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In order to improve the closure rate in complicated cases of macular holes while minimizing the possible anatomical consequences of an extensive ILM peeling; two research teams were established, one led by Michalewska et al. and second by Morizane et al., that introduced two novel surgical techniques based on the principle of ILM manipulation and conservation: the inverted flap technique and the free-flap technique [15, 16, 18]. Michalewska et al. proposed an approach in where the ILM is not completely removed, but a small remnant is left on the margin of the macular hole to cover it, while Morizane et al. proposed the creation of free ILM flap, starting from the outer border of a complete ILM peeling and then placed over the macular hole to cover it [15, 18, 19]. Both techniques aim to eliminate the anteroposterior and tangential traction exerted on the retinal surface by removing all cortical vitreous and surface components of the retina (epiretinal membranes, ILM) while stimulating cell proliferation and migration of glial cells into the macular hole. Therefore, they enhance the chances of closure and potentially improve the postoperative visual acuity [15, 16, 18].

All patients had standard three-port, sutureless, pars plana vitrectomy (PPV) and gas tamponade. The selection of the ILM peeling technique for each individual case was randomized with a Simple block randomization technique (3 3). The appointed ILM peeling technique was revealed to the surgeon moments before the surgery. The randomization resulted in three different groups: Patients in group A had conventional ILM peeling around the macular hole of 2 disk diameters in length at least. Patients in group B had the inverted flap technique, as described by Michalewska et al. [15, 19]. Patients in group C had the free-flap technique, either as described by Morizane et al. or Hernandez-da Mota and Bejar-Cornejo [18, 22]. All surgeries were performed by highly trained and experienced vitreoretinal surgeons (RVM, SHD, ARE and VMC) with more than 500 macular procedures each. All ILM peelings were assisted with 0.2 ml of brilliant blue G (BBG) 0.25 mg/ml, 0.025% (Sigma-Aldrich, St. Louis, MO) vital dye. PPV gauge selection (23 or 25) and tamponade selection [Sulfur Hexafluoride (SF6) or octafluoropropane (C3F8)] were done according to surgeon preferences with a non-expansile dilution (SF6: 18%, C3F8: 14%).

Regarding the free flap technique, Morizane et al. reported a closure rate of large macular holes of 90% on a small case series of ten patients [18]. They did observe a significant improvement in visual acuity of 0.2 logMAR in at least 8 patients (p

In our study, we conducted a prospective analysis comparing the inverted flap-technique, the free-flap technique, and the conventional 360 ILM peeling. We assessed the anatomical success in terms of closure rate after a single surgery and functional success in terms of change in visual acuity. Our results showed that the inverted-flap technique and the traditional 360 ILM peeling had a slightly higher closure rate than the free-flap technique (91 vs 85%; p = 0.85). However, it is important to point out that due to the small number of participants in all three groups, the 95% confidence intervals are wide and can easily overlap with each other. Regarding the closure rate after a single surgery of the inverted flap technique and the free-flap technique, our results are similar to those published so far, with high closure rate (above 80%). Nevertheless, conversely to the work by Michalewska et al. and Morizane et al., our prospective study did not find any difference with the conventional 360-ILM peeling, which also displayed a high closure rate.

In summary, large macular holes (minimum diameter > 400 µm) are surgical challenges with poorer than usual anatomical prognosis. The inverted-flap and free-flap technique are surgical alternatives that may improve the chances of a better anatomical outcome. Our results showed no difference between this techniques and conventional (360) ILM peeling after a single surgery. However, patients allocated into the inverted-flap group showed a trend to have faster visual recovery that might be significant in the short term (3 months of follow-up). Nevertheless, the study has considerable bias due to short follow-up, small sample size and the possibility that a slow-acting gas could have interfere with the 1-month BCVA assessment. A study with a larger sample and longer follow-up is needed in order to corroborate this observation and to assess if the visual changes are sustained over time.


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