Bożena Romanowska-Dixon

Circulating antiretinal antibodies predict the outcome of anti-VEGF therapy in patients with exudative age-related macular degeneration.

Purpose:  To determine serum antiretinal antibody (ARA) levels in response to treatment with intravitreal bevacizumab of exudative age‐related macular degeneration (AMD).

Experimental ruthenium plaque therapy of amelanotic and melanotic melanomas in the hamster eye.

&NA; The effects of &bgr;‐radiation on melanoma implanted into the hamsters eye were investigated. Two Bomirski hamster melanomas (BHMs), differing in their melanin content, were compared with regard to their radiosensitivity to ruthenium‐106 (106Ru) radiation. Tumours growing in the iris were irradiated with 3, 6 or 10 Gy of 106Ru given as a single dose or in four fractions at 24 h intervals. Tumour growth kinetics and distant metastases were studied, and the eyeballs were examined histologically. Dose‐dependent delay of tumour growth was observed in both melanomas. After treatment with a dose of 6 Gy, the Ab amelanotic tumours grew 2.6 times slower, and the Ma melanotic tumours 1.4 times slower than untreated ones. The location of metastases differed in the two tested lines — pigmented metastases were found mainly in the lungs, while unpigmented metastases were found mainly in the kidneys. Histopathological analysis showed signs of blood vessel damage such as endothelial cells swelling, erythrocyte extravasation and tumour necrosis. This last finding increased with the rising dose of &bgr;‐radiation. Pigmented tumours were found to be two times more resistant to &bgr;‐radiation than amelanotic ones. The pattern of metastases of BHMs is determined by the type of melanoma (Ab or Ma). Exposure to &bgr;‐radiation from 106Ru did not significantly affect either the number or size of metastases except at a dose of 10 Gy. This dose caused a statistically significant decrease in the number of metastases in the Ma melanotic subline.

Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration

To determine changes in anti‐retinal antibodies (ARAs) during anti‐VEGF therapy in patients with exudative age‐related macular degeneration (AMD) and to assess the correlations between ARAs and disease activity.

Proteomic Analysis of Proton Beam Irradiated Human Melanoma Cells

Proton beam irradiation is a form of advanced radiotherapy providing superior distributions of a low LET radiation dose relative to that of photon therapy for the treatment of cancer. Even though this clinical treatment has been developing for several decades, the proton radiobiology critical to the optimization of proton radiotherapy is far from being understood. Proteomic changes were analyzed in human melanoma cells treated with a sublethal dose (3 Gy) of proton beam irradiation. The results were compared with untreated cells. Two-dimensional electrophoresis was performed with mass spectrometry to identify the proteins. At the dose of 3 Gy a minimal slowdown in proliferation rate was seen, as well as some DNA damage. After allowing time for damage repair, the proteomic analysis was performed. In total 17 protein levels were found to significantly (more than 1.5 times) change: 4 downregulated and 13 upregulated. Functionally, they represent four categories: (i) DNA repair and RNA regulation (VCP, MVP, STRAP, FAB-2, Lamine A/C, GAPDH), (ii) cell survival and stress response (STRAP, MCM7, Annexin 7, MVP, Caprin-1, PDCD6, VCP, HSP70), (iii) cell metabolism (TIM, GAPDH, VCP), and (iv) cytoskeleton and motility (Moesin, Actinin 4, FAB-2, Vimentin, Annexin 7, Lamine A/C, Lamine B). A substantial decrease (2.3 x) was seen in the level of vimentin, a marker of epithelial to mesenchymal transition and the metastatic properties of melanoma.

