Optical coherence tomography-guided classification of epiretinal membranes

DOI 10.1007/s10792-014-9975-z ORIGINAL PAPER Optical coherence tomography-guided classification of epiretinal membranes Vasileios Konidaris Sofia Androudi Alexandros Alexandridis Anna Dastiridou Periklis Brazitikos Received: 15 June 2013 / Accepted: 9 July 2014 Ó Springer Science+Business Media Dordrecht 2014 Abstract To study and classify epiretinal membranes (ERMs) based on spectral domain optical coherence tomography (SD-OCT) findings. One hundred and twelve patients with ERMs were examined clinically and underwent OCT examination. The anatomical structure of the macula and vitreoretinal interface was studied. ERMs were classified in two categories: A, with posterior vitreous detachment (PVD) (91 cases), and B, with the absence of PVD (21 cases). Category A was divided into two subcategories: A1, without contraction of the ERM (37 cases), and A2, with the presence of membrane contraction (54 cases). A2 was further subdivided into A2.1, with retinal folding (15 cases), A2.2, with edema (23 cases), A2.3, with cystoid macular edema (9 cases), and A2.4, with lamellar macular hole (7 cases). Category B was divided in two subcategories: B1, without vitreomacular traction (VMT) (4 cases), and B2, with the presence of VMT (17 cases). Category B2 was subdivided into B2.1, with edema (9 cases), B2.2, presenting retinal detachment (5 cases), and B2.3, with schisis (3 cases). OCT classification of ERMs provides useful information on the anatomical structure of the V. Konidaris (&) S. Androudi A. Alexandridis A. Dastiridou P. Brazitikos 1st Ophthalmology Department, AHEPA University Hospital, St. Kiriakidi 1, P.O. 54636, Thessaloníki, Greece e-mail: vasiliskon@hotmail.com retina, and the accurate estimation of vitreoretinal interface. Keywords Epiretinal membranes Optical coherence tomography Classification Spectral domain Macular pucker Introduction Epiretinal membrane (ERM) is characterized by proliferation of abnormal tissues on the surface of the macula or central retina. It is an avascular, fibrocellular membrane that produces various degrees of macular dysfunction [1]. The prevalence of idiopathic ERM seen on eye examination in patients aged over 50 years is approximately 6 % [2]. Surgical membrane peeling is recommended for patients who have substantial visual acuity loss, metamorphopsia, or monocular diplopia. Following surgery, most of the macular distortion resolves and visual improvement of two or more Snellen lines occurs in 60 87 % of eyes [3 6]. Optical coherence tomography (OCT) is a technique that provides high-resolution, cross-sectional images of the retinal structure and is particularly useful in examining the macula [7 10]. Spectral domain OCT (SD-OCT) has many advantages, as it provides improved axial resolution in tissue, improved image quality, and shorter scanning time [11]. Many scientists have attempted to establish prognostic

indicators for postoperative success; these include preoperative vision, duration of symptoms [12 17], membrane location and thickness [18 20], retinal thickness [21], and cystoid macular edema (CME) [6, 14, 15, 22]. The aim of the present study was to investigate the significance of the above-mentioned factors using data of the quantitative measurements of SD-OCT. Materials and methods One hundred and twelve patients (53 males, 47.3 %), with ERM who visited the outpatients department of the first Ophthalmology Clinic of A.H.E.P.A., University Hospital, Thessaloniki, Greece, during 2009 to 2011, were included in this study. The age of patients ranged from 12 to 80 years (mean ± SD, 66.8 ± 12.3 years). Patients were eligible for the study if they presented with nonvascular-appearing ERM confined to the macula. Both idiopathic and secondary ERMs were included. ERMs were defined as idiopathic when they were observed in healthy eyes with no associated ocular abnormality. Secondary ERMs were those found in association with retinal vascular diseases (e.g., vascular occlusions, diabetic retinopathy), postsurgical conditions, posttraumatic conditions, or associated with ocular inflammations. Exclusion criteria were the