Infectious Scleritis: Pathophysiology, Diagnosis, and Management.

ABSTRACT: Infectious scleritis (IS) is a rare and severe ocular disorder responsible for approximately 5%-15% of all scleritis cases. It is often associated with a poor prognosis due to its similar clinical presentation to autoimmune scleritis, resulting in a delayed diagnosis and treatment. Therefore, differentiating between infectious and noninfectious entities is critical. Several details extracted from the patient's history and clinical examination can raise suspicion for infection. The most common predisposing factor is previous ocular surgery, especially pterygium, cataract, and vitreoretinal surgeries. Ocular trauma, poor contact lens hygiene, "eye-whitening" procedures, and subtenon triamcinolone injections have also been implicated. Clinical features of infection include the presence of scleral necrosis, hypopyon, unifocal or multifocal scleral abscesses, and mucopurulent discharge. Thorough diagnostic testing is essential before excluding infection as a possibility. Empiric broad-spectrum topical and systemic antibiotic therapy should be initiated while awaiting laboratory results and adjusted accordingly. Most IS cases require both aggressive medical and surgical treatment, and various studies have reported favorable outcomes with this combination. At this time, there is no consensus on the management of this severe ocular condition, and future studies are needed to establish clear treatment guidelines.

Unclassified Vasculitis with Episcleritis, Thrombophlebitis, Deep Vein Thrombosis, Pulmonary Vasculitis, and Intracranial Vasculitis: An Autopsy Case Report.

BACKGROUND Systemic vasculitides constitute heterogenous conditions affecting many organs and systems through blood vessel inflammation. Although there are some classifications for vasculitis, several vasculitides are "unclassified" because they cannot be clearly assigned to one of the known entities. CASE REPORT We report an autopsy case of a 67-year-old Japanese man who presented with fever, ocular pain, erythema, chest pain, and headache. The disease caused episcleritis, thrombophlebitis, extensive deep vein thrombosis, multiple pulmonary nodules and masses, hypertrophic pachymeningitis, and hyper-intensity areas in brain parenchyma on magnetic resonance images. Histopathology of the pulmonary nodule confirmed vasculitis affecting medium-to-small veins and arteries without necrotizing vasculitis or granulomatous inflammation. We diagnosed the patient with unclassified vasculitis based on the clinicopathological characteristics. Steroids in combination with immunosuppressants were used, but the disease was refractory and relapsing. The disease activity was eventually controlled with rituximab, but the patient died of bronchopneumonia. On autopsy, lung and brain findings indicated healed vascular inflammation. CONCLUSIONS This is the first case report of unclassified vasculitis, which is characterized as medium-to-small-sized arteritis and phlebitis, causing episcleritis, thrombophlebitis, deep vein thrombosis, pulmonary vasculitis, and intracranial vasculitis. The clinical conditions share some similarities with granulomatosis with polyangiitis and Behçet's disease; however, they meet no classification criteria of any specific vasculitis. More cases need to be analyzed to confirm our findings.

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.

Scedosporium apiospermum infectious scleritis following posterior subtenon triamcinolone acetonide injection: a case report and literature review.

BACKGROUND: Ubiquitous fungi of the Scedosporium apiospermum species complex (SASC) cause various opportunistic infections. Posterior subtenon triamcinolone acetonide (STTA) injection is a standard therapy for intraocular inflammation and macular edema. We report a case of Scedosporium apiospermum infectious scleritis after a posterior STTA injection. CASE PRESENTATION: A 75-year-old man received a posterior STTA injection to treat macular edema in his left eye. After 3 months, he complained of ocular pain and hyperemia in his left eye. Examination showed a subtenon abscess in the site corresponding with the STTA injection. After incising the abscess, the smear revealed numerous conidia-like structures. Although we suspected fungal infection and started topical voriconazole (VRCZ) and levofloxacin, the inflammation of the eye worsened. Fungal culture revealed filamentous fungus growth. Subsequently, we added systemic VRCZ and performed surgical debridement of the infected sclera and Tenon's capsule. Pathology of the sclera showed fungal hyphae. The antifungal susceptibility test revealed low minimum inhibitory concentrations for micafungin, VRCZ and miconazole (0.06, 0.25 and 0.5 µg/mL, respectively). After 2 months, the ciliary injection subsided and VRCZ therapy was stopped. However, subtenon abscess recurred 1 month after discontinuation of topical VRCZ. Surgical debridement and topical VRCZ were resumed, with the eye finally improving after 5 months of management. The fungal species was identified as Scedosporium apiospermum sensu stricto morphologically and by DNA sequencing. CONCLUSIONS: This case was successfully treated by topical and systemic VRCZ and repeated surgical debridement. Infectious scleritis caused by SASC rarely develops after posterior STTA. SASC can produce conidia in the enclosed subtenon space. Late-onset infectious scleritis after a posterior STTA injection suggests the presence of a fungal infection, including SASC, thereby requiring extensive and prolonged medical and surgical treatment.

[Scleritis and episcleritis]. / Sclérites et épisclérites.

Episcleritis is generally a benign disease with a self-limited course, while scleritis is a severe ocular condition due to a risk of impaired vision in one-fifth of patients and its association with systemic diseases in one third of them. Infectious scleritis, representing 8 % of the etiologies, is mainly of herpetic origin (varicella zoster and herpes simplex viruses). A systemic autoimmune disease is observed in roughly 30 % of scleritis patients: inflammatory rheumatisms (15 %), firstly rheumatoid polyarthritis, systemic vasculitides (8 %), mainly granulomatosis with polyangiitis (Wegener's) and polychondritis, and less often inflammatory bowel disease and systemic lupus erythematosus. Among the different types of scleritis, a clear distinction exists between necrotizing forms leading to decreased vision in 50 % of the cases and associated with systemic diseases in the vast majority, and non-necrotizing forms (either diffuse or nodular), with a better prognosis. However, recent publications show that necrotizing forms are much less frequent nowadays (around 5 % of the total), probably due to therapeutic innovations and progress made during the last 20 years. The medical management of scleritis requires collaboration between ophthalmologists and internists (or rheumatologists).

Management of Uveitis and Scleritis in Necrobiotic Xanthogranuloma.

Necrobiotic xanthogranuloma (NXG) is a chronic, progressive non-Langerhans histiocytic granulomatous disease. While case reports describing periorbital involvement of NXG are frequent, only a few case reports describing ocular involvement, such as scleritis and uveitis, exist. Herein, we present a case presenting initially as bilateral anterior and posterior scleritis, as well as a chronic bilateral granulomatous panuveitis, and discuss the immunosuppressant options that should be considered for this disease with protean manifestations.

Diagnosis and management of non-infectious immune-mediated scleritis: current status and future prospects.

Scleritis is an inflammatory process of the sclera and adjacent tissues with a wide spectrum of clinical presentations and co-morbidities. Careful clinical history taking, detailed ocular examination, and appropriate investigation for likelihood of an underlying systemic disease are essential for diagnosis. Treatment can be quite challenging in some cases. Conventional therapy with corticosteroids and immunosuppressive agents may not be sufficient to control ocular inflammation in refractory patients. In such cases new therapeutic agents, which have a more targeted and sustained effect on the immune response, so-called biologic response modifiers, are being used. This review focuses on both diagnosis and therapeutic options including traditional and emerging therapies of non-infectious scleritis.

Successful Treatment of Infectious Scleritis by Pseudomonas aeruginosa with Autologous Perichondrium Graft of Conchal Cartilage.

Infectious scleritis by Pseudomonas aeruginosa is a well-known vision-threatening disease. In particular, scleral trauma following pterygium surgery may increase the risk of sclera inflammation. Surgical debridement and repair is necessary in patients who do not respond to medical treatments, such as topical and intravenous antibiotics. We reports herein the effectiveness of an autologous perichondrium conchal cartilage graft for infectious scleritis caused by Pseudomonas aeruginosa. This procedure was performed on four eyes of four patients with infectious scleritis who had previously undergone pterygium surgery at Gyeongsang National University Hospital (GNUH), Jinju, Korea from December 2011 to May 2012. Pseudomonas aeruginosa was identified in cultures of necrotic scleral lesion before surgery. The conchal cartilage perichondrium graft was transplanted, and a conjunctival flap was created on the scleral lesion. The autologous perichondrium conchal cartilage graft was successful and visual outcome was stable in all patients, with no reports of graft failure or infection recurrence. In conclusion, autologous perichondrium conchal cartilage graft may be effective in surgical management of Pseudomonal infectious scleritis when non-surgical medical treatment is ineffective. Further studies in larger, diverse populations are warranted to establish the effectiveness of the procedure.

