'BLUES' procedure for assessing the blue level of the sclera in Osteogenesis Imperfecta

Valerio Di Martino; Fabiana Mallone; Alessandro Lambiase; Mauro Celli; Alice Mannocci; Luca Celli; Pietro Mangiantini; Pasquale Fino; Antonietta Moramarco

doi:10.1186/s13023-024-03192-z

'BLUES' procedure for assessing the blue level of the sclera in Osteogenesis Imperfecta

Orphanet J Rare Dis. 2024 Apr 27;19(1):176. doi: 10.1186/s13023-024-03192-z.

Authors

Valerio Di Martino¹, Fabiana Mallone¹, Alessandro Lambiase², Mauro Celli³, Alice Mannocci⁴, Luca Celli³, Pietro Mangiantini¹, Pasquale Fino⁵, Antonietta Moramarco¹

Affiliations

¹ Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, Italy.
² Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, Rome, 00161, Italy. Alessandro.lambiase@uniroma1.it.
³ Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, Rome, Italy.
⁴ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
⁵ Department of Clinical Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

Abstract

Purpose: Blue sclera is a characteristic and common clinical sign of Osteogenesis Imperfecta (OI). However, there is currently no widely accepted, objective method for assessing and grading blue sclera in individuals with OI. To address this medical need, this study is aimed to design and validate a new method called 'BLUES' (BLUe Eye Sclera) to objectively identify and quantify the blue color in the sclera of patients affected by OI.

Methods: Sixty-two patients affected by OI and 35 healthy controls were enrolled in the present prospective study, for a total of 194 eyes analyzed. In the 'BLUES' procedure, eye images from patients with OI and control subjects were analyzed to assess and grade the blue level of the sclera using Adobe Photoshop Software. The validation process then involved comparing the results obtained with the 'BLUES' procedure to the judgement of experienced ophthalmologists (JEO). A receiver-operating characteristic (ROC) curve analysis was used to examine the overall discriminatory power. The sensitivity and specificity levels and the Cohen's Kappa (K) indexes of 'BLUES' and 'JEO' were estimated versus the standard OI diagnosis. The K indexes of 'BLUES' versus 'JEO' were also evaluated.

Results: The optimal cut-off point of the scleral blue peak was calculated at 17%. Our findings demonstrated a sensitivity of 89% (CI95%: 0.835-0.945) and specificity of 87% (CI95%: 0.791-0.949) for the 'BLUES' procedure with an agreement versus the diagnosis of OI of 0.747. In comparison, the sensitivity and specificity of 'JEO' ranged from 89 to 94% and 77% to 100%, respectively, with an agreement ranging from 0.663 to 0.871 with the diagnosis of OI. The agreement between 'BLUES 'and 'JEO' evaluations ranged from 0.613 to 0.734.

Conclusions: Our findings demonstrated an 89% sensitivity and an impressive 87% specificity of our method to analyze the blue sclera in OI. The results indicated high agreement with disease diagnosis and were consistent with evaluations by experienced ophthalmologists. The 'BLUES' procedure appears to be a simple, reliable and objective method for effectively identify and quantify the blue color of the sclera in OI.

Keywords: Blue sclera; Computed analysis; Diagnosis; Osteogenesis Imperfecta (OI); Rare diseases; ‘BLUES’ procedure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Child
Child, Preschool
Female
Humans
Male
Osteogenesis Imperfecta* / diagnosis
Osteogenesis Imperfecta* / pathology
Prospective Studies
ROC Curve
Sclera* / pathology
Young Adult