Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment.

Topic: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment. Clinical relevance: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy. Methods: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction). Results: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors. Conclusion: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Saffron therapy for the ongoing treatment of age-related macular degeneration.

OBJECTIVE: To assess the long-term efficacy and safety of oral saffron, a natural antioxidant, in treating mild/moderate age-related macular degeneration (AMD). METHODS AND ANALYSIS: Open-label, extension trial of 93 adults (>50 years) with mild/moderate AMD and vision >20/70 Snellen equivalent in at least 1 eye. Exclusion criteria included confounding visual lesions or significant gastrointestinal disease impairing absorption.Participants were given oral saffron supplementation (20 mg/day) for 12 months. Those already consuming Age-Related Eye Diseases Study (AREDS) supplements or equivalent maintained these.Primary outcomes included changes in multifocal electroretinogram (mfERG) response density and latency, and changes in best-corrected visual acuity (BCVA). Secondary outcomes included safety outcomes, changes in mfERG and BCVA among participants on AREDS supplements and changes in microperimetry. RESULTS: At 12 months, mean mfERG response density was significantly higher in rings 1, 2 and overall (p<0.001 for all) but not in rings 3-6, and there was no difference in response between those taking AREDS supplements and those not (p>0.05). Mean mfERG latency was not significantly different in any of rings 1-6 or overall (p>0.05 for all), again with no difference between those taking AREDS supplements or not (p>0.05). Mean BCVA was 1.6 letters worse (p<0.05) with no difference between those on AREDS supplements or not, and this may have been related to cataract progression. No saffron-related serious adverse events were detected. CONCLUSION: Saffron supplementation modestly improved mfERG responses in participants with AMD, including those using AREDS supplements. Given the chronic nature of AMD, longer-term supplementation may produce greater benefits.

Leaffooted Bugs: Insect Pest Species of Growing Concern for Agriculture.

Leptoglossus (Hemiptera: Coreidae) are a diverse genus of phytophagous insects. Literature regarding Leptoglossus has increased as species are identified as emerging agricultural pests or reported outside of their native range. Within Leptoglossus, five species dominate the literature and are known pests and vectors of plant pathogenic microbes in several major crops. Despite the increasing profile of Leptoglossus, current monitoring and management methods rely primarily on visual inspection, and semiochemical tools have yet to be developed. This Perspective identifies and discusses gaps in the Leptoglossus literature as well as areas of research needed for the development of effective tools for monitoring insect populations and enabling informed pest-management practices.

Maize terpene synthase 1 impacts insect behavior via the production of monoterpene volatiles ß-myrcene and linalool.

Plant-derived volatiles are important mediators of plant-insect interactions as they can provide cues for host location and quality, or act as direct or indirect defense molecules. The volatiles produced by Zea mays (maize) include a range of terpenes, likely produced by several of the terpene synthases (TPS) present in maize. Determining the roles of specific terpene volatiles and individual TPSs in maize-insect interactions is challenging due to the promiscuous nature of TPSs in vitro and their potential for functional redundancy. In this study, we used metabolite GWAS of a sweetcorn diversity panel infested with Spodoptera frugiperda (fall armyworm) to identify genetic correlations between TPSs and individual volatiles. This analysis revealed a correlation between maize terpene synthase 1 (ZmTPS1) and emission of the monoterpene volatiles linalool and ß-myrcene. Electroantennogram assays showed gravid S. frugiperda could detect both linalool and ß-myrcene. Quantification of headspace volatiles in a maize tps1 loss-of-function mutant confirmed that ZmTPS1 is an important contributor to linalool and ß-myrcene emission in maize. Furthermore, pairwise choice assays between tps1 mutant and wild-type plants showed that ZmTPS1, and by extension its volatile products, aid host location in the chewing insect S. frugiperda, yet repel the sap-sucking pest, Rhopalosiphum maidis (corn leaf aphid). On the other hand, ZmTPS1 had no impact on indirect defense via the recruitment of the parasitoid Cotesia marginiventris. ZmTPS1 is therefore an important mediator of the interactions between maize and its insect pests.

Diabetic Macular Oedema Guidelines: An Australian Perspective.

The number of people living with diabetes is expected to rise to 578 million by 2030 and to 700 million by 2045, exacting a severe socioeconomic burden on healthcare systems around the globe. This is also reflected in the increasing numbers of people with ocular complications of diabetes (namely, diabetic macular oedema (DMO) and diabetic retinopathy (DR)). In one study examining the global prevalence of DR, 35% of people with diabetes had some form of DR, 7% had PDR, 7% had DMO, and 10% were affected by these vision-threatening stages. In many regions of the world (Australia included), DR is one of the top three leading causes of vision loss amongst working age adults (20-74 years). In the management of DMO, the landmark ETDRS study demonstrated that moderate visual loss, defined as doubling of the visual angle, can be reduced by 50% or more by focal/grid laser photocoagulation. However, over the last 20 years, antivascular endothelial growth factor (VEGF) and corticosteroid therapies have emerged as alternative options for the management of DMO and provided patients with choices that have higher chances of improving vision than laser alone. In Australia, since the 2008 NHMRC guidelines, there have been significant developments in both the treatment options and treatment schedules for DMO. This working group was therefore assembled to review and address the current management options available in Australia.

Early infestation volatile biomarkers of fruit fly Bactrocera dorsalis (Hendel) ovipositional activity in mango (Mangifera indica L.).

Infestation of agricultural commodities by insect pests results in significant economic, import and export, food safety, and invasive insect introduction issues for growers, consumers, and inspectors. The Oriental fruit fly (Bactrocera dorsalis) is considered a highly invasive insect pest with populations reported in more than 60 countries, with prevalent distributions in Asia and Africa. B. dorsalis is phytophagous with a host range encompassing hundreds of fruits and vegetables. Damage to the fruit or vegetable is inflicted through oviposition and subsequent larval feeding resulting in spoilage. Early detection of insect pest infestations is a critical component for ensuring food safety as well as controlling introduction and spread of invasive insects. However, detection of ovipositional activity and early larval development is visually difficult, thus rapid and non-destructive detection often relies on odors associated with infestation. We investigated the odors of mangoes (Mangifera indica L.) infested with B. dorsalis and compared the volatile profiles of infested mangoes to non-infested and mechanically damaged mangoes 24 h post-infestation. GC-MS and multivariate analyses provided the identification of eleven compounds unique to infested mangoes compared to mechanically damaged or non-infested fruit. Results indicated compositional and quantitative differentiation of volatile profiles among treatments for detection of infested fruit at quality checks or points of commerce.

Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults: The Age-Related Eye Disease Study (AREDS) and AREDS2.

Importance: Low dietary nitrate intake has previously been suggested to be a risk factor for age-related macular degeneration (AMD) progression; however, this finding has not been replicated in other cohorts or adjusted for dietary patterns. Objective: To determine whether there is an association between dietary nitrate intake and AMD progression. Design, Setting, and Participants: This cohort study analyzed data from the prospective Age-Related Eye Disease Study (AREDS) and AREDS2 randomized clinical trial cohorts and their extended follow-up studies, which were conducted in multicenter outpatient retinal practices. Participants in both trials had non-late AMD in at least 1 eye. Data were analyzed from March 1, 2020, to September 30, 2022. Exposure: Dietary nitrate intake. Main Outcomes and Measures: Association between dietary nitrate intake and development of late AMD (neovascular AMD [nAMD] or geographic atrophy [GA]) or large drusen. The interactions of dietary patterns, with common at-risk single-nucleotide polymorphisms, were also assessed. Results: In the combined AREDS/AREDS2 cohort of 7788 participants (4288 AREDS participants and 3610 AREDS2 participants [110 of whom participated in both studies]), there were 13 511 eligible eyes. The combined cohort comprised 4396 women (56%) and 3392 men (44%), and the combined mean (SD) age was 71.1 (6.6) years. Dietary nitrate intake was associated with a decreased risk of progression to late AMD in the combined AREDS/AREDS2 cohort (hazard ratio [HR], 0.77 [95% CI, 0.69-0.86] for quartile 4 vs quartile 1 of intake) and a decreased risk of GA (HR, 0.71 [95% CI, 0.61-0.83]) and nAMD (HR, 0.85 [95% CI, 0.73-0.99]). In AREDS, increased nitrate intake (quartile 4 vs quartile 1) was associated with a decreased risk of late AMD (HR, 0.77 [95% CI, 0.65-0.91]) and GA (HR, 0.80 [95% CI, 0.65-0.97]) but not nAMD; in AREDS2, there was no association between nitrate intake (quartile 4 vs quartile 1) and late AMD (HR, 0.90 [95% CI, 0.80-1.02]) or nAMD (HR, 0.93 [95% CI, 0.78-1.11]). There was a correlation between Mediterranean dietary patterns and dietary nitrate intake (r = 0.52, P < .001). Conclusions and Relevance: The findings of this cohort study suggest that dietary nitrate intake was associated with lower AMD risk. However, this association disappeared after adjusting for Mediterranean dietary patterns. These results are subject to potential bias and are hypothesis-generating in nature; therefore, they are insufficient to support new clinical recommendations. Previously described associations between dietary nitrate intake and AMD may in fact represent overall dietary patterns. Further research is needed before dietary nitrate intake can be recommended as a therapy for AMD.

