Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Contrast sensitivity assessment in primary open angle glaucoma and ocular hypertension.

INTRODUCTION: Contrast sensitivity assessment is an important additional examination, which enables the full insight into the patient's quality of vision, and early diagnosis of visual disturbances. MATERIAL AND METHODS: Forty six patients (92 eyes) with primary open angle glaucoma or ocular hypertension were enrolled in the study. The enrolment criteria were full or almost full visual acuity and the patients with visual field defects or any other ocular disease were excluded. Contrast sensitivity was assessed both under photopic and mesopic conditions (with and without glare) using the Functional Vision Analyzer separately for each eye. Furthermore, the retinal nerve fiber layer (RNFL) thickness was measured using scanning laser polarimetry (GDx). RESULTS: Contrast sensitivity was significantly reduced under both mesopic and photopic conditions in patients with primary open angle glaucoma or ocular hypertension. CONCLUSIONS: Evaluation of contrast sensitivity is a valuable diagnostic test, which enables the assessment of visual dysfunction in patients with primary open angle glaucoma or ocular hypertension persisting despite good visual acuity.

A model for the easy assessment of pressure-dependent damage to retinal ganglion cells using cyan fluorescent protein-expressing transgenic mice.

PURPOSE: To establish an animal model for the easy assessment of pressure-dependent damage to retinal ganglion cells (RGCs) using the B6.Cg-TgN(Thy1-CFP)23Jrs/J transgenic mouse strain (CFP mouse), which expresses cyan fluorescent protein (CFP) in RGCs, and to evaluate pressure-dependent RGC death. METHODS: In 20 CFP mice, right eyes were selected to receive laser-induced ocular hypertension eye and the contralateral eyes remained untouched to serve as controls. Intraocular pressure (IOP) was measured each week in both eyes using the microneedle method up to 8 weeks. Based on the line plot of time (x) and IOP (y) in laser-treated and control eyes, the area surrounded by both lines (∫ΔIOP(y) dx) was calculated as a surrogate value of the pressure insult. At 9 weeks, eyes were enucleated and RGCs expressing CFP were evaluated histologically in retinal whole mounts. The correlation between pressure insult and RGC density was evaluated in the whole eye, three concentric regions, and four quadrants. RESULTS: Laser-treated eyes showed a significantly higher IOP than control eyes from 1 to 7 weeks (p<0.01). The pressure insult and the RGC density showed a significant negative correlation (y=-0.070x+97.2, r=0.75, p=0.0008). Moreover, the central, middle, and peripheral areas measured from the optic disc and each of four retinal quadrant areas also showed significant negative correlations. Our data demonstrate that each retinal area was almost evenly damaged by IOP elevation. CONCLUSIONS: Laser photocoagulation causes a chronic elevation of IOP in CFP mice. The use of CFP mice enabled us to easily evaluate pressure-dependent RGC damage. This glaucomatous CFP mouse model may contribute to the molecular analysis of neurodegeneration and the development of neuroprotective drugs for glaucoma with a great increase in experimental efficiency.

A 6-month assessment of bimatoprost 0.03% vs timolol maleate 0.5%: hypotensive efficacy, macular thickness and flare in ocular-hypertensive and glaucoma patients.

AIM: To compare 6 months of treatment with bimatoprost and timolol in terms of their hypotensive efficacy and secondary effects, including changes in macular thickness and the inflammatory reaction induced in the anterior chamber. METHODS: A prospective, randomized, parallel-group trial performed on 30 eyes of 30 patients per group. The main outcome measure was the difference between the IOP value taken between the baseline visit and the 6-month-visit. Macular thickness determined through optical coherence tomography and anterior chamber inflammation estimated using the laser flare meter was also evaluated. Adverse events were recorded during the study period. RESULTS: Bimatoprost treatment gave rise to a significantly lower mean IOP than timolol in all follow-up visits as from the first month (P<0.05). Bimatoprost achieved high percentage IOP reductions from baseline in a significantly higher proportion of patients (P<0.05). Macular thickness and anterior chamber flare failed to vary significantly both between the two groups and within each group during the 6-month evaluation (P>0.05). CONCLUSIONS: Bimatoprost 0.03% once daily showed a greater efficacy then timolol 0.05% twice daily in patients with elevated IOP. No significant differences were detected in macular thickness or anterior uveitis using optical coherence tomography and laser flare photometry.

Morphometric assessment of normal, suspect and glaucomatous optic discs with Stratus OCT and HRT II.

AIMS: To compare morphometric parameters and diagnostic performance of the new Stratus Optical Coherence Tomograph (OCT) Disc mode and the Heidelberg Retina Tomograph (HRT); to evaluate OCT's accuracy in determining optic nerve head (ONH) borders. METHODS: Controls and patients with ocular hypertension, glaucoma-like discs, and glaucoma were imaged with OCT Disc mode, HRT II, and colour disc photography (DISC-PHOT). In a separate session, automatically depicted ONH shape and size in OCT were compared with DISC-PHOT, and disc borders adjusted manually where required. In a masked fashion, all print-outs and photographs were studied and discs classified as normal, borderline, and abnormal. The Cohen kappa method was then applied to test for agreement of classification. Bland-Altman analysis was used for comparison of disc measures. RESULTS: In all, 49 eyes were evaluated. Automated disc margin recognition failed in 53%. Misplaced margin points were more frequently found in myopic eyes, but only 31/187 were located in an area of peripapillary atrophy. Agreement of OCT with photography-based diagnosis was excellent in normally looking ONHs, but moderate in discs with large cups, where HRT performed better. OCT values were consistently larger than HRT values for disc and cup area. Compared with HRT, small rim areas and volumes tended to be minimized by OCT, and larger ones to be magnified. CONCLUSIONS: Stratus OCT Disc protocol performed overall well in differentiating between normal and glaucomatous ONHs. However, failure of disc border recognition was frequently observed, making manual correction necessary. ONH measures cannot be directly compared between HRT and OCT.

Vertical cup/disc ratio in relation to optic disc size: its value in the assessment of the glaucoma suspect.

AIMS: The vertical cup/disc ratio (CDR) has long been used in the assessment of the glaucoma suspect, though the wide range of CDR values in the normal population limits its use. Cup size is related physiologically to disc size and pathologically to glaucomatous damage. Disc size can be measured at the slit lamp as the vertical disc diameter (DD). The ability of the CDR, in relation to DD, to identify glaucomatous optic discs was investigated. METHODS: 88 normal, 53 early glaucoma, and 59 ocular hypertensive subjects underwent stereoscopic optic disc photography and clinical biometry. Photographs were analysed in a masked fashion by computer assisted planimetry. The relation between vertical cup diameter and DD was explored by linear regression, and expressed in terms of CDR. The upper limit of normal was defined by the 95% prediction intervals of this regression (method 1) and by the upper 97.5 percentile for CDR (method 2). The sensitivity and specificity of CDR to identify an optic disc as glaucomatous was tested with these disc size dependent and disc size independent cut offs in small, medium, and large discs. RESULTS: The CDR was related to DD by the equation CDR = (-1.31 + (1.194 x DD))/DD. The sensitivity in small, medium, and large discs was 80%, 60%, and 38% respectively for method 1 and 33%, 67%, and 63% respectively for method 2. Specificity was 98.9% (method 1) and 97.7% (method 2). CONCLUSIONS: The CDR, relative to disc size, is useful clinically, especially to assist in identifying small glaucomatous discs.

Retinal nerve fiber layer assessment by scanning laser polarimetry and standardized photography.

PURPOSE: To determine whether, in a clinical setting, scanning laser polarimetry and retinal nerve fiber layer photography provide equivalent information on the retinal nerve fiber layer. METHODS: We prospectively studied 60 patients with glaucoma or ocular hypertension and 24 healthy subjects. With scanning laser polarimetry, an estimate of the cross section of the retinal nerve fiber layer was obtained. By using a photographic reference set, we quantified photographs of the retinal nerve fiber layer. Visual fields were used to relate the results of both methods to functional damage. RESULTS: The scanning laser polarimetry measurements yielded reproducible cross-section values (coefficient of variation, 6.6%). Comparison of cross-section values and photograph scores gave Pearson correlation coefficients smaller than r = .4 (P < .01), improving to a maximum of r = .53 after compensation for offset. When cross-section values were compared to the mean deviation of the visual field, the Spearman correlation coefficients varied from an r of -.34 to -.53 (P < .01). Correction for offset resulted in an r of -.54 to -.65. When photograph scores and mean deviation of the visual field were compared, the Spearman correlation coefficients varied from an r of -.65 to -.71 (P < .01). CONCLUSIONS: Because r was maximal at .53, the information on the retinal nerve fiber layer obtained with scanning laser polarimetry and photography seems not equivalent. This result could not have been because of lack of reproducibility. Although the results suggested possible offset in scanning laser polarimetry, other methodologic differences must be considered to explain the differences between the two techniques.

Inter-observer variability in a computer-assisted optic nerve head assessment system.

A computer-assisted optic nerve head analysis system was used to measure parameters of the optic nerve head from one eye from each of 15 subjects. The subjects comprised three groups of five, being glaucomatous, ocular hypertensive, and normal. The 15 images produced were analysed in a randomized masked fashion by ten observers of varying levels of experience to test the inter-observer variability of the measurements. An analysis of variance demonstrated significant differences in the measurements made by the different observers. Fisher's F-test showed that all the parameters assessing the pallor area of the optic nerve head had significantly lower inter-image variance (reported previously) compared with inter-observer variance (at the 5% level). Variability in taking measurements of the pallor area of the optic nerve head is mainly due to observer variations rather than the image variations.

Inter- and intra-image variability in computer-assisted optic nerve head assessment.

A computer-assisted system for optic nerve head analysis was used to measure one eye from each of 15 subjects. These comprised three groups of five, being glaucomatous, ocular hypertensive, and normal subjects. Each eye was imaged with the system 10 times. The 150 images produced were analysed in a randomized masked fashion to test the inter-image variability of the measurements. Linear pallor: disc ratios had mean coefficients of variation of 6.6% (normal), 4.8% (ocular hypertensive) and 2.6% (glaucomatous). This trend of reducing coefficient of variation from normal to ocular hypertensive to glaucomatous was reflected in other parameters also. Intra-image variability was assessed by analysing one image from each subject 10 times, in a randomized masked fashion. The mean coefficients of variation of the linear pallor: disc ratios were 6.3% (normal), 3.6% (ocular hypertensive) and 3.2% (glaucomatous). Fisher's F-test showed that no parameters had significantly lower intra-image rather than inter-image variance (at the 5% level). Variability is apparently due to operator variations rather than the image variations.

Contact B-scan echography in the assessment of optic nerve cupping.

We determined the reliability of high-resolution contact B-scan echography for estimating the optic cup size in 56 eyes of 28 patients with glaucoma or ocular hypertension. Two trained observers independently evaluated horizontal and vertical cup/disk ratios in stereophotographs, and two skilled echographers independently estimated optic cup size in photoechograms in a masked fashion. The reliability of echographic interpretation varied (kappa 0.29 to 0.71), but it always exceeded that expected by chance alone, even for cups of 0.3 disk diameter or less. Subtly saucer-shaped cups (three of 50 eyes) and deep cups with intact neuroretinal rims (two of 50 eyes) were misinterpreted echographically. High-resolution contact B-scan echography may provide a useful and reliable estimate of the optic cup size in eyes with opaque media.

Evaluation of nerve fiber layer assessment.

More than 1,400 eyes with either ocular hypertension glaucomatous visual field loss, or normal pressures and fields (controls) were studied prospectively in standardized, masked fashion. The appearance of the nerve fiber layer was evaluated independently from red-free photographs with the discs blocked-out by two observers. The vast majority of photographs could be evaluated, the proportion varying with the observer and with the age and clinical status of the subject. Sensitivity (proportion of glaucomatous eyes with nerve fiber defects) and specificity (proportion of normal control eyes without defects) averaged 80% to 94%, varying with the observer and with the age, race, and severity of field loss. In two thirds of presumed false-positive eyes, but only 5% of true-positive eyes, the abnormalities were limited to focal slitlike defects. The prevalence of nerve fiber defects in eyes with elevated pressure and normal visual fields was similar to that in control eyes, approximately 10%. However, the proportion of eyes in which these defects included diffuse loss was considerably higher among the hypertensive eyes.