Perspective

No disadvantage seen in eyes treated surgically for macular hole after ocriplasmin failure

Macular hole closure rates are relatively low with ocriplasmin, but the therapy is safe and can be discussed as an option in specific cases.

A study published by the German EXPORT study group came to reassuring conclusions concerning vitrectomy surgery in eyes in which previous ocriplasmin treatment for macular hole has failed. The functional and anatomical results were comparable in these eyes to those of eyes that proceeded directly to surgery without ocriplasmin treatment.

“We noticed that eyes treated with ocriplasmin, in which the vitreomacular traction (VMT) had been released but the macular hole had not closed, often show an enlargement of the diameter of the hole. During recent years, diameter was discussed as a prognostic factor, as larger holes seemed to have lower vision after surgery than smaller holes. Therefore, we were afraid that patients treated with ocriplasmin might have a disadvantage compared to patients who had had no treatment. We decided to figure this out, at least in our department,” Ricarda G. Schumann, MD, lead study author, told Ocular Surgery News.

Because of the need to extend the analysis to a larger number of patients and to pool patients for more reliable results, seven other German university centers were involved and the study was converted into a multicenter study.

Ricarda G. Schumann

Study results

A total of 72 eyes of 72 patients who underwent pars plana vitrectomy for full-thickness macular hole between December 2013 and December 2015 were included. In 37 eyes, pharmacological vitreolysis had been previously and unsuccessfully attempted. The other 35 eyes were those of patients who had been offered Jetrea (ocriplasmin, ThromboGenics) injection but chose to proceed directly to surgery.

“Not rarely patients refuse ocriplasmin because it entails waiting for at least 4 weeks before seeing if the hole has closed or not. If it has not closed, this time adds up to the approximately 8 weeks that are normally needed for full recovery after vitrectomy. Patients who have busy lives and want to get back to work as early as possible often prefer to do surgery right away,” Schumann said.

When patients hear from a frank discussion with their doctor that the chances of macular hole closure with ocriplasmin are no more than 50% in the most favorable cases, often they consider these chances too low to be worth so much waiting.

Regarding the study, Schumann said that in 31 of the 37 eyes the hole diameter had enlarged after ocriplasmin injection, mostly in cases in which release of the VMT had been achieved. Success rate after vitrectomy surgery, however, was 97%, which is comparable to the 94% success rate obtained in the vitrectomy-only group. Visual acuity improved in both groups, also achieving comparable results.

“We also matched the patients by age and macular hole diameter, and again matched pairs showed no difference,” Schumann said.

Patient expectations

“I see ocriplasmin as a very important option in VMT, where it plays a major role as a treatment. [Macular hole] is an entirely different situation, as I can tell from the studies and from my own clinical experience,” Schumann said.

While ocriplasmin releases VMT in the majority of eyes, the success rate in macular hole closure does not exceed 40% to 50% in eyes with a small-diameter macular hole and decreases to 15% to 20% in medium-sized macular hole.

“This is an important distinction to make, something we should be aware of if we deal on one hand with patients who have just a pure vitreomacular traction and on the other hand with patients where this is associated with macular hole,” she said.

The closing rate varies according to macular hole size: The smaller the hole, the higher the chances that it can be closed by ocriplasmin alone. Successful closure of medium-sized holes might occur in a minority of cases, but the chances of needing surgical intervention afterward remain high.

“This is why I have long discussions with the patients who might be candidates for ocriplasmin treatment for macular hole. They must be aware that the chances to be operated afterward are at least 50% and must be prepared to invest quite a lot of extra time to give ocriplasmin a chance,” Schumann said.

Patients should also be told that they are likely to experience changes in visual acuity or other disturbances, such as dysphotopsia, mostly lasting only a few hours, but in some cases a few days and in rare situations a couple of weeks.

“These problems are transient and resolve spontaneously. We learned over the years that they are no big concern,” Schumann said.

Time and experience have also dispelled the concern that ocriplasmin might modify the texture of the vitreous collagen in a way that could affect vitrectomy surgery afterward.

“It is not more difficult to do vitrectomy after ocriplasmin than it is in eyes that have not been treated previously. This is definitely not a real problem,” Schumann said.

Surgical timing

The waiting time between ocriplasmin injection and the decision to perform vitrectomy surgery should be 4 to 6 weeks, according to Schumann.

“Theoretically we could wait longer, but this is the time interval that we consider to be safe. Macular hole is not an emergency, and normally you can schedule vitrectomy surgery within 3 to 4 months from diagnosis. However, if patients had ocriplasmin treatment, and it did not work, you should not wait too long. Four weeks was the average time in our study. We schedule patients for surgery already at the time of ocriplasmin injection because canceling in case the treatment works is not a problem. In this way, we are sure we can proceed to surgery without delays when it is needed,” she said.

