Reticular Pseudodrusen Research Articles

Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group

To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. Participants from prospective studies. The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas pigment changes and features of advanced AMD are less frequent. Age-related macular degeneration may be more than a "macular" condition but one that involves the entire retina. Future longitudinal studies of peripheral changes in AMD and their impact on visual function may contribute to understanding AMD pathogenesis.

Choroid morphometric analysis in non-neovascular age-related macular degeneration by means of optical coherence tomography angiography

AimsTo describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography...

The Role of New Imaging Methods in Managing Age-Related Macular Degeneration.

The use of imaging for age-related macular degeneration (AMD) depends on how it benefits clinical management and on reimbursement. The latter should relate to the former. This review assesses how different forms of AMD can be imaged and what information this provides. For nonneovascular AMD high-resolution optical coherence tomography (OCT), autofluorescence, and near infrared imaging can identify the type of drusen, such as reticular pseudodrusen, which influences prognosis, and the amount of atrophy, for which phase 3 trials are underway. Clarifying the correct diagnosis for late-onset Stargardt and macular telangiectasia, if treatment becomes available, will be especially important. Choroidal thickness can be measured and changes with anti‒vascular endothelial growth factor treatment, but how this influences management is less clear. The finding of a thick choroid may alter the diagnosis to pachychoroid neovasculopathy, which may have a different treatment response. Peripheral retinal changes are commonly found on ultrawide-field imaging but their importance is not yet determined. The mainstay of imaging is OCT, which can detect neovascular AMD by detecting thickening and be used for follow-up, as the presence or absence of thickening is the main determinant of treatment. Higher resolution systems and now OCT angiography are able to distinguish neovascular type, especially type 2 choroidal neovascularization but also polypoidal choroidal vasculopathy and retinal angiomatous proliferation. Fundus fluorescein and indocyanine green angiographies still have a role, although that partly depends on whether photodynamic therapy is being considered. Automated image analysis and machine learning will be increasingly important in supporting clinician decisions.

RETICULAR PSEUDODRUSEN ARE NOT A PREDICTIVE FACTOR FOR THE 1-YEAR RESPONSE TO INTRAVITREAL RANIBIZUMAB IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To investigate reticular pseudodrusen (RPD) as a potential baseline factor predictive of a poor 1-year response to intravitreal ranibizumab in eyes with neovascular age-related macular degeneration. Retrospective, monocentric case series including 98 consecutive naive neovascular age-related macular degeneration patients. Presence of RPD was assessed by two graders based on color, blue-light, fundus autofluorescence pictures, and spectral-domain optical coherence tomography. A correlation between the presence of RPD and the visual change was investigated. Other baseline characteristics studied in a monovariate and multivariate analysis were the following: age, gender, affected side, loading dose, type of neovascularization, presence of retinal pigment epithelial detachment >250 μm, subretinal or intraretinal fluid, blood over >50% of the lesion, and subfoveal choroidal thickness. The presence of RPD was not associated with a visual change (P = 0.96), but with a thin subfoveal choroidal thickness at baseline (P < 0.0001). The monovariate analysis showed that the presence of blood at baseline was associated with visual gain (P = 0.007). The presence of RPD at baseline was not identified as a factor associated with a poor 1-year response to ranibizumab in eyes with neovascular age-related macular degeneration. Studies with a longer follow-up may be needed to assess the impact of RPD on the visual prognosis of eyes with neovascular age-related macular degeneration.

Ocular Perfusion Pressure and Choroidal Thickness in Early Age-Related Macular Degeneration Patients With Reticular Pseudodrusen.

The purpose of this study was to investigate the relationship between the ocular perfusion pressure (OPP) and subfoveal choroidal thickness (CT) in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen (RPD). We evaluated the clinical history, blood pressure parameters, fundus photography, and optical coherence tomography images of consecutive patients with early AMD. We calculated the mean OPP from blood pressure and intraocular pressure. We included 103 eyes from 103 patients, classifying 45 as the RPD group and 58 as the non-RPD group. The mean OPP of the RPD group (46.1 ± 6.5 mm Hg) did not differ from that of the non-RPD group (45.1 ± 5.1 mm Hg, P = 0.325), but the RPD group showed a thinner mean subfoveal CT (158.3 ± 73.0 μm) than the non-RPD group (220.9 ± 67.0 μm, P < 0.001). Among 64 patients who underwent follow-up examination, the rate of change in subfoveal CT in the RPD group (-4.74 ± 0.86 μm/y) was greater than that in the non-RPD group (-2.46 ± 0.75 μm/y, P = 0.028). In the RPD group, a history of systemic hypertension and lower baseline OPP were associated with a higher rate of change in subfoveal CT (P = 0.019 and P = 0.010, respectively). Subfoveal CT was thinner in early AMD patients with RPD than in those without RPD. Lower baseline mean OPP and a history of systemic hypertension could be risk factors associated with the progression of choroidal thinning in early AMD patients with RPD.

RETINAL ANGIOMATOUS PROLIFERATION DIAGNOSIS: A Multiimaging Approach.

To identify signs occurring more frequently in retinal angiomatous proliferation (RAP) lesions compared with other types of choroidal neovascularization (CNV) in age-related macular degeneration. In this cross-sectional retrospective study, 30 patients were evaluated. These signs were correlated with the type of CNV: shunting of blood flow to the lesion by fluorescein angiography, late leakage by indocyanine green angiography, intraretinal cysts and retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment with a hyperreflective oval area by spectral domain optical coherence tomography, and presence of reticular pseudodrusen by infrared light. Shunting of blood flow was found in 56% of RAP, whereas it was absent in 100% of other CNVs. Late leakage in indocyanine green angiography occurred in all RAP cases, while it was found in 7% of other CNVs. Intraretinal cysts were detected in 100% of RAP cases and in 14% of other CNVs. Retinal pigmented epithelium interruption along the retinal pigmented epithelium detachment was evident in 93% of RAP cases and in 15% of other CNVs. Reticular pseudodrusen were present in 87% of RAP cases and in 21% of other CNVs. All the signs investigated were strongly associated to RAP lesions. A multimodal imaging approach may help differentiating subtypes of neovascularization.

Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging.

PurposeTo analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD.MethodsEyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study–like target centered on the fovea.ResultsTwenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 μm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD.ConclusionsOur fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD.

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.

Choriocapillaris Nonperfusion is Associated With Poor Visual Acuity in Eyes With Reticular Pseudodrusen

To study choriocapillaris blood flow in age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA) and study its correlation to visual acuity (VA) in eyes with reticular pseudodrusen (RPD) vs those with drusen without RPD (drusen). Cross-sectional study. Patients with either drusen or RPD in early AMD underwent OCTA imaging of the superior, inferior, and/or nasal macula. We quantified "percent choriocapillaris area of nonperfusion" (PCAN) in eyes with RPD vs those with drusen. We assessed the repeatability of PCAN and its correlations with VA. Twenty-nine eyes of 26 patients with RPD and 21 eyes of 16 age-matched AMD patients with drusen were included. Qualitatively, the choriocapillaris in areas with RPD showed focal dark regions without flow signal on OCTA (nonperfusion). The repeatability coefficient of PCAN was 0.49%. Eyes with RPD had significantly greater PCAN compared with eyes with drusen (7.31% and 3.88%, respectively; P < .001). We found a significant correlation between PCAN and VA for the entire dataset (r= 0.394, P= .005). When considering eyes with RPD separately, this correlation was stronger (r= 0.474, P= .009) but lost significance when considering eyes with drusen separately (r= 0.175, P= .45). Eyes with RPD have significantly larger areas of choriocapillaris nonperfusion compared with eyes with drusen and no RPD. The correlation between PCAN and VA in this RPD population provides a potential mechanistic explanation for vision compromise in RPD compared with other forms of drusen in AMD.

Epidemiology of Reticular Pseudodrusen in Age-Related Macular Degeneration: The Rotterdam Study.

Reticular pseudodrusen (RPD) are considered to be a distinct feature in AMD. Population studies have studied the epidemiology of RPD using standard color fundus photographs (CFP). However, recent studies have shown that RPD are better imaged using near-infrared (NIR) imaging. We studied the epidemiology of RPD in a large population-based study using NIR and CFP. Participants aged 65+ years from the Rotterdam Study underwent ophthalmologic examination including NIR and CFP. Both images were graded for the presence of RPD and soft indistinct drusen (SID). Associations with demographic and environmental factors, 26 genetic variants, and total genetic risk score were analyzed using logistic regression analysis. Reticular pseudodrusen were detected in 137 (4.9%) of 2774 study participants; of these, 92.7% were detected with NIR imaging and 38% on CFP. Most eyes with RPD showed presence of SID, whereas other drusen types coincided less frequently. Reticular pseudodrusen were significantly associated with age (odds ratio [OR] 1.21, 95% Confidence Interval [CI] 1.17-1.24) and female sex (OR 2.10, 95% CI 1.41-3.13). Environmental factors did not show a significant association with RPD. Major AMD risk variants were significantly associated with RPD and SID; however, ARMS2, C3, and VEGFA were more associated with RPD (RPD vs. SID P < 0.05). Total genetic risk score did not differ significantly (P = 0.88). Detection of RPD was better with NIR imaging than on CFP in a population-based setting. Presence of RPD often coincided with presence of SID; however, they showed quantitative differences in genetic risk profile.

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

Pilot evaluation of short-term changes in macular pigment and retinal sensitivity in different phenotypes of early age-related macular degeneration after carotenoid supplementation

PurposeTo investigate the response of carotenoid supplementation in different phenotypes of early age-related macular degeneration (AMD) by measuring macular pigment optical density (MPOD) and retinal sensitivity.MethodsConsecutive patients with only medium/large...

Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration.

To identify the prevalence and progression of macular atrophy (MA) in neovascular age-related macular degeneration (AMD) patients under long-term anti-vascular endothelial growth factor (VEGF) therapy and to determine risk factors. This retrospective study included patients with neovascular AMD and ≥30 anti-VEGF injections. Macular atrophy (MA) was measured using near infrared and spectral-domain optical coherence tomography (SD-OCT). Yearly growth rate was estimated using square-root transformation to adjust for baseline area and allow for linearization of growth rate. Multiple regression with Akaike information criterion (AIC) as model selection criterion was used to estimate the influence of various parameters on MA area. Forty-nine eyes (47 patients, mean age 77±14) were included with a mean of 48±13 intravitreal anti-VEGF injections (ranibizumab:37±11, aflibercept:11±6, mean number of injections/year 8±2.1) over a mean treatment period of 6.2±1.3years (range 4-8.5). Mean best-corrected visual acuity improved from 57±17 letters at baseline (= treatment start) to 60±16 letters at last follow-up. The MA prevalence within and outside the choroidal neovascularization (CNV) border at initial measurement was 45% and increased to 74%. Mean MA area increased from 1.8±2.7mm2 within and 0.5±0.98mm2 outside the CNV boundary to 2.7±3.4mm2 and 1.7±1.8mm2 , respectively. Multivariate regression determined posterior vitreous detachment (PVD) and presence/development of intraretinal cysts (IRCs) as significant factors for total MA size (R2 = 0.16, p=0.02). Macular atrophy (MA) area outside the CNV border was best explained by the presence of reticular pseudodrusen (RPD) and IRC (R2 = 0.24, p=0.02). A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the MA size.

Quantitative Fundus Autofluorescence in Early and Intermediate Age-Related Macular Degeneration

Increased lipofuscin accumulation is assumed to be an important factor in the pathogenesis of age-related macular degeneration (AMD), although direct evidence for this hypothesis is missing. To quantitatively investigate lipofuscin-associated fundus autofluorescence (AF) in patients with early and intermediate AMD. A prospective, single-center, case-control study was conducted from August 1, 2014, to October 31, 2015, at a university referral center. Participants included 40 patients aged 65 years or younger and 108 individuals without eye disease serving as controls. All participants underwent quantitative fundus AF (qAF) imaging with a modified scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF values of an 8-segment circular ring centered on the fovea (qAF8) were measured and compared between patients and controls. For subgroup analysis, drusen were categorized as soft drusen, cuticular drusen, and/or reticular pseudodrusen (RPD). The qAF8 levels. In the 40 patients with AMD, mean (SD) age was 54.8 (5.6) years, and 32 (80%) were women. None of the investigated patients had qAF8 values above the 95% prediction interval (PI) of the 108 controls. In the soft drusen (28 [70%]) and cuticular drusen (8 [20%]) groups, qAF8 levels within the 95% PI were noted in 22 patients (79%; 95% CI, 60% to 90%) and 7 patients (88%; 95% CI, 51% to 99%) respectively. The qAF8 values in the RPD group (4 [10%]) were below the 95% PI in 3 patients (75%; 95% CI, 29% to 97%). Compared with the controls, statistical analysis revealed lower qAF8 values in the overall AMD cohort after adjusting for age (difference, -19.9% [95% CI, -25.6% to -12.7%], P < .001) as well as in all subgroups (soft drusen, -17.1% [95% CI, -24.1% to -9.5%], P < .001; cuticular drusen, -19.6% [95% CI, -30.3% to -7.2%], P = .003; and RPD, -34.5% [95% CI, -47.1% to -21.3%]; P < .001). The qAF8 measurements in this sample showed no increased lipofuscin-related fundus AF in patients with early and intermediate AMD. Lower qAF levels in certain subgroups may point to subnormal lipofuscin levels in the retinal pigment epithelium or, alternatively, limitations to detection of true retinal pigment epithelial lipofuscin content. The results of this study might expand the understanding of the pathogenesis of AMD and may have an effect on upcoming treatment trials that aim to modify lipofuscin accumulation.

Multimodal Imaging of Reticular Pseudodrusen in a Population-Based Setting: The Alienor Study.

To document reticular pseudodrusen (RPD) using multimodal imaging in French elderly subjects. A total of 494 subjects (970 eyes) aged 77 years or more, from the Alienor study, were examined in 2011 and 2012. Reticular pseudodrusen were defined as definite if they were present with at least two imaging methods among color retinal photographs, macular cube (20° × 15°) of spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR). The Youden index was calculated as specificity + sensitivity - 1. The prevalence of definite RPD was 13.4% and was higher among women (15.6%) than men (10.2%). It increased with age and reached almost 50% in subjects over 85 years. Infrared reflectance was the most sensitive technique (100%) and color fundus photography the least sensitive (34.5% at left eyes and 48.1% at right eyes). The best Youden index was obtained with IR (0.96 at both eyes) followed by SD-OCT (0.87 at right eye and 0.78 at left eye). Reticular pseudodrusen were present in 4.6% of eyes without AMD, 13.0% with early AMD1, 62.6% with early AMD2, 34.6% with atrophic AMD, and 8.1% with neovascular AMD. Reticular pseudodrusen were significantly associated with central and pericentral intermediate soft drusen (odds ratio [OR]: 2.14; 95% confidence interval [CI] = 1.11-4.14 and OR: 1.49; 95% CI = 1.16-1.90, respectively) and central large soft drusen (OR: 1.67; 95% CI = 1.16-2.42). Using multimodal imaging, the prevalence of RPD appears higher than previously reported in studies based on retinal photography only. Reticular pseudodrusen frequently accompany other signs of AMD. Infrared reflectance and SD-OCT appear to be particularly relevant methods to diagnose RPD.

Frequency, Phenotypic Characteristics and Progression of Atrophy Associated With a Diseased Bruch's Membrane in Pseudoxanthoma Elasticum.

To characterize atrophy of the outer retina and the retinal pigment epithelium in patients with pseudoxanthoma elasticum (PXE). In this retrospective cross-sectional study, the frequency and phenotypic characteristics of manifest atrophy were investigated in 276 eyes of 139 patients using color fundus photography, fundus autofluorescence (AF) imaging, and spectral domain optical coherence tomography. Progression rates of atrophy were quantified in eyes with longitudinal AF recordings. Atrophy was present in 90 eyes (32%; mean age, 60; range, 32-88 years). In 19 eyes (7%; mean age, 56; range, 37-77 years) atrophy occurred without any signs for an active or fibrotic choroidal neovascularization (CNV). The frequency of both, atrophy and CNV, increased with age. In those > 60 years of age, atrophy and/or CNV were almost universally present but varied considerably in severity. Eyes with emerging pure atrophy (n = 13, no signs of CNV) showed pattern dystrophy-like changes (100%), reticular pseudodrusen (82%), and reduced choroidal thickness. Advanced atrophy was multifocal, reached beyond the arcades, and was present nasal to the optic disc. The average expansion rate of atrophy was 3.3 ± 1.3 and 1.6 ± 1.1 mm2/year (mean ± SD), in those without or with signs for CNV, respectively. Atrophy of the outer retina and the retinal pigment epithelium is a common finding in PXE patients characterized by early onset and fast progression with subsequent visual loss independent from CNV. This suggests that atrophy is the natural endpoint of Bruch's membrane disease. Phenotypic similarities with multifactorial geographic atrophy in age-related macular degeneration suggest common pathogenic pathways at the level of Bruch's membrane.

Fully Automated Prediction of Geographic Atrophy Growth Using Quantitative Spectral-Domain Optical Coherence Tomography Biomarkers

To develop a predictive model based on quantitative characteristics of geographic atrophy (GA) to estimate future potential regions of GA growth. Progression study and predictive model. One hundred eighteen spectral-domain (SD) optical coherence tomography (OCT) scans of 38 eyes in 29 patients. Imaging features of GA quantifying its extent and location, as well as characteristics at each topographic location related to individual retinal layer thickness and reflectivity, the presence of pathologic features (like reticular pseudodrusen or loss of photoreceptors), and other known risk factors of GA growth, were extracted automatically from 118 SD OCT scans of 38 eyes from 29 patients collected over a median follow-up of 2.25 years. We developed and evaluated a model to predict the magnitude and location of GA growth at given future times using the quantitative features as predictors in 3 possible scenarios. Potential regions of GA growth. In descending order of out-of-bag feature importance, the most predictive SD OCT biomarkers for predicting the future regions of GA growth were thickness loss of bands 11 through 14 (5.66), reflectivity of bands 11 and 12 (5.37), thickness of reticular pseudodrusen (5.01), thickness of bands 5 through 11 (4.82), reflectivity of bands 7 through 11 (4.78), GA projection image (4.73), increased minimum retinal intensity map (4.59), and GA eccentricity (4.49). The predicted GA regions in the 3 tested scenarios resulted in a Dice index mean ± standard deviation of 0.81±0.12, 0.84±0.10, and 0.87±0.06, respectively, when compared with the observed ground truth. Considering only the regions without evidence of GA at baseline, predicted regions of future GA growth showed relatively high Dice indices of 0.72±0.18, 0.74±0.17, and 0.72±0.22, respectively. Predictions and actual values of GA growth rate and future GA involvement in the central fovea showed high correlations. Experimental results demonstrated the potential of our predictive model to predict future regions where GA is likely to grow and to identify the most discriminant early indicator (thickness loss of bands 11 through 14) of regions susceptible to GA growth.

Factors Predictive of Visual Outcome 1 Year After Intravitreal Aflibercept Injection for Typical Neovascular Age-Related Macular Degeneration.

Several factors have been reported to be associated with visual outcomes after intravitreal ranibizumab treatment for neovascular age-related macular degeneration (AMD). In the present study, we investigated the factors associated with visual outcomes after intravitreal aflibercept injection (IAI) for typical neovascular AMD. We retrospectively studied the visual changes in 47 eyes of 51 patients with typical neovascular AMD, who had been initially treated with 3 monthly IAI followed by as-needed IAI. Mean best-corrected visual acuity (BCVA) improved during the 12-month follow-up period in 40 eyes of 37 patients without reticular pseudodrusen (RPD) in both eyes, whereas it deteriorated in 11 eyes of 10 patients with RPD in either eye. Multiple regression analysis revealed that visual gain at 12 months after the first IAI positively correlated with worse baseline BCVA and thicker baseline subfoveal choroidal thickness (P = 0.018, P = 0.004, respectively), but not with absence of RPD (P = 0.13). Subfoveal choroidal thickness was significantly thinner in eyes with RPD compared with that in eyes without RPD (P = 0.003). Visual gain after IAI in eyes with typical neovascular AMD appears to be limited in patients with RPD, which may reflect the poor visual outcome after IAI in eyes with a thinner subfoveal choroid that is seen predominately in patients with RPD.

Exploring choriocapillaris under reticular pseudodrusen using OCT-Angiography.

To evaluate if choriocapillaris (CC) vessel density and CC decorrelation signal index are compromised in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCT-A). Decorrelation values in OCT-A CC images of 20 RPD patients were measured in the outer superior and the outer inferior sector of the EDTRS grid and compared to age-matched healthy controls. CC vessel density and CC decorrelation signal index were measured within a 30 μm and a 10 μm OCT-A CC slab. CC data were correlated to number of RPD lesions, predominantly present RPD stage, predominantly present RPD type, retinal area affected by RPD and choroidal thickness (CT). CC vessel density and CC decorrelation signal index decreased in correlation to advancing age in healthy subjects particularly in subjects older than 60 years (CC vessel density: 30 μm: p=0.0019; 10 μm: p=0.0014; CC decorrelation signal index: 30 μm: p=0.0005; 10 μm: p=0.0003). In the RPD group, CC vessel density (outer superior sector, 10 μm: 98.299) and CC decorrelation signal index (89.07) were significantly reduced compared to controls (99.203, p=0.0002; 98.09, p=0.0010). The number of RPD lesions was correlated to a reduced CC vessel density (30 μm: p=0.0355) but not to changes in CC decorrelation signal index. No correlations were found between CC parameters and either RPD stage, RPD type, size of RPD affected area or CT. OCT-A reveals a distinct reduction in CC vessel density and CC decorrelation signal index in eyes affected by RPD, which emphasizes the relevance of the CC layer in RPD pathogenesis.

Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images.

To compare luminal and stromal area of the choroid in eyes with drusen and reticular pseudodrusen (RPD) and to investigate their changes over 24 months. In eyes with drusen and RPD and control subjects, total choroidal, luminal and stromal area were measured on optical coherence tomography B-scans converted to binary images, at baseline and after 24 months. Eighteen eyes of 18 subjects for each group were included. In drusen and RPD, we found reduction of mean total choroidal (p=0.0005 and p<0.0001, respectively), luminal (p=0.003 and p<0.0001, respectively) and stromal area (p=0.007 and p=0.0002, respectively) from baseline to month 24; no change of ratio between luminal-stromal and the choroidal area was recorded. Mean luminal, stromal and total choroidal areas were reduced in RPD, as compared with drusen and controls at both baseline and month 24 (p<0.05 for all). In RPD, the stromal area was more represented, as we found lower mean ratio of luminal and total choroidal area compared with drusen and control at both baseline and month 24 (p<0.05 for all). Mean total choroidal, luminal and stromal area decreased over 24 months similarly in eyes with drusen and RPD. Mean total choroidal, luminal and stromal area were more reduced in eyes with RPD, as compared with eyes with drusen and controls; however, stromal area was more represented in eyes with RPD suggesting a possible role of choroidal vascular depletion and fibrotic replacement in the pathogenesis and disease progression.