Fractional averaging theory for discrete fractional-order system with impulses.

In this paper, we improve the averaging theory on both finite and infinite time intervals for discrete fractional-order systems with impulses. By employing new techniques, generalized impulsive discrete fractional-order Gronwall inequality is introduced. In addition, the closeness of solutions for the discrete fractional-order systems with impulses and the averaged discrete fractional-order systems with impulses is derived. Finally, three examples are provided to illustrate the efficiency of our main results.

Longitudinal changes in peripapillary atrophy in the ocular hypertension treatment study: a case-control assessment.

PURPOSE: To explore the association between peripapillary atrophy (PPA) area and conversion from ocular hypertension (OHT) to glaucoma. DESIGN: Prospective, longitudinal cohort study of cases and controls. PARTICIPANTS: We included 279 age-matched and follow-up time-matched eyes with OHT that converted to glaucoma and 279 eyes with OHT that did not convert to glaucoma. METHODS: Initial and last acceptable optic disc photos were analyzed. Disc, α-zone, and ß-zone PPA were traced independently by 2 trained readers and their areas were measured with Photoshop. The α-zone and ß-zone areas were expressed as a percentage of optic disc area. MAIN OUTCOME MEASURES: α-Zone and ß-zone PPA size over time. RESULTS: Intraclass correlation coefficients (ICCs) demonstrated that readers had good agreement on disc area (ICC = 0.97) and ß-zone (ICC = 0.82), but not α-zone (ICC = 0.48). The ß-zone, as a percentage of disc area, increased in size (P < 0.001) in both eyes with incident primary open-angle glaucoma (mean, 10.6%; standard deviation, 22.6%) and matched controls (mean, 10.1%; standard deviation, 33.7) over follow-up (mean, 12.3 years). The increase in size did not differ between cases and controls (P = 0.82). Enlargement of the ß-zone was not correlated with follow-up time (P = 0.39). CONCLUSIONS: The results did not show a difference in size of the ß-zone at baseline between eyes that proceed to develop glaucoma and those that do not. Moreover, the ß-zone enlarges equally in case and control eyes during follow-up.

Comparison of Matrix with Humphrey Field Analyzer II with SITA.

PURPOSE: To study the performance of the Matrix perimeter compared with the Humphrey Field Analyzer II (HFA) with the Swedish Interactive Thresholding Algorithm over the range of contrast sensitivities each machine could estimate. METHODS: Fifty stable glaucoma subjects at various stages of disease and three normal subjects had visual fields testing done on five different days within 8 weeks with both perimeters. Intraclass correlation coefficient of mean deviation, pattern standard deviation, and the SD of repeat measurements were evaluated. The repeatability of the sensitivity estimates at individual locations and global indices was quantified, as well as their dependence on disease severity. The relationship between sensitivity determinations with the two instruments was explored (principal curve analysis). RESULTS: Mean deviation on the HFA ranged from -31 to +2.5 dB. The mean deviation and pattern standard deviation had intraclass correlation coefficients above 0.90 for both instruments. Over most of the useful range (above 20 dB on the HFA), a difference of 1 dB for the Matrix corresponded to a difference of 2 dB for the HFA. The SD of repeat measurements increased with disease severity with HFA, but not with Matrix, except that values of 12 or 34 dB were highly variable on repeat. Variability was reduced for both HFA and Matrix when duplicate sensitivity values were used. A single Matrix test provided only 15 possible sensitivity values, unevenly spaced, but the average of duplicate measurements provided more numerous sensitivity values. A learning effect was detected for Matrix. CONCLUSIONS: The decibel values reported by the two machines are not equivalent. Variability of sensitivity determinations is affected more by the sensitivity level with HFA than with Matrix. Duplicate measurements for baseline and follow-up evaluation could be important, especially for Matrix. Further information on learning effects is needed, as is commercially available progression software for Matrix.

Glaucoma Progression Analysis software compared with expert consensus opinion in the detection of visual field progression in glaucoma.

