Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Critical analysis of macular hole repair techniques: a comprehensive systematic review and meta-analysis comparing internal limiting membrane flap and internal limiting membrane peeling for any size of macular hole

BMC Ophthalmology volume 25, Article number: 174 (2025) Cite this article

Abstract

Background

Macular holes (MHs) are a leading cause of visual impairment and blindness worldwide defined as a partial or full thickness anatomical defect in the fovea of the retina. ILM peeling is an effective surgical procedure to repair the defect. However, this approach lacks efficacy for larger macular holes. ILM flap is a novel technique with demonstrated efficacy for repair of larger defects.

Objective

This systematic review and meta-analysis aims to compare the effectiveness of these two techniques in treating any size and type of MH.

Methods

A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases to identify the relevant articles. The primary outcome measures were MH closure rate and postoperative VA. The statistical power was ensured by performing heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Pooled odds ratios (ORs), mean differences (MD), and 95% confidence intervals (CIs) were calculated. All statistical analyses were performed using R Statistical Software and meta package v4.17-0.

Results

A total of thirty-two studies, comprising nine RCTs and twenty three retrospective studies were included in this meta-analysis, which involved 1220 eyes in the ILM flap group and 1277 eyes in the ILM peeling group. The overall MH closure rate significantly favored ILM flap technique (OR = 2.47, CI = 1.58 to 3.87; P < 0.001; I²= 30%). The overall pooled result for postoperative VA, no significant difference was observed between the two surgical methods. However, it favored ILM flap technique on subgroup analysis based on study type and MH size specifically in the RCTS with macular hole size > 400 μm (MD = -0.13, 95% CI = -0.17 to -0.08, p < 0.01; I2 = 13%), as well as on subgrouping based on follow-up duration (MD = -0.11, 95% CI = -0.14 to -0.08, p < 0.01; I2 = 25%).

Conclusion

ILM flap technique resulted in significantly better closure rate with all sizes of MHs, coupled with improved visual acuity in larger MHs and with follow-up duration.

Peer Review reports

Introduction

A macular hole (MH) is characterized as a structural defect, either partial or full thickness, within the foveolar region of the neurosensory retina. This defect is identified by the disruption of the retinal layers extending from the internal limiting membrane to the photoreceptor layer. It leads to significant impairment in central vision and is a prevalent cause of vision deterioration among elderly individuals. Common symptoms at presentation include metamorphopsia and visual deprivation, primarily due to the involvement of the central fovea. However, these symptoms can be ameliorated through successful surgical closure [1, 2].

The potential contribution of anteroposterior vitreous traction forces in the development of MH has long been a subject of inquiry. Subsequently, this theory gained support through biomicroscopic examinations, underscoring its significance [3,4,5]. Prior to the introduction of vitrectomy by Kelly and Wendel in 1991 [6], macular holes were considered incurable.

Currently, Internal limiting membrane (ILM) peeling is widely acknowledged as the most effective surgical approach for treating MH, boasting a success rate exceeding 90% in accordance with prior studies [7,8,9,10,11]. However, this success rate is not consistently high for larger macular holes exceeding 400 μm and has been reported to drop to as low as 60–70% [12, 13]. In 2010, a novel technique was introduced by Michalewska et al. [14], involving the use of an ILM flap to cover large idiopathic macular holes. In this method, the ILM is not entirely removed but is instead left attached to the edges of the macular hole and inverted to cover it. This approach significantly increased the success rate for the closure of larger macular holes to approximately 98%. Notably, numerous studies have shown that the ILM flap technique yields superior anatomical and visual outcomes when compared to the conventional ILM peeling approach, both for larger [13, 15,16,17,18,19,20,21] and smaller macular holes [22]. Nevertheless, some studies have suggested that the results are statistically similar [23,24,25,26,27], or even favor ILM peeling [28,29,30].

To the best of our knowledge, a similar meta-analysis, which exclusively focused on macular holes > 400 μm and compared the anatomical and visual outcomes of these two techniques, was published in 2021 [31]. However, it only included randomized clinical trials (RCTs), and since then a number of both original and retrospective studies have been published. Consequently, with the aim of augmenting the statistical robustness of preceding findings, we performed a comprehensive double-arm meta-analysis to assess the anatomical and visual function effectiveness of vitrectomy with the ILM flap technique for any size or type of MHs (both > 400 μm and < 400 μm) without retinal detachment, including both RCTs and retrospective studies.

Methods

Data sources and search

A comprehensive literature search was conducted in the PubMed, Medline, and Cochrane Library databases before November 2023 to identify relevant studies. The following medical subject heading terms and keywords were used for the database searches:

“ilm“[All Fields] AND (“peeled“[All Fields] OR “peeling“[All Fields] OR “peelings“[All Fields] OR “peels“[All Fields]) AND (“retinal perforations“[MeSH Terms] OR (“retinal“[All Fields] AND “perforations“[All Fields]) OR “retinal perforations“[All Fields] OR (“macular“[All Fields] AND “hole“[All Fields]) OR “macular hole“[All Fields]) AND “ilm“[All Fields] AND (“surgical flaps“[MeSH Terms] OR (“surgical“[All Fields] AND “flaps“[All Fields]) OR “surgical flaps“[All Fields] OR “flap“[All Fields]).

