MULTILAYERED PIGMENT EPITHELIAL DETACHMENT IN NEOVASCULAR AGERELATED MACULAR DEGENERATION EHSAN RAHIMY, MD,* K. BAILEY FREUND, MD,† MICHAEL LARSEN, MD,‡ RICHARD F. SPAIDE, MD,† ROGERIO A. COSTA, MD, PHD,§ QUAN HOANG, MD, PHD,†¶ CHRISTOS CHRISTAKOPOULOS, MD,‡ INGER C. MUNCH, MD,‡ DAVID SARRAF, MD* Purpose: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Retrospective observational case series of patients with chronic fibrovascular PEDs receiving serial intravitreal anti-VEGF therapy. Corresponding spectral domain optical coherence tomography scans of chronic PEDs were studied in detail over multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic features were identified, and then correlated with visual outcome. Results: Thirty-eight eyes of 34 patients with fibrovascular PEDs were included. Mean and median Snellen visual acuity was 20/50 (range, 20/20–20/400). Eyes received a mean of 28.2 intravitreal anti-VEGF injections (median, 23.0; range, 3–70) administered over a mean of 36.9 months (median, 37.5; range, 6–84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment epithelium. Additionally, 25 eyes demonstrated a hyporeflective cavity separating the choroidal neovascularization complex from the underlying choroid. Conclusion: Chronic fibrovascular PEDs receiving serial anti-VEGF therapy demonstrate a characteristic fusiform complex of highly organized, layered, hyperreflective bands, termed a “multilayered PED,” which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. An associated hyporeflective space, termed a “pre-choroidal cleft,” separates the fusiform complex from the underlying choroid and may be due to contraction, the exudation of fluid, or both. Many of these eyes maintain good visual acuity, presumably because the neovascular and cicatricial process is suppressed within the sub-retinal pigment epithelium space by chronic anti-VEGF therapy, thus permitting the viability of the photoreceptor population through preservation of the retinal pigment epithelium. RETINA 34:1289–1295, 2014

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with pigment epithelial detachment (PED).1–7 More conventional imaging systems such as fluorescein angiography only provide information regarding the contour and filling characteristics of the PED, whereas indocyanine green angiography can localize the focus of choroidal neovascularization (CNV). For the first time, detailed analysis of the sub-RPE compartment is possible with high-resolution SD-OCT images that are comparable with histopathologic grade specimens.8–12 Given the long-term experience we have accumulated in the imaging and treatment of neovascular agerelated macular degeneration (NVAMD), we set out to evaluate and better characterize the internal anatomy

pectral domain optical coherence tomography (SD-OCT) has revolutionized our ability to image the sub-retinal pigment epithelium (RPE) space in eyes

From the *Jules Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California; †Vitreous Retina Macula Consultants of New York, New York, New York; ‡Glostrup Hospital, Roskilde Hospital, University of Copenhagen, Copenhagen, Denmark; §Centro Brasileiro de Ciencias Visuais, Belo Horizonte, Brazil; and ¶Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York. None of the authors have any financial/conflicting interests to disclose. Reprint requests: David Sarraf, MD, Retinal Disorders and Ophthalmic Genetics Division, Jules Stein Eye Institute, UCLA, 100 Stein Plaza, Los Angeles, CA 90095; e-mail: [email protected]

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of chronic fibrovascular PEDs in eyes receiving serial intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Using SD-OCT, we have identified a distinctive feature associated with fibrovascular PEDs, termed “multilayered PED,” which appears as organized layers of hyperreflective bands between the RPE monolayer and Bruch’s membrane within vascularized PEDs (Figure 1). This article will further characterize these lesions and correlate these findings clinically with visual outcomes.

