A pathogenic autoimmune process targeted at a surrogate epitope.

Immunization with the retinal interphotoreceptor retinoid-binding protein (IRBP) induces in a variety of animals an inflammatory eye disease, experimental autoimmune uveoretinitis (EAU). We have previously shown that sequence 1181-1191 of bovine IRBP (BOV 1181-1191) is immunodominant and highly uveitogenic and immunogenic in Lewis rats. Sequence 1181-1191 of the rat IRBP (RAT 1181-1191) differs from BOV 1181-1191 by two residues, at positions 1188 and 1190, that are pivotal for the immunological activity of the bovine epitope. Here we show that, unlike its bovine homologue, RAT 1181-1191 did not induce EAU or an immune response in Lewis rats. The immunological inactivity of RAT 1181-1191 in Lewis rats is due at least in part to its poor affinity toward the antigen-presenting cells of these rats, as shown by its failure to compete with binding of BOV 1181-1191 to Lewis adherent spleen cells. Moreover, unlike all other known autologous homologues of immunopathogenic epitopes, RAT 1181-1191 was not recognized by lymphocytes sensitized against BOV 1181-1191 and failed to stimulate proliferation, uveitogenic capacity or signal transduction in these cells. These findings thus suggest that RAT 1181-1191 is not a likely target for lymphocytes sensitized against BOV 1181-1191 in the process in which these cells recognize IRBP in the rat eye and trigger the inflammatory reaction of EAU. Our data further suggest that the target for the disease-inducing lymphocytes is sequence 273-283 of the rat IRBP: (a) sequence 273-283 is highly conserved and is identical in the bovine and rat proteins; (b) determinant 273-283 is a "repeat" of 1181-1191 in the fourfold structure of IRBP and shares seven residues with BOV 1181-1191; (c) rat peptide 273-283 is recognized by lymphocytes sensitized against BOV 1181-1191 and stimulates them for proliferation and for acquisition of uveitogenicity; and (d) moreover, sequence 273-283 is superior to BOV 1181-1191 in its capacity to generate uveitogenicity in lymphocytes sensitized against this bovine peptide. The present study thus describes for the first time a system in which an autologous homologue of an immunopathogenic epitope is inactive and a "surrogate" determinant apparently serves as the target for lymphocytes sensitized against the immunopathogenic peptide.

Hepatocellular carcinoma metastatic to the orbit.

We report a rare case of orbital metastasis from hepatocellular carcinoma and review previously documented cases of this condition. The clinical, histopathological, and immunohistochemical characteristics of hepatocellular carcinoma metastatic to the orbit are described. Results from histopathological examination and histochemical findings of the orbital mass established the diagnosis. A review of 10 cases of metastatic hepatocellular carcinoma to the eye and orbit disclosed painful proptosis as the most common clinical sign of hepatocellular carcinoma metastatic to the orbit. In 5 (56%) of the 9 cases that had orbital metastasis (including the present case), the diagnosis was made after the patient first was examined with symptoms from the orbital mass. Metastatic hepatocellular carcinoma should be considered as a rare cause of painful proptosis. While patients usually are seen with signs and symptoms of widespread metastatic carcinoma, patients with hepatocellular carcinoma with orbital involvement may be first examined by the ophthalmologist because of the clinical manifestations of the disease, proptosis and pain. Other orbital lesions associated with painful proptosis are discussed briefly.

Optimal imaging protocol after intraocular silicone oil tamponade.

PURPOSE: Our purpose was to define the optimal protocol for imaging of the orbits after vitreous humor replacement with silicone oil. METHODS: Eleven eyes in 10 patients with tractional and/or rhegmatogenous retinal detachment were studied. Five CT scans and 18 high-field (1.5 T) MR images were obtained. Standard T1-weighted, T1-weighted with fat and silicone saturation, fast spin density-weighted, and T2-weighted orbital MR sequences were performed. Unique pulse sequences included fast spin density-weighted and T2-weighted imaging with and without fat saturation or silicone saturation, gradient-echo imaging, and short-tau inversion recovery imaging. RESULTS: The T1-weighted MR and CT studies were comparable in displaying the silicone. However, the fat- or silicone-saturated fast T2-weighted sequences always showed the fibrous bands and subretinal fluid to best advantage. In one case, the eye also contained inadvertently retained perfluorocarbon liquid, which blended with silicone oil on both saturated images, requiring companion T1-weighted sequences without saturation to demonstrate its presence. CONCLUSION: Simple, commonly available fat-saturated fast T2-weighted MR images supplemented by standard T1-weighted images are all that are needed to evaluate the eye efficiently after vitrectomy and tamponade.

Ultrastructural features and prevalence of tubuloreticular structures in the ocular vasculature of patients with AIDS: a study of 23 cases.

BACKGROUND: Tubuloreticular structures (TRS) are subcellular inclusions that are most commonly found in endothelial cells and lymphocytes of patients with autoimmune or collagen vascular disorders. In AIDS, TRS have been described in various tissues throughout the body including the lung, kidney, liver, muscle, and skin. METHODS: Ocular tissues from 23 patients with AIDS were examined by electron microscopy. These included 17 postmortem eyes in addition to three chorioretinal and three conjunctival biopsy specimens. RESULTS: The overall prevalence of TRS in the ocular and conjunctival endothelial cells was found to be 83% (19/23). CONCLUSIONS: This is the first documented study of the prevalence of these structures in the ocular structures of patients with AIDS. Given the high frequency of their occurrence in AIDS, it is recommended that the presence of TRS in ocular or conjunctival tissues be an indication for obtaining an HIV antibody titre. Additionally, a rheumatological examination for HIV seronegative patients is suggested.

