Ocular-Hypertensive and Anti-Inflammatory Response to Rimexolone Therapy in Children

CLINICAL SCIENCES Ocular-Hypertensive and Anti-inflammatory Response to Rimexolone Therapy in Children

Dorothy S. P. Fan, FRCS; Christopher B. O. Yu, FRCOphth; Thomas Y. H. Chiu, MRCS; Chun Yu Wong, FRCOphthHK, FRCS; Joan S. K. Ng, FRCS; Chi Pui Pang, DPhil; Dennis S. C. Lam, FRCS, FRCOphth

Objective: To compare the ocular-hypertensive and anti- study. Intraocular pressure increased significantly in inflammatory response to rimexolone (116-hydroxy- both treatment groups compared with the preoperative 16␣fluoro-6␣methylpresdnisolone) and fluorometho- values (PϽ.001). The mean (SD) peak intraocular pres- lone (21-deoxy-9␣fluoro-6␣methylprednisolone) therapy sure was significantly higher in the rimexolone-treated in children’s eyes. group, 19.7 (6.1) vs 17.6 (4.6) mm Hg (PϽ.001). Simi- larly, the mean (SD) net increase in intraocular pressure Methods: With parental consent, children who under- (PϽ.001), was also higher in the rimexolone-treated went surgical procedures for bilateral symmetric strabis- eyes, 5.9 (4.4) vs 3.9 (4.1) mm Hg (PϽ.001). In addi- mus from January 18, 2000, through November 16, 2001, tion, a greater percentage of the rimexolone-treated were recruited. One eye was randomized to receive topi- patients had no conjunctival erythema on days 13 cal 1% rimexolone while the contralateral eye received (11.1% vs 0.0%) and 20 (88.9% vs 55.6%) (P=.03). topical 0.1% fluorometholone, 4 times daily for 4 weeks. Conclusions: Rimexolone seems to be a more effective Main Outcome Measures: Intraocular pressures and anti-inflammatory agent than fluorometholone. How- anti-inflammatory responses were the main outcome mea- ever, unlike adults, the ocular-hypertensive effect in chil- sures and were serially measured postoperatively for 8 dren treated with rimexolone was higher. It would be de- weeks. sirable to monitor the intraocular pressure regularly when rimexolone therapy is used in children. Results: Fifty-four children, aged from 4 to 8 years (mean [SD] age, 5.33 [1.26] years), participated in the Arch Ophthalmol. 2003;121:1716-1721

ORTICOSTEROIDS ARE com- topical dermatologic,9 topical ocular,10,11 monly used anti-inflam- and periocular corticosteroid agents12 is matory agents.1 They are well established. Even inhalation and na- used in the treatment of sal corticosteroids have been reported to various ocular diseases be associated with ocular hypertension in and after cataract, glaucoma, or strabis- susceptible adults.13,14 C2-4 15 mus surgery. The duration of use de- Armaly studied the ocular-hyperten- pends on the indication, but treatments can sive response of healthy adults to the ap- last for weeks. The use of corticosteroids plication of topical dexamethasone eye- carries many significant adverse effects drops as early as 1963. He demonstrated that including glaucoma, corneal problems, there was an increase in IOP and a reduc- posterior subcapsular cataracts, and ex- tion in outflow facility in healthy subjects acerbations of infection.5,6 Corticosteroid- after 4 weeks of dexamethasone applica- From the Departments of induced glaucoma is usually character- tion. Moreover, he classified subjects into Ophthalmology & Visual ized by an elevated intraocular pressure the following 3 responder groups accord- Sciences, The Chinese (IOP) after corticosteroid use and can re- ing to the degree of their responses to the University of Hong Kong, Hong sult in irreversible visual field and vision treatment: a low responder had an in- Kong Eye Hospital, Kowloon loss. Clinically, corticosteroid-induced crease in IOP of less than 6 mm Hg; an in- (Drs Fan, Yu, Chiu, Pang, and glaucoma with an elevated IOP is usually termediate responder had an increase be- Lam) and the Prince of Wales Hospital, Shatin, New Territory symptom free until significant damage has tween 6 and 15 mm Hg; and a high (Drs Wong, Ng, and Lam), been done, and then only comes to light responder had an increase of more than 15 Hong Kong. The authors have when the disease has already reached an mm Hg. In the general healthy population, no relevant financial interest in advanced stage. The ocular-hypertensive 5% were high corticosteroid responders, this article. response in adults to oral,7 intravenous,8 35% were intermediate responders, and the