PURPOSE: To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss Meditec, Dublin, CA) to subjective expert consensus in the detection of glaucomatous visual field progression. DESIGN: Retrospective, observational case series. PARTICIPANTS: We included 100 eyes of 83 glaucoma patients. METHODS: Five serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were evaluated by 5 masked glaucoma subspecialists for determination of progression. Four months later, with a randomly reordered patient sequence, the same visual field series were reevaluated by the same graders, at which time they had access to the Glaucoma Progression Analysis (GPA) printout. MAIN OUTCOME MEASURES: The level of agreement between majority expert consensus and GPA, both before and after access to GPA data, was assessed using kappa statistics. RESULTS: On initial review and on reevaluation with access to the GPA printout, the level of agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI], 0.35-0.69 and kappa = 0.62; 95% CI, 0.46-0.78, respectively). Expert consensus was more likely to classify a series of fields as showing progression than was GPA (P ≤ 0.002). There was good agreement between expert consensus on initial review and reevaluation 4 months later (kappa = 0.77; 95% CI, 0.65-0.90). CONCLUSIONS: The level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is fair. In cases of disagreement with GPA, the expert consensus classification was usually progression. Access to the results of GPA did not significantly change the level of agreement between expert consensus and the GPA result; however, expert consensus did change in 11 of 100 cases.

Ability of cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes.

PURPOSE: To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) to discriminate between normal and glaucomatous eyes and to compare them with the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus HD-OCT. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Seventy-three subjects with glaucoma and 146 age-matched normal subjects. METHODS: Peripapillary ONH parameters and RNFL thickness were measured in 1 randomly selected eye of each participant within a 200 × 200 pixel A-scan acquired with Cirrus HD-OCT centered on the ONH. MAIN OUTCOME MEASURES: Optic nerve head topographic parameters, peripapillary RNFL thickness, and area under receiver operating characteristic curves (AUCs). RESULTS: To distinguish normal from glaucomatous eyes, regardless of disease stage, the 6 best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951), and average RNFL thickness (0.950). The AUC for distinguishing between normal eyes and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), rim area (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893), and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (P > 0.05). CONCLUSIONS: Cirrus HD-OCT ONH parameters are able to discriminate between normal eyes and eyes with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus OCT, to distinguish between normal and glaucomatous eyes.

Comparison of automated analysis of Cirrus HD OCT spectral-domain optical coherence tomography with stereo photographs of the optic disc.

OBJECTIVE: To evaluate a new automated analysis of optic disc images obtained by spectral-domain optical coherence tomography (SD OCT). Areas of the optic disc, cup, and neural rim in SD OCT images were compared with these areas from stereoscopic photographs to represent the current traditional optic nerve evaluation. The repeatability of measurements by each method was determined and compared. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One hundred nineteen healthy eyes, 23 eyes with glaucoma, and 7 glaucoma suspect eyes. METHODS: Optic disc and cup margins were traced from stereoscopic photographs by 3 individuals independently. Optic disc margins and rim widths were determined automatically in SD OCT. A subset of photographs was examined and traced a second time, and duplicate SD OCT images also were analyzed. MAIN OUTCOME MEASURES: Agreement among photograph readers, between duplicate readings, and between SD OCT and photographs were quantified by the intraclass correlation coefficient (ICC), by the root mean square, and by the standard deviation of the differences. RESULTS: Optic disc areas tended to be slightly larger when judged in photographs than by SD OCT, whereas cup areas were similar. Cup and optic disc areas showed good correlation (0.8) between the average photographic reading and SD OCT, but only fair correlation of rim areas (0.4). The SD OCT was highly reproducible (ICC, 0.96-0.99). Each reader also was consistent with himself on duplicate readings of 21 photographs (ICC, 0.80-0.88 for rim area and 0.95-0.98 for all other measurements), but reproducibility was not as good as SD OCT. Measurements derived from SD OCT did not differ from photographic readings more than the readings of photographs by different readers differed from each other. CONCLUSIONS: Designation of the cup and optic disc boundaries by an automated analysis of SD OCT was within the range of variable designations by different readers from color stereoscopic photographs, but use of different landmarks typically made the designation of the optic disc size somewhat smaller in the automated analysis. There was better repeatability among measurements from SD OCT than from among readers of photographs. The repeatability of automated measurement of SD OCT images is promising for use both in diagnosis and in monitoring of progression.

The first signs of glaucomatous cupping in the optic nerve.

Evaluation of the optic disc is important for both the diagnosis of glaucoma, and in monitoring the progress of glaucoma. Along with visual field examination, it allows the presence of glaucoma to be recognized, and for progressive damage to be seen. Glaucoma can occur despite intraocular pressure (IOP) in the normal range, but as importantly, can be absent even when the IOP is distinctly high.

Characteristics of optic nerve head drusen on optical coherence tomography images.

BACKGROUND AND OBJECTIVE: To describe the characteristics of optic nerve head drusen in optical coherence tomography (OCT) images. PATIENTS AND METHODS: Cross-sectional images of the optic nerve were obtained in seven patients with optic nerve head drusen with Stratus and spectral-domain OCT (Carl Zeiss Meditec, Dublin, CA). These were compared to optic disc photographs, autofluorescence, and echography images. For comparison, these tests were performed on four patients with papilledema and three patients with small optic discs. RESULTS: Optic nerve head drusen typically elevated the disc surface and appeared as an optically empty cavity, sometimes with a perceptible reflection from the posterior surface. The disc surface was also elevated in cases of papilledema, but had a strong anterior reflectance behind which there was no visible structure. The surface of the small optic nerves was slightly elevated, but with less anterior reflectance. CONCLUSION: Optic nerves with drusen showed features in these OCT images that were distinct from cases of papilledema or small optic discs.

Separation and thickness measurements of superficial and deep slabs of the retinal nerve fiber layer in healthy and glaucomatous eyes.

Purpose: Describe a new method to analyze retinal nerve fiber layer (RNFL) thickness maps. Design: Cross-sectional study. Subjects: RNFL thickness maps of healthy and glaucomatous eyes. Methods: Optical coherence tomography (OCT) RNFL raster scans from 98 healthy and 50 glaucomatous eyes were analyzed. The RNFL thickness maps were separated into superficial (SNFL) and deep (DNFL) slabs through a partial thickness plane set at the modal thickness (mode). Association between mode and OCT signal strength (SS), age, axial length, and visual field mean deviation (VFMD) was tested (Pearson coefficient, r). Thicknesses of inferior and superior SNFL regions (i-,s-SNFL), and inferior, superior, nasal, and temporal DNFL regions (i-,s-,n-,t-DNFL) were calculated. The regions thicknesses were compared between healthy and glaucomatous eyes (t-test) and between glaucomatous eyes with early, moderate, and severe disease (ANOVA and linear regressions of thickness on VFMD). Diagnostic accuracy and correlation with VFMD of RNFL regions thicknesses were calculated as the area under the receiver operating characteristic curve (AUC) and Pearson r, respectively. P<0.05 was considered significant. Main outcome: Thickness of regions in SNFL and DNFL slabs. Results: The mode was not associated with SS, age, axial length, or VFMD, it circumscribed the thicker RNFL around the optic disc of healthy and glaucomatous eyes, and it was used to separate the SNFL and DNFL slabs of RNFL thickness maps. The thickness of the SNFL slab was less in glaucomatous eyes than in healthy eyes (P<0.001). S-SNFL and i-SNFL thicknesses (respectively) were 86.0±8.2µm and 87.3±9.6µm in healthy eyes vs. 66.1±9.1µm and 63.4±8.2µm in glaucomatous eyes (P<0.001 for both). The thickness of the DNFL slab was similar between groups (P=0.19). T-DNFL thickness was 37.0±5.3µm in healthy eyes vs. 33.9±5.0µm in glaucomatous eyes (P<0.001); thicknesses of all other DNFL regions were similar. The SNFL regions only thinned with progressively worse glaucoma severity, had excellent AUCs (AUC≥0.95, P<0.001), and correlated strongly with VFMD (r≥0.60, P<0.001). Conclusions: Glaucomatous RNFL thinning is predominantly detected within a slab with thickness greater than the mode. SNFL thickness has great AUC and correlation with VFMD in glaucomatous eyes. The usefulness for diagnosis and monitoring of glaucoma needs further study.

Reproducibility of pattern electroretinogram in glaucoma patients with a range of severity of disease with the new glaucoma paradigm.

PURPOSE: To determine the reproducibility of the pattern electroretinogram with the new Pattern Electroretinogram for Glaucoma (PERGLA) recording paradigm in glaucoma patients with a range of severity. DESIGN: Experimental study. PARTICIPANTS: Fifty-three glaucoma patients were recruited for the study (mean age +/- standard deviation [SD], 69+/-11 years). Their mean deviation (MD) global indices on static automatic perimetry ranged from 2.16 to -31.36 decibels (mean MD, -9.05). INTERVENTION: All patients had pattern electroretinogram recordings done 5 times by the same operator, on 5 different days with the standardized PERGLA paradigm. MAIN OUTCOME MEASURES: Pattern electroretinogram amplitude (microvolts), phase (pi radians), response variability (coefficient of variation [CV] = SD/mean x 100) of amplitude and phase of 2 partial averages that build up the pattern electroretinogram waveform, interocular asymmetry in amplitude and phase (in terms of the CV generated by the pattern electroretinogram software), signal-to-noise (S/N) ratio, SDs, CV, and intraclass correlation coefficient (ICC). All analyses were done on one eye of each subject, except when interocular asymmetry was studied. RESULTS: The CVs of intrasession variabilities in amplitude and phase were 12.08% and 2.20%, respectively, and those of intersession variabilities were 20.82% and 4.17%. The pattern electroretinogram produced intersession ICCs in amplitude and phase of 0.791 and 0.765, respectively. These ICCs were significantly higher than the ICCs for pattern electroretinogram interocular asymmetry in amplitude and phase (0.659 [P<0.05] and 0.571 [P<0.05], respectively). On average, the pattern electroretinogram S/N ratio in glaucomatous patients was about 5:1. CONCLUSIONS: The reproducibility of PERGLA in glaucomatous patients is sufficiently good for it to be considered a useful complementary clinical tool. Being more reproducible, direct measures of amplitude and phase should be more useful in monitoring progression than interocular asymmetry comparisons.

Reproducibility of peripapillary retinal nerve fiber thickness measurements with stratus OCT in glaucomatous eyes.

PURPOSE: To determine the reproducibility of Stratus OCT peripapillary retinal nerve fiber layer (RNFL) measurements in glaucomatous eyes. DESIGN: Experimental study. PARTICIPANTS: Fifty-one stable glaucoma patients with a range of severity. METHODS: Peripapillary RNFL thickness was measured using the Standard and Fast scan protocols of Stratus optical coherence tomography (OCT) 3 times on the same day to determine intrasession variability and on 5 different days within a 2-month period to determine intersession variability. The same instrument was used by the same operator for all scans. MAIN OUTCOME MEASURES: Intraclass correlation coefficient (ICC), coefficient of variation (COV), and test-retest variability. RESULTS: For mean RNFL thickness, the intrasession and intersession ICCs for the Standard and Fast scans were 0.98 and 0.96, respectively. The COV ranged from 3.8% to 5.2%. Test-retest variability was approximately 7 microm between sessions, most of which can be attributed to the approximate 5-microm variability within each session. For quadrants, the ICC was 0.9 or higher and the COV was under 10% except nasally. Test-retest variability for quadrant measurements ranged from 6 to 16 microm. For clock hours, test-retest variability approached 20 microm between sessions in some sectors. In general, the ICC was lower in the nasal region than elsewhere. Variability was greater the smaller the area over which RNFL thickness was determined. Intrasession variability was not a predictor of intersession variability in individual subjects (P Standard = 0.72, P Fast = 0.28). There was no relationship between variability and mean RNFL thickness (P Standard = 0.28, P Fast = 0.93). CONCLUSIONS: The reproducibility of Stratus OCT for RNFL thickness is sufficiently good to be useful clinically as a measure of glaucoma progression. When comparing 2 mean RNFL values on different days in the same eye, an 8-microm decrease in thickness might be accepted as within normal limits of test-retest variability with 95% tolerance. For quadrants and clock-hour sectors, variability is higher, and more detailed calculations are necessary.

Effect of lowering intraocular pressure on optical coherence tomography measurement of peripapillary retinal nerve fiber layer thickness.

PURPOSE: To assess, with optical coherence tomography (OCT), any changes in peripapillary retinal nerve fiber layer (RNFL) thickness in glaucoma patients after reduction of intraocular pressure (IOP). DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-one eyes of 21 glaucoma patients who underwent medical or surgical intervention to lower IOP. METHODS: Patients with elevated IOP underwent fast peripapillary RNFL measurements with the Stratus OCT (model 3000, software version 4.04; Carl Zeiss Meditec, Dublin, CA) before and after the IOP was lowered by medical or surgical therapy. MAIN OUTCOME MEASURES: Changes in overall and quadrant RNFL thickness with respect to change in IOP. RESULTS: The OCT scans were performed before intervention (range, 0-38 days before; mean+/-standard deviation [SD], 9.8+/-9.3 days) and after intervention (range, 32-74 days; mean+/-SD, 46.8+/-11.2 days) to measure peripapillary RNFL thickness. Mean IOP (mean+/-SD) decreased from 31.5+/-8.2 mmHg to 12.8+/-4.6 mmHg with the intervention (P<0.001). Twenty of 21 eyes had an IOP reduction of more than 30%. There was no significant change in the overall RNFL thickness associated with the lowering of IOP (mean+/-SD, 1.02+/-10.3 microm; P = 0.653). Quadrant analysis did not show a significant change in the RNFL thickness of any of the 4 quadrants (superior, -1.71+/-14.5 microm, P = 0.593; inferior, 2.38+/-16.8 microm, P = 0.523; temporal, 2.19+/-9.50 microm, P = 0.303; and nasal, 1.24+/-12.5 microm, P = 0.655). No relationship was found between any of the changes in OCT parameters or percent change in OCT parameters and the extent of IOP reduction, or whether IOP was lowered medically or surgically, with or without adjusting for preintervention OCT measurements as an indication of disease severity (P values ranged from 0.331 to 0.985). CONCLUSIONS: No significant change in the RNFL thickness was associated with the lowering of IOP by medical or surgical therapy, as measured by OCT.

Determinants of normal retinal nerve fiber layer thickness measured by Stratus OCT.

PURPOSE: To determine the effects of age, optic disc area, ethnicity, eye, gender, and axial length on the retinal nerve fiber layer (RNFL) in the normal human eye as measured by Stratus OCT (optical coherence tomography). DESIGN: Cross-sectional observational study. PARTICIPANTS: Three hundred twenty-eight normal subjects 18 to 85 years old. METHODS: Peripapillary Fast RNFL scans performed by Stratus OCT with a nominal diameter of 3.46 mm centered on the optic disc were performed on one randomly selected eye of each subject. MAIN OUTCOME MEASURES: Linear regression analysis of the effects of age, ethnicity, gender, eye, axial length, and optic disc area on peripapillary RNFL thickness. RESULTS: The mean RNFL thickness for the entire population was 100.1 microm (standard deviation, 11.6). Thinner RNFL measurements were associated with older age (P<0.001); being Caucasian, versus being either Hispanic or Asian (P = 0.006); greater axial length (P<0.001); or smaller optic disc area (P = 0.010). For every decade of increased age, mean RNFL thickness measured thinner by approximately 2.0 microm (95% confidence interval [CI], 1.2-2.8). For every 1-mm-greater axial length, mean RNFL thickness measured thinner by approximately 2.2 microm (95% CI, 1.1-3.4). For every increase in square millimeter of optic disc area, mean RNFL thickness increased by approximately 3.3 microm (95% CI, 0.6-5.6). Comparisons between ethnic groups revealed that Caucasians had mean RNFL values (98.1+/-10.9 microm) slightly thinner than those of Hispanics (103.7+/-11.6 microm; P = 0.022) or Asians (105.8+/-9.2 microm; P = 0.043). There was no relationship between RNFL thickness and eye or gender. CONCLUSIONS: Retinal nerve fiber layer thickness, as measured by Stratus OCT, varies significantly with age, ethnicity, axial length, and optic disc area. These variables may need to be taken into account when evaluating patients for diagnosis and follow-up of glaucoma, particularly at the lower boundary of the normal range. Due to the relatively small numbers of subjects of Asian and African descent in the normative database, conclusions regarding the effect of ethnicity should be interpreted with caution.

Detection and prognostic significance of optic disc hemorrhages during the Ocular Hypertension Treatment Study.

PURPOSE: To compare the rates of detection of optic disc hemorrhages by clinical examination and by review of optic disc photographs at the Optic Disc Reading Center (ODRC), to assess the incidence of and the predictive factors for disc hemorrhages in the annual disc photographs of the Ocular Hypertension Treatment Study (OHTS), and to determine whether optic disc hemorrhages predict the development of primary open-angle glaucoma (POAG) in the OHTS. DESIGN: Cohort study. PARTICIPANTS: Three thousand two hundred thirty-six eyes of 1618 participants. METHODS: Both eyes of participants were examined for optic disc hemorrhages every 6 months by clinical examination, with dilated fundus examinations every 12 months, and by annual review of stereoscopic disc photographs at the ODRC. MAIN OUTCOME MEASURES: Incidence of optic disc hemorrhages and POAG end points. RESULTS: Median follow-up was 96.3 months. Stereophotography-confirmed glaucomatous optic disc hemorrhages were detected in 128 eyes of 123 participants before the POAG end point. Twenty-one cases (16%) were detected by both clinical examination and review of photographs, and 107 cases (84%) were detected only by review of photographs (P<0.0001). Baseline factors associated with disc hemorrhages were older age, thinner corneas, larger vertical cup-to-disc ratio, larger pattern standard deviation index on perimetry, family history of glaucoma, and smoking status. The occurrence of a disc hemorrhage increased the risk of developing POAG 6-fold in a univariate analysis (P<0.001; 95% confidence interval, 3.6-10.1) and 3.7-fold in a multivariate analysis that included baseline factors predictive of POAG (P<0.001; 95% confidence interval, 2.1-6.6). The 96-month cumulative incidence of POAG in the eyes without optic disc hemorrhage was 5.2%, compared with 13.6% in the eyes with optic disc hemorrhage. In eyes with a disc hemorrhage in which a POAG end point developed, the median time between the 2 events was 13 months. CONCLUSIONS: Review of stereophotographs was more sensitive at detecting optic disc hemorrhage than clinical examination. The occurrence of an optic disc hemorrhage was associated with an increased risk of developing a POAG end point in participants in the OHTS. However, most eyes (86.7%) in which a disc hemorrhage developed have not experienced a POAG end point to date.

The association between glaucomatous visual fields and optic nerve head features in the Ocular Hypertension Treatment Study.

