Management Of Age-related Macular Degeneration Research Articles

Trend and driving factors in burden of age-related macular degeneration in older adults aged 60-89years: a global analysis over three decades.

To explore temporal trends and determine driving factors of age-related macular degeneration (AMD) burden in older adults aged 60-89years at global, regional and national levels from 1990 to 2019. Prevalence and years lived with disability (YLDs) were extracted. Joinpoint regression analysis was adopted to calculate average annual percentage change and to identify the year with the most significant changes. Global trends were stratified by sex, age and sociodemographic index, and regional and national trends were explored. Decomposition analysis was conducted to determine what extent the forces of population size, age structure and epidemiologic change driving alterations of AMD burden. Globally, prevalence rate slightly increased whereas YLDs rate decreased. The year 2005 marked a turning point where both prevalence and YLDs started to decline. Regionally, Western Sub-Saharan Africa had the highest prevalence and YLDs rates in 2019, with East Asia experiencing the most notable rise in prevalence from 1990 to 2019. Global decomposition revealed that the increased case number was primarily driven by population growth and ageing, and epidemiological change was only detected to lessen but far from offset these impacts. Although there was only slight increase or even decrease in prevalence and YLDs rates of AMD in older adults, the case number still nearly doubled, which may be primarily attributed to population growth and ageing, coupled with the emerging growing pattern of prevalence rate from 2015, collectively suggesting a huge challenge in control and management of AMD.

Emerging Oral Pharmaceuticals for Dry Age-Related Macular Degeneration: Mechanism of Action, Current Clinical Status, and Future Directions.

Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:528-534.].

The Role of Reactive Oxygen Species in Age-Related Macular Degeneration: A Comprehensive Review of Antioxidant Therapies.

This review article delves into the intricate roles of reactive oxygen species (ROS) in the pathogenesis of age-related macular degeneration (AMD). It presents a detailed analysis of the oxidative stress mechanisms that contribute to the development and progression of these diseases. The review systematically explores the dual nature of ROS in ocular physiology and pathology, underscoring their essential roles in cellular signaling and detrimental effects when in excess. In the context of AMD, the focus is on the oxidative impairment in the retinal pigment epithelium and Bruch's membrane, culminating in the deterioration of macular health. Central to this review is the evaluation of various antioxidant strategies in the prevention and management of AMD. It encompasses a wide spectrum of antioxidants, ranging from dietary nutrients like vitamins C and E, lutein, and zeaxanthin to pharmacological agents with antioxidative properties. The review also addresses novel therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, aiming to enhance antioxidant defense mechanisms in ocular tissues. The article concludes by synthesizing current research findings, clinical trial data, and meta-analyses to provide evidence-based recommendations. It underscores the need for further research to optimize antioxidant therapies, considering individual patient factors and disease stages. This comprehensive review thus serves as a valuable resource for clinicians, researchers, and healthcare professionals in ophthalmology, offering insights into the potential of antioxidants in mitigating the burden of AMD.

Janus Kinase Inhibitor Therapy and Risk of Age-Related Macular Degeneration in Autoimmune Disease

