Histologic studies of the intraocular toxicity of imatinib mesylate in rabbits.

PURPOSE: To evaluate histologic signs of toxicity of the protein tyrosine kinase inhibitor, imatinib mesylate, in rabbit eyes. METHODS: Twenty Dutch-belted rabbits underwent intravitreal injections of 0.1 ml solutions of imatinib mesylate. Ten rabbits were killed and enucleated 1 week after injection of imatinib mesylate (1.65 mg (four eyes), 165 microg (four eyes), and 16.5 microg (two eyes)). Ten rabbits injected with imatinib mesylate (165 microg (five eyes) and 825 microg (five eyes)) were enucleated 1 month later. Eyes were fixed in 10% formalin and stained with haematoxylin and eosin for microscopic examination. RESULTS: All four eyes injected with 1.65 mg of imatinib mesylate and enucleated at 1 week demonstrated ocular toxicity. All four eyes injected with 165 microg and enucleated at 1 week showed no ocular toxicity. One of the two eyes injected with 16.5 microg and enucleated at 1 week revealed focal areas of subretinal fluid and retinal undulations, suggestive of retinal oedema. None of the 10 eyes injected with imatinib mesylate at either the 165 or 825 microg dose and enucleated at 1 month showed ocular toxicity. CONCLUSIONS: Imatinib mesylate at 1.65 mg caused extensive retinal toxicity in rabbit eyes. In contrast, lower doses did not appear to cause toxicity, but may be associated with retinal oedema.

Intraocular use of rituximab.

PURPOSE: To evaluate the toxicity of 1 mg of intraocular rituximab and to present a small case-series of patients treated with intravitreal rituximab. METHODS: Rituximab (1 mg/0.1 ml) was injected in the vitreous of one eye of three Dutch-belted rabbits. Two animals were injected with balanced salt solution as controls. At 1 month the rabbits were killed and the eyes examined by light microscopy. Three patients (five eyes) with intraocular lymphoma were also treated with a 1 mg injection of rituximab. RESULTS: The treated rabbit eyes and the control eyes showed no light microscopic evidence of ocular toxicity at 1 month following injection. The five human eyes of three patients have shown no evidence of intraocular toxicity with a median follow-up time of 3.6 months (range 2.0-6.4 months). One patient received a total of four injections in the right eye and three injections in the left eye. CONCLUSION: Intravitreal rituximab at a dose of 1 mg does not appear to cause toxicity in rabbit eyes and in the five eyes of three patients.

Histopathology of explanted collar button keratoprostheses: a clinicopathologic correlation.

PURPOSE: To compare the histopathology of three PMMA collar button type keratoprosthesis (KPro)/corneal specimens, explanted due to various complications, with that from one KPro/corneal specimen taken postmortem from an otherwise "healthy" enucleated eye. METHODS: Patient 1 (chemical injury) had no problems for 3 years after KPro placement; the entire eye was obtained postmortem. Patient 2 (repeated graft failures, nonautoimmune disease) developed an "unlaserable" retroprosthesis membrane 4 months after KPro placement. A new KPro was placed. Patient 3 [ocular cicatricial pemphigoid (OCP)] developed tissue melt at the KPro-cornea interface 7 months after KPro placement, and the KPro was replaced. Patient 4 (OCP) developed progressive corneal melt around the KPro 3.5 years after placement resulting in replacement. All KPro/cornea specimens were processed and sectioned for histology with the KPro in place. RESULTS: All patients exhibited growth of corneal or conjunctival derived epithelium under the KPro front plate. In patients 1 and 2, no epithelial downgrowth was noted and the keratocyte density appeared normal with few inflammatory cells present. Dense fibrous tissue was present behind the KPro in patient 2. Patients 3 and 4 showed massive inflammatory cell infiltration and tissue necrosis with "melt" adjacent to the stem resulting in epithelial downgrowth. CONCLUSIONS: Corneal inflammation and degradation after KPro placement correlate well with the preoperative diagnostic category. Patients with immune-related corneal surface disease can exhibit marked inflammatory responses leading to necrosis, stromal melting, and the formation of an epithelial fistula. In contrast, patients without autoimmune corneal disease demonstrate a remarkably noninflamed cornea with intact keratocytes and without epithelial ingrowth, commensurate with their clinical appearance.

Comparison of Chen Medium and Optisol-GS for human corneal preservation at 4 degrees C: results of transplantation.

PURPOSE: To compare results after transplantation of donor corneas stored in Chen Medium (containing beta-hydroxybutyrate without sodium bicarbonate or chondroitin sulfate) to corneas stored in Optisol-GS medium (containing sodium bicarbonate and 2.5% chondroitin sulfate). METHODS: We performed 32 consecutive penetrating keratoplasties with donor corneas stored at 4 degrees C in either Chen Medium or Optisol-GS by random assignment. Corneal thickness measurements were made at 1 day, 1 week, 3 weeks, 2 months, and 1 year postkeratoplasty. Specular microscopic images of the donor endothelium were obtained at the beginning of storage and 2 months and 1 year postkeratoplasty. The percentage of intact epithelium 1 day after keratoplasty and the graft epithelialization time were estimated by the surgeons. Donor rim cultures were performed. RESULTS: No statistically significant differences in corneal thickness or endothelial cell loss between the corneas stored in the two media were found at any time, although differences of less than 12% cell loss or 0.09-mm thickness at 2 months or less than 25% cell loss or 0.10-mm thickness at 1 year could not be excluded with 90% certainty in this small series. The mean percentages of intact graft epithelium on day 1, 64% for Chen Medium and 65% for Optisol-GS, were not significantly different. Endothelial cell density 2 months postkeratoplasty was significantly decreased for corneas stored in both media. Endothelial cell loss at 2 months was directly correlated with storage time in both media. CONCLUSIONS: After keratoplasty, no statistically significant differences in corneal thickness, epithelial survival, and endothelial cell loss were found between corneas stored in Chen Medium and Optisol-GS. Endothelial cell loss at 2 months was significantly correlated with storage time in both media.

Probability of Nd:YAG laser capsulotomy after cataract surgery in Olmsted County, Minnesota.

PURPOSE: To estimate the cumulative probability of Nd:YAG laser posterior capsulotomy after cataract extraction in a geographically defined population. METHODS: Rochester Epidemiology Project databases were used to identify retrospectively all Nd:YAG laser posterior capsulotomies performed on Olmsted County, Minnesota, residents who had previously undergone cataract extraction between 1988 and 1996, inclusive. Demographic data and potential risk factors for laser, including age, sex, surgical technique, year of surgery, and intraocular lens material, were obtained by chart review or by retrieval from computer databases. The cumulative probability of Nd:YAG laser posterior capsulotomy was calculated by Kaplan-Meier estimates, and risk factors were analyzed using the Cox proportional hazards model. RESULTS: A total of 925 Nd:YAG laser posterior capsulotomies were identified after 3541 cataract extractions in 2718 patients. The cumulative probability of Nd:YAG laser posterior capsulotomy after cataract surgery was 6% (95% confidence interval = 5% to 7%) at 1 year, increasing to 38% (35% to 40%) at 9 years. Young age at the time of surgery (P =.02), polymethylmethacrylate intraocular lens material (P <.001), earlier year of surgery (P <.001), and extracapsular extraction (in comparison with phacoemulsification, P <.001) were found to increase significantly the risk of subsequent Nd:YAG laser posterior capsulotomy. Women tended to have a greater probability of Nd:YAG laser posterior capsulotomy (P =.17), but this difference was not statistically significant. CONCLUSIONS: Nd:YAG laser posterior capsulotomy was common after cataract surgery but infrequent during the first postoperative year. Prolonged follow-up is necessary in investigations of the effects of new cataract surgery technologies on the probability of capsulotomy.

Indiscriminate use of corticosteroid-containing eyedrops.

Ocular complications may occur with the use of corticosteroid-containing eyedrops. We describe two cases of corticosteroid-induced glaucoma and one case of corticosteroid-associated fungal keratitis. Corticosteroid-containing eyedrops should be avoided unless the practitioner is knowledgeable about tonometry, slit-lamp examination techniques, and ocular differential diagnosis and treatment. Alternative pharmacologic approaches to topical administration of corticosteroid-containing eyedrops are discussed.

Factitious disease of periocular and facial skin.

PURPOSE: To describe the clinical appearance of factitious (or self-inflicted) lesions on periocular skin and face. METHODS: All patients with factitious cutaneous disease who were examined at Mayo Clinic, Rochester, Minnesota, between 1985 and 1997 were identified. For patients with lesions on the face and periocular skin, the demographic features, clinical descriptive characteristics of their lesions, associated psychopathology, and treatments were ascertained. RESULTS: Of 38 patients with factitious dermatitis, 18 (47%) had facial lesions. Of these 18 patients, 15 (83%) were female. The mean age (+/- SD) of the patients with facial lesions was 35.2 +/- 15.7 years (range, 9 to 66 years). Eight patients (44%) had neurotic excoriations, nine (50%) had dermatitis artefacta, and one (6%) had trichotillomania. The working diagnoses of five patients cared for initially in the Department of Ophthalmology were corneal epithelial and facial desquamation associated with severe pain of unknown cause, medial cicatricial ectropion of probable vasculitic cause, basal cell carcinoma of the nasojugal fold, recurrent preseptal cellulitis resistant to medical treatment, and madarosis of the upper eyelids of unknown cause. CONCLUSION: Cutaneous factitious disease may masquerade as numerous clinical entities and should be included in the differential diagnosis of lesions of the periocular skin.