Methods Institutional review board approval for this multicenter retrospective observational case series was obtained by the Western Institutional Review Board and the UCLA Office of the Human Research Protection Program. In Denmark, retrospective studies are exempt from review. Patients were evaluated and treated at one of the 4 tertiary referral centers. We retrospectively reviewed the charts of patients noted to demonstrate multilayered PEDs by SD-OCT imaging. Pertinent clinical data, including patient age, gender, baseline, and follow-up Snellen visual acuity, biomicroscopic examination findings, diagnosis, injection history, and length of follow-up were all recorded and tabulated. Multimodal imaging was performed on each eye at baseline and during the follow-up period as part of the routine management of eyes with NVAMD. Highresolution digital color photographs, red free photographs, and fluorescein angiography were obtained with the Zeiss (Carl Zeiss Meditec, Dublin, CA) or Topcon TRC-50XF fundus camera (Topcon Medical Systems, Paramus, NJ), and these data were analyzed and correlated with SD-OCT findings. Spectral domain optical coherence tomography examinations were obtained with the Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). Corresponding SD-OCTs of the chronic PEDs were carefully studied at multiple visits. The internal structure within the sub-PED compartment was analyzed, characteristic

Fig. 1. Schematic diagram of a multilayered PED.



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features were identified, and then correlated with visual outcome. Quantitative analysis of each PED was also performed whereby the maximal PED height was measured and recorded. Eyes that developed RPE tears after intravitreal antiVEGF injections were collected, graded, and analyzed according to the classification scheme first described by Sarraf et al.13 Briefly, RPE tears were graded from 1–4 based on the greatest length in the vector direction of the tear and involvement of the fovea. Grade 1 tears were defined as ,200 mm. Grade 2 tears were between 200 mm and 1-disk diameter. Grade 3 tears were .1-disk diameter. Grade 4 tears were defined as Grade 3 tears that involved the center of the fovea. Results Thirty-eight eyes of 34 patients were included in the study, with 4 individuals demonstrating bilateral involvement (Table 1). There were 28 females and 6 males, with a mean age of 79 years of age (median, 80; range, 61–94 years). Snellen best-corrected visual acuity at the most recent visit ranged from 20/20 to 20/400, with a mean and median of 20/50. Seventeen patients demonstrated best-corrected visual acuity of 20/40 or better in the involved eye. The underlying ocular disease associated with the Type I CNV complex was NVAMD in all cases. The most commonly administered treatment regimen was ranibizumab monotherapy in 21 eyes, whereas the remainder received various combinations of ranibizumab, bevacizumab, aflibercept, pegaptanib, and dexamethasone (Table 2). The mean number of intravitreal injections received was 28.2 (median, 23; Table 1. Patient Demographics and Ocular Findings Age, years Mean ± SD Median Range Gender (n = 34) Male, n (%) Female, n (%) Eye (n = 38) Right, n (%) Left, n (%) BCVA Snellen mean Snellen median Snellen range logMAR mean ± SD logMAR median logMAR range

79 ± 8.35 80 61–94 6 (17.6%) 28 (82.4%) 16 (42.1%) 22 (57.9%) 20/50 20/50 20/20–20/400 0.448 ± 0.315 0.397 0–1.301

BCVA, best-corrected visual acuity; CSR, central serous retinopathy.

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MULTILAYERED PED IN NEOVASCULAR AMD  RAHIMY ET AL Table 2. Treatment Received Intravitreal pharmacotherapy, n (%) Ranibizumab Ranibizumab + bevacizumab Ranibizumab + aflibercept Ranibizumab + bevacizumab + aflibercept Ranibizumab + bevacizumab + pegaptanib Ranibizumab + bevacizumab + aflibercept + pegaptanib Ranibizumab + bevacizumab + dexamethasone Ranibizumab + dexamethasone Ranibizumab + pegaptanib Bevacizumab Number of injections Mean ± SD Median Range Duration of therapy, months Mean ± SD Median Range

Table 3. Spectral Domain Optical Coherence Tomography Findings 21 (55.3) 5 (13.2) 4 (10.5) 2 (5.3) 1 (2.6) 1 (2.6)

Maximum PED height, mm Mean ± SD Median Range Lesion Extent, n (%) Subfoveal Extrafoveal Sub-RPE vascular networks, n (%) Pre-choroidal cleft, n (%)

384.2 ± 131.4 350.0 200–677 37 1 19 25

(97.4) (2.6) (50.0) (65.8)

