Parental experiences of educational supports offered during their child's cancer treatment.

BACKGROUND: To explore how parents of children with cancer offer educational supports during the treatment process. METHODS: Based on a descriptive qualitative method design, 29 mothers and 19 fathers of children with cancer were interviewed on their experiences of supporting their child's education during their child's treatment through semi-structured interviews. RESULT: Six themes were summarized from the parents' experiences in supporting their child's education during treatment: initial emphasis on survival over education; educational strategies important when returning to everyday life post-treatment; parents and educators have different expectations; child's extracurricular activities provided a sense of accomplishment; preparing for transition to school; and long-term concern was for the child's health and happiness. CONCLUSION: Education is part of children's normal development, but education is often placed on hold for a child receiving cancer treatment. Parents of children with cancer are unable to focus on the child's education because of the threat to their child's life. When their child's illness stabilizes, they will begin to utilize their resources to arrange lessons to facilitate returning to school. Through understanding parents' learning expectations, medical professionals can support adjustments to parents' attitudes.

Comparison of psychosocial adaptations among childhood cancer survivors, their siblings and peers in Taiwan.

PURPOSE: This study aimed to understand the difference in psychosocial adaptation among childhood cancer survivors, their healthy siblings and peers, and the factors affecting the psychosocial adaptation of these cancer survivors. DESIGN AND METHODS: A total of 222 children (ages 8-17) including childhood cancer survivors, their siblings, and healthy peers participated in this cross-sectional study. All the children completed the anxiety and quality of life scales for their age groups. RESULTS: Anxiety levels and quality of life were similar among the childhood cancer survivors, their siblings, and their peers. The anxiety of elementary school-age survivors of acute leukemia was higher than that of those with solid tumors. Elementary school-age survivors who completed three or more years of treatment had lower anxiety than those who completed treatment within the three years. For adolescent survivors, the higher their body mass index, the higher their anxiety, which was associated with low quality of life. Those diagnosed with anxiety and at an older age had lower quality of life. CONCLUSIONS: Although there were no differences in survivors' psychosocial adaptation compared to their siblings and healthy peers, more than half of these adolescents had moderate to severe anxiety. Future study may need to explore the causes of their anxiety. PRACTICE IMPLICATIONS: During the follow-ups of the childhood cancer survivors, age-specific adaptive strategies can be discussed to reduce their anxiety and improve their quality of life.

Maternal high-fructose diet induced early-onset retinopathy via the suppression of synaptic plasticity mediated by mitochondrial dysfunction.

Retinopathy is a leading cause of blindness, and there is currently no cure. Earlier identification of the progression of retinopathy could provide a better chance for intervention. Diet has profound effects on retinal function. A maternal high-fructose diet (HFD) triggers diseases in multiple organs. However, whether maternal HFD impairs retinal function in adult offspring is currently unknown. By using the rodent model of maternal HFD during pregnancy and lactation, our data indicated a reduced b-wave of electroretinography (ERG) in HFD female offspring at 3 mo of age compared with age-matched offspring of dams fed regular chow (ND). Immunofluorescence and Western blot analyses indicated that the distributions and expressions of synaptophysin, postsynaptic density protein 95 (PSD95), and phospho(p)-Ca2+/calmodulin-stimulated protein kinase IIα (CaMKIIα) were significantly suppressed in the HFD group. Furthermore, the ATP content and the mitochondrial respiratory protein, Mt CPX 4-2, were decreased. Moreover, the expressions of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and mitochondrial transcription factor A (TFAM) in the retina of the HFD group were downregulated. Treatment with coenzyme Q10 (Q10), a key mediator of the electron transport chain, effectively reversed these abovementioned dysfunctions. Together, these results suggested that maternal HFD impaired retinal function in adult female offspring. The mechanism underlying early-onset retinopathy may involve the reduction in the capacity of mitochondrial energy production and the suppression of synaptic plasticity. Most importantly, mitochondria could be a feasible target to reprogram maternal HFD-damaged retinal function.NEW & NOTEWORTHY In this study, we provide novel evidence that maternal high-fructose diet during gestation and lactation could induce early-onset retinopathy in adult female offspring. Of note, the insufficient energy content, downregulated mitochondrial respiratory complex 4-2, and impaired mitochondrial biogenesis might contribute to the decrease of synaptic plasticity resulting in retinal function suppression. Oral application with coenzyme Q10 for 4 wk could at least partially reverse the aforementioned molecular events and retinal function.

