Expression of Cytokines in Porcine Iris, Retina and Choroidal Tissues Stimulated by Microbe-associated Molecular Patterns.

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.

Dual lesion margins on fundus autofluorescence associated with paradoxical worsening following treatment for tubercular serpiginous-like choroiditis.

A 31-year-old male presented with decreased vision in the right eye associated with an active plaque-like serpiginoid choroiditis. The lesion showed a unique feature of dual margins of hyperautofluorescence of the lesion on fundus autofluoresence (FAF) imaging. Systemic investigations suggested a tubercular etiology. He was started on antitubercular treatment and a conventional dose of oral corticosteroids (1mg/kg body weight). However, the lesions showed paradoxical worsening and required increased immunosuppression in the form of local steroids and oral immunomodulators. The presence of dual margins of hyperautofluorescence could suggest increased inflammatory activity leading to paradoxical worsening on treatment requiring increased immunosuppression.

Resolution of Large Choroidal Tuberculoma following Monotherapy with Intravitreal Ranibizumab.

Background: Ocular tuberculosis can have protean manifestations. Anti-tubercular therapy (ATT) and oral steroids are employed in the management of this condition. There is evidence in the literature which has highlighted the use of intravitreal anti-vascular endothelial growth factor drugs as an adjunct to systemic therapy.Report of the Case: A 44-year-old male presented with a decrease of vision in the right eye was diagnosed choroidal tuberculoma with massive exudation and subretinal fluid. The patient was treated with intravitreal ranibizumab injection. The lesion regressed completely within 6 weeks without any additional systemic corticosteroids and ATT without any recurrence over 6 months during follow-up.Conclusions: Ranibizumab monotherapy may lead in complete regression of vascularized tubercular choroidal granulomas without the need of adjunctive ATT and corticosteroids. After intravitreal injection of ranibizumab, the lesion may be observed for regression over several weeks.

Multimodal imaging of a choroidal granuloma as a first sign of tuberculosis.

Choroidal granuloma is rarely seen as the first sign of tuberculosis(TB). Here we report a case of a 34-year old male with a choroidal mass which was associated with serous retinal detachment on EDI-OCT and the "contact sign" between the neurosensory retina and the retinal pigment epithelium. We analysed the macular microvascular features of tuberculoma with Optical Coherence Tomography Angiography(OCTA). After 3 months of antituberculosis treatment, we observed the shrinkage of granuloma with permanent changes of macular microvasculature in deep capillary plexus and choriocapillaris. In conclusion, OCT-A may provide useful information about the retinal microvascular involvement in patients with choroidal tuberculoma.

A CASE OF INTRAVESICAL BACILLUS CALMETTE-GUERIN-RELATED ENDOPHTHALMITIS AND RETINITIS CONFIRMED WITH RETINAL BIOPSY.

PURPOSE: To present a rare case of bilateral endogenous chorioretinitis and unilateral endophthalmitis due to Mycobacterium bovis in a patient who received intravesical bacillus Calmette-Guerin (BCG) treatment. METHODS: We present a case of a single male patient with bilateral endogenous chorioretinitis due to Mycobacterium bovis in a patient who received intravesical BCG, an attenuated strain of M. bovis widely used to treat superficial bladder cancer. The patient underwent intravitreal tap, vitrectomy, and chorioretinal biopsy with histologic examination. RESULTS: The patient presented with a visual acuity of light perception in the right eye and 20/25 in the left eye. Examination of the right eye revealed dense vitreous haze, whereas the left eye demonstrated multifocal, yellow, round subretinal pigment epithelial lesions in the macula. The patient underwent a vitreous tap with injection of antibiotics and was admitted to the hospital for empiric systemic antibacterial and antifungal treatment along with an endogenous endophthalmitis workup. His systemic evaluation and vitreous tap did not identify a causal organism, and the eyes failed to improve on empiric therapies. He underwent pars plana vitrectomy and retinal biopsy of the right eye that revealed vitreal and infiltrative retinal acid-fast bacilli. Cultures confirmed M. bovis to be susceptible to ethambutol, rifampin, and isoniazid. After starting antimycobacterials, his vision improved to finger counting in the right eye, and his vision and appearance of the lesions remained stable in the left eye at postoperative month one. CONCLUSION: Intravesical BCG stimulates a local cell-mediated response that destroys malignant cells. It is generally well tolerated, although it rarely can result in secondary systemic infection. Intravesical BCG-related endophthalmitis is rare and should be considered in the setting of ocular inflammation in patients with a history of bladder cancer who may not disclose previous treatment with BCG.

