Central subendothelial geographic deposits are formed as a fibrillar layer (FL) in advanced Fuchs endothelial corneal dystrophy (FECD). Previous studies demonstrated a significant decrease in corneal endothelial cell (CEC) density and an increase in focal corneal backscatter in the FL area. The present study investigated the association of the FL with edema formation and its localization. Patients (n = 96) presenting for Descemet membrane endothelial keratoplasty (DMEK) for advanced FECD were included. Slit-lamp biomicroscopy with FECD grading was followed by Scheimpflug imaging with en face backscatter analysis and pachymetric analysis. FL dimensions were measured, and correlation with pachymetric values was performed. An FL was detected in 74% of all eyes (n = 71). Pachymetric values in FL-positive versus FL-negative eyes were for corneal thickness at the apex (ACT) 614 ± 52 µm and 575 ± 46 µm (p = 0.001), for peripheral corneal thickness at 1 mm (PCT_1mm) 616 ± 50 µm and 580 ± 44 µm (p = 0.002), for PCT_2mm 625 ± 48 µm and 599 ± 41 µm (p = 0.017), for PCT_3mm 651 ± 46 µm and 635 ± 40 µm (p = 0.128) and for PCT_4mm 695 ± 52 µm and 686 ± 43 µm (p = 0.435), respectively. Correlation analysis indicated a weak correlation for the FL maximum vertical caliper diameter with ACT and PCT_1mm values but no further relevant correlations. In FL-positive eyes, increased focal corneal backscatter and increased corneal thickness showed primarily central and inferotemporal localization. In conclusion, Scheimpflug imaging shows an association of the FL with increased corneal thickness in advanced FECD and shows localization of the FL and increased corneal thickness in the central and inferotemporal region. This may provide important information for progression assessment and therapeutic decision making in FECD patients in the future.

To investigate the genetic cause, clinical characteristics, and potential therapeutic targets of infantile corneal myofibromatosis. Case series with genetic and functional in vitro analyses. Four individuals from 2 unrelated families with clinical signs of corneal myofibromatosis were investigated. Exome-based panel sequencing for platelet-derived growth factor receptor beta gene (PDGFRB) and notch homolog protein 3 gene (NOTCH3) was performed in the respective index patients. One clinically affected member of each family was tested for the pathogenic variant detected in the respective index by Sanger sequencing. Immunohistochemical staining on excised corneal tissue was conducted. Functional analysis of the individual PDGFRB variants was performed in vitro by luciferase reporter assays on transfected porcine aortic endothelial cells using tyrosine kinase inhibitors. Protein expression analysis of mutated PDGFRB was analyzed by Western blot. Sequencing data, immunohistochemical stainings, functional analysis of PDGFRB variants, and protein expression analysis. We identified 2 novel, heterozygous gain-of-function variants in PDGFRB in 4 individuals from 2 unrelated families with corneal myofibromatosis. Immunohistochemistry demonstrated positivity for alpha-smooth muscle actin and β-catenin, a low proliferation rate in Ki-67 (< 5%), marginal positivity for Desmin, and negative staining for Caldesmon and CD34. In all patients, recurrence of disease occurred after corneal surgery. When transfected in cultured cells, the PDGFRB variants conferred a constitutive activity to the receptor in the absence of its ligand and were sensitive to the tyrosine kinase inhibitor imatinib. The variants can both be classified as likely pathogenic regarding the American College of Medical Genetics and Genomics classification criteria. We describe 4 cases of corneal myofibromatosis caused by novel PDGFRB variants with autosomal dominant transmission. Imatinib sensitivity in vitro suggests perspectives for targeted therapy preventing recurrences in the future. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.