Annalisa Colucci

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.

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.

Serous Retinal Detachments Complicating Interferon-α and Ribavirin Treatment in Patients with Hepatitis C

Purpose: To report the cases of two patients with chronic hepatitis C infection showing serous retinal detachments similar to Vogt-Koyanagi-Harada (VKH) disease. Methods: We reviewed the clinical records of two patients who were diagnosed with VKH-like disease during combined interferon-α (IFNα) and ribavirin treatment. Results: Interruption of IFNα and ribavirin treatment in association with oral corticosteroids resulted in a favorable visual outcome in the case of diffuse retinal detachment (case 1). On the contrary, visual acuity did not improve when late cicatricial stage disease was already present (case 2). Conclusion: There is increasing evidence of a link between hepatitis C virus infection treated with pegylated IFNα-2b and the development of VKH-like disease. Knowing the potential side effects of IFNα and ribavirin administration is fundamentally important, as is the need to closely follow up those patients that need to undergo this treatment.

Birdshot retinochoroidopathy masquerading as intraocular lymphoma.

We present a case of a patient with bilateral posterior uveitis HLA-A29 positive, masquerading intraocular lymphoma. A 43 year-old woman presented with bilateral vitritis and chorioretinal lesions compatible with “birdshot lesions”. The patient was initially diagnosed with birdshot retinochoroidopathy and later on, during follow up, the occurrence of neurologic involvement and the lack of response to systemic immunosuppression led us to re-evaluate the diagnosis. A definite diagnosis of intraocular lymphoma with central nervous system involvement was made. This case is presented to highlight the importance of careful follow-up of patients with chronic uveitis and re-evaluation of systemic symptoms and signs, in particular when ocular findings are highly suggestive for masquerade syndrome.

Ex vivo enrichment of circulating anti-tumor T cells from both cutaneous and ocular melanoma patients: clinical implications for adoptive cell transfer therapy

Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible for a limited fraction of cutaneous melanoma patients. We assessed whether an effective protocol for ex vivo T-cell expansion from peripheral blood mononuclear cells (PBMCs), suitable for ACT of both cutaneous and ocular melanoma patients, could be identified. PBMCs from both cutaneous and ocular melanoma patients were stimulated in vitro with autologous, irradiated melanoma cells (mixed lymphocyte tumor cell culture; MLTCs) in the presence of IL-2 and IL-15 followed by the rapid expansion protocol (REP). The functional activity of these T lymphocytes was characterized and compared with that of TILs. In addition, the immune infiltration in vivo of ocular melanoma lesions was analyzed. An efficient in vitro MLTC expansion of melanoma reactive T cells was achieved from all PBMC’s samples obtained in 7 cutaneous and ocular metastatic melanoma patients. Large numbers of melanoma-specific T cells could be obtained when the REP protocol was applied to these MLTCs. Most MLTCs were enriched in non-terminally differentiated TEM cells homogeneously expressing co-stimulatory molecules (e.g., NKG2D, CD28, CD134, CD137). A similar pattern of anti-tumor activity, in association with a more variable expression of co-stimulatory molecules, was detected on short-term in vitro cultured TILs isolated from the same patients. In these ocular melanoma patients, we observed an immune infiltrate with suppressive characteristics and a low rate of ex vivo growing TILs (28.5% of our cases). Our MLTC protocol overcomes this limitation, allowing the isolation of T lymphocytes with effector functions even in these patients. Thus, anti-tumor circulating PBMC-derived T cells could be efficiently isolated from melanoma patients by our novel ex vivo enrichment protocol. This protocol appears suitable for ACT studies of cutaneous and ocular melanoma patients.

Marginal zone B-cell lymphoma of the conjunctiva

Lymphomas are the most common orbital malignancies, marginal zone B-cell lymphoma being the most common histotype. One quarter of these lymphomas exhibit conjunctival involvement, which is almost exclusively observed in indolent lymphomas (96% of conjunctival lymphomas). Primary conjunctival marginal zone B-cell lymphoma exhibits interesting and peculiar features, with some molecular, biological, clinical and prognostic differences from the rest of the ocular adnexal lymphomas. Recent studies demonstrate that chromosomal abnormalities, autoimmune disorders and infectious agents are variably associated with the development and behavior of this lymphoma. Conjunctival lymphomas are rarely lethal tumors and, in selected cases, may be managed without anti-tumor treatment. In other cases, conjunctival lymphomas cause symptoms that require immediate treatment. To date, no guidelines for the management of patients with conjunctival lymphoma exist. Surgical resection, radiotherapy and chemotherapy are the most common approaches to these malignancies, but the use of systemic immunotherapy, bacteria-eradicating antibiotic therapy and local treatments, such as intralesional injections of interferon or rituximab and eyedrops of cytostatics, is progressively growing.

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery

Our aim was to prospectively analyze the use of contrast‐enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma‐knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR.