Implementing new computational methods for the study of JCT and SC inner wall basement membrane biomechanics and hydrodynamics.

PURPOSE: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and the inner wall endothelium of Schlemm's canal (SC), regulates intraocular pressure (IOP) by controlling the aqueous humor outflow resistance. Despite its importance, our understanding of the biomechanics and hydrodynamics within this region remains limited. Fluid-structure interaction (FSI) offers a way to estimate the biomechanical properties of the JCT and SC under various loading and boundary conditions, providing valuable insights that are beyond the reach of current imaging techniques. METHODS: In this study, a normal human eye was fixed at a pressure of 7 mm Hg, and two radial wedges of the TM tissues, which included the SC inner wall basement membrane and JCT, were dissected, processed, and imaged using 3D serial block-face scanning electron microscopy (SBF-SEM). Four different sets of images were used to create 3D finite element (FE) models of the JCT and inner wall endothelial cells of SC with their basement membrane. The outer JCT portion was carefully removed as the outflow resistance is not in that region, leaving only the SCE inner wall and a few µm of the tissue, which does contain the resistance. An inverse iterative FE algorithm was then utilized to calculate the unloaded geometry of the JCT/SC complex at an aqueous humor pressure of 0 mm Hg. Then in the model, the intertrabecular spaces, pores, and giant vacuole contents were replaced by aqueous humor, and FSI was employed to pressurize the JCT/SC complex from 0 to 15 mm Hg. RESULTS: In the JCT/SC complex, the shear stress of the aqueous humor is not evenly distributed. Areas proximal to the inner wall of SC experience larger stresses, reaching up to 10 Pa, while those closer to the JCT undergo lower stresses, approximately 4 Pa. Within this complex, giant vacuoles with or without I-pore behave differently. Those without I-pores experience a more significant strain, around 14%, compared to those with I-pores, where the strain is roughly 9%. CONCLUSIONS: The distribution of aqueous humor wall shear stress is not uniform within the JCT/SC complex, which may contribute to our understanding of the underlying selective mechanisms in the pathway.

RESTORATION PROCESS OF THE OUTER RETINAL LAYERS AFTER SURGICAL MACULAR HOLE CLOSURE.

PURPOSE: To investigate the interrelationship among the outer retinal layers after macular hole surgery and elucidate the restoration process. METHODS: This retrospective observational study included 50 eyes of 47 consecutive patients with closed macular holes in the first vitrectomy. Optical coherence tomography was obtained before surgery; at 1, 3, and 6 months postsurgery; and at the last visit. The complete continuous layer rate and mean defect length were evaluated for the outer nuclear layer (ONL), external limiting membrane (ELM), and ellipsoid zone (EZ). RESULTS: At all postoperative visits, the complete continuous layer rate was in the descending order of ELM, ONL, and EZ and the mean defect length was in the ascending order of ELM, ONL, and EZ. External limiting membrane was necessary for ONL restoration. External limiting membrane and ONL were necessary for EZ restoration. Hyperreflective protrusions were observed from the area lacking ELM into the subretinal space after surgery. Ellipsoid zone was not formed in coexistence with the hyperreflective protrusions. Intermediate reflective protrusions appeared under the ONL plus ELM after surgery and were eventually replaced by EZ. CONCLUSION: Restoration of the outer retinal layers after surgical macular hole closure occurs in the order of ELM, ONL, and EZ.

THE SPECTRUM OF INTERNAL LIMITING MEMBRANE DISEASE IN ALPORT SYNDROME: A Multimodal Imaging Study.

