• Glaucoma

    Although clinical examination and fundus photography remain the reference standard for assessing glaucomatous optic disc and retinal nerve fiber layer (RNFL) damage, the development of optical imaging instruments has made possible objective and quantitative measurements of the optic nerve head (ONH) and RNFL. In contrast to clinical examination and fundus photography—which are limited by the need for maximal pupil dilation, clear media, and subjective, qualitative assessments—computer-based imaging instruments provide real-time, quantitative information on the optic disc and RNFL that is immediately available at the time of patient visit. This article aims to explicate the strengths and limitations of 4 of the most commonly used computer-based imaging instruments and to outline how these techniques can complement careful clinical examination and visual field testing.

    Scanning Laser Polarimetry

    Scanning laser polarimetry (SLP) provides objective and quantitative measures of the RNFL by measuring the change in polarization (retardation) that occurs when light illuminates birefringent tissue such as the RNFL. The parallel arrangement of the microtubules in the RNFL produces linear birefringence that changes the state of polarization (retardation) of light passing through it. The amount of retardation is linearly related to the thickness of the RNFL.

    However, the RNFL is not the only birefringent media in the eye; the cornea and to a lesser extent the lens also have polarizing properties that contribute to ocular retardation. The accuracy of SLP RNFL measurements depends on its ability to extract RNFL retardance from total ocular retardance. The latest commercially available version, the GDx with variable corneal compensation (GDx VCC; Carl Zeiss Meditec), has been designed to measure the axis and magnitude of corneal polarization for each eye and to individually compensate for corneal birefringence in order to provide more accurate measurements of the RNFL. The GDx VCC resulted in an improvement in the diagnostic accuracy of SLP compared to earlier versions of this technology that relied on fixed corneal compensation.

    SLP has been successfully applied to glaucoma diagnosis. GDx VCC RNFL thickness measurements are significantly lower in glaucomatous patients compared to healthy subjects. Also, measurements obtained by the GDx VCC correlate well with the appearance of the RNFL as seen on red-free photographs. Moreover, a recent report demonstrated that RNFL analysis with GDx VCC was able to detect abnormalities in patients with confirmed glaucomatous damage to the optic nerve but who exhibited no visual field loss on standard automated perimetry (preperimetric glaucoma) (Am J Ophthalmol. 2005;139(6):1010-1018). This suggests that the GDx VCC may be helpful in early glaucoma diagnosis.

    The diagnostic accuracy of the GDx VCC parameters is affected by disease severity and is adversely affected by the presence of atypical retardation patterns. Scans with atypical retardation patterns show irregular patches of elevated retardation values which do not match the expected retardation based on the RNFL anatomy. These scans are more common in eyes with light, pigmented fundus such as in cases of high myopia. An enhanced corneal compensation (ECC) algorithm has been proposed to correct atypical retardation patterns, but this method is still not commercially available. Ongoing studies suggest that ECC might provide a better cross-sectional representation of visual function than VCC (Fourth Annual Meeting of the International Society for Imaging in the Eye (ISIE); April 28-29, 2006; Fort Lauderdale, Fla).

    Since the process of compensation for anterior segment birefringence depends on scanning the macular area, its effectiveness in patients with macular disease has not been well demonstrated. At this time, there is no validated algorithm for longitudinal detection of glaucomatous progression with the GDx VCC.

    Optical Coherence Tomography

    Optical coherence tomography (OCT) provides real-time and cross-sectional measurements of various layers of the retina, including quantitative and objective assessments of RNFL thickness. OCT employs the principles of low-coherence interferometry and is analogous to ultrasound B-mode imaging but uses light instead of sound to acquire images of ocular structures.

    Several studies have provided evidence that RNFL measurements obtained with OCT are able to differentiate glaucomatous from normal subjects with relatively good sensitivity and specificity. Although OCT has been used for the most part to evaluate RNFL thickness, recent improvements in the software also have made possible the evaluation of ONH topography and macular thickness for glaucoma diagnosis and follow-up. A recent study investigating the performance of the parameters provided by Stratus OCT software (Stratus OCT; Carl Zeiss Meditec) showed that parapapillary RNFL measures and ONH topographic parameters had the highest power to discriminate glaucomatous from healthy eyes (Am J Ophthalmol. 2005;139(1):44-55). Among several OCT parameters, RNFL thickness in the inferior region and the parameter average thickness were often most successful in discriminating between healthy eyes and those with early to moderate glaucoma. Stratus ONH parameters also performed well for glaucoma detection with the parameter cup/disk area ratio demonstrating the best performance in differentiating healthy from glaucoma eyes. Stratus OCT macular thickness measurements had a limited ability to differentiate glaucomatous from healthy eyes in this same study (Am J Ophthalmol. 2005;139(1):44-55).

