The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure

Shiode, Yusuke; Morizane, Yuki; Matoba, Ryo; Hirano, Masayuki; Doi, Shinichiro; Toshima, Shinji; Takahashi, Kosuke; Araki, Ryoichi; Kanzaki, Yuki; Hosogi, Mika; Yonezawa, Tomoko; Yoshida, Akitoshi; Shiraga, Fumio

doi:10.1167/iovs.17-21756

Cited by 159 publications

(137 citation statements)

References 45 publications

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“…One theory is that the ILM flap may act as a scaffold for glial cells proliferation, resulting in MH filling with proliferating cells, which enhances MH closure. Another explanation might be that the ILM serves as a barrier, disabling the entrance of fluid from the vitreous cavity to the MH [9]. Moreover, the ILM flap is a source of Müller cells, which located at the surface of the ILM flap.…”

Section: Discussionmentioning

confidence: 99%

Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study

et al. 2020

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Background: To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the complete ILM removal in the treatment of large stage 4 macular hole (MH) > 400 μm and to evaluate reconstructive anatomical changes in foveal microstructure using spectral-domain optical coherence tomography. Methods: This is a retrospective, consecutive, nonrandomized comparative study of patients affected by idiopathic, myopic or traumatic stage 4 MH (minimum diameter > 400 μm) treated with 25-gauge pars-plana vitrectomy with either complete ILM peeling (n = 23, Group 1) or inverted ILM flap technique (n = 23, Group 2), between August 2016 and August 2018. Main outcomes measured were the MH closure rate assessed by spectral-domain optical coherence tomography and the best-corrected visual acuity (BCVA) at six months. Foveal microstructure reconstructive changes were evaluated using SD-OCT to determine predictive factors of postoperative BCVA. Results: Closure of MH was achieved in 16/23 cases of Group 1 (70%) and in 22/23 cases of the Group 2 (96%). Surgical failure was reported in 6 cases of Group 1 and 1 case of Group 2. The MH closure rate was significantly higher with the inverted ILM flap technique (P-value = 0.02). Average BCVA (LogMAR) changed from 1.04 ± 0.32 to 0.70 ± 0.31 in Group 1 and from 0.98 ± 0.22 to 0.45 ± 0.25 in Group 2 (P-value = 0.005) at 6 months. Improvement in BCVA (> 0.3 LogMAR units) was statistically higher in the Group 2 (P-value = 0.03). Restoration of foveal microstructure was significantly higher in the Group 2 at 6 months (52% vs 9%, P-value < 0.01). In Group 2, the integrity of the external limiting membrane at 3 months postoperatively was the only significant feature correlated with postoperative BCVA at 6 months (r = 0.562; P-Value = 0.01, forward stepwise regression analysis). Conclusion: Inverted ILM flap technique is more effective than the classic ILM peeling for the closure of large stage 4 MHs > 400 μm, improving both anatomical and functional outcomes. Early recovery of the external limiting membrane at 3 months is a positive predictive value of postoperative BCVA 6 months after inverted ILM flap technique.

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Section: Discussionmentioning

confidence: 99%

Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study

et al. 2020

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“…Shiode et al showed that the neurotrophic factors and basic fibroblast growth factors (bFGF) on the surface of the ILM flap promoted the proliferation and migration of the Müller cells, contributing to fill the MH and enhance closure [11]. Activated Müller cells also produced neurotrophic factors and growth factors that may promote the survival of retinal neurons [18]. Moreover, the ILM flaps create a closed compartment enabling the RPE to pump out fluid and keep hole dry [10].…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy evaluation of inverted internal limiting membrane flap technique and internal limiting membrane peeling in large macular holes: a systematic review and meta-analysis