Retinal detachment in Olmsted County, Minnesota, 1976 through 1995.

OBJECTIVE: To estimate the incidence of rhegmatogenous retinal detachment (RD) in a geographically defined population and to compare the probability of RD in residents after cataract extraction with the probability of RD in residents who did not have cataract extraction. DESIGN: Rochester Epidemiology Project databases were used to perform a retrospective population-based incidence study of RD diagnosed between 1976 and 1995 with cohort analyses of the influence of risk factors on the occurrence of RD. PARTICIPANTS: The population of Olmsted County, Minnesota, participated. MAIN OUTCOME MEASURE: Incidence rates of RD adjusted to the age and gender distribution of the 1990 U.S. white population were measured. RESULTS: Three hundred eleven incident cases of rhegmatogenous RD were identified. The mean annual age- and gender-adjusted incidence rate of rhegmatogenous RD was 17.9 per 100,000 persons (95% confidence interval [CI], 15.9-19.9). For idiopathic rhegmatogenous RD alone, the mean annual age- and gender-adjusted incidence rate was 12.6 (95% CI, 10.9-14.3) per 100,000 persons. Ten years after phacoemulsification and extracapsular cataract extraction, the estimated cumulative probability of RD was 5.5 (95% CI, 3.4-7.6) times as high as would have been expected in a similar group of county residents not undergoing cataract surgery. CONCLUSIONS: Cataract surgery is associated with a significantly elevated long-term cumulative probability of retinal detachment.

Ocular manifestations of systemic infections.

Systemic infections occasionally present with ocular involvement. Prompt diagnosis and management, aided by an internist, may lead to resolution of the infection without severe ocular sequelae. Recent literature discussing atypical ophthalmic manifestations, treatment options, or transmission risks of the following diseases is reviewed: infection with hepatitis viruses, toxoplasmosis, tuberculosis, bacteremia, and endogenous mycotic endophthalmitis.

Cataract extraction rates in Olmsted County, Minnesota, 1980 through 1994.

OBJECTIVE: To analyze population-based trends in cataract extraction. DESIGN: Rochester Epidemiology Project databases; which capture virtually all health care services provided to residents of Olmsted County, Minnesota, were used to perform retrospective cohort analyses of rates of primary cataract extractions performed between 1980 and 1994. PARTICIPANTS: The population of Olmsted County, Minnesota. MAIN OUTCOME MEASURES: Incidence rates adjusted to the age and sex distribution of the 1990 US white population were analyzed using Poisson regression. RESULTS: The 4257 procedures performed on 3176 patients of all ages represented overall annual age-adjusted rates of 404 procedures per 100,000 females and 320 per 100,000 males. Annual age- and sex-adjusted rates for both sexes combined rose from 133 procedures per 100,000 in 1980 to a peak of 507 per 100,000 in 1992. The rates fell to 470 per 100,000 in 1994. Manual review of a random sample of records estimated case overascertainment at 0.9%. CONCLUSIONS: With the exception of 1988 and 1989, rates of cataract surgery in this geographically circumscribed population increased every year between 1980 and 1992. Data from 1993-1994 indicate that rates may have plateaued and possibly declined slightly. If sustained, these patterns could have major implications for future utilization of ophthalmologic resources.

Concordance of Medicare data and population-based clinical data on cataract surgery utilization in Olmsted County, Minnesota.

The authors assessed concordance of local Medicare health care utilization data on cataract surgery and estimates generated using the databases of the Rochester Epidemiology Project, which capture virtually all medical care received by residents of Olmsted County, Minnesota. The Rochester Project databases identified 1,353 primary cataract extractions performed in Olmsted County between October 1989 and December 1993 among county residents aged > or = 65 years. Medicare data identified 1,148 claims-84.8% of the number of procedures identified by the Rochester Project. Ratios of numbers of encounters (Medicare/Rochester Project) were 189/350 (0.540) for 1992 versus 959/1,003 (0.956) for the other years combined. Changes in Medicare data file transfer procedures may have produced the 1992 data shortfall. Medicare data should periodically be compared with source data to assess concordance.

The contralateral corneal endothelium in the iridocorneal endothelial syndrome.

