Toluidine Blue 0.05% Vital Staining for the Diagnosis of Ocular Surface Squamous Neoplasia in Kenya

Abstract

Importance Clinical features are unreliable for distinguishing Ocular Surface Squamous Neoplasia (OSSN) from benign conjunctival lesions. Objective To evaluate the adverse effects, accuracy and inter-observer variation of Toluidine Blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions. Design, Setting and Participants Cross-sectional study in Kenya from July 2012 through July 2014 of 418 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded. Exposures Comprehensive ophthalmic slit-lamp examination was conducted. Vital staining with Toluidine Blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumours scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumours. We asked about pain or discomfort after staining and evaluated the cornea at the slit lamp for epithelial defects. Lesions were photographed before and after staining. Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a sub-set of 100 consecutive participants for staining and made a diagnosis of OSSN vs Non-OSSN. Main Outcomes and Measures Staining was compared with histopathology to estimate sensitivity, specificity and predictive values. Adverse effects were enumerated. Inter-observer agreement was estimated using the kappa statistic (k). Results 143/419 (34%) participants had OSSN by histopathology. The median (interquartile range) age of the 419 was 37 (32-45) years and 278 (66%) were female. 322/419 participants had positive staining while 2/419 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 31% (95%CI, 25%-36%), positive predictive value 41% (95%CI, 35%-46%), and negative predictive value 88% (95%CI, 80%-94%). Inter-observer agreement was substantial for staining (k=0.8) and moderate for diagnosis (k=0.4). Conclusion and Relevance 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, but not a good diagnostic tool due to a high frequency of false positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely.

HIV-associated malignancies in sub-Saharan Africa

“…For instance, for conjunctival squamous cell carcinoma, efforts to screen HIV-infected patients in Kenya using toluidine blue staining have been described [57*], as well as suggestions that resection followed by brachytherapy may be well tolerated and associated with low recurrence rates in South Africa [58*]. However, given the relatively immature nature of the field overall, there are not major recent studies for other HIVAM in LMIC that would clearly merit inclusion in this review, although it is hoped that more data related to these tumors will soon be forthcoming.…”

Prevalence and severity of ocular surface Neoplasia in African nations and need for early interventions

“…[20] 419 adult patients underwent comprehensive ophthalmic examination including slit lamp biomicroscopy that included ocular surface staining with toluidine blue 0.05%. [20] Photographs were taken of lesions with and without staining, and masked examiners reviewed 100 consecutive photographs.…”

“…[20] 419 adult patients underwent comprehensive ophthalmic examination including slit lamp biomicroscopy that included ocular surface staining with toluidine blue 0.05%. [20] Photographs were taken of lesions with and without staining, and masked examiners reviewed 100 consecutive photographs. [20] The authors reported that toluidine blue 0.05% had a high sensitivity (92%) but low specificity (31%) for diagnosis of OSSN compared to confirmation by histopathology.…”

“…[20] Photographs were taken of lesions with and without staining, and masked examiners reviewed 100 consecutive photographs. [20] The authors reported that toluidine blue 0.05% had a high sensitivity (92%) but low specificity (31%) for diagnosis of OSSN compared to confirmation by histopathology. [20] The authors conclude that toluidine blue staining may be a good screening tool but not a good diagnostic tool for OSSN due to the frequency of false-positives.…”

“…[20] The authors conclude that toluidine blue staining may be a good screening tool but not a good diagnostic tool for OSSN due to the frequency of false-positives. [20]…”