A team of researchers have introduced a novel imaging approach – transmission interference microscopy – that enables high-contrast, cellular-resolution imaging of the cornea and crystalline lens. The findings, published in Nature Communications in August 2025, demonstrate the technique’s clinical potential for diagnostics, surgical planning, and disease monitoring in the anterior segment.
Transmission imaging – long familiar from retroillumination slit-lamp exams first conducted in the 1970s – has until now provided only low-resolution views. To create higher resolution images, the Nature Communications study applied Ernst Abbe’s foundational principles of interference microscopy to achieve cellular detail in the anterior eye, using back-scattered scleral light as a secondary illumination source.
“Although the system was originally designed for corneal imaging, we were pleasantly surprised by how well the exact same design produced images of the crystalline lens,” says study co-author Viacheslav Mazlin, a postdoctoral researcher at the Langevin Institute, Paris.
To test their novel technique, the researchers performed in vivo imaging on four healthy volunteers and two patients with anterior eye disease. Using the technique they were able to see all layers of the corneal epithelium, visualize the sub-basal nerve plexus and immune cells, and count endothelial cells across a much larger field of view (FOV) than standard specular microscopy. “Pathological eyes often exhibited stronger contrast than healthy ones,” notes Mazlin. “For example, Fuchs’ guttae stood out clearly.”
The study indicates that transmission interference microscopy could hold promise across several domains:
Pre-surgical screening: Larger FOV endothelial counts may improve risk stratification for cataract/refractive procedures and avoid overlooking guttate-affected regions.
Disease diagnostics: Potential applications in Fuchs’ dystrophy, dry eye disease, keratoconus, and corneal infections – without the need for corneal contact or scraping.
Therapeutic monitoring: Non-invasive quantification of corneal nerves could provide reproducible endpoints for trials of nerve growth factor (NGF) drops and other emerging therapies.
Global eye health: Low-cost instrumentation and robust design make it suitable for screening in resource-limited settings, where anterior eye diseases are highly prevalent.
“As a high-resolution imaging method, this technique could potentially serve as a direct replacement for existing specular and confocal microscopy,” Mazlin states. “We envision it fitting into workflows alongside OCT: the OCT provides a global overview, while our instrument offers a detailed, local, and quantitative view for a more complete picture of anterior eye health.”
Alongside diagnosing conditions such as Fuchs’ endothelial corneal dystrophy (FECD), the researchers believe that a number of other ophthalmic conditions could benefit from transmission interference microscopy. “As this is a new method, we are excited to explore which other biomarkers become accessible,” says Mazlin. “For instance, quantifying corneal nerve density could help in staging dry eye disease, how it was previously demonstrated with confocal microscopy. Similarly, the quantification of dendritic cells might serve as an ‘inflammatory thermometer’ for the cornea. Keratoconus, other corneal dystrophies, and infections are natural early targets for clinical studies. Finally, the crystalline lens has not been widely explored at such high resolution before; this could yield new insights into the microstructural changes underlying cataract development.”
Because it’s a new modality, Mazlin does warn that interpreting the images will require additional training for ophthalmologists. However, he adds that “clinicians familiar with confocal microscopy should find the transition relatively straightforward: the cellular structures are similar, the field of view is larger, and there is no need for contact-imaging procedures.” He also believes that AI-driven analysis will become integral to the technology’s diagnostic potential: “Automated quantification of cellular and nerve densities can relieve orthoptists from tedious manual counts. AI can also be used for image enhancement and denoising, as we have previously demonstrated with Full-field OCT technologies developed in our lab. Finally, with a large enough dataset, AI could help directly forecast disease progression and patient outcomes even from the subtle cellular changes.”
By exploiting the eye’s own sclera as a light source, it does seem that transmission interference microscopy delivers a non-contact, affordable, and versatile method for anterior segment imaging. Its ability to capture corneal and lenticular microstructure over an extended field could complement or, in certain contexts, supplant existing modalities – expanding diagnostic reach and reducing existing barriers to care.
Transmission imaging – long familiar from retroillumination slit-lamp exams first conducted in the 1970s – has until now provided only low-resolution views. To create higher resolution images, the Nature Communications study applied Ernst Abbe’s foundational principles of interference microscopy to achieve cellular detail in the anterior eye, using back-scattered scleral light as a secondary illumination source.
“Although the system was originally designed for corneal imaging, we were pleasantly surprised by how well the exact same design produced images of the crystalline lens,” says study co-author Viacheslav Mazlin, a postdoctoral researcher at the Langevin Institute, Paris.
To test their novel technique, the researchers performed in vivo imaging on four healthy volunteers and two patients with anterior eye disease. Using the technique they were able to see all layers of the corneal epithelium, visualize the sub-basal nerve plexus and immune cells, and count endothelial cells across a much larger field of view (FOV) than standard specular microscopy. “Pathological eyes often exhibited stronger contrast than healthy ones,” notes Mazlin. “For example, Fuchs’ guttae stood out clearly.”
The study indicates that transmission interference microscopy could hold promise across several domains:
Pre-surgical screening: Larger FOV endothelial counts may improve risk stratification for cataract/refractive procedures and avoid overlooking guttate-affected regions.
Disease diagnostics: Potential applications in Fuchs’ dystrophy, dry eye disease, keratoconus, and corneal infections – without the need for corneal contact or scraping.
Therapeutic monitoring: Non-invasive quantification of corneal nerves could provide reproducible endpoints for trials of nerve growth factor (NGF) drops and other emerging therapies.
Global eye health: Low-cost instrumentation and robust design make it suitable for screening in resource-limited settings, where anterior eye diseases are highly prevalent.
“As a high-resolution imaging method, this technique could potentially serve as a direct replacement for existing specular and confocal microscopy,” Mazlin states. “We envision it fitting into workflows alongside OCT: the OCT provides a global overview, while our instrument offers a detailed, local, and quantitative view for a more complete picture of anterior eye health.”
Alongside diagnosing conditions such as Fuchs’ endothelial corneal dystrophy (FECD), the researchers believe that a number of other ophthalmic conditions could benefit from transmission interference microscopy. “As this is a new method, we are excited to explore which other biomarkers become accessible,” says Mazlin. “For instance, quantifying corneal nerve density could help in staging dry eye disease, how it was previously demonstrated with confocal microscopy. Similarly, the quantification of dendritic cells might serve as an ‘inflammatory thermometer’ for the cornea. Keratoconus, other corneal dystrophies, and infections are natural early targets for clinical studies. Finally, the crystalline lens has not been widely explored at such high resolution before; this could yield new insights into the microstructural changes underlying cataract development.”
Because it’s a new modality, Mazlin does warn that interpreting the images will require additional training for ophthalmologists. However, he adds that “clinicians familiar with confocal microscopy should find the transition relatively straightforward: the cellular structures are similar, the field of view is larger, and there is no need for contact-imaging procedures.” He also believes that AI-driven analysis will become integral to the technology’s diagnostic potential: “Automated quantification of cellular and nerve densities can relieve orthoptists from tedious manual counts. AI can also be used for image enhancement and denoising, as we have previously demonstrated with Full-field OCT technologies developed in our lab. Finally, with a large enough dataset, AI could help directly forecast disease progression and patient outcomes even from the subtle cellular changes.”
By exploiting the eye’s own sclera as a light source, it does seem that transmission interference microscopy delivers a non-contact, affordable, and versatile method for anterior segment imaging. Its ability to capture corneal and lenticular microstructure over an extended field could complement or, in certain contexts, supplant existing modalities – expanding diagnostic reach and reducing existing barriers to care.