Angiomorphology of the pigmented bomirski melanoma growing in hamster eye

An melanotic line of Bomirski Hamster Melanoma (BHM Ma) was implanted into the anterior chamber of the hamster eye and the ensuring vascular system was studied using scanning electron microscopy (SEM) of vascular corrosion casts. The tumor vasculature, induced mainly from the host iris vessels, showed generally disorganized and irregular patterns. Tortuous tumor capillaries of uneven contour with local dilatations and constrictions were drained by markedly dilated, thin-walled, venous vessels connected with the eye veins. Vascular sprouting and, less frequently, intussusceptive formation of new vessels were observed at the periphery and also within the tumor mass. The presence of numerous nodular outgrowths, varying in size, on the surface of dilated venules and venous vessels represent morphological evidence for continuous remodeling of the tumor vasculature. The observed features of the vascular system seem to provide a pathway for further tumor expansion. Our study showed that BHM Ma line, originating from an aggressive skin melanotic melanoma, implanted to the eye anterior chamber gave rise to rapidly growing tumors with the capability of inducing abundant vasculature which allows metastasis to the lungs, kidneys and regional lymph-nodes.

Ruthenium-106 Plaque Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome

Diffuse choroidal hemangiomas associated with Sturge-Weber syndrome (SWS) are classically treated with external beam radiotherapy (EBR), but there are a few reports usually of single cases indicating the usefulness of plaque therapy. We present our observations on two cases of diffuse choroidal hemangiomas with exudative retinal detachment associated with SWS treated with Ruthenium-106 plaque therapy. Outcomes included best-corrected visual acuity (BCVA) and regression in tumor thickness measured by ultrasonography. The initial BCVA of the affected eyes was counting fingers at 1 meter and light projection. Pretreatment tumors thickness was 3.5 mm and 4.7 mm. In a follow-up period of 18–24 months, significant reduction in thickness of choroidal hemangiomas up to 1.2 mm and 1.4 mm with prompt resolution of exudative retinal detachment was observed. BCVA achieved 20/200 and 20/400, respectively. The findings in this paper indicate that Ruthenium-106 plaque therapy is effective in treatment of diffuse choroidal hemangiomas associated with SWS.

Intraocular pressure and ocular hemodynamics in patients with primary open-angle glaucoma treated with the combination of morning dosing of bimatoprost and dorzolamide hydrochloride

Acta Ophthalmol. 2011: 89: e57–e63

Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

THE ANALYSIS OF SPONTANEOUS CLOSURE MECHANISMS AND REGENERATION OF RETINAL LAYERS OF A FULL-THICKNESS MACULAR HOLE: Relationship with Visual Acuity Improvement.

Purpose: To analyze the spontaneous closure mechanisms, retinal layer regeneration, and best corrected visual acuity (BCVA) in the full-thickness macular hole (FMTH). Methods: Ten eyes of 10 patients were studied. The measured outcomes included the time of persisting clinical symptoms and spontaneous closure of FTMH, BCVA, and spectral domain optical coherence tomography (SD-OCT) of vitreomacular interface. Results: In a follow-up period, all eyes showed closure of FTMH (closure range: 3–64 weeks). The “bridging” phenomenon was a main mechanism of a spontaneous FMTH closure. Additionally, posterior vitreous detachment with the release of vitreomacular traction was observed in 4 eyes (40%). The statistical analysis showed that shorter the duration of symptoms, shorter the duration of the spontaneous FTMH closure (r = 0 673, P < 0 05). No significant association was observed between the time of spontaneous closure FTMH, the age of patients, and BCVA. The regeneration of the outer nuclear layer (ONL) and external limiting membrane (ELM) was confirmed in 10 and 9 eyes, respectively. In six eyes, connections between inner and outer segments of photoreceptors were rebuilt; in these cases, the final BCVA was the best. None of the eyes showed the regeneration of the connections between the outer segments of photoreceptor and retinal pigment epithelium (RPE). Conclusion: The main mechanism leading to a spontaneous closure of FTMH is the “bridging” phenomenon. Vitreous detachment and vitreomacular traction release are not necessary conditions promoting the closure of FTMH. Shorter duration of symptoms and regeneration of photoreceptors IS/OS interface provide a better final BCVA.

The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group

PURPOSE To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN Retrospective, multicenter observational study. PARTICIPANTS Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups.