(FML) on the Intraocular Pressure of Corticosteroid Responders

Br J Ophthalmol: first published as 10.1136/bjo.68.8.581 on 1 August 1984. Downloaded from

British Journal of Ophthalmology, 1984, 68, 581-584

Effect of fluorometholone (FML) on the intraocular pressure of corticosteroid responders

E. MORRISON AND D. B. ARCHER From the Department ofOphthalmology, The Queen's University ofBelfast, Eye and Ear Clinic, Royal Victoria Hospital, Belfast, Northern Ireland

SUMMARY Steroid responsiveness to dexamethasone was determined in a large family with an established dominant form of chronic simple glaucoma. The high and intermediate steroid responders were then tested with fluorometholone-a steroid which is claimed to have a reduced risk of increasing intraocular pressure. It was found that fluorometholone had a much less pronounced ocular hypertensive effect than dexamethasone. However, one patient showed a comparable response on both drugs, and this suggests that some caution must still be exercised when using the drug on susceptible individuals. Fluorometholone was also found to be more irritable to the eye than dexamethasone.

In 1963 Becker and Mills' demonstrated that a corticosteroid preparations. Fluorometholone (21- proportion of normal individuals showed a rise in deoxy-9-fluoro-6-methyl presnisolone) is an anti- intraocular pressure after the topical administration inflammatory steroid with some structural charac- ofcorticosteroids (steroid responders). This response teristics in common with progesterone (Fig. 1). was more common in close relatives of patients with Progesterone is a steroid which lacks substantial anti- open-angle glaucoma, and this hypertensive inflammatory activity but does reduce intraocular phenomenon has proved a useful technique in study- pressure.8 Fluorometholone has been found to http://bjo.bmj.com/ ing the inheritance of this condition.2-3 Armaly4 and possess progestational activity equivalent to pro- Becker and Hahn' hypothesised that the intraocular gesterone and anti-inflammatory activity 25 to 30 pressure response to topical corticosteroids is in- times that of hydrocortisone.>" herited in an autosomal recessive manner. They based The anti-inflammatory and antihypertensive their conclusions on the finding of three levels of properties offluorometholone have been investigated response that corresponded to the homozygous by a number of workers. Castroviejo'2 studied the positive (high responder), homozygous negative (low effect of fluorometholone on patients who had on September 29, 2021 by guest. Protected copyright. responder), and heterozygous (intermediate cataract surgery or keratoplasty and demonstrated responder) states. Becker' administered topical good control ofpostoperative inflammation with little dexamethasone four times a day for six weeks and risk of increasing intraocular pressure. Mindel et al. '3 used the final intraocular pressure as a measurement compared the relative effects of fluorometholone, of the response. Armaly,7 on the other hand, used medrysone, and dexamethasone on the intraocular dexamethasone drops three times a day forfour weeks pressures of normal patients. Fluorometholone was and identified responders according to the change in less hypertensive than dexamthasone but caused a intraocular pressure. greater increase in intraocular pressure than The potential ocular hypertensive effect of local medrysone. Fairbairn and Thorson'4 used fluoro- corticosteroids has limited their unrestricted and pro- metholone on a group of patients with mild to severe longed use. Complications are most likely in glaucoma non-infectious inflammatory disorders ofthe eye who patients and their first degree relatives, and in such had previously shown an increase in intraocular instances prolonged use of corticosteroids may be pressure when treated with other steroids. They found hazardous if not contraindicated. A topical steroid that increases in intraocular pressure following the with both anti-inflammatory and ocular hypotensive administration of fluorometholone were not signifi- effects would be an attractive alternative to local cant compared with those produced by other steroids. Corrcspondencc to Miss E. Morrison, FRCS. They also examined the effects of fluorometholone 581 Br J Ophthalmol: first published as 10.1136/bjo.68.8.581 on 1 August 1984. Downloaded from

582 E. Morrison and D. B. Archer CH3I CO H3C HO --OH H3C Fig. 1 Chemicalstructure of progesterone andfluorometholone. 'F O V

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PROGESTERONE FLUOROMETHOLONE on a large random population, including many and of these eight (44-5%) were high responders, 6 patients with glaucoma, and found no significant rise (33-3%) were intermediate, and one (5.5%) was a in intraocular pressure. Stewart and Kimbrough,'5 low responder (Fig. 3). The high and intermediate on the other hand, showed that fluorometholone responders were tested with fluorometholone to raised the intraocular pressure significantly in a assess its effect on intraocular pressure. Seven (14 number ofcorticosteroid responders. We were unable eyes) of the eight high responders were available for to find any reference in the literature to studies on testing and three (6 eyes) of the intermediate close relatives of patients with glaucoma who had responders. Informed consent was obtained from all been shown to develop a high intraocular pressure patients. Each patient was examined by one person after the administration of dexamethasone. We con- (E.M.) and a mean of three intraocular pressure sidered that if such a group of steroid sensitive in- measurements taken as the baseline pressure. dividuals manifested no increase in intraocular Fluorometholone (0-1%) was prescribed four times pressure after the administration of fluorometholone a day for six weeks and the intraocular pressure it would be a significant finding. reassessed as described above. Excellent drug com- pliance was obtained in all patients.

Patients and methods http://bjo.bmj.com/ Results A large family with an established dominant form of chronic simple glaucoma was available to usfortesting Three of seven patients categorised as high cortico- (Fig. 2). From a pedigree of 65 members six persons steroid responders had a rise in intraocular pressure suffered from open-angle glaucoma. Eighteen un- in both eyes six weeks after the instillation of fluoro- affected members ofthe family were tested for steroid metholone drops (Fig. 4). Two patients (four eyes) responsiveness using the method described by Becker had a small increase in intraocular pressure in et al.3 that is, dexamethasone 0.1% four times a day comparison with the response to dexamethasone, but on September 29, 2021 by guest. Protected copyright. for six weeks. A low response was recorded as less one patient (two eyes) had a significant increase than 20 mmHg, an intermediate response as 20 to 30 comparable with the response obtained with mmHg, and a high response as greater than 31 mmHg. dexamethasone. Ofthe 18 individuals tested 15 attended for follow up, None of the patients graded as intermediate

Fig. 2 Pedigree offamily with dominantly inherited open-angle 11 11 glaucoma.

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Effect offluorometholone (FML) on the intraocularpressure ofcorticosteroid responders 583

Fig. 3 Pedigreeshown in Fig. 2 illustratingsteroid response to dexamethasone.

@ HIGH RESPONDER ITERMEDIATE RESPONDER responders had a significant rise in intraocular Tests with fluorometholone showed that the majority pressure with fluorometholone (Fig. 5). Two patients of the high steroid responders in the study did not complained of an unpleasant taste in the mouth that demonstrate a significant rise in intraocular pressure. persisted for 1 to 2 hours after instillation of the Two patients (four eyes) had a slight rise above drops. All patients, with one exception, volunteered normal, and one patient (two eyes) developed an that the fluorometholone drops were more irritant to intraocular pressure comparable with that induced by their eyes than dexamethasone drops. dexamethasone. None ofthe intermediate responders showed any abnormal rise in intraocular pressure Discussion with fluorometholone. These results provide further evidence that fluoro- Known corticosteroid responders who are the first metholone has a much less pronounced ocular hyper- degree relatives of patients with glaucoma are tensive effect than dexamethasone. The finding that probably the most sensitive group to test the ocular seven of eight high corticosteroid responders were hypertensive properties of a steroid preparation. The not affected by- fluorometholone is significant and

pedigree of patients with dominant open-angle suggests that fluorometholone is unlikely to induce a http://bjo.bmj.com/ glaucoma described in this report was sufficiently serious rise in intraocular pressure in the vast majority large to allow the identification of several cortico- of patients. Nevertheless, one high responder did steroid responders, most of whom were categorised show a rise comparable with that produced by as high responders. The result oftesting these patients dexamethasone, which shows that some caution must with dexamethasone correlated closely with the still be exercised when using this drug particularly in hypothesis of Becker and Armaly of an autosomal susceptible individuals. recessive-type inheritance of steroid responsiveness. It was notable that most patients complained of on September 29, 2021 by guest. Protected copyright. HIGH RESPONDERS Dexamethasone . Response 50 [] Fluorometholone Response

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30- Fig. 4 High steroid responders comparing intraocularpressure rise to dexamethasone and fluorometholone.

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584 E. Morrison and D. B. Archer INTERMEDIATE RESPONDERS References I Becker B, Mills DW. Corticosteroids and intraocular pressure. 50 Arch Ophthalmol 1963; 70: 5(X)-7. 2 Armaly MF. On the distribution of applanation pressure. 1. B~Dexamethasone Statistical features and the effect of age, sex and family history of Response glaucoma. Arch Ophthalmol 1965; 73: 11-8. 3 Becker B, Kolker AE, Roth RD. Glaucoma family study. Am J 401 Fluorometholone Response Ophthalmol 1960; 50: 557-67. 4 Armaly MF. Inheritance of dexamethasone hypertension and glaucoma. Arch Ophthalmol 1967; 77: 747-51. 5 Becker B, Hahn KA. Topical corticosteroids and heredity in 30- primary open-angle glaucoma. Am J Ophthalmol 1964; 57: 543- 51. 6 Becker B. Intraocular pressure response to topical corticosteroids. Invest Ophthalmol Visual Sci 1965; 4: 198-205. 7 Armaly MF. Topical dexamethasone and intraocular pressure. 2C ~~~UI1~~ In: Leydhecker W, ed. International symposium on glaucoma. Tutzing, 1966. Basel: Karger, 1967: 73-7. 8 Posthumus RG. The use and the possibilities of progesterone in the treatment of glaucoma. Ophthalmologica 1952; 124: 17-25. ic 9 Glenn EM, Miller W, Schlagel CA. Metabolic effects of adreno- cortical steroids in vivo and in vitro. Relationship to anti- .W~~p inflammatory effects. Recent Prog Horm Res 1963; 19: 107-99. 1) Schlagel CA, Northam JI, Comparative anti-inflammatory efficacy of topically applied steroids on human skin. Proc Soc CMr Exp Biol Med 1959; 101: 629-32. R L R L R L 1 1 Mass RE. Clinical evaluation of Oxylone (NSC-33()1). Cancer Treat Rep 1964; 38: 49-60. Fig. 5 Intermediate responders comparing pressure 12 Castroviejo R. Proceedings of the 79th Annual Meeting of the response to dexamethasone andfluorometholone. American Academy of Ophthalmology and Otolaryngology Dallas, Texas. 6-10 October 1974. Klin Monatsbl Augenheilkd 1975; 166: 518-20). 13 Mindel JS, Tavitian HO, Smith H, Walker EC. Comparative local irritation after the instillation of fluorometho- ocular pressure elevation by medrysone, fluorometholone and lone drops into the eye, a finding that has not been dexamethasone phosphase. Arch Ophthalmol 1980); 98: 1577-8. emphasised previously. Furthermore, two patients 14 Fairburn WD, Thorson JC. Fluorometholone anti-inflammatory complained of a persistent bad taste in the mouth and intraocular pressure effects. Arch Ophthalmol 1971; 86: 138-41. http://bjo.bmj.com/ following the use of fluorometholone, and it may be 15 Stewart RH, Kimbrough RL. Intraocular pressure response to that this response was related to the patients' genetic topically administered fluorometholone. Arch Ophthalmol 1971; constitution. 97: 2139-40. on September 29, 2021 by guest. Protected copyright.