1 (2.6) 1 (2.6) 1 (2.6) 1 (2.6) 28.2 ± 19.1 23 3–70 36.9 ± 14.4 37.5 6–84

range, 3–70). The duration of treatment with intravitreal anti-VEGF therapy averaged 36.9 months (median, 37.5; range, 6–84). One eye was treated for 6 months, one for 7 months, and one for 12 months, whereas the remaining 35 eyes received treatment for at least 24-month duration. Post-injection RPE tears were observed in 4 of 38 eyes (10.5% of eyes). Of these 4 instances, 3 Grade 2 tears and 1 Grade 3 tear were identified. No Grade 4 tears were encountered. On SD-OCT imaging, the mean maximum PED height for the 38 eyes measured 384.2 mm (median, 350; range, 200–677; Table 3). A subfoveal location of the vascularized PED was noted in 37 of 38 eyes. Within each PED, a fusiform, or spindle-shaped, complex of highly organized, layered, homogenous hyperreflective bands was visualized, which we have termed “multilayered PED” (Figures 1–5). These lamellae were found to localize beneath the hyperreflective RPE band and above the hyperreflective band believed to represent Bruch’s membrane and did not produce optical shadowing of the underlying tissues as would be seen with calcification. The number and density of layers were noted to increase over time with continued intravitreal anti-VEGF injections in isolated cases (Figure 3). The relation of the multilayered structure to Bruch’s membrane was difficult to ascertain; in some cases, the fusiform complex was contiguous with or embedded within Bruch’s membrane (Figure 2, J and K), whereas in other cases, a distinct separation was noted even with continued follow-up. Between the detached RPE and the fusiform complex, 19 eyes (50.0%) demonstrated heterogenous,

hyperreflective material consisting of large, irregular, dilated vascular profiles (Figures 1–5). This vascularlike tissue, consistent with the CNV complex, was typically adherent to the posterior surface of the RPE and exhibited marked variability in thickness and distribution along the PED undersurface (Figures 2–5). Underneath the fusiform complex, a hyporeflective space was noted to separate the CNV from the underlying choroid and Bruch’s membrane in 25 eyes (65.8%) (Figures 1, 2, and 4). We have selected the name “pre-choroidal cleft” to describe this lentiform, optically empty cavity between the multilayered lamellae and the outwardly bowed Bruch’s membrane. This finding was often associated with a peaked appearance of the roof of the PED and seemed to be the result of CNV contraction. However, some prechoroidal clefts partially resolved during the course of therapy, suggesting that their occurrence was at least partly because of serous fluid exudation.

Discussion Multilayered PED in eyes with NVAMD receiving serial intravitreal anti-VEGF injections appears to develop through a sequential layering of hyperreflective bands beneath the RPE in chronic fibrovascular PEDs. Spaide first observed “layers or lamella with clefts” within fibrovascular PEDs in 10 eyes with NVAMD that underwent enhanced depth imaging SD-OCT.1 We sought to expand on these observations by evaluation a larger cohort of eyes with extended follow-up. Detailed analysis of the SD-OCT images in this study revealed material within the sub PED compartment of differing optical density, indicative of the variable histological composition of the CNV complex. Near the base of the PED (adjacent to the choroid), a fusiform complex of homogenous, hyperreflective, lamella comprised the main body of this internal structure. These multilayered bands, we

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Fig. 2. Multilayered PED and associated SD-OCT features. Near-infrared reflectance (A), and corresponding SD-OCT line images at low (B), and high magnification (C) of a right eye demonstrating a multilayered PED: a fusiform, or spindle-shaped, complex of organized layers of homogenous hyperreflective bands (B, arrow, D) deep to the RPE within a chronic fibrovascular PED. Near-infrared reflectance (E), and corresponding SD-OCT line images at low (F) and high magnification (G) of a left eye showing heterogenous, hyperreflective, dilated, irregular vascular networks (F, arrow, H) adherent to the posterior surface of the RPE band. Near-infrared reflectance (I), and corresponding SD-OCT line images at low (J) and high magnification (K) of a right eye depicting a hyporeflective pre-choroidal cleft (J, arrow, L) separating the neovascular tissue complex from the underlying choroid and Bruch’s membrane.

