Vitreolysis viability?

The question of whether enzymatic vitreolysis with ocriplasmin (Jetrea®, ThromboGenics) has sufficient merit to compensate for its lower success rate compared with vitrectomy in the treatment of vitreomacular traction (VMT) and macular holes was the topic of an Amsterdam Retina Debate held at the 15th EURETINA Congress in Nice, France.

First up was Tim Jackson PhD, FRCOphth, of King’s College London, UK, who said that the MIVI-TRUST Trials provided very robust evidence for the agent’s efficacy compared to placebo and that in the right patients its efficacy is acceptable.

MIVI-TRUST was a combined analysis of two randomised, double-masked placebo-controlled phase III trials involving 652 patients with symptomatic VMT and macular holes up to 400µm in diameter. It showed that VMT was resolved in 26.7 per cent of those receiving a single intravitreal injection of ocriplasmin, compared to 10.1 per cent of the controls. In addition, the rate of macular hole closure was 41 per cent in the active treatment group, compared to 11 per cent in the controls.

BETTER RESULS IN SELECT PATIENTS

Furthermore, a subgroup analysis showed that in patients without epiretinal membranes the rate of VMT resolution reached 35 per cent. In addition, in those with macular holes smaller than 250µm the closure rate was nearly 60 per cent.

Regarding complications, retinal tears and retinal detachment (RD) occurred in only 2.2 per cent, and there were a range of other less serious complications, such as new or worsening macular hole in 6.7 per cent. There were also some unexpected complications, such as dyschromatopsia in 1.6 per cent and electroretinographic changes in 0.1 per cent.

He pointed out that in a more recent post-marketing surveillance study involving over 4,000 patients (Hahn et al, Retina 2015;35: 1128-1134), the rates of all complications were only a fraction of those seen in the MIVI-TRUST Trials.

Looking at vitrectomy, Dr Jackson noted that a meta-analysis of the literature involving VMT patients showed that the visual gains with vitrectomy were fairly modest and the rate of RD was 5.6 per cent, with postoperative visual acuity ranging from 6/28 to 6/16 (Jackson et al, Retina 2013; 33:2012-2017). Other major complications included epiretinal membranes in 7.2 per cent and cystoid macular oedema in 3.1 per cent. In addition, nearly two-thirds of phakic eyes developed cataracts within one year.

Furthermore, a recently published Cochrane review of vitrectomy in macular hole patients showed that they gained only 1.5 lines of visual acuity and the hole closure rate was 76 per cent. In addition, there was a five per cent incidence of RD, and one in 250 patients developed endophthalmitis after the surgery.

Dr Jackson suggested that ocriplasmin may find niche uses, for example, in patients who refuse vitrectomy and those with milder symptoms. He added that the science of chemical vitrectomy continues to evolve.

OCRIOLASMIN UNRELIABLE

Taking up the cudgel against enzymatic vitreolysis as a treatment for vitreomacular adhesion and macular holes, was Grazia Pertile MD, Sacro Cuore Hospital, Negrar, Italy. She said that, for a high proportion of patients, undergoing enzymatic vitreolysis was akin to buying a ticket for a cable car that only made it up the hill half the time.

“The effectiveness of vitrectomy is much higher than for ocriplasmin, so if you have a vitreomacular adhesion and you are rational kind of person you would probably choose a small gauge vitrectomy,” she said. She added that modern small-gauge technology has greatly improved the success rates of vitrectomy, and pointed out that the macular hole treatment failures in the MIVI-TRUST Trials all subsequently underwent vitrectomy with a success rate of 80 per cent. Vitrectomy is also safer than it used to be, she said. For example, in a study reviewing the outcome of vitrectomy for VMT, the incidence of endophthalmitis was only 0.03 on average.

Regarding RD, a review of a subset of the same patients who underwent 23-gauge vitrectomy showed that the RD occurred in only 0.2 per cent of patients.

In contrast, with ocriplasmin there have been numerous reports in the literature of strange unexpected complications including retinal breaks, transient but severe visual loss, transient electroretino graphic changes and toxicity to the outer retina.

Many of the transient complications most likely result from the proteolytic effect of ocriplasmin on Müller glia cells. The cells can fortunately regenerate, which explains the gradual, time-dependent nature of the visual disturbances.

However, it still compares unfavourably to vitrectomy in that respect, she said, adding: “If you want to take off the plastic film from the slice of cheese, would you pour some chemicals on it to melt it, even though they tell you that it may cause you stomach-ache for a couple of weeks? Probably not.”

Tim Jackson: t.jackson1@nhs.net

Grazia Pertile: grazia.pertile@sacrocuore.it