a randomized, double-masked trial of topical ketorolac versus

7/27/2019 A Randomized, Double-masked Trial of Topical Ketorolac Versus

1/6

A Randomized, Double-Masked Trial ofTopical Ketorolac versus Artificial Tears forTreatment of Viral Conjunctivitis

Yichieh Shiuey, MD, Balamurali K. Ambati, MD, Anthony P. Adamis, MD, the Viral Conjunctivitis StudyGroup*

Objective: To determine if topical ketorolac 0.5% relieves the symptoms and signs of viral conjunctivitisbetter than artificial tears.

Design: Randomized, controlled trial.Participants: One hundred seventeen patients with a clinical diagnosis of viral conjunctivitis were random-

ized to the treatment group or control group.Methods: Physicians and patients were masked to treatment. Patients in the treatment group received

topical ketorolac 0.5% four times daily. Patients in the control group received artificial tears four times daily.Symptom and sign scores were recorded on the day of recruitment and at the time of a follow-up examination

3 to 4 days later.Main Outcome Measures: Change in six symptoms of conjunctivitis (overall discomfort, itching, foreign

body sensation, tearing, redness, and lid swelling) and four signs of conjunctivitis (conjunctival injection,conjunctival chemosis, conjunctival mucus, and lid edema). Adverse effects were also studied.

Results: A total of 105 patients returned for their 3- to 4-day follow-up. Both the artificial tear and ketorolacgroups showed improvement in all symptom scores at their 3- to 4-day follow-up visit. There was no statisticallysignificant difference between the change in symptom scores between the treatment group and control group inany symptom category except redness. Patients in the control group were more likely to report improvement inredness than those in the treatment group, P 0.012. There was no statistically significant difference betweenthe change in sign scores between the treatment and control groups. Ketorolac 0.5% was more likely to producestinging than artificial tears, 59.2% versus 18.8%, P 0.001.

Conclusions: Topical ketorolac 0.5% used four times daily is no better than artificial tears at relieving thesymptoms or signs of viral conjunctivitis and produces more stinging than artificial tears. Ophthalmology 2000;

107:15121517 2000 by the American Academy of Ophthalmology.

Viral conjunctivitis is a common problem encountered byophthalmologists. It may be caused by a wide array ofviruses including adenovirus, herpes simplex virus, vari-cella zoster virus, enterovirus, picornavirus, influenza A

virus, Epstein-Barr virus, and Newcastle disease virus. Viralconjunctivitis causes redness, tearing, swelling, and irrita-tion of the eyes that typically lasts from 1 to 3 weeks.Current management of this condition focuses on supportivecare while the viral infection completes its course andresolves.1,2 However, many patients still experience sub-stantial discomfort despite standard treatments with coolcompresses, artificial tears, topical vasoconstrictors, oint-ment, or a combination thereof.

Inflammation of the conjunctiva is an essential feature of

viral conjunctivitis, and this inflammation is believed tocause many of the symptoms of the infection. At present,the most commonly used form of anti-inflammatory treat-ment in viral conjunctivitis is topical steroids. Topical ste-roids may be indicated to treat severe adenoviral conjunc-tivitis in the setting of visually significant subepithelialopacities or when conjunctival membrane formation occurs.However, topical steroids are not recommended for theroutine treatment of viral conjunctivitis because of a varietyof possible side effects.1 The use of topical steroids mayaggravate herpes simplex viral conjunctivitis and may pre-dispose the eye to corneal involvement.1 Animal models of

Originally received: October 14, 1999.Accepted: March 29, 2000. Manuscript no. 99710.

Massachusetts Eye and Ear Infirmary, Department of Ophthalmology,Harvard Medical School, Boston, Massachusetts.

*Sherleen Chen, MD, Mary Coday, MD, Ronald Farkas, MD, PhD, JeffreyFiner, MD, PhD, Kenneth Graham, MD, Melanie Graham, MD, LynnHalpern, MD, PhD, Eddie Harris, MD, Deeba Hussain, MD, Eugene Lit,MD, Subhransu Ray, MD, PhD, Ivana Kim, MD, Rosa Kim, MD, StellaKim, MD, Tueng Shen, MD, PhD, Kimberly Sippel, MD, Eric Strauss,MD, PhD, Michael Tolentino, MD, Lynette Watkins, MD.

