Abstract
Background
Albinism patients have poor visual acuity in addition to hypopigmentation. Their foveal anatomy is abnormal, but correlation with function is incompletely understood. This study correlates retinal electrophysiology, visual acuity and optical coherence tomography (OCT) anatomy in albinism patients and compares with age-similar controls.
Methods
Institutional Review Board approval was obtained (IRB# 201408782). Patients were recruited from clinical practice. Inclusion criteria were at least three clinical features of albinism including iris transillumination, nystagmus, fundus hypopigmentation, or foveal hypoplasia on OCT and/or molecular genetic confirmation. Diagnosys (Lowell, Mass) full-field ERG (ffERG) and VERIS multifocal ERG (mfERG; Electro-Diagnostic Imaging, Milpitas, California) were obtained using standard International Society for Clinical Electrophysiology of Vision protocols. The mfERG protocol was a 4-min 103-hexagon protocol covering approximately 40° in diameter of central retina. Control subjects without albinism were recruited by in-hospital notices and invitations in clinic. OCT central thickness was recorded, and an OCT foveal score was calculated. Nonparametric permutation testing was utilized to determine the statistical significance.
Results
A total of 16 albinism patients and 19 age-similar controls were recruited. Four of 16 albinism patients had no nystagmus. Seventeen non-albinism controls had no ocular disorder other than refractive error. Two controls had infantile nystagmus with normal maculas on OCT. There was no statistically significant difference in mfERG amplitude or latency between albinism patients with or without nystagmus (lowest p = 0.68; 0.54, respectively). mfERG: 12 of 16 (75%) albinism patients had average ring 1 amplitudes within one standard deviation of controls despite having abnormal foveal anatomy on OCT. Patients averaged shorter latencies in rings 1 and 2 than controls (p = 0.005, p = 0.02). Patients averaged higher amplitudes than controls in rings 4, 5 and 6 (p = 0.03, p = 0.006, p = 0.004). There was no significant correlation between visual acuity and mfERG amplitudes in any ring (smallest p = 0.15). ffERG: Patients averaged higher amplitudes on 30 Hz flicker (p = 0.008). In all conditions, albinism patients had higher amplitude a-waves (p ≤ 0.03). B-waves were higher amplitude than controls in light-adapted 3.0 (p = 0.03). There was no statistical correlation between ffERG amplitudes and visual acuity (smallest p = 0.45). OCT: In albinism patients, thicker central macula on OCT correlated with lower mfERG amplitudes in all rings except for ring 1 (p < 0.05) and lower ffERG a-wave amplitudes on dark-adapted 0.01 (p = 0.003). Macular thickness on OCT did not correlate with visual acuity (p = 0.51); OCT foveal score did (p = 0.0004).
Conclusions
Amplitude of mfERG does not correlate with visual acuity in any ring in patients with albinism. The slope of the change in amplitude from central to peripheral rings on the mferg is significantly different in albinism patients versus controls whether or not nystagmus is present. The decreased slope of change in amplitudes from center to periphery of the macula in albinism patients indicates changes in macular topography that are more important to visual deficits than the foveal depression
Similar content being viewed by others
References
Kamaraj B, Purohit R (2014) Mutational analysis of oculocutaneous albinism: a compact review. Biomed Res Int. https://doi.org/10.1155/2014/905472
Lewis RA (2013) Oculocutaneous albinism type 1 In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews®[Internet]. University of Washington, Seattle; 1993–2018. 2000 Jan 19 [updated 2013 May 16]
Park SH, Chae H, Kim Y, Kim M (2012) Molecular analysis of korean patients with oculocutaneous albinism. Jpn J Ophthalmol 56:98–103. https://doi.org/10.1007/s10384-011-0098-z
Lewis RA. Ocular Albinism, X-Linked (2004) In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews®[Internet]. University of Washington, Seattle; 1993–2018. 2004 Mar 12 [updated 2015 Nov 19]
