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Purpose: The innate immune system is strongly implicated in the pathogenesis of uveitis. This study was designed to clarify the responses of the innate immune system in uveal tissues., Materials and Methods: We utilized quantitative, real-time RT-PCR to measure mRNA of innate immune system receptors from porcine iris, choroid, and retina tissues. We used RT-PCR for cytokines to evaluate the responses of these tissues to specific ligands or extracts of whole bacteria that activate the innate immune system. We used ELISA for IL-6 on selected choroidal supernatants to confirm that the mRNA measurement correlated with protein levels., Results: In each of the studied tissues, we detected the expression of important receptors belonging to the innate immune system including dectin-1, TLR4, TLR8, and NOD2. Relative mRNA expression was generally lower in the retina compared to iris or choroid. All three tissues demonstrated upregulation of cytokine mRNA in response to a range of ligands that activate the innate immune system. The measurement of IL-6 protein was consistent with results based on mRNA. Notably, the expression of mRNA for IL-23 was more pronounced than IL-12 in all three tissues after stimulation with various innate immune system ligands., Conclusions: These data provide evidence of a potent innate immune response intrinsic to uveal tissues. Specific innate immune system ligands as well as bacterial extracts enhanced the production of several inflammatory cytokines. Furthermore, the observation of higher upregulation of IL-23 mRNA, compared to IL-12 in response to innate immune stimuli, suggested that a local TH17 response might be more robust than a local TH1 response in uveal tissues. Our results expand the understanding as to how the innate immune system may contribute to uveitis.

Purpose: To compare the safety and efficacy of intravitreal anidulafungin injection with voriconazole and amphotericin B (Amp B) in an experimental Candida endophthalmitis (CE) model., Methods: Intravitreal 1 × 10 5 CFU/0.1 ml Candida albicans was injected into the right eyes of 24 New Zealand rabbits, which were divided into 4 groups. Voriconazole 50 μg/0.1 ml, Amp B 10 μg/0.1 ml, and Anidulafungin 50 μg/0.1 ml were injected by intravitreal injection 72 h after inoculation. The control group was injected with 0.1 ml 0.9% NaCl. Clinical scoring was performed by assessing the cornea, conjunctiva, iris, and vitreous on days 3 and 7 of therapy. At the end of the study, the right eyes of all rabbits were enucleated and histopathological evaluation was performed. Therapy groups were compared according to the clinical, histopathological, and microbiological analysis scores., Results: Total clinical scores were significantly different between treatment groups and the control group (p < 0.05). On day 7 of the therapy, clinical scores of the anidulafungin group were found to be significantly lower when compared with the other therapy groups, while a significant improvement was observed in the eyes of rabbits in the anidulafungin group (p < 0.05). Also, microbiological scores of the anidulafungin group were lower than those of the control group (p < 0.05). Histopathological scores of the anidulafungin treatment group were significantly better than the voriconazole and control groups. Inflammation was evidently suppressed and marked retinal toxicity was not observed with anidulafungin., Conclusions: This is the first study comparing the efficacy of anidulafungin with other antifungal agents. In this CE model, an intravitreal single dose of anidulafungin was shown to be noninferior to voriconazole and Amp B. As an alternative to Amp B or voriconazole, intravitreal anidulafungin is suggested as an effective antifungal agent for the treatment of CE.

A polyphasic approach was used to characterize a novel nitrogen-fixing bacterial strain, designated YC6995(T), isolated from the rhizosphere soil of Iris ensata var. spontanea (Makino) Nakai inhabiting a wetland located at an altitude of 960 m on Jiri Mountain, Korea. Strain YC6995(T) cells were Gram-negative, and rod-shaped, with motility provided by a single polar flagellum. Optimal growth conditions were 30 °C and pH 7.0. The major fatty acids of strain YC6995(T) were C18:1 ω7c, C18:1 2-OH and C16:0 3-OH. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids were phosphatidylethanolamine, phosphatidyldimethylethanolamine, phosphatidylcholine, phosphatidylglycerol and unidentified glycolipids. The genomic DNA G+C content was 64.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed strain YC6995(T) to form a phyletic lineage with Nitrospirillum amazonense DSM 2787(T) with a high sequence similarity (97.2 %), but it displayed low sequence similarity with other remotely related genera, including Azospirillum (<93 %), Rhodocista (93.1-93.4 %), and Skermanella (91.2-93.3 %) in the family Alphaproteobacteria. Based on the phenotypic, chemotaxonomic, and phylogenetic evidences, strain YC6995(T) represents a novel species within the genus Nitrospirillum, for which the name Nitrospirillum irinus sp. nov. is proposed. The type strain is YC6995(T) (= KACC 13777(T) = DSM 22198(T)). An emended description of the genus Nitrospirillum is also proposed.

Purpose: To investigate the role of Helicobacter pylori in primary open-angle glaucoma (POAG) pathophysiology by detecting its presence in eye biopsies of POAG patients during trabeculectomy., Patients and Methods: Fifty-one consecutive patients who underwent trabeculectomy for POAG not responsive to antiglaucoma therapy, and 35 consecutive anemic controls were examined for H. pylori presence mainly by gastric mucosa histology. In POAG patients, eye biopsies were also obtained and stained for H. pylori presence in situ., Results: Forty-three of 51 (84.3%) POAG patients and 17 of 35 (48.6%) controls were tested H. pylori positive (p = 0.0004). In 5 H. pylori-positive POAG patients, H. pylori bacteria were identified in the trabeculum and iris specimens., Conclusion: For the first time, H. pylori bacteria have been detected histologically in eye biopsies of POAG patients., (Copyright © 2011 S. Karger AG, Basel.)

Purpose: To report a case of a cat-scratch uveitis caused by Bartonella henselae, which was confirmed by histology, serology, and polymerase chain reaction (PCR) methodology., Methods: An iris nodule was biopsied from a 4-year-old child who was scratched by a kitten on the side of his face and developed redness of the eye associated with cervical lymphadenopathy. Sections of the iridectomy specimen were stained with hematoxylin-eosin, periodic acid-Schiff, and Warthin-Starry technique for histopathologic evaluation. Additionally, serologic tests and molecular diagnosis using B. henselae-specific PCR were performed., Results: Histopathologically, sections of the iridectomy specimen showed a zonal granulomatous inflammation with a central iris necrotic abscess surrounded by a mantle of epithelioid histiocytes and more peripherally by lymphocytes and plasma cells. The Warthin-Starry stain disclosed scattered short bacilli within the necrotic abscess morphologically compatible with B. henselae. Report of serologic tests for B. henselae disclosed a negative immunoglobulin G antibody (negative: less than 12) and a positive immunoglobulin M antibody of 18 (positive: greater than 15). Other serologic studies including Toxocara, histoplasmin, blastomycin, coccidioidin, aspergillin, and Chlamydia were all negative. PCR was positive for B. henselae DNA., Conclusions: Our case showed a unilateral chronic granulomatous iritis with the histopathologic features compatible with CSD caused by B. henselae bacillus as demonstrated in the iris biopsy and confirmed by serology and PCR technique. This case is an example of a relatively rare uveal manifestation of CSD.

Background/aim: Iris nodules are an uncommon clinical sign in uveitis. The diseases most commonly associated with iris nodules and uveitis include sarcoidosis, Vogt-Koyanagi-Harada syndrome, multiple sclerosis, Fuchs' heterochromic iridocyclitis, and metastatic infection. While many of these diseases may be appropriately treated with immunosuppressive medication, the management of infectious uveitis is antimicrobial therapy. Inappropriate immunosuppressive therapy may result in a poor outcome for the patient with an infection. Consequently, cases of uveitis with iris nodules were reviewed to identify clinical features that may help differentiate infection from non-infectious inflammation., Methods: The clinical database of 1353 consecutive patients evaluated at a tertiary care referral based North American uveitis clinic were retrospectively reviewed to identify cases of infectious uveitis with iris nodules. A Medline search was performed to identify additional cases. From these cases information regarding clinical presentation, diagnosis, treatment, and outcome were collected., Results: Three cases (three eyes) were identified from the authors' own records of infectious uveitis with iris nodules. An additional 25 cases of infectious uveitis with iris nodules were identified in 22 published reports. Analysis of the authors' cases and these reports showed that infectious uveitis with iris nodules was specifically characterised by some or all of the following: (1) creamy, soft appearance to the nodule(s), (2) unilateral disease, (3) persistence or growth of the nodule(s) despite corticosteroid therapy, (4) marked inflammatory response in the anterior chamber and/or vitreous humour, and/or (5) history suggesting a potential source of septic emboli., Conclusion: Certain features of the clinical history and examination are useful in the diagnosis of metastatic infection in patients presenting with uveitis and iris nodules.

