Autonomous artificial intelligence versus teleophthalmology for diabetic retinopathy.

Purpose: To assess the role of artificial intelligence (AI) based automated software for detection of Diabetic Retinopathy (DR) compared with the evaluation of digital retinography by two double masked retina specialists. Methods: Two-hundred one patients (mean age 65 ± 13 years) with type 1 diabetes mellitus or type 2 diabetes mellitus were included. All patients were undergoing a retinography and spectral domain optical coherence tomography (SD-OCT, DRI 3D OCT-2000, Topcon) of the macula. The retinal photographs were graded using two validated AI DR screening software (Eye Art TM and IDx-DR) designed to identify more than mild DR. Results: Retinal images of 201 patients were graded. DR (more than mild DR) was detected by the ophthalmologists in 38 (18.9%) patients and by the AI-algorithms in 36 patients (with 30 eyes diagnosed by both algorithms). Ungradable patients by the AI software were 13 (6.5%) and 16 (8%) for the Eye Art and IDx-DR, respectively. Both AI software strategies showed a high sensitivity and specificity for detecting any more than mild DR without showing any statistically significant difference between them. Conclusions: The comparison between the diagnosis provided by artificial intelligence based automated software and the reference clinical diagnosis showed that they can work at a level of sensitivity that is similar to that achieved by experts.

Predictive role of systemic immune-inflammation index and neutrophil/lymphocyte ratio values in infants with retinopathy of prematurity.

PURPOSE: To search the relationship between serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) values with the development of retinopathy of prematurity (ROP) and the requirement for laser treatment. METHODS: This retrospective cohort study was carried out with 195 preterm infants between 2012 and 2023. The NLR, PLR, LMR, and SII values were calculated on both the first day and at the end of the first month after birth. The association between development of ROP and other risk factors were analyzed using univariate analysis and multivariate logistic regression analysis. RESULTS: Of patients, 92 infants were diagnosed with ROP. Laser treatment was administered to 36 infants. The postnatal first-day NLR and SII values were higher in infants with ROP than in infants without ROP (p < 0.001 for both). Postnatal first-month NLR, LMR, and SII values were higher in infants with ROP (p < 0.001, p = 0.007, and p < 0.001, respectively). In multivariate analyses, postnatal first-day NLR and first-month LMR values were regarded as independent risk factors for the development of ROP (OR:8.867 and 1.286, p = 0.002 and p = 0.009, respectively). In multivariate analyses performed for laser treatment requirement, postnatal first-month PLR and SII values were determined as independent risk factors (OR:0.951 and 1.011, respectively, p = 0.004 for both). CONCLUSIONS: Postnatal first-day NLR and first-month LMR values were determined as independent risk factors for the development of ROP. For the requirement of laser treatment, the postnatal first-month PLR and SII values were determined as independent risk factors.

Optical coherence tomography angiography for the differentiation of diabetic nephropathy from non-diabetic renal disease.

BACKGROUND: To provide a new non-invasive method for the differentiation of diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) by assessing retinal microstructure using optical coherence tomography angiography (OCTA). METHODS: OCTA parameters were recorded and their relationship with DN was analyzed. A differential diagnosis regression model for DN was established, and the diagnostic efficiency was evaluated. RESULTS: Based on the pathological results of renal biopsy, 31 DN patients and 35 NDRD patients were included. Multivariate logistic regression analysis showed that DN was independently associated with the following parameters: 15.3 mm-1 ≤ vessel density (VD) full < 17.369 mm-1 (odds ratio [OR]=8.523; 95% confidence interval [CI]=1.387-52.352; P=0.021), VD full < 15.3 mm-1 (OR=8.202; 95% CI=1.110-60.623; P=0.039), DM duration > 60 months (OR=7.588; 95% CI=1.569-36.692; P=0.012), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR=24.484; 95% CI=4.308-139.142; P < 0.001). The area under the receiver operating characteristic curve was 0.911, indicating a high diagnostic efficiency. CONCLUSIONS: VD full < 17.369 mm-1, DM duration > 60 months, and eGFR < 60 mL/min/1.73 m2 may indicate the presence of DN. OCTA may be an effective non-invasive method for identifying DN and NDRD.

