Drusenoid Pigment Epithelial Detachment Research Articles

PATHWAYS TO GEOGRAPHIC ATROPHY IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To characterize and quantify the precursor lesions of geographic atrophy in eyes with age-related macular degeneration. A retrospective study of eyes with a minimum of 6-month follow-up before developing geographic atrophy. Evaluations included color and autofluorescence imaging, along with spectral-domain optical coherence tomography, employing definitions from the Consensus of Atrophy Meeting Group and Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. There were 55 eyes of 44 patients, who had a mean age of 81.3 years at onset of atrophy; 35 (63.6%) were female. The mean duration of follow-up before and after the advent of geographic atrophy was 4.9 years and 1.2 years, respectively. Geographic atrophy was preceded by collapse of a druse in 41 eyes (74.5%). Of these, 29 (70.7%) were drusenoid pigment epithelial detachments. Among the eyes with regressing drusen, there were 9 with overlying vitelliform deposit, and all had concurrent subretinal drusenoid deposit; however, 19 of 30 eyes with no vitelliform deposit overlying the druse had concurrent subretinal drusenoid deposit, a difference that was significant ( P < 0.001). Regression of subretinal drusenoid deposit was found in 4 eyes (7.3%), regression of vitelliform deposit associated with subretinal drusenoid deposit in 5 (9.1%), and regression of vitelliform deposit in eyes concurrently harboring drusen was found in 3 (5.4%) and regression of vitelliform deposit alone in 2 (3.6%) at the site of eventual development of geographic atrophy. Geographic atrophy appears to develop from multiple pathways as manifested by the many precursor lesions, all various forms of extracellular deposit, that upon regression, result in a common end-stage appearance.

Sub retinal pigment epithelium hyporeflective spaces preceding large drusen collapse.

To describe and study hyporeflective sub retinal pigment epithelium (RPE) spaces in large drusen and drusenoid pigment epithelial detachment prior to collapse. Retrospective longitudinal study which enrolled patients with large and very large drusen due to intermediate age-related macular degeneration (AMD). The following optical coherence tomography (OCT) parameters were assessed: Drusen size (maximum width and height), OCT biomarkers of RPE atrophy, presence of intraretinal and subretinal fluid (IRF, SRF), acquired vitelliform lesion and sub RPE regions of hyporeflectivity within the PED compartment. Of the 50 eyes from 41 patients (mean age of 77.1 ± 9 years, 78% women) with large and very large drusen, 16 eyes progressed to collapse. Eyes with sub RPE hyporeflective spaces (n=8 eyes, 50%) were associated with greater drusen width and height than eyes without sub RPE hyporeflective spaces. At the collapse visit, eyes with sub RPE hyporeflective spaces displayed poorer visual acuity and greater iRORA (incomplete RPE outer retinal atrophy) and cRORA (complete RORA) length than eyes without sub RPE hyporeflective spaces (p=0.004 and p=0.04, respectively). Sub RPE hyporeflective spaces are a novel OCT finding of large and very large drusen that collapse to atrophy. Progressive RPE dysfunction and failure may lead to reduced drusenoid material formation and progressive degenerative hydration of the large drusen prior to collapse, but this awaits confirmation with histopathological analysis.

Dynamics of rheological and biochemical blood parameters of patients with an intermediate stage of the dry form of age-related macular degeneration before and after serum cascade filtration

