To assess whether baseline retinal nerve fiber layer (RNFL) measurements obtained with a scanning laser polarimeter, the GDx Nerve Fiber Analyzer, (Laser Diagnostic Technologies Inc., San Diego, ...California) are predictive of development of repeatable glaucomatous visual field damage in glaucoma suspect eyes.
Cohort study.
Participants were recruited from the UCSD longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). One eye from each of 160 glaucoma suspects with normal standard automated perimetry (SAP) visual fields at baseline was studied. Study eyes were divided into convert and nonconvert groups based on the development of three consecutive glaucomatous visual fields during follow-up. SLP parameters, IOP, vertical cup disk ratio, stereophotograph assessment as glaucoma or normal, corneal thickness, and visual field indices were included in univariate and multivariate Cox proportional hazards models to determine which SLP RNFL and ocular parameters were predictive of visual field conversion.
Sixteen (10%) eyes developed repeatable visual field damage (converts) and 144 (90%) did not (nonconverts). Mean (95%CI) follow-up time until visual field conversion for convert eyes was 2.7 (1.7, 3.6) years. Mean total follow-up of nonconvert eyes was 3.8 (3.5, 4.1) years. Four out of thirteen examined baseline SLP parameters and baseline SAP Mean Deviation (MD), SAP Pattern Standard Deviation (PSD), and glaucomatous stereophotograph assessment were significant univariate predictors of visual field conversion. In multivariate models adjusted for age, IOP and CCT, SLP parameters inferior ratio, ellipse modulation, and UCSD linear discriminant function (LDF) were significant predictors of visual field conversion. When SAP PSD and stereophotograph assessment were also included in the multivariate model inferior ratio and UCSD LDF remained independently predictive of visual field loss.
Thinner baseline SLP RNFL measurements were independent predictors of visual field damage. In addition to thinner SLP RNFL measurements, higher baseline SAP PSD, and baseline glaucomatous stereophotograph assessment each contributed to an increased risk of the development of abnormal visual fields in glaucoma suspect patients. SLP RNFL measurements were independently predictive of future visual loss even when age, IOP, CCT, vertical cup disk ratio, and SAP PSD were included in the model.
To assess the relationship between regional variation of axon loss and optic nerve head anatomy in laser-induced experimental glaucoma in the mouse.
Experimental glaucoma was induced unilaterally in ...eight NIH Swiss black mice. Intraocular pressure (IOP) was measured for 12 weeks, and the mice were killed. The eyes were enucleated, and both optic nerves were dissected and processed conventionally for electron microscopy. Low- and high-magnification images of the optic nerve cross sections 300 microm posterior to the globe were collected systematically and masked before analysis. For each nerve, cross-sectional area was measured in low-magnification micrographs. Axon number and density were determined in the high-magnification micrographs. Loss of axonal density was compared between the superior and inferior and nasal and temporal areas of the optic nerve cross section. Additional cross-section micrographs were collected at 10- or 20-microm intervals throughout the optic nerve head.
In the treated (glaucoma) eyes, mean IOP was 44% higher than that in the control eyes. The optic nerve cross-sectional area, mean axonal density, and total axonal number were significantly less than those in the control eyes (P < 0.01 for each). Axon loss in the superior optic nerve was greater than in the inferior optic nerve in each glaucomatous eye (P = 0.012). The ratio of axonal density in the superior and inferior optic nerve (superior-to-inferior S/I ratio) in all treated eyes was <1.0 and significantly lower than that in the control eyes (P = 0.012). The central retinal vessels occupied approximately 20% of the central optic nerve head cross-sectional area, gradually shifted position ventrally as they progressed toward the scleral foramen (the mouse does not have a lamina cribrosa), and exited the inferior retrobulbar optic nerve adjacent to the posterior of the globe.
Ocular hypertension in the mouse eye sufficient to cause optic nerve damage induces preferential loss of superior optic nerve axons. Optic nerve axon loss appeared less among the axons that were near the major optic nerve blood vessels at the scleral foramen. Topographic differences in optic nerve axon loss should be considered when evaluating optic nerve damage in experimental laser-induced glaucoma in the mouse.