PURPOSE: To determine the association between change from baseline in the optic nerve head (ONH) and the visual field (VF) during follow-up of ocular hypertension participants in the Ocular Hypertension Treatment Study. DESIGN: Longitudinal randomized clinical trial. PARTICIPANTS: One hundred sixty-eight eyes of 152 ocular hypertensive participants ages 40 to 80 years. METHODS: Cox hazard models were applied to 3232 eyes, which included 81 eyes that reached a study end point by developing a glaucomatous VF (VF end point) and 128 eyes that reached a study end point by developing an optic disc change (optic disc end point). MAIN OUTCOME MEASURES: Primary open-angle glaucoma end point as determined by changes in the VF or optic disc. RESULTS: Forty-one eyes reached an end point by both VF and optic disc criteria; 40 eyes reached only a VF end point, and 87 reached only an optic disc end point. Times to reach isolated disc or field end points were similar. Visual field end points were more likely (P<0.0001) in eyes that showed the following ONH features: an ONH hemorrhage, thinning of the optic disc rim, or enlargement of the horizontal cup-to-disc (C/D) ratio. Optic disc end points were more likely (P<0.0001) in eyes that showed the following VF features: some evidence of a nasal step or a partial arcuate VF defect, or an increase in the pattern standard deviation (PSD). CONCLUSIONS: Both the VF and the optic disc must be monitored with equal diligence, because either may show the first evidence of glaucomatous damage. Changes in the ONH based on stereophotographic observation (rim thinning, hemorrhage, or a slight increase in C/D ratio) and VF changes (evidence of a nasal step/partial arcuate defect or an increase in PSD) suggest that these cases have an increased risk of developing glaucoma. Confirmation of such subtle findings should be sought through repeat testing and correlation with other clinical results.

Management of ocular hypertension: a cost-effectiveness approach from the Ocular Hypertension Treatment Study.

PURPOSE: The Ocular Hypertension Treatment Study (OHTS) demonstrated that medical treatment of people with intraocular pressure (IOP) of > or =24 mm Hg reduces the risk of the development of primary open-angle glaucoma (POAG) by 60%. There is no consensus on which people with ocular hypertension would benefit from treatment. DESIGN: Cost-utility analysis with the use of a Markov model. METHODS: We modeled a hypothetic cohort of people with IOP of > or =24 mm Hg. Four treatment thresholds were considered: (1) Treat no one; (2) treat people with a > or =5% annual risk of the development of POAG; (3) treat people with a > or =2% annual risk of the development of POAG, and (4) treat everyone. The incremental cost-effectiveness ratio was evaluated. RESULTS: The incremental cost-effectiveness ratios for treatment of people with ocular hypertension were 3670 US dollars per quality adjusted life-year (QALY) for the Treat > or =5% threshold and 42,430 US dollars/QALY for the Treat > or =2% threshold. "Treat everyone" cost more and was less effective than other options. Assuming a cost-effectiveness threshold of 50,000 to 100,000 US dollars/QALY, the Treat > or =2% threshold would result in the most net health benefit. The decision was sensitive to the incidence of POAG without treatment, treatment effectiveness, and the utility loss because of POAG. CONCLUSION: Although the treatment of individual patients is largely dependent on their attitude toward the risk of disease progression and blindness, the treatment of those patients with IOP of > or =24 mm Hg and a > or =2% annual risk of the development of glaucoma is likely to be cost-effective. Delay of treatment for all people with ocular hypertension until glaucoma-related symptoms are present appears to be unnecessarily conservative.

Test-retest reproducibility of optic disk deterioration detected from stereophotographs by masked graders.

PURPOSE: To assess the reproducibility of determining whether an eye has developed optic disk deterioration by the Optic Disc Reading Center (ODRC) in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Test-retest reproducibility study. METHODS: Masked, certified graders at the ODRC determine the occurrence of optic disk deterioration in OHTS by comparing baseline with follow-up stereoscopic optic disk photographs. To assess reproducibility, re-gradings were obtained annually by inserting masked "quality control" photographs into the usual ODRC reading stream. RESULTS: Agreement (kappa) ranged from 0.65 to 0.83 over 5 years. Specificity ranged from 98% to 100%, and sensitivity ranged from 64% to 81%. CONCLUSIONS: The kappa statistic for test-retest agreement in OHTS is in the range considered good to excellent over 5 years. Consistency (specificity) in re-grading optic disks that did not develop deterioration was particularly high. The sensitivity results show that detecting subtle deterioration of optic disks is challenging.