The effect of binaural beat audio on anxiety in patients undergoing fiberoptic bronchoscopy: A prospective randomized controlled trial.

BACKGROUND: Fiberoptic bronchoscopy is an invasive procedure known to induce anxiety in patients. Binaural beat therapy, in which sounds of different frequencies are delivered to the 2 ears to entrain the brainwaves, has been used to reduce anxiety in some operations. This study aimed to determine the anxiolytic effects of binaural beat audio in patients undergoing fiberoptic bronchoscopy. METHODS: Eligible subjects were randomly assigned to receive binaural beat music, plain music, or no music. They were asked to wear earphones starting approximately 15 minutes before the bronchoscopy. The level of anxiety was measured using the State-Trait Anxiety Inventory questionnaire. Blood pressure, heart rate, and sedative drug administration were also recorded. RESULTS: One hundred and twelve subjects were randomized into binaural beat music (n = 38), plain music (n = 38), and no music (n = 36) groups. The mean change in post-bronchoscopy State-Trait Anxiety Inventory state score in the binaural beat music, plain music, and no music group was -7.26 (P < .001), -3.92 (P = .005), and -1.12 (P = .454), respectively. The mean systolic blood pressure and diastolic blood pressure significantly decreased from baseline by -9.89 (P = .002) and -5.76 (P = .005), respectively, in the binaural group. The mean heart rate increased from baseline by 3.32 (P = .035), 5.21 (P = .038), and 3.64 (P = .149) in the binaural beat music, plain music, and no music groups, respectively. CONCLUSION: Binaural beat music appeared to reduce anxiety among patients undergoing fiberoptic bronchoscopy.Trial registration: TCTR, TCTR20200915002. Registered 14 September 2020 - Retrospectively registered.

Accuracy of The Cancer Genome Atlas Classification vs American Joint Committee on Cancer Classification for Prediction of Metastasis in Patients With Uveal Melanoma.

Importance: The Cancer Genome Atlas (TCGA) classification is a newly emerging method for prediction of uveal melanoma (UM)-related metastasis and death. Limited information is available regarding the accuracy of the TCGA classification for prediction of metastasis in patients with UM. Objective: To investigate the accuracy of the TCGA classification for predicting UM-related metastasis compared with the American Joint Committee on Cancer (AJCC) classification. Design, Setting, and Participants: In this retrospective cohort study, patients with UM treated with plaque radiotherapy at a tertiary referral center from October 1, 2008, to December 31, 2018, were evaluated. All patients with tumors classified according to the American Joint Committee on Cancer Staging Manual, 8th Edition, and who completed pretreatment fine-needle aspiration biopsy sampling for genetic analysis of chromosomes 3 and 8 for TCGA classification were included. Tumors were classified into 4 categories, 17 subcategories, and 4 stages using AJCC classification and further grouped into 4 classes using TCGA classification. Main Outcomes and Measures: Value of TCGA classification vs AJCC classification for predicting UM-related metastasis. Results: Of 642 included patients, 331 (51.6%) were women, and the mean (SD) age was 58.0 (13.8) years. There were 642 tumors from 642 patients classified according to both AJCC and TCGA classifications. The mean (range) follow-up time for the entire cohort was 43.7 (1.4-159.2) months. At 5 years, TCGA classification showed higher value for prediction of metastasis (4 TCGA classes: Wald statistic, 94.8; hazard ratio [HR], 2.8; 95% CI, 2.3-3.5; P < .001; 4 AJCC categories: Wald statistic, 67.5; HR, 2.6; 95% CI, 2.1-3.2; P < .001; 17 AJCC subcategories: Wald statistic, 74.3; HR, 1.3; 95% CI, 1.2-1.3; P < .001; 4 AJCC stages: Wald statistic, 67.0; HR, not applicable; P < .001). After entering TCGA and AJCC classifications into a multivariate model, TCGA classification still showed higher value for prediction of metastasis (TCGA classification: Wald statistic, 61.5; HR, 2.4; 95% CI, 1.9-2.9; P < .001; AJCC classification: Wald statistic, 35.5; HR, 1.9; 95% CI, 1.5-2.4; P < .001). Conclusions and Relevance: These results suggest that TCGA classification provides accuracy that is superior to AJCC categories, subcategories, and stages for predicting metastasis from UM. When genetic testing is available, TCGA classification can provide a more accurate way to identify patients at high risk of metastasis who might benefit from adjuvant therapy.

Circumscribed Choroidal Hemangioma: Visual Outcome in the Pre-Photodynamic Therapy Era versus Photodynamic Therapy Era in 458 Cases.

PURPOSE: To analyze visual outcomes after treatment of choroidal hemangioma in the pre-photodynamic therapy (PDT) era versus PDT era. DESIGN: Retrospective, comparative case series. PARTICIPANTS: A total of 458 patients with circumscribed choroidal hemangioma. METHODS: Comparison of hemangioma managed in the pre-PDT (1967-2001) era versus PDT (2002-2018) era. MAIN OUTCOME MEASURE: Visual acuity outcome. RESULTS: A total of 458 tumors were treated over this 51-year period. A comparison (pre-PDT [n = 220 cases] vs. PDT [n = 238 cases]) revealed PDT era patients were of older mean age (48.9 vs. 53.8 years, P = 0.002) and were more likely to have systemic hypertension (17.7% vs. 33.8%, P < 0.001), tumor location in the macula (57.4% vs. 67.5%, P = 0.01), subretinal fluid on OCT (33.3% vs. 70.7%, P = 0.01), and greater extent of overlying lipofuscin (P = 0.001). Findings of tumor basal diameter and thickness and fluorescein and indocyanine green angiography were no different in the 2 eras. Treatment (pre-PDT vs. PDT) included argon laser photocoagulation (42.1% vs. 0.4%), PDT (0% vs. 43.8%), transpupillary thermotherapy (0% vs. 0.4%), plaque radiotherapy (7.0% vs. 5.2%), external beam radiotherapy (1.4% vs. 1.3%), enucleation (0.9% vs. 0.4%), and observation (48.6% vs. 47.6%). After treatment, patients in the PDT era demonstrated better mean logarithm of the minimum angle of resolution visual acuity (1.28 vs. 0.51, P < 0.001) (Snellen equivalent 20/400 vs. 20/63, P < 0.001). Final visual acuity was ≥20/40 for those with entering vision of ≥20/40 (59.6% vs. 74.7%, P = 0.001) and for those with entering vision of 20/50-20/200 (25.4% vs. 47.3%, P < 0.001). CONCLUSIONS: Management of choroidal hemangioma in the PDT era has allowed for significantly better visual outcome compared with the pre-PDT era, with mean final visual acuity of 20/400 (pre-PDT era) versus 20/63 (PDT era).

Delayed implant infection with Cutibacterium acnes (Propionibacterium acnes) 30 years after silicone sheet orbital floor implant.

Purpose: To report a case of delayed implant infection with Cutibacterium acnes (C. acnes, previously known as Propionibacterium acnes) 30 years after silicone sheet orbital floor implant.Methods: Case report with orbital imaging.Results: A 61-year-old male with a history of traumatic orbital floor fracture right eye (OD) repaired using a silicone sheet orbital floor implant 30 years prior, presented with 6 months of painless blepharoptosis and diplopia OD. On examination, there was 3 mm right upper eyelid blepharoptosis and hyperglobus. There was no globe proptosis, dysmotility, or compression and no cutaneous erythema, hyperthermia, discharge, or tenderness to palpation. Orbital magnetic resonance imaging (MRI) revealed a cystic mass in the inferior orbit in the region of the floor implant, measuring 25 mm in diameter and 10 mm in thickness. By MRI, T1-weighted images revealed a hypointense signal within the mass and T2-weighted images showed hyperintense signal with a flat hypointensity centrally representing the floor implant. Microbiologic cultures grew C. acnes.Conclusions: C. acnes can manifest several decades after placement of an orbital prosthetic implant, leading to delayed infection.

Visual Outcome at 4 Years Following Plaque Radiotherapy and Prophylactic Intravitreal Bevacizumab (Every 4 Months for 2 Years) for Uveal Melanoma: Comparison With Nonrandomized Historical Control Individuals.

