Case Study

Adding Nepafenac 0.1% to Resolve CME

BY STEPHEN S. LANE, M.D.

An 84-year-old man with a 27-year history of aphakia in his only eye became contact-lens intolerant due to discomfort of his rigid aphakic contact lens. The opposite eye had been blind since early childhood secondary to trauma.

Following a thorough discussion of the risks and alternatives, a secondary 20.5 D anterior chamber Kelman 4-point fixated lens was placed following a pars plana vitrectomy. The secondary IOL implantation and pars plana vitrectomy surgery were uncomplicated. Postoperatively, the patient had been placed on moxifloxacin 0.5% (Vigamox, Alcon) t.i.d. for 1 week, nepafenac 0.1% (Nevanac, Alcon) t.i.d. for 4 weeks and loteprednol etabonate 0.5% (Lotemax, B&L) for 4 weeks. When seen 1 month postoperatively, a BCVA of 20/25 was obtained and all eye meds were discontinued.

Postop Evaluation and Treatment

Four months later (5 months postop), the patient returned for evaluation due to decreased visual acuity (VA) that had developed over the last month. Clinical examination at that time demonstrated a BCVA of 20/60. The cornea was clear and there was no anterior segment inflammation noted. The IOL was in excellent position. There were no vitreous cells and the retina was flat. The macula demonstrated cysts within the foveal avascular zone, which was confirmed with OCT (Figure 1). Retinal thickness measured by OCT was 460 μm.

The diagnosis of cystoid macular edema (CME) was made and the patient was started on nepafenac 0.1% and prednisolone acetate 1%, both q.i.d. The patient was seen again 2 weeks later and he reported that VA was much improved. Indeed VA had improved to his pre-CME baseline of 20/25. His examination was unremarkable and there was no clinical CME. OCT also showed resolution of the CME (Figure 2) with a retinal thickness of 283 μm.

Figure 1. With CME: Pre-nepafenac 0.1% suspension; visual acuity: 20/60 BCVA; and retinal thickness: 460 μm.

The nepafenac 0.1% was reduced to b.i.d. and the prednisolone acetate 1% was discontinued. The patient was re-examined 2 months later and the examination was unchanged with a BCVA of 20/25. Nepafenac 0.1% was continued b.i.d. and the patient was re-examined 4 months later and then again 6 months later with no change in the examination and no evidence of corneal toxicity. The patient remains on nepafenac 0.1% b.i.d. and will remain so indefinitely with periodic examinations at 6-month intervals.

Figure 2. Resolved CME: Post-nepafenac 0.1% suspension; visual acuity: 20/25 VA; and retinal thickness: 283 μm.

Comments and Recommendations

Cystoid macular edema occurs in about 10% to 12% of uncomplicated cataract and IOL surgery.¹ Risk factors for CME include: preexisting ocular inflammation, epiretinal or vitreoretinal interface membrane problems, diabetic retinopathy, patients suffering from ocular vascular or cardiovascular disease and patients with history of retinitis pigmentosa.

Prophylaxis treatment should be started earlier and extended longer for these high-risk patients.² McColgin et al. demonstrated that steroids alone are not as effective as NSAIDs in the prevention or treatment of CME.¹ Similarly Warren et al. have shown that treatment with topical nepafenac 0.1% with or without concomitant steroids reduced retinal thickness and improved VA in patients with acute and chronic CME.³

The case presented illustrates these concepts nicely. The patient was at higher risk for CME due to manipulation of the vitreous at the time of secondary IOL implantation and possibly more associated inflammation. Addition of nepafenac 0.1% resolved the CME and improved visual acuity as a result.

Nepafenac 0.1% is a novel nonsteroidal anti-inflammatory prodrug that is converted to a potent cyclooxygenase inhibitor, amfenac, by intraocular hydrolases. Uncharged molecules of nepafenac allow for better permeation through the cornea,⁴ unlike the positively charged molecules of other commercially available topical NSAIDs. As a result, concentrations of Nevanac achieved in the aqueous humor are excellent.⁵

One concern with all topical NSAIDs is corneal toxicity. Symptoms include burning and irritation, superficial punctate keratitis, delayed wound healing,⁶ corneal thinning and even perforation due to melts.⁷ However, multiple clinical trials have shown nepafenac 0.1% to be safe with no delays in wound healing⁸ and a low incidence of adverse events which was no different than vehicle.⁹ For these reasons I feel comfortable with the long term usage of nepafenac 0.1% for chronic conditions or patients I feel are at high risk for the redevelopment of CME like the patient described here.

Effectiveness of NSAIDs

In summary, topical NSAIDs are effective in preventing post-surgical CME and have also been shown to have a beneficial effect on visual function.¹⁰ While steroids may be a synergistic adjunct to NSAIDs they are not as effective as NSAIDS in the prevention and treatment of CME. Finally, while we must always be aware of the potential corneal complications associated with topical NSAIDs, the safety profile is sufficiently good (especially with ongoing clinical monitoring) that I believe NSAIDs should become a part of the medical surgical prophylaxis regimen used in all cataract surgery and for the initial treatment of post-surgical CME. OM

References

1. McColgin AZ, Raizman MB. Efficacy of topical Voltaren in reducing the incidence of post operative cystoid macular edema. Invest Ophthmol Vis Sci. 1999;40:S289.
2. Heier, JS. Preventing post-cataract extraction CME: Early identification of patients at risk and prophylactic treatment may avert vision loss. Ophthalmology Management. 2004;8(10):63-72.
3. Warren K, Harisprasad S, Callanan D, Gainer S. Treatment of acute and chronic cystoid macular edema With nepafenac 0.1%. Invest Ophthalmol Vis Sci. 2007;48: ARVO E-Abstract B711.
4. Lindstrom R, Kim T. Nepafenac: ocular permeation and inhibition of retinal inflammation: An examination of data and opinion of clinical utility. Curr Med Res & Opin. 2006;22:397-404.
5. Walters TR, Raizman M, Ernest P, et al. A double-masked, randomized, single-dose, pharmacokinetic study of nepafenac, amfenac, ketorolac, and bromfenac in Human aqueous humor following topical administration of Nevanac, Acular LS, or Xibrom. Invest Ophthalmol Vis Sci. 2007;48: ARVO E-Abstract B1035.
6. Flach, AJ. Topical nonsteroidal antiinflammatory drugs in ophthalmology. Int Ophthalmol Clin. 2002;42:1-11.
7. Prescribing Information: Voltaren; Acular; Acular LS
8. Donnenfeld ED, Durrie DS, Holland EJ, Raizman MB. A double-masked study of nepafenac 0.1% and ketorolac 0.4% for pain and epithelial healing following PRK. Accepted for presentation to the American Academy of Ophthalmology, November 11-14, 2006, Las Vegas, NV.
9. Nevanac suspension [package insert]. Fort Worth, TX: Alcon Labs, 2006.
10. Samiy N, Foster CS. The role of nonsteroidal antiinflammatory drugs in ocular inflammation. Int Ophthalmol Clin. 1996;36:195-206.

Stephen S. Lane, M.D., is a cornea/external disease fellowship trained board certified ophthalmologist and clinical professor of ophthalmology at the University of Minnesota. Dr. Lane is actively involved in clinical research, having participated in over 35 national clinical trials investigating new products for cataract and refractive surgery. He is a consultant for Alcon.