Clinical and electron microscopic observations of the conjunctiva of adult patients with Bitot's spots.

Three adult patients with Bitot's spots of the conjunctiva were observed in the American Southwest; all were in good health without obvious cause for vitamin A deficiency. Serum vitamin A levels were low normal in two; the third patient was on replacement vitamin A therapy with resultant high serum levels. Serum beta-carotene levels were low in two and normal in one. Schirmer test without anesthesia was low normal in two and with topical anesthesia was abnormal in all. After 8 weeks of oral vitamin A therapy, the Schirmer test and Bitot's spots showed little response. Electron microscopy of Bitot's spots showed changes characteristic of keratinizing squamous epithelium: absence of goblet cells, increased tonofibrils, flattening of intermediate cells, loss of superficial cell nuclei, and a keratin layer. Light microscopy of the inferior cul-de-sac conjunctiva showed increased surface goblet cells in two and absence of such cells in the third; by electron microscopy the substructure of the majority of the goblet cell mucin granules had a reticulated appearance in which an electron-dense fibrillar network was present within the granule matrix. The non-mucin-containing epithelial cells of the inferior cul-de-sac for the most part appeared normal.

Inhibition of the enteroviruses that cause acute hemorrhagic conjunctivitis (AHC) by benzimidazoles; enviroxime (LY 122772) and enviradone (LY 127123).

Enviradone (EvirD, (E)-1-[(1-methylethyl) sulfonyl]-6-(1-phenyl-1-propenyl)-1 H- benzimidazole-2-amine) and Enviroxime (EvirX, 2-amino-1-(isopropyl-sulfonyl)-6-benzimidazole phenyl ketone oxime) inhibited enterovirus 70 (EV70) and coxsackievirus A24 variant (CA24v) infection of conjunctival and laryngeal cells. On average, the continuous presence of 1-3 micrograms of EvirD or EvirX/ml in cell cultures acutely infected with EV70 or CA24v inhibited virus production (> 2 log10 reduction) and 100% of the viral cytopathogenic effect (CPE). The 50% CPE inhibitory dose (ID50) for EvirD and EvirX against 11 EV70 and 15 CA24v isolates ranged from 0.01 to 0.3 microgram and 0.01-0.65 microgram/ml, respectively. The mean ID50 for EvirD and EvirX against the 26 AHC viruses was 0.17 +/- 0.12 microgram and 0.13 +/- 0.14 microgram/ml, respectively. Pretreatment for 15 min with 3 micrograms EvirX/ml or for 1-2 h with 3 micrograms EvirD/ml protected conjunctival cells against viral CPE. The cells were resistant to infection for 1-2 h at 33 and 37 degrees C after removal of EvirD and EvirX. The addition of 10 micrograms EvirD/ml up to 6 h or 10 micrograms EvirX/ml 1-2 h after low multiplicity infection inhibited viral CPE. Ten-fold less EvirD inhibited EV70 when added to glioma cells 2 h before infection than when added 2 h after infection. Our results indicate that EvirX and EvirD inhibit AHC viruses in vitro at concentrations that are not cytotoxic and suggest that EvirX or EvirD may be prove useful against AHC.

Epidemiologic study of time and space clustering of 4 cases of choroidal malignant melanoma.

OBJECTIVE: To identify common risk factors that might be associated with a cluster of 4 cases of choroidal malignant melanoma that occurred in a manufacturing plant between 1982 and 1985. DESIGN: Survey of choroidal malignant melanoma cases in Caddo and Bossier parishes during the same time frame. METHODS: We identified 4 additional individuals with choroidal malignant melanoma first diagnosed during the study period. Characteristics of the workplace were examined and a questionnaire was administered to all subjects to ascertain exposures to putative carcinogens and to putative risk factors for intraocular malignant melanoma. Observed and expected incidence rates were calculated. RESULTS: The overall incidence of intraocular malignant melanoma for the 2 parishes during the 4-year period was 0.56 cases per 100,000 population per year, similar to the expected rates for this population. The incidence rate for the manufacturing plant employees was 16.5 cases per 100,000 per year. The mean age at diagnosis for workers at the plant was 38.7 years compared with 69.2 years for nonplant employees. CONCLUSIONS: The close occurrence of manufacturing plant cases in time and space and the younger age of the people are consistent with a cluster of intraocular melanoma cases. No specific risk factors were found in the workplace environment to impute a causal association.

