Darkfield biomicrography of eye bank donor corneas.

PURPOSE: Evaluation of donated corneal tissue for transplantation relies on visual inspection by slit lamp biomicroscopy and specular micrography at the eye bank and then slit lamp biomicroscopy by the transplanting surgeon. An overall grade of tissue quality is assigned, but endpoints for biomicroscopic assessment are not universally accepted. We investigated the application of darkfield illumination to evaluate corneal transparency and provide a more standardized and reproducible method of tissue examination. METHODS: We built a fixture to securely hold a standard cornea storage container, and used two versions of photographic slit lamp biomicroscopes to examine donated corneal tissue with darkfield illumination. RESULTS: In every cornea we examined, darkfield illumination portrayed increased subject detail as compared with conventional methods of biomicroscopy. The epithelium appeared as a richly textured "ground-glass" field. We noted variations in transparency that could not be detected with conventional slit lamp biomicroscopy. The actual surface area of lesions such as cornea verticillata and herpetic dendrites appeared larger in darkfield illumination because of its high sensitivity to subtle alterations of transparency. CONCLUSION: Darkfield biomicrography of donated corneal tissue permits evaluation of the entire surface area, measurement of localized lesions of varying brightness, and assessment of epithelial cell coverage. As such, it extends our understanding of tissue clarity. Coupled with digital imaging technology, darkfield biomicrographs could be shared on the Internet and would allow transplanting surgeons to review tissue before selecting it for surgery. This technique could also be used in pharmaceutical research to measure changes in lesion size after therapy and could be incorporated into an eye bank quality assurance program. A new challenge for eye banking is to identify corneas in vitro that have undergone refractive surgeries such as laser in situ keratomileusis and photorefractive keratectomy-surgical alterations not easily seen at the slit lamp. Darkfield biomicrography may also be useful in detecting these lesions.

Identification of a herpes simplex virus-induced dendrite in an eye-bank donor cornea.

PURPOSE: To demonstrate the presence of an active herpetic dendrite in an eye-bank cornea. CASE REPORT: One eye-bank cornea was studied. Viral cultures and polymerase chain reaction (PCR) testing were performed 4 days after tissue preservation. The presence or absence of herpes simplex virus (HSV) type 1 was investigated. RESULTS: The presence of an active HSV dendrite in an eye-bank cornea was verified. HSV type 1 was confirmed using PCR amplification and restriction endonuclease DNA fragment analysis. CONCLUSION: This case suggests that HSV may remain viable in stored corneal tissue at 4 degrees C.

Clinical and molecular characterization of a family affected with X-linked ocular albinism (OA1)

Thirty-one members of a family affected with X-linked ocular albinism (OA1) were studied to characterize the clinical phenotype and identify the disease-causing mutation. The family members were examined with ophthalmoscopy, electroretinography, and Goldmann perimetry. Linkage analysis was performed with markers from the OA1 locus. Exons 2 and 8 of the OA1 gene were assayed with the polymerase chain reaction (PCR). The six affected males had visual acuities ranging from 20/40 to 20/200. All had nystagmus, iris transillumination, and foveal hypoplasia. The eldest affected male had 20/40 vision and was asymptomatic. The level of the visual acuity of the affected males was not related to the degree of retinal pigmentation. All seven female carriers had normal visual function but were found to have iris transillumination defects and variable retinal pigmentary appearance ranging from minimal pigmentary disturbance, patchy and diffuse hypopigmentation, to classic 'mud-splattered' appearance. Linkage analysis was consistent with a disease-causing mutation at the OA1 locus. PCR analysis revealed a deletion which includes at least the portion of the OA1 gene between exons 2 and 8. Affected males with X-linked ocular albinism can have a visual disability that ranges from almost none to legal blindness, and the female carriers can have variable retinal pigmentary appearance. Mutation screening of the OA1 gene can be used to confirm the diagnosis in isolated males of some families, and genetic linkage analysis can be used to accurately identify carriers even when the specific mutation cannot be identified.

Neuro-ophthalmologic findings in the Asperger disorder.

