Anthony Aldave

PURPOSE: To determine the prevalence of the transforming growth factor (TGF) β-induced gene corneal dystrophies in refractive surgery candidates in China. SETTING: Five hospitals in China. DESIGN: Prospective case series. METHOD: Refractive surgical candidates from 5 preselected eye hospitals/centers in China were recruited after providing informed consent. All patients had slitlamp biomicroscopy and collection of a buccal swab as a source of DNA for screening of the TGF β-induced gene for the 5 most common mutations associated with Reis-Bückler corneal dystrophy, Thiel-Behnke corneal dystrophy, granular corneal dystrophy type 1, granular corneal dystrophy type 2, and lattice corneal dystrophy type 1...

PURPOSE: To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases. METHODS: Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed. RESULTS: Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells...

Importance: Demonstrating that endothelial cell loss following Descemet stripping automated endothelial keratoplasty (DSAEK) is independent of donor cornea preservation time (PT) could increase the pool of corneal tissue available for keratoplasty. Objective: To determine whether endothelial cell loss 3 years after successful DSAEK is related to PT. Design, Setting, and Participants: A multicenter, double-masked, randomized clinical trial included 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks...

Importance: Demonstrating that success of Descemet stripping automated endothelial keratoplasty is similar across donor cornea preservation times (PTs) could increase the donor pool. Objective: To determine whether the 3-year rate of graft success using corneal donor tissue preserved 8 to 14 days is noninferior to that of donor tissue preserved 7 days or less. Design, Setting, and Participants: A multicenter, double-masked, randomized noninferiority clinical trial was conducted from April 16, 2012, to June 5, 2017, at 40 clinical sites (70 surgeons) in the United States, with donor corneas provided by 23 US eye banks...

PURPOSE: To investigate the functional role that the zinc e-box binding homeobox 1 ( ZEB1 ) gene, which underlies the genetic basis of posterior polymorphous corneal dystrophy 3 (PPCD3), plays in corneal endothelial cell proliferation, apoptosis, migration, and barrier function. METHODS: A human corneal endothelial cell line (HCEnC-21T) was transfected with siRNA targeting ZEB1 mRNA. Cell proliferation, apoptosis, migration, and barrier assays were performed: Cell proliferation was assessed with cell counting using a hemocytometer; cell apoptosis, induced by either ultraviolet C (UVC) radiation or doxorubicin treatment, was quantified by measuring cleaved caspase 3 (cCASP3) protein levels; and cell migration and barrier function were monitored with electric cell-substrate impedance sensing (ECIS)...

PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (KPro). METHODS: Data were collected regarding preoperative characteristics, surgical procedure(s) performed, and postoperative outcomes of patients who underwent KPro implantation from May 1, 2004, to May 1, 2011, and were followed for 5 years after surgery. RESULTS: Seventy-four KPro procedures were performed in 58 eyes (55 patients), with more than 1 KPro implanted in 10 eyes...

PURPOSE: To evaluate the reliability between pneumatonometry intraocular pressure (IOP) measurement in different scleral locations and corneal IOP in a penetrating keratoplasty (PK) setting. Our aim is to validate a method that can potentially be used for patients with keratoprostheses. METHODS: This is a prospective observational study of 40 patients who underwent monocular PK by a single surgeon and had no significant anterior segment condition in the contralateral eye...

Purpose: To investigate the molecular basis of posterior polymorphous corneal dystrophy (PPCD) by examining the PPCD transcriptome and the effect of decreased ZEB1 expression on corneal endothelial cell (CEnC) gene expression. Methods: Next-generation RNA sequencing (RNA-seq) analyses of corneal endothelium from two PPCD-affected individuals (one with PPCD3 and one of unknown genetic cause) compared with two age-matched controls, and primary human CEnC (pHCEnC) transfected with siRNA-mediated ZEB1 knockdown...

PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (Kpro) in eyes with prior herpes simplex virus (HSV) keratitis. METHODS: Retrospective review of all Kpro procedures performed by a single surgeon from 1 May 2004 to 1 January 2015. RESULTS: 13 of 173 Kpro procedures were performed in 11 eyes with prior HSV keratitis. There was not a significant difference in the percentage of eyes with and without prior HSV keratitis with preoperative (9% vs 8%, p=1...

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8 ): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114...

PURPOSE: To describe 2 unrelated families with multiple members demonstrating a less commonly recognized vortex pattern of corneal deposits confirmed to be granular corneal dystrophy type 1 (GCD1) after identification of the p.(Arg555Trp) mutation in the transforming growth factor β-induced gene (TGFBI). METHODS: A slit-lamp examination was performed on individuals from 2 families, one of Mexican descent and a second of Italian descent. After DNA extraction from affected individuals and their unaffected relatives, TGFBI screening was performed...

PURPOSE: To identify the genetic basis of posterior polymorphous corneal dystrophy (PPCD) in families mapped to the PPCD1 locus and in affected individuals without ZEB1 coding region mutations. METHODS: The promoter, 5' UTR, and coding regions of OVOL2 was screened in the PPCD family in which linkage analysis established the PPCD1 locus and in 26 PPCD probands who did not harbor a ZEB1 mutation. Copy number variation (CNV) analysis in the PPCD1 and PPCD3 intervals was performed on DNA samples from eight probands using aCGH...

PURPOSE: To describe 2 unrelated families with multiple members demonstrating a less commonly recognized vortex pattern of corneal deposits confirmed to be granular corneal dystrophy type 1 (GCD1) after identification of the p.(Arg555Trp) mutation in the transforming growth factor β-induced gene (TGFBI). METHODS: A slit-lamp examination was performed on individuals from 2 families, one of Mexican descent and a second of Italian descent. After DNA extraction from affected individuals and their unaffected relatives, TGFBI screening was performed...

PURPOSE: To evaluate the safety of concurrent Boston type I keratoprosthesis (KPro) and glaucoma drainage device (GDD) implantation. DESIGN: Retrospective comparative study of a consecutive cohort of patients. SUBJECTS: Patients who underwent KPro implantation by a single surgeon (A.J.A.) with or without 1 concurrent Ahmed GDD (New World Medical, Inc., Rancho Cucamonga, CA) implantation between January 1, 2005, and January 31, 2015, were included...

Congenital hereditary endothelial dystrophy (CHED), Harboyan syndrome (CHED with progressive sensorineural deafness), and potentially a subset of individuals with late-onset Fuchs' endothelial corneal dystrophy are caused by mutations in the SLC4A11 gene that results in corneal endothelial cell abnormalities. Originally classified as a borate transporter, the function of SLC4A11 as a transport protein remains poorly understood. Elucidating the transport function(s) of SLC4A11 is needed to better understand how its loss results in the aforementioned posterior corneal dystrophic disease processes...

PURPOSE: To investigate the role of the zinc finger e-box binding homeobox 1 (ZEB1) transcription factor in posterior polymorphous corneal dystrophy 3 by demonstrating its ability to regulate type IV collagen gene transcription via binding to putative E2 box motifs. METHODS: Putative E2 box motifs were identified by in silico analysis within the promoter region of collagen, type IV, alpha3 (COL4A3) and collagen, type IV, alpha4 (COL4A4). To test the ability of ZEB1 to bind to each identified E2 box, electrophoretic mobility shift assays were performed by incubating ZEB1-enriched nuclear extracts with DIG-labeled probes containing one of each of the identified E2 box motifs...

BACKGROUND/AIMS: To report the clinical, histopathological and genetic features of a variant of lattice corneal dystrophy (LCD) associated with two pathogenic mutations in the transforming growth factor-B-induced (TGFBI) gene. METHODS: Clinical characterisation was performed by slit lamp examination and in vivo confocal microscopic imaging (IVCM). Histopathological characterisation was performed with light microscopic examination of an excised corneal button and a peripheral blood samples were collected for TGFBI screening...

PURPOSE: To report the long-term outcomes of the Boston type I keratoprosthesis (KPro) in the management of limbal stem cell deficiency (LSCD). METHODS: Retrospective review of KPro procedures performed by a single surgeon from May 1, 2004, to January 1, 2015. RESULTS: One hundred seventy-three KPro procedures were performed in 149 eyes, including 68 in 54 eyes with LSCD. Glaucoma (48% vs. 82%, P < 0.0001) and a history of ≥2 keratoplasties (39% vs...

Purpose. To report the identification of the first de novo UBIAD1 missense mutation in an individual with Schnyder corneal dystrophy (SCD). Methods. A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband's parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries of UBIAD1 were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes...

Posterior polymorphous corneal dystrophy 1 (PPCD1) is a genetic disorder that affects corneal endothelial cell function and leads to loss of visual acuity. PPCD1 has been linked to a locus on chromosome 20 in multiple families; however, Sanger sequencing of protein-coding genes in the consensus region failed to identify any causative missense mutations. In this study, custom capture probes were utilized for targeted next-generation sequencing of the linked region in a previously reported family with PPCD1. Variants were detected through two bioinformatics pipelines and filtered according to multiple criteria...