Age-related differences in retinal function and structure in C57BL/6J and Thy1-YFPh mice.

Age-related neuronal adaptations are known to help maintain function. This study aims to examine gross age-related in vivo retinal functional adaptations (using electroretinography) in young and middle aged C57BL/6J and Thy1-YFPh mice and to relate this to in vivo retinal structure (using optical coherence tomography). Electroretinography responses were generally larger in Thy1-YFPh mice than in C57BL/6J mice, with similar in vivo retinal layer thicknesses except for longer inner/outer photoreceptor segment in Thy1-YFPh mice. Relative to 3-month-old mice, 12-month-old mice showed reduced photoreceptor (C57BL/6J 84.0±2.5 %; Thy1-YFPh 80.2±5.2 %) and bipolar cell (C57BL/6J 75.6±2.3 %; Thy1-YFPh 68.1±5.5 %) function. There was relative preservation of ganglion cell function (C57BL/6J 79.7±3.7 %; Thy1-YFPh 91.7±5.0 %) with age, which was associated with increased b-wave (bipolar cell) sensitivities to light. Ganglion cell function was correlated with both b-wave amplitude and sensitivity. This study shows that there are normal age-related adaptations to preserve functional output. Different mouse strains may have varied age-related adaptation capacity and should be taken into consideration when examining age-related susceptibility to injury.

Retinal hyperspectral imaging in mouse models of Parkinson's disease and healthy aging.

Retinal hyperspectral imaging (HSI) is a non-invasive in vivo approach that has shown promise in Alzheimer's disease. Parkinson's disease is another neurodegenerative disease where brain pathobiology such as alpha-synuclein and iron overaccumulation have been implicated in the retina. However, it remains unknown whether HSI is altered in in vivo models of Parkinson's disease, whether it differs from healthy aging, and the mechanisms which drive these changes. To address this, we conducted HSI in two mouse models of Parkinson's disease across different ages; an alpha-synuclein overaccumulation model (hA53T transgenic line M83, A53T) and an iron deposition model (Tau knock out, TauKO). In comparison to wild-type littermates the A53T and TauKO mice both demonstrated increased reflectivity at short wavelengths ~ 450 to 600 nm. In contrast, healthy aging in three background strains exhibited the opposite effect, a decreased reflectance in the short wavelength spectrum. We also demonstrate that the Parkinson's hyperspectral signature is similar to that from an Alzheimer's disease model, 5xFAD mice. Multivariate analyses of HSI were significant when plotted against age. Moreover, when alpha-synuclein, iron or retinal nerve fibre layer thickness were added as a cofactor this improved the R2 values of the correlations in certain groups. This study demonstrates an in vivo hyperspectral signature in Parkinson's disease that is consistent in two mouse models and is distinct from healthy aging. There is also a suggestion that factors including retinal deposition of alpha-synuclein and iron may play a role in driving the Parkinson's disease hyperspectral profile and retinal nerve fibre layer thickness in advanced aging. These findings suggest that HSI may be a promising translation tool in Parkinson's disease.

Platycodi radix aqueous extract salvages doxorubicin-induced senescence by mitochondrial reactive oxygen species reduction in umbilical cord matrix stem cells.

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox-2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox-2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low-dose (0.1 µM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox-damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox-induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox-challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence-associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging-associated ROS with P. radix provides additional insights into the underlying molecular mechanisms.

Altered Outer Retinal Structure, Electrophysiology and Visual Perception in Parkinson's Disease.

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation. OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing. METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls. RESULTS: PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time. CONCLUSIONS: We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD.

Understanding how ageing impacts ganglion cell susceptibility to injury in glaucoma.

Glaucoma is a leading cause of blindness worldwide, with a marked increase in prevalence with advancing age. Due to the multifactorial nature of glaucoma pathogenesis, dissecting how ageing impacts upon glaucoma risk requires analysis and synthesis of evidence from a vast literature. While there is a wealth of human clinical studies examining glaucoma pathogenesis and why older patients have increased risk, many aspects of the disease such as adaptations of retinal ganglion cells to stress, autophagy and the role of glial cells in glaucoma, require the use of animal models to study the complex cellular processes and interactions. Additionally, the accelerated nature of ageing in rodents facilitates the longitudinal study of changes that would not be feasible in human clinical studies. This review article examines evidence derived predominantly from rodent models on how the ageing process impacts upon various aspects of glaucoma pathology from the retinal ganglion cells themselves, to supporting cells and tissues such as glial cells, connective tissue and vasculature, in addition to oxidative stress and autophagy. An improved understanding of how ageing modifies these factors may lead to the development of different therapeutic strategies that target specific risk factors or processes involved in glaucoma.

