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This paper presents interdisciplinary research exploring the development of inclusive multisensory science books, communicating immunology data for blind, low-vision and diverse-needs audiences. The research adopted an inductive theory-building approach, practice-based art methods and music and design methods, leveraging the lived experience of a legally blind artist. The research also involved designers and scientists in a cocreation process, producing books that incorporate tactile artworks, Braille-inspired protein models, image sonification and interaction. Two multisensory book titles, "The Heroes Within You: A Multisensory Exploration of Infection and Immunity" and "My Goodness: A Multisensory Exploration of Nutrition and Immunity", were developed for the Monash Sensory Science 2023 Exhibition Day. The books offer an innovative way to make science and art more accessible and engaging, addressing the limitations of traditional museum methods. Feedback from audiences has been positive, emphasizing the fascination, sensory engagement and ease of understanding. This paper highlights the potential for an interdisciplinary and inclusive approach to science and art, demonstrating the value of multisensory books as tools for science communication. The findings highlight the positive reception of this novel approach and suggest its potential for broader applications, promoting inclusivity and accessibility., (© 2024 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Art is a powerful tool for conveying scientific discovery. Despite the perceived gap between art and science, as highlighted by CP Snow and others, examples of art communicating science can be found in the ancient world, the Renaissance and contemporary data visualization, demonstrating an enduring and historic connection. However, much of science relies on visual elements, excluding those with blindness, low vision and diverse needs, resulting in their low representation in STEM discourse. This paper introduces a novel science and art collaboration in the form of an exhibition program exploring the concepts of Immunology and Biomedicine to blind and vision-impaired audiences, capitalizing on the lived experience of a legally blind artist. Employing multisensory design, art and co-creation methodologies, it transcends traditional vision-based science communication, showcasing the potential for multisensory art to bridge the gap at the intersection of science and inclusion., (© 2024 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Immunology for all: Most scientific communication has historically been limited to visual imagery and the written or spoken word, often in the form of dense articles obscured by jargon. Clear communication of science is vital to enable the public to engage with important scientific discoveries and to limit medical distrust. However, scientific communication is often executed in a way which neglects people with blindness, low vision and diverse needs. Our aim for the exhibit at the Monash Sensory Science Exhibition on Autoimmunity 2023 at Monash University was to develop novel, tactile and informative models to help better communicate the scientific principles that underpin autoimmune disease and immunology. As B-cell biologists, we decided to focus our exhibit for this workshop on antibody-mediated autoimmunity. Antibodies are key components of the immune system, providing protection against a range of diverse pathogens. However, in the context of autoimmunity, they can also drive pathology., (© 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.)

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.

Antitumour necrosis factor alpha agents are important treatments in many inflammatory conditions including rheumatoid arthritis, psoriatic arthritis and the inflammatory bowel diseases. However, there have been case reports of optic neuritis and other demyelinating diseases as complications of these agents. This case report presents a patient with ulcerative colitis on infliximab who presented with sudden onset mono-ocular visual field loss and highlights the diagnosis and management of infliximab-induced optic neuritis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

A 53-year-old immunocompromised woman developed acute left eye blindness and paraparesis suspected to be due to neuromyelitis optica (NMO). During treatment for NMO, right eye blindness and progressive multiple cranial neuropathies developed. Cerebrospinal fluid polymerase chain reaction (PCR) revealed Varicella zoster virus (VZV). This case emphasizes the importance of considering VZV in individuals, particularly the immunocompromised, presenting with a constellation of neurological signs and symptoms, even in the absence of rash.

