title: In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study.
abstract: OBJECTIVE
  The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement.
  
  
  METHODS
  A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n=3), treatment-responsive MGD patients with improved symptoms (n=3) and asymptomatic healthy normals (n=11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured.
  
  
  RESULTS
  Despite clinical improvement (TBUT: 6.4±1.2 s to 10.1±2.1 s, P=0.03; MGYLS: 3.5±0.8 glands to 7.0±1.1 glands, P=0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC=592.6±110.1 cells/mm2 untreated MGD EIC=522.6±104.7 cells/mm2, P=0.69; responsive MGD EIC=194.9±119.4 cells/mm2, P<0.01; normals EIC=123.7±19.2 cells/mm2, P< 0.001), but not the cornea (refractory MGD DC=60.9±28.3 cells/mm2; normals DC=25.9±6.3 cells/mm2; P=0.43). EIC did not correlate with TBUT (Rs=-0.26, P=0.33). OSDI scores correlated with both EIC (Rs=0.76, P<0.001) and TBUT (Rs=-0.69, P<0.01) but not SIC. Intraglandular immune cells were also seen.
  
  
  CONCLUSIONS
  MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy.
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Qazi
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kheirkhah
authors.affiliation: Korb Associates, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Blackie
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cruzat
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Trinidad
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.affiliation: Korb Associates, Boston, MA, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Korb
authors.affiliation: Ocular Surface Imaging Center, Cornea Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: P
authors.identifier: 0000000293132939
authors.initials: P
authors.lastname: Hamrah
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015715:Corneal Edema / Q000209:etiology / Q000473:pathology*; D015352:Dry Eye Syndromes / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008537:Meibomian Glands / Q000378:metabolism*; D008875:Middle Aged; D010865:Pilot Projects; D012189:Retrospective Studies; D013666:Tears / Q000378:metabolism