive optics optical coherence tomography (AO-OCT)-based optoretinograms (ORGs)., Methods: Four patients with RP were imaged with AOSLO across the visual field covering the transition zone (TZ) of normal to diseased retina. Cone density was estimated in discrete regions spanning the TZ. Visual sensitivity was assessed by measuring increment thresholds for a 3-arcmin stimulus targeted via active eye tracking in AOSLO. ORGs were measured at the same locations using AO-OCT to assess the cones' functional response to a 528 ± 20-nm stimulus. Individual cone outer segment (COS) lengths were measured from AO-OCT in each subject., Results: Cone density was significantly reduced in patients with RP. Density reduction correlated with TZ location in 3 patients with RP, while a fourth had patches of reduced density throughout the retina. ORG amplitude was reduced in regions of normal and reduced cone density in all patients with RP. ORG response and COS length were positively correlated in controls but not in patients with RP. Despite deficits in cone density and ORG, visual sensitivity remained comparable to controls in three of four patients with RP., Conclusions: ORG-based measures of retinal dysfunction may precede deficits in cone structure and visual sensitivity. ORG is a sensitive measure of RP disease status and has significant potential to provide insight into disease progression and treatment efficacy.

Purpose: To investigate the temporal sequence of changes in the photoreceptor cell mosaic in patients with Stargardt disease type 1, using adaptive optics scanning laser ophthalmoscopy., Methods: Two brothers with genetically confirmed Stargardt disease type 1 underwent comprehensive eye exams, spectral-domain optical coherence tomography, fundus autofluorescence, and adaptive optics scanning laser ophthalmoscopy imaging 3 times over the course of 28 months. Confocal images of the cones and rods were obtained from the central fovea to 10° inferiorly. Photoreceptors were counted in sampling windows at 100- µ m intervals of 200 µ m × 200 µ m for cones and 50 µ m × 50 µ m for rods, using custom cell marking software with manual correction. Photoreceptor density and spacing were measured and compared across imaging sessions using one-way analysis of variance., Results: Adaptive optics scanning laser ophthalmoscopy revealed the younger brother had a 30% decline in foveal cone density after 8 months, followed by complete loss of foveal cones at 28 months; the older brother had no detectable foveal cones at baseline. In the peripheral macula, cone and rod spacings were greater than normal in both patients. The ratio of the cone spacing to rod spacing was greater than normal across all eccentricities, with a greater divergence closer to the foveal center., Conclusion: Cone cell loss may be an early pathogenetic step in Stargardt disease. Adaptive optics scanning laser ophthalmoscopy provides the capability to track individual photoreceptor changes longitudinally in Stargardt disease.

Purpose: Hypo-reflective clumps (HRCs) are structures associated with age-related macular degeneration (AMD) that were identified using flood-illumination adaptive optics ophthalmoscopy (FIAO) and hypothesized to be either macrophages that have accumulated melanin through the phagocytosis of retinal pigmented epithelial (RPE) cell organelles or transdifferentiated RPE cells. HRCs may be autofluorescent (AF) in the near infrared (NIR) but clinical NIR autofluorescence imaging lacks the resolution to answer this question definitively. Here, we used near infrared autofluorescence (NIRAF) imaging in fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to determine whether HRCs are AF., Methods: Patients with AMD and HRCs underwent imaging with FIAO, optical coherence tomography (OCT), and multi-modal AOSLO (confocal, NIRAF, and non-confocal multi-offset detection using a fiber bundle). HRCs were segmented on FIAO and images, co-registered across modalities, and HRC morphometry and AF were quantified., Results: Eight patients participated (mean age = 79 years, standard deviation [SD] = 5.7, range = 69-89 years, and 5 female patients). Most HRCs (86%, n = 153/178) were autofluorescent on AOSLO. HRC AF signal varied but most uniformly dark HRCs on FIAO showed corresponding AF on AOSLO, whereas heterogeneous HRCs showed a smaller AF area or no AF., Conclusions: These findings are consistent with the hypothesis that HRCs contain AF RPE organelles. A small proportion of HRCs were not AF; these may represent macrophages that have not yet accumulated enough organelles to become AF. HRCs may have clinical significance but further study is needed to understand the interplay among HRCs, RPE cells, and macrophages, and their relationship to geographic atrophy (GA) progression in AMD.

