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Liquid bandage shows promise in sealing corneal wounds

By Linda Roach, Contributing Writer

Italian researchers have reported positive clinical results using a hydrogel-forming bioadhesive, OcuSeal, to seal and protect sutureless cataract incisions in the first days after surgery.

OcuSeal (BD Medical Ophthalmic Systems, Waltham, Mass., United States) received the CE mark for European use more than a year ago. However, the current study, which was conducted in 89 eyes, represents some of the first clinical results to be reported for this alternative to cyanoacrylate- and fibrin-based corneal adhesives.

The study's author, Matteo Piovella, MD, presented the results this year in Europe and at ASCRS. He is also scheduled to discuss the results at the American Academy of Ophthalmology’s Annual Meeting in Chicago in October. He and co-author Barbara Kusa, MD, practice at Centro di Microchirurgia Ambulatoriale in Monza, Italy. Dr. Piovella is president of the Italian Ophthalmological Society.

Improved patient comfort
“The results are very positive,” Dr. Piovella said. “There have been no complications, and the operated eyes were much more comfortable during the one-day postoperative period.”

OcuSeal was applied unilaterally over the side port and main incisions of 89 patients at the conclusion of cataract surgery. The results were compared with 72 eyes with untreated clear corneal incisions from cataract surgery. 

The timetable for seeking FDA approval to sell OcuSeal in the United States is uncertain because Bectin, Dickinson and Company, the product's manufacturer, is in the process of selling its ophthalmics division to an investment firm.

Meanwhile, the maker of another self-gelling biodendrimer for sealing corneal wounds, ReSure Adherent Ocular Bandage (Ocular Therapeutix, Bedford, Mass.), is hoping to beat OcuSeal into the U.S. market, by gaining FDA marketing approval later this year. 

On-the-spot polymerization
OcuSeal is a biodendrimer that forms when its two components, polyethylene glycol (PEG), an ester in powder form, and poly(ethylenimine) (PEI), a water-soluble amine, are mixed together inside a small cylindrical applicator. The surgeon must break a seal separating the liquid and powder, mix them for about 10 seconds and then quickly spread the mixture over the incision with the applicator tip.

The liquid interacts with the underlying tissue to form a transparent, smooth, low-profile hydrogel seal. It has a water content of 85 percent and a pore size of 1 to 3 µm. This hydrogel bandage persists for two to three days, degrading by hydrolysis at roughly the same rate that the tissue beneath it heals.

In animal- and cadaver-eye studies of 23-gauge vitrectomy with 2.8 mm clear corneal incisions, OcuSeal-covered wounds did not leak or burst despite intraocular pressures of up to 246.2 mm Hg. ^1,2

Timing is critical
The timing is the trickiest part of the procedure, Dr. Piovella said. After the mixing is complete, the surgeon must apply the liquid within about 15 seconds before crosslinking transforms the mixture into a hydrogel.

In 16 of the 89 study eyes, the first attempt to apply OcuSeal failed when time ran out, and the surgeon had to mix a new batch, Dr. Piovella said.

“My learning curve was long because there was not enough experience in the initial trials to indicate the most efficient timetable,” Dr. Piovella said. “Now we know that the liquid and powder should be mixed for 10 seconds before use, instead of the 5 seconds originally recommended.”

No "foreign-body" feeling
“Usually on day one, a high percentage of cataract patients report feeling an uncomfortable foreign-body sensation. But 85 percent of the OcuSeal patients said that the eye with the liquid bandage was more comfortable than their other eye. They did not have this sensation,” Dr. Piovella said.

During three months of follow-up, the study subjects had no complications or adverse events, he said. When Dr. Piovella accidentally applied a little too much OcuSeal to some corneas during the study, the excess disappeared in all cases within 12 hours, apparently because of eye blinking, he said.

