Age-related Macular Degeneration Category Research Articles

Visual Functioning and Mortality of Age-Related Macular Degeneration Patients in a Colorado Cohort

To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and mortality in patients with various stages of age-related macular degeneration (AMD). Observational cohort study. Patients with AMD enrolled in the University of Colorado AMD Registry between July 9, 2014 and December 31, 2021 were included. Age-related macular degeneration cases were classified into early AMD, intermediate AMD, geographic atrophy, neovascular AMD, or both advanced types of AMD (neovasuclar and geographic atrophy both present) using multimodal imaging and the Beckman and Classification of Atrophy Meetings criteria. Visual Function Questionnaire-25 composite and subscale scores at the time of study enrollment were calculated. Cox proportional hazards modeling was used to assess time to event for mortality utilizing univariate and multivariable models, which adjusted for all variables significantly associated with mortality. The measures of association were hazard ratios (HRs) and 95% confidence intervals (CIs). All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Death rates through October 19, 2022 were compared by demographics and potential confounders. Analysis was completed on a cohort of 876 patients, of which 180 (20.6%) died during the follow-up period. Average follow-up time for this cohort was 52.5 (standard deviation: 26.6) months. In univariate analysis, composite VFQ-25 score and all subscale scores aside from ocular pain were significantly associated with time to mortality. Additionally, age, AMD category, marital status, history of smoking, and multiple chronic comorbid conditions were significantly associated with time to mortality. In multivariable analysis, for each 10-point increase in a patient's VFQ-25 scores for general health and driving, the risk of death decreased with HR of 0.85 (95% CI: 0.80, 0.91; P < 0.0001) and 0.92 (95% CI: 0.87, 0.97; P= 0.005), respectively. Composite and other subscale scores were not significantly associated with mortality after adjusting for confounding variables. This cohort of AMD patients had a 20% rate of death in the 52.5-month average follow-up time. Better general health and ability to drive, as measured by the VFQ-25, were each separately associated with significantly lower risk of death among individuals with AMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

RANTES (CCL5) in Patients With Geographic Atrophy Age-Related Macular Degeneration.

A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls. The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799-19,554] pg/mL vs. 5435 [3420-9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls. We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients. The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

Automated diagnosis of age-related macular degeneration using multi-modal vertical plane feature fusion via deep learning.

To develop a computer-aided diagnostic (CADx) system of age-related macular degeneration (AMD) through feature fusion between infrared reflectance (IR) and optical coherence tomography (OCT) modalities in order to explore the superiority of multi-modality CADx system and the optimal feature fusion patterns between multi-modality inputs. This is a dual center retrospective study. We retrospectively collected 2006 pairs of IR and OCT images to develop the algorithms. Two single-modality models and three multi-modality models were constructed for the comparison of the diagnostic efficacy. The multi-modality models were designed utilizing a novel feature fusion method, namely, vertical plane feature fusion (VPFF). The results were validated using an independent external validation dataset and compared by three ophthalmologists. In the test set of the ZJU dataset, our best model named OCT_MAIN demonstrated diagnostic efficiency with an overall accuracy of 0.9608 and area under the curve of 0.9944 for the normal category, 0.9659 for the dry AMD category, and 0.9930 for the wet AMD category. The external validation exhibited an overall accuracy of 0.9159. Its diagnostic efficiency was comparable to that of the senior ophthalmologist. The VPFF method was successfully employed to develop a multi-modal intelligent diagnostic system for the AMD classification. This is a valuable complement and optimization to the existing CADx system, which reveals a wide application prospect and research potential.

Sex Differences in RANTES (CCL5) in Patients With Intermediate Age-Related Macular Degeneration (AMD) and Controls With no AMD.

PurposeTo determine if there are sex differences in levels of regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with intermediate age-related macular degeneration (iAMD) and in controls with no AMD.MethodsPatients with iAMD and controls defined by multi-modal imaging were recruited into a Colorado AMD registry. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction.ResultsThe plasma level of RANTES was significantly higher in the control group in comparison with the iAMD group. When moderated by sex, RANTES was significantly lower (P = 0.005) in males (median, 4525.6 pg/mL; interquartile range, 2589–7861 pg/mL) compared with females (median, 6686 pg/mL; interquartile range, 3485–12488 pg/mL) within the iAMD cohort. No significant difference was found in levels of RANTES between males and females in the control group.ConclusionsWe found that levels of RANTES were moderated by sex in cases with iAMD with lower levels in males compared with females. The findings illustrate the importance of including sex as a biological variable in AMD research. There is a need for further studies of RANTES, stratified by sex, in the advanced phenotypes of AMD.Translational RelevanceThe biomarker RANTES identified in the plasma of patients with iAMD reflects systemic alterations when stratified by sex.

Haller's vessels patterns in non-neovascular age-related macular degeneration.

To investigate the optical coherence tomography (OCT) en face reconstruction of the choroid in different phenotypes of non-neovascular age-related macular degeneration (AMD), to identify the relative distribution of the vascular patterns of the Haller's layer in each AMD category. Retrospective study enrolling consecutive patients with non-neovascular AMD. Patients were divided into the following: (1) those with reticular pseudodrusen (RPD); (2) those with small (< 63μm) or medium-large drusen (63-124μm); (3) those with geographic atrophy (GA). Qualitative analysis of the en face images provided by CIRRUS HD-OCT 5000 (Carl Zeiss Meditech, Inc., Dublin, USA) was performed, identifying five arrangements of Haller's vessels: temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular. Choroidal thickness (CT) was measured from structural OCT. Healthy age-matched subjects were included as a control group. Fifty-eight eyes of 58 patients (20 eyes with RPD; 22 eyes with drusen; 16 eyes with GA) and 18 control eyes were enrolled. The laterally diagonal configuration was the most prevalent (40.0%) in the RPD group; the reticular pattern was the most frequent in the drusen group (50.0%); the double arcuate (62.5%) was the most recurrent pattern in patients with GA. In the control group, the temporal herringbone (38.9%) arrangement was the most represented. The CT associated with the temporal herringbone and reticular arrangement was significantly higher compared to the branched from below (p < 0.001), the laterally diagonal (p = 0.014), and the double arcuate pattern (p = 0.009). Different phenotypes of non-neovascular AMD present a specific distribution of vascular arrangement on en face OCT. The temporal herringbone and the reticular pattern (the ones more associated in a physiological setting) disclosed a thicker choroid compared to the arrangements more represented in non-neovascular AMD-correlated phenotypes.

To Peel or Not to Peel: Pars Plana Vitrectomy with Macular Membrane Peel in Eyes with Abnormalities of Vitreomacular Interface and Coexisting Dry Age-Related Macular Degeneration.

PurposeTo evaluate the outcome of macular surgery with ILM- and epiretinal membrane peel associated with significant dry age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS).Patients and MethodsInstitutional. Retrospective case-control study. A total of 42 pseudophacic eyes of 39 patients (7 with full thickness macular hole and 35 with epiretinal membrane) with coexisting dry AMD underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) and epiretinal membrane peel. Preoperative and postoperative data including best corrected visual acuity (BCVA), AMD grade according to AREDS, central retinal thickness (CRT), development of choroidal neovascularization (CNV), and central retinal atrophy have been evaluated. Twenty-eight fellow eyes with dry AMD of the included 39 patients served as a control group.ResultsA significant improvement in the visual acuity could be observed after surgery (initial BCVA 0.47±0.31 logarithm of the minimal angle of resolution (logMAR) vs 0.33±0.29logMAR 9 months postoperatively; p=0.006). CRT decreased significantly after surgery (p<0.001). In the surgery group, there were 4 eyes (9.5%) with CNV and 1 eye (2.5%) with new central retinal atrophy development after surgery. All these eyes had preoperative AREDS 3 (4 eyes) or AREDS 4 (1 eye) AMD category. In the control group, there was 1 eye (4%) with CNV and 4 eyes (14%) with new central retinal atrophy development during the follow-up of 9 months. These eyes had initially AREDS 2 (1 eye), AREDS 3 (3 eyes) or AREDS 4 (1 eye) AMD category.ConclusionEyes with dry AMD of AREDS 3 and AREDS 4 with coexisting VMI abnormalities improve significantly after PPV with membrane peel. While there is a higher risk of CNV development after surgery (9.5%) in these eyes, the vitrectomy does not seem to accelerate central retinal atrophy progression compared to the fellow eyes course.

The role of fundus fluorescein angiography in classification and diagnosis of macular diseases: A hospital-based study

AIMS AND OBJECTIVES: The aims and objectives of this study is to assess the role of fundus fluorescein angiography (FFA) in classification and diagnosis of macular diseases. SETTING AND DESIGN: This was an 1-year hospital-based study conducted at KLES, Dr. Prabhakar Kore Hospital, Belagavi, Karnataka. METHODOLOGY: The present study was conducted in the Department of Ophthalmology, KLES, Dr. Prabhakar Kore Hospital and Medical Research Centre, Belagavi, on 66 participants from January 1st, 2016 to December 31st, 2016. METHODS: An 1-year hospital-based study was conducted on 66 patients who attended the outpatient department. A detailed history was obtained from all the patients and a thorough ocular and systemic examination were done. All the patients were examined by conventional methods of ophthalmoscopy (direct, indirect, and slit lamp examination with +90 D lens) followed by FFA. The clinical ophthalmoscopy and fluorescein angiography findings were analyzed and categorized. RESULTS: Sixty-six participants were analyzed and sub-divided into categories of age-related macular degeneration (ARMD), diabetic maculopathy, vascular occlusive disorders, Central Serous Chorioretinopathy (CSCR), inflammatory causes, macular dystrophy, and macular hole. FFA confirmed the diagnosis in 62% of the cases and altered the diagnosis in 38% of cases. It also classified the lesions in 64% of cases. CONCLUSION: FFA has played a major role in diagnosing wet ARMD. It was of immense value in diagnosis and classification of diabetic maculopathy cases. It is a superior diagnostic modality in differentiating macular edema from macular ischemia in vascular disorders. It provides definitive diagnosis in CSCR by detecting the exact site of leakage. It is of immense value in the diagnosis of macular edema in inflammatory diseases. FFA played an important role in the diagnosis of macular dystrophy and macular hole cases.

Age-Related Macular Degeneration and Mortality in the Age-Related Eye Disease Study (AREDS): The Effect of Sex and Time

Age-related macular degeneration (AMD) shares similar risk factors and pathogeneses with cardiovascular diseases (CVDs). Epidemiologic studies over the past 2 decades analyzing the association between AMD and all-cause and CVD-specific mortality have failed to yield conclusive results. The purpose of this analysis is to investigate the sex-specific association between AMD and all-cause and CVD-specific mortality, and to assess whether duration of follow-up alters the strength of association. The database of Genotypes and Phenotypes (dbGaP) data set for the Age-Related Eye Disease Study, a randomized clinical trial of high-dose antioxidants in AMD prevention, with participants enrolled from 1992 to 1998 and followed through 2005, was used in the analysis. There were 4757 Age-Related Eye Disease Study participants aged 55 through 80 years (mean, 69.4 years; 44.1% male) recruited from 11 retinal specialty clinics. Participants had standard Age-Related Eye Disease Study AMD categories (category 1, n= 1117; category 2, n= 1062; category 3, n= 1621; category 4, n= 957). The sex-specific adjusted hazard ratio (HRadj) between baseline AMD and all-cause and CVD-specific mortality was determined at multiple time points (e.g., 5, 7, 10, and all years), adjusting for age, race, diabetes, hypertension, angina, cancer, smoking, obesity, clinical trial antioxidant treatment category, and education. Sex-specific all-cause and CVD-specific mortality. Mean follow-up was 9.6 years (range, 0.5-12.5 years), with 1087 deaths (category 1, n= 197 [17.6%]; category 2, n= 200 [18.8%]; category 3, n= 356 [22.0%]; category 4, n= 326 [34.1%]). Sex-stratified models demonstrated sex differences; in women, a significant association between AMD category 4 and all-cause mortality existed compared with category 1 at each period (HRadj, 1.5-2.3; all P ≤ 0.005); similar category 4 findings were present with CVD-specific mortality, strengthening with shorter periods (HRadj, 1.9-4.6; all P ≤ 0.01). Among men, a significant association between all AMD stages and all-cause (HRadj, 1.5-2.3; all P ≤ 0.05) and CVD-specific mortality (HRadj, 1.6-4.0; all P ≤ 0.05) existed for nearly all periods. Substantial late AMD cases and deaths exceed those in previous population-based studies to better test mortality-related hypotheses. Age-related macular degeneration was significantly associated with all-cause and CVD-specific mortality. Relationships weakened over a longer duration of follow-up, and sex seems to modify the association. Future analyses are warranted to interrogate the possible clinical usefulness of these relationships.

Macular Ganglion Cell Complex and Retinal Nerve Fiber Layer Comparison in Different Stages of Age-Related Macular Degeneration

To employ optical coherence tomography (OCT) to analyze the morphologic changes in the inner retina in different categories of age-related macular degeneration (AMD). Observational cross-sectional study. Single-center study. Inclusion criteria were age over 50, diagnosis of Age-Related Eye Disease Study (AREDS) category 2 and 3, naïve neovascular AMD, and atrophic AMD. Healthy patients of similar age acted as a control group. Primary outcome measures were the changes in ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Secondary outcomes included modifications of rim area and cup-to-disc ratio. One hundred and thirty eyes of 130 patients were recruited: 26 eyes for AREDS category 2, 26 for AREDS category 3, 26 for neovascular AMD, 26 with atrophic AMD, and 26 controls. Mean peripapillary RNFL thickness was significantly lower in neovascular AMD, compared to controls (P= .004); peripapillary RNFL did not significantly vary among AREDS category 2 and 3 and atrophic AMD groups, compared to controls. Mean GCC thickness was higher in the control group, becoming progressively thinner up to neovascular and atrophic AMD groups (P < .0001). Rim area was significantly thinner in the neovascular AMD group compared with controls (P= .047); cup-to-disc ratio was higher in the neovascular AMD group compared with the control group (P= .047). This study demonstrates that eyes with neovascular AMD display reduced RNFL and GCC thickness. RNFL is partially spared in atrophic advanced AMD. The identification of alteration in RNFL and GCC thickness may reveal useful for future therapeutic implications.

Comparison of Retinal Nerve Fiber Layers in Patients with Non-Neovascular Age-Related Macular Degeneration and Normal Controls

Purpose: In neovascular age-related macular degeneration (AMD), it is reported that retinal nerve fiber layer (RNFL) thickness becomes gradually thinner due to degeneration of the outer retinal layer. To our knowledge, there is no previous report regarding RNFL thickness in patients with non-neovascular AMD. Therefore, in this study, we compared RNFL thickness in patients with non-neovascular AMD and normal controls. Methods: Thirty-one eyes with AMD category 3a (AREDS research group), 11 eyes suffering foveal geographic atrophy AMD category 4a, and 31 age-matched normal eyes were evaluated. In every group, regional RNFL thickness (General, Temporal, Superotemporal, Superonasal, Superior, Nasal, Inferonasal, Inferotemporal, and Inferior) was measured using spectral domain optical coherence tomography (SD-OCT). Results: There were no significant differences in age or intraocular pressure among the 3 groups. The mean best corrected visual acuity (BCVA) (log MAR) of the category 4a group was significantly decreased compared to those of the other 2 groups. The mean RNFL thickness in total area in the category 3a group, category 4a group, and normal control group was 99.5 ± 14.0 μm, 99.3 ± 9.4 μm, and 99.4 ± 9.6 μm, respectively. The difference was not statistically significant. No other regional mean values of RNFL thickness in the three groups were significantly different. Conclusions: There was no significant difference in RNFL thickness between non-neovascular patients and the control group. J Korean Ophthalmol Soc 2014;55(9):1334-1339

Ten-Year Incidence Rates of Age-Related Cataract in the Age-Related Eye Disease Study (AREDS): AREDS Report No. 33

Purpose: To investigate the long-term incidence of age-related cataract and cataract surgery in the Age-Related Eye Disease Study (AREDS) cohort.Methods: Baseline and annual lens photographs of participants, aged 55–80 years, were graded centrally for nuclear, cortical, and posterior subcapsular (PSC) lens opacities using the AREDS System for Classifying Cataracts. Progression from a baseline status of no or mild lens opacity to at least moderate severity was analyzed and cumulative incidence estimated rates were calculated for each lens opacity type and cataract surgery stratified by age, sex, race, age-related macular degeneration category, multivitamin (Centrum) use and history of diabetes.Results: The ten-year cumulative incidence was 43.6% for any cataract, 23.1% for nuclear cataract, 22.0% for cortical cataract, 13.1% for PSC cataract, and 26.8% for cataract surgery. The 5- and 10-year incidence rates of all cataract types and cataract surgery were significantly higher with increasing age. Females had a higher incidence of any, nuclear and cortical cataract and cataract surgery (p = 0.02–0.05). Incidence of cortical cataract was higher in non-white participants (p = 0.001).Conclusions: These results are largely consistent with the results of previous observational studies. Long-term incidence rates of type-specific cataract can be useful in designing clinical studies of age-related cataract.

Quality of Life in Keratoconus Patients After Penetrating Keratoplasty

To determine vision-related quality of life (QoL) measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) in keratoconus (KCN) patients who have undergone penetrating keratoplasty (PK) in 1 or both eyes and to compare the results of our study to those of historical controls. Clinical-based, cross-sectional study. Wills Eye Institute, Cornea Service, Thomas Jefferson University, Philadelphia, Pennsylvania. This study included 149 consecutive patients who had undergone PK for KCN. Between June 1, 2008 and December 31, 2008, the NEI-VFQ was administered to 149 patients. The relationship between demographic and clinical factors and NEI-VFQ subscale scores was evaluated. Vision-related quality of life. Eighty-three of 149 patients (55.7%) were male. Approximately half of the patients (76/149; 51.0%) had PK in both eyes. Visual acuity with current correction in the better eye was better than 20/40 in 80% of patients (119/149). Our sample had significantly lower (worse) NEI-VFQ scores compared to Collaborative Longitudinal Evaluation of Keratoconus (CLEK) historical control group for the subscales of role difficulties, dependency, driving, and peripheral vision. In general, scores of our sample were between scores of patients with age-related macular degeneration (AMD) category 3 and 4. Patients with visual acuity better than 20/40 (in the better eye) showed significantly higher scores in all subscales except color vision. There was a significant relationship between minimum time since the graft of 5 years or greater and NEI-VFQ overall score better than AMD category 3 (P = .004). Despite satisfactory results on visual outcome measures obtained after PK, vision-related QoL in KCN patients remains impaired.

Assessment of the Effects of Morphological Changes Related to Age-Related Macular Degeneration on Optical Coherence Tomography Retinal Thickness Measurements

Age-related macular degeneration (AMD) leads to morphological changes that can interfere with optical coherence tomography retinal thickness measurements. The effects of AMD on two available retinal thickness scan modes were tested. Ninety-four scans, equally divided into Radial Line Scans (RLS) and Fast Macula Scans (FMS), of 42 patients with AMD were reviewed. Patients were graded into 4 categories regarding AMD severity. Each scan mode was evaluated for each AMD category. In dry moderate AMD, 2% of the RLS and 5% of the FMS thickness measurements failed. In dry progressed AMD, the RLS mode performed better (26% failure rate) than the FMS mode (42% failure rate). However, in exudative AMD the FMS mode performed better (6% failure rate) than the RLS mode (28% failure rate). The difference between the RLS and FMS performance in dry progressed AMD compared with exudative AMD was significant (P < .0001). The optical coherence tomography retinal thickness scan modes perform differently, depending on AMD severity. Retinal thickness algorithms with better performance are needed to facilitate measurements in patients with AMD.

Feasibility of Screening for High-Risk Age-Related Macular Degeneration With an Internet-Based Automated Fundus Camera

The objective of this pilot study was to determine whether a new screening system, the DigiScope (EyeTel Imaging, Inc., Columbia, MD), can detect the presence of age-related macular degeneration (AMD) at a level requiring referral to an ophthalmologist for further evaluation and possible treatment. The DigiScope is an Internet-based semi-automated digital imaging system designed to be in primary care physicians' offices. Forty-two eyes of 21 patients with different categories of AMD were imaged with both the DigiScope and a standard color fundus camera. The imaging capability of the two modalities was compared for identification of lesions associated with AMD and classification into stages. There was good agreement for low-risk lesions and excellent agreement for high-risk lesions. Thirty-five of 36 eyes with intermediate or advanced disease were correctly identified with DigiScope images. Choroidal neovascularization was identified in all cases with the DigiScope due to the presence of subretinal hemorrhage or subretinal fibrosis. The DigiScope was found less capable of detecting subretinal fluid than standard stereo fundus photographs. This pilot study suggests that the DigiScope may be a useful screening tool for AMD.

Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch's Membrane Correspond to the Distribution of Lesions Associated with Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.