We applied no language restrictions, non-English studies were translated for interpretation using Google translate service. The relevant literature’s references were carefully checked for potential eligible studies. Disagreements were resolved through consensus and, when necessary, arbitration by a third researcher (SAAR).

Inclusion and exclusion criteria

The inclusion criteria for eligibility were as follows: (a) double-arm studies, (b) prospective randomized control trial or retrospective case series, (c) studies included cases among patients with any size (smaller or larger than 400 μm) of MH who had been treated with the inverted ILM flap technique or ILM peeling, (d) anatomical hole closure rate and visual acuity (VA) were reported, and (e) the relevant data was provided. The exclusion criteria included: (a) patients with macular retinoschisis, age-related macular degeneration, retinal detachment, or proliferative diabetic retinopathy, (b) short -term follow-up that is less than three months, (c) nonhuman studies, phase I clinical trials, case reports, editorials, abstracts, reviews, comments and letters, expert opinions, studies without original data and duplicate publications, (d) and studies that lacked a control-treated group for comparison.

Data extraction

Two investigators (SMMA and SZS) independently extracted the following information from each included study: study characteristics (first author, year of publication, country, sample size and study type) surgical procedure, participant baseline characteristics, minimum diameter of MH, hole closure rate, preoperative and postoperative VA, and follow-up time. Any discrepancies between data extractions were resolved by discussion or consultation with a third investigator (MM).

Quality assessment

This review included Twenty-six studies: 9 RCTs and 23 retrospective studies. The included RCTs were evaluated for quality using Cochrane Risk of Bias assessment tool [32]. Seven components were assessed: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting, and (7) other bias. According to whether the included studies fully meet the above criteria, we assessed the quality of trials. The methodological quality of each study was assessed based on the Newcastle-Ottawa Scale (NOS) [33], (Range, 0 to 9 stars) for quality of case control studies in meta-analysis. Studies were rated in three areas, including selection, comparability, and exposure. Scores ≥ 5 indicated that the quality of research was relatively high. All items were independently assessed by two investigators (SMMA and SZS), with consensus reached after deliberation or consultation with the third author (SS).

Statistical analysis

The meta-analysis was carried out based on the guidelines of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements [34]. All statistical analyses were performed using R Statistical Software [54] and meta package v4.17-0 [55]. For the rate of MH closure, odds ratios (ORs), and 95% confidence intervals (Cl) were calculated using the Mantel–Haenszel (M-H) method. To compare the evaluation of VA, the mean difference (MD) of preoperative and postoperative measurements between the two surgical treatments were compared using mean difference (MD) and 95% CI.

To assess potential statistical heterogeneity among trials, the Higgins I2 statistics were used. The I2 statistic reveals the percentage of variation between studies that is due to heterogeneity rather than chance or sampling error. An outcome of over 75% indicates considerable heterogeneity. When the heterogeneity was high, subgroup analysis or sensitivity analysis was used to identify sources of heterogeneity. We used random effect model for the analysis. The results of meta-analysis were visually examined by forest plot, and the potential publication bias was shown by funnel plot and Egger’s test. A p < 0.05 was considered statistically significant.

Results

Study characteristics

The detailed flowchart of the study selection process is shown in [Figure. 1]. A total of 174 articles were found after the preliminary literature search, after removing the duplicates the articles were shortlisted first by the topics, then by reading the abstracts, and finally by the way of full text review, leaving a total thirty-two studies [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, 35,36,37,38,39,40,41,42,43,44,45,46,47,48] which were included in this meta-analysis.

The main characteristics of the included trials are presented in [Table 1]. Out of the included studies, twenty three were retrospective in nature and nine were RCTs. A total of 2497 eyes were included in this meta-analysis, 1277 in the ILM peeling group and 1220 in the ILM flap group. The mean age ranged from 54.38 to 71 years in the ILM flap group and from 56.26to 72.5 years in the ILM peeling group, the mean minimum diameter of the MH ranged from as low as 269 μm to as high as 803.33 μm in the flap group and 244 to 759.97 μm in the peeling group. The mean follow-up months durations across all studies ranged from 3 to 20.15 months.

Table 1 Study characteristics of the included studies
Full size table

Quality assessment

We assessed the quality of the nine RCTs using the Cochrane risk of bias tool and overall, all the studies were found to have low risk of bias and are comprehensively shown in Fig. 2. Six out of nine studies were deemed high quality as they had low risk of bias in all assessing criteria. However, the remaining three studies [14, 24, 39] had unclear risk in different domains.

