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1.  Prevalence and Risk Factors of Idiopathic Epiretinal Membranes in Beixinjing Blocks, Shanghai, China 
PLoS ONE  2012;7(12):e51445.
To determine the prevalence and risk factors associated with idiopathic epiretinal membranes (iERM) in a Chinese population aged 60 years or older in Beixinjing Blocks, Shanghai.
This population-based study consisted of 3727 participants (89.7% of the eligible). It was performed to describe the prevalence of iERM and possible demographic, systemic, and ocular factors associated with iERM. Each participant underwent a standardized interview and comprehensive ophthalmic examination. iERM was identified and graded from retinal photographs. Then, a case-control study comparing the participants with vs. without iERM was performed to further study the associations between iERM and blood biochemical test results (including fasting plasma glucose, serum creatinine, total cholesterol, and triglyceride), ocular biological parameters (including the axial length, corneal curvature, refractive diopter, intraocular press, and anterior chamber depth), and the data of optical coherence tomography.
The prevalence of iERM was 1.02%. iERM was significantly associated with diabetes (OR: 2.457; 95% CI: 1.137, 5.309) and a higher level of education (OR: 1.48; 95% CI: 1.123, 1.952). Blood biochemical test results and ocular biological parameters showed no significant differences between the iERM and control groups, whereas the incidence of posterior vitreous detachment in the iERM group was much higher than in the control group (26.5% vs. 8.8%), but this difference was not statistically significant. Moreover, the eyes with iERM had poorer visual acuity than the eyes without iERM (P<0.05).
In Beixinjing Blocks, Shanghai, iERM was relatively rare, was associated with diabetes and a higher level of education, and caused a substantial decrease in visual acuity.
PMCID: PMC3519558  PMID: 23251536
2.  Fourier-domain optical coherence tomography of eyes with idiopathic epiretinal membrane: correlation between macular morphology and visual function 
Eye  2011;25(6):775-783.
The purpose of this study is to evaluate the macular morphological changes associated with idiopathic epiretinal membrane (iERM) using high-resolution Fourier-domain optical coherence tomography (FD-OCT), as they correlate with visual acuity and microperimetry (MP-1).
In all, 24 eyes (19 subjects) with iERM were imaged prospectively using FD-OCT with axial resolution of 4.5 μm and transverse resolution of 10 to 15 μm. MP-1 and Stratus OCT were carried out in a subset of eyes.
The mean log of the minimum angle of resolution best-corrected visual acuity (BCVA) was 0.18±0.16 (range: −0.08 to 0.48, Snellen equivalent 20/15−1 to 20/60). ERM was visualized in all 24 eyes with FD-OCT and in 17 eyes (85%) of 20 eyes imaged with Stratus OCT. Although BCVA correlated with macular thickening in the central 1 mm sub-field of the Stratus ETDRS (P=0.0005) and macular volume (central 3 mm area) on FD-OCT (P<0.0001), macular thickening on thickness map and volume correlated poorly with decrease in macular sensitivity on MP-1 (P=0.16). On FD-OCT, foveal morphological changes correlated best with decrease in BCVA, the strongest being central foveal thickness (P<0.0001). Other significant changes included blurring of the foveal inner segment–outer segment (IS–OS) junction and/or Verhoeff's membrane, vitreal displacement of foveal outer nuclear layer and foveal detachment (P<0.05). Foveal IS–OS junction disruption was seen in 25% of eyes on Stratus OCT but in none of the eyes on FD-OCT.
FD-OCT allowed improved visualization of ERM and associated foveal morphological changes that correlated best with BCVA. Macular thickening correlated weakly with decreased macular function as assessed by MP-1.
PMCID: PMC3178120  PMID: 21436847
epiretinal membrane; Fourier-domain optical coherence tomography; macular morphology; Stratus OCT; microperimetry
3.  Inflammatory Mechanisms of Idiopathic Epiretinal Membrane Formation 
Mediators of Inflammation  2013;2013:192582.
The pathogenesis of idiopathic epiretinal membranes (iERMs), a common pathology found in retina clinics, still eludes researchers to date. Ultrastructural studies of iERMs in the past have failed to identify the cells of origin due to the striking morphologic changes of cells involved via transdifferentiation. Thus, immunohistochemical techniques that stain for the cytostructural components of cells have confirmed the importance of glial cells and hyalocytes in iERM formation. The cellular constituents of iERMs are thought to consist of glial cells, fibroblasts, hyalocytes, etc. that, in concert with cytokines and growth factors present in the vitreous, lead to iERM formation. Recently, research has focused on the role of the posterior hyaloid in iERM formation and contraction, particularly the process of anomalous PVD as it relates to iERM formation. Recent advances in proteomics techniques have also elucidated the growth factors and cytokines involved in iERM formation, most notably nerve growth factor, glial cell line-derived growth factor, and transforming growth factor β1.
PMCID: PMC3844245  PMID: 24324293
4.  Characterization of ex vivo cultured neuronal- and glial- like cells from human idiopathic epiretinal membranes 
BMC Ophthalmology  2014;14:165.