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 remaining 60% of the population had no response.15,16 A sent was obtained from parents of all study subjects after the na- 1997 study found that the ocular-hypertensive response ture and possible consequences of the study had been ex- to topical dexamethasone therapy occurred more fre- plained. The parents were informed that the children would receive quently, severely, and rapidly in children than in different treatments in their eyes after the operation. Children were adults.17 Sixty-two percent (10 of 16 children) were high examined 1 day before the operation. Intraocular pressure measurements were performed in an assigned room that was quiet corticosteroid responders compared with 5% of the and comfortable. Ophthalmic personnel who were experienced adults. Moreover, this ocular-hypertensive response to in dealing with children performed the IOP measurements.17 Non- topical dexamethasone therapy in children was dose contact tonometry (XPERT NCT Plus Non-Contact Tonometer; dependent. The higher the frequency of dexamethasone Leica, Depew, NY) was used because it could be more easily tol- application, the more significant was the ocular- erated by children and its reliability had been reported to be ex- hypertensive effect.18 cellent.26-28 Three consistent readings were obtained from each Less potent corticosteroids, such as fluorometho- eye and the mean value was used for analysis. lone (21-dexoxy-9␣fluoro-6␣methylprednisolone), have All operations were performed by 4 of us (D.S.P.F., C.B.O.Y., been reported to have a reduced risk of corticosteroid- C.Y.W., and J.S.K.N.) under general anesthesia. One eye of each induced elevation in IOP compared with dexamethasone child was randomized to receive 0.1% fluorometholone eye- therapy.17,19,20 However, the anti-inflammatory action is cor- drops (Flucon; Alcon Laboratories, Ft Worth, Tex), 4 times per respondingly reduced by using a less potent corticoste- day, and the contralateral eye would receive 1.0% rimexolone eyedrops (Vexol, Alcon Laboratories), 4 times per day, after un- roid. The current strategy for the development of new cor- dergoing a bilateral symmetric strabismus operation. Topical ticosteroid agents for ocular use is, therefore, to identify 0.25% chloramphenicol, 4 times per day, was also prescribed for drugs that exhibit marked anti-inflammatory activity while both eyes. The treatment commenced from the day of the op- decreasing the propensity to raise the IOP. eration and continued for 4 weeks. Patients, parents, optom- A new corticosteroid, 1% rimexolone ophthalmic etrists, and ophthalmologists responsible for assessing the study suspension (116-hydroxy-16␣fluoro-6␣methylpredniso- outcomes were masked by not knowing the eyedrop allocated lone), has shown similar anti-inflammatory activity com- for each eye. pared with corticosteroids such as 1.0% prednisolone ac- The IOP and the degree of inflammation were assessed. etate.21 Rimexolone lacks a hydroxyl substitute at the C-21 Intraocular pressure was measured on postoperative days 1, 3, position of its chemical structure. Thus, it is proposed 6, 13, 20, 27, 41, and 55. The procedure for IOP measurement to be less likely to elevate IOP. A double-masked, ran- was performed as described earlier. The IOP of each patient was measured within 2 hours of the assessment day. Corticoste- domized, crossover study of corticosteroid responders roid therapy was discontinued if any eye developed an IOP higher compared the effects on IOP of 1% rimexolone with those than 30 mm Hg and more frequent follow-up visits were ar- of 1.0% prednisolone and 0.1% fluorometholone. The re- ranged. Antiglaucomatous therapy (a ␤-adrenergic blocking sults suggested that the IOP-elevating potential was com- agent) was initiated until the patient’s baseline IOP was reached. parable to that of fluorometholone.22 This medication has In addition, the optic discs were evaluated with fundi exami- been used in the treatment of uveitis23 and postsurgical nation. inflammation in adults.24,25 Children’s eyes, however, tend The conjunctival inflammatory response was analyzed ob- to have a more exaggerated ocular-hypertensive re- jectively by comparing the degree of conjunctival hyperemia sponse to dexamethasone therapy than those of adults.17,18 over the sites of the muscle surgery against a series of color pho- To our knowledge, whether children would also have a tographs and by allocating a conjunctival inflammatory score for each eye on postoperative days 6, 13, 20, and 27.20,29 A score substantial ocular-hypertensive response to rimexolone of 3 denoted a severe inflammatory response; a score of 0 de- therapy is yet unknown. noted the absence of inflammation.20,29 Patient symptoms were also graded subjectively by both the patients and their parents regarding ocular discomfort and conjunctival discharge. The METHODS severity of symptoms was graded on a scale of 0 (asymptomatic) to 5 (severely affected).20,29 SUBJECTS STATISTICAL ANALYSIS With parental consent, children who underwent bilateral symmetric strabismus surgery at the Prince of Wales Hospital or Demographic data of the patients were analyzed by descrip- the Hong Kong Eye Hospital, Hong Kong, from January 28, 2000, tive statistics. The peak IOP and the rise in IOP (calculated as through November 16, 2001, were recruited for this study. Eli- peak IOP minus preoperative IOP) between the 2 eyes were com- gible candidates were children aged between 3 and 10 years for pared using paired t tests.15-18,20 The time taken to reach the peak the original study, but when recruited by us, the children were IOP was assessed between the 2 groups using the ␹2 test. The aged between 4 and 8 years, with a preoperative IOP of 21 inflammation scores between the 2 eyes were compared using mm Hg or less, and a cup-disc ratio of 0.3 or less with no other the Wilcoxon signed rank test. The inflammation scores were systemic and ocular diseases. Exclusionary criteria included a also used as the basis for assessing the percentage of eyes with history of corticosteroid use in the previous whole year; a fam- no inflammation. An eye was defined as having no inflamma- ily history of glaucoma; and failure to comply with treatment, tion if the inflammation score was 0 at that follow-up visit. ␹2 follow-up schedules, and IOP measurement. Test was used to compare the cumulative percentage in each group who presented with no inflammation at the follow-up PROCEDURE visits. PϽ.05 was defined as statistically significant. The sample size was calculated based on an estimated mean The study and the measurements followed the guidelines of the difference in IOP of 2 mm Hg between the 2 groups.20 With 49 Declaration of Helsinki. The study was approved by the ethics eyes in each group, the study had at least 80% power to detect committee of The Chinese University of Hong Kong. Written con- the clinically important IOP difference. Assuming a dropout