Proliferative Retinopathy Associated with Repeated High-Altitude Exposure in a Patient with Sickle Cell Trait.

Broadhead Geoffrey K., Henry E. Wiley, David Peprah, Kenneth Olumba, and Alisa T. Thavikulwat. Proliferative retinopathy associated with repeated high-altitude exposure in a patient with sickle cell trait. High Alt Med Biol. 23:369-371, 2022.-Sickle cell trait (SCT), a carrier state characterized by one normal copy of the beta-globin gene (producing hemoglobin A) and one abnormal variant (producing hemoglobin S), is typically asymptomatic and very low risk for manifestations of hemoglobinopathy, including development of retinopathy. Reported cases of proliferative retinopathy in patients with SCT have occurred in the context of concurrent ocular or systemic disease. We report a case of an otherwise healthy patient with SCT who developed proliferative retinopathy requiring surgical intervention in the setting of significant exposure to high altitude through increased work hours as a flight attendant in the month leading to her presentation. Significant high-altitude exposure may contribute to development of retinopathy in patients with sickle trait. Practitioners should consider the possibility of sickle cell retinopathy in patients with sickle trait in these circumstances.

Genetic and spatial variation in vegetative and floral traits across a hybrid zone.

PREMISE: Genetic variation influences the potential for evolution to rescue populations from impacts of environmental change. Most studies of genetic variation in fitness-related traits focus on either vegetative or floral traits, with few on floral scent. How vegetative and floral traits compare in potential for adaptive evolution is poorly understood. METHODS: We measured variation across source populations, planting sites, and genetic families for vegetative and floral traits in a hybrid zone. Seeds from families of Ipomopsis aggregata, I. tenuituba, and F1 and F2 hybrids of the two species were planted into three common gardens. Measured traits included specific leaf area (SLA), trichomes, water-use efficiency (WUE), floral morphology, petal color, nectar, and floral volatiles. RESULTS: Vegetative traits SLA and WUE varied greatly among planting sites, while showing weak or no genetic variation among source populations. Specific leaf area and trichomes responded plastically to snowmelt date, and SLA exhibited within-population genetic variation. All aspects of floral morphology varied genetically among source populations, and corolla length, corolla width, and sepal width varied genetically within populations. Heritability was not detected for volatiles due to high environmental variation, although one terpene had high evolvability, and high emission of two terpenes, a class of compounds emitted more strongly from the calyx than the corolla, correlated genetically with sepal width. Environmental variation across sites was weak for floral morphology and stronger for volatiles and vegetative traits. The inheritance of three of four volatiles departed from additive. CONCLUSIONS: Results indicate stronger genetic potential for evolutionary responses to selection in floral morphology compared with scent and vegetative traits and suggest potentially adaptive plasticity in some vegetative traits.

Evolution of selfing syndrome and its influence on genetic diversity and inbreeding: A range-wide study in Oenothera primiveris.

PREMISE: To avoid inbreeding depression, plants have evolved diverse breeding systems to favor outcrossing, such as self-incompatibility. However, changes in biotic and abiotic conditions can result in selective pressures that lead to a breakdown in self-incompatibility. The shift to increased selfing is commonly associated with reduced floral features, lower attractiveness to pollinators, and increased inbreeding. We tested the hypothesis that the loss of self-incompatibility, a shift to self-fertilization (autogamy), and concomitant evolution of the selfing syndrome (reduction in floral traits associated with cross-fertilization) will lead to increased inbreeding and population differentiation in Oenothera primiveris. Across its range, this species exhibits a shift in its breeding system and floral traits from a self-incompatible population with large flowers to self-compatible populations with smaller flowers. METHODS: We conducted a breeding system assessment, evaluated floral traits in the field and under controlled conditions, and measured population genetic parameters using RADseq data. RESULTS: Our results reveal a bimodal transition to the selfing syndrome from the west to the east of the range of O. primiveris. This shift includes variation in the breeding system and the mating system, a reduction in floral traits (flower diameter, herkogamy, and scent production), a shift to greater autogamy, reduced genetic diversity, and increased inbreeding. CONCLUSIONS: The observed variation highlights the importance of range-wide studies to understand breeding system variation and the evolution of the selfing syndrome within populations and species.

