Optic nerve biopsy in leukemic infiltrative optic neuropathy: a case report and review of the literature.

Optic nerve infiltration is a rare but known complication of the central nervous system (CNS)-involving lymphoma and leukemic disorders. The diagnosis is often presumed and patients are empirically treated with systemic therapy and/or local radiation. Optic nerve biopsy is usually avoided due to the risk of permanent vision loss secondary to the procedure. We present a case of biopsy-proven leukemic optic neuropathy without optic nerve sheath or cerebrospinal fluid (CSF) involvement in a patient previously in remission from T-cell prolymphocytic leukemia (T-PLL). To our knowledge, this is the first documented case of T-PLL with biopsy-proven optic nerve invasion without CSF involvement and suggests possible perineural invasion or a sanctuary site from chemotherapy. We suggest that for patients with poor vision and suspected leukemic infiltration without other evidence of CNS involvement, both optic nerve and optic sheath biopsy should be performed for diagnosis and treatment.

Ethambutol optic neuropathy.

PURPOSE OF REVIEW: We provide a summary of the epidemiology, clinical findings, management and outcomes of ethambutol-induced optic neuropathy (EON). Ethambutol-induced optic neuropathy is a well-known, potentially irreversible, blinding but largely preventable disease. Clinicians should be aware of the importance of patient and physician education as well as timely and appropriate screening. RECENT FINDINGS: Two of the largest epidemiologic studies investigating EON to date showed the prevalence of EON in all patients taking ethambutol to be between 0.7 and 1.29%, a value consistent with previous reports of patients taking the doses recommended by the World Health Organization (WHO). Several studies evaluated the utility of optical coherence tomography (OCT) in screening for EON. These showed decreased retinal nerve fiber layer (RNFL) thickness in patients with clinically significant EON, but mixed results in their ability to detect such changes in patients taking ethambutol without visual symptoms. SUMMARY: Ethambutol-induced optic neuropathy is a well-known and devastating complication of ethambutol therapy. It may occur in approximately 1% of patients taking ethambutol at the WHO recommended doses, though the risk increases substantially with increased dose. All patients on ethambutol should receive regular screening by an ophthalmologist including formal visual field testing. Visual evoked potentials and OCT may be helpful for EON screening, but more research is needed to clarify their clinical usefulness. Patients who develop signs or symptoms of EON should be referred to the ethambutol-prescribing physician immediately for discontinuation or a reduction in ethambutol dosing.

Assessing the risk of undesirable immunogenicity/allergenicity of plant-derived therapeutic proteins.

Therapeutic proteins have an intrinsic potential to induce undesirable immune and allergic responses. The nature of the expression system and the control of the manufacturing process represent extrinsic factors that could modify this potential. Accordingly, regulatory agencies require sponsors to assess the risk of clinical immune and allergic responses that could be associated with the production of therapeutic proteins in transgenic plants. Since factors related to the clinical use of the product--including the immune status and genetic background of subjects--are also relevant, the risk assessment needs to balance the probability of a response induced by a plant-specific factor relative to the likely consequences for the specific product and therapeutic indication.

Preoperative Prediction of the Optimal Toric Intraocular Lens Alignment Meridian.

PURPOSE: To determine whether any of three keratometry devices is superior to the others in predicting the ideal toric intraocular lens (IOL) alignment meridian. METHODS: A retrospective review was performed to identify patients who underwent cataract phacoemulsification with toric IOL implantation from November 2014 to November 2016 at a single academic institution. For each patient, corneal measurements were performed with an optical low-coherence reflectometer/autokeratometer (OLCR), a dual Scheimpflug/Placido analyzer, and a color light-emitting diode (LED) topographer. Postoperatively, the ideal toric IOL alignment meridian that would have resulted in the least amount of residual astigmatism was determined using the online Berdhal & Hardten Toric Results Analyzer (BHTRA). To determine the prediction error, this ideal alignment meridian was compared to the corneal meridian with the highest refractive power, as provided by the three devices. RESULTS: Fifty-six eyes of 56 patients were included in the study. The mean absolute errors in the toric IOL alignment meridians of the color LED topographer, dual Scheimpflug/Placido analyzer, and OLCR were 5.2° ± 5.2°, 7.6° ± 5.7°, and 5.4° ± 5.1°, respectively. There was no significant difference in the ability of each device to predict the ideal alignment meridian as determined by the BHTRA. CONCLUSIONS: The color LED topographer, dual Scheimpflug/Placido analyzer, and OLCR may all be used to preoperatively determine the best alignment meridian for toric IOL placement. Surgeons should use their best judgment in determining which device to use in preoperative planning for individual patients. [J Refract Surg. 2018;34(8):515-520.].

Prognostic value of p16 expression in Epstein-Barr virus-positive nasopharyngeal carcinomas.

