|Year : 2019 | Volume
| Issue : 3 | Page : 113-116
A comparative study between topical ophthalmic nepafenac (0.1%) and ketorolac (0.5%) for their analgesic and anti-inflammatory effects in postoperative senile cataract patients attending a tertiary care center in West Bengal
Prasanna Uday Patil1, Supriya Sudhir Pendke1, Mousumi Bandyopadhyay2, Purban Ganguly3
1 Department of Ophthalmology, GMC, Jalgaon, Maharashtra, India
2 Department of Ophthalmology, BMC, Burdwan, West Bengal, India
3 Department of Ophthalmology, Regional Institute of Ophthalmology, Kolkata, West Bengal, India
|Date of Submission||30-Jul-2018|
|Date of Acceptance||18-Mar-2019|
|Date of Web Publication||11-Dec-2019|
Supriya Sudhir Pendke
17, Shastri Lay Out, Subhash Nagar, Jaitala Road, Nagpur, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Ocular inflammation, which is common after cataract surgery, may cause patients to have postoperative pain and photophobia. Topical nonsteroidal anti-inflammatory drugs have been shown to be clinically effective in controlling inflammation after cataract surgery. Aim: The present study aims to compare topical ophthalmic nepafenac (0.1%) and ketorolac (0.5%) for their analgesic and anti-inflammatory effects in postoperative senile cataract patients. Materials and Methods: A total of 212 patients were included in the study and randomly allocated in two equal groups to receive either nepafenac (0.1%) or ketorolac (0.5%). Patients underwent cataract extraction on the scheduled date by manual small incision cataract extraction. The drug application was started on the day of operation. For both the groups, the drug was applied thrice daily. The ocular parameters were observed and noted down according to group assigned successively on day 1, day 3, day 7, day 14, and day 28. Results: There was no significant difference between the two drugs as far as visual acuity, and intraocular pressure outcome was concerned. The effect of nepafenac (0.1%) on anterior chamber cells and flare was more than ketorolac (0.5%) during 1st week (up to day 7), but at the end of the observation period (28 days), the effect was similar with both drugs. In nepafenac (0.1%) group, higher percentage of patients was free from pain and ocular discomfort than that of ketorolac (0.5%) group throughout the observation period. Conclusion: Nepafenac (0.1%) was found superior than ketorolac (0.5%) in dealing with ocular discomfort and pain and with respect to early recovery from anterior chamber inflammation.
Keywords: Cataract surgery, intraocular pressure, ketorolac, nepafenac, ocular inflammation, photophobia, visual acuity
|How to cite this article:|
Patil PU, Pendke SS, Bandyopadhyay M, Ganguly P. A comparative study between topical ophthalmic nepafenac (0.1%) and ketorolac (0.5%) for their analgesic and anti-inflammatory effects in postoperative senile cataract patients attending a tertiary care center in West Bengal. J Clin Ophthalmol Res 2019;7:113-6
|How to cite this URL:|
Patil PU, Pendke SS, Bandyopadhyay M, Ganguly P. A comparative study between topical ophthalmic nepafenac (0.1%) and ketorolac (0.5%) for their analgesic and anti-inflammatory effects in postoperative senile cataract patients attending a tertiary care center in West Bengal. J Clin Ophthalmol Res [serial online] 2019 [cited 2020 Sep 27];7:113-6. Available from: http://www.jcor.in/text.asp?2019/7/3/113/272711
Blindness, especially related to cataract, poses a major challenge all over the developing world. India, as one of the biggest developing countries, has a large number of blind people requiring sight-restoring cataract surgeries. Individuals undergoing cataract surgery should feel re-assured that it is an extremely safe surgery with a very low rate of complications. Wherever possible, careful postoperative follow-up with early detection and treatment of postoperative complications will allow a further improvement in outcome. Routine follow-up after 2 weeks and 8 weeks is recommended. An important cause of poor outcome is prolonged untreated postoperative inflammation.
Ocular inflammation after cataract surgery is generally managed by topical anti-inflammatory drugs such as corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs). The duration and degree of postoperative anti-inflammatory therapy have been debated as improved surgical approaches have minimized the need for aggressive inflammation control after cataract surgery compared with previous surgical techniques. Despite surgical advances, postcataract surgery inflammation is still a common cause of patient discomfort, delayed recovery, and reduced visual outcome., This study was aimed at providing the best nonsteroidal anti-inflammatory topical drug to tackle with postoperative ocular inflammation and discomfort, as steroids have its own side effects. These types of studies are insufficient in India. As cataract surgery is the most common ocular surgery performed in India, the present study comparing the two most commonly used NSAIDs in this population was need of the day.
| Materials and Methods|| |
An institution-based, single observer, prospective, interventional, comparative study was carried out on 212 patients who had undergone cataract extraction and implantation of a posterior chamber intraocular lens (IOL), after taking informed consent. The study was started after obtaining written permission from the institutional review board. Exclusion criteria were the use of topical, ocular, inhaled or systemic steroids within 14 days before surgery or topical, ocular, inhaled or systemic NSAIDs within 7 days of surgery, those patients who required topical steroids for severe anterior chamber inflammation, investigator-assessed ocular pain at the preoperative baseline visit, any corneal abnormality that prevented reliable Goldmann applanation tonometry, known or suspected hypersensitivity to NSAIDs or to any component of the study drugs, a prior history of chronic or recurrent inflammatory eye disease, with normal fundus examination, all other types of cataract such as congenital and traumatic were excluded from the study.
In all patients, comprehensive ophthalmological examination was carried out. Corneal surface abnormality or decompensation was noted and ruled out by examination under slit lamp. Thorough fundus examination was done to rule out any vision-threatening posterior chamber disease by indirect ophthalmoscopy. Best-corrected visual acuity was noted along with color vision. Keratometry and USG A-scan was done for IOL power calculation. Then, all the patients were randomly divided into two equal groups to receive either nepafenac (0.1%) or ketorolac (0.5%). Patients underwent cataract extraction on the scheduled date by manual small-incision cataract extraction. The drug application was started on the day of operation (after completion) as assigned. For both groups, the drug was applied thrice daily. The ocular parameters such as visual acuity by self-illuminated ETDRS visual acuity chart, intraocular pressure by Goldmann applanation tonometer, anterior chamber reaction graded according to SUN classification and assessment of ocular pain done by Ocular pain grading scale were observed and noted according to the group assigned successively on day 1, day 3, day 7, day 14, and day 28. Collected data were tabulated and analyzed using standard the SPSS software (version 22, SPSS, Inc., Chicago, Illinois, USA).
| Results|| |
The study was conducted on 212 patients out of which 131 patients were male (61.79%), and 81 patients were female (38.20%). The demographic data with respect to age and sex of the patients in both groups were comparable and were not statistically significant [Table 1].
As far as, the postoperative visual acuity recovery was concerned the two drugs, i.e., nepafenac (0.1%) and ketorolac (0.5%) did not have any significant difference [Table 2].
|Table 2: Comparison of mean logarithm minimum angle of resolution visual acuity between two groups|
Click here to view
As shown in [Table 3], it was observed that there was no significant difference between intraocular pressure (IOP) in postoperative period among the patients who were treated with either nepafenac (0.1%) or ketorolac (0.5%). Both the drugs were equally efficacious in maintaining IOP in postoperative period.
The effect of nepafenac (0.1%) on anterior chamber cells and flare was more than ketorolac (0.5%) during 1st week, i.e., up to day 7. This may be due to early C max (maximum concentration) achievement or rapid permeability properties of nepafenac. However, at the end of the observation period, i.e., 28 days, the effect was similar with both drugs. However, it was observed that there was statistically significant difference between two groups for their effect on anterior chamber reaction at the end of 1 week, but at the end of follow-up period, there was no difference [Figure 1].
|Figure 1: Percentage of cured case with respect to anterior chamber cells and flare at each observation day in nepafenac and ketorolac group|
Click here to view
Throughout the observation period, there was higher percentage of patients which were pain and ocular discomfort free in nepafenac (0.1%) group than that of ketorolac (0.5%) group. The P value throughout the observation period was P < 0.00, showing that nepafenac (0.1%) gives better ocular comfort and pain control than ketorolac (0.5%) in the postoperative period [Figure 2].
|Figure 2: Percentage of cases which were pain free at the end of each observation day in nepafenac and ketorolac group|
Click here to view
| Discussion|| |
As the technique of cataract extraction and IOL implantation is improving, the final visual and overall physical outcomes of patients are also improving along with it. To smoothen the postoperative recovery in patients who have undergone cataract extraction, anti-inflammatory drugs play a major role.
Both nepafenac and ketorolac are reported to be effective in the management of postoperative ocular pain and intraocular inflammation after cataract surgery. NSAIDS are known to damage corneal surface if used for longer period; hence, in this study, patients were advised to use either nepafenac or ketorolac for not more than 3 weeks. Nepafenac has unique properties, including rapid corneal permeability and targeted intraocular activation due to its prodrug structure. Its more neutral and less polarized prodrug structure facilitates it is much easier penetration into the cornea and anterior chamber, where conversion to the active form, Amfenac, by intraocular hydrolases happens. The prodrug mechanism of nepafenac may support the increased activity of Amfenac in the anterior and posterior chamber, with activation in specific areas such as the ciliary body, cornea, iris, retina, and choroid. The rapid distribution of nepafenac may minimize its surface accumulation and associated surface complications that are often observed with other conventional NSAIDs. Theoretically, nepafenac may have a better efficacy than conventional NSAIDs like ketorolac both in the management of pain and ocular inflammation associated with cataract surgery. However, several current studies failed to detect the superiority of nepafenac over ketorolac and many contradictory conclusions were found both on ocular bioavailability and potency of prostaglandin inhibition.,,,, Based on these backgrounds, the present study evaluated these two drugs for cataract surgery from the aspects of anterior chamber inflammation, postoperative visual acuity recovery, intraocular pressure, and assessment of ocular pain.
The demographic data in terms of sex distribution and mean age of patients were compared with study carried out by Nardi et al. The lesser mean age group in both the groups in the present study as compared to the mean age group in study by Nardi et al. may be attributed to the fact that due to increased awareness among the general population, more and more people are opting for cataract surgery at relatively earlier stages of cataract for professional or other reasons.
Duong et al. demonstrated postoperative ocular features such as visual outcome and anterior chamber inflammation in the form of anterior chamber cells and flare. They did not find any significant difference between the groups treated with nepafenac and ketorolac with respect to both the parameters. Similarly, in the current study, it was observed that there was no significant difference in visual acuity at any of the observation day between nepafenac and ketorolac. In a study carried out by Dave et al. on the Indian population, it was found that topical nepafenac does not increase IOP. Further, it was established that nepafenac can be safely used as alternative to steroid as an anti-inflammatory drug in steroid responders. In the current study too, it was found that there was no significant difference between nepafenac and ketorolac for their effect on IOP at any of the observation days. The study carried out by Nardi et al. also did not found any significant difference between IOP and Log mar visual acuity between the two groups.
The present study found that there was no significant difference in anti-inflammatory properties of the nepafenac and ketorolac, this finding was in sync with the findings of study done by Jones et al. However, there was significant difference observed between nepafenac and ketorolac for their effect on anterior chamber cells and flare in immediate postoperative period, i.e., 1st week (day 7), but ultimately at the end of the observation period, there was no significant difference observed between two drugs. In a similar study carried out by Nardi et al. which compares nepafenac, ketorolac, and placebo, there was a significant difference between Nepafenac and placebo at day 14, but they did not find any significant difference between nepafenac and ketorolac at the end of their observation period which supports observation of the current study.
Kessel et al. found that topical NSAIDs were more effective than steroid eye drops in reducing postoperative inflammation measured as the amount of flare. Steroids of low potency (fluorometholone) were significantly less effective in controlling inflammation than NSAIDs. Best-corrected distance visual acuity was slightly better in the NSAID group compared with steroid group, but the difference was not statistically significant. The NSAIDs were also compared between each other for their anti-inflammatory effects, and it was found that ketorolac and nepafenac seem equally effective in controlling intraocular inflammation, which matches with the observations made by this study. Walters et al. found that nepafenac has better bioavailability and Cmax (full form) achievement than compared to ketorolac. This may be the cause of slight early better results observed with nepafenac over the anterior chamber cells and flare with respect to ketorolac up to day 7, i.e., 1 week in our study.
