Keratoconus Pathogenesis and Management Approaches

Keratoconus is a progressive corneal ectatic disorder characterised by stromal thinning, anterior protrusion and irregular astigmatism leading to visual impairment. Its pathogenesis is multifactorial, involving genetic predisposition, environmental factors such as mechanical eye rubbing and ultraviolet exposure, and biochemical processes including oxidative stress and cytokine-mediated matrix remodelling. Recent insights suggest that dysregulation of matrix metalloproteinases, mitochondrial dysfunction and immune cell infiltration contribute to degradation of Bowman’s layer and disruption of stromal keratocyte homeostasis. Early detection relies on corneal topography, pachymetry and higher-order aberration mapping, while management spans optical correction with spectacles or contact lenses, structural reinforcement by corneal collagen cross-linking and implantation of intracorneal ring segments. Advanced cases may require front- or full-thickness keratoplasty or topography-guided photorefractive techniques. A seamless integration of molecular diagnostics, customised cross-linking protocols and novel imaging is reshaping both preventive and therapeutic strategies, with the aim of halting progression, improving optical quality and preserving long-term corneal integrity.

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Research from all publishers

Integrative single-cell and bulk RNA sequencing analyses have delineated distinct corneal stromal and immune cell subpopulations that drive keratoconus progression through altered cytokine networks and extracellular matrix turnover. These studies have identified prognostic biomarker panels and have yielded predictive nomograms to stratify progression risk. A comprehensive clinical review has updated diagnostic thresholds by combining tomographic indices, epithelial thickness mapping and machine-learning classifiers to detect subclinical forms. This work further refines staging systems and recommends personalised cross-linking regimens based on depth-resolved biomechanical assessment. Foundational genetic investigations have elucidated multiple susceptibility loci through genome-wide association studies and candidate gene analyses, highlighting variants in collagen, antioxidant and signalling pathways. Such discoveries inform familial screening and may underpin future gene-targeted therapies.

Keratoconus Pathogenesis and Management Approaches publication trend

The graph below shows the total number of articles in keratoconus pathogenesis and management approaches across all publications each year (not limited to Nature Index journals).

Technical terms

Corneal ectasia: Progressive bulging and thinning of the cornea resulting in irregular astigmatism and vision loss.

Matrix metalloproteinases (MMPs): Zinc-dependent enzymes that degrade extracellular matrix components and affect corneal structure.

Corneal collagen cross-linking: A photochemical treatment that induces covalent bonds within stromal collagen to increase biomechanical stiffness.

Corneal topography: Non-invasive imaging technique to map the curvature and elevation of the corneal surface for early keratoconus detection.

Stromal keratocyte: Resident fibroblast-like cell in the corneal stroma responsible for maintaining and repairing the extracellular matrix.

References

1. Identification of the immune-associated characteristics and predictive biomarkers of keratoconus based on single-cell RNA-sequencing and bulk RNA-sequencing. Frontiers in Immunology (2023).
2. Keratoconus: An updated review. Contact Lens and Anterior Eye (2022).
3. The Genetic and Environmental Factors for Keratoconus. BioMed Research International (2015).
4. Molecular and Histopathological Changes Associated with Keratoconus. BioMed Research International (2017).
5. Oxidative Stress in the Pathogenesis of Keratoconus and Fuchs Endothelial Corneal Dystrophy. International Journal of Molecular Sciences (2013).
6. Genetics of Keratoconus: Where Do We Stand?. Journal of Ophthalmology (2014).