PURPOSE: To characterize the spectrum of internal limiting membrane (ILM) disease in Alport syndrome using multimodal imaging, including widefield (WF) and ultra-widefield (UWF) modalities, and to report their relative prevalence according to the genetic pattern of inheritance. METHODS: Cross-sectional clinical study of patients diagnosed with Alport syndrome. All patients underwent UWF color photography and autofluorescence, WF-optical coherence tomography angiography and spectral-domain optical coherence tomography. Demographics, past medical and ophthalmic history, and genetic mutation history were collected. RESULTS: Forty-two eyes of 21 patients (11 men; age 36.6 ± 12.9 years) were included. Macular spectral-domain optical coherence tomography revealed ILM granularity, more frequent in X-linked Alport syndrome and corresponding to dot maculopathy on color fundus. Mid-peripheral spectral-domain optical coherence tomography scans revealed multilamellated ILM in eight eyes (19%), presumably progressive, which corresponded to a cavitary pattern on en-face OCT. En-face OCT revealed multiple areas of retinal nerve fiber layer dehiscence in the macula, overlapping with vascular lacunae on optical coherence tomography angiography, and a coarse arrangement of retinal nerve fiber layer above and below the temporal raphe in 20 eyes (52%). CONCLUSION: Multimodal imaging allowed for the detection/characterization of retinal findings (ILM granularity, progressive ILM lamellation, retinal nerve fiber layer dehiscence, vascular lacunae, and coarse arrangement of retinal nerve fiber layer toward the disc) as multifaceted manifestations of ILM disease in Alport syndrome.

Application of direct stochastic optical reconstruction microscopy (dSTORM) to the histological analysis of human glomerular disease.

Electron microscopy (EM) following immunofluorescence (IF) imaging is a vital tool for the diagnosis of human glomerular diseases, but the implementation of EM is limited to specialised institutions and it is not available in many countries. Recent progress in fluorescence microscopy now enables conventional widefield fluorescence microscopes to be adapted at modest cost to provide resolution below 50 nm in biological specimens. We show that stochastically switched single-molecule localisation microscopy can be applied to clinical histological sections stained with standard IF techniques and that such super-resolved IF may provide an alternative means to resolve ultrastructure to aid the diagnosis of kidney disease where EM is not available. We have implemented the direct stochastic optical reconstruction microscopy technique with human kidney biopsy frozen sections stained with clinically approved immunofluorescent probes for the basal laminae and immunoglobulin G deposits. Using cases of membranous glomerulonephritis, thin basement membrane lesion, and lupus nephritis, we compare this approach to clinical EM images and demonstrate enhanced imaging compared to conventional IF microscopy. With minor modifications in established IF protocols of clinical frozen renal biopsies, we believe the cost-effective adaptation of conventional widefield microscopes can be widely implemented to provide super-resolved image information to aid diagnosis of human glomerular disease.

The internal limiting membrane: Roles in retinal development and implications for emerging ocular therapies.

Basement membranes help to establish, maintain, and separate their associated tissues. They also provide growth and signaling substrates for nearby resident cells. The internal limiting membrane (ILM) is the basement membrane at the ocular vitreoretinal interface. While the ILM is essential for normal retinal development, it is dispensable in adulthood. Moreover, the ILM may constitute a significant barrier to emerging ocular therapeutics, such as viral gene therapy or stem cell transplantation. Here we take a neurodevelopmental perspective in examining how retinal neurons, glia, and vasculature interact with individual extracellular matrix constituents at the ILM. In addition, we review evidence that the ILM may impede novel ocular therapies and discuss approaches for achieving retinal parenchymal targeting of gene vectors and cell transplants delivered into the vitreous cavity by manipulating interactions with the ILM.

Epiretinal Membrane Surgery Using Intraoperative OCT-Guided Membrane Removal in the DISCOVER Study versus Conventional Membrane Removal.

PURPOSE: To provide a comparative assessment of clinical outcomes between patients undergoing intraoperative OCT (iOCT) and conventional surgery for pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peel. DESIGN: Case-control retrospective, comparative assessment. PARTICIPANTS: Patients undergoing PPV with membrane peel for ERM with eyes pooled from the prospective Determination of Feasibility of Intraoperative Spectral Domain Microscope Combined/Integrated OCT Visualization During En Face Retinal and Ophthalmic Surgery (DISCOVER) iOCT study and eyes undergoing conventional ERM surgery without iOCT. METHODS: Visual acuity and OCT assessment before ERM surgery and at 1-, 3-, 6-, and 12-month follow-up after standard small-gauge PPV with iOCT feedback (iOCT DISCOVER group) or PPV with compulsory internal limiting membrane (ILM) peeling (conventional group). Visual acuity, central subfield thickness (CST), reoperation rate, and ERM recurrence were determined by record review and post hoc assessment of clinical OCTs after ERM peel. MAIN OUTCOME MEASURES: Visual acuity and ERM recurrence. RESULTS: A total of 262 eyes were included. Visual acuity (VA) improved 11.9 letters in the iOCT group (P < 0.0001) and 12.1 letters in the conventional group (P < 0.0001) at 12 months after ERM surgery. Visual acuity improvement did not differ between the iOCT and conventional groups at 1, 3, 6, or 12 months after surgery (P > 0.05 for each time point). Preoperative mean CST decreased in the iOCT group (P < 0.0001) and conventional group (P < 0.0001) with no difference between groups in CST reduction at 12 months (P = 0.36). No reoperations or visually significant recurrent ERMs occurred in either cohort. CONCLUSIONS: Intraoperative OCT-guided ERM removal without mandated ILM peeling provided similar VA and anatomic results to conventional ILM peeling for ERM. Future randomized prospective studies are needed to assess fully the possible role of iOCT in ERM surgery and to evaluate the potential impact of nonfoveal ERM persistence or recurrence in comparison with conventional surgery.

Novel use of fluorescent microscopy in determining basement membrane integrity in ambiguous cases.

Indistinct basement membrane due to inflammation always poses a problem to the pathologists for commenting on micro-invasive squamous cell carcinoma. In such a situation, even a special stain would not be able to correctly demonstrate the basement membrane, which is necessary for estimating the depth of invasion. In this paper, we have proposed a novel fluorescent microscopy assisted visualization of basement membrane in such difficult situations. To further validate this approach, we then retrospectively investigated twenty such cases under a fluorescent microscope and could able to repeat the same result. As routine hematoxylin and eosin stained sections are required for evaluation, it is technically less demanding and less time-consuming.

Involvement of Anoikis in Dissociated Optic Nerve Fiber Layer Appearance.

Dissociated optic nerve fiber layer (DONFL) appearance is characterized by dimpling of the fundus when observed after vitrectomy with the internal limiting membrane (ILM) peeling in macular diseases. However, the cause of DONFL remains largely unknown. Optical coherence tomography (OCT) findings have indicated that the nerve fiber layer (NFL) and ganglion cells are likely to have been damaged in patients with DONFL appearance. Since DONFL appearance occurs at a certain postoperative period, it is unlikely to be retinal damage directly caused by ILM peeling because apoptosis occurs at a certain period after tissue damage and/or injury. However, it may be due to ILM peeling-induced apoptosis in the retinal tissue. Anoikis is a type of apoptosis that occurs in anchorage-dependent cells upon detachment of those cells from the surrounding extracellular matrix (i.e., the loss of cell anchorage). The anoikis-related proteins ßA3/A1 crystallin and E-cadherin are reportedly expressed in retinal ganglion cells. Thus, we theorize that one possible cause of DONFL appearance is ILM peeling-induced anoikis in retinal ganglion cells.

Evaluation of inner retinal dimples and internal limiting membrane flap configuration after temporal inverted ILM flap technique.

PURPOSE: To quantitatively evaluate structural changes associated with inner retinal dimples (IRDs) and qualitatively classify the internal limiting membrane (ILM) flap configuration after temporal inverted ILM flap technique using spectral domain optical coherence tomography (SD-OCT). METHODS: Twenty-three eyes of 23 patients with successfully closed idiopathic, large (>400 µm) macular hole were enrolled. Patients were treated with pars plana vitrectomy followed by temporal inverted ILM flap technique. A complete ophthalmologic examination including cross sectional and en face OCT in addition to multicolor blue reflectance imaging of confocal scanning laser ophthalmoscopy (cSLO) was performed preoperatively and at postoperative month-12. The location, number, depth, and width of the IRDs were analyzed using blue reflectance images of multicolor cSLO and en face OCT. The ILM flap is also classified as smooth, wrinkled, and folded with en face OCT. RESULTS: The mean number of IRDs visualized on en face OCT (n = 23.08 ± 22.05) was statistically significantly higher compared with multicolor cSLO blue reflectance module (5.91 ± 10.58; p < 0.001). The mean depth of IRDs measured on en face OCT was 8.08 ± 3.1 µm (3-14 µm) which referred to the nerve fiber layer. The final visual acuity was associated with neither ILM flap configuration (p = 0.408), nor number of the IRDs on en face OCT (p = 0.112). CONCLUSION: En face OCT is a novel imaging modality that offers improved visualization and accuracy in identifying the features of the IRDs and the ILM flap. Additionally, it provides clear visualization of the vitreoretinal interface to distinguish whether ILM was peeled or not in the initial surgery.

Conventional internal limiting membrane peeling versus temporal inverted internal limiting membrane flap for large macular holes.

PURPOSE: To compare the functional, anatomical, and morphological results of conventional internal limiting membrane peeling versus temporal inverted internal limiting membrane flap technique for the treatment of macular holes larger than 400 µm. DESIGN: Retrospective, comparative case series. METHODS: A total of 33 patients were included, of whom 18 were treated with internal limiting membrane peeling (Group 1) and 15 were treated with temporal inverted internal limiting membrane flap technique (Group 2). Complete ophthalmic examination, such as microperimetry and optical coherence tomography, was performed preoperatively and at 12 months after surgery. RESULTS: The closure rates accomplished in Groups 1 and 2 were 72.2% and 100%, respectively (p = 0.036). The mean improvement in best-corrected visual acuity was logMAR 0.49 ± 0.17 in Group 1 and logMAR 0.91 ± 0.15 in Group 2 (p = 0.037). U-shaped closure was achieved in one eye in Group 1 and 12 eyes in Group 2 (p < 0.001). Complete restoration of external limiting membrane and ellipsoid zone rates were significantly higher in Group 2 (p = 0.027 and p = 0.001, respectively). CONCLUSION: The single-layered temporal inverted internal limiting membrane flap technique improves not only anatomical and morphological but also functional outcomes of surgery for large macular holes. Furthermore, this technique seems to minimize the risk of iatrogenic trauma to the nasal part of the fovea and the corresponding papillomacular bundle fibers.

VALIDITY AND EFFICACY OF INTERNAL LIMITING MEMBRANE PEELING DURING INITIAL VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: VISUAL OUTCOMES IN MACULA-SPARING CASES.

PURPOSE: To compare the visual outcomes and prevalence of epiretinal membrane (ERM) growth postoperatively between eyes treated with and without internal limiting membrane peeling during vitrectomy for macula-sparing rhegmatogenous retinal detachment. METHODS: Fifty-five consecutive cases who underwent vitrectomy for macula-sparing rhegmatogenous retinal detachment were reviewed retrospectively. The inclusion criteria were a minimal 6-month follow-up postoperatively and spectral domain optical coherence tomographic images available at follow-up. Cases with any pre-existing macular condition possibly affecting the visual prognosis were excluded. All cases were divided into two groups: 22 cases without internal limiting membrane peeling (Group 1) and 33 cases with internal limiting membrane peeling (Group 2). The two groups were compared using the Mann-Whitney U test and Fisher exact test in terms of the best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) before vitrectomy, postoperative BCVA, and the presence of postoperative ERM growth. Postoperative BCVA and ERM growth were determined at 6 months, 12 months, and the last visit. The visual outcomes were also analyzed between cases with and without postoperative symptomatic ERM growth, which caused visual impairment and required surgical removal. RESULTS: The mean postoperative BCVAs were 0.00, -0.08, and -0.08 logarithm of the minimum angle of resolution in Group 1, and -0.08, -0.08, and -0.08 logarithm of the minimum angle of resolution in Group 2 at 6 months, 12 months, and the last visit, respectively, and did not differ significantly between the 2 groups at each time point except for at 12 months (P = 0.027). An ERM developed in 14 cases in Group 1, 7 of which were symptomatic. No cases in Group 2 had ERM growth. The prevalence of ERM growth was significantly (P < 0.001) higher in Group 1 than Group 2. The BCVA was significantly worse at 6 months (P = 0.011), 12 months (P = 0.003), and the last visit (P = 0.019) in 7 cases with symptomatic ERMs (median, 0.30, 0.15, and 0.10 logarithm of the minimum angle of resolution, respectively) than in 48 cases without symptomatic ERMs (median, -0.08, -0.08, and -0.08 logarithm of the minimum angle of resolution, respectively). CONCLUSION: Internal limiting membrane peeling did not result in decreased visual acuity postoperatively in cases with a macula-sparing rhegmatogenous retinal detachment, and the procedure significantly prevented postsurgical ERM growth. Symptomatic ERMs led to decreased visual acuity even after surgical removal. These results support the validity and efficacy of internal limiting membrane peeling for preventing ERM growth after rhegmatogenous retinal detachment repair.

