A German research study of ocriplasmin treated patients has recommended that clinicians should carefully select which patients may be suitable for such treatment and that any such treated patients should be monitored cautiously using SD-OCT, especially important for patients with full thickness macular holes (FTMHs). The researchers further suggest that clinical follow-up should exceed 4 weeks post injection in order to assess long-term effects and to allow for exclusion of any potential toxic effects. The research group highlighted that the study was conducted on only a small group of patients with limited follow-up however, no major adverse events were encountered by the researchers following ocriplasmin injection.
In the retrospective single centre, consecutive interventional case series study, conducted at the Department of Ophthalmology, Charite Universitätsmedizin Berlin and reported in the British Journal of Ophthalmology (Hager et al, doi:10.1136/bjophthalmol-2014-305620), five patients were treated with ocriplasmin injection. Vitreomacular traction (VMT) appeared to persist in four out of the five cases; the four patients then underwent pars-plana vitrectomy (PPV) to treat the VMT and FTMH (n=2, size of macular hole <400 mm). The research group reported that the FTMHs were closed within 1 week of surgery. However, after the PPV, in three eyes, newly developed subretinal fluid was detected, which lasted for several months postoperatively. According to the researchers, newly developed subretinal fluid has been described after ocriplasmin treatment in cases with resolution of VMT. The newly developed subretinal fluid is postulated to arise from a loosening of the photoreceptor complex due to ocriplasmin enzymatic activity. The authors noted that long-term effects of ocriplasmin are still to be evaluated using SD-OCT. The clinical trial data presented to regulators for ocriplasmin approval is understood to comprise two phase III randomized control trials (the “MIVI-TRUST” trials) comparing the effects of a single intravitreal injection of ocriplasmin with placebo saline injection. The primary end point for the clinical trials was the resolution of VMA without retinal defect at day 28 however, the authors of the current analysis state, “The primary end point, that is, the resolution of VMT, of the MIVI-TRUST trials is actually a non-validated surrogate parameter with indistinct clinical relevance”. The German research group commented that the results of the MIVI-TRUST trials showed that after 28 days, adhesions between vitreous and retina were cleared in 61/219 and 62/245 eyes of the ocriplasmin groups compared with 14/107 and 5/81 of the placebo groups (p<0.001).
In concluding their analysis the authors of the study stated that, “We suggest that patients should be selected carefully for ocriplasmin treatment and monitored cautiously using SD-OCT. This is especially important for patients with FTMHs. Follow-up visits should exceed 4 weeks after injection and, if necessary, after vitrectomy as well since long-term effects need to be investigated and potentially toxic effects excluded.”