OBJECTIVE: To evaluate the corneal endothelial morphometric measures of the contralateral, clinically uninvolved eye of patients with the iridocorneal endothelial (ICE) syndrome. DESIGN: A retrospective review of the specular microscopic photographs of the contralateral corneal endothelium of all patients with ICE syndrome seen at Mayo Clinic, Rochester, Minn. SETTING: Ophthalmology department, Mayo Clinic. PARTICIPANTS: Twenty-eight patients with unilateral ICE syndrome who had bilateral endothelial photographs (ICE group) and 28 normal, age-matched control subjects (control group). MAIN OUTCOME MEASURES: Percentage of hexagonal cells, coefficient of variation of cell area, and endothelial cell density. METHODS: For each patient and control, 100 endothelial cells were digitized from projected endothelial photomicrographs of the central corneas in the uninvolved eyes. RESULTS: A statistically significant decrease was noted in the mean percentage of hexagonal cells (ICE, 62%; control, 69%; P = .002), and an increase was noted in the mean coefficient of variation of cell area (ICE, 0.28; control, 0.25; P = .02) in the patients with ICE syndrome compared with normal, age-matched controls. The mean endothelial cell density did not differ significantly between the 2 groups (ICE, 2588; control, 2759; P = .10). CONCLUSION: Our data suggest that the clinically uninvolved, contralateral eyes in patients with ICE syndrome have subclinical endothelial abnormalities as evidenced by a relatively low percentage of hexagonal cells and a relatively high coefficient of variation of cell area.

Familial subepithelial corneal amyloidosis--a lactoferrin-related amyloidosis.

PURPOSE: To isolate the protein that collects in increased amounts beneath the corneal epithelium in familial subepithelial corneal amyloidosis (FSCA), also known as gelatinous droplike corneal dystrophy, and to identify it by N-terminal amino acid sequencing. METHODS: Peptides resulting from pepsin digestion of a unique protein isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from frozen tissue from two corneas with FSCA were purified by high-pressure liquid chromatography followed by protein sequence analysis. The protein was identified by amino acid sequencing, Western blotting, and immunohistochemistry. RESULTS: A protein was identified in two corneas with FSCA that was not present in normal corneas or in corneas with other disorders. The amino acid sequences of two peptides derived from this protein were identical to portions of lactoferrin. The unique protein reacted with rabbit antihuman lactoferrin after Western blotting. The presence of lactoferrin in the amyloid within affected corneas was confirmed using the immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections and lactoferrin antiserum. CONCLUSIONS: Corneal tissue with FSCA contains lactoferrin, and this is the first form of amyloidosis found to be associated with this protein. Because lactoferrin is a product of lacrimal glands, the corneal lactoferrin may be derived from the tears. Because the gene for lactoferrin is on chromosome 3 (3q21-q23), this locus is a potential site for the FSCA gene.

Acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty.

PURPOSE: A case of acyclovir-resistant herpes simplex virus keratouveitis after penetrating keratoplasty is reported. METHODS: Resistance to acyclovir was evident clinically and was confirmed by in vitro susceptibility testing. The susceptibility of the herpes simplex isolates to acyclovir and foscarnet was determined by a dye uptake assay that measured cytopathic effect, and thymidine kinase activity was measured by a plaque autoradiography technique. RESULTS: The viral isolate from postoperative day 22 was susceptible to acyclovir and foscarnet, and showed normal thymidine kinase activity. Isolates from postoperative days 29 and 32 (coinciding with deterioration in clinical appearance) were resistant to acyclovir, susceptible to foscarnet, and deficient in thymidine kinase activity. CONCLUSION: Practitioners should be aware of the potential for the emergence of resistance in this setting; prophylaxis and rational alternate therapies are discussed.

Cold-induced corneal edema in patients with trigeminal nerve dysfunction.

Two previous cases of cold-induced corneal edema have been reported in patients with corneal anesthesia secondary to a trigeminal nerve disorder. We studied six patients with complete unilateral corneal anesthesia after trigeminal ablation. Subjects' eyes were exposed to 4 C air from a fan for one hour. We measured corneal thickness, corneal surface temperature, and endothelial permeability to fluorescein. During cold exposure, two of the six study eyes exhibited reversible corneal swelling (11% and 26% over baseline value). All anesthetic corneas were consistently colder (13.8 +/- 0.7 C) than the contralateral corneas (21.0 +/- 1.7 C, P = .001). Baseline endothelial permeability and aqueous humor flow rates were similar in both the study and control groups. After cold exposure, the study eyes had a significant transient increase in permeability compared to the controls (7.5 +/- 2.4 x 10(-4) cm/min vs 2.9 +/- 1.4 x 10(-4) cm/min, P = .007). Baseline endothelial photomicrographs also showed increased pleomorphism (fewer hexagonal cells) in the anesthetic corneas. These data suggest that sensory denervation of the eye influences ocular temperature regulation and corneal endothelial cell morphologic characteristics. Some anesthetic corneas are prone to cold-induced edema, which may result from excessive cooling.

An eyelash nidus for dacryoliths of the lacrimal excretory and secretory systems.

We treated two patients with dacryolithiasis secondary to an eyelash. The first patient underwent dacryocystorhinostomy for a stone within the lacrimal sac. In the second patient the dacryolith was removed from a lacrimal gland ductule. Eyelashes found in the tear film or conjunctival fornices during routine examination should be removed to prevent the possible occurrence of dacryolithiasis.