Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis

Purpose We performed a case‐control study to search for genetic interactions and for differences in dry and wet age‐related macular degeneration (AMD) pathogenesis.Methods We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested.Results No association was found between either the exudative or the dry form and the genetic backround in the case of Apolipoprotein E, complement factor I, FXIII and MerTK polymorphisms. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR=0.50, 95%CI: 0.26‐0.97, p=0.04). Multiple regression models revealed a genetic interaction in the dry AMD subgroup. In the absence of a C3 risk allele, mutated alleles of both CFH and HTRA1 behaved as strongly significant risk factors (OR=7.96, 95%CI: 2.39=26.50, p=0.0007, and OR=36.02, 95%CI: 3.30‐393.02, p=0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near‐five‐fold relative increase in the odds of dry type AMD(OR=4.93, 95%CI: 1.98‐12.25, p=0.0006)Conclusion Our results shed light on the protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed in dry AMD pathogenesis.

Quantitative Proteomics: Comparison of the Macular Bruch Membrane/Choroid Complex from Age-related Macular Degeneration and Normal Eyes

Background Age related macular degeneration (AMD) is the most common cause of irreversible visual loss in elderly individuals. Purpose The aim of this study was to identify the potential role of serum pro-inflammatory cytokines, including interleukin-13 (IL-13), IL-17, tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF), in patients with AMD. Patients and methods The patients were divided into three groups: 20 patients with dry AMD, 20 patients with wet AMD before treatment with anti-VEGF injections, and 20 patients with wet AMD after anti-VEGF injections. Serum samples from patients with AMD and 20 age-matched controls were examined for the aforementioned cytokines using the ELISA technique. Results Serum levels of IL-13, IL-17, and TGF-β were significantly elevated in all patients with AMD compared with the controls (P=0.045, 0.047, and 0.042, respectively). There was a positive correlation (r=0.6, P=0.045) between the levels of IL-13 and TGF-β in these patients. In addition, the serum levels of TNF-α were significantly decreased in patients with AMD compared with the controls (P=0.037). The serum levels of IL-17 of the patients treated with anti-VEGF were significantly decreased compared with the untreated patients (P=0.032). In addition, the serum levels of TNF-α were significantly elevated in the treated patients compared with the untreated patients (P=0.024). There was no significant difference in the levels of IL-13, TGF-β, and VEGF in the treated patients compared with the untreated patients (P=0.07). Conclusion The study demonstrated that AMD is an inflammatory disease as patients with AMD had elevated levels of IL-13, IL-17, and TGF-β. In addition, serum IL-17 and TNF-α level could be significant predictors of the efficiency of anti-VEGF therapy. These findings may help in improvement of AMD diagnosis and may lead to the development of new therapeutic agents targeting these cytokines.

Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes—Wet and Dry AMD—while shedding light on the prevalence and risk factors, including age, genetics, and smoking. The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions. For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives. The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust. The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.

PurposePatients with age-related macular degeneration (AMD) experience difficulty with discriminating between faces. We aimed to use a new clinical test to quantify the impact of AMD on face perception and to determine the specific aspects that are affected.MethodsThe Caledonian face test uses an adaptive procedure to measure face discrimination thresholds: the minimum difference required between faces for reliable discrimination. Discrimination thresholds were measured for full-faces, external features (head-shape and hairline), internal features (nose, mouth, eyes, and eyebrows) and shapes (non-face task). Participants were 20 patients with dry AMD (logMAR VA = 0.14 to 0.62), 20 patients with wet AMD (0.10 to 0.60), and 20 age-matched control subjects (−0.18 to +0.06).ResultsRelative to controls, full-face discrimination thresholds were, on average, 1.76 and 1.73 times poorer in participants with dry and wet AMD, respectively. AMD also reduced sensitivity to face features, but discrimination of the internal, relative to external, features was disproportionately impaired. Both distance VA and contrast sensitivity were significant independent predictors of full-face discrimination thresholds (R2 = 0.66). Sensitivity to full-faces declined by a factor of approximately 1.19 per 0.1 logMAR reduction in VA.ConclusionsBoth dry and wet AMD significantly reduce sensitivity to full-faces and their component parts to similar extents. Distance VA and contrast sensitivity are closely associated with face discrimination sensitivity. These results quantify the extent of sensitivity impairment in patients with AMD and predict particular difficulty in everyday tasks that rely on internal feature information, including recognition of familiar faces and facial expressions.

AimThis study aimed to explore the prevalence of and risk factors for age-related macular degeneration (AMD) in an elderly population in Nepal.Subjects and methodsThis is a population-based, cross-sectional study. A sample size of 2,100 was calculated. A total of 1,860 (88.6%) subjects aged >60 years were enrolled for the study from 30 clusters in the district. Detailed history, visual acuity, and anterior segment and posterior segment examinations were performed. AMD was graded according to the International ARM Epidemiological Study Group.ResultsAmong the total study population, 659 subjects had any AMD (35.43%; 95% confidence interval [CI]: 33.25–37.65), 484 had mild dry AMD (26.02%; 95% CI: 24.04–28.08), 143 had intermediate dry AMD (7.69%; 95% CI: 6.52–8.99), 19 had geographic atrophy (1.02%; 95% CI: 0.61–1.59), and 13 had wet AMD (0.70%; 95% CI: 0.37–1.19). The overall prevalence of early and late AMD was 33.71% and 1.72%, respectively. Among subjects with dry and wet AMD, 36.53% and 46.1% had visual impairment, while 2.78% and 23.08% were blind, respectively. In multivariate analysis, AMD was significantly higher in subjects with an increased number of cigarettes smoked per day (odds ratio [OR] 1.02, 95% CI: 1.01–1.04; P=0.007) and in subjects with pseudophakia (OR 1.45, 95% CI: 1.12–1.87; P=0.005).ConclusionOne-third of the population aged ≥60 years have some form of AMD. There was a significant association with the number of cigarettes consumed and with previous cataract surgery.

Introduction Non-exudative (dry) age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss worldwide. Besides age-related eye disease study (AREDS) vitamin supplements, there are no efficacious pharmaceutical interventions for dry AMD available. While numerous pharmacologics are available to treat diabetic macular edema (DME), many patients respond suboptimally to existing therapies. Risuteganib is a novel anti-integrin peptide that targets the multiple integrin heterodimers involved in the pathophysiology of dry AMD and DME. Inhibiting these selected integrin heterodimers may benefit patients with these conditions. Areas covered This article offers a brief overview of current pharmaceuticals available for dry AMD and DME. The proposed role of integrins in AMD and DME is reviewed and later, risuteganib, a novel anti-integrin peptide is introduced. The data from initial Phase 1 and Phase 2 risuteganib clinical trials are discussed in the latter part of the paper. Expert opinion While there are currently limited treatment options for dry AMD, more data are needed before we can truly evaluate the benefits of adopting risuteganib into the clinic. Conversely, several effective treatment options exist for DME; hence, risuteganib must show that it can add to these results, especially in those with refractory disease, before retina specialists adopt risuteganib into their treatment regimens.

ABSTRACTPurpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly population. Although there are prevalence studies for AMD in Europe, data are scarce for the Slovakian population. Methods: This was a prospective, multicenter, non-interventional, mobile clinic-based cross-sectional study that assessed age-specific prevalence of AMD in the Slovakian population and risk factors associated with AMD. The type of AMD was graded based on the international age-related maculopathy grading system; optical coherence tomography (OCT) was used for the differential diagnosis. Overall, 3,278 patients were screened; the fundus photographs, OCT scans, and self-reports were collected at the mobile clinic in a single visit. Results: The prevalence of AMD in the study population was 8.99% (wet AMD 1.01%; dry AMD 7.85%), whereas the extrapolated estimate in the entire Slovakian population was 3.3% (wet AMD 0.3%; dry AMD 3.0%). Age, smoking, and hypertension were risk factors associated with AMD; however, contrary to reports in the literature, no gender-specific association was observed. Conclusion: Based on the results of this study, mobile clinics may be an effective way to extend health care access to a larger population. Early diagnosis of AMD will assist in early treatment and effective disease management of the population at risk.

Dry age-related macular degeneration(AMD)is a prevalent form of irreversible blindness worldwide in the elderly population with an increasing incidence in China.It is found that some dry AMD will develop to wet AMD and therefore damage visual function.Pathogenesis of AMD is below understand now,but it is thought to be related to the light-induced ocular damage,oxidative stress response,extracellular disposition and immunology.Up to now,effective and safe prevention and treatment methods of AMD are still studying,especially wet AMD,but the concern on dry AMD is not enough.Some basic and clinical pharmaceutics researches on AMD include antioxidants,anti-extracellular disposition drugs and anti-inflammatory agents.With the rise of aging population,we should pay special attention to the research on pathogenesis,diagnosis and treatment of dry AMD. Key words: Age-related macular degeneration/dry; Pathogenesis; Pharmaceutics research

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older individuals. Clinically, ophthalmologists visually inspect optical coherence tomography (OCT) volumes to diagnose the stage of AMD based on well-known biomarkers. An early characteristic of AMD is drusen, which appears as yellowish deposits under the retina. AMD is mainly categorized into two types: dry AMD (non-neovascular) and wet AMD (neovascular). Given the large number of OCT images in an individual volume, an efficacious computer-aided detection system can reduce the workload for ophthalmologists by automatically detecting biomarkers in the relevant images. Because the shape of the RPE is critical in defining the pathological changes caused by wet and dry AMD, we propose a novel approach to describe the RPE shape using Mel Frequency Cepstral Coefficients (MFCC). Our previous work indicates that Haralick texture features have the ability to distinguish drusen from healthy tissue on color photography, therefore, we also investigated Haralick texture features extracted from the region between Inner Limiting Membrane (ILM) and Bruchs Membrane (BM) layers in this study. We achieved a mean accuracy, sensitivity with respect to AMD image and specificity with respect to healthy image of 89.68%, 89.26% and 90.12% on testing sets and 69.22%, 67.40%, and 75.56% on new patient validation sets, respectively. Our binary classification results indicate that MFCC are uniquely suited for producing generalizable results to automatically detect AMD biomarker images.

