Skip to main content
Top
Published in: BMC Ophthalmology 1/2011

Open Access 01-12-2011 | Research article

Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis

Authors: Michael V Boland, Harry A Quigley

Published in: BMC Ophthalmology | Issue 1/2011

Login to get access

Abstract

Background

The definitive diagnosis of glaucoma is currently based on congruent damage to both optic nerve structure and function. Given widespread quantitative assessment of both structure (imaging) and function (automated perimetry) in glaucoma, it should be possible to combine these quantitative data to diagnose disease. We have therefore defined and tested a new approach to glaucoma diagnosis by combining imaging and visual field data, using the anatomical organization of retinal ganglion cells.

Methods

Data from 1499 eyes of glaucoma suspects and 895 eyes with glaucoma were identified at a single glaucoma center. Each underwent Heidelberg Retinal Tomograph (HRT) imaging and standard automated perimetry. A new measure combining these two tests, the structure function index (SFI), was defined in 3 steps: 1) calculate the probability that each visual field point is abnormal, 2) calculate the probability of abnormality for each of the six HRT optic disc sectors, and 3) combine those probabilities with the probability that a field point and disc sector are linked by ganglion cell anatomy. The SFI was compared to the HRT and visual field using receiver operating characteristic (ROC) analysis.

Results

The SFI produced an area under the ROC curve (0.78) that was similar to that for both visual field mean deviation (0.78) and pattern standard deviation (0.80) and larger than that for a normalized measure of HRT rim area (0.66). The cases classified as glaucoma by the various tests were significantly non-overlapping. Based on the distribution of test values in the population with mild disease, the SFI may be better able to stratify this group while still clearly identifying those with severe disease.

