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Biomedical subjects

Ehud Zamir

Publications and source records attributed to Ehud Zamir.

17 recordsLinked to original sources

Intraocular crystals in HIV-related hypergammaglobulinemia.

PURPOSE: To describe the occurrence of bilateral iris and retinal crystals in a patient with benign HIV-related gammopathy. DESIGN: Observational case report. METHODS: A 45-year-old HIV-positive male with a known, benign hypergammaglobulinemia was referred for routine ophthalmic assessment because of right ophthalmic zoster. RESULTS: Ophthalmoscopic examination revealed the presence of bilateral, multiple, refractile iris and macular crystals. No other signs of uveitis or stigmata of HIV were found. CONCLUSION: Intraocular crystals are a rare finding, usually seen in chronic uveitis with or without hypergammaglobulinemia. This finding has not been previously described in non-inflamed eyes, nor as an ocular manifestation of HIV. We hypothesize that HIV-related disruption of the blood-aqueous and blood-retinal barriers allows intraocular immunoglobulin deposition in patients with hypergammaglobulinemia.

Crystallization↗

The involvement of NK cells in ankylosing spondylitis.

A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.

Adult↗

Evaluation of subconjunctival triamcinolone for nonnecrotizing anterior scleritis.

PURPOSE: Subconjunctival corticosteroid injection (SCI) for nonnecrotizing anterior scleritis remains controversial, partly because long-term follow-up is not available. This study documents the efficacy and adverse effects of SCI. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Thirty-eight eyes of 35 patients with nonnecrotizing, noninfectious anterior scleritis resistant to prior systemic or local therapy. INTERVENTION: Subconjunctival triamcinolone acetonide injection. MAIN OUTCOME MEASURE: Persistence or resolution of signs and symptoms of anterior scleritis and development of complications. RESULTS: Thirty-six of 38 eyes had complete resolution of signs and symptoms within 6 weeks of SCI. Fifteen eyes had follow-up of > or =30 months. There were no instances of scleral melting or perforation; adverse events included subconjunctival hemorrhage (5 patients), transient ocular hypertension without evidence of glaucoma (4 patients), cataract (2 patients), and glaucoma (2 patients). Subconjunctival corticosteroid injection resulted in reduced dependence on systemic medications. CONCLUSION: Subconjunctival corticosteroid injection in eyes that failed other therapies is effective, reduces dependence on systemic medications, and did not result in scleral necrosis over a median follow-up period of 29 months.

Adolescent↗

Update on Fuchs' uveitis syndrome.

PURPOSE OF REVIEW: This update aims to summarize the current knowledge on Fuchs' uveitis syndrome and review publications in the last 10 years. Theories on the pathogenesis and etiology of Fuchs' uveitis syndrome are revisited and the management of cataract and glaucoma is updated to reflect recent surgical change. RECENT FINDINGS: Retrospective reviews have highlighted that patients with Fuchs' uveitis syndrome are often initially misdiagnosed. Studies comparing local inflammatory mediators and cell types have found differences in Fuchs' uveitis syndrome, but the differences in steroid response and degree of inflammation remain poorly understood. Local production of antibodies to rubella has been recently reported in the aqueous of all patients with Fuchs' uveitis syndrome and no controls. Excellent visual outcomes from phacoemulsification have been reported with reduced complications compared with extracapsular cataract extraction. SUMMARY: Although a single etiological agent and a sensitive laboratory test for the diagnosis of Fuchs' uveitis syndrome is alluring, the diagnosis of Fuchs' uveitis syndrome remains clinical, at least for now. Phacoemulsification has increased the safety of cataract extraction, and the use of intraocular lens is generally safe. The ideal lens material and design are not yet known, but silicone lenses may be best avoided. Glaucoma is often resistant to treatment and should actively be screened for in patients with Fuchs' uveitis syndrome. Medical and surgical treatment for reducing intraocular pressure should be especially aggressive in these patients. Vitrectomy appears to be safe in patients with visually significant vitreous opacification.

Cataract↗

Surgical management of corneal plaques in vernal keratoconjunctivitis: a clinicopathologic study.

