Abstract

The retinal pigment epithelial (RPE) cells contain intrinsic fluorophores that can be visualized using infrared autofluorescence (IRAF). Although IRAF is routinely utilized in the clinic for visualizing retinal health and disease, currently, it is not possible to discern cellular details using IRAF due to limits in resolution. We demonstrate that the combination of adaptive optics (AO) with IRAF (AO-IRAF) enables higher-resolution imaging of the IRAF signal, revealing the RPE mosaic in the living human eye. Quantitative analysis of visualized RPE cells in 10 healthy subjects across various eccentricities demonstrates the possibility for in vivo density measurements of RPE cells, which range from 6505 to 5388 cells/mm2 for the areas measured (peaking at the fovea). We also identified cone photoreceptors in relation to underlying RPE cells, and found that RPE cells support on average up to 18.74 cone photoreceptors in the fovea down to an average of 1.03 cone photoreceptors per RPE cell at an eccentricity of 6 mm. Clinical application of AO-IRAF to a patient with retinitis pigmentosa illustrates the potential for AO-IRAF imaging to become a valuable complementary approach to the current landscape of high resolution imaging modalities.

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2017 (3)

C. E. Granger, D. R. Williams, and E. A. Rossi, “Near-infrared autofluorescence imaging reveals the retinal pigment epithelial mosaic in the living human eye,” Invest. Ophthalmol. Vis. Sci. 58, 3429 (2017).

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

2016 (3)

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[Crossref] [PubMed]

2015 (2)

A. Roorda and J. L. Duncan, “Adaptive Optics Ophthalmoscopy,” Annu Rev Vis Sci 1(1), 19–50 (2015).
[Crossref] [PubMed]

A. V. Cideciyan, M. Swider, and S. G. Jacobson, “Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores,” Invest. Ophthalmol. Vis. Sci. 56(5), 3393–3406 (2015).
[Crossref] [PubMed]

2014 (3)

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

2013 (2)

2011 (2)

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
[Crossref] [PubMed]

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

2010 (1)

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 nm) and near-infrared autofluorescence (787 nm) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina 30(1), 6–15 (2010).
[Crossref] [PubMed]

2009 (4)

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

2007 (3)

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

A. Roorda, Y. Zhang, and J. L. Duncan, “High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007).
[Crossref] [PubMed]

K. Y. Li and A. Roorda, “Automated identification of cone photoreceptors in adaptive optics retinal images,” J. Opt. Soc. Am. A 24(5), 1358–1363 (2007).
[Crossref] [PubMed]

2006 (2)

2002 (2)

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

L. V. Del Priore, Y.-H. Kuo, and T. H. Tezel, “Age-related changes in human RPE cell density and apoptosis proportion in situ,” Invest. Ophthalmol. Vis. Sci. 43(10), 3312–3318 (2002).
[PubMed]

1997 (2)

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
[Crossref] [PubMed]

1996 (1)

S. Panda-Jonas, J. B. Jonas, and M. Jakobczyk-Zmija, “Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes,” Am. J. Ophthalmol. 121(2), 181–189 (1996).
[Crossref] [PubMed]

1993 (1)

R. C. Watzke, J. D. Soldevilla, and D. R. Trune, “Morphometric analysis of human retinal pigment epithelium: correlation with age and location,” Curr. Eye Res. 12(2), 133–142 (1993).
[Crossref] [PubMed]

1992 (1)

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

1991 (2)

M. Boulton, “Ageing of the retinal pigment epithelium,” Prog. Retinal Res. 11, 125–151 (1991).
[Crossref]

R. W. Rodieck, “The density recovery profile: A method for the analysis of points in the plane applicable to retinal studies,” Vis. Neurosci. 6(2), 95–111 (1991).
[Crossref] [PubMed]

1990 (2)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

L. Feeney-Burns, R. P. Burns, and C.-L. Gao, “Age-related macular changes in humans over 90 years old,” Am. J. Ophthalmol. 109(3), 265–278 (1990).
[Crossref] [PubMed]

