Medical, surgical advances rising to challenge of persistent epithelial defects

Take-home message: Autologous serum drops, amniotic membrane, and scleral lenses offer advanced options for management of persistent epithelial defects refractory to standard treatment modalities.

By Cheryl Guttman Krader; Reviewed by Bennie H. Jeng, MD

Baltimore-Advanced medical and surgical approaches are helping to address the challenge of treating persistent epithelial defects (PED).

In addition, several novel investigational strategies are also showing promise for the management of this uncommon, but potentially sight-threatening condition, said Bennie H. Jeng, MD.

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“Conventional medical management of PED can be arduous for the ophthalmologist and a burden on the patient,” said Dr. Jeng, professor and chairman, Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore.

“Surgical options exist when standard medical therapies fail, but several advanced treatment modalities have been proven to be very useful,” he said. “Should all else fail, experimental approaches are also under investigation and showing promise for helping our most challenging cases.”

NEXT: A systematic approach

The first consideration to achieve healing of a PED is to identify and control any underlying etiology, such as exposure keratopathy or other eyelid abnormalities.

A second general principle is to withdraw medications that are potentially toxic to the corneal epithelium.

“The latter strategy is often overlooked because the focus is on treating with medications rather than taking them away,” Dr. Jeng said.

Treatment for PED may be initiated with standard medical approaches based on frequent use of preservative-free lubricants with or without punctal occlusion, a soft bandage contact lens, or pressure patching.

If the PED does not heal, epithelial debridement may be an effective technique that works by removing thickened, stagnant epithelium from the borders of the defect, which may be acting as a barrier to the migration of healthy cells.

Tarsorrhaphy can also be an effective surgical option for promoting PED healing. Use of a conjunctival flap or limbal stem cell transplantation in eyes with stem cell deficiency are other surgical options.

In the past 10 to 15 years, several advanced options have been introduced for managing PED refractory to conventional methods. Successful treatment of PED with autologous serum was first described by Tsubota et al. in 1999. Using 20% autologous serum 6 to 10 times/day, 44% of 16 eyes healed within 2 weeks, and almost two-thirds of eyes healed by 1 month.

NEXT: Amniotic membrane technique

Dr. Jeng-in a paper written with William J. Dupps Jr., MD, PhD-reported slightly higher healing rates using 50% autologous serum drops to treat 25 eyes. Other investigators have achieved similar or better outcomes as well, he noted.

“We found the time to healing increased proportionally as the time between PED onset and autologous serum treatment initiation increased,” Dr. Jeng said. “That relationship suggests a potential role for using autologous serum as early aggressive management of corneal epithelial defects to prevent development of PED in eyes at high risk.”

Results of some published controlled studies support that approach, he noted. Treatment with autologous serum has been reported to expedite graft re-epithelialization after penetrating keratoplasty-particularly in patients with diabetes-and to accelerate closure of corneal epithelial abrasions created for better intraoperative visualization in diabetic patients undergoing vitrectomy.

Amniotic membrane technique

Application of amniotic membrane offers another advanced technique for managing PED. It is available as both fresh-frozen (Amnion, Bio-Tissue) and freeze-dried tissue (Ambiodry2, IOP Ophthalmics) and also with a self-retaining PMMA device (ProKera, Bio-Tissue Inc.).

The advantage of the freeze-dried tissue in that it has a much longer shelf life, Dr. Jeng noted.

He said he personally prefers the frozen tissue, and he fixates it onto the ocular surface at the limbus with a single running 8-0 Vicryl suture in a purse-string fashion. After trimming the edges, the amniotic membrane is covered with a contact lens.

NEXT: Scleral lens technique

Placement of a scleral lens has also demonstrated efficacy for healing PED. When using this technique, lenses of at least 17.5 mm diameter should be chosen since the smaller diameter, mini-scleral lenses do not completely vault over the cornea.

The larger-diameter scleral lenses are available from a variety of manufacturers or as the custom-manufactured PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem, Boston Foundation for Sight).

Other advances

Modalities under investigation for treatment of PED include thymosin beta 4 and a connexin43 antisense gel (Nexagon, CoDa Therapeutics)-both of which have shown promise in compassionate-use cases.

Thymosin beta 4 is a synthetically produced copy of a 43-amino acid peptide that is found in most tissues and has been shown to promote corneal wound re-epitheliailziation, decrease inflammation, and inhibit apoptosis.

The connexin43 antisense agent decreases the upregulation of connexin proteins that mediate bystander cell death (apoptosis induced by dying epithelial cells).

Mesenchymal stem cells-which are autologous adipose-derived multipotent cells-and a variety of products derived from whole blood are also being investigated for promoting epithelial healing.

Reference

1. Katzman LR, Jeng BH. Management strategies for persistent epithelial defects of the cornea. Saudi J Ophthlamol. 2014;28:168-172.

Bennie H. Jeng, MD

E: bjeng@som.umaryland.edu

This article was adapted from Dr. Jeng’s presentation during Cornea Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Jeng is a consultant to Jade Therapeutics, Kedrion, and Santen.