The enigma of sclera-specific autoimmunity in scleritis.

Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.

Clinical and pathological findings in five dogs with nodular histiocytic iritis in the United Kingdom: A case series.

PURPOSE: The aim of this study was to describe the clinical presentation, histopathology, management, and outcome of nodular histiocytic iritis, an intraocular variant of nodular granulomatous episcleritis (NGE). METHODS: A retrospective review of the medical records of five dogs with intraocular NGE-type inflammation as diagnosed by histopathology. RESULTS: Four Border Collies and one crossbreed dog, aged 1.5-3.4 years (mean age 2.38 years). The clinical presentation was an extensive, raised, pale iris lesion of variable location. All cases were unilateral. The physical examination was normal. Complete blood count/serum biochemistry (n = 1) and thoracic radiography (n = 1) were normal. Ocular ultrasound (n = 2) was normal apart from increased iris thickness. Enucleation (n = 4) or excisional biopsy (iridectomy, n = 1) was performed because of suspected neoplasia. Following enucleation, the remaining, contralateral eye did not develop additional lesions (9 days-3.7 years follow-up). There was no recurrence following sector iridectomy with 5 months topical 1% prednisolone acetate (3.9 years follow-up). The histopathologic findings in all five cases indicated a focal histiocytic and lymphoplasmacytic anterior uveitis (iritis), similar to that seen in cases of NGE. CONCLUSION: Nodular histiocytic iritis presents as unilateral iris thickening in isolation and young Collies appear to be predisposed. The histopathological findings are similar to NGE. Although the clinical presentation resembles intraocular neoplasia, an inflammatory process should be considered, which may be amenable to medical management. Definitive diagnosis may be obtained by iris sampling.

Masquerade syndrome in ocular surface squamous neoplasia.

The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.

Semilunar sign of cornea: A multimodal analysis of the posterior corneal opacity in non-infectious anterior scleritis.

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/mm2, 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 mm2. 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.

The clinical and pathogenic spectrum of surgically-induced scleral necrosis: A review.

The onset of scleral necrosis after ocular surgery may have catastrophic ocular and systemic consequences. The two most frequent surgeries causing surgically-induced scleral necrosis (SISN) are pterygium excision and cataract extraction. Several pathogenic mechanisms are involved in surgically induced scleral necrosis. All of them are poorly understood. Ocular trauma increasing lytic action of collagenases with subsequent collagen degradation, vascular disruption leading to local ischemia, and immune complex deposition activating the complement system represents some of the events that lead to scleral necrosis. The complex cascade of events involving different pathogenic mechanisms and the patient's abnormal immune response frequently leads to delayed wound healing that predisposes the development of scleral necrosis. The management of SISN ranges from short-term systemic anti-inflammatory drugs to aggressive immunosuppressive therapy and surgical repair. Therefore, before performing any ocular surgery involving the sclera, a thorough ophthalmic and systemic evaluation must be done to identify high-risk patients that may develop SISN.

Recalcitrant infective scleritis masquerading an autoimmune necrotising scleritis: a primary presentation of biopsy-proven granulomatosis with polyangiitis.

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.

Immunopathological Analysis of a Mouse Model of Arthritis-Associated Scleritis and Implications for Molecular Targeted Therapy for Severe Scleritis.

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.

Topical Erythropoietin as a Novel Treatment for Necrotizing Scleritis After Pterygium Surgery: A Pilot Study.

PURPOSE: To share our initial experience with the innovative use of topical erythropoietin for the treatment of necrotizing scleritis manifesting immediately after pterygium excision surgery. METHODS: This study enrolled 3 patients who developed necrotizing scleritis immediately after undergoing pterygium excision. All cases with pterygium were primary, and topical mitomycin C and conjunctival autografts were used at the time of surgery. Noninvasive therapy that included ophthalmic lubricants and topical and systemic corticosteroids failed to improve the avascular scleral lesions. The patients were prescribed erythropoietin-containing drops (3000 U/mL) every 6 hours in addition to topical antibiotics and lubricant. The effect of topical erythropoietin on the healing process of avascular scleral lesions was investigated, and its ocular and systemic side effects were evaluated. RESULTS: The mean age of the participants was 69.0 ± 14.8 years, and 2 of the 3 eyes belonged to male subjects. The time between pterygium surgery and presentation to our clinic was 33.0 ± 14.7 days. There were no infectious causes or underlying systemic diseases in any of the cases. After treatment with topical erythropoietin for an average of 34.3 ± 20.3 days, the lesions were completely vascularized in all 3 eyes without any ocular or systemic adverse effects. The patients were followed up for an average of 126 ± 94 days after discontinuation of erythropoietin. There was no evidence of recurrence during the last examination in any of the eyes. CONCLUSIONS: Topical erythropoietin might be a safe and an effective method for treating cases of necrotizing scleritis that manifests immediately after pterygium surgery.

A rare case of bilateral sequential posterior scleritis in an elderly woman.

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.

The Results of Preoperative Topical Brimonidine Usage in Pterygium Surgery.

