Multifocal pupillography identifies retinal dysfunction in early age-related macular degeneration

  • Faran Sabeti
  • Andrew C. James
  • Rohan W. Essex
  • Ted Maddess
Retinal Disorders



Early age-related macular degeneration (AMD) is common among the elderly. While only a small number progress to sight-threatening stages of AMD, identifying prognostic functional markers remains paramount. Here, we objectively evaluate retinal function in patients with large drusen by multifocal pupillographic objective perimetry (mfPOP). Different temporal presentation rates and luminances were compared to optimize parameters for high signal to noise ratios (SNR) and diagnosticity for early AMD.


Pupil responses were recorded from 19 early AMD patients (30 eyes) and 29 age-matched control subjects. We compared a luminance-balanced stimulus ensemble and two unbalanced stimulus variants, each consisting of 44 independent stimulus regions per eye extending from fixation to 15˚ eccentricity. Video cameras recorded pupil responses for each eye under infrared illumination. The amplitudes and delays of the peak responses were analysed by multivariate linear models. The diagnostic accuracy of the stimulus variants was compared using areas under the curve (AUC) of receiver operator characteristic (ROC) plots.


Early AMD eyes differed significantly from normal in their mean constriction amplitudes (−2.22 ± 0.15 dB, t = −14.8) and delays (17.92 ± 1.2 ms, t = 14.9). The brightest stimulus ensembles produced the highest median SNRs of 3.45 z-score units; however, the balanced method was found to be the most diagnostic. AUC values of 0.95 ± 0.03 (mean ± SE) for early AMD were obtained when the asymmetry of response amplitudes between eyes was considered.


The mfPOP responses of early AMD eyes showed significant abnormality in response amplitudes and peak time. The ROC AUCs of 95 % suggest that mfPOP is a sensitive tool for detecting early abnormalities in AMD and longitudinal studies measuring progression of retinal dysfunction are warranted.


Multifocal Objective perimetry Pupils Age-related macular degeneration 



Financial Support: Australian Research Council (ARC) through the ARC Centre of Excellence in Vision Science (CE0561903), AusIndustry, and Seeing Machines Ltd, Canberra.