BACKGROUND: One of the socially significant ophthalmic diseases is the dry form of the age-related macular degeneration, the key feature of which consists in a slowly progressing damage to the pigment epithelium and the formation of drusen. However, the basic mechanisms of pathogenesis are still not completely clear nowadays. AIM: The aim is, using the data of OCT, OCT-angiography and visometry, to study the dynamics of structural and functional parameters of the macular area, as well as the dynamics of rheological and biochemical blood parameters in patients with an intermediate stage of the dry form of age-related macular degeneration before and after the use of serum cascade filtration. MATERIALS AND METHODS: The study included 63 patients (94 eyes) with an intermediate stage of the dry form of age-related macular degeneration. Patients were randomly separated into two groups. The first (main) group consisted of 34 patients (52 eyes), in whom serum cascade filtration was performed; the second group (control) group included 29 patients (42 eyes) who did not receive any specific treatment. In patients of the main group, before and after the serum cascade filtration course (1 month after the start of follow-up), in 6 and 12 months, in addition to standard ophthalmological examination, as an indicator of the efficacy of performed serum cascade filtration, the ultrasound triplex scanning in color Doppler mapping mode with an assessment of blood flow velocity in the posterior short ciliary arteries, Fourier IR spectroscopy, and the testing of the serum and blood viscosity were performed. Patients in the control group also underwent a similar examination at 1, 6, 12 months after the start of follow-up. RESULTS: According to optical coherence tomography, optical coherence tomography-angiography and visometry data, we found a positive dynamics of structural and functional parameters of the macular retina and an improvement in blood rheological parameters with an increase in microcirculation indices against the background of the serum cascade filtration use in treatment of patients with an intermediate stage of the dry form of age-related macular degeneration. At the same time, a statistically significant difference between the two groups begins at 1 month and persists for 12 months of follow-up, being an evidence of the stabilization of the pathological process. CONCLUSIONS: This study showed that after the serum cascade filtration in patients with an intermediate stage of the dry form of age-related macular degeneration, against the background of an improvement in blood rheological and biochemical parameters, there was an improvement in structural and functional parameters of the macular area, which consisted in a decrease of the volume of the drusenoid retinal pigment epithelium detachment and in a visual acuity amelioration.

Reply to correspondence: Subretinal fluid associated with drusenoid pigment epithelial detachment.

Reply to correspondence: Subretinal fluid associated with drusenoid pigment epithelial detachment.

Topographic analysis of local OCT biomarkers which predict progression to atrophy in age-related macular degeneration

PurposeTo define optical coherence tomography (OCT) biomarkers that precede the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) at that location in eyes with age-related macular degeneration (AMD).MethodsIn this retrospective case–control study, patients with dry AMD who had evidence of cRORA and OCT data available for 4 years (48 ± 4 months) prior to the first visit with evidence of cRORA were included. The visit 4 years prior to the development of cRORA was defined as the baseline visit, and the region on the OCT B-scans of future cRORA development was termed the case region. A region in the same eye at the same distance from the foveal center as the case region that did not progress to cRORA was selected as the control region. OCT B-scans at the baseline visit through both the case and control regions were evaluated for the presence of soft and cuticular drusen, drusen with hyporeflective cores (hcD), drusenoid pigment epithelial detachments (PED), subretinal drusenoid deposits (SDD), thick and thin double-layer signs (DLS), intraretinal hyperreflective foci (IHRF), and acquired vitelliform lesions (AVL).ResultsA total of 57 eyes of 41 patients with dry AMD and evidence of cRORA were included. Mean time from the baseline visit to the first visit with cRORA was 44.7 ±\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\pm$$\\end{document} 6.5 months. The presence of soft drusen, drusenoid PED, AVL, thin DLS, and IHRF at the baseline visit was all associated with a significantly increased risk of cRORA at that location. Multivariable logistic regression revealed that IHRF (OR, 8.559; p < 0.001), drusenoid PED (OR, 7.148; p = 0.001), and a thin DLS (OR, 3.483; p = 0.021) were independent predictors of development of cRORA at that location.ConclusionsIHRF, drusenoid PED, and thin DLS are all local risk factors for the development of cRORA at that same location. These findings would support the inclusion of these features within a more granular staging system defining specific steps in the progression from early AMD to atrophy.

Influence of drusenoid pigment epithelial detachments on the progression of age-related macular degeneration and visual acuity

