Pituitary deficiencies related to optic nerve hypoplasia and visual acuity.

OBJECTIVE: Optic nerve hypoplasia (ONH), the congenital underdevelopment of the optic nerve, is an increasing cause of visual impairment and is associated with pituitary dysfunction. Past studies have focused on the relationship between ONH, pituitary deficiencies, and brain imaging. However, recent studies have demonstrated the true risk for hypopituitarism lies with the presence or absence of ONH, irrespective of midline brain findings. This study reviewed the relationship between the health of the optic nerve (visual acuity) and pituitary gland (number and age of development of pituitary deficiencies) as a way to stratify risk, regardless of imaging findings. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective chart review of 197 patients seen at a single center from 2013 to 2022. Visual assessment was defined by distance acuity, and the presence of nystagmus or afferent pupillary defect. Pituitary deficiencies were diagnosed per Endocrine Society guidelines. RESULTS: In children with bilateral ONH (bONH), profound visual impairment was associated with more pituitary deficiencies between 0 and 15 years of age. The odds of having any pituitary deficiency were 4.9 times higher (95% confidence interval [95% CI]: 2.4-10.1) for patients with bONH versus unilateral ONH (uONH). Central hypothyroidism was the most common first presenting pituitary deficiency followed by growth hormone across all patients. CONCLUSION: This study shows a significant association between severity of visual impairment and increased probability of pituitary deficiencies in children with bONH versus uONH. Children with ONH require urgent endocrine evaluation due to risk of pituitary deficiencies, but risk stratification may also be based on severity of visual impairment.

Pharmacotherapy for attention deficit/hyperactivity disorder in youth with avoidant restrictive food intake disorder: a case series of patients prescribed stimulant medication in a partial hospitalization program for eating disorders.

BACKGROUND: Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects may be especially problematic when using stimulants to treat ADHD in the context of a restrictive eating disorder, such as avoidant restrictive food intake disorder (ARFID), although these diagnoses are often comorbid in children. This paper presents a combined approach to treating ADHD comorbid with ARFID using stimulant medication and behavior management within a partial hospitalization program (PHP) and intensive outpatient program (IOP)for eating disorders. The aim of this paper is to determine if the continued or new use of stimulant medication allows for adequate weight restoration by reviewing a series of cases receiving the combined treatment. CASE PRESENTATIONS: Consecutive patients with a historical or new diagnosis of ADHD when presenting for treatment for ARFID were included in this case series. This series included 10 patients (8 male, 2 female) who received pharmacotherapy using stimulants and behavior management interventions involving structured mealtimes and contingency management. All treatment occurred within the context of a PHP/IOP for childhood eating disorders. All youth were able to effectively continue on stimulant medication, show clinical benefit in core ADHD symptoms, and able to gradually restore weight. In all cases, stimulant medications were not discontinued, but in some cases, doses were optimized (increased or decreased), switched to a different stimulant, or augmented with non-ADHD medication, such as mirtazapine, to support the management of ADHD while concurrently assisting in weight gain as necessary for the treatment of ARFID. Only one patient was newly started on a stimulant medication; as this was near the end of her treatment stay, limited conclusions can be drawn from this case. CONCLUSIONS: These findings support the use of pharmacotherapy, including continuing stimulant medication, when combined with behavior management strategies as a potentially effective treatment approach for ADHD in youth with ARFID in the PHP/IOP setting. Future studies using more rigorous methodology, longer follow-up times, and within other treatment settings are needed.

"Even though a lot of kids have it, not a lot of people have knowledge of it": A qualitative study exploring the perspectives of parents of children with cerebral/cortical visual impairment.

BACKGROUND: Cerebral/Cortical Visual Impairment (CVI) is the leading cause of visual impairment in children and can negatively impact participation in daily activities. METHODS AND PROCEDURE: This qualitative study used virtual focus groups and an online questionnaire to understand the perspectives of families with children who have CVI. Constant comparison analysis was used to analyze focus group transcripts and extract themes. The PEDI-CAT and an online questionnaire were administered to characterize the study population. OUTCOMES AND RESULTS: Four themes were identified: (1) Awareness of CVI and its effect on the child and family, (2) Parent experiences, (3) Child factors and functional implications, and (4) Supports that enhance child development/vision. CONCLUSIONS AND IMPLICATIONS: Findings from this study highlight the substantial impact that lack of CVI awareness had on parent experiences. Lack of awareness led to late diagnosis, missed intervention opportunities, and caregiver burden. Due to insufficient resources, parents had to educate themselves and service providers about CVI and advocate for their child's needs. Healthcare and educational providers who work with pediatric neurodevelopmental populations must be knowledgeable about clinical features of CVI, task and environmental adaptations to support vision and implementation of family-centered care.