Postoperative ocular pain is still an important concern among villagers in developing countries. Hence, postoperative ocular discomfort and pain were included as an important parameter of the present study. In the study, it has been found that the postoperative ocular discomfort and pain was less in the group that was treated with nepafenac than the group which was treated with ketorolac. There was statistically significant difference among the two groups with respect to their ocular discomfort and pain scale score, and this difference was observed throughout the observation period (day 28). This finding of the study was supported by previous studies.,,,,,,,
| Conclusion|| |
When the parameters under study were observed on each successive visit, it was found that nepafenac was superior to ketorolac in dealing with ocular discomfort and pain. Nepafenac was also found superior than ketorolac with respect to early recovery from anterior chamber inflammation. However, at the end of the total period of observation, no significant difference was found between the outcome with respect to visual acuity or IOP control or anterior chamber inflammation.
Authors would like to thank the Department of Ophthalmology, other staff of operation theatre and administration of Burdwan Medical College and Hospital, Burdwan, West Bengal, for granting permission to this study and providing facilities to carry out the research work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cook C. How to improve the outcome of cataract surgery. Community Eye Health 2000;13:37-8.
Asbell PA, Dualan I, Mindel J, Brocks D, Ahmad M, Epstein S, et al.
Age-related cataract. Lancet 2005;365:599-609.
DeCroos FC, Afshari NA. Perioperative antibiotics and anti-inflammatory agents in cataract surgery. Curr Opin Ophthalmol 2008;19:22-6.
McColgin AZ, Heier JS. Control of intraocular inflammation associated with cataract surgery. Curr Opin Ophthalmol 2000;11:3-6.
Mentes J, Erakgun T, Afrashi F, Kerci G. Incidence of cystoid macular edema after uncomplicated phacoemulsification. Ophthalmologica 2003;217:408-12.
Bowling B. Uveitis. In: Kanski's Clinical Ophthalmology a Systematic Approach. 8th
ed. Printed in China: Copyright Elsevier Ltd.; 2016. p. 397, 399.
Numaga J. Phase II placebo-controlled study of nepafenac ophthalmic suspension 0.1% for postoperative inflammation and ocular pain associated with cataract surgery in Japanese patients. J Ophthalmic Inflamm Infect 2011;1:147-55.
Jones BM, Neville MW. Nepafenac: An ophthalmic nonsteroidal antiinflammatory drug for pain after cataract surgery. Ann Pharmacother 2013;47:892-6.
Nardi M, Lobo C, Bereczki A, Cano J, Zagato E, Potts S, et al.
Analgesic and anti-inflammatory effectiveness of nepafenac 0.1% for cataract surgery. Clin Ophthalmol 2007;1:527-33.
Walters T, Raizman M, Ernest P, Gayton J, Lehmann R.In vivo
pharmacokinetics andin vitro
pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac. J Cataract Refract Surg 2007;33:1539-45.
Bucci FA Jr., Waterbury LD. A randomized comparison of to-aqueous penetration of ketorolac 0.45%, bromfenac 0.09% and nepafenac 0.1% in cataract patients undergoing phacoemulsification. Curr Med Res Opin 2011;27:2235-9.
Ramakrishnan S, Baskaran P, Talwar B, Venkatesh R. Prospective, randomized study comparing the effect of 0.1% nepafenac and 0.4% ketorolac tromethamine on macular thickness in cataract surgery patients with low risk for cystoid macular edema. Asia Pac J Ophthalmol (Phila) 2015;4:216-20.
Duong HV, Westfield KC, Chalkley TH. Ketorolac tromethamine LS 0.4% versus nepafenac 0.1% in patients having cataract surgery. Prospective randomized double-masked clinical trial. J Cataract Refract Surg 2007;33:1925-9.
Dave P, Shah K, Ramchandani B, Jain R. Effect of nepafenac eye drops on intraocular pressure: A randomized prospective study. Am J Ophthalmol 2014;157:735-80.
Kessel L, Tendal B, Jørgensen KJ, Erngaard D, Flesner P, Andresen JL, et al.
Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: A systematic review. Ophthalmology 2014;121:1915-24.
Nagpal M, Lambat S, Mehrotra N, Paranjpe G, Yadav H, Bhardwaj S, et al.
Topical nepafenac 0.1% alone versus prednisolone acetate 1% as postoperative anti-inflammatory agents in small gauge vitrectomy. Indian J Ophthalmol 2014;62:606-9.
] [Full text]
Modi SS, Lehmann RP, Walters TR, Fong R, Christie WC, Roel L, et al.
Once-daily nepafenac ophthalmic suspension 0.3% to prevent and treat ocular inflammation and pain after cataract surgery: Phase 3 study. J Cataract Refract Surg 2014;40:203-11.
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.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]