Enzyme-assisted membrane peeling may be an effective alternative for stage 3 macular holes

Eight of nine eyes achieve spontaneous, intraoperative, posterior vitreous separation.

Issue: March 1, 2000

ByBob Kronemyer

ORLANDO, Fla. — Enzymatic manipulation of the vitreoretinal juncture for the management of stage 3 macular holes may lead to excellent results, while reducing time and expense, according to a pilot study of nine eyes that were treated by injection with four international units of autologous plasmin enzyme.

“We chose to work with plasmin enzyme, a nonspecific protease, initially because of its effects on laminin and fibrinectin,” said senior author Michael T. Trese, MD, a retinal specialist in private group practice in Royal Oak, Mich. To a large degree, these two molecules are responsible for the adhesion between the anterior retina and the posterior hyaloid. “We then learned the enzyme’s effects on fibrin, collagenase and transforming growth factor (TGF) beta and basic fibroblasts growth factor (FGF), in addition to its manipulation of matrix metalloproteinases 2 and 9,” Dr. Trese said.

Dr. Trese said he and his associates are pioneers in chemical vitrectomy. This can result in a posterior vitreous detachment without mechanical suction or manipulation of the posterior hyaloid.

In the study, autologous plasmin was used as a surgical adjunct in macular hole surgery, together with irrigation with a vitreous cutter and an 80% fluid-gas exchange. “In order to generate a simplified technique that could even be an office procedure, we felt we had to eliminate meticulous, mechanical manipulation of the vitreoretinal juncture,” Dr. Trese said.

Study design

The technique was tested in nine eyes of eight patients (ages 61 to 82, average 66). Extensive testing ruled out posterior vitreous separation. Average follow-up was 23 months (range 6 to 48 months). Four holes were larger than 500 µm and, in two eyes, and the hole was present for more than 12 months.

Overall, eight of the nine eyes had a vitreous detachment throughout the entire macula. In addition, liquefaction in the vitreous cavity during surgery was graded as small (less than 25%) in five eyes, medium (25% to 50%) in all eyes and large (greater than 50%) in two eyes. All nine holes were closed at the last follow-up visit.

Average visual improvement was four lines. Preoperative visual acuities, which ranged from 20/70 to 20/400, improved to between 20/20 and 20/200. Four eyes achieved 20/30 or better. “The least improvement appeared to be in larger holes of longer duration, a common finding in macular hole surgery,” Dr. Trese said.

Two complications

The first eye undergoing the procedure did not receive postoperative steroids and developed a small hypopyon (less than 3%). “The patient had minimal irrigation,” Dr. Trese said. “We think that the hypopyon was due to the partially digested collagen, which resulted in a foreign body reaction.” Interestingly, though, the patient was phakic, had 48 months of follow-up and achieved 20/25 vision. “The lens and visual acuity have remained stable over that period,” Dr. Trese said. Another patient experienced a retinal break near one of the entry wounds, which was successfully repaired and the patient achieved 20/30 vision.

Despite the limitations of this feasibility study, “I believe it demonstrates that we may be able to find an acceptable enzymatic vitreous manipulation of the vitreoretinal juncture that would allow us to do this procedure at some point in an office setting,” Dr. Trese said.

Multiple goals

Jay S. Duker, MD, who at the annual American Academy of Ophthalmology meeting held here critiqued the study, noted that using autologous plasmin enzyme during macular hole surgery has six potential goals: reducing the suction levels (and, therefore, the traction on the retina when surgically inducing a posterior vitreous detachment); minimizing the need for the delicate and difficult dissection of the internal limiting membrane; decreasing operating time; improving visual out-come; decreasing complications; and enabling macular hole surgery to become an office-based procedure.

“The authors’ results are impressive enough that further study should be vigorously pursued,” Dr. Duker said. Because 89% of eyes showed a spontaneous, intraoperative, posterior vitreous separation, “this strongly suggests that intravitreal plasmin can significantly reduce the suction levels necessary in this surgery, thereby minimizing both retinal trauma and operating time,” he said.

On the other hand, “the fact that one eye suffered a retinal detachment is disturbing,” Dr. Duker said. “Retinal detachment is a known complication of macular hole surgery, with a reported incidence between 1% and 14%. However, if plasmin can nontraumatically create a posterior vitreous detachment, its use should minimize the risks of retinal detachment.” In any event, “it is premature to suggest that retinal detachment will be a problem with this technique,” he said.

Still, the potential for a postoperative inflammatory response, such as one mimicking endophthalmitis, is a genuine concern. “Severe postoperative inflammation occurring in a significant percentage of patients treated with intravitreal plasmin would limit the usefulness of this method,” Dr. Duker said.

Cost also was not addressed by the authors. “When the authors proceed with a large-scale, controlled, clinical trial, a cost-benefit analysis will definitely be in order,” Dr. Duker said.

For Your Information:

Michael T. Trese, MD, can be reached at 3535 W. 13 Mile, Ste. 632, Royal Oak, MI 48073; (248) 288-2280; fax: (248) 288-5644. Dr. Trese has no direct financial interest in any of the products mentioned, nor is he a paid consultant for any company mentioned.

Jay S. Duker, MD, can be reached at the New England Eye Center, 750 Washington St., Box 450, Boston, MA 02111; (617) 636-4604; fax: (617) 636-4866; e-mail: jay.dukerdes@nemc.org. Dr. Duker has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.