Presence Of Subretinal Drusenoid Deposits Research Articles

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration

PurposeSubretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ)...

Association between Subretinal Drusenoid Deposits and Age-Related Macular Degeneration in Multimodal Retinal Imaging.

Multimodal retinal imaging enables the detection of subretinal drusenoid deposits (SDD) with significantly greater accuracy compared to fundus photography. The study aimed to analyze a relationship between the presence of SDD, the clinical picture of AMD, and disease progression in a 3 year follow-up. A total of 602 eyes of 339 patients with a diagnosis of AMD, of which 121 (55%) had SDD confirmed in multimodal retinal imaging, were enrolled in the study. SDD was related to a more advanced stage of AMD (p = 0.008), especially with the presence of geographic atrophy (OR = 4.11, 95% CI 2.02-8.38, p < 0.001). Eyes with SDD presented significantly lower choroidal and retinal thickness (ATC: 210.5 μm, CRT: 277 μm, respectively) and volume (AVC: 0.17 mm3, CRV: 8.29 mm3, p < 0.001, respectively) compared to SDD-negative eyes (ATC: 203 μm, CRT: 277 μm; AVC: 7.08 mm3, 8.54 mm3, p < 0.001). Accordingly, the prevalence of pachychoroids and pachyvessels was significantly lower in the SDD present group than in eyes without SDD (p = 0.004; p = 0.04, respectively). Neither demographic factors, lipid profile, genetic predisposition, systemic vascular disease comorbidities, nor parameters of retinal vessels were affected by the presence of SDD. We found no effect of SDD presence on AMD progression (p = 0.12). The presence of SDD appeared to be related to local rather than systemic factors.

Choriocapillaris Impairment Is Associated With Delayed Rod-Mediated Dark Adaptation in Age-Related Macular Degeneration.

Progress toward treatment and prevention of age-related macular degeneration (AMD) requires imaging end points that relate to vision. We investigated choriocapillaris flow signal deficits (FD%) and visual function in eyes of individuals aged ≥60 years, with and without AMD. One eye of each participant in the baseline visit of the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2; NCT04112667) was studied. AMD presence and severity was determined using the Age-Related Eye Disease Study (AREDS) grading system. FD% was quantified using macular spectral domain optical coherence tomography angiography (OCTA) scans. Vision tests included rod-mediated dark adaptation (RMDA), best-corrected visual acuity, and contrast sensitivity (photopic and mesopic), and microperimetric light sensitivity (scotopic, mesopic, and photopic). Presence of subretinal drusenoid deposits (SDD) was determined using multimodal imaging. In 410 study eyes of 410 participants (mean [SD] age = 71.7 years [5.9]), FD% was higher in early AMD (mean [SD] = 54.0% [5.5], N = 122) and intermediate AMD (59.8% [7.4], N = 92), compared to normal (52.1% [5.3], N = 196) eyes. Among visual functions evaluated, RMDA showed the strongest association with FD% (r = 0.35, P < 0.0001), followed by contrast sensitivity (r = -0.22, P < 0.0001). Eyes with SDD had worse FD% (58.3% [7.4], N = 87), compared to eyes without SDD (53.4% [6.0], N = 323, P = < 0.0001). Choriocapillaris FD% were associated with AMD severity and with impaired vision, especially RMDA. Reduced metabolic transport and exchange across the choriocapillaris-Bruch's membrane retinal pigment epithelium (RPE) complex, a causal factor for high-risk soft drusen formation, also may impair photoreceptor sustenance from the circulation. This includes retinoid resupply, essential to dynamic rod function.

Hyperreflective foci distribution in eyes with dry age-related macular degeneration with subretinal drusenoid deposits.

To investigate the distribution of hyperreflective foci (HRF) in eyes with dry age-related macular degeneration (AMD). We retrospectively reviewed optical coherence tomography (OCT) images of 58 dry AMD eyes presenting HRF. The distribution of HRF according to the early treatment diabetic retinopathy study area was analyzed according to the presence of subretinal drusenoid deposits (SDDs). We classified 32 eyes and 26 eyes into the dry AMD with SDD group (SDD group) and dry AMD without SDD group (non-SDD group), respectively. The non-SDD group had higher prevalence and density of HRF at the fovea (65.4% and 1.71 ± 1.48) than the SDD group (37.5% and 0.48 ± 0.63, P = 0.035 and P < 0.001, respectively). However, the prevalence and density of HRF in the outer circle area of the SDD group (81.3% and 0.11 ± 0.09) were greater than those of the non-SDD group (53.8% and 0.05 ± 0.06, p = 0.025 and p = 0.004, respectively). The SDD group showed higher prevalence and mean densities of HRF in the superior and temporal area than in the non-SDD group (all, p < 0.05). HRF distributions in dry AMD varied according to the presence of SDDs. This might support that the degenerative features may be different between dry AMD eyes with and without SDDs.

Quantitative Autofluorescence in Non-Neovascular Age Related Macular Degeneration.

Quantitative autofluorescence (qAF8) level is a presumed surrogate marker of lipofuscin content in the retina. We investigated the changes in the qAF8 levels in non-neovascular AMD. In this prospective cohort study, Caucasians aged ≥50 years with varying severity of non-neovascular AMD in at least one eye and Snellen visual acuity ≥6/18 were recruited. The qAF8 levels were analysed in the middle eight segments of the Delori pattern (HEYEX software, Heidelberg, Germany). The AMD categories were graded using both the Beckman classification and multimodal imaging (MMI) to include the presence of subretinal drusenoid deposits (SDD). A total of 353 eyes from 231 participants were analyzed. Compared with the age-matched controls, the qAF8 values decreased in the eyes with AMD (adjusted % difference = -19.7% [95% CI -28.8%, -10.4%]; p < 0.001) and across the AMD categories, (adjusted % differences; Early, -13.1% (-24.4%, -1%), p = 0.04; intermediate AMD (iAMD), -22.9% (-32.3%, -13.1%), p < 0.001; geographic atrophy -25.2% (-38.1%, -10.4%), p = 0.002). On MMI, the qAF8 was reduced in the AMD subgroups relative to the controls, (adjusted % differences; Early, -5.8% (-18.9%, 8.3%); p = 0.40; iAMD, -26.7% (-36.2%, -15.6%); p < 0.001; SDD, -23.7% (-33.6%, -12.2%); p < 0.001; atrophy, -26.7% (-39.3%, -11.3%), p = 0.001). The qAF8 levels declined early in AMD and were not significantly different between the severity levels of non-neovascular AMD, suggesting the early and sustained loss of function of the retinal pigment epithelium in AMD.

Assessment of the Classification of Age-Related Macular Degeneration Severity from the Northern Ireland Sensory Ageing Study Using a Measure of Dark Adaptation.

To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification. Cross-sectional study. Participants from the Northern Ireland Sensory Ageing study (Queen's University Belfast). Complete RMDA (rod-intercept time [RIT]) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT. Rod-intercept time data (age-corrected). Data from 459 participants (median [interquartile range] age, 65 [59-71] years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0-3, with 3 being intermediate age-related macular degeneration [iAMD]) groups was 6.0 (4.5-8.7), 6.6 (4.7-10.5), 5.7 (4.4-7.4), and 13.2 (6-21.1) minutes, respectively. OCT classifications OCT0-OCT2 yielded different median (interquartile range) values: 5.8 (4.5-8.5), 8.4 (5.2-13.3), and 11.1 (5.3-20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P< 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P= 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P< 0.01) but not in OCT1 (P= 0.285). Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.

Subretinal Drusenoid Deposits and Lower Serum High-Density Lipoprotein Cholesterol Levels Possess Latent Relation to Cardiovascular Disease and Can Be a Feasible Predictor.

Objective To ascertain whether lipid-related subretinal drusenoid deposits (SDD) are correlated with coexisting cardiovascular disease (CVD), as well as to reveal latent serum markers of CVD. Methods Patients older than 50 years and plagued by age-related macular degeneration (AMD) were included. Subjects with other retinal degenerations and vascular diseases, any recent treatment at other medical care institutions, and any previous oculopathy or ophthalmic surgery were excluded. All subjects were examined to ascertain whether they possess SDD, to analyze serum cholesterols, including low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). Subjects were divided into SDD and non-SDD groups and further divided into subgroups by assessment of pump defect, valve defect, and carotid defect. Finally, logistic model trees and random forest algorithm analysis were performed. Results A total of 85 AMD patients including 43 with and 42 without SDD were involved. The 42 AMD (97.67%, 42/43) patients with SDD showed CVD, including 3 subjects presenting valve defect, 3 subjects presenting carotid defect, 8 subjects presenting pump defect, 14 subjects presenting both pump and valve defects, and 14 subjects presenting pump, valve, and carotid defects. By contrast, 5 AMD (11.90%, 5/42) patients without SDD showed CVD. Cholesterol level of SDD subjects presented significant higher TC (5.66 ± 1.01 vs. 5.58 ± 0.72, p = 0.032, Wilcoxon test) and lower HDL cholesterol (61 ± 17 vs. 70 ± 21, p = 0.031, Wilcoxon test) than that of non-SDD. The cases with HDL < 62 mg/dL were significantly related to CVD (p = 0.013, Wilcoxon test), and the cases with HDL < 40 mg/dL were not (p = 0.659, Wilcoxon test). Through machine learning based on the image from color fundus photography, the accuracy of predicting CVD was 95%. Conclusions The presence of SDD of AMD and lower serum HDL cholesterol level can predict certain CVD for AMD patients. The machine learning based on the SDD image and serum HDL cholesterol may open new avenue for the detection of CVD as a noninvasive approach.

Dark Adaptation and Its Role in Age-Related Macular Degeneration.

Dark adaptation (DA) refers to the slow recovery of visual sensitivity in darkness following exposure to intense or prolonged illumination, which bleaches a significant amount of the rhodopsin. This natural process also offers an opportunity to understand cellular function in the outer retina and evaluate for presence of disease. How our eyes adapt to darkness can be a key indicator of retinal health, which can be altered in the presence of certain diseases, such as age-related macular degeneration (AMD). A specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD has revealed essential findings underlying the pathobiology of the disease. The process of dark adaptation involves phototransduction taking place mainly between the photoreceptor outer segments and the retinal pigment epithelial (RPE) layer. DA occurs over a large range of luminance and is modulated by both cone and rod photoreceptors. In the photopic ranges, rods are saturated and cone cells adapt to the high luminance levels. However, under scotopic ranges, cones are unable to respond to the dim luminance and rods modulate the responses to lower levels of light as they can respond to even a single photon. Since the cone visual cycle is also based on the Muller cells, measuring the impairment in rod-based dark adaptation is thought to be particularly relevant to diseases such as AMD, which involves both photoreceptors and RPE. Dark adaptation parameters are metrics derived from curve-fitting dark adaptation sensitivities over time and can represent specific cellular function. Parameters such as the cone-rod break (CRB) and rod intercept time (RIT) are particularly sensitive to changes in the outer retina. There is some structural and functional continuum between normal aging and the AMD pathology. Many studies have shown an increase of the rod intercept time (RIT), i.e., delays in rod-mediated DA in AMD patients with increasing disease severity determined by increased drusen grade, pigment changes and the presence of subretinal drusenoid deposits (SDD) and association with certain morphological features in the peripheral retina. Specifications of spatial testing location, repeatability of the testing, ease and availability of the testing device in clinical settings, and test duration in elderly population are also important. We provide a detailed overview in light of all these factors.

Incidence and Risk Factors for Macular Atrophy in Acquired Vitelliform Lesions

To study the time course to macular atrophy (MA) and associated risk factors in eyes with acquired vitelliform lesions (AVLs) as they vary between patients and between eyes of an individual. Single-center, retrospective, observational cohort study. Consecutive patients registered between January 2009 and January 2014 with first diagnosis of AVL confirmed by multimodal imaging were included. Eyes with baseline MA or choroidal neovascularization were excluded. Patient demographics were collected. Serial OCT scans and fundus autofluorescence (FAF) scans were graded and analyzed. Turnbull's estimator was used, and time was censored at 5 years. Multivariable Weibull parametric proportional hazard models were used to assess the association of risk factors with MA after adjustment for age and gender. Hazard ratios (HRs) are reported with 95% confidence interval (CI). Time to the first OCT evidence of MA stratified by presenting visual acuity (VA) and AVL lesion subtypes. Secondary outcome included risk factors for incident MA. A total of 237 eyes (132 patients) met the inclusion criteria. Incident MA was detected in 52 of 237 eyes (21.9%) by 5 years. Stratified by baseline VA, 40.3% of eyes with VA ≤70 letters developed atrophy within 5 years of first diagnosis in contrast to 10.3% eyes with VA >70 letters (P < 0.001). Based on lesion type only, 12.9% of eyes with vitelliform lesion at baseline developed MA versus 39.8% and 44.2% of eyes with pseudohypopyon or vitelliruptive lesion type, respectively. In adjusted analysis, baseline factors associated with increased risk of MA included VA ≤70 letters (hazard ratio [HR], 5.54; 95% confidence interval [CI], 2.30-13.34), base width (HR, 1.22; 95% CI, 1.16-1.28), maximum height (HR, 2.61; 95% CI, 1.82-3.74), presence of subretinal drusenoid deposits (SDDs) (HR, 2.83; 95% CI, 1.34-5.96), and disrupted external limiting membrane (ELM) (HR, 2.81; 95% CI, 1.34-5.86). Baseline VA of ≤70 letters (Snellen ≤20/40) and pseudohypopyon or vitelliruptive lesion type attribute the highest risk for MA. Other prognostic indicators for MA include baseline presence of SDD, disrupted ELM, and larger lesion area.

Assessing the long-term evolution of type 3 neovascularization in age-related macular degeneration using optical coherence tomography angiography.

To analyze the evolution of type 3 neovascularization in eyes with age-related macular degeneration during anti-vascular endothelial growth factor (VEGF) treatment using optical coherence tomography angiography (OCTA) analysis. Forty-one treatment-naïve eyes (37 patients) with type 3 neovascularization were retrospectively included in the study. The growth and morphological changes in the type 3 lesions, which were recorded using OCTA, were compared across time. The high-flow signal of the lesion on OCTA was significantly increased at the sub-retinal pigment epithelium (RPE) and the choriocapillaris during anti-VEGF treatment. The detection rate of the flow signal in the sub-RPE increased from 50.0% at baseline and 51.2% at 12 months to 65.9% at 24 months (P = 0.013). The flow signal extending into the choriocapillaris was detected in 0% of the eyes at baseline, 9.8% of the eyes at 12 months, and 17.1% of the eyes at 24 months (P = 0.018). The presence of subretinal drusenoid deposits (SDD) was significantly more frequent in the group with extension into the choriocapillaris (100%) than in the group without (61.8%, P = 0.036). For the four eyes with extension into the choroid, the morphological feature of the lesion on en face OCTA evolved into a tangled vascular network, similar to type 1 neovascularization. OCTA analysis revealed that type 3 neovascularization gradually extended downward toward the sub-RPE and choroid during anti-VEGF treatment. The extension of the lesion into the choriocapillaris, suggesting retinal-choroidal anastomosis, was significantly more frequent in eyes with SDD.

Retinal layer thicknesses and neurodegeneration in early age-related macular degeneration: insights from the Coimbra Eye Study.

This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes. This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis. The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors' segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium-Bruch's membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid(p < 0.05). Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration.

Definition of Different Treatment Response Types In Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a common, degenerative disease of the retina presented as neovascular AMD (n-AMD) or non‐neovascular AMD. Several factors risk factors having been found associated with unresponsive to treatment and progression macular scar form, including subtype of the choroidal neovascular membrane (CNM), presence of subretinal drusenoid deposits, Pigment epithelial detachment (PED), decreased central choroidal thickness, preexisting Macular atopy (MA) in the fellow eye. There is no exact consensus about the term described the status of poor or non- response to any treatment regime. In this article definition of different therapeutic responses such as resistance, refractory, recurrence of anti-vascular endothelial growth factors (AntiVEGF), and its relation to retinal features are discussed.

Macular Thickness in Intermediate Age-Related Macular Degeneration Is Influenced by Disease Severity and Subretinal Drusenoid Deposit Presence.

