Clinical Characteristics and Outcomes of Ocular Cicatricial Pemphigoid: A Cohort Study and Literature Review.

PURPOSE: Ocular cicatricial pemphigoid (OCP) is a rare systemic autoimmune disease and a potentially blinding subepithelial blistering disorder. The purpose of this study was to describe the clinical spectrum of the disease and to assess the efficacy and safety of immunosuppressive agents in a cohort of patients with OCP. METHODS: We conducted a monocentric retrospective cross-sectional cohort study of all unselected consecutive patients diagnosed with progressive OCP. Ocular and extra ophthalmological involvement as well as histological findings were gathered. Other outcomes were exposures to immunosuppressive agents defined by the use of a particular treatment. For each exposure, success in controlling ocular inflammation was graded as a complete response, response, or failure. Relapses and adverse events (AE) were also recorded. RESULTS: Seventeen patients (34 affected eyes), 35% of whom were women, were included, with an age at diagnosis of 75 ± 11 years. Corneal involvement was diagnosed in 30 of 34 eyes, and 22 of 34 eyes had progressive fibrosing conjunctival involvement. Sixty-two exposures to immunosuppressive agents or biologics were recorded: dapsone, n = 26; mycophenolate mofetil, n = 6; azathioprine, n = 4; cyclophosphamide, n = 10; rituximab, n = 14; and intravenous immunoglobulin, n = 2. Rates of response and of complete response achievement during the first 3 months were 84% and 45%, respectively. Response rates were 100%, 100%, 86%, 85%, and 80% for intravenous immunoglobulin, mycophenolate mofetil, rituximab, dapsone, and cyclophosphamide, respectively. Thirteen percent of those drugs were discontinued because of an adverse event in 4 patients. CONCLUSIONS: This study describes the efficacy of immunosuppressants or biologics with an acceptable safety profile for OCP.

First Experience With the ICD 16.5 Mini-Scleral Lens for Optic and Therapeutic Purposes.

OBJECTIVES: To evaluate the success rate, efficacy, and safety of the ICD 16.5 mini-scleral gas permeable (GP) contact lens. METHODS: This prospective study included referred consecutive patients with irregular corneas and severe ocular surface disease (OSD) in treatment failure. All patients were fitted with the ICD 16.5 mini-scleral GP lens. Even though we had some limited experience with scleral lenses, it was our first experience with the ICD 16.5 mini-scleral GP lens. Efficacy was assessed by comparing best-corrected visual acuity (BCVA) with the mini-scleral lens to baseline BCVA. A subjective visual functioning questionnaire (comfort score, visual quality score, handling rating, and wearing time) was administered in a face-to-face structured interview. RESULTS: Thirty-nine eyes of 23 patients with a mean age of 43±16 years were included. Fitting indications were keratoconus (46%), post-penetrating keratoplasty (21%), other irregular astigmatism (15%), and severe OSD (18%). Twenty-five eyes (64%) were successfully fitted with an 18-month follow-up. The mini-scleral GP lens BCVA was 0.16 logarithm of the minimum angle of resolution (logMAR; 20/25) versus a baseline BCVA of 0.44 logMAR (20/63; P<0.001). Comfort and visual quality scores were 8.5/10 and 7.5/10, respectively. No complications were detected in 96% of the eyes (95% confidence interval, 76.1%-99.4%). One eye experienced corneal graft swelling. CONCLUSIONS: The present findings suggest that the ICD 16.5 mini-scleral GP lens is an effective and safe alternative for managing challenging corneas in a therapeutic impasse.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. METHODS AND RESULTS: A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband's mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. CONCLUSIONS: We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.