Non-neovascular Age-related Macular Degeneration Research Articles

Differences in imaging biomarkers between patients with intermediate and advanced non-neovascular age-related macular degeneration (AMD) in the University of Colorado AMD registry.

To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD). Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000 um and 2000 um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant. 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p = 0.001), calcified drusen (4.3% vs. 40.0%, p < 0.0001), RPD (26.2% vs. 53.3%, p < 0.0001), ORT (0.5% vs. 46.9%, p < 0.0001), RP (1.1% vs. 46.3%, p < 0.0001), pigment migration (53.2% vs. 100%, p < 0.0001), and iRORA (17.9% vs. 80.2%, p < 0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188 µm (SD: 60) and 194 µm (SD: 69), compared to the advanced nnAMD with measurements of 153 µm (SD: 68), and 161 µm (SD: 76). This difference was statistically significant (p < 0.0001 and p = 0.0002). Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.

Non-Neovascular Age-Related Macular Degeneration Assessment: Focus on Optical Coherence Tomography Biomarkers.

The imagistic evaluation of non-neovascular age-related macular degeneration (AMD) is crucial for diagnosis, monitoring progression, and guiding management of the disease. Dry AMD, characterized primarily by the presence of drusen and retinal pigment epithelium atrophy, requires detailed visualization of the retinal structure to assess its severity and progression. Several imaging modalities are pivotal in the evaluation of non-neovascular AMD, including optical coherence tomography, fundus autofluorescence, or color fundus photography. In the context of emerging therapies for geographic atrophy, like pegcetacoplan, it is critical to establish the baseline status of the disease, monitor the development and expansion of geographic atrophy, and to evaluate the retina's response to potential treatments in clinical trials. The present review, while initially providing a comprehensive description of the pathophysiology involved in AMD, aims to offer an overview of the imaging modalities employed in the evaluation of non-neovascular AMD. Special emphasis is placed on the assessment of progression biomarkers as discerned through optical coherence tomography. As the landscape of AMD treatment continues to evolve, advanced imaging techniques will remain at the forefront, enabling clinicians to offer the most effective and tailored treatments to their patients.

Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate

Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD). Prospective cohort study. One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated. Average GA growth rate was 1.430 mm2/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate. Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.

The potential key role of choroidal non-perfusion and rod degeneration in the pathogenesis of macular neovascularization type 3.

Macular neovascularization type 3 (MNV3) is a multifactorial disease with distinct epidemiological, clinical, pathomorphological and topographical characteristics. This review of the literature discusses the latest experimental and clinical outcomes that could explain the pathogenesis of retinal neovascularization. Although patients with MNV3 are usually older than those with MNV1 or 2, their lesions do not coexist with, precede, or follow other types in the same eye. The regional distribution of MNV3 lesions is characterized as confined to the parafoveal macula without any involvement of the rod-free foveal area. Focal outer retinal atrophy and choroidal non-perfusion are the main structural features that occur prior to the development of retinal neovascularization. Also, histological and experimental studies of MNV3 and other non-neovascular age-related macular degeneration diseases complicated with MNV3-like lesions strongly suggest rod degeneration contributes to the pathogenesis. Therefore, the retinal neovascularization in MNV3 has a different pathogenesis from the choroidal neovascularization in MNV1 and 2 and emerging evidence indicates that choroidal non-prefusion and rod degeneration play a key role in the pathogenesis of MNV3. Accordingly, we suggest a sequence of pathological events that start with choroidal non-perfusion due to advanced age followed by hypoxia of the outer retina at the parafoveal area. This induces a remarkable degeneration of rods that triggers the growth of retinal neovascularization due to the imbalance of the angiogenic factors in the outer retina.

Short term effects of extremely low irradiance photobiomodulation on retinal function, in age related macular degeneration.

recently much studies evidenced the potential role of photo-biomodulation (PBM) in patients affected by Age-related Macular Degeneration (AMD). We designed a new wearable device for self-medication that employs the same broadband red light described in literature, but with extremely low irradiance. to demonstrate the safety and effectiveness of low-fluence light stimulations emitted by a LED source with appropriate wavelengths through our new device in improving short-term visual function in patients affected by severe non neovascular AMD. we prospectively enrolled patients affected by severe non-neovascular AMD with a relative sparing of the foveal region. All the patients were randomly assigned in placebo or in treatment group. The treatment consisted of 10 sessions of 10-min each, using the new device comprised of micro-LEDs that emitted light onto an amorphous support assembled within Metallic eyeglasses. The placebo group blindly underwent the same number of PBM sessions with the micro-LED turned off. Before and after each placebo/treatment sessions all the patients received: optical coherence tomography (OCT), Best-Corrected Visual Acuity (BCVA) and Microperimetry (MP). no significant differences in the anatomical parameters were observed in the two groups. The MP mean sensitivity and the central visual function both far and near significantly improved in the treated group (respectively p < 0.001, p < 0.001). our pivotal demonstrated that the LED PBM delivered through our new device is a safe and effective tool for improving short-term visual function in patients affected by severe non-neovascular AMD.

Serous maculopathy with absence of retinal pigment epithelium (SMARPE) associated with large drusen

PurposeTo describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD).MethodsA retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography).ResultsTwelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature.ConclusionsBilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.

Telehealth improves follow-up and monitoring of age-related macular degeneration during the COVID-19 pandemic.

To prevent vision loss, it is important to monitor patients with age-related macular degeneration (AMD) for the development of choroidal neovascularization. The coronavirus disease 2019 (COVID-19) pandemic caused many patients to miss or delay visits. To offset those gaps in care, providers utilized telehealth (TH) to evaluate patients for symptoms of disease progression and provide health education on the importance of continuous monitoring. This study evaluates the impact of TH encounters on the rate of return for recommended in-person examinations for 1103 patients with non-neovascular (dry) AMD seen in an outpatient ophthalmology clinic in 2019 and due for return evaluation after the outbreak of COVID-19 in 2020. Logistic regression analysis was used to identify demographic, clinical, and sociomedical factors associated with TH utilization and in-person return. 422 patients (38%) utilized TH during the study period. Patients who completed a TH encounter were more likely to return for an in-person examination as compared with those who did not receive TH (OR: 1.8, CI 95%: 1.4-2.3, P < 0.001). Completing a TH visit was associated with the detection of new wet AMD (OR: 3.3, 95% CI 1.04-10.6, P = 0.043), as well as with an earlier return for those patients who were found to have disease progression (62 ± 54days vs. 100 ± 57days, P = 0.049). Completing a TH visit increased the rate at which patients with dry AMD returned for recommended in-person eye examinations. In many cases, this permitted the earlier detection of wet AMD, which is linked with achieving better outcomes.

Targeted High-Density Microperimetry Testing of Nascent Geographic Atrophy in Age-Related Macular Degeneration

To examine the effectiveness of a targeted high-density microperimetry testing strategy for detecting visual sensitivity abnormalities in eyes with nascent geographic atrophy (nGA) when compared with standard central microperimetry testing. Observational study. Three-hundred and twenty-one eyes from 176 individuals with nonneovascular age-related macular degeneration (AMD). Thirty-five eyes from 33 participants underwent targeted high-density microperimetry testing of atrophic lesions (either nGA or geographic atrophy [GA]) within a 1.75° radius (or approximately 1000 μm diameter) region. Another cohort of 286 eyes from 143 participants with bilateral large drusen at baseline underwent standard microperimetry testing of the central 6° radius region at 6-monthly intervals for up to 36 months and thus included eyes that developed nGA and GA over the follow-up. All eyes underwent 2 tests at each visit to evaluate intrasession measurement repeatability. Magnitude of visual sensitivity abnormalities based on mean sensitivity (MS), pointwise sensitivity standard deviation (PSD), and the number of test locations with a threshold of ≤ 10 decibels (dB; or deep defects) in eyes with nGA, compared between eyes that underwent targeted high-density microperimetry testing and standard central microperimetry testing. The magnitude of visual sensitivity abnormalities based on MS, PSD and the number of deep defects were all significantly greater in eyes with nGA using targeted, high-density microperimetry testing compared with eyes with nGA using standard central microperimetry testing (all P < 0.001) and were all significantly less than eyes with GA using targeted, high-density microperimetry testing (all P ≤ 0.004). The intrasession coefficient of repeatability, where 95% of the test-retest differences are expected to occur, for MS in eyes with atrophic changes was 0.9 dB with the targeted, high-density microperimetry testing, and 1.8 dB with standard central microperimetry testing. Targeted, high-density microperimetry testing enabled the detection of a significantly greater magnitude of visual sensitivity abnormalities in eyes with nGA than standard microperimetry testing. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.