PurposeTo investigate how macular thickness varies with intermediate age-related macular degeneration (iAMD) severity and the presence of subretinal drusenoid deposits (SDDs).MethodsA longitudinal prospective study of 143 participants >50 years of age with no to intermediate AMD who were followed with multimodal imaging and functional testing. Participants were stratified by iAMD severity according to imaging features. Macular thicknesses measurements over the central circles with 1-mm, 3-mm, and 6-mm diameters obtained from ocular coherence tomography imaging were compared across severity categories using cross-sectional (143 eyes) and longitudinal (subset of 77 eyes followed for 4 years) multivariate analyses.ResultsCompared with control eyes without large drusen or SDDs (Group 0), central maculas of lower risk eyes with unilateral large drusen (Group 1) were thicker (P = 0.014), whereas higher risk eyes with SDDs (Group SDD) were thinner (P = 0.02) in cross-sectional multivariate analyses. In longitudinal analyses, maculas with SDDs thinned more rapidly over 4 years relative to control eyes (P = 0.0058), which did not show significant thinning. More rapid central macular thinning was associated with worse baseline best-corrected visual acuity (BCVA) (P = 0.016) and more rapid BCVA decline (P = 0.0059).ConclusionsMacular thickness in iAMD varies with disease severity, showing small increases in eyes with large drusen and decreases in eyes with SDDs. Active processes possibly related to neuroinflammation and neurodegeneration may be contributory. Longitudinal central macular thickness evaluation is an accessible outcome measure relevant to functional measures and is potentially useful for iAMD interventional studies.

Association of Visual Function Measures with Drusen Volume in Early Stages of Age-Related Macular Degeneration.

PurposeTo assess which visual function measures are most strongly associated with overall retinal drusen volume in age-related macular degeneration (AMD).MethodsA total of 100 eyes (16 eyes with early AMD, 62 eyes with intermediate AMD, and 22 eyes from healthy controls) were recruited in this cross-sectional study. All subjects underwent several functional assessments: best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), visual acuity (VA) measured with the Moorfields Acuity Chart (MAC-VA), contrast sensitivity with the Pelli–Robson test, reading speed using the International Reading Speed texts, and mesopic and dark-adapted microperimetry. Drusen volume was automatically determined based on optical coherence tomography using an approach based on convolutional neural networks. The relationship between drusen volume and visual function was assessed with linear regressions controlling for confounders.ResultsMean drusen volume and MAC-VA differed significantly among all AMD stages and controls (P < 0.001). In univariate linear regression, LLVA, MAC-VA, contrast sensitivity, and mesopic and dark-adapted microperimetry were significantly negatively associated with the overall drusen volume (all P < 0.006). After controlling for AMD stage, age, and the presence of subretinal drusenoid deposits, MAC-VA and mesopic and dark-adapted microperimetry were still significantly associated with drusen volume (P = 0.008, P = 0.023, and P = 0.022, respectively).ConclusionsOur results suggest that MAC-VA, as well as mesopic and dark-adapted microperimetry, might indicate structural changes related to drusen volume in early stages of AMD.

Natural course of adult-onset vitelliform lesions in eyes with and without comorbid subretinal drusenoid deposits

PurposeAdult vitelliform lesions (AVL) are associated with age related macular degeneration (AMD) and subretinal drusenoid deposits (SRDD). We evaluated the natural course of AVL, assessing the influence of SRDD on disease progression, visual function and incidence of macular atrophy (MA) and choroidal neovascular membranes (CNVM).MethodsA retrospective cohort study was conducted between January 2011 and March 2016. Demographic, clinical and imaging data from 26 consecutive AVL patients were analysed following case note review. Optical coherence tomography images were graded for SRDD and patients divided into those with/without SRDD. Outcomes included presenting/changes in best corrected visual acuity (BCVA) and incidence of MA/CNVM.ResultsMean age was 78.6 ± 7.6 years. Mean follow-up was 51.5 ± 25.6 months. Twelve patients (46.2%) had SRDD at presentation with 3 more (11.5%) developing them. Subjects with SRDD were older (mean 81.7 ± 6.1 years vs 74.3 ± 7.6 years, p = 0.010). Mean presenting BCVA was worse in SRDD eyes (0.39 ± 0.31 logMAR vs 0.19 ± 0.18 logMAR, p = 0.017). Eight of 15 patients with SRDD (53.3%) developed incident MA or CNVM; higher than those with no SRDD (1/11, 9.1%; p = 0.036). Two patients (7.7%) developed full thickness macular holes.ConclusionsPatients with AVL and SRDD likely represent an advanced pathological stage or phenotype with worse visual outcome and higher risk of MA/CNVM. Possible overlap with AMD exists. Follow-up, counselling and provisions for early detection/treatment of complications should be made. Better classification including improved understanding of phenotypic and genetic variations with reference to comorbid diseases including AMD is required. Presence of SRDD in AVL offers a dichotomous classification, indicating risk of future MA/CNVM formation.

Retinal pigment epithelial atrophy after anti-vascular endothelial growth factor therapy for polypoidal choroidal vasculopathy

Background/aimsTo describe the risk factors for the development of retinal pigment epithelial (RPE) atrophy following intravitreal anti-vascular endothelial growth factor (VEGF) injection treatment for polypoidal choroidal vasculopathy (PCV).MethodsWe retrospectively included...

Subretinal Drusenoid Deposits in the Elderly in a Population-Based Study (the Montrachet Study).

The aim of this study was to investigate the prevalence of subretinal drusenoid deposits (SDD) and to identify associated factors in an elderly population. The participants of the population-based Montrachet study underwent an exhaustive ophthalmologic examination, including color fundus photography and macular spectral domain-optical coherence tomography (SD-OCT), coupled with infrared reflectance imaging. The presence of SDD and other age-related macular degeneration lesions, according to the European Eye Epidemiology SD-OCT classification of macular diseases, and subfoveal choroidal thickness were recorded. Moreover, the association of SDD and both clinical and demographic factors as well as plasma levels of vitamin E and lutein/zeaxanthin (L/Z) were analyzed. The mean age of patients was 82.3 ± 3.8 years and 62.7% were female. The prevalence of SDD was 18.1% (n = 205) in the subjects with at least one eye interpretable (n = 1135). In multivariate analysis, SDD was positively associated with increasing age (OR, 4.6; 95% CI, 2.8-7.7; P < 0.001 for subjects aged >85 years), female sex (OR, 1.7; 95% CI, 1.2-2.4; P = 0.005), and plasma L/Z level (OR, 1.2; 95% CI, 1.0-1.5; P = 0.039), and negatively associated with lipid-lowering drugs use (OR, 0.5; 95% CI, 0.3-0.9; P = 0.014 for statin medications) and subfoveal choroidal thickness (OR, 0.8; 95% CI, 0.7-0.9; P = 0.002). The prevalence of SDD was high in subjects older than 75 years, more frequent in women, and was associated with a thinner choroid. The association with lipid-lowering drugs deserves further investigation.

Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits

PurposeTo examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity.MethodsParticipants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a −3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography.ResultsScotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes.ConclusionsThree rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.

Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration.

PurposeTo explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy.MethodsThere were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness.ResultsSDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1–8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0–8.9, P = 0.0461 and 95% CI 1.3–32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype.ConclusionsMA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development.

Choroidal Changes Associated With Subretinal Drusenoid Deposits in Age-related Macular Degeneration Using Swept-source Optical Coherence Tomography

To compare choroidal vascular features of eyes with and without subretinal drusenoid deposits (SDD), using swept-source optical coherence tomography (SS OCT). Multicenter, cross-sectional study. We prospectively recruited patients with intermediate age-related macular degeneration (AMD), without other vitreoretinal pathology. All participants underwent complete ophthalmic examination, color fundus photography (used for AMD staging), and spectral-domain OCT (to evaluate the presence of SDD). SS OCT was used to obtain automatic macular choroidal thickness (CT) maps, according to the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For data analysis, we considered mean choroidal thickness as the arithmetic mean value of the 9 ETDRS sectors. SS OCT en face images of choroidal vasculature were also captured and converted to binary images. Choroidal vascular density (CVD) was calculated as a percent area occupied by choroidal vessels in a 6-mm-diameter submacular circular. Choroidal vessel volume was calculated by multiplying the average CVD by macular area and CT. Multilevel mixed linear models (to account for the inclusion of 2 eyes of same subject) were performed for analysis. We included 186 eyes (n= 118 subjects), 94 (50.5%) presenting SDD. Multiple regression analysis revealed that, controlling for age, eyes with SDD presented a statistically thinner mean CT (ß=-21.9, P= .006) and CT in all the individual ETDRS fields (ß ≤-18.79, P ≤ .026). Mean choroidal vessel volume was also significantly reduced in eyes with SDD (ß=-0.003, P= .007). No significant associations were observed with mean CVD. In subjects with intermediate AMD, choroidal thickness and vessel volume are reduced in the presence of subretinal drusenoid deposits.