Corneal Imaging And Clinical Presentation Of A Case Of Crisponi Syndrome/Cold-Induced Sweating Syndrome (Ciss)

Crisponi/ Cold-induced Sweat Syndrome (CISS1) is an extremely rare autosomal-recessive multisystemic disease, attributed to mutations of genes of the cytokine receptor-like factor 1 (CRLF1). The protein encoded by this gene is a receptor involved in the ciliary neurotrophic factor receptor pathway. This plays a critical role in corneal wound healing, making these patients susceptible to recurrent keratitis. The aim of this report is to present and discuss the corneal features observed with slit-lamp biomicroscopy, high resolution OCT scans and in vivo confocal microscopy. 

Ophthalmology Department, King’s College Hospital NHS Foundation Trust

We present a detailed description of the corneal features on slit-lamp biomicroscopy, OCT scans and confocal microscopy of a 21-year-old female with non-consanguineous parents and diagnosed with Crisponi syndrome. The patient first presented in 2021 when she was noticed to have corneal opacities and reduced vision. Her best corrected visual acuity was 6/18 (Snellen) in the right eye and 6/12 in the left eye. The patient presented a prolonged lid excursion with reduced blinking and an incomplete lid closure.

The slit-lamp biomicroscopy showed diffuse punctate epithelial breakdown and a dry ocular surface with anterior stromal opacities in the inferior quadrants and bilaterally enlarged and prominent corneal nerves. The OCT scan showed an increased signal corresponding to the islands of anterior stromal scarring with thickening of the stromal layer in the inferior corneal quadrants and evidence of reactive inflammatory keratitis. The enlarged corneal nerves were detectable on OCT scan and confocal microscopy and extending from the limbus to the central cornea around 360 degrees of the corneal surface. The patient developed recurrent episodes of keratitis that required the use of topical preservative-free steroids in association with lubricants and topical ciclosporin drops. Her ocular surface is currently stable on intensive lubrication and long-term use of topical ciclosporin eye drops.

Crisponi/CISS1 is an extremely rare syndrome resulting in microscopic corneal alterations. With the aid of high-resolution OCT of the cornea, slit-lamp biomicroscopy photographs and confocal microscopy, we have described and correlated alterations of the epithelial layer and the subepithelial structures including the corneal nerves and the anterior stroma. Patients with this condition need close ophthalmological monitoring and regular lubrication of the ocular surface to prevent sight-threatening complications secondary to compromised epithelial wound healing.