BACKGROUND: Overexpression of p16 is associated with improved outcomes among patients with oropharyngeal carcinoma. However, its role in the outcomes of patients with nasopharyngeal cancer (NPC) remains unclear. METHODS: Eighty-six patients with NPC treated at MD Anderson Cancer Center from 2000 to 2014 were identified. Epstein-Barr virus (EBV) and human papillomavirus (HPV) status were determined by in situ hybridization (ISH) and p16 by immunohistochemical staining. RESULTS: EBV positivity was associated with extended overall survival (OS; median, 95.0 vs 44.9 months; p < .004), progression-free survival (PFS; median, 80.4 vs 28.1 months; p < .013), and locoregional control (median, 104.4 vs 65.5 months; p < .043). In patients with EBV-positive tumors, p16 overexpression correlated with improved PFS (median, 106.3 vs 27.1 months; p < .02) and locoregional control (median, 93.6 vs 64.5 months; p < .02). CONCLUSION: P16 overexpression is associated with improved PFS and locoregional control in patients with EBV-positive NPC. P16 expression may complement EBV status in predicting treatment outcomes for patients with NPC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1459-E1466, 2016.

Enhanced decision making and risk avoidance in high-functioning autism spectrum disorder.

OBJECTIVE: Everyday decision making requires integration of a broad range of information from a variety of sources, including cognitive and emotional processes. For individuals with autism spectrum disorder (ASD), everyday decision making can be difficult. The mechanisms that underlie decision making in young people diagnosed with ASD have not been fully explored. METHOD: We studied children and young adolescents with autism spectrum disorder (ASD; n = 48) compared with an age- and ability-matched typical control group (CON; n = 54). We evaluated performance and psycho-physiological responsivity during the Iowa Gambling Task (IGT), an affective decision-making task. RESULTS: ASD participants were superior to control participants on overall performance (p < .05), especially because of significantly better learning in later stages of the task. While both groups showed robust and equal psycho-physiological arousal to disadvantageous decks, the groups differed in their choice of card type, with the CON group choosing more often from the frequent-gain disadvantageous deck, despite occasional large losses; while the ASD group chose prominently from the advantageous decks. CONCLUSIONS: A decision-making style characterized by a drive to avoid potential loss rather than to seek possible reward may help decision making for ASD in some situations, but ultimately hinder functioning in relation to prosocial engagement and other complex situations where gain rather than punishment is the most effective motivating factor.

A potentiated startle study of uncertainty and contextual anxiety in adolescents diagnosed with autism spectrum disorder.

BACKGROUND: Beyond the core symptoms of autism spectrum disorder (ASD), associated symptoms of anxiety can cause substantial impairment for individuals affected by ASD and those who care for them. METHODS: We utilized a potentiated startle paradigm with a puff of air to the neck as the unconditioned stimulus in order to investigate differences between response to cued fear and contextual anxiety among cognitively able adolescents diagnosed with ASD and an age- and IQ-matched typically developing group. RESULTS: In a threat-modulated startle paradigm, response patterns to neutral, predictable, and unpredictable conditions were comparable across typically developing and ASD youth in terms of startle response magnitude and latency. However, the ASD group showed significantly greater absolute startle responsivity at baseline and throughout the experiment, suggesting possibly enhanced general sensitivity to threatening contexts. The ASD group, but not the control group, demonstrated moderate to strong negative correlations between psychophysiological response to unpredictable threats (uncertainty) and questionnaire measures of generalized anxiety, intolerance of uncertainty, and repetitive behavior. CONCLUSIONS: Our data suggest enhanced general reactivity among the ASD group, possibly reflecting greater sensitivity to the threatening context of the startle paradigm. Associations with the response to uncertainty may help explain shared neurobehavioral mechanisms in ASD and anxiety. This task can provide useful targets for future neuroimaging and genetics studies as well as specific avenues for intervention. We emphasize the importance of further basic and clinical research into links among these important constructs.

Delayed reversal learning and association with repetitive behavior in autism spectrum disorders.

An important aspect of successful emotion regulation is the ability to adjust emotional responses to changing environmental cues. Difficulties with such adaptation may underlie both marked symptoms of behavioral inflexibility and frequent severe anxiety in the autism spectrum disorders (ASDs). Thirty children and adolescents diagnosed with ASD and 29 age- and intelligence quotient-matched controls completed a reversal learning paradigm following partial reinforcement Pavlovian fear conditioning, using a surprising air puff as the unconditioned stimulus. After initial reversal of cue contingencies, where a previously safe cue now predicted the air puff threat, the control group but not the ASD group responded more strongly to the new threat cue. The ASD group showed evidence for reversal learning only during later trials. Reversal learning in the ASD group was significantly negatively correlated with everyday symptoms of behavioral inflexibility but not with everyday anxiety. Understanding shared associations between inflexibility, anxiety, and autism, with regard both to clinical symptoms and neurobiological mechanisms, can provide important markers for better characterizing the substantial heterogeneity across the autism spectrum.