PURPOSE: We examined changes in optic disk topography using confocal scanning laser ophthalmoscopy after reducing intraocular pressure with administration of latanoprost.
METHODS: Twenty-nine ...patients with glaucoma or ocular hypertension were imaged using the Heidelberg Retina Tomograph before and after the administration of latanoprost to decrease intraocular pressure. Average time between pretreatment and posttreatment imaging was 2.7 ± 1.8 weeks. Heidelberg Retina Tomograph software–measured parameters were mean height of contour, cup area, cup volume, mean cup depth, maximum cup depth, cup shape, rim area, rim volume, cup-to-disk ratio, and retinal nerve fiber thickness.
RESULTS: Average intraocular pressure decreased significantly (mean ± SD) by 7.2 ± 5.4 mm Hg (25 ± 16% decrease). No statistically significant changes in measured topographic parameters were found. When data from patients with decreases in intraocular pressure of 7 mm Hg or greater were analyzed separately (mean intraocular pressure decrease = 10.79 ± 4.32 mm Hg, 36 ± 8% decrease), cup area (
P = .005), cup volume (
P = .002), and cup-to-disk ratio (
P = .005) decreased significantly, and rim area (
P = .005) increased significantly. Linear regression analysis of the data from all subjects showed that a change in intraocular pressure after latanoprost administration accounted for 12% or more of the variance in two measured topographic parameters (mean cup depth and cup shape).
CONCLUSIONS: These results suggest that, in some patients, moderate decreases in intraocular pressure may affect disk topography, as measured by Heidelberg Retina Tomograph. Intraocular pressure should be considered when analyzing consecutive confocal scanning laser ophthalmoscopy images for glaucomatous progression.
To evaluate the relation between the location of focal visual field defects and optic disk damage in eyes with glaucoma by short-wavelength automated perimetry and confocal scanning laser ...ophthalmoscopy.
In 14 patients (14 eyes) with open-angle glaucoma, focal optic disk damage, and focal visual field loss, we obtained visual fields with short-wavelength automated perimetry. The short-wavelength automated perimetry visual field was divided into 21 zones, representing retinal nerve fiber layer arcuate bundles. Test points were compared with a normative database. The optic disk was assessed with a confocal scanning laser ophthalmoscope. Optic disk measurements were calculated in 10-degree sectors and compared with a normative database using a new measure, the rim area ratio, which adjusts for individual differences in disk size.
The mean number (±SD) of damaged visual field zones was 3.9 (±1.9), and the mean number of damaged rim sectors was 5.0 (±2.9). Focal defects on the optic disk and on short-wavelength automated perimetry were topographically related with specific damaged visual field zones corresponding to specific damaged rim sectors.
In patients with open-angle glaucoma with focal optic disk damage and focal visual field loss, defects in optic disk and short-wavelength automated perimetry are topographically related. The rim area ratio can be used to identify focal optic nerve defects.
Experimental models have enhanced our understanding of the biology of glaucoma. Moreover, they have enabled the testing of potential therapies prior to the initiation of human trials. Each have ...advantages and limitations. In vitro cell and organ culture offer direct cellular accessibility and microenvironmental control, as well as efficient comparison between many experimental conditions or potential therapeutic compounds. However, they generally have less relevance to clinical glaucoma than in vivo models. Rat models allow moderate sized investigations of intact biological systems that have greater relevance to glaucoma than in vitro experiments, but less than primate experiments. Mouse models are similar to rat models but have the advantage of investigating mutant and transgenic strains mimicking specific aspects of glaucoma that are not available in other model systems. Primate models of glaucoma generally are the most relevant to human glaucoma but must be limited in scope because of availability and the high cost of experimentation.
