To determine the effects of age on perifoveal cone density in healthy subjects using adaptive optics.
Healthy subjects of various ages were imaged using an adaptive optics retinal camera (RTX-1® Imagine Eyes, Orsay, France). All patients underwent a comprehensive ophthalmologic examination and retinal imaging using spectral-domain optical coherence tomography (Spectralis®, Heidelberg Engineering, Heidelberg, Germany). Cone density together with cone spacing and cone mosaic packing were measured in the nasal and temporal area 450 µm from the fovea. A multivariate analysis was performed to determine which of the following parameters were related to a decrease in cone density: age, axial length, central macular thickness, and retrofoveal choroidal thickness.
One hundred and sixty-seven eyes of 101 subjects aged 6–78 years were studied. Perifoveal cone density significantly decreased with age (R2 = 0.17, p<0.01). Inversely, cone spacing increased with age (R2=0.18, p<0.01). There was no change in the cone packing mosaic (p>0.05). The mean coefficient of variation between fellow eyes was 3.9%. Age and axial length were related to a cone density decrease, while choroidal and retinal thicknesses did not affect cone metrics in healthy subjects.
A moderate perifoveal cone loss occurs with age. The precise consequences of these findings on visual function should be investigated. In addition to a better understanding of normal retinal anatomy, these results could act as a comparative database for further studies on normal and diseased retinas.
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Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science (New York, NY). 1997;278:412–19.
Audo I, Sanharawi MEl, Vignal-Clermont C, Villa A, Morin A, Conrath J, Fompeydie D, et al. Foveal damage in habitual poppers users. Arch Ophthalmol. 2011;129:703–8. https://doi.org/10.1001/archophthalmol.2011.6
Michalewski J, Michalewska Z, Nawrocka Z, Bednarski M, Nawrocki J. Correlation of choroidal thickness and volume measurements with axial length and age using swept-source optical coherence tomography and optical low-coherence reflectometry. Biomed Res Int. 2014;2014:639160.
Bowd C, Zangwill LM, Blumenthal EZ, Vasile C, Boehm AG, Gokhale PA, Mohammadi K, Amini P, Sankary TM, Weinreb. RN. Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender. J Opt Soc Am A. 2002;19:197–207.
Eriksson U, Alm A. Macular thickness decreases with age in normal eyes: a study on the macular thickness map protocol in the stratus OCT. Br J Ophthalmol. 2009;93:1448–52. https://doi.org/10.1136/bjo.2007.131094
Manjunath V, Mohammad T, Fujimoto JG, Duker JS. Choroidal thickness in normal eyes measured using cirrus HD optical coherence tomography. Am J Ophthalmol. 2010;150:325–9.e1. https://doi.org/10.1016/j.ajo.2010.04.018
Chui TYP, Song H, Clark CA, Papay JA, Burns SA, Elsner AE. Cone photoreceptor packing density and the outer nuclear layer thickness in healthy subjects. Invest Ophthalmol Vis Sci. 2012;53:3545–53.
Obata R, Yanagi Y. Quantitative analysis of cone photoreceptor distribution and its relationship with axial length, age, and early age-related macular degeneration. PLoS ONE. 2014;9:e91873.
Lombardo M, Lombardo G, Schiano Lomoriello D, Ducoli P, Stirpe M, Serrao S. Interocular symmetry of parafoveal photoreceptor cone density distribution. Retina (Phila, PA). 2013;33:1640–9.
Muthiah MN, Gias C, Chen FK, Zhong J, McClelland Z, Sallo FB, et al. Cone photoreceptor definition on adaptive optics retinal imaging. Br J Ophthalmol. 2014;98:1073–9.
Li KY, Tiruveedhula JS, Roorda A. Intersubject variability of foveal cone photoreceptor density in relation to eye length. Invest Ophthalmol Vis Sci. 2010;51:6858–67. https://doi.org/10.1167/iovs.10-5499
Choi SS, Zawadzki RJ, Lim MC, Brandt JD, Keltner JL, Doble N, Werner JS. Evidence of outer retinal changes in glaucoma patients as revealed by ultrahigh-resolution in vivo retinal imaging. Br J Ophthalmol. 2011;95:131–41. https://doi.org/10.1136/bjo.2010.183756
Duncan JL, Zhang Y, Gandhi J, Nakanishi C, Othman M, Branham KEH, Swaroop A, Roorda A. High-resolution imaging with adaptive optics in patients with inherited retinal degeneration. Invest Ophthalmol Vis Sci. 2007;48:3283–91. https://doi.org/10.1167/iovs.06-1422
Zayit-Soudry S, Jacque LD, Syed R, Menghini M, Austin JR. Cone structure imaged with adaptive optics scanning laser ophthalmoscopy in eyes with nonneovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013;54:7498–509. https://doi.org/10.1167/iovs.13-12433
Chen Y, Ratnam K, Sundquist SM, Lujan B, Ayyagari R, Gudiseva VH, Roorda A, Jacque LD. Cone photoreceptor abnormalities correlate with vision loss in patients with Stargardt disease. Invest Ophthalmol Vis Sci. 2011;52:3281–92. https://doi.org/10.1167/iovs.10-6538
Gocho K, Sarda V, Falah S, Sahel J-Al, Sennlaub F, Benchaboune M, Ullern M, Paques M. Adaptive optics imaging of geographic atrophy. Invest Ophthalmol Vis Sci. 2013;54:3673–80. https://doi.org/10.1167/iovs.12-10672
