Boel Bengtsson

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

Natural History of Open-Angle Glaucoma

OBJECTIVE This article, based on the Early Manifest Glaucoma Trial (EMGT), provides prospective natural history data on progression of glaucomatous field defects in 3 of the most common glaucoma types. DESIGN Cohort of EMGT patients randomized to the untreated control group and followed up to the time of progression, when treatment could be initiated. PARTICIPANTS We evaluated 118 control patients: 46 with high-tension glaucoma (HTG), 57 with normal-tension glaucoma (NTG), and 15 with pseudoexfoliation glaucoma (PEXG). METHODS Visual fields were tested every 3 months with the Humphrey 30-2 Full Threshold test program. MAIN OUTCOME MEASURES Linear regression analyses of the perimetric mean deviation (MD) values were performed, and the rate of progression was defined as the regression coefficient in decibels per year. Percentages of progressed eyes and time to progression were determined using EMGT event-based predetermined progression criteria derived from Glaucoma Change Probability Maps. RESULTS The median and interquartile rates of visual function loss were -0.40 (1.05) dB/year overall and -0.46 (1.61) in HTG, -0.22 (0.65) in NTG, and -1.13 (6.13) in PEXG. Thus, interpatient variability was large. Mean rates were considerably higher than medians: -1.08 dB/year overall, -1.31 in HTG, -0.36 in NTG, and -3.13 in PEXG. Differences in median visual function progression rates among groups were statistically significant (NTG vs. HTG, P = 0.003; PEXG vs. non-PEXG, P<0.001). Progression was considerably and significantly faster in older than in younger patients (P = 0.002). By 6 years, 68% of patients had progressed overall, 74% of those with HTG, 56% of those with NTG, and 93% of those with PEXG (P = 0.012). Median time to progression also differed considerably among groups: 19.5 months in PEXG, 44.8 months in HTG, and particularly 61.1 months in NTG (P<0.0001). CONCLUSIONS In this 6-year follow-up study, the median untreated rate of progression corresponded to advancing from normal visual function to blindness in approximately 70 years, whereas on the basis of the mean rate, visual function would show the same deterioration in approximately 25 years. Large differences existed among patients and different glaucoma types, with PEXG progressing considerably faster than HTG, and NTG progressing at the lowest rate.

Diurnal IOP fluctuation: not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension

PurposeTo establish whether intraocular pressure (IOP) fluctuations contribute to the risk of developing glaucoma in patients with high-risk ocular hypertension.MethodsNinety patients included in the Malmö Ocular Hypertension Study were examined every 3 months with office-hours diurnal tension curves and computerised perimetry. Patients were followed up prospectively for 10 years or until glaucomatous visual field loss could be demonstrated. Poststudy data were included in the analyses, extending maximum follow-up to 17 years.ResultsAfter 17 years, 37 patients had developed glaucomatous visual field defects. When applying univariate Cox regression analyses, mean IOP of all measurements during the prospective part of the study was a significant risk factor for developing glaucoma (95% confidence interval [CI] 1.08–1.39), while IOP fluctuations were almost significant (95% CI 0.98–1.93). When separating effects of mean IOP level and mean IOP fluctuation using Cox multiple regression analysis, only IOP level came out as significant (95% CI 1.09–1.38), and IOP fluctuations did not contribute to the risk (95% CI 0.80–1.60). IOP fluctuation depended linearly on IOP level (p<0.0001), i.e. IOP fluctuation was larger in eyes with higher IOP levels.ConclusionIOP fluctuations were not an independent risk factor for the incidence of glaucomatous visual field loss in subjects with ocular hypertension.

False-negative responses in glaucoma perimetry: indicators of patient performance or test reliability?

