Age-Related Macular Degeneration Eyes Presenting with Cuticular Drusen and Reticular Pseudodrusen

This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). The clinical records of 13 eyes of seven patients diagnosed with CD and RPD were retrospectively reviewed. All patients underwent a complete ocular examination and multimodal imaging. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.

Systemic and Genetic Risk Factors for Reticular Macular Disease and Soft Drusen in Age- Related Macular Degeneration

Purpose: Soft drusen and subretinal drusenoid deposits (SDD) aka reticular macular disease (RMD) characterize two pathways to advanced age-related macular degeneration (AMD). We propose these pathways are distinct diseases, with distinct genetic risks, serum risks and associated systemic diseases. Methods: 126 Subjects with AMD had: retinal imaging for RMD status, serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. Results: 62 subjects had RMD, 64 were nonRMD (drusen only), 51 had CVD or Stroke. RMD correlated significantly with: ARMS2 risk allele (p= 0.019); lower mean serum HDL (61 vs. 69 mg/dl, p= 0.038, t test); CVD and troke (34/51 RMD, p= 0.001). NonRMD correlated/trended with: APOE2 (p= 0.032) and CETP (p= 0.072) risk alleles. 97 subjects total had some drusen, which correlated with CFH risk (p= 0.016). Multivariate independent risks for RMD were: CVD and Stroke (p= 0.008), and ARMS2 homozygous risk (p= 0.038). Conclusion: The RMD and soft drusen AMD pathways have distinct systemic associations, serum and genetic risks. RMD is associated with CVD and stroke, ARMS2 risk, and lower HDL; drusen with CFH risk and two lipid risk genes. These pathways appear to be distinct diseases leading to advanced AMD.

Age-Related Macular Degeneration, Cardiovascular Disease and Stroke

Importance: High-risk vascular diseases (HRVs) may remain undetected until catastrophe ensues. Detection from non-invasive retinal imaging would be highly significant. Objective: To demonstrate that certain lesions of Age-Related Macular Degeneration (AMD) found on retinal imaging correlate with co-existing HRVs. Design: Cross-sectional cohort study. Two years. Retinal image graders blinded to HRV status. Setting: 2 retina referral clinics. Participants: 151 consecutive AMD patients, ages 50-90, 97 females, 54 males, with lesions of soft drusen and/or subretinal drusenoid deposits (SDD). 12 others approached, 10 refused, 2 excluded. Methods: Patients were classified by retinal imaging into SDD (SDD present, +/- drusen) or nonSDD (soft drusen only), and by history into HRV (cardiac pump defect (myocardial infarction (MI), coronary artery bypass grafting (CABG), congestive heart failure (CHF)), valve defect, and carotid stroke) or nonHRV, with serum risk factors and medical histories. Main Outcome Measures: Correlations of HRV with SDD and other covariates (Univariate chi-square and multivariate regression). Performance of Machine Learning predicting HRV. Results: 75 SDD subjects; 76 nonSDD subjects; HRV prevalence 19.2% (29/151). 1. High density lipoprotein (HDL) < 62 mg/Dl was found in 24/29 HRV, 42/122 nonHRV, OR 12.40, 95% Confidence Interval (CI) 5.125-30.014; p= 0.0002. 2. 15 Pump defects, 14/15 SDD, 8 Valve defects, 6/8 SDD (4 severe aortic stenosis), 6 carotid strokes, 5/6 SDD. Total HRVs 29, 25/29 SDD, OR 9.0, 95% CI 2.95-27.46; p= 0.000012. 3. Adjusted multivariate correlations. HRV with SDD (p= 0.000333). SDD and HDL < 62 with HRV (p= 0.000098 and 0.021). 4. Machine Learning prediction of HRVs from SDD status and HDL level: specificity 87.4%, sensitivity 77.4%, accuracy 84.9%; 95% CIs(%) 79.0-93.3, 58.0-90.4, 77.5-90.7, respectively. Conclusions and Relevance: High-risk vascular diseases were accurately identified in a cohort of AMD patients from the presence of characteristic deposits (SDDs) on imaging and HDL levels. The SDDs are directly consequent to inadequate ocular perfusion resulting from the systemic vasculopathies. Further validation in larger cohorts of both vasculopathic and AMD subjects could bring this system into widespread medical practice, to reduce mortality and morbidity from vascular disease, particularly in women, where undiagnosed cardiac disease remains a serious issue.

Integrative analysis of the choroid by quantifying Haller vessel and choriocapillaris parameters in different drusen subtypes

This study aimed to quantify the Haller vessel and choriocapillaris (CC) parameters in drusen subtypes in nonexudative age-related macular degeneration (AMD) and pachydrusen. Ninety-five eyes of 80 patients and 28 control eyes were categorized into soft drusen, subretinal drusenoid deposit (SDD), soft drusen plus SDD, pachydrusen, and control groups. The diameter, length and intersections of Haller vessels and the total area, size and number of CC flow voids were quantified using en face optical coherence tomography (OCT) or OCT angiography. The pachydrusen group showed the largest Haller vessel area and diameter and shortest total length but similar CC parameters to those in the control group. The soft drusen plus SDD group showed the largest CC flow void area and size, while the Haller parameters were similar to those in the control group. The area and size of the flow voids in the SDD group were smaller than those in the soft drusen plus SDD group. Based on unsupervised machine learning, the eyes were classified into 4 clusters—the control, pachydrusen, soft drusen plus SDD and soft drusen plus SDD groups. Cluster 3 showed a larger diameter and shorter total length of the Haller vessels than cluster 4.

Unaffected fellow eye neovascularization in patients with type 3 neovascularization: Incidence and risk factors

Purpose To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. Methods This retrospective study included 93 unaffected fellow eyes of 93 patients diagnosed with type 3 neovascularization. For initial type 3 neovascularization diagnosis, optical coherence tomography and angiography were conducted. These baseline data were compared between patients with and without neovascularization in their fellow eyes during the follow-up period. Results The mean follow-up period was 66.1±31.1 months. Neovascularization developed in 49 (52.8%) fellow eyes after a mean period of 29.5±19.6 months. In the fellow eye neovascularization group, the incidence of soft drusen and reticular pseudodrusen was significantly higher than that in the non-neovascularization group (83.7% vs. 36.5%, p<0.001; 67.3% vs. 40.9%, p = 0.017, respectively), but the choroidal vascularity index (CVI) showed a significantly lower value (60.7±2.0% vs. 61.7±2.5%; p = 0.047). The presence of reticular pseudodrusen was related with the duration from baseline to development of fellow eye neovascularization (p = 0.038). Conclusion Neovascularization developed in 52.8% of unaffected fellow eyes. The presence of soft drusen, reticular pseudodrusen, and lower CVI values can be considered risk factors of neovascularization in unaffected fellow eyes of patients with type 3 neovascularization. The lower CVI values suggest that choroidal ischemic change may affect the development of choroidal neovascularization in these patients.

Morphological changes of macular soft drusen and drusenoid DPED after subthreshold micropulse laser treatment

AIM: To analyze the morphological changes of macular soft drusen and drusenoid pigmental epithelium detachment (DPED) after subthreshold micropulse laser treatment (SMLT). METHODS: Fourteen patients (20 affected eyes) with soft drusen and DPED clinically confirmed from August 2016 to October 2018, were included in this study. 577 nm yellow laser of SMLT was applied for soft drusen and DPED. The changes of soft drusen and DPED in best corrected visual acuity (BCVA)(LogMAR)and height, diameter and cross-sessional area according to fundus autofluorescence and SD-OCT examinations were observed after SMLT RESULTS: BCVA was not significant difference after treatment of soft drusen (P=0.260), and the DPED (P=0.736) than that of the baseline. Compared with the baseline values, the height and cross-sessional area of soft drusen were reduced at the 6mo after treatment, and the differences were statistically significant (P=0.008, P=0.034). Compared with the baseline values, the differences were not statistically significant in height, diameter and cross-sectional area of DPED after treatment. CONCLUSION: BCVA was not reduced for drusen and DPED after SMLT, however, the height and cross-sessional area of soft drusen was reduced compared with those before treatment, and the differences were not statistically significant in height, diameter and cross-sectional area of DPED before and after treatment. The results indicated that SMLT was effective for soft drusen, but was not effective for short-term treatment of DPED. SMLT caused no damage to the visual acuity in treatment of soft drusen and DPED, but prospective, controlled, large sample and long-term follow-up studies should be required.

Clinical Characteristics of Neovascular Age-Related Macular Degeneration without Typical Drusen

Purpose. To evaluate the clinical characteristics of neovascular age-related macular degeneration (nAMD) patients without typical drusen. Methods. We retrospectively studied 165 eyes in 165 patients with treatment-naïve nAMD, including typical AMD and polypoidal choroidal vasculopathy (PCV). According to the fellow eye condition, the patients were divided into nAMD with and without typical drusen groups. Eyes with soft drusen or subretinal drusenoid deposits were classified into the nAMD with the typical drusen group. Smoking status and diagnoses of hypertension and diabetes were identified from hospital records and patient recall. We assessed best-corrected visual acuity (BCVA), central retinal thickness (CRT) at the fovea, subfoveal choroidal thickness (SFCT), and the number of injections received. Results. The nAMD without typical drusen group was significantly younger (77.9 ± 7.6 vs. 71.8 ± 8.3, P < 0.001 ) and had thicker SFCT at baseline (207.9 ± 99.5 vs. 260.1 ± 113.2 μm, P = 0.007 ) and a higher proportion of PCV (30.6 vs. 63.1%, P < 0.001 ). The proportion of ever-smokers was significantly higher in the nAMD without typical drusen group (54.8 vs. 70.9%, P = 0.036 ). There were no statistically significant differences in the proportion of patients with hypertension or diabetes; BCVA, CRT, or SFCT changes; or the number of injections between the nAMD with and without typical drusen groups. Conclusion. The clinical features of patients in the nAMD without typical drusen group were almost identical to those of pachychoroid-driven choroidal neovascularization (CNV) patients. The nAMD without typical drusen group had a significantly higher proportion of ever-smokers than the nAMD with typical drusen group. Smoking could be a risk factor for the development of pachychoroid-driven CNV.

Macular neovascularization in eyes with pachydrusen

The natural history and clinical significance of pachydrusen is unclear. This study aims to compare the longitudinal changes of eyes with pachydrusen and soft drusen and progression to exudative macular neovascularisation (MNV). Patients with a diagnosis of MNV in one eye only and the fellow eye was selected as the study eye. Study eyes were required to have pachydrusen or soft drusen on fundus photographs and follow up of at least 2 years or until exudative MNV occurred. Systematic grading was performed at baseline and change in drusen area and onset of exudative MNV recorded over the period of follow up. A total of 75 eyes from 75 patients (29 with pachydrusen and 46 with soft drusen) were included. There was no difference in the rate of progression to exudative MNV in the soft and pachydrusen groups (13.3% versus 24.1%, p = 0.38). Pachydrusen, as compared to soft drusen, was associated with polypoidal choroidal vasculopathy subtype (85.7% versus 16.7%, p < 0.01) and the location of exudation was co-localised with soft drusen but not with pachydrusen. There was a higher rate of increase in soft drusen area compared to pachydrusen area (27.7 ± 31.9%/year versus 8.7 ± 12.4%/year respectively, p < 0.01). We found no difference in the proportion of eyes that developed exudative MNV in this study however characterisation of drusen evolution patterns revealed a strong association with exudative MNV subtype.