OHTS
PubMed • Full text
Clinical Question
In patients with elevated IOP at baseline, do topical ocular hypotensive medications delay and/or prevent the onset of primary open-angle glaucoma (POAG)?
Bottom Line
For patients with elevated baseline IOP (24-32 mmHg), the use of topical ocular hypotensive medications can reduce the incidence of glaucomatous visual field loss and/or optic nerve deterioration.
Major Points
The OHTS was the largest randomized trial to date assessing the efficacy of topical ocular hypotensive medications in delaying and/or preventing the onset of POAG. The study demonstrated a statistically significant reduction in IOP and POAG for those treated with topical ocular hypotensive medications versus those who were note treated. There was no evidence of increases systemic or ocular risk with ocular hypotensive medications.
Design
- Multicenter, randomized clinical trial with 2 groups: topical ocular hypotensive medication and close observation
- N=1636
- Medication Group (n=817)
- Observation Group (n=819)
- Setting: 22 clinical centers in the United States
- Enrollment: February 1994 to October 1996
- Mean duration of follow-up: 72 months for African American participants, 78 months for other participants
- Analysis: Intention-to-treat
- Primary outcome: Development of reproducible visual vield abnormality or reproducible optic nerve deterioration due to POAG
Population
Inclusion Criteria
- IOP in at least 1 eye of each patient greater than or equal to 24 mm Hg and less than or equal to 32 mm Hg
- IOP in fellow eye greater than or equal to 21 mm Hg and less than or equal to 32 mm Hg
- Age 40 to 80 years, inclusive
- Normal and reliable Humphrey 30-2 visual fields for both eyes as determined by the Visual Field Reading Center
- Normal optic discs in both eyes on clinical examination and on stereoscopic photographs as determined by the Optic Disc Reading Center
- Informed consent
Exclusion Criteria
- Best-corrected visual acuity worse than 20/40 in either eye
- Previous intraocular surgery, except for uncomplicated extracapsular cataract extraction with posterior chamber–intraocular lens implant and no escape of vitreous to the anterior chamber, strabismus, cosmetic eyelid surgery, and radial keratotomy
- A life-threatening or debilitating disease
- Secondary causes of elevated IOP, including ocular and systemic corticosteroid use
- Angle closure glaucoma or anatomically narrow angles—75% of the circumference of the angle must be grade 2 or more by Shaffer criteria
- Other diseases that cause visual field loss or optic disc abnormalities
- Difference in cup-disc ratios (horizontal by contour) of the 2 eyes .0.2
- Background diabetic retinopathy, defined as at least 1 microaneurysm seen on direct ophthalmoscopy with dilated pupil. Retinal hemorrhage is not an exclusion unless associated with background or proliferative diabetic retinopathy
- Inability to visualize or photograph the optic discs
- Pregnant or nursing women as determined by patient self-report and testing
Baseline Characteristics
- Mean Age: 55.4
- Male Participants 705
- Female Participants 932
- Mean Intraocular Pressure (mmHg) 24.9
- Mean Refractive Error (D) -0.63
- Mean Cup-Disc Ratio 0.36
- Visual Field Mean Deviation (dB) 0.24
- Mean Visual Field Pattern SD, (dB) 1.91
- Mean Visual Field Corrected Pattern SD, (dB) 1.12
Interventions
- Randomized to topical ocular hypotensive medication(goal reduce IOP by 20% or more and to reach an IOP of 24 mmHg or less) or close observation
- Topical medication was changed/added until both goals were met or maximum-tolerated therapy achieved.
- Follow-up visits were scheduled 6 months from date of randomization
- Each semi-annual examination included ocular and medical history, refraction, best-corrected visual acuity, full-threshold Humphrey white-on-white 30 2 visual field tests, slitlamp exam, IOP measurement, direct ophthalmoscopy, and completion of Glaucoma Symptom Scale. During annual exam, Medical Outcomes Study Short Form was completed to assess health-related quality of life.
Outcomes
Comparisons are topical ocular hypotensive medication group vs close observation group
Primary Outcomes
- Primary Open-Angle Glaucoma
- 4.4% medication group vs. 9.5% observation group (HR 0.40; 95% CI 0.27-0.59; Mantel-Haenszel log-rank test, P=0<.0001)
Secondary Outcomes
- IOP Reduction Goal
- 22.5% medication group vs. 4.0% observation group
- Overall, IOP goal met in both eyes 87%, in one eye 7%
Subgroup Analysis
Evaluation of African American participants demonstrated lower treatment benefit than for other participants. This value was not statistically significant.
Adverse Events
Regarding safety of treatment, there was no evidence of excess risk in the medication group for mortality, hospitalizations, developing new medical conditions, or worsening or preexisting conditions.
Criticisms
The prevalence of adverse effects of ocular hypotensive medications may be greater than reported in this article as the sample size consisted of healthy volunteers whose mean age was less than 60 years.
Funding
Funded by grants EY09341 and EY09307 from the National Eye Institute and the National Center on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD; Merck Research Laboratories, White House Station, NJ; and by an unrestricted grant from Research to Prevent Blindness, New York, NY.
Drugs were donated by the following pharmaceutical companies: Alcon Laboratories Inc, Fort Worth, Tex; Allergan Therapeutics Group, Irvine, Calif; Bausch & Lomb Pharmaceutical Division, Tampa, Fla;CIBA Vision Corporation, Duluth, Ga; Merck Research Laboratories; Novartis Ophthalmics Inc, Duluth; Otsuka America Pharmaceutical Inc, Rockville, Md; and Pharmacia & Upjohn, Peapack, NJ. Pachymeters were loaned to the clinical centers by DGH Technology, Exton, Pa.
Further Reading
Kass MA, Heuer DK, Higginbotham EJ et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open angle glaucoma. Arch Ophthalmol 2002;120 (6) 701- 713