To investigate if metformin use is associated with decreased odds of developing new non-neovascular ("dry") age-related macular degeneration (AMD). Case-control study examining 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and 193,990 matched controls in the Merative MarketScan Research Databases. The diabetic subgroup included 49,988 cases and 49,460 controls. Multivariable conditional logistic regressions identified the risks of exposures on the development of dry AMD. Main outcome measures were odds ratios (ORs) of developing dry AMD with metformin use. In multivariable conditional logistic regression, any metformin use was associated with decreased odds of developing dry AMD (OR = 0.97; 95% confidence interval [CI], 0.95-0.99). This protective effect was noted for cumulative 2-year doses of metformin of 1 to 270 g (OR = 0.93; 95% CI, 0.90-0.97) and 271 to 600 g (OR = 0.92; 95% CI, 0.89-0.96). In a diabetic subgroup, metformin use below 601 g per 2 years decreased the odds of developing dry AMD (1-270 g: OR = 0.95; 95% CI, 0.91-0.99; 271-600 g: OR = 0.92; 95% CI, 0.89-0.96). Unlike in diabetic patients with diabetic retinopathy, diabetic patients without diabetic retinopathy had decreased odds of developing dry AMD with any metformin use (OR = 0.97; 95% CI, 0.94-0.998) and cumulative two-year doses of 1 to 270 g (OR 0.96; 95% CI, 0.91-0.998) and 271 to 600 g (OR = 0.92; 95% CI, 0.88-0.96). Metformin use was associated with decreased odds of developing dry AMD. The protective effect was observed for cumulative 2-year doses below 601 g. In diabetics, this association persisted, specifically in those without diabetic retinopathy. Therefore, metformin may be a strategy to prevent development of dry AMD.

Investigation of the choroidal structure in non-neovascular age-related macular degeneration patients with reticular pseudodrusen

BackgroundThis study aimed to compare choroidal thickness, total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) in patients with reticular pseudodrusen (RPD) and drusen. MethodsA total of 100 eyes of 100 patients with non-neovascular age related macular degeneration (AMD) with five or more medium drusen (63–125 µm) and RPD in two or more quadrants were recruited to the study. 48 eyes of 48 patients with RPD were assigned as Group 1 and 52 eyes of 52 patients with drusen were assigned as Group 2. 40 right eyes of 40 healthy subjects were included as controls. Patients with neovascular AMD or advanced non-neovascular AMD were excluded from the study. After a detailed ophthalmic examination, infrared reflectance images and OCT with enhanced depth imaging mode was obtained from all patients. TCA, SA, LA and CVI were calculated using the Image J program. The data were analyzed for statistics using SPSS software. ResultsThe female/male ratio was 56/44 in the patient groups and 20/20 in the control group. The mean age was 73.63±6.14 (61–91) years for Group 1 and 69.43± 6.97 (59–87) years for Group 2 (p=0.005). The mean age of Group 3 patients was 71.14±8.17 (60–79) years and was statistically similar to Groups 1 and 2 (p=0.09 and p=0.12, respectively). Choroidal thickness, TCA, SA and LA were significantly lower in Group 1 (p<0.001). CVI and foveal thicknesses were not significantly different between Group 1 and 2 (p=0.214 and p=0.384 respectively). CVI was significantly lower in Group 3 (p<0.01). RPD was most commonly seen in the superior quadrant followed by temporal, nasal, and inferior quadrants. ConclusionsTCA, SA and LA, which reflect choroidal vasculature, were decreased in patients with RPD. These parameters can help evaluate the pathophysiology of the disease.

Analysis of Retinol Binding Protein 4 and ABCA4 Gene Variation in Non-Neovascular Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) may be associated with ABCA4 variants and is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4), a retinol transporter protein, may reduce lipofuscin production. This study aims to assess the associations between plasma RBP4, the ABCA4 variation, and AMD severity. Sixty-seven participants were grouped into healthy/mild AMD (n = 32) and severe AMD (n = 35) groups. The latter group was older than the former group and had higher levels of RBP4 (36.8 ± 8.3 vs. 30.4 ± 7.0 μg/mL, p = 0.0012). The ten participants with six ABCA4 linked-variants had higher RBP4 than those without (37.8 ± 7.7 vs. 32.4 ± 7.9 μg/mL; p = 0.026), and eight of them had severe AMD. Univariate analyses showed that severe AMD was related to older age (OR, 1.26; 95% CI, 1.13-1.40; p < 0.0001) and to higher RBP4 levels (OR, 1.12; 95% CI, 1.04-1.20; p = 0.003), whereas the linked ABCA4 variants had no associations. After adjustment, however, only age remained significantly associated with severe AMD. This pilot study shows a trend of higher plasma RBP4 levels in severe AMD or the ABCA4-linked variants, and further age-matched studies are warranted.

