Vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with no peeling for idiopathic full-thickness macular hole (FTMH)

A full-thickness macular hole (FTMH) affects the centre of the macula, the area responsible for detailed vision and reading. It is believed to occur because of changes in the jelly that fills the inside of the eye, the vitreous. The vitreous is stuck to the macula but, at some point in life, it may detach from around the macula but remain attached to its centre. With the daily eye movements, the vitreous pulls where it remains attached (at the centre of the macula) and if pulling is strong enough it may break the macula causing a macular hole. To date, the treatment for macular hole has involved the removal of the vitreous by doing surgery (‘vitrectomy'). However, not all holes were closed with this surgery and new techniques were investigated. Among these is the 'peeling' (removal) of the internal limiting membrane (ILM) of the retina. 

The purpose of this review was to find out whether peeling the ILM around the macular hole could achieve better results after surgery than leaving it in place. 

This review found four studies in which people who had undergone macular hole surgery with no ILM peeling were compared with those in whom the ILM was removed during the first surgery they had received. As well as reviewing published data from these four studies, we undertook an 'individual patient data (IPD) meta-analysis'. To undertake IPD meta-analysis one needs to collect all the raw data for each participant included in each of these RCTs before and after surgery and then combine all data together and analyse them. We were able to obtain data for each individual participant included in three of these four studies, which we then analysed and present in this review. 

Our results showed that at six and 12 months after the initial surgery to treat the macular hole the vision was no different between participants that received ILM peel and those who did not. At three months, however, the vision was better in those participants that received ILM peeling. More macular holes were closed and less re-operations had to be performed in participants who received ILM peeling with no differences in the number of complications between patients receiving ILM peeling or no peeling in the first surgery. There were no differences in the way participants perceived the benefits of the surgery. ILM peeling was found to be highly likely cost-effective, i.e. the cost of the treatment was justifiable by the benefits obtained from it.

We conclude that ILM peeling compared with no peeling increases the chance for a macular hole to close with a single surgery and reduces the chances of people requiring additional surgery without unwanted side effects; as ILM peeling is very likely cost-effective, it may be considered the best available option for people with idiopathic FTMH.

Authors' conclusions: 

Although we found no evidence of a benefit of ILM peeling in terms of the primary outcome (visual acuity at six months), ILM peeling appears to be superior to its no-peeling counterpart as it offers more favourable cost effectiveness by increasing the likelihood of primary anatomical closure and subsequently decreasing the likelihood of further surgery, with no differences in unwanted side-effects compared with no peeling. 

Read the full abstract...

Several observational studies have suggested the potential benefit of internal limiting membrane (ILM) peeling to treat idiopathic full-thickness macular hole (FTMH). However, no strong evidence is available on the potential benefit(s) of this surgical manoeuvre and uncertainty remains among vitreoretinal surgeons about the indication for peeling the ILM, whether to use it in all cases or in long-standing and/or larger holes. 


To determine whether ILM peeling improves anatomical and functional outcomes of macular hole surgery compared with the no-peeling technique and to investigate the impact of different parameters such as presenting vision, stage/size of the hole and duration of symptoms in the success of the surgery.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Group Trials Register (The Cochrane Library 2013, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to February 2013), EMBASE (January 1980 to February 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2013), the metaRegister of Controlled Trials (mRCT) (, ( and the WHO International Clinical Trials Registry Platform (ICTRP) ( We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 February 2013.

We searched reference lists of the studies included in the review for information about other studies on ILM peeling in macular hole surgery. We searched Proceedings for the following conferences up to February 2013: American Academy of Ophthalmology (AAO), Annual Meeting of the American Society of Retina Specialists (ASRS), Annual Meeting of the Retina Society, Congress of the Asia-Pacific Academy of Ophthalmology (APAO), European Association for Vision and Eye Research (EVER) Annual Congress, European Vitreoretinal Society (EVRS) Annual Meeting, Association for Research in Vision and Ophthalmology (ARVO) Meeting, International Vitreoretinal Meeting, and World Ophthalmology Congress.

Selection criteria: 

Only randomised controlled trials (RCTs) comparing ILM peeling with the no-peeling counterpart were included.

Data collection and analysis: 

Two review authors (KSC and NL) independently assessed the titles and abstracts of all RCTs identified by electronic and manual searches.

We obtained Individual patient data (IPD) from three of the four identified eligible trials. The fourth identified RCT had only been published in abstract form and no IPD were available; we included data from this published abstract for one outcome (macular hole closure).

The primary outcome was distance visual acuity at six months. Secondary outcomes included distance and near  visual acuity at three and 12 months postoperatively, near visual acuity at six months postoperatively, primary (after a single surgery) and final (following more than one surgery) macular hole closure, need for additional surgical interventions, vision-related quality of life and intraoperative and postoperative complications.

We performed meta-analysis using standard techniques (the Mantel-Haenszel odds ratio (OR) for binary outcomes, mean difference (MD) for continuous outcomes) using a fixed-effect model. For two outcomes we also used the IPD to perform adjusted analyses using regression methods.

Main results: 

We identified and included four RCTs; these were conducted in Denmark, France, Hong Kong and the United Kingdom/Republic of Ireland and randomised 47, 80, 49 and 141 participants respectively.

There was no evidence of a difference in the primary outcome (distance visual acuity at six months), nor in distance visual acuity at 12 months between randomised groups. However, there was evidence of improved best corrected distance visual acuity in the ILM peeling group at three months (WMD -0.09, 95% CI -0.17 to -0.02). We found no evidence for a difference in near vision between groups at any of the time points investigated.

Overall, more participants in the ILM peeling group than in the no-peeling group had primary macular hole closure (OR 9.27, 95% CI 4.98 to 17.24); this held true when results were stratified by the stage of the macular hole. There was also evidence that those in the ILM peeling group were more likely to have final macular hole closure (OR 3.99, 95% CI 1.63 to 9.75). Fewer participants required further surgery in the ILM peeling group than in the no-peeling group (OR 0.11, 95% CI: 0.05 to 0.23).

Rates of intraoperative and postoperative complications were similar in both groups.

Based on the results of one study, there was no evidence that total VFQ-25 or EQ-5D scores differed between the groups at six months.  Based on this same study, ILM peeling is highly likely to be cost-effective.