Risk factors and clinical outcomes of bacterial and fungal scleritis at a tertiary eye care hospital.

PURPOSE: The aim was to analyze demographics, risk factors, pathogenic organisms, and clinical outcome in cases with microbiologically proven bacterial or fungal scleritis. MATERIALS AND METHODS: Retrospective review of all the medical records of patients with microbiologically proven infectious scleritis examined from March 2005 to December 2009 in the cornea services of L. V. Prasad Eye Institute, Hyderabad, India was done. RESULTS: Forty-two eyes of 42 patients were included in this study. The mean age at presentation was 48.52 ± 14.10 years (range: 12-70). Surgery was the major risk factor seen in 24 eyes (58.5%). Scleral infection was noted after vitreoretinal surgery (with scleral buckle) in 15 eyes, cataract surgery in 3 eyes, pterygium surgery in 3 eyes, corneoscleral tear repair and scleral buckle surgery in 3 eyes. Sixteen eyes (39%) were on systemic or topical steroids at the time of presentation. History of injury was noted in 9 eyes (22%) and diabetes mellitus in 7 patients (17%). Associated keratitis was noted in 9 eyes (21.4%). The scleral abscess was unifocal in 33 eyes (78.5%), multifocal in 6 eyes (14.2%) and diffuse in 3 eyes (7.14%). The final follow-up ranged from 24 days to 37 months. The final visual acuity was better in 18 eyes (42.8%), stable in 13 (30.9%), and deteriorated in 7 eyes (16.6%). Recurrence was seen in 4 eyes (9.5%). CONCLUSIONS: Surgery is a major risk factor for infectious scleritis in our series. Fungus was the most common organism isolated. Thorough debridement and intensive use of medications have improved the outcome.

Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and literature review.

To date, there has been only one published report on the infectious sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic fungus. Regarding corneal infection, three reports have been published to date. Although the prognoses of the corneal infections are favourable, prognosis when scleral infection is involved is very poor. A 76-year-old patient presented with foreign body sensation in the left eye. Microscopic examination with Fungi Flora Y staining of the corneal scraping revealed fungal infection. The conjunctiva was melted by the infection over a wide area. Although intensive medications were administered, an emergency surgery was necessary because scleral thinning, corneal perforation and lens prolapse occurred. The fungal isolate was identified as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we report the second known case worldwide of M. anisopliae sclerokeratitis, and we review the literature related to the ocular infections.

[Scleritis and episcleritis: diagnosis and treatment]. / Sclérites et épisclérites : prise en charge diagnostique et thérapeutique.

Episcleritis and scleritis are distinct entities with regard to visual prognosis, risk of associated systemic disease, and treatment. The pertinence of the clinical classification of episcleritis and scleritis established in 1976 still persists, with significant differences in terms of visual prognosis, associated general conditions, and therapeutic choices according to each scleritis subtype. Episcleritis requires rarely to be referred to a tertiary care centre, and if so it has to be monitored similarly to scleritis. In this paper, an analysis of 1358 scleritis cases from the main distinct large series published since 1976 shows a mean proportion of 8% of infectious aetiologies (mainly herpes viruses), and 28% of systemic diseases with two main subgroups: inflammatory rheumatisms 12.8%, and systemic vasculitis 7.8%. Overall, the risk for visual loss following scleritis is around 16%. However, the risks of associated systemic disease and visual loss are both highly variable according to the type of scleritis, and culminate at 80% and 50% in the necrotizing subtype respectively. As compared with older series, the proportion of necrotizing scleritis is lower in recent series which is likely due to the advances obtained over the past 20 years in immunomodulatory therapy, as well as its wide use in the treatment of the main systemic conditions associated with scleritis. The treatment of scleritis should be managed by physicians who are experts in the use of immunosuppressive drugs that may be required in one out of two affected patients.

Scleral and intraocular amoebic dissemination in Acanthamoeba keratitis.

PURPOSE: To review an Acanthamoeba keratitis case series for the documented extracorneal spread of the amoeba. METHODS: A retrospective review of an observational case series from a single institution. RESULTS: Three patients with 4 instances of microbiologically confirmed extracorneal amoebic spread were identified. Patient 1 had nodular scleritis after undergoing penetrating keratoplasty and was treated successfully with double freeze-thaw cryotherapy; patient 2 had intraocular dissemination of the amoeba detected in a retrocorneal membrane; and patient 3 had, after undergoing tectonic keratoplasty, intraocular dissemination of the amoeba that was treated successfully with intraocular and systemic voriconazole and, afterwards, a nodular scleritis treated with double freeze-thaw cryotherapy and a large-diameter corneal graft to treat corneal recurrence. CONCLUSIONS: Acanthamoeba can migrate to the sclera or to the intraocular tissues in some instances, such as in long-standing disease or in penetrating keratoplasty. A prompt biopsy for microbiological analysis and early treatment are required, if this is suspected. Voriconazole can be effective for intraocular invasion when used orally and intraocularly. Scleral involvement might require a surgical approach with double freeze-thaw cryotherapy to treat the localized disease.

Granulomatous inflammation in Acanthamoeba sclerokeratitis.

This report describes the histopathological findings in a patient with Acanthamoeba sclerokeratitis (ASK). A 58-year-old patient with ASK underwent enucleation and sections of the cornea and sclera were subjected to histopathology and immunohistochemistry with monoclonal mouse antihuman antibodies against T cell CD3 and B cell CD20 antigens. Hematoxylin and Eosin stained sections of the cornea revealed epithelial ulceration, Bowman's membrane destruction, stromal vascularization, infiltration with lymphocytes, plasma cells, and granulomatous inflammation with multinucleated giant cells (MNGC). The areas of scleritis showed complete disruption of sclera collagen, necrosis and infiltration with neutrophils, macrophages, lymphocytes, and granulomatous inflammation with MNGC. No cyst or trophozoites of Acanthamoeba were seen in the cornea or sclera. Immunophenotyping revealed that the population of lymphocytes was predominantly of T cells. Granulomatous inflammation in ASK is probably responsible for the continuance and progression of the scleritis and management protocols should include immunosuppressive agents alongside amoebicidal drugs.

Ocular inflammation and infection.

Ocular inflammation and infection may involve any part of the eye and surrounding tissue. A complete examination, including visual acuity, extraocular movements, pupillary response, slit lamp examination, and fluorescein staining, is often required to establish the diagnosis. Pain relief may be achieved with oral analgesics and cycloplegics. In most cases, prompt follow-up is required.

Epidemiology and visual outcomes in patients with infectious scleritis.

PURPOSE: To describe the epidemiology of patients with infectious scleritis and identify factors associated with poor visual prognosis. METHODS: Retrospective review of inciting factors, causative organisms, and visual outcomes of patients with infectious scleritis. RESULTS: Fifty-five patients (56 eyes) with confirmed infectious scleritis were included. The median time from inciting event to scleritis symptoms was 1.9 months. Eyes with a history of pterygium surgery had a longer time from surgery to development of scleritis (median 49 months, range 0-183) compared to those with a history of glaucoma, cataract, and retina surgery (median 1.0-1.6 months; P = 0.001). Fungal, nocardial, and mycobacterial infections (median 17-45 days) had a longer interval between symptoms and diagnosis than eyes with non-acid-fast gram-positive and gram-negative bacteria (median 7 days; P = 0.04). Patients were followed for a median of 11.1 months (0.5-47 months). Approximately 50% of eyes lost functional vision (worse than 20/200). Presenting VA of worse than 20/200 and concomitant keratitis or endophthalmitis were associated with poorer VA outcomes. CONCLUSIONS: Infectious scleritis can occur days to years after ocular surgery, with infection occurring after a longer interval in eyes with a history of pterygium surgery. Approximately 50% of eyes lost functional VA after infection with poor presenting VA being the strongest predictor for subsequent severe vision loss.