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Introduction: Detection of neurological conditions is of high importance in the current context of increasingly ageing populations. Imaging of the retina and the optic nerve head represents a unique opportunity to detect brain diseases, but requires specific human expertise. We review the current outcomes of artificial intelligence (AI) methods applied to retinal imaging for the detection of neurological and neuro-ophthalmic conditions. Method: Current and emerging concepts related to the detection of neurological conditions, using AI-based investigations of the retina in patients with brain disease were examined and summarised. Results: Papilloedema due to intracranial hypertension can be accurately identified with deep learning on standard retinal imaging at a human expert level. Emerging studies suggest that patients with Alzheimer’s disease can be discriminated from cognitively normal individuals, using AI applied to retinal images. Conclusion: Recent AI-based systems dedicated to scalable retinal imaging have opened new perspectives for the detection of brain conditions directly or indirectly affecting retinal structures. However, further validation and implementation studies are required to better understand their potential value in clinical practice. Keywords: Alzheimer’s disease, deep learning, dementia, optic neuropathy, papilloedema

To evaluate the ability of handheld chromatic pupillometry to reveal and localise retinal neural dysfunction in diabetic patients with and without diabetic retinopathy (DR).This cross-sectional study included 82 diabetics (DM) and 93 controls (60.4 ± 8.4 years, 44.1% males). DM patients included those without (n = 25, 64.7 ± 6.3 years, 44.0% males) and with DR (n = 57, 60.3 ± 8.5 years, 64.9% males). Changes in horizontal pupil radius in response to blue (469 nm) and red (640 nm) light stimuli were assessed monocularly, in clinics, using a custom-built handheld pupillometer. Pupillometric parameters (phasic constriction amplitudes [predominantly from the outer retina], maximal constriction amplitudes [from the inner and outer retina] and post-illumination pupillary responses [PIPRs; predominantly from the inner retina]) were extracted from baseline-adjusted pupillary light response traces and compared between controls, DM without DR, and DR. Net PIPR was defined as the difference between blue and red PIPRs.Phasic constriction amplitudes to blue and red lights were decreased in DR compared to controls (p 0.001; p 0.001). Maximal constriction amplitudes to blue and red lights were decreased in DR compared to DM without DR (p 0.001; p = 0.02), and in DM without DR compared to controls (p 0.001; p = 0.005). Net PIPR was decreased in both DR and DM without DR compared to controls (p = 0.02; p = 0.03), suggesting a wavelength-dependent (and hence retinal) pupillometric dysfunction in diabetic patients with or without DR.Handheld chromatic pupillometry can reveal retinal neural dysfunction in diabetes, even without DR. Patients with DM but no DR displayed primarily inner retinal dysfunction, while patients with DR showed both inner and outer retinal dysfunction.