The involvement of chronic inflammation in the pathogenesis of age-related macular degeneration (AMD) opens therapeutic possibilities to AMD management. To determine whether Janus kinase inhibitors (JAKis) are associated with a reduced risk of AMD development in patients with autoimmune diseases. This retrospective observational cohort study used administrative claims data from Merative MarketScan research databases (Commercial and Medicare Supplemental) and Optum Clinformatics Data Mart databases between January 1, 2010, and January 31, 2022. Patients with autoimmune diseases satisfying study eligibility criteria and who received JAKi treatment (9126 in MarketScan and 5667 in Optum) were propensity score matched (1:1) to identical numbers of study-eligible patients who received non-JAKi-based immunotherapy. Treatment duration of 6 months or longer. Incidence rates of AMD (exudative and nonexudative) over the first 6 to 18 months of treatment were determined, and bayesian Poisson regression models were used to estimate incidence rate ratios, 95% CIs, and posterior probabilities of AMD. After matching, female sex represented the majority of the patient population in both MarketScan and Optum (14 019/18 252 [76.6%] and 8563/3364 [75.2%], respectively in the JAKi patient population). More than 60% of the patient population was older than 55 years of age in both cohorts. Over the specified treatment period, a 49% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (10/9126 events; adjusted incidence rate ratio [AIRR], 0.51; 95% CI, 0.19-0.90) vs those who received non-JAKi therapy (43/9126 events; AIRR, 1 [reference]) in MarketScan, and a 73% relative reduction in incidence of AMD was observed among patients who received JAKi therapy (3/5667 events; AIRR, 0.27; 95% CI, 0.03-0.74) vs those who received non-JAKi therapy (21/5667 events; AIRR, 1 [reference]) in Optum. The absolute percentage reductions were 0.36% (MarketScan) and 0.32% (Optum), favoring patients who received JAKi therapy. Posterior probabilities of the adjusted risk being less than unity were 97.6% (MarketScan) and 98.9% (Optum) for those who received JAKi therapy vs those who received non-JAKi therapy in MarketScan and Optum, respectively. JAKi use may be associated with a reduced risk of incident AMD in US adults with major autoimmune diseases. The absolute percentage reduction is consistent with a potential role for JAKi in this population. Future studies with long-term follow-up are recommended to investigate the association between JAKi use and incident AMD in other disease indications. Investigation into the role of systemic inflammation and JAK-signal transducers and activators of transcription signaling in AMD may improve understanding of the pathophysiology of AMD and lead to new treatment options.

Genetic Insights into Age-Related Macular Degeneration.

One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the macula. AMD is a complex and multifaceted disease influenced by several factors such as aging, environmental risk factors, and a person's genetic susceptibility to the condition. The interaction among these factors leads to the initiation and advancement of AMD, where genetic predisposition plays a crucial role. With the advent of high-throughput genotyping technologies, many novel genetic loci associated with AMD have been identified, enhancing our knowledge of its genetic architecture. The common genetic variants linked to AMD are found on chromosome 1q32 (in the complement factor H gene) and 10q26 (age-related maculopathy susceptibility 2 and high-temperature requirement A serine peptidase 1 genes) loci, along with several other risk variants. This review summarizes the common genetic variants of complement pathways, lipid metabolism, and extracellular matrix proteins associated with AMD risk, highlighting the intricate pathways contributing to AMD pathogenesis. Knowledge of the genetic underpinnings of AMD will allow for the future development of personalized diagnostics and targeted therapeutic interventions, paving the way for more effective management of AMD and improved outcomes for affected individuals.

The Role of Oral Supplementation for the Management of Age-Related Macular Degeneration: A Narrative Review.

The majority of neurodegenerative eye disorders occur with aging and significantly impair quality of life. Age-related macular degeneration (AMD) is the third most common cause of visual impairment and blindness worldwide. One of the most important elements in the pathophysiology of neurodegenerative eye disease is certainly oxidative stress, with neuroinflammation and ocular ischemia which may also be significant factors. Antioxidants, either by food or oral supplementation, may be able to mitigate the deleterious effects of reactive oxygen species that build as a result of oxidative stress, ischemia, and inflammation. Over the past few decades, a number of research works examining the potential adjuvant impact of antioxidants in AMD have been published. In fact, there is not only more and more interest in already known molecules but also in new molecules that can help clinicians in the management of this complex multifactorial disease, such as astaxanthin and melatonin. However, while some studies showed encouraging outcomes, others were conflicting. In addition, more and more attention is also being paid to nutrition, considered a pivotal key point, especially to prevent AMD. For this reason, the purpose of this review is to analyze the main antioxidant molecules currently used as oral supplements for AMD treatment, as well as the role of diet and food intake in this ocular disease, to better understand how all these factors can improve the clinical management of AMD patients.

