To the Editor:

We read with interest the article by Frisina et al. [1]. In this meta-analysis, the articles screened were grouped according to different surgical techniques used in ten subgroups of patients with refractory full thickness macular hole (FTMH). Refractory FTMH closure rate and best-corrected visual acuity gain were the two analysed parameters. This article showed that the refractory FTMH closure rate is similar in the ten subgroups. In terms of visual recovery, the most efficient technique for treating refractory FTMH is human amniotic membrane plug (hAM). Therefore, the authors recommend the hAM technique as the first option for patients with refractory FTMH. However, the authors made some mistakes in describing the study design.

Firstly, despite large diversity in the trials, the authors did a meta-analysis and also examined the effectiveness of different interventions. The critical aspect of this article is for recommending the hAM technique solely based on a single prospective published article containing a small sample size (only eight cases) [2], and all cases were operated by a single surgeon.

Secondly, that owing to data unavailability, and heterogeneity in programme and trial designs a meta-analysis would be inappropriate in this case: a meta-analysis is only “properly” applicable if the data summarised are homogeneous (patients, treatment, and end points must be similar).

Finally, further prospective well-controlled multicentre studies are needed to demonstrate its regenerative potential before recommending or drawing conclusions for hAM as the best surgical option. In addition, special attention must be paid in the controlled studies to the correct calibration of the hAM dimensions with respect to the macular hole, which is not established.

Currently, the treatment of persistent macular holes is still a challenge.