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Purpose: To analyze the morphological outcomes of the posterior corneal opacity or "semilunar sign" in noninfectious anterior scleritis using multimodal imaging., Methods: This was a prospective observational case series. Patients with anterior scleritis from January 2018 to January 2019 were included. Clinical and demographic data were collected. Posterior cornea was visualized using the digital slit lamp photography (Elite, mega digital vision), spectral domain optical coherence tomography (MS39), and specular count analyzer (EM-3000). "Semilunar sign" was defined by the (1) presence of posterior corneal opacity, (2) concave semilunar pattern, (3) absence of blood vessels, and (4) normal anterior cornea. Incidence, clinical characteristics and significance, correlation with Mantoux sensitivity, and role of multimodal valuation were assessed., Results: Overall 76 eyes of 72 patients were recruited with anterior scleritis. Fifteen eyes of 11 patients (15.3%) presented with semilunar sign. The scleritis was both nonnecrotizing (n = 8) and necrotizing (n = 7). The semilunar configuration appeared as isolated (n = 9) and continuous lesion (n = 6). The extent was directly related to the scleral disease extent (P = 0.002). The mean thickness measured 212.5 ± 129.3 μm. The mean central endothelial cell density (ECD) was 2540.8 ± 351.7 cells/mm 2 , which was significantly higher than the involved peripheral cornea (P = 0.05). The mean surface area of the semilunar sign was 7.7 ± 5.2 mm 2 . There was no significant correlation between the opacity thickness and the best-corrected visual acuity (P = 0.895, r = -0.39), ECD (P = 0.52, r = -0.188), and Mantoux (P = 0.696, r =- 0.142)., Conclusion: Corneal semilunar sign of scleritis affected the peripheral cornea and caused no functional abnormality in early presentation. Multimodal analysis can aid in clinical assessment and severity., Competing Interests: None

Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund's adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.

Infectious scleritis is a rare but important cause of scleral inflammation. It is usually associated with an underlying ocular (prior ocular surgery or trauma) or systemic risk factor. A 53-year-old apparently systemically healthy woman presenting with spontaneous-onset pain, redness and watering in the left eye for 10 days was diagnosed with culture-proven Pseudomonas aeruginosa anterior scleritis. However, she was non-responsive to organism-sensitive antibiotics and scleral graft was performed twice, which showed graft re-infection. On repeated extensive systemic evaluations, the patient was diagnosed with biopsy-proven granulomatosis with polyangiitis (GPA). The patient was started on mycophenolate mofetil for both induction and maintenance phases and showed dramatic improvement with no recurrence till 1 year follow-up. High index of suspicion for autoimmune disorders, especially GPA, must be maintained for unilateral relentless infective scleritis masquerading as autoimmune necrotising scleritis. Mycophenolate mofetil holds a promising role for inducing as well as maintaining disease remission in ocular GPA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A 63-year-old woman came with complaints of decreased vision and minimal pain on extraocular movements in the left eye and, after investigations, was diagnosed with posterior scleritis. Systemic steroid treatment helped resolve the symptoms and signs. One year later, she presented with right eye involvement. She was evaluated for systemic illness and, based on clinical and investigational findings, it was deduced that probably a sarcoidosis was predisposing her to the eye problem. She was provisionally diagnosed with bilateral sequential posterior scleritis secondary to sarcoidosis. She was prescribed oral steroids, which helped resolve her eye problem. She was next referred to a rheumatologist and a pulmonologist for further evaluation and treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: : To present histopathological and immunohistochemical analysis of idiopathic inflammatory diseases of orbit and ocular adnexa., Methods: Design- A retrospective laboratory-based study. The study was carried out in an ocular pathology laboratory in a tertiary institute of northeast India where analysis of 93 cases was done in 5 years, during the period from 2011 to 2016. Hematoxylin--eosin and special stains were done for the diagnoses. Immunohistochemistry (IHC) panel was also carried out. For infectious pathology, Grocott's methenamine silver (GMS) stain for fungus, tissue Gram's stain for bacteria's, and acid-fast stains for tubercular bacilli were done. IHC panels were done for CD 20 (B-cells), CD-3 (T-cells), CD-45 (Leukocyte common antigen, LCA), BCL-2, CD-138 (Plasma cells), Kappa, Lambda, IgG-4 in tissue, IgG-4 in serum, etc. IHCs were done using kit methods (standardized) and adequate controls were taken for each sample., Results: 93 cases of nonspecific orbital inflammation were reported out of 1,467 specimens. Orbital pseudotumors (idiopathic orbital inflammatory disease, IOID) were seen in 27 cases (sclerosing variety-6); benign lymphoid hyperplasia in two cases; reactive lymphoid hyperplasia in 10 cases; atypical plasma lymphoproliferative reactive (polyclonal immunophenotypically, IgG4 negative) lesions in four cases; IgG-4 related disease in one case; nonspecific inflammatory reactions (conjunctiva, sclera, and lid) in 49 cases. In all the diagnoses, infections and lymphomas were excluded., Conclusion: Biopsy supported study on nonspecific orbital inflammation was important to know the pattern., Competing Interests: None

