Daniel Meira-Freitas

Corneal Hysteresis as a Risk Factor for Glaucoma Progression: A Prospective Longitudinal Study

PURPOSE To evaluate the role of corneal hysteresis (CH) as a risk factor for the rate of visual field progression in a cohort of patients with glaucoma followed prospectively over time. DESIGN Prospective observational cohort study. PARTICIPANTS The study group included 114 eyes of 68 patients with glaucoma followed for an average of 4.0 ± 1.1 years. Visual fields were obtained with standard automated perimetry. Included eyes had a median number of 7 (range, 5-12) tests during follow-up. METHODS The CH measurements were acquired at baseline using the Ocular Response Analyzer (Reichert Instruments, Depew, NY). Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). Linear mixed models were used to investigate the relationship between rates of visual field loss and baseline CH, baseline intraocular pressure (IOP), and central corneal thickness (CCT), while adjusting for potentially confounding factors. An interaction term between IOP and CH was included in the model to investigate whether the effect of IOP on rates of progression depended on the level of CH. MAIN OUTCOME MEASURES Effects of CH, IOP, and CCT on rates of VFI loss over time. RESULTS The CH had a significant effect on rates of visual field progression over time. In the univariable model including only CH as a predictive factor along with time and their interaction, each 1 mmHg lower CH was associated with a 0.25%/year faster rate of VFI decline over time (P<0.001). The multivariable model showed that the effect of IOP on rates of progression depended on CH. Eyes with high IOP and low CH were at increased risk for having fast rates of disease progression. The CH explained a larger proportion of the variation in slopes of VFI change than CCT (17.4% vs. 5.2%, respectively). CONCLUSIONS The CH measurements were significantly associated with risk of glaucoma progression. Eyes with lower CH had faster rates of visual field loss than those with higher CH. The prospective longitudinal design of this study supports the role of CH as an important factor to be considered in the assessment of the risk of progression in patients with glaucoma. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Predicting progression in glaucoma suspects with longitudinal estimates of retinal ganglion cell counts.

PURPOSE We evaluated the ability of baseline and longitudinal estimates of retinal ganglion cell (RGC) counts in predicting progression in eyes suspected of having glaucoma. METHODS The study included 288 glaucoma suspect eyes of 288 patients followed for an average of 3.8 ± 1.0 years. Participants had normal standard automated perimetry (SAP) at baseline. Retinal nerve fiber layer thickness assessment was performed with optical coherence tomography (OCT). Progression was defined as development of repeatable abnormal SAP or glaucomatous progressive optic disc changes. Estimates of RGC counts were obtained by combining data from SAP and OCT according to a previously described method. Joint longitudinal survival models were used to evaluate the ability of baseline and rates of change in estimated RGC counts for predicting progression over time, adjusting for confounding variables. RESULTS A total of 48 eyes (17%) showed progression during follow-up. The mean rate of change in estimated RGC counts was -18,987 cells/y in progressors versus -8,808 cells/y for nonprogressors (P < 0.001). Baseline RGC counts and slopes of RGC loss were significantly predictive of progression, with HRs of 1.56 per 100,000 cells lower (95% confidence interval [CI], 1.18-2.08; P = 0.002) and 2.68 per 10,000 cells/y faster loss (95% CI, 1.22-5.90; P = 0.014), respectively. The longitudinal model including estimates of RGC counts performed significantly better than models including only structural or functional indexes separately. CONCLUSIONS Baseline and longitudinal estimates of RGC counts may be helpful in predicting progression and performed significantly better than conventional approaches for risk stratification of glaucoma suspects.

Predicting progression of glaucoma from rates of frequency doubling technology perimetry change.

PURPOSE To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. DESIGN Prospective, observational cohort study. PARTICIPANTS The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7 ± 1.9 FDT tests during a mean follow-up time of 73.1 ± 28.0 months. METHODS Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). MAIN OUTCOME MEASURES The R(2) index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. RESULTS Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04-1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24), respectively. CONCLUSIONS Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma.

