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Identifying macular neovascularization (MNV) in eyes with central serous chorioretinopathy (CSC) has important implications for its management. Optical coherence tomography angiography (OCTA) is increasingly used for this purpose. Here, we systematically reviewed the literature and conducted meta‐analysis to determine the diagnostic accuracy of OCTA for detecting MNV in eyes with CSC. We systematically searched the literature in 12 databases for relevant studies from database inception until 18 November 2023. Eligible studies had eyes with CSC with MNV and CSC without MNV. Index test was OCTA. Reference test was retinal dye angiography. Study selection and data extraction were performed in duplicate, and study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2. Our main outcome of interest was the sensitivity and specificity of OCTA for detecting MNV in CSC. Pooled diagnostic test accuracy estimates were computed using MetaDTA. Of 177 records screened, seven fulfilled the eligibility criteria for our study. These studies summarized data from a total of 1061 eyes. Summary estimate sensitivity and specificity to diagnose MNV in eyes with CSC using OCTA was 92.9% (95% CI: 81.7%–97.5%) and 99.4% (95% CI: 84.1%–100.0%), respectively. The main source of bias across studies was the reference standard, as four studies used multimodal imaging including OCTA for the reference standard. OCTA alone is excellent for detecting MNV in CSC compared to retinal dye angiography or multimodal imaging. Using OCTA first before considering retinal dye angiography could potentially save an important number of retinal dye angiographies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the five‐year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR‐screening programme. Methods: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013–2018. According to the worse eye at first screening, DR was classified (levels 0–4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. Results: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five‐year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63–1.89, and HR 2.04, 95% CI 1.73–2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10–1.47, and HR 2.80, 95% CI 2.23–3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05–1.36, and HR 1.98, 95% CI 1.53–2.57). Conclusion: In a study of all patients with type 1 diabetes from the Danish DR‐screening programme, we identified duration of diabetes, systemic disease and use of anti‐hypertensive treatment as consistent risk markers for incident and progressive DR. [ABSTRACT FROM AUTHOR]

Background: Diabetic macular edema (DME) is a prevalent exudative maculopathy, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the first-line choice for treatment. Faricimab, a novel anti-VEGF and anti-angiopoietin-2 bispecific agent, has recently been approved for the treatment of DME. In this study, we systematically reviewed the real-world evidence of the efficacy of faricimab for the treatment of DME. Methods: We searched 11 databases for eligible studies. Study selection and data extraction were made independently by two authors in duplicate. Eligible studies were reviewed qualitatively. Results: We identified 10 eligible studies that summarized data from a total of 6054 eyes with a mean follow-up of between 55 days and 12 months. Five studies reported outcomes in a population of both treatment-naïve and previously treated eyes, and five studies reported outcomes exclusively in relation to eyes that were previously treated. Faricimab improved the best-corrected visual acuity and macular thickness. The extension of the treatment interval was possible in 61–81% of treatment-naïve eyes and 36–78% of previously treated eyes. Conclusions: Faricimab for DME yields clinical outcomes similar to those known from previous anti-VEGF treatments but with extended treatment intervals, thus lowering the burden of therapy for patients. Long-term real-world studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: A number of algorithms have been developed to calculate screening intervals for diabetic retinopathy on the basis of individual risk factors. However, these approaches have not considered proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DME) as separate end points and death as competing risk. Methods: A multi‐state survival model with death as competing risk was used to predict the screening interval for diabetic retinopathy based on information about all 2446 patients from a well‐defined population who had started treatment for either PDR or DME during 25 years. The performance of the model was tested on the existing database and at seven screening sites on patients who had not developed a treatment requiring condition. Results: Testing on the existing database showed that at a risk level of 2% the algorithm could predict a screening interval with a success rate higher than 90% and a 1.75 times average prolongation of the screening interval without failing to detect the development of verified PDR og DME. The model was limited to a diabetes duration shorter than 40 years and depended on knowledge of relevant risk factors. At the other participating screening sites the algorithm predicted shorter intervals than the screener. Conclusions: Algorithms for individualised screening for diabetic retinopathy can prolong screening intervals without losing patients who develop a vision threatening condition. The calculation of screening intervals requires access to relevant risk factors and should be developed on large data sets that reflect the population in which the algorithm should be used. [ABSTRACT FROM AUTHOR]

