June Fortin

Background After idiopathic epiretinal membrane (iERM) removal, it is unclear whether the internal limiting membrane (ILM) should be removed. The objective was to assess if active ILM peeling after iERM removal could induce microscotomas. Methods The PEELING study is a national randomised clinical trial. When no spontaneous ILM peeling occurred, patients were randomised either to the ILM peeling or no ILM peeling group. Groups were compared at the month 1 (M1), M6 and M12 visits in terms of microperimetry, best-corrected visual acuity (BCVA) and optical coherence tomography findings. The primary outcome was the difference in microscotoma number between baseline and M6. Results 213 patients were included, 101 experienced spontaneous ILM peeling and 100 were randomised to the ILM peeling (n=51) or no ILM peeling group (n=49). The difference in microscotoma number between both groups was significant at M1 (3.9 more microscotomas in ILM peeling group, (0.8;7.0) p=0.0155) but not at M6 (2.1 more microscotomas in ILM peeling group (−0.5;4.7) p=0.1155). Only in the no ILM peeling group, the number of microscotomas significantly decreased and the mean retinal sensitivity significantly improved. The ERM recurred in nine patients in the no ILM peeling group (19.6%) versus zero in the ILM peeling group (p=0.0008): two of them underwent revision surgery. There was no difference in mean BCVA and microperimetry between patients experiencing or not a recurrence at M12. Conclusion Spontaneous ILM peeling is very common. Active ILM peeling prevents anatomical ERM recurrence but may induce retinal impairments and delay visual recovery. Trial Registration NCT02146144.

The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .