Table 1. The sensitivity to identify early glaucoma, defined by visual field loss, of three imaging devices

Note: GDxVCC, GDx nerve fiber analyzer with variable corneal compensator; HRT II, Heidelberg retina tomograph II; Stratus OCT, Stratus optical coherence tomograph.

Table 2. The sensitivity to identify early glaucoma, defined by structural damage to the optic nerve head, of four vision function tests

Note: SAP, standard automated perimetry; SWAP, short-wave- length automated perimetry; HPRP, high-pass resolution perimetry.

glaucoma, but either one may be abnormal and the other normal. In the clinical environment, this leads to diagnostic uncertainty. Of course, these tests are never interpreted in isolation, and when considered in the context of the history and clinical examination, an otherwise borderline result in a quantitative test may be more useful. However, the results illustrate the difficulty in making a diagnosis early in the disease course.

Progression to make a diagnosis

Glaucoma is a chronic progressive neuropathy. In many eyes with early glaucoma, the diagnosis is uncertain when the patient is first seen. Given the progressive nature of glaucoma, careful follow-up to identify changes in the ONH, RNFL, or visual function will enable a diagnosis to be made. The degree of probability that glaucoma is present before a clinician offers a diagnosis to the patient will vary between clinicians. As the risk of symptomatic vision loss when a patient presents with very early disease is low, the impact of a false diagnosis on a patient is potentially great, and the

55

diagnosis can be made with greater certainty if change (progression) is identified, it may be wise to require a high probability for glaucoma before making the diagnosis. Those with a lower probability (uncertain cases) can be followed for signs of progression. At the same time, it should be remembered that making the diagnosis and making a treatment decision, although linked, are not the same thing. A clinician may decide to treat a patient even when the diagnosis is uncertain if there are significant risk factors for future vision loss, such as a high IOP.

Conclusions

Signs in early glaucoma are frequently equivocal, and either structural damage or vision function loss may be the first sign of glaucoma. Quantitative tests, such as SAP and imaging devices, are useful adjuncts to the clinical evaluation. The results of the tests raise or lower the probability that glaucoma is present, and the results of the tests may be combined mathematically to establish probability levels. The validity of test results from quantitative devices (including data quality and sources of error) should always be considered before the results are used for patient management.

Acknowledgments

The corresponding author has received a proportion of his funding from the Department of

56

Health’s National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital and the UCL Institute of Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.

References

Anderson, R.S. and O’brien, C. (1997) Psychophysical evidence for a selective loss of M ganglion cells in glaucoma. Vision Res., 37(8): 1079–1083.

Ansari, E.A., Morgan, J.E. and Snowden, R.J. (2002) Psychophysical characterisation of early functional loss in glaucoma and ocular hypertension. Br. J. Ophthalmol., 86(10): 1131–1135.

Boland, M.V. and Quigley, H.A. (2007) Risk factors and openangle glaucoma: classification and application. J. Glaucoma, 16(4): 406–418.

Bonomi, L., Marchini, G., Marraffa, M. and Morbio, R. (2001) The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna–Neumarkt Glaucoma Study. Ophthalmologica, 215(1): 34–38.

Centre for Evidence-Based Medicine. Fagan nomogram. http:// www.cebm.net/index.aspx?o ¼ 1043. Accessed 5th April, 2008.

Chen, P.P. (2003) Blindness in patients with treated open-angle glaucoma. Ophthalmology, 110(4): 726–733.

Deleon-Ortega, J.E., Arthur, S.N., Mcgwin, G., Jr., Xie, A., Monheit, B.E. and Girkin, C.A. (2006) Discrimination between glaucomatous and nonglaucomatous eyes using quantitative imaging devices and subjective optic nerve head assessment. Invest. Ophthalmol. Vis. Sci., 47(8): 3374–3380.

Fagan, T.J. (1975) Letter: nomogram for Bayes theorem. N. Engl. J. Med., 293(5): p. 257.

Forsman, E., Kivela, T. and Vesti, E. (2007) Lifetime visual disability in open-angle glaucoma and ocular hypertension. J. Glaucoma, 16(3): 313–319.

Garway-Heath, D.F., Caprioli, J., Fitzke, F.W. and Hitchings, R.A. (2000) Scaling the hill of vision: the physiological relationship between ganglion cell numbers and light sensitivity. Invest. Ophthalmol. Vis. Sci., 41(7): 1774–1782.

Garway-Heath, D.F. and Friedman, D.S. (2006) How should results from clinical tests be integrated into the diagnostic process?. Ophthalmology, 113(9): 1479–1480.

Garway-Heath, D.F. and Hitchings, R.A. (1998a) Quantitative evaluation of the optic nerve head in early glaucoma. Br. J. Ophthalmol., 82(4): 352–361.

Garway-Heath, D.F. and Hitchings, R.A. (1998b) Sources of bias in studies of optic disc and retinal nerve fibre layer morphology. Br. J. Ophthalmol., 82(9): p. 986.

Garway-Heath, D.F., Holder, G.E., Fitzke, F.W. and Hitchings, R.A. (2002) Relationship between electrophysiological, psychophysical, and anatomical measurements in glaucoma. Invest. Ophthalmol. Vis. Sci., 43(7): 2213–2220.

Halkin, A., Reichman, J., Schwaber, M., Paltiel, O. and Brezis, M. (1998) Likelihood ratios: getting diagnostic testing into perspective. Q.J. Med., 91(4): 247–258.

Harwerth, R.S., Carter-Dawson, L., Shen, F., Smith, E.L., 3rd and Crawford, ML. (1999) Ganglion cell losses underlying visual field defects from experimental glaucoma. Invest. Ophthalmol. Vis. Sci., 40(10): 2242–2250.

Harwerth, R.S., Carter-Dawson, L., Smith, E.L., 3rd., Barnes, G., Holt, W.F. and Crawford, M.L. (2004) Neural losses correlated with visual losses in clinical perimetry. Invest. Ophthalmol. Vis. Sci., 45(9): 3152–3160.

Harwerth, R.S. and Quigley, H.A. (2006) Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch. Ophthalmol., 124(6): 853–859.

Jaeschke, R., Guyatt, G.H. and Lijmer, J. (2001) Diagnostic tests. In: Guyatt G.H. and Rennie D. (Eds.), Users’ Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice. American Medical Association, Chicago.

Kerrigan-Baumrind, L.A., Quigley, H.A., Pease, M.E., Kerrigan, D.F. and Mitchell, R.S. (2000) Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest. Ophthalmol. Vis. Sci., 41(3): 741–748.

Medeiros, F.A. (2007) How should diagnostic tests be evaluated in glaucoma? Br. J. Ophthalmol., 91(3): 273–274.

Medeiros, F.A., Zangwill, L.M., Bowd, C. and Weinreb, R.N. (2004) 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., 122(6): 827–837.

Mitchell, P., Smith, W., Attebo, K. and Healey, P.R. (1996) Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology, 103(10): 1661–1669.

Mohammadi, K., Bowd, C., Weinreb, R.N., Medeiros, F.A., Sample, P.A. and Zangwill, L.M. (2004) Retinal nerve fiber layer thickness measurements with scanning laser polarimetry predict glaucomatous visual field loss. Am. J. Ophthalmol., 138(4): 592–601.

Morgan, J.E. (2002) Retinal ganglion cell shrinkage in glaucoma. J. Glaucoma, 11(4): 365–370.

Quigley, H.A., Dunkelberger, G.R. and Green, W.R. (1988) Chronic human glaucoma causing selectively greater loss of large optic nerve fibers. Ophthalmology, 95(3): 357–363.

Quigley, H.A., Sanchez, R.M., Dunkelberger, G.R., Nl, L.H. and Baginski, T.A. (1987) Chronic glaucoma selectively damages large optic nerve fibers. Invest. Ophthalmol. Vis. Sci., 28(6): 913–920.

Reus, N.J., De Graaf, M. and Lemij, H.G. (2007) Accuracy of GDx VCC, HRT I, and clinical assessment of stereoscopic optic nerve head photographs for diagnosing glaucoma. Br. J. Ophthalmol., 91(3): 313–318.

Sample, P.A., Medeiros, F.A., Racette, L., Pascual, J.P., Boden, C., Zangwill, L.M., Bowd, C. and Weinreb, R.N. (2006) Identifying glaucomatous vision loss with visual- function-specific perimetry in the diagnostic innovations in glaucoma study. Invest. Ophthalmol. Vis. Sci., 47(8): 3381–3389.

Sommer, A., Katz, J., Quigley, H.A., Miller, N.R., Robin, A.L., Richter, R.C. and Witt, K.A. (1991a) Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch. Ophthalmol., 109(1): 77–83.

Sommer, A., Tielsch, J.M., Katz, J., Quigley, H.A., Gottsch, J.D., Javitt, J. and Singh, K. (1991b) Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch. Ophthalmol., 109(8): 1090–1095.

Stroux, A., Korth, M., Junemann, A., Jonas, J.B., Horn, F., Ziegler, A. and Martus, P. (2003) A statistical model for the evaluation of sensory tests in glaucoma, depending on optic disc damage. Invest. Ophthalmol. Vis. Sci., 44(7): 2879–2884.

57

Swanson, W.H., Felius, J. and Pan, F. (2004) Perimetric defects and ganglion cell damage: interpreting linear relations using a two-stage neural model. Invest. Ophthalmol. Vis. Sci., 45(2): 466–472.

Wollstein, G., Garway-Heath, D.F., Fontana, L. and Hitchings, R.A. (2000) Identifying early glaucomatous changes: comparison between expert clinical assessment of optic disc photographs and confocal scanning ophthalmoscopy. Ophthalmology, 107(12): 2272–2277.

Yucel, Y.H., Zhang, Q., Weinreb, R.N., Kaufman, P.L. and Gupta, N. (2003) Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog. Retin. Eye Res., 22(4): 465–481.