Long-term Intraocular Pressure Fluctuations and Risk of Conversion from Ocular Hypertension to Glaucoma

Abstract

Purpose-To investigate whether long-term intraocular pressure (IOP) fluctuations are a risk factor for conversion from ocular hypertension to glaucoma. Design-Observational cohort study.Participants-The study included 252 eyes of 126 patients with ocular hypertension observed untreated as part of the Diagnostic Innovations in Glaucoma Study. At baseline, ocular hypertensive eyes had elevated IOP, normal visual fields (VFs) on standard automated perimetry, and normal optic discs as evaluated by stereophotograph assessment.Methods-Glaucoma conversion was defined as development of reproducible VF loss or optic disc damage. Analyses included all IOP measurements from the baseline visit to time of progression (for converters) and last follow-up (for nonconverters). Mean IOP and IOP fluctuation were calculated as the arithmetic mean and standard deviation (SD), respectively, of all available IOP measurements per eye.Main Outcome Measures-Univariable and multivariable Cox regression analyses were used to evaluate the association between IOP fluctuation and time to progression. Multivariable models adjusted for age, mean IOP, central corneal thickness, vertical cup-to-disc ratio, and pattern SD.Results-Forty eyes of 31 subjects developed glaucoma during follow-up. Mean IOPs during follow-up were 25.4±4.2 mmHg for the eyes that converted to glaucoma and 24.1±3.5 mmHg for the eyes that did not. Corresponding values for IOP fluctuation were 3.16±1.35 mmHg and 2.77±1.11 mmHg, respectively. Intraocular pressure fluctuation was not a risk factor for conversion to glaucoma both in univariable analysis (hazard ratio [HR], 1.30 per 1 mmHg higher; 95% confidence interval [CI], 0.76-1.96; P = 0.092) and in multivariable analysis (adjusted HR, 1.08 per 1 mmHg higher; 95% CI, 0.79-1.48; P = 0.620). Mean IOP during follow-up was a significant risk factor for progression both in univariable analysis (HR = 1.16 per 1 mmHg higher; 95% CI, 1.04-1.31; P = 0.010) and in multivariable analysis (adjusted HR, 1.20 per 1 mmHg higher; 95% CI, 1.06-1.36; P = 0.005).Conclusion-Long-term IOP fluctuations do not appear to be significantly associated with the risk of developing glaucoma in untreated ocular hypertensive subjects.Although elevated intraocular pressure (IOP) has been unquestionably demonstrated to be a risk factor for development and progression of glaucoma, 1-5 there has been controversy with regard to the IOP features that are the most relevant. Long-term (i.e., visit Both the AGIS and EMGT included only patients with definite glaucoma diagnosis at baseline. It is possible that the role of long-term IOP fluctuation as a risk factor for glaucoma development could be different than that for glaucoma progression. Two recent multicenter prospective randomized clinical trials reported on the predictive factors for conversion from ocular hypertension to glaucoma. In both the Ocular Hypertension Treatment Study 11 and the European Glaucoma Prevention Study, 12 higher IOP levels at the baseline visits were associated with a higher ...

Effect of Treatment on the Rate of Visual Field Change in the Ocular Hypertension Treatment Study Observation Group

“…3 The European Glaucoma Prevention Study (EGPS) suggested a similar effect attributable for each 1-mm Hg-higher IOP (11%), 8 and the Diagnostic Innovations in Glaucoma Study (DIGS) reported that each 1-mm Hg-higher mean follow-up IOP increased the risk of conversion from OHT to glaucoma by 20%. 23 Using trend analysis, Folgar et al 24 recently reported that an average IOP reduction of 40% following glaucoma surgery resulted in a 70% reduction in global rates of VF change and that locations progressing significantly before intervention had their progression either halted or slowed significantly. They also found that for each 1-mm Hg-lower postoperative IOP, the velocity of VF deterioration was slowed by 0.1 dB/year.…”

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation

“…94 In the EGPS, the area under the curve of IOP, a 'time-dependent' evaluation of IOP, taking into account the IOP behaviour for each 6-month period, was associated with the development of OAG yet IOP fluctuation during follow-up was not. 91 Medeiros and colleagues 95 found that longterm IOP fluctuations were not a significant risk factor for glaucoma development in untreated patients with OHT observed over time, but higher mean IOP levels were consistently associated with increased likelihood of developing glaucoma. Similarly, in the Malmö Ocular Hypertension Study, IOP fluctuations were not an independent risk factor for the incidence of glaucomatous visual field loss in patients with OHT, and higher IOP fluctuation was found in eyes with higher IOP levels.…”

Why Do People (Still) Go Blind from Glaucoma?

“…62 High mean IOP has also been consistently associated with glaucoma progression. 63,64 While peak IOP detection is based on measurements at office visits, the mean IOP requires longitudinal IOP data collection and may be affected by the interval between visits. Establishing a target peak IOP is clinically easier than establishing a target mean IOP in many patients.…”

“…[65][66][67] Other authors considered that IOP fluctuation is not an independent risk factor for glaucoma onset or progression. 63,64,68 This discrepancy may be due to the use of different hypotensive medications, different populations and study designs, as well as the lack of a standard definition and reproducibility of IOP fluctuation. 69,70 The true role of IOP fluctuation, including both short-and long-term variability, has not yet been adequately addressed in clinical trials given the difficulty in performing diurnal curves in all patients on a regular basis.…”