Fig. 1
figure 1

PRISMA Flow Diagram of the Literature Search Process

Full size image
Fig. 2
figure 2

Forest plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: MH closure rate. The subgroup analysis was based on study type I.e., RCT and Retrospective studies with MH sizes of either < 400 μm, > 400 μm and another subgroup based on retrospective studies including mixed sizes

Full size image
Fig. 3
figure 3

Leave- one-out of MH-closure rate

Full size image
Fig. 4
figure 4

Forest plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: Preoperative visual acuity. Michalewska’s study was not included in the analysis of preoperative VA since SD of preoperative VA was not given

Full size image
Fig. 5
figure 5

Forest plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: Postoperative visual acuity. The subgroup analysis was based on study type I.e., RCT and Retrospective studies with MH sizes of either < 400 μm, > 400 μm and another subgroup based on retrospective studies including mixed sizes. Michalewska’s study was not included in the analysis of postoperative VA since SD of preoperative VA was not given

Full size image
Fig. 6
figure 6

Forest plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: Postoperative VA based on follow-up duration (RCT of > 400 μm). The subgroup analysis was based on follow-up duration including only RCTs with MH > 400 μm that divided the studies into follow-up duration of 3,6 and 12 months. Michalewska’s study was not included in the analysis of postoperative VA since SD of preoperative VA was not given

Full size image
Fig. 7
figure 7

Funnel plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: MH closure rate

Full size image

As of the the twenty three retrospective studies, all of them were qualitatively assessed using NOS and all studies got five or more stars out of nine except these two studies [28, 30] which secured four out of nine stars as they had concerns regarding the reporting of selection of cases and comparability, shown comprehensively in [Supplementary Table S1].

Macular hole closure rate

All of the included studies reported this outcome, however, the study by Michalewska et al. [14] did not mention SD for postoperative VA.

The overall pooled data showed significantly higher MH closure rate with inverted ILM flap technique in comparison with the ILM peeling group (OR = 2.47, CI = 1.58 to 3.87; P < 0.001; I²= 30%), [Figure. 2]. A leave-one-out analysis was performed, which identified Iwasaki et al. [28] as an outlier. After removing this trial, the overall MH closure rate remained significantly higher with the flap technique (OR = 3.09, CI = 2.30 to 4.15, P < 0.001; I2 = 5%) and the heterogeneity lowered down to 5%, [Supplementary figure. 2].

Furthermore, the forest plot demonstrated that Rizzo et al. [43] carried significant weightage on the overall result. Leave-one-out analysis was performed, which validated the conclusion in favor of ILM flap technique (OR = 2.38, CI = 1.44 to 3.93, P = 0.003; I2= 30%), [Supplementary figure. 3]. A detailed leave-one-out analysis is shown in [Figure. 3].

Subgroup analysis was performed based on the different small (< 400 μm), large (> 400 μm), or mixed MH sizes given in the RCTs and retrospective studies separately. The test for subgroup differences did not reveal a significant difference between the two procedures, (p = 0.80), [Figure. 2].

Preoperative visual acuity

All of the included studies reported the preoperative visual acuity outcome except the study by Michalewska et al. [14] which did not mention standard deviation (SD) of preoperative VA. The forest plot for preoperative visual acuity showed no significant difference between ILM flap and ILM peeling technique (MD = 0.03, 95% CI= -0.01 to 0.07, P = 0.09; I2 = 57%), [Figure. 4].

Postoperative visual acuity

All of the included studies reported the postoperative VA outcome after treatment with ILM peeling or inverted ILM flap technique except the study by Michalewska et al. [14] which did not mention SD for postoperative VA.

The meta-analysis of overall pooled data showed postoperative VA with ILM flap technique was statistically insignificant in comparison with the ILM peeling group (MD = 0.01, 95% CI = -0.04 to 0.06, p = 0.63; I2 = 81%), [Figure. 5]. A detailed leave-one-out analysis was performed; however, it did not explain the high heterogeneity.

Subgroup analysis was performed based on the different small (< 400 μm), large (> 400 μm) or mixed MH sizes given in the RCTs and retrospective studies separately. The test for subgroup differences was statistically significant between ILM flap and ILM peeling groups for postoperative VA, (p < 0.01), implicating that the combined variables of study type and MH size significantly impact the pooled results.

In particular, the flap technique was favored over conventional peeling in RCTs with MH sizes > 400 μm, (MD = -0.13, 95% CI = -0.17 to -0.08, p < 0.01; I2 = 13%), [Figure. 5] in comparison to the other subgroups all of which showed insignificant difference between the two procedures I.e., RCTs with MH sizes < 400 μm (MD = 0.00, 95% CI = -0.04 to 0.05, p = 0.85; I2 = 0%), [Figure. 5], retrospective studies with > 400 μm (MD = -0.01, 95% CI = -0.11 to 0.08, p = 0.78; I2 = 83%), [Figure. 5], < 400 μm (MD = 0.16, 95% CI = -0.18 to 0.49, p = 0.36; I2 = 55%), [Figure. 5] and mixed MH sizes (MD = 0.10, 95% CI = -0.01 to 0.21, p = 0.07; I2 = 81%), [Figure. 5]. However, there is substantial unexplained heterogeneity between the studies within the retrospective subgroups (> 400 μm: I2 = 83%; <400 μm: I2 = 55%; mixed sizes: I2 = 81%). Therefore, the validity of the treatment effect estimate for these subgroups is uncertain.

Furthermore, to account for the impact of follow-up duration on the results, we conducted a subgroup analysis that categorized all the RCTs with > 400 μm sizes as they specifically showed significant improvement with the flap technique, based on their follow-up duration. Studies were divided into three categories: follow-up at 3, 6, and 12 months. The overall pooled effect was statistically significant in favor of the flap surgery as compared to peeling (MD = -0.11, 95% CI = -0.14 to -0.08, p < 0.01; I2 = 25%), [Figure. 6]. A detailed leave-one-out analysis is shown in [Supplementary figure. 5]. The test for subgroup differences for postoperative VA based on follow up duration was not significant between ILM flap and ILM peeling groups (p = 0.96).

