Irido-lenticular abscess as the initial sign of Candida albicans endogenous endophthalmitis.

A-33-year-old man presented with 9 days of conjunctival erythema, pain, and worsening vision in the left eye. Anterior segment examination was significant for a well-defined, cream-colored iridociliary mass. Ultrasound biomicroscopy demonstrated an iris lesion with ciliary body and lenticular involvement. The authors performed a pars plana vitrectomy and lensectomy with an iris biopsy. Culture of the vitreous cassette and iris mass yielded a diagnosis of Candida albicans endophthalmitis. Clinicians encountering an iris nodule with lenticular involvement, even in an immunocompetent adult, are urged to consider a diagnosis of an endogenous endophthalmitis secondary to C. albicans.

Endophthalmitis post complicated cataract surgery associated with Klebsiella pneumoniae.

An 82-year-old woman underwent complicated cataract surgery with subsequent endophthalmitis. She presented with a unique purulent collection with ciliary body involvement and Klebsiella pneumoniae was grown on culture. Klebsiella is a rare cause of endophthalmitis and ciliary body involvement has not previously been reported.

Intracameral toxicity of bacterial components muramyl dipeptide and staurosporine: ciliary cyst formation, epithelial cell apoptosis and necrosis.

The uveitogenic bacterial cell wall component muramyl dipeptide (MDP) is apoptogenic in rabbit kidney cells. The purpose of this investigation was to assess the cytotoxic activity of MDP and staurosporine (STSP; induces cultured corneal and lens cells apoptosis) in rabbit ciliary body tissue. Anterior uveitis was determined by clinical symptoms and increased aqueous humor (AH) protein. Ciliary body tissue was assessed for histological changes, caspase-3 activity, dye uptake, distribution of immunoreactive caspase-3 and DNA ladders at 4 and 6 hours postinjection. Increases in caspase-3 activity, APOPercentage dye uptake, and localization of immunoreactive caspase-3 in ciliary epithelial cells were associated with ciliary cysts of detached nonpigmented epithelial (NPE) cells, as well as apoptotic and necrotic DNA ladders in ciliary body tissues from eyes injected with MDP and/or STSP. The results suggest that intracameral injection of the bacterial components MDP and STSP can induce acute endophthalmic changes in uveal tissue including formation of ciliary body, NPE and pigmented epithelial (PE) cell apoptosis, and ciliary body tissue necrosis.

Intravitreal taurolidine against experimental Staphylococcus epidermidis endophthalmitis in rabbits.

PURPOSE: Taurolidine is a broad spectrum, non-antibiotic antimicrobial agent, not previously tested against infectious endophthalmitis. The efficacy of intravitreal taurolidine in the treatment of experimental Staphylococcus epidermidis endophthalmitis was evaluated and compared with vancomycin in a rabbit model. METHODS: The right eyes of 34 albino rabbits were infected with an intravitreal inoculum of S. epidermidis (10(5) colony-forming units/0.1 ml). The right eyes of four rabbits (group 7) were not infected and served as uninfected controls. 24 hours after inoculation of bacteria the animals were divided into the following treatment groups: group 1 (7 rabbits) received intravitreal taurolidine at 24 hours and group 2 (7 rabbits) received at 48 hours. Group 3 (7 rabbits) received vancomycin at 24 hours and group 4 (7 rabbits) at 48 hours. Group 5 (3 rabbits) received polyvinylpyrrolidone at 24 hours and group 6 (3 rabbits) at 48 hours. Clinical scoring was performed at 24, 48 and 72 hours. At 72 hours post inoculation, vitreous samples were collected for quantitative microbiological studies and then, the eyes were enucleated for histopathological scorings. RESULTS: The clinical and histopathological examinations revealed significant amelioration of inflammation in eyes treated with taurolidine and vancomycin when compared with polyvinylpyrrolidone. The eyes treated with taurolidine also had significantly lower colony forming units than the eyes treated with polyvinylpyrrolidone and taurolidine rendered many eyes sterile. CONCLUSION: Taurolidine is expected to be a potential agent for treatment of S. epidermidis endophthalmitis.

Expression of protein gene product 9.5 in lepromatous eyes showing ciliary body nerve damage and a "dying back" phenomenon in the posterior ciliary nerves.