Conclusions

The SFI reflects the traditional clinical diagnosis of glaucoma by combining optic nerve structure and function. In doing so, it identifies a different subset of patients than either visual field testing or optic nerve head imaging alone. Analysis of prospective data will allow us to determine whether the combined index of structure and function can provide an improved standard for glaucoma diagnosis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Shutt HK, Boyd TA, Salter AB: The relationship of visual fields, optic disc appearances and age in non-glaucomatous and glaucomatous eyes. Can J Ophthalmol. 1967, 2 (2): 83-90.PubMed Shutt HK, Boyd TA, Salter AB: The relationship of visual fields, optic disc appearances and age in non-glaucomatous and glaucomatous eyes. Can J Ophthalmol. 1967, 2 (2): 83-90.PubMed
2.
go back to reference Armaly MF: The correlation between appearance of the optic cup and visual function. Trans Am Acad Ophthalmol Otolaryngol. 1969, 73 (5): 898-913.PubMed Armaly MF: The correlation between appearance of the optic cup and visual function. Trans Am Acad Ophthalmol Otolaryngol. 1969, 73 (5): 898-913.PubMed
3.
go back to reference Douglas GR, Drance SM, Schulzer M: A correlation of fields and discs in open angle glaucoma. Can J Ophthalmol. 1974, 9 (4): 391-398.PubMed Douglas GR, Drance SM, Schulzer M: A correlation of fields and discs in open angle glaucoma. Can J Ophthalmol. 1974, 9 (4): 391-398.PubMed
4.
go back to reference Drance SM: Editorial: The optic disc and visual field in glaucoma. Can J Ophthalmol. 1974, 9 (4): 389-390.PubMed Drance SM: Editorial: The optic disc and visual field in glaucoma. Can J Ophthalmol. 1974, 9 (4): 389-390.PubMed
5.
go back to reference Burgoyne CF, Quigley HA, Thompson HW, Vitale S, Varma R: Early changes in optic disc compliance and surface position in experimental glaucoma. Ophthalmology. 1995, 102 (12): 1800-1809.CrossRefPubMed Burgoyne CF, Quigley HA, Thompson HW, Vitale S, Varma R: Early changes in optic disc compliance and surface position in experimental glaucoma. Ophthalmology. 1995, 102 (12): 1800-1809.CrossRefPubMed
6.
go back to reference Anonymous: The Advanced Glaucoma Intervention Study (AGIS): 1. Study design and methods and baseline characteristics of study patients. Control Clin Trials. 1994, 15 (4): 299-325. 10.1016/0197-2456(94)90046-9.CrossRef Anonymous: The Advanced Glaucoma Intervention Study (AGIS): 1. Study design and methods and baseline characteristics of study patients. Control Clin Trials. 1994, 15 (4): 299-325. 10.1016/0197-2456(94)90046-9.CrossRef
7.
go back to reference Leske MC, Heijl A, Hyman L, Bengtsson B: Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999, 106 (11): 2144-2153. 10.1016/S0161-6420(99)90497-9.CrossRefPubMed Leske MC, Heijl A, Hyman L, Bengtsson B: Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology. 1999, 106 (11): 2144-2153. 10.1016/S0161-6420(99)90497-9.CrossRefPubMed
8.
go back to reference Musch DC, Lichter PR, Guire KE, Standardi CL: The Collaborative Initial Glaucoma Treatment Study: study design, methods, and baseline characteristics of enrolled patients. Ophthalmology. 1999, 106 (4): 653-662. 10.1016/S0161-6420(99)90147-1.CrossRefPubMed Musch DC, Lichter PR, Guire KE, Standardi CL: The Collaborative Initial Glaucoma Treatment Study: study design, methods, and baseline characteristics of enrolled patients. Ophthalmology. 1999, 106 (4): 653-662. 10.1016/S0161-6420(99)90147-1.CrossRefPubMed
9.
go back to reference Gordon MO, Kass MA: The Ocular Hypertension Treatment Study: design and baseline description of the participants. Arch Ophthalmol. 1999, 117 (5): 573-583.CrossRefPubMed Gordon MO, Kass MA: The Ocular Hypertension Treatment Study: design and baseline description of the participants. Arch Ophthalmol. 1999, 117 (5): 573-583.CrossRefPubMed
10.
go back to reference Foster PJ, Buhrmann R, Quigley HA, Johnson GJ: The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002, 86 (2): 238-242. 10.1136/bjo.86.2.238.CrossRefPubMedPubMedCentral Foster PJ, Buhrmann R, Quigley HA, Johnson GJ: The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002, 86 (2): 238-242. 10.1136/bjo.86.2.238.CrossRefPubMedPubMedCentral
11.
go back to reference Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, Wilson MR, Gordon MO: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002, 120 (6): 701-13. discussion 829-30CrossRefPubMed Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, Wilson MR, Gordon MO: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002, 120 (6): 701-13. discussion 829-30CrossRefPubMed
12.
go back to reference Weber J, Ulrich H: A perimetric nerve fiber bundle map. Int Ophthalmol. 1991, 15 (3): 193-200. 10.1007/BF00153928.CrossRefPubMed Weber J, Ulrich H: A perimetric nerve fiber bundle map. Int Ophthalmol. 1991, 15 (3): 193-200. 10.1007/BF00153928.CrossRefPubMed
13.
go back to reference Yamagishi N, Anton A, Sample PA, Zangwill L, Lopez A, Weinreb RN: Mapping structural damage of the optic disk to visual field defect in glaucoma. Am J Ophthalmol. 1997, 123 (5): 667-676.CrossRefPubMed Yamagishi N, Anton A, Sample PA, Zangwill L, Lopez A, Weinreb RN: Mapping structural damage of the optic disk to visual field defect in glaucoma. Am J Ophthalmol. 1997, 123 (5): 667-676.CrossRefPubMed
14.
go back to reference Schlottmann PG, De Cilla S, Greenfield DS, Caprioli J, Garway-Heath DF: Relationship between visual field sensitivity and retinal nerve fiber layer thickness as measured by scanning laser polarimetry. Invest Ophthalmol Vis Sci. 2004, 45 (6): 1823-1829. 10.1167/iovs.03-0692.CrossRefPubMed Schlottmann PG, De Cilla S, Greenfield DS, Caprioli J, Garway-Heath DF: Relationship between visual field sensitivity and retinal nerve fiber layer thickness as measured by scanning laser polarimetry. Invest Ophthalmol Vis Sci. 2004, 45 (6): 1823-1829. 10.1167/iovs.03-0692.CrossRefPubMed
15.
go back to reference Gardiner SK, Johnson CA, Cioffi GA: Evaluation of the structure-function relationship in glaucoma. Invest Ophthalmol Vis Sci. 2005, 46 (10): 3712-3717. 10.1167/iovs.05-0266.CrossRefPubMed Gardiner SK, Johnson CA, Cioffi GA: Evaluation of the structure-function relationship in glaucoma. Invest Ophthalmol Vis Sci. 2005, 46 (10): 3712-3717. 10.1167/iovs.05-0266.CrossRefPubMed
16.
go back to reference Ferreras A, Pablo LE, Garway-Heath DF, Fogagnolo P, Garcia-Feijoo J: Mapping standard automated perimetry to the peripapillary retinal nerve fiber layer in glaucoma. Invest Ophthalmol Vis Sci. 2008, 49 (7): 3018-3025. 10.1167/iovs.08-1775.CrossRefPubMed Ferreras A, Pablo LE, Garway-Heath DF, Fogagnolo P, Garcia-Feijoo J: Mapping standard automated perimetry to the peripapillary retinal nerve fiber layer in glaucoma. Invest Ophthalmol Vis Sci. 2008, 49 (7): 3018-3025. 10.1167/iovs.08-1775.CrossRefPubMed
17.
go back to reference Sommer A, Katz J, Quigley HA, Miller NR, Robin AL, Richter RC, Witt KA: Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol. 1991, 109 (1): 77-83.CrossRefPubMed Sommer A, Katz J, Quigley HA, Miller NR, Robin AL, Richter RC, Witt KA: Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. Arch Ophthalmol. 1991, 109 (1): 77-83.CrossRefPubMed
18.
go back to reference Harwerth RS, Quigley HA: Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch Ophthalmol. 2006, 124 (6): 853-859. 10.1001/archopht.124.6.853.CrossRefPubMedPubMedCentral Harwerth RS, Quigley HA: Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch Ophthalmol. 2006, 124 (6): 853-859. 10.1001/archopht.124.6.853.CrossRefPubMedPubMedCentral
19.
go back to reference Mills RP, Budenz DL, Lee PP, Noecker RJ, Walt JG, Siegartel LR, Evans SJ, Doyle JJ: Categorizing the stage of glaucoma from pre-diagnosis to end-stage disease. Am J Ophthalmol. 2006, 141 (1): 24-30. 10.1016/j.ajo.2005.07.044.CrossRefPubMed Mills RP, Budenz DL, Lee PP, Noecker RJ, Walt JG, Siegartel LR, Evans SJ, Doyle JJ: Categorizing the stage of glaucoma from pre-diagnosis to end-stage disease. Am J Ophthalmol. 2006, 141 (1): 24-30. 10.1016/j.ajo.2005.07.044.CrossRefPubMed
