Frequency doubling perimetry and the detection of eye disease in the community.

PURPOSE: Frequency Doubling Technology (FDT) perimetry is a novel perimetric test that provides rapid screening (45 to 60 seconds) and full-threshold (4 to 5 minutes) testing for detection of vision loss. The purpose of this study was to determine the specificity and sensitivity of FDT perimetry for the detection of ocular disease. METHODS: A total of 130 participants (257 eyes of 42 men and 88 women) recruited from the community completed FDT perimetry, standard achromatic automated perimetry (SAP), anterior segment biomicroscopy, tonometry, and dilated ophthalmoscopy. FDT results were considered abnormal if 1 point was abnormal (depressed below the 5% level on the screening protocol C-20-5). SAP was considered abnormal if the glaucoma hemifield test or pattern standard deviation was outside normal limits (P < .05) or a hemifield cluster of 3 depressed points on the pattern deviation probability plot (P < .05) was present. An abnormal eye examination was defined as the presence of an abnormality in the anterior segment, lens, or posterior segment that was likely to cause a visual field defect or the presence of glaucomatous or other optic neuropathy. RESULTS: The mean age (+/- SD) of participants was 55.5 years (+/- 10.3). Ethnic groups, as reported by participants, included 77 (59%) African Americans, 40 (31%) Caucasians, and 13 (10%) in other groups. On clinical examination, 116 eyes (45%) were normal, 9 eyes (3.5%) had a cataract with best corrected visual acuity worse than 20/30, 16 eyes (6%) had open-angle glaucoma, and 17 eyes (7%) had retinal findings or lesions that were likely to cause a visual field defect. For FDT perimetry, 22 (8.6%) of 257 tests were unreliable, and for SAP, 65 (25.3%) of 257 tests were unreliable. The sensitivity and specificity of FDT perimetry for detecting an abnormal clinical examination were 55% and 90% and for detecting an abnormal examination that included an abnormal SAP, 64% and 86%. CONCLUSIONS: FDP demonstrated reasonable discriminatory power for detecting eye disease.

Effect of brimonidine on optic nerve blood flow in rabbits.

PURPOSE: Brimonidine is a highly selective alpha2-adrenoreceptor agonist that lowers intraocular pressure. The aim of the present study was to analyze in vivo the vasomotor effects and the influence of brimonidine on blood flow within the optic nerve, by means of intraluminal microvascular corrosion casting technique and intravascular injection of colored microspheres. METHODS: New Zealand white rabbits received either brimonidine tartrate 0.2% or placebo (vehicle) topical drops in one eye for 4 weeks. Intraocular pressures were measured at baseline and 4 weeks. The anterior optic nerve microvasculature of four rabbits was examined with corrosion castings for regions of focal vasoconstriction. Optic nerve blood flow was determined in 16 rabbits by means of nonradioactive colored microspheres. RESULTS: The vasoconstriction values of the short posterior ciliary arterial branches in the brimonidine eyes were 16.7%+/-3.7%. In the fellow untreated eyes, the mean vasoconstriction was 16.6%+/-2.4%. In the placebo-treated eyes, the average constriction was 15.9%+/-3.2%; the fellow eyes showed a mean constriction value of 16.1%+/-5.3%. There was no statistical difference between any of the groups (P = .2). The optic nerve blood flow in the brimonidine-treated rabbits was 0.18+/-0.06 ml/mg/min and 0.17+/-0.04 ml/mg/min in the treated and the fellow eyes, respectively. The difference between the optic nerve blood flow in the brimonidine-treated eyes and the optic nerve blood flow in all of the untreated eyes (0.19+/-0.06 ml/mg/min) also was not statistically different (P = .82). CONCLUSIONS: Long-term application of brimonidine 0.2% does not affect the blood flow or vasomotor activity of the anterior optic nerve.

The influence of ocular pulsatility on scanning laser Doppler flowmetry.

PURPOSE: To determine the effect of the cardiac cycle on scanning laser Doppler flowmeter measurements of retinal capillary blood flow in rhesus monkeys and humans. METHODS: Multiple scanning laser Doppler flowmetry images of rhesus monkey and human retinal capillary blood flow over a range of heart rates were obtained. Average flow values were determined for the 64 scan lines that compose the two-dimensional flow map. Cutaneous blood flow was measured simultaneously with a laser Doppler flowmeter. The temporal relationships between retinal capillary blood flow, peripheral arterial pulse, and cutaneous blood flow were determined. In addition, human retinal capillary blood flow in a 10 x 10-pixel area during different phases of the cardiac cycle was compared. RESULTS: Regular oscillations in human and rhesus monkey retinal capillary blood flow are evident as alternating bright and dark horizontal bands in scanning laser Doppler flowmetry images. These fluctuations are temporally correlated with cutaneous blood flow. Linear regression of actual vs predicted heart rate based on peaks in retinal capillary flow yielded r = 0.999 in a rhesus monkey and 0.938 in a human. Retinal capillary blood flow in a 10 x 10-pixel area fluctuated as much as 50% depending on the phase of the cardiac cycle. CONCLUSIONS: The alternating bright and dark banding pattern observed in scanning laser Doppler flowmetry scans of retinal capillary blood flow is related to the cardiac pulse. The errors introduced by pulse-related fluctuations in retinal capillary blood flow are significant and must be minimized or corrected for accurate and reproducible measurements of ocular hemodynamics.

Frequency doubling technology perimetry using a 24--2 stimulus presentation pattern.

PURPOSE: To assess whether smaller targets and a 24-2 stimulus presentation pattern would improve the ability of frequency doubling technology (FDT) perimetry to detect and characterize early glaucomatous visual field loss. METHODS: One hundred normal subjects between the ages of 20 and 85 participated in this study. In addition, 53 patients who either had early glaucomatous visual field loss (n = 23) or were high-risk glaucoma suspects with normal conventional visual fields (n = 30) were evaluated with the commercial version of FDT perimetry (full threshold test) with 17 stimuli (four 10 degrees diameter square targets per quadrant and a central 5 degrees circular target) and a custom version of FDT perimetry using 54 stimuli (4 degrees targets with 6 degrees grid spacing) arranged in a 24-2 stimulus presentation pattern. RESULTS: The custom FDT test using a 24-2 stimulus presentation pattern had a similar dynamic range, and demonstrated normal aging characteristics and test-retest reliability that were similar to the commercial version of FDT perimetry using 17 larger stimuli. Both FDT tests showed an age-related sensitivity reduction of approximately 0.6 dB per decade, and exhibited an average test-retest reliability of 1 to 1.5 dB. The custom 24-2 FDT perimetry test had a greater variation of sensitivity with eccentricity than the commercial version of FDT perimetry that was probably related to the difference in stimulus size. The custom 24-2 FDT perimetry test had a greater percentage of abnormal test locations than the commercial FDT test for both early glaucomas and high-risk glaucoma suspects. CONCLUSIONS: FDT perimetry can be performed with smaller targets using a presentation pattern that is similar to conventional automated perimetry. In comparison to the commercially available 17 target display, the 24-2 stimulus pattern appears to have modestly higher sensitivity for detection of early glaucomatous loss and provides better characterization of the pattern of visual field loss, but the test takes approximately twice as long.

Medicolegal aspects of glaucoma care.

Malpractice suits related to glaucoma fall into four general categories: failure to make the diagnosis of glaucoma or its progression, complications of glaucoma therapy, iatrogenic (especially steroid) induction of the disease, and treatment intervention beyond the physician's level of skill. The ophthalmologist's knowledge of possible pitfalls and the ability to communicate about risks and reasonable expectations are the basis of a long-term, litigation-free relationship with the glaucoma patient.

The vascular pattern of the optic nerve and its potential relevance in glaucoma.

Evidence that vascular factors contribute to the pathogenesis and development of glaucomatous optic neuropathy continues to accumulate. A higher than expected prevalence of systemic vascular disorders in individuals with glaucoma has been documented. New sophisticated in vivo analysis techniques, such as ultrasound color Doppler imaging, suggest that decreased blood flow velocity and increased vascular resistance are present in the vessels serving the optic nerve of human subjects with glaucoma, implying the presence of either organic or functional vascular disorders in these individuals. Recognizing that different analysis techniques have led to conflicting observations, experimental models have been developed to provide an additional tool with which to interpret the effects of compromised optic nerve perfusion.

Proteoglycan expression by human trabecular meshworks.

PURPOSE: Proteoglycans may serve important roles in trabecular meshwork structure or function. Detailed molecular characterization and identification of specific trabecular proteoglycan core proteins has been limited. METHODS: Radiolabeled proteoglycans were extracted from cultured human trabecular meshworks and subjected to ion exchange and molecular sieve chromatography. Peaks were subjected to glycosaminoglycan content analysis. Reverse transcription with polymerase chain reaction was used to identify trabecular mRNAs of several common proteoglycan core proteins. Western immunoblots of trabecular extracts were also utilized to identify these proteoglycan core proteins. RESULTS: The proteoglycans elute from ion exchange columns at high salt and molecular sieve column profiles, and they exhibit broad peaks typical of the proteoglycan microheterogeneity seen in other tissues. The four common glycosaminoglycan side-chains were identified on these proteoglycans. Trabecular cells in organ or cell culture contain mRNAs coding for decorin, biglycan, versican, perlecan and a basement membrane glycoprotein, SPARC. Syndecan-1 transcripts were present at very low levels, while aggrecan transcripts were not detectable. Decorin, biglycan, versican and perlecan core proteins were also identified by immunoblots of trabecular cell extracts. CONCLUSIONS: Several common proteoglycans are expressed by trabecular cells in organ explant or cell culture. Their general characteristics are not unlike those found in other tissues. These proteoglycans may serve important functions in the trabecular outflow pathway.

Variability of contour line alignment on sequential images with the Heidelberg Retina Tomograph.

BACKGROUND: The influence of the contour line alignment software algorithm on the variability of the Heidelberg Retina Tomograph (HRT) parameters remains unclear. METHODS: Nine discrete topographic images were acquired with the HRT from the right eye in six healthy, emmetropic subjects. The variability of topometric data obtained from the same topographic image, analyzed within different samples of images, was evaluated. A total of four mean topographic images was computed for each subject from: all nine discrete images (A), the first six of those images (B), the last six of those nine images (C), and the first three combined with the last three images (D). A contour line was computed on the mean topographic image generated from the nine discrete topographic images (A). This contour line was then applied to the three other mean topographic images (B, C, and D), using the contour line alignment in the HRT software. Subsequently, the contour line on the mean topographic images was applied to each of the discrete members of the particular images subsets used to compute the mean topographic image, and the topometric data for these discrete topographic images was computed successively for each subset. Prior to processing each subset, the contour line on the discrete topographic images was deleted. This strategy provided a total of three analyses on each discrete topographic image: as a member of the nine images (mean topographic image A), and as a member of two subsets of images (mean topographic image B, C, and/or D). The coefficient of variation (100 x SD/mean) of the topographic parameters within those three analyses was calculated for each discrete topographic image in each subject ("intraimage" coefficient of variation). In addition, a coefficient of variation between the nine discrete topographic images ("interimage" coefficient of variation) was calculated. RESULTS: The "intraimage" and "interimage" variability for the various topographic parameters ranged between 0.03% and 3.10% and between 0.03% and 24.07% respectively. The "intraimage" coefficients of variation and "interimage" coefficients of variation correlated significant (r2 = 0.77; P < 0.0001). CONCLUSION: A high "intraimage" variability, i.e. a high variability in contour line alignment between sequential images, might be an important source of test re-test variability between sequential images.