Xian Hui Lim,1 Monisha Esther Nongpiur,1– 3 Raymond P Najjar,2,3 Quan V Hoang,1– 4 Dan Milea,1– 3 Chee Wai Wong,1– 3 Rahat Husain,1,3 Hla Myint Htoon,2,3 Tin Aung,1– 3,5 Shamira Perera,1– 3 Tina Tzee Ling Wong1– 3,5 1Singapore National Eye Centre, Singapore; 2Singapore Eye Research Institute, Singapore; 3Duke-NUS Medical School, Singapore; 4Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia College of Physicians and Surgeons, New York, NY, USA; 5Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeCorrespondence: Tina Tzee Ling WongSingapore National Eye Centre, 11 Third Hospital Avenue, 168751, SingaporeEmail tina.wong.t.l@singhealth.com.sgPurpose: To investigate features of the steady-state pattern electroretinogram (ssPERG) in subjects with glaucoma (G), high myopia (HM; spherical equivalent ≤-6D) and glaucoma with high myopia (GHM).Patients and Methods: Our study included 48 participants divided into 3 groups (G, HM, and GHM) who each underwent monocular ssPERG testing with Diopsys NOVA PERG protocols. The ConStim protocol detects distinct topographic patterns of dysfunction 16° and 24° around the central macula. MagD is the amplitude of the average signal and MagD/Mag ratio indicates the consistency of the response. ssPERG indices were compared between groups and correlated with functional (ie, visual field mean deviation (VFMD)) and structural (ie, average retinal nerve fibre layer (RNFL) thickness; Cirrus optical coherence tomography) features.Results: Participants had an average age of 59.4± 7.6 years. Mean Humphrey VFMD was − 14.22 ± 2.88dB, − 2.62 ± 1.18dB and − 12.80 ± 2.60dB for G, HM and GHM groups, respectively. Mean RNFL thickness was 63.0 ± 8.20μm, 69.5 ± 15.7μm and 60.6 ± 5.0μm for G, HM and GHM groups, respectively. For the 24° setting, no significant differences were noted for any of the parameters. For the 16° setting, MagD was lower in the GHM group compared to the HM group (0.29μV vs 0.52μV; p = 0.02). Significant differences were noted for the MagD/Mag ratio between HM and G groups (0.58 vs 0.40; p = 0.02) and between HM and GHM groups (0.58 vs 0.35; p = 0.002). There were positive correlations between both MagD 16° and MagD/Mag ratio 16° with VFMD (correlation coefficient [r]=0.37, p = 0.009; and r = 0.44, p = 0.002, respectively) and RNFL (r = 0.43, p = 0.002; and r = 0.48, p = 0.001, respectively).Conclusion: MagD/Mag ratio at 16° was significantly lower in glaucomatous eyes (with or without high myopia) compared to those with high myopia without glaucoma, suggesting that glaucoma has a distinct impact on MagD/Mag ratio at 16° irrespective of the presence of myopia.Keywords: pattern electroretinogram, visual field mean deviation, optical coherence tomography, retinal nerve fibre layer

The quality of ocular fundus photographs can affect the accuracy of the morphologic assessment of the optic nerve head (ONH), either by humans or by deep learning systems (DLS). In order to automatically identify ONH photographs of optimal quality, we have developed, trained, and tested a DLS, using an international, multicentre, multi-ethnic dataset of 5015 ocular fundus photographs from 31 centres in 20 countries participating to the Brain and Optic Nerve Study with Artificial Intelligence (BONSAI). The reference standard in image quality was established by three experts who independently classified photographs as of “good”, “borderline”, or “poor” quality. The DLS was trained on 4208 fundus photographs and tested on an independent external dataset of 807 photographs, using a multi-class model, evaluated with a one-vs-rest classification strategy. In the external-testing dataset, the DLS could identify with excellent performance “good” quality photographs (AUC = 0.93 (95% CI, 0.91–0.95), accuracy = 91.4% (95% CI, 90.0–92.9%), sensitivity = 93.8% (95% CI, 92.5–95.2%), specificity = 75.9% (95% CI, 69.7–82.1%) and “poor” quality photographs (AUC = 1.00 (95% CI, 0.99–1.00), accuracy = 99.1% (95% CI, 98.6–99.6%), sensitivity = 81.5% (95% CI, 70.6–93.8%), specificity = 99.7% (95% CI, 99.6–100.0%). “Borderline” quality images were also accurately classified (AUC = 0.90 (95% CI, 0.88–0.93), accuracy = 90.6% (95% CI, 89.1–92.2%), sensitivity = 65.4% (95% CI, 56.6–72.9%), specificity = 93.4% (95% CI, 92.1–94.8%). The overall accuracy to distinguish among the three classes was 90.6% (95% CI, 89.1–92.1%), suggesting that this DLS could select optimal quality fundus photographs in patients with neuro-ophthalmic and neurological disorders affecting the ONH.

