Variability in Human Cone Topography Assessed by Adaptive Optics Scanning Laser Ophthalmoscopy

Abstract

Purpose To assess between- and within-individual variability of macular cone topography in the eyes of young adults. Design Observational case series. Methods Cone photoreceptors in 40 eyes of 20 subjects aged 19–29 years with normal maculae were imaged using a research adaptive optics scanning laser ophthalmoscope. Refractive errors ranged from −3.0 D to 0.63 D and differed by <0.50 D in fellow eyes. Cone density was assessed on a two-dimensional sampling grid over the central 2.4 mm × 2.4 mm. Between-individual variability was evaluated by coefficient of variation (CV). Within-individual variability was quantified by maximum difference and root-mean-square (RMS). Cones were cumulated over increasing eccentricity. Results Peak densities of foveal cones are 168,162 ± 23,529 cones/mm2 (mean ± SD) (CV = 0.14). The number of cones within the cone-dominated foveola (0.8–0.9 mm diameter) is 38,311 ± 2,319 (CV = 0.06). The RMS cone density difference between fellow eyes is 6.78%, and the maximum difference is 23.6%. Mixed model statistical analysis found no difference in the association between eccentricity and cone density in the superior/nasal (p=0.8503), superior/temporal (p=0.1551), inferior/nasal (p=0.8609), and inferior/temporal (p=0.6662) quadrants of fellow eyes. Conclusions New instrumentation imaged the smallest foveal cones, thus allowing accurate assignment of foveal centers and assessment of variability in macular cone density in a large sample of eyes. Though cone densities vary significantly in the fovea, the total number of foveolar cones are very similar both between- and within-subjects. Thus, the total number of foveolar cones may be an important measure of cone degeneration and loss.

Assessing the spatial relationship between fixation and foveal specializations

“…This two-fold range is consistent with previous in vivo studies (Li, Tiruveedhula & Roorda, 2010, Putnam et al, 2005, Wilk et al, 2014, Zhang, Godara, Blancob, Griffin, Wang, Curcio & Zhang, 2015) but lower than the range reported in histology (Curcio et al, 1990). …”

Evaluating outer segment length as a surrogate measure of peak foveal cone density

“…For example, optical coherence tomography (OCT) can be used to examine foveal pit morphology (Chui, Zhong, Song & Burns, 2012, Dubis, Hansen, Cooper, Beringer, Dubra & Carroll, 2012, Dubis, McAllister & Carroll, 2009, Hammer et al, 2008, Wagner-Schuman, Dubis, Nordgren, Lei, Odell, Chiao, Weh, Fischer, Sulai, Dubra & Carroll, 2011, Wilk, Dubis, Cooper, Summerfelt, Dubra & Carroll, 2016, Wilk et al, 2014b) and the avascular zone (Braaf, Vienola, Sheehy, Yang, Vermeer, Tiruveedhula, Arathorn, Roorda & de Boer, 2013, Samara, Say, Khoo, Higgins, Magrath, Ferenczy & Shields, 2015, Wilk et al, 2016). In addition, adaptive optics (AO) imaging enables direct visualization of individual rod and cone photoreceptors (Dubra, Sulai, Norris, Cooper, Dubis, Williams & Carroll, 2011, Li, Tiruveedhula & Roorda, 2010, Putnam, Hofer, Doble, Chen, Carroll & Williams, 2005, Wilk et al, 2014b, Zhang, Godara, Blancob, Griffin, Wang, Curcio & Zhang, 2015). While there has been success in measuring peak cone density in normal populations (Putnam et al, 2005, Wilk et al, 2016, Wilk et al, 2014b, Zhang et al, 2015), the presence of nystagmus in a range of retinal diseases often precludes high-resolution imaging (Langlo, Patterson, Higgins, Summerfelt, Razeen, Erker, Parker, Collison, Fishman, Kay, Zhang, Weleber, Yang, Wilson, Pennesi, Lam, Chiang, Chulay, Dubra, Hauswirth, Carroll & ACHM-001 Study Group, 2016, Wilk et al, 2014b).…”

Variation in rod and cone density from the fovea to the mid-periphery in healthy human retinas using adaptive optics scanning laser ophthalmoscopy

“…Although a number of AO-SLO studies have looked at cone and, more recently, rod distributions of the central retina, [18][19][20][21] studies imaging beyond 151 from the fovea are relatively few. Cone density as a function of refractive error has been described by Chui et al 22 28 acute macular neuroretinopathy, 29 congenital stationary night blindness, 30 Oguchi disease, 30 achromatopsia, 20 and acute zonal occult outer retinopathy.…”