Asperger disorder is a complex behavioral disorder that may be related to autism. We examined a 49-year-old man with Asperger disorder who had multiple neuro-ophthalmologic abnormalities, including colobomatous defects involving the optic discs and peripapillary retina, and abnormal ocular motility with an oculocephalic dyskinesia. Asperger disorder may be associated with a variety of neuro-ophthalmologic disturbances.

Blindness, deafness, quadriparesis, and a retinal malformation: the ravages of neurofibromatosis 2.

Advances in molecular biology have established that the diseases once collectively referred to as neurofibromatosis are actually genetically distinct and clinically heterogenous conditions. This realization has led to separate definitions for neurofibromatosis (NF) type 1 and 2. Although ophthalmologic manifestations of NF1 have long been recognized, the distinguishing ocular features of NF2 have only recently received attention. We describe an inferior retinopapillary malformation with an overlying glial hamartoma in a deaf, quadriparetic patient with NF2. Magnetic resonance (MR) imaging initially showed bilateral vestibular schwannomas and a large cervical ependymoma. Over six years of follow-up, the patient developed multiple intracranial meningiomas.

Diabetic retinopathy: a review for the primary care physician.

Hyperglycemia can result in key biochemical reactions that may contribute to thickening of basement membranes, dysfunction of pericytes and endothelial cells, and closure of retinal vessels. The Diabetes Control and Complications Trial has proved the value of good glycemic control in preventing retinopathy and/or delaying its progression. The primary care physician has a crucial role in translating these results into practice. Recognition and management of other risk factors, such as proteinuria, smoking, and hypertension, are easily done in the primary care setting. Also, appropriate referral to an ophthalmologist for retinal evaluation and treatment is both necessary and cost effective in reducing the burden of this devastating complication of diabetes.

Intraoral and intranasal photography using a retinal fundus camera.

Like other subspecialities in biomedical imaging, clinical ophthalmic photography requires specialized instrumentation to produce informative photographs. Photographic slit-lamps, external ocular cameras, and retinal fundus cameras each have optical and illumination components that are designed to yield optimal results within narrow subject contexts. A variety of ophthalmic pathologies are associated with lesions in other parts of the body. One disease, cicatricial pemphigoid, causes changes in the mucosal tissue of the nasal and oral passages in addition to conjunctival findings. Lacking endoscopic instrumentation, we capitalized on the design parameters of a retinal fundus camera to produce photographs of these remote lesions.

A comparison of corneal endothelial changes after use of Healon or Viscoat during phacoemulsification.

We conducted a prospective, randomized trial comparing the endothelial protective effects of Healon (Kabi Pharmacia Ophthalmics, Inc., Monrovia, California) and Viscoat (Alcon Surgical, Inc., Ft. Worth, Texas) in 59 eyes of 59 patients undergoing iris-plane or posterior-chamber phacoemulsification with posterior-chamber lens implantation. We evaluated postoperative central and superior changes in corneal thickness and corneal endothelial cell density, coefficient of variation in cell size, and percentage of hexagons. In the overall series, at one day postoperatively, corneal thickness increased 17% centrally and superiorly in eyes receiving Healon compared to 12% centrally and 11% superiorly in eyes receiving Viscoat (P < .05). Sixteen weeks postoperatively, superior endothelial cell loss was 11.6% in eyes receiving Healon compared to 2.1% in eyes receiving Viscoat (P < .01). In the iris-plane phacoemulsification group, superior cell loss at week 16 was 13.8% in eyes receiving Healon and 0.5% in eyes receiving Viscoat (P < .04). In the posterior-chamber phacoemulsification group, there were no significant differences between the Healon and Viscoat subgroups. Comparing the surgical techniques, in the Healon group, central cell loss at week 16 was 13.8% in the iris-plane phacoemulsification subgroup and 0.6% in the posterior-chamber phacoemulsification subgroup (P < .03), and coefficient of variation in cell size increased 3.7% in the iris-plane subgroup and decreased 6.8% in the posterior-chamber subgroup (P < .04). In the Viscoat group, there were no significant differences between surgical techniques at week 16. Viscoat provided greater corneal endothelial protection than Healon during iris-plane phacoemulsification. In eyes receiving Healon, posterior-chamber phacoemulsification resulted in less corneal endothelial trauma than the iris-plane technique.

Pupillary size and responsiveness. Implications for selection of a bifocal intraocular lens.

The authors measured the pupil sizes of 132 subjects and correlated these to selected designs of annular bifocal intraocular lenses (IOLs). Pupils were measured under five different testing conditions that simulated representative visual tasks: (1) driving at night, (2) reading in dim illumination, (3) reading in bright illumination, (4) distant viewing in indirect sunlight, and (5) distant viewing in direct sunlight. Pupil size diminished with age and with increased illumination. Because of accommodative pupillary constriction, there was little difference in pupil size measured while reading in bright indoor illumination and distant viewing in indirect sunlight. Evaluating a patient's pupil size permits the individualized estimation of the eye's bifocal function following implantation of each of the annular-design bifocal IOLs.

Dominant dysplasia of the lens in transgenic mice expressing the dbl oncogene.

To study the transforming activity of the dbl oncogene and its effect on normal development in vivo, we linked dbl cDNA to promoters with different cell type specificities and used the constructs to generate transgenic mice. The promoters included the mouse alpha A-crystallin promoter, the rat insulin II promoter, and a mouse metallothionein promoter. We also generated transgenic mice carrying a recombinant cosmid clone that contains the entire dbl gene. Mice with the crystallin promoter construct developed cataracts and expressed the dbl protein in their lenses. The architecture of the lenses suggested a block to the normal pattern of differentiation and elongation of the secondary fiber cells. Mice with the insulin II promoter expressed dbl protein in the pancreas but showed no evidence of diabetes and no apparent pancreatic beta-cell defects. Similarly, mice with the metallothionein promoter expressed dbl protein in heart and testes, but showed no pathologic abnormalities in these tissues even after treatment with heavy metals. However, one family of mice carrying the metallothionein promoter construct showed cataracts and a dramatic fibroblastic dysplasia of the lens. One family with the cosmid-dbl gene showed a nearly identical lenticular dysplasia, but with a slower developmental time course. Thus, although the dbl oncogene did not induce neoplasia in any of the mice studied, it is apparently capable of interfering with the ability of the lens epithelial cells to differentiate into lens fiber cells, and of inducing metaplasia of the epithelial cells into fibroblastic cells.

Improved resolution of specular micrographs.

The purpose of specular photomicrography of the corneal endothelium is to depict fine cellular morphology and to determine total cell density. The use of silver-based photographic films to record the cells and generate enlarged paper prints yields the highest resolution currently possible. Previously, the quality of these prints was diminished when the highly resolved cell image was combined with the standardized grid used for quantification, since the sub-optimal quality of the grid's plastic substrate caused optical aberrations. We present a prototype device and a modified technique that enables the full resolution of the microscope to be represented on photographic prints and allows highly detailed views of the endothelial mosaic to be depicted with or without the standardized grid.

Fluorescein angiography printouts.

Nineteen years after the pioneering efforts of Novotny and Alvis, fluorescein angiography has reached a level of acceptance and use which reflects its high value in ophthalmic diagnosis. Angiography laboratories are commonplace in hospitals, and many private physicians own fundus cameras and perform fluorescein angiograms routinely. As the use of this test has substantially increased, so has the number of methods used to present the film for analysis and interpretation. At this writing there are no fewer than 12 different ways of presenting fluorescein angiograms in common use (Table 1). Not all of these techniques are able to yield equal amounts of information, however, and as consultations between different laboratories occur, much difficulty results from the disparate styles. Evaluation of these varying techniques of fluorescein angiography presentation depends on the production complexity and the amount of useful information which each may yield.

Rapid access fluorescein angiography.

The time interval usually required for processing fluorescein angiography films has been dramatically shortened to 90 seconds by using Kodak Linagraph Shellburst Film 2474 processed in the automatic Kodak RP X-omat processing machine, with attendant increases in image clarity and contrast.