National Eye Institute (NEI) Ocular Hypertension Treatment Study (OHTS)

The Ocular Hypertension Treatment Study (OHTS) is an National Eye Institute-sponsored multi-center, randomized, prospective treatment trial designed to determine whether lowering intraocular pressure (IOP) in individuals with ocular hypertension delays or prevents the development of primary open angle glaucoma (POAG). A total of 1,636 individuals with ocular hypertension between 40 and 80 years old were enrolled in the study. In addition to ocular hypertension, subjects in the OHTS were required to have normal optic nerve appearance as determined by the OHTS Optic Disc Reading Center and normal and reliable visual field tests at the time of enrollment by the OHTS Visual Field Reading Center. OHTS subjects were randomly assigned to either an observational group which received close observation or a topical medication group which received medication as needed to achieve a 20% reduction in IOP from their baseline levels. Subjects then were examined at regular intervals for optic disc cupping or visual field defects. Other clinical measures were also obtained from OHTS subjects including central corneal thickness (CCT) and intraocular pressure. The primary outcome monitored for the OHTS was the development of glaucoma in one or both eyes as defined by reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG by the masked OHTS Endpoint Committee. The OHTS study design has been reported in detail (Gordon, 1999; PMID: 10326953).

The OHTS confirmed that ocular hypertension is a risk factor for developing POAG and showed that lowering IOP reduced the risk for developing POAG (Kass, 2002; PMID: 12049574). The OHTS also demonstrated that thin CCT is a significant risk factor for the development of POAG (Gordon, 2002; PMID: 12049575).

Blood samples were also collected from 1,077 OHTS participants for an ancillary genetics study. DNA was prepared from these samples and used in a genome-wide association scan (GWAS) designed to identify genetic factors that control the magnitude of quantitative features of glaucoma (baseline IOP, baseline cup-to-disc ratio, and CCT). Genotypes from the GWAS and these clinical data (IOP, cup-to-disc ratio, and CCT) have been provided to dbGaP.

• Study Design:
  • Case-Control
• Study Type:
  • Clinical Trial
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 1063
• Subject Sample Telemetry Report (SSTR)

Inclusion Criteria:

1. IOP between 24 and 32 in one eye and between 21 and 32 in the other eye
2. Age 40-80 years inclusively at the time of enrollment
3. Normal and reliable Humphrey 30-2 visual fields for both eyes as determined by the OHTS Visual Field Reading Center
4. Normal optic discs in both eyes on clinical examination and on stereoscopic photographs as determined by the OHTS Optic Disc Reading Center
5. Informed consent

Exclusion Criteria:

1. Best-corrected visual acuity worse than 20/40 in either eye
2. 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.
3. A life-threatening or debilitating disease
4. Secondary causes of elevated IOP, including ocular and systemic corticosteroid use.
5. Angle closure glaucoma or anatomically narrow angles - 75% of the circumference of the angle must be grade 2 or more by the Shaffer criteria.
6. Other diseases that cause visual field loss or optic disc abnormalities.
7. Difference in cup-disc ratios (horizontal by contour) of the 2 eyes > 0.2
8. 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 retinopahthy.
9. Inability to visualize or photograph the optic discs
10. Pregnant or nursing women as determined by patient self-report and testing.

• February 1994 - Enrollment opens
• October 1996 - Enrollment closes
• June 2002 - Report that topical ocular hypotensive medication delays or prevents the onset of POAG
• June 2002 - Report of baseline factors that predict the onset of POAG

• Primary Phenotype: Glaucoma, Open-Angle
• Ocular Hypertension

• Principal Investigator
  • John Fingert, MD, PhD. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, IA, USA.
• Co-Investigators
  • Jian Huang, PhD. Department of Statistics and Actuarial Sciences, University of Iowa, IA, USA.
  • Kai Wang, PhD. Department of Biostatistics, University of Iowa, IA, USA.
  • Todd Scheetz, PhD. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, IA, USA.
  • Michael Kass, MD. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Mae Gordon, PhD. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
• Institute
  • National Eye Institute, Bethesda, MD, USA.
• Funding Sources
  • R01 EY018825. National Eye Institute, Bethesda, MD, USA.
  • X01 HG005248. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
• Genotyping Center
  • Johns Hopkins University Center for Inherited Disease Research (CIDR), Baltimore, MD, USA.
• Funding Source for Genotyping
  • HHSN268200782096C. NIH contract "High throughput genotyping for studying the genetic contributions to human disease". National Institutes of Health, Bethesda, MD, USA.