Drusenoid Pigment Epithelial Detachment Research Articles

Clinical characteristics of cuticular drusen in the Japanese population.

To investigate the clinical characteristics of eyes with cuticular drusen in Japanese individuals, while paying special attention to large colloid drusen (LCD). Retrospective case series. Eyes with cuticular drusen, from patients of 4 medical institutes in Japan, were investigated. Multimodal imaging findings were used to diagnose cuticular drusen. LCD was defined as cuticular drusen > 200µm. Twenty-four eyes from 12 patients (8 women, 4 men) were diagnosed with cuticular drusen. The mean age of all patients (n = 12) was 60.8years. The mean age of patients without additional macular pathology (n = 5) was 55.4years. Of the 7 patients with additional macular pathology, 6 (85.7%) exhibited age-related macular degeneration-associated macular pathology, including drusenoid pigment epithelial detachment (PED) (8 eyes from 4 patients), geographic atrophy (2 eyes from 1 patient), and occult choroidal neovascularization (1 eye). LCD were found in 6 eyes of 3 patients (25%), those with LCD were on average 53.7 ± 8.7years old and those without 69.9 ± 14.1years of age (P = 0.064, Mann-Whitney U test). Cuticular drusen were predominantly seen in females, and drusenoid PED was most frequently seen in eyes with additional macular pathology. LCD were seen in 25% of eyes with cuticular drusen.

COMBINING EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY WITH STRUCTURAL OPTICAL COHERENCE TOMOGRAPHY AND BLOOD FLOW ANALYSIS FOR DETECTING CHOROIDAL NEOVASCULAR COMPLEXES IN PIGMENT EPITHELIAL DETACHMENTS

This work aimed to describe the morphology of pigment epithelial detachment (PED) using optical coherence tomography angiography and to investigate its potential to detect choroidal neovascularization in various types of PEDs. In this retrospective study, 53 patients diagnosed with PED after undergoing both optical coherence tomography angiography (AngioPlex, CIRRUS HD-OCT) and spectral domain optical coherence tomography (Spectralis SD-OCT) were included. Among the 53 eyes, flat vascularized PED (vPED) affected 21 eyes (40%), peaked vPED affected 10 eyes (19%), serous PED affected 12 eyes (23%), drusenoid PED affected 6 eyes (11%), and 4 eyes (7%) had multiple PED subtypes. The main underlying etiologies were pachychoroid spectrum disorder (30.2%), wet age-related macular degeneration (28.3%), central serous chorioretinopathy (18.9%), dry age-related macular degeneration (11.3%), and polypoidal choroidal vasculopathy (11.3%). Optical coherence tomography angiography identified neovascularization in 29 (94%) of the vPED eyes, 2 (17%) of the serous PED eyes, and all 4 (100%) mixed PED eyes. Optical coherence tomography angiography successfully identified neovascularization in both vPEDs and PEDs previously considered to be nonneovascular. However, structural OCT and blood flow analysis should be combined to interpret PED-associated neovascularization accurately in the clinic.

Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) in Eyes With Pigment Epithelial Detachments Due to Age-Related Macular Degeneration.

PurposeTo investigate fluorescence lifetime imaging ophthalmoscopy (FLIO) in neovascular AMD and pigment epithelial detachments (PEDs).MethodsA total of 46 eyes with PEDs (>350 μm) as well as age-matched healthy controls were included in this study. We found 28 eyes showed neovascular AMD (nvAMD), and 17 had nonneovascular (dry) AMD (dAMD). The Heidelberg Engineering FLIO excited fluorescence at 473 nm. Fluorescence decays were detected in two spectral channels (498–560 nm; 560–720 nm) to determine fluorescence lifetimes of endogenous fluorophores in their specific spectral emission ranges. Mean fluorescence lifetimes (τm) were investigated. Multimodal imaging was reviewed by two ophthalmologists who circumscribed and classified PEDs as either serous (n = 4), hemorrhagic (n = 4), fibrovascular (n = 16), drusenoid (n = 17), or mixed (n = 5). Blood samples from a healthy subject and a patient with PED were investigated in a quartz cuvette.ResultsEyes with nvAMD show similar FLIO patterns to dAMD: ring-shaped prolongations of τm 3 to 6 mm from the fovea. Different PED-forms show characteristic τm, while serous and hemorrhagic PEDs exhibit shortened τm, drusenoid PEDs show prolonged τm, and τm in fibrovascular PEDs is variable. Areas corresponding to sub-/intraretinal fluid display shortened τm. Ex vivo studies of blood also show short τm.ConclusionsThe previously described dAMD-related FLIO pattern is also present in nvAMD. Short τm in serous, fibrovascular, and hemorrhagic PEDs as well as sub/intraretinal fluid may disrupt this pattern. FLIO appears to differentiate between PEDs, hemorrhage, and fluid. Additionally, ex vivo studies of human blood help to better interpret FLIO images.