Effect of Foveal Vitreous Cortex Removal to Prevent Epiretinal Membrane after Vitrectomy for Rhegmatogenous Retinal Detachment.

PURPOSE: To determine the effect of foveal vitreous cortex removal during pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) on the prevention of postoperative epiretinal membrane (ERM) development without internal limiting membrane (ILM) peeling. DESIGN: Case-control study. PARTICIPANTS: A total of 105 consecutive eyes of 105 patients who underwent primary PPV for RRD between September 2018 and August 2019 and were followed for at least 6 months. METHODS: The presence of foveal vitreous cortex during PPV was determined by examining the images obtained by a widefield viewing system in 52 eyes (WF group) operated in the first half of the study period and obtained by a high-magnification floating lens in 53 eyes (FL group) operated in the latter half of the study period. Triamcinolone acetonide was used to make the vitreous cortex more visible during PPV. The foveal vitreous cortex was removed if detected by forceps with a high-magnification floating lens without ILM peeling or use of dye staining. The presence of postoperative ERM was examined by using OCT. MAIN OUTCOME MEASURES: The rate of detected and removed foveal vitreous cortex during PPV and the incidence of postoperative ERM of each group. RESULTS: The rate of detected and removed foveal vitreous cortex during PPV was significantly higher in the FL group than in the WF group (41.5% vs. 15.4%, P = 0.004). The incidence of postoperative ERM was significantly lower in the FL group than in the WF group (1.9% vs. 13.5%, P = 0.03). None of the eyes required additional surgery for the postoperative ERM during the follow-up period. The retinal reattachment rate was not significantly different (98.1% vs. 100%, P = 0.99), and the final retinal attachment rate was 100% in both groups. A dissociated optic nerve fiber layer appearance and a temporal macular thinning were not detected postoperatively in any of the eyes with removal of the foveal vitreous cortex during PPV. CONCLUSIONS: The detection and removal of foveal vitreous cortex with the high-magnification floating lens during PPV for RRD significantly reduce the incidence of postoperative ERM without adverse findings.

Optimizing Visualization of Membranes in Macular Surgery With Heads-Up Display.

BACKGROUND AND OBJECTIVE: To determine which optical parameter profiles (OPPs) can be utilized to improve the visualization of epiretinal membranes (ERMs) and the internal limiting membrane (ILM) using a three-dimensional heads-up microscope during 25-gauge pars plana vitrectomy. PATIENTS AND METHODS: Fourteen independent graders were asked to complete a questionnaire comparing each of the OPPs against the unaltered control image for each given surgical case. RESULTS: Analysis of the graders' responses indicated that higher values of hue are correlated with better visualization of ERM/ILM before and after dye application. There was overall agreement that OPPs could be used to enhance the visualization of the ERM and ILM during surgery. CONCLUSIONS: The use of OPPs to improve the visualization of specific structures is still new and heavily dependent on surgeon preference. The authors' study shows that some OPPs may enhance the visualization of the ERM and ILM during macular surgery. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:584-587.].

Multimodal imaging and adaptive optics in internal limiting membrane dystrophy.

An 18-year-old boy presented with a mild blurring of vision in both his eyes for the last 2 years. His best-corrected visual acuity was 20/60 in both the eyes with normal colour vision. Fundus evaluation showed exaggerated shiny reflex from the internal limiting membrane (ILM) with the wrinkled inner retinal surface at posterior pole. No vessel attenuation or retinal pigment epithelium changes were evident. Optical coherence tomography showed thickened ILM, which was appreciated in fundus photo also. The electrodiagnostic tests were normal, and the photoreceptors appeared normal in adaptive optics in the central macula at 2°-4° eccentricity. Among the very few reported cases of Muller cells sheen dystrophy, our patient was the probably the youngest and was picked up by a thoughtful ophthalmologist in detailed clinical examination. Adaptive optics in the case of ILM dystrophy is also not reported earlier.

Spontaneous Resolution of Foveal Sub-internal Limiting Membrane Hemorrhage with Excellent Visual and Anatomical Outcome in a Patient with Acute Myeloid Leukemia.

Sub-internal limiting membrane (sub-ILM) hemorrhage is a distinct type of retinal hemorrhage in which the blood accumulates between ILM and nerve fiber layer. Little is known about visual prognosis as well as ideal management of foveal sub-ILM hemorrhage in patients with acute leukemia. Herein, we presented a case of acute myeloid leukemia with foveal sub-ILM hemorrhage. Observation alone resulted in complete resolution of hemorrhage with good visual and anatomical outcome.

Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060-0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes.

The kidney is comprised of highly complex structures that rely on self-maintenance for their functions, and tissue repair and regeneration in renal diseases. We devised a proteomics assay to measure the turnover of individual proteins in mouse kidney. Mice were metabolically labeled with a specially formulated chow containing nitrogen-15 (15N) with the absence of normal 14N atoms. Newly synthesized proteins with 15N contents were distinguished from their 14N counterparts by mass spectrometry. In total, we identified over 4,000 proteins from the renal cortex with a majority of them contained only 15N. About 100 proteins had both 14N- and 15N-contents. Notably, the long-lived proteins that had large 14N/15N ratios were mostly matrix proteins. These included proteins such as type IV and type VI collagen, laminin, nidogen and perlecan/HSPG2 that constitute the axial core of the glomerular basement membrane (GBM). In contrast, the surface lamina rara proteins such as agrin and integrin had much shorter longevity, suggesting their faster regeneration cycle. The data illustrated matrix proteins that constitute the basement membranes in the renal cortex are constantly renewed in an ordered fashion. In perspective, the global profile of protein turnover is usefully in understanding the protein-basis of GBM maintenance and repair.

Sub-perfluoro-n-octane injection of ocular viscoelastic device assisted inverted internal limiting membrane flap for macular hole retinal detachment surgery: a novel technique.

BACKGROUND: To evaluate the feasibility of a surgical technique using a sub-perfluoro-n-octane (PFO) injection of ocular viscoelastic device (OVD) to stabilize inverted internal limiting membrane (ILM) flap for the treatment of macular hole retinal detachment (MHRD). METHODS: This study was a retrospective, consecutive, interventional case series. Patients who underwent MHRD surgery with sub-PFO injection of OVD to stabilize inverted ILM flap onto the macular hole (MH) were reviewed. The color fundus and optical coherence tomography (OCT) images were collected and evaluated. The best-corrected visual acuity (BCVA) before and after surgery were compared as the functional outcome. RESULTS: The study included 8 eyes of 8 consecutive patients (mean age: 61.8 ± 7.1 years; mean follow-up period: 9.0 ± 2.5 months). All eyes (100%) achieved successful MH closure; 7 eyes (87.5%) demonstrated complete retinal reattachment, and 1 eye (12.5%) had minimal residual subretinal fluid parafoveally. Of the 8 patients, 7 patients (87.5%) had achieved improvement in BCVA after the primary surgery, whereas 1 eye remained stable. The average BCVA before and after the surgery at the last visit improved from 20/843 (1.63 ± 0.48 logMAR) to 20/200 (1.00 ± 0.39 logMAR) (P = 0.016). Anatomically, near-normal foveal contour was noted in five (62.5%) eyes at the final follow-up. CONCLUSIONS: The use of sub-PFO injection of OVD in MHRD surgery could stabilize inverted ILM flaps, achieve good anatomical results and improve postoperative BCVA.