Purpose: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR‐screening programme and non‐diabetes adults. Methods: In this registry‐based matched case–cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age‐ and sex‐matched by five non‐diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models. Results: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20–1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08–1.30) as compared to non‐diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72–0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR‐levels 1–4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow‐up (HR 1.23; 95% CI, 1.02–1.49). Conclusion: In a nationwide matched case–cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether individuals with long‐term reduced stereopsis were able to obtain the same level of surgical skills in simulated vitreoretinal surgery on the Eyesi Surgical Simulator as individuals with normal stereopsis. Methods: Twenty‐four medical students were recruited and divided into two groups according to their degree of stereopsis: Group 1 (n = 12) included subjects with normal stereopsis (60 arcsec or lower) and Group 2 (n = 12) included subjects with reduced stereopsis (120 arcsec or higher). Stereopsis was tested using the TNO test (Lameris Ootech BV, Nieuwegein, the Netherlands). The participants were trained in virtual reality‐simulated vitreoretinal surgery and continuously measured using a test with solid validity evidence and a pre‐defined pass–fail score. All data were analysed using the Wilcoxon rank sum test. Results: We observed no differences in overall performance scores for any of the four modules. The participants with reduced stereopsis used 5.8 more attempts in bimanual training (p = 0.04), 8.8 more attempts in removal of posterior hyaloid (p = 0.04), 9.1 more attempts in navigation training (p = 0.20) and 0.3 fewer attempts in removal of internal limiting membrane (p = 0.69). Conclusion: The final performance scores on the Eyesi Surgical Simulator were independent of the degree of stereopsis. However, the number of attempts to achieve the pre‐defined pass–fail score increased significantly with reduced stereopsis in two of four modules. These results indicate that a high degree of stereopsis is not necessary to become proficient in microsurgery but may prolong the learning curve. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of β-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR. Article Highlights: Type 2 diabetes can be subcategorized on the basis of β-cell function and insulin sensitivity, but little is known about the association of subtypes of type 2 diabetes with risk of diabetic retinopathy (DR). Do individuals with hyperinsulinemic or insulinopenic type 2 diabetes have an increased risk of DR compared with individuals with classical type 2 diabetes? Individuals with hyperinsulinemic type 2 diabetes had almost half the risk of prevalent or incident DR or progression of DR compared with individuals with classical type 2 diabetes. These results suggest that more individualized screening intervals for DR may be possible within subgroups of type 2 diabetes. [ABSTRACT FROM AUTHOR]

We report a three-generation family with isolated Alport-like retinal abnormalities in the absence of lenticonus, hearing loss, kidney disease, and detectable molecular genetic defects in known Alport-related genes. Clinical examination includes ocular biomicroscopy, fundus photography, optical coherence tomography, dipstick urinalysis, serum creatinine assessment, and molecular genetic analysis. The proband, her mother, and her maternal grandmother had normal best-corrected visual acuity and normal visual fields in both eyes. The macula presented a petaloid stair-case profile with scarce vessels in both eyes of the proband and a flat temporal macula lacking a foveal avascular zone in her mother and her grandmother. No family member had renal symptoms, unexplained subnormal hearing, or lenticonus. Sequencing and MLPA found no defect in COL4A3, COL4A4, and COL4A5. Common SNPs around the genes ± 1Mb showed no segregation. Furthermore, none of the variants shared between the affected individuals in genes from a gene panel of genes relevant for ophthalmopathy nor whole exome- and genome sequencing explained the phenotype. A new condition with two retinal Alport-like phenotypes was found. No abnormalities of the kidneys and lens were found, neither abnormalities of the type IV collagen genes related to Alport syndrome. Homology with retinal abnormalities seen in patients after surgical removal of the inner limiting membrane of the retina suggests that this is where the defect is located. We therefore suggest that the new retinal phenotypes and similar phenotypes can be described with the new definition "frail inner limiting membrane maculopathy." [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate retinal vein occlusion (RVO) as an independent marker of incident dementia. Methods: In a prospective nationwide cohort study, we identified 2 225 568 individuals through the Danish national health registers. Individuals older than 65 years, without unspecified retinal vascular occlusion or dementia were included from 1998 to 2020 and followed until 2022. We calculated the incidence rate (IR) and performed a Cox regression analysis with a hazard ratio (HR) and 95% confidence interval (CI) for RVO (exposure) as a marker of all‐cause dementia adjusted for systemic comorbidity. Results: We identified 19 669 individuals with RVO who had a higher prevalence of systemic comorbidity at inclusion compared to those without RVO (n = 2 185 483). We performed a Cox regression analysis for age‐dependent exposure due to non‐proportional hazards in the pre‐planned analysis. Exposed individuals younger than 75 years had an increased risk of all‐cause dementia (adjusted HR 1.09, 95% CI 1.01–1.18), whereas individuals older than 75 years had a decreased risk of all‐cause dementia (adjusted HR 0.92, 95% CI 0.86–0.98). Conclusion: Individuals with RVO had an age‐dependent risk of dementia, with a 9% increased risk in individuals with RVO younger than 75 years and an 8% decreased risk in individuals older than 75 years at the time of exposure. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate if retinal vascular calibers and systemic risk factors in patients with no or minimal diabetic retinopathy (DR) can predict risk of long‐term progression to proliferative diabetic retinopathy (PDR). Methods: This was a matched case–control study of patients with diabetes having no or minimal DR at baseline with (cases) or without (controls) subsequent development of PDR. We collected six‐field, 45‐degree retinal images, demographic and clinical data from the Funen Diabetes Database. Results: We included 52 eyes from 39 cases and 107 eyes from 89 controls matched on sex, age, type of diabetes, time from first to last screening episode and baseline DR level. Cases had higher HbA1c (73 vs. 55 mmoL/moL; p < 0.001), triglycerides (1.32 vs. 1.16 mmoL/L; p = 0.02) and longer duration of diabetes (19 vs. 14 years; p = 0.01), but the groups did not differ in calibers of retinal arterioles (229 vs. 227 μm; p = 0.49), venules (289 vs. 290 μm; p = 0.83) or the arterio‐to‐venule ratio (0.78 vs. 0.77; p = 0.86).In a multivariable logistic regression model with cluster robust standard error, HbA1c (OR 1.54 per 10 mmoL/moL; 95%‐CI: 1.15–2.07; p = 0.004), triglyceride (OR 1.39 per 1 mmoL/L; 95%‐CI: 1.03–1.86; p = 0.03) and duration of diabetes (OR 1.09 per year; 95%‐CI: 1.03–1.16; p = 0.003) were independent risk factors for PDR. Conclusion: Retinal vascular calibers did not predict long‐term development of PDR in contrast to well‐established risk factors like HbA1c, triglyceride and duration of diabetes. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non‐steroidal anti‐inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta‐analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non‐randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta‐analyses of comparative studies revealed a statistically significant but clinically irrelevant best‐corrected visual acuity improvement of −0.04 logMAR (95% CI: −0.07 to −0.01 logMAR; p = 0.01) at 1‐month follow‐up, which became statistically insignificant at 3‐month follow‐up (−0.03 logMAR; 95% CI: −0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1‐month follow‐up (OR: 1.20; 95% CI: 0.81–1.76; p = 0.37) or 3‐month follow‐up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC. [ABSTRACT FROM AUTHOR]

Purpose: Prediction of the early treatment response is important in neovascular age‐related macular degeneration (nAMD). Hence, we aimed to test if non‐invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. Methods: In 58 eyes of 58 patients with treatment‐naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra‐ or subretinal fluid or macular haemorrhage. Results: Of 54 eyes attending follow‐up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length‐diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82–0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68–1.00, p = 0.05, for each 0.01 unit increment). Conclusion: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long‐term, prospective studies, this might help to guide treatment. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is associated with cognitive impairment and a twofold increased risk of dementia compared with age-matched individuals without diabetes. Given that the eye and the brain share similar embryologic origin and anatomical features, the retina offers a unique window to the brain. In this study, we wanted to determine whether there was a difference in retinal imaging–based neuronal and vascular markers in individuals with type 2 diabetes with or without mild cognitive impairment (MCI). We included 134 persons with type 2 diabetes. Based on neuropsychological tests, the prevalence of MCI was 28%. We performed seven-field color fundus photos, optical coherence tomography (OCT), OCT-angiography (OCT-A), and retinal oximetry to analyze retinal markers. In a multivariable cluster analysis, persons with MCI had a significantly thinner macular retinal nerve fiber layer and macular ganglion cell layer, and less venular oxygen saturation in the nasal quadrant compared with those without MCI. There were no differences in retinal vessel density, fractal dimension, width, tortuosity, or OCT-A markers. People with type 2 diabetes and MCI demonstrate alterations in retinal structure and metabolism, suggesting noninvasive retinal markers may be useful to detect people with type 2 diabetes at risk for cognitive dysfunction. Article Highlights: Type 2 diabetes is associated with mild cognitive impairment (MCI). Therefore, retinal and cerebral neurodegeneration may run in parallel. To assess whether there was a difference in retinal structure, vessel, and metabolic parameters in individuals with MCI. We found those with MCI had a thinner macular retinal nerve fiber layer, macular ganglion cell layer, and less venular oxygen saturation. We suggest noninvasive retinal markers may be useful to detect those at risk of cognitive dysfunction. [ABSTRACT FROM AUTHOR]

We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta‐analyses on age‐stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population‐based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%–0.8%), 1.5% (95% CI: 0.7%–2.6%), and 7.6% (95% CI: 4.6%–11.3%) for individuals aged 60–69, 70–79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing. [ABSTRACT FROM AUTHOR]

A study conducted in Denmark evaluated the risk of progression from no diabetic retinopathy (DR) to proliferative diabetic retinopathy (PDR) in individuals with diabetes. The study found that the risk of progression to PDR within 2 years was lower than expected in a national cohort. While individuals with impaired glycemic control had a higher risk of progression to PDR, this was only statistically significant in those with type 2 diabetes. The study suggests that biannual screening intervals for individuals without DR may be safely introduced in national DR screening programs. The study was supported by VELUX FONDEN. [Extracted from the article]