The evaluation of the effect of Helicobacter pylori infection on choroidal thickness.

BACKGROUND/AIMS: To evaluate the effects of Helicobacter pylori infection on choroidal thickness (CT) using enhanced depth imaging spectral domain-optical coherence tomography (SD-OCT). MATERIALS AND METHODS: A total of 63 right eyes of 63 patients who tested positive for H. pylori (Group 1) and 46 right eyes of 46 patients who tested negative for H. pylori (Group 2) were evaluated. The CTs at the subfoveal area and at 1 mm ranging up to 3 mm from the fovea at the nasal and temporal quadrants were measured and compared. After the eradication of H. pylori, the CT values were also compared with the pre-eradication values in 38 patients. RESULTS: The mean age of patients was 43.6}9.5 years in Group 1 and 46.6}11.5 years in Group 2 (p=0.13). Differences in CT values between Groups 1 and 2 before and after H. pylori eradication were not statistically significant (p>0.05 for all values). CONCLUSION: The CT values of H. pylori positive and H. pylori negative patients were similar. Eradication of H. pylori infection appears to have produced no change in short-term CT.

Splenic tuberculosis and multifocal serpiginoid choroiditis.

Serpiginoid multifocal choroiditis is a distinct morphological identity with a reported causal association with Mycobacterium tuberculosis. We report a case of serpiginoid multifocal choroiditis in a 17-year-old boy who was suffering from isolated splenic tuberculosis. He was treated with systemic steroids along with anti-tubercular treatment with good visual recovery. This case was unique as no other organs except spleen and choroid showed tubercular involvement. We hereby emphasize association of extrapulmonary sites with multifocal serpiginoid choroiditis and propose a thorough investigation for primary to be included in routine protocol of choroiditis workup.

Acute Angle Closure Secondary to Tubercular Choroidal Granuloma.

Acute angle closure is usually thought to be secondary to pupillary block, which is relieved by laser iridotomy. Anterior rotation of the ciliary body at the scleral spur following development of an inflammatory ciliochoroidal detachment may result in a presentation of acute angle closure. It is imperative to recognize this condition correctly, because the management is with cycloplegics and anti-inflammatory drugs, which is diametrically opposite to the treatment of primary angle closure. More importantly, it has been reported as a consequence of serious systemic disease such as HIV infection and Vogt Koyanagi Harada (VKH) syndrome. We report a patient who presented to the medical emergency with headache and vomiting and was subsequently found to have acute angle closure in 1 eye secondary to a tubercular choroidal granuloma. This presentation of ocular tuberculosis has not been reported previously.

CHORIORETINAL BIOPSY FOR THE DIAGNOSIS OF ENDOGENOUS ENDOPHTHALMITIS DUE TO ESCHERICHIA COLI.

PURPOSE: To describe the novel use of a chorioretinal biopsy technique to confirm the microbiological diagnosis of endogenous Escherichia coli (E. coli) endophthalmitis, when other investigations have been proven nondiagnostic. METHODS: Case report of an 82-year-old white man with endogenous endophthalmitis without a clearly identifiable source of infection. RESULTS: After systemic cultures and multiple aqueous and vitreous samples were unable to identify a causative organism, chorioretinal biopsy of a subretinal abscess was used to confirm the microbiological diagnosis. This ensured appropriate ophthalmic and systemic treatment of infection. CONCLUSION: Endogenous E. coli endophthalmitis is a rare and aggressive condition usually seen in patients with insulin-dependent diabetes with concurrent urinary tract infection. This case demonstrates chorioretinal biopsy to be a viable and effective method of establishing a firm microbiological diagnosis in cases of culture-negative endophthalmitis.