Tailored internal limiting membrane flap technique for primary macular hole.

PURPOSE: To investigate the outcomes of primary full-thickness macular hole (MH) after surgical intervention with tailored internal limiting membrane (ILM) flap technique. METHODS: Patients were reviewed for their clinical characteristics and surgical outcomes. The technique included incomplete circular peeling of the perifoveal ILM which was then trimmed according to the size of the MH. Fluid-gas exchange was done without further manipulation. RESULTS: Nineteen eyes of 19 patients were included. The patients were in average 61 years old (range 41-83) and had an average follow-up period of 11.0 months. At baseline visit, minimal linear diameter of the MH was 311.6 µm (range 80-768). After a single surgery, the MH closed in all cases with improvement of mean visual acuity (from 0.9 to 0.4 logarithm of the minimum angle of resolution units, p < 0.0001, Wilcoxon signed-rank test). At the final visit, 15 (78.9%) eyes achieved a visual acuity ≥ 20/40. Outer retinal gliosis was found to be associated with less favorable postoperative visual acuity. Factors related to the formation of outer retinal gliosis were worse preoperative visual acuity and a large MH with a diameter > 400 µm. CONCLUSION: Tailored ILM flap technique is an effective method for favorable anatomical and visual outcomes for treatment of primary MH.

Comparing the inverted internal limiting membrane flap with autologous blood technique to internal limiting membrane insertion for the repair of refractory macular hole.

PURPOSE: To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the autologous blood clot (ABC) to ILM insertion technique for the repair of refractory macular hole (RMH). METHODS: Fifty-two consecutive patients (52 eyes) diagnosed with RMH with a minimum diameter more than 700 µm were enrolled. All patients underwent vitrectomy and gas tamponade. Of these, 25 patients undergo inverted ILM flap combination with ABC (Group A). The remaining 27 patients underwent ILM insertion (Group B). The main outcome measures were macular hole (MH) closure, foveal configuration, logarithm of the minimum angle of resolution (logMAR), best-corrected visual acuity (BCVA), superficial foveal avascular zone (FAZ) and superficial parafoveal vessel density. RESULTS: Three months post-operation, MH was successfully anatomic closed in 24 of 25 eyes (96%) in Group A and 25 of 27 eyes (92.5%) in Group B (P = 0.599). A concave foveal configuration of MH closure was observed in 23 of 25 eyes (92%) in Group A and 2 of 27 eyes (7.4%) in Group B (P < 0.001). Mean BCVA (logMAR) had improved from 1.31 ± 0.61 to 0.68 ± 0.40 in Group A (P < 0.001) and from 1.34 ± 0.39 to 1.29 ± 0.62 in Group B (P = 0.584) at 3 months. Average superficial FAZ area and superficial parafoveal vessel density were 0.29 ± 0.08 mm2 and 51.41 ± 2.79% in Group A and 0.73 ± 0.15 mm2 and 43.77 ± 2.71% in Group B, respectively. There was a significant difference in both the average superficial FAZ area and parafoveal vessel density between Groups A and B (P < 0.001 for both). CONCLUSION: Anatomical foveal configuration, mean BCVA (logMAR), mean superficial FAZ and parafoveal vessel density outcomes for the inverted ILM flap combined with ABC approach were better than the outcomes obtained with ILM insertion in the treatment of RMH. This approach may promote better long-term, vision function outcomes for patients diagnosed with RMH.