In patients with inflammatory bowel disease (IBD), ocular extraintestinal manifestations (EIM) are less common than EIM of other systems, but they are clinically important because they can lead to complications that can cause catastrophic damage to the visual acuity and ocular structure. Anterior uveitis and episcleritis are the most common ocular EIM. Involvement of the orbit, posterior segment, and optic nerve can also occur. A variety of treatments are available ranging from topical steroids to systemic immunosuppressive therapies. The treatment of IBD is also essential if the activity of inflammatory bowel disease affects the ocular symptoms.

Objective: To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV)., Methods: Medical records of potential cases of AAV seen at Mayo Clinic from 2003 to 2013, inclusive, were reviewed to identify confirmed cases meeting the diagnosis of AAV using the Chapel Hill Consensus Conference 2012 descriptors. Records of confirmed cases of AAV were then further reviewed for IOD, and clinical characteristics, treatment and outcomes abstracted., Results: A total of 1171 confirmed cases of AAV were identified of which 183 patients (mean age 49.0 years; 51% female; 95% Caucasian) had IOD. The most common manifestation of IOD was injection of the eye (57%) followed by eye pain (46%) and visual acuity loss (18%). Scleritis was the most common type of IOD (22%) followed by episcleritis (21%), orbital inflammation (18%), lacrimal duct stenosis (10%) and uveitis (9%). Oral glucocorticoids were used to treat IOD in the majority of patients (96%). CYC and rituximab were the most frequently used immunosuppressive agents (54 and 36%, respectively). Of those with orbital inflammation, 52% underwent therapeutic surgical intervention. Clinical remission of IOD was achieved in 91% of patients but relapses were seen in 23%. Significant visual acuity loss was observed in only six patients., Conclusion: IOD is a common manifestation of AAV and seen in about 16% of patients with AAV. Scleritis, episcleritis and orbital inflammation are the most common subtypes. Most patients respond well to glucocorticoids and immunosuppression, but relapse of IOD is common., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

A 48-year-old woman who is a contact lens wearer presented with unilateral ACANTHAMOEBA keratitis, confirmed by PCR, which responded initially to topical polyhexamethylene biguanide (PHMB) and brolene. Three months later, despite continued treatment, she developed diffuse anterior scleritis with severe pain and marked scleral injection but without evidence of recurrence keratitis. Oral non-steroidal anti-inflammatories and oral high-dose corticosteroids were added without success. Subsequent treatment with intravenous methylprednisolone and high-dose cyclosporine led to a temporary improvement. Re-presenting with signs of recurrent scleritis and severe pain, the antitumor necrosis factor monoclonal antibody adalimumab, and later oral cyclophosphamide, were added. This led to complete quiescence of the scleritis. Unfortunately, frequent recurrences of ACANTHAMOEBA keratitis and anterior uveitis occurred on immunosuppression requiring continued treatment with PHMB, brolene and topical corticosteroids. This is the first case of severe refractory ACANTHAMOEBA scleritis requiring the concomitant use of four immunosuppressive agents to achieve continued disease control. The challenges in managing this case are discussed., (2015 BMJ Publishing Group Ltd.)

