Diagnostic capabilities of frequency-doubling technology, scanning laser polarimetry, and nerve fiber layer photographs to distinguish glaucomatous damage

Presented in part at the Association for Research in Vision and Ophthalmology 1999 Annual Meeting; Fort Lauderdale, FL.
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Abstract

PURPOSE: To investigate the ability of three diagnostic tests: frequency-doubling technology (FDT), scanning laser polarimetry (GDx), and nerve fiber layer (NFL) photographs to distinguish normal from glaucomatous eyes.

METHODS: Data were obtained in a cross-sectional, hospital clinic-based study, including one eye from each of 253 persons older than 40 years (68 normal, 94 glaucoma suspects and 91 glaucoma patients). We performed a comprehensive ocular examination, as well as static automated perimetry (Humphrey 24-2), screening FDT, GDx, optic nerve stereoscopic photographs and high-contrast NFL photographs.

RESULTS: The following were significantly different for glaucomatous patients compared with suspects and normals: mean values of mean deviation (MD, Humphrey 24-2) and corrected pattern standard deviation (CPSD), 11 GDx indices, mean FDT testing time and missed points, and NFL graded defects (ANOVA, Mantel-Haenszel test; p = 0.0001). Using Humphrey 24-2 test results and clinical assessment as the defining features of glaucoma, we found that the optimal mix of sensitivity and specificity values were 84% and 100% for FDT (presence of any defect); 62% and 96% for GDx (The Number, cut-off value of 27); and, 95% and 82% for NFL photographs (presence of any abnormality). FDT testing took the least time to be administered.

CONCLUSIONS: The FDT had the best diagnostic performance. Neural network analysis of GDx data outperformed other elements of its software.

Section snippets

Patients and methods

All subjects were examined at the Glaucoma Service of the Wilmer Ophthalmological Institute between November, 1997 and June, 1998. The Johns Hopkins University Joint Committee for Clinical Investigation approved the study and informed consent was obtained from all subjects. The study abided by the principles of the Declaration of Helsinki. Among 270 subjects originally recruited, complete data were obtained from 253 persons for this cross-sectional study. The 17 subjects who were excluded had

Recruitment

Subjects were classified as glaucoma patients, glaucoma suspects, or normal subjects. Eyes with best-corrected visual acuity less than 20/40 were not eligible for the study. We defined a glaucoma patient as a person whose optic disc photographs were judged compatible with glaucoma damage in at least one eye by a masked glaucoma specialist (HAQ) and whose 24-2 threshold test had either a Glaucoma Hemifield Test result of “outside normal limits” or a CPSD value whose probability of representing

Frequency-doubling technology

Detailed descriptions of the psychophysical principle and preliminary evaluation of frequency-doubling technology have been published elsewhere.20, 21, 25, 26 All the subjects were tested with presenting distance or bifocal correction in place. Subjects with small frames or tinted lenses were tested without their correction if the refraction was less than ±7 diopters in sphere or less than +3 diopters in cylinder. The FDT procedure was explained with a chart containing pictures of the stimulus;

Scanning laser polarimetry

The GDx/Nerve Fiber Analyzer is a confocal scanning ophthalmoscope with integrated polarimeter (Laser Diagnostic Technologies, Inc., San Diego, CA) incorporating a normative database structure (software version beta 1.11.01).17, 18, 27, 28 The system integrates a near infrared diode scanning laser ophthalmoscope with a polarization modulator, a corneal polarization compensator, and a polarization detection unit. The GDx software transforms the measured amount of light retardation by using

Optic nerve assessment

Stereoscopic color photographs of the optic disc were taken after pupillary dilation with a Zeiss fundus camera (FF4, Carl Zeiss, New York, U.S.A.). These were graded in a random order by an observer (HAQ) masked to any information about the person. The grades were: definite glaucomatous disc, suspicious glaucomatous disc, normal, and unreadable. Additional structural traits, such as the presence of notching, beta zone peripapillary atrophy, and disc hemorrhage, were also recorded. Finally,

Retinal nerve fiber layer grading

Two NFL photographs each were taken of the upper and lower part of the retina just superotemporal to the optic disc with a Zeiss fundus camera (FF4, Carl Zeiss, New York, NY) and green light, on high contrast, black and white film. These were printed on positive 35-mm transparencies and examined on a light box both with and without 5 times magnification.8 The process of taking photographs, processing, and grading took at least two days. The reproducibility and validity of this technique have

Statistical analysis

Data were entered into Excel 97 (Microsoft Corporation, Redmond, WA) and analyzed using SPSS statistical software package (SPSS Inc, Chicago, IL, 1993, release 6.0). Statistical tests included analysis of variance (ANOVA) and linear regression analysis, and age-, gender-, and race-adjustment for comparison of mean values among study groups. In addition, and Chi-square test was used for comparison of proportions, and the Mantel-Haenszel test was used as a test of linear association. A

Results

Glaucoma patients were significantly older and more myopic than glaucoma suspects or normals (Table 2). As expected, suspects had significantly higher mean IOP when compared with normals and glaucoma patients. Also as expected, both suspects and glaucoma patients more frequently had a positive family history of glaucoma, pigment dispersion, and pseudoexfoliation. Compared to normals, these two groups also had significantly more pseudophakic eyes. There were no statistically significant

Discussion

In comparing the screening performance of 3 examinations in the same subjects, we found that the FDT outperformed the other tests in separation of normals and glaucoma patients. One could use either one or more missed FDT locations or longer test time as outcomes. Test duration is shorter when the subject identifies the suprathreshold target on the first presentation, so longer test time is strongly associated with an increased number of missed points. The FDT provided a result on every subject

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    This work was supported in part by PHS Research Grant 01765 (Core Facility Grant, Wilmer Institute).

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