Comparing generative and retrieval-based chatbots in answering patient questions regarding age-related macular degeneration and diabetic retinopathy.

BACKGROUND/AIMS: To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR). METHODS: We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as 'Good', 'Borderline' or 'Poor' quality. RESULTS: Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p ≤8.4×10-3). Based on the consensus approach, 83.3% of ChatGPT-4's responses and 86.7% of ChatGPT-3.5's were rated as 'Good', surpassing Google Bard (50%) and OcularBERT (10%) (all p ≤1.4×10-2). ChatGPT-4 and ChatGPT-3.5 had no 'Poor' rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others. CONCLUSION: ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation.

A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.

Purpose: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration. Observation: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula. Conclusion and importance: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.

Imaging Modalities for Assessing the Vascular Component of Diabetic Retinal Disease: Review and Consensus for an Updated Staging System.

Purpose: To review the evidence for imaging modalities in assessing the vascular component of diabetic retinal disease (DRD), to inform updates to the DRD staging system. Design: Standardized narrative review of the literature by an international expert workgroup, as part of the DRD Staging System Update Effort, a project of the Mary Tyler Moore Vision Initiative. Overall, there were 6 workgroups: Vascular Retina, Neural Retina, Systemic Health, Basic and Cellular Mechanisms, Visual Function, and Quality of Life. Participants: The Vascular Retina workgroup, including 16 participants from 4 countries. Methods: Literature review was conducted using standardized evidence grids for 5 modalities: standard color fundus photography (CFP), widefield color photography (WFCP), standard fluorescein angiography (FA), widefield FA (WFFA), and OCT angiography (OCTA). Summary levels of evidence were determined on a validated scale from I (highest) to V (lowest). Five virtual workshops were held for discussion and consensus. Main Outcome Measures: Level of evidence for each modality. Results: Levels of evidence for standard CFP, WFCP, standard FA, WFFA, and OCTA were I, II, I, I, and II respectively. Traditional vascular lesions on standard CFP should continue to be included in an updated staging system, but more studies are required before they can be used in posttreatment eyes. Widefield color photographs can be used for severity grading within the area covered by standard CFPs, although these gradings may not be directly interchangeable with each other. Evaluation of the peripheral retina on WFCP can be considered, but the method of grading needs to be clarified and validated. Standard FA and WFFA provide independent prognostic value, but the need for dye administration should be considered. OCT angiography has significant potential for inclusion in the DRD staging system, but various barriers need to be addressed first. Conclusions: This study provides evidence-based recommendations on the utility of various imaging modalities for assessment of the vascular component of DRD, which can inform future updates to the DRD staging system. Although new imaging modalities offer a wealth of information, there are still major gaps and unmet research needs that need to be addressed before this potential can be realized. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Geometric Correspondence-Based Multimodal Learning for Ophthalmic Image Analysis.

Color fundus photography (CFP) and Optical coherence tomography (OCT) images are two of the most widely used modalities in the clinical diagnosis and management of retinal diseases. Despite the widespread use of multimodal imaging in clinical practice, few methods for automated diagnosis of eye diseases utilize correlated and complementary information from multiple modalities effectively. This paper explores how to leverage the information from CFP and OCT images to improve the automated diagnosis of retinal diseases. We propose a novel multimodal learning method, named geometric correspondence-based multimodal learning network (GeCoM-Net), to achieve the fusion of CFP and OCT images. Specifically, inspired by clinical observations, we consider the geometric correspondence between the OCT slice and the CFP region to learn the correlated features of the two modalities for robust fusion. Furthermore, we design a new feature selection strategy to extract discriminative OCT representations by automatically selecting the important feature maps from OCT slices. Unlike the existing multimodal learning methods, GeCoM-Net is the first method that formulates the geometric relationships between the OCT slice and the corresponding region of the CFP image explicitly for CFP and OCT fusion. Experiments have been conducted on a large-scale private dataset and a publicly available dataset to evaluate the effectiveness of GeCoM-Net for diagnosing diabetic macular edema (DME), impaired visual acuity (VA) and glaucoma. The empirical results show that our method outperforms the current state-of-the-art multimodal learning methods by improving the AUROC score 0.4%, 1.9% and 2.9% for DME, VA and glaucoma detection, respectively.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Diagnostic Challenges in ABCA4-Associated Retinal Degeneration: One Gene, Many Phenotypes.