Technological Perception with Rural and Urban Differentiation and Its Influence on the Quality of Life of Older People with Age-Related Macular Degeneration

The past decade has seen a global increase in population age, especially in developed countries, where aging involves visual diseases such as age-related macular degeneration (AMD), which severely affect quality of life (QoL) and mental health, as well as increase isolation and care costs. This study investigated how persons with AMD perceive the impact of technology use on their QoL, focusing on potential disparities between urban and rural contexts in Spain. Using a cross-sectional observational design, data from the 2020 National Statistics Institute’s Disability, Personal Autonomy, and Dependency Situations Survey were analyzed, focusing on QoL aspects based on the WHO items of the WHOQOL-100 scale. The results revealed a generally positive perception of technology among participants, with urban residents perceiving technology’s positive impact more favorably. Sex discrepancies in technology perception were also observed, as women exhibited a more positive outlook on technology’s influence on QoL. The analysis of QoL aspects, such as ‘Visibility’, ‘Learning’, ‘Mobility’, and ‘Domestic life’, highlighted distinct challenges faced by rural and urban populations, underscoring the importance of context-specific approaches in technology interventions. However, these perceptions were intertwined with comorbidities, which can exacerbate AMD-related issues. Furthermore, this study explored the role of technology in enhancing QoL among older adults with AMD, examining how it influences daily activities and independence, particularly in the context of AMD management. This study concluded that developing more-inclusive policies tailored to the specific needs of persons with AMD, with special attention to environmental and sex differences, is imperative to enhance the positive impact of technology on their QoL.

A New Generation of Gene Therapies as the Future of Wet AMD Treatment.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms, dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the concept of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the progress to the clinic of "one and done" therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

DeepAlienorNet: A deep learning model to extract clinical features from colour fundus photography in age-related macular degeneration.

This study aimed to develop a deep learning (DL) model, named 'DeepAlienorNet', to automatically extract clinical signs of age-related macular degeneration (AMD) from colour fundus photography (CFP). The ALIENOR Study is a cohort of French individuals 77 years of age or older. A multi-label DL model was developed to grade the presence of 7 clinical signs: large soft drusen (>125 μm), intermediate soft (63-125 μm), large area of soft drusen (total area >500 μm), presence of central soft drusen (large or intermediate), hyperpigmentation, hypopigmentation, and advanced AMD (defined as neovascular or atrophic AMD). Prediction performances were evaluated using cross-validation and the expert human interpretation of the clinical signs as the ground truth. A total of 1178 images were included in the study. Averaging the 7 clinical signs' detection performances, DeepAlienorNet achieved an overall sensitivity, specificity, and AUROC of 0.77, 0.83, and 0.87, respectively. The model demonstrated particularly strong performance in predicting advanced AMD and large areas of soft drusen. It can also generate heatmaps, highlighting the relevant image areas for interpretation. DeepAlienorNet demonstrates promising performance in automatically identifying clinical signs of AMD from CFP, offering several notable advantages. Its high interpretability reduces the black box effect, addressing ethical concerns. Additionally, the model can be easily integrated to automate well-established and validated AMD progression scores, and the user-friendly interface further enhances its usability. The main value of DeepAlienorNet lies in its ability to assist in precise severity scoring for further adapted AMD management, all while preserving interpretability.

Management of Wet Age-Related Macular Degeneration: A Case Report

Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the photoreceptors and retinal pigment epithelium (RPE). It is a leading cause of blindness and visual impairment in the elderly population, despite recent advances in treatment. We reported a case of wet AMD and its management.
 Case Presentation: A 69 years old woman complained of blurred vision, especially in the left eye, which she had experienced since 3 years ago, progressively worsen since the last 3 months. Fundoscopy and OCT examination was done. Fundoscopy found no foveal reflex with a drusen and perifoveal haemorrhage found on left eye. She was diagnosed with wet age-related macular degeneration type II of left eye. She had done intravitreal anti-VEGF injection with local anaesthesia.
 Conclusion: AMD management relies heavily on observation, lifestyle changes, frequent follow-up evaluations, early recognition of visual impairment and detection of CNV. Meanwhile, the current modality for wet AMD therapy is intravitreal anti-VEGF injection to preserve patient’s visual acuity and improve quality of life.

Single-cell RNA Sequencing Identifies Natural Kill Cell-Related Transcription Factors Associated With Age-Related Macular Degeneration.

Age-related Macular Degeneration (AMD) poses a growing global health concern as the leading cause of central vision loss in elderly people. This study focuses on unraveling the intricate involvement of Natural Killer (NK) cells in AMD, shedding light on their immune responses and cytokine regulatory roles. Transcriptomic data from the Gene Expression Omnibus database were utilized, employing single-cell RNA-seq analysis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and single-cell regulatory network inference and clustering (SCENIC) analysis were applied to reveal the regulatory mechanisms of NK cells in early-stage AMD patients. Machine learning models, such as random forests and decision trees, were employed to screen hub genes and key transcription factors (TFs) associated with AMD. Distinct cell clusters were identified in the present study, especially the T/NK cluster, with a notable increase in NK cell abundance observed in AMD. Cell-cell communication analyses revealed altered interactions, particularly in NK cells, indicating their potential role in AMD pathogenesis. HdWGCNA highlighted the turquoise module, enriched in inflammation-related pathways, as significantly associated with AMD in NK cells. The SCENIC analysis identified key TFs in NK cell regulatory networks. The integration of hub genes and TFs identified CREM, FOXP1, IRF1, NFKB2, and USF2 as potential predictors for AMD through machine learning. This comprehensive approach enhances our understanding of NK cell dynamics, signaling alterations, and potential predictive models for AMD. The identified TFs provide new avenues for molecular interventions and highlight the intricate relationship between NK cells and AMD pathogenesis. Overall, this study contributes valuable insights for advancing our understanding and management of AMD.

Recent Developments in Gene Therapy for Neovascular Age-Related Macular Degeneration: A Review.

Age-related macular degeneration (AMD) is a complex and multifactorial disease and a leading cause of irreversible blindness in the elderly population. The anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management and prognosis of neovascular AMD (nAMD) and is currently the standard of care for this disease. However, patients are required to receive repeated injections, imposing substantial social and economic burdens. The implementation of gene therapy methods to achieve sustained delivery of various therapeutic proteins holds the promise of a single treatment that could ameliorate the treatment challenges associated with chronic intravitreal therapy, and potentially improve visual outcomes. Several early-phase trials are currently underway, evaluating the safety and efficacy of gene therapy for nAMD; however, areas of controversy persist, including the therapeutic target, route of administration, and potential safety issues. In this review, we assess the evolution of gene therapy for nAMD and summarize several preclinical and early-stage clinical trials, exploring challenges and future directions.

Therapeutic Management and New Upcoming Approaches for Age Related Macular Degeneration.

Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.

Monocular and Binocular Visual Function Assessments and Activities of Daily Living Performance in Age-Related Macular Degeneration

To evaluate the relationship between specific monocular and binocular visual function (VF) assessments with binocularly performed activities of daily living task tests (ADLTTs) in patients with age-related macular degeneration (AMD) and healthy controls. Prospective case-control cohort study. Thirty-six AMD patients and 36 controls. Visual field assessments included monocular and binocular best-corrected visual acuity (BCVA), contrast sensitivity (CS), and monocular microperimetry testing for mean macula sensitivity, mean retina sensitivity (MRS), fixation area, and fixation distance from fovea (FDF). Age-related macular degeneration lesion area and sensitivity were measured on OCT and microperimetry, respectively. Participants performed 4 validated ADLTTs with binocular BCVA: (1) reading; (2) item-search; (3) money-counting; and (4) multi-step drink-making tasks. Spearman correlations and multivariate regression analysis, adjusted for age, sex, and potential correlation between the 2 eyes, were used to assess the relationship between monocular and binocular VF assessments, and ADLTT performance in both groups. Age-related macular degeneration patients had poorer VF (BCVA, CS, mean macula sensitivity, and MRS) compared with healthy controls. Monocular BCVA in both better- and worse-vision eyes was moderately correlated with the binocular reading speed and money-counting tasks in participants with AMD. In AMD, monocular worse eye CS, MRS, AMD lesion area on OCT, and lesion sensitivity on microperimetry showed moderate correlations to various ADLTTs, such as reading, money-counting, and drink-making. Similar findings were found in our AMD cohort on multivariate regression analysis. Fewer significant correlations were observed for the better-vision eye, whereas no correlations were observed for healthy controls between VF parameters and ADLTTs. In contrast, significant associations were observed between binocular BCVA and CS with binocular ADLTTs (reading and item-search tasks) but not in AMD patients. Although monocular BCVA remains the most common measure of VF, CS and microperimetry testing also show significant correlations with ADLTTs performance in AMD patients, and should be considered as complimentary VF-outcome measures in both clinical and research settings. Unlike healthy subjects, AMD patients do not rely on binocular VF for ADLTT function, with the worse-vision eye impacting binocular ADLTT function more than the better-vision eye. Therefore, the worse-vision eye should not be neglected during the management of AMD. Proprietary or commercial disclosure may be found after the references.

The Role of Inflammation in Age-Related Macular Degeneration-Therapeutic Landscapes in Geographic Atrophy.

Age-related macular degeneration (AMD) is the leading cause of vision loss and visual impairment in people over 50 years of age. In the current therapeutic landscape, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies have been central to the management of neovascular AMD (also known as wet AMD), whereas treatments for geographic atrophy have lagged behind. Several therapeutic approaches are being developed for geographic atrophy with the goal of either slowing down disease progression or reversing sight loss. Such strategies target the inflammatory pathways, complement cascade, visual cycle or neuroprotective mechanisms to slow down the degeneration. In addition, retinal implants have been tried for vision restoration and stem cell therapies for potentially a dual purpose of slowing down the degeneration and restoring visual function. In particular, therapies focusing on the complement pathway have shown promising results with the FDA approved pegcetacoplan, a complement C3 inhibitor, and avacincaptad pegol, a complement C5 inhibitor. In this review, we discuss the mechanisms of inflammation in AMD and outline the therapeutic landscapes of atrophy AMD. Improved understanding of the various pathway components and their interplay in this complex neuroinflammatory degeneration will guide the development of current and future therapeutic options, such as optogenetic therapy.

Deep Learning Applications to Classification and Detection of Age-Related Macular Degeneration on Optical Coherence Tomography Imaging: A Review.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly, more commonly in developed countries. Optical coherence tomography (OCT) is a non-invasive imaging device widely used for the diagnosis and management of AMD. Deep learning (DL) uses multilayered artificial neural networks (NN) for feature extraction, and is the cutting-edge technique for medical image analysis for diagnostic and prognostication purposes. Application of DL models to OCT image analysis has garnered significant interest in recent years. In this review, we aimed to summarize studies focusing on DL models used in classification and detection of AMD. Additionally, we provide a brief introduction to other DL applications in AMD, such as segmentation, prediction/prognostication, and models trained on multimodal imaging.

Efficacy and safety for the combination of lutein, vitamin C, zeaxanthin, zinc, copper, and vitamin E in Indian patients of age-related macular degeneration - Post marketing surveillance study

Age-related macular degeneration (AMD) is an ocular disease of complex nature which reduces the quality of life of the patient. Objectives behind the conduct of this study was to evaluate the efficacy as well as safety for the combination of Lutein, Vitamin C, Zeaxanthin, Zinc, Copper and Vitamin E in patients of AMD.For the study 660 patients were recruited and 627 patients completed the study throughout India at 44 clinical trial sites. The study duration was of 90 days and efficacy and safety assessment was made on day 45 (visit 2) and day 90 (visit 3). Efficacy assessment was made by 2 efficacy assessment parameters including, “vision related quality of life (VRQOL)” and “vision Impairment score” obtained using “Vision Impairment Questionnaire”. Safety assessment was made by adverse events reported by the patients.At baseline visit, the mean VRQOL score of all the patients completed the study was 5.733 which was increased to 6.682 on visit 2 and 7.476 on visit 3 where, percentage increase was of 16.550% and 30.403% respectively on visit 2 and 3 as compared to baseline. At baseline visit, the vision impairment score was 21.389 reduced to 17.352 on day 45 and further reduced to 14.135 on day 90.Fixed dose combination of Vitamin C 250mg, Zinc 40mg, Lutein 5mg, Zeaxanthin 1mg, Copper 1mg and Vitamin E 200 IU per capsule was found efficacious and safe for the medical management of AMD in Indian patients.

Suppressing Inflammation for the Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration: Dazdotuftide as a Potential New Multitarget Therapeutic Candidate.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are major causes of blindness globally. The primary treatment option for DME and neovascular AMD (nAMD) is anti-vascular endothelial growth factor (VEGF) compounds, but this treatment modality often yields insufficient results, and monthly injections can place a burden on the health system and patients. Although various inflammatory pathways and mediators have been recognized as key players in the development of DR and AMD, there are limited treatment options targeting these pathways. Molecular pathways that are interlinked, or triggers of multiple inflammatory pathways, could be promising targets for drug development. This review focuses on the role of inflammation in the pathogenesis of DME and AMD and presents current anti-inflammatory compounds, as well as a potential multitarget anti-inflammatory compound (dazdotuftide) that could be a candidate treatment option for the management of DME and AMD.