Mutualism has its limits: consequences of asymmetric interactions between a well-defended plant and its herbivorous pollinator.

Concern for pollinator health often focuses on social bees and their agricultural importance at the expense of other pollinators and their ecosystem services. When pollinating herbivores use the same plants as nectar sources and larval hosts, ecological conflicts emerge for both parties, as the pollinator's services are mitigated by herbivory and its larvae are harmed by plant defences. We tracked individual-level metrics of pollinator health-growth, survivorship, fecundity-across the life cycle of a pollinating herbivore, the common hawkmoth, Hyles lineata, interacting with a rare plant, Oenothera harringtonii, that is polymorphic for the common floral volatile (R)-(-)-linalool. Linalool had no impact on floral attraction, but its experimental addition suppressed oviposition on plants lacking linalool. Plants showed robust resistance against herbivory from leaf-disc to whole-plant scales, through poor larval growth and survivorship. Higher larval performance on other Oenothera species indicates that constitutive herbivore resistance by O. harringtonii is not a genus-wide trait. Leaf volatiles differed among populations of O. harringtonii but were not induced by larval herbivory. Similarly, elagitannins and other phenolics varied among plant tissues but were not herbivore-induced. Our findings highlight asymmetric plant-pollinator interactions and the importance of third parties, including alternative larval host plants, in maintaining pollinator health. This article is part of the theme issue 'Natural processes influencing pollinator health: from chemistry to landscapes'.

Differential gene expression associated with a floral scent polymorphism in the evening primrose Oenothera harringtonii (Onagraceae).

BACKGROUND: Plant volatiles play an important role in both plant-pollinator and plant-herbivore interactions. Intraspecific polymorphisms in volatile production are ubiquitous, but studies that explore underlying differential gene expression are rare. Oenothera harringtonii populations are polymorphic in floral emission of the monoterpene (R)-(-)-linalool; some plants emit (R)-(-)-linalool (linalool+ plants) while others do not (linalool- plants). However, the genes associated with differential production of this floral volatile in Oenothera are unknown. We used RNA-Seq to broadly characterize differential gene expression involved in (R)-(-)-linalool biosynthesis. To identify genes that may be associated with the polymorphism for this trait, we used RNA-Seq to compare gene expression in six different Oenothera harringtonii tissues from each of three linalool+ and linalool- plants. RESULTS: Three clusters of differentially expressed genes were enriched for terpene synthase activity: two were characterized by tissue-specific upregulation and one by upregulation only in plants with flowers that produce (R)-(-)-linalool. A molecular phylogeny of all terpene synthases identified two putative (R)-(-)-linalool synthase transcripts in Oenothera harringtonii, a single allele of which is found exclusively in linalool+ plants. CONCLUSIONS: By using a naturally occurring polymorphism and comparing different tissues, we were able to identify candidate genes putatively involved in the biosynthesis of (R)-(-)-linalool. Expression of these genes in linalool- plants, while low, suggests a regulatory polymorphism, rather than a population-specific loss-of-function allele. Additional terpene biosynthesis-related genes that are up-regulated in plants that emit (R)-(-)-linalool may be associated with herbivore defense, suggesting a potential economy of scale between plant reproduction and defense.

DeepLensNet: Deep Learning Automated Diagnosis and Quantitative Classification of Cataract Type and Severity.

