Contact lens-induced infection--a new model of Candida albicans keratitis.

PURPOSE: A model of experimental keratomycosis was established that mimics human disease in which the only fungi present are those that are actively growing within the cornea. METHODS: Dutch-belted rabbits received a subconjunctival injection of triamcinolone acetonide to one eye. One day later the epithelium was removed from the central cornea and a standardized inoculum of Candida albicans blastoconidia was placed on the corneal surface and covered with a contact lens. The lids were closed with a lateral tarsorrhaphy. After 24 hours, the lid sutures and contact lens were removed. Five days later the animals were killed, and their corneas were subjected to separate isolate recovery and histology studies. A group of similarly infected rabbits without corticosteroid injection served as controls. RESULTS: Both groups developed invasive corneal disease. Although isolate recovery was not significantly different from corticosteroid-treated rabbits compared with controls, fungal biomass was increased. Hyphal invasion was limited to the anterior cornea in control eyes, but penetrated deep stroma in most of the corticosteroid-treated rabbits. CONCLUSIONS: Invasive corneal disease can be established with a surface inoculum. Corticosteroid administration increased corneal penetration of hyphae. Quantitative isolate recovery is not a reliable measure of the fungal load within the cornea.

Differences in virulence between two Candida albicans strains in experimental keratitis.

PURPOSE: To study the differences in disease caused by two wild-type strains of Candida albicans in a model of contact lens-facilitated keratitis in rabbits. METHODS: Two strains, SC5314 and VE175, were examined. Standardized inocula were placed on the debrided corneal surface of one eye in Dutch belted rabbits and covered with a contact lens. A temporary tarsorrhaphy was opened after 24 hours with removal of the contact lens. Six days later, corneas were photographed and animals killed. Corneas were bisected with one half for quantitative isolate recovery and the other for stromal penetration by hyphae. RESULTS: Strain SC5314 was significantly more virulent. The mean hyphal penetration into the cornea was 24.4% +/- 8.5% of the corneal thickness, and in three of six corneas hyphae penetrated through the entire cornea. In contrast, for VE175, the mean hyphal penetration was 2.6% +/- 1.2%. The difference between these two strains was statistically significant (P = 0.0297). Hyphae did not penetrate into the deep layers of the cornea in any of the six rabbits infected with VE175. The grading of clinical disease was consistent with histology, in that strain SC5314 caused more severe infection than VE175 and the difference was statistically significant (P = 0.0048). There was no difference in isolate recovery. CONCLUSIONS: Wild-type strains of C. albicans can differ significantly in virulence as measured by depth of fungal invasion into corneas and clinical evaluation of infection. Further characterization of the intrinsic genetic differences between such strains may help identify factors responsible for fungal virulence.

Microscopic polyangiitis with ocular involvement.

Microscopic polyangiitis is an exclusively small-vessel (arterioles, capillaries, or venules) vasculitis that primarily involves the kidney and often involves the lungs, skin, or nervous system. Characteristic features include focal segmental glomerulonephritis, nongranulomatous necrotizing vasculitis, and serum positive for perinuclear-staining antineutrophil cytoplasmic antibodies (P-ANCA). We report a case of microscopic polyangiitis with previously unreported eyelid and conjunctival manifestations that responded well to immunosuppressive therapy.

A review of 340 orbital tumors in children during a 60-year period.

We reviewed cases of histopathologically verified orbital tumors in children at our institution over 60 years to determine the distribution of various pathologic processes and trends over time. We studied the medical records and pathology specimens from 340 patients aged 18 years or younger who underwent biopsy for orbital mass from 1932 through 1991. The most common tumors were cysts (79 of 340, 23.2%), vascular lesions (60 of 340, 17.6%), optic nerve and meningeal neoplasms (56 of 340, 16.5%), inflammatory masses (29 of 340, 8.5%), osseous and fibrocystic lesions (27 of 340, 7.9%), and rhabdomyosarcomas (24 of 340, 7.1%). The overall frequency of malignancies was 18.2% (62 of 340): 11.5% (39) were primary tumors and 6.8% (23) were secondary and metastatic. The frequency of orbital malignancies was 25.4% (36 of 142) in the first 30 years (1932 through 1961) and 13.1% (26 of 198) in the second 30 years (1962 through 1991). The percentage of primary orbital malignancies was almost identical during the first and second periods (11.9% [17 of 142] and 11.1% [22 of 198], respectively). However, secondary and metastatic orbital neoplasms occurred in 13.4% (19 of 142) of the patients during the first 30 years and in only 2.0% (four of 198) during the second 30 years. The frequency of primary orbital malignancies in biopsy material remained the same over 60 years. However, the overall incidence of orbital biopsy specimens containing a malignancy decreased as a result of a reduction in the number of secondary and metastatic neoplasms that underwent biopsy.

Endoscopic goniotomy with the free electron laser in congenital glaucoma rabbits.

PURPOSE: Goniotomy is a surgical treatment of choice to treat primary infantile glaucoma. Goniotomy has been studied in vitro in animal and human cadaver eyes with several lasers. The objective of this study was to investigate the functional and morphologic effectiveness of goniotomy with the free electron laser in comparison with conventional needle goniotomy in early congenital glaucoma rabbits. MATERIALS AND METHODS: Ten rabbits with early congenital glaucoma underwent goniotomy over 100 to 120 degrees with a needle or the free electron laser. The wavelength was 6.45 microm, and the energy level ranged from 2.2 to 3.5 mJ at 30 Hz. Because most corneas were edematous in these rabbits, an Olympus 0.8-mm diameter endoscope was coupled to the laser waveguide or the needle and inserted into the anterior chamber filled with a viscoelastic material to perform the goniotomy. Intraocular pressures were followed up to 3 weeks before an acute goniotomy was performed in the contralateral eye. All eye specimens were processed for light microscopic evaluation. RESULTS: Incision of the pectinate ligaments and underlying trabecular meshwork was visualized through the endoscope on a video monitor during the surgeries. The mean intraocular pressure decreased after free electron laser goniotomy and after needle goniotomy, and the edematous corneas became clear in some cases. Histologic study showed successful lysing of the pectinate ligaments by the free electron laser with no obvious collateral thermal damage. However, some areas of peripheral anterior synechiae occurred. Similar results were observed in needle goniotomy cases. CONCLUSIONS: The free electron laser is capable of performing goniotomy in rabbit eyes with lower intraocular pressures in treated eyes 3 weeks after surgery. The histologic results of free electron laser goniotomy are comparable to those of conventional goniotomy. The endoscope provides beneficial visualization to perform the goniotomy in eyes with edematous corneas. The rabbit with early congenital glaucoma is also a useful infantile glaucoma surgical model.

Neonicotinoid insecticides alter diapause behavior and survival of overwintering white grubs (Coleoptera: Scarabaeidae).

The chloronicotinyl, imidacloprid, and the thianicotinyl, thiamethoxam, are effective insecticides against white grubs when applied as preventative treatments during or immediately after egg laying. Their efficacy sharply declines when the grubs reach late-instar stage. As both imidacloprid and thiamethoxam act on post-synaptic nicotinic acetylcholine receptors and modify insect behavior, we hypothesized that the two compounds will interfere with overwintering behavior of scarabs, thus reducing their ecological fitness and exposing them to increased winter mortality. We tested this hypothesis by applying the two compounds curatively against late second-instar and early third-instar Popillia japonica and Cyclocephala borealis grubs in turfgrass. Imidacloprid provided control of P japonica equivalent to the most widely used curative organophosphate, trichlorfon, by 14 days after treatment, but thiamethoxam had no affect. In contrast, both imidacloprid and thiamethoxam caused significant reductions in C borealis populations. Both insecticides altered the overwintering behavior of P japonica by significantly reducing the normal downward movement of grubs in October. Halofenozide, an ecdysone agonist, also caused rapid mortality of the late second-instar C borealis equivalent to trichlorfon, but had no affect on P japonica. In another experiment on a site naturally infested with entomopathogenic nematodes, the exclusive treatment of third-instar P japonica with imidacloprid resulted in no significant mortality in the autumn (up to 15 days after treatment), but caused a significant reduction in the survival of overwintered grubs. There was an increase in the numbers of grubs infected with nematodes in the imidacloprid and trichlorfon treatments compared with control, but these differences were significant only for trichlorfon. These results indicate that imidacloprid can effectively control late second-instars of both P japonca and C borealis and can significantly reduce survival of overwintered third-instar P japonica by altering their normal overwintering behavior.

