The inverted internal limiting membrane flap technique is a surgical method for macular hole in which the internal limiting membrane (the innermost basement membrane of the retina) is left attached at the edge of the macular hole and then inverted and covered. It was developed as an advancement over the conventional “complete internal limiting membrane removal + gas tamponade” approach.
Surgical treatment for macular hole was first reported by Kelly and Wendel in 1991. Subsequently, in 1995, Brooks demonstrated that adding internal limiting membrane peeling improved closure rates, forming the basis of the current standard procedure.
The current standard procedure is vitrectomy + internal limiting membrane peeling + gas tamponade, which yields high primary closure rates for small to medium-sized idiopathic macular holes. 8) In large cases, closure may be difficult with the standard method alone, and the inverted internal limiting membrane flap technique becomes an option. 9)
As higher closure rates were sought for large or refractory macular holes, Michalewska et al. introduced the “inverted flap technique” in 2010, covering the macular hole with an inverted internal limiting membrane flap, and reported a high closure rate of 98% for macular holes larger than 400 μm. 9)
The prevalence of idiopathic macular hole is reported to be 0.2–0.7%, with an incidence of 3.14–7.8 per 100,000 person-years. 8) It is more common in women (72% female, female-to-male ratio 2–3.3:1), with a peak onset in the 60s and 70s. 8) In untreated full-thickness macular holes (FTMH), only 5% maintain corrected visual acuity of 20/50 or better. 8)
In untreated full-thickness macular holes, only 5% maintain corrected visual acuity of 20/50 or better. 8) Central scotoma, metamorphopsia, and severe vision loss often progress, and early surgery is recommended. For details on treatment outcomes, see the section “4. Surgical Outcomes and Complications”.
The main indications for the inverted internal limiting membrane flap technique are shown below.
Idiopathic giant macular hole
Target: Large macular holes with MLD > 400 μm.
Rationale: The closure rate with standard internal limiting membrane peeling is only 55–80%. 7) The closure rate is even lower for holes with a base diameter > 900 μm or in high myopia. 7)
Myopic macular hole
Target: Cases with high myopia and posterior staphyloma.
Rationale: Posterior staphyloma increases tangential traction. When closure is difficult with standard internal limiting membrane peeling alone, the inverted flap technique should be considered. 8)
Macular hole with retinal detachment
Target: Retinal detachment caused by a macular hole.
Rationale: In cases where closure is difficult with the standard procedure, the inverted flap technique is an option. 8)
In addition to standard indications, application to the following comorbid conditions has been reported.
No. For small to medium macular holes with MLD < 400 μm, standard internal limiting membrane peeling with gas tamponade can achieve a high closure rate. 8) The inverted internal limiting membrane flap technique is a procedure selected for cases where standard surgery is expected to be difficult, such as large macular holes, myopic macular holes, and macular holes with retinal detachment.
Temporal Internal Limiting Membrane Flap Technique
Method: Peel the internal limiting membrane only from the temporal side, covering approximately 2 disc diameters.
Advantages: Preserves the nasal papillomacular nerve fiber bundle. There is also a method of forming a 270° C-shaped temporal flap 7). The goal is to reduce postoperative retinal nerve fiber layer damage by modifying the flap harvesting site.
Autologous Blood Sandwich Technique
Method: Inject 0.1 mL of autologous blood into the macular hole, cover it with an internal limiting membrane flap, and then fix the flap with additional autologous blood. 7)
Advantages: Autologous blood supplies growth factors and collagen, preventing flap displacement. Closure was achieved in a case with MLD 742 μm, and best-corrected visual acuity improved from 1.30 to 0.70 LogMAR. 7)
Viscoelastic Substance-Assisted Technique
Method: Inject cohesive OVD (viscoelastic substance) subretinally to release the RPE adhesion at the edge of the macular hole, then cover with an internal limiting membrane flap (viscostretch technique). 4)
Advantages: Closure was achieved in large chronic macular holes with MLD 1,089 μm and 853 μm. 4) Note the risk of RPE detachment.
