Giulio Modorati

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.

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.

Immunoscintigraphy with three step monoclonal pretargeting technique in diagnosis of uveal melanoma: preliminary results.

Several problems still limit the full use of the diagnostic potential of immunoscintigraphy (IS) with technetium-99m labelled monoclonal antibodies (MoAbs) 225-28S directed to high molecular weight melanoma associated antigen (HMW-MAA). The principal problem is the unfavourable ratio of tumour to non-tumour activity (T/nT), due to the poor tumour uptake and the high aspecific uptake of the tissue surrounding the tumour. Recently, it was demonstrated that using the tumour pretargeting technique based on the injection of monoclonal antibody and the avidin/biotin system (three step immunoscintigraphy), an improvement in the T/nT ratio can be obtained in patients with carcinoembryonic antigen secreting tumours. The aim of this study was to compare the diagnostic sensitivity of traditional immunoscintigraphy with that of three step immunoscintigraphy in seven patients with uveal melanoma. All the patients underwent immunoscintigraphy with MoAb 225.28S radiolabelled with technetium-99m, and a three step immunoscintigraphy 1 week later. No patients demonstrated immediate toxic effects after receiving the reagents, no matter which of the two methods was used. The traditional immunoscintigraphy had a diagnostic sensitivity of 71.4%, diagnosing five out of seven melanomas tested. The three step study detected all the melanomas examined (7/7) with a diagnostic sensitivity of 100% and showed a drastic reduction in background. The preliminary results confirm the feasibility of visualising the uveal melanoma and show that the three step immunoscintigraphy is more diagnostically sensitive than traditional immunoscintigraphy, particularly in small lesions.

Glucose metabolism and pathological findings in uveal melanoma : Preliminary results

The aims of this study were to assess the sensitivity of positron emission tomography (PET) using [18F]fluorodeoxyglucose (18F-FDG) in the detection of uveal melanoma, and to establish the relationship between pre-operative 18F-FDG uptake and a number of pathological features of uveal melanoma. Twenty consecutive patients with a clinical diagnosis of uveal melanoma were enrolled in the study. 18F-FDG uptake was assessed in all subjects and the following parameters were assessed in 11 enucleated subjects: the mitotic index, the MIB-1 proliferating cell index, number of epithelioid cells, largest tumour diameter, tumoral necrosis and inflammatory infiltration. Tumours with a diameter less than 7.5 mm were not detected by PET, possibly because of limited spatial resolution, and only 7 of 12 tumours with a diameter greater than 7.5 mm were detected. With tumours greater than 7.5 mm in diameter, PET and 18F-FDG allow two subgroups to be distinguished: those with high and those with low glucose consumption. Apart from tumour size, 18F-FDG uptake was not related to the pathological features examined. We hypothesize that 18F-FDG uptake may be related to the ratio of viable to non-viable cells, or to the hypoxic cell fraction within the tumour.

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.

Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature.

Background:IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patients serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients. Case summary:A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV. Conclusion:The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD.

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.

Axial Length and Refraction in Retinal Vein Occlusions

To assess whether axial length and refraction are risk factors for retinal vein occlusion, we measured these parameters in 88 consecutive patients with unilateral branch retinal vein occlusion (BRVO), in 58 consecutive patients with unilateral central retinal vein occlusion (CRVO) and in 50 patients selected as a control group. Patients and controls were free or affected by systemic or local predisposing factors. We compared eyes with CRVO with control eyes, eyes with BRVO with control eyes, and eyes with CRVO with eyes with BRVO. Comparing CRVO eyes and controls, none of the investigated variables was shown to be significant. From the analysis of BRVO eyes versus controls, it resulted that refraction was the only variable which played the role of an independent prognostic factor. When comparing BRVO eyes with CRVO eyes, we found that age was slightly related to the development of BRVO. In conclusion, faulty refraction appeared to be a risk factor for the development of BRVO. We did not find any influence of axial length on the occlusion of retinal veins.