Purpose: To identify potential predictors of permanent vision loss in patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center., Design: Retrospective case-control study., Methods: The charts of 212 patients (338 eyes) with HLA-B27-associated uveitis that visited the University Medical Center Utrecht with a follow-up of at least 6 months were retrospectively studied. Clinical features at presentation and during follow-up were compared to final visual outcome in quiescent state. Eyes with (sub-) normal vision (>20/50) were compared with visually impaired (≤20/50) and blind (≤5/50, or a visual field of <10 degrees) eyes, using survival analysis. A multivariate Cox proportional hazards analysis was performed to analyze potential predictors for permanent vision loss., Results: Median follow-up was 10.4 years (range, 0.5-44.7 years). During follow-up 226 eyes (66%) experienced vision loss up to 20/50, but most recovered. Twenty patients (9%) became permanently visually impaired or blind in at least 1 eye because of uveitis, after a median of 9.7 years (range, 0-20.9 years). The main cause was secondary glaucoma or related to glaucoma surgery (12/22 eyes, 55%). Survival analysis showed, after adjustment for age and sex, an ocular pressure of >21 mm Hg, hypotony, and panuveitis to be potential predictors at presentation, and the development of secondary glaucoma or hypotony to be predictors of blindness or visual impairment during follow-up., Conclusions: The long-term visual prognosis of HLA-B27-associated uveitis is relatively good, but the true incidence of permanent vision loss is probably still underestimated. Our findings highlight the importance of proper control of intraocular pressure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Isolated sphenoid sinus disease is a rare entity with severe and potentially life threatening sequela. Because of the proximity of the sinus to the orbit, anatomical defects within the surrounding bony structures can facilitate communication with orbital content, predisposing the patient to substantial visual consequences. We report a case of a 51-year-old immunocompromised male who presented with headache and gradual unilateral decreases in vision. Computed tomography revealed opacification of the left sphenoid sinus accompanied by unusual bony dehiscence of the proximal optic canal. Early recognition and treatment of sphenoid sinusitis requires urgent surgical intervention with delay of treatment potentially leading to irreversible blindness or other devastating consequences. Bony dehiscence of the sphenoid sinus overlying the optic nerve has only been found in 4% of cadavers. It is associated with increased risk of orbital complications and predicts a poor prognosis. Immediate intervention is particularly important in immunocompromised individuals who are at greater risk of these severe complications.

Corneal transplantation is the primary treatment option to restore vision for patients with corneal endothelial blindness. Although the success rate of treatment is high, limited availability of transplant grade corneas is a major obstacle. Tissue-engineered corneal endothelial grafts constructed using cultivated human corneal endothelial cells (hCENC) isolated from cadaveric corneas may serve as a potential graft source. Currently, tools for the characterization of cultured hCENC and enrichment of hCENC from potential contaminating cells such as stromal fibroblasts are lacking. In this study, we describe the generation and characterization of novel cell surface monoclonal antibodies (mAbs) specific for hCENC. These mAbs could be used for enrichment and characterization of hCENC. Out of a total of 389 hybridomas, TAG-1A3 and TAG-2A12 were found to be specific to the corneal endothelial monolayer by immunostaining of frozen tissue sections. Both mAbs were able to clearly identify hCENC with good 'cobblestone-like' morphology from multiple donors. The antigen targets for TAG-1A3 and TAG-2A12 were found to be CD166/ALCAM and Peroxiredoxin-6 (Prdx-6), respectively, both of which have not been previously described as markers of hCENC. Additionally, unlike other Prdx-6 mAbs, TAG-2A12 was found to specifically bind cell surface Prdx-6, which was only expressed on hCENC and not on other cell types screened such as human corneal stromal fibroblasts (hCSF) and human pluripotent stem cells (hPSC). From our studies, we conclude that TAG-1A3 and TAG-2A12 are promising tools to quantitatively assess hCENC quality. It is also noteworthy that the binding specificity of TAG-2A12 could be used for the enrichment of hCENC from cell mixtures of hCSF and hPSC.

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.

Purpose: To report the prevalence of ocular manifestations in patients with HIV/AIDS and their correlation with the clinical stage of disease as well as the CD4 cell count., Methods: 100 HIV-positive patients, who presented to a tertiary care hospital, were included. The WHO clinical staging of HIV/AIDS, CD4 count, duration of disease, and presence and type of ocular manifestations were noted., Results: Overall, 46 patients (46%) had ocular manifestations related to HIV/AIDS. The most common manifestations were HIV retinopathy (12%) and cytomegalovirus (CMV) retinitis (7%). The prevalence of ocular manifestations correlated significantly with the WHO clinical stages 3 and 4 of HIV/AIDS (p = .001) and with low CD4 count (p = .001)., Conclusions: CD4 cell counts and WHO clinical stage of HIV disease are important predictors for the occurrence of ocular morbidity in HIV-positive individuals. Routine comprehensive ophthalmic screening and appropriate initiation of therapy in these patients can potentially decrease ocular morbidity.

