Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.

Vision on gyrate atrophy: why treat the eye?

In the April issue of this Journal, Boffa and coworkers put forward a new therapeutic approach for Gyrate Atrophy of the Choroid and Retina (GACR; OMIM 258870) (Boffa et al, 2023). The authors propose to apply gene therapy to the liver for GACR, a metabolic disease primarily affecting eyesight due to retinal degeneration. Their vision is enthusiastically supported by a News and Views comment in the same issue (Seker Yilmaz and Gissen, 2023). However, based on disease pathology, patient's needs, ethical considerations, therapeutic developmental time lines, and current state of the art of gene therapy for liver and eye, we have a different view on this issue: We argue below that local treatment of the eye is the preferred option for GACR.

Prediction of visual impairment in retinitis pigmentosa using deep learning and multimodal fundus images.

BACKGROUND: The efficiency of clinical trials for retinitis pigmentosa (RP) treatment is limited by the screening burden and lack of reliable surrogate markers for functional end points. Automated methods to determine visual acuity (VA) may help address these challenges. We aimed to determine if VA could be estimated using confocal scanning laser ophthalmoscopy (cSLO) imaging and deep learning (DL). METHODS: Snellen corrected VA and cSLO imaging were obtained retrospectively. The Johns Hopkins University (JHU) dataset was used for 10-fold cross-validations and internal testing. The Amsterdam University Medical Centers (AUMC) dataset was used for external independent testing. Both datasets had the same exclusion criteria: visually significant media opacities and images not centred on the central macula. The JHU dataset included patients with RP with and without molecular confirmation. The AUMC dataset only included molecularly confirmed patients with RP. Using transfer learning, three versions of the ResNet-152 neural network were trained: infrared (IR), optical coherence tomography (OCT) and combined image (CI). RESULTS: In internal testing (JHU dataset, 2569 images, 462 eyes, 231 patients), the area under the curve (AUC) for the binary classification task of distinguishing between Snellen VA 20/40 or better and worse than Snellen VA 20/40 was 0.83, 0.87 and 0.85 for IR, OCT and CI, respectively. In external testing (AUMC dataset, 349 images, 166 eyes, 83 patients), the AUC was 0.78, 0.87 and 0.85 for IR, OCT and CI, respectively. CONCLUSIONS: Our algorithm showed robust performance in predicting visual impairment in patients with RP, thus providing proof-of-concept for predicting structure-function correlation based solely on cSLO imaging in patients with RP.

Tips to optimize digital education in ophthalmology: Results from ESASO survey.

PURPOSE: To identify audience and faculty preferences to optimize digital education sessions in ophthalmology. METHODS: We distributed an online survey to ophthalmology trainees and specialists worldwide. The survey investigated respondents' preferences on various findings of hypothetical digital educational sessions. Data were analyzed using descriptive statistics, Fisher's exact probability and ANOVA tests. RESULTS: The survey was completed by 655 respondents, from 53 different countries. According to most respondents, the optimal duration and timeframe for a valuable digital education session would be 30-60 min, without a break (52%), in the evening time-slot (6-8 p.m.) (45%) of a weekday (Monday-Thursday) (46%), regardless of age (p-value = 0.84, 0.39, 0.89, respectively) and job position (p-value = 0.31, 0.29, 0.08, respectively). The availability of webinars and recorded surgical videos/clinical cases, associated with live discussion, represented the most important opportunity of digital educational channels for 46% and 42% of respondents, respectively. CONCLUSION: Appropriate planning of timing and structure of digital educational ophthalmology sessions may optimize their effectiveness. Using multiple e-learning formats may be helpful to ensure the continuity of learning activities, also in view of a long-term replacement of traditional in-person education.

Clinical spectrum of severe chronic central serous chorioretinopathy and outcome of photodynamic therapy.

PURPOSE: To describe a spectrum of severe chronic central serous chorioretinopathy (cCSC) cases and their response to photodynamic therapy (PDT). PATIENTS AND METHODS: A total of 66 patients (81 eyes) with active severe cCSC were studied, and their response to PDT was compared with a control group consisting of 35 active cCSCs (37 eyes) that did not display characteristics of severity. Best-corrected visual acuity (BCVA) and complete resolution of subretinal fluid (SRF) were considered as main outcome measures. RESULTS: In severe cCSC cases, we found cumulative areas of diffuse atrophic retinal pigment epithelium alterations in 48 eyes (59%), multiple "hot spots" of leakage in 36 eyes (44%), posterior cystoid retinal degeneration in 25 eyes (31%), and 13 eyes (16%) had a diffuse leakage on fluorescein angiography. After PDT treatment, BCVA increased in both groups, from 66 to 72 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the case group (P<0.001), and from 78 to 82 ETDRS letters in the control group (P<0.001). SRF had resolved completely in 87% of severe cCSC cases and 95% of controls at final follow-up visit. CONCLUSION: A spectrum of severe cCSC exists, and PDT seems to be an effective treatment in both severe cCSC and nonsevere cCSC in terms of resolution of SRF. Final BCVA shows a significant improvement in both groups after PDT treatment.