Some research suggests that the ease of use and nontoxic, nonimmunogenic nature of a self-assembling biodendrimer give it advantages over cyanoacrylate adhesives and fibrin-based glues. It also does not require laser light to initiate the polymerization, as do some biodendritic hydrogels in development.⁴

Talk of a new paradigm
After studying one of the self-assembling biodendrimers, Duke University and Boston University researchers wrote in 2009: “The experimental data does [sic] demonstrate that, theoretically, corneal adhesives specifically tailored for ophthalmic use could offer a practical alternative to sutures and represent a paradigm shift in wound closure.”¹

Dr. Piovella’s clinical study convinced him that this paradigm shift might be here already for cataract wounds if surgery centers can afford the cost. He now uses OcuSeal routinely after cataract surgery. The cost is about 25 euros per batch, which treats a single eye, he said.

Patient comfort on the first postop day was an important reason for his decision, he said. However, he also hopes that OcuSeal might be the easy-to-use “magic bullet” that prevents endophthalmitis after cataract surgery.

Barrier for bacteria?
Increasingly, studies have implicated unsealed clear-corneal incisions as a possible cause of endophthalmitis.⁶ Researchers suggest that rapid IOP fluctuations, such as those that might happen with eye rubbing, can cause unhealed cataract wounds to gape, allowing conjunctival fluid and bacteria into the eye.^7-9

Dr. Piovella said he cannot currently demonstrate that OcuSeal has the potential to decrease the risk of endophthalmitis, and a large number of cases would be required to detect any effect. However, he sees the use of OcuSeal at the close of cataract surgery as beneficial whether or not it provides this protection.

“If OcuSeal does prevent these horrible infections, then I will be protecting my patients’ eyes. And, at the least, this will help me serve my patients better by giving them greater comfort after surgery,” he said.

REFERENCES
1. Johnson CS, Wathier M, Grinstaff M, Kim T. In vitro sealing of clear corneal cataract incisions with a novel biodendrimer adhesive. Arch Ophthalmol. 2009;127(4):430-434.
2. Maddula S, Davis DK, Ness PJ, Olson RJ. A comparison of wound strength with and without hydrogel liquid ocular bandage in human cadaver eyes. Poster presentation at: The American Society of Cataract and Refractive Surgery meeting; April 2010; Boston, MA.
3. Berdahl JP, Johnson CS, Proia AD, Grinstaff MW, Kim T. Comparison of sutures and dendritic polymer adhesives for corneal laceration repair in an in vivo chicken model. Arch Ophthalmol. 2009;127(4):442-447.
4. Degoricija L, Johnson CS, Wathier M, Kim T, Grinstaff MW. Photocrosslinkable biodendrimers as ophthalmic adhesives for central lacerations and penetrating keratoplasties. Invest Ophthalmol Vis Sci. 2007;48(5):2037-2042.
5. Kim T, Kharod BV. Tissue adhesives in corneal cataract incisions. Curr Opin Ophthalmol. 2007;18(1):39-43.
6. Lundström M. Endophthalmitis and incision construction. Curr Opin Ophthalmol. 2006;17(1):68-71.
7. McDonnell PJ, Taban M, Sarayba M, et al. Dynamic morphology of clear corneal cataract incisions. Ophthalmology. 2003;110(12):2342-2348.
8. Sarayba MA, Taban M, Ignacio T, Behrens A, McDonnell PJ. Inflow of ocular surface fluid through clear corneal cataract incisions: a laboratory model. Am J Ophthalmol. 2004;138(2):206-210.
9. Taban M, Sarayba MA, Ignacio TS, Behrens A, McDonnell PJ. Ingress of India ink into the anterior chamber through sutureless clear corneal cataract wounds. Arch Ophthalmol. 2005;123(5):643-648.

CONFLICT OF INTEREST
Dr. Piovella is a consultant for Abbott Medical Optics and BD Medical Ophthalmic Systems. BD has announced plans to sell its ophthalmic unit this fall to an investment partnership to which Dr. Piovella has no ties.