Risk of visual impairment attributable to ocular histoplasmosis. Washington County Follow-up Eye Study Group.

PURPOSE: To compare 15-year incidence rates of visual impairment and vision-threatening conditions between cases with ocular histoplasmosis and controls residing in the same endemic community. METHODS: Controls and cases with and without disciform lesions who were between 30 and 69 years of age when selected, interviewed, and examined in 1970 were reinterviewed and reexamined in 1985. RESULTS: Of the 252 cases and controls examined in 1970, 216 were still alive in 1985. Of these, 202 (94%) were interviewed; 197 (91%) underwent visual acuity measurement; and 173 (80%) were examined by a study ophthalmologist. Both in 1970 and in 1985, cases with disciform macular lesions of ocular histoplasmosis had a higher prevalence of both unilateral and bilateral visual impairment and blindness. Although prevalence of visual impairment and blindness in 1985 was similar among controls and cases of ocular histoplasmosis without disciform lesions, this group of cases had about twice the incidence of visual impairment as that of controls. However, the 95% confidence intervals on estimates of relative risks were broad and included unity. No new disciform lesions attributable to ocular histoplasmosis were found in 28 eyes of 18 cases free of them in 1970 or among 148 controls. CONCLUSIONS: The 15-year risk of visual impairment and blindness appears to be somewhat higher among adults aged 30 years and older who have only peripheral atrophic scars characteristic of ocular histoplasmosis than among individuals without such scars who live in the same endemic community. Adults who already have a disciform lesion attributed to ocular histoplasmosis in one eye are at low risk of development of a disciform lesion in the fellow eye later in life.

Prevalence of chorioretinal scars associated with coccidioidomycosis.

A retrospective study was conducted to determine the prevalence and spectrum of chorioretinal involvement among individuals with previously documented systemic coccidioidomycosis. Fifty-four subjects were given a modified ocular examination, and their medical records were abstracted for clinical classification of the disease and its correlation with ocular findings. Five of 54 subjects with documented past infection with Coccidioides immitis had characteristic inactive peripheral chorioretinal scars. No relationship between the presence of scars and the extent of disease was evident; typical scars were found in patients who had experienced mild respiratory tract infection as well as in more extensively disseminated disease. We conclude that dissemination of C immitis to the eye can occur during benign pulmonary coccidioidomycosis as well as with more severe systemic disease, and the prevalence of chorioretinal lesions is more common than isolated case reports would indicate.

Lymphocyte transformation in presumed ocular histoplasmosis.

Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

Epidemiological aspects of ocular hypertension.

A number of epidemiologic factors have come to be associated with an elevated intraocular pressure. These factors include age, sex, blood pressure, juvenile diabetes mellitus, blood sugar, menstrual cycle, menopause, inheritance, obesity, pulse rate, stature, myopia, aqueous production, time of day and season of the year. These factors are discussed in some detail with speculation as to how they may relate to the ocular hypertensive state.

Ocular coccidioidomycosis.

Coccidioidomycosis has been recognized as a common systemic disease since the late 1930's. The occurrence of ocular lesions associated with the systemic infection is uncommon. The anterior segment manifestations appear to be a mild hypersensitivity response; the disease may present as a chronic granulomatous iridocyclitis. In the posterior eye, the manifestations may range from asymptomatic focal chorioretinitis (somewhat similar to the peripheral atrophic lesions of the ocular histoplasmosis syndrome) to a fulminating granulomatous process involving the entire eye. The ocular lesions can occur in the asymptomatic form of systemic coccidioidomycosis. Diagnosis may be confirmed by skin tests and serologic tests. Amphotericin B is usually the drug of choice when treatment is required; however, its adverse effects may be severe, and other drugs, notably Miconazole and Ketoconazole, are being investigated as potential alternatives.

The Framingham Eye Study monograph: An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975.

Ophthalmologic examinations for cataract, glaucoma, diabetic retinopathy, macular degeneration and visual acuity were performed on 2631 of the 3977 members of the Framingham (Massachusetts) Heart Study population still living in 1973-1975. The subjects ranged in age from 52 to 85 years. This monograph presents the detailed protocols and record forms for screening and diagnostic examinations, definitions of the specific abnormalities and characteristics used to screen for each disease, criteria for suspicion and diagnosis of diseases, detailed tables of the basic data from the study, evaluation of quality of the data, and discussion of selected findings. The tables provide data on the number and proportion of persons and of eyes with each type of abnormality and each disease, by age and sex. Where appropriate, the data are further classified by location of abnormality, severity, bilaterality and associated visual acuity limitation. The study was sponsored by the National Eye Institute.