Objective: Optical coherence tomography (OCT) investigations have revealed that the thickness of inner retinal layers becomes decreased in multiple sclerosis (MS) patients, compared to healthy control (HC) individuals. To date, a number of studies have applied machine learning to OCT thickness measurements, aiming to enable accurate and automated diagnosis of the disease. However, there have much less emphasis on other less common retinal imaging modalities, like infrared scanning laser ophthalmoscopy (IR-SLO), for classifying MS. IR-SLO uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position., Methods: We incorporated two independent datasets of IR-SLO images from the Isfahan and Johns Hopkins centers, consisting of 164 MS and 150 HC images. A subject-wise data splitting approach was employed to ensure that there was no leakage between training and test datasets. Several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, and a CNN with a custom architecture were employed. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features subsequently given as inputs to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP)., Results: The custom CNN (85 % accuracy, 85 % sensitivity, 87 % specificity, 93 % area under the receiver operating characteristics [AUROC], and 94 % area under the precision-recall curve [AUPRC]) outperformed state-of-the-art models (84 % accuracy, 83 % sensitivity, 87 % specificity, 92 % AUROC, and 94 % AUPRC); however, utilizing a combination of the CAE and MLP yields even superior results (88 % accuracy, 86 % sensitivity, 91 % specificity, 94 % AUROC, and 95 % AUPRC)., Conclusions: We utilized IR-SLO images to differentiate between MS and HC eyes, with promising results achieved using a combination of CAE and MLP. Future multi-center studies involving more heterogenous data are necessary to assess the feasibility of integrating IR-SLO images into routine clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Non-ophthalmologists often lack sufficient operational training to use a direct ophthalmoscope proficiently, resulting in a global deficit of basic ophthalmological skills among general practitioners. This deficiency hampers the timely diagnosis, referral, and intervention of patients. Consequently, the optimization of teaching tools and methods to enhance teaching efficiency is imperative. This study explores the effectiveness of the Eyesi Direct Ophthalmoscope Simulator (Eyesi) as an innovative tool for fundus examination training., Methods: Medical undergraduates were randomly assigned to Group A or B (n = 168). All participants completed a pre-training questionnaire. Group A received Eyesi training, while Group B underwent traditional direct ophthalmoscope (TDO) training. Subsequently, participants answered questionnaires relevant to their respective training methods. Both groups exchanged training tools and completed a summary questionnaire., Results: After training, 54.17% of participants believed that images presented by the Eyesi were consistent with the real fundus. Group A scored significantly higher than Group B in fundus structure recognition and self-confidence in examination. The degree of mastery over fundus theory score increased from 6.10 ± 0.13 to 7.74 ± 0.16 (P < 0.001) in Group A, but Group B did not demonstrate a significant difference. We also compared undergraduates' tendencies for different learning purposes, 75.59% of participants preferred the Eyesi to TDO as a training tool, and 88.41% of participants were receptive to introducing the Eyesi in training., Conclusion: According to subjective participant feedback, Eyesi outperformed TDO in fundus observation, operational practice, and theoretical learning. It effectively equips undergraduates with fundus examination skills, potentially promoting the use of direct ophthalmoscopes in primary medical institutions., (© 2024. The Author(s).)

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings., Competing Interests: Competing interests: JA: none; MS: Heidelberg Engineering (F), CenterVue (F), Carl Zeiss MedicTec (F); LvdE: Heidelberg Engineering (F), CenterVue (F), Carl Zeiss MedicTec (F); T. Ach: Bayer (C), Roche (C), Novartis (C), Novartis (R), Heidelberg Engineering (C), Apellis Pharmaceuticals (C), Nidek (C, R); FGH : Acucela (C, F), Allergan (F), Apellis (C, F), Bayer (C, F), Boehringer-Ingelheim (C), Bioeq/Formycon (F, C), CenterVue (F), Ellex (F), Roche/Genentech (C, F), Geuder (C, F), Graybug (C), Gyroscope (C), Heidelberg Engineering (C, F), IvericBio (C, F), Kanghong (C, F), LinBioscience (C), NightStarX (F), Novartis (C, F), Optos (F), Oxurion (C), Pixium Vision (C, F), Oxurion (C), Stealth BioTherapeutics (C), Zeiss (F, C); WMH: none, (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD)., Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO., Results: FEM were measured with high precision (RMS-S2S = 0.0015 degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea., Conclusions: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.

Purpose: Several machine learning studies have used optical coherence tomography (OCT) for multiple sclerosis (MS) classification with promising outcomes. Infrared reflectance scanning laser ophthalmoscopy (IR-SLO) captures high-resolution fundus images, commonly combined with OCT for fixed B-scan positions. However, no machine learning research has utilized IR-SLO images for automated MS diagnosis., Methods: This study utilized a dataset comprised of IR-SLO images and OCT data from Isfahan, Iran, encompassing 32 MS and 70 healthy individuals. A number of convolutional neural networks (CNNs)-namely, VGG-16, VGG-19, ResNet-50, ResNet-101, and a custom architecture-were trained with both IR-SLO images and OCT thickness maps as two separate input datasets. The highest performing models for each modality were then integrated to create a bimodal model that receives the combination of OCT thickness maps and IR-SLO images. Subject-wise data splitting was employed to prevent data leakage among training, validation, and testing sets., Results: Overall, images of the 102 patients from the internal dataset were divided into test, validation, and training subsets. Subsequently, we employed a bootstrapping approach on the training data through iterative sampling with replacement. The performance of the proposed bimodal model was evaluated on the internal test dataset, demonstrating an accuracy of 92.40% ± 4.1% (95% confidence interval [CI], 83.61-98.08), sensitivity of 95.43% ± 5.75% (95% CI, 83.71-100.0), specificity of 92.82% ± 3.72% (95% CI, 81.15-96.77), area under the receiver operating characteristic (AUROC) curve of 96.99% ± 2.99% (95% CI, 86.11-99.78), and area under the precision-recall curve (AUPRC) of 97.27% ± 2.94% (95% CI, 86.83-99.83). Furthermore, to assess the model generalization ability, we examined its performance on an external test dataset following the same bootstrap methodology, achieving promising results, with accuracy of 85.43% ± 0.08% (95% CI, 71.43-100.0), sensitivity of 97.33% ± 0.06% (95% CI, 83.33-100.0), specificity of 84.6% ± 0.10% (95% CI, 71.43-100.0), AUROC curve of 99.67% ± 0.02% (95% CI, 95.63-100.0), and AUPRC of 99.65% ± 0.02% (95% CI, 94.90-100.0)., Conclusions: Incorporating both modalities improves the performance of automated diagnosis of MS, showcasing the potential of utilizing IR-SLO as a complementary tool alongside OCT., Translational Relevance: Should the results of our proposed bimodal model be validated in future work with larger and more diverse datasets, diagnosis of MS based on both OCT and IR-SLO can be reliably integrated into routine clinical practice.

Purpose: The purpose of this study was to investigate the spatial distribution of human cone photoreceptors and examine cone density differences between the retinal meridians and quadrants., Method: Using adaptive optics scanning laser ophthalmoscopy, the maculae were imaged in 17 eyes of 11 subjects with normal chorioretinal health aged 54 to 72 years. We measured cone density at 325 points within the central 10 degrees radius of the retina. Cone density spatial distributions along the primary retinal meridians and in four macular quadrants (superior-nasal, superior-temporal, inferior-temporal, and inferior-nasal) were analytically modeled using the polynomial function to assess the meridional and quadrantal difference., Results: The mean and 95% confidence interval for the prediction of cone density along the primary retinal meridians was modeled with a 7-degree one-variable polynomial (R2 = 0.9761, root mean squared error [RMSE] = 0.0585). In the 4 retinal quadrants, cone density distribution was described by a 2-variable polynomial with X degree 3 and Y degree 4 (R² = 0.9834, RMSE = 0.0377). The models suggest no statistically significant difference between medians and between quadrants. However, cone density difference at corresponding spatial locations in different areas can be up to 25.6%. The superior-nasal region has more areas with high cone density, followed by quadrants of inferior-nasal, inferior-temporal, and superior-temporal., Conclusions: Analytical modeling provides comprehensive knowledge of cone distribution across the entire macula. Although modeling analysis suggests no statistically significant difference between medians and between quadrants, the remarkable cone density discrepancies in certain regions should be accounted for in applications requiring sensitive detection of cone variation.

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer's disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum., (© 2024. The Author(s).)

This study tested if a high-resolution, multi-modal, multi-scale retinal imaging instrument can provide novel information about structural abnormalities in vivo. The study examined 11 patients with very mild to moderate non-proliferative diabetic retinopathy (NPDR) and 10 healthy subjects using fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), adaptive optics scanning laser ophthalmoscopy (AO-SLO), adaptive optics OCT and OCTA (AO-OCT(A)). Of 21 eyes of 11 patients, 11 had very mild NPDR, 8 had mild NPDR, 2 had moderate NPDR, and 1 had no retinopathy. Using AO-SLO, capillary looping, inflections and dilations were detected in 8 patients with very mild or mild NPDR, and microaneurysms containing hyperreflective granular elements were visible in 9 patients with mild or moderate NPDR. Most of the abnormalities were seen to be perfused in the corresponding OCTA scans while a few capillary loops appeared to be occluded or perfused at a non-detectable flow rate, possibly because of hypoperfusion. In one patient with moderate NPDR, non-perfused capillaries, also called ghost vessels, were identified by alignment of corresponding en face AO-OCT and AO-OCTA images. The combination of multiple non-invasive imaging methods could identify prominent microscopic abnormalities in diabetic retinopathy earlier and more detailed than conventional fundus imaging devices., (© 2024. The Author(s).)

The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive optics scanning laser ophthalmoscope was used to minimize the effects of higher-order aberrations during simultaneous stimulus delivery and retinal imaging. In certain subjects, parafoveal cones were classified as L, M, or S, which permitted the comparison of unique yellow measurements with variations in local L/M ratios within and between observers. Unique yellow shifted to longer wavelengths as stimulus size or duration was reduced. This effect is most pronounced for changes in size and more apparent in the fovea than in the parafovea. The observed variations in unique yellow are not entirely predicted from variations in L/M ratio and therefore implicate neural processes beyond photoreception.

Purpose: To assess longitudinal reproducibility of metrics of foveal density (peak cone density [PCD], cone density centroid [CDC], and 80th percentile centroid area) in participants with normal vision., Methods: Participants (n = 19; five male and 14 female) were imaged at two time points (average interval of 3.2 years) using an adaptive optics scanning light ophthalmoscope (AOSLO). Foveally centered regions of interest (ROIs) were extracted from AOSLO montages. Cone coordinate matrices were semiautomatically derived for each ROI, and cone mosaic metrics were calculated., Results: On average, there were no significant changes in cone mosaic metrics between visits. The average ± SD PCD was 187,000 ± 20,000 cones/mm2 and 189,000 ± 21,700 cones/mm2 for visits 1 and 2, respectively (P = 0.52). The average ± SD density at the CDC was 183,000 ± 19,000 cones/mm2 and 184,000 ± 20,800 cones/mm2 for visits 1 and 2, respectively (P = 0.78). The average ± SD 80th percentile isodensity contour area was 15,400 ± 1800 µm2 and 15,600 ± 1910 µm2 for visits 1 and 2, respectively (P = 0.57)., Conclusions: Foveal cone mosaic density metrics were highly reproducible in the cohort examined here, although further study is required in more diverse populations., Translational Relevance: Determination of the normative longitudinal changes in foveal cone topography is key for evaluating longitudinal measures of foveal cone topography in patients with progressive retinal dystrophies.

