Effect of topical bromfenac on intraretinal cystoid lesion in simultaneous cataract and idiopathic epiretinal membrane surgery.

PURPOSE: To investigate the effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs,) bromfenac on the intraretinal cystic lesions (IRC) when performing simultaneous cataract and idiopathic epiretinal membrane (iERM) surgery. METHODS: This study included patients with iERM who had been followed up for 6 months after vitrectomy, membrane removal, and concurrent cataract surgery. Eyes were treated with topical bromfenac or not. The baseline fluorescein angiography (FA) was obtained to assess the microvascular leakage (ML). Structural changes of macula, including IRC and central macular thickness (CMT) were assessed using optical coherence tomography (OCT). The main outcome measures were changes in IRCs and best-corrected visual acuity (BCVA) regarding FA findings. RESULTS: One hundred eighteen eyes were included. IRC and ML were observed in 51 eyes (43.2%) and 63 eyes (53.4%), respectively. The IRC did not show any association with the ML. Of total, 29 eyes (24.6%) were treated with topical bromfenac (Group A). Compared to Group B, topical bromfenac did not show beneficial effects in aspect of preventions for the newly developed IRC and treatment for pre-existed IRC. Whether the ML existed or not, topical bromfenac did not show any different effect on the changes in BCVA and IRC. CONCLUSION: When performing simultaneous cataract and ERM surgery, topical NSAIDs, bromfenac did not show beneficial effects on the preventions and treatment of IRC in both eyes with and without the ML.

EVALUATION OF PARAVASCULAR INNER RETINAL DEFECTS USING EN FACE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the prevalence and risk factors for development of paravascular inner retinal defects (PIRDs) using en face optical coherence tomography. METHODS: This is a retrospective cross-sectional study. En face and cross-sectional optical coherence tomography images were reviewed (9 × 9 mm or 12 × 12 mm). Paravascular inner retinal defects were classified as either Grade 1 (i.e., paravascular inner retinal cysts) when the lesion was confined within the nerve fiber layer without any communication to the vitreous cavity or Grade 2 (i.e., paravascular lamellar hole) when the defects communicated to the vitreous. Paravascular inner retinal defect grading was correlated with presence of high myopia, stage of posterior vitreous detachment, and presence of epiretinal membrane and retinoschisis. RESULTS: Of 1,074 patients (2,148 eyes), PIRDs were detected in 261 eyes with a prevalence of 261 per 2,148 eyes (12.2%) and 176 per 1,074 patients (16.4%). A total of 116 eyes (44.4%) displayed Grade 2 PIRDs while 145 eyes (55.6%) were Grade 1. In the multivariate logistic regression model, the presence of partial/complete posterior vitreous detachment, retinoschisis, and epiretinal membrane was significantly correlated with PIRDs (OR = 2.78 [1.7-4.4], P < 0.001; OR = 2.93 [1.7-5], P < 0.001; and OR = 25.9 [2.8-242.5], P < 0.001, respectively). The presence of partial/complete posterior vitreous detachment and epiretinal membrane was also significantly associated with Grade 2 PIRDs versus Grade 1 PIRDs ( P = 0.03 and P < 0.001). CONCLUSION: Our results indicate that wide-field en face optical coherence tomography facilitates the identification of PIRDs over a large area of retina with a single capture. The presence of PIRDs was significantly associated with posterior vitreous detachment, epiretinal membrane, and retinoschisis, confirming the role of vitreoretinal traction in the pathogenesis of PIRDs.

Co-Expression of Podoplanin and CD44 in Proliferative Vitreoretinopathy Epiretinal Membranes.