presence of known or critically apparent macular disease (e.g., age-related macular degeneration) that could affect the functional status of the macula or could interfere with the visual acuity result. All patients provided written informed consent. Clinical diagnosis was determined with slitlamp biomicroscopy and fundus photography. OCT imaging of the macula was performed through a dilated pupil. ERMs were demonstrated as thin and highly reflective linear structures anterior to the retinal surface. The macular thickness was measured by the SD-OCT software. OCT was performed using Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA). The study followed the principles in the Declaration of Helsinki. Initial examinations Baseline data included age, sex, best-corrected visual acuity (BCVA) for both eyes measured on Snellen charts, slit-lamp examination, applanation tonometry, dilated fundus examination with a noncontact?90d lens as well as Goldman contact lens. Posterior vitreous detachment was defined as a separation between the posterior vitreous cortex and the ILM of the retina. Posterior vitreous detachment (PVD) was diagnosed based on ophthalmoscopy and/or OCT. To confirm the diagnosis of PVD, in equivocal cases, we did perform a raster scan above the optic nerve to identify whether the vitreous was attached to the optic nerve. Ultrasound B scan was not performed in any of our cases. The ERM contraction was defined as the presence of wrinkling on the retina (tangential traction). Vitreomacular traction was defined as a vitreomacular adhesion that involved the foveal region and caused morphologic alterations of the central macula (tractional maculopathy). In cases of VMT, the patients were categorized as having the vitreous attached on the retina. The anatomical structure of the macula was studied with the use of SD-OCT, following the Macular Cube 512 9 128 scanning protocol. Follow-up examinations Examination was performed after a 6-month period and included determination of BCVA, slit-lamp examination, applanation tonometry, fundus examination, and scanning of the macula with the SD-OCT. Statistical analysis All data were collected on a MS-Excel 2003 spreadsheet (Microsoft Corporation, Redmond, WA) and analyzed using SPSS version 14.0 for Windows (SPSS, Inc., Chicago, IL). Extended graphical analysis and methods such as regression models and analysis of variance models were applied when appropriate. Results The overall classification of the ERMs is shown in Fig. 1. Representative OCT images are shown in Fig. 2. Briefly, patients with ERMs were initially divided into two distinct categories based on the presence or absence of PVD, as identified with the SD- OCT or biomicroscopically: Category A included 91 (81.3 %) patients who presented with PVD, while category B included 21 (18.7 %) patients without

Fig. 1 Classification of epiretinal membranes PVD. The mean macular thickness measured with the SD-OCT preoperatively in category A was 365.77 ± 14.83 lm, whereas the macular thickness in category B was 445.43 ± 30.46 lm, a statistical significant difference (Mann Whitney test, p = 0.014) (Fig. 3a). Moreover, the correlation between macular thickness and visual acuity was found significant (ANOVA test, p = 0.012). Depending on the presence of membrane contraction, the 91 patients in category A were further subdivided into two subcategories: category A1, with 37 (40.66 %) patients with ERMs without contraction, and category A2, with 54 (59.34 %) patients with ERMs with apparent contraction. The mean macular thickness in category A1 was 286.86 ± 89.18 lm, whereas the respective value in category A2 was 420.85 ± 144.32 lm (p \ 0.05) (Fig. 3b). In addition, category A1 patients had less visual complaints comparing to all other categories. Category A1 patients had better best-corrected visual acuity (BCVA) than those of A2; however, the difference was not statistically significant (p [ 0.05) (Fig. 4a). A2 category was further subdivided into four subcategories: A2.1 included ERMs with folding of the retina (15 cases), A2.2, ERMs with edema of the macular area (diffuse retinal thickening affecting the macula) (23 cases), A2.3, ERMs