Significance: Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) provides a label-free approach to observe functional and molecular changes at cellular scale in vivo . Adding multispectral capabilities improves interpretation of lifetime fluctuations due to individual fluorophores in the retinal pigment epithelium (RPE)., Aim: To quantify the cellular-scale changes in autofluorescence with age and eccentricity due to variations in lipofuscin, melanin, and melanolipofuscin in RPE using multispectral AOFLIO., Approach: AOFLIO was performed on six subjects at seven eccentricities. Four imaging channels ( λ ex / λ em ) were used: 473/SSC, 473/LSC, 532/LSC, and 765/NIR. Cells were segmented and the timing signals of each pixel in a cell were combined into a single histogram, which were then used to compute the lifetime and phasor parameters. An ANOVA was performed to investigate eccentricity and spectral effects on each parameter., Results: A repeatability analysis revealed < 11.8 % change in lifetime parameters in repeat visits for 532/LSC. The 765/NIR and 532/LSC had eccentricity and age effects similar to previous reports. The 473/LSC had a change in eccentricity with mean lifetime and a phasor component. Both the 473/LSC and 473/SSC had changes in eccentricity in the short lifetime component and its relative contribution. The 473/SSC had no trend in eccentricity in phasor. The comparison across the four channels showed differences in lifetime and phasor parameters., Conclusions: Multispectral AOFLIO can provide a more comprehensive picture of changes with age and eccentricity. These results indicate that cell segmentation has the potential to allow investigations in low-photon scenarios such as in older or diseased subjects with the co-capture of an NIR channel (such as 765/NIR) with the desired spectral channel. This work represents the first multispectral, cellular-scale fluorescence lifetime comparison in vivo in the human RPE and may be a useful method for tracking diseases., (© 2024 The Authors.)

Background: Monitoring patients with idiopathic intracranial hypertension (IIH) and optic atrophy may be difficult as papilledema may not be appreciable on ophthalmoscopy. This retrospective chart review evaluated whether papilledema recurrence can be detected in this population using optical coherence tomography (OCT)., Methods: Serial clinical assessments, ophthalmoscopy, and peripapillary OCT were reviewed in a cohort of patients with IIH and optic atrophy. Atrophy was defined as moderate if average peripapillary retinal nerve fiber layer (pRNFL) thickness was ≤80 μm and severe if average pRNFL thickness was ≤60 μm on at least 2 consecutive high-quality OCT scans. Based on the upper tolerance limit of test-retest variability, mean pRNFL elevation of ≥6 μm with subsequent decrease to baseline thickness was considered papilledema., Results: In a cohort of 165 patients with IIH, 32 eyes of 20 patients and 22 eyes of 12 patients demonstrated moderate and severe optic atrophy, respectively. Over a median follow-up of 198.5 weeks (range, 14.0-428.9), 63.3% (19 of 30) of patients had at least 1 episode of relapse, and 50.0% (15 of 30) had at least 1 episode of papilledema. There was a total of 36 relapse episodes, of which 7 occurred in patients with clinical signs and symptoms but no OCT evidence of relapse, 12 occurred in patients with OCT changes but no clinical signs and symptoms of relapse, and 17 occurred in patients with both clinical and OCT evidence to support relapse. The median percent pRNFL increase in the latter 2 groups was 13.7% (range, 7.5-111.8), and 7 eyes (13.0%) of 5 patients (16.7%) showed thickening greater than 20.0% from baseline. The rate, magnitude, and concordance of pRNFL swelling were similar between moderately vs severely atrophic eyes., Conclusions: Papilledema recurrence can be detected in atrophic optic discs using OCT. All patients with atrophic IIH should be longitudinally monitored with pRNFL measurement. Concurrence of other relapse-suggestive features should prompt further evaluation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Background/aims: To investigate the progression of quantitative autofluorescence (qAF) measures and the potential as clinical trial endpoint in ABCA4 -related retinopathy., Methods: In this longitudinal monocentre study, 64 patients with ABCA4 -related retinopathy (age (mean±SD), 34.84±16.36 years) underwent serial retinal imaging, including optical coherence tomography (OCT) and qAF (488 nm excitation) imaging using a modified confocal scanning laser ophthalmoscope with a mean (±SD) review period of 20.32±10.90 months. A group of 110 healthy subjects served as controls. Retest variability, changes of qAF measures over time and its association with genotype and phenotype were analysed. Furthermore, individual prognostic feature importance was assessed, and sample size calculations for future interventional trials were performed., Results: Compared with controls, qAF levels of patients were significantly elevated. The test-retest reliability revealed a 95% coefficient of repeatability of 20.37. During the observation time, young patients, patients with a mild phenotype (morphological and functional) and patients with mild mutations showed an absolute and relative increase in qAF values, while patients with advanced disease manifestation (morphological and functional), and homozygous mutations at adulthood revealed a decrease in qAF. Considering these parameters, required sample size and study duration could significantly be reduced., Conclusion: Under standardised settings with elaborated conditions towards operators and analysis to counterbalance variability, qAF imaging might be reliable, suitable for quantifying disease progression and constitutes a potential clinical surrogate marker in ABCA4 -related retinopathy. Trial design based on patients' baseline characteristics and genotype has the potential to provide benefits regarding required cohort size and absolute number of visits., Competing Interests: Competing interests: PLM received grants and personal fees from Novartis, grants from Bayer and grants Santen outside the submitted work. AT received personal fees from Allergan, grants and personal fees from Bayer, personal fees from Kanghong, personal fees from Heidelberg Engineering, grants and personal fees from Novartis, personal fees from Roche/Genentech, personal fees from Iveric Bio, personal fees from Apellis and personal fees from Thea outside the submitted work. FGH received grants, personal fees and non-financial support from Heidelberg Engineering, grants and personal fees from Novartis, grants and personal fees from Bayer, grants and personal fees from Acucela, grants and personal fees from Alcon, grants and personal fees from Allergan, grants, personal fees and non-financial support from Optos, personal fees from Boehringer Ingelheim and non-financial support from Carl Zeiss MediTec AG outside the submitted work. No other conflicting relationship exists for any author., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the Versatile Teaching Eye (VT Eye), a 3D-printed model eye designed to provide an affordable examination simulator, and to report the results of a pilot program introducing the VT Eye and an ophthalmic training curriculum at a teaching hospital in Ghana., Methods: TinkerCAD was used to design the VT Eye, which was printed with ABS plastic. The design features an adapter that permits use of a smartphone as a digital fundus. We developed a set of digital flashcards allowing for an interactive review of a range of retinal pathologies. An analog fundus was developed for practicing traditional slit lamp and indirect examinations as well as retinal laser practice. The model was used for a period of 2 weeks by ophthalmic trainees at Komfo Anokye Teaching Hospital, Kumasi, Ghana, to practice indirect ophthalmoscopy, slit lamp biomicroscopy, smartphone funduscopy, and retinal image drawing. Results were assessed at by means of a pre-/post-training survey of 6 residents., Results: The VT Eye accommodates diverse fundus examination techniques. Its 3D-printed design ensures cost-effective, high-quality replication. When paired with a 20 D practice examination lens, the digital fundus provides a comprehensive, interactive training environment for <$30.00 (USD). This device allows for indirect examination practice without requiring an indirect headset, which may increase the amount of available practice for trainees early in their careers. In the Ghana pilot program, the model's use in indirect examination training sessions significantly boosted residents' confidence in various examination techniques. Comparing pre- and post-session ratings, average reported confidence levels rose by 30% for acquiring clear views of the posterior pole, 42% for visualizing the periphery, and 141% for capturing important pathology using personal smartphones combined with a 20 D lens (all P < 0.05)., Conclusions: The VT Eye is readily reproducible and can be easily integrated into ophthalmic training curricula, even in regions with limited resources. It offers an effective and affordable training solution, underscoring its potential for global adoption and the benefits of incorporating innovative technologies in medical education., (Copyright ©2024. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of the Digital Journal of Ophthalmology is prohibited.)

Background: Ophthalmoscopy is a valuable tool in clinical practice. We report the use of a novel smartphone-based handheld device for visualisation and photo-documentation of the ocular fundus in veterinary medicine., Methods: Selected veterinary patients of a referral ophthalmology service were included if one or both eyes had clear ocular media, allowing for examination of the fundus. Following pharmacological mydriasis, fundic images were obtained with a handheld fundus camera (Volk VistaView). For comparison, the fundus of a subset of animals was also imaged with a veterinary-specific fundus camera (Optomed Smartscope VET2)., Results: The large field of view achieved by the Volk VistaView allowed for rapid and thorough observation of the ocular fundus in animals, providing a tool to visualise and record common pathologies of the posterior segment. Captured fundic images were sometimes overexposed, with the tapetal fundus artificially appearing hyperreflective when using the Volk VistaView camera, a finding that was less frequent when activating a 'veterinary mode' that reduced the sensitivity of the camera's sensor. The Volk VistaView compared well with the Optomed Smartscope VET2., Limitation: The main study limitation was the small sample size., Conclusions: The Volk VistaView camera was easy to use and provided good-quality fundic images in veterinary patients with healthy or diseased eyes, offering a wide field of view that was ideal for screening purposes., (© 2024 The Authors. Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Purpose of Review: In this review, we explore the investigational applications of optical coherence tomography (OCT) in retinopathy of prematurity (ROP), the insights they have delivered thus far, and key milestones for its integration into the standard of care., Recent Findings: While OCT has been widely integrated into clinical management of common retinal diseases, its use in pediatric contexts has been undermined by limitations in ergonomics, image acquisition time, and field of view. Recently, investigational handheld OCT devices have been reported with advancements including ultra-widefield view, noncontact use, and high-speed image capture permitting real-time en face visualization. These developments are compelling for OCT as a more objective alternative with reduced neonatal stress compared to indirect ophthalmoscopy and/or fundus photography as a means of classifying and monitoring ROP., Summary: OCT may become a viable modality in management of ROP. Ongoing innovation surrounding handheld devices should aim to optimize patient comfort and image resolution in the retinal periphery. Future clinical investigations may seek to objectively characterize features of peripheral stage and explore novel biomarkers of disease activity., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Multicolor (MC) imaging is an innovative pseudocolor fundus imaging modality based on confocal scanning laser ophthalmoscopy. It effectively scans the retina at different depths to create a composite image. The green reflectance image depicts the middle retinal while blue reflectance image provides images of the retinal surface. The infrared reflectance image depicts retinal structures at the level of outer retina and choroid. We systematically analyze published case reports, case series, and original articles on MC imaging where it has helped in discovering additional clinical features of retinal diseases not readily apparent on conventional color fundus photography and played a role in monitoring the response to treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities., Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO., Results: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse., Conclusions: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.