BACKGROUND/AIM: Peripheral nerve destruction is the hallmark of leprosy. Ocular complications form a substantial part of the clinical manifestations but histopathology of nerve destruction within ocular structures has not been shown satisfactorily. The role of protein gene product (PGP) 9.5 in identifying nerve destruction in the ciliary body and posterior ciliary nerves of lepromatous eyes is shown. METHODS: Serial sections from two lepromatous eyes and two non-lepromatous eyes were stained with PGP 9.5. Histopathological comparison was done on the expression of the PGP 9.5 stain in nerves within the ciliary body, posterior ciliary nerves adjacent to the optic nerve, and nerves tracking through the sclera. RESULTS: In non-lepromatous eyes, PGP 9.5 was expressed in nerves within the ciliary body, the nerves within the sclera, and posterior ciliary nerves adjacent to the optic nerve. In lepromatous eyes no PGP 9.5 was expressed, signifying nerve destruction. CONCLUSIONS: Nerve destruction in lepromatous eyes has been confirmed histopathologically by the absence of or patchy staining with PGP 9.5. Nerve destruction in the ciliary body can extend to the posterior ciliary nerves by an ascending axonopathy. This "dying back" phenomenon is akin to the "glove and stocking" anaesthesia found in lepromatous leprosy.

Effects of Aspergillus fumigatus and Alternaria alternata on human ciliated epithelium in vitro.

Fungi represent the etiologic agent in a large number of patients with chronic sinusitis. Despite this, no study has examined the effects of fungi on ciliated epithelium. This study evaluates the effects of cultures and filtrates of Aspergillus fumigatus and Alternaria alternata on ciliary beat frequency (CBF) in vitro. CBF was recorded after exposure to either a control or experimental solution. A statistical comparison of control and experimental values was performed to determine significance at P < 0.05. A statistically significant inhibition of CBF in cultures and filtrates of A fumigatus and A alternata was demonstrated. We conclude that a soluble metabolite produced by clinical isolates of both A fumigatus and A alternata causes inhibition of CBF and may represent one virulence factor involved in the development of fungal sinusitis.

Pattern of uveitis in a referral uveitis clinic in India.

This report describes a retrospective study of all new patients in our uveitis clinic between January 1992 and December 1994, undertaken to identify the pattern of uveitis in the Indian subcontinent. A standard clinical protocol, and the naming-meshing system with tailored laboratory investigations were used to arrive at a final uveitic diagnosis. Uveitis comprised 1.5% of new cases seen at the centre. Out of 1,273 uveitis cases, anterior uveitis was the most common type (39.28%), followed by posterior uveitis (28.75%), intermediate uveitis (17.44%), and panuveitis (14.53%). The most commonly affected age group were patients in their forties (23.57%). Uveitis was less common in children below 10 years (3.61%) and in adults over 60 years of age (6.44%). Men (62.21%) were more commonly affected than women (37.79%). Aetiology remained undetermined in 59.31% of cases. Anterior uveitis was most commonly idiopathic (58.6%). The most common cause of posterior uveitis was toxoplasmosis (27.87%), and that of panuveitis was the Vogt-Koyanagi-Harada syndrome (21.08%). A higher incidence of microbiologically proven tubercular uveitis (5 cases), and uveitis due to live intraocular nematode (4 cases), and malaria (1 case), were seen, in contrast to other studies. Only 2 cases of AIDS with ocular lesions were seen. This paper reveals the pattern of uveitis seen at a major referral eye institute in India.

Dissemination and replication of MCMV after supraciliary inoculation in immunosuppressed BALB/c mice.

PURPOSE: To study replication and dissemination of murine cytomegalovirus (MCMV) in immunosuppressed (IS) and non-IS BALB/c mice after ocular inoculation via the supraciliary route. METHODS: BALB/c mice were immunosuppressed by injections of methylprednisolone, and MCMV was injected via the supraciliary route. Ocular and nonocular tissues from both IS and non-IS mice were studied by plaque assay of tissue homogenates. The frequency of virus-positive leukocytes was determined by PCR. RESULTS: In the inoculated eye, virus replication was significantly higher in both the anterior segment and the posterior segment of IS mice. Virus spread to extraocular sites in both IS and non-IS mice; however, significantly higher titers of virus were recovered from the salivary glands and lungs of IS mice than from non-IS mice, and clearance of virus from these sites was delayed in IS mice. Virus spread from the injected eye via leukocytes, and PCR amplification revealed that the frequency of virus-infected leukocytes was approximately 200-fold higher in IS mice. CONCLUSIONS: The results of these studies suggest that immunosuppression significantly enhances virus replication in the inoculated eye, salivary glands, and lungs, leads to a higher frequency of virus-positive leukocytes, and delays clearance of virus from ocular and nonocular tissues. These results also suggest that retinitis in the injected eye of IS mice correlates with significantly higher titers of virus in the posterior segment.