Characterization of the neuro-glial profile of cells growing out of human idiopathic epiretinal membranes (iERMs) and testing their proliferative and pluripotent properties ex vivo is needed to better understand the pathogenesis of their formation.
iERMs obtained during uneventful vitrectomies were cultivated ex vivo under adherent conditions and assessed by standard morphological and immunocytochemical methods. The intracellular calcium dynamics of the outgrowing cells was assessed by fluorescent dye Fura-2 in response to acetylcholine (ACh)- or mechano- stimulation.
The cells from the iERMs formed sphere-like structures when cultured ex vivo. The diameter of the spheres increased by 5% at day 6 and kept an increasing tendency over a month time. The outgrowing cells from the iERM spheres had mainly glial- and some neuronal- like morphology. ACh- or mechano- stimulation of these cells induced intracellular calcium propagation in both cell types; in the neuronal-like cells resembling action potential from the soma to the dendrites. Immunocytochemistry confirmed presence of glial- and neuronal cell phenotype (GFAP and Nestin-1 positivity, respectively) in the iERMs, as well as presence of pluripotency marker (Sox2).
iERMs contain cells of neuronal- and glial- like origin which have proliferative and pluripotent potential, show functionality reflected through calcium dynamics upon ACh and mechano- stimulation, and a corresponding molecular phenotype.
PMCID: PMC4324881  PMID: 25540050
Idiopathic epiretinal membrane; Glial- and neuronal cell growth; Pluripotency; Calcium dynamics; Acetylcholine; Mechanostimulation; GFAP; Nestin-1; Sox2; Pax2
5.  Association of Preoperative Optical Coherence Tomography Markers with Residual Inner Limiting Membrane in Epiretinal Membrane Peeling 
PLoS ONE  2013;8(6):e66217.
To identify preoperative markers on spectral domain optical coherence tomography (SD-OCT) for residual inner limiting membrane (ILM) in epiretinal membrane (ERM) peeling.
In this retrospective case series the preoperative SD-OCTs from 119 eyes of 119 consecutive patients who underwent surgery for idiopathic ERM by a single surgeon were evaluated for markers predisposing for ILM persistence after ERM removal. ILM persistence was determined via intraoperative indocyanine green staining. The main outcome measures were correlation of central foveal thickness (CFT), ERM thickness, extent of elevated ERM and retinal folding, intraretinal cysts, and discontinuation of the ERM, with ILM persistence after ERM peeling.
The persistence of the ILM was found in 50.4% (n = 60). After Bonferroni correction for multiple testing, a greater extent of elevated ERM and thicker ERMs were associated with persistence of the ILM (p<0.005). The other parameters showed no statistically significant correlations with the persistence of the ILM (p≥0.005).
Residual ILM can be found in nearly half of the eyes after ERM peeling. A loose connection between the ERM and the retinal surface predisposes for ILM persistence. Preoperative SD-OCT is helpful in identifying risk markers for the persistence of the ILM in ERM surgery.
PMCID: PMC3679048  PMID: 23776634
6.  Expression of erythropoietin receptor in human epiretinal membrane of proliferative diabetic retinopathy 
The British Journal of Ophthalmology  2007;91(10):1376-1378.
It is widely accepted that intravitreous levels of erythropoietin (Epo) are elevated in patients with ischaemic retinal diseases such as proliferative diabetic retinopathy (PDR). The aim of this study was to examine the expression of Epo and the Epo receptor (EpoR) in epiretinal membranes with and without diabetes.
Eighteen epiretinal membranes (PDR (n = 10), idiopathic epiretinal membranes (IERMs) without diabetes (n = 4) and inner limiting membranes (ILMs) (n = 4)) were obtained during pars plana vitrectomy. Formalin‐fixed and paraffin‐embedded tissues were examined by immunohistochemistry with anti‐Epo and EpoR antibodies.
The histopathological findings demonstrated that PDR membranes consisted of a variety of endothelial cells forming a microvascular cavity with red blood cells and non‐vascular stromal mononuclear cells. Membranous and cytoplasmic immunoreactivity for EpoR was strongly detected in endothelial cells and stromal cells in all PDR patients. Although microvessels were not observed in IERMs and ILMs, immunoreactivity for EpoR was noted in the cellular component of IERMs, and was weakly detected in ILMs. Epo was not expressed in any membrane.
EpoR was strongly expressed in microvessels of all PDR membranes. The in vivo evidence in this study suggests that Epo in the vitreous binds to EpoR in PDR membranes, which subsequently leads to the proliferation of new retinal vessels. EpoR immunoreactivity in non‐vascular stromal cells in PDR membranes, and IERMs and ILMs might be indirectly correlated with ischaemia.
PMCID: PMC2001006  PMID: 17522145
7.  Improvement of horizontal macular contraction after surgical removal of epiretinal membranes 
Eye  2011;25(6):754-761.
To determine whether horizontal macular contraction caused by epiretinal membranes (ERMs) improves after surgical removal.
In this prospective, single-center, observational study, 63 consecutive patients with unilateral idiopathic ERM in one eye and no retinal disease in the fellow eye underwent pars plana vitrectomy. Fundus photography and optical coherence tomography (OCT) were performed preoperatively and at 3 months postoperatively. The area enclosed by superior and inferior major vessels from the optic disc to the fovea (area under major vessel (AUV)) and the macroscopic diverging angle (MDA) between superior and inferior major vessels were calculated using digital image analysis of fundus photographs and compared pre- and postoperatively.
AUV was significantly smaller in the eyes with ERM compared with the normal fellow eyes (P<0.001). Significant postoperative change in AUV and MDA was demonstrated after ERM removal (P<0.001). However, postoperative AUV of grade 2 and 3 ERM eyes was still significantly smaller than that of normal fellow eyes. Macular thickness differences measured with stratus OCT were positively correlated with AUV differences.
Retinal topographic changes caused by ERM improved in part after ERM removal. The improvement of topographic changes were correlated with tomographic changes detected with OCT.
PMCID: PMC3178126  PMID: 21455247
epiretinal membrane; macular contraction; surgical removal
8.  Use of systemic steroid after successful macular surgery in eyes with epiretinal membrane: a randomized, controlled clinical study 
Eye  2011;25(10):1284-1293.
To evaluate the functional and morphological outcomes of postoperative systemic steroid therapy after successful macular surgery in eyes with macular edema due to idiopathic macular epiretinal membranes (ERMs).
Prospective, randomized, investigator-masked, controlled clinical study.
Twenty-eight patients scheduled for 23-gauge vitrectomy combined with ERM and inner limiting membrane (ILM) peeling for macular edema due to ERM were included in this single center trial. Patients were randomized to receive oral steroid therapy (Prednisolone, 100 mg per day for 5 days) or no oral steroid (control group) after surgery. Main outcome measures included best corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), central retinal thickness (CRT), retinal volume (RV), and macular morphology as determined by spectral domain optical coherence tomography (SD-OCT, Cirrus). Examinations were carried out preoperatively and at week 1, at months 1 and 3, postoperatively.
At month 3, mean BCVA improved to a eight-letter gain in each study group (P<0.01 compared with baseline for both groups), showing no statistically significant difference between both the groups (P=0.19). Morphologically, retinal surface folds resolved within 1 month after surgery in both treatment groups, followed by a progressive recovery of retinal layer integrity and a statistical significant (P<0.01) decrease in CRT and RV without significant differences between both groups (P=0.62, P=0.13, respectively, ANOVA between the groups).
The early postoperative use of systemic steroid treatment after successful vitrectomy combined with ERM and ILM peeling does not seem to improve significantly the anatomic and functional outcomes in eyes with ERM.
PMCID: PMC3194330  PMID: 21886189
epiretinal membrane; macular surgery; systemic steroid therapy; optical coherence tomography
9.  Epiretinal Membranes in Patients with Uveitis: Morphological and Functional Analysis with Spectral Domain Optical Coherence Tomography 
BioMed Research International  2013;2013:284821.
Purpose. To correlate the uveitic epiretinal membrane (ERM) features using spectral-domain optical coherence tomography (SD-OCT) with visual acuity (VA). Methods. Forty-one eyes of 32 patients were included in this retrospective study. SD-OCT was performed in all patients and data were collected at the time of ERM diagnosis and at the final visit. Both best corrected visual acuity (BCVA) and ERM thickness were correlated with the morphological and clinical features. Results. Final BCVA was positively correlated with male sex (P = 0.0055) and the focal pattern of ERM attachment (P = 0.031) and negatively correlated with IS/OS photoreceptor junction disruption (P = 0.042). BVCA change showed a positive correlation with the age of ERM onset (P = 0.056) but a negative correlation with IS/OS photoreceptor disruption at the ERM diagnosis (P = 0.029) and the increase of central subfield thickness (CST) (P = 0.95). Final ERM thickness correlated with the duration of uveitis (P = 0.0023) and the duration of ERM (P = 1.15  e-05). During the follow-up, ERM thickening correlated with male sex (P = 0.042), posterior uveitis (P = 0.036), uveitis duration (P = 0.026), and broad attachment pattern (P = 0.052). Conclusions. In the uveitic ERM, VA negatively correlates with IS/OS photoreceptor junction disruption and the increase of CST. ERM thickness is influenced by longer duration of both uveitis and ERM.
PMCID: PMC3835473  PMID: 24294602
10.  Quantitative analysis of macular contraction in idiopathic epiretinal membrane 
BMC Ophthalmology  2014;14:51.
We aimed to quantify the displacement of macular capillaries using infrared fundus photographs and image processing software (ImageJ) in patients with idiopathic epiretinal membrane (ERM) who have undergone vitrectomy and to analyze the correlation between vessel displacement and retinal thickness.
This prospective study included 16 patients who underwent vitrectomy for idiopathic ERM. Ophthalmic examination and optical coherence tomography (OCT) were performed before and 3 months after surgery. The length of radial vessel segment included in each area (VLA) and the length from the foveola to the vessel branching point (FBL) depending on the superior, inferior, nasal, and temporal areas of the macula were measured using infrared fundus images and image processing software (ImageJ). Preoperative and postoperative parameters were compared and correlations between VLA, FBL, macular thickness, and visual acuity were assessed.
The VLA of superior, inferior, and temporal areas showed a significant postoperative reduction. VLA differences showed a positive correlation with differences in macular thickness, which corresponded to the superior, inferior, and temporal areas; however, no correlation was observed in the nasal area. The FBL of the superior and inferior areas was significantly increased postoperatively. A positive correlation was observed between FBL differences and macular thickness differences in the superior area. Postoperative change in VLA and FBL did not show a significant correlation with postoperative best corrected visual acuity (BCVA) and BCVA differences.
Infrared fundus photographs and image processing software can be useful for quantifying progressive changes in retinal surface distortion after surgical removal of ERM. Macular edema and vascular distortion showed significant improvement after surgery. Furthermore, a correlation was observed between topographic and tomographic changes.
PMCID: PMC3996257  PMID: 24735324
Epiretinal membrane; ImageJ; Infrared fundus photography; Macular contraction; Macular thickness
11.  Three-dimensional characterization of epiretinal membrane using spectral domain optical coherence tomography☆ 
Saudi Journal of Ophthalmology  2010;24(2):37-43.
To describe epiretinal membrane (ERM) features using spectral domain optical coherence tomography “SD OCT” and to delineate the three-dimensional (3D) relationship in eyes with epiretinal membrane.
Fifty-two eyes of 44 patients with ERM were classified into two groups: idiopathic ERM and secondary ERM. Posterior vitreous face was evaluated. Pattern of ERM attachment was divided into: focal and global. A 3D SD OCT system (5 μm resolution) was used for scanning. Surface maps were used to study retinal topography.
Surface maps revealed manner and direction of epiretinal traction, pattern of attachment and blood vessel involvement. In 55.8% of eyes the membrane was globally adherent to the retina. There was a significant association (p = 0.02%) between pattern of membrane attachment and etiological classification of eyes. Posterior vitreous detachment (PVD) was associated with both groups, but no significant difference in between.
Spectral domain OCT allowed better characterization of ERM including: visualization, extension, cleavage plane and zones with free edges. Surface maps revealed the topography of ERM and retina pathology. Idiopathic ERM are significantly associated with global pattern. PVD plays an important role in the pathogenesis of primary as well as secondary ERM.
PMCID: PMC3729328  PMID: 23960873
Epiretinal membrane; Optical coherence tomography; Three-dimensional
12.  Redefining Lamellar Holes and the Vitreomacular Interface: An Ultrahigh-Resolution Optical Coherence Tomography Study 
Ophthalmology  2006;113(3):388-397.
To define optical coherence tomographic (OCT) criteria for the diagnosis of a lamellar macular hole, and to increase understanding of lamellar hole pathogenesis by examining fine anatomic features using ultrahigh-resolution optical coherence tomography (UHR OCT).
Retrospective observational case series.
Nineteen eyes of 18 patients with lamellar holes were imaged with UHR OCT between 2002 and 2004.
A UHR OCT system was developed for use in the ophthalmology clinic. All 6 UHR OCT images for each eye imaged were examined. Lamellar holes were diagnosed based on a characteristic OCT appearance. Criteria for the OCT diagnosis of a lamellar hole were as follows: (1) irregular foveal contour; (2) break in the inner fovea; (3) intraretinal split; and (4) intact foveal photoreceptors. From 1205 eyes of 664 patients imaged with UHR OCT, and retrospectively reviewed, 19 eyes of 18 patients were diagnosed with a lamellar hole based on these criteria. All 19 eyes were also imaged with standard resolution OCT. Their charts were retrospectively reviewed.
Main Outcome Measures
Standard and ultrahigh-resolution OCT images.
On chart review, clinical diagnosis of a lamellar hole was made in only 7 of 19 eyes (37%). Twelve of 19 eyes (63%) had an epiretinal membrane (ERM) on clinical examination. Ten of 19 eyes (53%) had a posterior vitreous detachment. On UHR OCT, 17 of 19 eyes (89%) had ERMs. Eleven ERMs had an unusual thick appearance on UHR OCT. Due to poor visual acuity, 4 eyes underwent vitrectomy. Only 1 of 4 surgeries (25%) was visually and anatomically successful. Another eye improved visually, but a lamellar hole persisted. One eye progressed to a full-thickness macular hole preoperatively, which reopened after surgery. One eye developed a full-thickness hole postoperatively.
The diagnosis of a lamellar hole can be made based on OCT criteria, which could be applied to both standard and ultrahigh-resolution OCT. The increased resolution of UHR OCT sheds light on the pathogenesis of the lamellar hole. Epiretinal membranes were visualized on UHR OCT in the majority of eyes. Many ERMs had an unusual thick appearance on UHR OCT, which may represent either trapped vitreous or posterior hyaloid, and may help stabilize retinal anatomy. Conversely, ERM contraction may play a role in lamellar hole formation. Vitrectomy surgery was anatomically and visually successful in only 1 of 4 patients, suggesting caution when performing vitrectomy on lamellar holes.
PMCID: PMC1940046  PMID: 16513456
13.  Morphometric Spectral-Domain Optical Coherence Tomography Features of Epiretinal Membrane Correlate With Visual Acuity in Patients with Uveitis 
American journal of ophthalmology  2012;154(1):78-86.e1.
To identify visually significant spectral-domain optical coherence tomography (SD-OCT) features of epiretinal membranes (ERM) in patients with uveitis.
Retrospective cohort and cross-sectional study.
Eighty consecutive eyes with uveitis and SD-OCT– documented ERM were included. Clinical data were collected at the time of diagnosis of ERM and at the final visit. SD-OCT images at the last visit were evaluated to identify fovea and ERM configuration and structural changes. Changes of 10% and 20% in central subfield thickness between initial and last SD-OCT were calculated and correlated with visual acuity (VA). An ERM thickness map was created using validated SD-OCT grading software.
VA improved significantly in eyes with more than 12 months of follow-up (P = .03). Although inflammation activity and medical treatment methods were no different in eyes with more or less than 12 months of follow-up, 16 eyes in the subset with longer follow-up underwent cataract extraction and intraocular lens implantation. Kaplan-Meier analysis demonstrated few vision losses during the follow-up period. Change in central subfield thickness did not correlate with VA. Foveal center involvement (P < .001), focal attachment of the ERM (P = .003), and foveal inner segment and outer segment junction disruption (P = .006) were associated independently with lower VA. ERM was thinner in eyes with 20/40 or better VA (4.6 ± 0.6 μm) compared with eyes with VA of less than 20/200 (P =.02). Longer duration of ERM was associated with thicker ERM (P < .05).
In most eyes with uveitis and ERM, VA remains stable if ocular inflammation and comorbidities are addressed appropriately.
PMCID: PMC3578738  PMID: 22541930
14.  Retinal thickness after vitrectomy and internal limiting membrane peeling for macular hole and epiretinal membrane 
To determine the retinal thickness (RT), after vitrectomy with internal limiting membrane (ILM) peeling, for an idiopathic macular hole (MH) or an epiretinal membrane (ERM). Also, to investigate the effect of a dissociated optic nerve fiber layer (DONFL) appearance on RT.
A non-randomized, retrospective chart review was performed for 159 patients who had successful closure of a MH, with (n = 148), or without (n = 11), ILM peeling. Also studied were 117 patients who had successful removal of an ERM, with (n = 104), or without (n = 13), ILM peeling. The RT of the nine Early Treatment Diabetic Retinopathy Study areas was measured by spectral domain optical coherence tomography (SD-OCT). In the MH-with-ILM peeling and ERM-with-ILM peeling groups, the RT of the operated eyes was compared to the corresponding areas of normal fellow eyes. The inner temporal/inner nasal ratio (TNR) was used to assess the effect of ILM peeling on RT. The effects of DONFL appearance on RT were evaluated in only the MH-with-ILM peeling group.
In the MH-with-ILM peeling group, the central, inner nasal, and outer nasal areas of the retina of operated eyes were significantly thicker than the corresponding areas of normal fellow eyes. In addition, the inner temporal, outer temporal, and inner superior retina was significantly thinner than in the corresponding areas of normal fellow eyes. Similar findings were observed regardless of the presence of a DONFL appearance. In the ERM-with-ILM peeling group, the retina of operated eyes was significantly thicker in all areas, except the inner and outer temporal areas. In the MH-with-ILM peeling group, the TNR was 0.86 in operated eyes, and 0.96 in fellow eyes (P < 0.001). In the ERM-with-ILM peeling group, the TNR was 0.84 in operated eyes, and 0.95 in fellow eyes (P < 0.001). TNR in operated eyes of the MH-without-ILM peeling group was 0.98, which was significantly greater than that of the MH-with-ILM peeling group (P < 0.001). TNR in the operated eyes of the ERM-without-ILM peeling group was 0.98, which was significantly greater than that of ERM-with-ILM peeling group (P < 0.001).
The thinning of the temporal retina and thickening of the nasal retina after ILM peeling does not appear to be disease-specific. In addition, changes in RT after ILM peeling are not related to the presence of a DONFL appearance.
PMCID: PMC3363315  PMID: 22654493
epiretinal membrane; macular hole; optical coherence tomography; retinal thickness; internal limiting membrane
15.  Scanning laser ‘en face’ retinal imaging of epiretinal membranes 
Saudi Journal of Ophthalmology  2014;28(2):134-138.
Comparison of scanning laser ophthalmoscopy (SLO) based ‘en face’ imaging techniques of patients with epiretinal membranes (ERM) and evaluation of the accuracy of preoperative diagnostic imaging.
A consecutive, prospective series of 53 study eyes of 46 patients with clinically diagnosed and in optical coherence tomography (OCT) confirmed symptomatic ERMs were included in this study. Spectral domain (SD-) OCT volume scans (20° × 20° with 49 horizontal sections, ART 15) including SLO en face and fundus autofluorescence (FAF) images of the macula were obtained with HRA2 (Heidelberg Retina Angiograph-Optical Coherence Tomography, Heidelberg Engineering, Heidelberg, Germany). In addition, wide-field SLO color and FAF images (Optomap 200Tx, Optos PLC, Dunfermline, UK) were performed also covering the macular area. En face images of both devices were graded for each included study eye based on SD-OCT cross sectional scans.
Grading of SD-OCT (HRA2) based SLO en face green–blue enhanced multi-color, green reflectance, blue reflectance and standard multi-color visualization revealed a better detectability of ERM than SD-OCT-based en face infrared or FAF images or wide-field SLO (Optomap) based pseudo-color, red laser separation, green laser separation, or FAF images. Both FAF visualizations, HRA2 and Optomap based, achieved low mean scores. SD-OCT based en face thickness map visualization revealed good visualization but poor demarcation of epiretinal membranes.
In summary, en face regular or enhanced multicolor SLO images acquired with HRA2 allow a better visualization of epiretinal membranes for preoperative evaluation compared to SD-OCT based en face thickness map or pseudo-color images acquired with Optomap while infrared or FAF images are least suitable to depict epiretinal membranes.
PMCID: PMC4023114  PMID: 24843307
Epiretinal membrane (ERM); Retinal imaging; Optical coherence tomography (OCT); En face; Fundus autofluorescence
16.  Indocyanine green-assisted epiretinal membrane peeling evaluated by optical coherence tomography and multifocal electroretinography 
To evaluate the anatomical and functional outcome in eyes with indocyanine green (ICG)-assisted idiopathic epiretinal membrane (ERM) peeling by optical coherence tomography (OCT) and multifocal electroretinogram (MFERG).
Prospective, interventional, noncomparative case series.
Twenty eyes of 20 patients with idiopathic ERM underwent pars plana vitrectomy and ICG-assisted ERM and internal limiting membrane (ILM) removal. Visual acuity (VA), OCT, and MFERG measurements were performed preoperatively and postoperatively at 1, 3, 6, and 12 months.
Best-corrected VA (BCVA) improved ≥2 Snellen lines in 70% of our patients at the 12th postoperative month. Mean VA increased from 20/100 preoperatively to 20/40 at 12 months. VA increased significantly at all postoperative examinations, compared to preoperative VA. Foveal thickness measured by OCT decreased significantly at all postoperative examinations. OCT mean values dropped from 472.3 μm preoperatively, to 249.2 μm at 12 months. Preoperative MFERG values significantly improved only at 12 months. OCT measurements and MFERG values did not correlate at any time. OCT values correlated with VA values only preoperatively while MFERG measurements correlated with VA at 12 months.
In our series of eyes with ERM surgery, OCT measurements and VA improved gradually throughout the first postoperative year, while MFERG values showed significant improvement at 12 months.
PMCID: PMC2704540  PMID: 19668533
17.  Spontaneous release of epiretinal membrane in a young weight-lifting athlete by presumed central rupture and centrifugal pull 
This patient presented for surgery at the age of 32 years, 14 months after his initial complaint of metamorphopsia and visual loss in the right eye. Past tests demonstrated a whitish epiretinal membrane (ERM) with translucent stress lines over a thickened macula. Visual acuity was found on last presentation to be normal with minimal alteration on Amsler grid testing. A torn ERM was found in the center with left-over ERM temporally and rolled-over ERM nasally at the site of the epicenter with no posterior vitreous detachment. Visual recovery occurred gradually over several days 2 months prior to presentation apparently following heavy weight-lifting with a sensation of severe eye pressure. Sequential funduscopy and optical coherence tomography scans demonstrated the peeling of an ERM accompanied by normalization of foveal thickness. Valsalva maneuver had put excessive tension on ERM which tore in its center at the weakest line with gradual contraction of the ERM away from the fovea towards the peripapillary area. This is a new mechanism of self-separation of ERM induced by Valsalva. ERM in young subjects is subject to rupture and subsequent separation by tangential traction. There are three mechanisms for spontaneous separation of ERM: 1) posterior vitreous detachment with pulling of ERM by detaching vitreous (most common in adults); 2) the contracting forces of the immature ERM become stronger than its adhesions to the retina resulting in slow tangential traction on the edges of the ERM and gradual separation from the edges towards the center (remodeling common in youngsters); and 3) acute tearing of ERM at its weakest central point and retraction of part of the membrane towards the epicenter (current case report).
PMCID: PMC4238755  PMID: 25484573
valsalva maneuver; posterior vitreous detachment
Retinal cases & brief reports  2009;3(3):233-236.
To describe a case of fine retinal striae visualized using an adaptive optics flood illuminated (AO-flood) fundus camera in a patient with vision loss from an idiopathic macular epiretinal membrane (ERM).
A case report of a 48-year-old woman with recent vision loss from ERM imaged using an AO-flood fundus camera and high resolution Fourier-domain optical coherence tomography (Fd-OCT) before and 3 months after vitrectomy.
Visual acuity improved from 20/70 to 20/20 after vitrectomy. Preoperative Fd-OCT showed severe cystoid macular edema with irregularities in the outer nuclear layer which consists of cell bodies of photoreceptors. Preoperative AO-flood en face images showed dark linear striae of approximately 10 μm width overlying the cone mosaic that improved following surgery, concurrent with improvement in visual acuity and morphologic changes on Fd-OCT.
Microstructural changes within the retinal layers resulting from macular traction from ERM can be visualized using an AO-flood fundus camera and Fd-OCT. They can appear as fine linear striae in AO-flood en face images. Further studies are needed to correlate these changes with vision loss associated with this condition.
PMCID: PMC3413271  PMID: 22880136
19.  Optical Coherence Tomography Evaluation in the Multicenter Uveitis Steroid Treatment (MUST) Trial 
Ocular immunology and inflammation  2012;20(6):10.3109/09273948.2012.719258.
To describe the evaluation of optical coherence tomography (OCT) scans in the Muliticenter Uveitis Steroid Treatment (MUST) trial and report baseline OCT features of enrolled participants.
Time domain OCTs acquired by certified photographers using a standardized scan protocol were evaluated at a Reading Center. Accuracy of retinal thickness data was confirmed with quality evaluation and caliper measurement of centerpoint thickness (CPT) was performed when unreliable. Morphological evaluation included cysts, subretinal fluid,epiretinal membranes (ERMs),and vitreomacular traction.
Of the 453 OCTs evaluated, automated retinal thickness was accurate in 69.5% of scans, caliper measurement was performed in 26%,and 4% were ungradable. Intraclass correlation was 0.98 for reproducibility of caliper measurement. Macular edema (centerpoint thickness ≥ 240um) was present in 36%. Cysts were present in 36.6% of scans and ERMs in 27.8%, predominantly central. Intergrader agreement ranged from 78 − 82% for morphological features.
Retinal thickness data can be retrieved in a majority of OCT scans in clinical trial submissions for uveitis studies. Small cysts and ERMs involving the center are common in intermediate and posterior/panuveitis requiring systemic corticosteroid therapy.
PMCID: PMC3824621  PMID: 23163490
20.  A Pilot Study of Morphometric Analysis of Choroidal Vasculature In Vivo, Using En Face Optical Coherence Tomography 
PLoS ONE  2012;7(11):e48631.
To study the ability of volumetric spectral domain optical coherence tomography (SD-OCT) to perform quantitative measurement of the choroidal vasculature in vivo.
Choroidal vascular density and vessel size were quantified using en face choroidal scans from various depths below the retinal pigment epithelium (RPE) in 58 eyes of 58 patients with either epiretinal membranes (ERM), early age-related macular degeneration (AMD), or reticular pseudo-drusen (RPD). For each patient, we used the macular volume scan (6×6 mm cube) for vessel quantification, while high-definition (HD) cross-section raster scans were used to qualitatively assess vascularity of the choroidal sub-layers, and measure choroidal thickness.
Of the 58 patients, more were female (66% versus 34% male), of whom 14 (24%) had ERM, 11 (19%) early AMD, and 33 (57%) RPD. Compared to intact choriocapillaris in all ERM (100%), none of the RPD and only 5/11 (45%) early AMD eyes had visible choriocapillaris on either cross section or C-scans (p-value<0.001). When comparing select regions from the most superficial C-scans, early AMD group had lowest vascular density and RPD had highest (p-value 0.04). Qualitative evaluation of C-scans from all three groups revealed a more granular appearance of the choriocapillaris in ERM versus increased stroma and larger vessels in the RPD eyes.
SD-OCT can be used to qualitatively and quantitatively assess choroidal vascularity in vivo. Our findings correlate to previously reported histopathologic studies. Lack of choriocapillaris on HD cross-sections or C-scans in all RPD and about half of early AMD eyes suggests earlier choroidal involvement in AMD and specifically, RPD.
PMCID: PMC3506620  PMID: 23189132
21.  Heavy trypan blue staining of epiretinal membranes: an alternative to infracyanine green 
By using dyes, it is easier to identify the extent of an epiretinal membrane (ERM) or the inner limiting membrane (ILM) during surgery. Trypan blue (TB) stains ERM and ILM weakly, but with less apparent toxicity than other intraocular dyes. Its main drawback in vitreoretinal surgery is the requirement of an air–fluid exchange (AFX) before its use.
To propose a modified form of TB denser than water, thus obviating the need for an AFX.
A prospective, consecutive trial with heavy trypan blue in vitreoretinal surgery.
A consecutive group of patients with ERMs was recruited prospectively. Patients were operated on using conventional methods. Heavy TB was prepared by mixing glucose 10% with Membrane blue (Dorc, Zuidland, The Netherlands) isovolumetrically. Patients were preoperatively and postoperatively assessed at 3 and 6 months (vision and ocular coherence tomography (OCT)). Ease of surgery was also assessed.
29 eyes were included in the study. Reapplication of dye was necessary in 25% of the cases, leading to improved contrast further facilitating the peeling process. In no case was an AFX necessary to obtain sufficient staining. All patients with ERM had an improvement in vision (from median 0.30 to 0.55) and macular volume and foveal thickness (from median 450 to 238 mm) on OCT. No retinal detachment or other complications developed as a result of surgery.
Heavy TB can be delivered efficiently to the retinal surface without an AFX. Staining was sufficient to allow a safe and efficient peeling of ERM. Repeat applications were easily performed. Its use was associated with vision improvement and decreased in foveal thickness, and the absence of adverse events in this small case series.
PMCID: PMC1955665  PMID: 17576712
22.  Optical coherence tomography guided peeling of macular epiretinal membrane 
Optical coherence tomography (OCT) has emerged as a powerful diagnostic aid in disorders of the vitreoretinal juncture. The purpose of this study is to determine whether OCT can be used as an additional tool for evaluating an architecture including the thickened area, and the identifiable edge of a macular epiretinal membrane (ERM), and helping us to dissect the ERM from the retinal surface more easily and safely. In two cases with ERM, the edges of the membranes were detected by OCT, and the peeling of the membrane was started at the area easily. OCT guided ERM peeling might be useful for dissecting ERM membranes without any hesitation.
PMCID: PMC3033001  PMID: 21311654
optical coherence tomography; epiretinal membrane; vitrectomy
23.  Characteristics of epiretinal membranes according to the presence or absence of posterior vitreous detachment 
Eye  2011;25(10):1341-1346.
The purpose of this study is to investigate the morphological features of epiretinal membrane (ERM) in the presence or absence of a posterior vitreous detachment (PVD).
Retrospective observational comparative case series.
This study involved 34 patients in whom the vitreoretinal relationship was confirmed during vitrectomy for treatment of ERM. We analyzed demography, direction of macular folds in fundus photographs, and foveal contours assessed by optical coherence tomography (OCT) in two groups of patients, the posterior vitreous attachment (PVA) group and the PVD group.
Mean age of the 14 patients in the PVA group was 58.2±8.2 years, and that of 20 patients in the PVD group was 66.7±6.7 years (P=0.0023). Funduscopic examination revealed radiating folds in 57.1% of patients in the PVA group and 10% of patients in the PVD group, and a flat-shaped foveal contour was observed on OCT in 71.5% of patients in the PVA group and 25.0% of patients in the PVD group. Significant differences were observed between the PVA group and the PVD group in both direction of the macular folds (P<0.01) and foveal contours (P=0.028).
Patients with ERM and PVA were usually younger than 60 years. Radiating macular folds and flat foveal contour in patients with ERM are highly sensitive and specific findings indicative of PVA.
PMCID: PMC3194324  PMID: 21760623
epiretinal membrane; posterior vitreous attachment; posterior vitreous detachment; retinal fold; foveal flattening; OCT
24.  Clinical Outcomes of Double Staining and Additional ILM Peeling during ERM Surgery 
To assess the clinical outcomes in idiopathic epiretinal membrane (ERM) patients after vitrectomy and ERM removal with or without additional indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling.
The medical records of 43 patients with an idiopathic ERM that underwent vitrectomy and ERM removal between July 2007 and April 2010 were reviewed. The patients were divided into two groups: triamcinolone-assisted simple ERM peeling only (group A, n = 23) and triamcinolone-assisted ERM peeling followed by ICG staining and peeling of the remaining internal ILM (group B, n = 20).
No difference was found between the two groups in terms of visual acuity, macular thickness, P1 amplitude or implicit time on multifocal-electroretinogram (mfERG) at six and 12 months postoperatively. In group B, ICG staining after ERM peeling demonstrated that the ILM had been removed together with the ERM in 12 eyes (60%), and all 12 eyes showed punctate retinal hemorrhages during ERM peeling. There was no recurrence of an ERM in either group.
Additional procedures involving ICG staining and ILM peeling during ERM surgery do not appear to have an additive effect on the clinical outcomes in terms of visual acuity, retinal function based on mfERG, or recurrence rate.
PMCID: PMC3730067  PMID: 23908571
Double staining; Epiretinal membrane; Internal limiting membrane
25.  Correlation between morphological features on spectral domain Optical Coherence Tomography and Angiographic leakage patterns in macular edema 
Retina (Philadelphia, Pa.)  2010;30(3):383-389.
To determine the morphological patterns of angiographic macular edema using simultaneous co-localization of fluorescein angiograms (FA) and spectral domain optical coherence tomography (SD-OCT) images in diabetes, epiretinal membrane, uveitic and pseudophakic cystoid macular edema and vein occlusion.
87 consecutive patients (107 eyes) with macular edema from five different etiologies were imaged by simultaneous SLO/OCT to study the morphological patterns of edema on SD-OCT and then correlated/co localized with the FA patterns of leakage. Statistical analysis was done to analyze the differences in the morphological OCT pattern by different disease.
SD-OCT characteristics of macular edema showed a significant difference across different diseases (p = 0.037). Cystic fluid pockets were found to be more commonly seen in patients with DME and retinal vein occlusions whereas those cases with macular edema secondary to ERM revealed non-cystic changes on OCT. 70 of the 107 eyes had diffuse angiographic leakage and rest of the 37 eyes had cystoid leakage on angiography. Of the 70 eyes with diffuse leakage, 24.28% showed microcysts on SD-OCT in the area of edema and 70% eyes had diffuse thickening or distorted architecture without cyst. All 37 eyes with cystoid leakage showed cysts in the area of edema by SD-OCT. 3.73% of eyes with FA leakage had no abnormality on SD-OCT.
Eyes with DME and retinal vein occlusions have a significantly higher incidence of cyst formation on SD-OCT. There was no correlation between visual acuity and cyst formation. Diffuse non-cystoid angiographic macular edema may show micro cysts on SD-OCT, but diffuse edema is more commonly associated with thickening or distortion of the retinal layers without cyst formation. Cystoid leakage on FA is always associated with cystic changes on SD-OCT.
PMCID: PMC2870721  PMID: 20216291

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