et al. 2020

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Background: The purpose of this study was to compare the anatomical and visual outcomes of inverted internal limiting membrane (ILM) flap technique and internal limiting membrane peeling in large macular holes (MH).Methods: Related studies were reviewed by searching electronic databases of Pubmed, Embase, Cochrane Library. We searched for articles that compared inverted ILM flap technique with ILM peeling for large MH (> 400 μm). Double-arm meta-analysis was performed for the primary end point that was the rate of MH closure, and the secondary end point was postoperative visual acuity (VA). Heterogeneity, publication bias, sensitivity analysis and subgroup analysis were conducted to guarantee the statistical power.Results: This review included eight studies involving 593 eyes, 4 randomized control trials and 4 retrospective studies. After sensitivity analysis for eliminating the heterogeneity of primary outcome, the pooled data showed the rate of MH closure with inverted ILM flap technique group was statistically significantly higher than ILM peeling group (odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.89 to 8.27; P = 0.0003). At the follow-up duration of 3 months, postoperative VA was significantly better in the group of inverted ILM flap than ILM peeling (mean difference (MD) = − 0.16, 95% CI = − 0.23 to 0.09; P < 0.00001). However, there was no difference in visual outcomes between the two groups of different surgical treatments at relatively long-term follow-up over 6 months (MD = 0.01, 95% CI = − 0.12 to 0.15; P = 0.86).Conclusion: Vitrectomy with inverted ILM flap technique had a better anatomical outcome than ILM peeling. Flap technique also had a signifcant visual gain in the short term, but the limitations in visual recovery at a longer follow-up was found.

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“…We found that the ILM, which is the basement membrane of Müller cells, functioned as a scaffold to promote the proliferation and migration of glial cells. Furthermore, the activated glial cells produced various neurotrophic factors as well as bFGF [ 20 ]. Therefore, it is reasonable to suppose that the inverted ILM might have acted as a scaffold of embedded glial cells and facilitated the repair process of the macula by glial cells in the current case.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, using an experimental monkey model for large macular hole, we performed an ILM inversion technique and showed that the ILM, which is the basement membrane of Müller cells, was able to facilitate glial cell proliferation and migration as well as the expression of neurotrophic factors and growth factors from glial cells [ 19 ]. This technique thus lead to an acceleration of the wound healing processes at the macula [ 20 ]. Based on these findings, we hypothesized that the ILM might be able to facilitate the therapeutic process of the LHEP embedding technique for the treatment of degenerative LMH.…”

Section: Introductionmentioning

confidence: 99%

Embedding of lamellar hole-associated epiretinal proliferation combined with internal limiting membrane inversion for the treatment of lamellar macular hole: a case report

et al. 2018

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BackgroundWe recently reported that lamellar macular hole (LMH) with lamellar hole-associated epiretinal proliferation (LHEP) can be effectively treated by embedding the LHEP into the retinal cleavage to improve foveal contour and visual acuity. Here, we report a case of LMH with LHEP for which we performed embedding of the LHEP combined with internal limiting membrane (ILM) inversion. We then evaluated the effects of this surgery on macular morphology and visual functions.Case presentationA 62-year-old man presented with visual disturbance (20/29) and metamorphopsia in his right eye. B-scan optical coherence tomography (OCT) imaging revealed the presence of both partial-thickness defect of the macula with degenerative retinal cleavage and LHEP at the surface of the retina. En face OCT imaging showed the absence of retinal fold. We performed phacoemulsification with intraocular lens implantation, vitrectomy, embedding of LHEP into the retinal cleavage, and ILM inversion. Three months after the surgery, both foveal contour and visual acuity (20/20) were improved and metamorphopsia was reduced.ConclusionEmbedding of the LHEP combined with ILM inversion may be an effective treatment for LMH with LHEP.Electronic supplementary materialThe online version of this article (10.1186/s12886-018-0926-8) contains supplementary material, which is available to authorized users.

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The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure

Abstract: During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.

Cited by 159 publications

References 45 publications

Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study

Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study

Comparative efficacy evaluation of inverted internal limiting membrane flap technique and internal limiting membrane peeling in large macular holes: a systematic review and meta-analysis

Embedding of lamellar hole-associated epiretinal proliferation combined with internal limiting membrane inversion for the treatment of lamellar macular hole: a case report

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