(1) Purpose: ABCA4-associated retinal degeneration (ABCA4-RD) is a phenotypically diverse disease that often evades diagnosis, even by experienced retinal specialists. This may lead to inappropriate management, delayed genetic testing, or inaccurate interpretation of genetic testing results. Here, we illustrate the phenotypic diversity of ABCA4-RD using a series of representative cases and compare these to other conditions that closely mimic ABCA4-RD. (2) Methods: Genetically confirmed ABCA4-RD cases with representative phenotypes were selected from an inherited retinal disease cohort in Singapore and compared to phenocopies involving other retinal diseases. (3) Results: ABCA4-RD phenotypes in this series included typical adolescent-onset Stargardt disease with flecks, bull's eye maculopathy without flecks, fundus flavimaculatus, late-onset Stargardt disease, and severe early-onset Stargardt disease. Phenocopies of ABCA4-RD in this series included macular dystrophy, pattern dystrophy, cone dystrophy, advanced retinitis pigmentosa, Leber congenital amaurosis, drug toxicity, and age-related macular degeneration. Key distinguishing features that often suggested a diagnosis of ABCA4-RD were the presence of peripapillary sparing, macular involvement and centrifugal distribution, and a recessive pedigree. (4) Conclusions: ABCA4-RD demonstrates a remarkable phenotypic spectrum that makes diagnosis challenging. Awareness of the clinical spectrum of disease can facilitate prompt recognition and accurate diagnostic testing.

Synthetic artificial intelligence using generative adversarial network for retinal imaging in detection of age-related macular degeneration.

Introduction: Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale. Methods: To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively. Results and discussion: The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61-0.66) and Cohen's kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos.

RETINITIS PIGMENTOSA ASSOCIATED WITH THE EYS C2139Y VARIANT : An Important Cause of Blindness in East Asian Populations.

PURPOSE: The study aimed to describe the phenotypic features of retinitis pigmentosa (RP) associated with the previously described EYS C2139Y variant in Singaporeans and establish the importance of this variant as a prevalent cause of RP among East Asians. METHODS: A clinical phenotyping and exome-sequencing study was conducted on consecutive patients with nonsyndromic RP. Epidemiological analysis was performed using Singaporean and global population-based genetic data. RESULTS: A study of 150 consecutive unrelated individuals with nonsyndromic RP found that 87 (58%) of cases had plausible genotypes. A previously described missense variant in the EYS gene, 6416G>A (C2139Y), occurred heterozygously or homozygously in 17 of 150 families (11.3%), all with autosomal recessive RP. Symptom onset in EYS C2139Y-related RP ranged from 6 to 45 years, with visual acuity ranging from 20/20 at 21 years to no light perception by 48 years. C2139Y-related RP had typical findings, including sectoral RP in cases with EYS E2703X in trans . The median age at presentation was 45 years and visual fields declined to less than 20° (Goldmann V4e isopter) by age 65 years. Intereye correlation for visual acuity, fields, and ellipsoid band width was high (r 2 = 0.77-0.95). Carrier prevalence was 0.66% (allele frequency of 0.33%) in Singaporean Chinese and 0.34% in East Asians, suggesting a global disease burden exceeding 10,000 individuals. CONCLUSION: The EYS C2139Y variant is common in Singaporean RP patients and other ethnic Chinese populations. Targeted molecular therapy for this single variant could potentially treat a significant proportion of RP cases worldwide.

The economic burden of inherited retinal disease in Singapore: a prevalence-based cost-of-illness study.

OBJECTIVE: To assess the economic impact of inherited retinal disease (IRD) among Singaporeans. METHODS: IRD prevalence was calculated using population-based data. Focused surveys were conducted for sequentially enrolled IRD patients from a tertiary hospital. The IRD cohort was compared to the age- and gender-matched general population. Economic costs were expanded to the national IRD population to estimate productivity and healthcare costs. RESULTS: National IRD caseload was 5202 cases (95% CI, 1734-11273). IRD patients (n = 95) had similar employment rates to the general population (67.4% vs. 70.7%; p = 0.479). Annual income was lower among IRD patients than the general population (SGD 19,500 vs. 27,161; p < 0.0001). Employed IRD patients had lower median income than the general population (SGD 39,000 vs. 52,650; p < 0.0001). Per capita cost of IRD was SGD 9382, with a national burden of SGD 48.8 million per year. Male gender (beta of SGD 6543, p = 0.003) and earlier onset (beta of SGD 150/year, p = 0.009) predicted productivity loss. Treatment of the most economically impacted 10% of IRD patients with an effective IRD therapy required initial treatment cost of less than SGD 250,000 (USD 188,000) for cost savings to be achieved within 20 years. CONCLUSIONS: Employment rates among Singaporean IRD patients were the same as the general population, but patient income was significantly lower. Economic losses were driven in part by male patients with early age of onset. Direct healthcare costs contributed relatively little to the financial burden.