Purpose: To evaluate the reduction of conjunctival and episcleral hyperemia and bleeding in pterygium surgery following the use of topical brimonidine preoperatively. Methods: In this study, 45 patients who had undergone pterygium surgery under topical anesthesia were enrolled. Brominidine tartrate 0.15% eye drops were applied topically to 25 eyes of 25 patients at the sixth and third minutes preoperatively, and no drops were applied to 20 eyes of 20 patients for vasoconstriction. Preoperative and postoperative photographs and video images were taken. Results: Vasoconstriction effects of topical brimonidine tartrate on surface vessels were observed. The surface area of blood vessels was reduced 60% within 5 min; this effect was observed with the help of Photoshop and ImageJ programs and it lasted for ∼20 min. The surgery lasts for 7 min, on average, so the conjunctival whitening formed by brimonidine tartrate provides a safe and comfortable operative area throughout the surgery. Conclusion: We recommend applying brimonidine tartrate before pterygium surgery due to its conjunctival whitening effect to provide a safe and comfortable operative area throughout the surgery.

Posterior Scleritis.

The patient is a 19-year-old female who presented with 3 weeks of right eye pain, eyelid swelling, blurry vision, and headache. Visual acuity was counting fingers at 1 foot. Intraocular pressure was normal, and there was diffuse scleral injection on anterior examination. She had a mild anterior chamber reaction with 15 cells/high-powered field and a mild vitreous inflammatory reaction. Fundus examination revealed diffuse choroidal thickening with multilobulated serous retinal detachments worse inferiorly (Figures 1 and 2). Fluorescein angiography demonstrated severe optic disc leakage. Ultrasonography demonstrated diffuse choroidal thickening, a serous retinal detachment, and a prominent "T-sign" (Figure 3). The patient was diagnosed with posterior scleritis and treated with 80 mg of oral prednisone. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:660.].

Idiopathic inflammatory diseases of orbit and ocular adnexa: Histopathological and immunochemical analysis.

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.

Ophthalmologic Manifestation of Inflammatory Bowel Disease: A Review.

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.

Clinical and pathological findings in three dogs with a corneocentric presentation of nodular granulomatous episcleritis.

PURPOSE: To describe the clinical signs, management, histopathologic findings, and outcome of three dogs with a corneocentric presentation of nodular granulomatous episcleritis (NGE). METHODS: Three dogs of varying breeds were presented for a unilateral, nonpainful, and infiltrative corneal lesion in the dorsal aspect of the eye. Clinical response to symptomatic topical treatment directed at a presumed inflammatory or immune-mediated cause was poor. Due to this, and concerns of neoplasia, ultrasonography (n = 1), incisional biopsy (n = 2), and/or enucleation (n = 2) were performed. RESULTS: The inflammatory infiltrate observed on histopathology was identical to that seen in nodular granulomatous episcleritis in all three cases. However, atypically the inflammation was confined to the cornea and limbus, without episcleral or conjunctival involvement. Inflammation of the cornea was full thickness to Descemet's membrane. Following enucleation (n = 2), there were no postoperative complications, and no reported ophthalmic disease in the remaining eye. Currently, the single non-enucleated case remains controlled with systemic and topical immunosuppression. CONCLUSION: To the best of the authors' knowledge, this is the first report of an NGE condition purely affecting the full thickness of the cornea, without episcleral or conjunctival involvement. The authors propose this to represent an atypical corneocentric variant of NGE. This clinical presentation can resemble neoplasia; incisional biopsy is recommended for a definitive diagnosis. Further research into the optimal treatment strategies for this variant of NGE is required.

Histopathological evaluation of scleritis.

The sclera is an uncommon site of primary inflammation. Biopsy is infrequently employed in the evaluation of scleritis, but familiarity with its differential diagnosis is instrumental in ensuring efficient histological evaluation. This review provides a clinical overview of scleritis and describes the context in which scleral biopsy might arise. Most cases are associated with systemic autoimmune disease, but a sizeable proportion occur as an isolated disorder. Conditions mimicking autoimmune scleritis include infection and neoplasm. Histological patterns of inflammation in eyes removed surgically or at autopsy have been placed into three groups: (1) autoimmune scleritis characterised by varying mixtures of palisading granulomas, necrosis and vasculitis; (2) infectious scleritis, characterised by acute inflammation and necrosis; and (3) idiopathic scleritis, characterised by chronic non-specific inflammation with follicles and varying amounts of fibrosis. This traditional system of classification may be oversimplified. Aetiological or categorical classification is not always possible on small biopsies given the histopathological overlap of infectious and non-infectious scleritis.

Clinicopathological case: rapid cognitive decline and myoclonus associated with fever, arthropathy and scleritis.

A 65-year-old man presented with transient neurological symptoms, followed by rapid cognitive decline, myoclonus and fevers. He had evidence of scleritis and an arthropathy. This paper reports the clinicopathological conference discussed at the Association of British Neurologists Annual Meeting 2017.