Publication bias

The funnel plots for the outcomes of MH closure rate [Figure. 7], and postoperative VA [Supplementary figure. 7] revealed that nearly all of the studies shown by scattered points in the funnel plot were distributed in the middle and top of the baseline and were in the range of the inverted funnel which implies that there is no significant publication bias and the results from this study are reliable. The funnel plot for preoperative VA [Supplementary figure. 6] showed most of the studies clustered at the top of the plot as it is a baseline variable and does not differ much between studies.

Furthermore, an eggers test was performed as the number of articles exceeded ten. Egger’s test for a regression intercept gave a p-value of 0.604 for the MH closure rate, indicating no evidence of publication bias.

Discussion

The objective of this meta-analysis was to assess the efficacy of the relatively new ILM flap technique compared to traditional ILM peeling on anatomic and visual outcomes in patients with any type or size of macular hole without retinal detachment.

Our meta-analysis showed a significant increase in MH closure rate with the ILM flap technique compared to the ILM peeling treated patient population. Additionally, to further evaluate the impact of the study type and macular hole size, subgroup analysis was performed which did not reveal any significant differences with respect to study type and MH size. Moreover, leave-one-out analysis to eliminate the source of heterogeneity was performed removing the study by Iwasaki et al. [28] (as it had a lot of limitations) and this reduced the heterogeneity to a negligible 5%. The study by Rizzo et al. [43] was also removed from the analysis to check the robustness of the overall finding as it carried substantial weightage on the overall result.

ILM flap involves attaching the edges of a hole in the retina to the margins of the ILM. This creates a smooth and uninterrupted scaffold that facilitates gliosis, which in turn allows for the migration and proliferation of glial cells, thereby maintaining the anatomical structure of the foveola. Additionally, the activated Müller cells secrete neurotrophic factors and basic fibroblast growth factors (bFGF), promoting the survival of retinal neurons and facilitating the growth of photoreceptor cells towards the center of the fovea [49]. Furthermore, the ILM flap creates a closed compartment that enables the retinal pigment epithelium to effectively remove sub retinal fluid from the affected area, keeping the hole dry and thus contributing to MH closure [15]. Inverted ILM flap technique may potentially result in a higher rate of anatomical closure compared to the ILM peeling technique, owing to the aforementioned factors.

Regarding the visual outcomes, there was no significant difference in preoperative VA between the two groups, which negated any pre-intervention effects on postoperative VA. While for the postoperative VA, the forest plot did not indicate any significant benefit of the flap technique over the other technique overall.

However, subgroup analysis based on study type and MH size showed that eyes treated with the ILM flap technique in RCTs with MH size > 400 μm exhibited significantly better postoperative VA than those treated with ILM peeling compared to all the other subgroups, suggesting the superiority of the use of ILM flap technique for larger MH repair. However, further research is warranted to fully establish the potential benefits of this technique over the conventional peeling procedure. This may be explained by some previous studies demonstrating the inadequacy of the conventional peeling in resulting in a type 1 closure and has a higher rate of a V or a W shaped closure which is associated with degradation of the photoreceptor layer, damage to the retinal pigment epithelium, and depletion of foveal tissue, as compared to the flap technique for large MHs [50].

We further sought to explore the differences in postoperative VA between the two surgical techniques based on follow-up duration set in RCTs with MH sizes > 400 μm I.e., postoperative VA at 3, 6, and 12 months.

ILM flap was again found to be significantly better than ILM peeling based on follow up duration. The reason for this could be the higher MH closure rate in the initial months with the flap technique and the observed proliferative processes associated with MH healing, such as Muller cell proliferation, regeneration of retinal tissue, photoreceptor migration, and repositioning [23, 51,52,53]. However, it should be mentioned that the included studies did not have a long follow up duration except one study by Agrawal et al. [16] which followed the treated participants till 12 months. Hence, more studies with longer follow-up periods are needed to further confirm this finding.

Finally, this meta-analysis stands out as a comprehensive study, using R core [54] encompassing a total of nine RCTs and twenty three retrospective studies, with a wide range of MH types and sizes. In contrast to previous studies, we did not limit our analysis to a specific MH size or type including idiopathic as well as myopic MH. This approach allowed us to gain a broader understanding and adds additional merit to our study. Moreover, we performed subgroup analysis based on the type of study and the size of the MH, which has not been previously conducted. While performing literature review, we found three similar meta-analysis on this topic, all of them focused on randomized clinical trials. However, our study included both randomized trials and retrospective studies. A comparison of previously published meta-analysis is presented in Table 2 [55–57]. Ghoraba et al. [56] did a sensitivity analysis better to separate type II closure from type I as they found type I closure is generally more predictive of good visual recovery.

