NSAIDS in the treatment of corneal disease

Case presentations for off-label use of NSAIDs

Topical NSAIDs for staphylococcus marginal hypersensitivity

I would like to present a case that demonstrates the successful use of an NSAID in the treatment of peripheral inflammatory keratitis caused by staphylococcus marginal hypersensitivity.

The patient was a 24-year-old male who presented with a 2-day history of photophobia and foreign body sensation. He had a prior history of frequent chalazia and presented with a visual acuity of 20/40. Focal limbal injection and a corneal infiltrate with breakdown of the overlying epithelium were present, although there were no white blood cells in the corneal stroma and no anterior chamber reaction. These findings were consistent with staphylococcal marginal hypersensitivity, which is generally manifested by chronic colonization of staphylococcus at the lid margin. In classic cases, fibrin collarettes will be present; however, this does not always occur. Patients also present with chalazia and phlyctenules due to bacterial exotoxins. Of note, the infiltrates are not infectious and are a Type IV sensitivity reaction caused by T lymphocytes; although neutrophils may cause further inflammation and irritation in later stages.

My previous approach to a case like this would have been to treat the patient with a topical steroid and antibiotic. However, several years ago I started using ketorolac with fairly good results. For this patient, I prescribed twice-daily bromfenac in combination with a topical fluoroquinolone. Eight days after treatment was initiated, the infiltrate completely resolved, the patient’s vision returned to 20/20 and the conjunctiva was quiet.

This case is a good example of the effective use of NSAIDs in place of steroids. I tend to avoid using topical steroids in patients with a herpetic history since the administration of these agents during late shedding of viral particles may allow the infection to develop by dampening the local immune response. Steroids should also be avoided in patients with glaucoma or polymicrobial infections.

NSAIDs for chemical keratitis

I would like to present a case of the effective use of a topical NSAID in a 57-year-old man who accidentally sprayed industrial cleansers in his left eye while cleaning a yacht in Florida. Immediately following the incident, the man was taken to the emergency room where his eye was irrigated with normal saline for 2 hours, which in itself can cause ocular surface irritation. The following day, he presented to my practice with significant ocular pain and 20/200 vision. His conjunctiva was red and irritated and his cornea lacked the normal lustrous appearance of a healthy eye. He had diffuse punctate epithelial keratopathy (PEK) with 1+ cells in the anterior chamber.

I prescribed twice-daily bromfenac and topical gatifloxacin. The patient was comfortable enough to return to work after 2 days of treatment. The patient’s condition improved substantially within 4 days of treatment. Corneal luster was restored, the anterior chamber cleared, there was less limbal injection and the patient’s vision improved to 20/60. By day 6 of treatment, the cornea was almost completely free of PEK, limbal injection was minimal, and the patient’s vision improved to 20/30. Treatment was stopped at day 10. When the patient returned several weeks later for follow-up, his vision was 20/20.

This case represents another good example of the clear benefits of NSAID therapy in specific clinical situations. Because the NSAID used in this case was highly effective when administered only twice a day, the patient was easily compliant with therapy. In my opinion, this strict compliance to therapy was a major factor in the rapid and successful resolution of his chemical keratitis. In addition, the patient missed only 2 days of work and did not require treatment with systemic analgesics. In the past, corneal abrasions were treated with a patch and oral opiates prescribed primarily by emergency room physicians. Patients were unable to return to work because of significant pain and side effects.

Discussion

William B. Trattler, MD: Dr. Schechter, why did you decide against using a steroid in the patient who presented with chemical conjunctivitis and keratitis?

Barry A. Schechter, MD: The patient’s ocular surface was compromised, and I did not want to risk compromising it further by administering a steroid. Although I had started him on an antibiotic, I was still concerned about this. Controlling both pain and inflammation with one medication was an optimal approach. It was also less expensive for the patient.

Trattler: I would have started with the steroid first; however, this case was interesting and will cause me to consider other options.

Schechter: The results in this patient were remarkable, and the inflammation resolved quickly.

Deepinder K. Dhaliwal, MD: Dr. Schechter, I have a question about the patient with the staphylococcus marginal keratitis. Did you use a mild steroid in addition to the bromfenac in this patient?

Schechter: No, I used only bromfenac. I know this sounds remarkable. It has been my experience that the anti-inflammatory effects of bromfenac are nearly equal to those of prednisolone acetate. As phase 3 trials of bromfenac have shown, this agent results in significant reduction of cells in the anterior chamber, which were initially present and rapidly reduced in the patient with chemical keratitis. I am impressed with this medication.

Roy S. Chuck, MD: The findings are exciting. Although I start with a steroid in my own patients, I am encouraged that another option is available.

Trattler: I also found your data on the dry eye patients to be interesting. I have a large dry eye practice and my current treatment algorithm is to start cyclosporine early and pulse the patients with a steroid for the first week or two of treatment. However, your data suggest that I could use a topical NSAID instead of the steroid. Or, do you use all three agents together?

Schechter: You could consider triple therapy, although I have rarely used a steroid since bromfenac has been in the marketplace. When I used ketorolac, my patients reported burning and stinging and I would occasionally use loteprednol etabonate or a similar medication with the NSAID.

Trattler: For my dry eye patients with moderate pain, the combination of cyclosporine and a steroid for 1 to 2 weeks usually leads to a 30% to 40% reduction in discomfort rates. Because patients report improvement, I believe that steroids are helpful in these cases. Has anyone else tried a nonsteroidal agent for dry eye?

Dhaliwal: We are using cyclosporine for dry eye with increasing frequency. This medication has been incredibly beneficial; however, it stings. I use a mild steroid during the induction phase of cyclosporine therapy because of the stinging. However, I think that the data just presented support the concomitant use of an NSAID in place of the steroid. Dr. Schechter, how many patients did you enroll in your study?

Schechter: There were 52 patients in the study; however, I have used this treatment approach in hundreds of patients.

Monte S. Dirks, MD: I would like to share a personal experience with my own case of episcleritis. I thought that cyclosporine was the ideal agent to use and one that would allow me to stop taking an oral NSAID. Then I decided to use bromfenac and cyclosporine together (as off-label usage), and the combination has worked well for me. Dr. Schechter, do you use an oral nonsteroidal agent in patients with episcleritis?

Schechter: I have used an oral NSAID in patients with recurrent disease. More specifically, I now tend to use bromfenac because of its long-term safety and efficacy demonstrated in Japan. In some cases, I use bromfenac once a day or once every other day; this dosing regimen seems to be adequate in keeping patients comfortable and inflammation under control.

Chuck: Dr. Schechter, in your study, did you also see early improvements in the corneal surfaces with bromfenac?

Schechter: Yes. I think this finding reflects a high level of patient compliance, although there may have been an additional anti-inflammatory effect.

Dhaliwal: Another benefit of twice-a-day dosing is that patients are exposed to less of the preservative benzalkonium chloride, which can cause further damage to already compromised corneas.

Chang: Do you add topical NSAIDs to steroids for increased comfort and inflammation suppression in post-surgical graft patients?

Chuck: I do not.

Dhaliwal: I do not use nonsteroidal agents in these patients because of concerns about their effects on the ocular surface.

Schechter: I have used NSAID therapy in these patients and I think it increased patient comfort. However, we watch these patients carefully in the first few weeks to ensure that the cornea re-epithelializes. If this process is impeded, I will stop the NSAID.

Dhaliwal: Surgeons must be careful because the cornea is completely denervated after a transplant.

Trattler: Dr. Schechter, do you also use an NSAID in your pterygium patients? Because I practice in South Florida, I see many patients with pterygium and I have been hesitant to use a nonsteroidal agent postoperatively.

Schechter: I have been using NSAIDs routinely in these patients for 12 years and have never had a complication.

Chang: I think that our collective experiences mirror those in other branches of medicine. The indications for NSAIDs are expanding, either as an adjunct to or replacement for steroids.

References

• Schechter BA, Wittpenn J. Evaluation of ketorolac 0.4% (ACULAR LS) during the induction phase of cyclosporin therapy to improve patient comfort. Presented at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO); May 1-5, 2005; Fort Lauderdale, Fla.