1989 (2)

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

A. G. Bennett and R. B. Rabbetts, “Proposals for new reduced and schematic eyes,” Ophthalmic Physiol. Opt. 9(2), 228–230 (1989).
[Crossref] [PubMed]

1969 (1)

B. W. Streeten, “Development of the human retinal pigment epithelium and the posterior segment,” Arch. Ophthalmol. 81(3), 383–394 (1969).
[Crossref] [PubMed]

1968 (1)

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. III. growth and development,” Arch. Ophthalmol. 80(2), 214–216 (1968).
[Crossref] [PubMed]

Ablonczy, Z.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Ach, T.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Ahamd, K.

Ayata, A.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Bandello, F.

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

Bennett, A. G.

A. G. Bennett and R. B. Rabbetts, “Proposals for new reduced and schematic eyes,” Ophthalmic Physiol. Opt. 9(2), 228–230 (1989).
[Crossref] [PubMed]

Bentley, M. J.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Bilge, A. H.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Boulton, M.

M. Boulton, “Ageing of the retinal pigment epithelium,” Prog. Retinal Res. 11, 125–151 (1991).
[Crossref]

Branham, K. E. H.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Burns, R. P.

L. Feeney-Burns, R. P. Burns, and C.-L. Gao, “Age-related macular changes in humans over 90 years old,” Am. J. Ophthalmol. 109(3), 265–278 (1990).
[Crossref] [PubMed]

Carroll, J.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Chung, M. M.

Cideciyan, A. V.

A. V. Cideciyan, M. Swider, and S. G. Jacobson, “Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores,” Invest. Ophthalmol. Vis. Sci. 56(5), 3393–3406 (2015).
[Crossref] [PubMed]

Cooper, R. F.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

Cordeiro, M. F.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Curcio, C. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

Del Priore, L. V.

L. V. Del Priore, Y.-H. Kuo, and T. H. Tezel, “Age-related changes in human RPE cell density and apoptosis proportion in situ,” Invest. Ophthalmol. Vis. Sci. 43(10), 3312–3318 (2002).
[PubMed]

Del Turco, C.

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

Delori, F. C.

C. N. Keilhauer and F. C. Delori, “Near-Infrared Autofluorescence Imaging of the Fundus: Visualization of Ocular Melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

Dorey, C. K.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

Dubis, A. M.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

Dubra, A.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

E. A. Rossi, P. Rangel-Fonseca, K. Parkins, W. Fischer, L. R. Latchney, M. A. Folwell, D. R. Williams, A. Dubra, and M. M. Chung, “In vivo imaging of retinal pigment epithelium cells in age related macular degeneration,” Biomed. Opt. Express 4(11), 2527–2539 (2013).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, and A. Dubra, “In vivo dark-field imaging of the retinal pigment epithelium cell mosaic,” Biomed. Opt. Express 4(9), 1710–1723 (2013).
[Crossref] [PubMed]

A. Dubra and Y. Sulai, “Reflective afocal broadband adaptive optics scanning ophthalmoscope,” Biomed. Opt. Express 2(6), 1757–1768 (2011).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

D. C. Gray, W. Merigan, J. I. Wolfing, B. P. Gee, J. Porter, A. Dubra, T. H. Twietmeyer, K. Ahamd, R. Tumbar, F. Reinholz, and D. R. Williams, “In vivo fluorescence imaging of primate retinal ganglion cells and retinal pigment epithelial cells,” Opt. Express 14(16), 7144–7158 (2006).
[Crossref] [PubMed]

Duncan, J. L.

A. Roorda and J. L. Duncan, “Adaptive Optics Ophthalmoscopy,” Annu Rev Vis Sci 1(1), 19–50 (2015).
[Crossref] [PubMed]

A. Roorda, Y. Zhang, and J. L. Duncan, “High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007).
[Crossref] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Ebenstein, D.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

Ersanli, D.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Fariss, R.

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

Feeney-Burns, L.

L. Feeney-Burns, R. P. Burns, and C.-L. Gao, “Age-related macular changes in humans over 90 years old,” Am. J. Ophthalmol. 109(3), 265–278 (1990).
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Fiebig, B.

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

Fischer, W.

Fishman, G. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Fitzke, F. W.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Fleming, P. A.

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

Folwell, M. A.

Friedman, E.

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. III. growth and development,” Arch. Ophthalmol. 80(2), 214–216 (1968).
[Crossref] [PubMed]

Gandhi, J.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Gao, C.-L.

L. Feeney-Burns, R. P. Burns, and C.-L. Gao, “Age-related macular changes in humans over 90 years old,” Am. J. Ophthalmol. 109(3), 265–278 (1990).
[Crossref] [PubMed]

Gao, H.

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

Garsd, A.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

Gee, B. P.

Granger, C. E.

C. E. Granger, D. R. Williams, and E. A. Rossi, “Near-infrared autofluorescence imaging reveals the retinal pigment epithelial mosaic in the living human eye,” Invest. Ophthalmol. Vis. Sci. 58, 3429 (2017).

Gray, D. C.

Guo, L.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Gutierrez, D. B.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Harman, A. M.

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

Hendrickson, A. E.

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

Hollyfield, J. G.

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

Holz, F. G.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Hoskins, R. V.

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

Huisingh, C.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Iacono, P.

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

Jacobson, S. G.

A. V. Cideciyan, M. Swider, and S. G. Jacobson, “Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores,” Invest. Ophthalmol. Vis. Sci. 56(5), 3393–3406 (2015).
[Crossref] [PubMed]

Jakobczyk-Zmija, M.

S. Panda-Jonas, J. B. Jonas, and M. Jakobczyk-Zmija, “Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes,” Am. J. Ophthalmol. 121(2), 181–189 (1996).
[Crossref] [PubMed]

Jonas, J. B.

S. Panda-Jonas, J. B. Jonas, and M. Jakobczyk-Zmija, “Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes,” Am. J. Ophthalmol. 121(2), 181–189 (1996).
[Crossref] [PubMed]

Jung, H.

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

Kalina, R. E.

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

Kar, T.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Keilhauer, C. N.

C. N. Keilhauer and F. C. Delori, “Near-Infrared Autofluorescence Imaging of the Fundus: Visualization of Ocular Melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

Kellner, S.

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 nm) and near-infrared autofluorescence (787 nm) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina 30(1), 6–15 (2010).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

Kellner, U.

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 nm) and near-infrared autofluorescence (787 nm) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina 30(1), 6–15 (2010).
[Crossref] [PubMed]

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

Kocaoglu, O. P.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[Crossref] [PubMed]

Kuo, Y.-H.

L. V. Del Priore, Y.-H. Kuo, and T. H. Tezel, “Age-related changes in human RPE cell density and apoptosis proportion in situ,” Invest. Ophthalmol. Vis. Sci. 43(10), 3312–3318 (2002).
[PubMed]

Langlo, C. S.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Lara, D.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Latchney, L. R.

Leung, I. Y.-F.

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

Li, K. Y.

Liang, J.

Liu, J.

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

Liu, Z.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[Crossref] [PubMed]

McGwin, G.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Merigan, W.

Merigan, W. H.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

Messinger, J. D.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Miller, D. T.

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[Crossref] [PubMed]

J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
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Moore, S. R.

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

Morgan, J. I. W.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

Nakanishi, C.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Neuringer, M.

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

Nizari, S.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Normando, E. M.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Othman, M.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Panda-Jonas, S.

S. Panda-Jonas, J. B. Jonas, and M. Jakobczyk-Zmija, “Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes,” Am. J. Ophthalmol. 121(2), 181–189 (1996).
[Crossref] [PubMed]

Parkins, K.