Intravitreal fluocinolone acetonide implant (Retisert) has a high potency, a low solubility, and a very short duration of action in the systemic circulation, enabling the steroid pellet to be small and reducing the risk of systemic side effects. Scleral melt has not been reported as a possible complication of Retisert implant. The authors describe the occurrence of scleral melt 18 months after the implantation of fluocinolone acetonide implant in a 42-year-old Caucasian woman. To the authors' knowledge, this is the first report of this possible complication.

Recent advances in the understanding of the initiation and perpetuation of the immune response strongly suggest that all forms of noninfective immunologically induced scleral inflammation have a common origin. Analysis of the progress of patients with scleritis corroborates the current clinical classification that, together with studies of the immunohistology fluoresceine/ICG angiography, 3D proteoglycan, and keratan sulphate electron microscopy of scleritis, strongly suggests that from the initiation of the inflammatory process, necrotizing scleritis and diffuse and nodular scleritis not only pursue a different course but also have a different pathogenesis; nonnecrotizing scleritis being the consequence of an auto immune response, whereas necrotizing scleritis being the complication of an already present (if not always manifest), systemic immune-mediated systemic disease and its associated vasculitis. The increasing imaging capacity of anterior segment ocular coherence tomography (OCT) and en face OCT enables the changes occurring in the sclera during the course of the disease to be observed for the first time. These observations suggest that the inflammatory changes involve the potential suprachoroidal space between choroid and sclera, an observation supported by the presence of subscleral granulomas on histopathology. New imaging techniques have also been able to explain the changes seen in the cornea as a complication of scleritis. These findings have implications for investigation and the treatment of these conditions.

We report a case of posterior scleritis effectively managed with intravitreal bevacizumab. A 71-year-old woman was diagnosed with posterior scleritis. Although she was initially treated with systemic steroids, her clinical presentation deteriorated. She was then treated with a single intravitreal injection of bevacizumab and aqueous humor collection. The aqueous level of vascular endothelial growth factor prior to the intravitreal injection was 880.51 pg/mL, greater than that in the healthy control group (p < 0.001). One month later, the scleritis was completely resolved, and the patient remained stable during six months of follow-up. Intravitreal bevacizumab appears to be an effective adjuvant therapy for patients with posterior scleritis.

We report on a case of necrotizing keratoscleritis in primary Sjogren's syndrome. A 66-year-old female patient who was complaining of ocular pain, tearing and decreased vision in her right eye for the previous two days was admitted to our hospital. Visual acuity in the right eye was hand movement, and initial examination showed a 3.0 × 1.8 mm uveal mass bulging through a corneoscleral melting site in the nasal region of the right eye. Positive anti-nuclear antibody was identified at a titer of 1:320 with a speckled pattern, and both Sjogren's syndrome A and Sjogren's syndrome B antibody tests were positive, with titers >200 U/mL. A technetium 99m pertechnetate salivary scan revealed chronic sialoadenitis in the submandibular glands. We diagnosed the lesion as necrotizing keratoscleritis due to primary Sjogren's syndrome. A corneoscleral patch graft was performed, followed by immunosuppression including oral cyclosporin and topical prednisolone. During a follow-up period of 12 months, the corneoscleral graft was well maintained with no recurrence.

Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with a number of extra-articular organ manifestations. Ocular manifestations involved with RA are keratoconjunctivitis sicca, episcleritis, scleritis , corneal changes, and retinal vasculitus. The etiopathogenesis of this autoimmune disorder is still unknown. Aim of our study was to present different ocular manifestations of RA and their frequency. We have examined 691 patient with the diagnoses of RA. All examined patients were in I or II stage of the disease according to criteria of The American College of Rheumatology. Ophthalmological exam obtained: visual acuity by Snellen sings, biomicroscopy of anterior segment, Schirmer test, tear break-up time (BUT), applanation tonometry and indirect ophthalmoscopy. In all patients with retinal vasculitis fotofundus and in indicated cases fluorescein angiography was preformed. The most common manifestation of ocular involvement was keratoconjunctivitis sicca. Episcleritis was diagnosed in 5.06% patients with RA, while scleritis was present in 2.06% of patients. Diffuse scleritis was present in one patient, while nodular was present in 13 patients. There were no patients with posterior or necrotizing scleritis among examined patients. Sclerosing keratitis was diagnosed in 11 female patients. It is characterized with peripheral thickening and opacification of the stroma adjacent to the site of inflammation. Posterior scleritis or scleromalacia of cornea was not present in our patients, because all of them were in I or II stage of disease. Retinal vasculitis was present in three patients, two male and one female patient (0.45%). Ocular manifestation was present in 27.2% of patients. Women were more affected.

Ocular rheumatoid disease manifests as hyperemia of the conjunctiva and episclera, and in severe cases, episcleritis can result in nodular sclerotic and scleromalacia perforans. A clinical case of scleromalacia perforans in a 56-year-old woman with 20 years of seropositive rheumatoid arthritis of functional class IV is presented here. During that period, she received exclusively non-steroidal anti-inflammatory drugs (NSAIDs). She developed acute episcleritis of the left ocular globe, which rapidly progressed to scleromalacia perforans. Since the left eye became perforated, it was surgically enucleated, and the patient was maintained with steroidal therapy. Nevertheless, two months later she developed new-onset episcleritis of the right eye followed by scleromalacia. She was first evaluated by a rheumatologist and treated with 200 mg/dose of infliximab, which was administered monthly for the following four months. The biological treatment was accompanied by methotrexate and prednisone. With this therapy, the ocular lesion dramatically improved, and complete remission of rheumatoid arthritis and scleritis was archived four months later. In conclusion, tumour necrosis factor (TNF) blockers are effective therapeutic agents in ocular complications of rheumatoid arthritis.

Aim: To document the presentation, management, and prognosis of three cases of surgically induced necrotising scleritis (SINS) following three-port-pars plana vitrectomy (PPV) without scleral buckling. To discuss potential pathogeneses and treatments., Methods: An interventional case series of three patients presenting to a tertiary referral unit over a 6-month period., Results: All cases were male, presenting within 6 weeks of PPV, with scleral necrosis around a sclerotomy site. Wound microbiology and systemic vasculitis screens were negative. Two cases had underlying systemic disease and had undergone previous ocular surgery. The necrosis resolved in all with aggressive immunosuppression., Conclusions: SINS following PPV is a rare occurrence requiring prompt and aggressive immunosuppression. Differentiation from an infective postoperative process is essential. The pathogenesis is poorly understood but may share features with classic SINS including hypersensitivity and ischaemia.

T-helper type 17 cells (T(H)17) are implicated in rodent models of immune-mediated diseases. Here we report their involvement in human uveitis and scleritis, and validate our findings in experimental autoimmune uveoretinitis (EAU), a model of uveitis. T(H)17 cells were present in human peripheral blood mononuclear cells (PBMC), and were expanded by interleukin (IL)-2 and inhibited by interferon (IFN)-gamma. Their numbers increased during active uveitis and scleritis and decreased following treatment. IL-17 was elevated in EAU and upregulated tumor necrosis factor (TNF)-alpha in retinal cells, suggesting a mechanism by which T(H)17 may contribute to ocular pathology. Furthermore, IL-27 was constitutively expressed in retinal ganglion and photoreceptor cells, was upregulated by IFN-gamma and inhibited proliferation of T(H)17. These findings suggest that T(H)1 cells may mitigate uveitis by antagonizing the T(H)17 phenotype through the IFN-gamma-mediated induction of IL-27 in target tissue. The finding that IL-2 promotes T(H)17 expansion provides explanations for the efficacy of IL-2R antibody therapy in uveitis, and suggests that antagonism of T(H)17 by IFN-gamma and/or IL-27 could be used for the treatment of chronic inflammation.