Aspirin and recurrent hyphema after blunt ocular trauma.

Recurrent hyphema after traumatic blunt injury to the eye is associated with a more serious prognosis than that occurring from the initial trauma, resulting in a higher risk of glaucoma, corneal staining, surgical intervention, poor visual acuity, and enucleation. Risk factors associated with the development of recurrent bleeding are not well defined, but recent evidence suggests a high association with concurrent aspirin ingestion. Of 25 consecutive patients with hyphemas (20 males and five females, ranging in age from 2 to 53 years), 12 took aspirin after the initial trauma and seven had recurrent hyphemas. Platelet aggregation determinations in these seven patients showed defects associated with aspirin. Only one of 13 patients without aspirin intake had recurrent bleeding.

Variability in grading diabetic retinopathy from stereo fundus photographs: comparison of physician and lay readers.

Two physicians and two lay readers were trained according to a detailed protocol in the grading of 17 lesions found in diabetic retinopathy by evaluation of stereo fundus photographs according to a modified Airlie House classification. Intraobserver and interobserver variability of these readers was assessed by two methods: weighted kappa, and frequency of agreement within one grade. In general, physician readers were found to be less variable on replicate readings than were lay leaders, and had slightly better agreement with each other than with the lay readers. The physiological significance of the direction and magnitude of the difference between physician and lay reader variability for individual lesions was often uncertain. Assessment of contribution to disagreement by individual readers was possible and permits future training directed at reducing disagreement to acceptable values.

Projected color slides as a method for mass screening of red-green color deficient individuals.

University students (111, both male and female) were screened for red-green color deficiency using projected 35 mm slides reproduced from Ishihara and H-R-R color plates. Ishihara and H-R-R color plates were tested in the same individuals at a second setting and the responses compared: 6.3% of the students were identified as color deficient by the Ishihara and 80.2% by the H-R-R projected slides while 5.4% were designated color blind by the Ishihara plates and 4.5% by the H-R-R plates. The sensitivity of both screening systems was 100%; the specificity of the Ishihara slides was 98.1% compared to only 20.8% for the H-R-R. The 9.8% prevalence of red-green deficiency detected by the Ishihara plates and 8.2% by the H-R-R plates for males is similar to the 6 to 9% frequency found for Caucasian males in other population studies. Within rigid guidelines, projected color slides have potential usefulness as a screening method for detecting individuals with red-green color deficiencies.

Isolation of a herpes simplex virus type 2 that is retinovirulent in mice.

The virulence of a herpes simplex virus type 2 (HSV-2) isolated from the urine of a patient (SL) with acquired immunodeficiency syndrome (AIDS) and bilateral acute retinal necrosis (ARN), was investigated in mice. The ratio of plaque forming units (PFU) in fibroblasts to the 50% lethal dose (LD50) of HSV-2(SL) in mice was 10 fold more than the PFU to LD50 ratio of a neurovirulent HSV-2, strain 186. Further, HSV-2(SL) caused retinitis with and without lethal encephalitis in mice inoculated intracranially (i.c.). In contrast, mice inoculated with HSV-2(186) died of encephalitis without ocular disease. HSV-2(SL) was isolated from eye and/or brain tissue 1 to 15 days post i.c. inoculation. Ocular disease progressed from an initial mild chorioretinitis on day 8 to total retinal necrosis with panuveitis by day 11 in mice given 10 PFU of HSV-2(SL) i.c. HSV antigen was detected initially in the cells of the optic nerve and spread into the ganglial cells of the nerve fiber layer, the neurosensory cells of the inner nuclear layer, and the cells of the retinal pigment epithelium (RPE) between days 8 and 10. Thus, this study supports the concept that HSV neurovirulence varies between strains and presents a HSV-2 neurotransmission animal model of ARN.

The natural history of non-disciform ocular histoplasmosis.

Nineteen of 21 asymptomatic individuals with non-disciform atrophic chorioretinal scars characteristics of the ocular histoplasmosis syndrome and identified in the Walkersville survey were re-examined three years later. During this period, of six subjects with peripapillary scars, one developed symptomatic serous detachment of the peripapillary retina; none of the three with macular or paramacular scars showed any change. Several peripheral scars showed increased pigmentation and others definite enlargement. One patient developed two new atrophic scars.