Measuring the Full-Field Electroretinogram in Rodents.

Electroretinography allows for noninvasive functional assessment of the retina and is a mainstay for preclinical studies of retinal function in health and disease. The full-field electroretinogram is useful for a variety of applications as it returns a functional readout from each of the major cell classes within the retina: photoreceptors, bipolar cells, amacrine cells, and retinal ganglion cells. Rodent models are commonly employed in ocular degeneration studies due to the fast throughput of these mammalian species and the conservation of the electroretinogram from the preclinic to the clinic. Here we describe approaches for in vivo electroretinography in rodent models.

Ohwia caudata aqueous extract attenuates doxorubicin-induced mitochondrial dysfunction in Wharton's jelly-derived mesenchymal stem cells.

Mitochondrial dysfunction has been linked to many diseases, including organ degeneration and cancer. Wharton's jelly-derived mesenchymal stem cells provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. This study focused on screening the senomorphic properties of Ohwia caudata aqueous extract as an emerging strategy for preventing or treating mitochondrial dysfunction in stem cells. Wharton's jelly-derived mesenchymal stem cells were incubated with 0.1 µM doxorubicin, for 24 h to induce mitochondrial dysfunction. Next, the cells were treated with a series concentration of Ohwia caudata aqueous extract (25, 50, 100, and 200 µg/mL) for another 24 h. In addition, an untreated control group and a doxorubicin-induced mitochondrial dysfunction positive control group were maintained under the same conditions. Our data showed that Ohwia caudata aqueous extract markedly suppressed doxorubicin-induced mitochondrial dysfunction by increasing Tid1 and Tom20 expression, decreased reactive oxygen species production, and maintained mitochondrial membrane potential to promote mitochondrial stability. Ohwia caudata aqueous extract retained the stemness of Wharton's jelly-derived mesenchymal stem cells and reduced the apoptotic rate. These results indicate that Ohwia caudata aqueous extract protects Wharton's jelly-derived mesenchymal stem cells against doxorubicin-induced mitochondrial dysfunction and can potentially prevent mitochondrial dysfunction in other cells. This study provides new directions for the medical application of Ohwia caudata.

Retinal Assessment Using In Vivo Electroretinography and Optical Coherence Tomography in Rodent Models of Diabetes.

Electroretinography and optical coherence tomography imaging allow for non-invasive quantitative assessment of the retina. These approaches have become mainstays for identifying the very earliest impact of hyperglycemia on retinal function and structure in animal models of diabetic eye disease. Moreover, they are essential for assessing the safety and efficacy of novel treatment approaches for diabetic retinopathy. Here, we describe approaches for in vivo electroretinography and optical coherence tomography imaging in rodent models of diabetes.

Synthetic Cathinone-Induced Myocarditis and Psychosis: A Case Report.

Psychoactive substances are a diverse group of chemical substances that are ever-evolving structurally. Novel psychoactive substances are being reported in and are becoming increasingly popular in East and Southeast Asia, with synthetic cathinones becoming the drugs of choice. The use of synthetic cathinones has increased significantly over the years. However, the easy accessibility of these substances and their potentially damaging health effects have raised many concerns. Herein, we present the case of a patient who ingested mixed synthetic cathinones and eventually developed acute myocarditis and subsequent psychotic symptoms. The delayed presentation of psychosis coupled with initial cardiovascular symptoms was a unique phenomenon, making differential diagnosis challenging. The association between the use of synthetic cathinones and psychosis and myocarditis should be explored in view of the lack of relevant clinical data and potentially dire outcomes.

The Effect of Aging on Retinal Function and Retinal Ganglion Cell Morphology Following Intraocular Pressure Elevation.

Aging and elevated intraocular pressure (IOP) are two major risk factors for glaucomatous optic neuropathy; a condition characterized by the selective, progressive injury, and subsequent loss of retinal ganglion cells (RGCs). We examined how age modified the capacity for RGCs to functionally recover following a reproducible IOP elevation (50 mmHg for 30 min). We found that RGC functional recovery (measured using electroretinography) was complete by 7 days in 3-month-old mice but was delayed in 12-month-old mice until 14 days. At the 7-day recovery endpoint when RGC function had recovered in young but not older eyes, we examined RGC structural responses to IOP-related stress by analyzing RGC dendritic morphology. ON-RGC cell volume was attenuated following IOP elevation in both young and older mice. We also found that following IOP elevation OFF-RGC dendritic morphology became less complex per cell volume in young mice, an effect that was not observed in older eyes. Our data suggest that adaptations in OFF-RGCs in young eyes were associated with better functional recovery 7 days after IOP elevation. Loss of RGC cellular adaptations may account for delayed functional recovery in older eyes.