Recent advances in artificial intelligence have provided ophthalmologists with fast, accurate, and automated means for diagnosing and treating ocular conditions, paving the way to a modern and scalable eye care system. Compared to other ophthalmic disciplines, neuro-ophthalmology has, until recently, not benefitted from significant advances in the area of artificial intelligence. In this narrative review, we summarize and discuss recent advancements utilizing artificial intelligence for the detection of structural and functional optic nerve head abnormalities, and ocular movement disorders in neuro-ophthalmology.

The purpose of this study is to characterize the retinal and choroidal vascular networks in some of the most common animal species using swept-source optical coherence tomography angiography (SS-OCTA). Retinal angiographic images were acquired from healthy, anesthetized animals of seven species (mouse, rat, pig, rabbit, guinea pig, chicken, and non-human primate). We generated the enface angiograms to visualize the different retinal vascular plexuses and the choroidal vascular plexus. Quantitative OCTA metrics, including perfusion density, vessel density, and fractal dimension, were compared amongst the different species. There was a noticeable difference in the OCTA enface maps of the distinct vascular layers amongst the various species. Specifically, the non-human primate retina has the highest level of perfusion density and vessel density, whereas the rabbit retina exhibited the lowest level of vessel density. The mouse and the rat retina shared similar vascular patterns, and there was no difference in the OCTA metrics. Using one specific SS-OCTA system for all experiments eliminated multiple instrument-dependent factors, but the lateral resolution was still affected by eye size. Effects of varying lateral resolution on vascular metrics were investigated via a simulation. Overall, we achieved a large field of view of the distinct retinal and choroidal vascular plexuses and quantified the vascular metrics in multiple species, which could serve as protocol guidance and atlas to study the retinal and choroidal vascular abnormalities and their roles in ocular diseases resembling in-vivo histology.

BackgroundTo evaluate the impact of full-spectrum light-emitting diodes (LEDs) mimicking sunlight on ocular axial elongation and refractive error development in a chicken model of myopia.MethodsA total of 39 chicks (Lohmann brown), 1 day-old, were randomly distributed into 3 groups. Animals were housed for 28 days in a temperature-controlled enclosure, under a 12/12h light/dark cycle of isoluminant (∼285 Lux) fluorescent [n = 18, (4000K, FL-4000)] or Sunlike-LED [n=12, (4000K, SL-4000); n = 9, (6500K, SL-6500)] white lights. Myopia was induced monocularly in all chicks by random occlusion of one eye with a frosted diffuser, from day 1 post-hatching (D1) until D14. On D14, diffusers were removed, and recovery from myopia was monitored under the same experimental light condition. Axial length (AL), refractive status, choroidal thickness and anterior chamber depth were recorded on days 1, 7, 14, 22 and 28.Ex vivoscleral collagen fibre thicknesses were measured from scanning electron microscopy images. Differences in outcome measures between eyes and groups were compared using 2-way repeated-measures ANOVA.ResultsThere was no significant difference between groups in the AL and refraction of form-deprived (FD) eyes during form-deprivation (D1 to D14). FD eyes of animals raised under SL-4000 and SL-6500 recovered more rapidly from excessive axial elongation than those of animals raised under FL-4000, by D22 and D28. Correspondingly, the refractive status of FD eyes exposed to SL-4000 and SL-6500 was close to that of control eyes by D28. The choroid became thicker during recovery in FD eyes compared to control eyes, in all groups. Choroidal thickness was significantly greater in FD eyes of chickens raised under SL-6500 than in animals raised under FL-4000 (P< 0.01). The diameter of scleral collagen fibrils was significantly greater in recovering FD eyes of chickens raised under SL-6500, than in those raised under FL-4000 (P= 0.04) and SL-4000 (P= 0.002).ConclusionsCompared to fluorescent light, moderate intensities of full-spectrum Sunlike-LEDs can accelerate recovery from form-deprivation myopia in chickens, potentially through choroid-mediated pathways increasing the diameter of scleral collagen fibrils. This study highlights an important implication of the spectral content of white light on ocular growth and emmetropization.

Deep learning (DL)-based retinal image quality assessment (RIQA) algorithms have been gaining popularity, as a solution to reduce the frequency of diagnostically unusable images. Most existing RIQA tools target retinal conditions, with a dearth of studies looking into RIQA models for optic nerve head (ONH) disorders. The recent success of DL systems in detecting ONH abnormalities on color fundus images prompts the development of tailored RIQA algorithms for these specific conditions. In this review, we discuss recent progress in DL-based RIQA models in general and the need for RIQA models tailored for ONH disorders. Finally, we propose suggestions for such models in the future.

Chromatic pupillometry is an emerging modality in the assessment of retinal and optic nerve disorders. Herein, we evaluate the effect of low and moderate refractive errors on pupillary responses to blue- and red-light stimuli in a healthy older population. This study included 139 participants (≥50 years) grouped by refractive error: moderate myopes (>−6.0D and ≤−3.0D, n = 24), low myopes (>−3.0D and 0.5D and R = −0.26, P R = 0.37, P R = 0.43, P P = 0.45), while constriction amplitudes to red light were greater in hyperopes compared to emmetropes (P = 0.04) at moderate to bright light intensities (12.25–14.0 Log photons/cm²/s). Our results demonstrate that low and moderate myopia do not alter pupillary responses to ramping-up blue- and red-light stimuli in healthy older individuals. Conversely, pupillary responses to red light should be interpreted cautiously in hyperopic eyes.

Background/aimsEarly detection and treatment of glaucoma can delay vision loss. In this study, we evaluate the performance of handheld chromatic pupillometry (HCP) for the objective and rapid detection of functional loss in glaucoma.MethodsIn this clinic-based, prospective study, we enrolled 149 patients (median (IQR) years: 68.5 (13.6) years) with confirmed glaucoma and 173 healthy controls (55.2 (26.7) years). Changes in pupil size in response to 9 s of exponentially increasing blue (469 nm) and red (640 nm) light-stimuli were assessed monocularly using a custom-built handheld pupillometer. Pupillometric features were extracted from individual traces and compared between groups. Features with the highest classification potential, selected using a gradient boosting machine technique, were incorporated into a generalised linear model for glaucoma classification. Receiver operating characteristic curve analyses (ROC) were used to compare the performance of HCP, optical coherence tomography (OCT) and Humphrey Visual Field (HVF).ResultsPupillary light responses were altered in glaucoma compared with controls. For glaucoma classification, HCP yielded an area under the ROC curve (AUC) of 0.94 (95% CI 0.91 to 0.96), a sensitivity of 87.9% and specificity of 88.4%. The classification performance of HCP in early-moderate glaucoma (visual field mean deviation (VFMD) > -12 dB; AUC=0.91 (95% CI 0.87 to 0.95)) was similar to HVF (AUC=0.91) and reduced compared with OCT (AUC=0.97; p=0.01). For severe glaucoma (VFMD ≤ -12 dB), HCP had an excellent classification performance (AUC=0.98, 95% CI 0.97 to 1) that was similar to HVF and OCT.ConclusionHCP allows for an accurate, objective and rapid detection of functional loss in glaucomatous eyes of different severities.

A method for rapid and objective assessment of ocular lens density and transmittance is needed for research and clinical practice. The aim of this study was to determine whether the Purkinje image-based technique can be used for objective and accurate quantification of spectral density and transmittance of ocular media (the mainly crystalline lens) in visible light. Twenty-six individuals (10 young, 9 middle-aged and 7 older individuals) participated in this study. Spectral lens density was evaluated by detecting the intensity of the IVth Purkinje image for different wavelengths. Subsequently, optical density index (ODI), the area under the curve in the lens density spectrum, was calculated and ODIs were compared with clinical lens opacification scales assessed subjectively using a slit lamp. Spectral lens transmittance was estimated from the lens density spectrum. Lens densities were higher in the short wavelength region of the visible spectrum across all age groups. ODI was highly correlated with the clinical opacification scale, while lens transmittance decreased with aging. Our results showed that spectral transmittance of the human crystalline lens can be easily estimated from optical density spectra evaluated objectively and rapidly using the Purkinje image-based technique. Our results provide clinicians and scientists with an accurate, rapid and objective technique for quantification of lens transmittance.

BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmos-copy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 coun-tries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk ap-pearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists RESULTS: The training and validation data sets from 6779 patients included 14,341 photo-graphs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnor-malities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1).CONCLUSIONSA deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke–NUS Ophthalmology and Visual Sci-ences Academic Clinical Program.)

Purpose To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. Design Cross-sectional study. Participants Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of −6 decibels or better on automated perimetry. Methods Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. Main Outcome Measures Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. Results Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm 2 /s) of blue ( P = 0.003) and red ( P r = 0.51, P r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. Conclusions Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.

Background Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by weakness of bodily skeletal muscles. Office-based diagnostic tests such as repetitive nerve stimulation (RNS), single fiber electromyography (SFEMG), and the ice test, are used to refine the differential clinical diagnosis of this disease. Evaluating the clinical sensitivity and specificity of these tests, however, may be confounded by lack of a gold standard, non-blinding, incorporation bias, use of non-representative populations and retrospective data. Objective In this study comprising a large Asian cohort of 127 patients recruited from a Neuro-ophthalmology clinic, we minimized aforementioned confounders and tested the diagnostic value of 3 office-based tests against 2 reference standards of MG by virtue of clinical features, antibody assay and response to treatment. Results Regardless of the reference standard used, the ice and SFEMG tests displayed a higher sensitivity (86.0 to 97.3%) compared to the RNS test (21.3 to 30.6%). Conversely, the specificity of the ice (31.3%) and SFEMG (21.7% and 17.2%) tests were reduced compared to the RNS test (82.6% and 84.4%). The combined use of the ice test and SFEMG, improved the specificity of MG diagnosis to 63.6% and 64.3%, without affecting the sensitivity of those tests. Conclusion Our findings indicate, in an Asian population, high sensitivity of the SFEMG test and suggest the ice test as a valid, affordable and less technically demanding approach to diagnose MG with ocular involvement. Both ice test and SFEMG alone, however, yielded poor specificity. We suggest that the combination of SFEMG and ice test provides a more reliable diagnosis of MG.

Photic stimulation of rods, cones and intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) mediates non-visual light responses, including entrainment of circadian rhythms and pupillary light reflex. Unlike visual responses to photic stimulation, the cerebral correlates of non-visual light responses in humans remains elusive. In this study, we used functional magnetic resonance imaging (fMRI) in 14 healthy young participants, to localize cerebral regions which are differentially activated by metameric light that gave rise to different levels of melanopic excitation. Mean blood oxygen-level dependent (BOLD) responses disclosed bilateral activation of the frontal eye fields during exposure to light geared towards melanopsin. Furthermore, multivariate pattern analyses showed distinct bilateral pattern activity in the inferior temporal gyri and the caudate nuclei. Taken together, our findings suggest that melanopsin-based photoreception activates a cerebral network including frontal regions, classically involved in attention and ocular motor responses.

International audience; BACKGROUND: Myoclonic epilepsy with ragged-red fibers (MERRF, OMIM, #545000) is a rare neurological condition mostly caused by the m.8344A>G mitochondrial DNA pathogenic variant, which can variably affect multiple tissues, including the retina and optic nerve. We report detection of visually asymptomatic neuroretinal loss in 3 patients with genetically confirmed MERRF, using spectral domain optical coherence tomography (SD-OCT).METHODS: All patients underwent a complete ophthalmic examination including assessments of visual acuity, color vision, pupillary reactions, extraocular movements, applanation tonometry, slit-lamp, and dilated fundus examinations. Standard automated perimetry or Goldmann kinetic perimetry was performed, as well as fundus photographs and SD-OCT of the optic nerve head and macula.RESULTS: Despite the absence of visual symptoms in all patients, and normal visual acuity and visual fields in 1 patient, the 3 genetically confirmed patients (point mutations m.8344A>G; age range: 18-62 years) with MERRF-related neurological manifestations, displayed thinning of the retinal nerve fiber layer and variable alterations of the macular ganglion cell complex.CONCLUSIONS: Visually asymptomatic patients with genetically confirmed MERRF can display features of structural neuroretinal loss, quantifiable with SD-OCT. Further investigations are needed to establish whether OCT can assess early neurodegeneration in MERRF.

Beyond image formation, the light that is detected by retinal photoreceptors influences subcortical functions, including circadian timing, sleep, and arousal. The physiology of nonimage-forming (NIF) photoresponses in humans is not well understood; therefore, the development of therapeutic interventions based on this physiology, such as bright light therapy to treat chronobiological disorders, remains challenging.Thirty-nine participants were exposed to 60 minutes of either continuous light (n = 8) or sequences of 2-millisecond light flashes (n = 31) with different interstimulus intervals (ISIs; ranging from 2.5 to 240 seconds). Melatonin phase shift and suppression, along with changes in alertness and sleepiness, were assessed.We determined that the human circadian system integrates flash sequences in a nonlinear fashion with a linear rise to a peak response (ISI = 7.6 ± 0.53 seconds) and a power function decrease following the peak of responsivity. At peak ISI, flashes were at least 2-fold more effective in phase delaying the circadian system as compared with exposure to equiluminous continuous light 3,800 times the duration. Flashes did not change melatonin concentrations or alertness in an ISI-dependent manner.We have demonstrated that intermittent light is more effective than continuous light at eliciting circadian changes. These findings cast light on the phenomenology of photic integration and suggest a dichotomous retinohypothalamic network leading to circadian phase shifting and other NIF photoresponses. Further clinical trials are required to judge the practicality of light flash protocols.Clinicaltrials.gov NCT01119365.National Heart, Lung, and Blood Institute (1R01HL108441-01A1) and Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center.

Deep learning has recently gained high interest in ophthalmology, due to its ability to detect clinically significant features for diagnosis and prognosis. Despite these significant advances, little is known about the ability of various deep learning systems to be embedded within ophthalmic imaging devices, allowing automated image acquisition. In this work, we will review the existing and future directions for "active acquisition" embedded deep learning, leading to as high quality images with little intervention by the human operator. In clinical practice, the improved image quality should translate into more robust deep learning-based clinical diagnostics. Embedded deep learning will be enabled by the constantly improving hardware performance with low cost. We will briefly review possible computation methods in larger clinical systems. Briefly, they can be included in a three-layer framework composed of edge, fog and cloud layers, the former being performed at a device-level. Improved edge layer performance via "active acquisition" serves as an automatic data curation operator translating to better quality data in electronic health records (EHRs), as well as on the cloud layer, for improved deep learning-based clinical data mining., This work has been submitted to "Therapeutic Advances in Ophthalmology" for possible publication 17 pages, 5 figures

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.

Purpose Lack of outdoor time is a known risk factor for myopia. Knowledge of the light levels reaching the eye and exposure settings, including sun-protective measures, is essential for outdoor programs and myopia. We evaluated the impact of sun-protective strategies (hat and sunglasses) on maintaining high illuminance levels to prevent myopia. Methods A child-sized mannequin head was developed to measure light illuminance levels with and without sun-protective equipment, across a wide range of environments in Singapore, outdoors (open park, under a tree, street) and indoors (under a fluorescent illumination with window, under white LED-based lighting without window). A comparison was made between indoor and outdoor light levels that are experienced while children are involved in day-to-day activities. Results Outdoor light levels were much higher (11,080-18,176 lux) than indoors (112-156 lux). The higher lux levels protective of myopia (>1000 lux) were measured at the tree shade (5556-7876 lux) and with hat (4112-8156 lux). Sunglasses showed lux levels between 1792 and 6800 lux. Although with sunglasses readings were lower than tree shade and hat, light levels were still 11 to 43 times higher than indoors. Conclusions Recommendations on spending time outdoors for myopia prevention with adequate sun protection should be provided while partaking in outdoor activities, including protection under shaded areas, wearing a hat or sunglasses, sunscreen, and adequate hydration. Translational relevance Light levels outdoors were higher than indoors and above the threshold illuminance for myopia prevention even with adequate sun-protective measures.

Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance.Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline.Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights.

PURPOSE. Primary open-angle glaucoma (POAG) can be associated with abnormal ocular motor behavior, possibly as a compensatory strategy following visual field loss. The aim of this study was to explore the characteristics of saccadic eye movements in patients with early-stage POAG without any detectable glaucomatous visual field loss (i.e., preperimetric POAG). METHODS. Binocular eye movements were explored in 16 patients with bilateral preperimetric POAG and 16 age-matched healthy controls in a cross-sectional, observational study. Visually guided horizontal prosaccades (58, 108, 158, and 208 amplitude) and antisaccades (128 amplitude) were measured using infrared oculography. The latency, average and peak velocities, amplitude and gain of prosaccades as well as the percentage of errors in the antisaccades task were compared between groups. RESULTS. POAG patients exhibited a reduced average velocity of saccades compared to controls across all amplitudes of peripheral visual target presentation (P = 0.03). Saccades performed by POAG patients were hypometric, and with reduced amplitude (P = 0.007) and gain (P = 0.01) compared to controls. On average, POAG patients displayed more antisaccade errors (40.6%), as compared to controls (23.4%; P = 0.04). CONCLUSIONS. Here, we show that patients with POAG without detectable glaucomatous visual field loss exhibit altered saccadic eye movements. These abnormalities may indicate disordered cortical and subcortical saccadic regulation, either on the basis of subthreshold visual impairment, or as a result of wider disease-associated neurodegeneration. Additional studies, controlling for glaucoma medications, are required to delineate the neural basis of eye movement abnormalities associated with POAG.

Studies in Polar Base stations, where personnel have no access to sunlight during winter, have reported circadian misalignment, free-running of the sleep-wake rhythm, and sleep problems. Here we tested light as a countermeasure to circadian misalignment in personnel of the Concordia Polar Base station during the polar winter. We hypothesized that entrainment of the circadian pacemaker to a 24-h light-dark schedule would not occur in all crew members (n = 10) exposed to 100-300 lux of standard fluorescent white (SW) light during the daytime, and that chronic non-time restricted daytime exposure to melanopsin-optimized blue-enriched white (BE) light would establish an a stable circadian phase, in participants, together with increased cognitive performance and mood levels. The lighting schedule consisted of an alternation between SW lighting (2 weeks), followed by a BE lighting (2 weeks) for a total of 9 weeks. Rest-activity cycles assessed by actigraphy showed a stable rest-activity pattern under both SW and BE light. No difference was found between light conditions on the intra-daily stability, variability and amplitude of activity, as assessed by non-parametric circadian analysis. As hypothesized, a significant delay of about 30 minutes in the onset of melatonin secretion occurred with SW, but not with BE light. BE light significantly enhanced well being and alertness compared to SW light. We propose that the superior efficacy of blue-enriched white light versus standard white light involves melanopsin-based mechanisms in the activation of the non-visual functions studied, and that their responses do not dampen with time (over 9-weeks). This work could lead to practical applications of light exposure in working environment where background light intensity is chronically low to moderate (polar base stations, power plants, space missions, etc.), and may help design lighting strategies to maintain health, productivity, and personnel safety.

The deterioration of sleep in the older population is a prevalent feature that contributes to a decrease in quality of life. Inappropriate entrainment of the circadian clock by light is considered to contribute to the alteration of sleep structure and circadian rhythms in the elderly. The present study investigates the effects of aging on non-visual spectral sensitivity to light and tests the hypothesis that circadian disturbances are related to a decreased light transmittance. In a within-subject design, eight aged and five young subjects were exposed at night to 60 minute monochromatic light stimulations at 9 different wavelengths (420-620 nm). Individual sensitivity spectra were derived from measures of melatonin suppression. Lens density was assessed using a validated psychophysical technique. Although lens transmittance was decreased for short wavelength light in the older participants, melatonin suppression was not reduced. Peak of non-visual sensitivity was, however, shifted to longer wavelengths in the aged participants (494 nm) compared to young (484 nm). Our results indicate that increased lens filtering does not necessarily lead to a decreased non-visual sensitivity to light. The lack of age-related decrease in non-visual sensitivity to light may involve as yet undefined adaptive mechanisms.

Aging is associated with important modifications in the sleep–wake cycle even among healthy individuals. These changes may be related to many factors including changes in the circadian regulation of the sleep–wake cycle (e.g., phase advance, reduced amplitude, vulnerability of the sleep–wake cycle to circadian challenges), in circadian entrainment mechanisms (e.g., habitual light exposure, nonvisual function sensitivity to light), and in molecular and neuronal states of the circadian timing system.

Purpose Although several methods have been proposed to evaluate lens transmittance, to date there is no consensual in vivo approach in clinical practice. The aim of this study was to compare ocular lens density and transmittance measurements obtained by an improved psychophysical scotopic heterochromatic flicker photometry (sHFP) technique to the results obtained by three other measures: a psychophysical threshold technique, a Scheimpflug imaging technique, and a clinical assessment using a validated subjective scale. Methods Forty-three subjects (18 young, 9 middle aged, and 16 older) were included in the study. Individual lens densities were measured and transmittance curves were derived from sHFP indexes. Ocular lens densities were compared across methods by using linear regression analysis. Results The four approaches showed a quadratic increase in lens opacification with age. The sHFP technique revealed that transmittance decreased with age over the entire visual spectrum. This decrease was particularly pronounced between young and older participants in the short (53.03% decrease in the 400-500 nm range) wavelength regions of the light spectrum. Lens density derived from sHFP highly correlated with the values obtained with the other approaches. Compared to other objective measures, sHFP also showed the lowest variability and the best fit with a quadratic trend (r2 = 0.71) of lens density increase as a function of age. Conclusions The sHFP technique offers a practical, reliable, and accurate method to measure lens density in vivo and predict lens transmittance over the visible spectrum. An accurate quantification of lens transmittance should be obtained in clinical practice, but also in research in visual and nonvisual photoreception.

This paper explores the role that measurements of changes in atmospheric oxygen, detected through changes in the O2/N2 ratio of air, can play in improving our understanding of the global carbon cycle. Simple conceptual models are presented in order to clarify the biological and physical controls on the exchanges of O2, CO2, N2, and Ar across the air-sea interface and in order to clarify the relationships between biologically mediated fluxes of oxygen across the air-sea interface and the cycles of organic carbon in the ocean. Predictions of large-scale seasonal variations and gradients in atmospheric oxygen are presented. A two-dimensional model is used to relate changes in the O2/N2 ratio of air to the sources of oxygen from terrestrial and marine ecosystems, the thermal ingassing and outgassing of seawater, and the burning of fossil fuel. The analysis indicates that measurements of seasonal variations in atmospheric oxygen can place new constraints on the large-scale marine biological productivity. Measurements of the north-south gradient and depletion rate of atmospheric oxygen can help determine the rates and geographical distribution of the net storage of carbon in terrestrial ecosystems.