title: Toluidine Blue 0.05% Vital Staining for the Diagnosis of Ocular Surface Squamous Neoplasia in Kenya.
abstract: OBJECTIVE
  Clinical features are unreliable for distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions.
  
  
  OBJECTIVE
  To evaluate the adverse effects, accuracy, and interobserver variation of toluidine blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions.
  
  
  METHODS
  Cross-sectional study in Kenya from July 2012 through July 2014 of 419 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded.
  
  
  METHODS
  Comprehensive ophthalmic slitlamp examination was conducted. Vital staining with toluidine blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumors scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumors. We asked about pain or discomfort after staining and evaluated the cornea at the slitlamp for epithelial defects. Lesions were photographed before and after staining.
  
  
  METHODS
  Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a subset of 100 consecutive participants for staining and made a diagnosis of OSSN vs non-OSSN. Staining was compared with histopathology to estimate sensitivity, specificity, and predictive values. Adverse effects were enumerated. Interobserver agreement was estimated using the κ statistic.
  
  
  RESULTS
  A total of 143 of 419 participants (34%) had OSSN by histopathology. The median age of all participants was 37 years (interquartile range, 32-45 years) and 278 (66%) were female. A total of 322 of the 419 participants had positive staining while 2 of 419 were equivocal. There was no histological evidence of corneal toxicity. Mild discomfort was reported by 88 (21%) and mild superficial punctate keratopathy seen in 7 (1.7%). For detecting OSSN, toluidine blue had a sensitivity of 92% (95% CI, 87%-96%), specificity of 31% (95% CI, 25%-36%), positive predictive value of 41% (95% CI, 35%-46%), and negative predictive value of 88% (95% CI, 80%-94%). Interobserver agreement was substantial for staining (κ = 0.76) and moderate for diagnosis (κ = 0.40).
  
  
  CONCLUSIONS
  With the high sensitivity and low specificity for OSSN compared with histopathology among patients with conjunctival lesions, toluidine blue 0.05% vital staining is a good screening tool. However, it is not a good diagnostic tool owing to a high frequency of false-positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, England2Department of Ophthalmology, University of Nairobi, Nairobi, Kenya.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gichuhi
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Ephantus
authors.initials: E
authors.lastname: Macharia
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Joy
authors.initials: J
authors.lastname: Kabiru
authors.affiliation: PCEA Kikuyu Eye Unit, Kikuyu, Kenya.
authors.forename: Alain M'bongo
authors.initials: AM
authors.lastname: Zindamoyen
authors.affiliation: Kitale District Hospital, Kitale, Kenya.
authors.forename: Hilary
authors.initials: H
authors.lastname: Rono
authors.affiliation: Sabatia Eye Hospital, Wodanga, Kenya.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ollando
authors.affiliation: Sabatia Eye Hospital, Wodanga, Kenya.
authors.forename: Leonard
authors.initials: L
authors.lastname: Wanyonyi
authors.affiliation: Kenyatta National Hospital, Nairobi, Kenya.
authors.forename: Joseph
authors.initials: J
authors.lastname: Wachira
authors.affiliation: Kenyatta National Hospital, Nairobi, Kenya.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Munene
authors.affiliation: Department of Pathology, MP Shah Hospital, Nairobi, Kenya.
authors.forename: Timothy
authors.initials: T
authors.lastname: Onyuma
authors.affiliation: KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya.
authors.forename: Walter G
authors.initials: WG
authors.lastname: Jaoko
authors.affiliation: University College London Institute of Ophthalmology, London, England10Moorfields Eye Hospital, London, England11St Bartholomew's Hospital, London, England.
authors.forename: Mandeep S
authors.initials: MS
authors.lastname: Sagoo
authors.affiliation: London School of Hygiene and Tropical Medicine, London, England.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.affiliation: London School of Hygiene and Tropical Medicine, London, England10Moorfields Eye Hospital, London, England.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burton
mesh_terms: D000328:Adult; D002278:Carcinoma in Situ / Q000175:diagnosis* / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000453:epidemiology; D004396:Coloring Agents / Q000009:adverse effects / Q000737:chemistry*; D003230:Conjunctival Neoplasms / Q000175:diagnosis* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D009883:Ophthalmic Solutions; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods; D014048:Tolonium Chloride / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D004396:Coloring Agents; D009883:Ophthalmic Solutions; D014048:Tolonium Chloride