Background/purpose: Central serous chorioretinopathy (CSC) is associated with pachychoroid and dysfunctional retinal pigment epithelium. Autofluorescence (AF) is typically altered. The authors performed this study to quantify these alterations using quantitative AF (qAF) in patients with CSC and in their fellow eye in comparison with a healthy control group., Methods: Patients with CSC and healthy controls were recruited prospectively. All patients received a full clinical examination including best-corrected visual acuity, enhanced depth imaging-optical coherence tomography, and qAF. Quantitative autofluorescence images were taken with a confocal scanning laser ophthalmoscope (Heidelberg Engineering). Quantitative autofluorescence values were assessed in specified regions of the inner eight and the middle ring of the Delori grid., Results: In total, 141 eyes of 77 patients with CSC were included. Ninety eyes had a manifest CSC (group 1) while 51 fellow eyes (group 2) did not show signs of CSC. There were no significant differences of qAF values between these two groups: mean qAF values were 241.3 (inner eight) and 212.8 (middle ring) in group 1 and 235.9 (inner eight) and 210.0 (middle ring) in group 2 ( P = 1.0 and 1.0). We compared these eyes with healthy controls comprising 39 eyes. Quantitative autofluorescence signals (inner eight: 164.7; middle ring: 148.9) differed significantly compared with both CSC manifest ( P < 0.001) and fellow eyes ( P < 0.001)., Conclusion: Our results show that patients with CSC have increased qAF values in both eyes with manifest CSC and asymptomatic, clinically unremarkable fellow eyes in comparison with healthy controls. This finding suggests that qAF alterations are present even before clinical signs can be observed.

Choroideremia (CHM) is an X-linked retinal degeneration leading to loss of the photoreceptors, retinal pigment epithelium (RPE), and choroid. Adaptive optics optoretinography is an emerging technique for noninvasive, objective assessment of photoreceptor function. Here, we investigate parafoveal cone function in CHM using adaptive optics optoretinography and compare with cone structure and clinical assessments of vision. Parafoveal cone mosaics of 10 CHM and four normal-sighted participants were imaged with an adaptive optics scanning light ophthalmoscope. While acquiring video sequences, a 2 s 550Δ10 nm, 450 nW/deg 2 stimulus was presented. Videos were registered and the intensity of each cone in each frame was extracted, normalized, standardized, and aggregated to generate the population optoretinogram (ORG) over time. A gamma-pdf was fit to the ORG and the peak was extracted as ORG amplitude. CHM ORG amplitudes were compared to normal and were correlated with bound cone density, ellipsoid zone to RPE/Bruch's membrane (EZ-to-RPE/BrM) distance, and foveal sensitivity using Pearson correlation analysis. ORG amplitude was significantly reduced in CHM compared to normal (0.22 ± 0.15 vs. 1.34 ± 0.31). In addition, CHM ORG amplitude was positively correlated with cone density, EZ-to-RPE/BrM distance, and foveal sensitivity. Our results demonstrate promise for using ORG as a biomarker of photoreceptor function., (© 2024. The Author(s).)

Purpose: Choroideremia is an X-linked inherited retinal degeneration involving the choriocapillaris, retinal pigment epithelium, and photoreceptors. Adaptive optics scanning light ophthalmoscopy allows visualization of retinal structure at the level of individual cells and is well poised to provide insight into the pathophysiologic mechanisms underpinning the retinal degeneration in choroideremia., Methods: Foveal adaptive optics scanning light ophthalmoscopy images of 102 eyes of 54 individuals with choroideremia were analyzed. Measures were compared with those from standard clinical imaging. Visual acuity was also measured and compared with quantitative foveal metrics., Results: The 3 distinct phenotypes observed were: relatively normal (5 eyes, 4 individuals), spiderweb (9 eyes, 7 individuals), and salt and pepper (87 eyes, 47 individuals). Peak cone density (86 eyes of 51 individuals) was significantly lower in choroideremia than in healthy retinas (P < 0.0001, range: 29,382-157,717 cones/mm2). Peak cone density was significantly related to extent of retained ellipsoid zone on en face optical coherence tomography (r2 = 0.47, P = 0.0009) and inversely related to visual acuity (r2 = 0.20, P = 0.001)., Conclusion: Distinct phenotypes can be observed on adaptive optics scanning light ophthalmoscopy imaging in choroideremia that cannot always be discerned on standard clinical imaging. Quantitative measures on adaptive optics imaging are related to the structural and functional severity of disease.