Stromal keratitis is a chronic immunopathological lesion of the eye caused by HSV-1 infection that can result in blindness. Because the inflammatory lesions are primarily orchestrated by Th1 cells, and to a lesser extent by Th17 cells, inhibiting their activity represents a useful form of therapy. In this study we evaluated the therapeutic potential of galectin-1 (gal-1), an endogenous lectin that in some autoimmune diseases was shown to suppress the functions of Th1 and Th17 cells. Treatment was begun at different times after ocular infection with HSV and the outcome was assessed clinically as well as for effects on various immune parameters. Treatment with recombinant gal-1 significantly diminished stromal keratitis lesion severity and the extent of corneal neovascularization. Treated mice had reduced numbers of IFN-γ- and IL-17-producing CD4(+) T cells, as well as neutrophil infiltration in the cornea. Furthermore, disease severity was greater in gal-1 knockout mice compared with their wild-type counterparts. The many effects of gal-1 treatment include reduction in the production of proinflammatory cytokines and chemokines, increased production of IL-10, and inhibitory effects on molecules involved in neovascularization. To our knowledge, our findings are the first to show that gal-1 treatment represents a useful approach to control lesion severity in a virally induced immunopathological disease.

CXCR3 and its ligands are important for the trafficking of activated CD4(+) T(H)1 T cells, CD8(+) T cells, and natural killer cells during inflammation. Recent functional studies demonstrate a more diverse role of CXCR3 in inflammatory diseases of the central nervous system (CNS). We examined the impact of CXCR3 on a less complex interferon-γ-dependent, type 1 cell-mediated immune response in the CNS, induced in mice by the transgenic production of glial fibrillary acidic protein IL-12 (GF-IL12) by astrocytes and retinal Müller cells. GF-IL12 mice develop ataxia because of severe cerebellar inflammation but have little overt ocular disease. Surprisingly, CXCR3-deficient GF-IL12 mice (GF-IL12/CXCR3KO) have drastically reduced ataxia but developed cataracts, severe ocular inflammation, and eye atrophy. Most GF-IL12/CXCR3KO mice had minimal cerebellar inflammation but severe retinal disorganization, loss of photoreceptors, and lens destruction in the eye. The number of CD3(+), CD11b(+), and natural killer 1.1(+) cells were reduced in the CNS but highly increased in the eyes of GF-IL12/CXCR3KO compared with GF-IL12 mice. High levels of interferon-γ, IL-1, tumor necrosis factor α, CXCL9, CXCL10, and CCL5 were found in GF-IL12 cerebelli and GF-IL12/CXCR3KO eyes. Our findings demonstrate key but paradoxical functions for CXCR3 in IL-12-induced immune disease in the CNS, promoting inflammation in the brain yet restricting it in the eye. We conclude that the function of CXCR3 in cellular immune disease is driven by a common trigger and is controlled by tissue-specific factors., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

Mucormycosis is rare in immunocompetent patients. We describe an unusual case of orbital apex syndrome secondary to mucormycosis that occurred in an immunocompetent 64-year-old man following multiple tooth extractions. We found no frank involvement of the maxillary sinus, which is the usual pathway of spread for this fungal infection. Therefore, we suggest two possible alternate pathways from the oral mucosa to the orbital apex: one via the anterosuperior and posterosuperior alveolar vessels and one via the infraorbital branch of the maxillary artery.

Background: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population., Methods: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses., Results: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2&#95;27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade., Conclusion: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma.

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed.

Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR) or the closely related melanoma-associated retinopathy (MAR) occur in a small subset of patients with retinal degeneration and systemic cancer. This autoimmune syndrome is characterized by sudden, progressive loss of vision in association with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous, may produce a number of ocular symptoms, and may be associated with several different neoplasms, including lung, breast, prostate, gynecological, and colon cancer, melanoma, and hematologic malignancies. We examined the onset of retinopathy in correlation to the diagnosis of cancer and the presence of specific anti-retinal autoantibodies in PR patients. In some patients without diagnosed malignant tumors, the onset of ocular symptoms and the presence of autoantibodies preceded the diagnosis of cancer by months to years, including anti-recoverin, anti-transducin-alpha, and anti-carbonic anhydrase II antibodies. Although anti-retinal autoantibodies may not be a good predictor of a specific neoplasm, they can be used as biomarkers for different subtypes of retinopathy. Identification of autoantibodies involved in autoimmune-mediated PR will help elucidate the mechanisms underlying the PR syndromes and develop targeted therapies for these sight-threatening disorders.

Background: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical., History and Signs: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia., Therapy and Outcome: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy., Conclusions: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Aim: The aspect of the retinal vessels may suggest the presence of the antiphospholipid antibodies that can be detected afterwards in the patient's blood by lab tests. The presence of antiphospholipid antibodies (aCL) seems to be the sign for brain ischemic lesions by clotting., Materials and Methods: Three cases of aspects of retinal vessels associated with aCL (antiphospholipid antibodies) present in patients with: slowly progressive memory problems, "atypical multiple sclerosis", amaurosis fugax in contraceptive treatment., Results: The presence of the aCL antibodies and the aspect of the retinal vessels signaled the possibility of an abnormal clotting leading to stroke. Discontinuities in the vessels pathways both in the retinopathy and AFG, suggesting an abnormal blood flow in the retinal vessels, while the aCL present signals a clotting with multiple brain ischemic lesions., Conclusion: This aspect of the retinal arterial or/and venous vessels requires laboratory blood dosing for antiphospholipid antibodies. Their presence will be a definite sign for a future thrombosis and multiple brain ischemic lesions. The treatment with sulodexide, initially injectable, then oral formula was used for 6 - 14 months, until the disappearance of the antiphospholipid antibodies, but, more than that until the aspect of the retinal vessels went back to normal

Objective: To examine the role of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual impairment and blindness., Methods: A retrospective study based on the Finnish Register of Visual Impairment. At the end of 1996, the Finnish Register of Visual Impairment included 296 uveitis patients in whom uveitis was the main cause of visual impairment. The patient records were examined retrospectively to investigate the etiology of severe uveitis. Due to the incompleteness of data obtained of the patients blinded a long time ago, we included only 174 uveitis patients whose visual handicap (best corrected visual acuity in the better eye < 20/60 or severe visual field loss) was stated during 1980-1996., Results: A total of 174 uveitis patients were found, 72 male and 102 female. A diagnosed or presumed inflammatory rheumatic disease or comparable condition was found in 38/174 (22%) patients: juvenile rheumatoid arthritis in 14 (8%), spondyloarthropathy (ankylosing spondylitis or reactive arthritis) in 10 (6%), sarcoidosis in 5 (3%), seronegative rheumatoid arthritis in 4 (2%); Behçet's disease was diagnosed in 2 (1%), 1 patient had polymyositis, 1 polyarteritis nodosa, and 1 juvenile systemic lupus erythematosus. In addition to the above, 10 (6%) patients had chronic back pain and 5 (3%) patients various noninflammatory joint problems. Diverse other ophthalmologic or systemic disease was detected in 38 (22%) cases. Trauma or surgery caused uveitis in 9 (5%) patients. For 74/174 (43%) uveitis patients no specific associating condition could be shown. Legal blindness was documented in 65/174 (37%) patients, including 8 totally blind persons., Conclusion: This study provides first data on the relative importance of inflammatory rheumatic diseases and comparable conditions in the etiology of severe uveitis leading to visual handicap and blindness.

