Elisabetta Miserocchi

Understanding uveitis: the impact of research on visual outcomes.

The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age. Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects. The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved.

Gamma knife radiosurgery for uveal melanoma: 12 years of experience

Aim: To present our treatment protocol and evaluate the results of Gamma knife radiosurgery (GKR) in treating patients with uveal melanoma. Methods: Seventy-eight consecutive patients with uveal melanoma underwent stereotactic radiosurgery (radiation dose 30–50 Gy) with a Leksell Gamma-Knife at the San Raffaele University Hospital, Milan, Italy between 1994 and 2006. The main outcome measures evaluated were: survival rate, local tumour control, eye retention rate, visual acuity and treatment-related complications. Results: Survival rate was 88.8% at 3 years and 81.9% at 5 years. Local tumour control was achieved in 91.0% of patients. The median tumour thickness reduction after treatment was 1.96 mm (p<0.0001) (−32.1%). The eye retention rate was 89.7%. A significant relative reduction of visual acuity was observed during follow-up. The most frequent treatment-related complications were: exudative retinopathy (33.3%), neovascular glaucoma (18.7%), radiogenic retinopathy (13.5%) and vitreous haemorrhages (10.4%). Conclusion: GKR can be considered an alternative to enucleation for the treatment of choroidal melanomas.

Review on the worldwide epidemiology of uveitis

Purpose We describe the worldwide epidemiology of uveitis through a systematic literature review. Methods Data obtained from the most relevant studies published until November 2012 were reported. Results Results of our research were structured in sections about the epidemiology of uveitis by anatomical location of inflammation (anterior, intermediate, posterior, and panuveitis), type of inflammation (infectious and noninfectious), and by age (children and elderly). Difficulties encountered analyzing the different epidemiologic studies were discussed in a dedicated section. Conclusions Limited information is available regarding the epidemiology of uveitis. Worldwide epidemiologic studies may help the clinician in the management of patients with inflammatory ocular diseases, enabling the comparison of different uveitis entities.

Long-term Treatment with Golimumab for Severe Uveitis

Abstract Purpose: To evaluate the long-term efficacy of golimumab in patients with severe recalcitrant uveitis who had inadequate response to previous biologics. Methods: Retrospective study (13 patients with JIA, 4 with HLA-B27-associated uveitis). Indication for treatment was active uveitis despite biologics. Golimumab dosing was 50 mg monthly/subcutaneously. Main outcome measures: uveitis activity, visual acuity improvement, reduction of systemic therapy (corticosteroids/immunosuppressants), adverse events. Results: Of 17 patients (34 affected eyes), response to golimumab was seen in 14 patients; at last visit uveitis was inactive in 12 patients. Three patients were nonresponders. Mean follow-up time on golimumab was 21.9 months. Visual acuity remained stable in 26 eyes, improved in 7, and worsened in 1. Mean systemic prednisolone dose before and after golimumab was 12.5–3.5 mg/day. One patient developed pulmonary infection. Conclusions: Golimumab may be a promising new therapeutic option for severe uveitis patients who have not responded to other biologics.

Abatacept in the Treatment of Severe, Longstanding, and Refractory Uveitis Associated with Juvenile Idiopathic Arthritis.

Objective. Abatacept (ABA), a selective T cell costimulation modulator that binds to CD80 and CD86 on antigen-presenting cells, was investigated for its antiinflammatory effect in treating severe chronic uveitis associated with juvenile idiopathic arthritis (JIA). Methods. Our retrospective study was conducted by members of the Multinational Interdisciplinary Working Group for Uveitis in Childhood (MIWGUC). Patients with JIA who are receiving ABA treatment for active uveitis were included. In all patients, uveitis had been refractory to previous topical and systemic corticosteroids, immunosuppressives, and at least 1 tumor necrosis factor–α inhibitor. A standardized protocol was used to document uveitis (MIWGUC) and arthritis. Baseline visit and visits at 3, 6, 9, and 12 months before and after ABA start were evaluated. Primary outcome measure was defined as achievement of uveitis inactivity; secondary outcome measures were tapering of corticosteroid and/or immunosuppressive treatment, and occurrence of complications. Results. In all, 21 patients (16 female) with active uveitis (n = 21) and arthritis (n = 18) were included (mean age 11.8 ± 3.6 yrs). In 7 of 18 patients with active arthritis at baseline, inactivity was achieved following ABA treatment. Uveitis inactivity was achieved in 11 patients, but recurred later in 8 of them, and remained active in another 10 cases. Systemic corticosteroids or immunosuppression were tapered in 3 patients, but uveitis recurred in all of them during further followup. Ocular complications secondary to uveitis were present in 17 patients at baseline, while 3 patients developed new ocular complications during followup. Conclusion. A sustained response to ABA was uncommon in patients with severe and refractory uveitis.

Quality of Life in Patients with Uveitis on Chronic Systemic Immunosuppressive Treatment

Objective: To assess health-related quality of life with Italian SF-36 in patients with uveitis on chronic systemic immunosuppressants. Methods: Consecutive patients with chronic noninfectious uveitis on systemic immunosuppressive treatment seen at the Ocular Immunology Service, San Raffaele Scientific Institute, Milan, were enrolled. Health status was evaluated with the Italian version of the SF-36 questionnaire in 8 dimensions: physical functioning, physical disability, body pain, general health, vitality, social functioning, emotional disability, mental health. Statistical analysis of variance was used to test for differences in SF-36 scores between subgroups of interest (age, sex, educational level, location and laterality of uveitis, systemic associated diseases, visual acuity, systemic treatment, duration of disease). Results: One hundred Caucasian patients (35 female, 65 male) with a median age of 46.31 years (range 10–76) were examined. Uveitis was bilateral in 88% of patients. Uveitis location was anterior (12%), intermediate (10%), posterior (34%), and panuveitis (44%). The most frequent diagnoses were idiopathic (32%), sarcoidosis (15%), and Behçet disease (15%). The SF-36 physical and mental component summary scores were lower among uveitis patients than those of the general Italian population; the most statistically significant differences found in subgroups were older age, female sex, low visual acuity (<20/40), and long-standing duration of the disease (>6 years). Conclusions: Italian patients with uveitis on chronic systemic immunosuppressants reported markedly poorer general health status than normal matched population subjects. The quality of life of these patients seems to be significantly related to visual acuity and disease duration.

