Soft Drusen Research Articles

Lipid metabolism and retinal diseases

The retina has enormous lipids demands and must meet those needs. Retinal lipid homeostasis appears to be based on the symbiosis between neurons, Müller glial cells (MGC), and retinal pigment epithelium (RPE) cells, which can be impacted in several retinal diseases. The current research challenge is to better understand lipid-related mechanisms involved in retinal diseases, such as age-related macular degeneration (AMD) and glaucoma. In a first axis, in vitro and focus on Müller glial cell, we aimed to characterize whether the 24S-hydroxycholesterol (24S-OHC), an overexpressed end-product of cholesterol elimination pathway in neural tissue and likely produced by suffering retinal ganglion cells in glaucoma, may modulate MGC membrane organization, such as lipid rafts, to trigger cellular signalling pathways related to retinal gliosis. We have found that lipid composition appears to be a key factor of membrane architecture, especially for lipid raft microdomain formation, in MGC. However, 24S-OHC did not appear to trigger retinal gliosis via the modulation of lipid or protein composition within lipid rafts microdomains. This study provided a better understanding of the complex mechanisms involved in the pathophysiology of glaucoma. On a second clinical ax, we focused on the lipid-related mechanisms involved in the dysfunction of aging RPE and the appearance of drusenoid deposits in AMD. Using the Montrachet population-based study, we intend to report the frequency of reticular pseudodrusen (RPD) and its ocular and systemic risk factors, particularly related to lipid metabolisms, such as plasma lipoprotein levels, carotenoids levels, and lipid-lowering drug intake. Our study showed that RPD was less common in subjects taking lipid-lowering drugs. Lipid-lowering drugs, such as statins, may reduce the risk of RPD through their effect on the production and function of lipoproteins. This observation highlights the potential role of retinal lipid trafficking via lipoproteins between photoreceptors and retinal pigment epithelium cells in RPD formation. Those findings have been complemented with preliminary results on the analysis of plasma fatty acid (FA) profile, a surrogate marker of short-term dietary lipid intake, according to the type of predominant drusenoid deposit, soft drusen or RPD, in age-related maculopathy. Further research on lipid metabolism in retinal diseases is warranted to better understand the pathophysiology of retinal diseases and develop new promising diagnostic, prognostic, and therapeutic tools for our patients.

SUBRETINAL DRUSENOID DEPOSITS AND SOFT DRUSEN: Are They Markers for Distinct Retinal Diseases?

Soft drusen and subretinal drusenoid deposits (SDDs) characterize two pathways to advanced age-related macular degeneration (AMD), with distinct genetic risks, serum risks, and associated systemic diseases. One hundred and twenty-six subjects with AMD were classified as SDD (with or without soft drusen) or non-SDD (drusen only) by retinal imaging, with serum risks, genetic testing, and histories of cardiovascular disease (CVD) and stroke. There were 62 subjects with SDD and 64 non-SDD subjects, of whom 51 had CVD or stroke. SDD correlated significantly with lower mean serum high-density lipoprotein (61 ± 18 vs. 69 ± 22 mg/dL, P = 0.038, t-test), CVD and stroke (34 of 51 SDD, P = 0.001, chi square), ARMS2 risk allele (P = 0.019, chi square), but not with CFH risk allele (P = 0.66). Non-SDD (drusen only) correlated/trended with APOE2 (P = 0.032) and CETP (P = 0.072) risk alleles (chi square). Multivariate independent risks for SDD were CVD and stroke (P = 0.008) and ARMS2 homozygous risk (P = 0.038). Subjects with subretinal drusenoid deposits and non-SDD subjects have distinct systemic associations and serum and genetic risks. Subretinal drusenoid deposits are associated with CVD and stroke, ARMS2 risk, and lower high-density lipoprotein; non-SDDs are associated with higher high-density lipoprotein, CFH risk, and two lipid risk genes. These and other distinct associations suggest that these lesions are markers for distinct diseases.

