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Purpose: To describe 2 cases of congenital corneal endothelial edema resulting from novel de novo mutations., Methods: Case A patient was a 15-month-old white child and case B patient was a 3-year-old Hispanic child presenting with bilateral cloudy corneas since birth. Clinicopathologic findings are presented. DNA samples were screened for mutations in candidate genes by Sanger sequencing., Results: Slit-lamp examination of case A patient revealed stromal edema and haze. Histology of the keratoplasty button showed stromal thickening with loss of endothelium and thin Descemet membrane. Sanger sequencing established the diagnosis of congenital hereditary endothelial dystrophy by detection of a compound heterozygous mutation in SLC4A11. The proband displayed a novel de novo frameshift mutation in one SLC4A11 allele, p.(Pro817Argfs*32), in conjunction with a maternally inherited missense mutation in SLC4A11, p.(Arg869His). Case B patient similarly presented with stromal edema and stromal haze. Histopathologic analysis revealed a spongy epithelium, focal discontinuities in Bowman layer, stromal thickening with areas of compacted posterior stroma, variable thickness of Descemet membrane, and regional multilayered endothelium. Sanger sequencing found a novel de novo nonsense mutation in the first exon of ZEB1, p.(Cys7*)., Conclusions: To the authors' knowledge, we report the earliest clinical presentation of posterior polymorphous corneal dystrophy resulting from a de novo mutation in ZEB1. Additionally, we present a congenital hereditary endothelial dystrophy case with a thin Descemet membrane with a novel compound heterozygous SLC4A11 mutation. In the absence of a family history or consanguinity, de novo mutations may result in congenital corneal endothelial dystrophies.

Purpose: The purpose of this study was to describe a new modification for big-bubble deep anterior lamellar keratoplasty (DALK) using pneumatic pressure to detach Descemet membrane (DM) via air injection followed by ophthalmic viscoelastic device (OVD) injection., Methods: After failure of big-bubble formation after air injection, OVD was injected from a different site other than the previous air injection using a 27-gauge cannula to detach DM, called air-visco bubble (AVB) DALK technique. The technique was used in 7 human corneoscleral rims that were investigated with anterior segment optical coherence tomography and histopathology and in 69 eyes that underwent DALK surgeries., Results: Big-bubble formation was noted in 4 of 7 of the donor corneoscleral rims. The anterior segment optical coherence tomography showed big-bubble formations together with intrastromal OVD accumulation. The histology of the donor corneas showed microdetachments at the DM in the periphery, deep intrastromal separation, and big-bubble formation filled with OVD. One hundred forty-one of 210 eyes (67%) underwent successful DALK with only air injection, and 69 of 210 eyes (33%) underwent AVB technique when a big bubble was not achieved with only air injection. All the corneas showed a clear interface with good wound healing when DM was bared with the AVB DALK technique., Conclusions: Additional OVD injection to detach DM may be useful in cases where air injection fails. Also, creating small DM detachments with air injection may facilitate the formation of a big bubble with further OVD injection.

Purpose: To correlate big-bubble deep anterior lamellar keratoplasty findings in donor corneas with anterior segment optical coherence tomography (OCT) and histology., Methods: This research was conducted entirely at the University of Texas Southwestern Medical Center in Dallas, Texas. We performed deep intrastromal air injections in donor corneas on artificial chambers. Surgical patterns (big bubble, intrastromal emphysema, and perforation) were assessed by spectral domain OCT with a handheld probe and histology., Results: Surgical patterns were evaluated by histology using a novel embedding technique. A classic big bubble may be a Descemet membrane (DM) detachment with a few attached stromal fibrils. There were no large intra-DM separations as previously reported. The emphysematous surgical patterns result from intrastromal emphysema, which can be accompanied by microdetachments of DM. We saw indirect OCT signs of big bubble, but scatter from intrastromal emphysema limits deeper imaging., Conclusions: Surgical patterns of big bubble and intrastromal emphysema correlate with characteristic histology findings. Marked scatter on OCT by intrastromal emphysema limits visualization of deeper corneal structures, but the presence of a big bubble may be inferred.

Purpose: To report the clinical and histopathologic findings of 2 patients who developed epithelial downgrowth after Descemet stripping automated endothelial keratoplasty (DSAEK)., Methods: A 64-year-old woman (case 1) underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. However, the graft failed to attach, and a repeat DSAEK was performed 3 weeks later. After 4 months, the patient developed herpes simplex virus keratitis that resulted in anterior stromal scarring. A penetrating keratoplasty was performed 15 months after the initial DSAEK. Our second patient (case 2) was an 87-year-old female who underwent DSAEK for corneal edema secondary to Fuchs endothelial dystrophy in left eye. Six months later, she had an episode of graft rejection and developed secondary glaucoma. At 14 months postoperatively, a retrocorneal membrane was seen involving the temporal half of the endothelial surface of the graft. The retrocorneal membrane extended from the inferior thickened edge of the endothelial keratoplasty graft to the iris stromal surface. An Ahmed shunt implantation followed by repeat DSAEK were then performed. The excised corneal buttons were examined., Results: Histopathologic evaluation showed multilayered epithelium on the interface and attenuated endothelium in the endothelial graft in case 1. The host cornea showed diffuse stromal scarring. Case 2 showed multilayered epithelium with early cyst formation at the edge of the graft. The epithelium extended to involve the endothelial surface without involvement of interface surface. Significant scar formation was observed between the edge of the endothelial keratoplasty graft and thickened host Descemet membrane. Some pigmented cells were present within the epithelial downgrowth. The epithelium stained positively with cytokeratin A1/A3 in both cases., Conclusions: Although rare, epithelial downgrowth can occur after DSAEK and can be associated with graft failure. Early recognition and surgical treatment of epithelial downgrowth is crucial in treating the complications of corneal decompensation and glaucoma.