Retinal detachment due to breaks in pars plicata of ciliary body after endogenous fungal endophthalmitis.

An eye with retinal detachment due to breaks in the nonpigmented epithelium in the pars plicata of the ciliary body was reported in a patient who had been infected by endogenous Candida endophthalmitis about 3 years previously. He had no history of ocular trauma or atopic dermatitis, and had undergone extracapsular cataract extraction because of secondary cataract following the endophthalmitis. Three months later, the breaks were detected in his right eye, distributed extensively between the 3:30 and 11:45 o'clock meridians in the pars plicata. The posterior edges of these breaks were pulled to the contracted posterior capsule by zonular fibers. Posterior capsulectomy, vitrectomy, encircling and scleral buckling were performed and resulted in the reattachment of the retina. It was suggested that the ciliary body which had been damaged by endophthalmitis played a role in the development of these breaks.

Retinitis in euthymic mice following inoculation of murine cytomegalovirus (MCMV) via the supraciliary route.

Cytomegalovirus (CMV) retinitis is the most frequent infectious ocular complication of the acquired immune deficiency syndrome (AIDS). Currently, there are few animal models to study the virologic and immunologic factors which contribute to the pathogenesis of CMV retinitis. In these experiments, 1-2 X 10(4) PFU of murine cytomegalovirus (MCMV) was inoculated into the supraciliary space of BALB/c mice. Within three days of inoculation, moderate iridocyclitis was observed which progressed to necrosis of the ciliary body by day 14. Approximately 60% of the mice developed typical retinitis characterized by virus-infected cytomegalic cells in the retina and retinal pigment epithelium, focal retinal infiltrates, transition zones between uninvolved and involved retina, and optic neuritis. The remaining animals exhibited atypical retinitis characterized by non-specific retinal inflammation in the absence of obvious viral infection. This murine model of CMV retinitis shares some features with retinitis observed in AIDS patients with CMV retinitis and may be useful to evaluate the efficacy of immunologic and/or pharmacologic treatment strategies for CMV retinitis.

Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease.

Intravenous (i.v.) injection of u.v. light-inactivated herpes simplex virus type 1 (UV HSV-1) at the time of HSV-1 corneal infection reduced the cytotoxic T lymphocyte (CTL) response to HSV-1, and significantly reduced the incidence of HSV-1-induced corneal stromal disease in A/J mice. The spread of HSV-1 through the eye after corneal infection, detected using engineered HSV-1 (US3::Tn5-lacZ) with the lacZ gene under the transcriptional control of the viral late gene promoter for glycoprotein C, was also markedly reduced by i.v. UV HSV-1 injection. The restriction of HSV-1 corneal invasiveness in i.v. UV HSV-1-injected mice preceded the onset of a detectable specific cell-mediated or humoral immune response to HSV-1, and was accompanied by an elevated serum titre of interferon (IFN-alpha), reversed by anti-IFN-alpha/beta antibody, and mimicked by systemic IFN-alpha treatment. IFN-alpha-treated mice developed a normal CTL response to HSV-1 after corneal infection, but the corneal invasiveness of the virus was markedly reduced and none of the treated mice developed corneal stromal disease. Together with our previous findings that HSV-1-specific CTLs participate in the pathogenesis of corneal stromal disease, these results indicate that i.v. injection of UV HSV-1 at the time of corneal infection may prevent stromal disease by the combined effects of IFN-mediated reduction of the spread of virus in the cornea and inhibition of the activity of the HSV-specific T lymphocytes that induce tissue destruction in the corneal stroma.

Ocular leprosy in nine-banded armadillos following intrastromal inoculation.

