Sir,

Ocriplasmin is a recombinant protease recently approved for the treatment of symptomatic vitreomacular adhesion (VMA). According to its FDA label, in the clinical trials of ocriplasmin, 2% of subjects experienced dyschromotopsia following its administration. In approximately half of these cases, there were electroretinographic (ERG) changes reported (a- and b-wave amplitude decrease).1 We describe a 67-year-old woman with a macular hole and VMA who received ocriplasmin and subsequently developed transient vision loss. Using eye-tracked spectral-domain optical coherence tomography (SD-OCT), we demonstrate that this vision loss appears to correlate with the disruption of the photoreceptor outer segments.

Case report

A 67-year-old female presented with a recent change in vision in her right eye. On presentation, visual acuity was 20/100 in her right eye. Clinical examination and SD-OCT showed a VMA, an epiretinal membrane, and a macular hole involving all but the inner retinal layers (Figure 1a). One week following intravitreal ocriplasmin (0.125 mg/0.1 ml), visual acuity had decreased to 20/400. Eye-tracked SD-OCT showed resolution of the VMA, a full-thickness macular hole, and damaged photoreceptor outer segments indicated by marked disruption of the ellipsoid zone (Figure 1b). Three weeks later, visual acuity had improved to 20/50. Eye-tracked SD-OCT showed persistence of the macular hole with a marked improvement in the integrity of the ellipsoid zone, indicative of partial recovery of photoreceptor outer segments (Figure 1c).

Figure 1
figure 1

Eye-tracked spectral-domain optical coherence tomography immediately before (a), 1 week following (b), and 4 weeks following a single intravitreal injection of ocriplasmin (c). (a) Before treatment, there is a vitreomacular adhesion (VMA), an epiretinal membrane, and a macular hole involving all but the inner retinal layers. (b) One week following treatment, there is resolution of the VMA, a full-thickness macular hole, and damaged photoreceptor outer segments indicated by marked disruption of the ellipsoid zone (arrows). (c) Four weeks following treatment, there is persistence of the macular hole with a marked improvement in the integrity of the ellipsoid zone.

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Comment

In the clinical trials of ocriplasmin, blurred vision, photopsia, dyschromotopsia, and ERG changes occurred in a significantly greater number of patients receiving ocriplasmin vs those receiving a placebo (drug vehicle diluted with saline).1, 2 These ocular adverse events appear to suggest a drug effect on the neurosensory retina, most likely involving the photoreceptors. The SD-OCT findings in our case appear to support this mechanism. We propose that in some eyes, ocriplasmin, a proteolytic enzyme, may produce a disruption of the photoreceptor outer segments that is at least partially reversible. Determining whether ocriplasmin, a protein with a molecular weight of 27.2 kDa, reaches the photoreceptors through the macular hole or via a trans-retinal route might help predict which eyes are at higher risk for this complication.