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Table 1. Summary of Intraocular Pressure (IOP) Changes in the 1% Rimexolone- and 0.1% Fluorometholone-Treated Groups*

Variable Rimexolone-Treated Group Fluorometholone-Treated Group P Value Preoperative IOP, mm Hg 13.8 (3.5) [7.5 to 20.0] 13.7 (3.3) [9.5 to 20.3] .38 Peak IOP, mm Hg 19.7 (6.1) [10.3 to 28.0] 17.6 (4.6) [12.3 to 26.0] Ͻ.001 Net IOP change, mm Hg 5.9 (4.3) [1.7 to 16.0] 3.9 (4.1) [−3.3 to 10.0] Ͻ.001

*Data are given as the mean (SD) [range].

50 24 Child’s Baseline IOP Peak IOP

22 40

20 30

18 20 Cumulative % of Eyes 16 Rimexolone- 10 Treated Group Fluorometholone- 14 Treated Group

95% Confidence Interval of IOP, mm Hg 95% Confidence Interval of IOP, 0 12 0136342027 41 48 54 Time of Measurement, d

10 Rimexolone-Treated Fluorometholone-Treated Figure 2. Cumulative percentages of eyes with intraocular pressure Group measurements greater than 21 mm Hg in the 1% rimexolone– and 0.1% fluorometholone–treated groups. Figure 1. The difference between peak intraocular pressure (IOP) measurements of the 1% rimexolone– and 0.1% fluorometholone–treated groups as well as their respective preoperative IOP measurements. The error fluorometholone-treated group. The mean (SD) peak IOPs bars indicate the 95% confidence intervals. were 19.7 (6.1) mm Hg (95% confidence interval [CI], 18.0-21.4 mm Hg) for the rimexolone-treated group and rate of 10%, 55 children were recruited; 54 children partici- 17.6 (4.6) mm Hg (95% CI, 16.3-18.8 mm Hg) for the pated in the study. fluorometholone-treated group (Figure 1). Both treatment groups had peak IOPs significantly higher than the Ͻ RESULTS preoperative values (paired t test, both P .001). More- over, the peak IOP in the rimexolone-treated group was Fifty-five children were recruited; however, only 54 chil- also significantly higher than that recorded in the fluo- dren (24 boys [44.4%] and 30 girls [55.6%]), aged 4 to 8 rometholone-treated group (95% CI, 1.1-3.1 mm Hg; years (mean [SD] age, 5.33 [1.26] years), participated in paired t test, PϽ.001), as given in Table 1. In both groups, the study, because 1 child had been uncooperative during none of the children had a peak IOP of 30 mm Hg or IOP measurement. They all underwent bilateral symmet- higher. ric strabismus operations. Forty children (74.1%) re- Eighteen eyes (33.3%) in the rimexolone-treated group ceived bilateral lateral rectus recessions, 11 children (20.4%) and 15 eyes (27.8%) in the fluorometholone-treated group had bilateral medial rectus recessions, and 3 children (5.6%) had IOPs higher than 21 mm Hg (␹2 test, P=.53) at some received bilateral inferior oblique recessions. (Owing to stage of the study. The cumulative percentages of eyes with rounding, these percentages do not total 100.)Fifty-four eyes elevated IOPs of more than 21 mm Hg are shown in received rimexolone eyedrops (24 right eyes and 30 left Figure 2. After installation of topical corticosteroid eye- eyes), and the fellow 54 eyes (30 right eyes and 24 left eyes) drops, the percentage of eyes having IOPs of more than 20 received fluorometholone eyedrops. mm Hg at days 6, 13, 20, and 27 were 14.8%, 33.3%, 42.6%, The mean (SD) preoperative IOP was 13.7 (3.4) and 46.3% in the rimexolone-treated group, and 9.3%, mm Hg. There was no statistically significant difference 11.1%, 22.2%, and 24.1% in the fluorometholone-treated between the rimexolone-treated group (13.8 [3.5] mm Hg) group, respectively (␹2 test, P=.82). and fluorometholone-treated group (13.7 [3.3] mm Hg) The net increase in IOP was calculated by subtract- (paired t test; P=.38) (Table 1). ing the preoperative IOP from the peak IOP. The net increase in IOP was also higher in children in the rimexo- OCULAR-HYPERTENSIVE EFFECT lone-treated group (mean [SD], 5.9 [4.4] mm Hg; range, 1.7-16.0 mm Hg) than those in the fluorometholone- The ranges of peak IOPs were 10.3 to 28.0 mm Hg in the treated group (3.9 [4.1] mm Hg; range, −3.3 to 10.0 rimexolone-treated group and 12.3 to 26.0 mm Hg in the mm Hg) (paired t test, PϽ.001), as given in Table 1. A

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 Table 2. Ocular-Hypertensive Responses to Topical 1% Rimexolone and 0.1% Fluorometholone Therapy

Type of Responder, No. of Children P Type of Classification Treatment Group Low Intermediate High Value Armaly15* Rimexolone 27 21 6 .02 Fluorometholone 36 18 0 Becker16† Rimexolone 24 30 0 .003 Fluorometholone 39 15 0

*In the Armaly classification the responder groups are defined as follows: low, a net increase in intraocular pressure (IOP) less than 6 mm Hg; intermediate, a net increase in IOP between 6 and 15 mm Hg; and high, a net increase in IOP exceeding 15 mm Hg. †In the Becker classification the responder groups are defined as follows: low, a peak IOP less than 20 mm Hg; intermediate, a peak IOP between 20 and 31 mm Hg; and high, a peak IOP exceeding 31 mm Hg.

clinically significant rise in IOP (defined as Ͼ10 mm Hg) The maximal discomfort score was 3 of 5. The number occurred more frequently in the rimexolone-treated group. of patients who had no discomfort (symptom score, 0) Six eyes (11.1%) in the rimexolone-treated group expe- in the rimexolone- and fluorometholone-treated groups rienced a rise in IOP of higher than 10 mm Hg com- were, respectively, 18 (33.3%) vs 6 (11.1%) at day 13, pared with none in the fluorometholone-treated group. 45 (83.3%) vs 33 (61.1%) at day 20, and 54 (100.0%) vs Table 2 lists the different levels of ocular- 54 (100.0%) at day 27 (␹2 test, P=.08). hypertensive response of the 2 groups according to the 15 16 classification system proposed by Armaly and Becker. COMMENT Results were similar between the 2 classifications. The proportion of high or intermediate responders was found Corticosteroids prevent or suppress the undesirable se- to be higher in the rimexolone-treated group. There were quelae of postoperative inflammation including redness, statistically significant differences in the various levels swelling, and tenderness.30 They are widely used in vari- of ocular-hypertensive response between the rimexolone- ous ocular diseases and after surgical procedures.2-4 Al- treated and the fluorometholone-treated groups accord- though the use of topical corticosteroid therapy carries less ing to the classifications of Armaly (␹2 test, P=.02) and risk of systemic complications, it can cause visual loss Becker (␹2 test, P=.003). In all children of whom the fluo- through its effect on aqueous outflow, an effect that is greater rometholone-treated eyes had an intermediate ocular- than that seen with systemic treatment.31 There are differ- hypertensive response, the fellow rimexolone-treated eyes ent types of corticosteroids with various potencies. Less po- also had an intermediate to high response. tent corticosteroids such as fluorometholone have been Eyes that had received rimexolone reached peak IOPs shown to be associated with a lesser degree of rise in IOP earlier than those that had received fluorometholone eye- in previous studies.19,32-34 However, this is accompanied by drops (Wilcoxon signed rank test, P=02). The median reduced anti-inflammatory activity. Thus, an anti- time to reach peak IOP was 6 days for the rimexolone- inflammatory agent that controls inflammation with little treated group (range, 1-27 days) vs 13 days for the fluo- effect on IOP would be an ideal agent. One percent rimexo- rometholone-treated group (range, 1-27 days). lone therapy has demonstrated satisfactory anti- There was no correlation between age and peak IOP inflammatory effect, comparable with dexamethasone (rimexolone-treated group, r=0.02, P=.88; fluorometho- therapy and may be less likely to elevate IOP.22-25 Struc- lone-treated group, r=0.13, P=.33). Moreover, age was turally, it contains a methyl group at the C-21 position. unrelated to the net increase in IOP (rimexolone- Omission of this hydroxyl group and substitution of a treated group, r =−0.01, P =.93; fluorometholone- methyl group may reduce the propensity for inducing an treated group, r=0.24, P=.08). increased IOP, as demonstrated with fluorometholone.35 In adults 1% rimexolone and 0.1% fluorometholone have ANTI-INFLAMMATORY EFFECT comparable ocular-hypertensive potential. However, it has been demonstrated in various studies that the ocular- The objective inflammatory scores decreased with time hypertensive responses of children to different types of tra- in both groups as shown in Figure 3. The conjunctival ditional corticosteroids including dexamethasone and fluo- inflammation in all cases subsided by day 27. A greater rometholone were more frequent, severe, and rapid cumulative percentage in the rimexolone-treated group compared with those of adults.17,18,20 than in the fluorometholone-treated group had no con- To our knowledge, this is the first study of the anti- junctival erythema (objective inflammatory score, 0) on inflammatory and ocular-hypertensive effects of rimexo- days 13 (rimexolone-treated group, 6 cases [11.1%]; fluo- lone therapy in children. We found that more than half rometholone-treated group, 0 cases) and 20 (rimexolone- (55.6%) of the children treated with 1% rimexolone were treated group, 48 cases [88.9%]; fluorometholone- intermediate responders (peak IOP between 20 and 31 treated group, 30 cases [55.6%]) (␹2 test, P=.03). mm Hg) according to Becker’s classification.16 Moreover, The subjective symptom scores also decreased with 6 patients (11.1%) had an IOP elevation of more than 10 time (Figure 3). However, most children had only mild mm Hg compared with preoperative values. This was more or no discomfort throughout the postoperative period. severe than what had been reported in adults. Assil et al24

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2.5 4.0

2.0 3.0

1.5

2.0 Symptom Score Inflammatory Score 1.0

1.0 0.5

0.0 0.0 6132027 6132027 Time of Assessment, d Time of Assessment, d

Figure 3. Comparison of the inflammatory (range, 3 [severe] to 0 [no]) and symptom (range, 5 [severely affected] to 0 [asymptomatic]) scores of the 1% rimexolone– and 0.1% fluorometholone–treated groups in the postoperative period. The error bars indicate the 95% confidence intervals.

found that only 2 (1.5%) of 133 rimexolone-treated adults tor will dilute and tend to undermine the severity of the had a similar IOP elevation. The more severe ocular- dose-dependent response. If the assumption is valid and hypertensive response in children compared with that in the systemic absorption is substantial, then the dose- adults can be explained by the structural and functional dependent phenomenon will be even more obvious when immaturity of the trabecular meshwork.36 Reme´ and the eyes are treated independently. Further studies in which d’Epinay37 reported that although chamber angle compo- patients are randomized to different regimens may be war- nents were fully present at birth, the maturation of angle ranted to clearly delineate the dose-dependent effect of fluo- cellular and extracellular components occurred only 1 to rometholone. Moreover, the corticosteroid eyedrops were 8 years after birth. This age-dependent response was also continued for 4 weeks postoperatively in our study. There demonstrated in rabbits.38 Owing to the limited sample are situations, such as in uveitis, in which the patients re- size, the exact relationship between age and ocular-hyper- quire corticosteroid treatment for months.43-45 The more tensive effect cannot be further differentiated in our study. pronounced dose-dependent ocular-hypertensive effect This warrants a larger-scale, prospective study to investi- might be more applicable to those patients. gate this relationship. On the other hand, TIGR protein was Our double-masked randomized study evaluated the proposed to regulate IOP during corticosteroid treat- anti-inflammatory potential of 1% rimexolone and 0.1% ment.39,40 In our previous study, TIGR mutation was con- fluorometholone, each given 4 times daily for 4 weeks, tributed to only 1 (1.1%) of the 91 Chinese patients with after bilateral symmetric strabismus operations in chil- primary open-angle glaucoma.41 Its role in corticosteroid- dren. The outcomes of treatment efficacy included the induced ocular hypertension might not be significant. How- degree of conjunctival erythema (inflammatory score) and ever, further study is required to study the effect of the TIGR severity of the patient’s discomfort (symptom score). gene in corticosteroid-induced glaucoma in children. Symptom scores did not demonstrate statistically signifi- Previous study results in adults showed that rimexo- cant differences favoring rimexolone-treated eyes. The lone therapy had an IOP-elevating potential comparable to lack of statistical significance (P=.08) for this may be ow- that of fluorometholone therapy.25,42 However, when com- ing to the mild discomfort associated with strabismus op- paring the response of the eyes receiving different types of erations. On the other hand, the rimexlone-treated group corticosteroids in this study, the rimexolone-treated eyes had lower inflammation scores then the fluorometholone- had a significantly higher peak IOP (19.7 mm Hg vs 17.6 treated group. Also, there were significantly more eyes mm Hg) as well as a net increase in IOP (5.9 mm Hg vs in the rimexlone-treated group than in the fluorometho- 3.9 mm Hg) than that of the fluorometholone-treated eyes. lone-treated group that had no conjunctival erythema. Moreover, the eyes treated with rimexolone (median, 6 days) In summary, the clinician’s follow-up impression of also reached a peak IOP earlier than those treated with fluo- inflammatory response was significantly in favor of the rometholone (median, 13 days). The mean difference in rimexolone-treated group. Although 1% rimexolone was IOP between the 2 groups was only 2 mm Hg. However, more effective in controlling inflammation, it was also we cannot exclude the systemic absorption and crossover more likely to cause corticosteroid-induced IOP eleva- effect of the topical corticosteroids. The eyes receiving the tion. Moreover, this ocular-hypertensive response was more potent corticosteroid may influence the other eye. This more pronounced in children compared with adults. In may have caused a stronger response in the eyes treated susceptible patients, other types of anti-inflammatory with the less potent regimen. The consequence of this fac- agents such as nonsteroidal anti-inflammatory drugs that