Background and Objective: Among patients with systemic lupus erythematosus (SLE), the presence of antiphospholipid antibodies (APA), notably the lupus anticoagulant, and anticardiolipin antibodies (aCL) characterizes a subset of patients with a thrombotic tendency. During the regular follow-up care of patients with SLE, we noticed that many described transient visual disturbances. Because a hypercoagulable state may cause transient monocular blindness (TMB), we determined the frequency of TMB and studied its relation to the presence of APA in patients with SLE., Methods: We asked 175 unselected patients with SLE whether they had transient visual disturbances and reviewed their medical charts. All patients were examined with specific attention to the presence of livedo reticularis. Blood was examined for APA., Results: Visual disturbances were recorded for 136 (78%) patients. According to predefined criteria, the symptoms were diagnosed as TMB for 10 (6%) patients and as visual disturbances associated with migraine for 18 (10%) patients. Five of the 10 patients with TMB had attacks in either eye. The 175 patients with SLE accrued a maximum total of 6,349 patient years in their lifetime. From this, the incidence of TMB can be calculated to be at least 158 per 100,000 per year. Lupus anticoagulant was detected in 3 of 10 patients with TMB and 41 of 165 patients without TMB (odds ratio, 1.3; 95% CI, 0.2 to 6.0). aCLs were found in 5 of 10 patients with TMB and 91 of 165 patients without TMB (odds ratio, 0.8; 95% CI, 0.2 to 3.7)., Conclusions: The frequency of TMB among patients with SLE is at least 158 per 100,000 compared with the normal population (14 per 100,000 per year). However, among patients with SLE, no significant relation could be shown between TMB and the presence of APA or livedo reticularis.

Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) may be an important mediator in the blinding ocular inflammation which develops following herpes simplex virus type 1 (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP-1alpha-deficient (-/-) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 x 10(5) PFU of HSV-1 strain RE and subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the mean corneal opacity score of -/- mice was 1.1 +/- 0.3 while that of the +/+ mice was 3.7 +/- 0.5. No detectable infiltrating CD4+ T cells were seen histologically at 14 or 21 days p.i. in -/- animals, whereas the mean CD4+ T-cell count per field (36 fields counted) in +/+ hosts was 26 +/- 2 (P < 0.001). In addition, neutrophil counts in the -/- mouse corneas were reduced by >80% in comparison to the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon could be detected in six of seven -/- mice, whereas both T-cell cytokines were readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte chemoattractant protein-1 protein levels were significantly lower in MIP-1alpha -/- mouse corneas than in +/+ host corneas, suggesting that MIP-1alpha directly, or more likely indirectly, influences the expression of other chemokines. Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from the eyes of -/- mice was not significantly different from that observed in +/+ hosts. We conclude that MIP-1alpha is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis.

Herpes stromal keratitis (HSK) is a blinding infectious disease that results from an array of immunopathogenic processes, including herpes simplex virus 1 (HSV-1)-specific T helper 1 (Th1) and Th2 cells, cytotoxic T cells and antibodies. As discussed here by Wayne Streilein and colleagues, strategies designed to prevent and treat this syndrome must be aware of the fact that the disease is multifactorial in its cause and pathogenesis.

A patient developed progressive, severe, recurrent bilateral iridocyclitis, retinal vasculitis, and hemorrhagic infarction of the retina that led to blindness despite immunosuppressive therapy. Histopathology of an enucleated blind and painful eye revealed marked nongranulomatous uveitis with a predominantly CD4+ T-lymphocytic infiltration, as well as B-cell and plasma cell aggregation. Extensive expression of adhesion molecules on vascular endothelial cells were found. This finding suggests that adhesion molecules play an important role in the vasculitic process, the trademark of Behçet's disease. The ocular pathology and the therapeutic approach to Behçet's disease are briefly reviewed.