Ocular leprosy is rarely seen in developed countries. We report the long-term follow-up of a patient with bilateral uveitis, glaucoma, and keratitis. Skin, iris and aqueous humor biopsies disclosed abundant Wade-Fite-positive organisms consistent with Mycobacterium leprae. Leprosy must be considered in the differential diagnosis of keratitis and uveitis.

Ocular tuberculosis is currently rare in developed countries. We report a case of tuberculous nodular anterior uveitis which revealed primary tuberculosis in a 2-year old girl. This diagnosis was established on microscopic examination of a surgical iridectomy specimen. Thus, a metastatic retinoblastoma was eliminated. The subsequent clinical investigations showed that the girl's father had active pulmonary tuberculosis.

The persistence of Borrelia burgdorferi in six patients is described. Borrelia burgdorferi has been cultivated from iris biopsy, skin biopsy, and cerebrospinal fluid also after antibiotic therapy for Lyme borreliosis. Lyme Serology: IgG antibodies to B. burgdorferi were positive, IgM negative in four patients; in two patients both IgM and IgG were negative. Antibiotic therapy may abrogate the antibody response to the infection as shown by our results. Patients may have subclinical or clinical disease without diagnostic antibody titers. Persistence of B. burgdorferi cannot be excluded when the serum is negative for antibodies against it.

Primary ocular herpes is usually seen as a follicular conjunctivitis and blepharitis, with or without involvement of the cornea. It is unknown, however, to what extent asymptomatic and/or subclinical primary disease occurs, and whether primary ocular herpes follows direct droplet spread to the eye. Previous models of murine ocular herpes have used trauma (scarification) to introduce virus into the cornea, producing disease which results in significant corneal scarring. To mimic a likely route of infection in humans, a droplet containing virus was placed on the mouse eye and clinical disease recorded. At least 1 month after inoculation, serum was assayed for neutralising antibodies and the cornea, iris, and trigeminal ganglion were investigated for evidence of herpes simplex virus type 1, by cocultivation and the polymerase chain reaction. Some animals showed a severe ulcerative blepharitis with little to no involvement of the cornea, while disease was undetectable in others. The development of disease depended on the dose and strain of virus and age of the animal, with older mice appearing more resistant. Virus was isolated from the trigeminal ganglion of younger animals inoculated with higher doses of virus, after 21 days in culture, suggesting that latency had been established. Neutralising antibodies were present in most mice irrespective of the presence of recognisable clinical disease. Using primers for the thymidine kinase and glycoprotein C regions of the viral genome, herpes simplex virus type 1 DNA was found in the cornea, iris, and trigeminal ganglion of most animals and showed a good correlation with the presence of neutralising antibodies. It would thus appear that herpes simplex virus type 1 is able to accede into the cornea, iris, and trigeminal ganglion following nontraumatic application of virus onto the mouse eye. This model mimics primary ocular disease in humans and may be useful for studies on recurrent disease and the spread of ocular herpes.

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.

The coronavirus mouse hepatitis virus (MHV, strain JHM) infects tissues in the anterior and posterior segments when injected intravitreally into adult mouse eyes. Infection causes progressive damage to the photoreceptors and retinal pigment epithelium (RPE), resulting in a disease the authors have termed JHM retinopathy. To determine whether this virus is retinotropic independent of route of inoculation, the authors injected mice with virus by several different routes: into the anterior chamber (AC), onto the cornea, intranasally, or intracerebrally. Inoculation into the AC produced effects similar to those after intravitreal inoculation, although slightly slower in onset. Viral antigen was detected in the anterior portion of the iris on day 3, and by day 6, was also located primarily in the inner nuclear layer, photoreceptors, Müller cells, and RPE. However, by day 10, viral antigens were only detected in a few cells in the ganglion cell layer. Infectious virus was isolated from neural retinas on days 3 and 6, but not on day 10. In contrast, infectious virus could not be isolated from contralateral eyes. After 14 weeks, specific regions of some retinas were atrophied, with most of the retinal layers involved. Inoculation by other routes also resulted in virus-induced disease. Scarification of the cornea with virus, but not application of virus droplets alone, caused pathologic changes in the corneal epithelium and stroma and subtle effects on the ganglion cell and inner plexiform layers. Intracerebral inoculation of virus affected mainly the RPE. Pathologic effects and viral antigens were not detected in eyes from four mice inoculated intranasally. These results show that a murine coronavirus is retinotropic when introduced by several direct routes and one indirect route. Moreover, these studies show that long-lasting retinal disorders ranging in intensity from mild to severe can occur after coronavirus infection.

