Prognostic Factors Associated with Ocriplasmin Efficacy for the Treatment of Symptomatic Vitreomacular Adhesion and Full-thickness Macular Hole: Analysis from Four Studies.

Brian C Joondeph,Luc Duchateau,Thomas Raber,Paul Willems,Joseph Markoff

doi:10.18502/jovr.v16i1.8250

Abstract

PurposeTo assess the effect of patient baseline characteristics on the efficacy of ocriplasmin treatment for symptomatic vitreomacular adhesion (VMA) with full-thickness macular hole (FTMH) from phase 3/4 studies.MethodsPatients with symptomatic VMA and FTMH at baseline and receiving ocriplasmin treatment 125 g were pooled from the MIVI-TRUST, OASIS, and ORBIT studies. Multivariable logistic regression analysis was used to evaluate whether patient baseline characteristics were predictors of having VMA resolution by Day 28 and FTMH closure by Month 6.ResultsTwo hundred and seventy-four patients receiving ocriplasmin treatment were assessed. Overall, 22.6% (62/274) of the patients experienced both VMA resolution by Day 28 and non-surgical FTMH closure by Month 6. Patients with FTMH 250 µm at baseline had a significantly higher success rate compared to those with FTMH 400 µm (29.9% [41/137] vs 2.2% [1/48]; P = 0.009). In patients with VMA resolution by Day 28, both small FTMH size (P = 0.001) and FTMH width at RPE (P = 0.012) were significantly associated with a higher FTMH closure rate. Patients with VMA resolution had higher rates of FTMH closure. Previously identified baseline predictive factors, including age, lens status, or presence of epiretinal membrane (ERM) were not found to be predictive of both VMA release and FTMH closure.ConclusionThe analysis revealed that FMTH 250 µm was the only factor predictive for achieving both pharmacological VMA resolution by Day 28 and nonsurgical FTMH closure by Month 6; neither lens status or presence of ERM, previously identified baseline characteristics favoring VMA resolution, showed statistically significant predictive power for both outcomes.

Highlights

Aging of the eye often leads to separation between the posterior vitreous cortex and the internal limiting membrane, known as posterior vitreous detachment (PVD).[1, 2] This process may be affected by vitreomacular adhesion (VMA), or adherence of the vitreous cortex to the macula after partial detachment.[3,4,5] Symptomatic VMA can occur if mechanical forces are large enough to cause anatomical changes to the macula.[6, 7] Effects resulting from symptomatic VMA may lead to the development of a full-thickness macular hole (FTMH).[4]
Age Mean (SD) Median Min, Max Age group, n (%) 250–400 μm >400 μm Missing VMA diameter, n (%) ≤1500 μm >1500 μm Missing FTMH width at retinal pigment epithelium (RPE)
Within the group of patients who had VMA resolution by Day 28, MH closure by Month 6 occurred significantly more for eyes with pseudophakic lens status at baseline, with smaller FTMH size and smaller FTMH width at RPE (Table 4)

Summary

INTRODUCTION

Aging of the eye often leads to separation between the posterior vitreous cortex and the internal limiting membrane, known as posterior vitreous detachment (PVD).[1, 2] This process may be affected by vitreomacular adhesion (VMA), or adherence of the vitreous cortex to the macula after partial detachment.[3,4,5] Symptomatic VMA ( referred to as vitreomacular traction) can occur if mechanical forces are large enough to cause anatomical changes to the macula.[6, 7] Effects resulting from symptomatic VMA may lead to the development of a full-thickness macular hole (FTMH).[4]. Ocriplasmin was approved in the US in 2012 and the EU in 2013 based on the results of two pivotal phase 3 clinical trials (MIVI-TRUST) that established its efficacy and safety in patients with symptomatic VMA with or without an associated FTMH ≤400 μm.[13] An earlier post hoc analysis of the pivotal trials suggested that the efficacy of ocriplasmin may be increased by patient baseline characteristics, including younger age, phakic lens status, focal VMA, absence of epiretinal membrane (ERM), and presence of FTMH.[14] Subsequently, both prospective and retrospective studies ranging from 5 to 74 eyes were undertaken that assessed the effect of these baseline factors with respect to VMA release.[13, 15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32] VMA release rates in these studies ranged from 0% to 71%, with 14 of 18 studies showing higher efficacy than the pivotal phase 3 trial rate of 26.5% VMA release at Day 28.[13] A meta-analysis of these studies, which included. The current study aimed at assessing the baseline factors that may be predictive of both VMA release together with FTMH closure in patients treated with ocriplasmin in the completed phase 3/4 studies

METHODS

RESULTS

DISCUSSION

Conflicts of Interest