Pseudoflow with OCT Angiography in Eyes with Hard Exudates and Macular Drusen.

PurposeTo analyze “pseudoflow,” a false positive flow-artifact observed with optical coherence tomography angiography (OCTA) of stationary hyperreflective structures corresponding to hard exudates and macular drusen.MethodsRetrospective case series of patients with hard exudates (due to diabetic macular edema [DME] or retinal vein occlusion [RVO]) or macular drusen (due to nonneovascular, or dry, age-related macular degeneration [AMD]) studied with OCTA by using volume-based projection artifact removal (3D PAR).ResultsOCTA of 20 eyes (10 DME/10 RVO) with hard exudates were analyzed. All eyes exhibited pseudoflow corresponding to hard exudates. Seven eyes concurrently demonstrated hard exudates without pseudoflow that were noted in areas lacking vascular flow in the overlying retina. Eight eyes exhibited suspended scattering particles in motion. In 26 of 30 eyes with nonneovascular AMD, pseudoflow associated with macular drusen of any type was noted. Two of 11 eyes with small drusen, 16 of 17 eyes with medium or large drusen, 5 of 5 eyes with drusenoid pigment epithelial detachment, 12 of 16 eyes with ribbon-like subretinal drusenoid deposits, and 13 of 17 eyes with dot-like SDD exhibited pseudoflow.ConclusionsPseudoflow due to projection artifact is common in eyes with hard exudates or macular drusen. 3D PAR reduces but does not eliminate pseudoflow, and pseudoflow may be detected within the foveal avascular zone, indicating that other factors, such as Z-axis micromotion, may also contribute to pseudoflow.Translational RelevanceThis study provides insight into the etiology of pseudoflow noted on OCTA and will guide more accurate clinical interpretation and investigation of OCTA images.

Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report No. 17

To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Retrospective analysis of a prospective cohort study. Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan-Meier analyses and multivariable proportional hazard regressions were performed. Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98-2.82; P < 0.001); 67% of eyes progressed to late AMD 5 years after DPED detection. Drusenoid pigment epithelial detachment was associated with increased risk of ≥3 lines of VA loss (HR, 3.08; CI, 2.41-3.93; P < 0.001) with 46% of eyes experiencing vision loss at 5 years (with or without progression to late AMD). ARMS2 risk alleles (1 vs. 0: HR, 2.72, CI, 1.58-4.70; 2 vs. 0: HR, 3.16, CI, 1.60-6.21, P < 0.001) and increasing GRS group (4 vs. 1) (HR, 12.17, CI, 3.66-40.45, P < 0.001) were significantly associated with DPED development in AREDS. There were no significant genetic results in AREDS2. This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

Regression patterns of choroidal melanoma: After palladium-103 (103Pd) plaque brachytherapy.