Rituximab for noninfectious uveitis.

Rituximab (RTX) is a monoclonal antibody directed against the CD20 antigen expressed on B cells. This drug has been successfully employed in the treatment of non-Hodgkins lymphoma and different systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis (Wegeners) and anti-neutrophil cytoplasmic antibody-associated vasculitis. At present, RTX may be used in patients with rheumatoid arthritis who qualify for treatment with tumor necrosis factor blockers and have had an inadequate response or intolerance to one or more of these agents. In ophthalmology, there is a growing amount of literature which suggests that RTX may be useful for inflammatory ocular diseases. Only few cases have been reported on treatment of ocular inflammatory disease mostly refractory scleritis, peripheral ulcerative keratitis, uveitis in adulthood and in children with juvenile idiopathic arthritis. RTX has also been employed in ocular surface diseases such as ocular cicatricial pemphigoid and conjunctival lymphoma. The tolerability and safety of RTX is good with the most common adverse events encountered being infusion reactions. RTX may be effective in the treatment of ocular inflammatory diseases, in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation and uveitis. Although further studies are needed to assess the efficacy of RTX and the exact dosing regimen, RTX may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and other biologic agents.

Anterior Uveitis Complicating Zoledronic Acid Infusion

Zoledronic acid is the most effective treatment in patients with hypercalcemia secondary to malignancy; occasionally it can be related to ocular inflammation. We report a case of severe unilateral anterior uveitis following administration of intravenous zoledronic acid in a patient with frontal hyperostosis secondary to breast cancer. The patient developed anterior uveitis 24 hours after the administration of intravenous zoledronate. The patient was treated with topical prednisone and cycloplegic eye drops, with complete recovery after one month. This report shows that, on rare occasions, zoledronic acid can be a possible cause of acute anterior uveitis.

Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis

Background/aims To evaluate retrospectively the long-term efficacy of rituximab in patients with severe juvenile idiopathic arthritis (JIA)-associated uveitis. Methods Eight patients (15 eyes) with severe and longstanding JIA uveitis, who had an inadequate response in controlling uveitis to one or more biologic agents including tumour necrosis factor blockers and abatacept, received rituximab therapy. Rituximab was given at a dose of 1000 mg per infusion on days 1 and 15 and then every 6 months. Clinical responses to treatment, including decrease in uveitis activity, visual acuity changes, reduction of concomitant local and systemic corticosteroid and/or immunosuppressants, and occurrence of adverse events, were assessed. Results Eight patients with a mean±SD age of 22.8±5.5 years were treated. The mean ocular disease duration was 17.7 years; the mean±SD follow-up time on rituximab was 44.75±4.9 months; and the mean number of rituximab infusions received was 8.75 (range 6–12). All patients achieved complete control of uveitis, but in two patients rituximab was discontinued due to inefficacy in treating arthritis. The decrease in uveitis activity was evident 4–5 months after the first infusion. Systemic corticosteroids and immunosuppressants used in association with rituximab were discontinued in five patients at the end of follow-up. None of the patients experienced visual worsening during the follow-up. No drug-related complications were encountered. Conclusions Rituximab may be a promising effective treatment option for refractory uveitis associated with JIA leading to long-term quiescence of uveitis, particularly for patients who have not previously responded to other biologic therapies.

Clinical features of ocular herpetic infection in an italian referral center.

Purpose: The aim of this study was to describe clinical manifestations of herpetic ocular infection caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) in a referral center in Northern Italy. Methods: This retrospective study included 241 patients with herpetic ocular infection referred to the tertiary-care Ocular Immunology and Uveitis Service, at the San Raffaele Scientific Institute in Milan, from January 2006 to August 2013. The main clinical parameters evaluated were etiology, clinical features, ocular complications, and recurrences of the infection. Results: Two hundred forty-one patients (144 female and 97 male) were followed for a mean time of 24.9 ± 18.2 months (range, 12–72). One hundred eighty-nine (78.4%) patients had HSV, 45 (18.7%) had VZV, and 7 (2.9%) had CMV infection. In the HSV and VZV groups, the most frequent manifestation was keratitis (41.3% and 31.1%, respectively), followed by anterior uveitis (33.3% and 28.9%, respectively). The most common CMV presentation was retinitis (71.4%). The main complications observed were glaucoma (38.1% in HSV group, 40% in the VZV group, and 28.6% in the CMV group) and cataract (27.5% in HSV group, 26.7% in VZV group, and 28.6% in CMV group), whereas retinal detachment frequently occurred in patients with retinitis (50%, 42.9%, and 40% among HSV, VZV, and CMV patients, respectively). Recurrences were observed in 65.1%, 51.1%, and 28.6% of patients with HSV, VZV, and CMV, respectively. Conclusions: Manifestations of herpetic ocular disease in our patients are comparable with other published series. However, the rate of ocular complications and recurrences during follow-up were higher compared with other series.