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Byline: Rabbia Mirza, Imran Basit, Sumayya Khan, Zahid Ullah, Muhammad Shahid and Muhammad Awais

Keywords: Cataract surgery, Miosis, Nepafenac, Prophylactic, Trans-operative mydriasis.


Phacoemulsification, because of the best visual results with intraocular lens (IOL) implantation, is currently the best surgical procedure in cataract surgery 1,2. Even though there is improvement in IOL material and surgical techniques have greatly advanced in the last decade, there is always the risk of inadvertent trauma to eyes during surgery. Such trauma results in the activation and release of inflammatory mediators including prostaglandins (PGs), cyclooxygenase-1 (COX-1) and COX-2 enzymes 4. The release of these inflammatory mediators results in ocular symptoms and signs such as pain, inflammation, miosis, posterior synechiae, posterior capsular opacity, changes in intraocular pressure (IOP) and glaucoma 5. Surgical trauma results in release of PGs which results in miosis of iris. Transoperative complications are greatly reduced, and adequate mydriasis maintained when topical NSAIDS are used to inhibit the release of PGs 6.

Two groups of drugs are chiefly used to inhibit trans-operative miosis and control postoperative inflammation. These are non-steroidal anti-inflammatory drugs (NSAIDs) and topical corticosteroids. NSAIDS directly inhibit the COX enzymes whereas steroids act at the level of phospholipase A2 resulting in inhibition of PG release 6-8. Using both groups of drugs simultaneously provide a synergistic effect in inhibiting transoperative miosis and controlling intraocular inflammation 9.

Topical ophthalmic suspension consisting of 0.1% nepafenac (Nevanac, Novartis) is very effective in inhibiting miosis as well as in pain relief and post-surgery inflammation 10. The purpose of this study was to evaluate inhibition of trans-operative miosis by using 0.1% nepafenac prophylactically.


It was prospective comparative study conducted in Armed Forces Institute of Ophthalmology, on patients undergoing phacoemulsification cataract surgery, After approved by the Hospital Ethics Review Committee. A total of 70 patients who met the inclusion/exclusion criteria and undergoing cataract surgery phacoemulsification for senile or/and metabolic cataract were included in the study. They were randomly placed in either the control group or the nepafenac group irrespective of the race or gender.

Uncomplicated cataracts were included in the study whereas the exclusion criteria included pregnancy, breastfeeding, history of ocular trauma or surgery, history of infectious eye disease or any prior ocular inflammation, dry eye, and history of any allergy or hypersensitivity to NSAIDS, steroids or any other component of the drug which is to be used in the study. Patients using PG analogs, NSAIDs or steroids within 4 weeks prior to surgerywere also excluded from the study. Patients with uncontrolled hypertension, diabetes mellitus (DM), proliferative diabetic retinopathy or macular degeneration/edema, chorioretinopathy and pre-operative mydriasis of <6mm were excluded from the study.

Medical history including review of concurrent diseases and medications along with ophthalmic examination was carried out for all seventy patients before surgery. The ophthalmic examination included visual acuity test, slit lamp examination, tonometry for measuring IOP and fundus examination. Topical 1% tropicamide along with 5% phenylephrine using as one drop every 15 minutes (total of 3 doses) were used in combination in both groups. In the nepafenac group, 4 doses of 0.1% Nepafenac were administered as one drop every 15 minutes one hour before surgery. All patients underwent cataract surgery by phacoemulsification and IOL implantation under either topical or retrobulbar anesthesia. The identity of both groups of patients was concealed from the surgeons.

Small standardized incision technique was use for the phacoemulsification in all patients. Nasal and temporal corneal incisions were made followed by capsulorhexis. Post phacoemulsification, implantation of foldable IOL in the capsular bag was carried out. The incisions were left open without sutures. The horizontal and vertical pupillary diameters were measured in mm post-surgery with the help of compass under the microscope. It was then followed by cortex aspiration. Post-surgery all the patients received one drop of tobradex 6 hourly daily for 10 days. Only the nepafenac group was given one drop of nepafenac 8 hourly daily for 3 days pre-surgery and one drop every 15 minutes one hour before surgery. Post-surgery all patients were assessed at day 1 st, 2 nd and 4 th week. At each visit, visual acuity, slit lamp examination and fundoscopy were carried out.

SPSS-19 and Microsoft excel were used for compilation of data. All the data was described in terms of mean values and proportions for both control and nepafenac groups. Student's t-test was used for comparative analysis. For determination of relative risk and association of qualitative variables Fisher exact test was used. For establishing statistical significance pvalue of a$?0.05 was used.

Table-I: Demographic and clinical data (pre-operatively).




Age in years###0.625

Mean +- SD###59.9 +- 10.8 58.8 +- 9.5

Range###39 to 82###39 to 88

Gender, n(%)###0.651



Eye, n(%)###0.788

Right eye###16(45.7)###17(48.5)

Left eye###19(54.3)###18(51.5)

Ocular and Systemic Pathology

Diabetes Mellitus n(%)###8###6###0.592

Hypertension n(%)###8###11###0.489

Heart disease n(%)###4###3###0.684

Table-II: Trans-surgical mean horizontal pupillary diameter.

Stages of###Group###p-



Before surgery###8.24 +- 0.59###8.55 +- 0.75###0.144

Following cortex###7.18 +- 0.89###8.10 +- 0.76 <0.001


Conclusion of###6.57 +- 0.93###7.88 +- 0.49 <0.001


Total loss of###1.67 +- 0.95###0.67 +- 0.46 <0.001


Percent total loss###20.26%###7.82%###<0.001

Table-III: Post-surgery decrease in pupil diameter.


###Control###Nepafenac value

Loss 1.5mm n(%)###21(60)###4(11)###1 +- inflammatory cells at the end of first post-operative week.

Table-II showed trans-operative maintenance of mydriasis in both groups at different stages of surgery. Preoperatively both the groups had comparable horizontal pupillary diameter (8.55 mm in nepafenac group and 8.24 in the control group) with p-value of 0.144. Post-surgery there was statistically significant difference between the two groups with p-value 1.5 mm whereas in the nepafenac group only 4 patients had reduction greater than 1.5 mm (p1.5mm trans-operatively is 4.9 times greater as compared to the nepafenac group.


Nepafenac is prodrug and is hydrolyzed to Amfenac in the intraocular tissues. Amfenac is its active form and is a powerful inhibitor of COX-1 and COX-2 enzymes. Nepafenac has excellent permeability and bioavailability in the ocular tissues. Nepafenac is a target specific NSAID due to its speedy bioactivation in ocular tissues. As a result, it inhibits PG synthesis in the posterior and anterior segments of the eye 11,12. During surgery there is trauma to the ocular tissue. This trauma leads to phospholipase A2 activation as well as the release of platelet-activating factors and arachidonic acid metabolites. Arachidonic acid, through cyclooxygenase (COX) pathway, forms prostaglandins (PGs) and through lipoxygenase pathway results in the production of leukotrienes (LTs). Endogenous PGs result in different ocular effects. These include conjunctival hyperemia, post-operative inflammation and miosis as well as increased blood-ocular barrier permeability and changes in intra ocular pressure 8.

Miosis during surgery makes cataract surgery difficult and there is increase the risk of trauma during surgery. It may also increase the risk of postoperative inflammation of the eye and rupture of posterior capsule. It has been reported that with >6mm of mydriasis, the risk of posterior capsule rupture was reduced by half. This clearly shows that maintaining adequate pupil dilatation is vitalin ensuring smooth cataract removal 9.

Prostaglandins play a crucial role during eye trauma including cataract surgery which stimulates the inflammatory cascade. The release of a great number of inflammatory mediators like prostaglandins, COX-1 and COX-2 enzymes, causes ocular signs and symptoms such as inflammation, edema, pain, miosis, posterior capsular opacity, changes in intraocular pressure (IOP) and glaucoma 10. These PGs and their release can be inhibited with topical NSAIDs. Their inhibition results in inhibition of miosis and therefor, adequate trans-surgical mydriasis can be maintained. Consequently, trans-operative complications are minimized. Nepafenac 0.1% is an NSAID and is aprodrug. Inside the intraocular tissues, nepafenac is hydrolyzed to amfenac which is a potent inhibitor of COX-1 and COX2 11. As a result, PG synthesis is blocked. It has excellent bioavailability and ocular tissue penetration. Numerous studies have established that NSAIDS such as nepafenac are effective in maintenance of trans-operative mydriasis 12.

This study has demonstrated that the use of 0.1% topical nepafenac was effective as an inhibitor of miosis during cataract surgery. During the entire surgical procedure, we found that the nepafenac group had consistent tendency towards much greater dm unlike the control group. In control group there was a gradual failure in maintenance of mydriasis during different stages of surgery. Mydriatic effects of topical flurbiprofen and prednisolone have been analyzed by Shaikh et al. They found no statistical difference between the two drugs 13. On the other hand, there were different studies which have reported greater mydriasis when flurbiprofen was used as compared to prednisolone 14,15. Similarly, it was reported that administration of ketorolac preoperatively for 3 days has better results in maintaining mydriasis as compared to 1 day and 1 hour regimen preoperatively 16-18.

In this study, we administered nepafenac 3 days before surgery and 4 times one hour before surgery. Moreover, though this study has shown significant results in maintenance of mydriasis during phacoemulsification future studies comparing nepafenac with other NSAIDs and its effects on macular edema in the long run are warranted.


The prophylactic use of nepafenac 0.1% topical eye drops was found effective and safe in maintaining trans-operative mydriasis during cataract surgery. It is the first known clinical study for evaluation of the effect of 0.1% nepafenac on pupil size during cataract surgery.


The study does not have any conflict of interest to be declared by any author.


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Author:Rabbia Mirza, Imran Basit, Sumayya Khan, Zahid Ullah, Muhammad Shahid and Muhammad Awais
Publication:Pakistan Armed Forces Medical Journal
Date:Aug 31, 2021

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