Assessment of rates of structural change in glaucoma using imaging technologies.

PURPOSE: To review the ability of current imaging technologies to provide estimates of rates of structural change in glaucoma patients. PATIENTS AND METHODS: Review of literature. RESULTS: Imaging technologies, such as confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT), provide quantifiable and reproducible measurements of the optic disc and parapapillary retinal nerve fibre layer (RNFL). Rates of change as quantified by the rim area (RA) (for CSLO) and RNFL thickness (for SLP and OCT) are related to glaucoma progression as detected by conventional methods (eg, visual fields and optic disc photography). Evidence shows that rates of RNFL and RA loss are significantly faster in progressing compared with non-progressing glaucoma patients. CONCLUSION: Measurements of rates of optic disc and RNFL change are becoming increasingly precise and individualized. Currently available imaging technologies have the ability to detect and quantify progression in glaucoma, and their measurements may be suitable end points in glaucoma clinical trials.

Pattern electroretinogram association with spectral domain-OCT structural measurements in glaucoma.

PURPOSE: To describe the association between pattern electroretinogram (PERG) amplitude and spectral domain-optical coherence tomography (SD-OCT) macular thickness, retinal nerve fibre layer (RNFL) thickness and optic disc topography measurements. SUBJECTS AND METHODS: Both eyes (n = 132) of 66 glaucoma patients (mean age = 67.9 years) enrolled in the University of California, San Diego, CA, USA, Diagnostic Innovations in Glaucoma Study (DIGS) were included. Eyes were tested with PERG (Glaid PERGLA, Lace Elettronica, Pisa, Italy), RTVue SD-OCT (Optovue Inc., Fremont, CA, USA) GCC, and NHM4 protocols on the same day. Of the 66 enrolled patients, 43 had glaucoma defined by repeated abnormal standard automated perimetry (SAP) results in at least one eye and 23 were glaucoma suspects defined by a glaucomatous-appearing optic disc by physicians' examination in at least one eye and normal SAP results in both eyes. Associations (R(2)) were determined between PERG amplitude (µV) and SD-OCT macular ganglion cell complex (GCC) thickness (µm), macular thickness (µm), macular outer retinal thickness (macular thickness minus GCC thickness) (µm), RNFL thickness (µm), neuroretinal rim area (mm(2)), and rim volume (mm(3)). RESULTS: PERG amplitude was significantly associated with GCC thickness (R(2) = 0.179, P < 0.001), RNFL thickness (R(2) = 0.174, P < 0.001), and macular thickness (R(2) = 0.095, P<0.001). R(2) associations with other parameters were not significant (all P > 0.624). Significant associations remained for GCC and average RNFL thickness when age and intraocular pressure at the time of testing were included in multivariate models (both P ≤ 0.030). CONCLUSIONS: PERG amplitude is significantly (but weakly) associated with macular GCC thickness, RNFL thickness, and macular thickness. The lack of association between PERG amplitude and macular outer retinal thickness supports previous results, possibly suggesting that that the PERG is driven primarily by retinal ganglion cell (inner retinal) responses.

Agreement between spectral-domain and time-domain OCT for measuring RNFL thickness.

BACKGROUND/AIMS: To evaluate spectral-domain (SD) optical coherence tomography (OCT) reproducibility and assess the agreement between SD-OCT and Time-Domain (TD) OCT retinal nerve fibre layer (RNFL) measurements. METHODS: Three Cirrus-SD-OCT scans and one Stratus-TD-OCT scan were obtained from Diagnostic Innovations in Glaucoma Study (DIGS) healthy participants and glaucoma patients on the same day. Repeatability was evaluated using Sw (within-subject standard deviation), CV (coefficient of variation) and ICC (intraclass correlation coefficient). Agreement was assessed using correlation and Bland-Altman plots. RESULTS: 16 healthy participants (32 eyes) and 39 patients (78 eyes) were included. SD-OCT reproducibility was excellent in both groups. The CV and ICC for Average RNFL thickness were 1.5% and 0.96, respectively, in healthy eyes and 1.6% and 0.98, respectively, in patient eyes. Correlations between RNFL parameters were strong, particularly for average RNFL thickness (R(2) = 0.92 in patient eyes). Bland-Altman plots showed good agreement between instruments, with better agreement for average RNFL thickness than for sectoral RNFL parameters (for example, at 90 microm average RNFL thickness, 95% limits of agreement were -13.1 to 0.9 for healthy eyes and -16.2 to -0.3 microm for patient eyes). CONCLUSIONS: SD-OCT measurements were highly repeatable in healthy and patient eyes. Although the agreement between instruments was good, TD-OCT provided thicker RNFL measurements than SD-OCT. Measurements with these instruments should not be considered interchangeable.

Comparison of retinal nerve fibre layer measurements using optical coherence tomography versions 1 and 3 in eyes with band atrophy of the optic nerve and normal controls.

AIMS: To compare retinal nerve fibre layer (RNFL) measurements were carried out with two different versions of an optical coherence tomography device in patients with band atrophy (BA) of the optic nerve and in normal controls. METHODS: The RNFL of 36 eyes (18 with BA and 18 normals) was measured using an earlier version of an optical coherence tomography device (OCT-1). The measurements were repeated using a later version of the same equipment (OCT-3), and the two sets of measurements were compared. RESULTS: Using OCT-1, the peripapillary RNFL thickness (mean+/-SD, in microm) in eyes with BA measured 80.42+/-6.94, 99.81+/-14.00, 61.69+/-13.02, 101.70+/-12.54, and 57.36+/-16.52 corresponding to the total RNFL average, superior, temporal, inferior, and nasal quadrants, respectively. Using OCT-3, the corresponding measurements were 63.11+/-6.76, 81.22+/-13.34, 39.50+/-8.27, 86.72+/-15.16, and 45.05+/-8.03. Each of these measurements was significantly smaller with OCT-3 than with OCT-1. In normal eyes, RNFL average and temporal quadrant OCT-3 values were significantly smaller than OCT-1 values, but there was no significant difference in measurements from the superior, inferior, and nasal quadrant. CONCLUSIONS: RNFL measurements were smaller with OCT-3 than with OCT-1 for almost all parameters in eyes with BA and in the global average and temporal quadrant measurements in normal eyes. Investigators should be aware of this fact when comparing old RNFL measurement with values obtained with later versions of the equipment.

Comparison of algorithms for detection of localised nerve fibre layer defects using scanning laser polarimetry.

AIMS: To evaluate different algorithms used to analyse retinal nerve fibre layer thickness (RNFL) data obtained by scanning laser polarimetry, in order to compare their relative abilities to discriminate between patients with glaucomatous localised nerve fibre layer defects and normal subjects. METHODS: 48 eyes of 48 glaucomatous patients with localised RNFL defects and 53 eyes of 53 healthy subjects were included in this study. The localised RNFL defects were identified by RNFL photography and/or slit lamp biomicroscopic examination. All patients were submitted to RNFL examination using scanning laser polarimetry (GDx nerve fibre analyser, Laser Diagnostic Technologies, Inc, San Diego, CA, USA). Three methods of analysis of polarimetry data were used: GDx software provided parameters; RNFL thickness measurements in 16 equal sectors around the optic disc (sectoral analysis); and Fourier analysis of the curve of distribution of RNFL thickness measurements. Linear discriminant functions were developed to assess sensitivity and specificity of the sectoral based analysis and Fourier analysis and were compared to the GDx parameters. In addition, areas under the receiver operating characteristic (ROC) curves were compared. RESULTS: At a fixed specificity of 91%, the sensitivity of the linear discriminant function from sectoral data (LDF sectoral) was 81%, with an area under the ROC curve of 0.93. The linear discriminant function from Fourier measures had a comparable performance, with an area under the ROC curve of 0.93, and sensitivity of 71% for specificity at 91%. At the same specificity, the sensitivities of the GDx software provided parameters ranged from 15% to 40%. The areas under the ROC curves for the LDF sectoral and LDF Fourier were significantly greater than the ROC curve area for the single best GDx parameter. CONCLUSION: The sectoral based analysis and the Fourier analysis of RNFL polarimetry data resulted in an improved detection of eyes with glaucomatous localised nerve fibre layer defects compared to the GDx software provided parameters.

Quantitative analysis of axonal loss in band atrophy of the optic nerve using scanning laser polarimetry.

AIMS: To measure axonal loss in patients with band atrophy from optic chiasm compression using scanning laser polarimetry (GDx, Laser Diagnostic Technologies, Inc, San Diego, CA, USA) and to evaluate the ability of this instrument to identify this pattern of retinal nerve fibre layer (RNFL) loss. METHODS: 19 eyes from 17 consecutive patients with band atrophy of the optic nerve and permanent temporal hemianopia due to chiasmal compression, and 19 eyes from an age and sex matched control group of 17 healthy individuals were prospectively studied. All patients were submitted to an ophthalmic examination including Goldmann perimetry and evaluation of the RNFL using scanning laser polarimetry. Mean RNFL thickness around the optic disc were compared between the two groups. The diagnostic performance of the deviation from normal analysis provided by the GDx software was also assessed. RESULTS: The peripapillary RNFL thickness (mean (SD)) of eyes with band atrophy was 47.9 (7.63) micro m, 37.1 (8.48) micro m, 57.0 (9.31) micro m, and 37.2 (8.86) micro m in the superior, temporal, inferior, and nasal regions, respectively. The total average was 43.7 (12.0) micro m. In the control group, the corresponding values were 71.1 (12.2) micro m, 40.4 (10.9) micro m, 85.4 (14.0) micro m, and 49.8 (10.1) micro m. The total average measured 67.9 (11.2) micro m. The measurements from eyes with optic atrophy were significantly different from those in the control group in all regions but the temporal. The deviation from normal analysis provided by the GDx software failed to identify the majority of abnormalities in the temporal and nasal regions of patients with band atrophy. CONCLUSIONS: Scanning laser polarimetry was able to identify axonal loss in the superior, inferior, and nasal regions, but failed to detect it in the temporal region of the optic disc, despite the fact that this area was clearly altered in eyes with band atrophy. This examination also showed poor sensitivity to detect axonal loss in the nasal region when GDx software analysis was used. The results of this study emphasise that RNFL evaluation using scanning laser polarimetry should be interpreted with caution in the study of eye diseases that lead to axonal loss predominantly in the nasal and temporal areas of the optic disc.

The pros and cons of different prostanoids in the medical management of glaucoma.

The prostaglandin analogs are new exciting drugs added to the therapeutic armamentarium for patients with glaucoma. Several studies have evaluated the ocular hypotensive properties and side effects of latanoprost in different forms of glaucoma. This drug, seems to be the most effective intraocular pressure (IOP)-reducing agent currently available, and has a low incidence of ocular and systemic side effects. Fewer data are available regarding unoprostone, but the IOP-reducing effect of this drug seems to be comparable or slightly inferior to that of timolol and it produces fewer side effects. When compared with unoprostone, latanoprost has been shown to effect a greater reduction in IOP. A major drawback to the use of prostaglandin analogues is the lack of long-term experience such as that currently available for other classes of agents.

Dietary habits of calcium stone formers.

1. Since dietary factors are known to be related to nephrolithiasis, calcium stone-forming (CSF) patients were evaluated in terms of calcium, total protein of both animal and plant origin, carbohydrate and energy intakes, on the basis of 72-h dietary records during the week plus 24-h dietary records during the week-end. 2. The data for 77 calcium stone formers (57 with absorptive hypercalciuria and 20 with renal hypercalciuria) were compared to those for 29 age-matched healthy subjects. The body mass index of the CSF group was higher than that of healthy subjects (P < 0.05). Consumption of all nutrients was similar for both groups during the week but week-end dietary records for CSF showed higher calcium intake (586 +/- 38 vs 438 +/- 82 mg/day, P < 0.05), protein to body weight ratio (1.2 +/- 0.1 vs 1.0 +/- 0.5 g kg-1 day-1, P < 0.05) and animal protein (56 +/- 3 vs 40 +/- 3 g/day, P < 0.05) when compared with healthy subjects. 3. Comparison of hypercalciuria subtypes (renal hypercalciuria and absorptive hypercalciuria) did not indicate any difference in calcium or energy intake between groups, either during the week or during the week-end. However, the absorptive hypercalciuric group presented higher protein and animal protein consumption during the week-end. 4. These data suggest a low calcium intake in this population, even by stone formers. The higher animal protein consumption by our calcium stone formers observed during week-ends seems to be more important than calcium intake for stone formation.

Dietary habits of calcium stone formers

1. Since dietary factors are known to be related to nephrolithiasis, calcium stone-forming (CSF) patients were evaluated in terms of calcium, total protein of both animal and plant origin, carbohydrate and energy intakes, on the basis of 72-h dietary records during the week plus 24-h dietary records during the week-end. 2. The data for 77 calcium stone formers (57 with absorptive hypercalciuria and 20 with renal hypercalciuria) were compared to those for 29 age-matched healthy subjects. The body mass index of the CSF group was higher than that of healthy subjects (P < 0.05). Consumption of all nutrients was similar for both groups during the week but week-end dietary records for CSF showed higher calcium intake (586 +/- 38 vs 438 +/- 82 mg/day, P < 0.05), protein to body weight ratio (1.2 +/- 0.1 vs 1.0 +/- 0.5 g kg-1 day-1, P < 0.05) and animal protein (56 +/- 3 vs 40 +/- 3 g/day, P < 0.05) when compared with healthy subjects. 3. Comparison of hypercalciuria subtypes (renal hypercalciuria and absorptive hypercalciuria) did not indicate any difference in calcium or energy intake between groups, either during the week or during the week-end. However, the absorptive hypercalciuric group presented higher protein and animal protein consumption during the week-end. 4. These data suggest a low calcium intake in this population, even by stone formers. The higher animal protein consumption by our calcium stone formers observed during week-ends seems to be more important than calcium intake for stone formation