Purpose: To examine leukocyte-endothelial cell rolling and arrest in human ocular vessels overlying sites of inflammation in various ocular inflammatory diseases in comparison to normal controls using the Heidelberg confocal laser microscope, which provides images with greater clarity and resolution than the tandem scanning microscope that uses white light., Methods: Healthy controls (n=8) and patients with active anterior scleritis (n=7) or allergic eye disease (n=4) were scanned using the Heidelberg confocal laser microscope (HRT II) with the Rostock cornea module attachment for a minimum of 5 min at a depth of 45-120 microm from the conjunctival epithelial surface., Results: There was a marked increase in the number of rolling leukocytes in scleritis patients (534+/-119 cells per mm2/min) versus controls (6+/-6 cells per mm2/min; p=0.0002) or allergic patients (59+/-44 cells per mm2/min; p=0.009). No statistically significant increase was seen in allergic patients compared to controls (p=0.059). A similar pattern was seen in the number of arrested leukocytes in patients with scleritis (56+/-23 cells per mm2) in comparison to either those with allergic eye disease or controls (each=0 cells per mm2; p=0.02)., Conclusions: Patients with scleritis have a significantly increased number of rolling and arrested leukocytes in superficial ocular vessels in comparison to patients with mild allergic conjunctivitis and controls. The image quality with this microscope is superior to prior studies with a scanning microscope.

Background: Episcleritis, though common in adults, is a rare disease in children. Episcleritis is associated with systemic diseases in a third of cases in adults. Here we describe systemic diseases associated with recurrent episcleritis in children less than five years of age., Methods: This Retrospective Observational case series study was conducted at the Department of Ophthalmology of Ayub Teaching Hospital, Abbottabad, from March 1995 till February, 2006. Six children diagnosed clinically with recurrent episcleritis were included in this study. Complete ophthalmologic as well as systemic evaluation was done in each case., Results: This study was conducted on 6 children with a diagnosis of recurrent episcleritis. There were four boys and two girls, with an age range of 35-52 months. Right eye was involved in three cases, left eye in two cases while one case had a bilateral disease. Recurrence occurred in the same eye in all cases, with one bilateral involvement. Four children (66%) had a history of upper respiratory tract infection in the recent past. No other systemic abnormality was detected in any case. Two cases had a history of contact with a pet animal., Conclusion: Recurrent episcleritis in young children is a benign condition. Upper respiratory tract infection is the most common systemic association. Pet animals may be a contributory factor.

We report a case of necrotizing scleritis following diode cyclo-photocoagulation (CPC). A-64-year-old-Asian Indian male presented with pseudophakic corneal decompensation with secondary angle closure glaucoma that was uncontrolled with maximum medical therapy. Trans-scleral diode CPC was performed in the inferior 180-degree section using a standard diode laser with a G-probe. One month later, the patient developed features suggestive of necrotizing scleritis that resolved with systemic steroid therapy. Necrotizing scleritis following diode CPC has been rarely reported. Ophthalmologists should be aware of the possible occurrence of surgically induced nectotizing scleritis following diode CPC.

A 45-year-old woman, complaining of sudden visual loss in the right eye (best-corrected visual acuity: 17/200), was suspected of having a malignant melanoma of the choroid. Fundus examination revealed a massive pale-colored subretinal mass temporal to the fovea, with adjoining choroidal folds and exudative retinal detachment. Ultrasonography was suggestive of posterior scleritis. Systemic evaluation was unremarkable. The patient was treated with high-dose systemic corticosteroids. The mass lesion resolved completely, with visual recovery to 20/20. Posterior scleritis should be suspected when evaluating subretinal mass-lesions, even when large and without overt inflammation. Early treatment may improve the visual prognosis and avoid misdirected management, including enucleation.

A case of Behçet's syndrome in a 32-year-old woman occurring shortly after her third vaccination against typhoid fever is described. Scleritis and pyoderma gangrenosum were unusual manifestations of BS that occurred in this case. Treatment benefit was provided by mycophenolate mofetil and etanercept. As bacterial antigens have been proposed as potential triggers for the onset of BS, it is possible that the syndrome was precipitated by typhoid vaccination in this patient.

Purpose: The purpose of this study was to report a case of bilateral blindness, bilateral necrotizing scleritis, and bilateral deafness in a patient with myelodysplastic syndrome (MDS). In such a patient, the possibility of relapsing polychondritis (RPC) associated with MDS must be considered., Case Report/methods: A 66-year-old patient suffered from myelodysplastic syndrome (MDS). Shortly before his death, he became bilaterally blind and deaf. A biopsy was taken from the conjunctiva and the bone marrow, and both eyes were obtained after death for further investigation. Findings of the clinical and laboratory work-up for the patient's hematologic disorder as well as an examination of the eyes by light microscopy and immunohistochemistry are presented., Results: Ocular sections showed a diffuse necrotizing scleritis with moderate uveitis and no identifiable infectious agent. Neither was there any evidence of a leukemic infiltration. The deafness had been due to inner ear failure, and the patient died of a cardiac failure., Conclusions: Non-infectious scleritis associated with inner ear deafness is a strong indication of relapsing polychondritis (RPC). Furthermore, RPC can be associated with MDS. Thus, in addition to leukemic infiltration and infection involving ocular structures, ophthalmologists and otolargyngologists should be aware of the association between MDS and RPC and the potential complications.

Purpose: To report a case of severe Acanthamoeba sclerokeratitis., Methods: A 70-year-old male non-contact lens wearer was examined for severe pain in the left eye which began about 40 days after cataract surgery. In spite of a careful search, it required 6 weeks to detect Acanthamoeba. Systemic and topical fluconazol and miconazol did not help and the keratitis progressed into necrotic sclerokeratitis with protrusion of uveal tissue through the thin sclera., Results: Those findings slowly got worse before the Acanthamoeba sclerokeratitis resolved 6 months later with scar formation., Conclusion: We describe the terminal and cicatricial stages of Acanthamoeba keratitis, and report that the healing process can follow the terminal stage and the eye does not need to be enucleated.

Posterior scleritis is relatively uncommon and is often misdiagnosed due to its protean manifestations. We report eight cases of posterior scleritis to analyse the clinical profile, ultrasonographic and computed tomography (CT) scan features of this rare disorder. Fundus findings included serous retinal detachment, choroidal folds, retinal folds, subretinal mass, choroidal detachment, disc edema, and macular edema. There was associated anterior scleritis and anterior uveitis in the majority of the cases. In all cases ultrasound with or without CT scan confirmed the clinical diagnosis. All patients responded to systemic steroids except one who required immunosuppressive therapy. This paper describes the clinical profile of a series of posterior scleritis cases highlighting varied clinical presentation, and the role of ultrasound and CT scan findings in the diagnosis.

Purpose: To report a case of surgically induced necrotising sclerokeratitis (SINS) with imminent uveal prolapse following uncomplicated cataract surgery., Methods: Case report., Results: The causative agent was found to be a subtarsal abscess and the condition responded to drainage of the localised infection and a course of topical antibiotics., Conclusion: This report represents the first account of postoperative scleral necrosis arising from a subconjunctival abscess, and illustrates the importance of identifying all aetiopathogenic factors in cases of postsurgical necrotizing scleritis.

