TOPICAL NEPAFENAC 0.1% FOR TREATMENT OF CHRONIC UVEITIC CYSTOID MACULAR EDEMA Seenu M. Hariprasad, MD,* David Callanan, MD†
Purpose: To describe the efficacy of nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc.) for treating cystoid macular edema (CME) resulting from uveitis. Design: Interventional case series Methods: Three patients with a history of decreased visual acuity due to uveitic CME despite previous treatment with topical steroids or traditional nonsteroidal antiinflammatory drugs, intravitreal triamcinolone acetonide (Kenalog; Bristol–Myers Squibb), or immunosuppressive agents were given topical nepafenac 0.1%. Patients were monitored for clinical improvement, decreased retinal thickness by optical coherence tomography, and improved Snellen visual acuity. Results: For all three patients, treatment with topical nepafenac for 4 weeks to 3 months led to improvement in visual acuity and decrease in retinal thickness. Conclusions: The improved visual acuity and decreased retinal thickness in these patients suggest that nepafenac is an effective treatment of inflammation and CME in the posterior segment of the eye for patients with chronic uveitis. RETINAL CASES & BRIEF REPORTS 2:304 –308, 2008
that nepafenac may have efficacy for treating retinal or posterior segment inflammation.2,4 This case series describes the efficacy of nepafenac in treating three patients with chronic uveitic CME.
From the *Vitreoretinal Service, Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois; and †Texas Retina Associates, Arlington, Texas.
C
ystoid macular edema (CME) due to inflammation of the retina is a common cause of decreased visual acuity that often responds poorly to traditional nonsteroidal antiinflammatory drugs or steroids.1 Nepafenac (Nevanac; Alcon Laboratories, Inc.) is a novel topical nonsteroidal antiinflammatory drug approved for treatment of pain or inflammation associated with cataract surgery.2,3 Nepafenac is a prodrug that undergoes intraocular conversion to the active agent amfenac.4,5 In vitro and animal studies suggest
Case Reports Case 1 A 42-year-old black man with chronic bilateral CME secondary to pars planitis initially presented with visual acuity of 20/80 in the right eye and 20/100 in the left eye after previous nonsteroidal antiinflammatory drug therapy with topical Predforte (Allergan Pharmaceuticals) 1% and Acular LS (Allergan Pharmaceuticals) (Figs. 1–5). The patient received treatment with intravitreal triamcinolone acetonide ([4 mg] Kenalog; Alcon Laboratories, Inc.) in the left eye but returned to the clinic after 3 weeks with intraocular pressure of 56 mmHg that was treated with three intraocular pressure–lowering drugs to achieve intraocular pressure of 22 mmHg and visual acuity of 20/25 (Fig. 6). To avoid the complications of elevated intraocular pressure in the right eye, the patient was treated with topical nepafenac 0.1% three times daily in the right eye for 3 months. There was a significant reduction in CME measured by optical coherence tomography
Supported by Research to Prevent Blindness, Inc. (New York, NY). Neither author received direct funding from Alcon Laboratories, Inc., for involvement in this project. Reprint requests: Seenu M. Hariprasad, MD, Department of Ophthalmology and Visual Science, University of Chicago, 5841 South Maryland Avenue (MC 2114), Chicago, IL 60637; e-mail: [email protected]
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Fig. 1. Funduscopic examination of the right eye showing cystoid macular edema due to chronic pars planitis and blunted foveal reflex.
and improvement in visual acuity to 20/20 after topical nepafenac treatment (Fig. 7).
Case 2 A 26-year-old man with a 3-year history of bilateral intermediate uveitis treated with oral prednisone (10 mg) and cyclosporine (100 mg) daily was seen for regular follow-up. Visual acuity was 20/25 in the right eye and 20/40 in the left eye despite the systemic medical therapy. Visual acuity in the left eye was limited to 20/40 due to cumulative damage. The patient had clinically visible CME in the right eye with retinal thickness of 358 m and 243 m in the left eye. The patient received topical therapy with nepafenac 0.1% in both eyes twice daily and after 6 weeks reported subjective improvement in vision. Improvement in CME was observed with retinal thickness of 220 m in the right eye and 224 m in the left eye.
Fig. 2. Funduscopic examination of the left eye showing cystoid macular edema due to chronic pars planitis and blunted foveal reflex.
Fig. 3. Early-phase fluorescein angiogram of the right eye demonstrating foveal petaloid leakage.
Case 3 A 44-year-old woman with a 6-year history of pars planitis previously treated with mycophenolate, periocular injections, and intraocular triamcinolone acetonide in the right eye and steroidinduced glaucoma requiring three topical intraocular pressure– lowering medications presented with decreased vision (20/40) in the right eye, CME, mild cells in the posterior chamber, and a mild posterior subcapsular cataract in both eyes. Treatment with nepafenac 0.1% twice daily was initiated in the right eye with slight improvement, but increased floaters were observed in the left eye after 1 month. After increasing nepafenac treatment to 3 times daily bilaterally, her symptoms resolved, and visual acuity improved to 20/25 in each eye, with normal foveal reflex in each eye.
Discussion CME is thought to be due to increased prostaglandin-mediated vascular permeability. Nepafenac is
Fig. 4. Middle-phase fluorescein angiogram of the left eye demonstrating foveal petaloid leakage.
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Fig. 5. Optical coherence tomography demonstrating increased central retinal thickness in excess of 650 m in each eye due to intraretinal cystic edema and small foveal serous retinal detachments (November 2005).
converted into the active drug amfenac by amidases in the iris/ciliary body and choroid/retina.4,5 The rate of hydrolysis of nepafenac to amfenac in the rabbit is ⬇20-fold greater in the retina/choroid than the cornea.5 In addition, the rate of corneal permeation of nepafenac is approximately fourfold faster than that of diclofenac.2,5 This increased absorption and intraocular activation should improve efficacy in the posterior chamber and minimize corneal irritation. Although the efficacy of nepafenac 0.1% for treating pain and inflammation due to cataract surgery has been established,2 the proposed clinical efficacy for alleviating posterior segment inflammation and CME
due to the pharmacodynamic differences of this drug compared with other nonsteroidal antiinflammatory drugs requires further study. The three patients described in this report had marked reduction in retinal edema, which resulted in improved visual acuity. These cases illustrate the efficacy of nepafenac 0.1% for treating uveitic CME that was otherwise resistant to traditional topical nonsteroidal antiinflammatory drugs or steroids. Acknowledgments Assistance in manuscript preparation was provided by Mary Ellen Shepard, PhD, and Alcon Laboratories, Inc.
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Fig. 6. Optical coherence tomography demonstrating increased central retinal thickness in excess of 650 m in the right eye due to intraretinal cystic edema and small foveal serous retinal detachment. The left eye had complete resolution of edema with restoration of normal foveal contour.
Fig. 7. Optical coherence tomography (OCT) of the right eye from December 2005 and March 2006 demonstrating complete resolution of intraretinal cystic edema and small foveal serous retinal detachment (before [left] and after [right] 3 months of topical treatment with nepafenac 0.1% in the right eye three times daily).
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References 1.
2.
3.
Kapin MA, Yanni JM, Brady MT, et al. Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation 2003;27:281–291. 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. O’Brien TP. Emerging guidelines for use of NSAID therapy to
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5.
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optimize cataract surgery patient care. Curr Med Res Opin 2005;21:1131–1137. 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 antiinflammatory efficacy. Inflammation 2000;24:357–370. 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;24:371–384.
Purpose: To describe the efficacy of nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories, Inc.) for treating cystoid macular edema (CME) resulting from uveitis. Design: Interventional case series Methods: Three patients with a history of decreased visual acuity due to uveitic CME despite previous treatment with topical steroids or traditional nonsteroidal antiinflammatory drugs, intravitreal triamcinolone acetonide (Kenalog; Bristol–Myers Squibb), or immunosuppressive agents were given topical nepafenac 0.1%. Patients were monitored for clinical improvement, decreased retinal thickness by optical coherence tomography, and improved Snellen visual acuity. Results: For all three patients, treatment with topical nepafenac for 4 weeks to 3 months led to improvement in visual acuity and decrease in retinal thickness. Conclusions: The improved visual acuity and decreased retinal thickness in these patients suggest that nepafenac is an effective treatment of inflammation and CME in the posterior segment of the eye for patients with chronic uveitis. RETINAL CASES & BRIEF REPORTS 2:304 –308, 2008
that nepafenac may have efficacy for treating retinal or posterior segment inflammation.2,4 This case series describes the efficacy of nepafenac in treating three patients with chronic uveitic CME.
From the *Vitreoretinal Service, Department of Ophthalmology and Visual Science, University of Chicago, Chicago, Illinois; and †Texas Retina Associates, Arlington, Texas.
C
ystoid macular edema (CME) due to inflammation of the retina is a common cause of decreased visual acuity that often responds poorly to traditional nonsteroidal antiinflammatory drugs or steroids.1 Nepafenac (Nevanac; Alcon Laboratories, Inc.) is a novel topical nonsteroidal antiinflammatory drug approved for treatment of pain or inflammation associated with cataract surgery.2,3 Nepafenac is a prodrug that undergoes intraocular conversion to the active agent amfenac.4,5 In vitro and animal studies suggest
Case Reports Case 1 A 42-year-old black man with chronic bilateral CME secondary to pars planitis initially presented with visual acuity of 20/80 in the right eye and 20/100 in the left eye after previous nonsteroidal antiinflammatory drug therapy with topical Predforte (Allergan Pharmaceuticals) 1% and Acular LS (Allergan Pharmaceuticals) (Figs. 1–5). The patient received treatment with intravitreal triamcinolone acetonide ([4 mg] Kenalog; Alcon Laboratories, Inc.) in the left eye but returned to the clinic after 3 weeks with intraocular pressure of 56 mmHg that was treated with three intraocular pressure–lowering drugs to achieve intraocular pressure of 22 mmHg and visual acuity of 20/25 (Fig. 6). To avoid the complications of elevated intraocular pressure in the right eye, the patient was treated with topical nepafenac 0.1% three times daily in the right eye for 3 months. There was a significant reduction in CME measured by optical coherence tomography
Supported by Research to Prevent Blindness, Inc. (New York, NY). Neither author received direct funding from Alcon Laboratories, Inc., for involvement in this project. Reprint requests: Seenu M. Hariprasad, MD, Department of Ophthalmology and Visual Science, University of Chicago, 5841 South Maryland Avenue (MC 2114), Chicago, IL 60637; e-mail: [email protected]
304
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Fig. 1. Funduscopic examination of the right eye showing cystoid macular edema due to chronic pars planitis and blunted foveal reflex.
and improvement in visual acuity to 20/20 after topical nepafenac treatment (Fig. 7).
Case 2 A 26-year-old man with a 3-year history of bilateral intermediate uveitis treated with oral prednisone (10 mg) and cyclosporine (100 mg) daily was seen for regular follow-up. Visual acuity was 20/25 in the right eye and 20/40 in the left eye despite the systemic medical therapy. Visual acuity in the left eye was limited to 20/40 due to cumulative damage. The patient had clinically visible CME in the right eye with retinal thickness of 358 m and 243 m in the left eye. The patient received topical therapy with nepafenac 0.1% in both eyes twice daily and after 6 weeks reported subjective improvement in vision. Improvement in CME was observed with retinal thickness of 220 m in the right eye and 224 m in the left eye.
Fig. 2. Funduscopic examination of the left eye showing cystoid macular edema due to chronic pars planitis and blunted foveal reflex.
Fig. 3. Early-phase fluorescein angiogram of the right eye demonstrating foveal petaloid leakage.
Case 3 A 44-year-old woman with a 6-year history of pars planitis previously treated with mycophenolate, periocular injections, and intraocular triamcinolone acetonide in the right eye and steroidinduced glaucoma requiring three topical intraocular pressure– lowering medications presented with decreased vision (20/40) in the right eye, CME, mild cells in the posterior chamber, and a mild posterior subcapsular cataract in both eyes. Treatment with nepafenac 0.1% twice daily was initiated in the right eye with slight improvement, but increased floaters were observed in the left eye after 1 month. After increasing nepafenac treatment to 3 times daily bilaterally, her symptoms resolved, and visual acuity improved to 20/25 in each eye, with normal foveal reflex in each eye.
Discussion CME is thought to be due to increased prostaglandin-mediated vascular permeability. Nepafenac is
Fig. 4. Middle-phase fluorescein angiogram of the left eye demonstrating foveal petaloid leakage.
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Fig. 5. Optical coherence tomography demonstrating increased central retinal thickness in excess of 650 m in each eye due to intraretinal cystic edema and small foveal serous retinal detachments (November 2005).
converted into the active drug amfenac by amidases in the iris/ciliary body and choroid/retina.4,5 The rate of hydrolysis of nepafenac to amfenac in the rabbit is ⬇20-fold greater in the retina/choroid than the cornea.5 In addition, the rate of corneal permeation of nepafenac is approximately fourfold faster than that of diclofenac.2,5 This increased absorption and intraocular activation should improve efficacy in the posterior chamber and minimize corneal irritation. Although the efficacy of nepafenac 0.1% for treating pain and inflammation due to cataract surgery has been established,2 the proposed clinical efficacy for alleviating posterior segment inflammation and CME
due to the pharmacodynamic differences of this drug compared with other nonsteroidal antiinflammatory drugs requires further study. The three patients described in this report had marked reduction in retinal edema, which resulted in improved visual acuity. These cases illustrate the efficacy of nepafenac 0.1% for treating uveitic CME that was otherwise resistant to traditional topical nonsteroidal antiinflammatory drugs or steroids. Acknowledgments Assistance in manuscript preparation was provided by Mary Ellen Shepard, PhD, and Alcon Laboratories, Inc.
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Fig. 6. Optical coherence tomography demonstrating increased central retinal thickness in excess of 650 m in the right eye due to intraretinal cystic edema and small foveal serous retinal detachment. The left eye had complete resolution of edema with restoration of normal foveal contour.
Fig. 7. Optical coherence tomography (OCT) of the right eye from December 2005 and March 2006 demonstrating complete resolution of intraretinal cystic edema and small foveal serous retinal detachment (before [left] and after [right] 3 months of topical treatment with nepafenac 0.1% in the right eye three times daily).
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References 1.
2.
3.
Kapin MA, Yanni JM, Brady MT, et al. Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac. Inflammation 2003;27:281–291. 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. O’Brien TP. Emerging guidelines for use of NSAID therapy to
4.
5.
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2008
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optimize cataract surgery patient care. Curr Med Res Opin 2005;21:1131–1137. 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 antiinflammatory efficacy. Inflammation 2000;24:357–370. 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;24:371–384.