believe, are comprised of fibrocellular tissue with contractile properties, resulting in the spindle-shaped appearance. Kinetic considerations suggest that fibrinous exudation from the overlying CNV complex may precipitate onto the surface of Bruch’s membrane, whereas the lower density fluid components are filtered out.14 The remaining fibrin may serve as a scaffolding matrix for blood vessel in-growth and connective tissue formation. Various histopathologic studies have shown that CNV is associated with not only neovascular ingrowth but also inflammatory cells, fibroblasts, myofibro-

blasts, glial cells, and RPE cells, which in chronic lesions become oriented in layers of fibrous tissue separated by clefts of lesser density.1,11,15–19 The involution and contraction that occurs with anti-VEGF therapy has been likened to a wound-healing response whereby the growth stimulus to the vascular component has been removed, allowing the inflammatory and fibrotic elements to predominate.16,20,21 Sequential deposition is further supported by the gradual increase in the lamellar component over time with repeated intravitreal anti-VEGF therapy and its propensity to fill more of the sub-RPE compartment of the

Fig. 3. Right eye of an 80-year-old woman with neovascular age-related macular degeneration after 25 intravitreal ranibizumab injections administered over 3 years. Most recent Snellen visual acuity was 20/30. Color fundus photograph (A) shows parafoveal pigment clumping associated with a PED. Late-phase fluorescein angiogram (B) demonstrates a fibrovascular PED with stippled late staining. Serial SD-OCT scans (C–E) show a predominantly serous PED with heterogenous, dilated, irregular vascular tissue adherent to the retinal pigment epithelial monolayer (D, arrows) in 2009. A progressively increasing fibrous component with more numerous multilayered hyperreflective bands within the fibrovascular PED is noted on SD-OCT in 2010 (F) and 2012 (H) associated with long-standing intravitreal ranibizumab therapy.

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Fig. 4. Left eye of an 88-yearold woman with neovascular age-related macular degeneration who has received intravitreal ranibizumab and aflibercept injections (41 total) for the previous 3 years. Most recent Snellen visual acuity was 20/50. Color fundus photograph (A) demonstrates pigment clumping consistent with a collapsed PED. Near-infrared reflectance (B) and corresponding spectral domain optical coherence tomography line image (C) shows a multilayered PED with an underlying hyporeflective pre-choroidal cleft (C, arrow) separating the neovascular tissue complex from the underlying choroid and Bruch’s membrane.

fibrovascular PED (Figure 3). Interestingly, although the majority of patients with multilayered PED were undergoing long-term anti-VEGF therapy, the finding had already developed in 2 patients as early as after 3 injections. Toward the apex of the PED (along the undersurface of the RPE monolayer), a transition into a more heterogenous, vascular-appearing tissue with large, irregular, dilated structures was identified in 50.0% of the eyes. A hyporeflective zone, presumably consisting of serous fluid exudate, occasionally separates this vascular material from the fusiform complex below. The detection of a layer of tissue behind the RPE within PEDs was initially made by Coscas et al3; however, this study was limited by the use of timedomain OCT and poor imaging resolution of the subRPE space. With the aid of enhanced depth imaging SD-OCT, Spaide1 subsequently proposed that this material abutting the undersurface of the RPE actually represented neovascularization. A histologic correlate of angiographically defined CNV tissue underlying the posterior surface of the RPE has since been described in the literature.12 More recently, Khan et al22 used

simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked SD-OCT to describe aneurysmal-like dilatations within a larger Type 1 CNV complex adherent to the undersurface of the RPE in 8 patients with polypoidal choroidal vasculopathy. Beneath the fusiform complex, formation of an outwardly bowed hyporeflective cavity, termed the pre-choroidal cleft, between the deeper fibrous component and the underlying hyperreflective choroid was indicative of horizontal contraction by the multilayered tissue complex and was observed in 65.8% of eyes in our study. In their aforementioned report, Khan et al22 also noted the presence of a pre-choroidal cleft in patients with polypoidal choroidal vasculopathy as one component of a “triple-layer” sign: sub-RPE neovascular tissue, followed by the hyporeflective space, and then the underlying choroid. Besides contractile forces, it is also possible that the cleft may develop because of hydrostatic forces generated by fluid leakage from the overlying neovascular complex. This is supported by our observations that some clefts resolved when more frequent intravitreal anti-VEGF

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Fig. 5. Right eye of a 79-year-old man with neovascular age-related macular degeneration who received 14 intravitreal ranibizumab and bevacizumab injections over the previous 21 months. Most recent Snellen visual acuity was 20/30. Color fundus photograph (A) demonstrates a central PED with concentric mottling of the RPE. Late-phase fluorescein angiogram (B) reveals stippled late staining of the fibrovascular PED. Near-infrared reflectance (C) and corresponding spectral domain optical coherence tomography line image (D, E) depict a multilayered PED (D, arrow) with heterogenous, hyperreflective vascular material located above the well-organized layered lamellar tissue complex.

treatment regimens were initiated or after switching to an alternative agent. Although the appearance of multilayered PED can be rather dramatic, these eyes maintain surprisingly good to excellent visual acuity, presumably because the neovascular and subsequent cicatricial process is confined to the sub-RPE space and effectively inhibited by continued anti-VEGF therapy.23 With isolation of the CNV complex within the sub-RPE compartment, the anatomical integrity of the outer retina is preserved, and mechanical disruption due to neovascular ingrowth and cicatrization in the subneurosensory space or toxicity due to accompanying hemorrhage is averted. Alternatively, it is plausible that the neovascular tissue may act as a surrogate for the choriocapillaris and provide oxygenation or nutritional support to the outer retina and RPE, thereby protecting against involution and geographic atrophy.24 Eyes with multilayered PED may be at lower risk of developing a high-grade RPE tear, a potentially devastating complication of therapy,25,26 due to the stabilizing effect of a fibrovascular tissue complex that fills the sub-RPE space and anchors the PED to the underlying Bruch’s complex. In our study, when tears did occur, they were less likely to present as severe high-grade tears (three Grade 2 tears and one Grade 3 tear), owing to the stabilizing properties of the lamellar complex.

Limitations of our study include its retrospective nature, lack of histopathologic confirmation, and no indocyanine green angiography correlate to delineate the sub-RPE vasculature. The absence of controls (i.e., treatment-naive patients with fibrovacular PEDs in which multilayered sub-RPE structures are not seen) limits the conclusions we can draw relating to the pathogenesis of these lesions. Because this was not a longitudinal study, we are unable determine what proportion of fibrovascular PEDs evolve into, or may even begin as multilayered PEDs. Furthermore, as there were no specific inclusion/exclusion criteria in this study, issues relating to the relative prevalence of multilayered PEDs cannot be adequately addressed; and at this time, we are unable to determine how common this finding is. A prospective study is currently underway and would be able to address many of the deficiencies stated herein. Despite these limitations, our series is the largest to date characterizing the multilayered PED, a signature SD-OCT finding in which a stereotypical lamellar fusiform complex develops within a chronic fibrovascular PED in eyes receiving ongoing anti-VEGF suppression. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile properties. Multilayered PED is typically seen in conjunction with neovascular tissue

MULTILAYERED PED IN NEOVASCULAR AMD  RAHIMY ET AL

adherent to the undersurface of the RPE monolayer. An associated hyporeflective space, the pre-choroidal cleft, often separates the fusiform complex from the underlying choroid and may be due to contraction and/ or the presence of fluid. We propose that anti-VEGF pharmacotherapy promotes stabilization and organization of the neovascular process within the sub-RPE space, resulting in preservation of the overlying RPE and photoreceptor populations. Thus, with continued treatment, most patients with chronic multilayered PEDs are able to retain an excellent long-term visual prognosis. Key words: age-related macular degeneration, antivascular endothelial growth factor, ranibizumab, choroidal neovascularization, vascularized pigment epithelial detachment, retinal pigment epithelialtears, spectral domain optical coherence tomography. References 1. Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol 2009;147:644–652. 2. Ahlers C, Michels S, Beckendorf A, et al. Three-dimensional imaging of pigment epithelial detachment in age-related macular degeneration using optical coherence tomography, retinal thickness analysis and topographic angiography. Graefes Arch Clin Exp Ophthalmol 2006;244:1233–1239. 3. Coscas F, Coscas G, Souied E, et al. Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol 2007;144: 592–599. 4. Sato T, Iida T, Hagimura N, Kishi S. Correlation of optical coherence tomography with angiography in retinal pigment epithelial detachment associated with age-related macular degeneration. Retina 2004;24:910–914. 5. Spaide RF, Curcio CA. Drusen characterization with multimodal imaging. Retina 2010;30:1441–1454. 6. Yasuno Y, Miura M, Kawana K, et al. Visualization of subretinal pigment epithelium morphologies of exudative macular diseases by high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci 2009;50:405–413. 7. Mukkamala SK, Costa RA, Fung A, et al. Optical coherence tomographic imaging of sub-retinal pigment epithelium lipid. Arch Ophthalmol 2012;130:1547–1553. 8. Hartnett ME, Weiter JJ, Garsd A, Jalkh AE. Classification of retinal pigment epithelial detachments associated with drusen. Graefes Arch Clin Exp Ophthalmol 1992;230:11–19. 9. Casswell AG, Kohen D, Bird AC. Retinal pigment epithelial detachments in the elderly: classification and outcome. Br J Ophthalmol 1985;69:397–403.

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10. Bressler NM, Silva JC, Bressler SB, et al. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. 1994. Retina 2005;25:130–142. 11. Green WR, Enger C. Age-related macular degeneration histopathologic studies. The 1992 Lorenz E. Zimmerman Lecture. Retina 2005;25:1519–1535. 12. Klein ML, Wilson DJ. Clinicopathologic correlation of choroidal and retinal neovascular lesions in age-related macular degeneration. Am J Ophthalmol 2011;151:161–169. 13. Sarraf D, Reddy S, Chiang A, et al. A new grading system for retinal pigment epithelial tears. Retina 2010;30:1039–1045. 14. Taarnhoj NC, Kjeka O, Larsen M. Kinetics of retinal lipoprotein precipitation and elimination after closure of subretinal new vessels. Invest Ophthalmol Vis Sci 2003;44:1680–1685. 15. Spaide RF. Rationale for combination therapies for choroidal neovascularization. Am J Ophthalmol 2006;141:149–156. 16. Grossniklaus HE, Ling JX, Wallace TM, et al. Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis 2002;8:119–126. 17. Tsutsumi-Miyahara C, Sonoda KH, Egashira K, et al. The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation. Br J Ophthalmol 2004;88:1217–1222. 18. Espinosa-Heidmann DG, Reinoso MA, Pina Y, et al. Quantitative enumeration of vascular smooth muscle cells and endothelial cells derived from bone marrow precursors in experimental choroidal neovascularization. Exp Eye Res 2005;80:369–378. 19. Killingsworth MC. Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1995;233:313–323. 20. Schlingemann RO. Role of growth factors and the wound healing response in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2004;242:91–101. 21. Gibran SK, Sachdev A, Stappler T, et al. Histological findings of a choroidal neovascular membrane removed at the time of macular translocation in a patient previously treated with intravitreal bevacizumab treatment (Avastin). Br J Ophthalmol 2007;91:602–604. 22. Khan S, Engelbert M, Imamura Y, Freund KB. Polypoidal choroidal vasculopathy: simultaneous indocyanine green angiography and eye-tracked spectral domain optical coherence tomography findings. Retina 2012;32:1057–1068. 23. Kumar N, Mrejen S, Fung AT, et al. Retinal pigment epithelial cell loss assessed by fundus autofluorescence imaging in neovascular age-related macular degeneration. Ophthalmology 2013;120:334–341. 24. Grossniklaus HE, Gass JD. Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes. Am J Ophthalmol 1998;126:59–69. 25. Chang LK, Flaxel CJ, Lauer AK, Sarraf D. RPE tears after pegaptanib treatment in age-related macular degeneration. Retina 2007;27:857–863. 26. Chang LK, Sarraf D. Tears of the retinal pigment epithelium: an old problem in a new era. Retina 2007;27:523–534.

Multilayered pigment epithelial detachment in neovascular age-related macular degeneration.

To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving...
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