Ocriplasmin should not be routinely recommended for macular hole, but rather discussed with the patient as a possible option in specific cases, Schumann said. Macular hole size is one of the criteria but not the only one. The long time involved should be compatible with the patient’s life situation, and it is important to make sure that the patient has accepted the risk that the treatment might fail.

Good candidates are those with low vision in the fellow eye who are dependent on the eye with macular hole.

“In these cases, I often go for ocriplasmin first. The risks of surgery are always higher, and it is worth attempting the safer and less invasive option first,” Schumann said.

The choice is based on subjective considerations and previously published predictive factors. However, it appears that traction diameter as one of the most important predictive factors in ocriplasmin treatment might have potential for improvement as reliable criteria for diagnosis and patient selection.

“Our current diagnostic tools are not precise enough. VMT is always an area of traction, sometimes the sum of multiple areas of traction, but we measure just the diameter of largest vitreomacular adhesion site. What we need is a three-dimensional evaluation of the vitreomacular traction, which requires new means to measure the area rather than the diameter. By relying on the diameter, we assume that VMT is a circle, which it is not in most cases,” Schumann said.

In an ongoing study, Schumann and colleagues have found that in a significant number of cases the actual area of traction differs greatly from the circle area that was calculated from the diameter, and a significant number of eyes showed a wider range of traction areas compared with what was measured based on diameter.

“All studies so far have relied on the diameter; therefore, we do not have accurate measurements. Although it is not proven yet, I believe this could possibly impact outcome prediction,” Schumann said. “Future advances in the technology will help us develop more reliable methods for evaluating individual cases and more precise criteria for patient selection, which will enable us to make a more frequent and effective use of ocriplasmin in our clinical practice.” – by Michela Cimberle

Disclosure: Schumann reports no relevant financial disclosures.

A study published by the German EXPORT study group came to reassuring conclusions concerning vitrectomy surgery in eyes in which previous ocriplasmin treatment for macular hole has failed. The functional and anatomical results were comparable in these eyes to those of eyes that proceeded directly to surgery without ocriplasmin treatment.

“We noticed that eyes treated with ocriplasmin, in which the vitreomacular traction (VMT) had been released but the macular hole had not closed, often show an enlargement of the diameter of the hole. During recent years, diameter was discussed as a prognostic factor, as larger holes seemed to have lower vision after surgery than smaller holes. Therefore, we were afraid that patients treated with ocriplasmin might have a disadvantage compared to patients who had had no treatment. We decided to figure this out, at least in our department,” Ricarda G. Schumann, MD, lead study author, told Ocular Surgery News.

Because of the need to extend the analysis to a larger number of patients and to pool patients for more reliable results, seven other German university centers were involved and the study was converted into a multicenter study.

Ricarda G. Schumann

Study results

A total of 72 eyes of 72 patients who underwent pars plana vitrectomy for full-thickness macular hole between December 2013 and December 2015 were included. In 37 eyes, pharmacological vitreolysis had been previously and unsuccessfully attempted. The other 35 eyes were those of patients who had been offered Jetrea (ocriplasmin, ThromboGenics) injection but chose to proceed directly to surgery.

“Not rarely patients refuse ocriplasmin because it entails waiting for at least 4 weeks before seeing if the hole has closed or not. If it has not closed, this time adds up to the approximately 8 weeks that are normally needed for full recovery after vitrectomy. Patients who have busy lives and want to get back to work as early as possible often prefer to do surgery right away,” Schumann said.

When patients hear from a frank discussion with their doctor that the chances of macular hole closure with ocriplasmin are no more than 50% in the most favorable cases, often they consider these chances too low to be worth so much waiting.

Regarding the study, Schumann said that in 31 of the 37 eyes the hole diameter had enlarged after ocriplasmin injection, mostly in cases in which release of the VMT had been achieved. Success rate after vitrectomy surgery, however, was 97%, which is comparable to the 94% success rate obtained in the vitrectomy-only group. Visual acuity improved in both groups, also achieving comparable results.

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“We also matched the patients by age and macular hole diameter, and again matched pairs showed no difference,” Schumann said.

Patient expectations

“I see ocriplasmin as a very important option in VMT, where it plays a major role as a treatment. [Macular hole] is an entirely different situation, as I can tell from the studies and from my own clinical experience,” Schumann said.

While ocriplasmin releases VMT in the majority of eyes, the success rate in macular hole closure does not exceed 40% to 50% in eyes with a small-diameter macular hole and decreases to 15% to 20% in medium-sized macular hole.

“This is an important distinction to make, something we should be aware of if we deal on one hand with patients who have just a pure vitreomacular traction and on the other hand with patients where this is associated with macular hole,” she said.

The closing rate varies according to macular hole size: The smaller the hole, the higher the chances that it can be closed by ocriplasmin alone. Successful closure of medium-sized holes might occur in a minority of cases, but the chances of needing surgical intervention afterward remain high.

“This is why I have long discussions with the patients who might be candidates for ocriplasmin treatment for macular hole. They must be aware that the chances to be operated afterward are at least 50% and must be prepared to invest quite a lot of extra time to give ocriplasmin a chance,” Schumann said.

Patients should also be told that they are likely to experience changes in visual acuity or other disturbances, such as dysphotopsia, mostly lasting only a few hours, but in some cases a few days and in rare situations a couple of weeks.

“These problems are transient and resolve spontaneously. We learned over the years that they are no big concern,” Schumann said.

Time and experience have also dispelled the concern that ocriplasmin might modify the texture of the vitreous collagen in a way that could affect vitrectomy surgery afterward.

“It is not more difficult to do vitrectomy after ocriplasmin than it is in eyes that have not been treated previously. This is definitely not a real problem,” Schumann said.

Surgical timing

The waiting time between ocriplasmin injection and the decision to perform vitrectomy surgery should be 4 to 6 weeks, according to Schumann.

“Theoretically we could wait longer, but this is the time interval that we consider to be safe. Macular hole is not an emergency, and normally you can schedule vitrectomy surgery within 3 to 4 months from diagnosis. However, if patients had ocriplasmin treatment, and it did not work, you should not wait too long. Four weeks was the average time in our study. We schedule patients for surgery already at the time of ocriplasmin injection because canceling in case the treatment works is not a problem. In this way, we are sure we can proceed to surgery without delays when it is needed,” she said.

PAGE BREAK

Ocriplasmin should not be routinely recommended for macular hole, but rather discussed with the patient as a possible option in specific cases, Schumann said. Macular hole size is one of the criteria but not the only one. The long time involved should be compatible with the patient’s life situation, and it is important to make sure that the patient has accepted the risk that the treatment might fail.

Good candidates are those with low vision in the fellow eye who are dependent on the eye with macular hole.

“In these cases, I often go for ocriplasmin first. The risks of surgery are always higher, and it is worth attempting the safer and less invasive option first,” Schumann said.

The choice is based on subjective considerations and previously published predictive factors. However, it appears that traction diameter as one of the most important predictive factors in ocriplasmin treatment might have potential for improvement as reliable criteria for diagnosis and patient selection.

“Our current diagnostic tools are not precise enough. VMT is always an area of traction, sometimes the sum of multiple areas of traction, but we measure just the diameter of largest vitreomacular adhesion site. What we need is a three-dimensional evaluation of the vitreomacular traction, which requires new means to measure the area rather than the diameter. By relying on the diameter, we assume that VMT is a circle, which it is not in most cases,” Schumann said.

In an ongoing study, Schumann and colleagues have found that in a significant number of cases the actual area of traction differs greatly from the circle area that was calculated from the diameter, and a significant number of eyes showed a wider range of traction areas compared with what was measured based on diameter.

“All studies so far have relied on the diameter; therefore, we do not have accurate measurements. Although it is not proven yet, I believe this could possibly impact outcome prediction,” Schumann said. “Future advances in the technology will help us develop more reliable methods for evaluating individual cases and more precise criteria for patient selection, which will enable us to make a more frequent and effective use of ocriplasmin in our clinical practice.” – by Michela Cimberle

Disclosure: Schumann reports no relevant financial disclosures.

    Perspective
    Timothy L. Jackson

    Timothy L. Jackson

    The study performed by the EXPORT group demonstrated that failed ocriplasmin treatment does not adversely affect the outcome of subsequent macular hole surgery. This might indeed encourage clinicians to try ocriplasmin in suitable cases of macular hole.

    As the authors acknowledged, this is a medium-sized retrospective study and not a large randomized controlled trial. Thus, bias and confounding are a possibility. However, if one accepts these limitations, the results are nonetheless of interest, as they offer some reassurance that ocriplasmin may be a reasonable option for small macular holes with persisting vitreomacular adhesion.

    • Timothy L. Jackson, FRCOphth, PhD
    • King's College London

    Disclosures: Jackson reports no relevant financial disclosures.