Intraocular Pressure Fluctuation : A Risk Factor for Visual Field Progression at Low Intraocular Pressures in the Advanced Glaucoma Intervention Study

What Biomechanical Properties of the Cornea Are Relevant for the Clinician

Purpose To analyze the correlation between corneal hysteresis (CH) measured with the Ocular Response Analyzer (ORA, Reichert) and ultrasonic corneal central thickness (CCT US) and intraocular pressure measured with Goldmann applanation tonometry (IOP GA). Setting Bordeaux 2 University, Ophthalmology Department, Bordeaux, France. Methods This study comprised 498 eyes of 258 patients. Corneal hysteresis, corneal resistance factor (CRF), and IOP corneal-compensated (IOPcc) were provided by the ORA device; CCT US and IOP GA were also measured in each eye. The study population was divided into 5 groups: normal (n = 122), glaucoma (n = 159), keratoconus (n = 88), laser in situ keratomileusis (LASIK) (n = 78), and photorefractive keratectomy (n = 39). The Pearson correlation was used for statistical analysis. Results Corneal hysteresis was not strongly correlated with IOP or CCT US. The mean CH in the LASIK (8.87 mm Hg) and keratoconus (8.34 mm Hg) groups was lower than in the glaucoma (9.48 mm Hg) and normal (10.26 mm Hg) groups. The lower the CH, the lower its correlation with IOPcc and IOP GA. A CH higher than the CRF was significantly associated with the keratoconus and post-LASIK groups. Conclusions Corneal hysteresis, a new corneal parameter, had a moderate dependence on IOP and CCT US. Weaker corneas could be screened with ORA parameters, and low CH could be considered a risk factor for underestimation of IOP. The CCT US should continue to be considered a useful parameter.

Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry

Purpose To investigate relationships between acute intraocular pressure (IOP)-induced optic nerve head surface deformation and corneal hysteresis and thickness in glaucomatous and nonglaucomatous human eyes. Methods This was a prospective experimental study of 100 subjects (38 with glaucoma, 62 without glaucoma). Data collected included spherical equivalent, optic disc diameter, central corneal thickness (CCT), axial length, cylinder, Goldmann IOP, Pascal IOP, and ocular pulse amplitude and ocular response analyzer (ORA) measurements of corneal hysteresis (CH). Elevation of IOP was induced in the right eye of each subject with a modified LASIK suction ring to an average of 64 mm Hg for less than 30 seconds. Heidelberg Retina Tomography II (HRT) was used to map the optic nerve surface before and during IOP elevation. Mean cup depth was calculated using built-in HRT data analysis software. Change in optic disc depth during IOP elevation was calculated for all right eyes, and tests for correlation with the parameters listed were performed. Results Both CH and CCT were lower in the glaucoma group (8.8 mm Hg and 532 microm) than in the control group (9.6 mm Hg, P = 0.012; 551 microm, P = 0.011, respectively). There were no statistically significant differences in spherical equivalent, cylinder, axial length, optic disc size, or ocular pulse amplitude between the glaucoma and the control groups. There was no difference between the amount of IOP elevation between the two groups (P = 0.41), and the average difference in mean cup depth between baseline (mean cup depth, 247 microm) and during IOP elevation was 33 microm (29.8 microm in glaucoma and 36.1 microm in control; P = 0.5). Multiple variable analysis, controlling for age and sex, showed that CH was correlated with mean cup depth increase (P = 0.032). This relationship persisted (P = 0.032) after controlling for glaucoma status in addition to age and sex. Other factors, including CCT (P = 0.3), axial length (P = 0.9), ocular pulse amplitude (P = 0.22), and spherical equivalent (P = 0.38), were not significant in this model. Conclusions In the glaucoma patients but not the control patients, CH but not CCT or other anterior segment parameters was associated with increased deformation of the optic nerve surface during transient elevations of IOP. (ClinicalTrials.gov number, NCT00328835.).

Corneal Hysteresis but Not Corneal Thickness Correlates with Optic Nerve Surface Compliance in Glaucoma Patients

Objectives: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. Design: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. Setting: Primary and secondary care. Participants: Adults with ocular hypertension (IOP > 21mmHg) and the public (surveillance preferences). Interventions: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. Main outcome measures: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). Results: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. Limitations: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. Conclusions: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. Funding: The National Institute for Health Research Health Technology Assessment Programme. © Queen's Printer and Controller of HMSO 2012.

https://njl-admin.nihr.ac.uk/document/download/2002258

Surveillance for Ocular Hypertension: An Evidence Synthesis and Economic Evaluation

PURPOSE. The Ocular Response Analyzer (ORA) is a new instrument that measures the corneal biomechanical response (corneal hysteresis, CH) to rapid indentation by an air jet. CH is the difference in applanation pressures (P1, P2) between the rising and falling phases of the air jet. The investigation had two parts: a characterization study and a validation study. In the characterization study, the purposes were to investigate the intraocular pressure (IOP)– dependence of CH and to characterize the performance of the ORA. In the validation study, the purposes were to investigate the association between CH and both age and central corneal thickness (CCT) and the agreement between ORA and Goldmann applanation tonometer (GAT) IOP measurements. METHODS. For the characterization study, data were collected from 105 untreated subjects (45 ocular hypertensive patients and 60 normal subjects; mean age, 60 years, range, 26 – 82). GAT and ORA measurements were performed before and after IOP lowering of one randomly selected eye with apraclonidine drops. The change in P1 and P2 (arbitrary units) in relation to change in GAT IOP was analyzed to calibrate the instrument. The relation between P1, P2, and CCT was explored and ORA IOP was derived from the analyses. For the validation study, ORA and GAT IOP and CCT were measured in 144 eyes of 144 untreated subjects (mean age, 58 years; range, 19 – 83). The characterization calculations were applied to the dataset and values of CH and ORA IOP were calculated. The relationship between CH and both subject age and CCT was determined. The associations between CH and CCT and between ORA and GAT IOPs, were investigated by linear regression analysis. The agreement between measuring devices was calculated. RESULTS. In the characterization study, P1 changed by 6.41 arbitrary units for every 1-mm Hg change in GAT IOP. CH (P1 P2) changed by 1.60 arbitrary units for every 1-mm Hg change in GAT IOP. For each unit change in P2, P1 changed by 1.27 units. From this association a new IOP-independent corneal factor was derived [P1 (P2/1.27)] and is termed the corneal constant factor (CCF; mm Hg). ORA IOP normalized for CCF was defined as P2 – CCF (mm Hg). The CCF (mm Hg) was associated with CCT (micrometers) and with age: CCF [(0.036 CCT) (0.028 age)] 1.06 (adjusted r 2 0.34; P 0.0001 for CCT, P 0.007 for age). Normalized ORA IOP measurements were not associated with CCT. GAT IOP was associated with CCT and CCF—more strongly with the latter: GAT IOP (0.03 CCT)1.52 (r 2 0.06, P 0.002); GAT IOP (0.65 CCF) 4.5 (r 2 0.13, P 0.0001). The mean difference (95% limits of agreement) between GAT and normalized ORA IOP was 0.1 (6.6 to 6.8) mm Hg. CONCLUSIONS. The CCF describes an IOP-independent biomechanical property of the cornea that increases with thicker CCT and decreases with greater age. It is moderately strongly associated with CCT and yet explains more of the interindividual variation in GAT IOP than does CCT. Normalized ORA IOP measurements are not associated with CCT. (Invest Ophthalmol Vis Sci. 2006;47:5337–5347) DOI:10.1167/iovs.060557

Cynthia R. Roberts

Papers

Corneal Thickness- and Age-Related Biomechanical Properties of the Cornea Measured with the Ocular Response Analyzer