Risk factors for early-onset high myopia after treatment for retinopathy of prematurity.

PURPOSE: To investigate the prevalence of myopia and high myopia and the risk factors for high myopia in infants at 3 years of age with retinopathy of prematurity (ROP). STUDY DESIGN: Retrospective, observational. METHODS: We retrospectively analyzed all 89 preterm infants (178 eyes) with medical records of ROP between October 2008 and March 2018 at Toho University Medical Center Omori Hospital; these infants had a birth weight of less than 1,500 g and were followed up at least until 3 years of age. Cycloplegic autorefraction was performed to measure refractive outcomes. Multivariate analysis was performed to determine the risk factors for early-onset high myopia at 3 years of age. RESULTS: The prevalence of myopia and high myopia was significantly higher in the treated group (59.7% and 17.9%, respectively) than in the untreated group (19.7% and 0%, respectively) (p<0.001). Spherical equivalent (SE) at age 3 was more myopic in the treatment group (-1.72 ± 3.53 D) than in the untreated group (0.54 ± 1.08 D) (p<0.001). In the sub-analysis of the treatment group, there was a significant correlation between SE at age 3 and the number of laser shots (R2 = 0.36, p<0.001). Multivariate logistic analysis showed that the number of laser shots was an independent risk factor for early onset high myopia (p<0.05). CONCLUSION: The number of laser shots is an independent risk factor for early onset high myopia, and preterm infants who have undergone laser treatment for severe ROP should be considered for early optical correction with cycloplegic refractive examination.

Intravitreal bevacizumab treatment reduces ocular blood flow in retinopathy of prematurity: a four-case report.

PURPOSE: To evaluate the relationship between ocular blood flow, expressed as mean blur rate (MBR) by laser speckle flowgraphy, and intravitreal bevacizumab (IVB) therapy in neonates with retinopathy of prematurity (ROP). METHODS: This was a case series study of 4 neonates with ROP under sedation before and after IVB and evaluated 8 eyes, in which the circulation could be measured three times consecutively. We performed optic nerve head blood flow measurement and fluorescein angiography (FA) before and 1 week after treatment. Blood flow was analyzed separately for MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean). Comparisons between the MBR (-A, -V, -T), body weight, and other systemic and ocular parameters before and after treatment were performed using a paired t test. RESULTS: The MBR values after IVB were lower than the pre-treatment values in all cases. All eyes showed leakage at neovascularization on FA before treatment. Although leakage improved 1 week after treatment, the neovascularization did not completely regress. CONCLUSIONS: IVB improves vein dilation and artery tortuosity, while reducing ocular blood flow in neonates with ROP. We suggest that neovascularization might not be involved in reducing ocular blood flow in the early stage of IVB treatment.

Reliability and validity of the Japanese version of the Glasgow Edinburgh Throat Scale (GETS-J): Use for a symptom scale of globus sensation.

OBJECTIVE: Globus sensation, a feeling of lump or something stuck in the throat, could be caused by structural, functional, and psychogenic diseases. Due to a possible multifactorial nature of the disease, neither diagnosing test battery nor standard treatment for globus sensation has been established. Therefore, a questionnaire to accurately identify globus patients and evaluate the severity of the disease is desired. Glasgow Edinburgh Throat Scale (GETS) is a 10-item questionnaire about the throat symptoms consisting of three subscales relating to dysphagia, globus sensation, and pain/swelling in the throat. It was reported that globus patients marked high scores specifically for the globus scale among three scales, indicating that GETS can be used as a valid symptom scale for globus sensation. Aims of this study were to translate GETS into Japanese and to test its reliability and validity. METHODS: Fifty-five patients complaining of globus sensation without abnormal endoscopic and CT findings were enrolled into the study. They were asked to answer the questions of GETS translated into Japanese (GETS-J). Reliability (internal consistency) of the questionnaire was tested using Cronbach's coefficient alpha. To test the validity, principal components analysis was used to identify the factorial structure of the questionnaire and GETS-J data were compared with those reported in the original GETS. Contribution of psychiatric comorbidities to globus sensation was also investigated by examining the correlation between Hospital Anxiety and Depression Scale (HADS) and GETS-J. RESULTS: Reliability of the questionnaire examined by the Cronbach's coefficient alpha was satisfactory and all higher than 0.75. Principal components analysis identified following three questions as the globus scale: Q1, Feeling something stuck in the throat; Q5, Throat closing off; Q9, Want to swallow all the time. Somatic distress, i.e., patients' reaction to throat symptoms, was significantly correlated with globus scale (r=0.680). Anxiety component of HADS was significantly correlated with somatic distress but not with globus scale. These results were consistent with those of the original GETS except for the replacement of Q3 (discomfort/irritation in the throat) to Q5 (throat closing off) for globus scale in GETS-J. CONCLUSION: Translation of GETS into Japanese showed high reliability and validity, suggesting that translation and cross-cultural adaptation were not problematic. High correlation of globus scale of GETS-J with somatic distress indicated that GETS-J could be a useful questionnaire to identify the globus patients and evaluate the severity of the disease. Anxiety may complicate the somatic distress in patients with globus sensation.

Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan.

OBJECTIVE: Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese. METHODS: Patients were eligible for inclusion if they had head and neck SCC that was treated with radical CCRT comprising whole-neck irradiation of the primary lesion and level II-IV lymph nodes on both sides. For the phase I study, a CDDP dose was 70mg/m2 for level 0, 80mg/m2 for level 1, and 100mg/m2 for level 2. Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) were examined by phase I trial, by which CDDP dose for phase II was determined. The primary endpoint for the phase II was CCRT completion rate, and the secondary endpoint was full-dose-CCRT completion rate, the percentage of patients receiving a total CDDP dose of ≥200mg/m2, response rate, and incidences of adverse events. RESULTS: A CDDP dose of 100mg/m2 was the MTD for phase I, and the recommended dose for phase II was 80 mg/m2. Forty-seven patients were evaluated in the phase II trial. CCRT completion rate, full-dose-CCRT rate, and the percentage of patients receiving a total CDDP dose of ≥200mg/m2, were 93.6%, 78.7%, and 93.6%, respectively. One patient (2.1%) developed grade 2 renal dysfunction, and no patient developed febrile neutropenia or a grade 4 adverse event. CONCLUSION: The present phase I study indicated that a CDDP dose of 80mg/m2 is the optimal dose in terms of safety. The phase II study revealed that CCRT completion rate, response rate, and rates of adverse events were not inferior for a CDDP dose of 80mg/m2 as compared with a dose of 100mg/m2, and a dose of 80mg/m2 is therefore recommended in CCRT for the Japanese. This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification No. UMIN000010369).

Decreased ocular blood flow after photocoagulation therapy in neonatal retinopathy of prematurity.

PURPOSE: To evaluate the relationships between optic nerve head blood flow, expressed as mean blur rate (MBR) measured by laser speckle flowgraphy (LSFG), and photocoagulation therapy in neonates with retinopathy of prematurity (ROP). STUDY DESIGN: Case series study. METHODS: We studied 5 ROP neonates either during sleep or under sedation both before and after photocoagulation, and evaluated 8 eyes in which the circulation could be measured three times consecutively. Correlations between the MBR-A (mean of all values), MBR-V (vessel mean) and MBR-T (tissue mean) and postmenstrual age were evaluated using Spearman's rank correlation coefficient. In addition, correlations between the relative MBR (-A, -V, -T) value and number of photocoagulation burns and the NV score were evaluated. Differences between post-treatment MBR in ROP subjects and normal neonates' MBR were estimated using analysis of covariance (ANCoVA), with adjustment for postmenstrual age. RESULTS: The relative MBR (-A, -V, -T) values after photocoagulation were 69.6 ± 16.0%, 66.7 ± 17.0% and 74.3 ± 14.6%, respectively. Postmenstrual age was significantly correlated with post-treatment MBR-A (r = 0.83, p = 0.0101), MBR-V (r = 0.85, p = 0.007) and MBR-T (r = 0.76, p = 0.0282). The relative MBR-T value was significantly correlated with the number of photocoagulation burns (r = -0.75, p = 0.033) and NV score (r = -0.72, p = 0.0437). The ANCoVA results showed no significant difference between post-treatment MBR and normal neonates' MBR. CONCLUSIONS: Photocoagulation improved the dilation of veins and tortuosity of arteries and reduced ocular blood flow in ROP subjects. Since the post-treatment MBR was not different from a normal neonate's MBR, it is suggested that the pre-treatment MBR was higher in severe ROP cases.

