The relationship between nerve fiber layer and perimetry measurements.

PURPOSE Losses of retinal ganglion cells (RGCs) in glaucoma are the cause of visual field defects and thinning of the retinal nerve fiber layer (RNFL), but methods of correlating these events have not been developed. The present study was conducted to investigate the relationship between standard automated perimetry (SAP) measures of RGCs and optical coherence tomography (OCT) measures of the ganglion cell axons entering the optic nerve from corresponding visual field locations. METHODS SAP and OCT data from normal monkeys were used to develop methods for estimating neuron counts and mapping SAP visual field locations onto the optic nerve head (ONH). The procedures developed for normal eyes were applied to monkeys with experimental glaucoma. RESULTS The number of neurons derived from SAP and OCT data for normal eyes were in close agreement. The estimates of the number of RGCs in retinal areas of the Humphrey Field Analyzer 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA) visual field and the axons entering the ONH were both approximately 1.5 million. The neural losses derived from subjective and objective measurements in monkeys with early experimental glaucoma correlated highly, with a mean +/- SD difference of 0.6% +/- 22% between the two estimates in control eyes and 3% +/- 24% in laser-treated eyes. CONCLUSIONS SAP measures of visual field defects and OCT measures of RNFL defects are correlated measures of glaucomatous neuropathy. The normal intersubject variability and the dynamic ranges of the measurements suggest that RNFL thickness may be a more sensitive measurement for early stages and perimetry a better measure for moderate to advanced stages of glaucoma.

[1]  J E Morgan,et al.  Histological measurement of retinal nerve fibre layer thickness , 2005, Eye.

[2]  D. Greenfield,et al.  Optic nerve and retinal nerve fiber layer analyzers in glaucoma , 2002, Current opinion in ophthalmology.

[3]  T. Ogden.  Nerve fiber layer of the primate retina: morphometric analysis. , 1984, Investigative ophthalmology & visual science.

[4]  Douglas R. Anderson.  Perimetry with and without automation , 1987 .

[5]  M. Araie,et al.  Morphometric evaluation of changes with time in optic disc structure and thickness of retinal nerve fibre layer in chronic ocular hypertensive monkeys. , 2004, Experimental eye research.

[6]  Christopher Bowd,et al.  Retinal nerve fiber layer analysis in the diagnosis of glaucoma. , 2006, Current opinion in ophthalmology.

[7]  R. Knighton,et al.  Reproducibility of retinal nerve fiber thickness measurements using the stratus OCT in normal and glaucomatous eyes. , 2005, Investigative ophthalmology & visual science.

[8]  Chris A Johnson,et al.  Evaluation of the structure-function relationship in glaucoma. , 2005, Investigative ophthalmology & visual science.

[9]  Chris A Johnson,et al.  Identification of progressive glaucomatous visual field loss. , 2002, Survey of ophthalmology.

[10]  Earl L. Smith,et al.  Scaling the structure--function relationship for clinical perimetry. , 2005, Acta ophthalmologica Scandinavica.

[11]  James G. Fujimoto,et al.  Optical Coherence Tomography of Ocular Diseases , 1995 .

[12]  P A Sample,et al.  Visual function-specific perimetry for indirect comparison of different ganglion cell populations in glaucoma. , 2000, Investigative ophthalmology & visual science.

[13]  B R Younge,et al.  Glaucoma visual field analysis by computed profile of nerve fiber function in optic disc sectors. , 1982, Ophthalmology.

[14]  Mei-Ling Huang,et al.  Discrimination between normal and glaucomatous eyes using Stratus optical coherence tomography in Taiwan Chinese subjects , 2005, Graefe's Archive for Clinical and Experimental Ophthalmology.

[15]  Earl L. Smith,et al.  Experimental Glaucoma: Perimetric Field Defects and Intraocular Pressure , 1997, Journal of glaucoma.

[16]  A Heijl,et al.  Visual field progression in glaucoma , 1998, The British journal of ophthalmology.

[17]  G. Dunkelberger,et al.  Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. , 1989, American journal of ophthalmology.

[18]  Lene Martin,et al.  Concordance of High-Pass Resolution Perimetry and Frequency-Doubling Technology Perimetry Results in Glaucoma: No Support for Selective Ganglion Cell Damage , 2003, Journal of glaucoma.