PURPOSE: To describe the surgical management and histopathologic and immunohistochemical findings in corneal plaques of shield ulcers in vernal keratoconjunctivitis. PATIENTS AND METHODS: Three children (ages 4, 7.5, and 9) presented with corneal plaques unresponsive to conservative systemic and topical medical treatment. Plaques were scraped under general anesthesia, and soft bandage contact lenses were placed. The excised tissue was evaluated by histopathology and immunohistochemistry. RESULTS: During surgery, plaques were found to extend beyond the ulcer margins. Histopathology revealed granular, deeply-eosinophilic, laminar material, firmly attached to the Bowman layer in all cases. Immunohistochemistry confirmed this to be eosinophil-derived major basic protein (MBP). After surgical removal, complete epithelization was evident within 1-4 weeks in all cases. CONCLUSIONS: Corneal plaque is a rare complication of vernal keratoconjunctivitis. These plaques usually do not resolve with standard conservative measures. Failure to epithelialize may be a result of the plaque material extending below the edges of adjacent epithelium. We suggest that MBP plaques precipitate on the denuded stromal bed, thereby playing a pathogenic role in nonhealing shield ulcers.

Blood Proteins↗

Conjunctival ulcers in Behçet's disease.

PURPOSE: To describe the occurrence of conjunctival ulcers as a manifestation of Behçet's disease. DESIGN: Retrospective, noncomparative, interventional case series with histopathologic correlation. METHODS: Six patients who fulfilled the diagnostic criteria for Behçet's disease and presented with painful conjunctival ulcers were included in the study. Three of these ulcers were biopsied and studied histologically and immunohistochemically. The lesions were treated with topical or subconjunctival injection of corticosteroids and, in one case, with oral indomethacin. RESULTS: Although all six patients fulfilled the diagnostic criteria for Behçet's disease, two developed uveitis and other signs of Behçet's disease only months to years after the appearance of the conjunctival ulcers. The 3- to 5-mm, round to oval ulcers were located in the limbal and/or bulbar conjunctiva. Histopathology revealed disrupted epithelium, infiltration of both acute and chronic inflammatory cells, and high endothelial venules. Immunohistochemical analysis of the infiltrating lymphocytes revealed primarily T-cell populations admixed with several B cells and CD68-positive histiocytes. After treatment, the conjunctival lesions invariably healed without scarring. CONCLUSIONS: In addition to the oral and genital ulceration, ulcers can also be found in the conjunctiva of patients with Behçet's disease. Although this is a rare clinical sign, when accompanied by uveitis or orogenital ulcers, it may suggest a diagnosis of Behçet's disease.

Adolescent↗

Pathogenic role of retinal microglia in experimental uveoretinitis.

PURPOSE: To devise methods for unequivocal identification of activated retinal microglia in experimental autoimmune uveoretinitis (EAU) and to investigate their role in the development of EAU. METHODS: A group of Lewis rats underwent optic nerve axotomy with the application of N-4-(4-didecylaminostyryl)-N methylpyridinium iodide (4Di-10ASP) at the axotomy site. On days 3, 14, and 38 after axotomy, the rats were killed, the eyes were enucleated, and the retinas were stained for OX42. Another group of such axotomized rats were immunized with S-antigen peptide and were killed on days 7 through 12 after the injection with peptide. The enucleated eyes were stained for OX42 and examined by confocal microscope. After axotomy, bone marrow (Y-->X) chimeric rats were injected with S-antigen peptide and were killed on days 10 and 12 after injection. The retinas were evaluated by PCR with Y-specific primers. Finally, a group of axotomized rats was injected with the S-antigen peptide and killed on days 6, 8, 9, and 10 after injection. Their enucleated eyes were examined for microglial expression of TNFalpha and for generation of peroxynitrite. RESULTS: In the axotomized, non-EAU eyes, 4Di-10ASP-labeled ganglion cells were detectable on days 3 and 14, and 4Di-10ASP-containing OX42-positive cells (microglia) were found in the nerve fiber and other inner retinal layers on days 14 and 38. The S-antigen peptide-injected rats showed migration of the microglia (4Di-10ASP-positive and OX42-positive) to the photoreceptor cell layer on day 9, and these cells increased in number at this site on day 10. No macrophages (OX42-positive and 4Di-10ASP-negative) were present at this early stage of EAU, but such cells appeared in the retina on days 11 and 12. PCR of the chimeric EAU retinas showed an absence of the Y chromosome-amplified product on day 10, but the presence of this product was detected on day 12. The expression of TNFalpha and generation of peroxynitrite were noted in the migrated microglia at the photoreceptor cell layer on days 9 and 10 of EAU. CONCLUSIONS: In the early phase of EAU, the microglia migrate to the photoreceptor cell layer where they generate TNFalpha and peroxynitrite. Such microglial migration and activation take place before infiltration of the macrophages. These findings indicate a novel pathogenic mechanism of EAU, in which retinal microglia may initiate retinitis with subsequent recruitment of circulation-derived phagocytes, leading to the amplification of uveoretinitis.

