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PubMed1987

Uveoscleral outflow using different-sized fluorescent tracers in normal and inflamed eyes.

Sodium fluorescein and fluorescinated dextrans (FD) of selected molecular weights were combined and perfused into the anterior chamber of normal and inflamed eyes of cynomolgus monkeys. The eyes were dissected into iris, anterior and posterior uvea, anterior and posterior sclera, retina and intraocular fluids (excluding aqueous). Each tissue was homogenized and centrifuged and the supernatant was run through a gel-filtration column to separate the fluorescent tracers. Each of the resultant peaks was quantitated and facility of uveoscleral outflow was determined. In control eyes the calculated facility of uveoscleral outflow was very similar with all tracers (from 0.047-to 0.052 microliter min-1 mmHg-1) and each tracer was found in highest concentration in the anterior sclera and anterior uvea. In inflamed eyes the calculated facility of uveoscleral outflow increased two- to five-fold with each tracer (0.12-; 0.17-; 0.29-; and 0.24 microliter min-1 mmHg-1 with fluorescein, and the fluorescinated dextrans of MWs 4000, 40,000 and 150,000, respectively). Each tracer was found in the anterior sclera and uvea in inflamed eyes whereas the posterior sclera and uvea contained predominantly the higher molecular-weight tracers (MWs 40,000 and 150,000). It is concluded that iridocyclitis causes an increase in uveoscleral outflow by increasing the permeability of the anterior uvea to all tracers and fluid. Small tracers may then diffuse into uveal blood vessels or across the sclera, yielding lower values for uveoscleral outflow. Of the four tracers studied, the optimal tracer size for studying uveoscleral outflow in either normal or inflamed eyes is MW 40,000.

Animals↗

PubMed2001

Typing of Herpes Simplex Virus in Patients with Uveitis.

Aim: To examine the type of herpes simplex virus (HSV) in cases with uveitis.Materials and Methods: Intraocular fluid specimens obtained from 3 cases with herpetic iridocyclitis and 6 cases with acute retinal necrosis (ARN) were examined by polymerase chain reaction (PCR). HSV typing was performed by the restriction patterns of the PCR products. Serum samples obtained from these cases and 33 cases with uveitis were examined by neutralization test (NT) for the availability of the typing of HSV.Results: The restriction patterns of the PCR products amplified from 3 specimens of iridocyclitis revealed HSV type 1 DNA. HSV type 2 DNA was identified in 5 of 6 cases of ARN and HSV type 1 DNA was found in only one case. The results of serum NT titers correlated with the typing of the amplicons.Conclusions: In the cases studied, HSV type 1 was the dominant etiological agent in herpetic iridocyclitis, while HSV type 2 plated a similar role in HSV-associated ARN. The examination of the serum NT may be helpful for the identification of the etiological types of HSV in patients with uveitis.

Journal Article↗

PubMedDate not supplied

The eye in systemic inflammatory diseases.

Systemic inflammatory diseases commonly affect the sclera, cornea, retina, and orbit, and can pose a serious threat to sight. They encompass both primary and secondary vasculitic disorders and specific granulomatous inflammatory conditions. As well as direct eye involvement from the systemic inflammatory process, there can be signs of ocular ischaemia due to carotid or ophthalmic arteritis, hypertensive retinopathy, and ocular complications such as chloroquine maculopathy related to anti-inflammatory drug treatment. Additionally, systemic infection relating to the eye, either as the result of primary infective disease processes or infection secondary to immunosuppression, might be mistaken as endogenous intraocular inflammation. Infection can closely mimic the ocular signs of endogenous inflammation, and in selected patients (such as those who have been immunosuppressed to treat vasculitis and who additionally have had invasive surgery, indwelling intravenous catheters, or systemic sepsis), it might be necessary to specifically exclude infection by the sampling and culturing of intraocular fluids and tissue.

Diagnosis, Differential↗

PubMed2000

Intraocular penetration of tamoxifen.

OBJECTIVE: To document ocular penetration of oral tamoxifen in patients being administered systemic therapy by measuring intraocular and serum levels of the drug in a series of patients undergoing elective ocular surgery. DESIGN: Nonrandomized, prospective, comparative trial. PARTICIPANTS: Twenty-one eyes of 21 patients undergoing elective ocular surgery (cataract extraction or vitrectomy). Twenty patients were using the antiestrogen, tamoxifen, and one participant was not. Nine patients were excluded in the final analysis because of inadequate sample size. INTERVENTION: Preoperative serum samples and perioperative aqueous samples, vitreous samples, or both were obtained for each patient, and these were analyzed for tamoxifen and its metabolites. Dilated fundus examination was performed before surgery on all patients. MAIN OUTCOME MEASURES: Evidence of tamoxifen, its metabolites, or both in the samples. RESULTS: Tamoxifen was detected in all analyzed serum samples (range, 82.4-290.0 ng/ml.) from patients taking the medication and was found to have penetrated into both vitreous (range, 0.5-7.8 ng/ml) and aqueous (range, 0.5-3.9 ng/ml) cavities. No relationship was found between serum and intraocular levels. CONCLUSIONS: This study shows that tamoxifen penetrates intraocular fluids to varying degrees. The drug levels in aqueous and vitreous do not appear to correlate with serum levels. Evidence of tamoxifen retinopathy or keratopathy was not seen.

Adult↗

PubMed1992

Active transport system of prostaglandins: clinical implications and considerations.

We hypothesize that two factors are essential in the development of epinephrine-induced cystoid macular edema (CME): (1) the stimulation of prostaglandin synthesis by some tissues, presumably the anterior uvea by epinephrine; (2) the dysfunction of the active transport (Bito's pump) which is responsible for the removal of prostaglandins from intraocular fluids. We conducted several experimental studies to confirm these hypotheses. The results strongly suggest that epinephrine maculopathy is induced by a mechanism involving prostaglandins or, possibly, other related eicosanoids and not simply by epinephrine itself, as has been postulated. This suggests the existence of some common factors in the pathogenesis of epinephrine maculopathy and aphakic or pseudophakic CME.

Animals↗

PubMed1999

A retrospective study of ocular toxocariasis in Japan: correlation with antibody prevalence and ophthalmological findings of patients with uveitis.

To classify the clinical characteristic of ocular toxocariasis in Japan, the prevalence of antibodies to Toxocara antigens was examined in patients with uveitis of unknown aetiology. From 1982 to 1993, serum specimens of 383 cases and intraocular fluid samples of 22 cases were serologically screened for Toxocara infection with five immunodiagnostic tests. Fifty-five sera and 11 intravitreous fluid samples were estimated to have significantly high antibody levels against larval excretory-secretory (ES) antigens of T. canis. Eight cases were positive in both serum and vitreous fluid, and three were positive only in the vitreous fluid. Among the 58 antibody positive samples, 20 cases were omitted due to a lack of detailed description of ocular findings. The remaining 38 cases are described in this study. Of these 38 cases, 34 (89%) were older than 20 years of age. Ocular lesions were located in the posterior fundus in 11 cases, in the peripheral fundus in 18 cases, and in both areas in seven cases. Of the eight cases in which papillary oedema or redness was observed, chorioretinal lesions were also present in seven of them. Tractional retinal detachment was present in five cases. These observations suggest that ocular toxocariasis in Japan has a different clinical profile compared with those in the other countries, and indicate a need for revised classification of ocular toxocariasis.

Adolescent↗

PubMed2002

Impact of irrigation in a new model for in vitro diffusion of mitomycin-C after episcleral application.

PURPOSE: Episcleral application of mitomycin-C (MMC) during glaucoma surgery hinders the post-operative wound healing but may lead to side effects to the ciliary body. We present an experimental model to investigate the influence of irrigation on diffusion of MMC through the sclera and into subscleral compartments. MATERIALS AND METHODS: Scleral quadrants of 10 human donor eyes were mounted on PMMA tubes filled with saline imitating the intraocular fluid. Beneath the sclera a subscleral sponge was fixed to mimic the ciliary body. The episcleral sides of the scleral quadrants were exposed to sponges soaked with 0.2 mg/ml MMC and thereafter irrigated with 0, 40, 100 and 200 ml saline. Mitomycin-C concentrations of the sclera and the subscleral compartments were analyzed by means of high-performance liquid chromatography. In a second experiment, after the application time of one minute, different times of free diffusion until analysis were allowed, to evaluate the time-course of MMC penetration. RESULTS: MMC concentrations declined from the scleral layers (1-13 microg/ml, depending on depth and irrigation) to the subscleral sponge (0.17-0.27 microg/ml) and to the subscleral fluid (0.002-0.05 microg/ml). Irrigation significantly reduced MMC concentrations in the superficial scleral layers and in the subscleral fluid to 10-30% of the no irrigation value. No effect was noted in the deep scleral layers and subscleral sponges. In the second experiment, the subscleral compartments showed higher MMC concentrations with longer diffusion times, whereas no effect on intrascleral MMC concentrations was observed. CONCLUSION: Irrigation reduced MMC concentrations in the superficial scleral layers and in the subscleral fluid by the same amount. The clinical value of irrigation should be reconsidered; a lower dose MMC application without irrigation might be a more rationale approach.

Analysis of Variance↗

PubMed1994

Murine chronic tubulointerstitial nephritis: induction by human uveitis mycoplasma-like organisms.

Mycoplasma-like organisms (MLO) are non-cultivated intracellular cell wall deficient pathogenic bacteria with a distinctive ultrastructural appearance. Diagnosis of MLO disease rests on finding the organisms in parasitized cells using a transmission electron microscope. MLO are a well studied cause of transmissible chronic plant vascular disease responsive to antibiotics. MLO have recently been found to cause human chronic progressive ophthalmic disease including uveitis. In human uveitis MLO are readily found within parasitized intraocular fluid leucocytes. Inoculation of human uveitis MLO into mouse eyelids produced a high incidence of chronic progressive ophthalmic disease including uveitis. MLO also disseminated to produce randomly distributed lethal systemic inflammatory disease. MLO parasitized leucocytes and microvascular alterations were found in the disease sites by electron microscopy. This report describes the chronic progressive tubulointerstitial nephritis in 12 of 100 human uveitis MLO eyelid inoculated mice versus 0 in 200 control mice (p < 0.0001). MLO parasitized leucocytes accompanied by tubular and microvascular alterations were found by electron microscopy in all 12 inflamed kidneys versus 0 of 4 control kidneys. Pathobiology of the MLO-induced murine nephritis, resemblance of this nephritis to human idiopathic chronic tubulointerstitial nephritis, bacterial molecular biology, and antibiotic therapy of MLO disease are discussed.

Animals↗

PubMed1998

T cells specific for the triggering virus infiltrate the eye in patients with herpes simplex virus-mediated acute retinal necrosis.

Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease resulting from ocular infections with herpes simplex virus (HSV) or varicella-zoster virus (VZV). To determine the antigen specificity and functional characteristics of ocular infiltrating T cells in ARN, T cells were isolated and expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV-mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+ and CD8+ T cell clones (TCCs) with differential T cell receptor usage. Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon-gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both patients, the antigen specificity of a substantial number of HSV-1-specific TCCs could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented suggest the contribution of T cells, specific for the triggering virus, to the pathogenesis of ARN.

Aged↗

PubMed1995

Effect of interferon-gamma on the expression of transforming growth factor-beta by human corneal fibroblasts: role in corneal immunoseclusion.

Human corneal fibroblasts (HCF) inhibit T cell alloresponse in mixed leukocyte response-human corneal fibroblast coculture. The inhibition is contact independent, insensitive to indomethacin, and is enhanced by pretreatment of HCF with interferon-gamma (IFN-gamma). To investigate cytokine-dependent mechanisms of inhibition of T cell alloresponse by HCF, the capacity of cultured HCF to produce transforming growth factor-beta (TGF-beta) and the modulatory role of IFN-gamma on their TGF-beta production were investigated by radioreceptor binding inhibition assay (RRA) and the standard mink cell bioassay (BIA). The net total TGF-beta concentration of 4 day culture supernatants from IFN-gamma-treated HCF, measured by RRA, was 11.5 ng/ml. The net total bioactive TGF-beta concentrations of 4 day culture supernatants from HCF, before and after treatment with IFN-gamma, measured by BIA, were 2.0 and 4.8 ng/ml, respectively. These findings indicate that HCF produce TGF-beta and increase their TGF-beta output under the influence of the proinflammatory cytokine IFN-gamma. Media-borne TGF-beta binding proteins appeared to be primarily responsible for the discrepancy between the TGF-beta values measured by RRA and BIA. Active exclusion of TGF-beta binding proteins from intraocular fluids may have an important role in the maintenance of TGF-beta-dependent ocular immune privilege. Corneal fibroblasts may utilize TGF-beta-dependent mechanisms to maintain the immunosecluded environment of the cornea and to preserve the homeostasis of corneal optical competency. Interferon-gamma may enhance corneal immunoseclusion by upregulating the TGF-beta output of the corneal fibroblasts.

Biological Assay↗

PubMed1994

The protective properties of liquid perfluorocarbons in phacofragmentation of dislocated lenses.

