Gut Microbiome in Retina Health. The Crucial Role of the Gut-Retina Axis

The term microbiome means not only a complex ecosystem of microbial species that colonize our body but also their genome and the surrounding environment in which they live. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age-related macular disorders. This review aims to underline the importance of the gut microbiome in relation to ocular health. After briefly introducing the characteristics of the gut microbiome in terms of composition and functions, the role of gut microbiome dysbiosis, in the development or progression of retinal diseases, is highlighted, focusing on the relationship between gut microbiome composition and retinal health based on the recently investigated gut-retina axis

Microbiota and age-related macular degeneration: where are we today?

Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. It is well known that age, family history, smoking, nutrition, and inflammation contribute to the development of AMD. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course

Differential vulnerability of retinal layers to early age-related macular degeneration: evidence by SD-OCT segmentation analysis.

PURPOSE We evaluated layer-by-layer retinal thickness in spectral-domain optical coherence tomography (SD-OCT), determined by automated segmentation analysis (ASA) software in healthy and early age-related maculopathy (ARM) eyes. METHODS There were 57 eyes (specifically, 19 healthy eyes under 60 years old, 19 healthy eyes over 60, and 19 ARM eyes) recruited into this cross-sectional study. The mean ages were 36.78 (SD, ±13.82), 69.89 (SD, ±6.14), and 66.10 (SD, ±8.67) years, respectively, in the three study groups. The SD-OCT scans were transferred into a dedicated software program that performed automated segmentation of different retinal layers. RESULTS Automated layer segmentation showed clear boundaries between the following layers: retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCL+IPL), inner nuclear layer plus outer plexiform layer (INL+OPL), outer nuclear layer (ONL), and RPE complex. The thickness of the RNFL, ONL, and RPE layers did not show a statistically significant change across the three groups by ANOVA (P = 0.10, P = 0.09, P = 0.15, respectively). The thickness of GCL+IPL and INL+OPL was significantly different across the groups (P < 0.01), being reduced in the ARM eyes compared to healthy eyes, under and over 60 years old. CONCLUSIONS The early morphologic involvement of the GCL+IPL and INL+OPL layers in ARM eyes, as revealed by the ASA, could be related to early anatomic changes described in the inner retina of ARM eyes. This finding may represent a morphologic correlation to the deficits in postreceptoral retinal function in ARM eyes

Macular Impairment in Fabry Disease: A Morpho-functional Assessment by Swept-Source OCT Angiography and Focal Electroretinography.

Purpose Fabry disease (FD) is a multiorgan X-linked condition characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in a progressive intralysosomal deposit of globotriaosylceramide. The aim of this study was to evaluate the macular ultrastructure of the vascular network using optical coherence tomography angiography (OCTA) and to evaluate macular function using focal electroretinography (fERG) in Fabry patients (FPs). Methods A total of 20 FPs (38 eyes, mean age 57 ± 2.12 SD, range of 27-80 years) and 17 healthy controls (27 eyes, mean age 45 years ± 20.50 SD, range of 24-65 years) were enrolled in the study. Color fundus photography, swept-source optical coherence tomography (SS-OCT), OCTA and fERG were performed in all subjects. The OCTA foveal avascular zone (FAZ), vasculature structure, superficial and deep retinal plexus densities (images of 4.5 × 4.5 mm) and fERG amplitudes were measured. Group differences were statistically assessed by Student's t-test and ANOVA. Results In the FP group, the FAZ areas of the superficial and deep plexuses were enlarged (P = 0.036, t = 2.138; P < 0.001, t = -3.889, respectively), the vessel density was increased in the superficial plexus, and the fERG amplitude was reduced (P < 0.001, t = -10.647) compared with those in healthy controls. No significant correlations were found between the structural and functional data. Conclusions OCTA vascular abnormalities and reduced fERG amplitudes indicate subclinical signs of microangiopathy with early retinal dysfunction in FPs. This study highlights the relevance of OCTA imaging analysis in the identification of abnormal macular vasculature as an ocular hallmark of FD

Intravitreal Fluocinolone Acetonide for Diabetic Macular Edema: Long-Term Effect and Structure/Function Correlation

The long-term effect of intravitreal Fluocinolone acetonide (FAc) on retinal morphology and function in diabetic macular edema (DME) was investigated. Seventeen eyes of twelve consecutive DME patients, treated by intravitreal FAc, were retrospectively evaluated. Retinal morphology was assessed with central macular thickness (CMT). Retinal function was assessed by best-corrected visual acuity (BCVA) and cone b-wave and photopic negative response (PhNR). The main outcome was a mean change in CMT at month 24. The secondary outcomes were changes in cone b-wave and PhNR at month 24. The incidence of adverse events was also recorded. Mean CMT decreased from 406.52 mu m (+/- 138.74) at baseline to 310 mu m (+/- 130.39) at 24 months (p = 0.008). No significant changes in the other parameters were found. At baseline, BCVA and PhNR amplitude were negatively correlated (r = -0.55) with CMT. At the end of follow-up, the change in CMT was negatively correlated with baseline CMT (r = -0.53, p = 0.03) and positively correlated with baseline PhNR amplitude (r = 0.58, p &lt; 0.01). A significant, long-term reduction in CMT was observed in DME patients after FAc implant. The anti-edema effect tended to be stronger in patients with the poorest baseline retinal morphology (CMT) and function (PhNR). Structure/function correlations might help to characterize the patients who may benefit from this treatment

Bilateral Symmetry of Visual Function Loss in Cone-Rod Dystrophies.

