EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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Dosing therapy for maximum effect Claxton reviewed 76 compliance studies that measured dosing through electronic monitoring. Mean dose-taking compliance was 71%±17% (range 34%–97%) and declined as the number of daily doses increased: 1 dose = 79%±14%, 2 doses = 69%±15%, 3 doses = 65%±16%, 4 doses = 51%±20% (P<0.001 among dose schedules). Compliance was significantly higher for once-daily versus 3-times-dai- ly (P=0.008), once-daily versus 4-times-daily (P<0.001), and twice daily versus 4-times-daily regimens (P=0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-daily and 3-times-daily regimens. In the subset of 14 studies that reported dose-timing results, mean dose-tim- ing compliance was 59%±24%; more frequent dosing was associated with lower compliance rates. 16 Patient compliance in the real world The science behind these medica- tions and their ophthalmic delivery is moot if patients do not adhere to the treatment regimen. Real world noncompliance is relatively high. 17– 19 In one study of 500 patients in Canada, Kholdebarin et al. found an overall 27.9% noncompliance with ocular therapeutics: 28.8% con- taminated the bottle tip and 33.8% demonstrated improper technique. 17 Winfield et al. found 69% of patients would refuse to tell their doctor about problems with drop adminis- tration even when directly asked. 19 Although the majority of patient compliance studies are concentrated on chronic illnesses such as glauco- ma, it has been noted that treatment duration of under 5 years increased patient-reported noncompliance. 17 Avoiding cystoid macular edema In today's environment, nepafenac and bromfenac are indicated for once-daily use, which should improve compliance and, there- fore, reduce postoperative events, 18 including cystoid macular edema (CME). 20–22 At our center, we evaluated the last 42 cases of clinically proven CME with optical coherence tomog- raphy. Follow-up was 1 year from time of detection. Our goal was to determine how easily treated CME is, the expense associated with treat- ment (see Figure 2), and the time to resolution. At last follow-up, only 14% had best corrected visual acuity (BCVA) of 20/20 or better, 26% were 20/40 or worse, and 1 patient was 20/100. We also found 31% pro- gressed to a permanent epiretinal membrane. At Wake Forest, our prophy- lactic treatment regimen includes prescribing an NSAID 2 days before cataract surgery and having patients continue for 30 days postop. Since implementing this regimen, our in- cidence of CME is about 1 in 1,000. We are currently evaluating NSAIDs alone (without the concomitant use of a steroid postop). To date: • 1 case in 1,300 when bromfenac 0.07% was used • 2 cases in 2,000 when bromfenac 0.09% was used • Ongoing analysis with nepafenac 0.3% alone All our patients have had good refractive outcomes. NSAIDs have been well estab- lished at reducing inflammation and decreasing postop pain. We are now finding they are also capable of pr - venting CME; none of the currently marketed NSAIDs are approved in the U.S. for CME prophylaxis. References 1. Ghate D, Edelhauser HF. Ocular drug deliv- ery. Expert Opin Drug Deliv. 2006;3(2):275–87. 2. Gaudana R, Ananthula HK, Parenky A, Mitra AK. Ocular drug delivery. AAPS J. 2010;12(3):348–60. 3. Coffey MJ, Decory HH, Lane SS. Develop- ment of a non-settling gel formulation of 0.5% loteprednol etabonate for anti-inflamm tory use as an ophthalmic drop. Clin Ophthalmol. 2013;7:299–312. 4. McGhee CN. An overview of topical oph- thalmic drugs and the therapeutics of ocular infection. Auckland, NZ, 2012. 5. Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002;28(5):473–93. 6. Shirasaki Y. Molecular design for enhancement of ocular penetration. J Pharm Sci. 2008;97(7):2462–96. 7. Barar J, Javadzadeh AR, Omidi Y. Ocular novel drug delivery: impacts of membranes and barriers. Expert Opin Drug Deliv. 2008;5(5):567–81. 8. Robin AL, Novack GD, Covert DW, et al. Ad- herence in glaucoma: objective measurements of once-daily and adjunctive medication use. Am J Ophthalmol. 2007;144(4):533–40. 9. Cho H, Wolf KJ, Wolf EJ. Management of ocular inflamm tion and pain following cata- ract surgery: focus on bromfenac ophthalmic solution. Clin Ophthalmol. 2009;3:199–210. 10. Ilevro [package insert]. Fort Worth, Texas: Alcon Laboratories Inc., 2013. 11. Lotemax gel [package insert]. Tampa, FL: Bausch & Lomb Incorporated, 2012. 12. Durezol [package insert]. Fort Worth, Texas: Alcon Laboratories Inc., 2013. 13. Bowman LM, Si E, Pang J, et al. Development of a topical polymeric mucoad- hesive ocular delivery system for azithromy- cin. J Ocul Pharmacol Ther. 2009;25(2):133–9. 14. Cantor LB. Ophthalmic generic drug approval process: implications for effica y and safety. J Glaucoma. 1997;6(5):344–9. 15. Mammo ZN, Flanagan JG, James DF, Trope GE. Generic versus brand-name North American topical glaucoma drops. Can J Ophthalmol. 2012;47(1):55–61. 16. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310. 17. Kholdebarin R, Campbell RJ, Jin YP, Buys YM. Multicenter study of compliance and drop administration in glaucoma. Can J Ophthalmol. 2008;43(4):454–61. 18. Richter A, Anton SE, Koch P, Dennett SL. The impact of reducing dose frequency on health outcomes. Clin Ther. 2003;25(8): 2307–35; discussion 6. 19. Winfield AJ, Jessiman D, Williams A, Esakowitz L. A study of the causes of non-compliance by patients prescribed eye- drops. Br J Ophthalmol. 1990;74(8):477–80. 20. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc. 1998;96:557–634. 21. Ray S, D'Amico DJ. Pseudophakic cystoid macular edema. Semin Ophthalmol. 2002;17(3–4):167-80. 22. Sahin M, Cingu AK, Gozum N. Eval- uation of cystoid macular edema using optical coherence tomography and fundus autofluorescence after uncomplic ted phacoemulsific tion surgery. J Ophthalmol. 2013;2013:376013. Dr. Walter is professor of ophthalmology, Wake Forest University in Winston-Salem, N.C. Supported by an unrestricted educational grant from Bausch + Lomb Figure 2. Medicare allowable payments. Medicare allowable payments (cost in U.S. dollars, North Carolina 2014 Revised Medicare Part B Fee Schedule) for services related to the diagnosis and treatment of CME. STK = sub-Tenon's triamcinolone; IVK = intravitreal triamcinolone; PPV = pars plana vitrectomy; EP = epiretinal membrane peel