Daytime sleepiness in Japanese patients with multiple system atrophy: prevalence and determinants.

BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. METHODS: We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients' degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients' ESS scores. RESULTS: A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 ± 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed.

[Concurrent chemoradiotherapy with either CDDP or CDGP, plus 5-FU for squamous cell carcinoma of the oropharynx and hypopharynx].

Clinical outcomes of 53 patients with oropharyngeal and hypopharyngeal squamous cell carcinoma, treated from January, 2000 to December, 2008 by concurrent chemoradiotherapy of either CDDP or CDGP, plus 5-FU were investigated. Patients were treated with either CDDP (70 mg/m2) or CDGP (100 mg/m2) on day 1 of the chemotherapy regime, with 5-FU (700 mg/m2/day) as a continuous infusion for 5 days. Each regimen was administered as two courses in the first and final weeks of radiotherapy. Radiotherapy was administered at a daily dose of 2 Gy for five days a week, with patients receiving a total of 70 Gy by the end of seven weeks. The primary cancer was located in the oropharynx and hypopharynx in 21 and 32 patients, respectively. Twenty-six patients (49.1%) had stage IVA disease and 10 patients (18.9%) had overall stage I to II disease. Acute adverse events such as pharyngeal mucositis and leucopenia occurred in 49.1% and 43.4% of patients, respectively, and second round chemotherapy was not commenced in 56.6% of patients (n=30) due to significant adverse events. Mean weight loss following treatment was 4.1 kg. After a median follow-up of 30.0 months, 3-year overall survival was 53.0% for advanced carcinoma of the oropharynx and hypopharynx. Five-year overall survival was 46.4%. Patients receiving two courses of chemotherapy had an improved 5-year survival compared to patients receiving one course (67.0% vs 32.8%). Results indicate a significant benefit from two courses of chemotherapy. As such, minimizing the incidence of adverse effects and thereby reducing treatment discontinuation will likely improve overall treatment outcomes.

Tremulous arytenoid movements predict severity of glottic stenosis in multiple system atrophy.

To determine whether tremulous arytenoid movements predict the severity of glottic stenosis in patients with multiple system atrophy (MSA), 28 MSA patients and 14 age-matched controls underwent fiberoptic laryngoscopy with video monitoring during wakefulness and under anesthesia induced by intravenous injection of propofol. Presence or absence of tremulous arytenoid movements was recorded during wakefulness. The ratio of glottic stenosis (%), which represents the extent of airway narrowing under anesthesia, was obtained by measuring the inspiratory glottic angle during wakefulness and under anesthesia. The median ratio of glottic stenosis was significantly higher in patients with MSA (57.5%) than in control subjects (0.5%). Tremulous arytenoid movements were characterized by shaking movements of the arytenoid region including the vocal folds, which are most apparent in the arytenoid cartilage. In this study, tremulous arytenoid movements were observed in 18 (64.2%) of 28 patients with MSA, who displayed a significantly higher median ratio of glottic stenosis (71.2%) than other patients (34.9%). None of the control subjects exhibited tremulous arytenoid movements. A clear correlation existed between the ratio of glottic stenosis and disease duration. Our observations indicate that tremulous arytenoid movements are a marker of the severity of glottic stenosis, which confers an increased risk of upper airway obstruction in patients with MSA.

[Clinical evaluation of patients with pyriform sinus fistula].

Thirteen patients with pyriform sinus fistula treated surgically at our department were clinically evaluated. Twelve (92%) fistulae occurred in the left pyriform sinus, and one (8%) in the right. There were a mean of 4 infectious episodes before the final diagnosis. The median age at the first infection was 5 years, and the median age at surgery was 13 years, although there were 2 elderly patients (over 60 years old) in this series. Association with pharyngeal foreign body was suspected in the case with onset at 81 years of age. There was a history of previous surgery for cervical disease in 54% of the patients. The final diagnosis was based on delineation of the fistula by hypopharyngography, although coronal section of CT and MRI were also useful for understanding the morphopathology. The surgical procedure consisted of identification and staining of the fistula under direct hypopharyngoscopy, followed by identification and extirpation of the fistula until the distal end via a cervical approach. There was no recurrence of infections, although resection of the thyroid gland and identification of the recurrent laryngeal nerve were not always performed. The most important surgical principle is considered to be complete disconnection of the lesion from the hypopharynx, and complete identification and extirpation of the fistula by the procedure used at our department is considered to be a useful surgical strategy.