The face-down position after surgery is necessary to allow the gas injected for gas tamponade to press against the macula. The direct pressure of the gas on the macula stabilizes the internal limiting membrane flap and promotes closure. The duration varies depending on the surgical technique, type of gas, and size of the macular hole, but generally 3 to 7 days is recommended.
Representative outcomes are shown by surgical technique and indication.
| Indication/Surgical Technique | Closure Rate | Notes |
|---|---|---|
| Large macular hole (inverted flap technique) | 98% | 2010 Michalewska9) |
| Macular hole with RP | 83.3% | 24-eye review5) |
In a randomized controlled trial by Michalewska et al. targeting large macular holes >400 μm, the closure rate was 98% with the inverted flap technique and 88% with the standard technique9). The frequency of flat-open was also lower with the inverted flap technique, and postoperative visual acuity was better9).
In the viscoelastic substance-assisted method, improvement in best-corrected visual acuity from 20/50 to 20/40 has been reported in a case with MLD of 1,089 μm.4) In MacTel type 2 cases, closure was achieved in all 3 cases and maintained for 2 years (best-corrected visual acuity 20/20 and 20/25).6)
The main complication specific to the inverted internal limiting membrane flap technique is macular pucker.
It is caused by excessive glial tissue proliferation on the internal limiting membrane flap, and its frequency varies among reports.
| Report | Incidence | Outcome |
|---|---|---|
| Kanda et al.1) | 2 out of 26 cases (7.7%) | Best-corrected visual acuity improved after reoperation |
| Buckle et al.2) | 1 case (MLD 629 μm) | Best-corrected visual acuity improved after reoperation |
Histopathological examination has confirmed proliferation of RPE cells on the vitreous side of the internal limiting membrane.1)
Risk factors for macular pucker include flap morphology (insertion type has significantly higher risk than bridging type, P=0.02), multilayer flap formation, high myopia, and silicone oil use.2) As treatment, reoperation to remove the internal limiting membrane flap has been reported to resolve the pucker and maintain macular hole closure.1)2)
Other complications include RPE detachment specific to the viscostretch method (subretinal injection of viscoelastic material). 4) Additionally, DONFL (dissociated optic nerve fiber layer) and postoperative retinal sensitivity reduction are known complications associated with internal limiting membrane peeling in general. 3)
Macular pucker is proliferative tissue that forms on the internal limiting membrane flap and can cause vision loss and metamorphopsia. Cases have been reported where reoperation to remove the internal limiting membrane flap resolved the pucker and improved vision while maintaining macular hole closure. 1)2) If you experience worsening vision or metamorphopsia after surgery, it is important to see your doctor early.
Central vitrectomy during vitreous surgery releases anteroposterior traction on the macular hole. Peeling the internal limiting membrane also removes tangential traction. If an epiretinal membrane is present, its removal also contributes to traction release.
The scaffold theory has been proposed as the main mechanism by which the inverted internal limiting membrane flap technique achieves a higher closure rate than standard internal limiting membrane peeling. 9)
Flap morphology has been shown to influence subsequent tissue response. The bridging type (flap bridges over the macular hole) has a lower incidence of macular pucker compared to the insertion type (flap inserted into the macular hole) (P = 0.02). 2) Since excessive tissue proliferation leads to pucker formation, appropriate flap placement is important.
It is believed that by isolating the vitreous cavity from the macular hole, the flap stabilizes the RPE microenvironment around the macular hole, creating favorable conditions for photoreceptor regeneration. 7)
A study using microperimetry-guided technique confirmed a significant increase in perifoveal retinal sensitivity postoperatively, suggesting contribution to visual function recovery. 3)
For reference, the formation mechanism of idiopathic macular hole is shown. Abnormal vitreous cortex adhesion to the fovea during posterior vitreous detachment (PVD) creates tangential traction, leading to stepwise progression from foveal cyst to pseudo-hole to full-thickness macular hole. 8)
In macular holes with glaucoma, retinal sensitivity decrease due to internal limiting membrane peeling is a concern. A method has been reported that identifies absolute scotoma areas preoperatively using microperimetry and harvests the internal limiting membrane only from those areas, aiming to preserve functionally important retinal regions. 3) One case was reported with a significant increase in perifoveal retinal sensitivity postoperatively. 3)
In very large and chronic macular holes, coverage with an internal limiting membrane flap alone may be insufficient. A method has been reported in which cohesive OVD is injected subretinally to release the RPE adhesion at the edge of the macular hole, enlarge the hole, and then cover it with a flap, achieving closure of ultra-large macular holes with MLD of 1,089 μm and 853 μm. 4) However, it carries a risk of RPE detachment, and careful evaluation is needed for widespread adoption.
The modified technique using autologous blood as a source of growth factors and flap fixation material has shown promising results in large chronic macular holes. 7) It is speculated that platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) from autologous blood promote macular hole closure, but standardization of optimal blood volume and injection technique remains a future challenge.
Applications to macular holes associated with retinitis pigmentosa (RP) and MacTel type 2 have been reported, but these are limited to small case reports and series, requiring further case accumulation. 5)6)
Lee CY et al. (2021) reported a literature review of 24 eyes with macular holes associated with retinitis pigmentosa, finding a total closure rate of 83.3% with the internal limiting membrane flap technique (inverted or free flap), with visual improvement in 62.5%. Anterior lens capsule flap transplantation serves as an alternative when ILM peeling is difficult, but prospective studies are needed to establish efficacy. 5)
Nishiyama et al. (2021) performed the inverted internal limiting membrane flap technique on 3 eyes with full-thickness macular holes associated with MacTel type 2, achieving closure in all cases. In 2 cases with follow-up, closure was maintained for 2 years, and best-corrected visual acuity was 20/20 and 20/25, respectively. 6)
Real-time intraoperative OCT is being used to confirm the position of the ILM flap, coverage of the macular hole, and residual subretinal fluid during surgery. 4) It may allow real-time verification of proper flap placement, contributing to improved surgical precision in the future.
In trials targeting large macular holes >400 μm, the closure rate of the inverted flap technique was superior to the standard method 9). However, for small macular holes, the difference between the two is small, and the benefit of the inverted ILM flap technique is particularly significant for large and refractory macular holes.
Kanda K, Nakashima H, Emi K. Macular pucker formation after inverted internal limiting membrane flap technique: two case reports. Am J Ophthalmol Case Rep. 2022;25:101282.
Buckle M, Jawaheer L, Keller J. Visual improvement despite macular pucker after inverted internal limiting membrane flap technique for idiopathic macular hole. J Vitreoretinal Dis. 2024;8(3):334-338.
Matoba R, Kanzaki Y, Morita T, et al. Microperimetry-guided inverted internal limiting membrane flap site selection to preserve retinal sensitivity in macular hole with glaucoma. Am J Ophthalmol Case Rep. 2024;33:102007.
Lu X, Yokoi T, Kataoka K, Inoue M. Inverted internal limiting membrane flap combined with subretinal viscoelastic injection for large or chronic macular holes. Am J Ophthalmol Case Rep. 2024;36:102100.
Lee CY, Yang CM, Yang CH, Hu FR, Chen TC. Flap technique-assisted surgeries for advanced retinitis pigmentosa complicated with macular hole: a case report and literature review. BMC Ophthalmol. 2021;21:322.
Nishiyama S, Iwase T. Two years outcomes of treating full-thickness macula hole associated with idiopathic macular telangiectasia type 2 by internal limiting membrane inverted flap technique: case reports. Medicine. 2021;100(36):e27078.
Li K, Zhou Y, Yang W, Jiang Q, Xu X. Modified internal limiting membrane flap technique for large chronic macular hole: two case reports. Medicine. 2022;101(1):e28412.
American Academy of Ophthalmology Retina/Vitreous Panel. Idiopathic Macular Hole Preferred Practice Pattern. AAO. 2024.
Michalewska Z, Michalewski J, Adelman RA, Nawrocki J. Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology. 2010;117(10):2018-2025. PMID: 20541263. doi:10.1016/j.ophtha.2010.02.011.