A new OCT finding in tuberculous serpiginous-like choroidopathy.

PURPOSE: To present a case of tubercular serpiginous-like choroiditis (SLC) with previously unreported choroidal findings on enhanced depth imaging OCT (EDI-OCT). DESIGN: Case report. METHODS: A 60-year-old female presented with decreased vision. Serpiginous choroidopathy was diagnosed. Laboratory workup revealed an infectious etiology. EDI-OCT revealed previously unreported choroidal findings. RESULTS: Laboratory workup revealed nonreactive Treponema pallidum antibodies and positive QuantiFERON Gold. CT chest showed scars of prior granulomatous disease. OCT with EDI of active lesions demonstrated infiltration of the choroid, elevation of the RPE-Bruch's membrane complex and focal increase of choroidal thickness. CONCLUSIONS: Choroidal infiltration with elevation of the RPE was demonstrated on EDI-OCT in active areas of tuberculous serpiginous-like choroiditis in this patient. This finding has not been described in imaging of patients with noninfectious serpiginous choroidopathy and may be a useful tool to differentiate serpiginous choroidopathy (SC) from serpiginous-like choroiditis (SLC). EDI-OCT may provide characterization of choroidal involvement.

[Role of Chlamydia trachomatis and Chlamydophila pneumoniae in damage of eye posterior segment structures].

AIM: Study the ability of Chlamydia trachomatis and Chlamydophila pneumoniae to damage structures of eye posterior segment, features of development of such infectious process, its morphological and clinical characteristics. MATERIALS AND METHODS: 6 rabbits with confirmed absence of C. trachomatis, C. pneumoniae were used in the study. 3 animals were infected with C. trachomatis culture and 3 animals--with C. pneumoniae culture. Subconjunctival and intravitreal mode of infectious agent introduction were used, as well as instillation of its culture into conjunctival sac. Microbiological diagnostics included microscopy with direct immunofluorescence, culture method and determination of antibody titers. Infectious process was studied by using ophthalmologic methods and histological examination. Observation period was 4 months. RESULTS: In all the animals a development of infectious process at early stages after the infection was confirmed. Conjunctivitis symptoms, inflammatory exudation into vitreous humor, chorioretinal inflammation loci, disorders in transparency of optical media and detachment of retina were clinical manifestations. In 2 animals infected with C. trachomatis severe panuveitis was noted. In 4 animals infectious process assumed subclinical characteristics (infection with both C. trachomatis or C. pneumoniae). In pathomorphologic studies data on the ability of C. trachomatis and C. pneumoniae to cause damage to cells of retina, pigment epithelium and choroid were obtained. CONCLUSION: C. trachomatis and C. pneumoniae may play a significant role in pathology of vitreous humor, retina, pigment epithelium and choroid.

Pseudomonas aeruginosa choroidal abscess in a patient with bronchiectasis.