Animals↗

A prospective evaluation of subconjunctival injection of triamcinolone acetonide for resistant anterior scleritis.

PURPOSE: Prospective evaluation of the efficacy and safety of subconjunctival triamcinolone injections for resistant, nonnecrotizing, anterior scleritis. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 10 consecutive patients seen in the Doheny Eye Institute between August 1999 and December 2000 with diffuse, nonnecrotizing anterior scleritis that was resistant to systemic antiinflammatory therapy. Eyes with a history of steroid response were excluded. INTERVENTION: Subconjunctival injection of triamcinolone acetonide to the areas of maximal inflammation. MAIN OUTCOME MEASURES: Scleritis activity, adverse treatment effects, and number of systemic medications required at the end of the follow-up period. RESULTS: Within 1 to 14 days after injection, complete resolution of signs and symptoms was achieved in 11 eyes and partial resolution in 1 eye. Two patients had one recurrence each, 2.5 and 11 months after injection. Six of 10 patients were able to discontinue all systemic therapy (prednisone +/- immunosuppressive drugs); the remaining 4 needed continued oral therapy for systemic indications. Transient ocular hypertension and subconjunctival hemorrhage occurred in one eye each. Median follow-up period was 15 months. No eye developed necrotizing scleritis. CONCLUSIONS: Subconjunctival injection of triamcinolone acetonide is a safe and effective treatment for resistant, nonnecrotizing anterior scleritis. It provides rapid effect, is well tolerated, and may spare patients the significant complications and side effects of systemic corticosteroid and immunosuppressive therapy.

Adult↗

Massive mycobacterial choroiditis during highly active antiretroviral therapy: another immune-recovery uveitis?

PURPOSE: To describe the ocular presentation of disseminated mycobacterial disease occurring during immune-recovery in a patient with acquired immune deficiency syndrome (AIDS). STUDY DESIGN: Case report and literature review. PARTICIPANTS: A 41-year-old AIDS patient with a prior diagnosis of cytomegalovirus retinitis. METHODS: The patient developed progressive, bilateral multifocal choroiditis with panuveitis 2 months after beginning and responding to highly active antiretroviral therapy. His left eye became blind and painful and was enucleated. Pathologic examination revealed massive choroiditis with well-formed, discrete granulomas and multiple intracellular and extracellular acid-fast organisms within the choroidal granulomas. Culture and polymerase chain reaction of vitreous specimens revealed Mycobacterium avium complex (MAC). RESULTS: Empiric, and later sensitivity-guided, local and systemic antibiotic therapy was used to treat the remaining right eye, but it continued to deteriorate. Despite medical therapy, three vitrectomies and repeated intravitreal injections of amikacin, a total retinal detachment ensued. One week after the third vitrectomy, the patient died from mesenteric artery thrombosis in the setting of disseminated mycobacterial disease. CONCLUSIONS: This is the first report of ocular inflammation as the presenting finding in the recently recognized syndrome of immune-recovery MAC disease. Pathogenesis of this entity is related to an enhanced immune response to a prior, subclinical, disseminated infection. The formation of discrete granulomas, normally absent in MAC infections in AIDS, reflects this mechanism.

AIDS-Related Opportunistic Infections↗

Progressive subretinal fibrosis and blindness associated with multifocal granulomatous chorioretinitis: A variant of sympathetic ophthalmia.

OBJECTIVE: To report a case of bilateral progressive subretinal fibrosis and blindness with multifocal granulomatous chorioretinitis occurring after intraocular surgery. We propose that this is a variant of sympathetic ophthalmia. DESIGN: Clinicopathologic case report. METHODS: The left enucleated globe was examined by histopathologic methods. The patient's sera were subjected to immunohistochemical studies against retinal antigens, and collagen 2 types in areas of fibrosis were identified. Polymerase chain reaction was used to test for herpes virus DNA in microdissected, formalin-fixed, paraffin-embedded tissue. RESULTS: The enucleated globe demonstrated histopathologic features similar to an entity previously described as progressive subretinal fibrosis with multifocal granulomatous chorioretinitis. The patient's sera demonstrated antibodies directed against retinal photoreceptors and pigment epithelium. Polymerase chain reaction for herpes virus was negative. Immunohistochemical studies demonstrated types III, IV, V, and VI collagen in areas of fibrosis. CONCLUSIONS: The clinical history along with the histopathologic and immunohistochemical findings suggest that progressive subretinal fibrosis with multifocal granulomatous chorioretinitis may represent a variant of sympathetic ophthalmia and that retinal autoimmunity may play a role in its pathogenesis.