PURPOSE: In vitro and animal experiments were performed to evaluate the character of retina and pigment epithelium (RPE) damage induced by ultrasonic stream from the tip of a phacofragmentor and to establish the protective properties of perfluorocarbon liquid (PFCL). METHODS: During mechanical vitrectomy in 12 rabbit eyes, the retina were exposed to ultrasound from different distances and with different powers, with and without PFCL. Electron microscopic examination was then performed to assess damage. RESULTS: Ultrasound failed to penetrate the layer of PFCL in vitro. In eyes not injected with PFCL, exposure to the stream from 2 mm and 4 mm at both 50% and 100% powers led to retinal hole formation within 45 to 155 seconds. Damage to the RPE was found in the projection of the hole and within 1 mm from its edge under intact retina. After exposure from 6 mm and in eyes injected with PFCL, the retina and RPE were unchanged. CONCLUSION: It is concluded that the ultrasonic stream from a phacofragmentor may damage the retina sufficiently to cause tears, but that the interface between perfluoro-n-octane and intraocular fluid provides a reflective surface that protects the posterior pole from the stream induced by ultrasound.

Animals↗

PubMed1995

Interpretation of intraocular and serum antibody levels in necrotizing retinitis.

BACKGROUND: Intraocular antibodies have been measured as a diagnostic aid in necrotizing retinitis but interpretation of results may be difficult. METHODS: Vitreous or aqueous and serum immunoglobulin G antibodies to toxoplasmosis, cytomegalovirus, herpes simplex virus I and II, and varicella zoster virus were subjected to enzyme-linked immunosorbent assay in 27 patients with necrotizing retinitis and 15 control patients. A quotient was derived quantitating the amount of excess antibody in the eye compared to serum. Different interpretative rules were analyzed to determine which yielded the highest sensitivity and specificity. RESULTS: The highest intraocular antibody relative to serum among the 4 antibodies correctly predicted the final clinical diagnosis in 21 of 27 patients, for a sensitivity of 78% and a specificity of 90%. Interpretive rules that relied on a high numeric value of the antibody quotient or did not consider the relative ranking of the four antibody quotients were less sensitive and specific because multiple antibodies were detected in most eyes. The technique was safe and rapid. CONCLUSION: Interpretation of antibody titers in intraocular fluids is facilitated by testing several relevant antibodies and comparing the results. The technique may be helpful to diagnose necrotizing retinitis and to ascertain viral cause in acute retinal necrosis.

Adolescent↗

PubMed1998

Use of an antimicrobial removal device in endophthalmitis cultures.

PURPOSE: This study sought to determine whether the use of an antimicrobial removal device (ARD) to process intraocular fluids increases microbial detection compared with conventional cultures. METHODS: The authors retrospectively reviewed all cases of endophthalmitis submitted to their laboratory from January 1982 through December 1996. Aqueous or vitreous specimens or both that were cultured on conventional media (blood agar, chocolate agar, anaerobic blood agar, and thiol broth) and by ARD processing were included in the study. Specimens were inoculated into tubes with ARD for 5 to 10 minutes. The fluid was then withdrawn and cultured using conventional media; thioglycolate broth was added to the tube containing the resin beads. The conventional and ARD-processed cultures were incubated at 35 degrees C for at least 7 days. RESULTS: Of the 338 endophthalmitis cultures processed using both conventional cultures and a parallel ARD, 166 (49.1%) yielded positive microbial growth on one or more media. Of the 166 culture-confirmed cases, 127 (76.5%) were positive in both the ARD-processed and direct cultures, 17 (10.2%) were positive by conventional culture only, and 22 (13.3%) were positive by the ARD-processed sample alone (P = 0.52). The spectrum of microorganisms was similar among all culture groups. The detection of coagulase-negative staphylococci and micrococci by ARD alone was slightly better than detection by conventional culture only (P = 0.06). Of 93 positive cultures from 179 patients in whom prior antibiotic use was documented, 75 (80.6%) were positive by both methods, 8 (8.6%) by conventional cultures only, and 10 (10.8%) only by the ARD-processed specimen (P = 0.81). CONCLUSION: Use of an antimicrobial removal device does not significantly increase the microbial yield of endophthalmitis cultures compared with conventional culture techniques, whether or not antimicrobial therapy is being used.

Anti-Bacterial Agents↗

PubMed1996

HTLV-I uveitis.