PURPOSE: To report a case of Pseudomonas aeruginosa endophthalmitis with choroidal abscess formation in a patient with bronchiectasis. METHODS: Case report. RESULTS: A 75-year-old gentleman with bronchiectasis and P. aeruginosa pneumonia developed painless loss of right eye vision. The patient had previously undergone bronchoscopy to exclude pulmonary neoplasm. Slit-lamp examination revealed intense anterior chamber inflammation with hypopyon and B-scan ophthalmic ultrasound showed a choroidal mass consistent with choroidal abscess. Systemic and topical antibiotics did not prevent further progression of the infection. Patient declined pars plana vitrectomy and opted for enucleation. Polymerase-chain-reaction-based restriction fragment-length polymorphism (PCR-RFLP) of the enucleated eye confirmed P. aeruginosa to be the causative organism. CONCLUSION: P. aeruginosa cannot be completely eradicated by systemic antibiotics, and bronchial colonization of P. aeruginosa can remain a potential source for metastatic infection. P. aeruginosa choroidal abscess, previously reported only in patients with cystic fibrosis, can also occur in bronchiectasis. Physicians should therefore have a high index of suspicion of endogenous endophthalmitis and treat aggressively, especially in patients with subretinal invasion and abscess formation.

[The role of Helicobacter pylori in etiopathogenesis of central serous choroidopathy]. / Rola zakazenia Helicobacter pylori w patogenezie centralnej surowiczej choroidopatii.

Central serous chorioretinopathy (CRS) is a serous macular detachment that usually affects young people and leads fortunately to a spontaneous resolution and a good visual prognosis in most patients. The etiopathogenesis of the disease is still not completely understood and no effective treatment is available at this time. However, an association has been recently highlighted between Helicobacter pylori infection and CRS connected with pathology of retinal vessels.

Infection of retinal neurons during murine cytomegalovirus retinitis.

PURPOSE: Previous results suggest that retinal neurons are infected early during murine cytomegalovirus (MCMV) infection of the inner retina. The purposes of this study were to identify which retinal neurons are infected and to determine the routes by which MCMV spreads in the retina. METHODS: Immunosuppressed (IS) BALB/c mice were inoculated with 5 x 10(3) PFU of MCMV (k181) through the supraciliary route. Injected eyes were collected at several times after inoculation, sectioned, and examined by electron microscopy and by staining for retinal cell antigens and for MCMV early (EA) or late (LA) antigen. RESULTS: MCMV-infected cells were observed in the choroid and RPE by day 3 after infection (PI) and in the inner retina beginning at day 5 PI. At this time, many horizontal and bipolar cells were MCMV-antigen-positive but only rare MCMV-infected amacrine cells (glycine positive or gamma-aminobutyric acid [GABA] positive) or MCMV-infected ganglion cells (NF positive) were observed in the inner retina. At day 10 PI, most virus-infected cells were glial fibrillary acidic protein (GFAP)- and GABA-positive glia. Virions were observed by electron microscopy in the choroid, RPE, and inner nuclear layer of the retina. Although virions were observed in the endothelium of the retinal vessels and the nearby retinal cells, the endothelial cell lining of the retinal vessels remained intact. Both apoptotic cells and necrotic cells were seen in the inner retina. CONCLUSIONS: In the inner retina, horizontal and bipolar cells were the early (< or = day 7 PI) targets of MCMV infection. Virus spread from the RPE and the photoreceptor layer to the inner retina through infected Muller cells and within the inner retina horizontally through infected horizontal cells.

Helicobacter pylori and idiopathic central serous chorioretinopathy.

Idiopathic central serous chorioretinopathy (ICSC) is a disease that typically affects middleaged adults and involves the sensory retina, the retinal pigment epithelium (RPE) and the choroid. Patients usually have mild visual loss. ICSC generally resolves without therapy, although the disease can become chronic with ensuing RPE decompensation. Some patients, particularly older adults, can also develop choroidal subretinal neovascularisations (CNV), which may lead to a severe loss in visual acuity. Although the aetiopathogenesis of the disease is still incompletely understood, a correlation with psychophysical stress supports the idea that the disease may be "adrenergically conditioned", leading to the development of one or several defects in the RPE, with subsequent focal leakage of serous fluid and its retention in the subretinal space. An association between ICSC and the Helicobacter pylori (HP) infection has also been recently documented, suggesting that this organism may possibly be involved in the development of some cases of ICSC. Pathogenetic mechanisms that may explain the contribution of HP in the development of ICSC are postulated.