Refractive: Drug Therapy Year in Review

By Lynda Charters; Reviewed by Jonathan Talamo, MD

Boston-An important drug therapy finding in 2013 was evidence that topical besifloxacin 0.6% (Besivance, Bausch + Lomb) used off-label as prophylaxis before PRK causes significant problems with healing of the corneal epithelium and delayed recovery of vision following the refractive procedure.

Jonathan Talamo, MD, and colleagues Kathryn Hatch, MD, and Emily Woodcock, FAOI, reported their evidence in Cornea (2013;32:1365-1368).

“We found that when we applied besifloxacin under a bandage contact lens at the time of surgery in the presence of an epithelial defect there were significant problems with impaired healing, prolonged re-epithelization, corneal haze, pain, and inflammation that ultimately led to scarring and some loss of vision in certain cases,” said Dr. Talamo, associate clinical professor of ophthalmology, Harvard Medical School, Boston.

After laser vision correction with surface ablation, standard medication regimens use off-label topical antibiotic prophylaxis until the epithelium heals.

Besifloxacin was a new drug used by Dr. Talamo and colleagues in the post-PRK treatment regimen. Their records of the use of the drop indicated problems with corneal epithelial healing after PRK in 7 eyes of 4 patients despite no other changes in the practice’s medication protocols use perioperatively.

All of the affected patients reported having substantial pain and photophobia 4 days postoperatively. The specific subjective complaints recorded in the medical records were ocular discomfort for prolonged periods postoperatively.

One patient complained of substantial photophobia 4 weeks after surgery, wheras another complained of photophobia for 1 week and foreign body sensation in the right eye for 2 weeks. A third patient had light sensitivity and pain that was described as hurting while blinking, foreign body sensation, and scratchiness in the operative eye for 1 week. The last patient complained of pain in both eyes for 1 week and photophobia for 1 month.

When Dr. Talamo and colleagues retrospectively reviewed the medical records of 7 eyes of the 4 patients treated with besifloxacin 0.6% applied under their bandage contact lens after PRK, they found that the drug was associated with delayed epithelial closure ranging from 5 and 13 days (mean, 8.85 ± 2.91 days; range, 5 to 13 days).

Substantial haze (grade 1 or greater) developed in 6 of the 7 affected eyes; 4 eyes of 3 patients had persistent haze 3 months postoperatively; grade 2 haze was present in 3 of the 4 eyes 6 months or longer postoperatively; the fourth eye had grade 1 haze at 6 months.

One patient continues to have grade 2+ haze in both eyes, a decreased best-spectacle corrected visual acuity (BSCVA) in both eyes, and glare 2 years postoperatively.

A second patient had grade 2 haze in the right eye 9 months postoperatively but the BSCVA was unaffected.

A third patient had grade 2 haze at 6 months after surgery, but the visual acuity was not affected.

The uncorrected visual acuity was 20/20 or better in only 1 eye of the 7 eyes under discussion 3 months postoperatively.

This was in contrast to 20/20 vision in 22 of the 23 eyes undergoing PRK on the same treatment dates in which besifloxacin 0.6% was either not used or placed on top of rather under the bandage contact lens at the end of surgery.

The best-corrected visual acuity (BCVA) recovered over an extended period. Six of the 7 eyes lost from 1 to 5 lines of BCVA 3 months postoperatively. Six months postoperatively, both eyes of one patient still had a 3-line loss of BCVA, at 2 years postoperatively, the same patient had a 1-line loss of BCVA compared with preoperatively.

Dr. Talamo and colleagues speculated that an ingredient in besifloxacin 0.6% (DuraSite) might be the culprit in these patients. This component prolongs the ability of besifloxacin to stay on the eye and it or similar vehicles might be toxic to the eye when applied under a bandage contact lens.

Another theory is that the vehicle may cause sustained contact of the drug and benzalkonium chloride 0.01%, the preservation, with the stroma and a healing epithelial defect. 

Dr. Talamo underscored the importance of awareness of the effects of besifloxacin in PRK patients as a public health issue. The American Society of Cataract and Refractive Surgery (ASCRS) Cornea and Refractive Surgery Committees issued an advisory in early 2013 urging caution against the use of such topical ophthalmic medications with vehicles that facilitate sustained release of drug in the presence of a corneal epithelial defect.

“All the patients treated with besifloxacin 0.6% on the stromal bed exhibited significant problems with corneal epithelial healing and delayed visual recovery. We caution the use of besifloxacin 0.6% underneath a bandage contact lens during PRK or other ocular surface surgeries requiring corneal epithelial debridement,” Dr. Talamo advised.

Jonathan Talamo, MD

E: jtalamo@lasikofboston.com

Dr. Talamo is a consultant to Abbott Medical Optics and OptiMedica.