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Laser & Optoelectronics Progress, Volume. 62, Issue 18, 1817007(2025)

Optical Microscopy for Probing Eye Diseases: Technologies, Applications, and Perspectives (Invited)

Bingyao Tan1, Wenjun Xiong2、**, and Qinrong Zhang3、*
Author Affiliations
  • 1Singapore Eye Research Institute, Singapore National Eye Center, Singapore 168751, Singapore
  • 2Department of Biomedical Sciences, College of Biomedicine, City University of Hong Kong, Hong Kong 999077, China
  • 3Department of Biomedical Engineering, College of Biomedicine, City University of Hong Kong, Hong Kong 999077, China
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    [1] Hampson K M, Turcotte R, Miller D T et al. Adaptive optics for high-resolution imaging[J]. Nature Reviews. Methods Primers, 1, 68(2021).

    [2] Cheung C Y, Ikram M K, Chen C et al. Imaging retina to study dementia and stroke[J]. Progress in Retinal and Eye Research, 57, 89-107(2017).

    [3] London A, Benhar I, Schwartz M. The retina as a window to the brain: from eye research to CNS disorders[J]. Nature Reviews Neurology, 9, 44-53(2013).

    [4] Lechner J, O’Leary O E, Stitt A W. The pathology associated with diabetic retinopathy[J]. Vision Research, 139, 7-14(2017).

    [5] Huang D, Swanson E A, Lin C P et al. Optical coherence tomography[J]. Science, 254, 1178-1181(1991).

    [6] Mazlin V, Irsch K, Paques M et al. Curved-field optical coherence tomography: large-field imaging of human corneal cells and nerves[J]. Optica, 7, 872-880(2020).

    [7] Auksorius E, Borycki D, Stremplewski P et al. In vivo imaging of the human cornea with high-speed and high-resolution Fourier-domain full-field optical coherence tomography[J]. Biomedical Optics Express, 11, 2849-2865(2020).

    [8] Han L, Tan B Y, Hosseinaee Z et al. Line-scanning SD-OCT for in-vivo, non-contact, volumetric, cellular resolution imaging of the human cornea and limbus[J]. Biomedical Optics Express, 13, 4007-4020(2022).

    [9] Tan B Y, Hosseinaee Z, Han L et al. 250 kHz, 1.5 µm resolution SD-OCT for in-vivo cellular imaging of the human cornea[J]. Biomedical Optics Express, 9, 6569-6583(2018).

    [10] Yao X W, Devarajan K, Werkmeister R M et al. In vivo corneal endothelium imaging using ultrahigh resolution OCT[J]. Biomedical Optics Express, 10, 5675-5686(2019).

    [11] Mazlin V, Xiao P, Scholler J et al. Real-time non-contact cellular imaging and angiography of human cornea and limbus with common-path full-field/SD OCT[J]. Nature Communications, 11, 1868(2020).

    [12] Hammer D X, Agrawal A, Villanueva R et al. Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics[J]. Proceedings of the National Academy of Sciences of the United States of America, 117, 30661-30669(2020).

    [13] Liu Z L, Kurokawa K, Zhang F R et al. Imaging and quantifying ganglion cells and other transparent neurons in the living human retina[J]. Proceedings of the National Academy of Sciences of the United States of America, 114, 12803-12808(2017).

    [14] Mozaffari S, Feroldi F, LaRocca F et al. Retinal imaging using adaptive optics optical coherence tomography with fast and accurate real-time tracking[J]. Biomedical Optics Express, 13, 5909-5925(2022).

    [15] Kurokawa K, Liu Z L, Miller D T. Adaptive optics optical coherence tomography angiography for morphometric analysis of choriocapillaris[J]. Biomedical Optics Express, 8, 1803-1822(2017).

    [16] Dong Z M, Wollstein G, Wang B et al. Adaptive optics optical coherence tomography in glaucoma[J]. Progress in Retinal and Eye Research, 57, 76-88(2017).

    [17] Pfäffle C, Spahr H, Kutzner L et al. Simultaneous functional imaging of neuronal and photoreceptor layers in living human retina[J]. Optics Letters, 44, 5671-5674(2019).

