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 PubMed, 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.

To determine functional visual improvement after cataract surgery in eyes with age related macular degeneration

To determine whether patients with Age related macular degeneration (ARMD) benefit from cataract surgery in terms of best corrected visual acuity (BCVA) and to assess impact of surgery on progression of ARMD.: A prospective study was carried out of patients with and without ARMD undergoing cataract surgery at our department. Patients were divided into two groups- Group A (cases) with ARMD and Group B (controls) without ARMD and other retinal pathology. BCVA of cases was recorded on day 1, day 14, 1 month and 1/month and compared to that of controls.: BCVA significantly improved but markedly less than that experienced by control eyes. No increased incidence in progression to wet form of ARMD. Cataract surgery is safe in ARMD patients with no evidence of increased complications or rates of disease advancement.

Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient’s disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts’ opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2–3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3–4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

Photodegradation of Lipofuscin in Suspension and in ARPE-19 Cells and the Similarity of Fluorescence of the Photodegradation Product with Oxidized Docosahexaenoate

Retinal lipofuscin accumulates with age in the retinal pigment epithelium (RPE), where its fluorescence properties are used to assess retinal health. It was observed that there is a decrease in lipofuscin fluorescence above the age of 75 years and in the early stages of age-related macular degeneration (AMD). The purpose of this study was to investigate the response of lipofuscin isolated from human RPE and lipofuscin-laden cells to visible light, and to determine whether an abundant component of lipofuscin, docosahexaenoate (DHA), can contribute to lipofuscin fluorescence upon oxidation. Exposure of lipofuscin to visible light leads to a decrease in its long-wavelength fluorescence at about 610 nm, with a concomitant increase in the short-wavelength fluorescence. The emission spectrum of photodegraded lipofuscin exhibits similarity with that of oxidized DHA. Exposure of lipofuscin-laden cells to light leads to a loss of lipofuscin granules from cells, while retaining cell viability. The spectral changes in fluorescence in lipofuscin-laden cells resemble those seen during photodegradation of isolated lipofuscin. Our results demonstrate that fluorescence emission spectra, together with quantitation of the intensity of long-wavelength fluorescence, can serve as a marker useful for lipofuscin quantification and for monitoring its oxidation, and hence useful for screening the retina for increased oxidative damage and early AMD-related changes.

Pigmentary abnormality without significant drusen as a risk factor for late age-related macular degeneration

We investigated the incidence and risk factors of late age-related macular degeneration (AMD) in the fellow eye (FE) without significant drusen of patients with unilateral exudative macular neovascularization (MNV). In this retrospective study, 241 eligible patients who were followed-up for more than 3 years were enrolled. We analyzed the incidence and hazard ratios (HRs) of late AMD in the FE according to demographic and ophthalmologic variables. Hypopigmentation on color fundus photography (CFP) corresponds to shallow irregular RPE elevation (SIRE), so-called “double-layer sign” and/or “attenuation or disruption of RPE and/or ellipsoid zone” on OCT. The 5-year incidence of FE exudative MNV conversion was 8.6%. The 5-year incidence of FE exudative MNV of large hypopigmentation (≥ 0.5 disc area; DA) and small hypopigmentation (< 0.5 DA) on CFP, and SIRE (≥ 1000 µm) and small RPE elevation (< 1000 µm) on OCT were 36.2%, 14.2%, 55.0%, and 15.6%, respectively. The multivariate Cox proportional hazard model revealed that large hypopigmentation, small hypopigmentation, SIRE, and small RPE elevation showed HRs of 23.230, 8.037, 132.589, and 41.823 for FE exudative MNV occurrence, respectively. Hypopigmentation on CFP and SIRE on OCT could represent the same lesion. Even small hypopigmentation and small RPE elevation were significant risk factors for progression to exudative MNV.

Visual Outcomes of Macula-Involving Rhegmatogenous Retinal Detachment in Patients with and Without Age-Related Macular Degeneration

Background Patients presenting with macula-off rhegmatogenous retinal detachment (RRD) with concomitant age-related macular degeneration (AMD) and their treating physicians would benefit from knowledge regarding the visual prognosis after repair. The prognosis for such patients is not well known. The purpose of this study is to compare visual outcomes in macula-off RRD in eyes with AMD versus a group of comparison eyes without AMD. Methods This was a retrospective chart review of 1,149 patients. A total of 191 eyes met study criteria, 162 non-AMD eyes (controls) and 29 AMD eyes. The main outcome measure was postoperative visual acuity in control eyes versus AMD eyes, and this was compared using Fisher’s exact test. Results There was a statistically significant difference in postoperative visual acuity by AMD status, with those without AMD having a higher frequency of Count Fingers (CF), Hand Motion (HM), Light Perception (LP), or No Light Perception (NLP) vision (p = 0.023). More specifically 5.56% of non-AMD eyes and 3.45% of AMD eyes were 20/40 or better, 77.16% of non-AMD and 55.17% of AMD eyes were worse than 20/40 and better than 20/200, 10.49% of non-AMD eyes and 37.93% of AMD eyes were 20/200 or worse, and there were 11 eyes in the non-AMD group with CF, HM, LP, or NLP vision while there was only 1 eye in the AMD group with CF vision. Conclusions Though postoperative visual acuity was worse in the non-AMD group with a higher frequency of patients having final vision of CF, HM, LP, or NLP, this is not likely a clinically significant finding. Rather, it is a function of the difference in sample size and composition between the two groups. Importantly, this study suggests AMD patients can expect similar outcomes to non-AMD patients after RRD repair. Our study suggests that approximately 58% of patients with AMD can expect to maintain functional vision better than 20/200. We conclude that AMD patients can achieve functional vision after RRD surgery, similar to those without AMD. These findings may be helpful in guiding realistic expectations of AMD patients with RRD.

Discovering the Potential of Natural Antioxidants in Age-Related Macular Degeneration: A Review

Age-related macular degeneration (AMD) is a multifactorial disease associated with anatomical changes in the inner retina. Despite tremendous advances in clinical care, there is currently no cure for AMD. This review aims to evaluate the published literature on the therapeutic roles of natural antioxidants in AMD. A literature search of PubMed, Web of Science and Google Scholar for peer-reviewed articles published between 1 January 2011 and 31 October 2021 was undertaken. A total of 82 preclinical and 18 clinical studies were eligible for inclusion in this review. We identified active compounds, carotenoids, extracts and polysaccharides, flavonoids, formulations, vitamins and whole foods with potential therapeutic roles in AMD. We evaluated the integral cellular signaling pathways including the activation of antioxidant pathways and angiogenesis pathways orchestrating their mode of action. In conclusion, we examined the therapeutic roles of natural antioxidants in AMD which warrant further study for application in clinical practice. Our current understanding is that natural antioxidants have the potential to improve or halt the progression of AMD, and tailoring therapeutics to the specific disease stages may be the key to preventing irreversible vision loss.