title: Conjunctival Neutrophils Predict Progressive Scarring in Ocular Mucous Membrane Pemphigoid.
abstract: OBJECTIVE
  Ocular mucous membrane pemphigoid (OcMMP) is a rare autoimmune disorder resulting in progressive conjunctival fibrosis and ocular surface failure leading to sight loss in up to 50%. This study was designed to optimize an ocular surface sampling technique for identification of novel biomarkers associated with disease activity and/or progressive fibrosis.
  
  
  METHODS
  Fifty-seven patients with OcMMP underwent detailed examination of conjunctival inflammation and fibrosis using fornix depth measurement. Ocular surface impression cytology (OSIC) to sample superior bulbar conjunctiva combined with flow cytometry (OSIC-flow) profiled infiltrating leukocytes. Profiles were compared with healthy controls (HC) and disease controls (primary Sjögren's syndrome, pSS). Thirty-five OcMMP patients were followed every 3 months for 12 months.
  
  
  RESULTS
  Overall neutrophils were elevated in OcMMP eyes when compared to pSS or HC (109 [18%] neutrophils/impression [NPI]; 2 [0.2%]; 6 [0.8%], respectively [P < 0.0001]) and in OcMMP patients with no visible inflammation when compared with HC (44.3 [7.9%]; 5.8 [0.8%]; P < 0.05). At 12 months follow-up, 53% of OcMMP eyes progressed, and this was associated with baseline conjunctival neutrophilia (P = 0.004). As a potential biomarker, a value of 44 NPI had sensitivity, specificity, and positive predictive values of 75%, 70%, and 73%, respectively. Notably, eyes with no visible inflammation and raised conjunctival neutrophils were more likely to progress and have a greater degree of conjunctival shrinkage compared to those without raised neutrophils.
  
  
  CONCLUSIONS
  These data suggest that OSIC-flow cytometric analyses may facilitate repeated patient sampling. Neutrophils may act as a biomarker for monitoring disease activity, progressive fibrosis, and response to therapy in OcMMP even when the eye appears clinically uninflamed.
authors.affiliation: Academic Unit of Ophthalmology, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom 2Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Geraint P
authors.initials: GP
authors.lastname: Williams
authors.affiliation: Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.affiliation: Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Sue
authors.initials: S
authors.lastname: Southworth
authors.affiliation: Academic Unit of Ophthalmology, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom 2Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Alastair K O
authors.initials: AK
authors.lastname: Denniston
authors.affiliation: Academic Unit of Ophthalmology, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom 2Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tomlins
authors.affiliation: Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Turner
authors.affiliation: School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Hamburger
authors.affiliation: Department of Rheumatology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Bowman
authors.affiliation: Academic Unit of Ophthalmology, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: S John
authors.initials: SJ
authors.lastname: Curnow
authors.affiliation: Academic Unit of Ophthalmology, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom 2Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
authors.forename: Saaeha
authors.initials: S
authors.lastname: Rauz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002921:Cicatrix / Q000209:etiology / Q000473:pathology*; D003228:Conjunctiva / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000473:pathology; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D010390:Pemphigoid, Benign Mucous Membrane / Q000150:complications / Q000175:diagnosis*; D013997:Time Factors