Surface ablation and NSAIDs: Clinical studies on analgesia and wound healing

ByPaul J. Dougherty, MD

Nonsteroidal anti-inflammatory drugs are primarily used for analgesia in surface ablation, such as PRK, which can cause patients significant pain. The use of bandage contact lenses and topical NSAIDs can control the pain after PRK, and several studies demonstrate that NSAIDs are efficacious in terms of analgesia without causing a delay in epithelial healing.

Controlling pain

The use of bandage contact lenses and topical NSAIDs can control the pain after PRK.

— Paul J. Dougherty, MD

NSAIDs should be administered to patients undergoing LASIK or surface ablation. Study results show that pre- and perioperative use of NSAIDs minimizes the risk of pain during and after LASIK.¹ Because of this, I treat LASIK patients with NSAIDs preoperatively. One drop is placed while the patient is in the waiting room, one drop is placed just prior to the pass of the keratome and another is placed after the flap is repositioned.

I am more aggressive with NSAID treatment for patients undergoing PRK. In PRK, the epithelium is removed, causing increased patient discomfort. The NSAID should be administered after the bandage contact lens is applied, because using the NSAID prior to the bandage contact lens can affect postoperative healing. NSAIDs should be applied for a maximum of 2 or 3 days after surgery to provide adequate analgesia without affecting epithelial healing.

I have developed a technique for PRK procedures to minimize pain that differs from the technique used by many ophthalmologists. Before removing the epithelium, I apply a Weck-cel sponge (Medtronic, Jacksonville, Fla.) soaked with balanced salt solution (BSS) (Alcon, Fort Worth, Texas) that has been placed under sterile condition in the freezer overnight on the eye for 10 seconds. I then remove the epithelium and perform laser ablation. The next step is to take another sponge soaked in frozen BSS and place it in the stromal bed for 10 seconds, which minimizes pain and decreases the risk of haze. I use a high oxygen permeable bandage contact lens until the patient is re-epithelialized, typically between day 5 and day 6.

The patient receives comfort drops of 1% tetracaine, 15 drops per milliliter of artificial tears, and is instructed to use them up to four times a day for the first 72 hours. An internal study published by Dr. Michel Pop of Montreal found that this method of pain control did not have an adverse effect on epithelial healing. The comfort drops performed identically to artificial tears alone.²

Finally, I use an NSAID for 48 hours postoperatively, but some ophthalmologists use an NSAID for 72 hours postoperatively.

Analgesia and epithelial healing data

Multiple studies have been published regarding the use of NSAIDs in surface ablation. Donnenfeld and colleagues conducted a multicenter study comparing ketorolac 0.4% solution and nepafenac 0.1% suspension in terms of pain control and wound healing.³ Eighty eyes undergoing PRK were dosed with a topical NSAID three times a day for the first 3 days. At each time period, patients treated with nepafenac reported less pain than patients treated with ketorolac, and the difference was statistically significant by day 3 (Figure 1). The epithelial defect closure rates of nepafenac and ketorolac were identical, however.

Durrie and colleagues conducted a prospective, randomized study evaluating epithelial healing rates and pain control after PRK surgery.⁴ One of three NSAIDs, nepafenac 0.1% suspension, ketorolac 0.4% solution and bromfenac 0.09% solution, was administered three times a day for 1 week after PRK. Pain control was tested with a subjective, self- administered questionnaire on day 1 and 3. The study concluded that pain relief occurred sooner and there was a higher rate of pain decrease with nepafenac than with the other two NSAIDs (Figure 2). Nepafenac and ketorolac demonstrated similar epithelial healing rates by day 5; bromfenac demonstrated epithelial healing rates comparable to day 5 rates from nepafenac and ketorolac by day 7 (Figure 3).

Figure 1: Average pain scores following PRK
Figure 1. At day 3 postoperatively, nepafenac 0.1% suspension demonstrated significantly better pain control than ketorolac 0.4%.

Source: Data adapted from Donnenfeld ED, Holland EJ, Durrie DS, Raizman MB. Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy. Adv Ther. 2007;24:852-862.

Figure 2: Pain relief effects per treatment group
Figure 2. Mean pain relief occurred earlier in patients treated with nepafenac than in those treated with ketorolac or bromfenac.

Source: Data adapted from Durrie DS, Kennard MG, Boghossian AJ. Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK). Adv Ther. 2007;24:1260-1267.

Figure 3: Mean time to re-ephithelialization
Figure 3. Treatment with nepafenac 0.1% and ketorolac 0.4% demonstrated complete re-epithelialization in significantly fewer days when compared to eyes treated with bromfenac 0.09%.

Toyos compared wound healing with nepafenac 0.1% suspension and ketorolac 0.4% solution in epi-LASIK in which the flap was discarded after removal.⁵ The study of 22 eyes found no difference between the NSAIDs in terms of epithelial healing. Additionally, visual acuity and corneal haze scores were statistically equal between nepafenac and ketorolac at each postoperative visit.

Conclusions

NSAIDs are safe and efficacious when used judiciously in surface ablation, but I do not recommend using them for more than 2 or 3 days. Based on studies mentioned in this article, nepafenac offers faster and more effective pain control than ketorolac and bromfenac,^3,4 and nepafenac and ketorolac have similar rates of wound healing after surface ablation (Table).

Table. Multiple studies have been conducted regarding healing in surface ablation when patients are treated with NSAIDs.

References

Dougherty PJ. Acular LS for control of pain with LASIK: A prospective, randomized, masked contralateral eye trial. J Refract Surg. 2008 (In press).
Personal communication with Michel Pop, MD.
Donnenfeld ED, Holland EJ, Durrie DS, Raizman MB. Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy. Adv Ther. 2007;24:852-862.
Durrie DS, Kennard MG, Boghossian AJ. Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK). Adv Ther. 2007;24:1278-1285.
Toyos R. Comparison of nepafenac sodium 0.1% and ketorolac tromethamine 0.4% in postoperative healing in epi-LASIK patients. Paper presented at American Society of Cataract and Refractive Surgical Meeting. April 30, 2007; San Diego, Calif.
Reilly C, Caldwell M. Double-masked study of nepafenac 0.1% and placebo on pain relief and epithelial healing following PRK. Paper presented at the annual meeting of the American Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nev.
Colin J, Paquette B. Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: A phase II, randomized, double-masked trial. Clin Ther. 2006;28:527-536.