Parodi, M. B.

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

Porter, J.

Rabbetts, R. B.

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Rangel-Fonseca, P.

Reinholz, F.

Rodieck, R. W.

R. W. Rodieck, “The density recovery profile: A method for the analysis of points in the plane applicable to retinal studies,” Vis. Neurosci. 6(2), 95–111 (1991).
[Crossref] [PubMed]

Roorda, A.

A. Roorda and J. L. Duncan, “Adaptive Optics Ophthalmoscopy,” Annu Rev Vis Sci 1(1), 19–50 (2015).
[Crossref] [PubMed]

A. Roorda, Y. Zhang, and J. L. Duncan, “High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007).
[Crossref] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

K. Y. Li and A. Roorda, “Automated identification of cone photoreceptors in adaptive optics retinal images,” J. Opt. Soc. Am. A 24(5), 1358–1363 (2007).
[Crossref] [PubMed]

Rossi, E. A.

C. E. Granger, D. R. Williams, and E. A. Rossi, “Near-infrared autofluorescence imaging reveals the retinal pigment epithelial mosaic in the living human eye,” Invest. Ophthalmol. Vis. Sci. 58, 3429 (2017).

E. A. Rossi, P. Rangel-Fonseca, K. Parkins, W. Fischer, L. R. Latchney, M. A. Folwell, D. R. Williams, A. Dubra, and M. M. Chung, “In vivo imaging of retinal pigment epithelium cells in age related macular degeneration,” Biomed. Opt. Express 4(11), 2527–2539 (2013).
[Crossref] [PubMed]

Ruether, K.

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

Sandstrom, M. M.

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

Schmitz-Valckenberg, S.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Scoles, D.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, and A. Dubra, “In vivo dark-field imaging of the retinal pigment epithelium cell mosaic,” Biomed. Opt. Express 4(9), 1710–1723 (2013).
[Crossref] [PubMed]

Sloan, K. R.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

Smith, R. T.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Snodderly, D. M.

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

Soldevilla, J. D.

R. C. Watzke, J. D. Soldevilla, and D. R. Trune, “Morphometric analysis of human retinal pigment epithelium: correlation with age and location,” Curr. Eye Res. 12(2), 133–142 (1993).
[Crossref] [PubMed]

Streeten, B. W.

B. W. Streeten, “Development of the human retinal pigment epithelium and the posterior segment,” Arch. Ophthalmol. 81(3), 383–394 (1969).
[Crossref] [PubMed]

Sulai, Y.

Sulai, Y. N.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, and A. Dubra, “In vivo dark-field imaging of the retinal pigment epithelium cell mosaic,” Biomed. Opt. Express 4(9), 1710–1723 (2013).
[Crossref] [PubMed]

Summerfelt, P.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

Swaroop, A.

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Swider, M.

A. V. Cideciyan, M. Swider, and S. G. Jacobson, “Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores,” Invest. Ophthalmol. Vis. Sci. 56(5), 3393–3406 (2015).
[Crossref] [PubMed]

Tam, J.

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

Tarima, S.

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

Tatlipinar, S.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Tezel, T. H.

L. V. Del Priore, Y.-H. Kuo, and T. H. Tezel, “Age-related changes in human RPE cell density and apoptosis proportion in situ,” Invest. Ophthalmol. Vis. Sci. 43(10), 3312–3318 (2002).
[PubMed]

Trune, D. R.

R. C. Watzke, J. D. Soldevilla, and D. R. Trune, “Morphometric analysis of human retinal pigment epithelium: correlation with age and location,” Curr. Eye Res. 12(2), 133–142 (1993).
[Crossref] [PubMed]

Ts’o, M. O.

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. III. growth and development,” Arch. Ophthalmol. 80(2), 214–216 (1968).
[Crossref] [PubMed]

Tufail, A.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Tumbar, R.

Twietmeyer, T. H.

Unal, M.