[19]  G. Wollstein,et al.  Optical coherence tomography longitudinal evaluation of retinal nerve fiber layer thickness in glaucoma. , 2005, Archives of ophthalmology.

[20]  R. Harwerth,et al.  Visual field defects and retinal ganglion cell losses in patients with glaucoma. , 2006, Archives of ophthalmology.

[21]  J. Fujimoto,et al.  Optical coherence tomography of the human retina. , 1995, Archives of ophthalmology.

[22]  F. Medeiros,et al.  Influence of disease severity and optic disc size on the diagnostic performance of imaging instruments in glaucoma. , 2006, Investigative ophthalmology & visual science.

[23]  J. Jonas,et al.  Retinal nerve fiber layer thickness in human eyes , 1999, Graefe's Archive for Clinical and Experimental Ophthalmology.

[24]  W. M. Grant,et al.  Chandler and Grant's Glaucoma , 1986 .

[25]  Grant Cull,et al.  Varicosities of intraretinal ganglion cell axons in human and nonhuman primates. , 2003, Investigative ophthalmology & visual science.

[26]  G. Savini,et al.  Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study , 2005, British Journal of Ophthalmology.

[27]  B. Alamouti,et al.  Retinal thickness decreases with age: an OCT study , 2003, The British journal of ophthalmology.

[28]  C. Johnson.  Selective versus nonselective losses in glaucoma. , 1994, Journal of glaucoma.

[29]  H. Quigley,et al.  Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. , 2000, Investigative ophthalmology & visual science.

[30]  Ronald S. Harwerth,et al.  Visual field defects and neural losses from experimental glaucoma , 2002, Progress in Retinal and Eye Research.

[31]  J. Weber,et al.  A perimetric nerve fiber bundle map , 1991, International Ophthalmology.

[32]  Lin Wang,et al.  Immunohistologic evidence for retinal glial cell changes in human glaucoma. , 2002, Investigative ophthalmology & visual science.

[33]  D. Gaasterland,et al.  Experimental glaucoma in the rhesus monkey. , 1974, Investigative ophthalmology.

[34]  Paul H Artes,et al.  Visual field progression in glaucoma: total versus pattern deviation analyses. , 2005, Investigative ophthalmology & visual science.

[35]  Georg Lindgren,et al.  A package for the statistical analysis of visual fields , 1987 .

[36]  A Heijl,et al.  Glaucoma Hemifield Test. Automated visual field evaluation. , 1992, Archives of ophthalmology.

[37]  R Varma,et al.  Retinal nerve fibre layer thickness profile in normal eyes using third-generation optical coherence tomography , 2006, Eye.

[38]  D. Gaasterland,et al.  Laser-induced primate glaucoma. I. Progression of cupping. , 1984, Archives of ophthalmology.

[39]  Earl L. Smith,et al.  Neural losses correlated with visual losses in clinical perimetry. , 2004, Investigative ophthalmology & visual science.

[40]  Lin Wang,et al.  Estimating normal optic nerve axon numbers in non-human primate eyes. , 2002, Journal of glaucoma.

[41]  Makoto Nakamura,et al.  Evaluation of the Effect of Aging on Retinal Nerve Fiber Layer Thickness Measured by Optical Coherence Tomography , 2003, Ophthalmologica.

[42]  R. T. Hart,et al.  Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve head connective tissues. , 2004, Investigative ophthalmology & visual science.

[43]  B. Lindblom,et al.  Frequency doubling technology and high-pass resolution perimetry in glaucoma and ocular hypertension. , 2003, Acta ophthalmologica Scandinavica.

[44]  C Kupfer,et al.  Quantitative histology of optic nerve, optic tract and lateral geniculate nucleus of man. , 1967, Journal of anatomy.

[45]  Parul Sony,et al.  Diagnostic capability of optical coherence tomography in evaluating the degree of glaucomatous retinal nerve fiber damage. , 2006, Investigative ophthalmology & visual science.

[46]  C. B. Shelman,et al.  Morphology of the primate optic nerve. I. Method and total fiber count. , 1972, Investigative ophthalmology.

[47]  J. Katz,et al.  Sensitivity and specificity of the StratusOCT for perimetric glaucoma. , 2005, Ophthalmology.

[48]  R S Harwerth,et al.  Ganglion cell losses underlying visual field defects from experimental glaucoma. , 1999, Investigative ophthalmology & visual science.

[49]  R. Snowden,et al.  Glaucoma: squaring the psychophysics and neurobiology , 2002, The British journal of ophthalmology.

[50]  H. Quigley,et al.  Laser energy levels for trabecular meshwork damage in the primate eye. , 1983, Investigative ophthalmology & visual science.

[51]  L. Zangwill,et al.  Detecting early glaucoma by assessment of retinal nerve fiber layer thickness and visual function. , 2001, Investigative ophthalmology & visual science.

[52]  G. Dunkelberger,et al.  Aging changes of the rhesus monkey optic nerve. , 1990, Investigative ophthalmology & visual science.

[53]  Robert N Weinreb,et al.  Retinal nerve fiber layer thickness measurements with scanning laser polarimetry predict glaucomatous visual field loss. , 2004, American journal of ophthalmology.

[54]  E. Smith,et al.  Mechanisms mediating visual detection in static perimetry. , 1993, Investigative ophthalmology & visual science.

[55]  R. Nickells,et al.  Retinal Ganglion Cell Death in Glaucoma: The How, the Why, and the Maybe , 1996, Journal of glaucoma.

[56]  Thomas E. Ogden,et al.  Nerve fiber layer of the primate retina: Thickness and glial content , 1983, Vision Research.

[57]  Rajvir Singh,et al.  Comparing glaucomatous optic neuropathy in primary open angle and chronic primary angle closure glaucoma eyes by optical coherence tomography , 2005, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[58]  E. Smith,et al.  Progressive visual field defects from experimental glaucoma: measurements with white and colored stimuli. , 1999, Optometry and vision science : official publication of the American Academy of Optometry.

[59]  E. Smith,et al.  Behavioral perimetry in monkeys. , 1993, Investigative ophthalmology & visual science.

[60]  W. Hare,et al.  Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, I: Functional measures. , 2004, Investigative ophthalmology & visual science.

[61]  H A Quigley,et al.  The effect of age on normal human optic nerve fiber number and diameter. , 1989, Ophthalmology.

[62]  M Schulzer,et al.  The normal human optic nerve. Axon count and axon diameter distribution. , 1989, Ophthalmology.

[63]  H. A. Quigley,et al.  Open-angle glaucoma. , 1993, The New England journal of medicine.

[64]  D. Garway-Heath,et al.  Mapping the visual field to the optic disc in normal tension glaucoma eyes. , 2000, Ophthalmology.

[65]  L. Zangwill,et al.  The retinal nerve fiber layer thickness in ocular hypertensive, normal, and glaucomatous eyes with optical coherence tomography. , 2000, Archives of ophthalmology.

[66]  L. Zangwill,et al.  Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures. , 2004, Investigative ophthalmology & visual science.

[67]  Chris A Johnson,et al.  Psychophysical Investigation of Ganglion Cell Loss in Early Glaucoma , 2005, Journal of glaucoma.

[68]  H. Quigley,et al.  Neuronal death in glaucoma , 1999, Progress in Retinal and Eye Research.

[69]  G. Dunkelberger,et al.  The number and diameter distribution of axons in the monkey optic nerve. , 1986, Investigative ophthalmology & visual science.

[70]  A. Sommer,et al.  Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. , 1991, Archives of ophthalmology.

[71]  R. Stout,et al.  Laser Doppler Flowmetry Study of Systemic Vasoconstriction after Topical 2.5% Phenylephrine Eye Drops , 2004 .

[72]  W. Feuer,et al.  Detection of psychophysical and structural injury in eyes with glaucomatous optic neuropathy and normal standard automated perimetry. , 2006, Archives of ophthalmology.

[73]  R. Weinreb,et al.  Motion automated perimetry identifies early glaucomatous field defects. , 1998, Archives of ophthalmology.

[74]  C. Johnson,et al.  Standardizing the measurement of visual fields for clinical research: Guidelines from the Eye Care Technology Forum. , 1996, Ophthalmology.

[75]  S. Shirato,et al.  Study of retinal nerve fiber layer thickness within normal hemivisual field in primary open-angle glaucoma and normal-tension glaucoma. , 2003, Japanese journal of ophthalmology.

[76]  Parul Sony,et al.  Quantification of the retinal nerve fibre layer thickness in normal Indian eyes with optical coherence tomography. , 2004, Indian journal of ophthalmology.