Early investigations into the pathogenesis of vision loss in cancer patients noted the higher incidence with small cell carcinoma of the lung (SCCL), a neoplasia with suspected neuroendocrine origins [2-5,12,20,25,56,63,64]. The cause and effect relationship between the cancer and retinal deterioration was recognized, but the processes involved were not understood. Research eventually identified a sub-group of paraneoplastic retinopathy patients who exhibited indications of retinal hypersensitivity through their production of autoantibodies reactive with a single photoreceptor protein. The discovery of a small cell lung cancer culture actively expressing this same retinal autoantigen, provided tangible evidence to define a molecular basis for at least one type of paraneoplastic retinopathy. The identification of this immunologic anomaly illustrates how blindness can occur in some cancer patients, through the serendipitous initiation of ocular hypersensitivity, with vision loss developing as a cancer-induced autoimmune retinopathy.

Crohn's disease is associated with a hypercoagulable state due to platelet or clotting abnormalities which may be responsible for the thromboembolic episodes seen in this condition. We report the occurrence of anticardiolipin antibodies in a patient with Crohn's disease who presented with Amaurosis fugax and suggest that these antibodies may be a further cause of the hypercoagulable state of Crohn's disease in some patients.

Background: The bilateral simultaneous optic neuritis is rarely associated with multiple sclerosis. Diagnosis and prognosis have to be dealt with independently., Patient: A 45-year-old woman presented with an acute bilateral simultaneous amaurosis which developed within one day with bilateral papilledema. Initially there were positive antinuclear and anticytoplasmatic antibodies and antibodies against heart and skeletal muscles. The serum titer was elevated for immunoglobulin A, lowered for complement factors C3 and C4. Antigens for polio-virus type 3 and coxsackievirus type B5 and B3 were borderline positive. An oncologic, toxic or vascular cause of the neuritis was unlikely., Therapy and Course: The amaurosis lasted for 4 days. Vision improved gradually under a combined therapy with steroids, antibiotics and virostatics. Nineteen months later the vision was 20/25 OD and 20/200 OS., Conclusion: The acute bilateral neuritis was probably of autoimmunological origin. Under combined antiinfectious and steroidal therapy vision improved more than expected.

Onchocerciasis is a leading cause of blindness in equatorial Africa and in endemic regions in Central America. Understanding of the pathologic processes involved in onchocercal eye disease and of the role of immunopathologic mechanisms in its development has been substantially limited by the shortage of eyes for histologic study and by the lack of a naturally occurring animal model. The inoculation of microfilariae of Onchocerca species into the eyes of laboratory animals may reproduce selected aspects of onchocercal eye disease, such as punctate keratitis. Studies in these models support the hypothesis that immunopathologic mechanisms mediated by IgE antibody are involved in the development of ocular lesions. In some laboratory animal models, diethylcarbamazine citrate, a microfilaricidal drug that causes severe inflammatory reactions to microfilariae in humans, increases the severity of ocular lesions, and stimulates IgE antibody responses. Laboratory animal studies are potentially highly useful for understanding the immunopathogenesis of ocular onchocerciasis.

Systemic immunization with purified homologous rhodopsin from retinal outer segments induced blindness in primates (Macaca mulatta). Inflammation and characteristic retinal changes were the earliest clinical signs of the disease. Perivasculitis, subretinal exudations and bullous detachments of the retina were progressive and unrelenting pathological processes leading to rapid and irreversible visual deterioration. Electroretinographic responses (ERG) at this stage of the disorder became abolished. Antibodies and delayed hypersensitivity to rhodopsin were demonstrated only in the experimental diseased animals. Homologous visual purple appears to be organ and immunopathologically specific. Histological confirmation of these findings showed a pathological spectrum of destructive alterations confirmed specifically to the outer segments of the entire retina. The pathologic reaction was supported by a distinct and pronounced granulomatous inflammatory response.

In more than 50% of amaurosis fugax patients under 45 years of age no cause for the episodes of visual loss is identifiable. We have encountered 6 young adults (4 women and 2 men) with episodes of amaurosis fugax associated with elevated levels of antiphospholipid antibodies. Splinter hemorrhages of the nail beds were present in most patients. Treatment with antiplatelet medications and anticoagulants appeared to reduce the frequency of episodes and might prevent central retinal artery occlusions or stroke.