A Screening Tool for Self-Evaluation of Risk for Age-Related Macular Degeneration: Validation in a Spanish Population.

PurposeThe objectives of this study were the creation and validation of a screening tool for age-related macular degeneration (AMD) for routine assessment by primary care physicians, ophthalmologists, other healthcare professionals, and the general population.MethodsA simple, self-administered questionnaire (Simplified Théa AMD Risk-Assessment Scale [STARS] version 4.0) which included well-established risk factors for AMD, such as family history, smoking, and dietary factors, was administered to patients during ophthalmology visits. A fundus examination was performed to determine presence of large soft drusen, pigmentary abnormalities, or late AMD. Based on data from the questionnaire and the clinical examination, predictive models were developed to estimate probability of the Age-Related Eye Disease Study (AREDS) score (categorized as low risk/high risk). The models were evaluated by area under the receiving operating characteristic curve analysis.ResultsA total of 3854 subjects completed the questionnaire and underwent a fundus examination. Early/intermediate and late AMD were detected in 15.9% and 23.8% of the patients, respectively. A predictive model was developed with training, validation, and test datasets. The model in the test set had an area under the curve of 0.745 (95% confidence interval [CI] = 0.705–0.784), a positive predictive value of 0.500 (95% CI = 0.449–0.557), and a negative predictive value of 0.810 (95% CI = 0.770–0.844).ConclusionsThe STARS questionnaire version 4.0 and the model identify patients at high risk of developing late AMD.Translational RelevanceThe screening instrument described could be useful to evaluate the risk of late AMD in patients >55 years without having an eye examination, which could lead to more timely referrals and encourage lifestyle changes.

Case series: pachychoroid pigment epitheliopathy transformed to polypoidal choroidal vasculopathy after long-term follow-up

BackgroundPachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported. Case presentationSeven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation.ConclusionsPPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.

Reticular Pseudodrusen: The Third Macular Risk Feature for Progression to Late Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report 30

To analyze reticular pseudodrusen (RPD) as an independent risk factor for progression to late age-related macular degeneration (AMD), alongside traditional macular risk factors (soft drusen and pigmentary abnormalities) considered simultaneously. Post hoc analysis of 2 clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2. Eyes with no late AMD at baseline in AREDS (6959 eyes, 3780 participants) and AREDS2 (3355 eyes, 2056 participants). Color fundus photographs (CFPs) from annual visits were graded for soft drusen, pigmentary abnormalities, and late AMD. Presence of RPD was from grading of fundus autofluorescence images (AREDS2) and deep learning grading of CFPs (AREDS). Proportional hazards regression analyses were performed, considering AREDS AMD severity scales (modified simplified severity scale [person] and 9-step scale [eye]) and RPD presence simultaneously. Progression to late AMD, geographic atrophy (GA), and neovascular AMD. In AREDS, for late AMD analyses by person, in a model considering the simplified severity scale simultaneously, RPD presence was associated with a higher risk of progression: hazard ratio (HR), 2.15 (95% confidence interval [CI], 1.75-2.64). However, the risk associated with RPD presence differed at different severity scale levels: HR, 3.23 (95% CI, 1.60-6.51), HR, 3.81 (95% CI, 2.38-6.10), HR, 2.28 (95% CI, 1.59-3.27), and HR, 1.64 (95% CI, 1.20-2.24), at levels 0-1, 2, 3, and 4, respectively. Considering the 9-step scale (by eye), RPD presence was associated with higher risk: HR, 2.54 (95% CI, 2.07-3.13). The HRs were 5.11 (95% CI, 3.93-6.66) at levels 1-6 and 1.78 (95% CI, 1.43-2.22) at levels 7 and 8. In AREDS2, by person, RPD presence was not associated with higher risk: HR, 1.18 (95% CI, 0.90-1.56); by eye, it was HR, 1.57 (95% CI, 1.31-1.89). In both cohorts, RPD presence carried a higher risk for GA than neovascular AMD. Reticular pseudodrusen represent an important risk factor for progression to late AMD, particularly GA. However, the added risk varies markedly by severity level, with highly increased risk at lower/moderate levels and less increased risk at higher levels. Reticular pseudodrusen status should be included in updated AMD classification systems, risk calculators, and clinical trials.

