The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.

Purpose To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. Design Modified Delphi process. Methods A survey of uveitis specialists in the American Uveitis Society (AUS), a face-to-face meeting (AIR Workshop) held at the National Eye Institute (NEI), and two iterations of expert panel surveys were utilized in a modified Delphi process. The expert panel consisted of 17 experts including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. Results There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR). Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as 1st or 2nd line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a two-tier design and that western blot (WB) and immunohistochemistry (IHC) should be the methods used to identify antiretinal antibodies. Conclusions Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized two-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

, and (iii) the overall radiation dose deposited by radiolabeled cells in the unlabeled cells within the growing tumor is <10 cGy, we conclude that the results obtained are a consequence of a bystander effect that is generated in vivo by factor(s) present within and͞or released from the 125 IUdR-labeled cells. These in vivo findings significantly impact the current dogma for assessing the therapeutic potential of internally administered radionuclides. They also call for reevaluation of the approaches currently used for estimating the risks to individuals and populations inadvertently exposed internally to radioactivity as well as to patients undergoing routine diagnostic nuclear medical procedures. Studies in recent years have demonstrated that a radiobiologic phenomenon termed the ''bystander effect'' can be observed in mammalian cells grown in vitro. Bystander damage describes biologic effects, originating from irradiated cells, that occur in unirradiated neighboring cells. Several investigators have reported that when ␣-particles traverse a small fraction of a cell population in vitro, lower rates of survival and higher rates of genetic change are observed than those predicted from directionization-only models (1-6). These changes include increased levels of sister chromatid exchanges, mutations, and micronuclei formation, changes in gene expression, and oncogenic transformation. Cell survival is likewise compromised when cells are cocultured with tritiated thymidine-labeled cells (7, 8) and iodine-125 (9). Similarly, the bystander effect has been reported for microcolonies that have been ␥ irradiated (10) and for cells exposed to media from ␥-irradiated cells (10, 11). Evidence from these reports challenges the past half-century's tenet that radiation produces effects only in cells whose DNA has been damaged either through direct ionization or indirectly (for example, through hydroxyl radicals produced in water molecules in the immediate vicinity of the DNA).Whether radiation-induced bystander effects represent a phenomenon that occurs only ex vivo, i.e., are a byproduct of in vitro conditions and manipulations, or whether they are factual in vivo events has not been fully examined. Consequently, the extension of conclusions derived from in vitro studies to the in vivo situation is uncertain. The demonstration of a bystander effect with an in vivo system and the elucidation of the underlying mechanisms of an in vivo bystander effect would go a long way in translating its implications for humans.Recently, Watson et al. (12) demonstrated chromosomal instability in the progeny of unirradiated bone marrow cells mixed with cells exposed ex vivo to neutrons and transplanted into recipient mice. In this novel system, a sex-mismatch transplantation protocol provides a three-way marker system and allows the investigators to distinguish not only host-derived cells from donor-derived cells, but also irradiated donor stemcell-derived cells from nonirradiated donor stem-cell-derived cells. These studies thus provide the...

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