Purpose:To report the prevalence of pachydrusen in Indian population and their characteristics in relation to subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI) in comparison to eyes with soft drusen and subretinal drusenoid deposits (SDD) in age-related macular degeneration (AMD).Methods:The study was a retrospective, cross-sectional study involving patients with a diagnosis of dry AMD in at least one eye. The diagnosis of soft drusen, SDD, and pachydrusen was made on the basis of color fundus photograph and optical coherence tomography (OCT). SFCT and CVI was calculated and compared among the different subtypes of drusen.Results:A total of 169 eyes (143 dry and 26 wet AMD) of 85 patients with a mean age of 67.67 ± 9.57 years were included. In eyes with dry AMD, pachydrusen were seen in 12 eyes (8.4%) with a mean (±SD) SFCT of 289.66 ± 91.01 μ. The difference in SFCT was statistically significant (P = 0.001) using analysis of variance (ANOVA) test. The eyes with pachydrusen had significantly thickened choroid compared to the eyes with SDD (30 eyes; 21.0%) or combination of soft drusen and SDD (29 eyes; 20.3%) but not soft drusen (72 eyes; 50.3%). The difference of CVI in different subgroups was significant (P = 0.03). One eye in wet AMD group had concurrent pachydrusen. Comparison of SFCT and CVI in wet AMD and fellow dry AMD eyes were not significant.Conclusion:In Indian eyes with dry AMD, prevalence of pachydrusen (8.4%) is slightly lower compared to western literature (11.7%) and is associated with thicker choroid and higher CVI.

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

Objective To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in southern Xinjiang Uyghur residents aged≥ 50 years. Methods A cross-sectional study was carried out.Randomized cluster sampling was used in this survey of Uyghur residents aged 50 or above in Kuche and Kashi County of Xinjiang from January to May 2017.A total of 1 202 individuals received questionnaire survey, visual acuity test and eye examination.The AMD was diagnosed according to the Consensus of the 2012 International Beckmann AMD Classification Study Group, and the prevalence rate and risk factors of AMD in the population was analyzed. Results In 1490 Uyghur residents, a total of 1 202 subjects were included, with the response rate 80.67%.The 113 eyes of 73 patients were diagnosed as AMD, with the prevalence rate 6.07%.The prevalence of early- and mid-term AMD was 3.99%, and dry AMD was 1.00% and wet AMD was 1.08%.The prevalence rate of AMD in 50-59 years group, 60-69 years group, 70-79 years group and more than 80-year group was 4.35%, 5.85%, 11.38% and 14.81%, respectively.The prevalence of AMD was elevated with aging (χ2=15.008, P=0.002). Aging and region are the risk factors of AMD (Age: OR=1.000, P=0.001; region: OR=0.515, P=0022). Conclusions The prevalence rate of AMD among Uyghur residents aged 50 or above in southern Xinjiang is significantly lower than that in Europe and United States.Aging is an uncontrollable risk factor for AMD. Key words: Age-related macular degeneration; Prevalence; Risk factors; Uyghur; Epidemiology

To characterize inner retinal damage in patients with dry age-related macular degeneration (AMD) using high-resolution spectral domain optical coherence tomography images. Sixty eyes of 60 patients with AMD were categorized using the Age-Related Eye Disease Study (AREDS) severity scale. Spectral domain optical coherence tomography images of these patients were quantified by manually correcting the segmentation of each retinal layer, including the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer to ensure accurate delineation of layers. The mean ganglion cell complex thickness values (ganglion cell layer + inner plexiform layer + retinal nerve fiber layer) were compared with 30 eyes of 30 healthy subjects. Ninety percent of eyes (81 eyes) required manual correction of segmentation. Compared with healthy subjects, mean ganglion cell complex thicknesses significantly decreased in more advanced dry AMD eyes, and this decrease was predominantly related to a change in inner plexiform layer thickness. There was no significant difference in thickness-related measurements between milder dry AMD (AREDS-2) eyes and healthy eyes (P > 0.05). In patients with dry AMD, automatic optical coherence tomography segmentation algorithms may be erroneous. As the severity of dry AMD increases, the inner plexiform layer layer becomes thinned, suggesting that transsynaptic degeneration may be occurring, as the photoreceptor layer is affected by AMD.

ABSTRACTBackground: To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD).Methods: A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case–control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software.Results: The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10−4; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11–41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71–0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed.Conclusions: The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.