A Modified Bicanalicular Crawford Placement Method for Congenital Nasolacrimal Duct Obstruction: Reducing Need for Operative Room Removal.

PURPOSE: This study introduces a method for Crawford bicanalicular stent placement for congenital nasolacrimal duct obstruction by looping the ends to themselves which are tied together with dissolvable sutures to ease in-office removal. METHODS: This is a single institution, retrospective study that evaluates outcomes of patients aged 5 years and under who underwent bicanalicular stenting for congenital nasolacrimal duct obstruction by a single surgeon (G.S.E.) between 2004 and 2020. Only primary surgeries were included in the analysis. Stenting could be accompanied by balloon dilatation and/or turbinate infracture. Age, sex, follow-up time, complications, type of intervention, extrusion, recurrence, and operative room removal were recorded. RESULTS: This study included 56 eyes from 54 patients with a mean age of 19.0 ± 9.5 months (range, 8-50 months). There was a 30.3% extrusion rate, a 5.4% rate of recurrence of disease, and a 3.6% rate of operative room removal. The average follow-up time was 25.1 ± 39.8 months (range, 1-132 months). For patients with or without extrusion, there were no significant differences between age, sex, laterality, type of intervention, follow-up time, or rate of recurrence. Each eye that had recurrence (3 total) or needed operative room removal (2 total) underwent only bicanalicular stenting without accompanying procedures, although the difference in rates between procedures was also not statistically significant. CONCLUSIONS: This method had a low recurrence and operative room removal rate, with similar extrusion and complication rates to other bicanalicular stent and intubation methods for the treatment of congenital nasolacrimal duct obstruction.

Nanophthalmos patient with a THR518MET mutation in MYRF, a case report.

BACKGROUND: Nanophthalmos has a significant genetic background and disease-causing mutations have been recently been reported in the myelin regulatory factor (MYRF) gene. We report clinical features in a patient with nanophthalmos and a Thr518Met MYRF mutation. CASE PRESENTATION: A three-year-old male was discovered to have nanophthalmos after first presenting to the emergency department for a frontal headache, eye pain, emesis, and lethargy. Imaging studies (CT and MRI) were negative except for increased posterior fossa cerebrospinal fluid. Subsequent examinations revealed nanophthalmos (short axial eye lengths 18.1 mm OD and 18.3 mm OS), microcornea, and a large crystalline lens. Peripheral chorioretinal pigment abnormalities were also observed. He experienced episodes of marked ocular hypertension (53 mmHg OD and 60 mmHg) likely due to intermittent angle closure precipitated by nanophthalmos. The ocular hypertension was responsive to topical medicines. Genetic analysis of known nanophthalmos genes MFRP and TMEM98 were negative, while a novel mutation, Thr518Met was detected in MYRF. The Thr518Met mutation was absent from 362 matched normal controls and was extremely rare in a large population database, allele frequency of 0.000024. The Thr518Met mutation altered a highly conserved amino acid in the MYRF protein and three of four algorithms suggested that this mutation is likely pathogenic. Finally, molecular modeling showed that the Thr518Met mutation is damaging to MYRF structure. Together these data suggest that the Thr518Met mutation causes nanophthalmos. CONCLUSIONS: Nanophthalmos may present at an early age with features of angle closure glaucoma and a Thr518Met mutation in MYRF was detected in a patient with nanophthalmos. Prevalence data, homology data, mutation analysis data, and protein modeling data suggest that this variant is pathogenic and may expand the phenotypic range of syndromic nanophthalmos caused by MYRF mutations to include central nervous system abnormalities (increased posterior fossa cerebrospinal fluid).

LADD syndrome with glaucoma is caused by a novel gene.

PURPOSE: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder displaying variable expression of multiple congenital anomalies including hypoplasia or aplasia of the lacrimal and salivary systems causing abnormal tearing and dry mouth. Mutations in the FGF10, FGFR2, and FGFR3 genes were found to cause some cases of LADD syndrome in prior genetic studies. The goal of this study is to identify the genetic basis of a case of LADD syndrome with glaucoma and thin central corneal thickness (CCT). METHODS: Whole exome sequencing was performed, and previously described disease-causing genes (FGF10, FGFR2, and FGFR3) were first evaluated for mutations. Fifty-eight additional prioritized candidate genes were identified by searching gene annotations for features of LADD syndrome. The potential pathogenicity of the identified mutations was assessed by determining their frequency in large public exome databases; through sequence analysis using the Blosum62 matrix, PolyPhen2, and SIFT algorithms; and through homology analyses. A structural analysis of the effects of the top candidate mutation in tumor protein 63 (TP63) was also conducted by superimposing the mutation over the solved crystal structure. RESULTS: No mutations were detected in FGF10, FGFR2, or FGFR3. The LADD syndrome patient's exome data was searched for mutations in the 58 candidate genes and only one mutation was detected, an Arg343Trp mutation in the tumor protein 63 (TP63) gene. This TP63 mutation is absent from the gnomAD sequence database. Analysis of the Arg343Trp mutation with Blosum62, PolyPhen2, and SIFT all suggest it is pathogenic. This arginine residue is highly conserved in orthologous genes. Finally, crystal structure analysis showed that the Arg343Trp mutation causes a significant alteration in the structure of TP63's DNA binding domain. CONCLUSIONS: We report a patient with no mutations in known LADD syndrome genes (FGF10, FGFR2, and FGFR3). Our analysis provides strong evidence that the Arg343Trp mutation in TP63 caused LADD syndrome in our patient and that TP63 is a fourth gene contributing to this condition. TP63 encodes a transcription factor involved in the development and differentiation of tissues affected by LADD syndrome. These data suggest that TP63 is a novel LADD syndrome gene and may also influence corneal thickness and risk for open-angle glaucoma.