Glaucomatous Retinal Nerve Fiber Layer Thickness Loss Is Associated With Slower Reaction Times Under a Divided Attention Task

PURPOSE To examine the relationship between glaucomatous structural damage and ability to divide attention during simulated driving. DESIGN Cross-sectional observational study. METHODS SETTING Hamilton Glaucoma Center, University of California San Diego. PATIENT POPULATION Total of 158 subjects from the Diagnostic Innovations in Glaucoma Study, including 82 with glaucoma and 76 similarly aged controls. OBSERVATION PROCEDURE Ability to divide attention was investigated by measuring reaction times to peripheral stimuli (at low, medium, or high contrast) while concomitantly performing a central driving task (car following or curve negotiation). All subjects had standard automated perimetry (SAP) and optical coherence tomography was used to measure retinal nerve fiber layer (RNFL) thickness. Cognitive ability was assessed using the Montreal Cognitive Assessment and subjects completed a driving history questionnaire. MAIN OUTCOME MEASURES Reaction times to the driving simulator divided attention task. RESULTS The mean reaction times to the low-contrast stimulus were 1.05 s and 0.64 s in glaucoma and controls, respectively, during curve negotiation (P < .001), and 1.19 s and 0.77 s (P = .025), respectively, during car following. There was a nonlinear relationship between reaction times and RNFL thickness in the better eye. RNFL thickness remained significantly associated with reaction times even after adjusting for age, SAP mean deviation in the better eye, cognitive ability, and central driving task performance. CONCLUSIONS Although worse SAP sensitivity was associated with worse ability to divide attention, RNFL thickness measurements provided additional information. Information from structural tests may improve our ability to determine which patients are likely to have problems performing daily activities, such as driving.

Use of Statistical Analyses in the Ophthalmic Literature

PURPOSE To identify the most commonly used statistical analyses in the ophthalmic literature and to determine the likely gain in comprehension of the literature that readers could expect if they were to add knowledge of more advanced techniques sequentially to their statistical repertoire. DESIGN Cross-sectional study. METHODS All articles published from January 2012 through December 2012 in Ophthalmology, the American Journal of Ophthalmology, and Archives of Ophthalmology were reviewed. A total of 780 peer-reviewed articles were included. Two reviewers examined each article and assigned categories to each one depending on the type of statistical analyses used. Discrepancies between reviewers were resolved by consensus. MAIN OUTCOME MEASURES Total number and percentage of articles containing each category of statistical analysis were obtained. Additionally, we estimated the accumulated number and percentage of articles that a reader would be expected to be able to interpret depending on their statistical repertoire. RESULTS Readers with little or no statistical knowledge would be expected to be able to interpret the statistical methods presented in only 20.8% of articles. To understand more than half (51.4%) of the articles published, readers would be expected to be familiar with at least 15 different statistical methods. Knowledge of 21 categories of statistical methods was necessary to comprehend 70.9% of articles, whereas knowledge of more than 29 categories was necessary to comprehend more than 90% of articles. Articles related to retina and glaucoma subspecialties showed a tendency for using more complex analysis when compared with articles from the cornea subspecialty. CONCLUSIONS Readers of clinical journals in ophthalmology need to have substantial knowledge of statistical methodology to understand the results of studies published in the literature. The frequency of the use of complex statistical analyses also indicates that those involved in the editorial peer-review process must have sound statistical knowledge to appraise critically the articles submitted for publication. The results of this study could provide guidance to direct the statistical learning of clinical ophthalmologists, researchers, and educators involved in the design of courses for residents and medical students.

Advances in the Structural Evaluation of Glaucoma with Optical Coherence Tomography

Optical coherence tomography (OCT) is capable of providing quantitative and objective assessments of the optic disc, macula and retinal nerve fiber layer in glaucoma. The recent advent of spectral domain OCT (SD-OCT) has enhanced the resolution, decreased scan acquisition time, and improved the reproducibility of measurements compared to older versions of this technology. However, although OCT has been successfully used for detection of disease and evaluation of progression, the limited agreement between structural and functional tests indicates the strong need for a combined approach for detecting and monitoring the disease. A recently described approach for estimation of rates of retinal ganglion cell loss from a combination of SD-OCT and functional data is a promising method for diagnosing, staging, detecting progression, and estimating rates of glaucomatous deterioration.