Early vitreomacular separation with delayed macular hole closure after ocriplasmin treatment.

Based on the indications, one-third to one-half of patients can achieve full-thickness macular hole (FTMH) closure with or without the separation of vitreomacular adhesion (VMA) within 28 days of ocriplasmin treatment. The authors report the case of a 63-year-old man with early VMA separation and delayed FTMH closure after ocriplasmin treatment. Four weeks posttreatment, the posterior vitreous detachment occurred at the optic disk, and the macular hole (MH) started decreasing thereafter. MH closure was finally achieved at 10 weeks posttreatment, leaving minimal subretinal fluid. The patient's vision improved from 0.8 LogMAR (pretreatment) to 0.3 LogMAR (12 weeks posttreatment). This case suggests that FTMH closure can be achieved within 28 days of ocriplasmin treatment.

The characterization of patients with full-thickness macular hole (FTMH) in ocriplasmin (Jetrea®; Thromo Genics, Leuven, Belgium) phase-3 clinical trials revealed that 43 of 106 (40.6%) patients achieved FTMH closure by day 28 postinjection.[1] At month 6, the FTMH reopened in 4 patients, while the FTMH closure rate remained 40.6%, suggesting that the 4 patients achieved FTMH closure between day 28 and month 6. However, a detailed clinical course for these patients was not reported. A PubMed search using the keyword “ocriplasmin and macular hole (MH)” conducted on August 10, 2015, yielded 55 articles; however, none of them reported on delayed closure in FTMH. In this study, we describe the presentation of an early vitreoretinal separation with delayed FTMH closure.

Case Report

A 63-year-old male experienced decreased vision in his left eye for several weeks; he had no history of ocular trauma. His vision was 0.00 LogMAR and 0.80 LogMAR in his right and left eyes, respectively. Spectral domain optical coherence tomography (OCT; Cirrus, Carl Zeiss Meditec, Dublin, CA, USA) of the left eye revealed a small, stage 2 FTMH with vitreomacular adhesion (VMA) but no epiretinal membrane [Fig. 1a and b]. The FTMH was measured using software-based calipers according to a previously described method[2] with some modifications. Furthermore, 6-mm-long vertical and horizontal high-definition 5-line raster images across the fovea were used instead of the six radial images of the macular thickness map. The pretreatment minimum linear diameter (MLD) and base diameter (BD) of the FTMH were 211 and 768 µm, respectively. The patient was informed that ocriplasmin has proven statistically significant in resolving VMA compared with placebo in clinical trials, and the option of vitrectomy was discussed. Informed consent was obtained, and the risk of complications with intravitreal injections such as vision loss, retinal detachment, crystalline lens damage, and endophthalmitis was documented on the consent form. The patient was informed of a guarded prognosis for vision improvement; thereafter, he was treated with an intravitreal injection of ocriplasmin (0.125 mg/0.1 mL) in his left eye.

Figure 1

Optical coherence tomography. Pretreatment (a and b); posttreatment day 1 (c and d); day 4 (e and f); 2 weeks (g and h); 4 weeks (i and j); 6 weeks (k and l); 8 weeks (m and n); 10 weeks (o and p); 12 weeks (q and r); 16 weeks (s and t)

Day 1 posttreatment, the VMA persisted with a slightly enlarged FTMH (MLD = 282 µm and BD = 941 µm; Fig. 1c and d). Day 4 posttreatment, VMA separation was achieved; however, FTMH enlargement was observed with an MLD of 353 µm and a BD of 950 µm [Fig. 1e and f]. Furthermore, the patient reported about photopsia. Ocular examination revealed a normal intraocular pressure and no sign of endophthalmitis, retinal detachment, or hemorrhage. The photopsia disappeared thereafter and was not reported by the patient at the week 2 follow-up. However, the FTMH enlarged further (MLD = 384 µm and BD = 953 µm; Fig. 1g and h), and his vision was 1.00 LogMAR. A large floater was reported at the week 4 follow-up. Fundus examination revealed a Weiss ring, and the posterior hyaloid membrane was no longer detected through OCT. The FTMH became smaller with an MLD of 237 µm and a BD of 792 µm [Fig. 1i and j]. The sixth and eighth week follow-ups showed that the FTMH was decreasing continuously (week 6: MLD = 198 µm and BD = 731 µm; week 8: MLD = 211 µm and BD = 678 µm; Fig. 1k–n); however, no obvious vision improvement was observed. Further intervention was discussed with the patient, including the choice of gas tamponade or vitrectomy with internal limiting peeling; however, the patient selected observation. His vision improved abruptly to 0.4 LogMAR at week 10 postinjection. FTMH closure was achieved with minimal subretinal fluid [Fig. 1o and p]. His vision further improved to 0.3 LogMAR at the week 12 follow-up, and OCT revealed a small subfoveal space [Fig. 1q and r]. Further vision improvement to 0.1 LogMAR was achieved at week 16 postinjection, with only a small disruption of the inner and outer segment junction observed through OCT [Fig. 1s and t].

Discussion

The physiology of the vitreous liquefies with aging and separates from the retina through a process called posterior vitreous detachment (PVD). The strongest points of vitreoretinal attachment are at the optic nerve, macula, blood vessels, and ora serrata. The vitreous can abnormally adhere to the macula, leading to vitreomacular traction and an MH.[3] Plasmin, the key enzyme of the fibrinolytic cascade, is known to cleave other extracellular matrix components, particularly laminin and fibronectin.[4] Both of these molecules are found at the vitreoretinal interface, where they are postulated to play a central role in the adherence of collagen fibers between the vitreous and internal limiting membrane (ILM).[5] Furthermore, pharmacological vitreolysis with ocriplasmin was approved by the US Food and Drug Administration in October 2012 for patients with symptomatic VMA and by the European Medicines Agency for the treatment of VMA, including the association with an MH of 400 µm in diameter.[67] Intravitreal ocriplasmin creates a cleavage between the posterior hyaloid membrane and the ILM, without any adverse effects on the retinal structure.[8]

Ocriplasmin levels in the vitreous rapidly decrease after an intravitreal administration and are below the quantification threshold at day 7. However, vitreous degeneration and PVD continue and extend wider once initiated. In our case, the reduction in the FTMH was clear after the Weiss ring formation, suggesting a release of the previous attachment between the posterior hyaloid membrane and the optic disk. This separation might have provided more tension release and promoted FTMH closure in our case.

The FTMH was slightly enlarged during and immediately after VMA separation in our case. Steel et al. examined 12 patients with a failure of FTMH closure who had undergone vitrectomy and reported clear MH enlargement after ocriplasmin treatment,[9] suggesting some association between the enlargement of the FTMH posttreatment and the failure of FTMH closure. However, the FTMH enlargement in our case was minimal and was possibly caused by mechanical force during VMA separation.

We report the detailed clinical course of a patient with early VMA separation but without FTMH closure within 28 days of ocriplasmin treatment. The minimal FTMH enlargement after VMA separation may not be of concern. However, if FTMH closure is not achieved after 28 days and PVD does not occur at the optic disk, longer observation and delayed FTMH closure might be expected.

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Conflicts of interest

There are no conflicts of interest.