Uveal melanoma (UM) is the most common intraocular malignancy and arises from melanocytes in the iris, ciliary body, or choroid. Early diagnosis and local treatment is crucial, as survival correlates with primary tumor size. However, approximately 50% of patients will develop metastatic disease with 6-12 months' survival from metastatic diagnosis. Genomic analyses have led to the development of gene-expression profiles that effectively predict metastatic progression; unfortunately, no adjuvant therapy has been shown to prolong survival to date. New insights into the molecular biology of UM have found frequent activating mutations in genes encoding for the G-protein α-subunit, GNAQ and GNA11, and improved understanding of the downstream signaling pathways MAPK, PI3K/Akt, and Hippo have afforded an array of new targets for treatment of this disease. Studies are under way with rationally developed regimens targeting these pathways, and novel agents are under development. We review the diagnosis, management, and surveillance of primary UM and the adjuvant therapy trials under way.

/pdf/uveal-melanoma-epidemiology-etiology-and-treatment-of-3vovismy5b.pdf

Uveal Melanoma: Epidemiology, Etiology, and Treatment of Primary Disease

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

https://journals.sagepub.com/doi/pdf/10.1177/1758834018757175

Treatment of uveal melanoma: where are we now?

Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

/pdf/combinations-of-radiation-therapy-and-immunotherapy-for-51mwp7ajji.pdf

Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes.

Iodine brachytherapy as an alternative to enucleation for large uveal melanomas

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 were treated with the stereotactic radiosurgery (radiation dose 30-50 Gy) with Leksell Gamma-Knife at the San Raffaele University Hospital, Milan, Italy between 1994 and 2006. The main outcome measures evaluated were: survival rate, local tumor control, eye retention rate, visual acuity, treatment-related complications. Results: Survival rate was 88.8% at 3 years and 81.9% at 5 years. Local tumor control was achieved in 91.0% of patients. The median tumor thickness reduction after treatment was 1.96 mm (p Conclusion: GKR can be considered an alternative to enucleation for the treatment of choroidal melanomas.

https://bjo.bmj.com/content/bjophthalmol/93/1/40.full.pdf

Gamma knife radiosurgery for uveal melanoma: 12 years of experience

Incidence of radiation retinopathy after high-dosage single-fraction gamma knife radiosurgery for choroidal melanoma.

Object. The authors compared the results of gamma knife radiosurgery in patients with uveal melanoma who underwent high-dose (treated from 1992–1995) and low-dose irradiation (treated from 1996–2002). Methods. Thirty-one patients with uveal melanomas were treated with a mean margin dose of 52.1 Gy (high dose) and 33 with a mean dose of 41.5 Gy (low dose), and results were compared between groups. The technical procedure was the same in each group except for radiation dose. In the low-dose group, complete tumor regression (scar formation) occurred in 12% and in the high-dose group in 26%. Partial regression (reduction of the tumor prominence between 50 and 80%) occurred in 81% of the low-dose group and in 58% of the high-dose group. Neovascular glaucoma as a severe complication developed in 9% of the low-dose group and in 48% of the high-dose group. Conclusions. Reduction of the margin dose from 52.1 to 41.5 Gy appears to achieve the same rate of tumor regression but is associated with a lower rate of seve...