Shen B, Samaraweera P, Rosenberg B, Orlow SJ (2001) Ocular albinism type 1: more than meets the eye. Pigment Cell Res 14(4):243–248
King RA, Hearing VJ, Creel DJ, Oetting WS (1995) Albinism. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, vol 3. McGraw-Hill, New York, pp 4353–4392
McCafferty BK, Wilk MA, McAllister JT, Stepien KE, Dubis AM, Brilliant MH, Anderson JL, Carroll J (2015) Summers CG (2015) Clinical insights into foveal morphology in albinism. J Pediatr Ophthalmol Strabismus 52(3):167–172. https://doi.org/10.3928/01913913-20150427-06
Meyer CH, Lapolice DJ, Freedman SF (2002) Foveal hypoplasia in oculocutaneous albinism demonstrated by optical coherence tomography. Am J Opthalmol 133(3):409–410
McAllister JT, Dubis AM, Tait DM et al (2010) Arrested development: high-resolution imaging of foveal morphology in albinism. Vis Res 50:810–817
Marmor MF, Choi SS, Zawadzki RJ, Werner JS (2008) Visual insignificance of the foveal pit: reassessment of foveal hypoplasia as fovea plana. Arch Ophthalmol 126:907–913
Thomas MG, Kumar A, Mohammad S et al (2011) Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity? Ophthalmology 118:1653–1660
Seo JH, Yu YS, Kim JH, Choung HK, Heo JW, Kim SJ (2007) Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism. Ophthalmology 114:1547–1551
Wilk MA, McAllister JT, Cooper RF et al (2014) Relationship between foveal cone specialization and pit morphology in albinism. Invest Ophthalmol Vis Sci 55(7):4186–4198
Krill AE, Lee GB (1963) The electroretinogram in albinos and carriers of the ocular albino trait. Arch Ophthalmol 69(1):32–38
Wack MA, Peachey NS, Fishman GA (1989) Electroretinographic findings in human oculocutaneous albinism. Ophthalmology 96(12):1778–1785
Azarmina M (2013) Full-field versus multifocal electroretinography. J Ophthalmic Vis Res 8(3):191–192
Kelly JP, Weiss AH (2006) Topographical retinal function in oculocutaneous albinism. Am J Ophthalmol 14(6):1156–1158
McCulloch DL, Marmor MF, Brigell MG, Hamilton R, Holder GE, Tzekov R, Bach M (2015) ISCEV standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol 130:1–12
Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, Marmor MF, McCulloch DL, Palmowski-Wolfe AM (2012) ISCEV standard for clinical multifocal electroretinography (2011 edition). Doc Ophthalmol 124:1–13
Sutter EE, Tran D (1992) The field topography of the ERG components in man—I. The photopic luminance response. Vis Res 32:433–466
Thomas MG, Kumar A, Mohammad S, Proudlock FA, Engle EC, Andrews C, Chan W, Thomas S, Gottlob I (2011) Structural grading of foveal hypoplasia using spectral-domain optical coherence tomography a predictor of visual acuity? Ophthalmology 118(8):1653–1660
Nusinowitz S, Sarraf D (2008) Retinal function in X-linked ocular albinism (OA1). Curr Eye Res 33:789–803
Acknowledgement
Frank Bertsch kindly supplied the graphic for Fig. 3. Portions of this study were presented at International Society for Clinic Electrophysiology of Vision (ISCEV) 2017, American Association for Pediatric Ophthalmology and Strabismus (AAPOS) 2017 and The Association for Research in Vision and Ophthalmology (ARVO) 2016.
Funding
Vision for Tomorrow foundation funded this research (Drack). Additional support came from the NIH (T35 HL007485) training grant, the Ronald Keech Professorship, Foundation Fighting Blindness and Research to Prevent Blindness grant funding. The sponsors had no role in the design or conduct of this research.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership or other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Statement on the welfare of animals
No animals were used in this study; it is a human study, performed with IRB approval for the human subjects.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hu, Z., Wang, K., Bertsch, M. et al. Correlation between electroretinography, foveal anatomy and visual acuity in albinism. Doc Ophthalmol 139, 21–32 (2019). https://doi.org/10.1007/s10633-019-09692-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10633-019-09692-9