Objective: Assessment of the utility of smartphone fundoscopy in diagnosing posterior pole pathologies. Methods: An iPhone 12 and a 20D Volk lens were used for smartphone fundoscopy. Patients needing bedside consultation were examined with direct ophthalmoscopy and smartphone fundoscopy. Some patients were examined with this technique after slit lamp examination. Results: Over one year 23 bedside fundus examinations were performed and 2 papilledema were diagnosed. After initial slit lamp examination, photos of various pathologies were taken: age-related macular degeneration, branch retinal artery occlusion, arterial embolus, branch retinal vein occlusion, non-arteritic anterior ischemic optic neuropathy, myelinated retinal nerve fiber layer, choroidal naevus. Discussion: With the 20D lens, the image is overturned, magnified 3,13X, and the field of view is 46°. The utility was demonstrated in literature by teaching students this technique and using it in screening for retinopathy of prematurity. The weighted retinal irradiance was measured in two studies. It was 4,6 mW/cm2 in one and from 0,58 to 2,30 mW/cm2 in the other, within safe limits. Conclusions: Smartphone fundoscopy is a fast, accessible, and safe technique for fundus examinations. Other departments could use it for the diagnosis of papilledema., (#x00A9; The Authors.Romanian Society of Ophthalmology.)

Purpose: Fluorescence lifetime ophthalmoscopy (FLIO) is an emerging clinical modality that could provide biomarkers of retinal health beyond fluorescence intensity. Adaptive optics (AO) ophthalmoscopy provides the confocality to measure fluorescence lifetime (FL) primarily from the retinal pigment epithelium (RPE) whereas clinical FLIO has greater influence from fluorophores in the inner retina and lens. Adaptive optics fluorescence lifetime ophthalmoscopy (AOFLIO) measures of FL in vivo could provide insight into RPE health at different stages of disease. In this study, we assess changes in pentosan polysulfate sodium (PPS) toxicity, a recently described toxicity that has clinical findings similar to advanced age-related macular degeneration., Methods: AOFLIO was performed on three subjects with PPS toxicity (57-67 years old) and six age-matched controls (50-64 years old). FL was analyzed with a double exponential decay curve fit and with phasor analysis. Regions of interest (ROIs) were subcategorized based on retinal features on optical coherence tomography (OCT) and compared to age-matched controls., Results: Twelve ROIs from PPS toxicity subjects met the threshold for analysis by curve fitting and 15 ROIs met the threshold for phasor analysis. Subjects with PPS toxicity had prolonged FL compared to age-matched controls. ROIs of RPE degeneration had the longest FLs, with individual pixels extending longer than 900 ps., Conclusions: Our study shows evidence that AOFLIO can provide meaningful information in outer retinal disease beyond what is obtainable from fluorescence intensity alone. More studies are needed to determine the prognostic value of AOFLIO.

Background/aims: The purpose of this study was to investigate retinal structure in detail of subjects with autosomal-dominant (AD) and autosomal-recessive (AR) PROM1 -associated retinal degeneration ( PROM1 -RD), study design: institutional, cross-sectional study., Methods: Four eyes from four subjects (three with AD and one with AR) PROM1 -RD were investigated by ophthalmic examination including best-corrected visual acuity (BCVA) and multimodal retinal imaging: fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning light ophthalmoscopy. Quantitative assessment of atrophic lesions determined by FAF, thickness of individual retinal layers and cone photoreceptor quantification was performed., Results: BCVA ranged from 20/16 to 20/200. Initial pathological changes included the presence of hyperautofluorescent spots on FAF imaging, while later stages demonstrated discrete areas of atrophy. In all patients, thinning of the outer retinal layers on SD-OCT with varying degrees of atrophy could be detected depending on disease-causing variants and age. Cone density was quantified both in central and/or at different eccentricities from the fovea. Longitudinal assessments were possible in two patients., Conclusions: PROM1 -RD comprises a wide range of clinical phenotypes. Depending on the stage of disease, the cone mosaic in PROM1 -RD is relatively preserved and can potentially be targeted by cone-directed interventions., Competing Interests: Competing interests: SS serves as a consultant for Amgen, Apellis, Alnylam, Pfizer, Abbvie/Allergan, Roche/Genentech, Novartis, Regeneron, 4DMT, Oxurion, Gyroscope, Nanoscope, Heidelberg, Optos, and Centervue. He has received speaker fees from Heidelberg, Carl Zeiss Meditec, Nidek, Topcon, Optos, and Novartis. He has received research instruments from Heidelberg, Carl Zeiss Meditec, Nidek, Topcon, Optos and Centervue., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare peak cone density predicted from outer segment length measured on optical coherence tomography with direct measures of peak cone density from adaptive optics scanning light ophthalmoscopy., Methods: Data from 42 healthy participants with direct peak cone density measures and optical coherence tomography line scans available were used in this study. Longitudinal reflectivity profiles were analyzed using two methods of identifying the boundaries of the ellipsoid and interdigitation zones to estimate maximum outer segment length: peak-to-peak and the slope method. These maximum outer segment length values were then used to predict peak cone density using a previously described geometrical model. A comparison between predicted and direct peak cone density measures was then performed., Results: The mean bias between observers for estimating maximum outer segment length across methods was less than 2 µm. Cone density predicted from the peak-to-peak method against direct cone density measures showed a mean bias of 6,812 cones/mm 2 with 50% of participants displaying a 10% difference or less between predicted and direct cone density values. Cone density derived from the slope method showed a mean bias of -17,929 cones/mm 2 relative to direct cone density measures, with only 41% of participants demonstrating less than a 10% difference between direct and predicted cone density values., Conclusion: Predicted foveal cone density derived from peak-to-peak outer segment length measurements using commercial optical coherence tomography show modest agreement with direct measures of peak cone density from adaptive optics scanning light ophthalmoscopy. The methods used here are imperfect predictors of cone density, however, further exploration of this relationship could reveal a clinically relevant marker of cone structure.

