Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Foveal structure and vasculature in eyes with idiopathic epiretinal membrane

Foveal structure and vasculature in eyes with idiopathic epiretinal membrane a1111111111 a1111111111 a1111111111 Purpose To examine the foveal structure and vasculature in eyes with an idiopathic epiretinal mem- brane (ERM). OPENACCESS Methods Citation: Okawa Y, Maruko I, Kawai M, Hasegawa T, Arakawa H, Iida T (2019) Foveal structure and Forty-nine eyes of 48 patients with an idiopathic ERM were studied. The superficial foveal vasculature in eyes with idiopathic epiretinal avascular zone (FAZ) was measured by optical coherence tomography angiography membrane. PLoS ONE 14(4): e0214881. https:// (OCTA; RTVue XR Avanti, Optovue Inc., Fremont, CA), and the central foveal thickness doi.org/10.1371/journal.pone.0214881 (CFT) was measured by swept source OCT (DRI-OCT, Topcon, Japan). Twenty eyes Editor: Pukhraj Rishi, Sankara Nethralya, Medical underwent vitrectomy with internal limiting membrane (ILM) peeling, and the FAZ and CFT Research Foundation, INDIA were evaluated pre- and postoperatively. Forty-nine eyes of 49 age-matched healthy sub- Received: December 25, 2018 jects were also examined as control. Accepted: March 21, 2019 Published: April 2, 2019 Results Copyright:© 2019 Okawa et al. This is an open The FAZ in eyes with an ERM was significantly smaller than that of the control eyes (0.188 access article distributed under the terms of the 2 2 ±0.16 mm vs 0.328±0.14 mm , P<0.01). The CFT in eyes with an ERM was significantly Creative Commons Attribution License, which thicker than that of control eyes (315±0.14μm vs 193±0.14μm, P<0.01). The size of the permits unrestricted use, distribution, and reproduction in any medium, provided the original FAZ was strongly correlated with the CFT (ERM, R = -0.753; control, R = -0.61, both author and source are credited. P<0.01). The postoperative size of the FAZ was not significantly different from the preopera- 2 2 Data Availability Statement: All relevant data are tive size (0.115 mm vs 0.128 mm , P = 0.17) but the CFT was significantly thinner (370μm within the manuscript and its Supporting vs 288μm, P<0.01) after the vitrectomy with ILM peeling in 20 eyes. Information files. Funding: Dr. Okawa has nothing to disclose. Dr. Conclusions Maruko reports grants from JSPS KAKENHI (Grant The results indicate that an ERM might affect the morphology and vasculature of not only Number JP16K11274), grants and personal fees from Novartis Pharma K.K., personal fees from the inner but also the outer retina before and after vitrectomy with ILM peeling. The FAZ Bayer Yakuhin, Ltd., personal fees from Santen area might have been affected by the ILM peeling. Pharmaceutical Inc., personal fees from Alcon Japan, Ltd., personal fees from Topcon Co., Ltd., personal fees from Senju Pharmaceutical Co., Ltd., personal fees from NIDEK Co., Ltd., outside the PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 1 / 8 Foveal structure and vasculature in eyes with ERM submitted work. Dr. Kawai has nothing to disclose. Introduction Dr. Hasegawa has nothing to disclose. Dr. Arakawa An idiopathic epiretinal membrane (ERM) can alter the foveal morphology by its traction on has nothing to disclose. Dr. Iida reports grants and the retina, and the morphological changes can cause distortions of vision and reductions of the personal fees from Novartis Pharma K.K. (Japan), personal fees from Bayer Yakuhin, Ltd. (Japan), visual acuity. The results of optical coherence tomographic (OCT) studies have shown a thick- grants and personal fees from Santen ening of the fovea and a disruption of the ellipsoid zone of the photoreceptors in eyes with an Pharmaceutical Co., Ltd. (Japan), grants from ERM [1–5]. The disruption of the ellipsoid zone indicates a disorder in the alignment of the Nidek, research support from Chuosangyo (Japan), photoreceptors which most likely accounts for the visual dysfunctions. Inoue et al [4] reported outside the submitted work. The funders had no that the improvement of the visual acuity after removing an ERM was not significant after vit- role in the study design, data collection and analysis, decision to publish, or preparation of the reous surgery. However, because there is no inner retina at the fovea, these reports only evalu- manuscript. ated the changes of the outer retina in eyes with an idiopathic ERM. There are recent studies that report that the visual abnormalities can be present in eyes with Competing interests: The authors have no proprietary interest in any aspect of this paper. good visual acuities and without any disruption of the ellipsoid zone. This was suggested to There are no patents, products in development or result from changes in the inner retina caused by the ERM [6–8]. marketed products to declare. This does not alter However, it has not been adequately reported that the inner retina is altered in eyes with an our adherence to all the PLOS ONE policies on ERM. sharing data and materials, as detailed online in the Thus, the purpose of this study was to determine the effect of an ERM on the inner retina. guide for authors. To accomplish this, the superficial foveal avascular zone (FAZ) was measured by optical coher- ence tomography angiography (OCTA), and the central foveal thickness (CFT) was measured by swept source OCT in eyes with an ERM. In addition, the areas of the FAZ and CFT were evaluated after vitrectomy with ERM and internal limiting membrane (ILM) peeling. Materials and methods This was a retrospective study, and the procedures used conformed to the tenets of the Decla- ration of Helsinki. The Institutional Review Board of the Tokyo Women’s Medical University, School of Medicine approved the procedures used. All examinations were performed after an informed consent was obtained. Forty-nine eyes of 48 patients (25 men, 24 women; average age, 67.1 years) with an idio- pathic ERM were examined by OCTA (RTVue XR Avanti, Optovue Inc., Fremont, CA) with a scan of 3 x 3 mm centered on the fovea. Eyes with high myopia, diabetic retinopathy, retinal vein occlusion, a history of pars plana vitrectomy, and inflammation other than secondary to an ERM were excluded. Eyes without a posterior vitreous detachment were also excluded to avoid cases of secondary ERM. In 20 eyes among all eyes, the FAZ was evaluated after pars plana vitrectomy with ERM and ILM peeling. Cataract surgery was performed at the time of vitrectomy in all eyes. Forty-nine eyes of 49 age-matched healthy individuals were also exam- ined as controls. None of these eyes had an ERM and had undergone vitrectomy. The OCTA (RTVue XR Avanti) instrument can record the microvascular structures using a split spectrum amplitude-decorrelation angiography without fluorescein or indocyanine green dye. This device records 70,000 A-scans/second with motion correction which helps in record- ing clear en face OCTA images. The software embedded in the OCTA device automatically shows four en face OCTA images divided into four depths; the superficial capillary plexus, deep capillary plexus, outer retina, and choriocapillaris layers. In this study, the superficial cap- illary plexus was used to avoid segmentation errors. Eyes with blurred OCTA images were excluded even if the motion correction technology was used. The area of the FAZ was measured by the polygon selection tool of the ImageJ software (National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index. html). The measurement of the FAZ area was done for only the superficial layer images because the FAZ area in the deep plexus layer can be affected by projection artifacts. All FAZ areas were measured by two co-authors (YO and IM), and their values were averaged. The PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 2 / 8 Foveal structure and vasculature in eyes with ERM change in the ratio of FAZ area after vitrectomy was calculated as, (postoperative FAZ area– preoperative FAZ area)/preoperative FAZ area. All eyes were also examined by swept-source OCT (DRI-OCT, Topcon, Japan), and the images were used to measure the central foveal thickness (CFT). The CFT was determined with the caliper tool in the OCT software. The change in the ratio of CFT after vitrectomy was calculated as, (postoperative CFT–preoperative CFT)/preoperative CFT. We also evaluated the irregularity and/or disruption of the ellipsoid zone of the photorecep- tors in the cross-sectional images. Twenty eyes underwent vitrectomy with ERM and ILM peeling, and we determined whether the foveal contour was restored in the DRI-OCT images. We classified eyes as having a restored foveal contour when the retinal thickness at the center of the fovea was at least 50 μm thinner than that of the retina 1 mm away from the foveola without intraretinal edema [9]. The BCVA was measured with a Japanese standard decimal visual chart, and the decimal visual acuities were converted to the logarithm of the minimum angle of resolution (logMAR) for the statistical analyses. Statistical analyses Mann–Whitney U-tests were used to determine the significance of the differences in the FAZ area and CFT between the ERM and control groups. Wilcoxon signed-rank tests were used to determine the significance of the differences in the FAZ area, CFT, and BCVA before and after the ERM surgery. Spearman’s tests were used to determine the significance of the correlations. All P-values were two-sided and values <0.05 were considered statically significant. All statisti- cal analyses were performed with free software EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [10]. More exactly, it is a modified version of the R commander designed to add statistical functions frequently used in biostatistics. Results The mean area of the FAZ was 0.188 ± 0.16 mm in the eyes with an ERM which was signifi- cantly smaller than the 0.328 ± 0.14 mm in the control eyes (P <0.01). The FAZ area in the eyes with an ERM was not significantly correlated with the age (R = 0.048, P = 0.74) or the 2 2 BCVA (R = -0.233, P = 0.11). The area of the FAZ increased from 0.115 mm to 0.128 mm after vitrectomy in the 20 eyes with a mean follow-up period of 147 days (range 23–443 days). This increase was not significant (P = 0.17). The mean postoperative FAZ area was signifi- cantly smaller than that of the control eyes (P <0.01). The FAZ area enlarged in 14 eyes (Fig 1) and decreased in 6 eyes (Fig 2). The mean area of the FAZ with enlargement after vitrectomy 2 2 was smaller than decrease in the area of the FAZ in the other eyes (0.091 mm vs 0.171 mm , P = 0.06). The mean change in the ratio was not significantly correlated with the age (R = 0.421, P = 0.06) and the length of the follow-up period (R = -0.357, P = 0.12). Seven eyes were followed for more than 6 months, and the FAZ area increased in 2 eyes and decreased in 5 eyes. Although there was no significant difference between pre- and postoperative FAZ areas 2 2 (0.166 mm vs 0.11 mm , P = 0.30) in these eyes, the change in the ratio of the areas in the eyes with more than 6 months of follow-up was significantly smaller than that of eyes with less than 6 months of follow-up (-0.170 vs 0.750, P <0.01). The mean CFT in the eyes with an ERM was significantly thicker than that of the control eyes (315 ± 22 μm vs 193 ± 100 μm, P <0.01), and the CFT was significantly correlated with the BCVA (R = 0.315, P = 0.03) but not with the age (R = -0.102, P = 0.49). The CFT decreased significantly from 370 μm to 288 μm after vitrectomy in the 20 eyes (P <0.01), however the PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 3 / 8 Foveal structure and vasculature in eyes with ERM Fig 1. Representative case with an epiretinal membrane (EM). The foveal avascular zone (FAZ) increased and the central foveal thickness (CFT) decreased after vitrectomy with peeling of the internal limiting membrane (ILM). A: Superficial optical coherence tomography angiography (OCTA) image before vitrectomy. Area of FAZ is 0.072 mm . B: Superficial OCTA image after vitrectomy. Area of FAZ is 0.148 mm . C: Cross-sectional OCT image before vitrectomy. The central foveal thickness (CFT) is 405 μm. D: Cross-sectional OCT image after vitrectomy. The CFT is 270 μm. https://doi.org/10.1371/journal.pone.0214881.g001 mean postoperative CFT was still significantly thicker than that of the control eyes (P <0.01). In the eyes that underwent vitrectomy and had an increase in the area of the FAZ, the CFT was significantly thicker than in the eyes with a reduction in the size of the FAZ (393 μm vs 316 μm, P <0.01). The mean change in the ratio of the areas was not correlated with the age (R = -0.046, P = 0.85) and the duration of the follow-up period (R = 0.371, P = 0.11). The area of the FAZ was negatively and significantly correlated with the CFT in the eyes with an ERM (R = -0.753, P <0.01, Fig 3A) and also in the control eyes (R = -0.610, P <0.01, Fig 3B). The change in the ratios of both the FAZ area and the CFT were significantly corre- lated (R = -0.743, P <0.01). There were no abnormalities of the ellipsoid zone at the fovea in the cross-sectional OCT images. The restoration of the foveal contour after vitrectomy was detected in 12 (63.2%) of 19 eyes without a foveal contour before the vitrectomy. An enlargement of the FAZ was found after vitrectomy in 10 (83.3%) of 12 eyes with the restoration of the foveal contour. The mean decimal BCVA in all eyes with an ERM was 0.90, and that of the 20 eyes treated with vitrectomy was 0.88 at the baseline and 1.02 after the surgery. The BCVA after the vitrec- tomy was not significantly changed (P = 0.13). The findings in all of the eyes with an ERM are summarized in Supplemental Table (S1 Table). Discussion The results showed that the area of the FAZ was smaller and the CFT was thicker in the eyes with an ERM than in age-matched control eyes. This difference was still present after PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 4 / 8 Foveal structure and vasculature in eyes with ERM Fig 2. Representative case with a reduction of the FAZ and an increase in the CFT after vitrectomy with ILM peeling. A: Superficial OCTA image before vitrectomy. Area of FAZ is 0.426 mm . B: Superficial OCTA image after vitrectomy. Area of FAZ is 0.119 mm . C: Cross-sectional OCT image before vitrectomy. CFT is 280 μm. D: Cross- sectional OCT image after vitrectomy. CFT is 335 μm. https://doi.org/10.1371/journal.pone.0214881.g002 successful removal of the ERM by vitrectomy with ILM peeling. This indicated that the trac- tional effects of ERM might persist even after its removal. Although the CFT became signifi- cantly thinner after vitrectomy, the decrease in the FAZ area was not significant. These results may be due to not only the centrifugal effect of ERM removal but also the centripetal move- ment of the retina after the ILM peeling. An ERM can cause distortions of vision and visual dysfunction through a traction on the surface of the retina. Thus, vitrectomy is required to release the traction. Since the early times of OCT [1–5], alterations of various parameters associated with the visual function were Fig 3. Plot showing the relationship between the FAZ area and the CFT. The FAZ is negatively and significantly correlated with the CFT in the eyes with an ERM (A), and control eyes (B). https://doi.org/10.1371/journal.pone.0214881.g003 PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 5 / 8 Foveal structure and vasculature in eyes with ERM detected in eyes with an ERM, e.g., thicker CFT, greater distortion of vision, good preoperative vision, better postoperative vision, greater postoperative reduction of the CFT, better visual prognosis, changes in the postoperative foveal depression correlated with the postoperative vision, and the integrity of the ellipsoid zone that were significantly correlated with the postop- erative vision. However, these studies mainly evaluated the changes of the outer retina because an inner retina did not exist at the fovea. In our cohort, none of the eyes had a disruption of the ellipsoid zone. Most recent studies focused on the inner retinal layer in eyes with an ERM and without any abnormalities of the outer retina. Koo et al [6] evaluated the inner retina from volume scans of eyes with an ERM, and they reported that the thickness of the inner retina at the parafovea (within 3 mm) was significantly associated with the visual dysfunction even with an intact photoreceptor layer. Joe et al [7] reported that the presence of an inner retinal layer at the fovea was the major determinant of the visual acuity in eyes with an ERM. Zur et al [8] reported the extent of the disorganization of the retinal inner layers (DRIL), a biomarker that can predict the vision change in patients with diabetic macular edema, had been associated with the visual prognosis after macular surgery for ERM. OCTA has recently been used to evaluate ERM cases. Thus, Neris et al [11] reported that the foveal vessel density (VD) in eyes with an ERM was significantly higher than that of normal controls. They attributed this to a central displacement of the foveal capillaries. Kim et al [12] reported that the postoperative area of the FAZ was smaller in postoperative eyes with an ERM than the fellow eyes. Chen et al [13] compared the FAZ area and foveal VD before to that after vitrectomy for an ERM, and they reported an enlargement in FAZ area and a reduction in foveal VD. Kitagawa et al [14] also reported that the area of the FAZ increased significantly after vitrectomy for ERM, although the increase was small. Thus, evaluations of the retinal blood vessels of the inner retina by OCTA can be considered to be an evaluation of the struc- ture of the inner retina. OCTA can be used to evaluate not only the FAZ and VD but also the foveal morphology using the depth and morphologic information obtained at the same time as the structure. Samara et al. described a significant negative correlation between the FAZ area and CFT in normal eyes [15]. Our results confirmed the negative correlation between FAZ area and CFT even in ERM cases. Although it was possible that the slow foveal structure changes after vitrectomy with ILM peeling, the mean FAZ area after vitrectomy was still significantly smaller at least 6 months fol- low-up than that of the control eyes. Interestingly, the FAZ area did not change significantly after vitrectomy although the CFT became thinner. These results suggest that the ERM affected the outer retina more than the inner retina. Because the postoperative BCVA was not significantly correlated with the FAZ area but was significantly correlated with the CFT, the morphological changes of the outer retina might affect the BCVA more than the changes of the inner retina. In our cohort, there were six eyes that had a reduction of the FAZ area after the vitrectomy. Kumagai et al [16] observed a centripetal displacement of the foveal capillaries after ILM peel- ing for various macular diseases including an ERM. This suggests that the ILM peeling could be the cause of the smaller FAZ. Traction relief of centrifugal force after ILM peeling might be responsible for FAZ decrease. In eyes with an ERM, the enlargement or reduction of the FAZ area may depend on the degree of traction on the retina. In the 6 eyes with a reduction of FAZ area, the mean FAZ was larger than in the other eyes with the enlargement although the differ- ence was not significant. For the CFT before the vitrectomy, there were significant differences in the eyes between the enlargement and reduction of the FAZ area after vitrectomy. Such cases were more likely to have a shorter duration of ERM, and the effects of ILM peeling may be greater than that of the ERM removal. Further studies with a larger number of cases are needed to prove the effect of ILM peeling on the reduction of the FAZ area. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 6 / 8 Foveal structure and vasculature in eyes with ERM We know that the dynamic changes of the foveal structures long periods after vitrectomy with ILM peeling [17]. Our results included only seven eyes with postoperative periods >6 months. However, the FAZ area was reduced in five of the seven eyes in spite of such cases having smaller FAZ areas compared to the normal control eyes. These results suggest that the area of the FAZ after surgery does not always enlarged even in the eyes with longer follow-up periods. It is also important to evaluate the recovery of the foveal depression after vitrectomy. Our results showed a restoration of the foveal contour in about 60% of the eyes after the vitrectomy. About 80% of these eyes had an enlargement of the FAZ area. This suggests that the recovery of the foveal morphology including the FAZ area is associated with the restoration of foveal contour. There are several limitations in this study including the small number of cases, especially the small number of vitrectomy cases. Another limitation was the short follow-up periods. In addition, the VD at the fovea was not evaluated to determine the degree of alterations of the capillaries. We also analyzed only the superficial capillary plexus because segmentation errors can occur in ERM eyes [18]. Thus, further studies are needed to evaluate the VD in the superfi- cial and deep capillary plexus using the projection-resolved OCTA and other advanced devices. In conclusion, our results demonstrate the importance of examining the FAZ area to evalu- ate the effects of an ERM on the structure and vasculature of the inner retina. The changes in the FAZ area after vitrectomy might be due to the release in the afferent retinal traction of the ERM and the centripetal displacement of the retina caused by the ILM peeling. We conclude that the traction of an ERM can alter the area of the FAZ and the thickness of the inner retina. Supporting information S1 Table. Baseline characteristics and changes before and after vitrectomy with ILM peel- ing for all eyes. (DOCX) Author Contributions Conceptualization: Yuka Okawa, Ichiro Maruko, Hisaya Arakawa. Data curation: Yuka Okawa, Ichiro Maruko, Moeko Kawai, Taiji Hasegawa. Formal analysis: Yuka Okawa, Ichiro Maruko. Methodology: Ichiro Maruko, Taiji Hasegawa, Tomohiro Iida. Project administration: Yuka Okawa, Ichiro Maruko. Supervision: Ichiro Maruko, Tomohiro Iida. Writing – original draft: Yuka Okawa, Ichiro Maruko. Writing – review & editing: Yuka Okawa, Ichiro Maruko, Moeko Kawai, Taiji Hasegawa, Hisaya Arakawa, Tomohiro Iida. References 1. Michalewski J, Michalewska Z, Cisiecki S, Nawrocki J. Morphologically functional correlations of macu- lar pathology connected with epiretinal membrane formation in spectral optical coherence tomography (SOCT). Graefes Arch Clin Exp Ophthalmol. 2007; 245(11):1623–1631. https://doi.org/10.1007/ s00417-007-0579-4 PMID: 17479277. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 7 / 8 Foveal structure and vasculature in eyes with ERM 2. Watanabe A, Arimoto S, Nishi O. Correlation between metamorphopsia and epiretinal membrane opti- cal coherence tomography findings. Ophthalmology. 2009; 116(9):1788–1793. https://doi.org/10.1016/ j.ophtha.2009.04.046 PMID: 19643494. 3. Ooto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A, Oshima S, et al. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy. Ophthalmology. 2011; 118(5):873–881. https://doi.org/10.1016/j.ophtha.2010.08.032 PMID: 4. Inoue M, Morita S, Watanabe Y, Kaneko T, Yamane S, Kobayashi S, et al. Inner segment/outer seg- ment junction assessed by spectral-domain optical coherence tomography in patients with idiopathic epiretinal membrane. Am J Ophthalmol. 2010; 150(6):834–839. https://doi.org/10.1016/j.ajo.2010.06. 006 PMID: 20719295. 5. Okamoto F, Sugiura Y, Okamoto Y, Hiraoka T, Oshika T. Inner nuclear layer thickness as a prognostic factor for metamorphopsia after epiretinal membrane surgery. Retina. 2015; 35(10):2107–2114. https:// doi.org/10.1097/IAE.0000000000000602 PMID: 25978729. 6. Joe SG, Lee KS, Lee JY, Hwang JU, Kim JG, Yoon YH. Inner retinal layer thickness is the major deter- minant of visual acuity in patients with idiopathic epiretinal membrane. Acta Ophthalmol. 2013; 91(3): e242–243. https://doi.org/10.1111/aos.12017 PMID: 23280145. 7. Koo HC, Rhim WI, Lee EK. Morphologic and functional association of retinal layers beneath the epiret- inal membrane with spectral-domain optical coherence tomography in eyes without photoreceptor abnormality. Graefes Arch Clin Exp Ophthalmol. 2012; 250(4):491–498. https://doi.org/10.1007/ s00417-011-1848-9 PMID: 22086759. 8. Zur D, Iglicki M, Feldinger L, Schwartz S, Goldstein M, Loewenstein A, et al. Disorganization of Retinal Inner Layers as a Biomarker for Idiopathic Epiretinal Membrane After Macular Surgery-The DREAM Study. Am J Ophthalmol. 2018; 196:129–135. https://doi.org/10.1016/j.ajo.2018.08.037 PMID: 9. Lee JW, Kim IT. Outcomes of idiopathic macular epiretinal membrane removal with and without internal limiting membrane peeling: a comparative study. Jpn J Ophthalmol. 2010; 54(2):129–134. https://doi. org/10.1007/s10384-009-0778-0 PMID: 20401561. 10. Kanda Y. Investigation of the freely available easy-to-use software ’EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48(3):452–458. https://doi.org/10.1038/bmt.2012.244 PMID: 23208313. 11. Nelis P, Alten F, Clemens CR, Heiduschka P, Eter N. Quantification of changes in foveal capillary archi- tecture caused by idiopathic epiretinal membrane using OCT angiography. Graefes Arch Clin Exp Ophthalmol. 2017; 255(7):1319–1324. https://doi.org/10.1007/s00417-017-3640-y PMID: 28353013. 12. Kim YJ, Kim S, Lee JY, Kim JG, Yoon YH. Macular capillary plexuses after epiretinal membrane sur- gery: an optical coherence tomography angiography study. Br J Ophthalmol. 2018; 102(8):1086–1091. https://doi.org/10.1136/bjophthalmol-2017-311188 PMID: 29089353. 13. Chen H, Chi W, Cai X, Deng Y, Jiang X, Wei Y, et al. Macular microvasculature features before and after vitrectomy in idiopathic macular epiretinal membrane: an OCT angiography analysis. Eye (Lond). 2018 Nov 22. https://doi.org/10.1038/s41433-018-0272-3 PMID: 30467423. 14. Kitagawa Y, Shimada H, Shinojima A, Nakashizuka H. Foveal avascular zone area analysis using opti- cal coherence tomography angiography before and after idiopathic epiretinal membrane surgery. Ret- ina. 2017 Dec 11. https://doi.org/10.1097/IAE.0000000000001972 PMID: 29232330. 15. Samara WA, Say EA, Khoo CT, Higgins TP, Magrath G, Ferenczy S, et al. Correlation of foveal avascu- lar zone size with foveal morphology in normal eyes using optical coherence tomography angiography. Retina. 2015; 35(11):2188–2195. https://doi.org/10.1097/IAE.0000000000000847 PMID: 26469536. 16. Kumagai K, Furukawa M, Suetsugu T, Ogino N. Foveal avascular zone area after internal limiting mem- brane peeling for epiretinal membrane and macular hole compared with that of fellow eyes and healthy controls. Retina. 2018; 38(9):1786–1794. https://doi.org/10.1097/IAE.0000000000001778 PMID: 17. Bottoni F, De Angelis S, Luccarelli S, Cigada M, Staurenghi G. The dynamic healing process of idio- pathic macular holes after surgical repair: a spectral-domain optical coherence tomography study. Invest Ophthalmol Vis Sci. 2011; 52(7):4439–4446. https://doi.org/10.1167/iovs.10-6732 PMID: 18. Spaide RF, Curcio CA. Evaluation of Segmentation of the Superficial and Deep Vascular Layers of the Retina by Optical Coherence Tomography Angiography Instruments in Normal Eyes. JAMA Ophthal- mol. 2017; 135(3):259–262. https://doi.org/10.1001/jamaophthalmol.2016.5327 PMID: 28097291. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 8 / 8 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png PLoS ONE Public Library of Science (PLoS) Journal

Foveal structure and vasculature in eyes with idiopathic epiretinal membrane

Loading next page...
