Assessment of conjunctival, episcleral and scleral thickness in healthy individuals using anterior segment optical coherence tomography.

PURPOSE: To determine the thickness of the conjunctiva, episclera and sclera in healthy individuals using anterior segment optical coherence tomography (AS-OCT). METHODS: We prospectively included 107 healthy individuals of different age groups (18-39 years, 40-54 years, 55-69 years and ≥70 years). For each eye, AS-OCT scans of four quadrants (temporal, nasal, superior and inferior) were acquired. The thickness of the conjunctiva, episclera and sclera was measured for each scan. In addition, the axial length of both eyes was measured, and general characteristics, including smoking, allergies and contact lens use, were collected. RESULTS: The mean conjunctival thickness was significantly different between the nasal and superior quadrants (87 ± 30 µm vs. 77 ± 16 µm; p < 0.001), as well as the superior and inferior quadrants (77 ± 16 µm vs. 86 ± 19 µm; p = 0.001). The mean episcleral thickness was larger in the superior (174 ± 54 µm) and inferior (141 ± 43 µm) quadrants, compared to the nasal (83 ± 38 µm) and temporal quadrants (90 ± 44 µm). The mean scleral thickness of the inferior quadrant was the largest (596 ± 64 µm), followed by the nasal (567 ± 76 µm), temporal (516 ± 67 µm) and superior (467 ± 52 µm) quadrants (all p < 0.001). The averaged scleral thickness increased 0.96 µm per age year (0.41-1.47 µm, p < 0.001). CONCLUSIONS: This study provides an assessment of the thickness of scleral and adjacent superficial layers in healthy individuals determined on AS-OCT, which could enable future research into the use of AS-OCT in diseases affecting the anterior eye wall.

Subconjunctival Rituximab Administration for the Treatment of Scleritis.

PURPOSE: Scleritis is a sight-threatening inflammation, which is commonly accompanied by severe complications. Aggressive systemic immunosuppressive treatment, which is frequently needed, can be associated with serious complications, and might therefore be (temporarily) contraindicated. METHODS: We report on the outcomes of three patients with severe, active, non-infectious scleritis, refractory or intolerant to systemic treatment, who received subconjunctival rituximab (RTX) injections. A dose of 2.5 to 7.5 mg was administered after topical anesthesia, and follow-up varied from 8 to 10 months. RESULTS: Subconjunctival RTX showed minimal to no effect on subjective symptoms, clinical features and/or ultrasound images. No serious adverse effects occurred. CONCLUSION: Further studies are needed to assess the effect of local administration of RTX in scleritis, but our limited observation is not promising.

Clinical Relevance of Autoantibodies and Inflammatory Parameters in Non-infectious Scleritis.

PURPOSE: Scleritis is a potentially blinding disorder, with highly unpredictable course and outcome. We analyzed the prevalence and clinical relevance of autoantibodies and inflammatory parameters in non-infectious scleritis. METHODS: Retrospective analysis of laboratory findings in all consecutive patients at the department of Ophthalmology of the Erasmus MC with non-infectious scleritis. RESULTS: We included 81 patients with non-infectious scleritis. A systemic autoimmune disease was present in 46%. Positive anti-nuclear antibodies were found in 30%, anti-neutrophil cytoplasmic antibodies were positive in 19%, and the presence of rheumatoid factor was shown in 17%. The aforementioned autoantibodies, as well as inflammatory parameters, failed to show prognostic clinical value. In contrast, anti-citrullinated peptide antibodies (ACPA), found in 9% of scleritis patients, were significantly associated with the development of scleral necrosis (P = .01). CONCLUSIONS: The presence of ACPA in patients with non-infectious scleritis was associated with the development of scleral necrosis.

Current insights in the pathogenesis of scleritis.

Scleritis is a sight-threatening inflammation characterized by severe pain and redness of the eye. It can cause blindness by severe complications like scleral and corneal necrosis, keratitis, and uveitis. The pathogenesis of scleritis is largely unknown due to a combination of the rarity of the disease, the little available human tissue-based research material, and the lack of animal models. The immune system is assumed to play a crucial role in the pathogenesis of scleritis. Multiple clues indicate probable antigenic stimuli in scleritis, and the involvement of matrix metalloproteinases in the destruction of scleral tissue. In this article we review the current insights into the pathogenesis of scleritis, and we suggest new hypotheses by implementing knowledge of systemic autoimmune disease pathogenesis. Understanding the pathogenesis of scleritis is crucial to improve the clinical management, as well as to find novel treatment modalities.

