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Original Investigation
November 2017

Genotype-Phenotype Associations of IL6 and PRG4 With Conjunctival Fibrosis After Glaucoma Surgery

Author Affiliations
  • 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and University College London Institute of Ophthalmology, London, England
  • 2Experimental and Personalised Medicine Section, University College London Great Ormond Street Institute of Child Health, London, England
  • 3Department of Mechanical Engineering, University College London, London, England
  • 4Department of Histopathology, Great Ormond Street Hospital for Children National Health Service Foundation Trust, London, England
JAMA Ophthalmol. 2017;135(11):1147-1155. doi:10.1001/jamaophthalmol.2017.3407
Key Points

Question  Are IL6 and PRG4 potential novel tissue biomarkers of conjunctival fibrosis after glaucoma surgery?

Findings  In this cross-sectional study, IL6 expression was upregulated and PRG4 expression was downregulated in fibrotic conjunctiva, and both correlated strongly with the number of glaucoma operations and logMAR visual acuity.

Meaning  These results support IL6 and PRG4 as potential tissue biomarkers of disease severity and prognosis in conjunctival fibrosis after glaucoma surgery; longitudinal studies are needed to validate these biomarkers of fibrosis in the future.

Abstract

Importance  Postsurgical fibrosis is a critical determinant of the long-term success of glaucoma surgery, but no reliable biomarkers are currently available to stratify the risk of scarring.

Objective  To compare the clinical phenotype of patients with conjunctival fibrosis after glaucoma surgery with candidate gene expression tissue biomarkers of fibrosis.

Design, Setting, and Participants  In this cross-sectional study, 42 patients were recruited at the time of glaucoma surgery at the Moorfields Eye Hospital from September 1, 2014, to September 1, 2016. The participants were divided into those with fibrosis and those without fibrosis.

Main Outcomes and Measures  Genotype-phenotype correlations of the IL6 or PRG4 gene and detailed clinical phenotype. The IL6 and PRG4 protein expression in conjunctival tissues was also assessed using in situ immunohistochemical analysis. Central bleb area, maximal bleb area, and bleb height were graded on a scale of 1 to 5 (1 indicating 0%; 2, 25%; 3, 50%; 4, 75%; and 5, 100%). Bleb vascularity was graded on a scale of 1 to 5 (1 indicating avascularity; 2, normal; 3, mild; 4, moderate; and 5, severe hyperemia).

Results  A total of 42 patients were recruited during the study period; 28 participants (67%) had previously undergone glaucoma surgery (fibrotic group) (mean [SD] age, 43.8 [3.6 years]; 16 [57%] female; 22 [79%] white), and 14 participants (33%) had not previously undergone glaucoma surgery (nonfibrotic group) (mean [SD] age, 47.7 [6.9] years; 4 [29%] female; 9 [64%] white). The fibrotic group had marked bleb scarring and vascularization and worse logMAR visual acuity. The mean (SD) grades were 1.4 (0.1) for central bleb area, 1.4 (0.1) for bleb height, and 3.4 (0.2) for bleb vascularity. The IL6 gene was upregulated in fibrotic cell lines (mean, 0.040) compared with nonfibrotic cell lines (mean, 0.011) (difference, 0.029; 95% CI, 0.015-0.043; P = .003). The PRG4 gene was also downregulated in fibrotic cell lines (0.002) compared with nonfibrotic cell lines (mean, 0.109; difference, 0.107; 95% CI, 0.104-0.110; P = .03). The study found a strong correlation between the IL6 gene and the number of glaucoma operations (r = 0.94, P < .001) and logMAR visual acuity (r = 0.64, P = .03). A moderate correlation was found between the PRG4 gene and the number of glaucoma operations (r = −0.72, P = .005) and logMAR visual acuity (r = −0.62, P = .03).

Conclusions and Relevance  IL6 and PRG4 represent potential novel tissue biomarkers of disease severity and prognosis in conjunctival fibrosis after glaucoma surgery. Future longitudinal studies with multiple postoperative measures are needed to validate the effect of these potential biomarkers of fibrosis.

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