Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study

Purpose: To evaluate the short-term efficacy of intravitreal adalimumab (IVA) for the treatment of eyes with active noninfectious uveitis.

Methods: Consecutive eyes with active noninfectious uveitis were injected with IVA at 0, 2, then every 4 weeks for total of 26 weeks.

Results: Six out of 7 patients (12 of 13 eyes) completed 26 weeks of treatment. One patient (1 eye) failed treatment. Seven out of 12 eyes had improvement of ≥2 ETDRS lines. Three out of three eyes had resolution of anterior chamber cells. And 9 of 10 eyes with vitreous haze had zero haze at 26 weeks. Five out of 8 eyes with macular edema had complete resolution. Median fluorescein angiography score improved from 14 to 4 on last follow-up.

Conclusions: IVA was effective in controlling the inflammation, decreasing the macular edema, and improving the best corrected visual acuity in the majority of eyes in this series.     

Patterns of Uveitis at Two University-Based Referral Centres in Cape Town,South Africa

Purpose: To analyze the pattern of uveitis at two tertiary hospitals in South Africa which has a high prevalence of HIV, TB and syphilis.

Methods: Data of 198 patients were obtained retrospectively between August 2014 and August 2016, including patient demographics, clinical examination, special investigations and final diagnosis.

Results: Infectious uveitis was the most common aetiological category (47%), followed by idiopathic (34.8%) and non-infectious (18.2%). Syphilis was the most common identifiable cause (16.2%). Other important causes were toxoplasmosis, herpes viruses, tuberculosis and HLA-B27. HIV positive patients, who constituted 40% of the study population, were more likely to present with a posterior or panuveitis (relative risk 1.50, 95% CI 1.19–1.89) and more likely to have an infectious cause compared to HIV negative patients (relative risk 2.47, 95% CI 1.82–3.35).

Conclusions: This study emphasizes the importance of HIV testing and investigations for infectious causes of uveitis, especially syphilis, in this population.     

Visual Functioning and Health-related Quality-of-Life are Compromised in Patients with Uveitis

Purpose: To assess the vision-related (VR) and health-related (HR) quality-of-life (QoL) of patients with uveitis.

Methods: In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form.

Results: Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.05) and lower VR-QoL (p<0.001) than patients with DR. For patients with uveitis, multiple linear regression analyses indicated that lower HR-QoL scores were predicted by younger age (p<0.01), while lower VR-QoL scores were predicted by poorer visual acuity (p<0.001), ocular comorbidities (p<0.05), and female sex (p<0.05).

Conclusions: Patients with uveitis have significantly poorer VR- and HR-QoL than healthy control subjects. Uveitis has a more debilitating impact on VR-QoL than DR.     

Complications in Intermediate Uveitis: Prevalence,Time of Onset,and Effects on Vision in Short-Term and Long-Term Follow-Up

Purpose: To study the prevalence and time of onset of ocular complications in intermediate uveitis (IU) and to assess their effects on visual outcome in short-term and long-term follow-up.

Methods: A retrospective cohort study of patients with IU who had a minimal follow-up of one year.

Results: 96 patients (174 eyes, 70% females) were included with a mean age at presentation of 30 years. Children constituted 38% of all patients. Mean follow- up was 64.9 months. Pars planitis was the most common form followed by sarcoidosis and multiple sclerosis. Cystoid macular edema (CME), cataract, epiretinal membrane and posterior synechiae were the most prevalent complications. Posterior synechiae, band keratopathy, cataract and papillitis at presentation were associated with worse presenting visual acuity (VA). Of the late-onset complications, glaucoma/ocular hypertension (OHT) was the most significantly associated with worse long-term VA. Most sight-threatening complications (namely CME and glaucoma) were diagnosed at presentation while late complications predominantly affected the posterior segment and included among others peripheral retinal elevations, vasoproliferative tumors, and vitreous hemorrhage. Median LogMAR VA improved at short-term and long-term follow-up, from 0.2 to 0.1 (p<0.001). Subgroup analysis revealed significant VA improvement for eyes with all the different complications except for eyes with glaucoma/OHT.

Conclusion: IU is a chronic low-grade uveitis that may be associated with protean early and late complications of the anterior or posterior segments or both. Optimal treatment regimens are imperative for the strict control of inflammation and proper management of complications thus allowing a favorable long-term prognosis.     

Anxiety and Depression among Patients with Uveitis and Ocular Inflammatory Disease at a Tertiary Center in Southern Thailand: Vision-Related Quality of Life,Sociodemographics, and Clinical Characteristics Associated

Purpose: To estimate the prevalence of positive anxiety and depression screening in patients with ocular inflammatory disease (OID). The predictors associated with anxiety and depressive symptoms were investigated.

Methods: A cross-sectional study was conducted. The Thai Hospital Anxiety and Depression Scale (HADS), a sociodemographic questionnaire, and the Thai Visual Functioning Questionnaire 28 were administered to all participants. Associations were estimated using the Cox regression.

Results: Of the 86 participants, 12.8% and 8.1% screened positive for anxiety and depression, respectively. Predictors of an increase in both HADS-Anxiety and HADS-Depression scores comprised poor understanding of OIDs [adjusted relative probability (aRP) = 1.56; p = 0.021 and 1.59; p = 0.012, respectively], and low overall composite score (aRP = 1.45; p = 0.022 and 1.6; p = 0.002, respectively).

Conclusions: Approximately one-tenth of our patients screened positive for anxiety and depression. Patients with poor understanding of their OID and poor self-reported visual function were at an increased risk.     

Uveitis in Patients Treated with CTLA-4 and PD-1 Checkpoint Blockade Inhibition

ABSTRACT

Purpose: To investigate the link between treatment with CTLA-4 and PD-1 checkpoint blockade inhibitors and the development of noninfectious uveitis.

Methods: A survey was distributed to uveitis specialists to identify patients who developed uveitis while receiving either PD-1 inhibitors pembrolizumab and nivolumab; PD-L1 inhibitors atezolizumab, avelumab, and durvalumab; or the CTLA-4 inhibitor ipilimumab.

Results: Fifteen patients from seven institutions were identified. The most common cancer diagnosis (13/15) was malignant melanoma. Fourteen patients had a new uveitis diagnosis following checkpoint blockade administration (six anterior uveitis, six panuveitis, one posterior uveitis, one anterior/intermediate combined); one patient developed optic neuritis. Uveitis was diagnosed within 6 months after drug initiation for 11/12 patients (median 63 days). Corticosteroid treatment was effective for most patients, although two patients had permanent loss of vision.

Conclusions: Patients on checkpoint inhibitor therapy should be educated to seek care if they develop ocular symptoms, and prompt referral to specialists should be incorporated into oncology protocols.     

Clinical Patterns and Causes of Intraocular Inflammation in a Uveitis Patient Cohort from Egypt

Purpose: To analyze the patterns and causes of intraocular inflammation in patients attending uveitis referral clinics in Egypt.

Methods: The study included 454 patients with uveitis examined both at the Department of Ophthalmology, Alexandria Faculty of Medicine, and tertiary uveitis referral clinics in Cairo and the International Eye Clinic in Upper Egypt, between August 2013 and March 2016. All patients had a comprehensive ocular examination and systemic work-up. Standard diagnostic criteria for uveitis syndromes were employed for all patients and ancillary ocular or systemic investigations were ordered as required by the suspected uveitis entity.

Results: The mean age at presentation was 30 years (range: 4–75). The male to female ratio was 1.1:1. Panuveitis was the most common anatomic pattern (43%), followed by anterior (40.7%), posterior (9%), and intermediate uveitis (7.3%). Anterior uveitis was most commonly attributed to pediatric parasitic anterior chamber granulomas (22.2%). Intermediate uveitis was most commonly idiopathic (81.8%). Toxoplasma retinitis was the most common cause of posterior uveitis (31.7%). Behçet disease was the most common cause of panuveitis followed by Vogt–Koyanagi–Harada (VKH) disease (45.6% and 22.1%, respectively). Among non-infectious etiologies, Behçet disease was the most frequent etiology (28.6%), while for infectious causes, herpetic uveitis was found to be the most frequent cause (39.8%).

Conclusions: In this uveitis patient population from Egypt, panuveitis was the most commonly encountered anatomic diagnosis. Behçet disease was the most common identified cause of uveitis followed by VKH disease. Herpes-related uveitides and parasitic granulomas represented the most evident causes of infectious uveitis.     

非感染性眼部炎症治疗进展

非感染性眼部炎症是世界范围内主要的致盲性眼病之一，常常提示系统性自身免疫性疾病的发生。目前的治疗方法主要是使用皮质类固醇激素和免疫抑制剂。然而，常规治疗并非对所有患者均有效，因此还需给予生物反应调节剂治疗。生物反应调节剂从本质上更为有效，但通常不是首选药物。尽管如此，由于眼部独特的生理解剖学特征和自身免疫性疾病的整体复杂性，非感染性眼部炎症的治疗后缓解率无明显改善。新出现的生物药物制剂和纳米技术在药物传输系统中的应用，有望大大改善非感染性眼部炎症的临床疗效。     

Ocular toxoplasmosis II: clinical features,pathology and management

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis.     

Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis

In this article, we report a literature-based metanalysis we have conducted to outline the clinical features of the HLA-B27 Acute Anterior Uveitis (AAU). The examined material was based on observational studies in which participants were affected by Acute Anterior Uveitis and divided into HLA B27+ and HLA B27–. We performed a search on articles with the words “HLA B27 uveitis” dated before May 2014. Among these, 29 articles were selected for a second review. After a further evaluation, 22 articles were analyzed. The clinical characteristics studied in the metanalysis were: (1) systemic disease; (2) sex distribution; (3) laterality; (4) visual acuity; (5) hypopion; (6) anterior chamber’s fibrin; (7) elevated intraocular pressure (IOP) during inflammation; (8) glaucoma; (9) posterior synechiae; (10) cataract; (11) cystoid macular edema; (12) papillitis. We have calculated a relative risk (RR) for each outcome measured. The results obtained remark some of the peculiar features linked to the HLA B27 Acute Anterior Uveitis, such as strong association with ankylosing spondylitis (RR = 6.80) and systemic diseases (RR = 9.9), male prevalence (RR = 1.2), unilateral (RR = 1.1) or alternating bilateral (RR = 2.2) involvement, hypopion (RR = 5.5), fibrinous reaction and even papillitis (R = 7.7). Simultaneous bilateral (RR = 0.3) AAU is more frequent in HLA-B27 negative form. We report higher risk of elevated IOP and glaucoma (RR = 0.6) in B27– Acute Anterior Uveitis. No significant difference between HLA B 27 positive and negative AAU was observed according to final visual acuity and complications such as posterior synechiae, cataract, and maculare edema. We trust that this will inform on the clinical evaluation and therapeutic decision in addressing a still ill-defined ophthalmologic condition.     

Clinical Features and Prognosis of Uveitis in a Turkish Patient Population with Ankylosing Spondylitis: Incidence and Management of Ocular Complications

Purpose: To investigate clinical features, visual prognosis, and ocular complications in patients with ankylosing spondylitis (AS)-associated anterior uveitis (AU).

Methods: Data of 211 eyes of 145 patients with AU associated with AS were reviewed retrospectively.

Results: Mean follow-up time was 6.31 ± 6.33 years. Men were younger than women at AS diagnosis (p = 0.035). The mean number of uveitis flares was highest during the first quarter of the year and lowest during the third quarter (p = 0.017). Immunosuppressive agent use was higher in women than men (p = 0.052). Ocular complications developed in 120 eyes (56.9%), and the complication rate was 0.146/eye year. Males developed cystoid macular edema more frequently than females (p = 0.05). Glaucoma was observed more often in early-onset disease (age at AS onset <45 years) than late-onset disease (p = 0.028).

Conclusions: Visual prognosis of AU in patients with AS was good, although more than half of the eyes developed ocular complications (56.9%).     

Analysis of HLA Class I and Class II Gene Polymorphisms in Japanese Patients with Human T-Cell Lymphotropic Virus Type 1-Associated Uveitis

Purpose: To investigate the immunogenetic background of human T-cell lymphotropic virus type 1 (HTLV-1)-associated uveitis (HAU) that presents immune-mediated reactive changes in the uvea. Methods: HLA class I and class II genes were studied in 51 patients with HAU, 192 asymptomatic HTLV-1 carriers, and 266 HTLV-1-seronegative controls using a high-resolution method of HLA DNA typing. The HLA alleles of HAU were compared with those of HTLV-1 carriers and healthy controls. Results: We identified 62 distinct alleles of HLA-A, HLA-Cw, and HLA-B and 49 distinct alleles of HLA-DRB1 and HLA-DQB1 in patients with HAU, asymptomatic HTLV-1 carriers, and healthy controls. The relative frequencies of these HLA alleles did not differ among the three groups. Conclusion: The results suggest that HLA class I and class II genes do not contribute to susceptibility to HAU.     

Increased Circulating Proinflammatory T Lymphocytes in Children with Different Forms of Anterior Uveitis: Results from a Pilot Study

Purpose: To characterize peripheral blood T cells in juvenile idiopathic arthritis-associated uveitis (JIAU).

Methods: Blood samples were taken from children with JIAU (n = 18), JIA without ocular involvement (n = 11), idiopathic anterior uveitis (IAU, n = 12), and healthy controls (n = 11). Cells were stained for T cell surface markers, and intracellular cytokine staining was performed after cell stimulation and analyzed by flow cytometry.

Results: The Th1/Th2 ratio was increased in JIAU patients. Numbers of IL-13-expressing cells an level of IL-13 and IL-10 expression per cell were increased in all patient groups; whereas, percentages of IL-5-expressing T cells were decreased. Numbers of proinflammatory Th17 cells and T cells expressing CTLA-4 were increased in all patient groups; whereas, γ/δ T cell numbers were decreased. Results from JIA and IAU were similar.

Conclusion: T cell subtypes and potential T cell function are altered in pediatric patients with uveitis and arthritis as compared to healthy children.     

Comparison of the Treatment Results for Behçet Uveitis in Patients Treated with Infliximab and Interferon

ABSTRACT

Purpose: To compare the efficacy and safety of infliximab and interferon in patients with refractory Behçet uveitis.

Methods: Medical records of 20 patients treated with infliximab (IFX) and 33 patients treated with interferon (IFN) were retrospectively analyzed by evaluating the number of uveitis attacks, visual acuity and ocular inflammation at 6 and 12 months after initiation of treatment.

Results: Mean duration of treatment was 22 ± 18 months in IFX group and 30.3 ± 22.5 months in IFN group. Sixteen patients of IFX group (80%) and 28 patients of IFN group (85%) achieved remission. In both groups, the mean best-corrected visual acuity and all inflammatory parameters improved. In terms of these parameters, there was no significant difference between the two groups.

Conclusion: Infliximab and interferon improve control of ocular inflammation and efficiently decrease the relapse rate. Our results determined no significant difference between two agents in controlling intraocular inflammation.