Contraction Of Epiretinal Membrane Research Articles

Delayed manifestation of a full-thickness traumatic macular hole: Probable causes and consequences – A case report

A 23-year-old male experienced a cricket ball injury to his right eye 1 day ago. Right eye visual acuity was counting fingers close to face. He presented with anterior uveitis, commotio retinae, and vitreous hemorrhage. Steroids and cycloplegics were given. Fundus showed resolved vitreous hemorrhage, a healthy optic disc, patchy epiretinal membrane, choroidal ruptures, peripapillary scarring, and 20/80 vision on follow-up. Patient developed a full-thickness macular hole 11 months after trauma, decreasing vision to 20/120. Exam and optical coherence tomography showed no abnormal posterior vitreous detachment. Macular hole surgery closed the hole with a normal foveal contour without improving vision. At the last follow-up 6 months after surgery, the hole was closed and vision improved to 20/120. A delayed traumatic macular hole unrelated to vitreomacular traction or cystoid macular edema deroofing has not been reported in literature. Traumatic macular hole development may be delayed by secondary epiretinal membrane contraction, ocular movements, or expansion of choroidal rupture.

MACULAR PIGMENT OPTICAL DENSITY ASSESSED BY HETEROCHROMATIC FLICKER PHOTOMETRY IN EYES AFFECTED BY PRIMARY EPIRETINAL MEMBRANE.

To compare macular pigment optical density (MPOD) in healthy eyes versus eyes affected by primary epiretinal membrane (ERM) in different stages and to assess the relation between MPOD and optical coherence tomography findings. Prospective cross-sectional study of 62 eyes of 62 patients affected by unilateral primary ERM. Contralateral healthy eyes from the same patients were used as a control group. Main outcome measures were MPOD, ERM stage, central foveal thickness (CFT), outer nuclear layer thickness (ONLT), integrity of outer retinal bands, and presence of central bouquet abnormalities. In the study group, mean CFT was 444 ± 75 μm and mean ONLT was 245 ± 40 μm, whereas in the control group, mean CFT was 230 ± 21 μm and mean ONLT was 102 ± 14 μm (P < 0.001). Mean MPOD was 0.86 ± 0.07 in eyes with ERM and 0.48 ± 0.09 in contralateral healthy eyes (P < 0.001). Macular pigment optical density was associated with CFT (P = 0.006) and ONLT (P < 0.001), whereas no significant associations were observed between MPOD and outer retinal bands integrity (P = 0.14) and central bouquet abnormalities (P = 0.08). Macular pigment optical density increased in eyes affected by primary ERM proportionally to CFT and, especially, ONLT. Probably, centripetal forces exerted by ERM contraction on the retinal surface lead to a progressive foveal packing of foveal Müller cells.

Finite Element Analysis of the Epiretinal Membrane Contraction

The epiretinal membrane is a thin sheet of fibrous tissue that can form over the macular area of the retina, and may result in the loss of visual acuity or metamorphopsia, due to superficial retinal folds. A vitrectomy surgery, the current treatment procedure for this pathology, is only performed after symptoms are present. However, sometimes the patients do not present any vision improvements after the surgery. The use of computational methods for a patient-specific biomechanical analysis can contribute to better understanding the mechanisms behind the success or failure of a vitrectomy. Using medical data from two patients who underwent a vitrectomy, one with substantial improvements and another with no improvements, an analysis of the retinal displacement due to the contraction of the epiretinal membrane was performed. Our results suggest a causal effect between the magnitude of the retinal displacements caused by the epiretinal membrane contraction and the outcome of the vitrectomy procedure.

Müller cells and astrocytes in tractional macular disorders.

Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with cystoid macular edema or high myopia. Traction to the fovea may cause partial- and full-thickness macular defects. Partial-thickness defects are foveal pseudocysts, macular pseudoholes, and tractional, degenerative, and outer lamellar holes. The morphology of the foveal defects can be partly explained by the shape of Müller cells and the location of tissue layer interfaces of low mechanical stability. Because Müller cells and astrocytes provide the structural scaffold of the fovea, they are active players in mediating tractional alterations of the fovea, in protecting the fovea from such alterations, and in the regeneration of the foveal structure. Tractional and degenerative lamellar holes are characterized by a disruption of the Müller cell cone in the foveola. After detachment or disruption of the cone, Müller cells of the foveal walls support the structural stability of the foveal center. After tractional elevation of the inner layers of the foveal walls, possibly resulting in foveoschisis, Müller cells transmit tractional forces from the inner to the outer retina leading to central photoreceptor layer defects and a detachment of the neuroretina from the retinal pigment epithelium. This mechanism plays a role in the widening of outer lameller and full-thickness macular holes, and contributes to visual impairment in eyes with macular disorders caused by conractile epiretinal membranes. Müller cells of the foveal walls may seal holes in the outer fovea and mediate the regeneration of the fovea after closure of full-thickness holes. The latter is mediated by the formation of temporary glial scars whereas persistent glial scars impede regular foveal regeneration. Further research is required to improve our understanding of the roles of glial cells in the pathogenesis and healing of tractional macular disorders.

Macular Pseudohole: Pathophysiology, Classification, Clinical Findings, Diagnosis, and Treatment

Macular pseudohole is characterized by a specific appearance of epiretinal membranes (ERM) that spares the foveal center resembling a macular hole in the ophthalmoscopic examination. The foveal center is displaced by the contraction of ERM. The differential diagnosis of pseudoholes from full-thickness and lamellar macular holes may not be easy. The natural history of macular pseudoholes is good but vision may decrease if the distortion in foveal center increases. The outcome of early surgical treatment of full-thickness macular holes is good and several methods and tests have been used for the differential diagnosis of full-thickness macular holes and pseudoholes. The diagnosis, determination of pathogenetic mechanisms, and subgroups of macular pseudoholes have become relatively easy after the availability of optical coherence tomography in ophthalmological practice. The macular pseudoholes may be classified as a subgroup of ERM’s and the treatment is either observation or vitreoretinal surgery with a good outcome in cases with decreased visual acuity.

Long-term evaluation of spontaneous release of epiretinal membrane and its possible pathogenesis

PurposeTo investigate the characteristics in spontaneous release of epiretinal membrane (ERM) during watchful waiting and to introduce a possible mechanism of pathogenesis as a photo essay.MethodsRecords from all patients with ERM were obtained from Osaka Medical College Hospital from January 2001 to October 2012. Visual acuity (VA), fundus photo, and optical coherence tomography (OCT) were reviewed using the medical records. For statistical analysis, VA measured with a Landolt chart was converted to the logarithm of the minimum angle of resolution (logMAR). To investigate the pathogenesis of ERM, tryptase activity in vitreous, which plays a role in tissue fibrosis and remodeling, was measured in patients that underwent a vitrectomy for ERM, macular hole, and proliferative diabetic retinopathy (PDR).ResultsERM was observed in 604 patients and spontaneous release of the ERM was observed in 13 patients with 14 eyes (four males and nine females, aged 33–78 years). Among the 14 eyes, mean VA did not change significantly through the release of the ERMs (0.17±0.18 before and 0.24±0.40 after release, P=0.544). Nine eyes showed posterior vitreous detachment or vitreomacular traction on OCT images and five eyes did not. ERM was released in five eyes with no accompanying vitreous traction by OCT during watchful waiting and seems to have peeled off by itself by contracting and rolling from the inferior side. Three eyes with deteriorated VA underwent vitrectomy due to macular hole or pseudomacular hole. Vitreal tryptase activity was significantly higher in patients with ERM compared to those with PDR (P<0.05).ConclusionFundus photos of ERM auto-peeling were taken during long-term follow-up. Spontaneous release of ERM is possibly involved in vitreous traction or membrane contraction. In addition, tryptase may be involved in the development and contraction of ERM.

Focal adhesion kinase family is involved in matrix contraction by transdifferentiated Müller cells

Transdifferentiated Müller cells that adopt a fibroblastic/myofibroblastic phenotype have been identified in epiretinal membranes (ERMs) in several ocular disorders, and have been implicated to play a role in the formation and/or the contraction of ERMs. We have previously demonstrated that dasatinib, a dual inhibitor of Src-family kinases and Abl kinase, can prevent matrix contraction by transdifferentiated Müller cells. In this study, we examined molecules involved in matrix contraction downstream of primary dasatinib targets. Tyrosine phosphorylation of focal adhesion kinase (FAK) family members FAK and PYK2 was significantly reduced by dasatinib, and select inhibitors for these kinases PF431396, which inhibits both FAK and PYK2, and PF573228, which only inhibits FAK and not PYK2, significantly reduced matrix contraction by transdifferentiated Müller cells. Dasatinib and PF431396 significantly reduced phosphorylation of Hic-5, a protein implicated to play a role in focal adhesions and cell signaling. Our data shows that FAK family members are involved in matrix contraction by transdifferentiated Müller cells, and also implicates that Hic-5 is situated downstream of the FAK family within the signaling pathway.

Role of epithelial–mesenchymal transition in proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is a potentially blinding fibrotic complication. It is caused by the formation and contraction of epiretinal membranes (ERMs) that ultimately lead to retinal folds and traction retinal detachments. While multiple cell types have been identified in ERMs, retinal pigment epithelial (RPE) cells have long been implicated as a key player in the pathophysiology of PVR. Clinical and experimental evidence has shown that RPE cells undergo epithelial–mesenchymal transition (EMT) to adopt a fibroblastic phenotype. Cell–cell adhesions maintained by adherens and tight junctions are important for the maintenance of RPE phenotype, and disruption of these junctional complexes results in EMT via activation of signaling pathways such as β-catenin/Wnt and Hippo signaling, as well as transcription factors involving Zeb1, Snail, and ZONAB. Upon EMT, RPE cells can further differentiate into myofibroblasts in the presence of TGF-β with cytoskeletal tension mediated by RhoGTPase. These fibroblasts and myofibroblasts derived from RPE cells can contribute to ERM formation by cell migration, proliferation and matrix modification, and play a key role in ERM contraction. It is not solely the proliferation of these cells that results in PVR but rather the contraction of these cells in the ERM.

Retinal Cavernous Hemangioma

An asymptomatic 14-year-old boy was incidentally found to have a “bunch-of-grapes”−like retinal lesion, consistent with a retinal cavernous hemangioma. Although typically sporadic and unilateral, these lesions can be familial and associated with cutaneous, hepatic, or intracranial hemangiomas. Vitreous hemorrhage may result from epiretinal membrane contraction and vitreous traction. Fundus photograph showing the retinal cavernous haemangioma (Fig A). Near-infrared spectroscopy (Fig B) and spectral-domain optical coherence tomography (Fig C) demonstrating the epiretinal membrane and vitreous traction.

Evolution from macular pseudohole to lamellar macular hole — spectral domain OCT study

The pathogenesis of macular pseudohole (MPH) is supposed to be different from that of macular lamellar hole (LMH). MPH is thought to be caused by centripetal contraction of previously present epiretinal membrane. LMH is considered to be an effect of abortive process of full-thickness macular hole formation, or a result of de-roofing of a foveal cyst in persistent cystoid macular oedema. In most cases of LMH, epiretinal membranes are present. The aim of this paper is to show that LMH and MPH may have a common origin and that LMH may evolve from MPH as an epiretinal membrane contracts. Observational two-case series of patients with MPH and epiretinal membrane. Spectral domain optical coherence tomography (SD-OCT) was performed during follow-up. In 6months of follow-up in case 1 and 2months in case 2, MPH progressed to non-full-thickness macular defect, fulfilling the criterion of LMH in SD-OCT. Non-vitreous interface traction was detected. SD-OCT proves that MPH may progress to LMH without any vitreous traction. Progressive contraction of epiretinal membranes may be a cause of both MPH and LMH, being an advanced stage of the same non-full-thickness macular disorder.

Progression of traumatic lamellar macular hole to full-thickness macular hole and retinal detachment in a 3-year-old child.

Traumatic macular holes in children are uncommon, and retinal detachment from a macular hole is even more uncommon because the vitreous is formed. Interventional case report. A 3-year-old boy presented after trauma with a lamellar macular hole in his left eye. Over the next month, progression to a full-thickness macular hole with epiretinal membrane and then subsequent retinal detachment was documented with high-resolution optical coherence tomography. The patient underwent a pars plana vitrectomy, membrane peel, and perfluoropropane tamponade. Six months after surgery, the hole remained anatomically closed, and visual acuity was 20/20. Retinal detachment after a traumatic macular hole in this child was because of hyaloidal traction and epiretinal membrane contraction. Pars plana vitrectomy with surgical peeling of the epiretinal membrane and internal limiting membrane enabled the macular hole to close and the retina to reattach.

Redefining Lamellar Holes and the Vitreomacular Interface: An Ultrahigh-Resolution Optical Coherence Tomography Study

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. 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.

Diagnosis of macular pseudoholes and lamellar macular holes by optical coherence tomography

To assess the usefulness of optical coherence tomography (OCT) for better differential diagnosis of macular pseudoholes (MPH) and lamellar macular holes (LMH). Observational case series. setting: Institutional practice. patients: We reviewed the files of 71 eyes of 70 consecutive patients who were diagnosed as having a pseudohole or lamellar hole on OCT examination. All patients referred for suspected pseudohole or lamellar hole on biomicroscopy were evaluated by OCT. main outcome measures: Each eye underwent six radial 3-mm OCT scans centered on the macula, one 6-mm vertical and one 6-mm horizontal scan. Retinal thickness was measured at the foveal center and 750 microm from the center, vertically, and horizontally. The diameter of the macular contour was also measured on vertical and horizontal scans. In 40 cases, OCT showed a macular profile characteristic of MPH: a steepened foveal pit combined with thickened foveal edges and a small foveal pit diameter. Central foveal thickness was normal or slightly increased (167 +/- 42 microm). Mean perifoveal thickness was greater than normal (363 +/- 65 microm). In 29 other cases corresponding to LMH, OCT showed a profile characterized by a thin irregular foveal floor, split foveal edges, and near-normal perifoveal retinal thickness. Central foveolar thickness was thinner than normal (72 +/- 19 microm). Mean perifoveal thickness was near normal (283 +/- 36). Optical coherence tomography did not allow the classification of the remaining two cases. Optical coherence tomography is very useful in distinguishing MPH attributable to epiretinal membrane contraction from LMH because of partial opening of a macular cyst.

Influence of pigment content, intracellular calcium and cyclic AMP on the ability of human retinal pigment epithelial cells to contract collagen gels

The aim of the study was to determine to what extent collagen gel contraction could be reduced by calcium and calmodulin antagonists and agents that elevate cyclic AMP in order to develop a pharmacological approach to prevent/arrest RPE contraction of epiretinal membranes in proliferative vitreoretinopathy. We also explored a possible role of pigment in collagen gel contraction. We measured RPE mediated contraction of 3D collagen gels in the presence and absence of the calcium and calmodulin antagonists TMB8, Verapamil and Tamoxifen and the cAMP elevating agents IBMX and Forskolin. The effect of pigment on collagen gel contraction was assessed by comparing gel contraction mediated by RPE cells re-pigmented with melanin with that mediated by unpigmented RPE. The effect of IBMX on RPE proliferation was assessed using a BrdU ELISA and the effects of IBMX on RPE cytoskeleton and cell shape were assessed using Actin and Cytokeratin immunocytochemistry. We report that both cAMP elevating agents and calcium and calmodulin antagonists reduce RPE mediated collagen gel contraction. Cyclic AMP elevation was more effective than a reduction in calcium in reducing contraction. There were no significant advantages in combining both approaches. The presence of melanin had no effect on gel contraction. Calcium antagonists and particularly agents which elevate cAMP caused RPE cells in collagen gels to extend fewer and shorter processes. cAMP elevation in particular caused RPE cells to become more rounded and develop arborized cell processes. Immunostaining for actin and cytokeratin revealed changes in cytoskeletal organisation in response to IBMX in that cells contained less actin than untreated cells and concentrated cytokeratins more centrally. We have identified two possible pharmacological approaches which may provide a new direction for preventing or slowing down the development of PVR.

Influence of pigment content, intracellular calcium and cyclic AMP on the ability of human retinal pigment epithelial cells to contract collagen gels

Purpose. The aim of the study was to determine to what extent collagen gel contraction could be reduced by calcium and calmodulin antagonists and agents that elevate cyclic AMP in order to develop a pharmacological approach to prevent/arrest RPE contraction of epiretinal membranes in proliferative vitreoretinopathy. We also explored a possible role of pigment in collagen gel contraction. Method. We measured RPE mediated contraction of 3D collagen gels in the presence and absence of the calcium and calmodulin antagonists TMB8, Verapamil and Tamoxifen and the cAMP elevating agents IBMX and Forskolin. The effect of pigment on collagen gel contraction was assessed by comparing gel contraction mediated by RPE cells re-pigmented with melanin with that mediated by unpigmented RPE. The effect of IBMX on RPE proliferation was assessed using a BrdU ELISA and the effects of IBMX on RPE cytoskeleton and cell shape were assessed using Actin and Cytokeratin immunocytochemistry. Results. We report that both cAMP elevating agents and calcium and calmodulin antagonists reduce RPE mediated collagen gel contraction. Cyclic AMP elevation was more effective than a reduction in calcium in reducing contraction. There were no significant advantages in combining both approaches. The presence of melanin had no effect on gel contraction. Calcium antagonists and particularly agents which elevate cAMP caused RPE cells in collagen gels to extend fewer and shorter processes. cAMP elevation in particular caused RPE cells to become more rounded and develop arborised cell processes. Immunostaining for actin and cytokeratin revealed changes in cytoskeletal organisation in response to IBMX in that cells contained less actin than untreated cells and concentrated cytokeratins more centrally. Conclusion. We have identified two possible pharmacological approaches which may provide a new direction for preventing or slowing down the development of PVR.

Retinal Distortion and Cottonwool Spots Associated with Epiretinal Membrane Contraction

Several articles on surgery for macular pucker have noted the presence of intraretinal white spots, presumably cotton-wool spots, associated with epiretinal membranes. It was proposed that membrane contraction and resultant nerve fiber layer distortion might lead to blockage of axoplasmic flow and thus a cotton-wool spot. To see whether the observations supported this concept, the authors studied patients with epiretinal membranes associated with intraretinal white spots involving the center of the fovea, where there are normally no retinal vessels and the only axons are in Henle fiber layer. Four patients with epiretinal membranes associated with prominent areas of intraretinal whitening involving the center of the fovea were examined before and after surgery. Observations and measurements were made from projected fundus photographs. The intraretinal white spots, which appeared preoperatively to lie in the center of the fovea, proved to have been pulled in from more peripheral retina by the epiretinal membrane. These white areas were associated with surprisingly great distortion of the inner retina. Stretching of the inner retina seemed to play a larger role in the retinal distortion than full-thickness retinal folding. The appearance and time course of these intraretinal white lesions were consistent with cotton-wool spots caused by mechanical disruption of axonal flow. The marked retinal stretching and distortion of the innermost layers of the retina were the most striking findings in this study and also seemed consistent with the concept that membrane contraction and resultant nerve fiber layer distortion might lead to blockage of axoplasmic flow and thus a cotton-wool spot.

Retinal pigment epithelial cells in epiretinal membranes: an immunohistochemical study.

Immunohistochemical techniques were used to identify cells containing cytokeratins in sections or tissue-culture monolayers from ocular (reference) tissues and also from 22 epiretinal membranes obtained during closed microsurgery for macular pucker or massive preretinal retraction. Results of cytokeratin immunostaining in reference tissues indicated that this is a valuable means of determining the contribution and distribution of epithelial cells in epiretinal membranes, and that the epithelial cells in the membranes were probably derived from the retinal pigment epithelium. Epithelial cells were identified in 17 of the 22 epiretinal membranes, but they did not usually constitute the predominant cell type. We concluded that the fibroblasts or fibroblast-like cells thought to be responsible for the contraction of epiretinal membranes are seldom of retinal pigment epithelial origin. Biomicroscopic pigmentation of a membrane was shown to be a poor guide to its epithelial cell population.

Mechanisms in traction retinal detachment.

We have developed a reproducible model of traction retinal detachment in the rhesus monkey secondary to a penetrating eye injury. The model is characterized histologically by intravitreal fibroblastic proliferation and by epiretinal and by retroretinal membranes. Cells proliferating within the vitreous and in the epiretinal membranes have the ultrastructural characteristics of myofibroblasts. The presence of these contractile cells suggests that vitreous traction and the contraction of epiretinal membranes may be cell mediated. Our findings suggest that the pathophysiology of traction retinal detachment has many features in common with the normal process of wound healing and in particular with the mechanisms responsible for wound contraction and cicatrization.

Method of Production and Natural History of Experimental Posterior Penetrating eye Injury in the Rhesus Monkey

We developed an experimental model for a posterior penetrating eye injury that resulted in traction retinal detachment in 21 rhesus monkey eyes. The standard injury was an incision through the pars plana with vitreous prolapse and incarceration; the wound was then carefully closed with microsurgical techniques. At one to two weeks after injury, detachment of the posterior vitreous occurred and detachment of the retina occurred between seven and 11 weeks. The development of retinal detachment was related to traction on the peripheral retina over the vitreous base; and to the contraction of epiretinal membranes on the peripheral and equatorial retina. Our study supports clinical observations on the importance of blood in the vitreous in the development of vitreous traction and traction retinal detachment after a posterior penetrating injury.