Glaucoma is the leading cause of irreversible blindness worldwide. Often asymptomatic for years, this disease can progress significantly before patients become aware of the loss of visual function. Critical examination of the optic nerve through ophthalmoscopy or using fundus images is a crucial component of glaucoma detection before the onset of vision loss. The vertical cup-to-disc ratio (VCDR) is a key structural indicator for glaucoma, as thinning of the superior and inferior neuroretinal rim is a hallmark of the disease. However, manual assessment of fundus images is both time-consuming and subject to variability based on clinician expertise and interpretation. In this study, we develop a robust and accurate automated system employing deep learning (DL) techniques, specifically the YOLOv7 architecture, for the detection of optic disc and optic cup in fundus images and the subsequent calculation of VCDR. We also address the often-overlooked issue of adapting a DL model, initially trained on a specific population (e.g., European), for VCDR estimation in a different population. Our model was initially trained on ten publicly available datasets and subsequently fine-tuned on the REFUGE dataset, which comprises images collected from Chinese patients. The DL-derived VCDR displayed exceptional accuracy, achieving a Pearson correlation coefficient of 0.91 (P = 4.12 × 10 -412 ) and a mean absolute error (MAE) of 0.0347 when compared to assessments by human experts. Our models also surpassed existing approaches on the REFUGE dataset, demonstrating higher Dice similarity coefficients and lower MAEs. Moreover, we developed an optimization approach capable of calibrating DL results for new populations. Our novel approaches for detecting optic discs and optic cups and calculating VCDR, offers clinicians a promising tool that significantly reduces manual workload in image assessment while improving both speed and accuracy. Most importantly, this automated method effectively differentiates between glaucoma and non-glaucoma cases, making it a valuable asset for glaucoma detection., (© 2024. The Author(s).)

We propose and design a multi-stage cascaded scanning laser ophthalmoscope (SLO) for ultra-wide field (UWF), which uses conicoid mirrors, constructed by conjugation of pupil plane. The vergence uniformity and the angular magnification of a cascaded conicoid mirrors (CCM) system are analyzed recursively and optimized preliminarily to achieve high quality imaging with UWF, and the optimal system with the model eye are obtained by simulation and optimization. Two-stage and three-stage cascaded systems are designed with this method, and the formulas of beam vergence and angular magnification are obtained by theoretical derivation. As compared to the two-stage CCM system, the proposed three-stage cascaded UWF SLO has superior performance in imaging quality. Its average RMS radius of spot diagram is calculated to be 26.372 µm, close to the diffractive limit resolution. The image resolution of human retina can be up to 30 µm with 135° FOV in theory. The three-stage cascaded SLO is more suitable for UWF fundus imaging. This study will be helpful for early screening and accurate diagnosis of various diseases in the peripheral retina.

Aim: To clarify the possibilities and role of posterior segment imaging in patients with neurofibromatosis type I (NF1), and to show the prevalence of this disease in the pediatric population in Slovakia., Material and Methods: Until recently, ophthalmologic consultations in patients with NF1 were limited mainly to the observation of Lisch nodules of the iris and the presence of optic nerve glioma. However, advances in imaging capabilities have made it possible to investigate and describe new f indings concerning the ocular manifestations of this disease. Between October 2020 and November 2021, we examined the anterior and posterior segment of 76 eyes (38 children – 12 boys and 26 girls) with genetically confirmed NF1 gene mutation at our clinic. The age of the patients ranged from 4 to 18 years. The anterior segment was checked for the presence of Lisch nodules biomicroscopically with a slit lamp. On the posterior segment, the presence of choroidal nodules was checked by various imaging methods – fundus camera, infrared confocal selective laser ophthalmoscopy, MultiColor imaging, OCT, and OCT angiography. All the patients had magnetic resonance imaging performed in order to detect potential optic nerve gliomas for the purpose of diagnosis. We observed the correlation between the patients’ age, presence of Lisch nodules and the presence of choroidal nodules. Eight patients also had other manifestations of the disease – optic nerve gliomas or microvascular changes (so-called “corkscrew” vessels)., Results: Out of 38 patients, Lisch iris nodules were present in 20 patients (53%) and choroidal nodules in 24 patients (63%). There was no positive correlation between the presence of these two manifestations within the same patient or eye, but there is a clear correlation between the presence of choroidal nodules and patient age., Conclusion: The results suggest that a previously unknown ocular manifestation of neurofibromatosis type I, namely choroidal nodules, has a higher prevalence than Lisch nodules also in the pediatric population and can be easily visualized using various imaging modalities. It will be important to include follow-up observation of this finding among the standard controls for ocular findings in NF1, and it will be very interesting to correlate this f inding with the exact NF1 mutation