Ocular-Hypertensive and Anti-Inflammatory Response to Rimexolone Therapy in Children
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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 (REPRINTED) ARCH OPHTHALMOL / VOL 121, DEC 2003 WWW.ARCHOPHTHALMOL.COM 1716 ©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 mea- surements 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 (asymptom- atic) to 5 (severely affected).20,29 SUBJECTS STATISTICAL ANALYSIS With parental consent, children who underwent bilateral sym- metric 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.