Genetic variants in the adenosine triphosphate-binding cassette transporter A1 and risk of age-related macular degeneration

Genetic variants in ABCA1 are associated with higher concentrations of high-density lipoprotein (HDL) cholesterol. Higher HDL cholesterol concentrations are observationally and genetically associated with higher risk of age-related macular degeneration (AMD). However, whether amino acid-changing genetic variants in ABCA1 associated with high HDL cholesterol concentrations confer a higher risk of AMD in the general population is currently unknown. We tested this hypothesis. The study included 80,972 individuals (1,370 AMD cases) from the Copenhagen General Population Study (CGPS) and 9,584 individuals (142 AMD cases) from the Copenhagen City Heart Study (CCHS) with 10 to 18 years of follow-up. We created an HDL cholesterol weighted allele score based on amino acid-changing ABCA1 variants with a minor allele frequency above 0.001 and divided it into tertiles. The study included 55% women. Mean age was 58 years. The ABCA1 allele score for the third versus the first tertile was associated with HRs (95% confidence intervals (CIs)) of 1.30 (1.14–1.49) for all-cause AMD, 1.26 (1.06–1.50) for nonneovascular AMD, and 1.31 (1.12–1.53) for neovascular AMD in a multivariable adjusted model. On a continuous scale, higher concentrations of genetically determined HDL cholesterol were associated with higher risk of all-cause AMD, nonneovascular AMD, and neovascular AMD in an age- and sex adjusted model and in a multivariable adjusted model. In conclusion, amino acid-changing genetic variants in ABCA1 associated with higher HDL cholesterol concentrations were also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.

Progression Dynamics of Early versus Later Stage Atrophic Lesions in Nonneovascular Age-Related Macular Degeneration Using Quantitative OCT Biomarker Segmentation

To investigate the progression of geographic atrophy (GA) secondary to non-neovascular age-related macular degeneration (AMD) in early and later stage lesions using AI-based precision tools. Retrospective analysis of an observational cohort study. Seventy-four eyes of forty-nine patients with at least one complete retinal pigment epithelial and outer retinal atrophy (cRORA) lesion secondary to AMD were included. Patients were divided between recently developed cRORA and lesions with advanced disease status. Patients were prospectively imaged by spectral domain optical coherence tomography (SD-OCT) volume scans. The study period encompassed 18 months with scheduled visits every 6 months. Growth rates of recently to cRORA converted lesions were compared with lesions in an advanced disease status using mixed effect models. The progression of retinal pigment epithelial loss (RPEL) was considered the primary endpoint. Secondary endpoints consisted of external limiting membrane disruption (ELMD) and ellipsoid zone loss (EZL). These pathognomonic imaging biomarkers were quantified using validated deep learning algorithms. Further the EZ/RPE-Loss ratio was analysed in both study cohorts. Mean [95%CI] square root progression of recently converted lesions was 79.676[-77.140 - 236.493], 68.219[-101.210 - 237.648) and 84.825[-124.816 - 294.467] mm/half year for RPEL, ELML and EZL respectively. Mean square root progression of advanced lesions was 131.737[-22.574 - 286.047], 129.964[-36.666 - 296.594] and 116.837[-90.556 - 324.301] mm/half year for RPEL, ELML and EZL respectively. RPEL (p=0.038) and ELMD (p=0.026) progression showed significant differences between the two study cohorts. Further recent converters had significantly (p<0.001) higher EZ/RPE-Loss ratios in all time points compared to patients in an advanced disease status (1.716 [1.135 - 2.296] versus 1.153 [0.576 - 1.729]). Early cRORA lesions have a slower growth rate in comparison to atrophic lesions in advanced disease stages. Differences in growth dynamics may play a crucial role in understanding the pathophysiology of non-neovascular AMD and for the interpretation of clinical trials in GA. Individual disease monitoring using AI-based quantification paves the way towards optimized GA management.

Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1-2) and case-control analysis in the Merative MarketScan Research Databases (#3). Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Eyes were divided into 2 groups (#1-2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100-300 mg, and approximately > 300 mg per day, #3). Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2-3) after adjusting for AMD risk factors. In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N= 84 088 control vs. 530 L-DOPA eyes, P= 0.006). In eyes with nonneovascular AMD (N= 42 081-203 155 control vs. 314-1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P= 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P= 0.024). In the MarketScan databases (N= 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75-0.97) and 23% (OR, 0.77; 95% CI, 0.67-0.87), respectively. Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal Pigment Epithelium Aperture Preceding Collapse of Vascular and Avascular Pigment Epithelial Detachments Secondary to AMD.