Table 2 Comparison of key findings in previously published meta-analyses
Full size table

Limitations

There were some limitations with this study that must be considered when referring to the outcomes of this meta-analysis. Firstly, in this meta-analysis retrospective studies were included alongside RCTs, which may have inherent possibilities of selection bias. Secondly, the comparison of primary and secondary endpoints revealed some heterogeneity among the studies, although we conducted sensitivity analysis and subgroup analysis to alleviate the heterogeneity, we were not able to eliminate it. Thirdly, the follow-up periods in the trials that were included were inadequate for making improved observations of VA recovery in the long term. Fourthly, the type of closure (i.e., type 1 and 2) may potentially influence the postoperative visual acuity outcome. However, we were unable to perform a subgroup analysis for these variables due to insufficient data. Lastly, factors such as the extent of ILM peeling, toxicity of the ILM stain, type of dye used for ILM staining, duration of air or longer-acting gas tamponade, postoperative face-down timing, and the specific form of ILM flap technique across studies could potentially serve as sources of heterogeneity. Unfortunately, due to the scarcity of data on these factors, we were unable to carry out a subgroup analysis. Hence, more original studies with large sample sizes and longer follow-up measurement for improved VA to evaluate these variables in detail are required. The manuscript was available as a pre-print publication as well [58].

Conclusion

Our meta-analysis comparing ILM flap technique and ILM peeling for the treatment of any type or size of MH showed that the ILM flap technique has a higher closure rate than ILM peeling. Notably, the improvement in VA with the flap technique was significant compared to ILM peeling specifically for larger MHs and based on follow up duration. Our findings support the use of the ILM flap technique for all sizes of MHs, and especially the larger MHs, but more large-scale and longer duration studies are needed to validate the efficacy of these findings especially running a multicenter trial with standardized surgical technique and large numbers focused on small and medium full thickness macular hole (FTMH) may be more novel.

Data availability

There are no new datasets generated in this article. All data supporting the conclusions of this article is included in the supplementary material.

Abbreviations

BCVA:

Best Corrected Visual Acuity

FTMH:

Full thickness macular hole

bFGF:

Basic fibroblast growth factors

MH:

Macular hole

ILM:

Internal limiting membrane

logMAR:

Logarithm of minimal angle of resolution

MD:

Mean difference

NOS:

Newcastle-Ottawa Scale

OR:

Odds ratio

RCT:

Randomized control trial

SD:

Standard deviation

VA:

Visual acuity

RD:

Retinal Detachment

References

  1. Majumdar S, Tripathy K. Macular hole. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 25, 2023.

  2. Mann DF. Idiopathic macular hole. Optom Clin. 1996;5(1):95–110.

    CAS  PubMed  Google Scholar 

  3. Schepens CL. Fundus changes caused by alterations of the vitreous body. Am J Ophthalmol. 1955;39:631–3.

    Article  CAS  PubMed  Google Scholar 

  4. Avila MP, Jalkh AE, Murakami K, Trempe CL, Schepens CL. Biomicroscopic study of the vitreous in macular breaks. Ophthalmology. 1983;90:1277–83.

    Article  CAS  PubMed  Google Scholar 

  5. Kakehashi A, Schepens CL, Trempe CL. Vitreomacular observations II. Data on the pathogenesis of idiopathic macular breaks. Graefe’s Archive Clin Experimental Ophthalmol. 1996;234:425–33.

    Article  CAS  Google Scholar 

  6. Kelly NEWR. Vitreous surgery for idiopathic macular holes. Results of a pilot study.

  7. Lai MM, Williams GA. Anatomical and visual outcomes of idiopathic macular hole surgery with internal limiting membrane removal using Low-Concentration indocyanine green. Retina. 2007;27:477–82.

    Article  PubMed  Google Scholar 

  8. Park DW, Sipperley JO, Sneed SR, Dugel PU, Jacobsen J. Macular hole surgery with internal-limiting membrane peeling and intravitreous air. Ophthalmology. 1999;106:1392–8.

    Article  CAS  PubMed  Google Scholar 

  9. Wolf S, Reichel MB, Wiedemann P, Schnurrbusch UEK. Clinical findings in macular hole surgery with indocyanine green-assisted peeling of the internal limiting membrane. Graefe’s Archive Clin Experimental Ophthalmol. 2003;241:589–92.

    Article  CAS  Google Scholar 

  10. Beutel J. Internal limiting membrane peeling with indocyanine green or Trypan blue in macular hole surgery. Arch Ophthalmol. 2007;125:326.

    Article  PubMed  Google Scholar 

  11. Williamson TH, Lee E. Idiopathic macular hole: analysis of visual outcomes and the use of indocyanine green or brilliant blue for internal limiting membrane Peel. Graefe’s Archive Clin Experimental Ophthalmol. 2014;252:395–400.

    Article  Google Scholar 

  12. Ip MS. Anatomical outcomes of surgery for idiopathic macular hole as determined by optical coherence tomography. Arch Ophthalmol. 2002;120:29.

    Article  PubMed  Google Scholar 

  13. Ramtohul P, Parrat E, Denis D, Lorenzi U. Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study. BMC Ophthalmol. 2020;20:11.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Michalewska Z, Michalewski J, Adelman RA, Nawrocki J. Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology. 2010;117:2018–25.