Scleritis is a sight-threatening inflammatory disorder of the eye characterized by the degradation of scleral matrix. Matrix metalloproteinases (MMPs) are ubiquitous proteolytic enzymes important in physiological and pathological processes, the activity of which is stringently controlled by the action of a family of natural antagonists, the tissue inhibitors of matrix metalloproteinases (TIMPs). We hypothesized that enhanced expression of MMPs, without the negative regulatory influence of TIMPs, may be a key feature of tissue destruction in inflammatory eye diseases, such as scleritis. The aim of this study was to localize and characterize cells expressing MMPs and TIMPs in sclera affected by necrotizing scleritis and, in a parallel study, to establish whether cytokines modulate MMP expression in cultured human scleral fibroblasts. In situ hybridization and immunohistochemical analyses indicated that resident scleral fibroblasts as well as inflammatory cells such as macrophages and T lymphocytes express stromelysin, gelatinase B, and TIMP-1 in necrotizing scleritis tissue. In addition, cytoplasmic immunoreactivity for tumor necrosis factor-alpha, an inducer of MMPs, was detected in infiltrating inflammatory cells. Cultured scleral fibroblasts stimulated with the combination of interleukin-1 alpha plus tumor necrosis factor-alpha increased TIMP-1 mRNA twofold above constitutive levels. By contrast, these cytokines induced a sevenfold increase in the steady-state levels of stromelysin mRNA. Using Western blotting, stromelysin and TIMP-1 protein production paralleled mRNA induction in cytokine-stimulated human scleral fibroblasts. Culture supernatants harvested from cytokine-stimulated human scleral fibroblasts were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis gelatin substrate zymography. Our results revealed a prominent 92-kd gelatinolytic band corresponding to gelatinase B, which was inducible with interleukin-1 alpha. These data provide evidence for our hypothesis, that an imbalance between enzyme/inhibitor ratios may be the underlying mechanism of the tissue destruction characteristic of scleritis. Our results demonstrate the potential involvement of MMPs and their modulation by cytokines produced by infiltrating inflammatory cells in destructive ocular inflammation.

Purpose: MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop an autoimmune disease characterized by lymphoproliferation, vasculitis, glomerulonephritis, autoantibody production, and ocular and lacrimal gland inflammation. Lacrimal gland lesions in MRL/lpr mice are a model for the human disorder Sjögren's syndrome. The target organ lesions in MRL/lpr mice, including those in the eye and lacrimal gland, are composed largely of CD4+ T cells, with lesser numbers of CD8+ T cells and B cells. Cyclosporine therapy was evaluated for its effect on the autoimmune disease, particularly in the eye and lacrimal gland., Methods: MRL/lpr mice were administered cyclosporine intraperitoneally at a dosage of 2 mg daily from age 1 to 5 months. Animals were killed at 5 months and evaluated for the presence of autoimmune disease. Control groups consisted of animals given daily injections with either saline or the cyclosporine diluent., Results: Cyclosporine therapy was effective in reducing the ocular and lacrimal gland disease. Intraocular inflammation was present in 73% of control animals but in only 15% of cyclosporine-treated animals (P < 0.003). Multifocal lacrimal gland inflammatory infiltrates were present in 100% of controls but in only 23% of cyclosporine-treated animals (P < 0.0001). Mean percent area involved by lacrimal gland inflammation was reduced from 19.7% to 4.7% by cyclosporine therapy (P = 0.0003). Systemic autoimmune disease manifestations, including lymphoproliferation, vasculitis, glomerulonephritis, and serologic abnormalities, also were improved., Conclusions: Chronic cyclosporine therapy, started at an early age, is effective in controlling the autoimmune disease in MRL/lpr mice, including the ocular and lacrimal gland lesions.

Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyse the inflammatory cellular infiltrate in scleritis. Six episcleral biopsies and two enucleated eyes were studied. The episcleral biopsies were taken from patients with nodular scleritis. In one patient enucleation was done after perforation in anterior necrotising scleritis and, in the other after misdiagnosis of posterior scleritis as intraocular tumour. Morphological criteria and immunohistochemical methods were used to characterise the inflammatory cellular infiltrate. The inflammatory cells infiltrating the episcleral tissue were mainly T lymphocytes and macrophages. There was a predominance of CD4 positive cells, but only few lymphocytes were activated (expressed IL-2 receptor). The cells infiltrating the scleral fibres in the enucleated eyes consisted in both cases predominantly of T cells. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epithelioid and giant cells) were present in necrotising scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T cell mediated (autoimmune) disorder, which may have major therapeutic implications.