Clinical characteristics and long-term visual outcome of severe phenotypes of chronic central serous chorioretinopathy.

PURPOSE: The aim of this study was to investigate disease onset and disease progression in patients with severe chronic central serous chorioretinopathy (cCSC). PATIENTS AND METHODS: The medical records of 143 cCSC patients (199 eyes) were reviewed. All cases had visual complaints for >6 months and showed signs of a severe disease phenotype on optical coherence tomography (OCT) and fluorescein angiography (FA). Clinical presentation at onset was evaluated, together with disease progression on multimodal imaging and final treatment outcome. RESULTS: Twenty-eight cases (14%) had a documented history of an acute episode of CSC, whereas 145 cases (73%) showed pre-existing features of chronicity already at first presentation. The first clinical presentation could not be evaluated in 13% of cases. Best-corrected visual acuity (BCVA) was 70 ± 18 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at onset and 70 ± 22 ETDRS letters at final visit (p = 0.770). Among all studied cases, 173 eyes (87%) were treated, which resulted in complete resolution of subretinal fluid (SRF) in 76% of eyes at final visit. In eyes with fluorescein angiographic follow-up, the area of diffuse atrophic retinal pigment epithelium (RPE) abnormalities (diffuse atrophic RPE alterations [DARA]) had increased significantly in 43 eyes (68%) at final visit. CONCLUSION: CSC encompasses a clinical spectrum that includes a range of severe phenotypes, in which retinal abnormalities tend to be progressive. Nevertheless, the long-term visual acuity may remain fairly stable with treatment. Few patients with severe chronic CSC have a history of acute CSC, which could indicate that there may be pathogenetic differences between these 2 CSC variants.

Diagnostic exome sequencing in 266 Dutch patients with visual impairment.

Inherited eye disorders have a large clinical and genetic heterogeneity, which makes genetic diagnosis cumbersome. An exome-sequencing approach was developed in which data analysis was divided into two steps: the vision gene panel and exome analysis. In the vision gene panel analysis, variants in genes known to cause inherited eye disorders were assessed for pathogenicity. If no causative variants were detected and when the patient consented, the entire exome data was analyzed. A total of 266 Dutch patients with different types of inherited eye disorders, including inherited retinal dystrophies, cataract, developmental eye disorders and optic atrophy, were investigated. In the vision gene panel analysis (likely), causative variants were detected in 49% and in the exome analysis in an additional 2% of the patients. The highest detection rate of (likely) causative variants was in patients with inherited retinal dystrophies, for instance a yield of 63% in patients with retinitis pigmentosa. In patients with developmental eye defects, cataract and optic atrophy, the detection rate was 50, 33 and 17%, respectively. An exome-sequencing approach enables a genetic diagnosis in patients with different types of inherited eye disorders using one test. The exome approach has the same detection rate as targeted panel sequencing tests, but offers a number of advantages. For instance, the vision gene panel can be frequently and easily updated with additional (novel) eye disorder genes. Determination of the genetic diagnosis improved the clinical diagnosis, regarding the assessment of the inheritance pattern as well as future disease perspective.

Chronic central serous chorioretinopathy: long-term follow-up and vision-related quality of life.

PURPOSE: To describe the clinical findings and long-term outcome of patients with chronic central serous chorioretinopathy (cCSC). MATERIALS AND METHODS: This was a retrospective case series in 52 eyes of 36 patients with a follow-up period of at least 1 year. Extensive ophthalmic examination and a validated questionnaire concerning vision-related quality of life (National Eye Institute Visual Function Questionnaire [NEI-VFQ]-39) were analyzed. RESULTS: Mean visual acuity showed a significant decline over time of 0.16 logarithm of minimum angle of resolution ([logMAR] range: -0.22 to 1.3; P=0.009) after a mean follow-up period of 10.6 years. Also, patients reported lower vision-related quality of life based on the NEI-VFQ-39 for almost all categories compared to healthy controls. Macular atrophy was diagnosed more often on optical coherence tomography compared to other diagnostic entities. Retinal pigment epithelium detachments in the macula were documented on optical coherence tomography in 56% of the patients. A significant thinning of foveal thickness was measured over time compared to unaffected fellow eyes (P=0.002). On long-term follow-up, 13 eyes (37%) showed an increase in number of hot spots on fluorescein angiography. CONCLUSION: This study indicates that cCSC is a progressive disease in many patients, causing a progressive decline in visual acuity, accompanied by lower reported vision-related quality of life. In deciding whether or not to treat, the progressive nature of cCSC should be taken into account in this relatively young and often still professionally active patient group.