Impact of Nicotine Exposure on Hair Cell Toxicity and Embryotoxicity During Zebrafish Development

OBJECTIVES: Nicotine has various adverse effects including negative impacts associated with maternal exposure. In the current study, we examined nicotine-induced damage of hair cells and embryotoxicity during zebrafish development. METHODS: Zebrafish embryos were exposed to nicotine at several concentrations (5, 10, 20, and 40 μM) and embryotoxicity were evaluated at 72 hours, including hatching rate, mortality, teratogenicity rate, and heart rate. Hair cells within the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) neuromasts were identified at 120 hours. Apoptosis and mitochondrial damage of hair cells were analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) and DASPEI (2-[4-(dimethylamino)styryl]-N-ethylpyridinium iodide) assays, respectively, and changes of ultrastructure were observed by scanning electron microscopy. RESULTS: The control group without nicotine appeared normal with overall mortality and teratogenicity rate < 5%. The hatching rate and mortality rate was not significantly different according to nicotine concentration (n=400 each). The abnormal morphology rate (n=400) increased and heart rate (n=150) decreased with increasing nicotine concentration (P < 0.05). Nicotine-induced hair cell damage significantly increased as nicotine concentration increased. A significantly greater number of TUNEL-positive cells (P < 0.01) and markedly smaller DASPEI area (P < 0.01) were shown as nicotine concentration increased. CONCLUSION: The current results suggest that nicotine induces dose-dependent hair cell toxicity in embryos by promoting apoptosis and mitochondrial and structural damage.

A Case of Choroidal Metastasis from Renal Cell Carcinoma

PURPOSE: To report a rare case of choroidal metastasis from renal cell carcinoma. CASE SUMMARY: A 61-year-old man visited our clinic with the chief complaint of decreased vision in the right eye. Three years earlier, he underwent right nephrectomy due to renal cell carcinoma. Best corrected visual acuity was 0.2 in the right eye and 1.0 in the left eye. Fundoscopic examination of the right eye revealed a yellowish, dome-shaped elevated choroidal mass with serous retinal detachment, measuring 5.0 x 4.0 disc diameter and located lateral to the macular area. Systemic evaluations showed multiple lung and brain metastases. A diagnosis of choroidal metastasis from renal cell carcinoma was made for the right eye, and the patient received local treatments with oral sorafenib therapy, composed of subtenon triamcinolone injection and intravitreal ranibizumab injection. Tumor progression continued, and visual acuity declined to hand motion. Enucleation was recommended, but the patient refused and is on a regular follow-up after transpupillary thermotherapy. CONCLUSIONS: Ocular manifestation may be the initial presenting sign of a recurrent tumor, and an extensive systemic evaluation for metastatic malignancy should be performed. The present example showed a rare case of choroidal metastasis from renal cell carcinoma.

Progressive Localized Retinal Nerve Fiber Layer Defect Following Cotton Wool Spots and a Dot Hemorrhage

We report two cases of progressive localized retinal nerve fiber layer (RNFL) defect following cotton wool spots and a dot hemorrhage, 63-year-old woman with RNFL defect in inferior temporal retina of the right eye and 43-year-old man with RNFL defect in superior temporal retina of the right eye. Case 1 showed a dot hemorrhage adjacent to RNFL defect in the right eye and a new slit-like localized RNFL defect in the left eye 5 months later. The visual field in the left eye demonstrated corresponding field defect 9 months later. Case 2 showed a slit-like RNFL defect starting from cotton wool spots in the right eye and corresponding visual field defect. Cotton wool spots and dot hemorrhages represented ischemic damages at the nerve fiber layer. Two noticeable cases showed the progression of RNFL defect caused by repetitive localized microvascular ischemic events, resulting in visual field loss.

Study for Analysis of the Multifocal Visual Evoked Potential

PURPOSE: To introduce the clinical utility of the absolute value of the reconstructed waveform method in the analysis of multifocal visual evoked potential (mfVEP). METHODS: The mfVEP with 4-channel recording was performed using RETIscan(R) on 10 eyes of 10 normal subjects. Amplitudes were obtained from ring-shaped 6 areas and 4 sectors. The best visual evoked potential (VEP) response method and the absolute value of the reconstructed waveform method were compared in terms of analysis of the amplitudes. In order to assess the false positive rate of the examination, stimuli were administered with one-half of the cathode ray tube (CRT) monitor completely covered and the results were compared using 2 methods. RESULTS: The amplitudes in 6 areas and 4 sectors analyzed with the best VEP response method and the absolute value of the reconstructed waveform method showed no statistical difference (p > 0.05). The amplitude in the stimuli-blocked area of the absolute value of the reconstructed waveform method was smaller than that of the best VEP response method (p 0.05). CONCLUSIONS: The absolute value of the reconstructed waveform method has similar reproducibility and lower level of false positives relative to the best VEP response method. Therefore, it can be considered as a useful method in the analysis of the mfVEP.

Study for Analysis of the Multifocal Visual Evoked Potential

PURPOSE: To introduce the clinical utility of the absolute value of the reconstructed waveform method in the analysis of multifocal visual evoked potential (mfVEP). METHODS: The mfVEP with 4-channel recording was performed using RETIscan(R) on 10 eyes of 10 normal subjects. Amplitudes were obtained from ring-shaped 6 areas and 4 sectors. The best visual evoked potential (VEP) response method and the absolute value of the reconstructed waveform method were compared in terms of analysis of the amplitudes. In order to assess the false positive rate of the examination, stimuli were administered with one-half of the cathode ray tube (CRT) monitor completely covered and the results were compared using 2 methods. RESULTS: The amplitudes in 6 areas and 4 sectors analyzed with the best VEP response method and the absolute value of the reconstructed waveform method showed no statistical difference (p > 0.05). The amplitude in the stimuli-blocked area of the absolute value of the reconstructed waveform method was smaller than that of the best VEP response method (p 0.05). CONCLUSIONS: The absolute value of the reconstructed waveform method has similar reproducibility and lower level of false positives relative to the best VEP response method. Therefore, it can be considered as a useful method in the analysis of the mfVEP.

Leukemic Infiltration of the Optic Nerve Head as the Initial Manifestation of Leukemic Relapse

PURPOSE: To present a case of leukemic infiltration of the optic nerve head as the initial manifestation of leukemic relapse. CASE SUMMARY: A 65-year-old woman was diagnosed with acute myeloid leukemia. Complete remission was achieved after 4 complete courses of chemotherapy. She complained of a sudden decrease in visual acuity in her left eye. Fundus examination showed severe optic disc edema with peripapillary hemorrhage and serous retinal detachment. Visual acuity and fundus continued to aggravate and high-dose intravenous steroid therapy was instituted. Visual acuity and fundus deteriorated more after treatment. Brain magnetic resonance imaging and CSF study were normal but intrathecal chemotherapy and focal irradiation were performed on account of the suspected CNS involvement of leukemia. Morphologic improvement in the retinal structure was achieved, however, optic atrophy remained and her vision did not recover. CONCLUSIONS: The present case shows the involvement of the optic nerve head as the initial isolated manifestation for the relapse in a patient with complete remission. CNS involvement is rare in acute myeloid leukemia and in particular, the optic nerve is rarely reported as the initial isolated presentation for the relapse. Moreover, the disease progression relatively aggravated after treatment. In the atypical aspects of leukemic relapse, the present case was noticeable.