Epiretinal membranes (ERMs) are sheets of tissue that pathologically develop in the vitreoretinal interface leading to progressive vision loss. They are formed by different cell types and by an exuberant deposition of extracellular matrix proteins. Recently, we reviewed ERMs' extracellular matrix components to better understand molecular dysfunctions that trigger and fuel the onset and development of this disease. The bioinformatics approach we applied delineated a comprehensive overview on this fibrocellular tissue and on critical proteins that could really impact ERM physiopathology. Our interactomic analysis proposed the hyaluronic-acid-receptor cluster of differentiation 44 (CD44) as a central regulator of ERM aberrant dynamics and progression. Interestingly, the interaction between CD44 and podoplanin (PDPN) was shown to promote directional migration in epithelial cells. PDPN is a glycoprotein overexpressed in various cancers and a growing body of evidence indicates its relevant function in several fibrotic and inflammatory pathologies. The binding of PDPN to partner proteins and/or its ligand results in the modulation of signaling pathways regulating proliferation, contractility, migration, epithelial-mesenchymal transition, and extracellular matrix remodeling, all processes that are vital in ERM formation. In this context, the understanding of the PDPN role can help to modulate signaling during fibrosis, hence opening a new line of therapy.

Characterization of Different Types of Epiretinal Proliferations by Synchrotron Radiation-Based Fourier Transform Infrared Micro-Spectroscopy.

Pathological tissue on the surface of the retina that can be of different etiology and pathogenesis can cause changes in the retina that have a direct consequence on vision. Tissues of different etiology and pathogenesis have different morphological structures and also different macromolecule compositions usually characteristic of specific diseases. In this study, we evaluated and compared biochemical differences among samples of three different types of epiretinal proliferations: idiopathic epiretinal membrane (ERMi), membranes in proliferative vitreoretinopathy (PVRm), and proliferative diabetic retinopathy (PDRm). The membranes were analyzed by using synchrotron radiation-based Fourier transform infrared micro-spectroscopy (SR-FTIR). We used the SR-FTIR micro-spectroscopy setup, where measurements were set to achieve a high resolution that was capable of showing clear biochemical spectra in biological tissue. We were able to identify differences between PVRm, PDRm, and ERMi in protein and lipid structure; collagen content and collagen maturity; differences in proteoglycan presence; protein phosphorylation; and DNA expression. Collagen showed the strongest expression in PDRm, lower expression in ERMi, and very low expression in PVRm. We also demonstrated the presence of silicone oil (SO) or polydimethylsiloxane in the structure of PVRm after SO endotamponade. This finding suggests that SO, in addition to its many benefits as an important tool in vitreoretinal surgery, could be involved in PVRm formation.

Update on the utility of en face optical coherence tomography in the assessment of vitreoretinal diseases.

En face optical coherence tomography (EF-OCT) is a rapid, non-invasive, high-resolution imaging technique that has evolved in recent years to be a routine examination for the assessment and follow-up of various vitreoretinal diseases. With the introduction of swept-source OCT (SS-OCT), which can achieve up to 100,000 A-scans per second and better-quality imaging of deeper structures using a longer wavelength (1050nm), EF-OCT reconstruction can produce high-resolution frontal images of the retina and choroid (C-Scans) that give an overview of disease extent. These images allow a more accurate study of vitreoretinal interface pathologies such as epiretinal membranes, macular holes, and vitreomacular traction. They also provide key information in the study of various retinal vascular diseases and the differential diagnosis of cystic macular edema. EF-OCT provides valuable information about the severity of vitreoretinal interface alterations and precisely assesses the choriocapillaris and choroidal vasculature in pachychoroid disorders. Finally, this technique provides valuable information about atrophic and neovascular age-related macular degeneration and various uveitic entities. This review aims to describe the current clinical applications of EF-OCT in various vitreoretinal diseases as well as the latest findings and future perspectives.

INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA.

PURPOSE: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. METHODS: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. RESULTS: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67-19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). CONCLUSION: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

Epiretinal Membrane Surgery in Eyes with Glaucoma: Visual Outcomes and Clinical Significance of Inner Microcystoid Changes.

OBJECTIVE: To investigate visual acuity (VA) outcomes and OCT-based biomarkers of vision outcomes in eyes with glaucoma undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, consecutive case-control series. A previously described ERM grading scale was utilized for OCT analysis. SUBJECTS: Eyes with glaucoma undergoing PPV for idiopathic ERM. INTERVENTION: PPV with membrane peel (MP) surgery. MAIN OUTCOME MEASURES: The primary outcome was VA at postoperative month 6. Outcomes were compared to a contemporary, matched control group of eyes without concurrent glaucoma undergoing PPV for idiopathic ERM. RESULTS: A total of 103 eyes from 103 patients with ERM and glaucoma were followed for a mean (± standard deviation) of 656 (± 421) days after PPV with MP surgery. Glaucoma was classified as open angle in 98 (95.1%) eyes and closed angle in 5 (4.9%) eyes. Visual acuity improved from 0.72 ± 0.48 (20/105) to 0.55 ± 0.51 (20/71) at 6 months and to 0.50 ± 0.56 (20/63) at final follow-up (P < 0.001 for both the time points). Eyes with preoperative inner microcystoid changes (n = 59; 57.3%) had significantly worse preoperative VA, postoperative VA at month 6, and final VA compared to eyes without inner microcystoid changes (P = 0.028, 0.004, and 0.007, respectively). Eyes were then compared to a matched control group of 139 eyes without glaucoma. Eyes with ERM and glaucoma had a higher rate of microcystic changes both before surgery (P < 0.001) and at postoperative month 6 (P < 0.001), and had a worse VA at 6 months (P = 0.03) and final follow-up (P = 0.04) compared to control eyes without glaucoma. Advanced disc cupping was the only factor independently correlated with worse 6-month (P = 0.01) and final (P = 0.007) VA in multivariate analysis. CONCLUSIONS: Preoperative inner microcystoid changes on OCT were present in over half of eyes with ERM and concurrent glaucoma, and may be a poor prognostic OCT biomarker. Eyes with ERM and concurrent glaucoma experienced worse vision outcomes compared to eyes with ERM alone, particularly those with advanced disc cupping.

Influence of postoperative ectopic inner foveal layer on visual function after removal of idiopathic epiretinal membrane.

PURPOSE: To investigate the functional and anatomical parameters and their postoperative changes according to the ectopic inner foveal layer (EIFL) staging scheme for idiopathic epiretinal membrane (ERM). METHODS: In this prospective study, patients with idiopathic ERM underwent pars plana vitrectomy and ERM removal, and were followed-up for 6 months. The associations of EIFL with pre- and postoperative functional and anatomical parameters were analyzed. RESULTS: A total of 84 eyes (84 patients) were included: 39 (46.4%), 33 (39.3%), and 12 (14.3%) as EIFL stages 2, 3, and 4, respectively. At 6 months after surgery, the mean best-corrected visual acuity (BCVA) significantly improved in all EIFL stages (P ≤ 0.003); however, metamorphopsia improved only in eyes with EIFL stage 2 (P = 0.039) and 3 (P = 0.011). The aniseikonia and foveal avascular zone (FAZ) area showed no significant postoperative changes in any of the EIFL stages. Both preoperatively and during 6 months after surgery, the EIFL stage showed a significant correlation with BCVA (P ≤ 0.033), metamorphopsia (P ≤ 0.008), central macular thickness (P < 0.001), and FAZ parameters (P ≤ 0.016) at each time point, but not with aniseikonia. Significant correlations of EIFL thickness with BCVA (P = 0.028) and metamorphopsia (P = 0.006) before surgery were not persistent after surgery. CONCLUSION: Both pre- and postoperatively, the staging of EIFL, rather than its thickness, is a simple and adequate surrogate marker for visual acuity and metamorphopsia in eyes with idiopathic ERM.

Contractility of temporal inverted internal limiting membrane flap after vitrectomy for macular hole.

We investigated the postoperative visual outcomes and morphological changes of the internal limiting membrane (ILM) flap, in patients who underwent the temporal inverted ILM flap technique for macular hole (MH). Between August 2018 and February 2020, 22 eyes of 22 patients with idiopathic or myopic MH who underwent vitrectomy with ILM flap were included in this study and followed-up for more than 6 months. Postoperative MH status, comparison of best-corrected visual acuity (BCVA) before and 6 months after surgery, changes in the ILM flap area at 1 and 6 months postoperatively, and the factors related to changes in ILM flap size, were analyzed. MH closure was achieved in all of the patients. The BCVA at 6 months postoperatively (0.18 ± 0.15) was significantly better than the preoperative BCVA of 0.63 ± 0.37 (P < 0.001, paired t test). The area of the ILM flap decreased significantly from 3.25 ± 1.27 mm2 at 1 month to 3.13 ± 1.23 mm2 at 6 months (P = 0.024, Wilcoxon signed-rank test). Two eyes showed an ILM flap contraction of more than 20%, and one eye required reoperation due to an increase in metamorphopsia and decreased visual acuity. Among age, sex, ILM flap area at 1 month, preoperative BCVA, and axial length, ILM flap contraction was correlated with patient age and ILM flap area. Although vitrectomy with the inverted ILM flap technique confers a good visual outcome, the ILM flap may contract in younger patients.

The effect of phacoemulsification performed with vitrectomy on choroidal vascularity index in eyes with vitreomacular diseases.

This study evaluated the effects of cataract surgery combined with pars plana vitrectomy (ppV) on choroidal vascularity index (CVI) in eyes with epiretinal membrane (ERM) and full thickness macular hole (FTMH). Medical records of 132 eyes with ERM or FTMH were retrospectively reviewed and classified into a ppV group and a ppV combined with cataract surgery group (phaco + ppV group). The CVI were measured at baseline, 1, 3 and 6 months after the surgery, using the selected swept-source (SS) optical coherence tomography (OCT) scan passing through the central fovea, which was then segmented into luminal and stromal area by image binarization. The mean CVI of phaco + ppV group were 61.25 ± 1.97%, 61.66 ± 1.81%, and 62.30 ± 1.92% at baseline, 1 and 3 months, respectively (p < 0.001). The mean CVI of ppV group were 62.69 ± 1.92%, 62.03 ± 1.51%, and 61.45 ± 1.71% at baseline, 1 and 3 months, respectively (p < 0.001). The final CVI were measured at 6 months and compared with the baseline CVI. The mean CVI of phaco + ppV group were 61.21 ± 1.99% at baseline and 60.68 ± 2.02% at 6 months (p < 0.001). The mean CVI of ppV group were 62.93 ± 1.70% at baseline and 61.77 ± 1.74% at 6 months (p < 0.001). Vitrectomy significantly decreases CVI in vitreomacular diseases possibly due to the removal of vitreomacular traction or postoperative oxygenation change in the eye. On the contrary, combined surgery of vitrectomy and cataract surgery significantly increases CVI in the early stage of postoperative period, which suggests choroidal vascular dilatation or congestion due to postoperative inflammation. Although the CVI were measured lower than the baseline in the end, more thorough inflammation control may be essential after combined surgery.

Total venous nature of retinal deep capillary plexus inferred by continuity of prominent middle limiting membrane sign in optical coherence tomography.

This study aimed to theoretically identify the vascular nature of the deep capillary plexus (DCP) by examining patients presenting with both paracentral acute middle maculopathy (PAMM) and prominent middle limiting membrane (p-MLM) sign and p-MLM sign alone in spectral-domain optical coherence tomography (SD-OCT). A retrospective review of the medical records of patients with retinal vein or artery occlusion from two tertiary medical centers was performed. Consecutive patients with a clinical diagnosis of all categories of retinal artery occlusion (RAO) and retinal vein occlusion (RVO) (branch or central and ischemic or non-ischemic) who had undergone SD-OCT imaging from January 2015 to May 2020 were recruited and their p-MLM signs and PAMM lesions were assessed. We included 118 patients who presented with p-MLM sign with or without PAMM lesions. Amon them, 40 were female and 78 were male, with a mean age of 61.1 years. Of the 109 patients with both p-MLM sign and PAMM lesions, 23 had branch RAO, two had branch RVO, 67 had central RAO, 13 had central RVO, and four had a combination of central RAO and central RVO. All nine patients with the p-MLM sign alone had central RVO accompanied by cystoid macular edema. In all the enrolled patients, the hyperreflective lines of the p-MLM sign were continuous, regardless of the type of PAMM lesions. In conclusion, when PAMM and p-MLM sign are examined together, further proof regarding the possible complete venous nature of the vasculature of the retinal DCP might be speculated.

With or without internal limiting membrane peeling during idiopathic epiretinal membrane surgery: A meta-analysis.

BACKGROUND: Although previously published meta-analyses have compared the surgical effects between the methods of Idiopathic epiretinal membrane (iERM) removal with or without ILM peeling, they did not reach an agreement. PURPOSE: We aimed to provide more evidence for the treatment of iERM and whether additional ILM peeling was better or not by analyzing more updated studies and randomized control trials (RCTs). METHOD: The search was conducted in Pubmed, Embase, Cochrane Library, Web of Science and Open Grey without language limitation and the studies included were from inception to December 2019. All studies of iERM with or without ILM peeling showed at least one of outcomes, such as best-corrected visual acuity (BCVA), central macular thickness (CMT) and recurrence of ERM. The pooled results between above groups were showed by the mean differences (MDs) and risk ratios (RR) with corresponding 95% confidence intervals (CIs). RESULT: In total, 1645 eyes of five randomized controlled trials (RCTs) and fifteen retrospective studies were included. The short-term (<12 months) BCVA improvement in both groups showed no significant difference (MD = -0.01; 95% CI = -0.02 to 0.01; P = 0.36). However, the BCVA improvement was significantly better in ILM peeling eyes than in those without ILM peeling when considering the risk bias (MD = -0.04; 95% CI = -0.07 to -0.01; P = 0.008). The short-term (<12 months) CMT had a higher reduction in non ILM peeling group (MD = -9.02; 95% CI = -12.51 to -5.54; P < 0.00001) and the recurrence of ERM in ILM peeling group was lower (P < 0.00001). The long-term (≥12months) BCVA improvement ((MD = -0.00; 95% CI = -0.03 to 0.03; P = 0.97) and reduction of long-term (≥12months) CMT (MD = -1.14; 95% CI = -7.14 to -4.86; P = 0.71) were similar in both groups. CONCLUSION: By considering the risk of bias, we should determine whether ILM peeling is beneficial for short-term changes in BCVA in patients with iERM. Nevertheless, further studies are needed to confirm this. iERM removal without ILM peeling can improve the short-term decrease in CMT and ILM peeling decreases the recurrence of ERM, but the long-term changes in BCVA and CMT are similar with or without ILM peeling. There is a need for a true large scale randomized trial that will also include microperimetry and other functional measures.

A child with unilateral disk elevation.

A healthy 7-year-old girl underwent a routine eye examination and was referred for unilateral, left optic nerve swelling. Best-corrected visual acuity in the affected eye was 20/20 with full Ishihara color plates and no relative afferent pupillary defect. Initial extensive workup was normal for any cause of unilateral disk swelling. When the patient returned a few years later with decreased vision, a thickened, gray-white preretinal tissue with surrounding retinal contraction and a surrounding charcoal gray lesion had developed in her optic nerve. Spectral-domain optical coherence tomography over the optic nerve demonstrated distortion of the inner retinal architecture, a dense epiretinal membrane, and high internal reflectivity. Clinical examination and imaging revealed a diagnosis of combined hamartoma of the retina and retinal pigment epithelium.

Characteristics of secondary epiretinal membrane due to peripheral break.

This study aimed to investigate morphological differences between idiopathic epiretinal membrane (ERM) and secondary ERM due to peripheral break (SEPB) and to identify clinical characteristics in eyes with SEPB to facilitate peripheral retinal examination. The retrospective cross-sectional study involved 93 consecutive eyes in 91 patients who underwent ERM removal surgery. Eyes were divided into two groups: the macular pucker group and the idiopathic ERM group. En-face Optical Coherence Tomography (OCT) images, fundus photographs, severity of metamorphopsia (M-score) and clinical characteristics of each group were compared. ERM extent and eccentricity (ratio of the shortest and longest distances from the foveal center to the boundary) were obtained through en-face OCT imaging. Fundus photographs were used to judge whether the membrane was turbid or not. Patients with SEPB were younger than patients with idiopathic ERM (61.3 ± 7.5 vs. 66.6 ± 8.3 years; p < 0.05). Preoperative M-score and myopic refractive error, axial length were also significantly higher in the macular pucker group than in the idiopathic ERM group (all p < 0.05). There was no difference in ERM extent between the two groups. The incidence of ERM eccentricity was 23 of the 34 eyes (67.6%) in the SEPB group and 26 of the 59 eyes (44.1%) in the idiopathic ERM group (p < 0.05). The incidence of turbid ERM was 18 of the 34 eyes (52.9%) in the SEPB group and 10 of the 59 eyes (16.9%) in the idiopathic ERM group (p < 0.01). The SEPB group, compared with the idiopathic ERM group, tended to have eccentric, turbid ERM at a younger age and with more severe metamorphopsia and myopic refractive error.

Association of macular choroidal thickness with optical coherent tomography morphology in patients with idiopathic epiretinal membrane.

PURPOSE: To compare macular choroidal thickness of idiopathic epiretinal membrane (ERM) and fellow eyes, and before and after vitrectomy in terms of the morphological features on spectral-domain optical coherent tomography (SD-OCT). METHODS: Eighty-four patients with unilateral idiopathic ERM were involved. Patients were categorized into: Group 1, ERM without membrane contraction; Group 2, ERM with membrane contraction and retinal folding; and Group 3, ERM with membrane contraction and macular edema. Twenty-two patients received surgical removal of ERM. Choroidal thickness was compared between ERM and fellow eyes, and before and after treatment. RESULTS: Mean choroidal thickness was significantly greater in ERM eyes than in fellow eyes (234.4 ± 22.5 vs 220.6 ± 20.8 µm; P<0.01). Group 1 (n = 20) showed no significant difference in choroidal thickness between ERM and fellow eyes. Eyes in Group 2 (n = 27) and Group 3 (n = 37) showed statistically significant differences in mean choroidal thickness between ERM and fellow eyes (229.6 ± 23.8 vs 220.8 ± 19.6 µm; 242.6 ± 27.8 vs 221.0 ± 21.8 µm, respectively; P<0.05). In Group 2 (n = 8) and Group 3 (n = 16), choroidal thickness in ERM eyes decreased significantly at 1 month and 6 months after surgery, compared with that before surgery (P<0.05 for all comparisons). CONCLUSIONS: Membrane contraction contributed to the increase in choroidal thickness in idiopathic ERM patients. This finding may help to elucidate the pathophysiologic features of idiopathic ERM as well as the response to treatment in these patients.

Association between displacement and thickness of macula after vitrectomy in eyes with epiretinal membrane.

The purpose of this cross-sectional retrospective study was to determine the relationship between the retinal displacements and the retinal thickness in eyes with epiretinal membrane (ERM) after vitrectomy with internal limiting membrane (ILM) peeling. To accomplish this, we measured the retinal thickness using optical coherence tomography (OCT) and the retinal displacement using OCT angiography to obtain 3 mm × 3 mm en face images before, and 2, 4, and 8 weeks following the surgery from 20 eyes of 20 patients. The distance between the retinal vessel bifurcations and the fovea was significantly displaced centrifugally and asymmetrically in the 4 quadrants postoperatively (P < 0.001). The foveal avascular zone (FAZ) was significantly enlarged, and the central foveal thickness (CFT) and the inner nuclear layer (INL) thickness were significantly thinner postoperatively. The displacements were significantly correlated with the changes in the FAZ area (r = 0.717, P < 0.001), the CFT (r = - 0.702, P < 0.001), and the INL thickness (r = - 0.702, P < 0.001). In conclusion, the distance between the retinal bifurcations and the fovea was asymmetrically expanded after the surgery and was significantly correlated with the morphological changes. These results indicate that a horizontal macular contraction is correlated with vertical retinal contraction in the eyes with an ERM.

Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes.

Idiopathic epiretinal membranes (ERMs) are fibrocellular membranes containing extracellular matrix proteins and epiretinal cells of retinal and extraretinal origin. iERMs lead to decreased visual acuity and their pathogenesis has not been completely defined. Aim of this study was to provide a molecular characterization of iERMs by gene expression analysis. To this purpose, 56 iERMs obtained by pars plana vitrectomy were analyzed for the expression levels of genes encoding biomarkers of the cellular and molecular events occurring in iERMs. RT-qPCR analysis showed significant differences in the levels of cell population, extracellular matrix and cytokine/growth factor biomarkers among the iERMs investigated. Hierarchical clustering of RT-qPCR data identified two distinct iERM clusters, Cluster B samples representing transcriptionally "activated" iERMs when compared to transcriptionally "quiescent" Cluster A specimens. Further, Cluster B could be subdivided in two subgroups, Cluster B1 iERMs, characterized by a marked glial cell activation, and Cluster B2 samples characterized by a more pro-fibrotic phenotype. Preoperative decimal best-corrected visual acuity and post-surgery inner segment/outer grading values were higher in Cluster A patients, that showed a prevalence of fovea-attached type iERMs with near-normal inner retina, than in Cluster B patients, that presented more severe clinical and spectral domain optical coherence tomography (SD-OCT) features. In conclusion, this molecular characterization has identified two major clusters of iERM specimens with distinct transcriptional activities that reflect different clinical and SD-OCT features of iERM patients. This retrospective work paves the way to prospective whole-genome transcriptomic studies to allow a molecular classification of iERMs and for the identification of molecular signature(s) of prognostic and therapeutic significance.

Epigenomic and Transcriptomic Changes During Human RPE EMT in a Stem Cell Model of Epiretinal Membrane Pathogenesis and Prevention by Nicotinamide.

Epithelial to mesenchymal transition (EMT) is a biological process involved in tissue morphogenesis and disease that causes dramatic changes in cell morphology, migration, proliferation, and gene expression. The retinal pigment epithelium (RPE), which supports the neural retina, can undergo EMT, producing fibrous epiretinal membranes (ERMs) associated with vision-impairing clinical conditions, such as macular pucker and proliferative vitreoretinopathy (PVR). We found that co-treatment with TGF-ß and TNF-α (TNT) accelerates EMT in adult human RPE stem cell-derived RPE cell cultures. We captured the global epigenomic and transcriptional changes elicited by TNT treatment of RPE and identified putative active enhancers associated with actively transcribed genes, including a set of upregulated transcription factors that are candidate regulators. We found that the vitamin B derivative nicotinamide downregulates these key transcriptional changes, and inhibits and partially reverses RPE EMT, revealing potential therapeutic routes to benefit patients with ERM, macular pucker and PVR.

EPIRETINAL FIBROSIS REMOVAL IN AN ARGUS II-IMPLANTED EYE: Histological Characteristics and Functional Results.

PURPOSE: 1) To investigate morphologic and histochemical characteristics of an epiretinal fibrosis removed in an Argus II-implanted eye; 2) to evaluate the Argus II function before and after the fibrosis removal, and 3) to compare morphologic and functional data. METHODS: Fibrosis, which developed between the Argus II prosthesis and the retina two years after implant, was surgically removed. Its morphologic and histochemical characteristics were evaluated both in light and transmission electron microscopy, with special stains and immunohistochemistry. The Argus II function was evaluated during the follow-up before surgical removal and 1 month later. RESULTS: Fibrosis was successfully removed. It was composed of a fibrotic tissue with spindle cells arranged in nodular aggregates with a symmetric distribution, mixed with an inflammatory infiltrate. Extra- and intracellular, irregular, small iron particles were found and confirmed ultrastructural characterization with degenerative cellular changes. The repositioned Argus II restored, and its function was partially nearly to normal values 1 month after surgery. CONCLUSION: Fibrosis can develop between the Argus II and the retina with increasing reduced function. Morphologic characteristics of the removed fibrosis suggested a pathogenesis based on an inflammatory process involved in a foreign body reaction with progressing connective tissue deposition leading to sclerosis. Adequate clinical follow-up is critical to successful removal of the fibrosis with reactivation of the Argus II function.