    [18] Tan B Y, Li H K, Zhuo Y M et al. Light-evoked deformations in rod photoreceptors, pigment epithelium and subretinal space revealed by prolonged and multilayered optoretinography[J]. Nature Communications, 15, 5156(2024).

    [19] Zhang P F, Zawadzki R J, Goswami M et al. In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors[J]. Proceedings of the National Academy of Sciences of the United States of America, 114, E2937-E2946(2017).

    [20] Pandiyan V P, Maloney-Bertelli A, Kuchenbecker J A et al. The optoretinogram reveals the primary steps of phototransduction in the living human eye[J]. Science Advances, 6, eabc1124(2020).

    [21] Hillmann D, Spahr H, Pfäffle C et al. In vivo optical imaging of physiological responses to photostimulation in human photoreceptors[J]. Proceedings of the National Academy of Sciences of the United States of America, 113, 13138-13143(2016).

    [22] Azimipour M, Valente D, Vienola K V et al. Optoretinogram: optical measurement of human cone and rod photoreceptor responses to light[J]. Optics Letters, 45, 4658-4661(2020).

    [23] Tomczewski S, Curatolo A, Foik A et al. Photopic flicker optoretinography captures the light-driven length modulation of photoreceptors during phototransduction[J]. Proceedings of the National Academy of Sciences of the United States of America, 122, e2421722122(2025).

    [24] Zhang F R, Kurokawa K, Lassoued A et al. Cone photoreceptor classification in the living human eye from photostimulation-induced phase dynamics[J]. Proceedings of the National Academy of Sciences of the United States of America, 116, 7951-7956(2019).

    [25] Li H K, Weiss C E, Pandiyan V P et al. Optoretinography reveals rapid rod photoreceptor movement upon photoisomerization[EB/OL]. https://www.biorxiv.org/content/10.1101/2025.03.22.644466v1

    [26] Valente D, Vienola K V, Zawadzki R J et al. Insight into human photoreceptor function: modeling optoretinographic responses to diverse stimuli[J]. Science Advances, 11, eadq7332(2025).

    [27] Lassoued A, Zhang F R, Kurokawa K et al. Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography[J]. Proceedings of the National Academy of Sciences of the United States of America, 118, e2107444118(2021).

    [28] Liu T, Wendel B J, Huey J et al. Longitudinal changes in optoretinography provide an early and sensitive biomarker of outer retinal disease[J]. American Journal of Ophthalmology, 277, 375-386(2025).

    [29] Mertz J[M]. Introduction to optical microscopy(2019).

    [30] Zhang Y, Rózsa M, Liang Y J et al. Fast and sensitive GCaMP calcium indicators for imaging neural populations[J]. Nature, 615, 884-891(2023).

    [31] Feng G, Mellor R H, Bernstein M et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP[J]. Neuron, 28, 41-51(2000).

    [32] Novotny H R, Alvis D L. A method of photographing fluorescence in circulating blood in the human retina[J]. Circulation, 24, 82-86(1961).

    [33] Minsky M. Memoir on inventing the confocal scanning microscope[J]. Scanning, 10, 128-138(1988).

    [34] Egger M D, Petráň M. New reflected-light microscope for viewing unstained brain and ganglion cells[J]. Science, 157, 305-307(1967).

    [35] Göppert-Mayer M. Über elementarakte mit zwei quantensprüngen[J]. Annalen der Physik, 401, 273-294(1931).

    [36] Denk W, Strickler J H, Webb W W. Two-photon laser scanning fluorescence microscopy[J]. Science, 248, 73-76(1990).

    [37] Euler T, Detwiler P B, Denk W. Directionally selective calcium signals in dendrites of starburst amacrine cells[J]. Nature, 418, 845-852(2002).

    [38] Baden T, Berens P, Franke K et al. The functional diversity of retinal ganglion cells in the mouse[J]. Nature, 529, 345-350(2016).

    [39] Biss D P, Sumorok D, Burns S A et al. In vivo fluorescent imaging of the mouse retina using adaptive optics[J]. Optics Letters, 32, 659-661(2007).

    [40] Wahl D J, Zhang P F, Mocci J et al. Adaptive optics in the mouse eye: wavefront sensing based vs. image-guided aberration correction[J]. Biomedical Optics Express, 10, 4757-4774(2019).

    [41] Li L, Feng X, Fang F et al. Longitudinal in vivo Ca2+ imaging reveals dynamic activity changes of diseased retinal ganglion cells at the single-cell level[J]. Proceedings of the National Academy of Sciences of the United States of America, 119, e2206829119(2022).

    [42] Zhang Q R, Yang Y H, Cao K J et al. Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy[J]. eLife, 12, e84853(2023).

    [43] Palczewska G, Dong Z Q, Golczak M et al. Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye[J]. Nature Medicine, 20, 785-789(2014).

    [44] Qin Z Y, He S C, Yang C et al. Adaptive optics two-photon microscopy enables near-diffraction-limited and functional retinal imaging in vivo[J]. Light: Science & Applications, 9, 79(2020).

    [45] Paidi S K, Zhang Q R, Yang Y H et al. Adaptive optical two-photon fluorescence microscopy probes cellular organization of ocular lenses in vivo[J]. Investigative Ophthalmology & Visual Science, 64, 20(2023).

    [46] Chen X Y, Nadiarynkh O, Plotnikov S et al. Second harmonic generation microscopy for quantitative analysis of collagen fibrillar structure[J]. Nature Protocols, 7, 654-669(2012).

    [47] Johnson A W, Ammar D A, Kahook M Y. Two-photon imaging of the mouse eye[J]. Investigative Opthalmology & Visual Science, 52, 4098-4105(2011).

    [48] Sharoukhov D, Bucinca-Cupallari F, Lim H. Microtubule imaging reveals cytoskeletal deficit predisposing the retinal ganglion cell axons to atrophy in DBA/2J[J]. Investigative Ophthalmology & Visual Science, 59, 5292-5300(2018).

    [49] Han M, Giese G, Bille J F. Second harmonic generation imaging of collagen fibrils in cornea and sclera[J]. Optics Express, 13, 5791-5797(2005).

    [50] Raoux C, Chessel A, Mahou P et al. Unveiling the lamellar structure of the human cornea over its full thickness using polarization-resolved SHG microscopy[J]. Light: Science & Applications, 12, 190(2023).

    [51] Raoux C, Schmeltz M, Bied M et al. Quantitative structural imaging of keratoconic corneas using polarization-resolved SHG microscopy[J]. Biomedical Optics Express, 12, 4163-4178(2021).

    [52] Robertson D M, Rogers N A, Petroll W M et al. Second harmonic generation imaging of corneal stroma after infection by Pseudomonas aeruginosa[J]. Scientific Reports, 7, 46116(2017).

    [53] Hsueh C M, Lo W, Chen W L et al. Structural characterization of edematous corneas by forward and backward second harmonic generation imaging[J]. Biophysical Journal, 97, 1198-1205(2009).

    [54] Farid M, Morishige N, Lam L et al. Detection of corneal fibrosis by imaging second harmonic-generated signals in rabbit corneas treated with mitomycin C after excimer laser surface ablation[J]. Investigative Ophthalmology & Visual Science, 49, 4377-4383(2008).

    [55] Zyablitskaya M, Takaoka A, Munteanu E L et al. Evaluation of therapeutic tissue crosslinking (TXL) for myopia using second harmonic generation signal microscopy in rabbit sclera[J]. Investigative Ophthalmology & Visual Science, 58, 21-29(2017).

    [56] Sadda S R, Schachat A, Wilkinson C P et al[M]. Ryanʼs retina e-book(2022).

    [57] Ji N. Adaptive optical fluorescence microscopy[J]. Nature Methods, 14, 374-380(2017).

    [58] Zhang Q R, Hu Q, Berlage C et al. Adaptive optics for optical microscopy[J]. Biomedical Optics Express, 14, 1732-1756(2023).

    [59] Williams D R, Burns S A, Miller D T et al. Evolution of adaptive optics retinal imaging[J]. Biomedical Optics Express, 14, 1307-1338(2023).

    [60] Miller D T, Kurokawa K. Cellular-scale imaging of transparent retinal structures and processes using adaptive optics optical coherence tomography[J]. Annual Review of Vision Science, 6, 115-148(2020).

    [61] Kang I, Zhang Q R, Yu S X et al. Coordinate-based neural representations for computational adaptive optics in widefield microscopy[J]. Nature Machine Intelligence, 6, 714-725(2024).

    [62] Wu J M, Lu Z, Jiang D et al. Iterative tomography with digital adaptive optics permits hour-long intravital observation of 3D subcellular dynamics at millisecond scale[J]. Cell, 184, 3318-3332(2021).

    [63] Lu Z, Cai Y Y, Nie Y X et al. A practical guide to scanning light-field microscopy with digital adaptive optics[J]. Nature Protocols, 17, 1953-1979(2022).

    [64] Zhang H Y, Asroui L, Tarib I et al. Motion-tracking Brillouin microscopy evaluation of normal, keratoconic, and post-laser vision correction corneas[J]. American Journal of Ophthalmology, 254, 128-140(2023).

    [65] Weinreb R N, Aung T, Medeiros F A. The pathophysiology and treatment of glaucoma: a review[J]. Jama, 311, 1901-1911(2014).

    [66] Liu Z L, Saeedi O, Zhang F R et al. Quantification of retinal ganglion cell morphology in human glaucomatous eyes[J]. Investigative Ophthalmology & Visual Science, 62, 34(2021).

    [67] Medeiros F A, Jammal A A, Mariottoni E B. Detection of progressive glaucomatous optic nerve damage on fundus photographs with deep learning[J]. Ophthalmology, 128, 383-392(2021).

    [68] El Hajji S, Shiga Y, Belforte N et al. Insulin restores retinal ganglion cell functional connectivity and promotes visual recovery in glaucoma[J]. Science Advances, 10, eadl5722(2024).

    [69] Muench N A, Patel S, Maes M E et al. The influence of mitochondrial dynamics and function on retinal ganglion cell susceptibility in optic nerve disease[J]. Cells, 10, 1593(2021).

    [70] Liang J Z, Williams D R, Miller D T. Supernormal vision and high-resolution retinal imaging through adaptive optics[J]. Journal of the Optical Society of America A, 14, 2884-2892(1997).

    [71] Lammer J, Prager S G, Cheney M C et al. Cone photoreceptor irregularity on adaptive optics scanning laser ophthalmoscopy correlates with severity of diabetic retinopathy and macular edema[J]. Investigative Ophthalmology & Visual Science, 57, 6624-6632(2016).

    [72] Power D, Elstrott J, Schallek J. Photoreceptor loss does not recruit neutrophils despite strong microglial activation[J]. eLife, 13, 98662(2024).

    [73] Dubow M, Pinhas A, Shah N et al. Classification of human retinal microaneurysms using adaptive optics scanning light ophthalmoscope fluorescein angiography[J]. Investigative Ophthalmology & Visual Science, 55, 1299-1309(2014).

    [74] Akyol E, Hagag A M, Sivaprasad S et al. Adaptive optics: principles and applications in ophthalmology[J]. Eye, 35, 244-264(2020).

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    Bingyao Tan, Wenjun Xiong, Qinrong Zhang. Optical Microscopy for Probing Eye Diseases: Technologies, Applications, and Perspectives (Invited)[J]. Laser & Optoelectronics Progress, 2025, 62(18): 1817007

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    Paper Information

    Category: Medical Optics and Biotechnology

    Received: Jul. 23, 2025

    Accepted: Aug. 25, 2025

    Published Online: Sep. 17, 2025

    The Author Email: Wenjun Xiong (wenjun.xiong@cityu.edu.hk), Qinrong Zhang (qzhan32@cityu.edu.hk)

    DOI:10.3788/LOP251737

    CSTR:32186.14.LOP251737

    Topics

    laser devices and laser physics
    Lasers and Laser Optics
    Laser physics
    laser manufacturing
    Instrumentation, Measurement and Metrology