INVESTIGATION OF THE PATHOPHYSIOLOGY OF EPIRETINAL MEMBRANE FOVEOSCHISIS: Analysis of Longitudinal Changes in Visual Functions, Retinal Structures, and Retinal Traction Force.

PURPOSE: To analyze the pathophysiology of epiretinal membrane foveoschisis (FS) by evaluating the longitudinal changes in visual function and several optical coherence tomography parameters. METHODS: The medical records of 33 consecutive patients (35 eyes) with untreated epiretinal membrane foveoschisis were retrospectively reviewed. Best-corrected visual acuity, M-CHARTS score, and optical coherence tomography parameters including epiretinal membrane area, maximum depth of retinal folds, FS area, and FS circularity were evaluated. RESULTS: A wide range of FS area changes was observed at the final follow-up visit (59.68%-240.45% of the baseline FS area). In the FS enlargement group, best-corrected visual acuity and mean M-CHARTS scores significantly worsened and maximum depth of retinal folds significantly increased over time, whereas in the FS non-enlargement group, no significant change was observed in the best-corrected visual acuity, mean M-CHARTS scores, or maximum depth of retinal folds during the follow-up period. Multivariate logistic regression analyses revealed that maximum depth of retinal folds (odds ratio: 1.05, 95% confidence interval: 1.00-1.10, P = 0.048) and FS circularity (odds ratio: 0.91, 95% confidence interval: 0.83-1.00, P = 0.043) were significantly associated with FS enlargement. CONCLUSION: Epiretinal membrane foveoschisis encompasses diverse pathophysiologies. Since visual functions do not worsen in some cases, monitoring the changes in visual functions and retinal morphology over time is recommended to determine surgical indications.

MIXED PATHOPHYSIOLOGIES OF LAMELLAR MACULAR HOLES AND RELATED DISEASES: A Multimodal Optical Coherence Tomography-Based Study.

PURPOSE: To investigate the characteristics of mixed pathophysiologies in lamellar macular holes (LMHs) and related diseases using multimodal optical coherence tomography. METHODS: Overall, 126 eyes diagnosed with LMH, epiretinal membrane foveoschisis, or macular pseudohole using the horizontal B-scan image according to the definition proposed by Hubschman et al in 2020 were analyzed using multimodal optical coherence tomography imaging including horizontal and vertical 5-line B-scan, radial scan, and macular three-dimensional volume scan images. If at least two diagnostic criteria for LMH, epiretinal membrane foveoschisis, or macular pseudohole were satisfied in these scans, the patient was diagnosed as having a "mixed type." Retinal traction force was quantitatively evaluated by measuring the maximum depth of the retinal folds using en-face images. RESULTS: Mixed types constituted 34.1% of the cases. The LMH-related mixed group demonstrated intermediate characteristics between the epiretinal membrane foveoschisis/macular pseudohole and true LMH groups in terms of retinal traction and LMH-specific features and had a significant positive correlation between the maximum depth of the retinal folds and mean M-CHARTS scores (P = 0.034). CONCLUSION: A thorough optical coherence tomography analysis is necessary to accurately diagnose LMH and related diseases. A significant positive correlation was observed between the maximum depth of the retinal folds and the degree of metamorphopsia in the LMH-related mixed group.

OBJECTIVE AND QUANTITATIVE ESTIMATION OF THE OPTIMAL TIMING FOR EPIRETINAL MEMBRANE SURGERY ON THE BASIS OF METAMORPHOPSIA.

PURPOSE: To establish an objective and quantitative biomarker of metamorphopsia in epiretinal membranes (ERMs) and determine the optimal timing for ERM surgery. METHODS: Retrospectively, 172 eyes with ERM were reviewed. Retinal folds because of tangential traction by ERM were visualized by en-face optical coherence tomography. The maximum depth of retinal folds (MDRF) within the parafovea was quantified. Metamorphopsia was quantified by M-CHARTS. The change in the distance between the retinal vessels after ERM surgery and the preoperative total depth of retinal folds between the vessels were quantified using en-face optical coherence tomography and optical coherence tomography angiography. RESULTS: Significant correlations were observed between preoperative MDRF and M-CHARTS scores before and at 6 months after surgery (r = 0.617 and 0.460, respectively; P < 0.001) and change in the distance between the retinal vessels after ERM surgery and preoperative total depth of retinal folds between the vessels (r = 0.471; P = 0.013). The preoperative MDRF values at which M-CHARTS scores were 0.5 before and 6 months after the surgery were 69 µm and 118 µm, respectively. CONCLUSION: The MDRF is an objective and quantitative biomarker of metamorphopsia in ERM. To maintain patients' quality of vision, ERM surgery may be performed when the preoperative MDRF ranges between 69 µm and 118 µm.

