Anterior Segment, Ocular Immunology
Read Time: 2 mins

Nepafenac in the Prevention and Treatment of Ocular Inflammation and Pain Following Cataract Surgery and in the Prevention of Post-operative Macular Oedema in Diabetic Patients

Copy Link
Published Online: May 22nd 2012 European Ophthalmic Review, 2012;6(3):169–72 DOI:
Authors: Marco Nardi
Quick Links:
Article Information

Nepafenac ophthalmic suspension is a topical non-steroidal anti-inflammatory drug (NSAID) approved in the US and Europe for prevention and treatment of post-operative pain and inflammation associated with cataract surgery, and recently approved in Europe for reduction in risk of post-operative macular oedema associated with cataract surgery in diabetic patients. Unlike conventional NSAIDs, nepafenac is a prodrug that is uncharged and this results in great corneal permeability. Experimental studies on nepafenac demonstrated enhanced permeability compared with other NSAIDs, and rapid bioactivation to amfenac by intraocular hydrolases within ocular tissues including ciliary body epithelium, retina, choroid and cornea, which results in targeted delivery of active drug to anterior and posterior segments. Furthermore, these study results have been confirmed in clinical trials. Nepafenac may have prolonged activity in vascularised tissues of the eye because bioconversion is targeted to the iris/ciliary body, and to a greater extent the retina and choroid. Nepafenac and amfenac are potent inhibitors of cyclo-oxygenase (COX) enzyme isoforms, COX-1 and COX-2. Topical nepafenac penetrated into the posterior segment in a rabbit model of concanavalin-A induced retinal inflammation, where it diminished vitreous protein and prostaglandin E2 concentrations and reduced breakdown of the blood–retinal barrier. Other NSAIDs, including ketorolac, failed to reduce the increase of these inflammatory markers in the same study. A randomised clinical study showed that based on retinal thickening and vision, treatment with nepafenac beginning pre-surgery and used for up to 90 days post-cataract surgery is effective in preventing macular oedema and associated loss of visual acuity in diabetic patients.


Non-steroidal anti-inflammatory drugs (NSAIDs), cataract surgery, pain, inflammation, nepafenac, prodrug, permeability


During ophthalmic surgery, surgical trauma causes activation of cyclo-oxygenase (COX) COX-1 and COX-2, which metabolise arachidonic acid to prostaglandins (PGs). PGs are mediators of the inflammatory response, and increased production of these molecules can result in discomfort, pain and ocular inflammation. As inhibitors of PGs, non-steroidal anti-inflammatory drugs (NSAIDs) are often employed by ophthalmic surgeons to provide anti-inflammatory control post-surgery and work synergistically with steroid therapy to minimise pain and inflammation following ocular surgery,1,2 albeit by different mechanisms. NSAIDS primarily act on cyclo-oxygenase-1 (COX-1) and COX-2 to minimise PG formation,3 and while steroids also reduce PG synthesis, this is due to the inhibition of phospholipase A2.4

Moreover, NSAID treatment has been demonstrated to have a beneficial effect on visual outcomes,5 preventing macular oedema after cataract surgery, however, it is essential to attain therapeutic concentrations in the posterior chamber to obtain the effect of NSAID treatment on the target retina tissue. Thus, for maximum therapeutic benefit, the ideal NSAID is one that reaches therapeutic levels in both the aqueous humour and in the posterior segment tissues. Nepafenac is a NSAID with a unique prodrug structure that has superior corneal permeability to other currently available NSAIDs.6 This review aims to consider the properties, existing efficacy and safety data, other possible indications of nepafenac in inflammation treatment and the advantages it provides over existing NSAIDs in cataract surgery.

Mode of Action of Nepafenac
Nepafenac has a unique prodrug structure and is converted to a potent cyclo-oxygenase inhibitor, amfenac, by intraocular hydrolases (see Figure 1).6,7 Upon ocular dosing, nepafenac permeates the cornea, is metabolised by intraocular tissues8 and is converted into amfenac for optimal efficacy. The prodrug mechanism of action maximises bioactivation to amfenac in the iris, ciliary body, retina, choroid and cornea to a lesser extent, making nepafenac a target-specific NSAID.9 xperimental studies on nepafenac demonstrated properties of enhanced permeability and rapid bioactivation to amfenac, to inhibit PG synthesis in the anterior and posterior eye segments.7

To view the full article in PDF or eBook formats, please click on the icons above.

Article Information:

Marco Nardi has participated in the European registration study of nepafenac and has given presentations on this for which he has received honoraria.


Marco Nardi, Ophthalmology Unit, Neuroscience Department, University of Pisa, Via Roma 56, IT-56100 Pisa, Italy. E:


The publication of this article was funded by Alcon. The views and opinions expressed are those of the author and not necessarily those of Alcon.




  1. Flach AJ, Discussion by Allan J. Flach, MD, Ophthalmology, 2000;107:2039.
  2. Heier JS, Topping TM, Baumann W, et al., Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema, Ophthalmology, 2000;107:2034-8;discussion 2039.
  3. Kim SJ, Flach AJ, Jampol LM, Nonsteroidal anti-inflammatory drugs in ophthalmology, Surv Ophthalmol, 2010;55:108–33.
  4. Flower RJ, Blackwell GJ, Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation, Nature, 1979;278:456–9.
  5. Samiy N, Foster CS, The role of nonsteroidal antiinflammatory drugs in ocular inflammation, Int Ophthalmol Clin, 1996;36:195–206.
  6. Lindstrom R, Kim T, Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac, Curr Med Res Opin, 2006;22:397–404.
  7. Ke TL, Graff G, Spellman JM, Yanni JM, Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers, Inflammation, 2000;24:371–84.
  8. Gamache DA, Graff G, Brady MT, et al., Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy, Inflammation, 2000;24:357–70.
  9. O'Brien TP, Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care, Curr Med Res Opin, 2005;21:1131–7.
  10. Heaton J, Hiddemen JW, Hackett RB, et al., Ocular Effects of Nepafenac Ophthalmic Suspension Following Six Months of Topical Ocular Administration to Pigmented Rabbits, Invest Ophthalmol Vis Sci, 2005;46:2650.
  11. Walker LM, Rice RL, Heaton JD, et al., Ocular Effects of Nepafenac Ophthalmic Suspension Following Three Months of Topical Ocular Administration to Cynomolgus Monkeys, Invest Ophthalmol Vis Sci, 2005;46:2649.
  12. Hariprasad SM, Sanders M, Chastain J, et al., Periocular Distribution of Nepafenac and Amfenac after Topical Administration of Nepafenac in the Rabbit, Invest Ophthalmol Vis Sci, 2009;50:5999.
  13. Walters T, Raizman M, Ernest P, et al., In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac, J Cataract Refract Surg, 2007;33:1539–45.
  14. Lane SS, Modi SS, Lehmann RP, Holland EJ, Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery, J Cataract Refract Surg, 2007;33:53–8.
  15. Nardi M, Lobo C, Bereczki A, et al., Analgesic and anti–inflammatory effectiveness of nepafenac 0.1% for cataract surgery, Clin Ophthalmol, 2007;1:527–33.
  16. Kapin MA, Yanni JM, Brady MT, et al., Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac, Inflammation, 2003;27:281–91.
  17. Menchini U, Bandello F, Brancato R, et al., Cystoid macular oedema after extracapsular cataract extraction and intraocular lens implantation in diabetic patients without retinopathy, Br J Ophthalmol, 1993;77:208–11.
  18. Dowler JG, Sehmi KS, Hykin PG, Hamilton AM, The natural history of macular edema after cataract surgery in diabetes, Ophthalmology, 1999;106:663–8.
  19. Pollack A, Leiba H, Bukelman A, Oliver M, Cystoid macular oedema following cataract extraction in patients with diabetes, Br J Ophthalmol, 1992;76:221–4.
  20. Krepler K, Biowski R, Schrey S, et al., Cataract surgery in patients with diabetic retinopathy: visual outcome, progression of diabetic retinopathy, and incidence of diabetic macular oedema, Graefes Arch Clin Exp Ophthalmol, 2002;240:735–8.
  21. Singh RP, Alpern LM, Lehmann RP, et al., Comparison of Nepafenac 0.1% with vehicle in prevention of macular edema following cataract surgery in diabetic retinopathy patients, Abstract. Presented at: American Society of Cataract and Refractive Surgery, San Diego, CA, US, 25–29 March 2011.
  22. Flach AJ, Topical nonsteroidal antiinflammatory drugs in ophthalmology, Int Ophthalmol Clin, 2002;42:1–11.
  23. Nevanac 1 mg/ml eye drops, suspension. Summary of product characteristics. Available at: _Product_Information/human/000818/WC500027158.pdf (accessed 13 April 2012).
  24. McGee DH, Heaton JD, Gruebbel MM, et al., Ocular Effects of Nepafenac Ophthalmic Suspension in New Zealand White Rabbits Undergoing Partial Corneal Incisions, Invest Ophthalmol Vis Sci, 2005;46:2648.
  25. ClinicalTrials.Gov, NSAID Phase II for Non-central Involved Diabetic Macular Edema (DME) #NCT01331005. Available at: nac&rank=24 (accessed 27 June 2012).
  26. Future sight loss UK (2): An epidemiological and economic model for sight loss in the decade 2010 to 2020. Report prepared for RNIB by Darwin Minassian and Angela Reidy. EpiVision, 2009. Available at: FSUK_2.pdf (accessed 24 February 2012).

Further Resources

Share this Article
Related Content In Ocular Immunology
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72