The authors determine which optic disc topographic parameters obtained by the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany) are most useful in detecting individuals ...with early glaucomatous visual field loss.
Ninety-nine eyes of 49 healthy individuals and 50 age-matched individuals with early glaucomatous visual field loss were included. Three images were obtained and the mean topography image was created and used in the analyses. The HRT discriminant analysis function (software version 2.01) was applied and compared to the Fisher linear discriminant function developed in this population. Analysis was repeated after stratifying by disc area (< 2 mm2 or 2-3 mm2).
There were statistically significant differences between the healthy and glaucomatous groups for all optic disc topographic parameters (p < 0.05) measured. These differences remained after the analysis was repeated controlling for disc size, except for height variation contour. Applying the HRT discriminant function to this study population resulted in sensitivity and specificity of 62% and 94%, respectively. The sensitivity was 83% while specificity remained high (91%) for larger disc sizes. Using this data, additional discriminant functions that differentiated similarly between the two groups were found. The best formula used cup-shape measure (third moment), rim area, height variation contour, and retinal nerve fiber layer thickness and had a sensitivity and specificity of 78% and 88%, respectively.
Several different discriminant analysis formulas are capable of detecting early glaucomatous visual field loss in a comparable manner. The characteristics of the study population are likely to influence the discriminating power of these various formulas.
Topical high-precision piezo-print delivery of microdoses of latanoprost achieved significant IOP reduction consistent with the eyedropper effect but with a 75% reduced exposure to drugs and ...preservatives. Prostaglandin analogs are a mainstay glaucoma therapy. However, conventional eyedroppers deliver 30-50 µL drops that greatly exceed the physiologic 7-µL ocular tear film capacity. Eyedropper overdosing floods the eye with excess drug compounds and preservatives, resulting in ocular surface toxicity, periorbitopathy, and other well-characterized ocular side effects. Piezoelectric high-precision microdosing provides targeted delivery that can reduce exposure to both drug and preservatives compared to conventional eyedropper delivery, with the potential to deliver similar biologic effect.
Both eyes (N=60) of 30 healthy volunteers received single 8-µL microdoses of 0.005% latanoprost (0.4 µg; µRx-latanoprost) on the morning of Days 1 and 2 using a high-precision, piezo-print horizontal delivery system. Diurnal IOP was measured before and 2 days after microdosing. Main efficacy outcomes were diurnal IOP change after µRx-latanoprost microdosing and accurate microdosing success rates, and the primary safety outcome was adverse event (AE) incidence.
µRx-latanoprost reduced baseline IOP by 26% and 30% at 1 and 2 days postadministration, respectively. Successful topical dosing was achieved in 100% of technician-assisted deliveries. All patients successfully self-administered microdoses after receiving training. Microdose administration was well tolerated and did not result in any AEs.
Microdosing of 0.4 µg of µRx-latanoprost achieved significant IOP reduction. Lower ocular exposure with topical prostaglandin analog microdosing can enable new therapeutic opportunities for optimizing glaucoma treatment. Microdosing may also be beneficial in reducing ocular side effects associated with excessive drug product and preservatives often used to treat chronic ocular diseases such as glaucoma.
To determine whether central corneal thickness (CCT) is a risk factor for visual field loss development among patients diagnosed with preperimetric glaucomatous optic neuropathy (GON).
Observational ...cohort study.
The study included 98 eyes of 98 patients with GON, with a mean follow-up time of 4.3 ± 2.7 years. Diagnosis of GON was based on masked assessment of optic disk stereophotographs. All patients had normal standard automated perimetry visual fields at baseline. Criteria for visual field abnormality were derived from a prior study. Several clinical factors (CCT, intraocular pressure, vertical cup-to-disk ratio, refraction, age, gender, family history of glaucoma, high blood pressure, cardiovascular disease, and migraine) were investigated to ascertain whether there is an association with development of repeatable visual field loss. Cox proportional hazards models were used to obtain hazard ratios (HR) and identify factors that predicted which individuals developed glaucomatous visual field loss during the follow-up period.
Thirty-four patients (35%) developed repeatable visual field abnormality during follow-up. In multivariate analysis, risk factors that predicted the development of visual field loss were a thinner CCT (adjusted HR = 1.62/40 μm thinner; P = .023; 95% confidence interval CI: 1.07–2.45), higher baseline intraocular pressure (adjusted HR = 1.07/mm Hg; P = .022; 95% CI: 1.01–1.14), and larger baseline vertical cup-to-disk ratio (adjusted HR = 1.63/0.1 larger; P = .009; 95% CI: 1.13–2.35). The mean ± standard deviation CCT of GON patients who developed visual field loss was 543 ± 36 μm compared with 565 ± 35 μm of those who did not develop visual field abnormalities (P = .005, Student
t test).
Central corneal thickness is a risk factor for development of visual field loss among patients diagnosed with preperimetric GON. It is important to consider CCT when establishing target intraocular pressure of patients with GON.
Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.
We used Illumina 660W-Quad array ...genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.
The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.
Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.
An assumption for the one-eye therapeutic trial of ocular hypotensive drugs is the symmetrical variation of intraocular pressure (IOP) between the two eyes. We evaluated whether or not 24-hour ...variations of IOP in the two eyes are similar in healthy individuals.
Experimental study with human subjects.
Ninety-one healthy individuals.
We reviewed bilateral IOP data collected from 38 younger (18-25 years) and 53 older (40-74 years) experimental subjects housed for 24 hours in a sleep laboratory. Intraocular pressure was measured every 2 hours using a pneumatonometer in the sitting and supine positions during the 16-hour diurnal/wake period and in the supine position during the 8-hour nocturnal/sleep period. Measurements were always taken first in the right eye. For each age group, the two eyes' means, peaks, troughs, and ranges of IOP during office hours, the diurnal period, the nocturnal period, and the 24-hour period were compared. The coefficient of determination was used to examine the strength of association between the right and left IOPs.
Bilateral IOP.
For each age group, the profiles of IOP variations were similar in the two eyes with either the habitual body positions (diurnal sitting and nocturnal supine) or the 24-hour supine position. Mean, peak, and trough IOPs in the right eye were slightly higher than those in the left eye during the defined periods. There was no difference in the IOP range, except for the supine IOP in the younger group during the diurnal period. Cosine fits of the 24-hour supine IOP indicate no difference in the estimated phase timing or the 24-hour variation between the two eyes. Coefficients of determination for single pairs of right and left IOPs were in the range of 0.311 to 0.741.
Variations of 24-hour IOP in the right and left eyes are similar. However, because the strength of association between the two eyes is only moderate, it may be difficult to perform a one-eye therapeutic trial using single pairs of right and left eye IOP measurements.
Glaucoma suspect eyes were seen during a five-year study on color visual fields that used a 440-nm test on a bright-yellow background (96 normal eyes, 55 suspect eyes, and 110 eyes that developed ...glaucoma). The predictive ability of the test was assessed in 25 eyes followed up for more than one year, five of which developed glaucoma. These five eyes and those at high risk showed higher mean defect (P < .0001) and number of defective points (P < .0001) than the other suspect groups, which were not significantly different from normal eyes. The mean defects (+/- standard deviations) and average number of defective points were 1.4 +/- 2.3 dB with 8.9 points (low-risk eyes), 1.1 +/- 1.2 dB with 8.0 points (medium-risk eyes), 6.7 +/- 2.8 dB with 27.7 points (high-risk eyes), and 9.3 +/- 1.8 dB with 39.4 points (eyes that developed glaucoma). Normal eyes had an average of 3.4 defective points. These results were similar when all 55 suspect eyes were analyzed. Color visual fields identify early functional loss in eyes at greatest risk for primary open-angle glaucoma.
To compare measurements of optic nerve topography of ocular hypertensive patients with those of normal subjects and primary open-angle glaucoma patients.
Three age-matched study groups of 46 ocular ...hypertensive patients, 46 primary open-angle glaucoma patients, and 46 normal subjects were recruited from patients and volunteers of a glaucoma referral practice. Optic nerve topography was measured using a confocal scanning laser tomograph, the Heidelberg Retina Tomograph. The following optic nerve parameters were evaluated: disk area, cup/disk area ratio, cup shape, height in contour, rim area, rim volume, maximum cup depth, cup area, cup volume, retinal height, and retinal cross-section area. For this cross-sectional study, analysis of variance was used to evaluate overall differences among the three subject groups and the Tukey-Kramer multiple comparison test to evaluate differences between the means of two groups.
Statistically significant differences among study groups were found for all topographic optic nerve parameters evaluated. Despite considerable overlap in optic nerve parameter measurements among the study groups, mean values of ocular hypertensive eyes were intermediate between those for normal and primary open-angle glaucoma eyes. Statistically significant differences were found between ocular hypertensive and glaucomatous eyes for all optic nerve parameters measured, and between ocular hypertensive and normal eyes for disk area, height in contour, rim area, and rim volume.
In age-matched groups, mean measurements of certain topographic optic nerve parameters of ocular hypertensive eyes differ from those of normal and glaucomatous eyes.
To develop a model for estimating the global risk of disease progression in patients with ocular hypertension and to calculate the “number-needed-to-treat” (NNT) to prevent progression to blindness ...as an aid to practitioners in clinical decision making.
Development of a mathematical model for estimating risk of glaucoma progression.
Population-based studies of patients with ocular hypertension and glaucoma were reviewed by a panel of glaucoma specialists. Measures of disease progression risks derived from three long-term studies and assumptions based on the available data were used to estimate the risk of progression from ocular hypertension to glaucoma and glaucoma to unilateral blindness for untreated and treated patients over a 15-year period. Using these estimates, the NNT (1/absolute risk reduction on treatment) to prevent unilateral blindness in one patient with ocular hypertension was calculated.
In untreated patients, the estimated risk of progression from ocular hypertension to unilateral blindness was 1.5% to 10.5% and in treated patients, the estimated risk of progression was 0.3% to 2.4% over 15 years. From these estimates, between 12 and 83 patients with ocular hypertension will require treatment to prevent one patient from progressing to unilateral blindness over a 15-year period.
Global risk assessment that incorporates all available data plays a vital role in managing patients with ocular hypertension. A more precise understanding of long-term vision loss should be factored into decisions pertaining to the initiation of glaucoma therapy. Undoubtedly, these estimates will evolve and change with the availability of new population-based epidemiologic information and improvements in multivariable model testing.
To compare retinal nerve fiber layer (RNFL) measurements between two ocular coherence tomography (OCT) instruments (OCT 2000 and Stratus OCT; Carl Zeiss Meditec, Dublin, CA) and compare their ...diagnostic precision.
One hundred thirty-nine consecutive subjects were imaged (3 x 3.4-mm diameter circular scans) on the same day with each instrument. Thirty-five patients were excluded due to poor-quality images. RNFL thicknesses measured by the two instruments were compared, and receiver operating characteristic (ROC) curves were used to determine diagnostic precision.
A randomly selected eye of each of 104 participants (28 with open-angle glaucoma, 40 with suspected glaucoma, and 36 healthy subjects) was analyzed. RNFL thickness measurements generally were thicker with OCT 2000 than with Stratus OCT. The difference in global RNFL thickness between instruments was within 20 microm in 66 (65%) of subjects and within 10 microm (the instrument's limit of resolution) in 25 (25%) subjects. Application of a correction factor to OCT 2000 measurements predicted Stratus OCT RNFL thickness within 10 microm of the observed measurement in 75% of the eyes. For both instruments, highest ROC curve areas (better discrimination between glaucomatous and normal eyes) were found in the inferior sector. Discrimination using global RNFL thickness was better with Stratus OCT than OCT 2000 (P = 0.043).
RNFL thickness measurements measured by OCT 2000 can be approximated to measurements made by Stratus OCT using correction factors calculated by this study. However, there remains considerable variability that exceeds the limits of resolution afforded by the instruments themselves. Therefore comparisons between instruments using these approximations should be interpreted with caution.
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