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 have been shown to cause minimal or no ocular- metholone 0.1% versus dexamethasone 0.1%. Br J Ophthalmol. 1983;67:661- 46-48 663. hypertensive effects should be considered instead. 20. Fan DS, Ng JS, Lam DS. A prospective study on ocular hypertensive and anti- inflammatory response to different dosages of fluorometholone in children. Oph- thalmology. 2001;108:1973-1977. CONCLUSIONS 21. Leibowitz HM, Kupferman A. Bioavailability and therapeutic effectiveness of topi- cally administered corticosteroids. Trans Am Acad Ophthalmol Otolaryngol. 1975; The findings from this study have suggested that 1% ri- 79:78-88. mexolone is a more effective anti-inflammatory drug than 22. Solomon KD, Vroman DT, Barker D, Gehlken J. Comparison of ketorolac tro- methamine 0.5% and rimexolone 1% to control inflammation after cataract ex- 0.1% fluorometholone. However, rimexolone also causes traction: prospective randomized double- masked study. J Cataract Refract Surg. significant ocular hypertension in children. To reduce the 2001;27:1232-1237. 23. Foster CS, Alter G, DeBarge LR, et al. Efficacy and safety of rimexolone 1% oph- chance of provocation of such an IOP rise, corticoste- thalmic suspension vs 1% prednisolone acetate in the treatment of uveitis. Am roid use should be minimized with respect to the type J Ophthalmol. 1996;122:171-182. of corticosteroid prescribed, the frequency of instilla- 24. Assil KK, Massry G, Lehmann R, et al. Control of ocular inflammation after cataract extraction with rimexolone 1% ophthalmic suspension. J Cataract Refract tion, and the duration of use. Moreover, it is necessary Surg. 1997;23:750-757. to monitor IOP in children who receive rimexolone eye- 25. Leibowitz HM, Bartlett JD, Rich R, et al. Intraocular pressure-raising potential of drops especially for those who require treatment for a pro- 1.0% rimexolone in patients responding to corticosteroids. Arch Ophthalmol. 1996; 114:933-937. longed period or at an increased frequency. 26. Eisenberg DL, Sherman BG, McKeown CA, Schuman JS. Tonometry in adults and children: a manometric evaluation of pneumatonometry, applanation, and Submitted for publication April 15, 2003; final revision re- TonoPen in vitro and in vivo. Ophthalmology. 1998;105:1173-1181. 27. Myers KJ, Lalle P, Litwak A, et al. XPERT NCT–a clinical evaluation. J Am Optom ceived July 15, 2003; accepted July 23, 2003. Assoc. 1990;61:863-869. This study was supported in part by the Action for Vi- 28. Shields MB. The non-contact tonometer: its value and limitations. Surv Ophthal- sion Eye Foundation, Hong Kong. mol. 1980;24:211-219. 29. Wright M, Butt Z, McIlwaine G, Fleck B. Comparison of the efficacy of diclofenac Corresponding author and reprints: Dorothy S. P. 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