    Article  PubMed  Google Scholar 

  15. Manasa S, Kakkar P, Kumar A, Chandra P, Kumar V, Ravani R. Comparative evaluation of standard ILM Peel with inverted ILM flap technique in large macular holes: A prospective, randomized study. Ophthalmic Surg Lasers Imaging Retina. 2018;49:236–40.

    Article  CAS  PubMed  Google Scholar 

  16. Agrawal V, Jindal K, Dhakad Y, Rathore P, Khilnani K. Multilayered inverted internal limiting membrane flap technique versus standard internal limiting membrane peeling for large macular holes: A comparative study. Indian J Ophthalmol. 2022;70:909.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kannan NB, Kohli P, Parida H, Adenuga OO, Ramasamy K. Comparative study of inverted internal limiting membrane (ILM) flap and ILM peeling technique in large macular holes: a randomized-control trial. BMC Ophthalmol. 2018;18:177.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Narayanan R, Singh SR, Taylor S, Berrocal MH, Chhablani J, Tyagi M, et al. Surgical outcomes after inverted internal limiting membrane flap versus conventional peeling for very large macular holes. Retina. 2019;39:1465–9.

    Article  PubMed  Google Scholar 

  19. Yamashita T, Sakamoto T, Terasaki H, Iwasaki M, Ogushi Y, Okamoto F, et al. Best surgical technique and outcomes for large macular holes: retrospective multicentre study in Japan. Acta Ophthalmol. 2018;96:e904–10.

    Article  PubMed  Google Scholar 

  20. Pak KY, Park JY, Park SW, Byon IS, Lee JE. Efficacy of the Perfluoro-N-Octane-Assisted Single-Layered inverted internal limiting membrane flap technique for large macular holes. Ophthalmologica. 2017;238:133–8.

    Article  CAS  PubMed  Google Scholar 

  21. Baumann C, Kaye S, Iannetta D, Sultan Z, Dwivedi R, Pearce I. Effect of inverted internal limiting membrane flap on closure rate, postoperative visual acuity, and restoration of outer retinal layers in primary idiopathic macular hole surgery. Retina. 2020;40:1955–63.

    Article  CAS  PubMed  Google Scholar 

  22. Wu T-T, Kung Y-H, Chang C-Y, Chang S-P. Surgical outcomes in eyes with extremely high myopia for macular hole without retinal detachment. Retina. 2018;38:2051–5.

    Article  PubMed  Google Scholar 

  23. Velez-Montoya R, Ramirez-Estudillo JA, Sjoholm-Gomez de Liano C, Bejar-Cornejo F, Sanchez-Ramos J, Guerrero-Naranjo JL, et al. Inverted ILM flap, free ILM flap and conventional ILM peeling for large macular holes. Int J Retina Vitreous. 2018;4:8.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Iovino C, Caminiti G, Miccoli M, Nasini F, Casini G, Peiretti E. Comparison of inverted flap and subretinal aspiration technique in full-thickness macular hole surgery: a randomized controlled study. Eur J Ophthalmol. 2018;28:324–8.

    Article  PubMed  Google Scholar 

  25. Yilmaz S, Mavi Yildiz A, Avci R. Foveal displacement following Temporal inverted internal limiting membrane technique for full thickness macular holes: 12 months results. Curr Eye Res. 2021;46:1923–30.

    Article  CAS  PubMed  Google Scholar 

  26. Ventre L, Fallico M, Longo A, Parisi G, Russo A, Bonfiglio V, et al. Conventional internal limiting membrane peeling versus inverted flap for small-to-medium idiopathic macular hole. Retina. 2022;42:2251–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Leisser C, Ruiss M, Pilwachs C, Findl O. ILM peeling with ILM flap transposition vs. classic ILM peeling for small and medium macula holes—a prospective randomized trial. Spektrum Der Augenheilkunde. 2023;37:9–14.

    Article  PubMed  Google Scholar 

  28. Iwasaki M, Kinoshita T, Miyamoto H, Imaizumi H, Influence of inverted, internal limiting membrane flap technique on the outer retinal layer structures after a large macular hole surgery. Retina. 2019;39:1470–7.

    Article  PubMed  Google Scholar 

  29. Bottoni F, Parrulli S, Mete M, D’Agostino I, Cereda M, Cigada M, et al. Large idiopathic macular hole surgery: remodelling of outer retinal layers after traditional internal limiting membrane peeling or inverted flap technique. Ophthalmologica. 2020;243:334–41.

    Article  PubMed  Google Scholar 

  30. Yamada K, Oishi A, Kusano M, Kinoshita H, Tsuiki E, Kitaoka T. Effect of inverted internal limiting membrane flap technique on small-medium size macular holes. Sci Rep. 2022;12:731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yu J-G, Wang J, Xiang Y. Inverted internal limiting membrane flap technique versus internal limiting membrane peeling for large macular holes: A Meta-Analysis of randomized controlled trials. Ophthalmic Res. 2021;64:713–22.

    Article  CAS  PubMed  Google Scholar 

  32. Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343(oct18 2):d5928–5928.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hartling L, Milne A, Hamm MP, Vandermeer B, Ansari M, Tsertsvadze A, et al. Testing the Newcastle Ottawa scale showed low reliability between individual reviewers. J Clin Epidemiol. 2013;66:982–93.