 
/lp/public-library-of-science-plos-journal/foveal-structure-and-vasculature-in-eyes-with-idiopathic-epiretinal-Tio604X8EG

References (18)

Publisher
Public Library of Science (PLoS) Journal
Copyright
Copyright: © 2019 Okawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the manuscript and its Supporting Information files. Funding: Dr. Okawa has nothing to disclose. Dr. Maruko reports grants from JSPS KAKENHI (Grant Number JP16K11274), grants and personal fees from Novartis Pharma K.K., personal fees from Bayer Yakuhin, Ltd., personal fees from Santen Pharmaceutical Inc., personal fees from Alcon Japan, Ltd., personal fees from Topcon Co., Ltd., personal fees from Senju Pharmaceutical Co., Ltd., personal fees from NIDEK Co., Ltd., outside the submitted work. Dr. Kawai has nothing to disclose. Dr. Hasegawa has nothing to disclose. Dr. Arakawa has nothing to disclose. Dr. Iida reports grants and personal fees from Novartis Pharma K.K. (Japan), personal fees from Bayer Yakuhin, Ltd. (Japan), grants and personal fees from Santen Pharmaceutical Co., Ltd. (Japan), grants from Nidek, research support from Chuosangyo (Japan), outside the submitted work. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have no proprietary interest in any aspect of this paper. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
eISSN
1932-6203
DOI
10.1371/journal.pone.0214881
Publisher site
See Article on Publisher Site

Abstract

a1111111111 a1111111111 a1111111111 Purpose To examine the foveal structure and vasculature in eyes with an idiopathic epiretinal mem- brane (ERM). OPENACCESS Methods Citation: Okawa Y, Maruko I, Kawai M, Hasegawa T, Arakawa H, Iida T (2019) Foveal structure and Forty-nine eyes of 48 patients with an idiopathic ERM were studied. The superficial foveal vasculature in eyes with idiopathic epiretinal avascular zone (FAZ) was measured by optical coherence tomography angiography membrane. PLoS ONE 14(4): e0214881. https:// (OCTA; RTVue XR Avanti, Optovue Inc., Fremont, CA), and the central foveal thickness doi.org/10.1371/journal.pone.0214881 (CFT) was measured by swept source OCT (DRI-OCT, Topcon, Japan). Twenty eyes Editor: Pukhraj Rishi, Sankara Nethralya, Medical underwent vitrectomy with internal limiting membrane (ILM) peeling, and the FAZ and CFT Research Foundation, INDIA were evaluated pre- and postoperatively. Forty-nine eyes of 49 age-matched healthy sub- Received: December 25, 2018 jects were also examined as control. Accepted: March 21, 2019 Published: April 2, 2019 Results Copyright:© 2019 Okawa et al. This is an open The FAZ in eyes with an ERM was significantly smaller than that of the control eyes (0.188 access article distributed under the terms of the 2 2 ±0.16 mm vs 0.328±0.14 mm , P<0.01). The CFT in eyes with an ERM was significantly Creative Commons Attribution License, which thicker than that of control eyes (315±0.14μm vs 193±0.14μm, P<0.01). The size of the permits unrestricted use, distribution, and reproduction in any medium, provided the original FAZ was strongly correlated with the CFT (ERM, R = -0.753; control, R = -0.61, both author and source are credited. P<0.01). The postoperative size of the FAZ was not significantly different from the preopera- 2 2 Data Availability Statement: All relevant data are tive size (0.115 mm vs 0.128 mm , P = 0.17) but the CFT was significantly thinner (370μm within the manuscript and its Supporting vs 288μm, P<0.01) after the vitrectomy with ILM peeling in 20 eyes. Information files. Funding: Dr. Okawa has nothing to disclose. Dr. Conclusions Maruko reports grants from JSPS KAKENHI (Grant The results indicate that an ERM might affect the morphology and vasculature of not only Number JP16K11274), grants and personal fees from Novartis Pharma K.K., personal fees from the inner but also the outer retina before and after vitrectomy with ILM peeling. The FAZ Bayer Yakuhin, Ltd., personal fees from Santen area might have been affected by the ILM peeling. Pharmaceutical Inc., personal fees from Alcon Japan, Ltd., personal fees from Topcon Co., Ltd., personal fees from Senju Pharmaceutical Co., Ltd., personal fees from NIDEK Co., Ltd., outside the PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 1 / 8 Foveal structure and vasculature in eyes with ERM submitted work. Dr. Kawai has nothing to disclose. Introduction Dr. Hasegawa has nothing to disclose. Dr. Arakawa An idiopathic epiretinal membrane (ERM) can alter the foveal morphology by its traction on has nothing to disclose. Dr. Iida reports grants and the retina, and the morphological changes can cause distortions of vision and reductions of the personal fees from Novartis Pharma K.K. (Japan), personal fees from Bayer Yakuhin, Ltd. (Japan), visual acuity. The results of optical coherence tomographic (OCT) studies have shown a thick- grants and personal fees from Santen ening of the fovea and a disruption of the ellipsoid zone of the photoreceptors in eyes with an Pharmaceutical Co., Ltd. (Japan), grants from ERM [1–5]. The disruption of the ellipsoid zone indicates a disorder in the alignment of the Nidek, research support from Chuosangyo (Japan), photoreceptors which most likely accounts for the visual dysfunctions. Inoue et al [4] reported outside the submitted work. The funders had no that the improvement of the visual acuity after removing an ERM was not significant after vit- role in the study design, data collection and analysis, decision to publish, or preparation of the reous surgery. However, because there is no inner retina at the fovea, these reports only evalu- manuscript. ated the changes of the outer retina in eyes with an idiopathic ERM. There are recent studies that report that the visual abnormalities can be present in eyes with Competing interests: The authors have no proprietary interest in any aspect of this paper. good visual acuities and without any disruption of the ellipsoid zone. This was suggested to There are no patents, products in development or result from changes in the inner retina caused by the ERM [6–8]. marketed products to declare. This does not alter However, it has not been adequately reported that the inner retina is altered in eyes with an our adherence to all the PLOS ONE policies on ERM. sharing data and materials, as detailed online in the Thus, the purpose of this study was to determine the effect of an ERM on the inner retina. guide for authors. To accomplish this, the superficial foveal avascular zone (FAZ) was measured by optical coher- ence tomography angiography (OCTA), and the central foveal thickness (CFT) was measured by swept source OCT in eyes with an ERM. In addition, the areas of the FAZ and CFT were evaluated after vitrectomy with ERM and internal limiting membrane (ILM) peeling. Materials and methods This was a retrospective study, and the procedures used conformed to the tenets of the Decla- ration of Helsinki. The Institutional Review Board of the Tokyo Women’s Medical University, School of Medicine approved the procedures used. All examinations were performed after an informed consent was obtained. Forty-nine eyes of 48 patients (25 men, 24 women; average age, 67.1 years) with an idio- pathic ERM were examined by OCTA (RTVue XR Avanti, Optovue Inc., Fremont, CA) with a scan of 3 x 3 mm centered on the fovea. Eyes with high myopia, diabetic retinopathy, retinal vein occlusion, a history of pars plana vitrectomy, and inflammation other than secondary to an ERM were excluded. Eyes without a posterior vitreous detachment were also excluded to avoid cases of secondary ERM. In 20 eyes among all eyes, the FAZ was evaluated after pars plana vitrectomy with ERM and ILM peeling. Cataract surgery was performed at the time of vitrectomy in all eyes. Forty-nine eyes of 49 age-matched healthy individuals were also exam- ined as controls. None of these eyes had an ERM and had undergone vitrectomy. The OCTA (RTVue XR Avanti) instrument can record the microvascular structures using a split spectrum amplitude-decorrelation angiography without fluorescein or indocyanine green dye. This device records 70,000 A-scans/second with motion correction which helps in record- ing clear en face OCTA images. The software embedded in the OCTA device automatically shows four en face OCTA images divided into four depths; the superficial capillary plexus, deep capillary plexus, outer retina, and choriocapillaris layers. In this study, the superficial cap- illary plexus was used to avoid segmentation errors. Eyes with blurred OCTA images were excluded even if the motion correction technology was used. The area of the FAZ was measured by the polygon selection tool of the ImageJ software (National Institutes of Health, Bethesda, MD; available at http://rsb.info.nih.gov/ij/index. html). The measurement of the FAZ area was done for only the superficial layer images because the FAZ area in the deep plexus layer can be affected by projection artifacts. All FAZ areas were measured by two co-authors (YO and IM), and their values were averaged. The PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 2 / 8 Foveal structure and vasculature in eyes with ERM change in the ratio of FAZ area after vitrectomy was calculated as, (postoperative FAZ area– preoperative FAZ area)/preoperative FAZ area. All eyes were also examined by swept-source OCT (DRI-OCT, Topcon, Japan), and the images were used to measure the central foveal thickness (CFT). The CFT was determined with the caliper tool in the OCT software. The change in the ratio of CFT after vitrectomy was calculated as, (postoperative CFT–preoperative CFT)/preoperative CFT. We also evaluated the irregularity and/or disruption of the ellipsoid zone of the photorecep- tors in the cross-sectional images. Twenty eyes underwent vitrectomy with ERM and ILM peeling, and we determined whether the foveal contour was restored in the DRI-OCT images. We classified eyes as having a restored foveal contour when the retinal thickness at the center of the fovea was at least 50 μm thinner than that of the retina 1 mm away from the foveola without intraretinal edema [9]. The BCVA was measured with a Japanese standard decimal visual chart, and the decimal visual acuities were converted to the logarithm of the minimum angle of resolution (logMAR) for the statistical analyses. Statistical analyses Mann–Whitney U-tests were used to determine the significance of the differences in the FAZ area and CFT between the ERM and control groups. Wilcoxon signed-rank tests were used to determine the significance of the differences in the FAZ area, CFT, and BCVA before and after the ERM surgery. Spearman’s tests were used to determine the significance of the correlations. All P-values were two-sided and values <0.05 were considered statically significant. All statisti- cal analyses were performed with free software EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [10]. More exactly, it is a modified version of the R commander designed to add statistical functions frequently used in biostatistics. Results The mean area of the FAZ was 0.188 ± 0.16 mm in the eyes with an ERM which was signifi- cantly smaller than the 0.328 ± 0.14 mm in the control eyes (P <0.01). The FAZ area in the eyes with an ERM was not significantly correlated with the age (R = 0.048, P = 0.74) or the 2 2 BCVA (R = -0.233, P = 0.11). The area of the FAZ increased from 0.115 mm to 0.128 mm after vitrectomy in the 20 eyes with a mean follow-up period of 147 days (range 23–443 days). This increase was not significant (P = 0.17). The mean postoperative FAZ area was signifi- cantly smaller than that of the control eyes (P <0.01). The FAZ area enlarged in 14 eyes (Fig 1) and decreased in 6 eyes (Fig 2). The mean area of the FAZ with enlargement after vitrectomy 2 2 was smaller than decrease in the area of the FAZ in the other eyes (0.091 mm vs 0.171 mm , P = 0.06). The mean change in the ratio was not significantly correlated with the age (R = 0.421, P = 0.06) and the length of the follow-up period (R = -0.357, P = 0.12). Seven eyes were followed for more than 6 months, and the FAZ area increased in 2 eyes and decreased in 5 eyes. Although there was no significant difference between pre- and postoperative FAZ areas 2 2 (0.166 mm vs 0.11 mm , P = 0.30) in these eyes, the change in the ratio of the areas in the eyes with more than 6 months of follow-up was significantly smaller than that of eyes with less than 6 months of follow-up (-0.170 vs 0.750, P <0.01). The mean CFT in the eyes with an ERM was significantly thicker than that of the control eyes (315 ± 22 μm vs 193 ± 100 μm, P <0.01), and the CFT was significantly correlated with the BCVA (R = 0.315, P = 0.03) but not with the age (R = -0.102, P = 0.49). The CFT decreased significantly from 370 μm to 288 μm after vitrectomy in the 20 eyes (P <0.01), however the PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 3 / 8 Foveal structure and vasculature in eyes with ERM Fig 1. Representative case with an epiretinal membrane (EM). The foveal avascular zone (FAZ) increased and the central foveal thickness (CFT) decreased after vitrectomy with peeling of the internal limiting membrane (ILM). A: Superficial optical coherence tomography angiography (OCTA) image before vitrectomy. Area of FAZ is 0.072 mm . B: Superficial OCTA image after vitrectomy. Area of FAZ is 0.148 mm . C: Cross-sectional OCT image before vitrectomy. The central foveal thickness (CFT) is 405 μm. D: Cross-sectional OCT image after vitrectomy. The CFT is 270 μm. https://doi.org/10.1371/journal.pone.0214881.g001 mean postoperative CFT was still significantly thicker than that of the control eyes (P <0.01). In the eyes that underwent vitrectomy and had an increase in the area of the FAZ, the CFT was significantly thicker than in the eyes with a reduction in the size of the FAZ (393 μm vs 316 μm, P <0.01). The mean change in the ratio of the areas was not correlated with the age (R = -0.046, P = 0.85) and the duration of the follow-up period (R = 0.371, P = 0.11). The area of the FAZ was negatively and significantly correlated with the CFT in the eyes with an ERM (R = -0.753, P <0.01, Fig 3A) and also in the control eyes (R = -0.610, P <0.01, Fig 3B). The change in the ratios of both the FAZ area and the CFT were significantly corre- lated (R = -0.743, P <0.01). There were no abnormalities of the ellipsoid zone at the fovea in the cross-sectional OCT images. The restoration of the foveal contour after vitrectomy was detected in 12 (63.2%) of 19 eyes without a foveal contour before the vitrectomy. An enlargement of the FAZ was found after vitrectomy in 10 (83.3%) of 12 eyes with the restoration of the foveal contour. The mean decimal BCVA in all eyes with an ERM was 0.90, and that of the 20 eyes treated with vitrectomy was 0.88 at the baseline and 1.02 after the surgery. The BCVA after the vitrec- tomy was not significantly changed (P = 0.13). The findings in all of the eyes with an ERM are summarized in Supplemental Table (S1 Table). Discussion The results showed that the area of the FAZ was smaller and the CFT was thicker in the eyes with an ERM than in age-matched control eyes. This difference was still present after PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 4 / 8 Foveal structure and vasculature in eyes with ERM Fig 2. Representative case with a reduction of the FAZ and an increase in the CFT after vitrectomy with ILM peeling. A: Superficial OCTA image before vitrectomy. Area of FAZ is 0.426 mm . B: Superficial OCTA image after vitrectomy. Area of FAZ is 0.119 mm . C: Cross-sectional OCT image before vitrectomy. CFT is 280 μm. D: Cross- sectional OCT image after vitrectomy. CFT is 335 μm. https://doi.org/10.1371/journal.pone.0214881.g002 successful removal of the ERM by vitrectomy with ILM peeling. This indicated that the trac- tional effects of ERM might persist even after its removal. Although the CFT became signifi- cantly thinner after vitrectomy, the decrease in the FAZ area was not significant. These results may be due to not only the centrifugal effect of ERM removal but also the centripetal move- ment of the retina after the ILM peeling. An ERM can cause distortions of vision and visual dysfunction through a traction on the surface of the retina. Thus, vitrectomy is required to release the traction. Since the early times of OCT [1–5], alterations of various parameters associated with the visual function were Fig 3. Plot showing the relationship between the FAZ area and the CFT. The FAZ is negatively and significantly correlated with the CFT in the eyes with an ERM (A), and control eyes (B). https://doi.org/10.1371/journal.pone.0214881.g003 PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 5 / 8 Foveal structure and vasculature in eyes with ERM detected in eyes with an ERM, e.g., thicker CFT, greater distortion of vision, good preoperative vision, better postoperative vision, greater postoperative reduction of the CFT, better visual prognosis, changes in the postoperative foveal depression correlated with the postoperative vision, and the integrity of the ellipsoid zone that were significantly correlated with the postop- erative vision. However, these studies mainly evaluated the changes of the outer retina because an inner retina did not exist at the fovea. In our cohort, none of the eyes had a disruption of the ellipsoid zone. Most recent studies focused on the inner retinal layer in eyes with an ERM and without any abnormalities of the outer retina. Koo et al [6] evaluated the inner retina from volume scans of eyes with an ERM, and they reported that the thickness of the inner retina at the parafovea (within 3 mm) was significantly associated with the visual dysfunction even with an intact photoreceptor layer. Joe et al [7] reported that the presence of an inner retinal layer at the fovea was the major determinant of the visual acuity in eyes with an ERM. Zur et al [8] reported the extent of the disorganization of the retinal inner layers (DRIL), a biomarker that can predict the vision change in patients with diabetic macular edema, had been associated with the visual prognosis after macular surgery for ERM. OCTA has recently been used to evaluate ERM cases. Thus, Neris et al [11] reported that the foveal vessel density (VD) in eyes with an ERM was significantly higher than that of normal controls. They attributed this to a central displacement of the foveal capillaries. Kim et al [12] reported that the postoperative area of the FAZ was smaller in postoperative eyes with an ERM than the fellow eyes. Chen et al [13] compared the FAZ area and foveal VD before to that after vitrectomy for an ERM, and they reported an enlargement in FAZ area and a reduction in foveal VD. Kitagawa et al [14] also reported that the area of the FAZ increased significantly after vitrectomy for ERM, although the increase was small. Thus, evaluations of the retinal blood vessels of the inner retina by OCTA can be considered to be an evaluation of the struc- ture of the inner retina. OCTA can be used to evaluate not only the FAZ and VD but also the foveal morphology using the depth and morphologic information obtained at the same time as the structure. Samara et al. described a significant negative correlation between the FAZ area and CFT in normal eyes [15]. Our results confirmed the negative correlation between FAZ area and CFT even in ERM cases. Although it was possible that the slow foveal structure changes after vitrectomy with ILM peeling, the mean FAZ area after vitrectomy was still significantly smaller at least 6 months fol- low-up than that of the control eyes. Interestingly, the FAZ area did not change significantly after vitrectomy although the CFT became thinner. These results suggest that the ERM affected the outer retina more than the inner retina. Because the postoperative BCVA was not significantly correlated with the FAZ area but was significantly correlated with the CFT, the morphological changes of the outer retina might affect the BCVA more than the changes of the inner retina. In our cohort, there were six eyes that had a reduction of the FAZ area after the vitrectomy. Kumagai et al [16] observed a centripetal displacement of the foveal capillaries after ILM peel- ing for various macular diseases including an ERM. This suggests that the ILM peeling could be the cause of the smaller FAZ. Traction relief of centrifugal force after ILM peeling might be responsible for FAZ decrease. In eyes with an ERM, the enlargement or reduction of the FAZ area may depend on the degree of traction on the retina. In the 6 eyes with a reduction of FAZ area, the mean FAZ was larger than in the other eyes with the enlargement although the differ- ence was not significant. For the CFT before the vitrectomy, there were significant differences in the eyes between the enlargement and reduction of the FAZ area after vitrectomy. Such cases were more likely to have a shorter duration of ERM, and the effects of ILM peeling may be greater than that of the ERM removal. Further studies with a larger number of cases are needed to prove the effect of ILM peeling on the reduction of the FAZ area. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 6 / 8 Foveal structure and vasculature in eyes with ERM We know that the dynamic changes of the foveal structures long periods after vitrectomy with ILM peeling [17]. Our results included only seven eyes with postoperative periods >6 months. However, the FAZ area was reduced in five of the seven eyes in spite of such cases having smaller FAZ areas compared to the normal control eyes. These results suggest that the area of the FAZ after surgery does not always enlarged even in the eyes with longer follow-up periods. It is also important to evaluate the recovery of the foveal depression after vitrectomy. Our results showed a restoration of the foveal contour in about 60% of the eyes after the vitrectomy. About 80% of these eyes had an enlargement of the FAZ area. This suggests that the recovery of the foveal morphology including the FAZ area is associated with the restoration of foveal contour. There are several limitations in this study including the small number of cases, especially the small number of vitrectomy cases. Another limitation was the short follow-up periods. In addition, the VD at the fovea was not evaluated to determine the degree of alterations of the capillaries. We also analyzed only the superficial capillary plexus because segmentation errors can occur in ERM eyes [18]. Thus, further studies are needed to evaluate the VD in the superfi- cial and deep capillary plexus using the projection-resolved OCTA and other advanced devices. In conclusion, our results demonstrate the importance of examining the FAZ area to evalu- ate the effects of an ERM on the structure and vasculature of the inner retina. The changes in the FAZ area after vitrectomy might be due to the release in the afferent retinal traction of the ERM and the centripetal displacement of the retina caused by the ILM peeling. We conclude that the traction of an ERM can alter the area of the FAZ and the thickness of the inner retina. Supporting information S1 Table. Baseline characteristics and changes before and after vitrectomy with ILM peel- ing for all eyes. (DOCX) Author Contributions Conceptualization: Yuka Okawa, Ichiro Maruko, Hisaya Arakawa. Data curation: Yuka Okawa, Ichiro Maruko, Moeko Kawai, Taiji Hasegawa. Formal analysis: Yuka Okawa, Ichiro Maruko. Methodology: Ichiro Maruko, Taiji Hasegawa, Tomohiro Iida. Project administration: Yuka Okawa, Ichiro Maruko. Supervision: Ichiro Maruko, Tomohiro Iida. Writing – original draft: Yuka Okawa, Ichiro Maruko. Writing – review & editing: Yuka Okawa, Ichiro Maruko, Moeko Kawai, Taiji Hasegawa, Hisaya Arakawa, Tomohiro Iida. References 1. Michalewski J, Michalewska Z, Cisiecki S, Nawrocki J. Morphologically functional correlations of macu- lar pathology connected with epiretinal membrane formation in spectral optical coherence tomography (SOCT). Graefes Arch Clin Exp Ophthalmol. 2007; 245(11):1623–1631. https://doi.org/10.1007/ s00417-007-0579-4 PMID: 17479277. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 7 / 8 Foveal structure and vasculature in eyes with ERM 2. Watanabe A, Arimoto S, Nishi O. Correlation between metamorphopsia and epiretinal membrane opti- cal coherence tomography findings. Ophthalmology. 2009; 116(9):1788–1793. https://doi.org/10.1016/ j.ophtha.2009.04.046 PMID: 19643494. 3. Ooto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A, Oshima S, et al. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy. Ophthalmology. 2011; 118(5):873–881. https://doi.org/10.1016/j.ophtha.2010.08.032 PMID: 4. Inoue M, Morita S, Watanabe Y, Kaneko T, Yamane S, Kobayashi S, et al. Inner segment/outer seg- ment junction assessed by spectral-domain optical coherence tomography in patients with idiopathic epiretinal membrane. Am J Ophthalmol. 2010; 150(6):834–839. https://doi.org/10.1016/j.ajo.2010.06. 006 PMID: 20719295. 5. Okamoto F, Sugiura Y, Okamoto Y, Hiraoka T, Oshika T. Inner nuclear layer thickness as a prognostic factor for metamorphopsia after epiretinal membrane surgery. Retina. 2015; 35(10):2107–2114. https:// doi.org/10.1097/IAE.0000000000000602 PMID: 25978729. 6. Joe SG, Lee KS, Lee JY, Hwang JU, Kim JG, Yoon YH. Inner retinal layer thickness is the major deter- minant of visual acuity in patients with idiopathic epiretinal membrane. Acta Ophthalmol. 2013; 91(3): e242–243. https://doi.org/10.1111/aos.12017 PMID: 23280145. 7. Koo HC, Rhim WI, Lee EK. Morphologic and functional association of retinal layers beneath the epiret- inal membrane with spectral-domain optical coherence tomography in eyes without photoreceptor abnormality. Graefes Arch Clin Exp Ophthalmol. 2012; 250(4):491–498. https://doi.org/10.1007/ s00417-011-1848-9 PMID: 22086759. 8. Zur D, Iglicki M, Feldinger L, Schwartz S, Goldstein M, Loewenstein A, et al. Disorganization of Retinal Inner Layers as a Biomarker for Idiopathic Epiretinal Membrane After Macular Surgery-The DREAM Study. Am J Ophthalmol. 2018; 196:129–135. https://doi.org/10.1016/j.ajo.2018.08.037 PMID: 9. Lee JW, Kim IT. Outcomes of idiopathic macular epiretinal membrane removal with and without internal limiting membrane peeling: a comparative study. Jpn J Ophthalmol. 2010; 54(2):129–134. https://doi. org/10.1007/s10384-009-0778-0 PMID: 20401561. 10. Kanda Y. Investigation of the freely available easy-to-use software ’EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48(3):452–458. https://doi.org/10.1038/bmt.2012.244 PMID: 23208313. 11. Nelis P, Alten F, Clemens CR, Heiduschka P, Eter N. Quantification of changes in foveal capillary archi- tecture caused by idiopathic epiretinal membrane using OCT angiography. Graefes Arch Clin Exp Ophthalmol. 2017; 255(7):1319–1324. https://doi.org/10.1007/s00417-017-3640-y PMID: 28353013. 12. Kim YJ, Kim S, Lee JY, Kim JG, Yoon YH. Macular capillary plexuses after epiretinal membrane sur- gery: an optical coherence tomography angiography study. Br J Ophthalmol. 2018; 102(8):1086–1091. https://doi.org/10.1136/bjophthalmol-2017-311188 PMID: 29089353. 13. Chen H, Chi W, Cai X, Deng Y, Jiang X, Wei Y, et al. Macular microvasculature features before and after vitrectomy in idiopathic macular epiretinal membrane: an OCT angiography analysis. Eye (Lond). 2018 Nov 22. https://doi.org/10.1038/s41433-018-0272-3 PMID: 30467423. 14. Kitagawa Y, Shimada H, Shinojima A, Nakashizuka H. Foveal avascular zone area analysis using opti- cal coherence tomography angiography before and after idiopathic epiretinal membrane surgery. Ret- ina. 2017 Dec 11. https://doi.org/10.1097/IAE.0000000000001972 PMID: 29232330. 15. Samara WA, Say EA, Khoo CT, Higgins TP, Magrath G, Ferenczy S, et al. Correlation of foveal avascu- lar zone size with foveal morphology in normal eyes using optical coherence tomography angiography. Retina. 2015; 35(11):2188–2195. https://doi.org/10.1097/IAE.0000000000000847 PMID: 26469536. 16. Kumagai K, Furukawa M, Suetsugu T, Ogino N. Foveal avascular zone area after internal limiting mem- brane peeling for epiretinal membrane and macular hole compared with that of fellow eyes and healthy controls. Retina. 2018; 38(9):1786–1794. https://doi.org/10.1097/IAE.0000000000001778 PMID: 17. Bottoni F, De Angelis S, Luccarelli S, Cigada M, Staurenghi G. The dynamic healing process of idio- pathic macular holes after surgical repair: a spectral-domain optical coherence tomography study. Invest Ophthalmol Vis Sci. 2011; 52(7):4439–4446. https://doi.org/10.1167/iovs.10-6732 PMID: 18. Spaide RF, Curcio CA. Evaluation of Segmentation of the Superficial and Deep Vascular Layers of the Retina by Optical Coherence Tomography Angiography Instruments in Normal Eyes. JAMA Ophthal- mol. 2017; 135(3):259–262. https://doi.org/10.1001/jamaophthalmol.2016.5327 PMID: 28097291. PLOS ONE | https://doi.org/10.1371/journal.pone.0214881 April 2, 2019 8 / 8

Journal

PLoS ONEPublic Library of Science (PLoS) Journal

Published: Apr 2, 2019

There are no references for this article.