BASELINE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHIC RETINAL LAYER FEATURES IDENTIFIED BY ARTIFICIAL INTELLIGENCE PREDICT THE COURSE OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To identify optical coherence tomography (OCT) features to predict the course of central serous chorioretinopathy (CSC) with an artificial intelligence-based program. METHODS: Multicenter, observational study with a retrospective design. Treatment-naïve patients with acute CSC and chronic CSC were enrolled. Baseline OCTs were examined by an artificial intelligence-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). Through this platform, automated retinal layer thicknesses and volumes, including intaretinal and subretinal fluid, and pigment epithelium detachment were measured. Baseline OCT features were compared between acute CSC and chronic CSC patients. RESULTS: One hundred and sixty eyes of 144 patients with CSC were enrolled, of which 100 had chronic CSC and 60 acute CSC. Retinal layer analysis of baseline OCT scans showed that the inner nuclear layer, the outer nuclear layer, and the photoreceptor-retinal pigmented epithelium complex were significantly thicker at baseline in eyes with acute CSC in comparison with those with chronic CSC ( P < 0.001). Similarly, choriocapillaris and choroidal stroma and retinal thickness (RT) were thicker in acute CSC than chronic CSC eyes ( P = 0.001). Volume analysis revealed average greater subretinal fluid volumes in the acute CSC group in comparison with chronic CSC ( P = 0.041). CONCLUSION: Optical coherence tomography features may be helpful to predict the clinical course of CSC. The baseline presence of an increased thickness in the outer retinal layers, choriocapillaris and choroidal stroma, and subretinal fluid volume seems to be associated with acute course of the disease.

VASCULAR ABNORMALITIES IN DIABETIC RETINOPATHY ASSESSED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WIDEFIELD IMAGING.

PURPOSE: To detect vascular abnormalities in diabetic retinopathy using swept-source optical coherence tomography angiography (SS-OCTA) widefield images, and to compare the findings with color fundus photographs (CFPs) using Early Treatment Diabetic Retinopathy Study severity grading. METHODS: 3 mm × 3 mm and 12 mm × 12 mm scans were acquired to cover 70° to 80° of the posterior pole using a 100-kHz SS-OCTA instrument. Two masked graders assessed the presence of vascular abnormalities on SS-OCTA and the Early Treatment Diabetic Retinopathy Study level on CFP. The grading results were then compared. RESULTS: A total of 120 diabetic eyes (60 patients) were imaged with the SS-OCTA instrument. Cohort 1 (91 eyes; SS-OCTA grading only) showed microaneurysms in 91% (n = 83), intraretinal microvascular abnormalities in 79% (n = 72), and neovascularization in 21% (n = 19) of cases. Cohort 2 (52 eyes; CFP grading compared with SS-OCTA) showed microaneurysms on CFP in 90% (n = 47) and on SS-OCTA in 96% (n = 50) of cases. Agreement in intraretinal microvascular abnormality detection was fair (k = 0.2). Swept-source optical coherence tomography angiography detected 50% of intraretinal microvascular abnormality cases (n = 26), which were missed on CFP. Agreement in detecting neovascularization was moderate (k = 0.5). CONCLUSION: Agreement in detection of diabetic retinopathy features on CFP and SS-OCTA varies depending on the vascular changes examined. Swept-source optical coherence tomography angiography shows a higher detection rate of intraretinal microvascular abnormalities (P = 0.039), compared with Early Treatment Diabetic Retinopathy Study grading.

Analysis of optical coherence tomography biomarker probability detection in central serous chorioretinopathy by using an artificial intelligence-based biomarker detector.

AIM: To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC). METHODS: Multicenter, observational study with a retrospective design enrolling treatment-naïve patients with aCSC and cCSC. The diagnosis of aCSC and cCSC was established with multimodal imaging and for the current study subsequent follow-up visits were also considered. Baseline OCTs were analyzed by an AI-based platform (Discovery® OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). This software allows to detect several different biomarkers in each single OCT scan, including subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HF) and flat irregular pigment epithelium detachment (FIPED). The presence of SRF was considered as a necessary inclusion criterion for performing biomarker analysis and OCT slabs without SRF presence were excluded from the analysis. RESULTS: Overall, 160 eyes of 144 patients with CSC were enrolled, out of which 100 (62.5%) eyes were diagnosed with cCSC and 60 eyes (34.5%) with aCSC. In the OCT slabs showing presence of SRF the presence of biomarkers was found to be clinically relevant (> 50%) for HF and FIPED in aCSC and cCSC. HF had an average percentage of 81% (± 20) in the cCSC group and 81% (± 15) in the aCSC group (p = 0.4295) and FIPED had a mean percentage of 88% (± 18) in cCSC vs. 89% (± 15) in the aCSC (p = 0.3197). CONCLUSION: We demonstrate that HF and FIPED are OCT biomarkers positively associated with CSC when present at baseline. While both HF and FIPED biomarkers could aid in CSC diagnosis, they could not distinguish between aCSC and cCSC at the first visit. AI-assisted biomarker detection shows promise for reducing invasive imaging needs, but further validation through longitudinal studies is needed.