    Article  PubMed  Google Scholar 

  34. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;:n71.

  35. Yan Y, Zhao T, Sun C, Zhao H, Jia X, Wang Z. Anatomical and functional outcomes in eyes with idiopathic macular holes that underwent surgery using the inverted internal limiting membrane (ILM) flap technique versus the conventional ILM peeling technique. Adv Ther. 2021;38:1931–45.

    Article  PubMed  Google Scholar 

  36. Chen Y, Xu Y, Ye X, Yu J, Wang C, Zhang Z et al. The effect comparison of ILM flap and traditional ILM peeling in iMH. Front Med (Lausanne). 2023;10.

  37. Zhang K, Yang X, Qi B, Wu X, Wang X, Liu W. Internal limiting membrane peeling or inverted flap technique combined with air tamponade in the treatment of macular holes in high myopia. Ophthalmic Res. 2023;66:561.

    Google Scholar 

  38. Ozbek M, Ozcaliskan S, Alagoz C, Artunay O. Comparison of anatomical and functional outcomes of different surgical techniques in myopic macular hole without retinal detachment. Int J Ophthalmol. 2023;16:1651–6.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ehrhardt A, Delpuech M, Luc A, Zessler A, Pastor G, Angioi-Duprez K, et al. Dissociated optic nerve fiber layer appearance after macular hole surgery: A randomized controlled trial comparing the Temporal inverted internal limiting membrane flap technique with conventional peeling. Ophthalmol Retina. 2023;7:227–35.

    Article  PubMed  Google Scholar 

  40. Carballés MJC, Sastre-Ibáñez M, Cura MP, Del HR, De, Garcia-Saenz MC. Modification of the inverted flap technique compared to conventional internal limiting membrane peeling in complete macular hole surgery. https://doiorg.publicaciones.saludcastillayleon.es/101177/11206721231163616. 2023. https://doiorg.publicaciones.saludcastillayleon.es/10.1177/11206721231163616

  41. Hu XT, Pan QT, Zheng JW, Zhang ZD. Foveal microstructure and visual outcomes of myopic macular hole surgery with or without the inverted internal limiting membrane flap technique. Br J Ophthalmol. 2019;103:1495–502.

    Article  PubMed  Google Scholar 

  42. Peralta Iturburu F, Garcia-Arumi C, Bové Alvarez M, Garcia-Arumi J, Azzolini C. Comparison of Anatomical and Visual Outcomes between Idiopathic and Myopic Macular Holes Using the Internal Limiting Membrane or Inverted Internal Limiting Membrane Flap Technique. J Ophthalmol. 2019;2019.

  43. Rizzo S, Tartaro R, Barca F, Caporossi T, Giansanti F. Internal limiting membrane bacherinid, peeling versus inverted flap technique for treatment of full-thickness macular holes. A comparative study in a large series of patients. Retina. 2018;38(Suppl 1):S73–8.

    Article  PubMed  Google Scholar 

  44. Alvarez MB, Sabate S, Gomez-Resa M, Garcia-Arumi J. Anatomical and visual outcomes of inverted internal limiting membrane flap technique versus internal limiting membrane peeling in myopic macular hole without retinal detachment: A preliminary retrospective study. Retina. 2020;40:233–40.

    Article  Google Scholar 

  45. Lumi X, Mahnic M, Petrovski BÉ, Petrovski G. Outcomes of vitrectomy for Long-Duration macular hole. J Clin Med. 2020;9.

  46. Mete M, Alfano A, Guerriero M, Prigione G, Sartore M, Polito A, et al. Inverted internal limiting membrane flap technique versus complete internal limiting membrane removal in myopic macular hole surgery: A comparative study. Retina. 2017;37:1923–30.

    Article  PubMed  Google Scholar 

  47. Friedrich J, Bleidißel N, Klaas J, Feucht N, Nasseri A, Lohmann CP, et al. Großes Makulaforamen– immer eine schlechte prognose?? Der Ophthalmologe. 2021;118:257.

    Article  CAS  PubMed  Google Scholar 

  48. Koçak N, Yeter V, Birinci H. Comparative study of conventional internal limiting membrane peeling versus Temporal inverted internal limiting membrane flap for large macular hole treatment. Indian J Ophthalmol. 2023;71:188.

    Article  PubMed  Google Scholar 

  49. Shiode Y, Morizane Y, Matoba R, Hirano M, Doi S, Toshima S et al. The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure. Investigative Opthalmology & Visual Science. 2017;58:4847.

  50. Michalewska Z, Michalewski J, Dulczewska-Cichecka K, Adelman RA, Nawrocki J. Temporal inverted internal limiting membrane flap technique versus classic inverted internal limiting membrane flap technique. Retina. 2015;35:1844–50.

    Article  PubMed  Google Scholar 

  51. Michalewska Z, Michalewski J, Cisiecki S, Adelman R, Nawrocki J. Correlation between foveal structure and visual outcome following macular hole surgery: a spectral optical coherence tomography study. Graefe’s Archive Clin Experimental Ophthalmol. 2008;246:823–30.

