Confirmation and refinement of the heterozygous deletion of the small leucine-rich proteoglycans associated with posterior amorphous corneal dystrophy.

PURPOSE: To present the clinical and cytogenetic features of a previously unreported family with posterior amorphous corneal dystrophy (PACD) associated with a heterozygous deletion of the small leucine-rich proteoglycan (SRLP) genes on chromosome 12. METHODS: Clinical characterization was performed using slit lamp biomicroscopic and optical coherence tomography (OCT) imaging. Genomic DNA was collected from affected and unaffected family members, and a cytogenomic array was used to identify copy number variations (CNV) present in the PACD locus. RESULTS: Three members of a Guatemalan family presented with clinical characteristics consistent with PACD: bilateral posterior stromal lamellar opacification, decreased corneal curvature, and iridocorneal adhesions. OCT imaging demonstrated decreased corneal thickness and hyperreflectivity of the posterior third of the corneal stroma. CNV analysis confirmed the presumed clinical diagnosis of PACD by revealing a 0.304 Mb heterozygous deletion in the PACD locus on chromosome 12 that included the four SLRP genes (KERA, LUM, DCN, and EPYC) deleted in each of the PACD families in which CNV analysis has been reported. CONCLUSIONS: This is the first report of the OCT appearance of PACD and the second confirmation of a heterozygous deletion of chromosome 12q21.33 as the cause of PACD, highlighting the utility of array-based cytogenomics to confirm the suspected clinical diagnosis of PACD. As the smallest previously reported pathogenic deletion was 0.701 Mb, the 0.304-Mb deletion we report is the smallest identified to date and reduces the size of the PACD locus to 0.275 Mb.

The Effect of Chronic Pulmonary Disease and Mechanical Ventilation on Corneal Donor Endothelial Cell Density and Transplant Suitability.

PURPOSE: To determine how chronic obstructive pulmonary disease (COPD) and mechanical ventilation time affect corneal donor endothelial cell density (ECD) and transplant suitability. DESIGN: Retrospective cohort study. METHODS: Setting: Institutional. STUDY POPULATION: Total of 39 679 cornea donor eyes from SightLife Eye Bank between 2012 and 2016. Demographics, death-to-preservation time, ECD, lens status, medical history, time on mechanical ventilation, and suitability for transplantation were included. MAIN OUTCOME MEASURES: ECD and transplant suitability. RESULTS: Mean ECD was 2733 cells/mm2. Mean age was 59 years. COPD affected 34.2% of donors. Mechanical ventilation was required in 35% of donors. Mean ventilation time was 1.3 days. After controlling for covariates, COPD was not found to be associated with poor transplant suitability (P = .22). Ventilation >7 days was associated with poor transplant suitability (P = .04). Donors with COPD and donors who were mechanically ventilated exhibited lower cell counts (P < .001, P < .01, respectively). Longer ventilation led to reduced endothelial cell density: ventilation time >7 days (-46.5 cells/mm2, P < .001) and >30 days (-101.4 cells/mm2, P = .02). Limitations of the study included the retrospective nature, dataset obtained from a single eye bank, and medical history documentation completed by eye bank technicians. CONCLUSIONS: A high proportion of cornea donors have respiratory disease prior to donation. Ventilation time >7 days affected transplant suitability but the presence of COPD did not. Donors with COPD and donors who were mechanically ventilated had reduced cell counts. Longer ventilation times lead to increased cell loss. The presence of respiratory disease may affect tissue oxygenation and endothelial cell health.