Project description:PurposePrimary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS).DesignComparative series.ParticipantsOne thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study.MethodsSamples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox proportional hazards analyses.Main outcome measuresAssociation of POAG with known genetic factors.ResultsNo association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (P = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure).ConclusionsThe size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.

Project description: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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/10326953" target="_blank">10326953</a>). 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: <a href="http://www.ncbi.nlm.nih.gov/pubmed/12049574" target="_blank">12049574</a>). The OHTS also demonstrated that thin CCT is a significant risk factor for the development of POAG (Gordon, 2002; PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/12049575" target="_blank">12049575</a>). 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.

Project description:PurposeTo describe variability of intraocular pressure (IOP) measurements within the same eye and between right and left eyes over a 60-month period in participants in the Ocular Hypertension Treatment Study.DesignAnalysis of data from a prospective, randomized clinical trial.ParticipantsEight hundred ten participants randomized to the observation group.MethodsIntraocular pressure measurements were obtained at the baseline visit and every 6 months thereafter. Pearson correlation coefficients were calculated for IOP measurements in the same eye between visits and for IOP measurements between right and left eyes of participants at each visit. Differences in IOP measurements between visits are reported in percent change (>15%, >20%, and >30%) and in millimeters of mercury (<3 mmHg, 3-5 mmHg, and >5 mmHg). The effects of regression to the mean, consistency in time of day, and sequence of IOP measurement of right and left eyes were examined.Main outcome measuresCorrelation of IOP measurements between consecutive 6-month visits.ResultsThe correlation of IOP measurements within the same eye between consecutive visits was r = 0.62, whereas the correlation of IOP measurements between right and left eyes at the same visit was r = 0.72. Thirteen percent of eyes had >20% change in IOP between consecutive visits. Sixty-six percent of eyes had a change in IOP within 3 mmHg, and 10% of eyes had a change in IOP >5 mmHg between visits. Eyes with a higher baseline IOP had a lower IOP at 6 months. There was a stronger correlation of IOP measured within 2 hours of the time of day between visits (r = 0.56) than >2 hours apart (r = 0.39). IOP of the right eye, which was measured first, was 0.3+/-2.8 mmHg higher than the left eye.ConclusionsThe variability of IOP measurements in the same eye between consecutive visits is moderate and is greater than the variability of IOP measurements between right and left eyes at the same visit. Factors affecting the variability of IOP measurement include regression to the mean, time of day, and measurement order. Knowledge of variability in IOP and its measurements may help clinicians establish a more accurate baseline IOP, target IOP, and assessment of medication effect.

Project description:PurposeLongitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects.DesignComparative case series.ParticipantsA total of 33 873 visits by 1636 participants enrolled in the Ocular Hypertension Treatment Study. Participants were split into 6 geographic zones according to the prevailing climate in their location.TestingAt each visit, standard automated perimetry was conducted on each eye, and IOP was measured.Main outcome measuresMixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (?MD) and on IOP, both overall and within each zone.ResultsWhen all the data were included, a significant seasonal effect on ?MD was found with magnitude 0.06 dB, peaking in February (P < 0.001). Five of the 6 geographic zones exhibited significant seasonal effects on ?MD, peaking between January and April, with magnitudes ranging from 0.04 dB (P = 0.049) to 0.21 dB (P < 0.001). Zones with greater climactic variation showed larger seasonal effects on ?MD. All 6 zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (P ? 0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the 2 seasonal effects.ConclusionsThe mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations. The cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test-retest variability.

Project description:PurposeTo compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change.DesignLongitudinal, randomized clinical trial.MethodsFour hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models.ResultsIn both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, -0.0131 mm(2)/year and -0.0026 mm(2)/year, respectively). The significantly faster rate of rim area loss in black persons found in the univariate analysis did not remain significant when baseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint.ConclusionsThe rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods.

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Delaying treatment of ocular hypertension: the ocular hypertension treatment study.

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Delaying treatment of ocular hypertension: the ocular hypertension treatment study.

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