    Article  Google Scholar 

  52. Bonińska K, Nawrocki J, Michalewska Z. Mechanism of flap closure after the inverted internal limiting membrane flap technique. Retina. 2018;38:2184–9.

    Article  PubMed  Google Scholar 

  53. Morizane Y, Shiraga F, Kimura S, Hosokawa M, Shiode Y, Kawata T, et al. Autologous transplantation of the internal limiting membrane for refractory macular holes. Am J Ophthalmol. 2014;157:861–e8691.

    Article  PubMed  Google Scholar 

  54. R Core Team. (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Available from: https://www.R-project.org

  55. Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019. pp. 153–60.

  56. Ghoraba H, Rittiphairoj T, Akhavanrezayat A, Karaca I, Matsumiya W, Pham B, Mishra K, Yasar C, Mobasserian A, Abdelkarem AA, Nguyen QD. Pars plana vitrectomy with internal limiting membrane flap versus Pars plana vitrectomy with conventional internal limiting membrane peeling for large macular hole. Cochrane Database Syst Rev. 2023;8.

  57. Chen G, Tzekov R. Jiang F, mao s, tong y, li w. Inverted ILM flap technique versus conventional ILM peeling for idiopathic large macular holes: a meta-analysis of randomized controlled trials. PLoS ONE. 2020;15(7):e0236431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Akhtar SMM, Saleem SZ, Rizvi SAA. Critical Analysis of Macular Hole Repair Techniques: A Comprehensive Systematic Review and Meta-analysis Comparing Internal Limiting Membrane Flap and Internal Limiting Membrane Peeling For Any Size of Macular Hole. Research Square (Pre-print) version. Available from: https://www.researchsquare.com/article/rs-2901021/v1/

Download references

Acknowledgements

The pre-publication presentation of the manuscript published as a preprint is available from: https://www.researchsquare.com/article/rs-2901021/v1”/.

Funding

The authors received no financial support for this research.

Author information

Authors and Affiliations

  1. Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan

    Syed Muhammad Muneeb Akhtar, Syed Zia Saleem & Syed Ali Asad Rizvi

  2. Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan

    Areeba Fareed

  3. Dr. Ruth K. M. Pfau Civil Hospital, Karachi, Pakistan

    Munazza Mumtaz

  4. Department of Medicine, Hamdard College of Medicine & Dentistry, Karachi, Pakistan

    Shiza Saleem

  5. Department of Medicine, Liaquat National Hospital & Medical College, Karachi, Pakistan

    Anusha Bai

  6. Mayo Clinic, Rochester, MN, USA

    Afsana Ansari Shaik

  7. Department of Internal Medicine, Mayo Clinic, Phoenix, AZ, USA

    Robert Kirchoff

  8. AdventHealth, Sebring, FL, USA

    Muhammad Sohaib Asghar

Authors
  1. Syed Muhammad Muneeb Akhtar
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Syed Zia Saleem
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Syed Ali Asad Rizvi
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Areeba Fareed
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Munazza Mumtaz
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Shiza Saleem
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Anusha Bai
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Afsana Ansari Shaik
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Robert Kirchoff
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Muhammad Sohaib Asghar
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Every author participated in formulating and designing the study. The literature search and screening, as well as the collection and analysis of data, documenting the figures, interpreting the data, and preparing the manuscript, were all carried out by SMMA, SZS and SAAR. SMMA was responsible for the study’s design and analysis, MSA and SZS for writing the discussion and revising the manuscript. All authors read and gave consent for the final version of the manuscript.

Corresponding author

Correspondence to Muhammad Sohaib Asghar.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Clinical trial number

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

: Supplementary Fig.1. Risk of bias summary. The Cochrane “risk of bias” tool was used for quality assessment.

Supplementary Material 2

: Supplementary Fig.2. Forest plot of comparison between inverted ILM flap vs. ILM peeling, outcome: MH closure rate (excluding Iwasaki). Sensitivity analysis showed Iwasaki’s study to be the cause of heterogeneity.

Supplementary Material 3

: Supplementary Fig.3. Forest plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: MH closure rate (excluding Rizzo). Leave one out analysis was performed excluding Rizzo’s study confirming the robustness of our study.

Supplementary Material 4

: Supplementary Fig.4. Leave- one-out of Postoperative visual acuity.

Supplementary Material 5

: Supplementary Fig.5. Leave- one-out of Postoperative visual acuity for RCT > 400μm (excluding Iovino).

Supplementary Material 6

: Supplementary Fig.6. Funnel plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: Preoperative visual acuity.

Supplementary Material 7

: Supplementary Fig.7. Funnel plot of comparison: Inverted ILM flap vs. ILM peeling, outcome: Postoperative visual acuity.

Supplementary Material 8

: Supplementary Table S1. New Castle Ottawa Scale For Assessment Of Publication Bias Of Non-RCT Studies.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Akhtar, S.M.M., Saleem, S.Z., Rizvi, S.A.A. et al. Critical analysis of macular hole repair techniques: a comprehensive systematic review and meta-analysis comparing internal limiting membrane flap and internal limiting membrane peeling for any size of macular hole. BMC Ophthalmol 25, 174 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12886-025-04011-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12886-025-04011-0

Keywords

BMC Ophthalmology

ISSN: 1471-2415

Contact us