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.
Aims: To establish the effects of central corneal thickness (CCT) on intraocular pressure (IOP) measured with a prototype Pascal dynamic contour tonometer (DCT), to evaluate the effect of CCT and age ...on the agreement between IOP measured with the Pascal DCT and Goldmann applanation tonometer (GAT), and to compare the interobserver and intraobserver variation of the DCT with the GAT. Methods: GAT and DCT IOP measurements were made on 130 eyes of 130 patients and agreement was assessed by means of Bland-Altman plots. The effect of CCT and age on GAT/DCT IOP differences was assessed by linear regression analysis. Interobserver and intraobserver variations for GAT and DCT were assessed in 100 eyes of 100 patients. Results: The mean difference (95% limits of agreement) between GAT and DCT was −0.7 (−6.3 to 4.9) mm Hg. GAT/DCT IOP differences increased with thicker CCT (slope 0.017 mm Hg/μm, 95% CI 0.004 to 0.03, r2 = 0.05, p = 0.01), and with greater age, slope 0.05 mm Hg/year (95% CI 0.012 to 0.084, r2 = 0.05, p = 0.01). The intraobserver variability of GAT and DCT was 1.7 mm Hg and 3.2 mm Hg, respectively. The interobserver variability was (mean difference (95% limits of agreement)) 0.4 (−3.5 to 4.2) mm Hg for GAT and 0.2 (−4.9 to 5.3) mm Hg for DCT. Conclusions: GAT is significantly more affected than DCT by both CCT and subject age. The effect of age suggests an age related corneal biomechanical change that may induce measurement error additional to that of CCT. The prototype DCT has greater measurement variability than the GAT.
To establish the anatomical relationship between visual field test points in the Humphrey 24-2 test pattern and regions of the optic nerve head (ONH)
Cross-sectional study.
Glaucoma patients and ...suspects from the Normal Tension Glaucoma Clinic at Moorfields Eye Hospital.
Sixty-nine retinal nerve fiber layer (RNFL) photographs with well-defined RNFL defects and/or prominent bundles were digitized. An appropriately scaled Humphrey 24-2 visual field grid and an ONH reference circle, divided into 30° sectors, were generated digitally. These were superimposed onto the RNFL images. The relationship of visual field test points to the circumference of the ONH was estimated by noting the proximity of test points to RNFL defects and/or prominent bundles. The position of the ONH in relation to the fovea was also noted.
The sector at the ONH corresponding to each visual field test point, the position of the ONH in relation to the fovea, and the effect of the latter on the former.
A median 22 (range, 4–58), of a possible 69, ONH positions were assigned to each visual field test point. The standard deviation of estimations was 7.2°. The position of the ONH was 15.5° (standard deviation 0.9°) nasal and 1.9° (standard deviation 1.0°) above the fovea. The location of the ONH had a significant effect on the corresponding position at the ONH for 28 of 52 visual field test points.
A clinically useful map that relates visual field test points to regions of the ONH has been produced. The map will aid clinical evaluation of glaucoma patients and suspects, as well as form the basis for investigations of the relationship between retinal light sensitivity and ONH structure.
This study aimed to define the confocal laser scanning ophthalmoscope (Heidelberg Retina Tomograph HRT) parameters that best separate patients with early glaucoma from normal subjects.
A ...cross-sectional study.
A total of 80 normal subjects and 51 patients with early glaucoma participated (average visual field mean deviation = −3.6 dB).
Imaging of the optic nerve head with the HRT and analysis using software version 1.11 were performed.
The relation between neuroretinal rim area and optic disc area, and cup-disc area ratio and optic disc area, was defined by linear regression of data derived from the normal subjects. The normal ranges for these two parameters were defined by the 99% prediction intervals of the linear regression between the parameter and optic disc area, for the whole disc, and for each of the predefined segments. Normal subjects and patients were labeled as abnormal if the parameter for either the whole disc or any of the predefined segments was outside the normal range. The sensitivity and specificity values of the method were calculated.
The highest specificity (96.3%) and sensitivity (84.3%) values to separate normal subjects and those patients with early glaucoma were obtained using the 99% prediction interval from the linear regression between the optic disc area and the log of the neuroretinal rim area. Similar specificity (97.5%) and lower sensitivity (74.5%) values were obtained with the 99% prediction interval derived from regression between the disc area and cup-disc area ratios. Poor separation between groups was obtained with the other parameters.
The HRT, using the technique of linear regression to account for the relationship between optic disc size and rim area or cup-disc area ratio, provides good separation between control subjects and patients with early glaucoma in this population.
Thinning of the retinal nerve fiber layer (RNFL) of clinically unaffected eyes is seen in patients with multiple sclerosis (MS). It is uncertain when this thinning occurs, and whether ongoing RNFL ...loss can be measured over time with optical coherence tomography (OCT). Using time-domain OCT, we studied 34 patients with progressive MS (16 primary progressive MS, 18 secondary progressive; 14 male; 20 female; mean age at study entry 51 years; median EDSS 6; mean disease duration at study entry 12 years) on two occasions with a median interval of 575 (range 411–895) days apart. Eighteen healthy controls (10 male; eight female; mean age at study entry 46 years) were also studied twice, with a median interval of 656 days (range 398–890). Compared to controls, the patients had significant decreases in the RNFL thickness and macular volume of their clinically unaffected eyes at study entry. No significant decrease in RNFL thickness was observed between baseline and follow-up in either patients or controls. Macular volume declined significantly in patients and controls, but there was no difference in this change between the two groups. The study findings suggest that time domain OCT detects little disease-related ongoing loss of retinal axons in progressive forms of MS and has limited use for monitoring potential neuroprotective therapies at this stage of disease. Further studies are needed using higher-resolution OCT systems and in larger groups of patients, to elucidate the timing and mechanism of RNFL loss that is observed in clinically unaffected nerves in MS.
Axonal loss is thought to be a likely cause of persistent disability after a multiple sclerosis relapse; therefore, noninvasive in vivo markers specific for axonal loss are needed. We used optic ...neuritis as a model of multiple sclerosis relapse to quantify axonal loss of the retinal nerve fiber layer (RNFL) and secondary retinal ganglion cell loss in the macula with optical coherence tomography. We studied 25 patients who had a previous single episode of optic neuritis with a recruitment bias to those with incomplete recovery and 15 control subjects. Optical coherence tomography measurement of RNFL thickness and macular volume, quantitative visual testing, and electrophysiological examination were performed. There were highly significant reductions (p < 0.001) of RNFL thickness and macular volume in affected patient eyes compared with control eyes and clinically unaffected fellow eyes. There were significant relationships among RNFL thickness and visual acuity, visual field, color vision, and visual‐evoked potential amplitude. This study has demonstrated functionally relevant changes indicative of axonal loss and retinal ganglion cell loss in the RNFL and macula, respectively, after optic neuritis. This noninvasive RNFL imaging technique could be used in trials of experimental treatments that aim to protect optic nerves from axonal loss. Ann Neurol 2005
Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently ...the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production—essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.
Aims: To evaluate the test-retest variability of stereometric parameter measurements made with the Heidelberg retina tomograph (HRT) and Heidelberg retina tomograph-II (HRT-II), and to establish ...which parameter(s) provided the most repeatable and reliable measurements with both devices. An investigation into the factors affecting the repeatability of the measurements of this parameter(s) was conducted. Methods: 43 ocular hypertensive and 31 glaucoma subjects were recruited to a test-retest study. One eye from each subject underwent HRT and HRT-II imaging by two observers on each of two occasions within 6 weeks of each other. Lens grading was carried out by LOCS III grading and Scheimpflug camera generated densitogram analysis. Results: Rim area (RA) and mean cup depth measurements were found to be least variable. Both inter-test reference height difference and image quality had a strong relation (R2>0.5, p<0.0001) with inter-test RA difference and, together, are responsible for 70% of RA measurement variability. Image quality was influenced by lens opacity, cylindrical error, and age. Inter-test RA measurement differences were unrelated to the observer or visit interval. Conclusions: RA represents an appropriate measure for monitoring glaucomatous progression. Reference height difference and image quality were the factors that most influenced RA measurement variability. Image analysis strategies that address these factors may reduce test-retest variability.
To compare the ability of qualitative assessment of optic nerve head stereophotographs (ONHPs), confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence ...tomography (OCT) to distinguish normal eyes from those with early to moderate glaucomatous visual field defects.
Eighty-nine eyes (63 normal, 63 age-matched with glaucoma) of 89 subjects more than 40 years of age were studied. Receiver operating characteristic (ROC) curves were generated from discriminant analysis of CSLO, SLP, and OCT measurements and from ONHP scores. Sensitivity at 80% and specificity at 90% were calculated. Differences between individual methods and combinations of methods were assessed for statistical significance. Agreement on categorization between methods (kappa) was assessed.
The average visual field mean deviation (MD +/- SD) in patients with glaucoma was -3.9 +/- 2.2 dB, and the average pattern standard deviation (PSD) was 4.7 +/- 3.4 dB. In normal subjects the average MD was 0.1 +/- 0.9 dB and the average PSD was 1.5 +/- 0.3 dB. Optimal sensitivities, specificities, and areas under ROC curves were, respectively: ONHP (0.94, 0.87, 0.93), CSLO (0.84, 0.90, 0.92), SLP (0.89, 0.87, 0.94), and OCT (0.82, 0.84, 0.88). Best agreement on categorization (kappa) was between ONHPs and CSLO (0.70). The ROC area for the combination of methods was 0.99, higher than for any method alone. The ROC area for the combination of methods was significantly better than the CLSO rim area (P = 0.012) and the OCT retinal nerve fiber layer (RNFL) thickness (P = 0.002).
The quantitative methods CSLO, SLP, and OCT were no better than qualitative assessment of disc ONHPs by experienced observers at distinguishing normal eyes from those with early to moderate glaucoma. A combination of the imaging methods significantly improves this capability.
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