Black cutworm (Lepidoptera: Noctuidae) larval emigration and biomass in mixtures of endophytic perennial ryegrass and Kentucky bluegrass.

Studies examined the possibility that mixtures of endophytic perennial ryegrass and Kentucky bluegrass provide resistance against larvae of the black cutworm, Agrotis ipsilon (Hufnagel). We hypothesized that resistance against A. ipsilon in such stands would stem from the influence of Kentucky bluegrass on A. ipsilon growth and behavior rather than the influence of endophytic perennial rvegrass. In replicated greenhouse experiments, black cutworm larvae initially emigrated more quickly from pots containing monocultures of endophytic perennial ryegrass than from Kentucky bluegrass monocultures or polycultures of Kentucky bluegrass and endophytic perennial ryegrass. However, biomass of emigrating larvae decreased linearly as the proportion of Kentucky bluegrass increased. Turfgrass mixtures containing endophytic perennial ryegrass and Kentucky bluegrass may provide resistance against A. ipsilon mainly through the physiological effects of Kentucky bluegrass on A. ipsilon growth and development, but possibly through the influence of endophytic perennial ryegrass on A. ipsilon movement and foraging behavior as well.

Hairy chinch bug (Hemiptera: Lygaeidae) damage, population density, and movement in relation to the incidence of perennial ryegrass infected by Neotyphodium endophytes.

Studies examined hairy chinch bug, Blissus leucopterus hirtus Montandon, damage, population density, and movement in stands of perennial ryegrass, Lolium perenne L., containing various proportions of endophyte infected plants (E+). Our main objective was to determine the utility of mixtures containing E+ for management of chinch bugs. Chinch bug damage and population density decreased linearly as the proportion of E+ increased. This trend held true even when chinch bug populations were extremely high. Chinch bug nymphs emigrated more quickly from stands containing 100% E+ than they did from stands containing 50 or 0% E+, whereas adult chinch bug emigration was relatively unaffected by the proportion of E+. Our results indicate that turfgrass mixtures containing E+ can reduce chinch bug damage and population density.

Overseeding endophytic perennial ryegrass into stands of Kentucky bluegrass to manage bluegrass billbug (Coleoptera: Curculionidae).

Studies were conducted to determine the utility of overseeding endophyte enhanced varieties of perennial ryegrass, Lolium perenne L., into existing stands of Kentucky bluegrass, Poa pratensis L., to manage bluegrass billbug, Sphenophorus parvulus Gyllenhal, larval populations and their damage. Two commercial varieties of endophyte enhanced perennial ryegrass (Repell II and Triple Play) were overseeded at two different rates in the field. S. parvulus larval populations, their damage, and turfgrass composition were monitored over the course of 3 yr. Significantly fewer larvae were found in plots overseeded with Repell II, whereas Triple Play had no significant effect on larval population density. Endophyte infection was confirmed in approximately 58% of all Repell II shoots, whereas only approximately 31% of Triple Play shoots were infected. Regression analysis, using a segmented model, demonstrated that larval populations declined as the proportion of endophyte-infected perennial ryegrass increased. However, no additional reductions in larval population density were achieved in stands containing >40% endophyte-infected perennial ryegrass. Visual damage varied with cultivar, seeding rate, and year, but generally decreased as the proportion of endophyte-infected perennial ryegrass increased. Although seeding rate had an initial effect on turfgrass composition, these differences were not detected after the first year of the study. Results indicate overseeding existing stands of Kentucky bluegrass with endophytic varieties of perennial ryegrass can reduce S. parvulus larval populations and their damage. However, plant genetic characteristics (i.e., different cultivars) may be overriding determinants of many aspects of plant performance including establishment, tolerance to insect feeding, and expression of endophyte-mediated resistance.

