Investigating the causal link between gut microbiota and dry age-related macular degeneration:a bidirectional Mendelian randomization study

AIM:To assess the causal link between 211 gut microbiota(GM)taxa and dry age-related macular degeneration(dAMD)risk.METHODS:Mendelian randomization using instrumental factors taken from a genome-wide association study(GWAS)were used.Inverse variance weighted(IVW)analysis and sensitivity analysis were performed on the FinnGen project,which included 5095 cases and 222590 controls.RESULTS:The IVW analysis showed substantial genusand family-level relationships between GM taxa and dAMD risk.Specifically,the family Peptococcaceae(P=0.03),genus Bilophila(P=3.91×10^(-3)),genus Faecalibacterium(P=6.55×10^(-3)),and genus Roseburia(P=0.04)were linked to a higher risk of developing dAMD,while the genus Candidatus Soleaferrea(P=7.75×10^(-4)),genus Desulfovibrio(P=0.04)and genus Eubacterium ventriosum group(P=0.04)exhibited a protective effect against dAMD.No significant causal relationships were observed at higher taxonomic levels.Additionally,in the reverse IVW analysis,no meaningful causal effects of the 7 GM taxa.CONCLUSION:These findings give support for the gutretina axis participation in dAMD and shed light on putative underlying processes.Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.

Progress of clinical therapies for dry age-related macular degeneration

Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.

Evaluating role of bone marrow-derived stem cells in dry age-related macular degeneration using multifocal electroretinogram and fundus autofluorescence imaging

AIM：To evaluate the role of bone marrow-derived stem cells in the treatment of advanced dry age-related macular degeneration（AMD）using multifocal electroretinogram（mf-ERG）and fundus autofluorescence imaging.METHODS：Thirty patients（60 eyes）with bilateral central geographic atrophy（GA）were recruited.Worse eye of each patient received autologous bone marrow-derived hematopoietic stem cells（BM-HSCs）（group 1）and the fellow eye with better visual acuity served as control（group2）.The effect of stem cell therapy was determined in terms of visual acuity,amplitude and implicit time in mf-ERG and size of GA on fundus autofluorescence imaging.These tests were performed at presentation and first,third and sixth month follow up.Adverse events（if any）were also monitored.RESULTS：At 6mo follow-up there was no statistically significant improvement in median log MAR best corrected visual acuity（BCVA）in either group.Mf-ERG revealed significant improvement in amplitude and implicit time in the intervention group.A significant decrease was also noted in greatest linear dimension（GLD）of GA in the eyes receiving stem cells[6.78±2.60 mm at baseline to 6.56±2.59 mm at 6mo（P=0.021）].However,no such improvement was noted in the control group.CONCLUSION：Electrophysiological and anatomical improvement in the intervention group sheds light on the therapeutic role of BM-HSCs.Further studies are required to determine the stage of disease at which the maximal benefit can be achieved and to standardize the dose andfrequency of stem cell injection.

Narrative review of risuteganib for the treatment of dry age-related macular degeneration (AMD)

Age-related macular degeneration(AMD)is a leading cause of blindness worldwide.AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina.Currently,there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation.Risuteganib[Luminate(ALG-1001),Allegro Ophthalmics,CA,USA]is an intravitreally administered inhibitor of integrin heterodimersαVβ3,αVβ5,α5β1,andαMβ2.It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema(DME).Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis,inflammation,and vascular permeability.Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity(BCVA)and reduced central macular thickness measured by optical coherence tomography(OCT).There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients,more data are needed before one can truly evaluate its efficacy.This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.

Dobesilate for dry age-related macular degeneration

We have evaluated the effects of intravitreal dobesilate, a synthetic fibroblast growth factor inhibitor, in patients with dry age-related macular degeneration, an inflammatory-related retinal disease without available treatment up to date. 36 eyes from 36 patients with dry age-related macular degeneration were treated with a single intravitreal dobesilate injection. The end points were the improvement from baseline visual acuity and normalization of retinal histology at one month. Intravitreal dobesilate injection resulted in a significant improvement in functional and anatomical outcomes at one month after injection. Our results suggest that intravitreal dobesilate may increase the chance of visual acuity gain in dry age-related macular degeneration, even in cases with initial low vision. This study supports the findings of previously published case reports, regarding the short-term improvement in visual acuity by intravitreal dobesilate injection in different degenerative retinal diseases.

Choriocapillaris changes in dry age-related macular degeneration and geographic atrophy: a review

Age-related macular degeneration(AMD)is a leading cause of central vision loss worldwide.The progression of dry AMD from early to intermediate stages is primarily characterized by increasing drusen formation and adverse impact on outer retinal cells.Late stage AMD consists of either geographic atrophy(GA),the non-exudative(dry)AMD subtype,or choroidal neovascularization,the exudative(wet)AMD subtype.GA is characterized by outer retinal and choroidal atrophy,specifically the photoreceptor layer,RPE,and choriocapillaris.Much remains to be discovered regarding the pathogenesis of AMD progression and subsequent development of GA.As the functionality of all three layers is closely linked,the temporal sequence of events that end up in atrophy is important in the understanding of the pathogenic pathway of the disease.The advent of OCTA,and particularly of swept-source technology,has allowed for depth-resolved imaging of retinal vasculature and the choriocapillaris.With the use of OCTA,recent studies demonstrate that choriocapillaris flow alterations are closely associated with the development and progression of AMD.Such changes may even possibly offer predictive value in determining progression of GA.This article reviews studies demonstrating choriocapillaris changes in dry AMD and summarizes the existing literature on the potential role of the choriocapillaris as a key factor in the pathogenesis of AMD.