Ooto S, Hangai M, Sakamoto A, Tsujikawa A, Yamashiro K, Ojima Y, Yamada Y, et al. High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy. Ophthalmology. 2010;117:1800–9.e1-2. https://doi.org/10.1016/j.ophtha.2010.01.042
Ooto S, Hangai M, Takayama K, Ueda-Arakawa N, Hanebuchi M, Yoshimura N. Photoreceptor damage and foveal sensitivity in surgically closed macular holes: an adaptive optics scanning laser ophthalmoscopy study. Am J Ophthalmol. 2012;154:174–86.e2. https://doi.org/10.1016/j.ajo.2012.01.031
Saleh, M, Debellemanière G, Meillat M, Tumahai P, Bidaut Garnier M, Flores M, Schwartz C, Delbosc B. Quantification of cone loss after surgery for retinal detachment involving the macula using adaptive optics. Br J Ophthalmology. 2014;98(10):1343-8. https://doi.org/10.1136/bjophthalmol-2013-304813
Bae EJ, Kim KR, Tsang SH, Park SP, Chang S. Retinal damage in chloroquine maculopathy, revealed by high resolution imaging: a case report utilizing adaptive optics scanning laser ophthalmoscopy. Korean J Ophthalmol. 2014;28:100–7. https://doi.org/10.3341/kjo.2014.28.1.100
Song H, Chui TYP, Zhong Z, Elsner AE, Stephen AB. Variation of cone photoreceptor packing density with retinal eccentricity and age. Invest Ophthalmol Vis Sci. 2011;52:7376–84. https://doi.org/10.1167/iovs.11-7199
Park S, Pyo JKC, Vivienne G, Stephen HT, Stanley C. A study of factors affecting the human cone photoreceptor density measured by adaptive optics scanning laser ophthalmoscope. Exp Eye Res. 2013;108:1–9. https://doi.org/10.1016/j.exer.2012.12.011
Bidaut Garnier M, Flores M, Debellemanière G, Puyraveau M, Tumahai P, Mathieu M, Schwartz C, Montard M, Delbosc B, Saleh M. Reliability of cone counts using an adaptive optics retinal camera. Clin Exp Ophthalmol. 2014;42(9):833-40. https://doi.org/10.1111/ceo.12356
Gartner S, Henkind P. Aging and degeneration of the human macula. 1. Outer Nuclear layer and photoreceptors. Br J Ophthalmol. 1981;65:23–28.
NATO Advanced Research Workshop on the Changing Visual System: From Early to Late Stages of Life—Maturation and Aging in the Central Nervous System, and North Atlantic Treaty Organization. In: Bagnoli P, Hodos W, editors. The changing visual system: maturation and aging in the central nervous system. NATO ASI Series, v. 222. New York: Plenum Press; 1991. p. 119–36.
Nag TC, Wadhwa S. Ultrastructure of the human retina in aging and various pathological states. Micron. 2012;43:759–81.
Adler R, Curcio C, Hicks D, Price D, Wong F. Cell death in age-related macular degeneration. Mol Vis. 1999;5:31.
Tucker GS. Refractile bodies in the inner segments of cones in the aging human retina. Invest Ophthalmol Vis Sci. 1986;27:708–15.
Iwasaki M, Inomata H. Lipofuscin granules in human photoreceptor cells. Invest Ophthalmol Vis Sci. 1988;29:671–79.
Curcio CA. Photoreceptor topography in ageing and age-related maculopathy. Eye. 2001;15:376–83. https://doi.org/10.1038/eye.2001.140
Eckmiller MS, Marion S. Defective cone photoreceptor cytoskeleton, alignment, feedback, and energetics can lead to energy depletion in macular degeneration. Prog Retin Eye Res. 2004;23:495–522. https://doi.org/10.1016/j.preteyeres.2004.04.005
Yoshida S, Beverly MY, Hiriyanna S, Swaroop A. Microarray analysis of gene expression in the aging human retina. Invest Ophthalmol Vis Sci. 2002;43:2554–60.
Panda-Jonas S, Jonas JB, Jakobczyk-Zmija M. Retinal photoreceptor density decreases with age. Ophthalmology. 1995;102:1853–59.
Curcio CA, Millican CL, Allen KA, Kalina RE. Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci. 1993;34:3278–96.
Marshall J. Ageing changes in human cones. In: ShimuzuK, editor. Ophthalmology. Vol 1. Proc. XXIII International Congr (Kyoto); 1979. p. 375–8
Noia LdaC, Berezovsky A, Freitas Dd, Sacai PY, Salomão SR. Clinical and electroretinographic profile of commotio retinae. Arq Bras Oftalmol. 2006;69:895–906.
Westheimer G. Directional sensitivity of the retina: 75 years of Stiles–Crawford effect. Proc Biol Sci. 2008;275:2777–86.
Scoles D, Sulai YN, Langlo CS, Fishman GA, Curcio CA, Carroll J, et al. In vivo imaging of human cone photoreceptor inner segments. Invest Ophthalmol Vis Sci. 2014;55:4244–51.
Lombardo M, Serrao S, Ducoli P, Lombardo G. Eccentricity dependent changes of density, spacing and packing arrangement of parafoveal cones. Ophthalmic Physiol Opt. 2013;33:516–26.
Garrioch R, Langlo C, Dubis AM, Cooper RF, Dubra A, Carroll J. Repeatability of in vivo parafoveal cone density and spacing measurements. Optom Vis Sci. 2012;89:632–43.
Lombardo M, Serrao S, Ducoli P, Lombardo G. Influence of sampling window size and orientation on parafoveal cone packing density. Biomed Opt Express. 2013;4:1318–31.
Feeney-Burns L, Burns RP, Gao CL. Age-related macular changes in humans over 90 years old. Am J Ophthalmol. 1990;109:265–78.
Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res. 2010;29:144–68.
Owsley C. Contrast sensitivity. Ophthalmol Clin N Am. 2003;16:171–7.