20.
go back to reference Asman P, Heijl A: Glaucoma Hemifield Test. Automated visual field evaluation. Arch Ophthalmol. 1992, 110 (6): 812-819.CrossRefPubMed Asman P, Heijl A: Glaucoma Hemifield Test. Automated visual field evaluation. Arch Ophthalmol. 1992, 110 (6): 812-819.CrossRefPubMed
21.
go back to reference Mills RP, Heijl A, (Eds): Proceedings of the Perimetry Update 1990/1991. 1991, New York, NY: Kugler & Ghedini Mills RP, Heijl A, (Eds): Proceedings of the Perimetry Update 1990/1991. 1991, New York, NY: Kugler & Ghedini
22.
go back to reference Wollstein G, Garway-Heath DF, Hitchings RA: Identification of early glaucoma cases with the scanning laser ophthalmoscope. Ophthalmology. 1998, 105 (8): 1557-1563. 10.1016/S0161-6420(98)98047-2.CrossRefPubMed Wollstein G, Garway-Heath DF, Hitchings RA: Identification of early glaucoma cases with the scanning laser ophthalmoscope. Ophthalmology. 1998, 105 (8): 1557-1563. 10.1016/S0161-6420(98)98047-2.CrossRefPubMed
23.
go back to reference Burgansky-Eliash Z, Wollstein G, Bilonick RA, Ishikawa H, Kagemann L, Schuman JS: Glaucoma detection with the Heidelberg retina tomograph 3. Ophthalmology. 2007, 114 (3): 466-471. 10.1016/j.ophtha.2006.08.022.CrossRefPubMed Burgansky-Eliash Z, Wollstein G, Bilonick RA, Ishikawa H, Kagemann L, Schuman JS: Glaucoma detection with the Heidelberg retina tomograph 3. Ophthalmology. 2007, 114 (3): 466-471. 10.1016/j.ophtha.2006.08.022.CrossRefPubMed
24.
go back to reference Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA: Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology. 2000, 107 (10): 1809-1815. 10.1016/S0161-6420(00)00284-0.CrossRefPubMed Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA: Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology. 2000, 107 (10): 1809-1815. 10.1016/S0161-6420(00)00284-0.CrossRefPubMed
25.
go back to reference Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982, 143 (1): 29-36.CrossRefPubMed Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982, 143 (1): 29-36.CrossRefPubMed
26.
go back to reference Ross TD: Accurate confidence intervals for binomial proportion and Poisson rate estimation. Comput Biol Med. 2003, 33 (6): 509-531. 10.1016/S0010-4825(03)00019-2.CrossRefPubMed Ross TD: Accurate confidence intervals for binomial proportion and Poisson rate estimation. Comput Biol Med. 2003, 33 (6): 509-531. 10.1016/S0010-4825(03)00019-2.CrossRefPubMed
27.
go back to reference R Development Core Team: R: A Language and Environment for Statistical Computing. 2009, Vienna, Austria: R Foundation for Statistical Computing R Development Core Team: R: A Language and Environment for Statistical Computing. 2009, Vienna, Austria: R Foundation for Statistical Computing
28.
go back to reference Harrell FE, with contributions from many other users: Hmisc: Harrell Miscellaneous. 2009 Harrell FE, with contributions from many other users: Hmisc: Harrell Miscellaneous. 2009
29.
go back to reference Sing T, Sander O, Beerenwinkel N, Lengauer T: ROCR: Visualizing the performance of scoring classifiers. 2007 Sing T, Sander O, Beerenwinkel N, Lengauer T: ROCR: Visualizing the performance of scoring classifiers. 2007
30.
go back to reference Brett KM, Burt CW: Utilization of Ambulatory Medical Care by Women: United States, 1997-98. 2001, 13 (149): Brett KM, Burt CW: Utilization of Ambulatory Medical Care by Women: United States, 1997-98. 2001, 13 (149):
31.
go back to reference Varma R, Tielsch JM, Quigley HA, Hilton SC, Katz J, Spaeth GL, Sommer A: Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol. 1994, 112 (8): 1068-1076.CrossRefPubMed Varma R, Tielsch JM, Quigley HA, Hilton SC, Katz J, Spaeth GL, Sommer A: Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol. 1994, 112 (8): 1068-1076.CrossRefPubMed