Associations of the obesity gene FTO variant with complications and comorbidities in patients with type 1 diabetes.

BACKGROUND AND AIMS: Because FTO gene is connected with the risk of obesity, cardiovascular disease and hypertension, as well as type 2 diabetes, we hypothesize that the rs9939609 FTO polymorphism may affect type 1 diabetes (T1D) complications and comorbidities. METHODS: We have investigated the associations of the FTO gene variant with the T1D and its complications and comorbidities, as well as the serum levels of pro- and anti-inflammatory markers and lipid profiles. RESULTS: The key results of our study are as follows: (1) the rs9939609 FTO polymorphism does not predispose individuals to T1D; (2) AA genotype is associated with an increased risk of overweight and obesity, retinopathy, hypertension, dyslipidemia and celiac disease; (3) AT genotype is associated with a decreased risk of retinopathy and celiac disease, whereas TT genotype is connected with decreased risk of dyslipidemia; (4) the FTO rs9939609 polymorphism affects the inflammatory status as well as lipid profile in T1D patients. CONCLUSIONS: Our results, for the first time, comprehensively indicate that the rs9939609 FTO polymorphism could be considered a genetic marker for increased susceptibility to T1D complications and comorbidities as well as suggests importance of FTO-mediated pathways in their etiology.

Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes.

BACKGROUND: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. METHODS: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. RESULTS: During median 18.0 (14.1-19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no-very mild (ETDRS 10-20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02-3.15) in non-proliferative (ETDRS 35-53), and 1.69 (1.02-2.82) in proliferative (ETDRS 61-85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91-3.10) in non-proliferative and 1.35 (0.77-2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66-12.28) in non-proliferative and 4.31 (1.16-16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). CONCLUSIONS: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

Sight-Threatening Immune Retinopathy Developing Secondary to Durvalumab Treatment of Small-Cell Lung Cancer: A Case Report.

Introduction: Given the recent additions of immune checkpoint inhibitors (ICIs) to various cancer treatments, adverse effects, especially involving the eyes, have been on the rise. Here, we report an acute exacerbation of cancer-associated retinopathy (CAR) triggered by durvalumab treatment of small-cell lung cancer (SCLC). Case Presentation: An 81-year-old Asian male complained of a scotoma in the left eye after durvalumab administration, to treat SCLC. Humphrey visual field examination revealed a C-shaped temporal scotoma. Spectralis domain optical coherence tomography revealed outer retinal layer atrophy and progressive loss of the ellipsoid zone in the atrophic peripapillary area. Fundus autofluorescence (AF) images evidenced a large C-shaped hypo-AF with enhanced AF at the margin of the atrophic area, thus at the position of the scotoma. We prescribed subtenon triamcinolone injections under suspicion of CAR exacerbation, supported by positive Western blotting results for Rab6 and aldolase, and immunohistochemical staining of photoreceptor cells. The disrupted ellipsoid zone evident on OCT partially recovered, and a visual field test showed that the scotoma had improved. Conclusion: ICI-triggered exacerbation of CAR should be considered in SCLC patients before ICI treatment commences; an optimal treatment should preserve functional vision.

Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

[Evaluation of the management and follow-up of diabetic patients in the prevention of diabetic retinopathy]. / Evaluación del manejo y seguimiento de los pacientes diabéticos en la prevención de la retinopatía diabética.

