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Objective <p>The natural history of Graves’ orbitopathy (GO) is believed to be characterized by a late phase of inactivation, possibly related to fibrosis involving orbital tissues. However, to our knowledge, this notion is anecdotal. Thus, the present study aimed to investigate fibrosis in orbital tissues and relate it with the features of GO.</p> Methods <p>This retrospective cohort study included 56 consecutive patients with GO who underwent orbital decompression surgery. Fibronectin, CD3- and CD20-positive cells were detected by immunohistochemistry in orbital tissue samples. Collagen was detected by Masson’s trichrome staining. The primary endpoint was the relationship between staining for fibronectin and duration of GO.</p> Results <p>Staining for fibronectin was observed in 47 patients (83.9%) and correlated inversely with GO duration (P = 0.0014), which was shorter in patients with a positive staining (30&#xa0;months, IQR 15–47.5) than in those with a negative staining (55&#xa0;months, IQR 33–70). In spite of the relationship between fibronectin and GO duration, the clinical activity score (CAS), which correlated inversely with GO duration (R = -0.528; P &lt; 0.0001), was similar in patients with a negative [3.6 (1.4) points] or a positive staining for fibronectin [3.2 (1.6) points; mean difference 0.4; 95%CI from -0.7 to 1.5; P = 0.48]. Unlike fibronectin, collagen did not correlate with GO duration. However, there was a direct correlation between collagen and CAS (R = 0.336; P = 0.041). Staining for collagen was similar in patients with a negative staining for fibronectin [15.6% (8.7–28.4)] and those with a positive staining [14.8% (9.8–24.4); P = 0.79]. By multivariate linear regression analysis, both fibronectin and collagen correlated with CD3-positive (fibronectin: R = 0.565; P = 0.00081; collagen: R = 0.567; P = 0.00049) but not with CD20-positive cells.</p> Conclusions <p>Fibrosis does not seem to be a late event in the natural history of GO and it may be part of the inflammatory process that occurs relatively early in orbital tissues, possibly as an attempt to repair tissue damage. The notion that fibrosis occurs exclusively in a late stage of GO should be revised. Our findings may have implications in GO treatment with anti-fibrotic drugs.</p>

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Markers of fibrosis in orbital tissues from patients graves’ orbitopathy: a retrospective cohort study

  • 期刊论文

  • 发表日期：

    2025年12月23日

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  • Giovanna Rotondo Dottore,
  • Liborio Torregrossa,
  • Elena Sabini,
  • Simone Comi,
  • Giada Cosentino,
  • Maria Novella Maglionico,
  • Chiara Posarelli,
  • Dalì Antonia Ciampa,
  • Francesca Menconi,
  • Lodovica Cristofani Mencacci,
  • Michele Figus,
  • Iacopo Dallan,
  • Ferruccio Santini,
  • Michele Marinò

摘要

Objective

The natural history of Graves’ orbitopathy (GO) is believed to be characterized by a late phase of inactivation, possibly related to fibrosis involving orbital tissues. However, to our knowledge, this notion is anecdotal. Thus, the present study aimed to investigate fibrosis in orbital tissues and relate it with the features of GO.

Methods

This retrospective cohort study included 56 consecutive patients with GO who underwent orbital decompression surgery. Fibronectin, CD3- and CD20-positive cells were detected by immunohistochemistry in orbital tissue samples. Collagen was detected by Masson’s trichrome staining. The primary endpoint was the relationship between staining for fibronectin and duration of GO.

Results

Staining for fibronectin was observed in 47 patients (83.9%) and correlated inversely with GO duration (P = 0.0014), which was shorter in patients with a positive staining (30 months, IQR 15–47.5) than in those with a negative staining (55 months, IQR 33–70). In spite of the relationship between fibronectin and GO duration, the clinical activity score (CAS), which correlated inversely with GO duration (R = -0.528; P < 0.0001), was similar in patients with a negative [3.6 (1.4) points] or a positive staining for fibronectin [3.2 (1.6) points; mean difference 0.4; 95%CI from -0.7 to 1.5; P = 0.48]. Unlike fibronectin, collagen did not correlate with GO duration. However, there was a direct correlation between collagen and CAS (R = 0.336; P = 0.041). Staining for collagen was similar in patients with a negative staining for fibronectin [15.6% (8.7–28.4)] and those with a positive staining [14.8% (9.8–24.4); P = 0.79]. By multivariate linear regression analysis, both fibronectin and collagen correlated with CD3-positive (fibronectin: R = 0.565; P = 0.00081; collagen: R = 0.567; P = 0.00049) but not with CD20-positive cells.

Conclusions

Fibrosis does not seem to be a late event in the natural history of GO and it may be part of the inflammatory process that occurs relatively early in orbital tissues, possibly as an attempt to repair tissue damage. The notion that fibrosis occurs exclusively in a late stage of GO should be revised. Our findings may have implications in GO treatment with anti-fibrotic drugs.