Purpose:To describe the patterns of regression of choroidal melanoma after treatment with plaque brachytherapy.Methods:Retrospective interventional case series including 170 consecutive patients treated with 103Pd eye plaque radiation for choroidal melanoma. Outcome measures were changes in tumor thickness, surface characteristics, tumor vascularity, ultrasonography, fluorescein angiography, optical coherence tomography, and histopathology.Results:The mean initial tumor thickness was 3.9 mm (median 2.8 mm; range 2–11.3 mm) that decreased to 1.7 mm (median 1.2 mm; range 0–7.1 mm) after plaque brachytherapy. On imaging, tumors were pigmented in 51% (n = 86/170), amelanotic in 10% (n = 17/170), and variably pigmented in 39% (n = 67/170). Tumor pigmentation increased in 64% (n = 106/166), decreased in 18% (n = 30/166), and was unchanged in 18% (n = 30/166). Of the 120 that demonstrated intrinsic vascularity, 10% (n = 12/120) had decreased tumor-related vascularity and 90% (n = 108/120) showed complete resolution. Subretinal fluid was present in 34% (n = 58/170) of eyes at presentation. Of them, 15% (9; n = 9/58) had persistent SRF at last follow-up. On ultrasound imaging, 88% (n = 149/170) tumors presented with low to moderate internal reflectivity of which 61% (n = 91/149) showed increased reflectivity on regression. We noted a crescendo–decrescendo fluctuation in the presence of orange pigment lipofuscin along with complete resolution of drusenoid retinal pigment epithelial detachments. In the entire series of 170 patients, there was 0.5% (1) failure of local control, 2% (4) secondary enucleations, and 6% (10) patients developing metastasis.Conclusion:Findings related to choroidal melanoma regression after 103Pd plaque brachytherapy included decreased intrinsic tumor vascularity, decreased tumor-related subretinal fluid, increased pigmentation, specific changes in orange pigment lipofuscin and resolution of drusenoid retinal pigment epithelial detachments, as well as decreased tumor thickness with an increase in internal reflectivity on ultrasound.

Long-term Choroidal Thickness Changes in Eyes With Drusenoid Pigment Epithelium Detachment

To analyze the changes in visual acuity and subfoveal choroidal thickness in patients with non-neovascular age-related macular degeneration (AMD) and drusenoid pigment epithelium detachments (PED). Consecutive observational case series. Observational retrospective review of eyes diagnosed with drusenoid PED in a single clinical setting. Demographic and clinical data included age, sex, laterality, best-corrected visual acuity (BCVA), and subfoveal choroidal thickness measured at baseline. before and after the collapse of the PED, and at the last available follow-up. The presence of geographic atrophy (GA) was also assessed. Thirty-seven eyes of 25 patients (18 female) were included in the analysis. Mean age at baseline was 71 ± 8.4 years. During a mean follow-up period of 4.9 ±1.9 years, PED collapse was observed in 25 eyes (68%). Mean BCVA, mean maximum PED height, and mean subfoveal choroidal thickness significantly decreased from baseline to the last available follow-up (P < .001) in patients showing PED collapse. Choroidal thinning was faster during the PED collapse (speed rate of 35.9μm/year). From those, 23 eyes (92%) developed GA. A significant correlation between the area of GA and the decrease in choroidal thickness was found (P= .010). Choroidal thickness significantly decreased in eyes showing drusenoid PED collapse, but not in eyes in which the PED persisted. A significant correlation with resultant GA area following PED collapse and the magnitude of choroidal thinning was found. Further studies are warranted to better understand the mechanisms involved in the occurrence of choroidal changes during the life cycle of drusenoid PEDs.

Retinal pigment epithelium changes in Kartagener syndrome

PurposeWe present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. ObservationsA 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. Conclusions and importanceWe hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

PREDICTIVE FACTORS FOR DEVELOPMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Spectral-Domain Optical Coherence Tomography Study.

To investigate the risk factors predictive for the development of neovascular age-related macular degeneration (NVAMD) by means of spectral-domain optical coherence tomography. Retrospective study of 73 eyes graded Stage 2 and Stage 3 according to the AMD International Grading System with minimum follow-up of 24 months. Drusenoid pigment epithelial detachment, hyperreflective foci, external limiting membrane, inner ellipsoid band, and retinal pigment epithelium integrity were analyzed at baseline and last follow-up. Binary logistic regression model analyzed significant predictors of neovascular conversion. The discontinuity of external limiting membrane, inner ellipsoid band, and retinal pigment epithelium bands were significantly more prevalent in the NVAMD group at baseline and last follow-up (P < 0.001). Hyperreflective foci represented the single most important predictor of neovascular conversion (Exp [B], 15.15; P = 0.005) as confirmed by Kaplan-Meier curve (P = 0.002). Drusenoid pigment epithelial detachment width was significantly greater in NVAMD group than control subjects at baseline and last follow-up (P < 0.001), and its delta value also resulted a significant neovascular predictor (Exp [B], 0.99; P = 0.04). Hyperreflective foci significantly increase the risk of NVAMD progression. The delta width of drusenoid pigment epithelial detachment also predicts disease progression, integrating the stratification of NVAMD progression risk.