To describe retinal pigment epithelium (RPE) aperture preceding the collapse of retinal pigment epithelium detachments (RPED) in eyes with neovascular and non-neovascular age-related macular degeneration (AMD). Medical records from five patients with RPE aperture associated with vascular and avascular RPED were reviewed between 2010 and 2021 at the New England Eye Center at Tufts Medical Center. Main outcome measures were analysis of RPE aperture characteristics and temporal course of RPED collapse. RPE apertures were identified in six eyes from five women (mean age of 72.6 years). Two eyes had neovasacular AMD and four eyes had non-neovascular AMD. The RPE aperture initially appeared as a discontinuity at the apex of the RPED without rippling or retraction. Each aperture was associated with hypertransmission of OCT signal into the choroid as well as hyperreflective foci. The mean time between the appearance of the RPE aperture to near complete collapse of the RPED was 9 months. Following RPED collapse, one eye developed choroidal neovascularization, three eyes progressed to geographic atrophy, one eye had recurrence of the RPED, and one eye remained unchanged. RPE aperture is a characteristic OCT finding that can be observed in avascular or vascularized RPED secondary to AMD. RPE apertures precede RPED collapse, which are most likely to occur within nine months of RPE aperture detection.

LONG-TERM PRESERVATION OF VISUAL ACUITY AFTER RESORPTION OF ACQUIRED VITELLIFORM LESIONS IN AGE-RELATED MACULAR DEGENERATION

To report the long-term (23 years) clinical and multimodal imaging features of acquired vitelliform lesions (AVLs) associated with non-neovascular age-related macular degeneration (AMD). Retrospective case report. Color and red free fundus photographs, high-resolution optical coherence tomography (High-Res OCT), fluorescein (FA) and indocyanine green angiography (ICGA), and OCT-angiography (OCTA) were performed. A 58-year-old man presented with bilateral AVLs in the setting of non-neovascular AMD. At baseline, his best-corrected visual acuity (BCVA) was 20/30 in his right eye and 20/20 in his left eye. Red free fundus photographs showed AVLs with cuticular drusen in both eyes corresponding to a "stars-in-the-sky" pattern on FA. ICGA showed no evidence of macular neovascularization (MNV). Throughout the 23-year follow-up, the patient reported consuming 20mg/day of lutein supplement. At the end of follow-up, his BCVA was 20/20 in both eyes. Color fundus photographs showed resorption of the AVLs in both eyes and High-Res OCT showed relative preservation of the outer retinal bands in the fovea. OCTA confirmed the absence of MNV. In non-neovascular AMD, spontaneous resorption of AVLs may be associated with long-term maintenance of visual acuity and relative preservation of the outer retinal morphology.

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.

Diagnostic Accuracy of the Amsler Grid Test for Detecting Neovascular Age-Related Macular Degeneration

Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring. To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses. A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022. Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.). Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.). Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD. Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies. Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

Emerging Treatment Options for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is characterized as a chronic, multifactorial disease and is the leading cause of irreversible blindness. Advanced AMD is classified as neovascular (wet) AMD and non-neovascular (dry) AMD. Dry AMD can progress to a more advanced form that manifests as geographic atrophy (GA), which significantly threatens vision, leading to progressive and irreversible loss of visual function. There are currently no approved therapeutics commercially available for GA patients. However, data from various clinical trials have demonstrated favorable results with significant reduction in GA lesion growth. This review furthers the understanding of the pathophysiology of GA, as well as current clinical trial data on investigational therapeutics.

A Clinical and Preclinical Assessment of Clinical Trials for Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness for the elderly in high-income countries. Although multivitamin antioxidant nutrients can slow the progression of intermediate "dry" or nonneovascular AMD, no treatment can halt or reverse any stage of dry disease. Multiple biologic pathways have been implicated in AMD pathobiology, including the complement pathway. These pathways have been targeted by various approaches in clinical trials. To date, no treatment has reached their prespecified primary end point in 2 phase III trials, a requirement by the US Food and Drug Administration for a new drug approval. Here, we describe perspectives on the failures and possible successes of various clinical trials that will guide further investigation. These perspectives will also discuss clinical trial design issues to consider in future investigations, and how recent insights into AMD pathobiology might both provide additional explanation for trials not reaching the prespecified primary end points and offer direction for identifying prioritized treatment targets.