Diabetic retinopathy in China: Epidemiology, screening and treatment trends-A review.

Diabetic retinopathy (DR) is the leading cause of vision impairment in the global working-age population. In China, with one-third of the world's diabetes population estimated at 141 million, the blindness prevalence due to DR has increased significantly. The country's geographic variations in socioeconomic status have led to prominent disparities in DR prevalence, screening and management. Reported risk factors for DR in China include the classic ones, such as long diabetes duration, hyperglycaemia, hypertension and rural habitats. There is no national-level DR screening programme in China, but significant pilot efforts are underway for screening innovations. Novel agents with longer durations, noninvasive delivery or multi-target are undergoing clinical trials in China. Although optimised medical insurance policies have enhanced accessibility for expensive therapies like anti-VEGF drugs, further efforts in DR prevention and management in China are required to establish nationwide cost-effective screening programmes, including telemedicine and AI-based solutions, and to improve insurance coverage for related out-of-pocket expenses.

Clinical utility of ultra-widefield fluorescein angiography and optical coherence tomography angiography for retinal vein occlusions.

Retinal vein occlusions (RVOs) are the second most common retinal vascular disease after diabetic retinopathy, and are a significant cause of visual impairment, especially in the elderly population. RVOs result in visual loss due to macular ischemia, cystoid macular edema (CME), and complications related to neovascularization. Vascular assessment in RVOs traditionally relies on standard fluorescein angiography (FA) for assessment of macular and retinal ischemia, which aids in prognostication and guides intervention. Standard FA has significant limitations-it is time-consuming, requires invasive dye administration, allows for limited assessment of the peripheral retina, and is usually evaluated semi-qualitatively, by ophthalmologists with tertiary expertise. More recently, the introduction of ultra-widefield FA (UWF FA) and optical coherence tomography angiography (OCTA) into clinical practice has changed the tools available for vascular evaluation in RVOs. UWF FA allows for evaluation of peripheral retinal perfusion, and OCTA is non-invasive, rapidly-acquired, and provides more information on capillary perfusion. Both modalities can be used to provide more quantitative parameters related to retinal perfusion. In this article, we review the clinical utility and impact of UWF FA and OCTA in the evaluation and management of patients with RVOs.

Optical Coherence Tomography Angiography in Retinal Vascular Disorders.

Traditionally, abnormalities of the retinal vasculature and perfusion in retinal vascular disorders, such as diabetic retinopathy and retinal vascular occlusions, have been visualized with dye-based fluorescein angiography (FA). Optical coherence tomography angiography (OCTA) is a newer, alternative modality for imaging the retinal vasculature, which has some advantages over FA, such as its dye-free, non-invasive nature, and depth resolution. The depth resolution of OCTA allows for characterization of the retinal microvasculature in distinct anatomic layers, and commercial OCTA platforms also provide automated quantitative vascular and perfusion metrics. Quantitative and qualitative OCTA analysis in various retinal vascular disorders has facilitated the detection of pre-clinical vascular changes, greater understanding of known clinical signs, and the development of imaging biomarkers to prognosticate and guide treatment. With further technological improvements, such as a greater field of view and better image quality processing algorithms, it is likely that OCTA will play an integral role in the study and management of retinal vascular disorders. Artificial intelligence methods-in particular, deep learning-show promise in refining the insights to be gained from the use of OCTA in retinal vascular disorders. This review aims to summarize the current literature on this imaging modality in relation to common retinal vascular disorders.

Characterizing the genotypic spectrum of retinitis pigmentosa in East Asian populations: a systematic review.

BACKGROUND: Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries and populations, these therapies may not be efficacious in East Asians. MATERIALS AND METHODS: A literature search was conducted from 1966 to September 2022 for cohort studies on East Asian populations reporting on non-syndromic RP genotypes and variants. Population-weighted prevalence was used to determine the genotypes and individual variants across the entire cohort. The carrier prevalence of common variants was compared against those in Europe. RESULTS: A total of 12 articles describing 2,932 clinically diagnosed East Asian RP probands were included. We identified 876 variants across 54 genes. The most common genotypes included USH2A, EYS, RPGR, ABCA4, PRPF31, RHO, RP1, RP2, PDE6B and SNRNP200, with USH2A as the most common (17.1%). Overall, 60.5% of probands with clinically relevant variants were found to have one of the genotypes above, with 543/876 (62.0%) of the variants occurring in these genes. The most frequently reported variant was USH2A missense variant c.2802T>G/p.C934W (4.9%). Carrier prevalence of these variants was significantly different (p < 0.0001) than in Europe. CONCLUSIONS: USH2A was the most commonly affected RP gene in this East Asian cohort, although sub-population analysis revealed distinct genotype prevalence patterns. While the genotypes are similar between East Asia and European cohorts, variants are specific to East Asia. The identification of several prevalent variants in USH2A and EYS provides an opportunity for the development of therapeutics that are relevant for East Asia patients.

