Evaluating changes in pro- and anti-inflammatory mediators in keratoconus following corneal collagen cross-linking: A systematic review
Bibliographic record
Abstract
To investigate the changes in pro- and anti-inflammatory mediators following corneal collagen cross-linking (CXL) in patients with keratoconus (KC). Systematic review. A comprehensive literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Library from inception to September 2024. Eligibility criteria included English studies reporting pre- and post-CXL changes in cytokine, chemokine, matrix metalloproteinase (MMP), and growth factor concentrations in adult patients with KC. The primary endpoint was the change in pro- and anti-inflammatory mediator concentrations following CXL. The secondary endpoint focused on correlations between post-CXL changes in inflammatory mediators and corneal tomography measurements. Descriptive statistics were used to report findings. Six prospective cohort studies were included, encompassing 173 eyes from 168 patients diagnosed with progressive KC. The mean age of participants was 25.3 years, and 69% were male. Three studies reported on cytokine and chemokine levels, demonstrating a significant increase in interleukin-6 (IL-6) concentrations up to three months post-CXL, followed by a decline to levels below pre-CXL at 12 months. Additionally, MMP-9 levels and growth factors, such as nerve growth factor (NGF) and epidermal growth factor (EGF), significantly decreased 12 months post-CXL in two studies, respectively. Significant positive correlations were observed between changes in cytokine levels and tomographic parameters, including keratometry (Ks and Kf) and corneal thickness. IL-6 levels may rise within the first three months post-CXL, followed by a decline to below baseline levels by 12 months. In contrast, MMP-13 concentrations may decrease within days of treatment, and MMP-9 levels may decline after one year. Similarly, both EGF and NGF may show post-CXL reductions, with NGF levels potentially reflecting underlying KC severity. Altogether, these patterns suggest an initial acute inflammatory response, followed by subsequent changes likely associated with the promotion of corneal healing. However, interpretation may be limited by the relatively small number of included studies and heterogeneity in patient severity, sample sizes, sampling methods, assays, and follow-up timepoints. Further research is required to elucidate their role in monitoring treatment response in patients with KC undergoing CXL.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".