The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.

PURPOSE: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). METHODS: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined. RESULTS: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm2, OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). CONCLUSIONS: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

Progression from Type 2 Macular Neovascularization to Fibrovascular Pigment Epithelial Detachment.

The aim of this study was to report unusual progression of type 2 macular neovascularization (MNV) associated with age-related macular degeneration (AMD), high myopia or angioid streaks. Retrospective multicentric observational case series data were used. Eyes that progressed from type 2 MNV secondary to AMD, high myopia or angioid streaks to fibrovascular pigment epithelial detachment (PED) were included. A total of 29 treatment-naive eyes from 29 patients with type 2 MNV secondary to AMD (n = 14), high myopia (n = 10) or angioid streaks (n = 5) that progressed to a fibrovascular PED on Spectral Domain-Optical Coherence Tomography were used. This progression occurred within 3 months after anti-VEGF therapy initiation. Logarithm of minimum angle of resolution (LogMAR) visual acuity improved significantly after anti-VEGF therapy, from 0.55 (SD ± 0.30) (20/63-20/80) at baseline to 0.30 (20/40) at 3 months, and 0.33 (20/40) at the final follow-up (mean follow up: 3.68 years). Mean number of intravitreal injections per year for patients with a total follow-up ≥ 12 months (n = 24) was 4.3 ± 2.1 per year. Progression from type 2 MNV to a fibrovascular PED may occur in patients suffering from AMD, high myopia or angioid streaks. This progression appears early after initiation of anti-VEGF therapy and is associated with a favorable visual and anatomical outcome, at least on a short follow up basis.

Long-Term Visual/Anatomic Outcome in Patients with Fovea-Involving Fibrovascular Pigment Epithelium Detachment Presenting Choroidal Neovascularization on Optical Coherence Tomography Angiography.

BACKGROUND: To evaluate long-term visual/anatomic outcome after anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with fovea-involving fibrovascular pigment epithelium detachment (PED) presenting with choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA). METHODS: Patients with fibrovascular PED or subretinal CNV confirmed by OCTA who were treated by a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. The best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) before and after anti-VEGF injection were analyzed. Furthermore, changes in photoreceptor layer (PRL) thickness and outer retinal bands in the fovea after injection were evaluated. RESULTS: A total of 31 eyes with fibrovascular PED and 24 eyes with subretinal CNV were included. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST were improved, and the PRL thickness was decreased significantly. There were no differences in BCVA, CST, changes in PRL thickness, or the status of outer retinal bands between the groups. However, the difference in the amount of decrease in PRL thickness between the two groups was increased at 2 years, and the slope tended to be steeper in the subretinal CNV group. CONCLUSIONS: Exudative age-related macular degeneration (AMD) with fibrovascular PED or subretinal CNV showed good visual/anatomic outcomes after anti-VEGF treatment, regardless of the CNV type. By 2 years, fibrovascular PED did not have an additional protective effect on the outer retina, compared with subretinal CNV over 2 years. Further follow-up study might be needed to conclude that fibrovascular PED has a protective effect on the surrounding photoreceptor area.

Treatment outcomes of conventional or high-dose ranibizumab for vascularized pigment epithelial detachment based on lesion subtypes.

INTRODUCTION:: A post hoc study was conducted to compare visual and anatomic outcomes of vascularized serous pigment epithelial detachment (Group 1) with fibrovascular pigment epithelial detachment (Group 2) due to age-related macular degeneration treated with either 0.5 or 2.0 mg ranibizumab injections. METHODS:: A prospective, randomized trial was performed with the following regimens for 12 months: (1) 0.5 mg monthly, (2) 0.5 mg monthly for 4 months followed by pro re nata injections, (3) 2.0 mg monthly, and (4) 2.0 mg monthly for 4 months followed by pro re nata injections. Primary measure was best-corrected standardized vision. Secondary measures included central subfield, thickness surface area A2, greatest linear diameter, heights of pigment epithelial detachment and choroidal neovascularization (CNV), subretinal fluid, cystoid macular edema, and adverse events. RESULTS:: For 36 eyes (8 in Group 1 and 28 in Group 2), follow-up time was 12 months. There were no differences in baseline features between groups except for pigment epithelial detachment A2 (Group 2 > Group 1). Two-way analysis of variance showed comparable improvements in anatomic and vision outcomes. Three-way analysis of variance also showed similar responses for both lesion subtypes with high-dose treatment. There was a trend toward greater pigment epithelial detachment resolution in Group 1 eyes. There were no differences in retinochoroidal angiomatous proliferation (Type-3 CNV) and cataracts between groups, although greater percentages of eyes in Group 1 developed retinal pigment epithelial tears (25% vs 10.7%). CONCLUSION:: There were no differences in vision and anatomic outcomes between lesion subtypes, and similarly, more rapid responses to high-dose than conventional-dose ranibizumab occurred for eyes with both lesion subtypes. More retinal pigment epithelial tears may develop in eyes with vascularized serous pigment epithelial detachment.

Anatomical Characteristics of End-stage Exudative Age-related Macular Degeneration Refractory to Intravitreal Anti-vascular Endothelial Growth Factor Injection

PURPOSE: To analyze the anatomical characteristics on spectral-domain optical coherence tomography (SD-OCT) of patients who are legally blind (less than 20/1,000) due to end-stage exudative age-related macular degeneration (AMD) that does not require intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection. METHODS: After anti-VEGF injections (active group), 120 eyes of 103 exudative AMD patients experienced visual acuity improved by at least 2 lines or improvement on SD-OCT. In addition, 55 eyes of 54 end-stage exudative AMD patients who did not respond to treatment or who were legally blind due to foveal scar at the first visit (end-stage group) were evaluated retrospectively. Changes in retinal structures of the 2 groups were analyzed by SD-OCT at the last visit. RESULTS: The mean age of the end-stage group was about 5 years older than the active group. During the follow-up period, subretinal hemorrhage, intraretinal hemorrhage and retinal pigment epithelium tear occurred more frequently in the end-stage group than in the active group (p < 0.05). Intra-retinal fluids and subretinal fluids were more frequently administered in the active group than in the end-stage group, and thick subretinal hyper-reflective materials (SRHRM), fibrovascular pigment epithelial detachment (PED) and extensive inner segment/outer segment (IS/OS) line disruption were observed in all eyes of the end-stage group. The size and thickness of PED, foveal thickness and SRHRM thickness were significantly larger in the end-stage group than in the active group (p < 0.05). Disciform retinal scars were eventually formed in most of the end-stage group. CONCLUSIONS: In end-stage exudative AMD, the presence of retinal hemorrhage and retinal pigment epithelium tear during follow-up, or the findings of thick SRHRM, fibrovascular PED, and extensive IS/OS line disruption on SD-OCT suggest weak expected effect of intravitreal anti-VEGF injection, which can act as a reference for determining the timing of treatment termination.

Anatomical Characteristics of End-stage Exudative Age-related Macular Degeneration Refractory to Intravitreal Anti-vascular Endothelial Growth Factor Injection

PURPOSE: To analyze the anatomical characteristics on spectral-domain optical coherence tomography (SD-OCT) of patients who are legally blind (less than 20/1,000) due to end-stage exudative age-related macular degeneration (AMD) that does not require intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection. METHODS: After anti-VEGF injections (active group), 120 eyes of 103 exudative AMD patients experienced visual acuity improved by at least 2 lines or improvement on SD-OCT. In addition, 55 eyes of 54 end-stage exudative AMD patients who did not respond to treatment or who were legally blind due to foveal scar at the first visit (end-stage group) were evaluated retrospectively. Changes in retinal structures of the 2 groups were analyzed by SD-OCT at the last visit. RESULTS: The mean age of the end-stage group was about 5 years older than the active group. During the follow-up period, subretinal hemorrhage, intraretinal hemorrhage and retinal pigment epithelium tear occurred more frequently in the end-stage group than in the active group (p < 0.05). Intra-retinal fluids and subretinal fluids were more frequently administered in the active group than in the end-stage group, and thick subretinal hyper-reflective materials (SRHRM), fibrovascular pigment epithelial detachment (PED) and extensive inner segment/outer segment (IS/OS) line disruption were observed in all eyes of the end-stage group. The size and thickness of PED, foveal thickness and SRHRM thickness were significantly larger in the end-stage group than in the active group (p < 0.05). Disciform retinal scars were eventually formed in most of the end-stage group. CONCLUSIONS: In end-stage exudative AMD, the presence of retinal hemorrhage and retinal pigment epithelium tear during follow-up, or the findings of thick SRHRM, fibrovascular PED, and extensive IS/OS line disruption on SD-OCT suggest weak expected effect of intravitreal anti-VEGF injection, which can act as a reference for determining the timing of treatment termination.

Optical coherence tomographic correlates of angiographic subtypes of occult choroidal neovascularization.

PURPOSE: To compare the optical coherence tomographic (OCT) correlates of two previously described angiographic subtypes of occult choroidal neovascularization (CNV). METHODS: We retrospectively analyzed 17 consecutive patients with previously untreated occult CNV who underwent both fluorescein angiography (FA) and volume spectral domain (SD)-OCT imaging on the same visit. Planimetric grading was performed on the FA images by certified reading center graders to precisely outline the boundaries of the fibrovascular pigment epithelial detachment (FVPED) and/or late leakage of undetermined source (LLUS) components of occult CNV for each case. In the SD-OCT images, the outer retinal pigment epithelial (RPE) and inner choroidal boundaries were manually segmented on all B-scans to generate a PED thickness map. Fluorescein angiography images were manually registered with the OCT fundus image, and the PED thickness was correlated with the angiographic lesion component present at each corresponding point in the fundus. RESULTS: Point-to-point correlations revealed that PED thickness was significantly different in areas of FVPED versus areas of LLUS. Whereas the mean PED thickness in areas of FVPED was 196.1 ± 120.36 µm, it was only 38.42 ± 8.14 µm in areas of LLUS (P = 0.003). Normalized internal reflectivity in areas of FVPED was lower than in areas of LLUS (0.12 ± 0.11 vs. 0.24 ± 0.07; P = 0.03). The integrity or continuity of the overlying RPE band on OCT, however, did not appear to differ between areas of LLUS and FVPED (P = 0.33). CONCLUSIONS: Although LLUS and FVPED appear to be distinct angiographic subtypes of CNV, the major difference between the two is the height of the RPE elevation and the internal reflectivity, with areas of LLUS representing much shallower RPE elevations with brighter mean internal reflectivity.

Characteristic findings of optical coherence tomography in retinal angiomatous proliferation.

PURPOSE: To identify the unique pathologic findings of retinal angiomatous proliferation (RAP) in optical coherence tomography (OCT). METHODS: Retrospectively, 29 eyes of 25 patients with age-related macular degeneration and complicated RAP were analyzed. All 29 eyes had choroidal neovascularization (CNV) in the area of pigment epithelial detachment (PED) or adjacent to it, which was visible with fluorescein angiography or indocyanine green angiography. Cross-sectional images were obtained by OCT scanning through the CNV lesions. RESULTS: Six distinctive findings of OCT included drusen (100%), inner retinal cyst (80%), outer retinal cyst (68%), fibrovascular PED (84%), serous retinal detachment (40%), and PED (68%). CONCLUSIONS: Through analysis of OCT findings, we revealed six different types of lesions distinctive of RAP which may provide helpful diagnostic information for subsequent treatment and predicting the prognosis of RAP.

Characteristic Findings of Optical Coherence Tomography in Retinal Angiomatous Proliferation

PURPOSE: To identify the unique pathologic findings of retinal angiomatous proliferation (RAP) in optical coherence tomography (OCT). METHODS: Retrospectively, 29 eyes of 25 patients with age-related macular degeneration and complicated RAP were analyzed. All 29 eyes had choroidal neovascularization (CNV) in the area of pigment epithelial detachment (PED) or adjacent to it, which was visible with fluorescein angiography or indocyanine green angiography. Cross-sectional images were obtained by OCT scanning through the CNV lesions. RESULTS: Six distinctive findings of OCT included drusen (100%), inner retinal cyst (80%), outer retinal cyst (68%), fibrovascular PED (84%), serous retinal detachment (40%), and PED (68%). CONCLUSIONS: Through analysis of OCT findings, we revealed six different types of lesions distinctive of RAP which may provide helpful diagnostic information for subsequent treatment and predicting the prognosis of RAP.