Three children developed endophthalmitis after cataract surgery. Each had signs and symptoms of either nasolacrimal duct obstruction or upper respiratory infection at the time of surgery. The causative organisms were Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pneumoniae. Final visual acuities were 6/24, LP, and NLP, respectively. Endophthalmitis after cataract surgery in infants has never been reported. These three cases drawn from two pediatric ophthalmology practices represent an incidence of postoperative endophthalmitis of 0.45%. Although this incidence report is potentially spurious, it indicates that postoperative endophthalmitis is a very real threat in infants. We recommend a thorough systems review and exam of upper airways and lacrimal system before undertaking intraocular surgery in young children. We also caution against simultaneous bilateral surgery.

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.

From 43 Nepalese leprosy patients skin smear negative, and treated with dapsone (diamino diphenyl sulphone), and without any sign of active leprosy or iritis, specimens from iridectomy during cataract surgery were studied histopathologically. Of 49 iris specimens only six (12%) were found to be without any histopathological change. Atrophy of the iris stroma was seen in 63% and neovascularisation in 6% of all cases. In 16% in which the dilator muscle could be detected, it was atrophic, and in 11% the pigmented epithelium was thinned and atrophic. Cellular inflammatory infiltrations were seen in 88% of all specimens. They were mostly slight in eyes which before operation had been without posterior synechiae of the iris. In most of the eyes in which posterior synechiae had been present moderate or heavy inflammatory cell infiltrates composed of lymphocytes and plasma cells, often associated with macrophages, neutrophils, or eosinophils, were found. In five iris specimens acid fast bacilli were present. This raises the question whether these can survive systemically despite dapsone chemotherapy in the iris, thus leading to dapsone-resistant leprosy and to recurrent iritis.

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.

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.

Fourteen albino rabbits were inoculated intravenously with 10(3.5)-10(4.0) mouse ICLD(50) of Chlamydia psittaci (strain M56) of mammalian origin. Ocular lesions accompanied the chlamydial infection in the rabbits. Bilateral anterior uveitis, a common occurrence, began on the second or third day and subsided by the tenth day whereas keratoconjunctivitis was observed infrequently. After 15 days the most prominent microscopic lesion was iritis. Accumulations of inflammatory cells, mainly plasma cells, were observed in the iris and ciliary body and elementary bodies were found infrequently in macrophages. Chlamydiae were recovered consistently by conjunctival swabbing from the fifth to the twenty-fourth day. The agent was present within the eye (viz. iris-ciliary body) in three of four rabbits killed at 15 days and in five of ten rabbits killed 60 days after inoculation. Chlamydiae had persisted in the cerebrum and joints as well. Although neutralizing antibody was consistently present in sera at 60 days none of the samples of aqueous humor were capable of neutralizing the agent. It is suggested that systemic chlamydial infections in the rabbit provide a model for the study of endogenous uveitis, a common ophthalmological problem.

Spread of herpes simplex virus to and within the mouse eye after inoculation of the cornea or the skin of the snout was examined by peroxidase-antiperoxidase (PAP) staining of viral antigen in flat mounts of the eye and by isolation of virus from nervous tissue. Following inoculation of virus at either site, viral antigen was found in ocular nerves. One to three days later antigen was also found in the iris, ciliary body and choroid/sclera suggesting that virus spread to these tissues occurred via their nerve supply. Viral antigen was also found in the retina of the uninoculated eye after corneal inoculation. After inoculation of the snout, virus was isolated from ophthalmic and maxillary parts of the trigeminal ganglion and the superior cervical ganglion and then from the brainstem, eye and mandibular part of the trigeminal ganglion. This sequence also suggested that virus reached the eye via the nerves and that this may occur indirectly via the brainstem. The PAP method allows rapid determination of the distribution of antigen in various tissues. Our observations suggest that widespread involvement of ocular tissue may occur by spread of virus in nerves within the eye.

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.