Long-Term Anatomic and Visual Outcomes of Planned Preterm Delivery and Treatment of Norrie Disease.

We previously reported that planned preterm delivery at 34 weeks gestational age provided an opportunity to treat Norrie disease in the vasoproliferative phase, prevented infantile retinal detachment, and preserved functional vision without further treatment after infancy. Although retinal vascularization did not proceed postnatally, after 8 years of follow-up, the retinas remained attached, and rudimentary foveal development was observed by optical coherence tomography. Best corrected visual acuity gradually improved to 20/80 with both eyes, and visual fields and real-world visual performance were remarkably functional. Global development progressed appropriately, and no long-term sequelae of premature delivery were observed. [Ophthalmic Surg Lasers Imaging Retina 2022;53:464-467.].

Evaluating the use of lamotrigine to reduce mood lability and impulsive behaviors in adults with chronic and severe eating disorders.

BACKGROUND: Gold-standard psychological and pharmacological treatments for bulimic-spectrum eating disorders only result in remission for around 50% of patients; patients with affective lability and impulsivity represent a subgroup with particularly poor outcomes. Both dialectical behavior therapy (DBT), a treatment for emotion dysregulation, and lamotrigine, a mood stabilizer, have demonstrated promise for targeting affective lability and impulsivity; however, data exploring the combination of these interventions remain limited. OBJECTIVE: We followed a group of women with recurrent dysregulated eating behaviors (N = 62) throughout intensive DBT treatment and compared the symptom trajectory of those prescribed lamotrigine (n = 28) and those who were not (n = 34). METHOD: Participants completed surveys every 2 weeks throughout treatment. RESULTS: Group analyses suggested that all participants self-reported decreases in emotional reactivity, negative urgency, and symptoms of borderline personality disorder (BPD). The lamotrigine group reported greater elevations in BPD symptoms at baseline, but demonstrated steeper decreases in emotion and behavioral dysregulation than the non-matched comparison group. Within-subject analyses suggested that within the lamotrigine group, subjects reported greater decreases in symptoms following prescription of lamotrigine. CONCLUSIONS: Findings provide initial data suggesting that lamotrigine could be useful as an adjunctive treatment for patients with affective lability and impulsivity. LEVEL OF EVIDENCE: IV, time series without randomization.

Brain microstructural antecedents of visual difficulties in infants born very preterm.

Infants born very preterm (VPT) are at risk of later visual problems. Although neonatal screening can identify ophthalmologic abnormalities, subtle perinatal brain injury and/or delayed brain maturation may be significant contributors to complex visual-behavioral problems. Our aim was to assess the micro and macrostructural antecedents of early visual-behavioral difficulties in VPT infants by using diffusion MRI (dMRI) at term-equivalent age. We prospectively recruited a cohort of 262 VPT infants (≤32 weeks gestational age [GA]) from five neonatal intensive care units. We obtained structural and diffusion MRI at term-equivalent age and administered the Preverbal Visual Assessment (PreViAs) questionnaire to parents at 3-4 months corrected age. We used constrained spherical deconvolution to reconstruct nine white matter tracts of the visual pathways with high reliability and performed fixel-based analysis to derive fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC). In multiple logistic regression analyses, we related these tract metrics to visual-behavioral function. Of 262 infants, 191 had both high-quality dMRI and completed PreViAs, constituting the final cohort: mean (SD) GA was 29.3 (2.4) weeks, 90 (47.1%) were males, and postmenstrual age (PMA) at MRI was 42.8 (1.3) weeks. FD and FC of several tracts were altered in infants with (N = 59) versus those without retinopathy of prematurity (N = 132). FDC of the left posterior thalamic radiations (PTR), left inferior longitudinal fasciculus (ILF), right superior longitudinal fasciculus (SLF), and left inferior fronto-occipital fasciculus (IFOF) were significantly associated with visual attention scores, prior to adjusting for confounders. After adjustment for PMA at MRI, GA, severe retinopathy of prematurity, and total brain volume, FDC of the left PTR, left ILF, and left IFOF remained significantly associated with visual attention. Early visual-behavioral difficulties in VPT infants are preceded by micro and macrostructural abnormalities in several major visual pathways at term-equivalent age.

Physician Prescribing and Referral Patterns in Children with Cerebral Visual Impairment.

SIGNIFICANCE: Cerebral visual impairment (CVI) is the leading cause of visual impairment in the developed world. Providing children with CVI with the appropriate treatment ensures the best possible visual outcome and potentially improves quality of life. PURPOSE: The purpose of this study was to determine physician prescribing and visual rehabilitation referral patterns in children with CVI. METHODS: A retrospective chart review was completed on children with CVI examined at Cincinnati Children's Hospital Medical Center from January 1, 2008, to March 1, 2018. Significant refractive error warranting correction was determined using the American Academy of Ophthalmology Preferred Guidelines and the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee Guidelines. The CVI Range was used as a surrogate to categorize CVI severity. RESULTS: A total of 194 children were included. Sixty-eight (35%) had refractive error warranting correction and were prescribed glasses (group RC), 99 (51%) did not have refractive error warranting correction and were not prescribed glasses (group NRNC), 20 (10%) had refractive error warranting correction but were not prescribed glasses (group RNC), and 7 (4%) did not have refractive error warranting correction but were prescribed glasses (group NRC). There was greater than one-line Snellen equivalent difference between group RC (20/156) and group RNC (20/221). There was greater than six-line Snellen equivalent difference between group NRNC (20/149) and group NRC (20/35). Mean CVI Range score 2 values for each group were 5.9, 4.6, 4.8, and 7.1. CONCLUSIONS: Children with less severe CVI were less likely to have significant refractive error but given glasses. Despite significant refractive error, children with more severe CVI were not prescribed glasses. Children with very low visual function were not prescribed glasses as frequently, possibly limiting their visual rehabilitation. Providers should ensure that all children with CVI are correctly prescribed glasses to provide the best possible visual outcome.

A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment-resistant depression.

Severe and enduring eating disorders (EDs) have the highest mortality rate of all psychiatric illnesses (Arch Gen Psychiatry, 2011, 68, 724), especially when comorbid with treatment-resistant depression (TRD) (Psychiatr Res, 2016, 244, 45). We report on four patients with enduring EDs and TRD treated with repeat ketamine over 12 + months, showing improvement in depression with only modest changes in ED symptoms.

Mirtazapine and Weight Gain in Avoidant and Restrictive Food Intake Disorder.

Avoidant and restrictive food intake disorder (ARFID) is a newly classified disorder in the DSM-5 that describes a pattern of restrictive eating across the lifespan that results in significant weight loss, nutritional deficiency, dependence on enteral feeding or nutritional supplements, or marked interference in psychosocial functioning.1 Currently, there are no evidence-based treatment approaches or medications for this disorder.2 We have administered a range of psychoactive medications to those with ARFID in our treatment program in an attempt to find an effective medication. One medication of interest has been mirtazapine because it promotes appetite and weight gain, decreases nausea and vomiting, and improves gastric emptying. Although mirtazapine is an off-label approach in a pediatric population and carries a black box warning for an increased risk of suicide, it is an effective treatment for depression and anxiety symptoms in adults and is generally well tolerated.3,4 There are no studies to date reporting on the use of mirtazapine in patients with ARFID.

A pilot open series of lamotrigine in DBT-treated eating disorders characterized by significant affective dysregulation and poor impulse control.

BACKGROUND: There is little effective psychopharmacological treatment for individuals with eating disorders who struggle with pervasive, severe affective and behavioral dysregulation. METHODS: This pilot open series evaluated lamotrigine, a mood stabilizer, in the treatment of patients with eating disorders who did not respond adequately to antidepressant medications. Nine women with anorexia nervosa- or bulimia nervosa-spectrum eating disorders in partial hospital or intensive outpatient dialectical behavior therapy (DBT)-based eating disorder treatment took lamotrigine for 147 ± 79 days (mean final dose = 161.1 ± 48.6 mg/day). Participants completed standardized self-report measures of emotion dysregulation and impulsivity after lamotrigine initiation and approximately biweekly thereafter. Mood and eating disorder symptomatology were measured at lamotrigine initiation and at time of final assessment. RESULTS: Lamotrigine and concurrent DBT were associated with large reductions in self-reported affective and behavioral dysregulation (ps < 0.01). Eating disorder and mood symptoms decreased moderately. CONCLUSIONS: Although our findings are limited by the confounds inherent in an open series, lamotrigine showed initial promise in reducing emotional instability and behavioral impulsivity in severely dysregulated eating-disordered patients. These preliminary results support further investigation of lamotrigine for eating disorders in rigorous controlled trials.

