Magnetic Hyperthermia in Y79 Retinoblastoma and ARPE-19 Retinal Epithelial Cells: Tumor Selective Apoptotic Activity of Iron Oxide Nanoparticle.

PURPOSE: To evaluate selective apoptosis of Y79 retinoblastoma versus ARPE-19 retinal pigment epithelial cells by using different doses of dextran-coated iron oxide nanoparticles (DCIONs) in a magnetic hyperthermia paradigm. METHODS: Y79 and ARPE-19 cells were exposed to different concentrations of DCIONs, namely, 0.25, 0.5, 0.75, and 1 mg/ml. After 2 hours of incubation, cells were exposed to a magnetic field with a frequency of 250 kHz and an amplitude of 4 kA/m for 30 minutes to raise the cellular temperature between 42 and 46°C. Y79 and ARPE-19 cells incubated with DCION without magnetic field exposure were used as controls. Cell viability and apoptosis were assessed at 4, 24, and 72 hours after hyperthermia treatment. RESULTS: At 4 hours following magnetic hyperthermia, cell death for Y79 cells was 1%, 8%, 17%, and 17% for 0.25, 0.5, 0.75 and 1 mg/ml of DCION, respectively. Cell death increased to 47%, 59%, 70%, and 75% at 24 hours and 16%, 45%, 50%, and 56% at 72 hours for 0.25, 0.5, 0.75, and 1 mg/ml of DCIONs, respectively. Magnetic hyperthermia did not have any significant toxic effects on ARPE-19 cells at all DCION concentrations, and minimal baseline cytotoxicity of DCIONs on Y79 and ARPE-19 cells was observed without magnetic field activation. Gene expression profiling showed that genes involved in FAS and tumor necrosis factor alpha signaling pathways were activated in Y79 cells following hyperthermia. Caspase 3/7 activity in Y79 cells increased following treatment, consistent with the activation of caspase-mediated apoptosis and loss of cell viability by magnetic hyperthermia. CONCLUSION: Magnetic hyperthermia using DCIONs selectively kills Y79 cells at 0.5 mg/ml or higher concentrations via the activation of apoptotic pathways. TRANSLATIONAL RELEVANCE: Magnetic hyperthermia using DCIONs might play a role in targeted management of retinoblastoma.

Do Largest Basal Tumor Diameter and the American Joint Committee on Cancer's Cancer Staging Influence Prognostication by Gene Expression Profiling in Choroidal Melanoma.

PURPOSE: To evaluate the prognostication of choroidal melanoma (CM) by the gene expression profiling (GEP) test. DESIGN: Cohort study. METHODS: Retrospective review of 293 CM patients from 2 centers. RESULTS: Of 293 patients, 132 (45%) were class 1A by GEP, 63 (22%) were class 1B, and 98 (33%) were class 2. Class 2 tumors had more ciliary body involvement and greater largest basal dimension (LBD), and were thicker. GEP results and increasing LBD were independently predictive of time to metastasis. Kaplan-Meier survival analysis estimated the probability of 3-year metastasis-free survival (MFS) of 0.99 in class 1A, 0.90 in class 1B, and 0.60 in class 2. The probability of 3-year MFS was 0.49 in class 2 patients with LBD ≥ 12 mm vs 1.00 in those with LBD < 12 mm, 0.89 in class 1B with LBD ≥ 12 mm vs 0.93 in those with LBD < 12 mm, and 0.99 in class 1A with LBD ≥ 12 mm vs 1.00 in those with LBD < 12 mm. In American Joint Committee on Cancer (AJCC) stage I CMs, the probability of 3-year MFS was 1.0 for class 1A and 1B, and 0.79 for class 2. In stage II CMs, the probability of 3-year MFS was 0.99 for class 1A, 0.89 for class 1B, and 0.61 for class 2. In stage III CM, the probability of 3-year MFS was 1.0 for class 1A, 0.60 for class 1B, and 0.41 for class 2. CONCLUSIONS: GEP testing provided significant prognostic information for CM. Class 2 tumors with LBD ≥ 12 mm and class 2 and 1B tumors with AJCC stage III showed significantly worse prognosis.

Evaluation of Choroidal Hemangioma and Treatment With Photodynamic Therapy by Using Enhanced Depth Imaging Optical Coherence Tomography.

BACKGROUND AND OBJECTIVE: To evaluate enhanced depth imaging optical coherence tomography (EDI-OCT) features of choroidal hemangioma and changes following photodynamic therapy (PDT). PATIENTS AND METHODS: Retrospective review of 21 choroidal hemangiomas. RESULTS: On EDI-OCT, choroidal hemangioma showed low internal reflectivity in 47% of lesions and high internal reflectivity in 53%. The most common associated features were normal-looking honeycomb-like pattern in choriocapillaris in all lesions, inner segment/outer segment abnormality in 62%, photoreceptor outer segment abnormality in 62%, subretinal fluid with speckles in 62%, and shaggy photoreceptors in 57% of lesions. Internal reflectivity changed from low to high in 67% of lesions. Photoreceptor outer segment and plexiform layer abnormalities became more noticeable and shaggy photoreceptors improved. CONCLUSION: On EDI-OCT, choroidal hemangioma showed normal-looking honeycomb-like pattern in the choriocapillaris, subretinal fluid with speckles, and abnormalities in the photoreceptor outer segment and plexiform layers. Following PDT, the choriocapillaris became sclerotic, and photoreceptor outer segment layer abnormalities were prominent. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:171-178.].

Photoacoustic imaging features of intraocular tumors: Retinoblastoma and uveal melanoma.

The purpose of this study is to examine the capability of photoacoustic (PA) imaging (PAI) in assessing the unique molecular and architectural features in ocular tumors. A real-time PA and ultrasonography (US) parallel imaging system based on a research US platform was developed to examine retinoblastoma in mice in vivo and human retinoblastoma and uveal melanoma ex vivo. PA signals were generated by optical illumination at 720, 750, 800, 850, 900 and 950 nm delivered through a fiber optical bundle. The optical absorption spectra of the tumors were derived from the PA images. The optical absorption spectrum of each tumor was quantified by fitting to a polynomial model. The microscopic architectures of the tumors were quantified by frequency domain analysis of the PA signals. Both the optical spectral and architectural features agree with the histological findings of the tumors. The mouse and human retinoblastoma showed comparable total optical absorption spectra at a correlation of 0.95 (p<0.005). The quantitative PAI features of human retinoblastoma and uveal melanoma have shown statistically significant difference in two tailed t-tests (p<0.05). Fully compatible with the concurrent procedures, PAI could be a potential tool complementary to other diagnostic modalities for characterizing intraocular tumors.