Botulinum toxin type A in multimodal management of age-related macular degeneration and related diseases

Age related macular degeneration (AMD) is the major cause of visual loss in the aging population in the Western world. In past decade, intra ocular injections of anti-vascular endothelial growth factor (anti-VEGF) pharmaceuticals have revolutionized therapy for exudative (edematous-wet) AMD and become standard practice for the near term. However repeated intra-ocular injections are required for years and long terms results have been limited. The pathogenesis of this condition is multifactorial involving genetic, ischemic, inflammatory factors leading to neovascularization, edema and retinal pigment epithelial scaring resulting in photoreceptor destruction. Based on coincidental observation in reduction in AMD related macular edema on ocular coherence tomography (OCT) in a BoNT A treated patient with facial movement disease, BoNT-A at conventional doses targeting the para orbital area was added to therapeutic regiment in a small number of patients with exudative macular degeneration or related diseases. Measurements of edema and choriocapillaris using Spectral Doman (OCT) and Ocular Coherence Angiography (OCT-A) and Snellen visual acuity were made over the evaluation period. 15 eyes in 14 patients averaged 361 μm central sub foveal edema (CSFT) pre injection and average of 266 μm (CSFT) post injection over an average of 21 months and 5.7 cycles using BoNT A alone at conventional doses (n = 86 post injection measurements, paired t-test p < 0.001 two tailed). Visions at baseline in patients with 20/40 or worse averaged 20/100- pre injection improved to an average of 20/40- in the post injection period (n = 49 measurements p < 0.002 paired t-test). The previous data was added to a group of 12 more severely afflicted patients receiving anti VEGF (aflibercept or bevacizumab) (total 27 patients). With this 27-patient group, patients were followed for an average of 20 months and receiving average of 6 cycles at conventional doses. Improvement in exudative edema and vision were noted with pre injection baseline CSFT average 399.5, post injection average 267, n = 303 post measurement, independent t-test P < 0.0001.). Snellen vision 20/128 baseline average improved to average of 20/60- during post injection period (n = 157 post injection measurements, p < 0.0001 paired t-test to baseline). No substantial adverse effects were noted. Cyclic effects were noted corresponding to duration of action of BoNT-A on a number of patients. The above data is preliminary and is skewed toward early leakage for all conditions.BoNT A may have a role in the treatment of aged related macular degeneration.Controlled studies are needed with careful staging and baseline stratifications for multi-modal management paradigms. The findings are discussed relative to known botulinum toxin type A pharmacology and AMD pathogenesis.

Dietary supplements and drugs available in India along with the mechanism of action and clinical trial data for the medical management of age related macular degeneration (AMD)

Age related macular degeneration (AMD) is one of the leading cause of blindness among elderly population which diminishes the visual quality. The main objective behind this review is to give the brief information about the dietary supplements and drugs which are available in India along with the mechanism of action and clinical trial data for the management for AMD. Also, we have commented, wherever any additional clinical trial data or regulatory approvals would be needed for using the pharmaceutical or nutraceutical product in Indian patients. The dietary supplements reviewed in this article includes Lutein and Zeaxanthin which are also referred as macular pigments and have important role in absorption of blue light prior reaching to the retina and have antioxidant functions, Zinc which has structural role in antioxidant enzymes, Copper which is cofactor for several ocular-enzymes, Astaxanthin, Vitamin C, Vitamin E, Resveratrol and Glutathione which are antioxidants. We have also reviewed Brimonidine for the management of non-neovascular AMD. Brimonidine is an alpha 2-adrenergic agonist but along with that it has neuroprotective as well as cytoprotective activities because of which it can be used for the management of non-neovascular AMD. In this review we have discussed many clinical trials for different combinations of above-mentioned dietary supplements and out of which AREDS 2 clinical trial was conducted on comparatively larger number of patients and for longer study duration.