Human T-cell lymphotropic virus type I (HTLV-I) is known to cause adult T-cell leukemia/T-cell lymphoma and tropical spastic paraparesis/HTLV-I-associated myelopathy. Recent seroepidemiologic, clinical, and virologic studies indicate that the virus is also related to a certain type of uveitis, which has been classified as uveitis without defined etiologies or idiopathic uveitis. According to the seroepidemiologic survey, the seroprevalence of HTLV-I in patients with idiopathic uveitis was significantly higher than that of two control groups, that is, patients with uveitis with defined etiologies and patients with nonuveitic ocular diseases. Clinically, the uveitis seen in HTLV-I carriers is characterized by moderate to severe cellular infiltration in the eye and by moderate retinal vasculitis, and the intraocular inflammation responds well to corticosteroid therapy. Interestingly, 25% of female patients with the disease had a previous history of Graves disease with hyperthyroidisms. The following virologic, molecular biologic findings suggest that cytokines produced by HTLV-I-infected T cells in the eye play the central role in the pathogenic mechanisms of the uveitis: (a) the virus load in the peripheral blood monocytes analyzed by the quantitative polymerase chain reaction methods was significantly greater in patients with the uveitis than in asymptomatic carriers, (b) the proviral DNA of HTLV-I and the gene expression of the virus at the mRNA level was detected in the infiltrating cells from the eyes of the patients, (c) the virus particles were detected by electron-microscopic examination in the T-cell clones established from the intraocular fluid of the patients, and (d) the HTLV-I-infected T cells produced a variety of cytokines without any stimuli, such as interleukin (IL)-1 alpha, IL-2, IL-3, IL-6, IL-8, IL-10, tumor necrosis factor alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor. Based on the seroepidemiologic, clinical, and virologic data, the uveitis seen in HTLV-I carriers is considered to be a distinct clinical entity related to HTLV-I infection, and the disease is designated as HTLV-I uveitis.

Adolescent↗

PubMed2006

Inflammatory mediators of uveitis: cytokines and chemokines.

PURPOSE OF REVIEW: The study of uveitis has been restricted by the difficulty in obtaining sufficient intraocular material from both human disease and experimental models. Recent developments in cytokine and chemokine detection have overcome many of these problems. This review presents a summary of the technologic advances in this area. RECENT FINDINGS: Recent advances in cytokine analysis, in particular multiplexed bead immunoassays, have allowed the measurement of an extensive array of cytokines and chemokines from very small sample volumes. This has revolutionized uveitis research, enabling measurement of a large profile of cytokines and chemokines in intraocular fluid, such as aqueous humour. This allows us to recognize complex patterns of cytokines and chemokines from different forms of uveitis and to examine relationships between different molecules. SUMMARY: The spectrum of proinflammatory cytokines and chemokines known to be implicated in uveitis has increased over recent years. Many of these molecules have also been found in experimental models of disease and may represent attractive therapeutic targets for the future. With recent advances in cytokine detection, an extension of these techniques with a more detailed analysis of different uveitis conditions may provide useful diagnostic and prognostic information for this potentially blinding group of diseases.

Animals↗

PubMed1995

Perfluorocarbon heavy liquids.

Perfluorocarbon heavy liquids (PFCL) facilitate the transfer of intraocular fluids and other surgical manoeuvres in the posterior segment. The indications for their use have extended since first described in the management of giant retinal tears and proliferative vitreoretinopathy. We reviewed our personal experience and experimental evidence, including adverse effects, in order to identify the current role of PFCL in vitreoretinal surgery. High-density perfluorocarbon liquids represent a major advance in vitreoretinal surgery. Clinical experience and the results of experimental investigations have demonstrated their efficacy and safety as an intraoperative device.

Fluorocarbons↗

PubMed1987

Silicone oil with high specific gravity for intraocular use.

Silicone oil with a higher specific gravity than that of intraocular fluid or polydimethylsiloxane may have special indications in vitreoretinal surgery. Trifluorsiloxane is such a substance, and therefore its biological compatibility was investigated in rabbit eyes. It was found that this substance was clinically well tolerated within the observation time of up to 6 months, even if there was some neovascularisation from the inferior limbus. Histologically both an inflammatory response and tissue impregnation were more pronounced than with normal polydimethylsiloxane.

Animals↗

PubMed1989

Ferroxidase activity increases in the aqueous humor during the ocular inflammatory response.

Ferroxidase activity was increased in the aqueous humor from inflamed eyes compared to their uninflamed contralateral controls 24 h after intravitreal injection of 10 ng of endotoxin. Changes in ferroxidase activity and copper concentration paralleled each other indicating that the plasma copper transport protein ceruloplasmin (plasma ferroxidase) entered the inflamed aqueous humor from plasma through disrupted blood ocular barriers. The presence of ferroxidase activity would facilitate the removal of potentially damaging, free radical generating Fe+2. Therefore, plasma proteins may perform important protective functions in the inflamed intraocular fluids.

Animals↗