PURPOSE: To develop deep learning models to perform automated diagnosis and quantitative classification of age-related cataract from anterior segment photographs. DESIGN: DeepLensNet was trained by applying deep learning models to the Age-Related Eye Disease Study (AREDS) dataset. PARTICIPANTS: A total of 18 999 photographs (6333 triplets) from longitudinal follow-up of 1137 eyes (576 AREDS participants). METHODS: Deep learning models were trained to detect and quantify nuclear sclerosis (NS; scale 0.9-7.1) from 45-degree slit-lamp photographs and cortical lens opacity (CLO; scale 0%-100%) and posterior subcapsular cataract (PSC; scale 0%-100%) from retroillumination photographs. DeepLensNet performance was compared with that of 14 ophthalmologists and 24 medical students. MAIN OUTCOME MEASURES: Mean squared error (MSE). RESULTS: On the full test set, mean MSE for DeepLensNet was 0.23 (standard deviation [SD], 0.01) for NS, 13.1 (SD, 1.6) for CLO, and 16.6 (SD, 2.4) for PSC. On a subset of the test set (substantially enriched for positive cases of CLO and PSC), for NS, mean MSE for DeepLensNet was 0.23 (SD, 0.02), compared with 0.98 (SD, 0.24; P = 0.000001) for the ophthalmologists and 1.24 (SD, 0.34; P = 0.000005) for the medical students. For CLO, mean MSE was 53.5 (SD, 14.8), compared with 134.9 (SD, 89.9; P = 0.003) for the ophthalmologists and 433.6 (SD, 962.1; P = 0.0007) for the medical students. For PSC, mean MSE was 171.9 (SD, 38.9), compared with 176.8 (SD, 98.0; P = 0.67) for the ophthalmologists and 398.2 (SD, 645.4; P = 0.18) for the medical students. In external validation on the Singapore Malay Eye Study (sampled to reflect the cataract severity distribution in AREDS), the MSE for DeepSeeNet was 1.27 for NS and 25.5 for PSC. CONCLUSIONS: DeepLensNet performed automated and quantitative classification of cataract severity for all 3 types of age-related cataract. For the 2 most common types (NS and CLO), the accuracy was significantly superior to that of ophthalmologists; for the least common type (PSC), it was similar. DeepLensNet may have wide potential applications in both clinical and research domains. In the future, such approaches may increase the accessibility of cataract assessment globally. The code and models are available at https://github.com/ncbi/deeplensnet.

Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3 mg aflibercept, 0.75 mg or 1.0 mg ranibizumab, and 1.8 mg or 2.5 mg bevacizumab. The eyes were analyzed at standardized time points up to 48 months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6 months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. RESULTS: There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7-6.4 weeks). Mean follow-up was 22.8 months. CONCLUSIONS: Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.

Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration - Current Perspectives.

Visual acuity is a key outcome measure in the treatment of neovascular age-related macular degeneration (nAMD) using anti-vascular endothelial growth factor agents. Large variations in visual responses between individuals within clinical trials and real-world studies may relate to underlying differences in patient and treatment factors. Most notably, a better baseline visual acuity, younger age and smaller choroidal neovascularization lesion size have been strongly associated with achieving better visual outcomes. In addition, there is emerging evidence for other roles including genetic factors and anatomical variables such as fluid status. Apart from patient-related factors, treatments that favor a higher number of injections tend to provide better visual outcomes. Overall, the identification of predictive factors does not currently play an essential role in the clinical management of patients with nAMD. However, they have allowed for the understanding that early detection, timely management and close monitoring of the disease are required to achieve optimal visual outcomes. Further investigation into predictive factors alongside the development of novel therapeutic agents may one day provide a means to accurately predict patient outcomes. Treatment regimens that offer flexible dosing patterns such as the treat-and-extend strategy currently provide a degree of personalization during treatment.

Associative learning of non-sugar nectar components: amino acids modify nectar preference in a hawkmoth.

The nearly ubiquitous presence of amino acids in the nectar of flowering plants has led to significant interest in the relevance of these compounds to pollinator behavior and physiology. A number of flower-visiting animals exhibit behavioral preferences for nectar solutions containing amino acids, but these preferences vary by species and are often context or condition dependent. Furthermore, the relative strength of these preferences and potential influence on the foraging behavior of flower-visiting animals remains unclear. Here, we used innate preference tests and associative learning paradigms to examine the nectar preferences of the flower-visiting hawkmoth Manduca sexta, in relation to both sugar and amino acid content. Manduca sexta exhibited a strong preference for higher sucrose concentrations, while the effect of amino acids on innate feeding preference was only marginally significant. However, with experience, moths were able to learn nectar composition and flower color associations and to forage preferentially (against innate color preference) for nectar with a realistic amino acid composition. Foraging moths responding to learned color cues of nectar amino acid content exhibited a behavioral preference comparable to that observed in response to a 5% difference in nectar sucrose concentration. These results demonstrate that experienced foragers may assess nectar amino acid content in addition to nectar sugar content and caloric value during nectar-foraging bouts.

Improving Interpretability in Machine Diagnosis: Detection of Geographic Atrophy in OCT Scans.