Presented in part as a poster at the American Academy of Ophthalmologyannual meeting, Orlando, Florida, October 1999.

Supported in part by an unrestricted grant from Allergan Pharmaceuticals,Irvine, California.

The authors have no proprietary interest in any of the products mentionedin this study.

Reprint requests to Yichieh Shiuey, MD, 331 Bloomfield Avenue, Nutley,NJ 07110.

1512 2000 by the American Academy of Ophthalmology ISSN 0161-6420/00/$see front matterPublished by Elsevier Science Inc. PII S0161-6420(00)00177-9


2/6

viral conjunctivitis have shown that topical steroids enhancevirus replication and prolong the duration of virus shed-ding.3 There have also been reports of chronic adenoviralconjunctivitis in patients who have been treated with ste-roids.4 Other potential side effects of topical steroids in-clude increased intraocular pressure, cataract formation, de-layed wound healing, and promotion of infections. Becauseof the many possible adverse effects of topical steroids in

the treatment of viral conjunctivitis, we explored the possi-bility of using a nonsteroidal anti-inflammatory agent totreat the signs and symptoms of viral conjunctivitis.

Topical ketorolac, a nonsteroidal anti-inflammatoryagent, has previously been shown to be safe and effective inthe symptomatic treatment of seasonal allergic conjunctivi-tis and has approval for this indication by the United StatesFood and Drug Administration. However, it has not beenpreviously studied for the treatment of human viral conjunc-tivitis.5 Ocular application of topical ketorolac has beenshown to have anti-inflammatory effects without the sideeffects of topical steroids.611 In contrast to topical steroids,animal models of viral conjunctivitis have not demonstrated

enhanced virus replication with administration of topicalketorolac.12 For these reasons, we chose to study the effi-cacy of topical ketorolac in treating the symptoms and signsof viral conjunctivitis.

Methods

The study was designed as a prospective, double-masked, con-trolled study of the efficacy of ketorolac 0.5% ophthalmic solution(Acular, Allergan, Irvine, CA) compared with artificial tears(Moisture Drops, Allergan). Patients were recruited from the eyeemergency room of the Massachusetts Eye and Ear Infirmary,Boston, Massachusetts. Eligible patients were required to have an

acute unilateral or bilateral conjunctivitis of less than 2 weeks. Inaddition, they were required to have at least one of the followingfeatures compatible with viral conjunctivitis: unilateral or asym-metric conjunctivitis, follicles on the inferior tarsal conjunctiva,preauricular lymphadenopathy, an associated upper respiratoryinfection, and recent contact with a person with a red eye. Exclu-sion criteria included history of seasonal allergic conjunctivitis,use of ocular medication after the beginning of symptoms, contactlens wear, history of herpetic eye disease, history of ocular sur-gery, history of chronic ocular disease other than refractive error,allergy to aspirin or nonsteroidal anti-inflammatory drugs, preg-nancy, age less than 18 years, bleeding disorder, significant bleph-aritis or dry eyes on slit lamp examination, purulent ocular dis-charge, corneal epithelial staining with fluorescein, or intraocularinflammation. Patients were also required to grade their overallsymptoms from the conjunctivitis as none, mild, moderate, orsevere. Only patients reporting initial overall discomfort as mod-erate or severe were asked to participate in the study. Patients whomet the study criteria and who agreed to participate in the studywere randomly assigned to receive either ketorolac 0.5% or arti-ficial tears. Sealed, randomly numbered opaque manila envelopescontaining unlabeled bottles of either ketorolac or artificial tearswere given to the patient. Patients were instructed to put one dropinto each symptomatic eye four times daily for 7 days.

The manila envelopes containing the eyedrops were preparedprofessionally by the DEllis Group, Irvine, California. The ran-domization scheme was created using a computer program by theDEllis Group. The identity of the drops was masked to both the

investigators and patients until the study was closed. At the end ofthe study, the code for the randomization scheme was obtainedfrom the DEllis Group. This study was approved by the institu-tional review board, and written informed consent was obtainedfrom all patients. A nominal fee was paid to each of the patients tocover their expenses for participating in the study.

Efficacy VariablesPatients were evaluated at baseline and were asked to return either3 or 4 days later for a follow-up evaluation. The principal efficacyvariables were six symptoms of viral conjunctivitis: overall dis-comfort, itching, foreign body sensation, tearing, redness, and lidswelling. Four signs of viral conjunctivitis were also evaluated:conjunctival injection, conjunctival chemosis, conjunctival mucus,and lid edema.