The clinical features, treatment, and visual outcome of 52 eyes from 43 patients who developed scleritis following surgery were reviewed. In all patients the scleral inflammation developed adjacent to a surgical wound. Ninety six per cent had necrotising disease and 23% also had evidence of secondary posterior scleritis. Many different types of ocular surgery were implicated and the majority (75%) of the patients had two or more surgical procedures before the onset of the scleritis. Although cataract extraction through a limbal incision resulted in the largest subgroup, scleritis also followed glaucoma, strabismus, and retinal detachment surgery. The latent period between surgery and the appearance of inflammation was short (mean 9 months) except for a small group in whom scleritis occurred many years after squint surgery. Sixty three per cent of patients had evidence of a systemic disease. Early diagnosis and aggressive medical treatment significantly improved the visual outcome. The precipitating factors, pathogenesis, and course of this condition are discussed.

MRL/Mp-lpr/lpr(MRL/lpr) mice spontaneously have a systemic autoimmune disease, characterized by vasculitis, lymphadenopathy, glomerulonephritis, and autoantibody formation. Among the many autoimmune lesions present are focal ocular inflammatory infiltrates, involving the choroid and sclera. These lesions appear to be related to the vasculitis seen in MRL/lpr mice and are mediated by L3T4-positive helper T-cells (CD4-positive T-cells). Systemic treatment of MRL/lpr mice with a monoclonal anti-L3T4 antibody (anti-CD4) resulted in a dramatic reduction of both the frequency and severity of the ocular disease, supporting the hypothesis that the CD4-positive T-cells play an essential role in the pathogenesis of the choroiditis and scleritis in this strain.

The ocular and systemic features of 10 patients whose Wegener's granulomatosis presented with corneoscleral inflammatory disease are described. Marginal corneal infiltrates were seen in all patients with anterior scleritis and were a valuable sign of disease activity. Nine out of 10 patients had symptoms of systemic vasculitis on presentation; seven had renal impairment; three had chest x-ray abnormalities. Autoantibodies against neutrophil cytoplasmic determinants (ANCA) were present in all cases. In seven patients the scleritis responded well to pulsed immunosuppressive therapy followed by long term oral steroids and cyclophosphamide. Oral steroid therapy alone failed to control severe disease. Corneoscleral disease was not a cause of visual loss. It is important to realise that inflammatory corneoscleral disease may be the presenting feature of a severe systemic vasculitis.

A randomised double blind trial of 2-(2-Hydroxy-4-methylphenyl) Aminothiazole Hydrochloride 0.1% (CBS 113A) versus placebo was carried out in 43 eyes with episcleritis. Our results show that CBS 113A is effective in reducing the signs of conjunctival and episcleral inflammation in mild episcleritis within the first week of administration of the drug (Day 3: Total Score p = 0.0013, Conjunctival Injection p = 0.017, Episcleral Injection p = 0.0018 and Day 7: Total Score p = 0.01, Conjunctival Injection p = 0.014, Episcleral Injection p = 0.027). CBS 113A was not effective against severe episcleritis. No significant side effects were found apart from a stinging sensation. There was no effect on intraocular pressure. The potential use of this new drug is discussed.

Posterior scleritis rarely presents as a large 'intraocular tumour' and continues to be a challenge in diagnosis and management. We present the case of a 66-year-old male with no known rheumatic disease, pain, proptosis, or diplopia, but with progressively decreasing visual acuity and a large, discrete 'subretinal tumour', 15 X 17 mm basal diameter and 8.3 mm apical height. Histologically the tumour was shown to be grossly thickened and necrotic sclera.