Cross-correlation and joint spectro-temporal receptive field properties in auditory cortex.

Recordings were made from the right primary auditory cortex in 17 adult cats using two eight-electrode arrays. We recorded the neural activity under spontaneous firing conditions and during random, multi-frequency stimulation, at 65 dB SPL, from the same units. Multiple single-unit (MSU) recordings (281) were stationary through 900 s of silence and during 900 s of stimulation. The cross-correlograms of 545 MSU pairs with peak lag times within 10 ms from zero lag time were analyzed. Stimulation reduced the correlation in background activity, and as a result, the signal-to-noise ratio of correlated activity in response to the stimulus was enhanced. Reconstructed spectro-temporal receptive fields (STRFs) for coincident spikes showed larger STRF overlaps, suggesting that coincident neural activity serves to sharpen the resolution in the spectro-temporal domain. The cross-correlation for spikes contributing to the STRF depended much stronger on the STRF overlap than the cross-correlation during either silence or for spikes that did not contribute to the STRF (OUT-STRF). Compared with that for firings during silence, the cross-correlation for the OUT-STRF spikes was much reduced despite the unchanged firing rate. This suggests that stimulation breaks up the large neural assembly that exists during long periods of silence into a stimulus related one and maybe several others. As a result, the OUT-STRF spikes of the unit pairs, now likely distributed across several assemblies, are less correlated than during long periods of silence. Thus the ongoing network activity is significantly different from that during stimulation and changes afterng arousal during stimulation.

Effects of an acute acoustic trauma on the representation of a voice onset time continuum in cat primary auditory cortex.

Here we show that hearing loss associated with an impairment of speech recognition causes a decrease in neural temporal resolution. In order to assess central auditory system changes in temporal resolution, we investigated the effect of an acute hearing loss on the representation of a voice onset time (VOT) and gap-duration continuum in primary auditory cortex (AI) of the ketamine-anesthetized cat. Multiple single-unit activity related to the presentation of a /ba/-/pa/ continuum--in which VOT was varied in 5-ms step from 0 to 70 ms-- was recorded from the same sites before and after an acoustic trauma using two 8-electrode arrays. We also obtained data for gaps, of duration equal to the VOT, embedded in noise 5 ms after the onset. We specifically analyzed the maximum firing rate (FRmax), related to the presentation of the vowel or trailing noise burst, as a function of VOT and gap duration. The changes in FRmax for /ba/-/pa/ continuum as a function of VOT match the psychometric function for categorical perception of /ba/-/pa/ modeled by a sigmoid function. An acoustic trauma made the sigmoid fitting functions shallower, and shifted them toward higher values of VOT. The less steep fitting function may be a neural correlate of an impaired psychoacoustic temporal resolution, because the ambiguity between /ba/ and /pa/ should consequently be increased. The present study is the first one in showing an impairment of the temporal resolution of neurons in AI caused by an acute acoustic trauma.

Neural changes in cat auditory cortex after a transient pure-tone trauma.

Here we present the changes in cortical activity occurring within a few hours after a 1-h exposure to a 120-dB SPL pure tone (5 or 6 kHz). The changes in primary auditory cortex of 16 ketamine-anesthetized cats were assessed by recording, with two 8-microelectrode arrays, from the same multiunit clusters before and after the trauma. The exposure resulted in a peripheral threshold increase that stabilized after a few hours to on average 40 dB in the frequency range of 6-32 kHz, as measured by the auditory brain stem response. The trauma induced a shift in characteristic frequency toward lower frequencies, an emergence of new responses, a broadening of the tuning curve, and an increase in the maximum of driven discharges. In addition, the onset response after the trauma was of shorter duration than before the trauma. The results suggest the involvement of both a decrease and an increase in inhibition. They are discussed in terms of changes in central inhibition and its implications for tonotopic map plasticity.