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Watzke, R. C.

R. C. Watzke, J. D. Soldevilla, and D. R. Trune, “Morphometric analysis of human retinal pigment epithelium: correlation with age and location,” Curr. Eye Res. 12(2), 133–142 (1993).
[Crossref] [PubMed]

Weber, B. H. F.

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

Wegener, A. R.

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

Weinitz, S.

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 nm) and near-infrared autofluorescence (787 nm) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina 30(1), 6–15 (2010).
[Crossref] [PubMed]

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

Weiter, J. J.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

Wilk, M. A.

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

Williams, D. R.

Wolfe, R.

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

Wolfing, J. I.

Wu, G.

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

Zhang, T.

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

Zhang, Y.

A. Roorda, Y. Zhang, and J. L. Duncan, “High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007).
[Crossref] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

Zucker, C. L.

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

Am. J. Ophthalmol. (4)

S. Kellner, U. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and Melanin-related Fundus Autofluorescence in Patients with ABCA4-associated Retinal Dystrophies,” Am. J. Ophthalmol. 147(5), 895–902 (2009).
[Crossref] [PubMed]

M. B. Parodi, P. Iacono, C. Del Turco, and F. Bandello, “Near-Infrared Fundus Autofluorescence in Subclinical Best Vitelliform Macular Dystrophy,” Am. J. Ophthalmol. 158(6), 1247–1252 (2014).
[Crossref] [PubMed]

S. Panda-Jonas, J. B. Jonas, and M. Jakobczyk-Zmija, “Retinal Pigment Epithelial Cell Count, Distribution, and Correlations in Normal Human Eyes,” Am. J. Ophthalmol. 121(2), 181–189 (1996).
[Crossref] [PubMed]

L. Feeney-Burns, R. P. Burns, and C.-L. Gao, “Age-related macular changes in humans over 90 years old,” Am. J. Ophthalmol. 109(3), 265–278 (1990).
[Crossref] [PubMed]

Annu Rev Vis Sci (1)

A. Roorda and J. L. Duncan, “Adaptive Optics Ophthalmoscopy,” Annu Rev Vis Sci 1(1), 19–50 (2015).
[Crossref] [PubMed]

Arch. Ophthalmol. (2)

M. O. Ts’o and E. Friedman, “The retinal pigment epithelium. III. growth and development,” Arch. Ophthalmol. 80(2), 214–216 (1968).
[Crossref] [PubMed]

B. W. Streeten, “Development of the human retinal pigment epithelium and the posterior segment,” Arch. Ophthalmol. 81(3), 383–394 (1969).
[Crossref] [PubMed]

Biomed. Opt. Express (3)

Br. J. Ophthalmol. (2)

S. Schmitz-Valckenberg, D. Lara, S. Nizari, E. M. Normando, L. Guo, A. R. Wegener, A. Tufail, F. W. Fitzke, F. G. Holz, and M. F. Cordeiro, “Localisation and significance of in vivo near-infrared autofluorescent signal in retinal imaging,” Br. J. Ophthalmol. 95(8), 1134–1139 (2011).
[Crossref] [PubMed]

A. Ayata, S. Tatlipinar, T. Kar, M. Unal, D. Ersanli, and A. H. Bilge, “Near-infrared and short-wavelength autofluorescence imaging in central serous chorioretinopathy,” Br. J. Ophthalmol. 93(1), 79–82 (2009).
[Crossref] [PubMed]

Curr. Eye Res. (1)

R. C. Watzke, J. D. Soldevilla, and D. R. Trune, “Morphometric analysis of human retinal pigment epithelium: correlation with age and location,” Curr. Eye Res. 12(2), 133–142 (1993).
[Crossref] [PubMed]

Eye (Lond.) (1)

U. Kellner, S. Kellner, B. H. F. Weber, B. Fiebig, S. Weinitz, and K. Ruether, “Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa,” Eye (Lond.) 23(6), 1349–1359 (2009).
[Crossref] [PubMed]

