Testing the clinical value of multifocal electroretinography and microperimetry and the effects of intravitreal therapy with ranibizumab on macular function in the course of wet age-related macular degeneration: a 1-year prospective study.

PURPOSE: To investigate the clinical value of multifocal electroretinography (mfERG) and microperimetry and the effects of intravitreal therapy with ranibizumab (Lucentis®) on macular function in the course of neovascular age-related macular degeneration (nAMD). MATERIALS AND METHODS: We conducted a prospective single-arm interventional cohort study with 20 nAMD patients older than 50 years. Examinations were scheduled monthly for 1 year during intravitreal therapy with ranibizumab. The examinations included mfERG, microperimetry, spectral domain optical coherence tomography, and best-corrected visual acuity using ETDRS score. RESULTS: During the 12-month observation period, a significant positive linear correlation between the logarithm of minimum angle of resolution (logMAR) and scotoma area (r=0.28, 95% confidence interval [CI] 0.21-0.35), between logMAR and fovea thickness in optical coherence tomography (r=0.11, 95% CI 0.04-0.2), and a significant negative correlation between logMAR and mfERG (-0.37, 95% CI -0.43 to -0.31) were observed. A significant ranibizumab effect on logMAR was found (P=0.0065). From a total of 25 relapses, 14 were able to be predicted correctly by mfERG P1 decrease in the preceding month. However, there was no statistically significant relation between prediction and observed relapses (Fisher's exact test, P=0.6726). CONCLUSION: Our results indicate a possible role of mfERG and microperimetry in the monitoring of macular function and prediction of recurrence during intravitreal pharmacotherapy in wet AMD.

Analysis of monosomy-3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients.

Monosomy-3 in primary uveal melanoma (UM) is associated with a high risk of metastasis and mortality. Although circulating melanoma cells (CMC) can be found in most UM patients, only approximately 50% of the patients develop metastases. We utilized a novel immuno-FISH assay to detect chromosome-3 in intact CMC isolated by dual immunomagnetic enrichment. Circulating melanoma cells were detected in 91% of the patients (n = 44) with primary non-metastatic UM, of which 58% were positive for monosomy-3. The monosomy-3 status of CMC corresponded to the monosomy-3 status of the primary tumor in 10 of the 11 patients where this could be tested. Monosomy-3 in the CMC was associated with an advanced tumor stage (P = 0.046) and was detected in all four patients who developed metastasis within the follow-up period of 4 yr. This non-invasive technique may enable the identification of UM patients at risk for metastasis particularly when a primary tumor specimen is unavailable.

Identification of circulating melanoma cells in uveal melanoma patients by dual-marker immunoenrichment.

PURPOSE: Despite successful local tumor control, uveal melanoma (UM) patients may develop lethal metastases. To reliably identify circulating melanoma cells (CMC) in UM patients, we set out to test a new immunomagnetic enrichment assay and screened UM patients for the presence of CMC. We also determined whether we could find CMC in culture; for example, for future drug testing. METHODS: A dual-immunomagnetic enrichment assay using antibodies against two melanoma markers (NKI/C3 and NKI/beteb) was used to determine the presence of UM cells in blood. The sensitivity of the assay was determined by spiking normal blood with 92.1 cells (concentration range, 1-10(4) cells/mL). Isolated cells were characterized by immunocytochemistry directly after immunoenrichment and after a 2-week culture. The presence of CMC was determined in the peripheral blood of 31 patients with UM, and results were compared to clinical prognostic factors at the time of presentation. RESULTS: The CMC were detected in 93.5% (n = 29 of 31) of the patients with primary nonmetastatic UM at a median density of 3.5 cells/10 mL blood (range, 0-10.2 cells), as well as in blood cultures. No significant association was observed between the presence or number of CMC and any clinical prognostic factors. CONCLUSIONS: The improved dual-immunoenrichment assay enabled the detection of intact and viable CMC in the majority of UM patients. We also were able to identify CMC after short-term culturing. Molecular characterization of the CMC rather than the prevalence of these cells is expected to provide relevant information on the individual risk of metastasis.

The concentration-dependent effects of indocyanine green on retinal function in the electrophysiological ex vivo model of isolated perfused vertebrate retina.

BACKGROUND: Dye solutions such as indocyanine green (ICG) are used for the staining of intraocular structures. The aim of the presented study was to investigate the effects of ICG on bovine retinal function using different concentrations of ICG. METHODS: Bovine retina preparations were perfused with a standard solution and the electroretinogram was recorded. The nutrient solution was substituted by an ICG solution at varying concentrations for 45 min. Afterwards the preparations were reperfused with standard solution for at least 85 min. RESULTS: Significant reductions in b-wave amplitude were found for concentrations of 0.0025% (p = 0.0099) and 0.025% (p = 0.0378). For the concentration of 0.025%, the b-wave amplitude remained significantly decreased (p = 0.0082) after the observation period, but a full recovery of the b-wave was observed for the concentration of 0.0025% (p = 0.1917). CONCLUSION: Intraocular application of sufficient ICG concentrations for internal limiting membrane staining seems not possible without interfering with retinal function.