OBJECTIVE: Diabetes mellitus is a chronic disease with high morbidity and mortality, affecting 537 million adults worldwide. Spain is the second European country in prevalence, with 14.8% in the population aged twenty/seventy-nine years; with 11.6 cases per 1,000 people/year. Diabetic retinopathy (DR) is the fifth cause of vision loss worldwide and the seventh cause of blindness/visual impairment among members of the National Organization of the Blind in Spain (ONCE). Early detection of DR prevents blindness in diabetics and is conditioned by glycosylated hemoglobin. The aim of this paper was to analyze the management of diabetic patients in Aljarafe region (Seville) and identify opportunities for improvement in the coordination of their follow-up between the Primary Care physician and the ophthalmologist. METHODS: A retrospective observational study (2016-2019) was carried out, with patients registered in the diabetic census of the twenty-eight municipalities of Aljarafe. The primary care and hospital health history, and telemedicine program were consulted. About statistical analysis, for qualitative variables, totals and percentages were calculated; for quantitative variables, mean and standard deviation (if normally distributed) and median and quartiles (if non-normally distributed). RESULTS: There were 17,175 diabetics registered in Aljarafe (5.7% of the population); 14,440 patients (84.1%) had some determination of hemoglobin during the period, 9,228 (63.9%) had all of them in the appropriate range. Fundoscopic control was performed on 12,040 diabetics (70.1%), and of those who did not, 346 (10.6%) had all of them out of range. There were 1,878 (10.9%) patients without fundoscopic or metabolic control, 1,019 (54.3%) were women, 1,219 (64.9%) were under sixty-five years of age, 1,019 (54.3%) had severe comorbidity. CONCLUSIONS: Most patients have adequate screening, and more than half have determinations within range. However, a significant percentage with no glycated hemoglobin within range lack fundoscopic control, and another smaller group lack fundoscopic or metabolic control, with inter-municipal variability. We propose to improve communication channels between levels.

OBJECTIVE: La diabetes mellitus es una enfermedad crónica con alta morbimortalidad que afecta a 537 millones de adultos en el mundo. España es el segundo país europeo en prevalencia, con un 14,8% en población de veinte-setenta y nueve años, con 11,6 casos por cada 1.000 personas/año. La retinopatía diabética (RD) es la quinta causa de pérdida de visión a nivel mundial y la séptima causa de ceguera/discapacidad visual entre afiliados a la Organización Nacional de Ciegos de España (ONCE). La detección precoz de RD previene la ceguera en diabéticos y está condicionada por la hemoglobina glicosilada. El objetivo de este trabajo fue analizar el manejo de los pacientes diabéticos en la comarca del Aljarafe (Sevilla) e identificar oportunidades de mejora en la coordinación de su seguimiento entre el médico de Atención Primaria y el médico oftalmólogo. METHODS: Se realizó un estudio observacional retrospectivo (2016-2019) con los pacientes registrados en el censo de diabéticos de los veintiocho municipios del Aljarafe. Se consultó la historia de salud de Atención Primaria y Hospital, así como el programa de Telemedicina. En cuanto al análisis estadístico, para variables cualitativas se calcularon totales y porcentajes; para variables cuantitativas, media y distribución estándar (si distribución normal), y la mediana y cuartiles (distribución no normal). RESULTS: Se registraron 17.175 diabéticos en el Aljarafe (5,7% de población); 14.440 pacientes (84,1%) tenían alguna determinación de hemoglobina durante el periodo, 9.228 (63,9%) las tenían todas en rango adecuado. Tenían control fundoscópico 12.040 diabéticos (70,1%), y de los que no, 346 (10,6%) tenían todas fuera de rango. Hubo 1.878 (10,9%) pacientes sin control fundoscópico ni metabólico, 1.019 (54,3%) eran mujeres, 1.219 (64,9%) menores de sesenta y cinco años, 1.019 (54,3%) con comorbilidad grave. CONCLUSIONS: La mayoría de los pacientes presentan un cribado adecuado y, más de la mitad, determinaciones en rango. Sin embargo, un porcentaje relevante con ninguna hemoglobina glicosilada en rango carecen de control fundoscópico, y otro grupo menor está sin control fundoscópico ni metabólico, con variabilidad intermunicipios. Planteamos mejorar los circuitos de comunicación entre niveles.

Artificial intelligence-based prediction of diabetic retinopathy evolution (EviRed): protocol for a prospective cohort.

INTRODUCTION: An important obstacle in the fight against diabetic retinopathy (DR) is the use of a classification system based on old imaging techniques and insufficient data to accurately predict its evolution. New imaging techniques generate new valuable data, but we lack an adapted classification based on these data. The main objective of the Evaluation Intelligente de la Rétinopathie Diabétique, Intelligent evaluation of DR (EviRed) project is to develop and validate a system assisting the ophthalmologist in decision-making during DR follow-up by improving the prediction of its evolution. METHODS AND ANALYSIS: A cohort of up to 5000 patients with diabetes will be recruited from 18 diabetology departments and 14 ophthalmology departments, in public or private hospitals in France and followed for an average of 2 years. Each year, systemic health data as well as ophthalmological data will be collected. Both eyes will be imaged by using different imaging modalities including widefield photography, optical coherence tomography (OCT) and OCT-angiography. The EviRed cohort will be divided into two groups: one group will be randomly selected in each stratum during the inclusion period to be representative of the general diabetic population. Their data will be used for validating the algorithms (validation cohort). The data for the remaining patients (training cohort) will be used to train the algorithms. ETHICS AND DISSEMINATION: The study protocol was approved by the French South-West and Overseas Ethics Committee 4 on 28 August 2020 (CPP2020-07-060b/2020-A01725-34/20.06.16.41433). Prior to the start of the study, each patient will provide a written informed consent documenting his or her agreement to participate in the clinical trial. Results of this research will be disseminated in peer-reviewed publications and conference presentations. The database will also be available for further study or development that could benefit patients. TRIAL REGISTRATION NUMBER: NCT04624737.

Public Awareness of Common Age-Related Eye Diseases in Northern Saudi Arabia.

Background: Visual impairment and blindness pose substantial public health challenges in Saudi Arabia, especially among the elderly susceptible to blinding eye diseases. Assessing awareness of age-related eye diseases (AREDs) is vital for addressing vision loss in this demographic. However, there is a lack of research on ARED awareness in Northern Saudi Arabia, underscoring the need for evidence-based data from adult populations to craft effective health promotion strategies. METHODS: This population-based descriptive survey was conducted on 411 Saudi adults aged 18-70 residing in Arar City, Saudi Arabia, over six months from September 2023. Random sampling was employed, and awareness levels were assessed using a pre-designed questionnaire. Data analysis was performed using Statistical Product and Service Solutions (SPSS, version 20.0; IBM SPSS Statistics for Windows, Armonk, NY). RESULTS:  Among the 411 participants, 225 (54.7%) were aged 18-29 years, 312 (76%) were females, and 299 (72.6%) held a bachelor's degree or diploma. Regarding awareness, 71.3% knew about cataracts, but nearly half erroneously believed it could be treated solely medically. For diabetic retinopathy (DR), 366 (89%) recognized lifestyle modifications, and 378 (92%) understood screening as preventive measures. Most participants understood prevention methods for all four diseases, but misconceptions about treatment options were observed. Awareness of glaucoma and age-related macular degeneration (ARMD) was lower. No significant age-related differences were found in awareness, except for cataracts (P = 0.001). Education significantly influenced awareness of cataracts, DR, and glaucoma (P = 0.001, 0.013, and 0.008, respectively), but not ARMD (P = 0.606). The study found that the internet is the primary source of information on AREDs for most participants, except for cataracts, where friends and relatives are prominent. CONCLUSION: The study reveals varying awareness levels of AREDs among Saudi adults. Although most participants understood preventive measures, misconceptions about treatment underscore the need for accurate education channels. Healthcare professionals must ensure information reliability to effectively combat misinformation and enhance awareness of AREDs.

Recognizing Lipofuscinosis as a Guide in Antiepileptic Treatment: Clinical Description of the First Mexican Case With Neuronal Ceroid Lipofuscinosis Type 7 (NCL7).

Neuronal ceroid lipofuscinosis type 7 (NCL7) is a rare form of childhood dementia; it is part of a group of diseases characterized by rapid progressive cognitive decline, blindness associated with retinitis pigmentosa, and seizures. We report the clinical and molecular characteristics of the first Mexican patient with NCL7, highlighting a particularly atypical disease course. The typical presentation form is expected to have reduced life expectancy and an average age of ambulation loss at 12 years. Our 27-year-old patient retains the ability to walk. The patient's unique presentation could, in part, be attributed to her genetic profile: a hypomorphic allele carrying a missense variant (c.1390G>A) and an almost null allele with a frameshift variant (c.1086del), contributing to the preservation of some protein function. Throughout her childhood and early adulthood, our patient experienced a variable response to antiseizure drugs, attributed to a lack of recognition of the disease and the specific efficacy of certain antiseizure medications. Our findings underscore the significance of considering this genetic condition and acknowledging its clinical heterogeneity.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Association of Hypomagnesemia With Diabetic Complications.