Morphologic evaluation of Descemet's membrane and corneal endothelium in diabetes mellitus.

Diabetes mellitus is characterized by abnormally thickened basement membranes throughout the body and the eye. In addition, abnormal corneal endothelial cell morphology has been found in eyes of diabetics. The authors examined Descemet's membrane (the basement of the corneal endothelium) and the endothelial cells in 19 diabetic corneas and 19 age-matched nondiabetic normal corneas in a masked fashion by transmission electron microscopy and specular microscopy. No statistically significant quantitative or qualitative differences were found between the two groups.

A clinicopathologic study of three carcinoid tumors metastatic to the orbit. Immunohistochemical, ultrastructural, and DNA flow cytometric studies.

Three patients with histopathologically proven orbital metastatic lesions from a carcinoid tumor are reported. Computed tomography (CT) disclosed a well-circumscribed orbital mass in two of three cases. Each tumor was studied by both light and electron microscopy as well as immunohistochemistry and DNA flow cytometry. A review of the literature discloses the relatively rare occurrence of carcinoid tumors metastasizing to the eye and orbit. With the exception of one case, the reported metastatic carcinoid tumors to the uvea all developed from primary bronchial carcinoids. In contrast, the vast majority of the reported orbital metastases arose from ileal carcinoids. Immunohistochemical markers such as chromogranin A, synaptophysin, and serotonin have proven to be useful diagnostic tools in evaluating carcinoid tumors. Furthermore, DNA flow cytometry may be of prognostic value in patients with metastatic carcinoid tumor.

Optic nerve sheath fenestration with a novel wavelength produced by the free electron laser (FEL).

BACKGROUND AND OBJECTIVE: To determine whether 6.45-microm free electron laser (FEL) energy can successfully perform optic nerve sheath fenestration and to compare the acute and chronic cellular responses with this surgery. STUDY DESIGN/MATERIALS AND METHODS: Optic nerve sheath fenestration was performed in rabbits by using either FEL energy (< 2.5 mJ, 10 Hz, 325-microm spot size) or a knife. The optic nerve integrity and glial response were evaluated histologically acutely or 1 month postoperatively. RESULTS: The FEL at low energy effectively cut the optic nerve sheaths with minimal reaction in the underlying nerve. With FEL or knife surgical techniques, a mild astrocytic hypertrophy only adjacent to the fenestration was observed acutely in the glial fibrillary acidic protein (GFAP) -immunoreacted sections. The chronic healing responses after either technique appeared similar with: (1) a thin fibrous scar at the fenestration site, (2) cells uniformly distributed (hematoxylin and eosin), and (3) up-regulation of GFAP and S100beta in astrocytes adjacent to the fenestration site. CONCLUSION: The FEL at low energy performs an optic nerve sheath fenestration in a small space with ease. Both FEL and knife incisions cause a similar rapid glial response near the fenestration site that remains 1 month later.

Alterations in norepinephrine and dopamine content in selected brain areas of guinea pigs adapted to simulated high altitude.

The alterations in brain content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs adapted to simulated high altitude (hypobaric hypoxia) equivalent to 5500 meters. The animals were adapted for 46 days over a period of 82 days to a pressure of 375 mm Hg. The animals were then killed and the following brain parts dissected: cerebellum, neocortex, caudate head/basal forebrain, diencephalon/rhinencephalon, and brain stem. NE and DA content were analyzed by high pressure liquid chromatography with electrochemical detection by a technique described. Results showed a significant increase of NE and DA in neocortex; a significant increase of DA but not NE in caudate/basal forebrain, and a significant decrease of NE and not DA in diencephalon/rhinencephalon.

