Drusenoid Deposits Research Articles

Retinal dystrophy and subretinal drusenoid deposits in female choroideremia carriers.

To describe clinical and molecular characteristics in a group of Italian female choroideremia (CHM) carriers and report fundus patterns. We retrospectively studied 11 female carriers belonging to six CHM families examined at the Regional Reference Center for Hereditary Retinal Degenerations at the Eye Clinic in Florence. We took into consideration patients with a comprehensive ophthalmological examination, fundus photography, optical coherence tomography (OCT), full field electro-retinography (ERG), and visual field (VF). All patients were screened for mutations of the CHM gene. Fundus examination revealed retinal abnormalities in all female carriers (11/11) in the study; in particular four fundus patterns were identified: pattern A (RPE dystrophy involving only the peripheral retina), pattern B (RPE dystrophy involving the peripheral retina and the posterior pole with small hypo-pigmented RPE areas), pattern C (RPE dystrophy involving the peripheral retina and the posterior pole with small yellowish well-defined dots), and pattern D (RPE dystrophy involving the peripheral retina and the posterior pole with large hypo-pigmented RPE areas and well-defined yellowish dots). Pattern D was characterized by widespread macular subretinal drusenoid deposits (SDD). Half of the observed mutations were novel mutations. A genotype-phenotype correlation was not identified. Retinal dystrophy and SDD were detected in our female CHM carriers, and fundus patterns have been described in this study. The recognition of specific fundoscopic patterns may permit a correct diagnosis, an appropriate molecular investigation and genetic counseling.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Diabetic choroidopathy

Early histopathological studies of diabetic choroids demonstrated loss of choriocapillaris (CC), tortuous blood vessels, microaneurysms, drusenoid deposits on Bruchs membrane, and choroidal neovascularization. The preponderance of histopathological changes were at and beyond equator. Studies from my lab suggest that diabetic choroidopathy is an inflammatory disease in that leukocyte adhesion molecules are elevated in the choroidal vasculature and polymorphonuclear neutrophils are often associated with sites of vascular loss. Modern imaging techniques demonstrate that blood flow is reduced in subfoveal choroidal vasculature. Angiography has shown areas of hypofluorescence and late filling that probably represent areas of vascular loss and/or compromise. Perhaps, as a result of vascular insufficiency, the choroid appears to thin in DC unless macular edema is present. Enhanced depth imaging (EDI-SD) OCT and swept source (SS) OCT have documented the tortuosity and loss in intermediate and large blood vessels in Sattler’s and Haller’s layer seen previously with histological techniques. The risk factors for DC include diabetic retinopathy, degree of diabetic control, and the treatment regimen. In the future, OCT angiography could be used to document loss of CC. Because most of the measurement and imaging are in the posterior pole, the severity of DC may be underappreciated in the published accounts of DC assessed with imaging techniques. However, it is now possible to document DC and quantify these changes clinically. This suggests that DC should be evaluated in future clinical trials of drugs targeting DR because vascular changes similar to those in DR are occurring in DC.

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.

Proposal of a simple optical coherence tomography-based scoring system for progression of age-related macular degeneration.

To develop a simple, clinically practical, optical coherence tomography (OCT)-based scoring system for early age-related macular degeneration (AMD) to prognosticate risk for progression to late AMD. We retrospectively reviewed OCT images (512×128 macular cube, Cirrus) from 138 patients diagnosed of early AMD in at least one eye and follow-up of at least 12months. For patients with early AMD in both eyes, only the right eye was chosen as the study eye for longitudinal assessment. Scans were graded on four SD-OCT criteria associated with disease progression in previous studies: drusen volume within a central 3-mm circle ≥0.03mm3, intraretinal hyperreflective foci (HRF), hyporeflective foci (hRF) within a drusenoid lesion (DL), and subretinal drusenoid deposits (SDD). Each criterion was assigned one point. For risk assessment of the study eye, the baseline status of the fellow eye was also considered, and thus these four features were also assessed in the fellow eye. The number of risk factors were summed for both eyes, yielding a total score (TS) of 0 to 8 for each patient. A fellow eye with evident choroidal neovascularization (CNV) or atrophy automatically received 4 points. Scores were then grouped into four categories to facilitate comparative analysis: I. (TS of 0, 1, 2), II. (TS of 3, 4), III. (TS of 5, 6) and IV. (TS of 7, 8). Correlation of baseline category assignment with progression to late AMD (defined as the presence of atrophy or CNV on OCT) by the last follow-up visit was evaluated with logistic regression analysis. The rate of progression to late AMD was 39.9% (55/138). Progression rates by category (I to IV) were 0, 14.3, 47.5, and 73.3%, respectively. Logistic regression analysis showed risk of progression to late AMD was 3.0 times (95% CI: 1.2-7.9) higher for an eye assigned to category IV than for an eye in category III and 16.4 (95% CI: 4.7-58.8) times higher than for an eye in category II. A simple scoring system relevant to prognosis for early AMD, and practical for use in a busy clinic, can be developed using SD-OCT criteria alone.

Structural Changes Associated with Delayed Dark Adaptation in Age-Related Macular Degeneration

To examine the relationship between dark adaptation (DA) and optical coherence tomography (OCT)-based macular morphology in age-related macular degeneration (AMD). Prospective, cross-sectional study. Patients with AMD and a comparison group (>50 years) without any vitreoretinal disease. All participants were imaged with spectral-domain OCT and color fundus photographs, and then staged for AMD (Age-related Eye Disease Study system). Both eyes were tested with the AdaptDx (MacuLogix, Middletown, PA) DA extended protocol (20 minutes). A software program was developed to map the DA testing spot (2° circle, 5° superior to the fovea) to the OCT B-scans. Two independent graders evaluated the B-scans within this testing spot, as well as the entire macula, recording the presence of several AMD-associated abnormalities. Multilevel mixed-effects models (accounting for correlated outcomes between 2 eyes) were used for analyses. The primary outcome was rod-intercept time (RIT), defined in minutes, as a continuous variable. For subjects unable to reach RIT within the 20 minutes of testing, the value of 20 was assigned. We included 137 eyes (n= 77 subjects), 72.3% (n= 99 eyes) with AMD and the remainder belonging to the comparison group. Multivariable analysis revealed that even after adjusting for age and AMD stage, the presence of any abnormalities within the DA testing spot (ß= 4.8, P < 0.001), as well as any abnormalities in the macula (ß= 2.4, P= 0.047), were significantly associated with delayed RITs and therefore impaired DA. In eyes with no structural changes within the DA testing spot (n= 76, 55.5%), the presence of any abnormalities in the remaining macula was still associated with delayed RITs (ß= 2.00, P= 0.046). Presence of subretinal drusenoid deposits and ellipsoid zone disruption were a consistent predictor of RIT, whether located within the DA testing spot (P= 0.001 for both) or anywhere in the macula (P < 0.001 for both). Within the testing spot, the presence of classic drusen or serous pigment epithelium detachment was also significantly associated with impairments in DA (P ≤ 0.018). Our results suggest a significant association between macular morphology evaluated by OCT and time to dark-adapt. Subretinal drusenoid deposits and ellipsoid zone changes seem to be strongly associated with impaired dark adaptation.

Retinal Pigment Epithelium Degeneration Associated With Subretinal Drusenoid Deposits in Age-Related Macular Degeneration

To test whether increased light transmission (hypertransmission) through subretinal drusenoid deposits (SDD) into the choroid in age-related macular degeneration (AMD) represented retinal pigment epithelium (RPE) degeneration. Cross-sectional study. Nineteen eyes of 12 patients with early- to intermediate-stage AMD and 18 eyes of 12 normal subjects were evaluated with color fundus photography, optical coherence tomography (OCT), and high-resolution adaptive optics scanning laser ophthalmoscopy (AOSLO) at baseline and 24months later. SDD were classified using an OCT-based 3-stage grading system. Hypertransmission beneath SDD into the choroid was examined in OCT. SDD microstructure was assessed with AOSLO. To characterize the hypertransmission-associated chorioretinal degeneration, choroidal thickness and photoreceptor length were measured in OCT at 1mm and 2mm superior, inferior, temporal, and nasal to the foveal center. OCT disclosed hypertransmission beneath stage 3 SDD in 8 eyes. These lesions showed a distinctive regressing structure in AOSLO, compared with stage 3 lesions without hypertransmission. The phenomenon persisted at follow-up, and new hypertransmission developed as SDD advanced. In eyes with hypertransmission, choroids were thinner than those of normal eyes at all sites (by 44%-56%, P ≤ .0028) and those of eyes with SDD but without hypertransmission at superior and temporal sites (by 31%-46%, P ≤ .039). Photoreceptors were significantly shorter than those in normal eyes (by 6%-26%, P ≤ .0379). Hypertransmission into the choroid, accompanied with SDD regression and thinning of choroid and photoreceptor layers, indicates RPE degeneration associated with advanced stages in the SDD life cycle.

Association between Decreased Renal Function and Reticular Macular Disease in Age-Related Macular Degeneration

To compare renal function in patients with age-related macular degeneration (AMD) with and without concurrent reticular macular disease (RMD). Retrospective cohort study. Patients with documented AMD with and without RMD. Via our electronic health record system, we retrospectively identified patients assigned an International Classification of Diseases, Ninth Edition, code associated with AMD between January 2012 and January 2016. Patients met inclusion criteria if they had at least 1 macular spectral-domain optical coherence tomography volume scan, 1 provider note, and 1 glomerular filtration rate (GFR) value in the electronic medical record. We evaluated images for the presence or absence of RMD; we defined RMD as the presence of at least 1 subretinal drusenoid deposit in at least 1 macular slice. Patients with RMD in at least 1 eye were deemed RMD positive. Patients with bilateral choroidal neovascularization were excluded from analysis. Observation of renal function in RMD patients. Inclusion criteria were met by 119 patients (mean age, 75 years; range, 46-101 years). To account for the significant difference in RMD prevalence at extreme ages, we limited our study population to 107 patients 50 to 90 years of age. A GFR less than 60 ml/min/1.73 m2 was found in 45.0% (27/60) of those with RMD compared with 12.8% (6/47) of those without RMD (odds ratio, 5.6; 95% confidence interval, 2.1-15). Multivariate logistic regression indicated that low GFR was a significant predictor for RMD, even after accounting for differences in age, diabetes, hypertension, hyperlipidemia, and other potential confounders. When comparing within classification subsets for RMD and GFR in patients with choroidal thickness data, significant choroidal thinning was associated with RMD (170 vs. 228 μm; P= 0.01) and GFR less than 60 ml/min/1.73 m2 (144 vs. 219μm; P= 0.0008). Our analysis showed an association between RMD and renal dysfunction. Larger cross-sectional and longitudinal studies of the association of RMD with kidney function are warranted to betterunderstand the nature and biological basis of this observed connection.

Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen

The ability to detect reticular pseudodrusen (RPD)/subretinal drusenoid deposits (SDDs) using 12×12-mm widefield en face swept-source optical coherence tomography (SS-OCT) imaging was compared with conventional multimodal imaging (color, fundus autofluorescence (FAF), and infrared reflectance [IR] imaging) in eyes with nonexudative age-related macular degeneration (AMD). Cross-sectional study. Patients with nonexudative AMD were prospectively enrolled in an SS-OCT imaging study at the Bascom Palmer Eye Institute. On the same day, all participants underwent color, FAF, and IR fundus imaging, as well as imaging with a prototype Zeiss 100 kHz SS-OCT instrument (Carl Zeiss Meditec Inc, Dublin, CA). Two masked graders assessed the presence, absence, or uncertainty of RPD/SDDs on conventional multimodal images and separately on 4 different SS-OCT en face images derived from the same volumetric dataset. The results from grading the conventional images and the SS-OCT en face images were compared. Agreement in the detection of RPD/SDDs using different imaging modalities. A total of 307 eyes (209 patients) were graded for the presence or absence of RPD/SDDs. The agreement between SS-OCT and multimodal imaging was 83%. The difference in RPD/SDD detection with either image modality was not statistically significant (P= 0.21). The sensitivity of SS-OCT in RPD/SDD detection was 83%, and when using conventional imaging, the sensitivity was 75%. When using SS-OCT imaging alone, 10% of RPD/SDD cases would be missed, and when using conventional imaging alone, 14% of RPD/SDD cases would be missed. The presence of RPD/SDD was confirmed retrospectively in 48 of 52 cases once the overall grading was unmasked and the graders reevaluated the conventional multimodal images and the widefield SS-OCT en face images. All 4 imaging modalities used together provided the best strategy for the detection of RPD/SDDs. However, when using widefield en face SS-OCT slab imaging alone, the detection of RPD/SDDs was at least as good as conventional imaging.

The association of geographic atrophy and decreased renal function in patients with age-related macular degeneration.

PurposeThe purpose of the study was to investigate the association between area and presence of geographic atrophy (GA) and renal function, as measured by glomerular filtration rate (GFR).Patients and methodsWe retrospectively identified patients aged 50-90 years who were assigned an ICD-9 diagnosis code for age-related macular generation (AMD) between January 2012 and January 2016. Patients met inclusion criteria if they had at least one macular spectral domain optical coherence tomography volume scan, one provider note, and one GFR value in the electronic medical record. Images were evaluated for the presence of GA, area of GA, drusen, and subretinal drusenoid deposits (SDD) and for subfoveal choroidal thickness (CTh) by standard criteria. Imaging findings were correlated with the most recent GFR from the patient's chart.ResultsWe identified 107 patients who met our inclusion criteria (mean age=74 years, range 50-90 years). Overall, we found a significant correlation between the presence of GA and reduced GFR (P=0.002), which was maintained even after accounting for age and other confounders. No association between GFR and GA area was found. CTh was significantly lower in patients with GA (P=0.038) and those with decreased GFR (P=0.004). Within the SDD-positive population, GA was associated with reduced GFR (P=0.007) but only trended toward significance after controlling for age.ConclusionOur study findings demonstrate an association between impaired renal function and the presence, but not area, of GA within an AMD population. These findings may shed light on common pathogenic mechanisms for these two diseases.

Characterization, structural analysis, evolution of AMD drusenoid deposits ‘L’, Lipid type and ‘P’, Protein‐cellular type, with multimodal imaging and morphology‐structural software

PurposeTo study AMD drusenoid deposits ‘L'and ‘P’ with multimodal imaging and morphology‐structural software, see the input of this technique, software on their knowledge, etiopathogenyMethods284 eyes of 142 patients, 44 men, 98 women, with AMD drusenoid deposits ‘L’, Lipid Type (soft Drusen, Drusenoid PED ‘L’) and ‘P’, Protein‐cellular type (Pseudovitellifom AMD, Cuticular drusen, Subretinal drusenoid deposits (SDD),Drusenoid PED, ‘P’).Deposits were evaluated by Autofluorescence, IR imaging, OCT, OCT en Face (Spectralis HRA‐OCT),Morphology‐Structural software (M‐S software); Size, characteristics, number, topography of ‘L’, ‘P’ deposits, their environment above and below too;ETDRS visual acuity (VA),complete ophthalmic examination, Fundus exam added. M‐S software let analyze drusenoid deposit volume and contours, 3D deposit reconstruction, let volume, density (deposits grey levels),structure (structural measures, texture parameters),composition (density calculation) evaluation and characterization of ‘L’ and ‘P’ type depositsResultsAMD Drusenoid Deposits: ‘L’ are roughly uniform, dome‐shaped, dark grey, translucent, equal and the same in all cross‐section, fatty, under the Retinal Pigment epithelium (RPE),abnormal RPE above, but layer quite preserved, evolution to atrophy; ‘P’ are dense, white, heterogeneous PED, below RPE, granular, as Protein, cellular component, different in all cross‐sections, abnormal RPE above, heavily unstructured, layer interrupted, cells disappeared, evolution to neovascularization. M‐S software allows selective drusenoid deposits characterization, differentiation: ‘L’ type, lipid components, ‘P’ type, protein composition, so entities determination, so get morphologic, structural BiomarkersConclusionsMultimodal Imaging, Morphology‐Structural Software contribute to and improve AMD Drusenoid deposits ‘L’, ‘P’, knowledge, identity, so, let define AMD biomarkers and better understand etiopathogeny.

Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification in Photoreceptor Cells

The process of vision is impossible without the photoreceptor cells, which have a unique structure and specific maintenance of cholesterol. Herein we report on the previously unrecognized cholesterol-related pathway in the retina discovered during follow-up characterizations of Cyp27a1(-/-)Cyp46a1(-/-) mice. These animals have retinal hypercholesterolemia and convert excess retinal cholesterol into cholesterol esters, normally present in the retina in very small amounts. We established that in the Cyp27a1(-/-)Cyp46a1(-/-) retina, cholesterol esters are generated by and accumulate in the photoreceptor outer segments (OS), which is the retinal layer with the lowest cholesterol content. Mouse OS were also found to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol esters were discovered to be abundant in human OS. We suggest a mechanism for cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in humans may underlie the development of subretinal drusenoid deposits, a hallmark of age-related macular degeneration, which is a common blinding disease. We generated Cyp27a1(-/-)Cyp46a1(-/-)Acat1(-/-) mice, characterized their retina by different imaging modalities, and confirmed that unesterified cholesterol does accumulate in their OS and that there is photoreceptor apoptosis and OS degeneration in this line. Our results provide insights into the retinal response to local hypercholesterolemia and the retinal significance of cholesterol esterification, which could be cell-specific and both beneficial and detrimental for retinal structure and function.

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes.

Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.

Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration

ABSTRACTPurpose: Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45–80 years, documented either with or without CAD, to determine if CAD is associated with RMD.Design: A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution.Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years).Methods: Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen.Main Outcome Measures: Presence or absence of RMD/SDD and soft drusen.Results: RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08–3.95, P = 0.03). There was no association of CAD with soft drusen.Conclusions: A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

The Relationship Between Reticular Macular Disease and Choroidal Thickness

ABSTRACTPurpose: Subretinal drusenoid deposits (SDD) are the main structural lesion of reticular macular disease (RMD), a phenotype of age-related macular degeneration (AMD). We aim to demonstrate spatiotemporal relationships between SDD and choroidal thickness (CTh) alterations in RMD+ and RMD– eyes.Methods: Thirty-three eyes (26 subjects) with early AMD/no SDD (RMD–) and 18 eyes (16 subjects) with early AMD/SDD (RMD+) underwent enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) for CTh measurements at 11 points per scan, in 5 horizontal B scans, creating a grid of 55 points/eye. The 55 points were treated as a cluster, controlling within-subject correlation. Marginal generalized estimating equation modeling was used to estimate the association between CTh and RMD status. All eyes were divided by their median age (≤82 and >82 years) for stratified analyses.Results: CTh was not significantly reduced in RMD+ eyes compared with RMD– eyes (mean difference [MD] −16.84 μm, P = 0.24). Among younger subjects, mean CTh was significantly reduced in RMD+ versus RMD– eyes (MD −53.72 μm, P = 0.01). Conversely, among older subjects, there was no significant difference in CTh between RMD+ and RMD–.Conclusions: In RMD, the association of SDD and CTh alterations varies with age but not by macular region. Among younger subjects (<82 years old), CTh was significantly thinner in RMD+ versus RMD– eyes.

Relating Retinal Morphology and Function in Aging and Early to Intermediate Age-related Macular Degeneration Subjects

To evaluate relationships between age-related macular degeneration (AMD) morphology on spectral-domain optical coherence tomography (SDOCT) and visual function. Cross-sectional, observational. From the Alabama Study on Early AMD baseline visit, visual acuity, cone-mediated sensitivity, rod-mediated dark adaptation, and SDOCT were obtained in 1 eye per subject with no apparent retinal aging (n= 15), normal aging (n= 15), early AMD (n= 15), and intermediate AMD (n= 46). The volumes of retinal pigment epithelium (RPE)-drusen complex, RPE-drusen complex abnormal thinning, RPE-drusen complex abnormal thickening, and inner and outer retina were calculated in specified regions using semi-automated SDOCT segmentation. Better cone-mediated sensitivity was associated with greater RPE-drusen complex volume (r=0.34, P < .001) and less RPE-drusen complex abnormal thinning volume (r=-0.31, P= .003). Longer rod-mediated dark adaptation time, the duration for rod-mediated sensitivity to recover from photo-bleach exposure, correlated with lower RPE-drusen complex volume (r=-0.34, P= .005) and greater RPE-drusen complex abnormal thinning volume (r= 0.280, P= .023). In 19 eyes with subretinal drusenoid deposits (SDD) vs 47 eyes without SDD, rod-mediated dark adaptation time was longer (mean ± SD 13.5 ± 7.0 vs 10.2 ± 3.1minutes, P= .004), RPE-drusen complex abnormal thinning volume was greater (P < .0001), and visual acuity and cone sensitivity did not differ. Decreased function relates to structural markers on SDOCT in AMD. Because the RPE-drusen complex includes the interdigitation of outer segments and RPE apical processes and SDD in eyes with AMD, slower dark adaptation might be related to structural abnormalities of the RPE, the RPE-photoreceptor interface, or both.

The Association Between Subretinal Drusenoid Deposits in Older Adults in Normal Macular Health and Incident Age-Related Macular Degeneration.

PurposeSubretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later.MethodsSubjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age-related macular degeneration was defined as eyes having an AREDS grade ≥2 at the 3-year follow-up.ResultsTwenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36–3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted.ConclusionsResults suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD.

Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age-Related Macular Degeneration, by Multimodal Imaging

To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. Cross-sectional study. A total of 651 subjects aged ≥60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on ≥1 en face modality plus SD OCT or on ≥2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. Prevalence of SDD in participants with and without AMD. Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P= 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance.

Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment

ImportanceAge-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. ObjectiveWe were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD. DesignPilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80mg of atorvastatin daily and were monitored at baseline and every 3months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women). ResultsTwenty-three subjects completed a minimum follow-up of 12months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+3.3 letters, p=0.06) in 10 patients. No subjects progressed to advanced neovascular AMD. ConclusionsHigh-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

Targeting Tissue Lipids in Age-related Macular Degeneration

Targeting Tissue Lipids in Age-related Macular Degeneration