32.
go back to reference Wall M, Johnson CA, Kardon RH, Crabb DP: Use of a Continuous Probability Scale to Display Visual Field Damage. Arch Ophthalmol. 2009, 127 (6): 749-756. 10.1001/archophthalmol.2009.111.CrossRefPubMed Wall M, Johnson CA, Kardon RH, Crabb DP: Use of a Continuous Probability Scale to Display Visual Field Damage. Arch Ophthalmol. 2009, 127 (6): 749-756. 10.1001/archophthalmol.2009.111.CrossRefPubMed
33.
go back to reference Caprioli J: Discrimination between normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 1992, 33 (1): 153-159.PubMed Caprioli J: Discrimination between normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 1992, 33 (1): 153-159.PubMed
34.
go back to reference Brigatti L, Hoffman D, Caprioli J: Neural networks to identify glaucoma with structural and functional measurements. Am J Ophthalmol. 1996, 121 (5): 511-521.CrossRefPubMed Brigatti L, Hoffman D, Caprioli J: Neural networks to identify glaucoma with structural and functional measurements. Am J Ophthalmol. 1996, 121 (5): 511-521.CrossRefPubMed
35.
go back to reference Shah NN, Bowd C, Medeiros FA, Weinreb RN, Sample PA, Hoffmann EM, Zangwill LM: Combining Structural and Functional Testing for Detection of Glaucoma. Ophthalmology. 2006, 113 (9): 1593-1602. 10.1016/j.ophtha.2006.06.004.CrossRefPubMed Shah NN, Bowd C, Medeiros FA, Weinreb RN, Sample PA, Hoffmann EM, Zangwill LM: Combining Structural and Functional Testing for Detection of Glaucoma. Ophthalmology. 2006, 113 (9): 1593-1602. 10.1016/j.ophtha.2006.06.004.CrossRefPubMed
36.
go back to reference Mardin CY, Peters A, Horn F, Junemann AG, Lausen B: Improving Glaucoma Diagnosis by the Combination of Perimetry and HRT Measurements. J Glaucoma. 2006, 15 (4): 299-305. 10.1097/01.ijg.0000212232.03664.ee.CrossRefPubMed Mardin CY, Peters A, Horn F, Junemann AG, Lausen B: Improving Glaucoma Diagnosis by the Combination of Perimetry and HRT Measurements. J Glaucoma. 2006, 15 (4): 299-305. 10.1097/01.ijg.0000212232.03664.ee.CrossRefPubMed
37.
go back to reference Bowd C, Hao J, Tavares IM, Medeiros FA, Zangwill LM, Lee TW, Sample PA, Weinreb RN, Goldbaum MH: Bayesian machine learning classifiers for combining structural and functional measurements to classify healthy and glaucomatous eyes. Invest Ophthalmol Vis Sci. 2008, 49 (3): 945-953. 10.1167/iovs.07-1083.CrossRefPubMed Bowd C, Hao J, Tavares IM, Medeiros FA, Zangwill LM, Lee TW, Sample PA, Weinreb RN, Goldbaum MH: Bayesian machine learning classifiers for combining structural and functional measurements to classify healthy and glaucomatous eyes. Invest Ophthalmol Vis Sci. 2008, 49 (3): 945-953. 10.1167/iovs.07-1083.CrossRefPubMed
38.
go back to reference Harwerth RS, Vilupuru AS, Rangaswamy NV, Smith EL: The relationship between nerve fiber layer and perimetry measurements. Invest Ophthalmol Vis Sci. 2007, 48 (2): 763-773. 10.1167/iovs.06-0688.CrossRefPubMed Harwerth RS, Vilupuru AS, Rangaswamy NV, Smith EL: The relationship between nerve fiber layer and perimetry measurements. Invest Ophthalmol Vis Sci. 2007, 48 (2): 763-773. 10.1167/iovs.06-0688.CrossRefPubMed
39.
go back to reference Hood DC, Anderson SC, Wall M, Kardon RH: Structure versus function in glaucoma: an application of a linear model. Invest Ophthalmol Vis Sci. 2007, 48 (8): 3662-3668. 10.1167/iovs.06-1401.CrossRefPubMed Hood DC, Anderson SC, Wall M, Kardon RH: Structure versus function in glaucoma: an application of a linear model. Invest Ophthalmol Vis Sci. 2007, 48 (8): 3662-3668. 10.1167/iovs.06-1401.CrossRefPubMed
Metadata
Title
Evaluation of a combined index of optic nerve structure and function for glaucoma diagnosis
Authors
Michael V Boland
Harry A Quigley
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2011
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/1471-2415-11-6

Other articles of this Issue 1/2011

BMC Ophthalmology 1/2011 Go to the issue