Each of the symptoms was rated by the patient at presentationand at follow-up on a 4 point scale: none (0), mild (1), moderate(2), or severe (3). In addition, each patient was asked to report theiropinion on the usefulness of the treatment in relieving their symp-toms on a 4point scale: did not help (0), unsure (1), think ithelped (2), and sure it helped (3). After the 3 to 4 day follow-up

evaluation, patients were given a questionnaire to mail in thatreported on their overall symptoms at 7 and 14 days after theirinitial evaluation (Fig 1).

Each of the signs was rated in the more badly affected eye bythe examiner at presentation and at the 3 to 4 day followup visiton a 4point scale: none (0), mild (1), moderate (2), or severe (3).For the sign of conjunctival injection, a grade of none (0) indicatedno detectable hyperemia of the conjunctiva, a grade of mild (1)indicated conjunctival hyperemia that was barely detectable, agrade of moderate (2) indicated conjunctival hyperemia that wasreadily detectable, and a grade of severe (3) indicated intenseconjunctival hyperemia that could be mistaken for subconjunctivalhemorrhage without slitlamp examination. For the sign of che-mosis, a grade of none (0) indicated no detectable conjunctival

edema, a grade of mild (1) indicated conjunctival edema that wasbarely detectable, a grade of moderate (2) indicated conjunctivaledema that was readily detectable in the form of swollen redundantconjunctiva, and a grade of severe (3) indicated conjunctivaledema sufficient to cause protrusion of swollen redundant con-junctiva through closed lids. For the sign of conjunctival mucus, agrade of none (0) indicated no detectable mucus discharge, a gradeof mild (1) indicated mucus discharge that was barely detectable,a grade of moderate (2) indicated mucus discharge that was readilydetectable, and a grade of severe (3) indicated mucus dischargeassociated with an inflammatory conjunctival pseudomembrane ortrue membrane. For the sign of lid edema, a grade of none (0)indicated no detectable eyelid swelling, a grade of mild (1) indi-cated barely detectable eyelid swelling, a grade of moderate (2)indicated readily detectable eyelid swelling, and a grade of severe

(3) indicated eyelid swelling sufficient to cause partial or completeptosis. Examiners of each patient were the same at the initial andfollow-up evaluations.

Safety Variables

Patients were instructed to contact one of the principal investiga-tors by telephone if they were experiencing any significant sideeffect from the study eyedrops. If the investigator was unavailable,the patients were to report to an eye emergency room that wasopen 24 hours a day. In addition, patients were asked to report anyside effects at the 3 to 4 day follow-up evaluation.

Shiuey et al Topical Ketorolac versus Artificial Tears for Viral Conjunctivitis

1513


3/6

Statistical Methods

At the completion of the study, the identity of the drops given toeach patient was unmasked and the data analyzed. Fishers exacttest and the Wilcoxon ranksum test were used to look for differ-ences in demographics, baseline symptoms, and clinical scores inthe artificial tear and ketorolac groups. Fishers exact test was also

used to see if the patients perception of benefit was related totreatment with ketorolac. Fishers exact test was used to examinewhether paired changes in symptom and clinical scores betweenbaseline and followup were different in the artificial tear andketorolac groups. Fishers exact test was also used to see if thelikelihood of having an adverse effect was related to the artificialtear or ketorolac group.

Results

A total of 117 patients met eligibility criteria and were initiallyenrolled in the study. Twelve patients did not return for followup,

seven of whom had been assigned to the artificial tears group andfive of whom had been assigned to the ketorolac group. Onehundred five patients returned for the 3 to 4 day followupexamination. Of the these patients, 55 returned the questionnairethat reported on their symptoms at days 7 and 14.

The baseline characteristics of the 105 patients who completedthe 3 to 4 day follow up examination are shown in Table 1. The

artificial tear and ketorolac groups were similar at baseline withregard to demographic and clinical characteristics. One examina-tion finding that was of borderline statistical significance was of apalpable preauricular node, which was more common in the arti-ficial tear group, P 0.05.

The comparison of symptom scores between the initial evalu-ation and followup at day 3 or 4 has been summarized as thenumber and percentage of patients whose conditions wereworse, did not change, or were better after treatment (Table 2).There was no statistically significant difference between thechange in symptom scores between the artificial tear group andthe ketorolac group in any symptom category except for red-ness. Patients were more likely to report improvement in red-

Figure 1. Mail-in questionnaire for grading of symptoms on days 7 and 14.

Ophthalmology Volume 107, Number 8, August 2000

1514


4/6

ness in the artificial tear group than in the ketorolac group, P 0.012.

The opinions of the patients on day 3 or 4 regarding theusefulness of their treatment is summarized in Table 3. There was

no statistically significant difference between the responses of thepatients who received artificial tears and of those who receivedketorolac.

The comparison of sign scores between the initial evaluationand followup at day 3 or 4 is summarized in Table 4. There wasno statistically significant difference between the change in signscores between the artificial tear group and the ketorolac group inany sign category.

A comparison of the overall symptom scores at the initialevaluation and from the questionnaire at days 7 and 14 is summa-rized in Table 5. Nearly 90% of the patients who returned the

questionnaire in both the artificial tear and ketorolac groupsreported an improvement in their overall symptom score by day7. At day 14, nearly all patients reported improvement in theiroverall symptom score. There was no statistically significantdifference between artificial tears group and ketorolac group ateither day 7 or 14.

A comparison of the reported adverse effects is shown in Table6. Ketorolac was found to cause stinging in 59.2% of patients as

compared with 18.8% in the artificial tear group. This was statis-tically significant, P 0.001. There was one patient in the studywho reported at the 3 day followup examination that she believedthat the drops were worsening her symptoms. The study medica-tion was discontinued and unmasked. It was identified as ketoro-lac. By slitlamp examination, there was no appreciable change inthe patients examination findings from the initial evaluation. Thispatients conjunctivitis resolved without sequelae by 2 weeks afterthe initial visit.

Discussion

We studied the effect of topical ketorolac, a nonsteroidal

antiinflammatory drug, on the symptoms and signs of viralconjunctivitis. We chose to test topical ketorolac becauseof its known antiinflammatory effects when adminis-tered to the eye and its lack of serious side effects. Our

Table 1. Patient Characteristics

Artificial Tears(n 48)

Ketorolac(n 57) P value

Median age (yrs) 31 31 0.96Male (%) 46 53 0.31White (%) 66 65 0.54Median days with symptoms 2 2 0.98Bilateral symptoms (%) 46 49 0.44

Unilateral or asymmetricsymptoms (%)

73 65 0.25

Associated upper respiratoryinfection (%)

52 42 0.44

Follicles on inferior tarsalconjunctiva (%)

96 98 0.44

Preauricular node (%) 27 12 0.05Contact with person with a

red eye (%)19 30 0.14

Table 2. Summary of the Change in Patient Symptom Scores,Baseline Compared with Day 3 or 4

ConjunctivitisSymptom Artificial Tears Ketorolac 0.5% P Value*

OverallWorse 0 (0.0%) 1 (1.7%)

No change 5 (10.4%) 10 (17.5%) 0.404Better 43 (89.6%) 46 (80.7%)

ItchingWorse 0 (0.0%) 5 (8.8%)

No change 17 (35.4%) 16 (28.1%) 0.107Better 31 (64.6%) 36 (63.2%)

Foreign body sensationWorse 4 (8.3%) 4 (7.0%)

No change 13 (27.1%) 17 (29.8%) 0.953Better 31 (64.6%) 36 (63.2%)

TearingWorse 4 (8.3%) 3 (5.3%)

No change 8 (16.7%) 12 (21.1%) 0.786Better 36 (75.0%) 42 (73.7%)

RednessWorse 0 (0.0%) 6 (10.5%)

No change 5 (10.4%) 12 (21.1%) 0.012Better 43 (89.6%) 39 (68.4%)

Lid swellingWorse 5 (10.4%) 5 (8.8%)

No change 11 (22.9%) 19 (33.3%) 0.481Better 32 (66.7%) 33 (57.9%)

*Fishers exact test.

Table 3. Patients Perception of Benefit of Treatment atDay 3 or 4

PatientResponse Artificial Tears Ketorolac 0.5% P Value*

Did not help 5 (10.4%) 8 (14.0%)Unsure 6 (12.5%) 5 (8.8%) 0.867Think it helped 19 (40.6%) 21 (36.8%)Sure it helped 18 (37.5%) 23 (40.4%)

Total 48 (100.0%) 57 (100.0%)


Table 4. Summary of the Change in Investigator Sign Scores,Baseline Compared with Day 3 or 4

Artificial Tears Ketorolac 0.5% P Value*

InjectionWorse 1 (2.1%) 3 (5.3%)

No change 9 (18.8%) 13 (22.8%) 0.692Better 38 (79.2%) 41 (71.9%)

ChemosisWorse 3 (6.3%) 7 (12.2%)

No change 19 (39.6%) 28 (49.1%) 0.266Better 26 (54.2%) 22 (38.6%)

MucusWorse 1 (2.1%) 5 (8.8%)

No change 19 (39.6%) 15 (26.3%) 0.206Better 28 (58.3%) 37 (64.9%)

Lid edemaWorse 0 (0.0%) 3 (5.3%)

No change 23 (47.9%) 20 (35.1%) 0.179Better 25 (52.1%) 34 (59.6%)



1515


5/6

hypothesis was that ketorolac would relieve some of thesymptoms of viral conjunctivitis through its antiinflam-matory effects.

Both the artificial tear and ketorolac groups showedimprovement in all symptom scores after using the dropsfour times daily for 3 to 4 days. However, we found that

there were no statistically significant differences betweenthe artificial tear and ketorolac groups with respect to over-all discomfort, itching, foreign body sensation, tearing, oreyelid swelling. There was a statistically significant differ-ence in the symptom of redness. Patients who receivedketorolac were less likely to experience improvement inredness, P 0.012. Patients were also more likely toexperience stinging with instillation of the ketorolac drops,P 0.001.

There were no statistically significant differences be-tween the conjunctivitis sign scores of the two groups at the3 to 4 day follow-up. Patients were not reexamined at day 7after initiation of treatment. We chose not to have a second

clinical examination at day 7 because we anticipated that thenumber of patients returning for followup would be unac-ceptably low. Our patients were young, working class per-sons with a median age of 31 years who could not easilytake time off. We believed that at day 7 a significantproportion of the study patients would have minimal symp-toms and, as a result, would be less likely to return forfollow up. Because we did not reexamine patients at day 7,it is unknown if topical ketorolac has any benefit in reducingthe signs of viral conjunctivitis after 1 week of treatment.However, we do know that we could not detect a differencein the overall symptom score of patients receiving topicalketorolac or artificial tears at either day 7 or 14 afterinitiation of treatment.

Our study did not show any benefit to the use of topicalketorolac 0.5% as compared with artificial tears in relieving

the symptoms of viral conjunctivitis. Moreover, there was agreater likelihood of stinging with the use of ketorolac.Topical ketorolac is also substantially more expensive thanartificial tears. For these reasons, our study does not supportthe use of topical ketorolac for the treatment of patients witha clinical diagnosis of viral conjunctivitis.

We are aware of only one other study addressing the useof a topical nonsteroidal antiinflammatory drug in thetreatment of viral conjunctivitis.13 This was a randomizedstudy of the effects of topical piroxicam on the symptomsand signs of patients with a clinical diagnosis of coxsackievirus infection. The authors concluded that topical pi-roxicam reduced foreign body sensation, pain, tearing,and mean time to recovery in these patients. A potentiallysignificant confounder of the results and conclusions ofthis piroxicam study was that neither the investigatorsnor patients were masked to the treatment. Therefore,both the patients and the investigators may have beensubject to bias.

Our study is unlikely to be biased. It was a prospective,

randomized, double-masked study. It is also unlikely thatthere was a substantial benefit to ketorolac that could not bedetected with the number of patients in the study. Foreach of the symptom categories, overall, itching, redness,foreign body sensation, tearing, and lid swelling, patientsusing artificial tears were more likely to report improve-ment than those using ketorolac. This was only statisti-cally significant for redness, but indicates an overalltrend favoring artificial tears. Thus it would be unlikelythat a larger study would demonstrate a beneficial effectof ketorolac.

We used clinical criteria to diagnose acute viral conjunc-tivitis. This is the method by which most ophthalmologists

diagnose viral conjunctivitis, because laboratory testing forthe multiple types of viral conjunctivitis is not widely avail-able and is also expensive. Ninety-seven percent of ourpatients were found to have an acute follicular conjunctivitisof less than 2 weeks in duration in the absence of any use oftopical medications. In addition, patients who had a historyor examination findings suggestive of either seasonal aller-gic conjunctivitis or bacterial conjunctivitis were excluded.Therefore, by using these strict clinical criteria, the diagno-sis of viral conjunctivitis was most likely correct in the greatmajority of patients in our study.