ObjectiveTo analyze the presence and morphologic characteristics of drusenoid pigment epithelial detachments (DPEDs) in spectral-domain optical coherence tomography (SD-OCT) in Caucasian patients with early and intermediate age-related macular degeneration (AMD) as well as the influence of these characteristics on best-corrected visual acuity (BCVA) and disease progression. DesignProspective observational cohort study. Participants: 89 eyes of 56 patients with early and intermediate AMD. MethodsExaminations consisted of BCVA, SD-OCT, and indocyanine green angiography. Evaluated parameters included drusen type, mean drusen height and -volume, the presence of DPED, DPED maximum height, -maximum diameter, -volume, topographic location, the rate of DPED collapse, and the development of macular neovascularization (MNV) or geographic atrophy (GA). ResultsDPED maximum height (162.34 µm ± 75.70 μm, p = 0.019) was significantly associated with the development of GA and MNV. For each additional 100 μm in maximum height, the odds of developing any late AMD (GA or MNV) increased by 2.23 (95% CI = 1.14–4.35). The presence of DPED (44 eyes, p = 0.01), its volume (0.20 mm ± 0.20 mm, p = 0.01), maximum diameter (1860.87 μm ± 880.74 μm, p = 0.03), maximum height (p < 0.001) and topographical location in the central millimetre (p = 0.004) of the Early Treatment Diabetic Retinopathy Study (ETDRS)-Grid were significantly correlated with BCVA at the last follow-up (0.15logMAR ± 0.20logMAR; Snellen equivalent approximately 20/28). DPEDs occurred significantly less in the outer quadrants than in the central millimetre and inner quadrants of ETDRS-Grid (all p values < 0.001). ConclusionsThe height of drusen and DPEDs is a biomarker that is significantly associated with the development of late AMD and visual loss. DPEDs affect predominantly the center and inner quadrants of the ETDRS-Grid.

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.

Acute atrophic evolution of drusenoid pigment epithelium detachment after photobiomodulation

Purpose: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). Methods: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. Results: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. Conclusion: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion’s natural history towards atrophic evolution.

Multimodal imaging in early onset non-neovascular pigment epithelial detachments.

To describe multimodal imaging of two cases of bilateral non-vascularized pigment epithelial detachments (PED) in young patients with a long-term follow-up. A complete ophthalmological examination was performed at each follow-up visit including best corrected visual acuity (BCVA), intraocular pressure, slit lamp examination, spectral domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography, OCT angiography. Multimodal imaging of two women presenting avascular PED, aged 43 and 57, respectively, was described. In both patients, SD-OCT revealed a high central macular hyporeflective elevation corresponding with PED. Both patients showed a choroidal layer thicker than 420 μm. Fluorescein and indocyanine green angiography didn't show any choroidal neovascularization either at early or late frames. Cross-sectional and en face optical coherence tomography angiography (OCTA) didn't show any flow beneath the PED. During the follow up period one eye showed a retinal pigment epithelium tear and all eyes showed the presence of apical sub-retinal fluid and hyperreflective material on the top of the PED. None of the two patients showed any sign of atrophy during the follow-up period. The peculiar characteristics of the presented cases suggest that specific pathogenetic mechanisms, not necessarily related to age related macular degeneration, may play a key role in the development of these lesions. Whether early onset of such drusenoid PED is a specific entity resulting from a genetic deficit of lipid transporters in the RPE is unknown. Further genetic and metabolic studies should be conducted.

Geographic Atrophy after Reabsorption of Pigment Epithelial Detachment (GARPED) study

BackgroundTo describe the occurrence, rate of geographic atrophy (GA) expansion, and changes in visual acuity (VA) after reabsorption of subfoveal pigment epithelial detachments (PED).MethodsIncluded patients had reabsorption of a PED followed by GA. Patients underwent clinical examination with SD-OCT. Images were classified by size with grading occurring post reabsorption. VA was recorded pre-reabsorption, post-reabsorption, and over time.ResultsThe average age of the cohort, consisting of 22 eyes from 19 participants, was 86.9 years at reabsorption. Prior to reabsorption, the VA was 20/80 and then declined to 20/200 (p = 0.001) with an average follow-up time of 30.2 months. There was no significant VA change after the initial loss with reabsorption. The average initial lesion size of GA was 0.987 mm2 with an average growth rate of 0.274 mm/year.ConclusionsThis study longitudinally examined GA growth rate in patients with reabsorbed PEDs. These patients started with a drusenoid or serous PED, had a dramatic reduction in vision and GA that occurred in place of the PED. These GA lesions have a slower growth rate and a smaller area of onset compared to rates previously reported in the literature. They do not show significant VA change after reabsorption. As we have entered the era of GA therapy, these patients may not benefit from current treatments.