Ageing fundus degenerations of Macaca fascicularis on multi-modal imaging and histopathology: Similarities and differences compared to human

To characterize the ageing fundus degenerations in Macaca fascicularis, we used multimodal imaging including color fundus photograph, spectral domain optical coherence tomography, fundus autofluorescence, fundus fluorescence angiography, and indocyanine green angiography (ICGA) to survey and track fundus changes of 84 Macaca fascicularis, ranging from 5 to 24 years old over 2 years, and followed by hematoxylin-eosin (HE) and immunofluorescence (IF) staining. The Macaca fascicularis in our cohort showed ageing characteristics different from human, including the more common yellow dot maculopathy, the unique appearance of patchy hyperautoflurescence, and the absence of subretinal drusenoid deposit, basal laminar deposit, geographic atrophy or choroidal neovascularization. Same with human, hard drusen, soft drusen, atherosclerosis, tessellated retina, staining of vessels in peripheral choroid on late-phase ICGA, and peripheral hard drusen were detected. HE and IF staining suggested the patchy hyperautoflurescence to be drusenoid deposits. BMI were significantly higher in the Macaca fascicularis with yellow dot maculopathy and hard drusen, compared to the ones without (p < 0.05). Our study reveals fundus degenerations that develop with ageing in the nonhuman primate of Macaca fascicularis. Their differences and similarities compared to human worth notice by future translational research in degenerative fundus diseases, especially age-related macular degeneration.

AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT VIEWED WITH INDOCYANINE GREEN ANGIOGRAPHY.

Age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) might represent hydrophobic neutral lipid deposits in the Bruch membrane. This study aimed to report retentional avascular pigment epithelial detachment (PED) associated with ASHS-LIA. Patients aged ≥50 years who presented a single avascular serous PED without soft drusen or any other retinal or choroidal diseases were retrospectively included. Pigment epithelial detachment was classified as retentional, effusional, or mixed PED based on indocyanine green angiography. Multimodal images were qualitatively and quantitatively evaluated. This study included 74 eyes of 57 patients. Retentional PED, effusional PED, and mixed PED accounted for 91.9%, 4.1%, and 4.1%, respectively. All PEDs were located in the macular region. Seventeen (29.8%) included patients had bilateral PEDs and all were retentional PEDs with a high level of bilateral consistency in the characteristics of PED and ASHS-LIA. All retentional PEDs were within the bounds of ASHS-LIA. The area of retentional PED increased with the ASHS-LIA grade ( P = 0.030). Most age-related avascular serous PEDs are retentional PEDs. The location and area of retentional PEDs are consistent with the distribution of ASHS-LIA. These findings suggest that the hydrophobic neutral lipid deposits in the Bruch membrane might be involved in the pathogenesis and be a therapeutic target in age-related retentional avascular PED.

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). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. 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. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. 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.

Visualizing lipid behind the retina in aging and age-related macular degeneration, via indocyanine green angiography (ASHS-LIA).

Age-related macular degeneration (AMD) causes legal blindness in older adults worldwide. Soft drusen are the most extensively documented intraocular risk factor for progression to advanced AMD. A long-standing paradox in AMD pathophysiology has been the vulnerability of Asian populations to polypoidal choroidal vasculopathy (PCV) in the presence of relatively few drusen. Age-related scattered hypofluorescent spots on late phase indocyanine green angiography (ASHS-LIA) was recently proposed as precursors of PCV. Herein, we offer a resolution to the paradox by reviewing evidence that ASHS-LIA indicates the diffuse form of lipoprotein-related lipids accumulating in Bruch's membrane (BrM) throughout adulthood. Deposition of these lipids leads to soft drusen and basal linear deposit (BLinD), a thin layer of soft drusen material in AMD; Pre-BLinD is the precursor. This evidence includes: 1. Both ASHS-LIA and pre-BLinD/BLinD accumulate in older adults and start under the macula; 2. ASHS-LIA shares hypofluorescence with soft drusen, known to be physically continuous with pre-BLinD/BLinD. 3. Model system studies illuminated a mechanism for indocyanine green uptake by retinal pigment epithelium. 4. Neither ASHS-LIA nor pre-BLinD/ BLinD are visible by multimodal imaging anchored on current optical coherence tomography, as confirmed with direct clinicopathologic correlation. To contextualize ASHS-LIA, we also summarize angiographic characteristics of different drusen subtypes in AMD. As possible precursors for PCV, lipid accumulation in forms beyond soft drusen may contribute to the pathogenesis of this prevalent disease in Asia. ASHS-LIA also might help identify patients at risk for progression, of value to clinical trials for therapies targeting early or intermediate AMD.

Soft drusen accumulation within a full-thickness macular hole: new insights into the mechanisms of lipid cycling pathways in age-related macular degeneration.

Soft drusen accumulation within a full-thickness macular hole: new insights into the mechanisms of lipid cycling pathways in age-related macular degeneration.

The Phenotypic Course of Age-Related Macular Degeneration for ARMS2/HTRA1: The EYE-RISK Consortium

Age-related maculopathy susceptibility 2 (ARMS2) is considered the most enigmatic of the genes for age-related macular degeneration (AMD). We investigated the phenotypic course and spectrum of AMD for the risk haplotype at the ARMS2 and high-temperature requirement A serine peptidase 1 (HTRA1) locus in a large European consortium. Pooled analysis of 4 case-control and 6 cohort studies. Individuals (N = 17 204) aged 55 years or older participating in the European Eye Epidemiology consortium. Age-related macular degeneration features and macular thickness were determined on multimodal images; data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and were compared with a genetic risk score (GRS) of 19 variants at the complement pathway. Lifetime risks were estimated with Kaplan-Meier analyses in population-based cohorts. Age-related macular degeneration features and stage. Of 2068 individuals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. For homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5-11.4), of choroidal neovascularization (CNV) was 11.2 (95% CI, 9.4-13.3), and of mixed late AMD was 12.2 (95% CI, 7.3-20.6). Cumulative lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. The latter received the diagnosis of late AMD 9.6 years (95% CI, 8.0-11.2) earlier than carriers of the nonrisk genotype. The risk haplotype was not associated with hard or soft drusen < 125 μm (OR, 1.2; 95% CI, 0.9-1.7), but risks increased significantly for soft drusen ≥ 125 μm (OR, 2.1; 95% CI, 1.5-3.0), up to an OR of 7.2 (95% CI, 3.8-13.8) for reticular pseudodrusen. Compared with persons with a high GRS for complement, homozygous carriers of ARMS2/HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2-5.4); risks of other characteristics were not different. Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a relatively early age. Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early signs are present. The phenotypic spectrum resembles that of complement genes, only with higher risks of CNV.

Autofluorescent Organelles Within the Retinal Pigment Epithelium in Human Donor Eyes With and Without Age-Related Macular Degeneration.

PurposeHuman retinal pigment epithelium (RPE) cells contain lipofuscin, melanolipofuscin, and melanosome organelles that impact clinical autofluorescence (AF) imaging. Here, we quantified the effect of age-related macular degeneration (AMD) on granule count and histologic AF of RPE cell bodies.MethodsSeven AMD-affected human RPE-Bruch's membrane flatmounts (early and intermediate = 3, late dry = 1, and neovascular = 3) were imaged at fovea, perifovea, and near periphery using structured illumination and confocal AF microscopy (excitation 488 nm) and compared to RPE-flatmounts with unremarkable macula (n = 7, >80 years). Subsequently, granules were marked with computer assistance, and classified by their AF properties. The AF/cell was calculated from confocal images. The total number of granules and AF/cell was analyzed implementing a mixed effect analysis of covariance (ANCOVA).ResultsA total of 152 AMD-affected RPE cells were analyzed (fovea = 22, perifovea = 60, and near-periphery = 70). AMD-affected RPE cells showed increased variability in size and a significantly increased granule load independent of the retinal location (fovea: P = 0.02, perifovea: P = 0.04, and near periphery: P < 0.01). The lipofuscin fraction of total organelles decreased and the melanolipofuscin fraction increased in AMD, at all locations (especially the fovea). AF was significantly lower in AMD-affected cells (fovea: <0.01, perifovea: <0.01, and near periphery: 0.02).ConclusionsIn AMD RPE, lipofuscin was proportionately lowest in the fovea, a location also known to be affected by accumulation of soft drusen and preservation of cone-mediated visual acuity. Enlarged RPE cell bodies displayed increased net granule count but diminished total AF. Future studies should also assess the impact on AF imaging of RPE apical processes containing melanosomes.

Dry age-related macular degeneration in the Japanese population.

To elucidate the clinical characteristics of eyes with dry age-related macular degeneration (AMD) in Japan. Retrospective. We performed a nationwide survey of dry AMD. A questionnaire on dry AMD was sent to 3,801 major hospitals and eye clinics nationwide. Whenever both eyes met the diagnostic criteria, only the eye with more advanced geographic atrophy was included. In the current survey, 81 patients (81 eyes) with dry AMD were included. Of the 81 patients, 56 (69.1%) were men, and the mean age of the patients was 76.6 ± 8.4 (range, 54-94) years. Twenty-four patients (29.6%) had a history of smoking. The decimal best corrected-visual acuity (BCVA) was equal to or better than 0.7 in 25 eyes (30.9%), but worse than 0.1 in 17 eyes (21.0%). The mean BCVA was 0.62 ± 0.59 in logarithm of the minimum angle of resolution. Lesion size (the greatest linear dimension of the largest geographic atrophy) was ≥ 2 disc diameter in 33 eyes (40.7%) and < 1 disc diameter in 21 eyes (25.9%). Soft drusen was observed in 27 eyes (33.3%), and reticular pseudodrusen was observed in 31 eyes (38.3%). Of the 81 patients, the other eye was diagnosed as dry AMD in 26 eyes (32.1%), neovascular AMD in 16 eyes (19.8%), and intermediate AMD in 18 eyes (22.2%). Dry AMD in the Japanese population has characteristics of male predominance, older age, high prevalence of reticular pseudodrusen, and high bilaterality.

T and genetic variations between Asian and Caucasian polypoidal choroidal vasculopathy

PurposeTo compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients.MethodsWe analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research...

Population-Based Prevalence and 5-Year Change of Soft Drusen, Pseudodrusen, and Pachydrusen in a Japanese Population.

PurposeTo elucidate the prevalence of soft drusen, pseudodrusen, and pachydrusen and their 5-year changes in a Japanese population.DesignLongitudinal population-based cohort study conducted from 2013 through 2017.ParticipantsResidents 40 years of age or older.MethodsNonmydriatic color fundus photographs were used to grade drusen subtypes and retinal pigment epithelium (RPE) abnormalities according to the Three Continent Age-Related Macular Degeneration Consortium. The 5-year changes of each drusen were investigated.Main Outcome MeasuresThe prevalence of each drusen subtype and the 5-year changes of each drusen.ResultsAmong 1731 participants, 1660 participants had gradable photographs that were assessed. The age-adjusted prevalence of soft drusen, pachydrusen, and pseudodrusen was 4.3% (95% confidence interval [CI], 3.2%–5.8%), 7.7% (95% CI, 6.2%–9.7%), and 2.8% (95% CI, 1.7%–4.2%), respectively. Pachydrusen accounted for 82.0% (n = 50) of the extramacular drusen (n = 61). Pigment abnormalities were seen in 28.3% and 8.3% of eyes with soft drusen and pachydrusen, respectively (P < 0.0001). Longitudinal changes were investigated in 1444 participants with follow-up examinations, which showed an increase in size in 8.3% and 3.7% and regression in 1.7% and 5.5% for eyes with soft drusen and pachydrusen, respectively. No participants demonstrated RPE atrophy after pachydrusen regression.ConclusionsThe prevalence of pachydrusen was higher than that of soft drusen and pseudodrusen combined. Pachydrusen may regress over time and typically is not associated with RPE atrophy as detected using color fundus photographs.

Vascular and structural alterations of the choroid evaluated by optical coherence tomography angiography and enhanced-depth imaging optical coherence tomography in eyes with reticular pseudodrusen and soft drusen

BackgroundTo assess the vascularity of choriocapillaris and structural choroidal differences in eyes with reticular pseudodrusen (RPD) and soft drusen. Methods21 eyes with RPD (group 1), 17 eyes with soft drusen (group 2), and 19 eyes as a control group (group 3) were included in this study. Choriocapillaris vascular density and flow area were measured by optical coherence tomography angiography. Total choroidal area, luminal area, stromal area, and lumen/stroma ratios were measured on optical coherence tomography B-scans converted to binary images. ResultsMean choriocapillaris vascular density was higher in group 3 than other groups (group 1 vs 3, p = 0.001; group 2 vs 3, p = 0.003). Mean flow area in choriocapillaris was higher in group 3 than other groups (group 1 vs 3, p = 0.001; group 2 vs 3, p = 0.001). Mean luminal, stromal, and total choroidal areas decreased in group 1 and group 2 compared to controls (p < 0.001, p < 0.001, and p < 0.001, respectively). The stroma ratio decreased in group 1 compared to group 3 (p = 0.013). The lumen ratio and lumen/stroma ratio increased in group 1 compared to group 3 (p = 0.012 and p = 0.008, respectively). ConclusionsThe choroid of eyes with RPD and soft drusen was affected in both choriocapillaris and whole choroid layer.

Progression from intermediate to neovascular age-related macular degeneration according to drusen subtypes: Bundang AMD cohort study report 3.

To investigate the ophthalmic risk factors related to neovascular change and the subtype-wise incidence of progression from intermediate to neovascular age-related macular degeneration (AMD). In this retrospective cohort study, 632 eyes with intermediate AMD from 418 patients (older than 50 years) were enrolled. The systemic factors and ophthalmic factors were statistically analysed with respect to neovascular change. The 5-year cumulative incidence of progression to neovascular AMD (nAMD) from intermediate AMD was 17.8% and 17.0% in eyes with soft drusen and pachydrusen (p = 0.316). Older age (p = 0.025), preexisting nAMD in the fellow eye (p < 0.001), and reticular pseudodrusen (RPD; p = 0.007) were associated with the risk of progression to nAMD. In reference to soft drusen, pachydrusen was associated with progression to polypoidal choroidal vasculopathy (PCV; p < 0.001) and not to typical nAMD (p = 0.064). The ophthalmic risk factors related to the progression of nAMD from intermediate AMD were found to be preexisting nAMD in the fellow eye and RPD. Pachydrusen showed a similar incidence of neovascular change with soft drusen, and was associated with the progression to PCV but not to typical nAMD.

GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION OF DIFFERENT DRUSEN SUBTYPES.

We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration. We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups. We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001). The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

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.

To evaluate the incidence and risk factors of neovascularization in unaffected fellow eyes of patients diagnosed with type 3 neovascularization in Korea. 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. 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). 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.