Retinal neural dysfunction in diabetes revealed with handheld chromatic pupillometry.

BACKGROUND: To evaluate the ability of handheld chromatic pupillometry to reveal and localise retinal neural dysfunction in diabetic patients with and without diabetic retinopathy (DR). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Classification of diabetic retinopathy: Past, present and future.

Diabetic retinopathy (DR) is a leading cause of visual impairment and blindness worldwide. Since DR was first recognized as an important complication of diabetes, there have been many attempts to accurately classify the severity and stages of disease. These historical classification systems evolved as understanding of disease pathophysiology improved, methods of imaging and assessing DR changed, and effective treatments were developed. Current DR classification systems are effective, and have been the basis of major research trials and clinical management guidelines for decades. However, with further new developments such as recognition of diabetic retinal neurodegeneration, new imaging platforms such as optical coherence tomography and ultra wide-field retinal imaging, artificial intelligence and new treatments, our current classification systems have significant limitations that need to be addressed. In this paper, we provide a historical review of different classification systems for DR, and discuss the limitations of our current classification systems in the context of new developments. We also review the implications of new developments in the field, to see how they might feature in a future, updated classification.

Clinical operational considerations and responses to lockdown and reopening in the Covid-19 pandemic: experience of a tertiary ophthalmology centre in Singapore.

BACKGROUND: Much has been written on infection control and clinical measures for ophthalmic institutions and departments to cope with the COVID-19 pandemic. However, few articles have detailed implementation plans to manage lockdowns and subsequent re-openings. In this article, specific operational responses and their outcomes in a large tertiary ophthalmology centre are described. METHOD: Through a concerted effort led by a dedicated task force, the Singapore National Eye Centre (SNEC) planned and executed an operational transformation to respond to the restrictions imposed on healthcare delivery during a national lock down. A carefully calibrated re-starting of services was carried out with the subsequent phased reopening of the country, taking into consideration unique constraints faced at that time. Strategies for operating in the new normal environment were also developed. RESULTS: Outpatient attendances were safely and expediently reduced by 70% (8749 vs. 29,311) and 82% (5164 vs. 29,342) in April and May 2020, respectively, compared to the corresponding months in 2019. A correspondingly large reduction in surgical load was also achieved through a similar triaging and prioritization system. Through optimizing the center's use of space and time, as well as expanding on new models of care, a return to pre-pandemic patient load was achieved 3 months into the phased reopening of the country, and subsequently exceeded in the following months. CONCLUSION: The lessons gleaned from SNEC's experience may be useful for institutions currently facing the same challenges, and for future responses to COVID-19 resurgences or other pandemics.

Diabetic retinopathy: Looking forward to 2030.

Diabetic retinopathy (DR) is the major ocular complication of diabetes mellitus, and is a problem with significant global health impact. Major advances in diagnostics, technology and treatment have already revolutionized how we manage DR in the early part of the 21st century. For example, the accessibility of imaging with optical coherence tomography, and the development of anti-vascular endothelial growth factor (VEGF) treatment are just some of the landmark developments that have shaped the DR landscape over the last few decades. Yet, there are still more exciting advances being made. Looking forward to 2030, many of these ongoing developments are likely to further transform the field. First, epidemiologic projections show that the global burden of DR is not only increasing, but also shifting from high-income countries towards middle- and low-income areas. Second, better understanding of disease pathophysiology is placing greater emphasis on retinal neural dysfunction and non-vascular aspects of diabetic retinal disease. Third, a wealth of information is becoming available from newer imaging modalities such as widefield imaging systems and optical coherence tomography angiography. Fourth, artificial intelligence for screening, diagnosis and prognostication of DR will become increasingly accessible and important. Fifth, new pharmacologic agents targeting other non-VEGF-driven pathways, and novel therapeutic strategies such as gene therapy are being developed for DR. Finally, the classification system for diabetic retinal disease will need to be continually updated to keep pace with new developments. In this article, we discuss these major trends in DR that we expect to see in 2030 and beyond.

Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress.

Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field.