PHOTOBIOMODULATION THERAPY FOR LARGE SOFT DRUSEN AND DRUSENOID PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: A Single-Center Prospective Pilot Study.

To evaluate visual acuity and morphologic changes after photobiomodulation (PBM) for patients affected with large soft drusen and/or drusenoid pigment epithelial detachment associated with dry age-related macular degeneration. Twenty eyes with large soft drusen and/or drusenoid pigment epithelial detachment age-related macular degeneration were included and treated using the LumiThera Valeda Light Delivery System. All patients underwent two treatments per week for 5 weeks. Outcome measures included best-corrected visual acuity, microperimetry-scotopic testing, drusen volume, central drusen thickness, and quality of life score at baseline and month 6 (M6) follow-up. Data of best-corrected visual acuity, drusen volume, and central drusen thickness were also recorded at week 5 (W5). Best-corrected visual acuity significantly improved at M6 with a mean score gain of 5.5 letters ( P = 0.007). Retinal sensitivity decreased by 0.1 dB ( P = 0.17). The mean fixation stability increased by 0.45% ( P = 0.72). Drusen volume decreased by 0.11 mm 3 ( P = 0.03). Central drusen thickness was reduced by a mean of 17.05 µ m ( P = 0.01). Geographic atrophy area increased by 0.06 mm 2 ( P = 0.01) over a 6-month follow-up, and quality of life score increased by 3,07 points on average ( P = 0.05). One patient presented a drusenoid pigment epithelial detachment rupture at M6 after PBM treatment. The visual and anatomical improvements in our patients support previous reports on PBM. PBM may provide a valid therapeutic option for large soft drusen and drusenoid pigment epithelial detachment age-related macular degeneration and may potentially slow the natural course of the disease.

Collapse of drusenoid pigment epithelial detachment following macular hole surgery

The effect of vitrectomy on the course of dry age-related macular degeneration (AMD) in eyes with full-thickness macular holes (FTMHs) is not well understood and has been variably reported in existing studies. The phenomenon of disappearance of confluent soft drusen (drusenoid pigment epithelial detachment [PED]) after macular hole surgery is, however, a rarely reported occurrence. We report a case of a 61-year-old female patient with a large full-thickness macular hole of minimum diameter 586 μm with an underlying drusenoid PED, who underwent a pars plana vitrectomy with inverted internal limiting membrane flap and 20% sulfur hexafluoride gas injection. The macular hole was successfully closed along with collapse of the underlying drusenoid PED during the postoperative follow-up period.

Subretinal Fluid associated with Drusenoid Pigment Epithelial Detachment.

To analyze the clinical characteristics of drusenoid pigment epithelial detachment (PED) with subretinal fluid (SRF) and to evaluate the impact of SRF on the long-term visual and anatomical outcomes. Forty-seven eyes with drusenoid PED (47 patients) who completed more than 24 months follow-up were retrospectively analyzed. Intergroup comparisons of the visual and anatomical outcomes with and without SRF were made. The mean duration of follow-up was 32.9 ± 18.7 months. The group with drusenoid PED with SRF (14 eyes) showed significantly higher PED height (468 ± 130 µm vs. 313 ± 88 µm, P < 0.001), larger PED diameter (2328 ± 953 µm vs. 1227 ± 882 µm, P < 0.001), and larger PED volume (1.88 ± 1.73 mm3 vs. 1.12 ± 1.35 mm3, P = 0.021) than that in the group with drusenoid PED without SRF (33 eyes) at baseline. No significant intergroup difference was found regarding the best-corrected visual acuity at the final visit. In addition, the incidence of complete retinal pigment epithelial and outer retinal atrophy (cRORA; 21.4%) and the development of macular neovascularization (MNV; 7.1%) for the group with drusenoid PED with SRF showed no difference compared to those (39.4% for cRORA development and 9.1% for MNV development) with drusenoid PED without SRF. The size, height, and volume of drusenoid PED were associated with the development of SRF. The SRF in drusenoid PED did not affect the visual prognosis or the development of macular atrophy during long-term follow-up.

Faricimab in neovascular AMD: first report of real-world outcomes in an independent retina clinic.

Assess short-term real-world outcomes in neovascular aged-related macular degeneration (nAMD) treated with novel faricimab. Retrospective case series of nine patients with nAMD (11 eyes) treated with faricimab between May and November 2022. Treatment-naïve patients and non-naïve patients underwent logMAR best corrected visual acuity (BCVA), optical coherence tomography (OCT) DRI OCT-1 Triton (Topcon Corp, Tokyo, Japan), ultra-widefield (UWF) and fundus autofluorescence (FAF) (California Optomap, Optos plc, Dunfermline, Scotland, UK). Previous treatment intervals, number of intravitreal injections, sub/intra retinal fluid (SRF/IRF), central retinal thickness (CRT) and presence/changes in pigment epithelial detachments (PEDs) were recorded. Mean baseline BCVA and CRT values of patients who switched from other agents were 0.612 ± 0.75 logMAR and 256.16 ± 12.98 µm respectively, with a mean 36-day previous treatment interval. The median number of other previous anti-VEGF intravitreal injections was 8. Mean BCVA at one month significantly improved to 0.387 ± 0.54 logMAR, as well as CRT values which decreased to 245.43 ± 15.34 µm. In the 3 naïve patients, mean baseline BVCA and CRT values were 0.33 ± 0.29 and 874.67 ± 510.86 µm, respectively. At one month follow-up, mean BCVA improved to 0.30 ± 0.29 logMAR and mean CRT was 536.04 ± 36.15 µm. Overall, a significant improvement in BCVA of 0.21 ± 41 logMAR and 238.44 ± 114.9 µm was achieved at one month after the first faricimab intravitreal injection. In addition, a complete resolution of SRF was observed in 6 out of 8 eyes (75%) and of IRF in 2 out of 3 eyes (66.67%), respectively. Drusenoid PED morphology changes were observed in all patients and no drug-related adverse events were observed. Real-world outcomes showed improvement in BCVA and anatomic parameters at an early timepoint, demonstrating the efficacy and durability of faricimab in nAMD patients. Larger numbers of patients and longer follow-up are needed to determine whether the loading dose is required in all, what percentage of patients experience an improvement, and whether improvement it is maintained.

Efficacy and safety of brolucizumab for serous drusenoid pigment epithelium detachment non-responder to bevacizumab and aflibercept.

We report the case of a woman with drusenoid pigment epithelial detachment (DPED) in age-related macular degeneration who was successfully treated with two monthly intravitreal injections of brolucizumab after failing to respond to previous intravitreal injections of bevacizumab and aflibercept. A 56-year-old woman with mixed DPED and overlying subretinal fluid in her right eye was initially treated with three intravitreal injections of bevacizumab and three intravitreal injections of aflibercept with no visual and anatomical improvement. Switching to intravitreal injection of brolucizumab was performed. After two consecutive monthly intravitreal injections of brolucizumab, optical coherence tomography (OCT) showed first subretinal fluid resolution and then DPED collapse in the following months. After nine months, the best corrected visual acuity had improved from 20/40 to 20/20. There were no signs of retinal atrophy and exudative activity on OCT examination. No serious or minor adverse events were reported during the follow-up period. Switching to intravitreal brolucizumab injection might be an effective therapeutic option for treatment of mixed DPED with subretinal fluid refractory to other anti-VEGF drugs.

Non-neovascular fluid in age-related macular degeneration: observe-and-extend regimen in a case-series study