Purpose: Manually identifying geographic atrophy (GA) presence and location on OCT volume scans can be challenging and time consuming. This study developed a deep learning model simultaneously (1) to perform automated detection of GA presence or absence from OCT volume scans and (2) to provide interpretability by demonstrating which regions of which B-scans show GA. Design: Med-XAI-Net, an interpretable deep learning model was developed to detect GA presence or absence from OCT volume scans using only volume scan labels, as well as to interpret the most relevant B-scans and B-scan regions. Participants: One thousand two hundred eighty-four OCT volume scans (each containing 100 B-scans) from 311 participants, including 321 volumes with GA and 963 volumes without GA. Methods: Med-XAI-Net simulates the human diagnostic process by using a region-attention module to locate the most relevant region in each B-scan, followed by an image-attention module to select the most relevant B-scans for classifying GA presence or absence in each OCT volume scan. Med-XAI-Net was trained and tested (80% and 20% participants, respectively) using gold standard volume scan labels from human expert graders. Main Outcome Measures: Accuracy, area under the receiver operating characteristic (ROC) curve, F1 score, sensitivity, and specificity. Results: In the detection of GA presence or absence, Med-XAI-Net obtained superior performance (91.5%, 93.5%, 82.3%, 82.8%, and 94.6% on accuracy, area under the ROC curve, F1 score, sensitivity, and specificity, respectively) to that of 2 other state-of-the-art deep learning methods. The performance of ophthalmologists grading only the 5 B-scans selected by Med-XAI-Net as most relevant (95.7%, 95.4%, 91.2%, and 100%, respectively) was almost identical to that of ophthalmologists grading all volume scans (96.0%, 95.7%, 91.8%, and 100%, respectively). Even grading only 1 region in 1 B-scan, the ophthalmologists demonstrated moderately high performance (89.0%, 87.4%, 77.6%, and 100%, respectively). Conclusions: Despite using ground truth labels during training at the volume scan level only, Med-XAI-Net was effective in locating GA in B-scans and selecting relevant B-scans within each volume scan for GA diagnosis. These results illustrate the strengths of Med-XAI-Net in interpreting which regions and B-scans contribute to GA detection in the volume scan.

Diet and risk of visual impairment: a review of dietary factors and risk of common causes of visual impairment.

Age-related macular degeneration, diabetic retinopathy, cataract, and glaucoma remain the leading causes of visual impairment in developed nations, resulting in a substantial treatment burden on sufferers and health care systems. Despite significant advances in diagnostic testing and therapeutics, population-based strategies to reduce the burden of these diseases remain limited. However, there is some evidence that these diseases may share overlapping risk factors, particularly in regard to dietary intake and antioxidant status, and it is thus possible that dietary modification may reduce both the prevalence and severity of these conditions. In particular, dietary intake of green leafy vegetables, hyperglycemia/glycemia index, and omega-3 fatty acid intake, as well as overall dietary patterns, may affect risk of one or more of these conditions. In this review, we analyse the evidence for dietary intake and the association with these conditions, and provide insights into possible modifications that may thus simultaneously reduce the risk of visual impairment from multiple causes, including improving dietary intake of green leafy vegetables and reducing dietary glycemic index, both of which have been associated with a decreased risk of multiple causes of visual impairment.

Does functional assessment predict everyday visual functioning? Visual function testing and quality of life in mild/moderate age-related macular degeneration.

PURPOSE: To prospectively assess correlations between self-reported vision-related quality of life (VR-QoL) and clinical functional assessments in mild/moderate age-related macular degeneration (AMD). METHODS: Cross-sectional analysis of 64 participants with bilateral mild/moderate AMD. Microperimetry (MP), flicker perimetry (FP), multifocal electroretinogram (mfERG) findings, best-corrected visual acuity (BCVA) and the National Eye Institute Visual-Function Questionnaire-25 (NEI VFQ-25) were assessed for correlation between clinical testing results and NEI VFQ-25 findings. RESULTS: MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p < 0.05 and R2 < 0.3 for all). FP findings and mfERG response density were not correlated with any subscale, apart from mfERG ring 1 response density and general health (p < 0.05, R2 = 0.41). mfERG latency was weakly correlated with general vision in the better eye in rings 2 and 4 (p < 0.05, R2 < 0.2). CONCLUSION: Functional assessment in mild/moderate AMD is at best, weakly correlated with patient-reported VR-QoL. Despite the growing awareness of the importance of VR-QoL outcomes in improving patient outcomes and satisfaction, surrogate markers of these outcomes remain elusive, and testing of VR-QoL in regular clinical settings remains difficult.