Evidence map›Paper›PMID 35044454›Full record

ReviewInvestigative ophthalmology & visual science2022

Corneal Opacity: Cell Biological Determinants of the Transition From Transparency to Transient Haze to Scarring Fibrosis, and Resolution, After Injury.

Steven E Wilson, Lycia Pedral Sampaio, Thomas Michael Shiju, Guilherme S L Hilgert, Rodrigo Carlos de Oliveira

Registry-linked trialOpen access · goldAbstract readReview
In one paragraph

Review in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07449000 (Topical Losartan as Treatment to Reduce Corneal Scarring Fibrosis), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT07449000 narecruitingnot on this mapstarted 2026, after this paper: background citation

Topical Losartan as Treatment to Reduce Corneal Scarring Fibrosis

TypeinterventionalSponsorUniversidad Autonoma de Nuevo LeonRan2026 to 2027Enrolled46ConditionsCorneal Scarring FibrosisArmsTopical losartan, Placebo Control
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Topical losartan ophthalmic drops - a review of corneal wound healing and topical losartan for managing corneal haze and potential future indications.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025
    Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Soluble Epoxide Hydrolase Inhibitors Improve Cornea Alkali Wound Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  8. Article
  9. Article
  10. Long-Term Tolerability and Safety of AAV5-Id3 Gene Therapy to Eyes.Translational vision science & technology · 2026
    Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Steven E WilsonCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States.
Lycia Pedral SampaioCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States.
Thomas Michael ShijuCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States.
Guilherme S L HilgertCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States.
Rodrigo Carlos de OliveiraDepartment of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil.
Cleveland Clinic · USUniversidade de São Paulo · BRCleveland Eye Clinic · US

Funding

RESOURCE/SERVICE CORE C - MOLECULAR INFORMATICS MODULEP30EY025585 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI BELA ANAND-APTE · 2016 to 2026
$7.7M
NEI NIH HHS P30 EY025585
6 · The paper itself

Abstract

Purpose: To highlight the cellular, matrix, and hydration changes associated with opacity that occurs in the corneal stroma after injury. Methods: Review of the literature. Results: The regulated transition of keratocytes to corneal fibroblasts and myofibroblasts, and of bone marrow-derived fibrocytes to myofibroblasts, is in large part modulated by transforming growth factor beta (TGFβ) entry into the stroma after injury to the epithelial basement membrane (EBM) and/or Descemet's membrane. The composition, stoichiometry, and organization of the stromal extracellular matrix components and water is altered by corneal fibroblast and myofibroblast production of large amounts of collagen type I and other extracellular matrix components-resulting in varying levels of stromal opacity, depending on the intensity of the healing response. Regeneration of EBM and/or Descemet's membrane, and stromal cell production of non-EBM collagen type IV, reestablishes control of TGFβ entry and activity, and triggers TGFβ-dependent myofibroblast apoptosis. Eventually, corneal fibroblasts also disappear, and repopulating keratocytes reorganize the disordered extracellular matrix to reestablish transparency. Conclusions: Injuries to the cornea produce varying amounts of corneal opacity depending on the magnitude of cellular and molecular responses to injury. The EBM and Descemet's membrane are key regulators of stromal cellularity through their modulation of TGFβ. After injury to the cornea, depending on the severity of the insult, and possibly genetic factors, trace opacity to severe scarring fibrosis develops. Stromal cellularity, and the functions of different cell types, are the major determinants of the level of the stromal opacity.

Indexed as

Wound HealingAnimalsApoptosisBasement MembraneCicatrixCorneal InjuriesCorneal OpacityEpithelium, CornealFibrosisHumans

Identifiers

PMID35044454
PMCPMC8787546
OpenAlexW4205583174

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.