Epiretinal Membrane Specimens Research Articles

Sphingosine-1-phosphate expression in human epiretinal membranes

The abnormal posterior vitreous detachment (PVD) is speculated as an important mechanism of the development of the epiretinal membrane (ERM). However, there is only limited information about the molecular mechanism. Sphingosine-1-phosphate (S1P) is a mediator of the mechanosensitive response in several cell types that may have a role in the pathogenesis of ERM during abnormal PVD. Therefore, we evaluated the expression of S1P in the human ERM and the role of S1P in cultured human Muller glial cells. Among 24 ERM specimens, seven specimens (29.2%) exhibited S1P expression. Patients with secondary ERM or ellipsoid zone defects, which suggest abnormal PVD presented a significantly higher S1P+ cell density (secondary ERM: 128.20 ± 135.61 and 9.68 ± 36.01 cells, p = 0.002; EZ defects: 87.56 ± 117.79 vs 2.80 ± 8.85, p = 0.036). The addition of S1P increased the migrative ability and expression of N-cadherin and α-SMA in human Muller glial cells, suggesting S1P is a potential causative molecule for the development of ERM during abnormal PVD.

Epithelial-mesenchymal transition suppresses ERas to activate autophagy in retinal pigment epithelial cells in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is a complex ocular disease that leads to detached retinas and irreversible vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays a critical role in PVR occurrence. However, the core targets driven by the EMT process that lead to the pathogenesis of PVR remain unclear. In our study, the relationship between embryonic stem cell-expressed Ras (ERas) and EMT in RPE cells was investigated. The subretinal and epiretinal membrane specimens of human PVR were examined for ERas and hallmarks of autophagy and EMT using Western blotting and immunofluorescence. EMT was induced by transforming growth factor (TGF)-β1 or epidermal growth factor (EGF) in ARPE-19 cells. Autophagy was inhibited by U0126 or bafilomycin A1 in ARPE-19 cells. ERas was decreased and the classical autophagy biomarker microtubule associated protein 1 light chain 3 alpha (LC3) was upregulated in the subretinal and epiretinal membranes of PVR patients in vivo. Moreover, ERas was downregulated and autophagy was activated in RPE ARPE-19 cells in response to transforming growth factor (TGF)-β1 and epidermal growth factor (EGF) induction. Finally, overexpression of ERas in RPE cells inhibited autophagy via impaired formation of autophagosomes and lysosomes. Our study revealed the role of ERas in the pathogenesis of PVR through EMT and provided a novel therapeutic target for PVR prevention and treatment.

Pathogenesis of idiopathic epiretinal membrane

AbstractTo describe the pathophysiological events involved in the formation and progression of epiretinal membranes (ERMs).Epidemiologic studies have found a clear relationship between ERM formation, ageing, and posterior vitreous detachment. Increased prevalence of ERM is noted in the population older than 60 years, with peak prevalence between 70 and 79 years. Histologic studies of surgically obtained ERM specimens identified cellular and extracellular matrix components. A key element in ERM formation and its progression toward a contractile membrane is the transdifferentiation of those cellular components toward myofibroblasts. ERMs stiffness is a result of the proportion between its collagenous and non‐collagenous elements. Additionally, modifications of membrane macromolecules, such as accumulation of advanced glycation end products, which constitutes an age‐related phenomenon, may increase stiffness of the membrane and contribute to the fibrotic process.Retinal membranes have been described for more than 150 years and comprise the most common type of fibrocellular proliferation found at the vitreoretinal interface. Although patients with ERM can be asymptomatic when the membrane is thin and translucent, its progression to a thick, and contractile membrane may result in macular distortion, inducing metamorphopsia and loss of visual function. Understanding disease pathogenesis is essential in order to develop appropriate therapeutic approaches.

Microscopic Observation of Proliferative Membranes in Fibrocontractive Retinal Disorders.

Proliferative membranes of fibrocontractive retinal disorders are extensively studied from the morphological and evolutive point of view. Despite this, little is known of their cellular composition. In this study, the authors investigated the morphological characteristics and cell composition of various types of surgically excised proliferative membranes and internal limiting membranes (ILMs), in order to provide new data supporting or challenging the pathogenic theories proposed until now. Sixty-nine specimens from 64 eyes of 64 consecutive patients were collected at surgery and subjected to a multilevel analysis by means of optical and electron microscopy. Membrane samples were semiquantitatively evaluated for the amount and distribution of cell nuclei and pigment. Immunohistochemical staining was performed with antibodies to alpha smooth muscle actin and CD68. Data were analyzed after grouping according to the following tissue types: ILM (20 specimens), epiretinal membrane (ERM) (22 specimens), ILM + ERM (20 specimens), and proliferative vitreoretinopathy (PVR) (7 specimens). The cell components found in the ERM specimens, like myofibroblasts, macrophages, and polymorphonuclear cells, were recognized as the expression of cell migration and differentiation that induced an inflammatory process and a fibroproliferative repair process. The detection of pigments in specific types of ERM, like those associated with lamellar macular hole (LMH) or secondary to retinal detachment (RD), diabetes, and PVR, suggested that retinal pigment epithelium (RPE) cells may have a role in the development of these vitreoretinal disorders. The reduction of the ERM cellularity with the patient's age supports the hypothesis that ERM evolves in time up to a fibrous tissue formation.

In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema.

Diabetic macular edema (DME) is characterized by an accumulation of fluid in the macula due to diabetic retinopathy. Currently, anti-VEGF drugs are the standard treatment worldwide for DME. This study aimed to assess whether the existence of epiretinal membrane (ERM) affects anti-VEGF efficacy, due to reduced permeability of the antibody through the ERM. We retrospectively examined clinical data of DME patients who underwent anti-VEGF treatment and evaluated whether clinical differences existed between DME eyes with ERM and those without ERM. We then created an in vitro ERM model using MIO-M1, ARPE-19, and NTI-4 cells on Transwell membranes and evaluated antibody permeability through this in vitro ERM model using fluorescently labeled antibodies. Central retinal thickness (CRT) change between before and 1 month after first anti-VEGF treatment, as well as final CRT and final visual acuity 12 months after first anti-VEGF treatment, significantly differed between DME eyes with ERM and those without ERM. The in vitro ERM model led to production of collagen I in a manner similar to that of human ERM specimens. Fluorescence intensity of the lower chamber of the in vitro ERM model was significantly reduced in a dose-dependent manner. Clinical data analysis indicated that the existence of ERM in DME eyes lowered the efficacy of anti-VEGF treatment. Reduced antibody permeability through the in vitro ERM model suggested ERM presence was associated with resistance to anti-VEGF treatment in DME eyes with ERM.

Gli1 Expression in Human Epiretinal Membranes.

We evaluate the expression of Gli1 in human epiretinal membranes (ERM) and correlate this with clinical data. We prospectively recruited patients with ERM. A total of 33 human ERM specimens were immunolabeled with anti-Gli1 antibody and the number of total cells/hyperfield (HF), Gli1(+) cells/HF, and the percentage of Gli1(+) cells/total cells were calculated. We evaluated the interrelationship of cellular properties and clinical findings, such as presence of diabetic retinopathy (DR), retinal breaks, intraocular inflammation, central foveal thickness, maximal retinal thickness, retinal contraction, lamellar holes, pseudoholes, the attenuation or absence of an inner segment/outer segment (IS/OS) junction/external limiting membrane (ELM), cystic changes, and paravascular inner retinal defects. Among 33 specimens, 25 specimens (75.8%) showed nuclear Gli1 expression. The mean Gli1(+) cells/total cells was 54.0 ± 36.7% (range, 0%-92.8%). There was significantly higher expression of Gli1(+) cells in ERM specimens from patients with DR (P = 0.014), and lower expression from patients with retinal breaks (P = 0.022). Epiretinal membrane specimens from patients with alteration of IS/OS junction/ELM or cystic changes on OCT showed higher percentage of Gli1(+) cells/total cells. Gli1 expression was detected in most ERM specimens. Patients who had DR or OCT findings indicating chronic retinal insults showed higher Gli1 expression. Gli1 may have a role in the pathogenesis of ERM after chronic retinal insults.

Lamellar Hole–Associated Epiretinal Proliferation in Comparison to Epiretinal Membranes of Macular Pseudoholes

To compare immunocytochemical and ultrastructural characteristics of "lamellar hole-associated epiretinal proliferation" in lamellar macular holes with "conventional epiretinal membrane" in macular pseudoholes. A consecutive observational case series, laboratory investigation. We analyzed surgically excised flat-mounted internal limiting membrane specimens and epiretinal membrane specimens removed from 25 eyes of 25 patients with lamellar macular holes (11 eyes) and macular pseudoholes (14 eyes) using interference and phase-contrast microscopy, immunocytochemistry, and transmission electron microscopy. By spectral-domain optical coherence tomography, epiretinal material of homogenous reflectivity without contractive properties was categorized as lamellar hole-associated epiretinal proliferation, whereas tractional epiretinal membranes presenting contractive properties were termed conventional epiretinal membrane. Lamellar hole-associated epiretinal proliferation was seen in 73% of eyes with lamellar macular hole. Eyes with macular pseudohole presented with conventional epiretinal membrane. In lamellar hole-associated epiretinal proliferation, positive immunoreactivity for anti-glial fibrillary acidic protein, hyalocyte markers, and anti-collagen type I and III was seen. In contrast, specimens of macular pseudoholes were positive for α-smooth muscle actin and anti-glial fibrillary acidic protein, predominantly. Cellular ultrastructure showed that lamellar hole-associated epiretinal proliferation of lamellar macular holes mainly consisted of fibroblasts and hyalocytes, whereas myofibroblasts dominated in conventional epiretinal membranes of macular pseudoholes. Cells within lamellar hole-associated epiretinal proliferation appear to originate from vitreous and possess less contractive properties than cells of conventional epiretinal membranes. Our findings point to differences in pathogenesis in a subgroup of lamellar macular holes presenting lamellar hole-associated epiretinal proliferation on the retinal surface.

Assessment of retinal pigment epithelial cells in epiretinal membrane formation

BackgroundThe definite etiology of epiretinal membrane (ERM) is unknown. Clinically, ERM may cause metamorphopsia and decreased vision during the disease exacerbation. Several theories of pathogenesis emphasize a glial tissue origin. However, in some studies, surgically removed ERM specimens were found to contain retinal pigment epithelial (RPE) cells. The actual mechanism by which RPE cells gain access into the inner retina and what roles they play in the formation of ERM remain controversial. The purpose of this study was to evaluate the incidence of RPE cells in ERM and discuss the possible mechanisms. MethodsA retrospective review of the histological findings in 23 surgically removed specimens of ERM was done. The samples were studied using light microscopy and immunohistochemistry. ResultsGlial cells were the main components in all 23 cases, and RPE cells were found in five of the specimens. Two of these five cases were clinically diagnosed as idiopathic macular pucker, whereas the other three cases were identified as macular pucker associated with previous retinal detachment. A much higher density of myofibroblasts was noted in these five specimens than in the other 18 cases. ConclusionThe incidence of RPE cells found in ERM is 21.7% (5 out of 23 specimens). A strong association between RPE cells and myofibroblasts in cases of ERM with or without retinal detachment indicates that RPE cells may contribute to the formation of ERM via a wound healing process.

Morphology of surgical ILM‐specimens in epiretinal membranes, macular holes, and diabetic retinopathy

AbstractPurpose Myofibroblasts play a major role in the production of retractile phenomena causing contraction or shrinkage of the epiretinal membranes (ERM) in proliferative vitreoretinopathy and diabetic retinopathy. The purpose of our study was to evaluate the expression of myofibroblasts on epiretinal tissues in eyes with epiretinal membranes, diabetic macular edema (DME) or macular holes.Methods Samples of ERM and ILMs (internal limiting membranes) following macular epiretinal membrane removal in eyes with diabetic maculopathy, refractory to conservative treatment, idiopathic epiretinal membrane and macular holes, were collected. Double immunofluorescence staining, with antibodies recognizing a smooth muscle actin (a‐SMA) and fibronectin (ED‐A FN) or vimentin in myofibroblasts, followed by confocal and electronic microscopy was performed.Results a‐SMA in association with either ED‐A FN or vimentin were detected in all ERM specimens. a‐SMA and ED‐A FN were also detected in ILMs removed in cases of stage IV macular holes. ED‐A FN was expressed in close relation to a‐SMA–positive myofibroblasts, predominately located close to the border of the macular hole area. In all idiopathic ERMs, ED‐A FN was expressed in close relation to a‐SMA–positive myofibroblasts. In those cases, no a‐SMA staining was observed in ILM specimens.Conclusion Scanning electron microscopy indicated that active contraction mechanisms are always expressed in epiretinal macular membrane and underling ILM tissues in eyes with diabetic maculopathy and late stages of macular hole.ILM folding seems to be myofibroblast‐independent in idiopathic epiretinal membrane cases.

RESIDUAL CELLULAR PROLIFERATION ON THE INTERNAL LIMITING MEMBRANE IN MACULAR PUCKER SURGERY

To provide pathology data on the completeness of epiretinal membrane (ERM) removal with and without internal limiting membrane (ILM) peeling. Twenty-two patients with idiopathic ERM formation underwent vitrectomy with ERM removal and subsequent staining of the vitreomacular interface with brilliant blue. If the ILM was still present after ERM removal, it was peeled off. Both ERM and ILM specimens were harvested in different containers and prepared for flat-mount phase-contrast and interference microscopy, immunocytochemistry, and transmission electron microscopy. In 14 patients (64%), the ILM was still present at the macula after ERM removal. On average, 20% (range, 2-51%) of the total cell count was left behind at the ILM if the ERM was removed only. There were mainly glial cells on the ILM, and few hyalocytes. In nine eyes, the cells were forming cell clusters. In 8 patients (36%), both ERM and ILM were removed together. Electron microscopy showed cellular proliferation directly attached to the ILM in these eyes, whereas in the sequentially peeled group, there was collagen interposed between the ERM and the ILM. Surgical ERM removal resulted in splitting of the vitreous cortex in these eyes, leaving the ILM with residual cells behind. Simple ERM removal results in sufficient separation of fibrocellular tissue in one third of cases, only. In 2 of 3 patients with idiopathic ERM, the vitreous cortex splits when the ERM is removed, leaving an average of 20% of the total cell count behind on the ILM. As these cells are capable of proliferation and causing ERM recurrence, staining of the ILM with subsequent removal seems beneficial in macular pucker surgery.

Lamellar Macular Hole: A Clinicopathologic Correlation of Surgically Excised Epiretinal Membranes

To correlate clinical and optical coherence tomographic (OCT) features with morphologic and immunohistochemical findings of epiretinal membranes (ERMs) in lamellar macular holes (LMHs). Nineteen specimens were removed from 19 eyes during vitrectomy for lamellar macular hole with ERM and internal limiting membrane peeling, and were processed for transmission electron microscopy and immunohistochemistry by cross-sectional and flat-mount preparation techniques. By using OCT criteria and intraoperative observations, ERM specimens were divided into two groups: 13 "dense" and 6 "tractional" membranes. Patients' records were reviewed. "Dense" ERMs were seen with abundant clusters of fibrous long-spacing collagen embedded in compactly folded native vitreous collagen strands. Posterior hyaloids were attached to the retina in the majority of cases. Both groups of ERMs showed positive immunoreactivity for glial fibrillic acidic protein and hyalocyte markers. Anti-α-smooth muscle actin labeling was most positive in "tractional" ERMs. Surgery resulted in significant improvement (74%) of visual acuity, with a mean gain of 2 Snellen lines in both groups. All other patients (26%) preserved vision. Three patients (16%) developed a full-thickness macular defect requiring additional surgery. Morphologic components differ in epiretinal cell proliferations of LMHs. In association with degradation of vitreous collagen, glial cells and hyalocytes seem to play an important role in LMH development. Since functional benefit after surgery was limited and progression to a full-thickness macular defect was a notable complication, we recommend caution in proceeding with surgical intervention. Further investigations are needed to elucidate whether "dense" and "tractional" LMHs represent different disease entities or different stages of one disorder.

Peel and peel again

Aim:To determine if the internal limiting membrane (ILM) was present in the epiretinal membrane (ERM) when we deliberately tried to perform a “double peel” for macular pucker.Methods:Pars-plana vitrectomy and a...

Intravitreous hepatocyte growth factor in patients with proliferative diabetic retinopathy: A case-control study

The aim of the present study was to evaluate the vitreous levels of hepatocyte growth factor (HGF) in patients with proliferative diabetic retinopathy (PDR) and to investigate its relationship with vascular endothelial growth factor (VEGF) and retinopathy activity. In addition, the relationship between intravitreous HGF levels and the presence of epiretinal membranes (ERM), as well as the expression of c-Met in ERM were also investigated. In this case-control study, serum and vitreous samples as well as ERM specimens were obtained during vitrectomy from 28 diabetic patients with PDR and 30 non-diabetic control subjects. HGF and VEGF were determined by ELISA and c-Met expression by immunohistochemistry. Vitreal levels of both VEGF and HGF were higher in patients with PDR in comparison with the control group ( p < 0.0001). However, after correcting for total vitreous protein concentration, HGF (ng/mg of proteins) was lower in diabetic patients than in non-diabetic control subjects ( p = 0.02). No correlation was detected between the vitreal levels of HGF and VEGF. In addition, intravitreous VEGF but not HGF was found to be related to PDR activity. Both diabetic patients and non-diabetic patients in whom ERM had been excised presented higher HGF intravitreous levels. Finally, a significant expression of c-Met in ERM membranes were observed in both diabetic patients with PDR and in non-diabetic subjects. In conclusion, both HGF and VEGF increased, but were not related, in the vitreous fluid of diabetic patients with PDR. Our findings suggest that HGF is related to pathological conditions in which fibroproliferative processes or wound healing are involved rather than with angiogenesis itself.

A rationale for membrane peeling in the repair of stage 4 macular holes

To examine the histological and immunocytochemical characteristics of epiretinal membranes (ERM) associated with stage 4 macular holes (MH) so as to establish a vitreoretinal rationale for surgery in stage 4 MH. Consecutive patients with stage 4 MH undergoing vitrectomy and membrane peeling were recruited. Preoperatively, the eyes were examined for ERM formation over the macula and completeness of posterior hyaloid membrane (PHM) separation from the retina. ERM peel specimens obtained during surgery were sent for histological and immunocytochemical studies and were compared with the PHM specimens taken from a previous post-mortem study of eyes with physiological posterior vitreous detachment but without macular holes. A total of 13 patients with stage 4 MH fulfilled the inclusion criteria and were recruited. Preoperatively, all eyes had an ERM over the macula and incomplete separation of the PHM seen as a defect in the PHM on specular biomicroscopy. Histologically, the ERM specimens had very similar morphological characteristics to PHM, consisting of an eosinophilic membrane of varying thickness with scattered spindle-shaped cells. The membranes stained positively for type IV collagen while the cells were glial fibrillary acidic protein positive. Postoperatively, successful closure of MH was achieved in all cases. Stage 4 MH is characterised by incomplete separation of the PHM from the retina with remnants overlying the macula manifesting as ERM. Removal of the ERM is required during vitrectomy in order to relieve the tangential forces involved in the development of MH.

Intérêt de la microscopie confocale in vitro dans l’étude des membranes épirétiniennes et des membranes limitantes internes après chirurgie maculaire

To study specimens obtained from epiretinal membrane (ERM) and macular hole surgery with confocal microscopy and to evaluate its advantages in understanding their pathophysiology.This retrospective study included 50 patients undergoing surgery for epiretinal membrane (40 patients) or idiopathic macular hole (10 patients). Infracyanine green was used in 45 cases. Immunohistological examination of the excised tissues was undertaken using confocal microscopy after labeling with antibodies to glial fibrillary acidic protein (GFAP) and vimentin.Confocal microscopic analysis of epiretinal membranes identified three types of tissues: 13 ERMs, which appeared thick and rich in cells, 20 internal limiting membranes (ILMs), which appeared thin, wrinkled and poor in cells, and seven composite tissues, where ERM and ILM were removed at the same time. The analysis of ten specimens obtained from macular hole surgery revealed nine ILMs and one composite tissue that were quite similar to those removed in epiretinal membrane surgery. In all, 27 specimens (10 ERMs, 12 ILMs and five composite tissues) contained GFAP-positive glial cells.The confocal microscope provided a fast, three-dimensional analysis of ERMs and ILMs. An immunohistological study identified cells that take part in the genesis of the membranes. Glial cells were found both in ERM and ILM specimens. Our findings suggest that Müller's cells may contribute to the pathogenesis of ERM and macular hole development.

Indocyanine green-assisted internal limiting membrane removal in epiretinal membrane surgery: A clinical and histologic study

Purpose To evaluate the clinical outcome and quantify histologically the amount of microscopic internal limiting membrane (ILM) and epiretinal membrane (ERM) present in ILM and ERM specimens obtained from ERM surgery. Design Interventional consecutive case series. Methods Patients scheduled for ERM surgery were recruited prospectively. Pars plana vitrectomy, removal of ERM, and ILM peeling with indocyanine green (ICG) staining were performed in all patients. Epiretinal membrane and ILM specimens were sent for histologic examination. The amount of ERM present in ILM specimens and the amount of ILM present in ERM specimens were quantified by manual counting. Outcome measures include change in best-corrected visual acuity (BCVA), proportion of cases with 2 or more lines of visual improvement, anatomic outcome, proportions of microscopic ERM within ILM, and microscopic ILM within ERM. Results Eighteen eyes in 18 patients were operated with a mean follow-up of 19.3 months. There were 13 primary ERMs and five secondary ERMs. The mean logMAR BCVA improved from 0.83 preoperatively to 0.49 postoperatively ( P < .001). The mean lines of improvement in BCVA was 3.3 lines with 14 patients (77.8%) who had 2 or more lines of BCVA improvement. Histologic evaluation of the specimens showed no significant correlation with the final BCVA of 20/50 or better. Eleven (61.1%) of the ILM specimens showed various amount of microscopic ERM and 16 (88.9%) of the ERM specimens showed various amount of ILM fragments. The mean proportion of ERM within ILM specimens was 4.69% and that of ILM within ERM specimens was 51.5%. No significant recurrence of ERM was found. Conclusion Recurrence of ERM may be minimized by removing residual microscopic ERM present on the ILM. Indocyanine green-assisted ILM peeling in ERM surgery appears to have favorable visual and anatomic outcomes.

Visual field defect caused by nerve fiber layer damage associated with an internal limiting lamina defect after uneventful epiretinal membrane surgery

PURPOSE: To report a case of visual field defect caused by damage of the nerve fiber layer associated with an internal limiting lamina defect after uneventful epiretinal membrane peeling. DESIGN: Interventional case report. METHODS: In the right eye, a 43-year-old male patient developed a nasal step and mild inferior arcuate scotoma after uneventful epiretinal membrane surgery without any associated glaucoma. Transmission electron microscopy was performed on the epiretinal membrane specimens. RESULTS: An epiretinal membrane specimen showed adhesion between epiretinal membrane and axons of nerve fiber layer in the area of the internal limiting lamina defect. CONCLUSION: Adhesion between epiretinal membrane and retinal tissue in the area of the internal limiting lamina defect may cause damage of the nerve fiber layer and visual field defect after epiretinal membrane peeling.

Trypan blue staining of epiretinal membranes in proliferative vitreoretinopathy.

To determine whether trypan blue staining facilitates epiretinal membrane (ERM) removal in proliferative vitreoretinopathy. In 10 patients undergoing vitrectomy for proliferative vitreoretinopathy, ERM peeling was performed without staining the tissue, until no additional ERMs were clearly visible. Then, after a fluid-air exchange, 0.06% trypan blue solution was applied onto the retinal surface. After 1 minute, all excess dye was removed and, after an air-fluid exchange, ERM peeling was completed. Excised ERM specimens were analyzed by transmission electron microscopy. For each patient, the efficacy of trypan blue staining of ERMs during surgery was scored. In all patients, intraoperative staining of ERMs with trypan blue was found to be a useful adjunct, since the dye consistently improved direct visualization and delineation of ERMs and facilitated ERM removal. A clear contrast was created between the stained ERMs and the nonstaining, underlying retina. Electron microscopy showed that only ERM tissue was removed. No adverse reactions related to the use of the dye were observed up to 3 months after surgery. Trypan blue may be an important new tool in the surgical management of proliferative vitreoretinopathy, since it may allow a more complete and safer ERM removal.

Dissociated optic nerve fiber layer appearance of the fundus after idiopathic epiretinal membrane removal

Purpose To report the appearance of the fundus, that is seen frequently after removal of an idiopathic epiretinal membrane and which we refer to as the dissociated optic nerve fiber layer appearance. Design Interventional, noncomparative retrospective case series. Participants One hundred consecutive patients with an epiretinal membrane who underwent pars plana vitrectomy and epiretinal membrane peeling in one eye. Methods Only patients with an idiopathic epiretinal membrane or a membrane associated with a peripheral retinal tear, but without retinal detachment, were considered for this study. Sixty-one patients met these criteria for one eye. Preoperative and postoperative best-corrected visual acuity and preoperative and postoperative blue filter fundus photographs were reviewed. Histopathologic specimens of epiretinal membranes were available for 14 eyes. Main outcome measures The postoperative incidence of the dissociated optic nerve fiber layer appearance on blue filter photographs, visual acuity changes, and the presence of internal limiting membrane in epiretinal membrane specimens. Results The postoperative incidence of this feature on blue filter fundus photographs was 43%. No difference was found between eyes with or without this feature concerning the average preoperative and postoperative best-corrected visual acuity or the average change in visual acuity. Internal limiting membrane was present in all 14 epiretinal membrane specimens available. Five of these 14 patients concerned exhibited a dissociated optic nerve fiber layer appearance and 9 did not. Conclusions The dissociated optic nerve fiber layer appearance occurred frequently after removal of an epiretinal membrane. As far as we know, this feature has not been previously reported. It consisted of numerous arcuate striae within the posterior pole in the direction of the optic nerve fibers and slightly darker than the surrounding retina. This feature had no functional effect noticeable by the patient and did not preclude good visual recovery. The small number of histologic samples and the impossibility of quantifying the area of internal limiting membrane peeled off did not allow us to supply proof that this feature is due to the extensive peeling of the internal limiting membrane, although this is the most likely hypothesis.

Activated T lymphocytes in epiretinal membranes from eyes of patients with proliferative diabetic retinopathy.

To investigate the potential contribution of immune-mediated processes to the development of proliferative diabetic retinopathy (PDR), an immunohistochemical study was undertaken to characterize the infiltrating immune cells in epiretinal membranes from the eyes of patients with PDR. A total of 18 PDR epiretinal membrane specimens obtained surgically from pars plana vitrectomy were studied by using a panel of monoclonal antibodies against T lymphocytes (CD4 and CD8), interleukin-2 (IL-2) and interleukin-2 receptors (IL-2R). Twelve of 18 specimens (67%) contained CD4-positive cells and 13 of 18 (73%) contained CD8-positive cells. IL-2 was found in 12 of 18 samples (67%), of which 11 also contained CD4-positive cells, and IL-2R was detected in 10 of 18 membranes (56%), of which 9 contained CD4-positive cells and released IL-2. Most of the IL-2R-positive membranes were from type I diabetic patients, 40% of them from patients younger than 40 years. Our study demonstrated the involvement of activated immune cells and release of lymphokine(s) in more than half of the diabetic epiretinal membranes tested and revealed that the processes of immune responses and the biological effects of lymphokine(s) may play an important part in the development of epiretinal membranes of PDR, especially in young-onset and type I diabetes.