Leprosy shows a higher percentage of ocular involvement than any other systemic infection. In humans, the cornea is the first ocular tissue affected. Our previous studies in armadillos with naturally acquired and experimental disseminated leprosy showed that 44% had corneal infection. Mycobacterium leprae is found in armadillo burrows in Louisiana, U.S.A., and ocular abrasions may be the portal of entry for these organisms in wild armadillos. To test the cornea as a route of infection, we injected eight armadillos intrastromally with 2 x 10(6) M. leprae in 1 microliters. Two and 4 months later, the armadillos were sacrificed and their eyes processed for light- and electron-microscopy. After 2 months, M. leprae were found in histiocytes mainly in the corneal limbus, sclera and bulbar conjunctiva. At 4 months, however, there was a visible corneal leproma in one animal. Microscopically, it was found to be a histiocytic granuloma with heavy M. leprae invasion. In addition, cells were seen in the anterior chamber. Leprosy is endemic in regions where other corneal infections which compromise the epithelial barrier property are prevalent and where leprosy bacilli are found in the environment. The entry of leprosy bacilli into the cornea may produce lesions which spread posteriorly in the eye.

Interactions of cultured rat synovial and ocular ciliary body cells with two strains of Mycoplasma arthritidis.

Strains of Mycoplasma arthritidis differ in their ability to cause joint and ocular inflammations. Although the reasons for this difference are not fully understood, pathogenic mycoplasmas commonly require close associations with the cells they damage. Using 3H-uridine labeled mycoplasma, we compared cellular interactions of in vitro cultivated rat synovial and ocular ciliary body epithelial cells with two American Type Culture Collection strains of M. arthriditis shown to differ in their virulence. Radiolabeling assays gave evidence of a stronger retention capability on cultured cells by the more pathogenic strain, 14152. Scanning electron microscopy demonstrated cellular associations with the two strains of mycoplasma, with more of the 14152 adhering to both cell types. Examination by transmission electron microscopy showed evidence of contact between the more virulent 14152 strain and both cell types, but no similar evidence with the comparatively less virulent strain, 19611. The pathogenicity of different strains of M. arthritidis may vary according to their ability to closely associate with specific target cells involved in the disease process.

Histopathologic study of herpes virus-induced retinitis in athymic BALB/c mice: evidence for an immunopathogenic process.

In order to determine whether antiviral immunity is pathogenic in mouse eyes, HSV-1 was injected into the anterior chamber of one eye of adult athymic BALB/c mice. The eyes of these T cell deficient mice were examined clinically and histopathologically for ocular disease. The anterior segment of injected eyes developed progressive inflammatory reactions that eventually destroyed the ciliary body and then progressed to the posterior compartment where partial necrosis occurred, but only in the inner layers of the retina. A milder form of the same process developed between 7 and 10 days in the contralateral eye. Uninoculated eyes displayed little evidence of choroiditis, hemorrhage, massive necrosis, or disintegration of the architecture of the retina. Since these are features that are found in contralateral retinas of euthymic BALB/c mice infected in one eye via the anterior chamber route, it is concluded that acute retinitis found in contralateral eyes of immunocompetent mice has an immunopathogenic basis. However since euthymic mice develop anterior chamber associated immune deviation (ACAID) (and therefore do not display virus-specific delayed hypersensitivity), the identity of the relevant immune effector remains unknown. Based on these observations and our previous ocular findings following intracameral inoculation of HSV-2, we suggest that in susceptible mice, herpes simplex viruses can induce several pathogenetically distinct forms of retinitis, some of which are mediated by virus-specific immune effector cells.

Active cytomegalovirus particles in the eyes of an AIDS patient being treated with 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (Ganciclovir).

The eyes of an AIDS patient with cytomegalovirus (CMV) retinitis and pneumonitis who died while receiving maintenance therapy with the antiviral agent 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (Ganciclovir) were obtained for pathological examination. While under treatment the patient had significant improvement but not complete regression of retinitis. Electron microscopic and immunofluorescent techniques revealed cytomegalovirus particles in the retina, sclera, iris, and ciliary body. These findings are consistent with a virostatic type of inhibition of CMV by this agent. They also suggest that CMV involvement in the eye and other organs may be more widespread than is clinically apparent in AIDS patients.

Does virus persist in the uvea in multiple sclerosis, as in canine distemper encephalomyelitis?

Epidemiological studies suggest that multiple sclerosis (MS) might be triggered by an infectious agent. Uveitis has been observed in a small percentage of MS patients. Dogs with canine distemper encephalomyelitis, another demyelinating disease of the central nervous system, have an anterior uveitis which is usually mild and asymptomatic, and dogs with persistent CNS infection and chronic distemper encephalomyelitis harbour virus persistently in the uvea. These observations in dogs suggest that pathological and virological studies of the uveitis associated with MS would be worth while.