Transmission interference microscopy of anterior human eye

Abstract Cellular imaging of the human anterior eye is critical for understanding complex ophthalmic diseases, yet current techniques are constrained by a limited field of view or insufficient contrast. Here, we demonstrate that Ernst Abbe’s foundational principles on the interference nature of tran...

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Main Authors: Samer Alhaddad, Wajdene Ghouali, Christophe Baudouin, Albert Claude Boccara, Viacheslav Mazlin
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62718-6
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author Samer Alhaddad
Wajdene Ghouali
Christophe Baudouin
Albert Claude Boccara
Viacheslav Mazlin
author_facet Samer Alhaddad
Wajdene Ghouali
Christophe Baudouin
Albert Claude Boccara
Viacheslav Mazlin
author_sort Samer Alhaddad
collection DOAJ
description Abstract Cellular imaging of the human anterior eye is critical for understanding complex ophthalmic diseases, yet current techniques are constrained by a limited field of view or insufficient contrast. Here, we demonstrate that Ernst Abbe’s foundational principles on the interference nature of transmission microscopy can be applied in vivo to the human eye to overcome these limitations. The transmission geometry in the eye is achieved by projecting illumination onto the posterior eye (sclera) and using the back-reflected light as a secondary illumination source for anterior eye structures. Specifically, we show that the tightly localized illumination spot at the sclera functions analogously to a closed condenser aperture in conventional microscopy, significantly enhancing interference contrast. This enables clear visualization of cells and nerves across all corneal layers within an extended 2 mm field of view. Notably, the crystalline lens epithelial cells, fibers, and sutures are also distinctly resolved. In patients, Fuch’s endothelial dystrophy - a major ophthalmic disease affecting 300 million people - is highlighted under a transmission contrast, providing complementary information to traditional reflection contrast. Constructed using consumer-grade cameras, the instrument offers a path toward broad adoption for pre-screening and surgical follow-up, as well as for diagnosing corneal infections in low-resource settings, where anterior eye diseases are most prevalent.
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spelling doaj-art-f027af6eb6954ccdad7cfdab418dc81e2025-08-24T11:37:09ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-62718-6Transmission interference microscopy of anterior human eyeSamer Alhaddad0Wajdene Ghouali1Christophe Baudouin2Albert Claude Boccara3Viacheslav Mazlin4Institut Langevin, ESPCI Paris, Université PSL, CNRSQuinze-Vingts National Ophthalmology HospitalQuinze-Vingts National Ophthalmology HospitalInstitut Langevin, ESPCI Paris, Université PSL, CNRSInstitut Langevin, ESPCI Paris, Université PSL, CNRSAbstract Cellular imaging of the human anterior eye is critical for understanding complex ophthalmic diseases, yet current techniques are constrained by a limited field of view or insufficient contrast. Here, we demonstrate that Ernst Abbe’s foundational principles on the interference nature of transmission microscopy can be applied in vivo to the human eye to overcome these limitations. The transmission geometry in the eye is achieved by projecting illumination onto the posterior eye (sclera) and using the back-reflected light as a secondary illumination source for anterior eye structures. Specifically, we show that the tightly localized illumination spot at the sclera functions analogously to a closed condenser aperture in conventional microscopy, significantly enhancing interference contrast. This enables clear visualization of cells and nerves across all corneal layers within an extended 2 mm field of view. Notably, the crystalline lens epithelial cells, fibers, and sutures are also distinctly resolved. In patients, Fuch’s endothelial dystrophy - a major ophthalmic disease affecting 300 million people - is highlighted under a transmission contrast, providing complementary information to traditional reflection contrast. Constructed using consumer-grade cameras, the instrument offers a path toward broad adoption for pre-screening and surgical follow-up, as well as for diagnosing corneal infections in low-resource settings, where anterior eye diseases are most prevalent.https://doi.org/10.1038/s41467-025-62718-6
spellingShingle Samer Alhaddad
Wajdene Ghouali
Christophe Baudouin
Albert Claude Boccara
Viacheslav Mazlin
Transmission interference microscopy of anterior human eye
Nature Communications
title Transmission interference microscopy of anterior human eye
title_full Transmission interference microscopy of anterior human eye
title_fullStr Transmission interference microscopy of anterior human eye
title_full_unstemmed Transmission interference microscopy of anterior human eye
title_short Transmission interference microscopy of anterior human eye
title_sort transmission interference microscopy of anterior human eye
url https://doi.org/10.1038/s41467-025-62718-6
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AT wajdeneghouali transmissioninterferencemicroscopyofanteriorhumaneye
AT christophebaudouin transmissioninterferencemicroscopyofanteriorhumaneye
AT albertclaudeboccara transmissioninterferencemicroscopyofanteriorhumaneye
AT viacheslavmazlin transmissioninterferencemicroscopyofanteriorhumaneye