1,4-Bis((9H-Carbazol-9-yl)Methyl)Benzene-Containing Electrochromic Polymers as Potential Electrodes for High-Contrast Electrochromic Devices.

Four 1,4-bis((9H-carbazol-9-yl)methyl)benzene-containing polymers (PbCmB, P(bCmB-co-bTP), P(bCmB-co-dbBT), and P(bCmB-co-TF)) were electrosynthesized onto ITO transparent conductive glass and their spectral and electrochromic switching performances were characterized. The PbCmB film displayed four types of color variations (bright gray, dark gray, dark khaki, and dark olive green) from 0.0 to 1.2 V. P(bCmB-co-bTP) displayed a high transmittance variation (∆T = 39.56% at 685 nm) and a satisfactory coloration efficiency (η = 160.5 cm2∙C-1 at 685 nm). Dual-layer organic electrochromic devices (ECDs) were built using four bCmB-containing polycarbazoles and poly(3,4-ethylenedioxythiophene) (PEDOT) as anodes and a cathode, respectively. PbCmB/PEDOT ECD displayed gainsboro, dark gray, and bright slate gray colors at -0.4 V, 1.0 V, and 2.0 V, respectively. The P(bCmB-co-bTP)/PEDOT ECD showed a high ∆T (40.7% at 635 nm) and a high coloration efficiency (η = 428.4 cm2∙C-1 at 635 nm). The polycarbazole/PEDOT ECDs exhibited moderate open circuit memories and electrochemical redox stability. The characterized electrochromic properties depicted that the as-prepared polycarbazoles had a satisfactory application prospect as an electrode for the ECDs.

Hypoxic mesenchymal stem cells ameliorate acute kidney ischemia-reperfusion injury via enhancing renal tubular autophagy.

BACKGROUND: Acute kidney injury (AKI) is an emerging global healthcare issue without effective therapy yet. Autophagy recycles damaged organelles and helps maintain tissue homeostasis in acute renal ischemia-reperfusion (I/R) injury. Hypoxic mesenchymal stem cells (HMSCs) represent an innovative cell-based therapy in AKI. Moreover, the conditioned medium of HMSCs (HMSC-CM) rich in beneficial trophic factors may serve as a cell-free alternative therapy. Nonetheless, whether HMSCs or HMSC-CM mitigate renal I/R injury via modulating tubular autophagy remains unclear. METHODS: Renal I/R injury was induced by clamping of the left renal artery with right nephrectomy in male Sprague-Dawley rats. The rats were injected with either PBS, HMSCs, or HMSC-CM immediately after the surgery and sacrificed 48 h later. Renal tubular NRK-52E cells subjected to hypoxia-reoxygenation (H/R) injury were co-cultured with HMSCs or treated with HMSC-CM to assess the regulatory effects of HSMCs on tubular autophagy and apoptosis. The association of tubular autophagy gene expression and renal recovery was also investigated in patients with ischemic AKI. RESULT: HMSCs had a superior anti-oxidative effect in I/R-injured rat kidneys as compared to normoxia-cultured mesenchymal stem cells. HMSCs further attenuated renal macrophage infiltration and inflammation, reduced tubular apoptosis, enhanced tubular proliferation, and improved kidney function decline in rats with renal I/R injury. Moreover, HMSCs suppressed superoxide formation, reduced DNA damage and lipid peroxidation, and increased anti-oxidants expression in renal tubular epithelial cells during I/R injury. Co-culture of HMSCs with H/R-injured NRK-52E cells also lessened tubular cell death. Mechanistically, HMSCs downregulated the expression of pro-inflammatory interleukin-1ß, proapoptotic Bax, and caspase 3. Notably, HMSCs also upregulated the expression of autophagy-related LC3B, Atg5 and Beclin 1 in renal tubular cells both in vivo and in vitro. Addition of 3-methyladenine suppressed the activity of autophagy and abrogated the renoprotective effects of HMSCs. The renoprotective effect of tubular autophagy was further validated in patients with ischemic AKI. AKI patients with higher renal LC3B expression were associated with better renal recovery. CONCLUSION: The present study describes that the enhancing effect of MSCs, and especially of HMCSs, on tissue autophagy can be applied to suppress renal tubular apoptosis and attenuate renal impairment during renal I/R injury in the rat. Our findings provide further mechanistic support to HMSCs therapy and its investigation in clinical trials of ischemic AKI.

Electrodeposited Copolymers Based on 9,9'-(5-Bromo-1,3-phenylene)biscarbazole and Dithiophene Derivatives for High-Performance Electrochromic Devices.

A 1,3-bis(carbazol-9-yl)benzene derivative (BPBC) was synthesized and its related homopolymer (PBPBC) and copolymers (P(BPBC-co-BT), P(BPBC-co-CDT), and P(BPBC-co-CDTK)) were prepared using electrochemical polymerization. Investigations of polymeric spectra showed that PBPBC film was grey, iron-grey, yellowish-grey, and greyish-green from the neutral to the oxidized state. P(BPBC-co-BT), P(BPBC-co-CDT), and P(BPBC-co-CDTK) films showed multicolor transitions from the reduced to the oxidized state. The transmittance change (ΔT) of PBPBC, P(BPBC-co-BT), P(BPBC-co-CDT), and P(BPBC-co-CDTK) films were 29.6% at 1040 nm, 44.4% at 1030 nm, 22.3% at 1050 nm, and 41.4% at 1070 nm. The coloration efficiency (η) of PBPBC and P(BPBC-co-CDTK) films were evaluated to be 140.3 cm2 C-1 at 1040 nm and 283.7 cm2 C-1 at 1070 nm, respectively. A P(BPBC-co-BT)/PEDOT electrochromic device (ECD) showed a large ΔT (36.2% at 625 nm) and a fast response time (less than 0.5 s), whereas a P(BPBC-co-CDTK)/PEDOT ECD revealed a large η (534.4 cm2 C-1 at 610 nm) and sufficient optical circuit memory.

Retinal ganglion cell dysfunction in mice following acute intraocular pressure is exacerbated by P2X7 receptor knockout.

There is increasing evidence for the vulnerability of specific retinal ganglion cell (RGC) types in those with glaucoma and in animal models. In addition, the P2X7-receptor (P2X7-R) has been suggested to contribute to RGC death following stimulation and elevated IOP, though its role in RGC dysfunction prior to death has not been examined. Therefore, we examined the effect of an acute, non-ischemic intraocular pressure (IOP) insult (50 mmHg for 30 min) on RGC function in wildtype mice and P2X7-R knockout (P2X7-KO) mice. We examined retinal function using electroretinogram recordings and individual RGC responses using multielectrode arrays, 3 days following acute IOP elevation. Immunohistochemistry was used to examine RGC cell death and P2X7-R expression in several RGC types. Acute intraocular pressure elevation produced pronounced dysfunction in RGCs; whilst other retinal neuronal responses showed lesser changes. Dysfunction at 3 days post-injury was not associated with RGC loss or changes in receptive field size. However, in wildtype animals, OFF-RGCs showed reduced spontaneous and light-elicited activity. In the P2X7-KO, both ON- and OFF-RGC light-elicited responses were reduced. Expression of P2X7-R in wildtype ON-RGC dendrites was higher than in other RGC types. In conclusion, OFF-RGCs were vulnerable to acute IOP elevation and their dysfunction was not rescued by genetic ablation of P2X7-R. Indeed, knockout of P2X7-R also caused ON-RGC dysfunction. These findings aid our understanding of how pressure affects RGC function and suggest treatments targeting the P2X7-R need to be carefully considered.

Electrosynthesis of Electrochromic Polymer Membranes Based on 3,6-Di(2-thienyl)carbazole and Thiophene Derivatives.

Five carbazole-containing polymeric membranes (PDTC, P(DTC-co-BTP), P(DTC-co-BTP2), P(DTC-co-TF), and P(DTC-co-TF2)) were electrodeposited on transparent conductive electrodes. P(DTC-co-BTP2) shows a high ΔT (68.4%) at 855 nm. The multichromic properties of P(DTC-co-TF2) membrane range between dark yellow, yellowish-green, gunmetal gray, and dark gray in various reduced and oxidized states. Polymer-based organic electrochromic devices are assembled using 2,2'-bithiophene- and 2-(2-thienyl)furan-based copolymers as anodic membranes, and poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonic acid) (PEDOT-PSS) as the cathodic membrane. P(DTC-co-TF)/PEDOT-PSS electrochromic device (ECD) displays a high transmittance change (ΔT%) (43.4%) at 627 nm as well as a rapid switching time (less than 0.6 s) from a colored to a bleached state. Moreover, P(DTC-co-TF2)/PEDOT-PSS ECD shows satisfactory optical memory (the transmittance change is less than 2.9% in the colored state) and high coloration efficiency (512.6 cm2 C-1) at 627 nm.

Potential mechanisms of retinal ganglion cell type-specific vulnerability in glaucoma.

Glaucoma is a neurodegenerative disease characterised by progressive damage to the retinal ganglion cells (RGCs), the output neurons of the retina. RGCs are a heterogenous class of retinal neurons which can be classified into multiple types based on morphological, functional and genetic characteristics. This review examines the body of evidence supporting type-specific vulnerability of RGCs in glaucoma and explores potential mechanisms by which this might come about. Studies of donor tissue from glaucoma patients have generally noted greater vulnerability of larger RGC types. Models of glaucoma induced in primates, cats and mice also show selective effects on RGC types - particularly OFF RGCs. Several mechanisms may contribute to type-specific vulnerability, including differences in the expression of calcium-permeable receptors (for example pannexin-1, P2X7, AMPA and transient receptor potential vanilloid receptors), the relative proximity of RGCs and their dendrites to blood supply in the inner plexiform layer, as well as differing metabolic requirements of RGC types. Such differences may make certain RGCs more sensitive to intraocular pressure elevation and its associated biomechanical and vascular stress. A greater understanding of selective RGC vulnerability and its underlying causes will likely reveal a rich area of investigation for potential treatment targets.

Prevalence of glaucoma in the Australian National Eye Health Survey.

AIM: To estimate the prevalence of glaucoma in Australia. METHODS: This was a population-based study of 3098 non-Indigenous Australians (50-98 years) and 1738 Indigenous Australians (40-92 years) stratified by remoteness. Each participant underwent a standard examination that included visual field assessment, tonometry and non-mydriatic fundus photography. Two fellowship-trained glaucoma specialists independently assessed relevant case notes (past ocular history, best-corrected visual acuity, frequency doubling technology visual fields, Van Herick grade, intraocular pressure and optic disc-centred photographs) and assigned a diagnosis ranked on a scale of certainty: none, possible, probable or definite glaucoma. RESULTS: A total of 4792 (99.1%, 3062 non-Indigenous and 1730 Indigenous) participants had retinal photographs in at least one eye that were gradable for glaucoma. The weighted prevalence of glaucoma (definite) in non-Indigenous Australians and Indigenous Australians was 1.5% (95% CI 1.0 to 2.2) and 0.6% (95% CI 0.4 to 1.1), respectively. When definite and probable cases of glaucoma were combined, rates were 3.4% (95% CI 2.7 to 4.3) among non-Indigenous and 1.6% (95% CI 1.1 to 2.3) in Indigenous Australians. Only 52.4% of non-Indigenous Australians and 28.0% of Indigenous Australians with glaucoma self-reported a known history of glaucoma. CONCLUSION: We estimate that 198 923 non-Indigenous Australians aged 50 years and over and 2139 Indigenous Australians aged 40 years and over have glaucoma. Given the high rates of undiagnosed glaucoma coupled with a significant ageing of the Australian population, improvements in case detection and access to low vision rehabilitation services may be required to cope with the growing burden of glaucoma.

Incidence and correction of vision impairment among elderly population in southern urban China.

IMPORTANCE: Data on the incidence of presenting vision impairment (PVI) and spectacle coverage rate (SCR) in urban China is limited. BACKGROUND: To estimate the 6-year incidence and risk factors for PVI and the SCR in urban Southern China. DESIGN: Population-based cohort study. PARTICIPANTS: A total of 1817 participants aged ≥35 years were identified from Guangzhou in 2008 at baseline and 1427 attended follow-up examination in 2014. METHODS: Presenting visual acuity (PVA) was measured using the ETDRS chart with habitual spectacles. Participants with PVA ≤20/40 underwent subjective refraction at the follow-up visit. Incidence of PVI was calculated using the WHO and US criteria, respectively. The met-need SCR was defined as the percentage of participants with PVA <20/40 that had been improved to ≥20/40 after correction. MAIN OUTCOME MEASURES: Incidence of PVI and SCR. RESULTS: Incidence of PVI was 8.3% (95%CI, 6.9-9.8) and 12.2% (95%CI, 10.5-14.0) based on the WHO and US definition, respectively. Older age, female, lower education level, more myopic spherical equivalent and worse PVA at baseline were significantly related to a higher PVI incidence based on the WHO criteria, with similar associations identified using the US criteria except for gender. The overall met-need SCR was 42.5%, and was lower among the elderly, more hyperopic participants or participants with lower education level. CONCLUSIONS AND RELEVANCE: The incidence of PVI is high in urban Southern China and spectacle wearing is available in less than half of those in need. This highlights the needs to promote spectacle coverage even in the urban population.

