Elevated Intraocular Pressure: Making the Case for Treatment

Reducing intraocularpressure (IOP)slows the progressionof glaucoma--or does it? Until recently,no evidence from arandomized controlled trialsupported the practice oftreating elevated IOP withdrug therapy or surgery.Indeed, a 1988 studyfound no benefit in loweringIOP in patients with glaucoma.¹ Since the publicationof this study's results, thedisease has been consideredan optic neuropathy,and IOP has been relegatedto a risk factor for primaryopen-angle glaucoma(Table).^2-4 Many currentdefinitions of glaucomaused by researchers andprofessional organizationsdo not even mention IOP.^5,6AN IMPORTANTNEW STUDYThe Early ManifestGlaucoma Trial (EMGT)is the first randomized,controlled study of the effectof lowering IOP on thecourse of the eye disease.The recently publishedresults show that immediatetreatment of newly diagnosed open-angle glaucomaslows the rate of diseaseprogression.⁷This Swedish trial laysto rest much of the ongoinguncertainty concerningthe significance of IOP.⁸The investigators evaluatedthe effects of treatment inpatients with early manifestopen-angle glaucoma, includingprimary open-angleglaucoma, normal-tensiondisease, and exfoliativeglaucoma (Figure). Personswith angle-closureglaucoma were not studied.A total of 255 studyparticipants between theages of 50 and 80 years(median age, 68 years) withmild to moderate forms ofglaucoma were randomlyassigned to 360-degree argonlaser trabeculoplastyplus 0.5% betaxolol hydrochlorideeye drops twicedaily (129 patients) or to noinitial treatment (126 patients).Most participantswere white; 66% were women.All had visual field defects;the average mean deviationwas -4 dB. Meanbaseline IOP was 20.6 mmHg for the treatment groupand 20.9 mm Hg for thecontrol group. Baseline IOPfor all patients ranged from13 to 31 mm Hg.IOP was measuredand Humphrey full-threshold30-2 perimetry performedevery 3 months; optic disc photographywas done every 6 months.Patients were monitored4 times a year for 6 yearsafter initial randomization.SIGNIFICANTRESULTSIn treated patients,IOP decreased by 5.1 mmHg, or 25%; this reductionwas maintained throughoutthe follow-up period.Visual field damage worsenedin 58 (45%) of thetreated patients, with a mediantime to disease progressionof 66 months. Diseaseprogressed in 78(62%) of the controls in amedian of 48 months. Thebenefit of treatment was seen in all age groups withoutregard to the severityof visual field involvementor to the presence of normal-tension or primaryopen-angle glaucoma. Fewside effects from the laserand medical therapieswere reported.An intriguing findingis that glaucoma progressedin as many as 30%of patients 4 years aftercombination laser surgeryand medical therapy. Conversely,the disease did notprogress in many untreatedpatients. These resultshighlight the need for carefulpatient follow-up.Exfoliative glaucomawas the most aggressiveform of open-angle glaucoma studied. The diseaseprogressed more rapidly inboth treated and untreatedpatients.ETHICAL ISSUESThe issue of withholdingtreatment from patientswith a known, potentiallyblinding disease, such asglaucoma, for a scientificstudy needs to be explored.The US Department ofHealth and Human ServicesOffice for Human ResearchProtections is increasinglymore watchful ofhuman research projects,and the United States Congressis considering strictlegislation that is more protectiveof patients involvedin research studies.⁹These concerns wereaddressed by the scientistswho reviewed the EMGT'soriginal grant applicationand by both the NationalEye Institute and theSwedish Research Council,who cosponsored the trial.Control group participantswho showed the earliestprogression of diseasewere immediately offeredtreatment. Latanoprost,50 μg/mL once daily, wasgiven to patients whoseIOP exceeded 25 mm Hgin treated eyes or to thosein the control group withIOP greater than 35 mmHg or in whom visual fieldchanges were detected.

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