Purpose: To report the clinical, histopathologic, and confocal findings of corneal siderosis., Methods: A 35-year-old man presented after a car battery explosion with diffuse left corneal anterior stromal pigment deposition and an intraocular metallic foreign body of the left iris. The corneal pigment was analyzed by confocal microscopy and a lamellar corneal biopsy., Results: Confocal microscopy showed the pigment to be highly reflective material in the corneal stroma with greatest density anteriorly. Histologic examination revealed the pigment to be iron with a diagnosis consistent with corneal siderosis., Conclusions: Corneal biopsy with Prussian blue established siderosis as the etiology of corneal pigmentation. A short delay in the removal of the foreign body contributed to the development of siderosis. The location of the foreign body on the iris may account for the predominant corneal involvement and relative sparing of the retina. Confocal microscopy may be useful in the evaluation of corneal siderosis.

Purpose: Recent new reports of possible iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) in Europe have prompted renewed scrutiny of current Eye Bank Association of America criteria for evaluation of potential corneal donors in this country. A prior study evaluated the risk of CJD occurring in U.S. corneal donors by using data to 1994. This report updates these data, analyses the risk by using data to 1997, and predicts potential risk into the next decade., Methods: EBAA data inclusive through 1997 were reviewed and correlated with incidence figures for CJD in the United States as provided by the Communicable Disease Center in Atlanta., Results: The annual incidence of CJD has remained stable at 1 case per million population. Thus approximately 270 new cases of CJD would be expected to occur each year in the United States. From this, the calculated risk of a prion-infected corneal donor appearing in the donor pool is 0.045 cases per year. If the data are corrected for age (90% of CJD patients are older than 60 years) and for possible infected but asymptomatic CJD patients (prevalence, 70 cases per million), at worst, 2.12 cases per year would appear for potential corneal donation (0.005% of all donors). Whereas donors completely without any neurologic symptoms cannot be screened by using any currently available laboratory method, those with a characteristic quadrate clinical prodrome including cognitive changes, speech abnormalities, cerebellar findings, and myoclonus could all be potentially excluded by using tightened medical record and historical screening criteria. Although no cases of bovine spongiform encephalopathy (mad-cow disease) or new variant CJD have been reported in the United States, if such should occur, only 4.2 cases of CJD would be expected in potential donors each year (0.009% of all donors). Tightening of exclusionary queries would significantly reduce the risk of even this number of patients appearing for corneal donation., Conclusions: Historical queries of potential corneal donors should be tightened to assure exclusion of donors with early neurologic alterations. Any patient undergoing autopsy for evaluation of possible central nervous system (CNS) disease should be absolutely excluded. With this approach, the risk of inclusion of CJD-infected transplant tissues derived from ocular sources is very small, and all previously reported cases would have been prospectively excluded from surgical use. Clearly, the benefits of corneal transplantation in the overall population continue significantly to outweigh the risks of transmission of prion disease.

A great deal of controversy and concern exists over potential transmission of central nervous system diseases by corneal transplant. The purpose of this study was to evaluate the available data relative to this question, pertaining especially to transmission of infectious dementia. From these data, determination of conveyance risks are possible, and rational policies for donor inclusion criteria can be constructed. Retrospective analysis of available published data regarding transmission of infectious dementias was performed. Risk of disease transmission was calculated from population data. Of the various forms of dementia, only rabies, hepatitis B, and Creutzfeldt-Jakob disease (CJD) have been transmitted by corneal transplantation. Transmission of the first two viruses is preventable by serologic testing. Prevention of CJD transmission relies on clinical history. Despite the possibility of transmission and the lack of available testing, slow virus disease (CJD) has been transmitted only once. That this case represents an extremely rare event is supported by a lack of successful transmission via corneal transplant in monkeys; lower levels of infectious agent in cornea than in brain; lack of successful transmission of similar human dementias, including Alzheimer's disease to primates; the apparent requirement for homozygosity at codon 129 of chromosome 20 for transmission; lack of transmission in 5-10% of CJD cases even after brain inoculation; and low numerical risk of transmission based on population data. Only 0.5-4 CJD infected donors per year would be expected. Current Eye Bank Association of America criteria for donor exclusion based on suspicious history are adequate to protect against accidental conveyance of transmissible dementia.