It is unclear why topical ketorolac does not relieve thesymptoms of viral conjunctivitis when it has been shown to

be efficacious in seasonal allergic conjunctivitis. In a rabbitmodel of adenovirus keratoconjunctivitis, topical pred-nisolone was found to inhibit immune corneal infiltrates,whereas topical ketorolac did not.12 This may indicate thatthe inflammation of viral conjunctivitis is qualitatively dif-ferent from that found in seasonal allergic conjunctivitis andis not effectively suppressed by topical ketorolac. Based onthe results of this study, we do not recommend the use oftopical ketorolac 0.5% for the symptomatic relief of viralconjunctivitis. Further studies to find safe and effectivetreatments for the symptoms of this very common conditionshould be pursued.

Table 5. Overall Patient Symptom Score at Day 7 and 14Compared with Initial Evaluation

Artificial Tears Ketorolac 0.5% P Value*

Day 7Worse 1 (3.9%) 0 (0.0%)

No change 2 (7.7%) 3 (10.3%) 0.822Better 23 (88.5%) 26 (89.7%)

Day 14

Worse 0 (0.0%) 0 (0.0%)No change 0 (0.0%) 1 (3.4%) 1.000Better 26 (100.0%) 28 (96.6%)


Table 6. Adverse Events

Adverse Events Artificial Tears Ketorolac 0.5% P Value*

Stinging 9 (18.8%) 34 (59.6%) 0.001Headache 0 (0%) 1 (1.7%)Photophobia 0 (0%) 1 (1.7%)


Ophthalmology Volume 107, Number 8, August 2000

1516


6/6

References

1. American Academy of Ophthalmology. Conjunctivitis. Pre-ferred Practice Patterns. San Francisco, CA: American Acad-emy of Ophthalmology, 1998.

2. Cullom RD Jr, Chang B, eds. The Wills Eye Manual: Officeand Emergency Room Diagnosis and Treatment of Eye Dis-eases, 2nd ed. Philadelphia: J.B. Lippincott, 1994; chap 5.

3. Romanowski EG, Roba LA, Wiley L, et al. The effects ofcorticosteroids on adenoviral replication. Arch Ophthalmol1996;114:5815.

4. Pettit TH, Holland GN. Chronic keratoconjunctivitis associ-ated with ocular adenovirus infection. Am J Ophthalmol 1979;88:74851.

5. Tinkelman DG, Rupp G, Kaufman H, et al. Double-masked,paired-comparison clinical study of ketorolac tromethamine0.5% ophthalmic solution compared with placebo eyedrops inthe treatment of seasonal allergic conjunctivitis. Surv Oph-thalmol 1993;38(Suppl):13340.

6. Flach AJ, Lavelle CJ, Olander KW, et al. The effect of

ketorolac tromethamine solution 0.5% in reducing postopera-tive inflammation after cataract extraction and intraocular lensimplantation. Ophthalmology 1988;95:127984.

7. Flach AJ. Cyclo-oxygenase inhibitors in ophthalmology. SurvOphthalmol 1992;36:259 84.

8. Flach AJ. Nonsteroidal anti-inflammatory drugs in ophthal-mology [review]. Int Ophthalmol Clin 1993;33:17.

9. Fraser-Smith EB, Matthews TR. Effect of ketorolac on herpessimplex virus type one ocular infection in rabbits. J Ocul

Pharmacol 1988;4:3216.10. Fraser-Smith EB, Matthews TR. Effect of ketorolac on

Pseudomonas aeruginosa ocular infection in rabbits. J OculPharmacol 1988;4:1019.

11. Fraser-Smith EB, Matthews TR. Effect of ketorolac on Can-dida albicans ocular infection in rabbits. Arch Ophthalmol1987;105:2647.

12. Gordon YJ, Araullo-Cruz T, Romanowski EG. The effects oftopical nonsteroidal anti-inflammatory drugs on adenoviralreplication. Arch Ophthalmol 1998;116:9005.

13. Kosrirukvongs P. Topical piroxicam and conjunctivitis. J MedAssoc Thai 1997;80:28792.


1517

a randomized, double-masked trial of topical ketorolac versus

Documents