6-amino-2-benzothiazole-sulfonamide. The effect of a topical carbonic anhydrase inhibitor on aqueous humor formation in the normal human eye.

The carbonic anhydrase inhibitor, 6-amino-2-benzothiazolesulfonamide, formulated as a 3% suspension in a gel vehicle was instilled in one eye of 21 human subjects in a single dose study to determine its effect on aqueous dynamics. A small but statistically significant effect on aqueous humor flow was observed 2 to 7 hours after application. By 8 hours, the effect had disappeared, and intraocular pressure (IOP) measured 8 hours after application of a single dose was unchanged in these normal volunteers. The drug and its vehicle caused local side effects including irritation, hyperemia, and blurred vision. The authors wondered if multiple doses would produce a greater effect. Four subjects received up to four doses of the drug over 2 days and were restudied. Marked bulbar injection and follicular conjunctivitis, attributable to either the drug or the vehicle, developed in two of the subjects, both contact lens wearers. A milder form of bulbar injection and follicular conjunctivitis developed in a third subject, who received three doses of the drug and was not a contact lens wearer. These side effects precluded additional multiple-dose testing of this formulation of the drug, and no conclusions about the effect of the drug on aqueous flow can be drawn from this portion of the study.

Combined hamartoma of sensory retina and retinal pigment epithelium.

We report two cases of combined hamartoma of the sensory retina and retinal pigment epithelium (CHR-RPE) in which apparent growth of the lesion was observed. In case 1, the eye was enucleated with a presumed diagnosis of juxtapapillary malignant melanoma. Histopathologically, the enucleated globe showed an elevated peripapillary mass containing disorganized retinal tissue intermixed with vascular and glial elements as well as tubules of proliferating retinal pigment epithelium. We have summarized the clinical features of 53 patients with CHR-RPE reported between 1952 and 1988 excluding the cases compiled by the Macular Society Collaborative Study. While the latter study found an equal sex predilection among their cases, we found a 70% male preponderance among the 53 patients. Of the 54 lesions observed in 53 patients, 76% were juxtapapillary, 17% were macular, and 7% were peripheral. Furthermore, periodic follow-up examination disclosed apparent enlargement of the mass in six patients, five of whom underwent enucleation of the globe for suspected melanoma.

Involution of keloid implants in athymic mice treated with pirfenidone or with triamcinolone.

The experimental drug pirfenidone (PFD) has been evaluated as an inhibitor of keloid proliferation and compared with triamcinolone (TAC) injections by studying the involution of active human keloid implants in athymic nude mice (nu-nu). PFD was fed to mice with keloid implants at a level of 2.75 mg/g of feed. At this level PFD had no adverse effect on the body weights of the mice. Implant weights in both PFD-fed and control mice decreased with time. The weights of the implants from the PFD group were significantly lower than those of the control implants at 60 and 90 days after implantation. Consequently PFD may cause an increased degradation and absorption of keloid tissue. The implants from the PFD mice were not significantly different histologically from the implants of the mice with corresponding implants. The chondroitin-4-sulfate (C4S) levels of the implants from PFD-fed mice were not significantly different from those of the implants from control mice. Therefore the mechanism of action of PFD apparently is not mediated by an effect on C4S metabolism. In contrast, the injections of TAC at a level that caused temporary body weight loss in the mice resulted in significant decreases in both hyaluronic acid (HA) and C4S in the keloid implants. Histologically, fibroblasts disappeared from the implants treated with TAC by 20 days after injection. At 30 days after TAC injection, HA and C4S were not detected by electrophoresis in keloid implants; only dermatan sulfate appeared to be present.