with CME (9 cases), and A2.4, ERMs with lamellar macular hole (LMH) (7 cases). LMHs were defined by the presence of a partial thickness macular hole, with residual outer retinal tissue covering the foveal retinal pigment epithelium, caused by the tangential traction forces from ERMs. The mean macular thickness for the four categories of ERMs was calculated: 383.4 ± 27.82 lm in category A2.1, 423.83 ± 55.68 lm in category A2.2, 579.4 ± 54.79 lm in category A2.3, and 267 ± 53.38 lm in category A2.4. The macular thickness among the four subcategories was significantly different (Kruskal Wallis test, p \ 0.001); however, the difference of the macular thickness between categories A2.1 and A2.2, although existing, was not statistically significant (p = 0.086), while it was significant between all other

Fig. 2 Epiretinal membranes with posterior vitreous detachment without contraction (a), with folding (b), with edema (c), with cystoid macular edema (d), and with lamellar macular hole (e). Epiretinal membranes with vitreous attachment without traction (f), with VMT and the presence of edema (g), and with schisis (h)

Fig. 3 Mean macular thickness in the different categories. a Categories A (with PVD) and B (without PVD). b Categories A1 (without contraction) and A2 (with contraction). c Categories A2.1 (with folding), A2.2 (with edema), A2.3 (with cystoid macular edema), and A2.4 (with lamellar macular holes). d Categories B1 (without VMT) and B2 (with VMT). e Category B1 and subcategories of B2: B2.1 (with edema), B2.2 (with retinal detachment), and B2.3 (with schisis) (PVD posterior vitreous detachment; CME cystoid macular edema; LMH lamellar macular hole; VMT vitreomacular traction; RD retinal detachment) subcategories of A2 (Fig. 3c). The difference of BCVA among all four subcategories was also significant (p \ 0.05) (Fig. 4b). Patients of category A2.4 were found minimally symptomatic and had less affected BCVA (with normal or almost normal limits). This fact can explain why no statistically significant difference concerning the V.A. (p = 0.414) and the macular thickness (p = 0.676) between category A1 and A2.4 was observed. Depending on the presence of vitreomacular traction (VMT), category B was subdivided into B1 (the absence of VMT) (4 cases) and B2 (the presence of VMT) (17 cases). The mean macular thickness in category B1 was 296.25 ± 68.13 lm, whereas in B2, the mean macular thickness was 480.53 ± 128.86 lm. Macular thickness was statistically higher in category B2 (p = 0.013) (Fig. 3d). BCVA was accordingly different with statistic significance (p = 0.027) (Fig. 4c). ERMs of B2 category were further classified into 3 subcategories: B2.1, with presence of edema (9 cases), B2.2, with retinal detachment (RD) (foveal RD, defined as subretinal accumulation of fluid in the foveal region) (5 cases), and B2.3, with schisis (3 cases). The mean macular thickness in the category B2.1, B2.2, and B2.3 was 412.89 ± 41.29, 528.2 ± 40.31, and 604 ± 44.96 lm, respectively. The difference of macular thickness among the three subcategories, although existing, was not statistically significant (p = 0.39). However, the difference of macular thickness between these three subcategories and category B1 was statistically significant (p = 0.027) (Fig. 3e). Out of the 112 patients, surgical removal of the ERMs was performed in 54 (48.2 %), whereas for 58 (51.8 %), a decision for observation without intervention was made. Improvement in visual acuity was observed in 45 (83.4 %) of the patients who underwent surgical treatment, in 7 (12.5 %) visual acuity remained unchanged, while in 2 (4.1 %) vision

Fig. 4 Mean visual acuity in a patients with and without ERM contraction. b Patients with folding, edema, cystoid macular edema and lamellar macular holes. c Patients with and without VMT (CME cystoid macular edema; LMH lamellar macular hole) deteriorated slightly. The mean visual acuity increased postoperatively by three Snellen lines (p \ 0.05). Similarly, macular thickness of surgically treated patients was reduced statistically significantly, approaching the mean macular thickness of patients who were on observation. Macular thickness preoperatively in patients who underwent surgical treatment was 436.19 ± 149.53 lm, while thickness in the rest of the patients was 328.4 ± 115.8 lm (p \ 0.05). Regarding the 58 patients who were observed, macular thickness did not change statistically significantly during the follow-up period of the study (p = 0.485). Specifically, the mean macular thickness at baseline was 328.4 ± 115.8 lm, and at the end of the study, it was 346.83 ± 81.69 lm. Accordingly, it was found that the change in mean visual acuity was not statistically significant. Discussion Current classification of ERMs is mainly based on the biomicroscopical examination of the fundus and on the fluorescein angiography. Gass first in 1987 suggested a graded classification of the ERMs, according to their clinical appearance, in cellophane maculopathy, crinkled cellophane maculopathy, and macular pucker [23]. Depending on their pathogenesis, ERMs are characterized as idiopathic or secondary; VMT syndrome represents a distinct entity of tractional maculopathy. However, till today, a more detailed classification has not prevailed. In the present study, OCT was applied as an additional method of imaging, for the classification of ERMs, which were classified according to their anatomical features and the consequent morphologic appearance of the fundus. OCT enabled the observation of the architectural changes on the retina, which correspond to each different forms of ERMs. Based on data and images from OCT, ERMs were classified into 9 distinct categories. It was observed that ERMs appeared in different forms, which had a respectively different impact on the architecture of the retina and consequently on the visual ability of the patients. PVD was observed in 81.3 % of patients, incidence similar to that described by other authors (range 75 93 %) [3, 24 27]. PVD was present in all eyes with LMHs. There was a statistically significant difference of macular thickness as measured by the built-in protocols of OCT, in all subcategories of ERMs. Moreover, macular thickness was correlated with visual acuity, a result that corresponds to the literature findings [18 21, 28]. The difference of BCVA between categories A1 and A2 is due to the fact that contracted ERMs produce tangential traction on the full-thickness neural retina, which results in more severe damage of macular function and consequently in visual changes, such as metamorphopsia or diplopia [29]. However, differences of visual acuity between some groups were not always statistically significant. Further studies are necessary to further estimate the findings of this study. The morphology of ERMs is clinically important, with respect to prognosis and treatment response. The OCT classification of ERMs will enhance the more accurate estimation of prognostic factors, such as macular thickness, loss of the architectural structure of the retina, and the presence of CME, and will therefore help in correct surgical indication and accurate estimation of the postoperative results. Using SD- OCT, the cross-sectional structure of the affected

retina can be reviewed easily and the retinal thickness can be measured objectively, enabling the classification of ERMs into nine different categories, depending on their anatomical structure. In conclusion, this study was a first attempt to classify the ERMs by the use of OCT, which contributed to the accurate estimation of the anatomical vitreoretinal interface. Whether this classification is of clinical relevance remains to be elucidated. Correlation between morphology of the ERMs and the retina, together with the clinical features of the ERMs, can be of clinical significance with respect to natural history, prognostic factors, and response to treatment. Conflict of interest The authors report no conflict of interests. The authors alone are responsible for the content and writing of the paper. The manuscript has not been published elsewhere, and it has not been submitted simultaneously for publication elsewhere. References 1. Brazitikos P, Dereklis D, Stangos NT (2002) Epiretinal membrane (ERM). In: Stangos NT (ed) Clinical ophthalmology. University Studio Press, Thessaloniki, pp 580 583 2. Roth AM, Foos RY (1971) Surface wrinkling retinopathy in eyes enucleated at autopsy. Trans Am Acad Ophthalmol Otolaryngol 75:1047 1058 3. de Bustros S, Thompson JT, Michels RG, Rice TA, Glaser BM (1988) Vitrectomy for idiopathic epiretinal membranes causing macular pucker. Br J Ophthalmol 72:692 695 4. Margheiro RM (1994) Epiretinal macular membranes. In: Albert DM, Jakobiec FA (eds) Principles and practice of ophthalmology. W.B Saunders, Philadelphia, pp 919 926 5. Wickham L, Zdenek G (2013) Epiretinal membranes. In: Ryan SJ (ed) Retina. Saunders, St. Louis, pp 1954 1961 6. von Gunten S, Pournaras CJ, de Gottrau P, Brazitikos P (1994) Prognostic factors in surgical treatment of epiretinal membranes. Klin Monatsbl Augenheilkd 204:309 312 7. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254:1178 1181 8. Izatt JA, Hee MR, Swanson EA, Lin CP, Huang D, Schuman JS, Puliafito CA, Fujimoto JG (1994) Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol 112:1584 1589 9. Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, Puliafito CA, Fujimoto JG (1995) Optical coherence tomography of the human retina. Arch Ophthalmol 113: 325 332 10. Fujimoto JG (2003) Optical coherence tomography for ultrahigh resolution in vivo imaging. Nat Biotechnol 21:1361 1367 11. Gamulescu MA, Helbig H (2011) OCT in macular diagnostics possibilities and limitations. Klin Monbl Augenheilkd 228:599 606 12. Dellaporta A (1973) Macular pucker and peripheral retinal lesions. Trans Am Ophthalmol Soc 71:329 340 13. Charles S (1987) Vitreous microsurgery, 2nd edn. Williams and Wilkins Co, Baltimore 14. Poliner LS, Olk RJ, Grand MG, Escoffery RF, Okun E, Boniuk I (1988) Surgical management of premacular fibroplasia. Arch Ophthalmol 106:761 764 15. Rice TA, De Bustros S, Michels RG, Thompson JT, Debanne SM, Rowland DY (1986) Prognostic factors in vitrectomy for epiretinal membranes of the macula. Ophthalmology 93:602 610 16. Pesin SR, Olk RJ, Grand MG, Boniuk I, Arribas NP, Thomas MA, Williams DF, Burgess D (1991) Vitrectomy for premacular fibroplasia. Prognostic factors, long-term follow-up, and time course of visual improvement. Ophthalmology 98:1109 1114 17. Immonen I, Vaheri A, Tommila P, Siren V (1996) Plasminogen activation in epiretinal membranes. Graefe s Arch Clin Exp Ophthalmol 234:664 669 18. Nussenblatt RB, Kaufman SC, Palestine AG, Davis MD, Ferris FL III (1987) Macular thickening and visual acuity: measurements in patients with cystoid macular edema. Ophthalmology 94:1134 1139 19. Liu X, Ling Y, Huang J, Zheng X (2002) Optic coherence tomography of idiopathic macular epiretinal membranes. Yan Ke Xue Bao 18:14 19 20. Michalewski J, Michalewska Z, Cisiecki S, Nawrocki J (2007) Morphologically functional correlations of macular pathology connected with epiretinal membrane formation in spectral optical coherence tomography (SOCT). Graefe s Arch Clin Exp Ophthalmol 245:1623 1631 21. Suzuki T, Terasaki H, Niwa T, Mori M, Kondo M, Miyake Y (2003) Optical coherence tomography and focal macular electroretinogram in eyes with epiretinal membrane and macular pseudohole. Am J Ophthalmol 136:62 67 22. Trese M, Chandler D, Machemer R (1983) Macular pucker. II ultrastructure. Graefe s Arch Clin Exp Ophthalmol 221:16 26 23. Gass JDM (1997) stereoscopic atlas of macular diseases; diagnosis and treatment, 4th edn. Mosby, St. Louis, pp 938 951 24. Wise GN (1975) Clinical features of idiopathic preretinal macular fibrosis. Am J Ophthalmol 79:349 357 25. Appiah AP, Hirose T, Kado M (1988) A review of 324 cases of idiopathic premacular gliosis. Am J Ophthalmol 106:533 535 26. Sidd RJ, Fine SL, Owens SL, Patz A (1982) Idiopathic preretinal gliosis. Am J Ophthalmol 94:44 48 27. Hirokawa H, Jalkh AE, Takahashi M, Takahashi M, Trempe CL, Schepens CL (1986) Role of the vitreous in idiopathic preretinal fibrosis. Am J Ophthalmol 101:166 169 28. Wilkins JR, Puliafito CA, Hee MR, Duker JS, Reichel E, Coker JG, Schuman JS, Swanson EA, Fujimoto JG (1996) Characterization of epiretinal membranes using optical coherence tomography. Ophthalmology 103:2142 2151 29. Johnson MW (2004) Epiretinal membrane. In: Yanoff M, Duker JS (eds) Ophthalmology, 2nd edn. Mosby, St. Louis, pp 947 950