  1. 1.
    VanNewkirk MR, Nanjan MB, Wang JJ, Mitchell P, Taylor HR, McCarty CA (2000) The prevalence of age-related maculopathy: the visual impairment project. Ophthalmology 107:1593–1600PubMedCrossRefGoogle Scholar
  2. 2.
    Klein R, Klein BE, Linton KL (1992) Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology 99:933–943PubMedGoogle Scholar
  3. 3.
    Klein R, Klein BE, Tomany SC, Meuer SM, Huang GH (2002) Ten-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 109:1767–1779PubMedCrossRefGoogle Scholar
  4. 4.
    Mitchell P, Wang JJ, Foran S, Smith W (2002) Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye Study. Ophthalmology 109:1092–1097PubMedCrossRefGoogle Scholar
  5. 5.
    Bressler NM, Munoz B, Maguire MG, Vitale SE, Schein OD, Taylor HR, West SK (1995) Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalities. Waterman study. Arch Ophthalmol 113:301–308PubMedCrossRefGoogle Scholar
  6. 6.
    Owsley C, Jackson GR, Cideciyan AV, Huang Y, Fine SL, Ho AC, Maguire MG, Lolley V, Jacobson SG (2000) Psychophysical evidence for rod vulnerability in age-related macular degeneration. Invest Ophthalmol Vis Sci 41:267–273PubMedGoogle Scholar
  7. 7.
    Owsley C, Jackson GR, White M, Feist R, Edwards D (2001) Delays in rod-mediated dark adaptation in early age-related maculopathy. Ophthalmology 108:1196–1202PubMedCrossRefGoogle Scholar
  8. 8.
    Haimovici R, Owens SL, Fitzke FW, Bird AC (2002) Dark adaptation in age-related macular degeneration: relationship to the fellow eye. Graefes Arch Clin Exp Ophthalmol 240:90–95PubMedCrossRefGoogle Scholar
  9. 9.
    Eisner A, Fleming SA, Klein ML, Mauldin WM (1987) Sensitivities in older eyes with good acuity: eyes whose fellow eye has exudative AMD. Invest Ophthalmol Vis Sci 28:1832–1837PubMedGoogle Scholar
  10. 10.
    Swann PG, Lovie-Kitchin JE (1991) Age-related maculopathy. II: the nature of the central visual field loss. Ophthalmic Physiol Opt 11:59–70PubMedCrossRefGoogle Scholar
  11. 11.
    Midena E, Degli Angeli C, Blarzino MC, Valenti M, Segato T (1997) Macular function impairment in eyes with early age-related macular degeneration. Invest Ophthalmol Vis Sci 38:469–477PubMedGoogle Scholar
  12. 12.
    Midena E, Segato T, Blarzino MC, Degli Angeli C (1994) Macular drusen and the sensitivity of the central visual field. Doc Ophthalmol 88:179–185PubMedCrossRefGoogle Scholar
  13. 13.
    Sunness JS, Massof RW, Johnson MA, Finkelstein D, Fine SL (1985) Peripheral retinal function in age-related macular degeneration. Arch Ophthalmol 103:811–816PubMedCrossRefGoogle Scholar
  14. 14.
    Sunness JS, Johnson MA, Massof RW, Marcus S (1988) Retinal sensitivity over drusen and nondrusen areas. A study using fundus perimetry. Arch Ophthalmol 106:1081–1084PubMedCrossRefGoogle Scholar
  15. 15.
    Tolentino MJ, Miller S, Gaudio AR, Sandberg MA (1994) Visual field deficits in early age-related macular degeneration. Vis Res 34:409–413PubMedCrossRefGoogle Scholar
  16. 16.
    Takamine Y, Shiraki K, Moriwaki M, Yasunari T, Miki T (1998) Retinal sensitivity measurement over drusen using scanning laser ophthalmoscope microperimetry. Graefes Arch Clin Exp Ophthalmol 236:285–290PubMedCrossRefGoogle Scholar
  17. 17.
    Midena E, Vujosevic S, Convento E, Manfre A, Cavarzeran F, Pilotto E (2007) Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration. Br J Ophthalmol 91:1499–1503PubMedCrossRefGoogle Scholar
  18. 18.
    Kardon R, Anderson SC, Damarjian TG, Grace EM, Stone E, Kawasaki A (2009) Chromatic pupil responses: preferential activation of the melanopsin-mediated versus outer photoreceptor-mediated pupil light reflex. Ophthalmology 116:1564–1573PubMedCrossRefGoogle Scholar
  19. 19.
    Maddess T, Bedford SM, Goh XL, James AC (2009) Multifocal pupillographic visual field testing in glaucoma. Clin Exp Ophthalmol 37:678–686CrossRefGoogle Scholar
  20. 20.
    James AC, Kolic M, Bedford SM, Maddess T (2012) Stimulus parameters for multifocal pupillographic objective perimetry. J Glaucoma. doi: 10.1097/IJG.1090b1013e31821e38413
  21. 21.
    Bell A, James AC, Kolic M, Essex RW, Maddess T (2010) Dichoptic multifocal pupillography reveals afferent visual field defects in early type 2 diabetes. Invest Ophthalmol Vis Sci 51:602–608PubMedCrossRefGoogle Scholar
  22. 22.
    Rosli Y, Bedford SM, James AC, Maddess T (2012) Photopic and scotopic multifocal pupillographic responses in age-related macular degeneration. Vis Res 69:42–48PubMedCrossRefGoogle Scholar
  23. 23.
    Sabeti F, James AC, Maddess T (2011) Spatial and temporal stimulus variants for multifocal pupillography of the central visual field. Vis Res 51:303–310PubMedCrossRefGoogle Scholar
  24. 24.
    Sabeti F, Maddess T, Essex RW, James AC (2011) Multifocal pupillographic assessment of age-related macular degeneration. Optom Vis Sci 88:1477–1485PubMedGoogle Scholar
  25. 25.
    Sabeti F, Maddess T, Essex RW, James AC (2012) Multifocal pupillography identifies ranibizumab-induced changes in retinal function for exudative age-related macular degeneration. Invest Ophthalmol Vis Sci 53:253–260PubMedCrossRefGoogle Scholar
  26. 26.
    Kolic M, Maddess T, Essex RW, James AC (2009) Attempting balanced multifocal pupillographic perimetry. ARVO-IOVS, Ft. Lauderdale, pp. E-Abstract 5280Google Scholar
  27. 27.
    Maddess TL, Kolic M, Essex RW, James AC (2009) Balanced luminance multifocal pupillographic perimetry. ARVO-IOVS, Ft. Lauderdale, pp. E-Abstract 5281Google Scholar
  28. 28.
    Maddess T, Ho YL, Wong SS, Kolic M, Goh XL, Carle CF, James AC (2011) Multifocal pupillographic perimetry with white and colored stimuli. J Glaucoma 20:336–343PubMedCrossRefGoogle Scholar
  29. 29.
    James AC, Ruseckaite R, Maddess T (2005) Effect of temporal sparseness and dichoptic presentation on multifocal visual evoked potentials. Vis Neurosci 22:45–54PubMedCrossRefGoogle Scholar
  30. 30.
    Egan J (1975) Signal detection theory and ROC analysis. Academic, New YorkGoogle Scholar
  31. 31.
    Bell A, James AC, Kolic M, Essex RW, Maddess T (2010) Dichoptic multifocal pupillography reveals afferent visual field defects in early type 2 diabetes. Invest Ophthalmol Vis Sci 51:602–608PubMedCrossRefGoogle Scholar
  32. 32.
    Ivers RQ, Macaskill P, Cumming RG, Mitchell P (2001) Sensitivity and specificity of tests to detect eye disease in an older population. Ophthalmology 108:968–975PubMedCrossRefGoogle Scholar
  33. 33.
    Gerth C, Hauser D, Delahunt PB, Morse LS, Werner JS (2003) Assessment of multifocal electroretinogram abnormalities and their relation to morphologic characteristics in patients with large drusen. Arch Ophthalmol 121:1404–1414PubMedCrossRefGoogle Scholar
  34. 34.
    Hood DC, Holopigian K, Greenstein V, Seiple W, Li J, Sutter EE, Carr RE (1998) Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique. Vis Res 38:163–179PubMedCrossRefGoogle Scholar
  35. 35.
    Hong S, Narkiewicz J, Kardon RH (2001) Comparison of pupil perimetry and visual perimetry in normal eyes: decibel sensitivity and variability. Invest Ophthalmol Vis Sci 42:957–965PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Faran Sabeti
    • 1
  • Andrew C. James
    • 1
  • Rohan W. Essex
    • 1
    • 2
  • Ted Maddess
    • 1
  1. 1.ARC Centre of Excellence in Vision Science, John Curtin School of Medical ResearchAustralian National UniversityCanberraAustralia
  2. 2.Ophthalmology DepartmentAustralian National University, Canberra HospitalCanberraAustralia

Personalised recommendations