Perfluoro-N-octane (PFO) in the repair of complicated retinal detachments due to severe proliferative diabetic retinopathy.

PURPOSE: To report our experience with perfluoro-N-octane (PFO) in the surgical management of complicated retinal detachments due to proliferative diabetic retinopathy. METHODS: Retrospective review of 18 consecutive eyes of 18 patients with tractional or combined tractional and rhegmatogenous retinal detachments due to severe proliferative diabetic retinopathy managed by pars plana vitrectomy and the intraoperative use of PFO. Preoperative characteristics, intraoperative findings and procedures and postoperative results were recorded. RESULTS: The mean preoperative acuity was 2/200 (range, 20/25 to light perception). The mean final visual acuity was 4/200 (range, 20/20 to no light perception). With a mean follow-up of 6 months, there was an 89% anatomic reattachment rate at the last visit and visual acuity was stable or improved in 72% of eyes. CONCLUSIONS: In our experience, PFO is a helpful surgical adjunct in the anatomic reattachment of tractional or combined tractional and rhegmatogenous diabetic retinal detachments. Visual acuity was stabilized or improved in the majority of eyes.

Non-cytochrome mediated mitochondrial ATP production in bloodstream form Trypanosoma brucei brucei.

The life cycle of Trypanosoma brucei brucei involves a series of differentiation steps characterized by marked changes in mitochondrial development and function. The bloodstream forms of this parasite completely lack cytochromes and have not been considered to have any Krebs cycle function. It has been suggested that glycolysis is the sole source of ATP in all bloodstream forms. However, earlier results indicated that in the mitochondria of the transitional intermediate/short stumpy bloodstream forms, the biochemical pathways are present that could allow intra-mitochondrial production of ATP. Using a high mannitol buffer to enhance permeability, we confirm previous observations showing that transitional forms maintain motility and respiratory activity with 2-oxoglutarate as the sole substrate. Using a luminometer to measure intracellular ATP levels via the luciferin/luciferase chemiluminescence assay, we show that these same transitional forms, but not long slender forms, maintain high levels of intracellular ATP in the presence of 2-oxoglutarate. Further, in the presence of bongkrekic acid, an inhibitor of the mitochondrial adenine nucleotide translocase, ATP levels are reduced with subsequent death and lysis of the cells when 2-oxoglutarate, but not glucose, is used as sole substrate. These data are direct evidence of ATP production by transitional bloodstream form mitochondria.

Multifocal electroretinography in multifocal choroiditis and the multiple evanescent white dot syndrome.

PURPOSE: To study and compare the findings on multifocal electroretinography (MERG) between multifocal choroiditis (MFC) and the multiple evanescent white dot syndrome (MEWDS). SUBJECT AND METHODS: Patients were recruited prospectively from the Department of Ophthalmology & Visual Sciences at the University of Iowa Hospitals & Clinics. They were evaluated using Goldmann visual fields (GVF) and MERG. Patients were diagnosed as having either MFC or MEWDS based on their clinical findings before MERG testing. RESULTS: Nineteen patients (23 eyes) were included in the study. Eleven patients were diagnosed with MFC and eight patients with MEWDS. Fourteen eyes with MFC and seven eyes with MEWDS were tested with MERG during the acute phase of their respective conditions. Fourteen patients (8 MFC and 6 MEWDS) were followed serially with MERG. Patients with MEWDS demonstrated focal depression corresponding to GVF defects with subsequent near total recovery of the MERG to baseline. Patients with MFC typically demonstrated diffuse loss of function over the entire test field. Focal scotomata, in addition to the diffuse depression, could be identified in 7 of 14 patients. Patients with MFC demonstrated only partial or no recovery of MERG following acute episodes, which was significantly different from the course followed by patients with MEWDS (P < 0.001, Fisher's exact test). CONCLUSION: Multifocal electroretinography differentiates MFC from MEWDS. Patients with MFC have permanent damage to the retina with diffuse depression of MERG. Patients with MEWDS, however, typically demonstrate greater focal loss initially on MERG followed by nearly full recovery of first order retinal function.

Evaluation of patients with visual field defects following macular hole surgery using multifocal electroretinography.

PURPOSE: To investigate patients with visual field defects following macular hole surgery to determine the cause of such defects, specifically with reference to ischemic damage versus mechanical trauma. METHODS: Five patients with known visual field defects following macular hole surgery were studied with Goldmann perimetry, Humphrey automated perimetry, and multifocal electroretinography (MERG). Three patients returned at a later date for nerve fiber layer analysis. RESULTS: None of the five patients demonstrated evidence of a- or b-wave loss on MERG in the regions corresponding to the visual field defects. Two of three patients studied with the nerve fiber layer analyzer demonstrated significant loss of nerve fiber layer thickness in the quadrant corresponding to the field defect. CONCLUSION: The normal MERG results indicate that the possibility of an arteriolar occlusion as the principal cause for the defects is unlikely in most cases. Data suggest that the site of damage is in the nerve fiber layer, although the specific cause of this damage remains to be determined.

MR imaging of the eyelids: normal and pathologic findings.

MR imaging is commonly used to evaluate orbital and facial soft-tissue disease. Although the eyelids are visible on these images, the radiographic appearance and the detailed anatomy of these structures has received little attention in the literature [1-4]. Anatomic correlation with MR images may be extremely helpful in the accurate interpretation and staging of eyelid malignancies and infections.