Retrospective Study of Ellipsoid Zone Integrity Following Treatment with Intravitreal Ocriplasmin (OZONE Study)

Abstract

Purpose: To assess generalized (GD) and focal ellipsoid zone disruption (FD) in patients with symptomatic vitreomacular adhesion (sVMA) using spectral domain optical coherence tomography (SD-OCT) following ocriplasmin.

Patients and methods: OZONE was a Phase 4, retrospective study of patients with sVMA treated with a single intravitreal injection of ocriplasmin (0.125 mg). Data from adult patients with at least 6-month follow-up after ocriplasmin were included. SD-OCT was performed at baseline (within 30 days before ocriplasmin), before Day 21 post-injection (early observation, EO), and by last observation (LO) which was maximally 6 months post-injection. The main outcome measure was the development of new and the evolution of existing FD/GD at EO and LO.

Results: The study enrolled 134 eyes/patients from 22 sites in the USA. At baseline, 87 eyes (64.9%) had FD, 21 eyes (15.7%) had GD and 26 eyes (19.4%) had no FD/GD. Among the eyes without FD/GD at baseline, 13 (50%) and 8 (30.8%) developed FD or GD, respectively, by EO. By LO, FD/GD improvement or resolution was seen in >80% of these eyes. Among the eyes with FD/GD at baseline, <40% had improving/resolving EZ integrity at LO. The absence of FD/GD at baseline was associated with less persistent FD/GD at LO (P<0.0005). The presence of FD with MH at baseline was associated with persistent FD at LO (P=0.027).

Conclusion: The fact that a large majority of eyes had FD/GD prior to ocriplasmin was unexpected and demonstrates that EZ disruptions are common in sVMA. This suggests that loss of EZ integrity may be part of the natural history of this disorder. It is hypothesized that the status of the EZ at baseline is a contributing, ocriplasmin independent modulator of subsequent EZ changes after ocriplasmin. Prospective analyses which include a sham control group would be required to test this hypothesis.

Keywords: macular hole; spectral domain optical coherence tomography; symptomatic vitreomacular adhesion; vitreomacular traction.

Figure 1

Example SD-OCT images depicting ellipsoid zone disruptions prior to treatment with ocriplasmin. Panel (A) Example of an eye with generalized disruptions of the ellipsoid zone. Arrows depict multiple areas of ellipsoid zone disruption not solely localized around a corresponding anatomic lesion. Panel (B) Example of an eye with focal disruption of the ellipsoid zone. Arrows depict areas of ellipsoid zone disruption localized around the area of vitreomacular traction.

Figure 2

Percentage distributions of the ellipsoid zone status at early and last observation, prior to vitrectomy (if any), for the subgroup of patients without focal or generalized ellipsoid zone disruptions at baseline. Status with regard to focal, and generalized disruptions are shown in the left- and right-hand columns, respectively. The number of patients with readable scans is shown above each bar. Scans were unavailable or uninterpretable at EO for 3 eyes with FD and 2 eyes with GD.

Figure 3

Percentage distributions of the ellipsoid zone status at early and last observation, prior to vitrectomy (if any), for the subgroup of patients with focal ellipsoid zone disruptions at baseline. Status for patients without and with macular hole at baseline are shown in the left- and right-hand columns, respectively. The number of patients with readable scans is shown above each bar. Scans were unavailable or uninterpretable at EO for 5 eyes with no MH and for 3 eyes with MH.

Figure 4

Percentage distributions of the ellipsoid zone status at early and last observation, prior to vitrectomy (if any), for the subgroup of patients with generalized ellipsoid zone disruptions at baseline. Status for patients without and with macular hole are shown in the left- and right-hand columns, respectively. The number of patients with readable scans is shown above each bar. Scans were unavailable or uninterpretable at EO for 2 eyes with MH.