Functional and structural connectivity of the visual system in infants with perinatal brain injury.

BACKGROUND: Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. METHODS: Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. RESULTS: Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. CONCLUSION: Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

Lamotrigine use in patients with binge eating and purging, significant affect dysregulation, and poor impulse control.

OBJECTIVE: Some patients with symptoms of binge eating and purging are successfully treated with specific serotonin reuptake inhibitors (SSRIs), but others experience only partial or no benefit. Significant affect dysregulation and poor impulse control may be characteristics that limit responsiveness. METHOD: We report on the treatment of five patients with bulimia nervosa (BN), anorexia nervosa-binge/purge type (AN-B/P) or eating disorder not otherwise specified (EDNOS), using the anticonvulsant lamotrigine after inadequate response to SSRIs. RESULTS: Following addition of lamotrigine to an antidepressant in four cases, and switch from an antidepressant to lamotrigine in one case, patients experienced substantial improvement in mood reactivity and instability, impulsive drives and behaviors, and eating-disordered symptoms. DISCUSSION: These findings raise the possibility that lamotrigine, either as monotherapy or as an augmenting agent to antidepressants, may be useful in patients who binge eat and purge, and have significant affect dysregulation with poor impulse control.

Health-related quality of life after surgical removal of an eye.

PURPOSE: This study compared the general health-related quality of life (HRQOL) and the vision-specific HRQOL in patients following the surgical removal of 1 eye who had good vision in the remaining eye to a group of binocular patients with good vision in OU. METHODS: The Medical Outcomes Study Short Form 12 and the National Eye Institute Visual Function Questionnaire HRQOL surveys were administered to 29 patients who had surgical removal of an eye who attended an ocular prosthetics clinic and to 25 binocular persons who accompanied a patient. All subjects in each group had best-corrected visual acuity of 20/40 or better. Overall statistical significance was tested using Cramer's V followed by individual t tests for independent groups for each of the scales on the 2 questionnaires to determine whether the means between the 2 groups differed statistically. RESULTS: The patient group had a mean age of 50.98 years (range, 19-76 years). The control group had a mean age of 49.46 years (range, 18-76 years). The mean time after loss of vision was 28.03 years (range, 1-71 years), and the mean time from surgical removal of the eye was 23.6 years (range, 0.5-59.5 years). There was an overall significant difference between the 2 groups on the 15 derived subscales of the 2 forms (Cramer's V, p = 0.0025). Three general HRQOL subscales (Short Form 12-mental component summary, Short Form 12 physical component summary, and National Eye Institute Visual Function Questionnaire-General Health) showed no differences between the 2 groups (p = 0.48, p = 0.81, and p = 0.78, respectively). Three of the 12 vision-specific National Eye Institute Visual Function Questionnaire subscales demonstrated statistically significant differences between the patient and control groups: peripheral vision (p = 0.0006), role difficulties (p = 0.015), and the composite score (p = 0.014). In addition, 2 monocular patients had given up driving compared with no binocular subjects (p = 0.056). CONCLUSIONS: This population of monocular patients had general physical and mental HRQOL equivalent to the normal binocular group despite the surgical removal of 1 eye. However, the reduced vision-specific HRQOL of monocular patients on the National Eye Institute Visual Function Questionnaire indicates that there are substantial residual visual deficits even after prolonged monocular status.

Aripiprazole in anorexia nervosa and low-weight bulimia nervosa: case reports.

OBJECTIVE: There has been much interest in the use of atypical antipsychotics in anorexia nervosa (AN). However, newer, more weight-neutral medications have not been studied in AN, and there are no reports of the use of antipsychotics in bulimia nervosa (BN). METHOD: We report on the treatment of eight patients (five with AN and three with BN) with aripiprazole for time periods of four months to more than three years. RESULTS: All individuals had reduced distress around eating, fewer obsessional thoughts about food, weight and body image, significant lessening of eating-disordered behaviors, and gradual weight restoration where appropriate. Depression, generalized anxiety, and cognitive flexibility improved as well. DISCUSSION: In summary, these findings support the need to perform controlled trials of aripiprazole in AN and BN.

Retinotopic maps and foveal suppression in the visual cortex of amblyopic adults.

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early-onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.

Monocular activation of V1 and V2 in amblyopic adults measured with functional magnetic resonance imaging.

PURPOSE: Although previous neuroimaging efforts clearly indicate visual cortical dysfunction in adults with amblyopia, the extent of abnormalities remains unclear. METHODS: This functional magnetic resonance imaging (fMRI) study directly compared activity in visual cortex produced by monocular stimulation in 18 adults (six esotropic strabismics, six anisometropes, and six controls). Measures were made in three cortical regions-of-interest, individually defined using standard retinotopic mapping techniques in the nonamblyopic eye, corresponding to extrafoveal V1, extrafoveal V2, and the foveal representation at the occipital pole. Fixation stability was monitored and found not to differ significantly between subject groups. RESULTS: Overall results showed depressed fMRI signal magnitude for amblyopic eyes compared with sound eyes, although a few subjects did not show this trend. Assessment of the spatial extent of activation using an ocular dominance index did show significantly larger interocular differences for both strabismics and anisometropes compared with control subjects for whom eye dominance was carefully defined. In addition, both amblyopic groups showed less cortical area able to be significantly driven by either eye. The magnitude of these effects was equivalent in V1, V2, and the foveal representation, as well as between amblyopic groups. No difference was detected in the strength of signal from the nasal versus temporal retina in either amblyopic group. CONCLUSIONS: Asymmetries in magnitude of monocular activation do occur in subjects with amblyopia, but these basic measures are limited in terms of sensitivity for mild to moderate amblyopia and for specificity between subtypes.

Relating binocular and monocular vision in strabismic and anisometropic amblyopia.

OBJECTIVES: To examine deficits in monocular and binocular vision in adults with amblyopia and to test the following 2 hypotheses: (1) Regardless of clinical subtype, the degree of impairment in binocular integration predicts the pattern of monocular acuity deficits. (2) Subjects who lack binocular integration exhibit the most severe interocular suppression. METHODS: Seven subjects with anisometropia, 6 subjects with strabismus, and 7 control subjects were tested. Monocular tests included Snellen acuity, grating acuity, Vernier acuity, and contrast sensitivity. Binocular tests included Titmus stereo test, binocular motion integration, and dichoptic contrast masking. RESULTS: As expected, both groups showed deficits in monocular acuity, with subjects with strabismus showing greater deficits in Vernier acuity. Both amblyopic groups were then characterized according to the degree of residual stereoacuity and binocular motion integration ability, and 67% of subjects with strabismus compared with 29% of subjects with anisometropia were classified as having "nonbinocular" vision according to our criterion. For this nonbinocular group, Vernier acuity is most impaired. In addition, the nonbinocular group showed the most dichoptic contrast masking of the amblyopic eye and the least dichoptic contrast masking of the fellow eye. CONCLUSION: The degree of residual binocularity and interocular suppression predicts monocular acuity and may be a significant etiological mechanism of vision loss.

Voxel-based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia.

Amblyopia, sometimes called "lazy eye," is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience-dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7-12 years and 18-35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high-resolution MRI brain images were analyzed quantitatively with optimized voxel-based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region-of-interest analysis. For the children with amblyopia, additional gray matter reductions in parietal-occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia.

Suicide risk management for the sequenced treatment alternatives to relieve depression study: applied NIMH guidelines.

NIMH guidelines to manage subjects who are suicidal during their participation in clinical trials include a full range of procedures to minimize suicidal risk, yet no reports to date have shown how researchers should best implement these guidelines. The architects of the sequenced treatment alternatives to relieve depression (STAR*D) study operationalized and implemented the NIMH guidelines by developing a comprehensive set of procedures to detect, monitor, and manage suicidal subjects during a large, complex, multisite clinical trial. Because of the large size of the study (anticipated n = 4000), the wide geographic distribution, the large number of treating STAR*D clinicians, the broad array of subjects with psychiatric and medical comorbidities, and the focus on treatment-resistant depression, along with the complexity of multiple treatment steps and randomization points in STAR*D, the risk of suicide, safety monitoring of suicidal subjects presented a unique challenge. This paper describes methods derived from the NIMH guidelines used to manage suicidal risk in STAR*D including the use of an interactive voice response system to alert clinicians, regional center directors, and safety officers.