High- compared with low-dose radiosurgery for uveal melanomas

BACKGROUND/AIM Until recently, diagnosis of disorders of the lacrimal system has depended on digital dacryocystography and on clinical examinations such as the fluorescein dye test, lacrimal probing, and irrigation. The lacrimal system and its mucous membranes can now be viewed directly with a lacrimal endoscope. While the first endoscopes were rigid and limited by poor picture quality in axial illuminations, the new generation of endoscopes are a great leap forward for new diagnostic and therapeutic approaches. METHODS 132 patients ranging in age from 8 months to 73 years with nasolacrimal obstruction were referred to the lacrimal department. Diagnostic lacrimal imaging utilising various small calibre endoscopes less than 0.5 mm in external diameter was performed. The endoscopes are coupled to specially designed lacrimal probes as well as a CCD camera and a video recorder. The imaging was performed during standard lacrimal probing and irrigation in an outpatient clinic setting in 120 of 132 patients RESULTS All patients reported the pain of endoscopy as being similar to that of standard lacrimal probing and irrigation. No adverse effects such as bleeding or lacrimal perforation were noted. Endoscopic manipulation was not too difficult and the picture quality, depth of focus, and illumination were satisfactory in all cases. The most common site of stenosis was the nasolacrimal duct (59 patients), followed by the lacrimal sac (39 patients) and the canaliculi (34 patients). In 25 patients, partial obstruction, rather than complete stenosis, was visualised as a narrow lumen, which widened during irrigation. In 14 of 28 patients, obstruction was due to canalicular submucosal folds and was removed with laser. In addition, the colour and consistency of the lining mucosa correlated with type of obstruction. Normal mucosa is smooth and light pink in colour. Inflammatory changes manifest as thickened and reddish grey mucosa. More complete stenosis is shown as fibrotic plaques with grey white inelastic membranes. CONCLUSION Lacrimal endoscopy is a new, non-invasive method used to view directly and localise obstructions precisely. It allows differentiation between inflammatory, partial, and complete stenosis. Endoscopy enables one to choose the appropriate surgical therapy for patients. Patients tolerated the procedure well without any adverse reactions or effects. While it may not replace standard probing and irrigation, this technique is an extremely useful adjunct in determining the proper surgical modality, ease, and tolerance of the endoscopic manipulation by patients, and obtaining sharp and clear images of the nasolacrimal outflow system anatomy and pathology. Differentiation of various types of obstruction by precise location and severity can be achieved.

https://bjo.bmj.com/content/bjophthalmol/83/8/949.full.pdf

Endoscopy of the lacrimal system

In diesem Beitrag wird uber die Erfahrungen bezuglich Vertraglichkeit und Wirksamkeit einer adjuvanten Interferon-alfa-2b-Behandlung beim Aderhautmelanom berichtet. 39 Patienten (23 Manner und 16 Frauen im Alter von 35–78 Jahren, Durchschnittsalter 56,5 Jahre) mit Aderhautmelanom wurden nach Abschluss der Behandlung ihres Primartumors einer adjuvanten Therapie mit Interferon alfa-2b (3 Mio Einheiten 3-mal pro Woche subkutan) fur 1 Jahr unterzogen. Bei allen Patienten wurde Alter, Geschlecht, Horizontaldurchmesser und Vertikaldurchmesser des Melanoms, Behandlung des Primartumors, Nebenwirkungen der Interferontherapie und Uberleben dokumentiert. Bei 31 der 39 Patienten (80%) wurde die Behandlung uber 1 Jahr durchgefuhrt. Bei 18 Patienten (46%) kam es zum Auftreten von Nebenwirkungen wie Leukopenie, Thrombopenie, Herzbeschwerden, Erhohung der Leberwerte und Schwindel (WHO Grad I–III) die zu einer Dosisreduktion fuhrten. Bei 8 Patienten musste die Behandlung abgebrochen werden: bei 5 Patienten wegen des Auftretens schwerster Nebenwirkungen und bei 3 Patienten wegen Metastasierung. Weder in der univariaten Analyse noch in der multivariaten Analyse konnte ein verbessertes Uberleben durch die Interferonbehandlung gezeigt werden. Eine adjuvante Behandlung des Aderhautmelanoms mit Interferon alfa sollte erst durchgefuhrt werden, wenn die Frage von Dosis und Administration fur das kutane Melanom gelost ist.

Verträglichkeit und Wirksamkeit einer adjuvanten Interferon- alfa-2b-Behandlung beim Aderhautmelanom

The development of the orbits in 70 human fetal skulls was investigated by measuring the width and height of the orbital entrance, as well as the volume and depth of the orbital cavity and the interorbital width. For determination of the orbital volume, we used the imprint method; the remaining parameters were estimated. Our measurements showed a linear growth rate for the orbital width, height, and depth. After transformation to the cubic root, the values of the orbital volume also demonstrated a linear increase. The orbital index (height/width × 100) expressed the change in the oval outline of the orbital entrance during fetal development from a flat, wide form to a nearly round form at birth. No statistically significant difference between the right and left orbit was found.

Fetal development of the human orbit

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