ADVERSE EFFECT OF MACULAR INTRARETINAL HEMORRHAGE ON THE PROGNOSIS OF SUBMACULAR HEMORRHAGE DUE TO RETINAL ARTERIAL MACROANEURYSM RUPTURE.

PURPOSE: To investigate the clinical course of submacular hemorrhage associated with ruptured retinal arterial macroaneurysm using swept-source optical coherence tomography. METHODS: This study included 23 eyes of 23 consecutive patients diagnosed with submacular hemorrhage associated with ruptured retinal arterial macroaneurysm. Cases underwent displacement of submacular hemorrhage (vitrectomy + subretinal injection of tissue plasminogen activator + air tamponade) and were followed up for 6 months after surgery. Localization of the preoperative hemorrhage and its effect on preoperative and postoperative best-corrected visual acuity, central retinal thickness, and continuity of the ellipsoid zone were measured. RESULTS: Macular intraretinal hemorrhage (IRH) was observed in 17 eyes (73.9%, IRH [+] group) and was not observed in 6 eyes (26.1%, IRH [-] group). The IRH (+) group showed worse postoperative best-corrected visual acuity values compared with the IRH (-) group (0.89 ± 0.47 in logarithm of the minimal angle of resolution units, Snellen equivalent 20/155 and 0.16 ± 0.23, 20/29, respectively; P < 0.01), smaller central retinal thickness values (97.7 ± 53.5 µm, 173.0 ± 32.3 µm, respectively; P < 0.01), and a higher rate of ellipsoid zone disruption (100%, 33.3%, respectively; P < 0.01). CONCLUSION: Patients with preoperative macular IRH showed lower postoperative visual acuity and worse macular contour after submacular hemorrhage displacement compared with patients without macular IRH.

Microperimetry-guided inverted internal limiting membrane flap site selection to preserve retinal sensitivity in macular hole with glaucoma.

Purpose: In cases of macular hole (MH) that is difficult to close, including large, chronic, or highly myopic cases, the inverted internal limiting membrane (ILM) flap technique is often preferred and yields favorable surgical outcomes as compared to those yielded by conventional ILM peeling. However, no consensus exists on the optimal location and area for peeling and inverting the ILM, since multiple alternative methods have been reported alongside the original method. Several adverse effects associated with ILM peeling have been documented, including mechanical impairment of the retinal nerve fiber layer and decreased retinal sensitivity. Particularly, when glaucoma is concomitant, the retinal nerve fiber layer is fragile, raising concerns about a decrease in retinal sensitivity. Consequently, in patients with large MH alongside glaucoma, the goal is to select a procedure that maximizes the closure rate of the MH while minimizing any negative impact on glaucomatous visual field impairment. However, a technique for this purpose has not yet been validated. Observations: A woman in her 60s presented with visual impairment (20/50), metamorphopsia, and central scotoma of unknown onset in the right eye. A full-thickness MH accompanied by epiretinal proliferation (EP) was identified, with a minimum diameter of 506 µm. Although a retinal nerve fiber layer defect was not evident on ophthalmoscopy, thinning of the ganglion cell complex (GCC), extending from the superotemporal aspect of the optic disc, was observed on optical coherence tomography. Both microperimetry and static visual field testing revealed reduced retinal sensitivity in the thinned GCC areas. A pars plana vitrectomy combined with cataract surgery was performed to address her condition. The EP was embedded into the foveal cavity. On the basis of the microperimetry results, the ILM within the absolute scotoma region was peeled on the superotemporal side of the fovea to create a flap, which was then placed over the MH. A gas tamponade was applied, and the patient was maintained in a prone position postoperatively. The MH was successfully closed after the surgery, resulting in visual improvement (20/25). No decline in retinal sensitivity after the surgery was observed. Conclusions and importance: Determining the location and area of the inverted ILM flap on the basis of microperimetry results is a promising patient-tailored strategy for treating MH concomitant with glaucoma while preventing further ILM peeling-associated reduction in the retinal sensitivity.

A factor for predicting simultaneous internal limiting membrane peeling during epiretinal membrane removal: swept-source optical coherence tomography-based evaluation of epiretinal membrane adhesion to the retina.

PURPOSE: To investigate preoperative factors associated with simultaneous internal limiting membrane (ILM) peeling during epiretinal membrane (ERM) removal. STUDY DESIGN: Observational cross-sectional study. METHODS: We retrospectively reviewed 60 eyes with idiopathic ERM that underwent vitrectomy. The gap between the ERM and ILM was visualized using en face optical coherence tomography. The depth and width of the ERM-ILM gap at the initiation site of ERM removal were measured, and the relationship between preoperative factors including these parameters and simultaneous ILM peeling during ERM removal was investigated. RESULTS: The ILM was simultaneously peeled during ERM removal in 30 eyes, but not in the other 30 eyes. Age was significantly higher (P = 0.017) and the width of the ERM-ILM gap was significantly smaller (P < 0.001) in the simultaneous ILM peeling (+) group than in the simultaneous ILM peeling (-) group. Multivariate logistic regression analysis confirmed the width of the ERM-ILM gap as a significant negative predictor for simultaneous ILM peeling (odds ratio, 0.992; 95% confidence interval, 0.986-0.997; P = 0.003). Receiver operating characteristic curve analysis of the width of the ERM-ILM gap revealed that the optimal cutoff for predicting simultaneous ILM peeling was 187.1 µm. CONCLUSION: The small width of the ERM-ILM gap at the initiation site of ERM removal was significantly associated with simultaneous ILM peeling, indicating that the adhesion strength between the ERM and ILM at the initial ERM grasping site determines whether simultaneous ILM peeling will occur during ERM removal.

Quantitative Analyses of Retinal Traction Force and Metamorphopsia in Lamellar Macular Hole and Related Diseases.

Purpose: To investigate the involvement of retinal traction in the pathogenesis of lamellar macular hole (LMH) and related diseases based on OCT-based consensus definition. Design: Retrospective, observational study. Participants: Seventy-two eyes with LMH, epiretinal membrane foveoschisis (ERM-FS), or macular pseudohole (MPH). Methods: To quantitatively evaluate the involvement and strength of retinal traction in their pathogenesis, retinal folds were visualized with en face OCT imaging, and the maximum depth of the parafoveal retinal folds (MDRF) was measured. Metamorphopsia was quantified by measuring the minimum visual angle of dotted lines needed to cause it to disappear using M-CHARTS (Inami). Main Outcome Measures: Maximum depth of retinal folds and M-CHARTS scores. Results: Of the 72 eyes, 26 were classified as having LMH, 25 as having ERM-FS, and 21 as having MPH. Parafoveal retinal folds were observed in 7 (26.9%) eyes with LMH, 25 (100%) with ERM-FS, and 21 (100%) with MPH. The MDRF (7.5 ± 17.6 µm) was significantly smaller in LMH than in ERM-FS (86.3 ± 31.4 µm) and MPH (74.5 ± 24.6 µm) (both P < 0.001), whereas no significant difference in MDRF between MPH and ERM-FS was observed (P = 0.43). A significant positive correlation between MDRF and M-CHARTS scores was observed in ERM-FS and MPH (P = 0.008 and 0.040, respectively) but not in LMH (P = 0.073). Conclusions: Retinal traction was significantly weaker in the LMH group than in the ERM-FS and MPH groups. The MDRF was significantly associated with the degree of metamorphopsia in the ERM-FS and MPH groups. These results provide insights into the diseases' pathophysiology and treatment strategy.

Epiretinal Membrane Impairs the Inner Retinal Layer in a Traction Force-Dependent Manner.

Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = -0.657, P = 0.015; r = -0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P < 0.001; r = 0.210, P = 0.007, respectively). However, only the INL thickness progression rate was significantly correlated with the MDRF progression rate (r = 0.770, P < 0.001). On case stratification by localization of MDRF based on the ETDRS chart, in regions other than temporal regions, the INL thickness was significantly greater in regions with MDRF than in other regions. The MDRF significantly correlated with α-SMA expression in the ERM specimens (r = 0.555, P = 0.009). Conclusions: The findings suggest that ERM impairs the inner retinal layer in a traction force-dependent manner. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.