The Usefulness of Aqueous Fluid Analysis for Epstein-Barr Virus in Patients with Uveitis.

Purpose: To determine characteristics of patients with laboratory findings indicative of intraocular Epstein-Barr-virus (EBV) infection and to establish the usefulness of the laboratory analysis in patients with uveitis.Methods: Retrospective study of patients who underwent diagnostic aqueous fluid analysis. Diverse demographic data of patients were registered.Results: EBV-PCR tested positive in 3/201 (1%) and EBV-GWC in 22/245 (9%). The prevalence of immunosuppression was similar in EBV positive (by PCR/GWC) and EBV negative patients (7/25; 28% vs. 50/272;18%, P = 0.29). Out of all 22 EBV-GWC positive patients, GWC was between 3 and 10 in 91%. In total, 14 patients had laboratory results indicating only EBV infection. Patients without an alternative explanation for uveitis (6/14; 43%) had a chronic recurrent course and good visual prognosis.Conclusion: Low EBV-GWC values combined with multiple positive GWC and/or PCR for other infectious agents. Intraocular assessment for EBV in the initial examination of uveitis patients has limited value.

Successful Tocilizumab Treatment for Scleritis.

Purpose: To present a rare case of scleritis associated with a prior diagnosis of giant cell arteritis (GCA) that was unresponsive to glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and azathioprine, but reached and maintained a full remission with tocilizumab.Observations: A 62-year-old Caucasian female presented with scleritis and headache. Four years earlier, the patient was diagnosed with GCA. Treatment with topical and systemic NSAIDs, prednisone and diverse disease-modifying antirheumatic drugsonly had a partial effect on the scleritis whilst the arthralgia and headaches increased. Despite the absence of laboratory evidence of active GCA, tocilizumab was started and the scleritis and headaches disappeared within several days. Prednisone could be fully tapered within 3 months and to date, 12 months after the start of tocilizumab, the patient has maintained a sustained remission.Conclusions: Our patient demonstrates that tocilizumab might represent a therapeutic option for scleritis, and its further evaluation for this severe ocular disease is worthwhile.

An Intraocular Inflammatory Profile of Rubella Associated Uveitis.

Purpose: To analyze intraocular cytokine levels and cell profiles in patients with rubella virus-associated uveitis (RVU). Methods: We collected intraocular fluid samples from patients with RVU (n = 10), uveitis of other causes (n = 27), and cataract (n = 22). Levels of 15 cytokines (IL-1ß, IL-1ra, IL-2, IL-6, IL-6rα, IL-7, IL-8, IL-10, IL-17A, IL-23, TARC, MCP-1, TNF-α, PlGF, and VEGF) were measured using multiplex assay, and intraocular cell populations were determined by multiparameter flowcytometry. Clinical characteristics of RVU patients were collected and compared to laboratory outcomes. Results: RVU patients exhibited high intraocular levels of MCP-1, IL-6rα, and TARC, whilst patients with noninfectious uveitis were characterized by high levels of PlGF. Cataract patients showed high levels of IL-2 and IL-23. Intraocular cell population of RVU patients disclosed mainly T-cells and monocytes/macrophages and B-cells were scarcely detected. Conclusion: RVU patients exhibit a cytokine profile distinct from noninfectious uveitis and cataract.

Tuberculosis and other causes of uveitis in Indonesia.

PurposeThe purpose of this study is to assess the causes of uveitis in Indonesia and determine the importance of tuberculosis (TB) as a cause of uveitis.Patients and methodsProspective cohort study examining 146 consecutive new human immunodeficiency virus-negative patients with active uveitis between June 2014 and May 2015. We assessed the anatomic locations and specific causes of uveitis, as well as associations with infectious and non-infectious systemic diseases. We determined the prevalence of positive QuantiFERON Tb Gold test (QFT) results in Indonesian patients with uveitis and calculated the number of patients with active systemic TB.ResultsPosterior and panuveitis were the most common anatomic entities (38% each). Infections represented the most frequent cause of uveitis (33%); the most prevalent were toxoplasmosis (19%) and active systemic TB (8%). The majority of patients were QFT positive (61%). A specific diagnosis could not be established in 45% of the patients. At first presentation to the ophthalmologist, the majority of patients (66%) had a visual acuity of less than finger counting at 3 m and already exhibited various complications of uveitis. When classifying the QFT-positive patients with unexplained uveitis into a TB-related group, the percentage of 'TB-associated' uveitis cases increased from 8-48%. Highly elevated QFT levels were observed in patients with uveitis of unknown cause and no signs of active systemic TB.ConclusionsIn Indonesia, infectious uveitis was the most common type of uveitis and the leading causes consisted of toxoplasmosis and TB. The association observed between highly elevated QFT results and uveitis of otherwise unexplained origins indicates that a link exists between the latent TB infection and the development of uveitis.

Visual outcomes and ocular morbidity of patients with uveitis referred to a tertiary center during first year of follow-up.

PURPOSE: To describe the visual outcomes and morbidity of newly referred uveitis patients. METHODS: Retrospective cohort study of 133 newly referred uveitis patients with active uveitis who required care in a tertiary center for at least 1 year. Main outcomes were best-corrected visual acuity (BCVA) at referral and 1 year after referral, duration of visual impairment, systemic medications used, as well as all complications and surgeries during the first year of follow-up. Generalized estimating equation models was used to assess prognosticators for poor BCVA. RESULTS: The mean age at onset of uveitis was 43 years. The proportion of patients with at least one eye with BCVA ≤0.3 decreased from 35% at referral to 26% (P=0.45) at 1-year follow-up. The mean duration of visual impairment in the first year after referral was 4 months per affected eye. At 1-year follow-up, bilateral visual impairment was observed in 4% but at least one ocular complication developed in 66% and 30% of patients required at least one intraocular surgery. Systemic immunosuppressive treatment was required in 35% of patients and the mean number of visits to ophthalmologist was 11 per year, while 8% of patients required hospital admission. Prognosticators for poor visual outcome included surgery undergone before referral (odds ratio (OR), 3; 95% CI, 1-11; P=0.047), visual impairment at referral (OR, 21; 95% CI, 8-54; P<0.001), and glaucoma before referral (OR, 7; 95% CI, 2-28; P=0.007). CONCLUSIONS: Patients with severe uveitis had a favorable BCVA 1 year after referral with only 4% of patients having bilateral visual impairment. This, in contrast to the prolonged duration of visual impairment during the first year of follow-up and the demanding care.

Molecular and Serological Intraocular Fluid Analysis of Coxiella burnetii-seropositive Patients with Concurrent Idiopathic Uveitis.

PURPOSE: Previous studies have suggested a link between Q fever and uveitis. We determined whether Coxiella burnetii causes intraocular infection in C. burnetii-seropositive patients with idiopathic uveitis. METHODS: From a retrospective observational case series, paired aqueous humor and serum samples from 10 C. burnetii-seropositive patients with idiopathic uveitis were examined for intraocular antibody production by using the Goldmann-Witmer coefficient and by polymerase chain reaction (PCR). RESULTS: Although intraocular IgG against C. burnetii was detected, no intraocular antibody production was observed (low Goldmann Wittmer coefficients). All PCR results were negative. CONCLUSIONS: Uveitis due to an intraocular infection with C. burnetii is unlikely.

Viral causes of unexplained anterior uveitis in Thailand.

AIMS: To assess the possible role of virus infection in patients with unexplained anterior uveitis (AU). METHODS: Intraocular fluid and plasma samples of 30 HIV-negative AU patients who were unresponsive or poorly responsive to topical steroid therapy were analyzed for nucleic acid of cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) by real-time polymerase chain reaction (PCR) and for intraocular antibodies against these viruses by Goldmann-Witmer coefficient (GWC) analysis. Of these 30 cases, 21 were tested for rubella virus by GWC analysis, 16 of which also had PCR assessment of aqueous for rubella virus. RESULTS: Viral uveitis determined by either real-time PCR and/or GWC was documented in 20 out of 30 patients (67%). Of 30 paired samples tested by both methods for HSV, CMV, and VZV, 15 showed positive results (CMV (10), HSV (4), and VZV (1)). Real-time PCR was positive in 8/15 (53%), whereas GWC was positive in 10/15 (67%). Out of 10 CMV-positive patients, four had endotheliitis, two had Posner-Schlossman syndrome, and one Fuchs heterochromic uveitis syndrome (FHUS). Five out of 21 (24%) samples tested by GWC for Rubella virus were positive, three of which exhibited clinical features of FHUS. CONCLUSIONS: Our results indicate that CMV is a major cause of AU in Thailand and show that FHUS can be caused by both CMV and Rubella virus.

Young age as a risk factor for complicated course and visual outcome in intermediate uveitis in children.

OBJECTIVE: To identify prognostic factors in intermediate uveitis (IU) in children. METHODS: Retrospective case series of 35 patients with onset of IU ≤16 years and a minimum follow-up of 1 year. Demographic and numerous clinical data were documented. Visual outcomes and development of complications were analysed in relation to age of onset and ocular signs at presentation. RESULTS: Forty-six per cent of patients had onset ≤7 years, and 54% >7 years. The younger-onset group had a shorter event-free survival for secondary glaucoma (p=0.04) and vitreous haemorrhage (p=0.01). The mean age of onset in children with cataract (5.9 vs 8.7 years), glaucoma (5.0 vs 8.4) and vitreous haemorrhage (5.6 vs 8.5) was lower than in children without these complications (all p=0.03). Frequencies of other complications did not differ between both groups. The younger-onset group had worse BCVAs at presentation (0.3 vs 0.6), at 1 year (0.4 vs 0.9) and at 3 years' follow-up (0.6 vs 0.9; all p≤0.04), and they needed longer treatment (p=0.01). Children with young onset of IU reached remission less frequently (p=0.05). Development of cystoid macular oedema was independently associated with papillitis (adjusted HR=3.4; p=0.02) and snowbanking (adjusted HR=3.3; p=0.03) at presentation. Other complications at onset were not predictive for future complications. CONCLUSIONS: Children with young onset of IU carry a higher risk of complications and worse visual outcome. The authors would recommend considering more intensive monitoring and earlier threshold for systemic treatment in those children with risk factors as early onset, papillitis and/or snowbanking at initial presentation.

Ocular sarcoidosis in Thailand.

PURPOSE: To determine the prevalence of pulmonary sarcoidosis in patients with uveitis from the University Referral Centre in Thailand and to report on their clinical characteristics. METHODS: We performed a retrospective review of results of radiological examinations of 209 consecutive new patients, diagnosed with uveitis. In patients with signs of pulmonary sarcoidosis, we reviewed clinical characteristics including age, gender, laterality and anatomical location of uveitis, and complications. RESULTS: From 209 chest X-ray (CXR) examinations, one patient exhibited radiological signs typical of stage 1 sarcoidosis. Chest CT of three patients with posterior multifocal chorioretinitis (PMC) revealed abnormalities suggesting the diagnosis of pulmonary sarcoidosis. All PMC patients were females older than 50 years; they had no pulmonary complaints and their CXRs were without abnormalities. CONCLUSION: Ocular sarcoidosis is prevalent in Thailand and our findings suggest that possibly more patients with sarcoidosis would be identified if diagnosis was thought of and ancillary tests were performed.

Long-term ocular complications in aphakic versus pseudophakic eyes of children with juvenile idiopathic arthritis-associated uveitis.

AIM: To evaluate the long-term follow-up of aphakic and pseudophakic eyes of children with juvenile idiopathic arthritis (JIA)-associated uveitis with a special interest in whether intraocular lens implantation increases the risk of developing ocular complications. METHODS: Data were obtained from the medical records of 29 children (48 eyes) with JIA-associated uveitis operated on for cataract before the age of 16 years from January 1990 up to and including March 2007. Main outcome measures were long-term postsurgical complications and visual acuity in aphakic and pseudophakic eyes of children with JIA-associated uveitis. RESULTS: The number of complications after cataract extraction including new onset of ocular hypertension and secondary glaucoma, cystoid macular oedema and optic disc swelling did not differ between aphakic and pseudophakic eyes. Moreover, no hypotony, perilenticular membranes and phthisis were encountered in the pseudophakic group. Better visual acuity was observed in the pseudophakic eyes up to and including 7 years of follow-up (p=0.012 at 7 years of follow-up). No differences in the preoperative or adjuvant perioperative treatment with periocular or systemic corticosteroids were found between the two groups; however, significantly more children were treated with methotrexate in the pseudophakic group (p=0.006). CONCLUSION: With maximum control of perioperative inflammation and intensive follow-up, the implantation of an intraocular lens in well-selected eyes of children with JIA-associated uveitis is not associated with an increased risk of ocular hypertension, secondary glaucoma, cystoid macular oedema and optic disc swelling and showed better visual results up to and including 7 years after cataract extraction.

Intermediate uveitis: long-term course and visual outcome.

AIM: In this retrospective cohort study we investigated the long-term course and visual outcomes of intermediate uveitis (IU). METHODS: We performed an institutional study of patients with IU with a follow-up of at least 10 years, followed at a tertiary referral centre. RESULTS: We studied 29 patients with unilateral or bilateral IU. The average age at onset of IU was 31 (range 8-64) years. At onset, three patients (10%) had associated systemic disease (two with sarcoidosis and one with multiple sclerosis) and one patient had granuloma annulare. During the follow-up period, one additional patient was diagnosed with sarcoidosis and one with multiple sclerosis. The percentage of eyes with legal blindness and visual impairment gradually increased over time (from 9/53 (17%) at onset to 15/53 (28%) at 10-year follow-up), with macular oedema, cataract and vitreous opacities being the most common causes of vision loss. The presence of associated anterior uveitis was more frequently noted in patients younger than 20 years at onset. Remissions of intraocular inflammation of at least 1 year were noted in 10/29 (34%) of patients. The mean time-to-remission was 8.6 years; patients who had remissions were younger at the onset of IU than those with ongoing active IU (p = 0.036). Remissions of IU showed borderline association with the absence of systemic disease (p = 0.046). CONCLUSIONS: One-third of IU patients achieved a remission of their intraocular inflammation for longer than 1 year and had a mean time-to-remission of 8.6 years. Patients who were younger at onset of IU were more likely to achieve remission than those who were older at onset.

Uveitis in a tertiary ophthalmology centre in Thailand.

PURPOSE: To determine the aetiology and clinical characteristics of patients with uveitis in a tertiary ophthalmology centre in northern Thailand. METHODS: Standard ophthalmological examination and laboratory screening blood tests were performed in 200 consecutive new patients with uveitis. Patients were classified according to the location and aetiology of the uveitis. Specific clinical characteristics were recorded. DESIGN: Prospective case series. RESULTS: The case series included 106 male and 94 female patients with a mean age of 38 years. HIV-associated uveitis was noted in 31% (62/200), and included mostly patients with cytomegalovirus retinitis (85%, 53/62). In the non-HIV group, the most common anatomical type was anterior uveitis (34%, 47/138). Infectious uveitis was diagnosed in 22% (30/138) of non-HIV patients, and toxoplasmosis was the most common infection (12/138, 8.7%). The most common non-infectious clinical entities were Vogt-Koyanagi-Harada disease (20%, 22/108) and HLA-B27-associated acute anterior uveitis (9%, 10/108). CONCLUSIONS: The spectrum of uveitis in northern Thailand included 27% of HIV-infected patients with cytomegalovirus retinitis. Causes of non-HIV uveitis were similar to those often observed in the Far East, but the specific prevalences of these disorders were distinct from that found in India and Japan.

Risk factors for cystoid macular oedema in patients with uveitis.

PURPOSE: To determine ophthalmologic and systemic factors associated with the presence of cystoid macular oedema (CMO) in patients with uveitis. METHODS: Retrospective cross-sectional study in which 97 consecutive patients with uveitis filled in an extensive questionnaire for the presence of cardiovascular diseases and its risk factors. An analysis of the ophthalmologic and questionnaire data was conducted. RESULTS: CMO was present in 44% (43/97) of patients. Its presence was strongly associated with increasing age (P=0.001) and age at onset of uveitis (P<0.001). For patients older than 50 years, the risk of having CMO was 3.8-fold (95% confidence intervals 1.6-9.0) larger than for younger patients. The most frequent anatomic location of uveitis associated with CMO was panuveitis (49%). Papillary leakage on fluorescein angiography was associated with CMO (P<0.001), independently of other risk factors. After adjustment for age, multivariate logistic regression showed no association between cardiovascular disease and its risk factors and the presence of CMO. CONCLUSIONS: Age, independent of duration of uveitis, was a major risk factor for the presence of CMO in uveitis. A positive correlation between CMO and papillary leakage on angiography was noted.