The role of the gut microbiome in eye diseases.

The gut microbiome is a complex ecosystem of microorganisms and their genetic entities colonizing the gastrointestinal tract. When in balanced composition, the gut microbiome is in symbiotic interaction with its host and maintains intestinal homeostasis. It is involved in essential functions such as nutrient metabolism, inhibition of pathogens and regulation of immune function. Through translocation of microbes and their metabolites along the epithelial barrier, microbial dysbiosis induces systemic inflammation that may lead to tissue destruction and promote the onset of various diseases. Using whole-metagenome shotgun sequencing, several studies have shown that the composition and associated functional capacities of the gut microbiome are associated with age-related macular degeneration, retinal artery occlusion, central serous chorioretinopathy and uveitis. In this review, we provide an overview of the current knowledge about the gut microbiome in eye diseases, with a focus on interactions between the microbiome, specific microbial-derived metabolites and the immune system. We explain how these interactions may be involved in the pathogenesis of age-related macular degeneration, retinal artery occlusion, central serous chorioretinopathy and uveitis and guide the development of new therapeutic approaches by microbiome-altering interventions for these diseases.

Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a shotgun metagenomics analysis of 57 neovascular AMD and 58 healthy controls as well as of 16 complement C3-deficient mice and 16 wildtypes was performed. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and species Bacteroides had a significantly higher prevalence in persons without AMD. Similar taxonomic features were identified that distinguished wildtype mice from C3-deficient mice. Moreover, several purine signaling pathways were associated with both, neovascular AMD and C3 deficiency. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with neovascular AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. This study suggests an association between the intestinal microbiome and the complement system in neovascular AMD.

Retinal artery occlusion is associated with compositional and functional shifts in the gut microbiome and altered trimethylamine-N-oxide levels.

Retinal artery occlusion (RAO) is a sight threatening complication of cardiovascular disease and commonly occurs due to underlying atherosclerosis. As cardiovascular disease and atherosclerosis in particular has been associated with compositional alterations in the gut microbiome, we investigated this association in patients with clinically confirmed non-arteritic RAO compared to age- and sex-matched controls. On the phylum level, the relative abundance of Bacteroidetes was decreased in patients with RAO compared to controls, whereas the opposite applied for the phylum of Proteobacteria. Several genera and species such as Actinobacter, Bifidobacterium spp., Bacteroides stercoris, Faecalibacterium prausnitzii were relatively enriched in patients with RAO, whereas others such as Odoribacter, Parasutterella or Lachnospiraceae were significantly lower. Patient's gut microbiomes were enriched in genes of the cholesterol metabolism pathway. The gut derived, pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) was significantly higher in patients with RAO compared to controls (p = 0.023) and a negative correlation between relative abundances of genera Parasutterella and Lachnospiraceae and TMAO levels and a positive correlation between relative abundance of genus Akkermansia and TMAO levels was found in study subjects. Our findings proposes that RAO is associated with alterations in the gut microbiome and with elevated TMAO levels, suggesting that RAO could be targeted by microbiome-altering interventions.

Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. There is evidence that nutrition, inflammation and genetic risk factors play an important role in the development of AMD. Recent studies suggest that the composition of the intestinal microbiome is associated with metabolic diseases through modulation of inflammation and host metabolism. To investigate whether compositional and functional alterations of the intestinal microbiome are associated with AMD, we sequenced the gut metagenomes of patients with AMD and controls. The genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum were relatively enriched in patients with AMD, whereas Bacteroides eggerthii was enriched in controls. Patient's intestinal microbiomes were enriched in genes of the L-alanine fermentation, glutamate degradation and arginine biosynthesis pathways and decreased in genes of the fatty acid elongation pathway. These findings suggest that modifications in the intestinal microbiome are associated with AMD, inferring that this common sight threatening disease may be targeted by microbiome-altering interventions.