OBJECTIVE: The study aimed to study the association of hypomagnesemia with diabetic complications in type 2 diabetics. MATERIALS AND METHOD: This cross-sectional study, conducted at a Ghurki Trust Teaching Hospital, spanned from January to June 2023 and included 100 randomly selected diabetic patients aged 30-70. With institutional board approval and informed consent, the study focused on assessing hypomagnesemia, using a standard level of below 1.6 mg/dL, ensuring participant confidentiality and privacy. Data collected through physical assessments were analyzed using IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States), including descriptive statistics, analysis of variance (ANOVA), and paired t-test. RESULTS: A total of 100 diabetic admitted patients were randomly selected for the study ages from 30 to 70 years irrespective of their gender. The mean age of the participants was 53.86±9.74 years. The mean HbA1c of the participants was 8.7±2.32. Forty-eight percent of them had HbA1c less than 8, while 52% had greater than 8 HbA1c. The mean HbA1c in the hypomagnesemia group was 10.8±1.98, while in the normomagnesemia group, it was 8.9±2.2. There were 58.97% of foot ulcers in Group 1, while in Group 2, there were 31.14%. Around 38.46% and 14.75% had neuropathy in Groups 1 and 2, respectively. Nephropathy in Group 1 was 28.20%, while in Group 2, it was 11.47%. Around 69.23% of Group 1 had retinopathy and 37.70% had retinopathy in Group 2. Hypertension was 23.07% in Group 1 and 37.70% in Group 2; moreover, 7.69% and 8.19% had coronary diseases in Groups 1 and 2 accordingly. CONCLUSION:  The current study concluded that hypomagnesemia was found to have an association with diabetic complications like neuropathy, nephropathy, foot ulcers, and poor glycemic control as evidenced by HbA1c.

Understanding the Clinical Relationship Between Diabetic Retinopathy, Nephropathy, and Neuropathy: A Comprehensive Review.

Diabetic retinopathy, nephropathy, and neuropathy are significant microvascular complications of diabetes mellitus, contributing to substantial morbidity and mortality worldwide. This comprehensive review examines the clinical relationship between these complications, focusing on shared pathophysiological mechanisms, bidirectional relationships, and implications for patient management. The review highlights the importance of understanding the interconnected nature of diabetic complications and adopting a holistic approach to diabetes care. Insights gleaned from this review underscore the necessity for early detection, timely intervention, and integrated care models involving collaboration among healthcare professionals. Furthermore, the review emphasizes the need for continued research to elucidate underlying mechanisms, identify novel therapeutic targets, and assess the efficacy of integrated care strategies in improving patient outcomes. By fostering interdisciplinary collaboration and knowledge exchange, future research endeavors hold the potential to advance our understanding and management of diabetic complications, ultimately enhancing patient care and quality of life.

Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

BACKGROUND: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME. OBJECTIVE: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity. METHODS: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups. KEY SAFETY: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3. DISCUSSION: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs. TRIAL REGISTRATION: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

Referable Diabetic Retinopathy Prediction Algorithm Applied to a Population of 120,389 Type 2 Diabetics over 11 Years Follow-Up.

(1) Background: Although DR screening is effective, one of its most significant problems is a lack of attendance. The aim of the present study was to demonstrate the effectiveness of our algorithm in predicting the development of any type of DR and referable DR. (2) Methods: A retrospective study with an 11-year follow-up of a population of 120,389 T2DM patients was undertaken. (3) Results: Applying the results of the algorithm showed an AUC of 0.93 (95% CI, 0.92-0.94) for any DR and 0.90 (95% CI, 0.89-0.91) for referable DR. Therefore, we achieved a promising level of agreement when applying our algorithm. (4) Conclusions: The algorithm is useful for predicting which patients may develop referable forms of DR and also any type of DR. This would allow a personalized screening plan to be drawn up for each patient.

Using a smartphone-based digital fundus camera for screening of retinal and optic nerve diseases in veterinary medicine: A preliminary investigation.

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

Search engine optimization and its association with readability and accessibility of diabetic retinopathy websites.

PURPOSE: This study investigated whether websites regarding diabetic retinopathy are readable for patients, and adequately designed to be found by search engines. METHODS: The term "diabetic retinopathy" was queried in the Google search engine. Patient-oriented websites from the first 10 pages were categorized by search result page number and website organization type. Metrics of search engine optimization (SEO) and readability were then calculated. RESULTS: Among the 71 sites meeting inclusion criteria, informational and organizational sites were best optimized for search engines, and informational sites were the most visited. Better optimization as measured by authority score was correlated with lower Flesch Kincaid Grade Level (r = 0.267, P = 0.024). There was a significant increase in Flesch Kincaid Grade Level with successive search result pages (r = 0.275, P = 0.020). Only 2 sites met the 6th grade reading level AMA recommendation by Flesch Kincaid Grade Level; the average reading level was 10.5. There was no significant difference in readability between website categories. CONCLUSION: While the readability of diabetic retinopathy patient information was poor, better readability was correlated to better SEO metrics. While we cannot assess causality, we recommend websites improve their readability, which may increase uptake of their resources.

MSC-derived small extracellular vesicles mitigate diabetic retinopathy by stabilizing Nrf2 through miR-143-3p-mediated inhibition of neddylation.

Diabetic retinopathy (DR) is a highly hazardous and widespread complication of diabetes mellitus (DM). The accumulated reactive oxygen species (ROS) play a central role in DR development. The aim of this research was to examine the impact and mechanisms of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEV) on regulating ROS and retinal damage in DR. Intravitreal injection of sEV inhibited Cullin3 neddylation, stabilized Nrf2, decreased ROS, reduced retinal inflammation, suppressed Müller gliosis, and mitigated DR. Based on MSC-sEV miRNA sequencing, bioinformatics software, and dual-luciferase reporter assay, miR-143-3p was identified to be the key effector for MSC-sEV's role in regulating neural precursor cell expressed developmentally down-regulated 8 (NEDD8)-mediated neddylation. sEV were able to be internalized by Müller cells. Compared to advanced glycation end-products (AGEs)-induced Müller cells, sEV coculture decreased Cullin3 neddylation, activated Nrf2 signal pathway to combat ROS-induced inflammation. The barrier function of endothelial cells was impaired when endothelial cells were treated with the supernatant of AGEs-induced Müller cells, but was restored when treated with supernatant of AGEs-induced Müller cells cocultured with sEV. The protective effect of sEV was, however, compromised when miR-143-3p was inhibited in sEV. Moreover, the protective efficacy of sEV was diminished when NEDD8 was overexpressed in Müller cells. These findings showed MSC-sEV delivered miR-143-3p to inhibit Cullin3 neddylation, stabilizing Nrf2 to counteract ROS-induced inflammation and reducing vascular leakage. Our findings suggest that MSC-sEV may be a potential nanotherapeutic agent for DR, and that Cullin3 neddylation could be a new target for DR therapy.

Algorithm of automatic identification of diabetic retinopathy foci based on ultra-widefield scanning laser ophthalmoscopy.

AIM: To propose an algorithm for automatic detection of diabetic retinopathy (DR) lesions based on ultra-widefield scanning laser ophthalmoscopy (SLO). METHODS: The algorithm utilized the FasterRCNN (Faster Regions with CNN features)+ResNet50 (Residua Network 50)+FPN (Feature Pyramid Networks) method for detecting hemorrhagic spots, cotton wool spots, exudates, and microaneurysms in DR ultra-widefield SLO. Subimage segmentation combined with a deeper residual network FasterRCNN+ResNet50 was employed for feature extraction to enhance intelligent learning rate. Feature fusion was carried out by the feature pyramid network FPN, which significantly improved lesion detection rates in SLO fundus images. RESULTS: By analyzing 1076 ultra-widefield SLO images provided by our hospital, with a resolution of 2600×2048 dpi, the accuracy rates for hemorrhagic spots, cotton wool spots, exudates, and microaneurysms were found to be 87.23%, 83.57%, 86.75%, and 54.94%, respectively. CONCLUSION: The proposed algorithm demonstrates intelligent detection of DR lesions in ultra-widefield SLO, providing significant advantages over traditional fundus color imaging intelligent diagnosis algorithms.