Multimodal imaging of retinal pigment epithelial detachments in patients with C3 glomerulopathy: case report and review of the literature

BackgroundTo describe the optical coherence tomography angiograhy (OCTA) of drusenoid pigment epithelial detachments (PEDs) in a woman affected by Complement 3 (C3) glomerulopathy, which represents a spectrum of glomerular diseases characterized on fluorescent microscopy by C3 accumulation with absent, or scanty, immunoglobulin deposits. It is due to acquired or genetically defective alternative pathway control and is generally associated with drusen-like deposits in Bruch’s membrane, as well as choriocapillaris. These retinal lesions can be associated with choroidal neovascularization and central serous chorioretinopathy (CSCR). OCTA is useful to detect neovascularization without injecting a contrast product, particularly in these patients who may have renal insufficiency.Case presentationA 28-year-old woman affected by C3 glomerulpathy was diagnosed with asymptomatic multiple bilateral PEDs during a routine ophthalmologic consultation. To better characterize the lesions, multimodal imaging was performed and included: optic coherence tomography (OCT), en-face OCT, OCTA, fluorescence and indocyanine angiography. The OCTA clearly identified vascular network rarefaction with decreased choriocapillary vascularization. It confirmed that PEDs associated with C3 glomerulonephritis are not vascularized, but rather of serous type.ConclusionsPatients affected by C3 glomerulopathy can develop neovascular membranes as retinal complications of pigment epithelial detachments. Optical coherence angiography may be indicated to identify this complication, without injecting any contrast product that could produce further kidney damage.

Clinicopathologic Correlation of Anti–Vascular Endothelial Growth Factor–Treated Type 3 Neovascularization in Age-Related Macular Degeneration

To correlate histologic results with previously recorded multimodal imaging results from a patient with type 3 neovascularization secondary to age-related macular degeneration (AMD). Case study, clinical imaging, laboratory imaging, and eye-tracked clinicopathologic correlation. An 86-year-old white woman with type 3 neovascularization secondary to AMD treated with 6 intravitreal injections of bevacizumab. Multimodal retinal imaging at each clinic visit was correlated with exvivo and high-resolution histologic images of the preserved donor eye. Clinical imaging included serial near-infrared reflectance and eye-tracked spectral-domain OCT. Eye tracking, applied to the donor eye, enabled identification of histologic features corresponding to clinical OCT signatures. Histologic correlates for clinical OCT signatures were sought, including reflectivity of the vascular complex, intraretinal hyperreflective foci and intraretinal cellularity, analysis of the topography of pathologic features, and evaluation of the sub-retinal pigment epithelium (RPE) plus basal lamina (BL) space. Clinical imaging showed a deep neovascular lesion in close relationship with a mixed serous and drusenoid pigment epithelium detachment (PED), characteristic of type 3 neovascularization. Antiangiogenic therapy achieved a complete resolution of exudation. The PED progressively flattened with each treatment, leaving a persistent triangular hyperreflectivity in the outer retina. This persistent deep lesion histologically correlated with a vascular complex implanted into sub-RPE basal laminar deposit. No connection between the choriocapillaris and the sub-RPE plus BL space was observed. Both RPE-derived and lipid-filled cells were correlated with clinical intraretinal hyperreflective foci. The sub-RPE plus BL space contained macrophages, lymphocytes, Müller cell processes, and subducted RPE. Clinicopathologic correlation of type 3 neovascularization showed vascular elements of retinalorigin accompanied by collagenous material and Müller cell processes implanting into thick sub-RPE basallaminar deposit, which may simulate the appearance of chorioretinal anastomosis. Surrounding RPE-derived and lipid-filled cells thought to be microglia correlated with clinical intraretinal hyperreflective foci.

Evaluation of intraretinal migration of retinal pigment epithelial cells in age-related macular degeneration using polarimetric imaging

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R2 = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED.

