ArticlePloS one2018
Collagen cross-linking impact on keratoconus extracellular matrix.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.PloS one · 2024Pooled it
- Early findings in a randomised controlled trial on crosslinking protocols using isoosmolar and hypoosmolar riboflavin for the treatment of progressive keratoconus.Acta ophthalmologica · 2025Trial
- Early findings in a prospective randomised study on three cross-linking treatment protocols: interruption of the iontophoresis treatment protocol.BMJ open ophthalmology · 2023Trial
- Evaluation of stability and visual quality in Chinese myopic eyes 2 years following FS-LASIK combined with prophylactic corneal crosslinking.BMC ophthalmology · 2026Article
- Construction and characteristics of an adjustable biomechanical in vitro corneal stromal model simulating keratoconus pathological features.Materials today. Bio · 2025Article
- The microenvironment of ocular surface in keratoconus: a systematic review.Eye and vision (London, England) · 2025Review
- Retinal and choroidal changes following corneal collagen cross-linking in keratoconus: a systematic review and meta-analysis of OCT and OCTA studies.International journal of retina and vitreous · 2025Review
- Exosomes in Ocular Health: Recent Insights into Pathology, Diagnostic Applications and Therapeutic Functions.Biomedicines · 2025Review
- Cell sheet-based approach to study the diabetic corneal stroma.Experimental eye research · 2023Article
- Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH.The American journal of pathology · 2023Article
- A review of the epithelial and stromal effects of corneal collagen crosslinking.The ocular surface · 2023Review
- The impact of UV cross-linking on corneal stromal cell migration, differentiation and patterning.Experimental eye research · 2023Article
- Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface.The ocular surface · 2023Review
- Collagen Crosslinking for Keratoconus: Cellular Signaling Mechanisms.Biomolecules · 2023Article
- Unravelling the Impact of Cyclic Mechanical Stretch in Keratoconus-A Transcriptomic Profiling Study.International journal of molecular sciences · 2023Article
- Current clinical practice in corneal crosslinking for treatment of progressive keratoconus in four Nordic countries.Acta ophthalmologica · 2023Article
- Revealing the presence of tear extracellular vesicles in Keratoconus.Experimental eye research · 2022Article
- Comparison of Long-Term Outcomes and Refractive Stability following SMILE versus SMILE Combined with Accelerated Cross-Linking (SMILE XTRA).Journal of ophthalmology · 2022Article
- Identification of Key Genes and Molecular Pathways in Keratoconus: Integrating Text Mining and Bioinformatics Analysis.BioMed research international · 2022Article
- Ultrastructural study of collagen fibrils, proteoglycans and lamellae of the cornea treated with iontophoresis - UVA cross-linking and hypotonic riboflavin solution.Saudi journal of biological sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundKeratoconus (KC) is a common multifactorial ectatic corneal disease with unknown onset. KC most commonly appears in adolescence and affects approximately 1:400 people worldwide. Treatment options, for advanced KC cases, are collagen cross-linking (CXL) and corneal transplants. CXL is a new KC treatment that helps arrest the disease. Unfortunately, only a fraction of KC patients will qualify for CXL treatment. Our goal, in this study, was to begin to understand how CXL affects the corneal microenvironment and pave the way towards a more patient-driven CXL treatment.
methodsPrimary human corneal fibroblasts from healthy and KC donors were plated on transwell polycarbonate membranes and stimulated by a stable vitamin C. At 4 weeks, riboflavin was added followed by UVA irradiation. Transmission Electron Microscopy (TEM) and western blots were used to assess the effect of CXL on the extracellular matrix (ECM) and the resident cells, pre- and post CXL.
resultsData shows CXL improved lamellar organization showing more organized collagen fibrils decorated with proteoglycans (PGs). The distribution of the collagen fibrils and interfibrillar spacing was also visibly improved, post-CXL. Lumican, mimecan, and decorin were the dominant PGs and were significantly upregulated in post-CXL cultures. ECM degradation proteins, matrix metalloproteinases (MMPs), MMP-1, -3, and -9, but not MMP-2, were significantly downregulated post-CXL. TIMP-1 and -2 were not modulated by CXL.
conclusionThe unknown effects of CXL on the human corneal microenvironment have hampered our ability to make CXL available to all KC patients. Our current study provides a deeper understanding on CXL activity, using our unique 3D in vitro model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.