    Strengths of OCT include its ability to measure peripapillary RNFL thickness without the need for a reference plane or magnification correction. Also, with the Stratus OCT it is possible to obtain images without pupillary dilation. However, OCT provides no objective, immediate feedback regarding image quality, and many patients still need pupillary dilation for the acquisition of good quality images, even with the Stratus OCT. A recent investigation suggested that OCT RNFL thickness measurements were able to detect glaucomatous progression more frequently than visual field examinations (Arch Ophthalmol. 2005;123(4):464-470). However, a statistical package for evaluation of progression is not yet available for the Stratus OCT.

    Confocal Scanning Laser Ophthalmoscopy

    The Heidelberg retina tomograph (HRT II; Heidelberg Engineering) employs confocal scanning diode technology to provide topographical measures of the optic disc and parapapillary retina. In brief, this instrument employs a diode laser (670-nm wavelength) to sequentially scan the retinal surface in the x and y directions at multiple focal planes. Using confocal scanning principles, a three-dimensional topographic image is constructed from a series of optical image sections at consecutive focal planes.

    Despite the large individual differences in optic disc characteristics in healthy eyes, the sensitivity and specificity of HRT parameters for detecting glaucomatous damage are good. Nonetheless, only a few studies have examined the ability of this device to detect change in optic disc topography over time. A recent investigation has shown that HRT disc abnormalities can precede and predict repeatable visual field loss detected by standard automated perimetry (SAP), although the strength of these predictors is not absolute (Invest Ophthalmol Vis Sci. 2004;45(7):2255-2262). Furthermore, it has been shown that several baseline, topographic optic disc measurements alone or combined with baseline clinical and demographic factors were significantly associated with the development of glaucoma among patients with ocular hypertension (Arch Ophthalmol. 2005;123(9):1188-1197). HRT measurements are influenced by fluctuations in intraocular pressure (Graefes Arch Clin Exp Ophthalmol. 2005:1-6), by the subjectively placed contour line, and by the size of the optic disc.

    The new HRT III (software version 3.0) brings a large and ethnically corrected database, an enhanced progression analysis, and enhanced quality control. It also includes the Glaucoma Progression Score (GPS) and a new automated analysis that combines 3D modeling of the entire topographical image with an advanced neural network classification technique (relevance vector machine&emdash;RVM), which is independent of contour line and reference plane.

    Retinal Thickness Analyzer

    The retinal thickness analyzer (RTA version 2; Talia Technology) is based on the principle of slit-lamp biomicroscopy and analyzes the optic disc topography. A laser slit is projected obliquely and scanned in steps across the retina.

    So far, insufficient data have been published on optic disc topography measurements using the RTA. Repeatability and reproducibility of the optic disc topography analysis using the RTA revealed a high variation, and results should, therefore, be interpreted carefully for glaucoma diagnosis and disease monitoring (Graefes Arch Clin Exp Ophthalmol. 2006;244(2):192-198). Moreover, no studies have evaluated the ability of the RTA to detect glaucomatous changes over time. As in the HRT II, some RTA measurements are based on a subjectively placed contour line, which constitutes one of the limitations of this technique.

    Final Considerations

    Assessment of the ONH and RNFL is important for the diagnosis and management of glaucoma. Changes in the appearance of these structures have been shown to frequently precede glaucomatous visual field loss. Until recently, evaluation of the optic disc and RNFL has been subjective, and descriptions of change were primarily qualitative. When utilizing computer-based imaging techniques to measure optic disc topography, examiners should be aware that results are likely to be influenced by the method of measurement that is used, and that each of the instruments may provide different results when tested on the same individual. A recent study indicates that even significantly correlated measurements provided by HRT II, Stratus OCT, and RTA should not be used interchangeably for the assessment of optic disc topography in glaucoma (Ophthalmology. 2005;112(12):2149-2156).

    For example, significant correlations were observed between Stratus OCT and GDx VCC RNFL measurements despite substantial differences in the values of RNFL thickness, and the GDx VCC was found to be as effective as the Stratus OCT in detecting the loss of RNFL in glaucoma (Invest Ophthalmol Vis Sci. 2005;46(9):3214-3220). However, a higher association with visual function in Stratus OCT RNFL measurements compared with that in GDx VCC measurements suggests that OCT might be a better approach for evaluating structure/function relationships (Invest Ophthalmol Vis Sci. 2005;46(10):3702-3711).

    Additionally, the performance of all these technologies in cases of high myopia, high hyperopia, tilted discs, optic disc drusen, other disc anomalies, and parapapillary atrophy has not been well studied.

    References

    1. Medeiros FA, Zangwill LM, Bowd C, Sample PA, Weinreb RN. Use of progressive glaucomatous optic disk change as the reference standard for evaluation of diagnostic tests in glaucoma. Am J Ophthalmol. 2005;139(6):1010-1018.
    2. Tavares IM, Bowd C, Medeiros FA, Zangwill LM, Sample PA, Weinreb RN. Structure-function associations using Scanning Laser Polarimetry (SLP) with Variable Corneal Compensation (VCC) and Enhanced Corneal Compensation (ECC). Paper presented at: Fourth Annual Meeting of the International Society for Imaging in the Eye (ISIE); April 28-29, 2006; Fort Lauderdale, Fla.
    3. Medeiros FA, Zangwill LM, Bowd C, Vessani RM, Susanna R Jr, Weinreb RN. Evaluation of retinal nerve fiber layer, optic nerve head, and macular thickness measurements for glaucoma detection using optical coherence tomography. Am J Ophthalmol. 2005;139(1):44-55.
    4. Wollstein G, Schuman JS, Price LL, et al. Optical coherence tomography longitudinal evaluation of retinal nerve fiber layer thickness in glaucoma. Arch Ophthalmol. 2005;123(4):464-470.
    5. Bowd C, Zangwill LM, Medeiros FA, et al. Confocal scanning laser ophthalmoscopy classifiers and stereophotograph evaluation for prediction of visual field abnormalities in glaucoma-suspect eyes. Invest Ophthalmol Vis Sci. 2004;45(7):2255-2262.
    6. Zangwill LM, Weinreb RN, Beiser JA, et al. Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2005;123(9):1188-1197.
    7. Tavares IM, Melo LA Jr, Prata JA Jr, Galhardo R, Paranhos A Jr, Mello PA. No changes in anatomical and functional glaucoma evaluation after trabeculectomy. Graefes Arch Clin Exp Ophthalmol. 2005:1-6. [Electronic only]
    8. Hoffmann EM, Medeiros FA, Kramann C, Pfeiffer N, Grus FH. Repeatability and reproducibility of optic nerve head topography using the retinal thickness analyzer. Graefes Arch Clin Exp Ophthalmol. 2006;244(2):192-198.
    9. Hoffmann EM, Bowd C, Medeiros FA, et al. Agreement among 3 optical imaging methods for the assessment of optic disc topography. Ophthalmology. 2005;112(12):2149-2156.
    10. Leung CK, Chan WM, Chong KK, et al. Comparative study of retinal nerve fiber layer measurement by StratusOCT and GDx VCC, I: correlation analysis in glaucoma. Invest Ophthalmol Vis Sci. 2005;46(9):3214-3220.
    11. Leung CK, Chong KK, Chan WM, et al. Comparative study of retinal nerve fiber layer measurement by StratusOCT and GDx VCC, II: structure/function regression analysis in glaucoma. Invest Ophthalmol Vis Sci. 2005;46(10):3702-3711.

    Suggested Reading

    1. Zangwill LM, Medeiros FA, Bowd C, Weinreb RN. Optic Nerve Imaging: Recent Advances. In: Grehn F, Stamper R, eds. Glaucoma: Essentials in Ophthalmology. Berlin: Springer; 2004:63-91.
    2. Bowd C, Zangwill LM, Blumenthal EZ, et al. Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender. J Opt Soc Am A Opt Image Sci Vis. 2002;19(1):197-207.
    3. Medeiros FA, Zangwill LM, Bowd C, Weinreb RN. Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and stratus OCT optical coherence tomograph for the detection of glaucoma. Arch Ophthalmol. 2004;122(6):827-837.
    4. Toth M, Hollo G. Evaluation of enhanced corneal compensation in scanning laser polarimetry: comparison with variable corneal compensation on human eyes undergoing LASIK. J Glaucoma. 2006;15(1):53-9.

    Author Disclosure

    The authors state that they have no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.