Cutaneous squamous cell carcinoma of the eyelid masquerading as a chalazion.

Chalazia are among the most common eyelid lesions presenting to eye care providers. Often successfully managed conservatively, some require more invasive intervention such as incision and drainage or steroid injection. Lesions that recur, do not respond to treatment, or are atypical in appearance or natural history should prompt more thorough analysis, often with biopsy and subsequent microscopic analysis. Not uncommonly, such atypical chalazia may be masking a more serious diagnosis. Eyelid cutaneous squamous cell carcinoma masquerading as a chalazion is exceedingly rare. We present a case report of an atypical chalazion that was refractory to incision and drainage as well as intralesional steroid injection. Incisional biopsy revealed the lesion to be a cutaneous squamous cell carcinoma requiring full-thickness excision and subsequent reconstruction. The patient provided written informed consent, and the contents herein are acceptable under the provisions of the institutional review board. Following Mohs excision and oculoplastic reconstruction with a Hughes flap, the patient has had a good outcome and is currently free of recurrence. Recurrent chalazia that are defiant to surgical and medical interventions should prompt biopsy and evaluation by pathology. Cutaneous squamous cell carcinoma should be considered in the differential diagnosis as early intervention can save a patient's eye and, not infrequently, their life.

Epithelial downgrowth after descemet stripping automated endothelial keratoplasty.

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.

Reduction of hyperopia associated with manual excision of Salzmann's nodular degeneration.

PURPOSE: Removing central corneal pathology often leads to a hyperopic shift secondary to corneal flattening. A myopic shift, or reduction in hyperopia, would be expected after removal of peripheral corneal pathology with central corneal steepening. This case illustrates the refractive changes induced by Salzmann's nodular degeneration and the myopic shift associated with their excision. METHODS: A 53-year-old female presented with a slowly progressive increase in hyperopia. Vision in the right eye was 20/40 with a refraction of +10.00 -4.00 x 90 degrees. Vision in the left eye was 20/30 with a refraction of +5.75 -2.00 x 105 degrees. Both corneas exhibited nodular subepithelial opacities in the mid-periphery. A superficial keratectomy was performed on each eye, 1 year apart. RESULTS: Twelve days postoperatively, uncorrected visual acuity in the right eye was 20/25, and 20/20 with a refraction of -0.75 -0.50 x 31 degrees, 6 months later. Six days postoperatively, uncorrected visual acuity in the left eye was 20/40, and 20/30 with a refraction of -1.25 D, 1 month later. CONCLUSION: Superficial keratectomy provides a means of restoring the original corneal contour, especially when the pathology is easily dissected from Bowman's layer. The surgeon should investigate the refractive status prior to the development of the nodules and be aware of the possible refractive change upon removal of the pathology.

Eye banking and screening for Creutzfeldt-Jakob disease.

OBJECTIVES: To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. METHODS: Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. RESULTS: Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. CONCLUSIONS: Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.

Intraocular lacrimal gland choristoma involving iris and ciliary body.

PURPOSE: To describe clinical and pathologic features of an iridociliary lacrimal gland choristoma in which the diagnosis was made clinically and confirmed histopathologically. METHODS: Case report with clinical, ultrasound biomicroscopic, and histopathologic observations. RESULTS: We examined a 12-month-old male for a large iris mass that had been present since birth. We suspected it to be a lacrimal gland choristoma based on characteristic clinical features. The lesion was removed by iridocyclectomy, and the diagnosis of lacrimal gland choristoma was confirmed. CONCLUSION: Intraocular lacrimal gland choristoma has unique clinical features that should suggest the diagnosis.

Risk of prion disease transmission from ocular donor tissue transplantation.

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.

Primary varicella-zoster keratitis: diagnosis by polymerase chain reaction.

PURPOSE: To report the value of polymerase chain reaction in the diagnosis of a worsening corneal ulcer. METHODS: A 6-year-old boy underwent an emergent penetrating keratoplasty for a corneal ulcer that continued to worsen despite intensive antibiotic therapy. RESULTS: Examination of the corneal specimen by polymerase chain reaction was positive for varicella-zoster virus but negative for herpes simplex. Based on polymerase chain reaction studies, we diagnosed primary varicella-zoster keratitis with corneal perforation. Electron microscopy showed herpetic virus particles in the cornea. CONCLUSIONS: Polymerase chain reaction analysis of corneal buttons at the time of penetrating keratoplasty may benefit patients with undiagnosed recalcitrant corneal ulcers.

Osseous metaplasia in a preretinal membrane.

A highly myopic patient had surgery for retinal detachment in both eyes. After 3 procedures, the left eye developed phthisis bulbi. After multiple procedures, the right eye underwent a vitrectomy for proliferative vitreoretinopathy. A plaque of preretinal tissue was removed. We found bone on pathologic examination. The retina remains attached, and visual acuity is 20/200. Ultrasonography showed additional evidence of calcification of both eyes, presumably metaplastic bone.

Transplantation of corneal tissue from donors with diseases of the central nervous system.

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.

Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi analysis.

An altered morphology of neuronal dendrites has been shown to be associated with many degenerative diseases of the central nervous system (CNS). Scrapie is a CNS degenerative disorder caused by a novel infectious particle or prion. Golgi impregnation studies showed that neurons in the scrapie-infected brains of hamsters contained varicose swellings and diminished numbers of dendritic spines. In order to ascertain whether or not these differences were statistically significant, quantitative methods were applied to brain samples from scrapie-infected hamsters and compared to uninfected controls. Golgi impregnated layer III pyramidal neurons from both motor and visual cortex exhibited two types of changes in infected animals. First, loss of dendritic spines on the apical shaft of both motor and visual neurons were found from 50 to 200 microns from the cell body (p less than 0.001). Second, spherical varicosities on dendritic stalks ranging from 7 to 25 microns in diameter were found. The average number of varicosities per cell was 18.1 in infected animals with varicosities on dendrites of controls numbering less than 3 per cell. Less than 2% of the control cells exhibited these varicosities, while greater than 80% of the scrapie dendrites exhibited varicosities. These changes in scrapie are similar to those reported in Creutzfeldt-Jakob and Alzheimer's disease in human patients.

Interaction between myelin basic protein-sensitized T lymphocytes and murine cerebral vascular endothelial cells.

Lymph node cells from SJL mice immunized with guinea pig myelin basic protein proliferate in vitro to the same antigen. This proliferative response is abolished by depletion of macrophages-monocytes, but can be reconstituted by the addition of cerebral vascular endothelial cells (EC) freshly isolated from syngeneic mice with adoptively transferred acute experimental allergic encephalomyelitis (EAE). Reconstitution by EC from mice with EAE can be blocked by pretreatment of EC with syngeneic anti-I-A antisera. Freshly isolated EC from normal syngeneic mice do not restore responsiveness, but can be induced to present antigen by culture with murine recombinant immune interferon-gamma or supernatants from a variety of immune cell cultures. These findings are consistent with the hypothesis that immune cells release interferon and/or other soluble factors which induce I-A molecules on EC, which subsequently acquire the capacity to present antigen. The implications of these findings relate to the migration of cells across the blood-brain-barrier into the central nervous system, and are of importance in the understanding of the pathogenesis of several neurologic disorders.

Acceleration of scrapie disease in mice by an adenovirus.

Coinfected mice were examined for a possible interaction between the scrapie agent and an adenovirus. A low titer (10(2) TCD50) of mouse adenovirus (MAdV) caused a significant acceleration of clinical signs of scrapie in mice infected 128 days previously with scrapie. In this experiment, the coinfected mice died 19 days earlier than mice infected with scrapie alone. When a higher titer of MAdV (10(4)-10(5) PFU) was used, a more drastic acceleration of scrapie disease was seen in mice infected 85 and 110 days previously with scrapie. At 85 days, coinfection caused mice to die 37 days earlier than mice infected with scrapie alone, whereas at 110 days, coinfection caused mice to die 52 days earlier than mice infected with scrapie alone. MAdV alone caused no clinical disease in normal mice. The brains of coinfected mice and mice that had been infected with scrapie alone showed a histopathology consistent with scrapie. A possible explanation for these findings is that the replication of the scrapie agent is accelerated by adenovirus. Defective parvoviruses are known to be helped by adenoviruses. Spleens from coinfected mice but not from mice infected with MAdV alone yielded, in cultures of BALB 3T3 cells, infectious MAdV and one or two smaller agents with the dimension and shape of a parvovirus.

Replication of scrapie prions in hamster eyes precedes retinal degeneration.

Progressive degeneration of outer retinal structures occurs in hamsters with scrapie. In order to determine the relationship between histopathologic changes and replication of the scrapie agent, hamsters were inoculated intracerebrally with approximately 10(7) ID50 units. Animals sacrificed at 50 days after inoculation showed no signs of neurologic dysfunction, but had high titers of the scrapie agent or prions in both neural and nonneural portions of the eye. Prion titers in retina were greater than 10(7) ID50 units/ml of 10% (w/v) homogenate and equal to those found in optic nerve and brain. No histopathologic changes were seen by light microscopy in any ocular structure. At 70 days after inoculation, neurologic dysfunction was profound. The titers of the scrapie agent in brain, lens, retinal pigment epithelium, cornea, retina, and optic nerve were not significantly changed compared to those found at 50 days; however, retinal degeneration was severe. No morphologic changes were observed in cornea, pigment epithelium or optic nerve. These findings show that scrapie prion replication to maximal levels precedes the onset of degenerative changes in retina. Furthermore, the retina is preferentially susceptible to the degeneration induced by the scrapie agent while the other ocular structures containing significant levels of prions seem to escape injury.

Experimental murine cytomegalovirus infection of ocular structures.

To study experimental cytomegalovirus (CMV) infection of ocular structures, 3-week-old Swiss-Webster mice were inoculated intraperitoneally with a 0% to 20% lethal inoculum of murine CMV (MCMV). Murine cytomegalovirus was recovered from homogenates of eye tissues on days 3, 5, and 7 after inoculation. Peak virus titers, mean of 2.93 +/- 0.67 log plaque-forming units of MCMV per gram of ocular tissue occurred on day 5. Urine cytomegalovirus was recovered from explant cultures of eye and optic nerve 14, 21, 60, 90, and 120 days after MCMV inoculation. Murine cytomegalovirus also persisted in intraocular fluids for as long as 90 days. Murine cytomegalovirus infection was confirmed by immunofluorescence antibody staining and transmission electron microscopy. These experiments indicate that MCMV infects the ocular tissues of mice during systemic MCMV infection, and persists in ocular tissues for as long as 120 days after infection. These studies may be directly relevant to ocular disorders that occur during acquired CMV infections of humans, and suggest that ocular tissues may be a site of CMV persistence or latency.

Retinal degeneration in experimental Creutzfeldt-Jakob disease.

Mice with experimental Creutzfeldt-Jakob disease (CJD) develop a progressive retinal degeneration after a prolonged incubation period. Sections of the eyes stained with hematoxylin and eosin revealed pathologic changes in the optic nerve and a marked degeneration of photoreceptor cell inner and outer segment areas. Both peripheral and central retina, normally 10 cells thick, were reduced to one photoreceptor cell or less in thickness. Ultrastructural analysis revealed total loss of outer segment and most inner segment elements. Only Müller cell microvilli and macrophages remained in the subretinal space. Macrophages were also visible in the remnant photoreceptor cell layer. The inner nuclear layer and pigment epithelial cell layers appeared normal. Müller cell hypertrophy was evident but was not accompanied by spongiform vacuolation. Several of the degenerative changes of the eye in mice with experimental Creutzfeldt-Jakob disease differ from those observed for scrapie in rodents. The pathologic similarities between the retinal degenerations occurring in mice with experimental Creutzfeldt-Jakob disease and those found in some forms of human retinal degeneration are provocative. These similarities raise the question whether or not other retinal degenerative diseases might be caused by infectious agents such as prions or slow viruses.