Pulsed corticosteroid regimen reduces postoperative ocular inflammation

Eric D. Donnenfeld

A novel dosing protocol for a topical steroid prevented inflammation after cataract surgery, a study found.

Durezol (difluprednate ophthalmic emulsion 0.05%, Alcon) administered in a high-dose pulsed therapy regimen protected the cornea and minimized macular thickening more effectively than did prednisolone acetate 1%, the current standard of care, the study authors said.

Difluprednate also sped visual recovery and yielded high patient satisfaction.

Eric D. Donnenfeld, MD, OSN Cornea/External Disease Board Member and lead study author, attributed the safety and efficacy of difluprednate to a neuroprotective effect associated with high-dose pulsed corticosteroids.

“The take-home message is that pulse-dosing with a strong corticosteroid improves visual outcomes because of the neuroprotective effect of a stronger steroid and that the use of difluprednate was superior to prednisolone acetate in providing a rapid return of vision, protecting the cornea and reducing macular thickening following cataract surgery,” Dr. Donnenfeld told Ocular Surgery News.

Treatment, visual acuity, IOP

The study included 104 eyes of 52 patients who underwent bilateral phacoemulsification. Eyes were randomized to receive difluprednate 0.05% in one eye and prednisolone acetate 1% in the other.

“It was a self-controlled bilateral eye trial, which is the most scientifically sound way of evaluating a medication,” Dr. Donnenfeld said.

Patients received seven corticosteroid doses over 2 hours preoperatively and three doses before discharge, followed by dosing every 2 hours for the remainder of the first postoperative day. Corticosteroids were then administered four times daily for 1 week and then twice daily for the subsequent week.

Corneal pachymetry, corneal edema, visual acuity and IOP were evaluated preoperatively and at 1, 15 and 30 days after surgery. Endothelial cell counts were evaluated before surgery and 30 days after surgery, and retinal thickness was evaluated preoperatively and at 15 and 30 days after surgery.

Study results showed that at day 1, nineteen patients in the difluprednate group and six patients in the prednisolone group had best corrected visual acuity of 20/20.

“We want our patients to have a return of uncorrected visual acuity in a safe and effective manner,” Dr. Donnenfeld said. “This is the way all of ophthalmology is moving. A significant advantage of pulsed-dosing steroids is providing these patients with a refractive result as quickly as possible.”

IOP increased an average of 3.52 mm Hg in the difluprednate-treated eyes and 2.92 mm Hg in the prednisolone-treated eyes on day 1. However, the IOP spike was resolved in both groups at 15 days. IOP in both groups was statistically similar at all follow-up points.

“This showed that it’s also safe and confirmed the data from the [U.S. Food and Drug Administration] trial of difluprednate,” Dr. Donnenfeld said.

Corneal, retinal outcomes

On day 1, mean central corneal thickness increased from 562 µm to 590 µm in the difluprednate-treated eyes and from 562 µm to 619 µm in the prednisolone-treated eyes. Average central corneal thickness was 32.59 µm lower in the difluprednate-treated eyes than in the prednisolone-treated eyes (P = .026).

“This was statistically significant. There was dramatically less corneal edema in patients who received difluprednate,” Dr. Donnenfeld said.

There were no statistically significant differences in central corneal thickness at other follow-up points, he said.

Mean endothelial cell density decreased 8% in difluprednate-treated eyes and 17% in prednisolone-treated eyes from baseline to 30 days after surgery.

At day 15, mean retinal thickness was 7.74 µm less in the difluprednate-treated eyes than in the prednisolone-treated eyes (P = .001). Retinal thickness increased 11.66 µm less in the difluprednate-treated eyes than in the prednisolone-treated eyes at 15 days (P < .0001).

“I think the important finding was where [difluprednate] protected against retinal edema, especially in diabetic patients,” Dr. Donnenfeld said.

He attributed lower corneal and retinal thickness in the difluprednate-treated eyes to the neuroprotective property of high-dose steroids commonly used in neurosurgery.

“The corneal endothelium is neuro-ectoderm, as are the ganglion cells of the retina, which are identical to brain cells or to spinal cord cells,” Dr. Donnenfeld said. “There has been a long history of the use of high-dosed pulse corticosteroid in treating brain trauma and spinal cord injuries. I think this study shows that the same idea behind using pulsed steroids in neurosurgery also applies to ophthalmology, where pulsed-dosing provides a neuroprotective effect.” – by Matt Hasson

References:

• Donnenfeld ED, Holland EJ, Solomon KD, et al. A multicenter randomized controlled fellow eye trial of pulse-dosed difluprednate 0.05% versus prednisolone acetate 1% in cataract surgery [published online ahead of print June 24, 2011]. Am J Ophthalmol. doi:10.1016/ajo.2011.03.018.
• Donnenfeld ED. Difluprednate for the prevention of ocular inflammation postsurgery: an update. Clin Ophthalmol. 2011;5:811-816.

• Eric D. Donnenfeld, MD, can be reached at Ophthalmic Consultants of Long Island, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; email: eddoph@aol.com.
• Disclosure: Dr. Donnenfeld is a consultant for Alcon, Allergan and Bausch + Lomb.

In this study, the authors utilized intense steroid therapy before and immediately after cataract surgery, an idea stimulated by lessons learned from spinal cord injury protocols. However, the control employed was a corticosteroid with less intraocular penetration but the same intense dosing schedule, leaving unanswered the question of relative benefit of a higher potency corticosteroid vs. a more intense dosing regimen. We can look forward to follow-up investigations exploring these issues and intriguing findings.

– Roger F. Steinert, MD
OSN Cornea/External Disease Board Member
Disclosure: Dr. Steinert has no relevant financial disclosures.