The 24-hr pattern of intraocular pressure in the mouse eye remains poorly characterized. The present study was undertaken to determine the magnitude, dynamic pattern, and synchrony of the 24-hr ...pattern of intraocular pressure (IOP) in NIH Swiss mice exposed to a 12-hr light/dark cycle or to constant light. IOP was measured every 3
hr using a microneedle method. Mice exposed to a 12-hr light /dark cycle were either measured repeatedly at 1 week interval (group 1) or were only measured once (group 2). A third group was exposed to constant light for 2 weeks prior to IOP measurements. The 24-hr IOP pattern in the first and second groups showed a similar rhythmic pattern that appeared to be sinusoidal. This IOP pattern declined in the morning until 12:00, and then increased in the early evening until 21:00. In contrast, IOP in the third group was asynchronous with some mice exhibiting multiple peaks and troughs during the 24-hr period. These results show that 24-hr IOP pattern in mouse eyes is biphasic and that extended exposure to constant light disrupts this 24-hr IOP pattern.
We assessed agreement between cup/disk ratio measurements obtained by glaucoma expert evaluation of stereoscopic photographs of the optic disk and those obtained with a confocal scanning laser ...ophthalmoscope.
Three glaucoma experts estimated vertical and horizontal cup/disk ratios from stereoscopic photographs of 15 normal subjects and 15 patients with glaucoma. These estimates were compared to vertical, horizontal, and area cup/disk ratios measured with a confocal scanning laser ophthalmoscope. Intraobserver and interobserver agreements were also estimated.
Agreement between clinicians and the confocal scanning laser ophthalmoscope varied by clinician. Agreement was moderate to substantial for vertical cup/disk ratio and fair to moderate for horizontal cup/disk ratio; kappas ranged from 0.57 to 0.72 and from 0.21 to 0.55, respectively. The mean confocal scanning laser ophthalmoscope area cup/disk ratio measurements were smaller than each clinician's mean vertical and horizontal cup/disk ratio estimates; differences ranged from 0.10 to 0.24 and from 0.06 to 0.16, respectively. Differences were smaller between clinician estimates and instrument measurements of horizontal and vertical cup/disk ratios of patients with glaucoma than normal subjects.
These results demonstrate good agreement between confocal scanning laser ophthalmoscope measurements and clinician estimates of the vertical cup/disk ratios from stereoscopic photographs, particularly of patients with glaucoma. However, as differences between clinician and instrument estimates of cup/disk ratios were found, new quantitative criteria must be established for characterizing a disk as glaucomatous using confocal scanning laser ophthalmoscopy.
To assess the asymmetry of 24-hour intraocular pressures (IOPs) between right and left eyes of untreated open-angle glaucoma (OAG) patients, and its influence on the monocular therapeutic trial.
...Experimental study with human patients.
Forty-one subjects (40-78 years old) with untreated OAG.
Subjects were housed in a sleep laboratory for 24 hours. Intraocular pressures of both eyes were measured with a pneumatonometer every 2 hours with the patient in the sitting and supine positions from 7 am to 11 pm and in the supine position only from 11 pm to 7 am. Mean, peak, and trough IOPs were compared in right versus left eyes. The strength of association between right and left IOPs was assessed using coefficients of determination (R2). Validity of the monocular therapeutic trial was assessed by examining residual values from 2 linear regression models of right versus left IOP.
Strength of association between IOPs of right and left eyes, and residual values from linear models of IOP.
No statistically significant difference was found between mean, peak, or trough IOPs of right and left eyes over a 24-hour period. The strength of association for mean IOP was only moderate (R(2) = 0.421-0.623). Residual values of > or =3 mmHg were found in 14.0%+/-12.0% (mean +/- standard deviation) of IOP measurements for a symmetric linear regression model, and 8.5%+/-10.6% of IOP measurements for a best-fit linear regression model over 24 hours.
In this group of untreated glaucoma patients, the strength of association between the right and left eye mean IOPs is only moderate. Residual values of > or =3 mmHg were more common using a symmetric model than with a best-fit model. The current method of performing monocular therapeutic trials in glaucoma patients is unreliable, but it may be possible to improve reliability by using several IOP measurements obtained at different times of the day instead of a single office measurement.