PURPOSE: To investigate bilateral symmetry of visual impairment in cone-rod dystrophy (CRD) patients and understand the feasibility of clinical trial designs treating one eye and using the untreated eye as an internal control. METHODS: This was a retrospective study of visual function loss measures in 436 CRD patients followed at the Ophthalmology Department of the Catholic University in Rome. Clinical measures considered were best-corrected visual acuity, focal macular cone electroretinogram (fERG), and Ganzfeld cone-mediated and rod-mediated electroretinograms. Interocular agreement in each of these clinical indexes was assessed by t- and Wilcoxon tests for paired samples, structural (Deming) regression analysis, and intraclass correlation. Baseline and follow-up measures were analyzed. A separate analysis was performed on the subset of 61 CRD patients carrying likely disease-causing mutations in the ABCA4 gene. RESULTS: Statistical tests show a very high degree of bilateral symmetry in the extent and progression of visual impairment in the fellow eyes of CRD patients. CONCLUSIONS: These data contribute to a better understanding of CRDs and support the feasibility of clinical trial designs involving unilateral eye treatment with the use of fellow eye as internal control

Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report.

Abstract BACKGROUND: To determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes. METHODS: Thirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6--12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18[degree sign]) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures. RESULTS: After three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p &lt; 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes. CONCLUSIONS: The present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease

Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Correlation with Macular Function

The purpose of this study was to investigate the relationship between the retinal pigment epithelium (RPE) and outer retina changes, expressed in terms of sub-RPE illumination (SRI) on optical-coherence tomography (OCT), and central retinal function, measured by visual acuity and focal electroretinogram (fERG), in patients with non-exudative age-related macular degeneration (neAMD). In this retrospective study, 29 eyes of 29 patients affected by early (24.14%), intermediate (41.38%), and advanced (34.48%) neAMD were evaluated. All enrolled eyes were studied with OCT to measure the total area of SRI, by using an automated standardized algorithm. Visual acuity and fERG were assessed. The area of SRI was negatively correlated with fERG amplitude (r &lt;= -0.4, p &lt;= 0.02) and best-corrected visual acuity (BCVA) (r &lt;= 0.4, p &lt;= 0.04). Our results indicate that the severity of retinal pigment epithelium and outer retina atrophy (RORA), indirectly quantified through the detection of SRI areas by commercial OCT algorithms, is correlated with central retinal dysfunction, as determined by visual acuity and fERG, supporting the combined use of structural exams and functional tests as valid tools to detect the extent of RPE and photoreceptors' disruption

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut–Retina Axis

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged &ge;65 years in developed countries. Globally, it affects 30&ndash;50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression

Combined Intravitreal Dexamethasone Implant and Cataract Surgery in Patients with Diabetic Retinopathy: Effect on Retinal Morphology and Function

Introduction: Cataract surgery can be associated with vision-threatening complications in patients with diabetes. This study aimed to assess the functional and anatomic outcomes of the intravitreal dexamethasone (DEX) implant, administered at the time as cataract surgery, in patients with diabetic retinopathy and diabetic macular edema (DME). Methods: This was a retrospective, observational, and single-center study. The primary endpoint was the mean change in central macular thickness (CMT) from baseline to month 1. Secondary endpoints included mean change in best corrected visual acuity (BCVA) from baseline to month 1 and 3, mean change in CMT from baseline to month 3, the photopic negative response (PhNR) and the b wave of flash full-field electroretinogram from baseline to month 1, and the incidence of adverse events. Results: Twenty-four eyes of 21 patients were included in the study. The mean (range) age of patients was 69 (63\u201387) years and 13 (61.9%) were men. Mean (standard deviation) CMT significantly decreased from 447 (134) lm at baseline to 341 (134) lm at month 1 (mean difference - 106 \ub1 134 lm, 95% CI - 183.9 to - 28.1 lm; p = 0.0087). BCVA significantly improved from 46 (20) ETDRS letters at baseline to 59 (22) ETDRS letters at month 1 (mean difference 13 \ub1 21 letters, 95% CI 0.8\u201325.2 letters; p = 0.0375). Regarding electrophysiology, there was a statistically significant reduction in mean PhNR from 5.24 (1.67) lV at baseline to 3.73 (1.19) lV at month 1 (mean difference - 1.51 \ub1 0.42 lV, 95% CI - 2.4 to - 0.7 lV, p = 0.0008); whereas b wave amplitude did not change (12.69 \ub1 6.89 lV at baseline versus 12.29 \ub1 6.30 lV at month 1; p = 0.8347). Four (16.7%) eyes developed ocular hypertension over the course of follow-up, which was successfully controlled with topical hypotensive medication. Conclusion: Perioperative DEX implant significantly improved both anatomic and functional outcomes in patients with DME who underwent cataract surgery