Aged↗

Inflamed juvenile conjunctival naevus: clinicopathological characterisation.

AIM: Inflamed juvenile conjunctival naevi (IJCN) are often erroneously suspected to be malignant because of rapid growth. Their clinical and histopathological features have not been characterised in series of patients. The aim of the study is to characterise IJCN clinically and histopathologically. METHODS: This is a retrospective non-randomised clinicopathological study. All patients younger than 20 years with conjunctival naevi which were excised between 1990 and 2000 were included. The clinical signs of the affected patients and the histopathological findings of the excised lesions were characterised. RESULTS: A total of 63 conjunctival naevi were resected. 25% of the patients had simple compound conjunctival naevi and 75% had compound naevi with prominent inflammatory histological features (discrete lymphocyte aggregates, plasma cells, and eosinophils). Epithelial cysts and solid epithelial islands were common in the IJCN. The IJCN were all located at or near the limbus, and characterised by recurrent periods of congestion and growth. 75% of the IJCN patients with complete medical records had a history of allergic disease. Marked conjunctival papillary reaction was present in all of the patients, indicating a possible conjunctival allergy. CONCLUSIONS: IJCN is a unique entity, different from simple compound conjunctival naevus. Its association with allergic conjunctivitis is suggestive, and despite periods of alarmingly rapid growth, is histologically benign.

Adolescent↗

Nerve growth factor and eosinophils in inflamed juvenile conjunctival nevus.

PURPOSE: To study both systemic and ocular nerve growth factor (NGF) in inflamed juvenile conjunctival nevus (IJCN), a benign, inflammatory juxtalimbal lesion characterized by many intralesional eosinophils, and to investigate the behavior of eosinophils cocultured on lesional and extralesional fibroblasts obtained from IJCN biopsies, in relation to NGF. METHODS: Eight patients with IJCN (7-15 years old) and six with noninflamed conjunctival compound nevus (12-30 years old) participated in the study. Conjunctival biopsy specimens were used for routine histology, immunohistochemistry (NGF, trkA, eosinophil cationic protein, and tryptase determination), in situ hybridization (NGF mRNA), and determination of fibroblast growth. Blood of patients with IJCN was used to measure NGF levels (by ELISA) and to isolate eosinophils (magnet activated cell sorter [MACS]). Eosinophils were seeded on lesional and extralesional fibroblasts and their adherence, survival (by trypan blue staining), and functional activity (by eosinophil peroxidase [EPO] assay) were assessed after 4 days. RESULTS: NGF in the blood of patients with IJCN and eosinophils and mast cells in their conjunctivas, were significantly elevated. NGF protein, NGF mRNA, and trkA were found to be increased in IJCN biopsy specimens compared with noninflamed compound nevi. Some NGF and trkA colocalized with eosinophils and mast cells. Lesional fibroblasts produced high amounts of NGF in comparison with extralesional fibroblasts and significantly enhanced eosinophil adherence, without influencing either their viability or activation. Adherence and EPO release were increased, in both lesional and extralesional fibroblasts. CONCLUSIONS: The triggering factors that lead to the prominent inflammation in IJCN are unknown. The data in the current study, showing the presence of increased NG-trkA, eosinophils, and mast cells in IJCN and the modulation of eosinophil properties by lesional fibroblasts partly through NGF, suggest a possible association between IJCN and allergic inflammation. Alternatively, this process may represent a direct immune response induced by the nevus itself.

Adolescent↗

Neoplastic masquerade syndromes.

Masquerade syndromes are classically defined as entities which emulate inflammatory conditions but which are in fact due to a neoplastic process. Careful history and examination in concert with appropriate ancillary investigations and histopathologic evaluation of tissue specimens are required in order to make the correct diagnosis. Many conditions may result in an appearance mimicking an inflammatory condition. The authors review neoplastic conditions which may be considered masquerades. The most common of these is primary intraocular lymphoma or primary central nervous system lymphoma, occurring predominately in older individuals. Diagnostic strategies, therapy, and prognosis are reviewed in detail. Other conditions that can be considered masquerade syndromes are reviewed as well, including lymphomatous and nonlymphomatous conditions, such as melanoma, retinoblastoma, juvenile xanthogranuloma, metastatic lesions, and paraneoplastic syndromes, among others.

Central Nervous System Neoplasms↗