PURPOSE. To study whether false-negative answers in computerized glaucoma perimetry indicate the patients ability to perform perimetry or test result reliability. METHODS. A retrospective evaluation was performed of visual field test results obtained with a perimetry program (Humphrey 30-2 Sita Standard; Humphrey Instruments, San Leandro, CA) in 70 consecutive patients with unilateral glaucomatous field loss. Frequencies of false-negative answers were compared between the two eyes of each patient and related to amount of visual field damage in the glaucomatous eyes using linear regression analysis. RESULTS. Frequencies of false-negative answers were higher in eyes with field loss. The intrapatient intereye difference was 6.6% on average (P < 0.0001). In seven subjects with false-negative frequency of 5% or more in both eyes, the mean difference was 12.7% between eyes. The differences in false-negative answers depended significantly on the amount of field loss in the glaucomatous eyes (P = 0.0003). Larger differences were seen in patients with advanced field loss in the affected eye. CONCLUSIONS. The increased frequencies of false-negative answers in eyes with field loss were strongly associated with field status. The higher false-negative frequencies in eyes with glaucomatous field loss compared with unaffected eyes may be explained by the increased variability in threshold values typically found in such eyes. False-negative answers in patients with glaucoma therefore represent eye rather than patient status.

Prediction of glaucomatous visual field loss by extrapolation of linear trends.

OBJECTIVE To investigate how well short-term progression rates can predict long-term visual field outcomes in patients with glaucoma. METHODS We calculated visual field rates of progression using linear regression analysis of the Visual Field Index (VFI) for 100 consecutive patients with glaucoma having 10 or more Swedish Interactive Thresholding Algorithm standard field tests. Final VFI was predicted on the basis of linear extrapolation of the slope defined by the initial 5 field test results. Final VFI also was estimated using linear regression of all qualifying examination results for each patient. Primary outcome measures were the absolute difference and the correlation between predicted and estimated final VFI values. RESULTS Patient follow-up averaged 8.2 years and 11 field examinations. Median VFI progression rate was -1.1% per year both for the initial 5 test results and also for the complete series. Seventy percent of patients had a predicted final VFI within +/-10% of the estimated final VFI, and the 2 VFI calculations had a correlation coefficient of 0.84. CONCLUSION Linear extrapolation based on 5 initial visual field test results was a reliable predictor of future field loss in most patients. Patients in whom linear regression analysis suggests dangerously rapid rates of visual field progression may be candidates for significant alterations in therapy.

Disc Hemorrhages and Treatment in the Early Manifest Glaucoma Trial.

PURPOSE To evaluate the effect of intraocular pressure (IOP)-reducing treatment on the development of disc hemorrhages in patients with glaucoma. DESIGN Prospective cohort study of patients in the Early Manifest Glaucoma Trial, followed up to 11 years (median = 8 years). PARTICIPANTS Patients with newly detected glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no initial treatment (n = 126), followed with tonometry, perimetry, and ophthalmoscopy every 3 months, and fundus photography every 6 months. METHODS Logistic regression expressed as odds ratios (OR) and 95% confidence intervals (CIs), analysis of variance, and Cox time-dependent models, expressed as hazard ratios (HRs) and CIs. MAIN OUTCOME MEASURES Presence (yes/no) and frequency of disc hemorrhages. RESULTS Disc hemorrhages were identified in approximately 55% of all patients, whether by ophthalmoscopy or review of photographs. In analyses including data up to the time of progression, disc hemorrhages were equally common among treated and control patients: 51.2% versus 45.2%, respectively (P = 0.34), based on ophthalmoscopy, and 50.4% versus 44.4%, respectively (P = 0.34), based on photographs. Gender was the only factor related to the presence of disc hemorrhages detected by both ophthalmoscopy (OR = 0.48; CI, 0.26-0.88; P = 0.022) and photographs (OR = 0.64; CI, 0.38-1.09; P = 0.099) for male patients. The frequency of disc hemorrhages over time did not differ between treated and control patients: 8.4% versus 8.5%, respectively (P = 0.93), based on ophthalmoscopy, and 12.4% versus 11.2%, respectively (P = 0.36), based on photographs. Disc hemorrhages were significantly associated with time to progression (HR = 1.02; CI, 1.01-1.04), and there was no evidence of interaction between treatment group and disc hemorrhages. CONCLUSIONS IOP-reducing treatment was unrelated to the presence or frequency of disc hemorrhages. The results may suggest that disc hemorrhages cannot be considered an indication of insufficient IOP-lowering treatment, and that glaucoma progression in eyes with disc hemorrhages cannot be totally halted by IOP reduction. The results also suggest that disc hemorrhages do not occur in all patients with glaucoma.

A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients

PURPOSE Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. DESIGN Longitudinal, comparative study of diagnostic criteria. PARTICIPANTS AND CONTROLS Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). METHODS Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensitivity, specificity, time to progression, and sustainability were calculated. MAIN OUTCOME MEASURES Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. RESULTS Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogressing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P<0.001), and pairwise (P<0.01). The specificity for EMGT criteria was 89%, lower (P<0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30-36 months) than with AGIS (66 months; 95% CI, 57-78 months) and CIGTS (55 months; 95% CI, 48-66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. CONCLUSIONS The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression.

Rates of visual field progression in clinical glaucoma care

Purpose:  To investigate rates of visual field progression and factors associated with progression rate in open‐angle glaucoma in clinical glaucoma care.

TNF-alpha is an independent serum marker for proliferative retinopathy in type 1 diabetic patients.

PURPOSE This study aimed to determine if there are any associations between serum levels of inflammatory markers and proliferative retinopathy (PDR) in type 1 diabetic patients. DESIGN A cross-sectional design was utilized for this study. METHODS One hundred twenty-eight type 1 diabetic patients underwent stereo fundus photography according to the Early Treatment Diabetic Retinopathy Study and were divided into two retinopathy groups: no or nonproliferative retinopathy (NDR/NPDR; n=62) and PDR (n=66). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, soluble vascular cellular adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), P-selectin, and high-sensitivity C-reactive protein (hsCRP) were analyzed. Statistical analysis was performed using nonparametric Mann-Whitney U test and multivariate logistic regression analysis. RESULTS Patients with PDR had higher levels of TNF-alpha [7.0 pg/ml (<4-17) vs. 6.0 pg/ml (<4-25); P=.009], sVCAM-1 [860 ng/ml (360-2120) vs. 700 ng/ml (310-1820); P<.001], and P-selectin [180 ng/ml (39-400) vs. 150 ng/ml (42-440); P=.017; figures are expressed as median (range)]. There were no differences in serum levels of sICAM-1 or hsCRP. IL-1 beta was not detectable in any patient, and IL-6 was detectable in only 22.7% of the patients. In multivariate logistic regression analysis, TNF-alpha was the single, persistent, independent determinant inflammatory marker for PDR. CONCLUSION The association between TNF-alpha and PDR in type 1 diabetic patients suggests that inflammation might play a role in the pathogenesis of proliferative diabetic retinopathy.

Glaucoma detection by Stratus OCT

Purpose To investigate the diagnostic accuracy of retinal nerve fiber layer thickness (RNFLT) summary report parameters from Stratus optical coherence tomography (OCT) in glaucoma patients. Patients and Methods We obtained Stratus OCT measurements of peripapillary circle scans (average values) of the regular image resolution “FAST RNFLT” protocol, and of 1 circle scan of the high resolution “RNFLT” protocol in one eye of each of 62 glaucoma patients with mild or moderate visual field (VF) loss and 90 healthy subjects. Sensitivity, specificity, and diagnostic accuracy [(true positive+true negative)/all] were evaluated for all summary report parameters including the newer (eg, “Imax,” the maximum thickness point in the inferior quadrant) at the normative limits of the Stratus OCT. Results The diagnostic accuracy of full circle RNFLT using the 5% normal limit was 89% with the FAST RNFLT and 87% with the RNFLT protocol; this was at least as good as any other parameter. The diagnostic performance of the 2 protocols did not differ significantly for most parameters. In eyes with mild VF loss (n=39) diagnostic sensitivities reached 72% and 77% at specificities ≥95% using the FAST RNFLT and RNFLT protocol, respectively. Conclusions The diagnostic accuracy of the full circle RNFLT was as good as any Stratus OCT parameter on the basis of the peripapillary RNFL thickness measurements, including localized measurements. The sensitivity was moderately high in patients with mild glaucomatous VF loss. There seems to be room for further development of OCT interpretation tools for early diagnosis of glaucoma.