BACKGROUND: The aim of this study was to identify the main features of a cohort of Caucasian patients with idiopathic (I) and systemic disease-associated (SDA) autoimmune uveitis (AU) who were followed up at a single tertiary reference center. The study consisted of a retrospective analysis of the demographic, clinical, and laboratory features and the response to treatment of 104 patients with AU evaluated between 2004 and 2013, with a median follow-up of 4.8 years. The primary outcome measure was the response to systemic treatment after 24 months of therapy. The data are expressed as the range, percentage, or mean ± standard error. Categorical variables were assessed by Fisher's exact test. RESULTS: The mean age at diagnosis was 40.1 ± 17.8 years for men and 44.1 ± 15.3 years for women. There was a slight female predominance. Of the 104 patients, 72.1% had I-AU and 27.9% SDA-AU. The most frequent associations were with ankylosing spondyloarthritis, autoimmune thyroiditis, inflammatory bowel diseases, and Behcet's disease. Symptoms at presentation consisted of eye redness and pain (28.8%), decreased visual acuity (25.9%), and floaters (18.3%). Complications included cataracts (24%), retinal neovascularization (16.3%), chorio-retinal scars (10.6%), cystoid macular edema (8.6%), glaucoma/ocular hypertension (7.7%), epiretinal membranes (4.8%), and retinal detachment (3.8%). The prevalence of autoantibodies, mostly antinuclear antibodies, was comparable between the I-AU and SDA-AU groups. Fisher's exact test showed a direct correlation between patients with class I HLA B27, Cw8, B5 (51, 52), B51, or Cw2 and the presence of AU, whereas among patients with class II HLA, only DQ1 was a predisposing factor for AU. The therapeutic spectrum included corticosteroids and immunosuppressive agents, given either alone or in various combinations according to the severity of AU and the extent of the clinical response. Among the immunosuppressive drugs, azathioprine was preferentially used for anterior uveitis, and cyclosporine-A for intermediate and posterior uveitis. An assessment of the patients after 24 months of therapy showed a complete remission in 43.3% and a significant clinical improvement in 26.9%. CONCLUSIONS: At our tertiary reference center, the prevalence in Caucasian patients of I-AU was approximately 2.5-fold higher than that of SDA-AU. Our findings point to the need for a patient-tailored therapeutic approach according to the anatomic site and the severity of AU. Therapy should be prolonged, over a period of months and even up to 1-2 years, in order to achieve stable control of the disease and to prevent severe complications. The outcome of SDA-AU is also influenced by treatment of the underlying systemic disease. Additional controlled trials are needed to assess the efficacy and the long-term safety of both the prescribed therapeutic agents and their combinations. KEYWORDS: Ankylosing spondyloarthritis; Autoimmune uveitis; Behcet's disease; Class I and II HLA; Corticosteroids; Immunosuppressive drugs

Autoimmune uveitis (AU), an inflammatory non-infectious process of the vascular layer of the eye, can lead to visual impairment and, in the absence of a timely diagnosis and suitable therapy, can even result in total blindness. The majority of AU cases are idiopathic, whereas fewer than 20 % are associated with systemic diseases. The clinical severity of AU depends on whether the anterior, intermediate, or posterior part of the uvea is involved and may range from almost asymptomatic to rapidly sight-threatening forms. Race, genetic background, and environmental factors can also influence the clinical picture. The pathogenetic mechanism of AU is still poorly defined, given its remarkable heterogeneity and the many discrepancies between experimental and human uveitis. Even so, the onset of AU is thought to be related to an aberrant T cell-mediated immune response, triggered by inflammation and directed against retinal or cross-reactive antigens. B cells may also play a role in uveal antigen presentation and in the subsequent activation of T cells. The management of AU remains a challenge for clinicians, especially because of the paucity of randomized clinical trials that have systematically evaluated the effectiveness of different drugs. In addition to topical treatment, several different therapeutic options are available, although a standardized regimen is thus far lacking. Current guidelines recommend corticosteroids as the first-line therapy for patients with active AU. Immunosuppressive drugs may be subsequently required to treat steroid-resistant AU and for steroid-sparing purposes. The recent introduction of biological agents, such as those targeting tumor necrosis factor-α, is expected to remarkably increase the percentages of responders and to prevent irreversible sight impairment. This paper reviews the clinical features of AU and its crucial pathogenetic targets in relation to the current therapeutic perspectives. Also, the largest clinical trials conducted in the last 12 years for the treatment of AU are summarized and critically discussed.

Background To evaluate the efficacy and safety of low-fluence-rate photodynamic therapy (LFPDT) to treat choroidal neovascularisation (CNV) secondary to pathological myopia (PM). Methods Twenty-five eyes with CNV in PM underwent LFPDT, with a standard dose of verteporfin and timing but adopting fluence and irradiance rates reduced to 25 mJ/cm2 and 300 mW/cm2, respectively. Best corrected visual acuity (BCVA) was measured and biomicroscopy and fluorescein angiography (FA) were evaluated. Particular attention was paid to choroidal hypoperfusion, and to changes (depigmentation/atrophy) at the RPE level in areas exposed to laser light. Results After a mean follow-up of 13.4 ± 2.46 months (range: 12–21), and 1.37 ± 0.66 treatments (range: 1–3), BCVA was stable in 29 (91%) eyes. Two (6%) patients gained more than three lines and one (3%) eye lost more than three lines. Mean greatest linear dimension did not change significantly (p = 0.08) at the end of follow-up. RPE depigmentation was present in six eyes (18%) and no patient showed RPE atrophy. Conclusions LFPDT is effective and safe for CNV secondary to PM treatment, stabilizing visual acuity and lesion size and determining only mild RPE changes. Further controlled studies are needed to demonstrate the long-term efficacy and safety of this treatment option.

Orbital pseudotumor is a benign, idiopathic, non-infectious and non-neoplastic clinical syndrome characterized by the presence of an inflammatory mass at orbital level with no identifiable cause. The disease is rarely observed in the pediatric population. This article describes a relapsing bilateral orbital pseudotumor in a young girl. The diagnostic implications and treatment strategies are discussed.

Purpose: Description of a patient with a solitary cyst of the pupillary margin iris pigment epithelium (IPE). Methods: A 63-year-old man referred a suspected iris-ciliary body melanoma in his left eye. Based on both clinical examination and ultrasound biomicroscopy, melanoma was considered unlikely. Surgery was under-taken to correct recurrent deterioration of vision due to movement of the lesion across the visual axis. Results: The lesion was excised completely. Ultrasound biomicroscopy and histopathological examination ruled out melanoma and allowed a final diagnosis of primary pupillary margin cyst of the IPE, characterized of pig-mented epithelium, with no connective tissue or vessels. No recurrences or fresh lesions appeared during a one-year follow-up. Conclusions: Primary epithelial iris cysts are usually benign. Treatment is required only in symptomatic patients and those with an uncertain diagnosis. Ultrasound biomicroscopy is indispensable to confirm the clinical diagnosis, follow the clinical course and intervene if surgery is required.

Purpose: To evaluate circulating CD4+CD25+ regulatory T-cell populations in patients with autoimmune uveitis and to assess whether T-regulatory cell populations correlate with clinical features. Methods: Sixty-four patients with noninfectious uveitis were enrolled. Following isolation and purification of peripheral blood mononuclear cells, Tregs were analyzed by assessing FOXP3 expression on T cells with an APC anti-human FOXP3 staining kit. Samples were simultaneously stained with anti-CD25-PeCy7, anti-CD3- FITC, anti-CD4-PercP, and anti-CD152 (CTLA-4)-PE monoclonal antibodies. Results: A decrease in CD4+CD25+FOXP3+ T cells was detected in patients with active uveitis compared with healthy controls (p < .05). In patients achieving clinical remission, the percentage of CD4+CD25+FOXP3+ T cells increased up to values comparable to those of healthy controls, in step with an increased expression of CTLA4. Conclusion: Therapy of autoimmune uveitis results in the increase of T-regulatory lymphocyte population and restoration of their functional state. These changes are likely to contribute to the patients' clinical improvement or disease regression.