Visualizing Deep Learning Models for the Detection of Referable Diabetic Retinopathy and Glaucoma.

Importance: Convolutional neural networks have recently been applied to ophthalmic diseases; however, the rationale for the outputs generated by these systems is inscrutable to clinicians. A visualization tool is needed that would enable clinicians to understand important exposure variables in real time. Objective: To systematically visualize the convolutional neural networks of 2 validated deep learning models for the detection of referable diabetic retinopathy (DR) and glaucomatous optic neuropathy (GON). Design, Setting, and Participants: The GON and referable DR algorithms were previously developed and validated (holdout method) using 48 116 and 66 790 retinal photographs, respectively, derived from a third-party database (LabelMe) of deidentified photographs from various clinical settings in China. In the present cross-sectional study, a random sample of 100 true-positive photographs and all false-positive cases from each of the GON and DR validation data sets were selected. All data were collected from March to June 2017. The original color fundus images were processed using an adaptive kernel visualization technique. The images were preprocessed by applying a sliding window with a size of 28 × 28 pixels and a stride of 3 pixels to crop images into smaller subimages to produce a feature map. Threshold scales were adjusted to optimal levels for each model to generate heat maps highlighting localized landmarks on the input image. A single optometrist allocated each image to predefined categories based on the generated heat map. Main Outcomes and Measures: Visualization regions of the fundus. Results: In the GON data set, 90 of 100 true-positive cases (90%; 95% CI, 82%-95%) and 15 of 22 false-positive cases (68%; 95% CI, 45%-86%) displayed heat map visualization within regions of the optic nerve head only. Lesions typically seen in cases of referable DR (exudate, hemorrhage, or vessel abnormality) were identified as the most important prognostic regions in 96 of 100 true-positive DR cases (96%; 95% CI, 90%-99%). In 39 of 46 false-positive DR cases (85%; 95% CI, 71%-94%), the heat map displayed visualization of nontraditional fundus regions with or without retinal venules. Conclusions and Relevance: These findings suggest that this visualization method can highlight traditional regions in disease diagnosis, substantiating the validity of the deep learning models investigated. This visualization technique may promote the clinical adoption of these models.

An Automated Grading System for Detection of Vision-Threatening Referable Diabetic Retinopathy on the Basis of Color Fundus Photographs.

OBJECTIVE: The goal of this study was to describe the development and validation of an artificial intelligence-based, deep learning algorithm (DLA) for the detection of referable diabetic retinopathy (DR). RESEARCH DESIGN AND METHODS: A DLA using a convolutional neural network was developed for automated detection of vision-threatening referable DR (preproliferative DR or worse, diabetic macular edema, or both). The DLA was tested by using a set of 106,244 nonstereoscopic retinal images. A panel of ophthalmologists graded DR severity in retinal photographs included in the development and internal validation data sets (n = 71,043); a reference standard grading was assigned once three graders achieved consistent grading outcomes. For external validation, we tested our DLA using 35,201 images of 14,520 eyes (904 eyes with any DR; 401 eyes with vision-threatening referable DR) from population-based cohorts of Malays, Caucasian Australians, and Indigenous Australians. RESULTS: Among the 71,043 retinal images in the training and validation data sets, 12,329 showed vision-threatening referable DR. In the internal validation data set, the area under the curve (AUC), sensitivity, and specificity of the DLA for vision-threatening referable DR were 0.989, 97.0%, and 91.4%, respectively. Testing against the independent, multiethnic data set achieved an AUC, sensitivity, and specificity of 0.955, 92.5%, and 98.5%, respectively. Among false-positive cases, 85.6% were due to a misclassification of mild or moderate DR. Undetected intraretinal microvascular abnormalities accounted for 77.3% of all false-negative cases. CONCLUSIONS: This artificial intelligence-based DLA can be used with high accuracy in the detection of vision-threatening referable DR in retinal images. This technology offers potential to increase the efficiency and accessibility of DR screening programs.