Invest. Ophthalmol. Vis. Sci. (17)

C. N. Keilhauer and F. C. Delori, “Near-Infrared Autofluorescence Imaging of the Fundus: Visualization of Ocular Melanin,” Invest. Ophthalmol. Vis. Sci. 47(8), 3556–3564 (2006).
[Crossref] [PubMed]

A. Roorda, Y. Zhang, and J. L. Duncan, “High-Resolution In Vivo Imaging of the RPE Mosaic in Eyes with Retinal Disease,” Invest. Ophthalmol. Vis. Sci. 48(5), 2297–2303 (2007).
[Crossref] [PubMed]

Z. Liu, O. P. Kocaoglu, and D. T. Miller, “3D Imaging of Retinal Pigment Epithelial Cells in the Living Human Retina,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT533 (2016).
[Crossref] [PubMed]

J. I. W. Morgan, A. Dubra, R. Wolfe, W. H. Merigan, and D. R. Williams, “In Vivo Autofluorescence Imaging of the Human and Macaque Retinal Pigment Epithelial Cell Mosaic,” Invest. Ophthalmol. Vis. Sci. 50(3), 1350–1359 (2009).
[Crossref] [PubMed]

J. Tam, J. Liu, A. Dubra, and R. Fariss, “In Vivo Imaging of the Human Retinal Pigment Epithelial Mosaic Using Adaptive Optics Enhanced Indocyanine Green Ophthalmoscopy,” Invest. Ophthalmol. Vis. Sci. 57(10), 4376–4384 (2016).
[Crossref] [PubMed]

C. E. Granger, D. R. Williams, and E. A. Rossi, “Near-infrared autofluorescence imaging reveals the retinal pigment epithelial mosaic in the living human eye,” Invest. Ophthalmol. Vis. Sci. 58, 3429 (2017).

J. Liu, H. Jung, A. Dubra, and J. Tam, “Automated Photoreceptor Cell Identification on Nonconfocal Adaptive Optics Images Using Multiscale Circular Voting,” Invest. Ophthalmol. Vis. Sci. 58(11), 4477–4489 (2017).

T. Ach, C. Huisingh, G. McGwin, J. D. Messinger, T. Zhang, M. J. Bentley, D. B. Gutierrez, Z. Ablonczy, R. T. Smith, K. R. Sloan, and C. A. Curcio, “Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium,” Invest. Ophthalmol. Vis. Sci. 55(8), 4832–4841 (2014).
[Crossref] [PubMed]

H. Gao and J. G. Hollyfield, “Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells,” Invest. Ophthalmol. Vis. Sci. 33(1), 1–17 (1992).
[PubMed]

A. M. Harman, P. A. Fleming, R. V. Hoskins, and S. R. Moore, “Development and aging of cell topography in the human retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 38(10), 2016–2026 (1997).
[PubMed]

L. V. Del Priore, Y.-H. Kuo, and T. H. Tezel, “Age-related changes in human RPE cell density and apoptosis proportion in situ,” Invest. Ophthalmol. Vis. Sci. 43(10), 3312–3318 (2002).
[PubMed]

C. K. Dorey, G. Wu, D. Ebenstein, A. Garsd, and J. J. Weiter, “Cell loss in the aging retina. Relationship to lipofuscin accumulation and macular degeneration,” Invest. Ophthalmol. Vis. Sci. 30(8), 1691–1699 (1989).
[PubMed]

R. F. Cooper, M. A. Wilk, S. Tarima, and J. Carroll, “Evaluating Descriptive Metrics of the Human Cone Mosaic,” Invest. Ophthalmol. Vis. Sci. 57(7), 2992–3001 (2016).
[Crossref] [PubMed]

J. L. Duncan, Y. Zhang, J. Gandhi, C. Nakanishi, M. Othman, K. E. H. Branham, A. Swaroop, and A. Roorda, “High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration,” Invest. Ophthalmol. Vis. Sci. 48(7), 3283–3291 (2007).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

D. M. Snodderly, M. M. Sandstrom, I. Y.-F. Leung, C. L. Zucker, and M. Neuringer, “Retinal pigment epithelial cell distribution in central retina of rhesus monkeys,” Invest. Ophthalmol. Vis. Sci. 43(9), 2815–2818 (2002).
[PubMed]

A. V. Cideciyan, M. Swider, and S. G. Jacobson, “Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores,” Invest. Ophthalmol. Vis. Sci. 56(5), 3393–3406 (2015).
[Crossref] [PubMed]

J. Comp. Neurol. (1)

C. A. Curcio, K. R. Sloan, R. E. Kalina, and A. E. Hendrickson, “Human photoreceptor topography,” J. Comp. Neurol. 292(4), 497–523 (1990).
[Crossref] [PubMed]

J. Opt. Soc. Am. A (2)

Ophthalmic Physiol. Opt. (1)

A. G. Bennett and R. B. Rabbetts, “Proposals for new reduced and schematic eyes,” Ophthalmic Physiol. Opt. 9(2), 228–230 (1989).
[Crossref] [PubMed]

Opt. Express (1)

Prog. Retinal Res. (1)

M. Boulton, “Ageing of the retinal pigment epithelium,” Prog. Retinal Res. 11, 125–151 (1991).
[Crossref]

Retina (1)

U. Kellner, S. Kellner, and S. Weinitz, “Fundus autofluorescence (488 nm) and near-infrared autofluorescence (787 nm) visualize different retinal pigment epithelium alterations in patients with age-related macular degeneration,” Retina 30(1), 6–15 (2010).
[Crossref] [PubMed]

Vis. Neurosci. (1)

R. W. Rodieck, “The density recovery profile: A method for the analysis of points in the plane applicable to retinal studies,” Vis. Neurosci. 6(2), 95–111 (1991).
[Crossref] [PubMed]

Vision Res. (1)

M. A. Wilk, A. M. Dubis, R. F. Cooper, P. Summerfelt, A. Dubra, and J. Carroll, “Assessing the spatial relationship between fixation and foveal specializations,” Vision Res. 132, 53–61 (2017).
[Crossref] [PubMed]

Other (6)

ANSI Z136.1 - 2014 (American National Standard for Safe Use of Lasers, Laser Institute of America, 2014).

J. Liu, A. Dubra, and J. Tam, “Computer-aided detection of human cone photoreceptor inner segments using multi-scale circular voting,” in G. D. Tourassi and S. G. Armato, eds. Proc. SPIE 9785, Medical Imaging 2016: Computer-Aided Diagnosis (2016), p. 97851A.

J. Liu, A. Dubra, and J. Tam, “A fully automatic framework for cell segmentation on non-confocal adaptive optics images,” in G. D. Tourassi and S. G. Armato, eds. Proc. SPIE 9785, Medical Imaging 2016: Computer-Aided Diagnosis (2016), p. 97852J.

J. Tam, M. Droettboom, J. Liu, and H. Jung, “Noninvasive infrared autofluorescence imaging of intrinsic fluorophores in the human retina at cellular-level resolution using adaptive optics,” Opt. Soc. Am. Bio-Opt. Des. Appl. JTu5A.1 (2017).

R. J. Zawadzki and D. T. Miller, “Retinal AO OCT,” in Optical Coherence Tomography, W. Drexler and J. G. Fujimoto, eds. (Springer International Publishing, 2015), pp. 1849–1920.

A. Dubra and Z. Harvey, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, B. Fischer, B. M. Dawant, and C. Lorenz, eds., Lecture Notes in Computer Science No. 6204 (Springer Berlin Heidelberg, 2010), pp. 60–71.

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Figures (6)

Fig. 1
Fig. 1

Comparison of conventional IRAF to AO-IRAF for a patient with retinitis pigmentosa. (A) Conventional IRAF image acquired using a Heidelberg Spectralis. Black outline shows the location where AO-IRAF images were taken. (B) AO-IRAF montage (inside larger black outline) overlaid on the conventional IRAF image. Scale bar, 0.5 mm. (C-H) Zooms of three areas outlined by the small black squares in (B) comparing conventional IRAF (C,E,G) to AO-IRAF (D,F,H). Scale bar, 100 µm. The RPE mosaic is visible in (D) and (F) in some portions of the image. Additional details about hypofluorescent areas can be observed using AO-IRAF (arrows). The hyperfluorescent ring in (A) is less visible in (B) due to the stretching of each individual image within the AO-IRAF montage, an artifact of montaging.

Fig. 2
Fig. 2

Comparison of foveal RPE cells imaged using (A) AO-IRAF and (B) darkfield in subject 10. Images were simultaneously acquired and are exactly registered with each other. (C) False color image showing the AO-IRAF image in green and darkfield image in red. Outlines of RPE cells are colocalized with each other. Scale bar, 50 µm.

Fig. 3
Fig. 3

The RPE mosaic can be visualized across the temporal meridian using AO-IRAF acquired using short exposures (this montage was constructed from 145 overlapping videos, each with an acquisition time of 9 seconds; subject 7). There are some small patches of hypofluorescence throughout the retina which were also visualized in many of the other healthy subjects (arrows). One small area which was not covered during AO imaging (circle). Scale bars: 200 µm (top), 50 µm (bottom).

Fig. 4
Fig. 4

Comparison of AO-IRAF-based measurements of RPE cell density and cell-to-cell spacing (black) with previously-published data from in vivo (umber color) and ex vivo (persimmon color) studies. Symbols denote the mean value averaged over all subjects from each study, and error bars show standard deviation. For comparison, published data with a mean age less than 50 years were selected wherever possible, with the exceptions of Feeney-Burns (mean age 58.9 ± 7.4 years) and Panda-Jonas (58.6 ± 18 years). The region showing the range (within 1 SD) of all published data combined is delineated by the gray dashed lines. (A) RPE density measurements. (B) RPE cell-to-cell spacing measurements. Note that only direct measurements of spacing are included, and in particular no spacing values are inferred from density based on the assumption of a perfectly triangularly-packed mosaic, due to the previously-reported decrease in regularity at the peripheral locations [14]. (C) The subset of regions with a contiguous array of RPE cells that could be identified for this analysis is shown in green; areas that were imaged but not analyzable are labeled with small dashed lines. Retinal locations that were not imaged are shown in gray.

Fig. 5
Fig. 5

Relationship between RPE cells visualized using AO-IRAF (A,B,E,F) and overlying cone photoreceptors visualized using confocal reflectance (C) in the fovea and split detection at eccentric locations (G), illustrated in subject 3. Panels (B) and (F) depict ROIs selected for analysis from (A) and (E), with Voronoi boundaries calculated from the estimated cell centers overlaid (white lines indicate the actual Voronoi regions that were used for analysis; black lines, not used). The size of the ROI was further reduced in the fovea (C). Cone identifications were plotted relative to RPE cell voronoi neighborhoods (D,H) to quantify the average number of cone photoreceptors per RPE cell. Scale bar, 50 µm.

Fig. 6
Fig. 6

Relationship between RPE cells and photoreceptor cells along temporal eccentricity from the fovea with previously published data from in vivo (umber color) and ex vivo (persimmon color) human studies as well as from animal studies (blue color). Symbols denote the mean value averaged over all subjects from each study. Error bars represent the standard deviation.

Tables (4)

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Table 1 Overview of Healthy Subjects

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Table 2 RPE cell density in cells/mm2 at different retinal eccentricities.

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Table 3 RPE cell spacing in µm at different retinal eccentricities.

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Table 4 Cone:RPE ratio at different retinal eccentricities.

Metrics