Importance: Radiation retinopathy following plaque radiotherapy for uveal melanoma can lead to vision loss that might be avoided with prophylactic anti-vascular endothelial growth factor treatment. Objective: To determine visual outcome following prophylactic intravitreal bevacizumab in patients with plaque-irradiated uveal melanoma. Design, Setting, and Participants: Retrospective, nonrandomized, interventional cohort study at Wills Eye Hospital, Philadelphia, Pennsylvania. Prophylactic bevacizumab was administered between 2008 and 2018 to 1131 eyes with irradiated uveal melanoma (bevacizumab group) and compared with 117 eyes with irradiated uveal melanoma between 2007 and 2009 (no bevacizumab [historical control] group). Interventions: Prophylactic intravitreal bevacizumab was provided at the time of plaque removal as well as 6 subsequent injections at 4-month intervals over 2 years. Main Outcomes and Measures: Visual acuity. Results: The median patient age was 61 years, 1195 of 1248 patients were white (96%), and 632 of 1248 were women (51%). The median tumor thickness was 4.0 mm, and median distance to foveola was 3.0 mm. A difference was not identified (bevacizumab vs control group) in demographic features, clinical features, or radiation parameters. The mean follow-up was 40 months vs 56 months (mean difference, -18; 95% CI, -24 to -13; P < .001). By survival analysis, the bevacizumab group demonstrated less optical coherence tomography evidence of cystoid macular edema at 24 months (28% vs 37%; hazard ratio [HR], 1.5; 95% CI, 1.1-2.2; P = .02) and 36 months (44% vs 54%; HR, 1.5; 95% CI, 1.1-2.1; P = .01), less clinical evidence of radiation maculopathy at 24 months (27% vs 36%; HR, 1.5; 95% CI, 1.0-2.2; P = .03), 36 months (44% vs 55%; HR, 1.50; 95% CI, 1.1-2.0; P = .01), and 48 months (61% vs 66%; HR, 1.4; 95% CI, 1.0-1.9; P = .03), and less clinical evidence of radiation papillopathy at 18 months (6% vs 12%; HR, 2.0; 95% CI, 1.1-3.9; P = .04). Nonparametric analysis documented better visual acuity outcomes in the bevacizumab group at all points, including 12 months (median logMAR visual acuity [Snellen equivalent]: 0.30 [20/40] vs 0.48 [20/60]; mean difference, -0.28; 95% CI, -0.48 to -0.07; P = .02), 24 months (0.40 [20/50] vs 0.70 [20/100]; mean difference, -0.52; 95% CI, -0.75 to -0.29; P < .001), 36 months (0.48 [20/60] vs 1.00 [20/200]; mean difference, -0.49; 95% CI, -0.76 to -0.21; P = .003), and 48 months (0.54 [20/70] vs 2.00 [counting fingers]; mean difference, -0.71; 95% CI, -1.03 to -0.38; P < .001). Conclusions and Relevance: These findings from a retrospective cohort of plaque radiotherapy and prophylactic intravitreal bevacizumab in patients with uveal melanoma suggest better visual outcomes when compared with nonrandomized historical control individuals through 4 years.

Prognostication of uveal melanoma is simple and highly predictive using The Cancer Genome Atlas (TCGA) classification: A review.

Purpose: The cancer genome atlas (TCGA) is a comprehensive project supported by the National Cancer Institute (NCI) in the United States to explore molecular alterations in cancer, including uveal melanoma (UM). This led to TCGA classification for UM. In this report, we review the American Joint Committee on Cancer (AJCC) classification and TCGA classification for UM from the NCI's Center for Cancer Genomics (NCI CCG) (based on enucleation specimens [n = 80 eyes]) and from Wills Eye Hospital (WEH) (based on fine needle aspiration biopsy [FNAB] specimens [n = 658 eyes]). We then compare accuracy and predictability of AJCC versus (vs.) TCGA. Methods: Review of published reports on AJCC and TCGA classification for UM was performed. Outcomes based on AJCC 7th and 8th editions were assessed. For TCGA, UM was classified based on chromosomes 3 and 8 findings including disomy 3 (D3), monosomy 3 (M3), disomy 8 (D8), 8q gain (8qG), or 8q gain multiple (8qGm) and combined into four classes including Class A (D3/D8), Class B (D3/8qG), Class C (M3/8qG), and Class D (M3/8qGm). Outcomes of metastasis and death were explored and a comparison (AJCC vs. TCGA) was performed. Results: In the NCI CCG study, there were 80 eyes with UM sampled by enucleation (n = 77), resection (n = 2), or orbitotomy (n = 1) and analysis revealed four distinct genetic classes. Metastasis and death outcomes were subsequently evaluated per class in the WEH study. The WEH study reviewed 658 eyes with UM, sampled by FNAB, and found Class A (n = 342, 52%), B (n = 91, 14%), C (n = 118, 18%), and D (n = 107, 16%). Comparison by increasing class (A vs. B vs. C vs. D) revealed older mean patient age (P < 0.001), worse entering visual acuity (P < 0.001), greater distance from the optic disc (P < 0.001), larger tumor diameter (P < 0.001), and greater tumor thickness (P < 0.001). Regarding outcomes, more advanced TCGA class demonstrated increased 5-year risk for metastasis (4% vs. 20% vs. 33% vs. 63%,P < 0.001) with corresponding increasing hazard ratio (HR) (1.0 vs. 4.1, 10.1, 30.0,P= 0.01 for B vs. A andP < 0.001 for C vs. A and D vs. A) as well as increased 5-year estimated risk for death (1% vs. 0% vs. 9% vs. 23%,P < 0.001) with corresponding increasing HR (1 vs. NA vs. 3.1 vs. 13.7,P= 0.11 for C vs. A andP < 0.001 for D vs. A). Comparison of AJCC to TCGA classification revealed TCGA was superior in prediction of metastasis and death from UM. Conclusion: TCGA classification for UM is simple, accurate, and highly predictive of melanoma-related metastasis and death, more so than the AJCC classification.

Circumscribed choroidal hemangioma: Clinical features and outcomes by age category in 458 cases.

PURPOSE: To investigate features and outcomes of circumscribed choroidal hemangioma by patient age. METHODS: Retrospective review of circumscribed choroidal hemangioma from 3/29/1967-6/4/2018 based on age at presentation (≤20 vs. >20-50 vs. >50 years). RESULTS: There were 458 circumscribed choroidal hemangiomas diagnosed at mean age (13 vs. 41 vs. 64 years, p < 0.001). The youngest age group had worse presenting visual acuity (20/400 vs. 20/150 vs. 20/100, p < 0.001), larger tumor basal diameter (13.5 vs. 6.6 vs. 6.2, p < 0.001), greater tumor thickness (5.8 vs. 3.1 vs. 2.9, p < 0.001), closer distance to foveola (0.5 vs. 1.4 vs. 1.2, p = 0.03), and greater extent of subretinal fluid (4 quadrants, 26% vs. 8% vs. 2%, p < 0.001). The youngest patients were less likely to be treated with primary observation (39% vs. 39% vs. 56%) or photodynamic therapy (10% vs. 27% vs. 22%) and more likely to be treated with plaque radiotherapy (26% vs. 6% vs. 3%) or external beam radiotherapy (13% vs. 1% vs. 0%) (p < 0.001). The youngest patients required greater total number of treatments (mean 4 vs. 2 vs. 1, p < 0.001). At mean follow-up (44 vs. 68 vs. 60 months, p = 0.37), the youngest patients had worse visual acuity (20/400 vs. 20/200 vs. 20/100, p = 0.03), but no difference in visual acuity loss of 3 or more Snellen lines (27% vs. 13% vs. 16%, p = 0.55). CONCLUSION: Younger patients (≤20 years) with circumscribed choroidal hemangioma present with worse visual acuity and larger, more posterior tumors. Future studies are needed to improve early detection and treatment for this subgroup of patients.

Genetic Analysis of Uveal Melanoma in 658 Patients Using the Cancer Genome Atlas Classification of Uveal Melanoma as A, B, C, and D.

PURPOSE: The Cancer Genome Atlas (TCGA) classification has been validated for uveal melanoma (UM) prognostication. We applied TCGA classification to UM biopsied using fine-needle aspiration biopsy (FNAB) to determine the predictability for metastasis and death. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with UM treated with plaque radiotherapy at Wills Eye Hospital, Philadelphia, Pennsylvania, from October 1, 2008, through December 31, 2018, who completed genetic analysis of chromosomes 3 and 8 after FNAB. METHODS: Tumors were classified as A, B, C, or D and were compared using the chi-square test, Fisher exact test, analysis of variance, and Kaplan-Meier analysis. MAIN OUTCOME MEASURES: Metastasis and death. RESULTS: Six hundred fifty-eight UM patients were categorized accordingly as TCGA class A (n = 342 [52%]), B (n = 91 [14%]), C (n = 118 [18%]), and D (n = 107 [16%]). More advanced tumor classification revealed older mean patient age (56 vs. 53 vs. 60 vs. 63 years, respectively; P < 0.001), worse presenting visual acuity (20/20-20/50: 81% vs. 67% vs. 71% vs. 66%, respectively; P < 0.001), greater distance from the optic disc (3.5 vs. 4.9 vs. 5.7 vs. 5.3 mm, respectively; P < 0.001), larger tumor basal diameter (10.3 vs. 12.9 vs. 13.9 vs. 15.3 mm, respectively; P < 0.001), and greater tumor thickness (4.3 vs. 6.1 vs. 6.6 vs. 7.5 mm, respectively; P < 0.001). After mean follow-up (47.6 vs. 47.6 vs. 42.9 vs. 28.7 months, respectively; P < 0.001), more advanced TCGA class was associated with increased risk of metastasis (3% vs. 10% vs. 25% vs. 41%, respectively; P < 0.001) and death (1% vs. 0% vs. 3% vs. 9%, respectively; P < 0.001). Compared with class A, the 5-year hazard ratio for metastasis increased at 4.1 (B vs. A; P = 0.01), 10.1 (C vs. A; P < 0.001), and 30.0 (D vs. A; P < 0.001). The 5-year hazard ratio for death increased at 3.1 (C vs. A; P = 0.11) and 13.7 (D vs. A; P < 0.001) with no deaths in class B. CONCLUSIONS: Grouping of UM using TCGA classification predicts the risk of melanoma-related metastasis and death.

Ocular Malformations with Presumable Intraocular Calcification.

This is a case of ocular malformations with presumable intraocular calcification based on computed tomography (CT) imaging, magnetic resonance imaging (MRI) and ocular ultrasound (US) findings. The authors presented the clinical, imaging and pathological findings of this case. Intraocular calcification is the most important finding in retinoblastoma, which requires aggressive management. It is important to distinguish it from other intraocular lesions, especially intraocular calcified hematoma.

Retinal detachment associated with AIDS-related cytomegalovirus retinitis: risk factors in a resource-limited setting.

PURPOSE: To determine risk factors predictive of retinal detachment in patients with cytomegalovirus (CMV) retinitis in a setting with limited access to ophthalmic care. DESIGN: Case-control study. METHODS: Sixty-four patients with CMV retinitis and retinal detachment were identified from the Ocular Infectious Diseases and Retina Clinics at Chiang Mai University. Three control patients with CMV retinitis but no retinal detachment were selected for each case, matched by calendar date. The medical records of each patient were reviewed, with patient-level and eye-level features recorded for the clinic visit used to match cases and controls, and also for the initial clinic visit at which CMV retinitis was diagnosed. Risk factors for retinal detachment were assessed separately for each of these time points using multivariate conditional logistic regression models that included 1 eye from each patient. RESULTS: Patients with a retinal detachment were more likely than controls to have low visual acuity (odds ratio [OR], 1.24 per line of worse vision on the logMAR scale; 95% confidence interval [CI], 1.16-1.33) and bilateral disease (OR, 2.12; 95% CI, 0.92-4.90). Features present at the time of the initial diagnosis of CMV retinitis that predicted subsequent retinal detachment included bilateral disease (OR, 2.68; 95% CI, 1.18-6.08) and lesion size (OR, 2.64 per 10% increase in lesion size; 95% CI, 1.41-4.94). CONCLUSION: Bilateral CMV retinitis and larger lesion sizes, each of which is a marker of advanced disease, were associated with subsequent retinal detachment. Earlier detection and treatment may reduce the likelihood that patients with CMV retinitis develop a retinal detachment.

Atypical manifestation of progressive outer retinal necrosis in AIDS patient with CD4+ T-cell counts more than 100 cells/microL on highly active antiretroviral therapy.

Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome.