Event-based analysis of visual field change can miss fast glaucoma progression detected by a combined structure and function index

  • Chunwei Zhang
  • Andrew J. Tatham
  • Fábio B. Daga
  • Alessandro A. Jammal
  • Felipe A. Medeiros



To investigate the relationship between progression assessed by the visual field guided progression analysis (GPA) and rates of structural and functional change in glaucoma eyes.


This was a longitudinal observational study of 135 eyes of 97 patients with glaucoma followed for an average of 3.5 ± 0.9 years. All patients had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) analysis with spectral domain optical coherence tomography (SDOCT), with an average of 6.8 ± 2.3 visits. A control group of healthy eyes followed longitudinally was used to estimate age-related change. Visual field progression was assessed using the Humphrey Field Analyzer GPA. Estimates of retinal ganglion cell counts from SAP and SDOCT were used to obtain a combined index of glaucomatous damage (RGC index) according to a previously described algorithm. Progression by SDOCT and the retinal ganglion cell (RGC) index were defined as statistically significant (P < 0.05) slopes of change that were also faster than age-related change estimated from healthy eyes.


From the 135 eyes, 15 (11%) progressed by GPA, 21 (16%) progressed by SDOCT, and 31 (23%) progressed by the RGC index. Twenty-one eyes showed progression by the RGC index that was missed by the GPA. These eyes had an average rate of change in estimated RGC counts of − 28,910 cells/year, ranging from two to nine times faster than expected age-related losses.


Many glaucomatous eyes that are not found to be progressing by GPA may actually have fast rates of change as detected by a combined index of structure and function.


Optical coherence tomography Visual field Combined structure function index Glaucoma progression 



National Institutes of Health/National Eye Institute provided financial support in part in the form of grant EY021818 (F.A.M.); Natural Science Foundation of Heilongjiang Province for Returned Scholars, China, provided financial support in the form of grant no. LC2012C21 (C.Z.); Innovation research special fund of the Science and Technology of Harbin of Heilong Jiang Province, China, provided financial support in the form of grant no. 2011RFLYS029 (C.Z.). The sponsors had no role in the design or conduct of this research.

Compliance with ethical standards

Conflict of interest

The authors have made the following disclosures: C.Z.—none; A.J.T.—research support from Heidelberg Engineering; F.B.D.—none; A.A.J.—none; F.A.M.—F: Alcon Laboratories, Bausch & Lomb, Carl Zeiss Meditec, Heidelberg Engineering, Merck, Allergan, Sensimed, Topcon, Reichert, National Eye Institute, R: Alcon Laboratories, Allergan, Carl Zeiss Meditec, Reichert, C: Allergan, Carl Zeiss Meditec, Novartis.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and human subjects committee of the Duke University and University of California San Diego (UCSD) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Weinreb RN, Aung T, Medeiros FA (2014) The pathophysiology and treatment of glaucoma: a review. JAMA 311(18):1901–1911. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    No authors listed (1994) Advanced glaucoma intervention study. 2. Visual field test scoring and reliability. Ophthalmology 101(8):1445–1455CrossRefGoogle Scholar
  3. 3.
    Katz J (1999) Scoring systems for measuring progression of visual field loss in clinical trials of glaucoma treatment. Ophthalmology 106(2):391–395. CrossRefPubMedGoogle Scholar
  4. 4.
    Gordon MO, Kass MA (1999) The ocular hypertension treatment study: design and baseline description of the participants. Arch Ophthalmol (Chicago, Ill : 1960) 117(5):573–583CrossRefGoogle Scholar
  5. 5.
    Heijl A, Leske MC, Bengtsson B, Bengtsson B, Hussein M (2003) Measuring visual field progression in the early manifest glaucoma trial. Acta Ophthalmol Scand 81(3):286–293CrossRefPubMedGoogle Scholar
  6. 6.
    Cho JW, Sung KR, Yun SC, Na JH, Lee Y, Kook MS (2012) Progression detection in different stages of glaucoma: mean deviation versus visual field index. Jpn J Ophthalmol 56(2):128–133. CrossRefPubMedGoogle Scholar
  7. 7.
    Quigley HA, Addicks EM, Green WR (1982) Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol (Chicago, Ill : 1960) 100(1):135–146CrossRefGoogle Scholar
  8. 8.
    Medeiros FA, Zangwill LM, Bowd C, Mansouri K, Weinreb RN (2012) The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change. Invest Ophthalmol Vis Sci 53(11):6939–6946. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Medeiros FA, Lisboa R, Weinreb RN, Girkin CA, Liebmann JM, Zangwill LM (2012) A combined index of structure and function for staging glaucomatous damage. Arch Ophthalmol (Chicago, Ill : 1960) 130(9):1107–1116. Google Scholar
  10. 10.
    Zhang C, Tatham AJ, Weinreb RN, Zangwill LM, Yang Z, Zhang JZ, Medeiros FA (2014) Relationship between ganglion cell layer thickness and estimated retinal ganglion cell counts in the glaucomatous macula. Ophthalmology 121(12):2371–2379. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gracitelli CP, Tatham AJ, Zangwill LM, Weinreb RN, Liu T, Medeiros FA (2014) Estimated rates of retinal ganglion cell loss in glaucomatous eyes with and without optic disc hemorrhages. PLoS One 9(8):e105611. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Tatham AJ, Weinreb RN, Zangwill LM, Liebmann JM, Girkin CA, Medeiros FA (2013) The relationship between cup-to-disc ratio and estimated number of retinal ganglion cells. Invest Ophthalmol Vis Sci 54(5):3205–3214. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Medeiros FA, Zangwill LM, Anderson DR, Liebmann JM, Girkin CA, Harwerth RS, Fredette MJ, Weinreb RN (2012) Estimating the rate of retinal ganglion cell loss in glaucoma. Am J Ophthalmol 154(5):814–824 e811. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Medeiros FA, Lisboa R, Weinreb RN, Liebmann JM, Girkin C, Zangwill LM (2013) Retinal ganglion cell count estimates associated with early development of visual field defects in glaucoma. Ophthalmology 120(4):736–744. CrossRefPubMedGoogle Scholar
  15. 15.
    Meira-Freitas D, Lisboa R, Tatham A, Zangwill LM, Weinreb RN, Girkin CA, Liebmann JM, Medeiros FA (2013) Predicting progression in glaucoma suspects with longitudinal estimates of retinal ganglion cell counts. Invest Ophthalmol Vis Sci 54(6):4174–4183. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Harwerth RS, Wheat JL, Fredette MJ, Anderson DR (2010) Linking structure and function in glaucoma. Prog Retin Eye Res 29(4):249–271. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Williams RL (2000) A note on robust variance estimation for cluster-correlated data. Biometrics 56(2):645–646CrossRefPubMedGoogle Scholar
  18. 18.
    Leung CK, Cheung CY, Weinreb RN, Qiu K, Liu S, Li H, Xu G, Fan N, Pang CP, Tse KK, Lam DS (2010) Evaluation of retinal nerve fiber layer progression in glaucoma: a study on optical coherence tomography guided progression analysis. Invest Ophthalmol Vis Sci 51(1):217–222. CrossRefPubMedGoogle Scholar
  19. 19.
    Harwerth RS, Quigley HA (2006) Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch Ophthalmol (Chicago, Ill : 1960) 124(6):853–859. CrossRefGoogle Scholar
  20. 20.
    Quigley HA, Dunkelberger GR, Green WR (1989) Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 107(5):453–464CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Chunwei Zhang
    • 1
    • 2
  • Andrew J. Tatham
    • 1
    • 3
  • Fábio B. Daga
    • 1
  • Alessandro A. Jammal
    • 1
  • Felipe A. Medeiros
    • 1
  1. 1.Visual Performance Laboratory, Duke Eye Center and Department of OphthalmologyDuke University School of MedicineDurhamUSA
  2. 2.Department of Ophthalmology, the First Affiliated HospitalHarbin Medical UniversityHarbinChina
  3. 3.Princess Alexandra Eye Pavilion and Department of OphthalmologyUniversity of EdinburghEdinburghUK

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