ObjectifDécrire l’évolution du liquide non néovasculaire dans la dégénérescence maculaire liée à l’âge (DMLA) après l'administration d'anti-VEGF (facteur de croissance endothélial vasculaire) ou après une période d'observation sans injection. NatureÉtude rétrospective portant sur une série de cas. MéthodesOnt été inclus des yeux qui présentaient une DMLA s'accompagnant de drusens maculaires et/ou d'un décollement drusénoïde de l’épithélium pigmentaire associée à l'apparition d'un liquide non néovasculaire. On a réalisé une angiographie-tomographie par cohérence optique (OCTA) dans tous les yeux afin d'exclure la présence d'une néovascularisation maculaire. Le liquide sous-rétinien (LSR) a été mesuré afin de déterminer la réponse à la suite de l'administration d'anti-VEGF et après une période d'observation sans injection. RésultatsAinsi, 10 yeux de 9 patients qui présentaient une DMLA intermédiaire s'accompagnant de LSR ont été étudiés pendant une médiane de 59,5 mois (fourchette : 7–128 mois). De ce nombre, 6 patients (6 yeux) avaient déjà reçu un anti-VEGF. La durée médiane du suivi sans injection était de 13,5 mois (fourchette : 4–44 mois). L’épaisseur du LSR est demeurée stable et n'a pas changé pendant le suivi sans injection dans tous les yeux (n = 6) qui avaient reçu des injections et dans tous les yeux (n = 4) qui n'avaient jamais reçu d'injection. Par ailleurs, on a observé une atrophie complète de l’épithélium pigmentaire rétinien (EPR) et des couches externes de la rétine dans 6 yeux, tandis qu'on a noté une atrophie incomplète de l'EPR et des couches externes de la rétine dans 1 seul œil. Tous les yeux présentaient au moins 2 biomarqueurs visibles à l'OCT et associés à un risque élevé de progression vers l'atrophie. ConclusionNotre étude fournit des données préliminaires sur la progression du liquide non néovasculaire dans la DMLA, avec ou sans injection d'anti-VEGF. L'apparition de liquide pourrait tenir à une dysfonction de la pompe de l'EPR. Il est essentiel de faire la distinction entre le liquide néovasculaire et le liquide non néovasculaire par l'intermédiaire de techniques d'imagerie multimodale, notamment l'OCTA, pour éviter d'administrer inutilement un anti-VEGF. On peut envisager un regime « d'observation-et-extension » (observe-and-extend) en présence de DMLA qui s'accompagne d'un liquide non néovasculaire.

Sub-retinal pigment epithelium tubules in non-neovascular age-related macular degeneration

To describe a novel optical coherence tomography (OCT) signature resembling sub-retinal pigment epithelium (RPE) tubules (SRT) in non-neovascular age-related macular degeneration (AMD). Patients suffering from non-neovascular AMD with complete medical records and multimodal imaging were retrospectively revised in three different tertiary care centers. Multimodal imaging included color fundus photograph, spectral-domain OCT (Spectralis, Heidelberg Engineering, Germany), fundus autofluorescence, OCT angiography (RTVue XR Avanti, Optovue, Inc., Fremont, CA). A total of 7 eyes of 7 patients with drusenoid pigment epithelium detachment (PED) were consecutively analyzed. The sub-RPE tubules appeared as ovoidal structures with a hyperreflective contour and hyporeflective interior appreciable in the sub-RPE-basal lamina (BL) space on OCT B-scan. The anatomical location of the sub-RPE formations was lying above the Bruch’s membrane in 5/7 cases (71.4%) or floating in the sub-RPE-BL space in 2/7 cases (28.6%). En-face OCTA revealed a curvilinear tubulation-like structure corresponding to SRT without flow signal. Sub-RPE tubules represent a newly identified OCT signature observed in eyes with drusenoid PED. The presumed origin may include a variant of calcified structure or alternatively activated RPE cells with some residual BL or basal laminar deposits attracted to BrM for craving oxygen.

Risk Factors for Progression of Age-Related Macular Degeneration: Population-Based Amish Eye Study.

Objective: To evaluate the optical coherence tomography (OCT)-based risk factors for progression to late age-related macular degeneration (AMD) in a population-based study of elderly Amish. Methods: A total of 1332 eyes of 666 consecutive subjects who completed a 2-year follow-up visit were included in this multicenter, prospective, longitudinal, observational study. Imaging features were correlated with 2-year incidence of late AMD development. Odds ratios for imaging features were estimated from logistic regression. Baseline OCT images were reviewed for the presence of drusen volume ≥0.03 mm3 in the central 3 mm ring, intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), subretinal drusenoid deposits (SDD), and drusenoid pigment epithelium detachment (PED). Subfoveal choroidal thickness, drusen area, and drusen volume within 3 and 5 mm circles centered on the fovea were also assessed. Results: Twenty-one (1.5%) of 1332 eyes progressed to late AMD by 2 years. The mean age of the study subjects was 65 ± 10.17 (±SD) years and 410 subjects were female. Univariate logistic regression showed that drusen area and volume in both 3 mm and 5 mm circles, subfoveal choroidal thickness, drusen volume ≥ 0.03 mm3 in the 3 mm ring, SDD, IHRF, and hDC were all associated with an increased risk for development of late AMD. The multivariate regression model identified that drusen volume in the 3 mm ring (OR: 2.59, p = 0.049) and presence of IHRF (OR: 57.06, p < 0.001) remained as independent and significant risk factors for progression to late AMD. Conclusions: This population-based study confirms previous findings from clinic-based studies that high central drusen volume and IHRF are associated with an increased risk of progression to late AMD. These findings may be of value in risk-stratifying patients in clinical practice or identifying subjects for early intervention clinical trials.

MULTIMODAL ASSESSMENTS OF DRUSENOID PIGMENT EPITHELIAL DETACHMENTS IN THE AGE-RELATED EYE DISEASE STUDY 2 ANCILLARY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY STUDY COHORT.

To identify features correlating with drusenoid pigment epithelial detachment (DPED) progression in the Age-Related Eye Disease Study 2 Ancillary spectral-domain optical coherence tomography study cohort. In this retrospective analysis of a prospective longitudinal study, eyes with intermediate age-related macular degeneration and DPEDs were followed longitudinally with annual multimodal imaging. Thirty-one eyes of 25 participants (mean age 72.6 years) in the Age-Related Eye Disease Study 2 Ancillary spectral-domain OCT substudy (A2A study) had DPED identified in color fundus images. Spectral-domain optical coherence tomography inspection confirmed a subretinal pigment epithelium drusenoid elevation of ≥433 µm diameter in 25 eyes (80.6%). Twenty-four of these eyes were followed longitudinally (median 4.0 years), during which 7 eyes (29.2%) underwent DPED collapse (with 3/7 further progressing to geographic atrophy), 6 (25.0%) developing neovascular age-related macular degeneration, and 11 (45.8%) maintaining DPED persistence without late age-related macular degeneration. On Kaplan-Meier analysis, mean time to DPED collapse was 3.9 years. Both DPED collapse and progression to neovascular age-related macular degeneration were preceded by the presence of hyperreflective foci over the DPED. The natural history of DPED comprises collapse (sometimes followed by the development of atrophy), vascularization followed by exudation, or DPED persistence. Spectral-domain optical coherence tomography can confirm retinal pigment epithelial elevation caused by drusenoid accumulation and facilitate the identification of high-risk features that correlate with progression.

Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration: 24-month outcomes.

After the 12-month interim safety analysis, we investigated the 24-month primary endpoint outcomes of drusenoid pigment epithelial detachment (dPED) after laser and intravitreal anti-VEGF treatment. Twenty-one patients with treatment-naïve bilateral intermediate AMD with dPED and visual acuity ≤ 83 letters (Snellen 20/23) were enrolled. The subject eye received low-energy PASCAL® laser (532nm) treatment, and the fellow eye was used as the control. Intravitreal injections were administered at 3-month intervals from baseline to 12months. Treatment outcomes, safety and development of advanced AMD lesions were analyzed. The mean drusen area and dPED height were significantly reduced (17.3 ± 2.7% vs. 112.8 ± 3.1%, P < 0.001 and 11.8 ± 4.7% vs. 119.1 ± 4.6%, P < 0.001, respectively) and the mean BCVA improved (5.11 ± 1.35 vs. 0.83 ± 1.03 letters, P = 0.014) in the study eyes compared to those in the control eyes. Development of parafoveal iRORA (nGA) (67%, 12 of 18 eyes) and cRORA (GA) (22%, 4 of 18 eyes) was observed in the study eyes, whereas three cases of iRORA and cRORA in the control eyes (17%, 3 of 18 eyes; P = 0.010 and P = 0.791, respectively). Laser and anti-VEGF treatment may be a potential treatment option for intermediate AMD with dPED. However, considering the relatively high rate of secondary iRORA and cRORA development, long-term follow-up is mandatory to clarify the safety and efficacy of this treatment.