Atypical retinal pigment epithelial defects with retained photoreceptor layers: a so far disregarded finding in age related macular degeneration

BackgroundTo report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers.MethodsMultimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA).ResultsTen patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71–87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch’s membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion.ConclusionsBeside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

Correlation between retinal function and microstructural foveal changes in intermediate age related macular degeneration

Purpose To assess foveal microstructural changes influencing retinal sensitivity (RS) and fixation stability using microperimeter MP-1 in intermediate age-related macular degeneration (AMD).Methods In this cross-sectional study, 22 eyes of 22 patients (mean age: 75 ± 9.02 years) with intermediate AMD were enrolled. Retinal sensitivity and bivariate contour ellipse area (BCEA) were obtained by microperimetry MP-1 (Humphrey 10-2 68-loci grid) under mesopic conditions. Drusen type, drusenoid pigment epithelial detachment, hyperreflective foci (HF), integrity of external limiting membrane (ELM), inner ellipsoid zone (ISel), RPE/Bruch’s membrane complex (RPE/B) and subfoveal choroidal thickness were analyzed in the foveal region and compared with RS and BCEA. Spearman’s rank correlation coefficient was used to evaluate the relationship between variables. Logistic regression analysis was also used to assess morphological predictor influencing RS or BCEA.ResultsRS was strongly and inversely related with the presence of HF (r = −0.66, P = 0.001), integrity of ELM (r = −0.70, P < 0.001), ellipsoid zone (r = −0.45, P = 0.03). Instead, BCEA is positively related to the ellipsoid zone integrity (r = 0.45, P = 0.03). Logistic regression analysis confirmed that disruption of ISel influenced fixation stability (ExpB: 9.69, P = 0.04) but not RS. Instead, the presence of HF and disruption of ELM predicted RS reduction (ExpB: 0.55, P = 0.02 and ExpB: 0.29, P = 0.04, respectively).ConclusionsThe integrity of ELM and the presence of HF are both predictors of RS. The ELM status may be considered a new biomarker of retinal function together with HF. Instead, the integrity of ISel band seems to be a more selective predictor of BCEA than RS.

Activated Retinal Pigment Epithelium, an Optical Coherence Tomography Biomarker for Progression in Age-Related Macular Degeneration.

PurposeTo summarize and contextualize recent histology and clinical imaging publications on retinal pigment epithelium (RPE) fate in advanced age-related macular degeneration (AMD); to support RPE activation and migration as important precursors to atrophy, manifest as intraretinal hyperreflective foci in spectral-domain optical coherence tomography (SDOCT).MethodsThe Project MACULA online resource for AMD histopathology was surveyed systematically to form a catalog of 15 phenotypes of RPE and RPE-derived cells and layer thicknesses in advanced disease. Phenotypes were also sought in correlations with clinical longitudinal eye-tracked SDOCT and with ex vivo imaging–histopathology correlations in geographic atrophy (GA) and pigment epithelium detachments (PED).ResultsThe morphology catalog suggested two main pathways of RPE fate: basolateral shedding of intracellular organelles (apparent apoptosis in situ) and activation with anterior migration. Acquired vitelliform lesions may represent a third pathway. Migrated cells are packed with RPE organelles and confirmed as hyperreflective on SDOCT. RPE layer thickening due to cellular dysmorphia and thick basal laminar deposit is observed near the border of GA. Drusenoid PED show a life cycle of slow growth and rapid collapse preceded by RPE layer disruption and anterior migration.ConclusionsRPE activation and migration comprise an important precursor to atrophy that can be observed at the cellular level in vivo via validated SDOCT. Collapse of large drusen and drusenoid PED appears to occur when RPE death and migration prevent continued production of druse components. Data implicate excessive diffusion distance from choriocapillaris in RPE death as well as support a potential benefit in targeting drusen in GA.

The Evolution of the Plateau, an Optical Coherence Tomography Signature Seen in Geographic Atrophy.

PurposeHistologic details of progression routes to geographic atrophy (GA) in AMD are becoming available through optical coherence tomography (OCT). We studied the origins and evolution of an OCT signature called plateau in eyes with GA and suggested a histologic correlate.MethodsSerial eye-tracked OCT scans and multimodal imaging were acquired from eight eyes of seven patients with GA and plateau signatures over a mean follow-up of 7.7 years (range, 3.7–11.6). The histology of unrelated donor eyes with AMD was reviewed.ResultsDrusenoid pigment epithelial detachment (PED) on OCT imaging progressed into wide-based mound-like signatures with flattened apices characterized by a hyporeflective yet heterogeneous interior and an overlying hyperreflective exterior, similar to outer retinal corrugations previously ascribed to persistent basal laminar deposit (BLamD) but larger. These new signatures are described as “plateaus.” An initial increase of the PED volume and hyporeflectivity of its contents was followed by a decrease in PED volume and thinning of an overlying hyperreflective band attributable to the loss of the overlying RPE leaving persistent BLamD. Both imaging and histology revealed persistent BLamD with defects through which gliotic Müller cell processes pass.ConclusionsPlateaus can be traced back to drusenoid PEDs on OCT imaging. We hypothesize that during progressive RPE atrophy, Müller cell extension through focal defects in the residual persistent BLamD may contribute to the heterogeneous internal reflectivity of these entities. The role of Müller cell activation and extension in the pathogenesis of AMD should be explored in future studies.

Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration

Drusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes. Laboratory imaging and histologic comparison, and retrospective, observational cohort study. Four donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter. Donor eyes underwent multimodal exvivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography. Histologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD. Intraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits. Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.

Correlation of fundus autofluorescence patterns in early dry age-related macular degeneration with optical coherence tomography findings

Background: Correlation of abnormal fundus autofluorescence (FAF) patterns with optical coherence tomography (OCT) findings. Aims: The aim of this study was to evaluate FAF patterns in eyes with early dry age-related macular degeneration (AMD) and correlate these patterns with OCT findings. Settings and Design: This was an institutional, observational, cross-sectional study. Subjects and Methods: One hundred and fifty-six eyes of 102 patients with early dry AMD were recruited, FAF imaging was done for all patients with the aid of confocal scanning laser ophthalmoscopy. In addition, OCT imaging was done for all patients. Statistical Analysis Used: Chi-square test was used for analysis. Results: Six FAF patterns have been identified (normal, minimal change, focal increased, linear, patchy, and reticular pattern). There was a statistically significant difference in OCT findings (drusenoid retinal pigment epithelial detachment and inner- and outer-segment junction integrity) among various FAF patterns. Conclusions: The OCT findings were statistically significant variable among different FAF patterns in eyes with early AMD suggesting a possible link between each FAF pattern and the changes which take place in retinal structure. This finding can aid in determining the visual prognosis of eyes with early AMD according to FAF pattern in large sample studies.

AN UPDATED STAGING SYSTEM OF TYPE 3 NEOVASCULARIZATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY

To comprehensively investigate spectral domain optical coherence tomography features associated with Type 3 neovascularization and determine the prevalence of each feature and to develop an updated staging system for Type 3 neovascularization based on spectral domain optical coherence tomography findings. The authors retrospectively analyzed 34 eyes with new-onset Type 3 neovascularization. Spectral domain optical coherence tomography images at onset of Type 3 neovascularization, immediately after the first injection, and at the final quiescent visit were analyzed for the presence of specific optical coherence tomography features. In addition, when available, optical coherence tomography images from the visit before onset were studied. Among 18 eyes with preonset optical coherence tomography, 77.8% had preexisting intraretinal hyperreflective foci (precursor lesion). In the same group of eyes, 44.4% and 27.8% exhibited outer plexiform layer disruption and outer plexiform layer downward deflection, respectively. At the onset of detectable Type 3 neovascularization, all 34 eyes demonstrated a hyperreflective focus with cystoid macular edema and 85.3% exhibited disruption of the retinal pigment epithelium. Serous pigment epithelial detachment and subretinal fluid were present in 67.6% and 23.5% of eyes at onset, respectively. The rate of cystoid macular edema decreased from 100% to 17.6% after a single injection. At the final quiescent visit, focal atrophy at the site of Type 3 lesions, as evidenced by outer retinal and retinal pigment epithelium disruption developed in 88.2% and 52.9% of eyes, respectively. An updated staging system of Type 3 lesions was developed based on spectral domain optical coherence tomography findings. A precursor stage consists of a punctate hyperreflective focus in the outer retina. The subtle detection of associated outer plexiform layer disruption and downward deflection may indicate that this precursor lesion is more likely to progress to an active Type 3 neovascular lesion. Stage 1 consists of a larger intraretinal hyperreflective lesion associated with cystoid macular edema but without outer retinal disruption. Stage 2 is notable for outer retinal disruption that occurs with retinal pigment epithelium disruption in most of the cases. Stage 3 is defined by an intraretinal hyperreflective lesion that extends through the retinal pigment epithelium to vascularize a drusenoid pigment epithelial detachment creating a serous component of the pigment epithelial detachment.

Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments.

PurposeDrusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT).MethodsTwenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity.ResultsMean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6–6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001).ConclusionsSpectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.