Natural history and visual outcome of nonarteritic anterior ischemic optic neuropathy in Southern Taiwan: a pilot study.

PURPOSE: To investigate the natural course, visual outcome, and risk factors for visual loss after nonarteritic anterior ischemic optic neuropathy (NAION) attack in Chinese patients from a tertiary medical center in Southern Taiwan. METHODS: This is a longitudinal observational study that included sixty NAION patients, who were seen in our neuro-ophthalmology clinic from 2007 to 2016. Records of their ophthalmic history, medical history, best-corrected visual acuity (BCVA), visual field (VF) testing, and optical coherence tomography (OCT) were obtained for analysis. RESULTS: When the first visit was within two weeks after NAION onset, 62% of patients had BCVA of less than 0.1 (logMAR BCVA ≥ 1) and 38% had at least moderate-severe depression (VF grade ≥ 3) on VF on the initial visit. VA stabilized at three months after onset and was predictive of VA at 12 months. Diabetes mellitus was a risk factor associated with VA worsening. Sixty-one percent of patients had BCVA of less than 0.1 at 12 months after onset. VF remained relatively unchanged during the disease, with 41% eyes having VF grade ≥ 3 at 12 months after onset. On OCT, all quadrants of retinal nerve fiber layer thickened initially, returned to the level of the fellow eye at one month, and continued thinning up to 12 months slowly. CONCLUSION: In Southern Taiwan, a higher proportion of Chinese patients (over half) presented with severe visual loss during the first two weeks of NAION attack and at 12 months after the onset of NAION as compared to the findings previously reported in Caucasians. Understanding the natural course of NAION in Chinese patients may provide insights toward a possible therapeutic window for NAION treatments in this group of patients.

Mediating effects of depression on anxiety and leisure constraints in patients with breast cancer.

BACKGROUND: Patients with breast cancer often exhibit high levels of anxiety and depression and a considerable decrease in their ability to participate in leisure activities, which result in the long-term disruption of their daily lives. This study intended to explore the relationships among anxiety, leisure constraints, and depression and evaluate whether depression mediates the effects of anxiety on leisure constraints in patients with breast cancer. METHOD: This prospective study included 106 patients with breast cancer. All the patients completed the Taiwanese version of the Hospital Anxiety and Depression Scale and Leisure constraints questionnaire. Path analysis was used to test the mediating role of depression. RESULTS: Leisure constraints, anxiety, and depression were positively interrelated and co-occurred in the patients. The accelerated bootstrapping confidence intervals of the indirect effect did not include zero (0.276-1.663). Moreover, depression completely mediated the effects of anxiety on leisure constraints in patients with earlier cancer stages but not in patients with advanced cancer stages. CONCLUSIONS: Depression is a crucial mechanism underlying the relationship between anxiety and leisure constraints in patients with breast cancer. Although many patients experience minimal disruption of activities and roles during survivorship, they are unable to perform functional activities and satisfactorily play their roles. This is the first study to explore leisure constraints in patients with breast cancer and investigate the mediating role of depression that underlies the relationship between anxiety and leisure constraints. The current findings are clinically crucial because they suggest the need to consider the simultaneous management of anxiety and depression for alleviating leisure constraints.

The difference of surgical outcomes between manifest exotropia and esotropia.

PURPOSE: To determine the factors that affect ocular alignment and binocular sensory functions after strabismus surgery and compare surgical outcomes between manifest exotropia (XT) and esotropia (ET). METHODS: In a retrospective study, 41 XT and 17 ET patients who had undergone strabismus surgery were recruited. Information on type and duration of strabismus, age at onset of deviation and surgery, pre- and postoperative strabismus deviation angles, and binocular sensory functions including stereoacuity and macular fusion capacity was recorded. RESULTS: In all patients, the ocular alignment and binocular sensory functions improved with time following surgery. Residue strabismus deviation angles (≦ 10 prism diopters) at postoperative 1 month determined the final successful ocular alignment. In patients with final excellent binocular sensory functions, XT group restored macular fusion capacity and stereoacuity at postoperative 1 month, but ET group regained macular fusion capacity at postoperative 1 month and then restored stereoacuity at postoperative 3 months. Though XT patients showed better pre- and postoperative stereoacuity than ET patients, patients with successful ocular alignment had an odd of 4.5 in XT group and 22.5 in ET group to achieve excellent and fair binocular sensory functions. CONCLUSION: Surgical correction of strabismus could improve ocular alignment and binocular sensory functions in patients with manifest strabismus, regardless of onset age, strabismus duration, or type. Postoperative 1-month status may help to predict the final motor and sensory outcomes. ET patients would benefit more final successful ocular alignment and excellent binocular sensory functions from early surgery and maintaining postoperative small deviation angle than XT patients.

Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster Randomized Trial.

PURPOSE: To investigate the effectiveness of a school-based program promoting outdoor activities in Taiwan for myopia prevention and to identify protective light intensities. DESIGN: Multi-area, cluster-randomized intervention controlled trial. PARTICIPANTS: A total 693 grade 1 schoolchildren in 16 schools participated. Two hundred sixty-seven schoolchildren were in the intervention group and 426 were in the control group. METHODS: Initially, 24 schools were randomized into the intervention and control groups, but 5 and 3 schools in the intervention and control groups, respectively, withdrew before enrollment. A school-based Recess Outside Classroom Trial was implemented in the intervention group, in which schoolchildren were encouraged to go outdoors for up to 11 hours weekly. Data collection included eye examinations, cycloplegic refraction, noncontact axial length measurements, light meter recorders, diary logs, and questionnaires. MAIN OUTCOME MEASURES: Change in spherical equivalent and axial length after 1 year and the intensity and duration of outdoor light exposures. RESULTS: The intervention group showed significantly less myopic shift and axial elongation compared with the control group (0.35 diopter [D] vs. 0.47 D; 0.28 vs. 0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia progression (odds ratio, 0.46; 95% confidence interval [CI], 0.28-0.77; P = 0.003). The myopic protective effects were significant in both nonmyopic and myopic children compared with controls. Regarding spending outdoor time of at least 11 hours weekly with exposure to 1000 lux or more of light, the intervention group had significantly more participants compared with the control group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in school (≥200 minutes) showed significantly less myopic shift (measured by light meters; ≥1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; ≥3000 lux: 0.16 D; 95% CI, 0.002-0.32; P = 0.048). CONCLUSIONS: The school-based outdoor promotion program effectively reduced the myopia change in both nonmyopic and myopic children. Outdoor activities with strong sunlight exposure may not be necessary for myopia prevention. Relatively lower outdoor light intensity activity with longer time outdoors, such as in hallways or under trees, also can be considered.

Unilateral malignant optic glioma following glioblastoma multiforme in the young: a case report and literature review.

BACKGROUND: Malignant optic gliomas are rare, but they rapidly become lethal visual pathway tumors. We present the clinical course, treatment, and prognosis of a case of unilateral malignant optic glioma in a young man with a history of brain glioblastoma multiforme (GBM). CASE PRESENTATION: A 21-year-old man, who had GBM 7 years ago complained of a transient shadow in his vision and presented with normal visual acuity but optic disc edema and an enlarged blind spot in the right eye (oculus dexter, OD). Magnetic resonance imaging (MRI) showed a right intraorbital optic nerve tumor without a brain lesion. Chiasm involvement and severe vision deterioration occurred 3 months later. A biopsy of the right optic nerve revealed glioblastoma. Concurrent chemoradiotherapy (CCRT) prevented involvement of the fellow eye 1 year after symptom onset. CONCLUSION: This report demonstrated that a regular ocular exam should be recommended for several years after GBM. In young healthy patients who are able to undergo chemotherapy and radiotherapy, visual function in the fellow eye can be preserved.

Pattern visual evoked potentials for identifying malingering.

PURPOSE: To investigate the efficacy of pattern visual evoked potentials (VEPs) in evaluating objective visual acuity (VA) and discriminating malingerers. METHODS: Two hundred and forty-nine eyes of 249 patients aged 20-65 years were included. There were 147 eyes with macular diseases (group 1) and 102 eyes with optic nerve diseases (group 2). Amplitudes and latencies were analyzed and correlated with best-corrected visual acuity by a regression analysis. We found the best-correlated mode of pattern VEP, determined the relations, and then calculated the pattern VEP-estimated VA (PVEP-VA) of all 249 eyes, another 30 malingering eyes, 13 eyes with macular diseases, and 17 eyes with optic nerve diseases, and used a receiver operating characteristic (ROC) curve to determine a cutoff for acceptable variance between PVEP-VA and subjective VA to discriminate malingerers. RESULTS: The best correlation was between the amplitude of 50' checkerboard size (Amp50') and VA in every group. Significant correlation was between Amp50' and VA, where p < 0.0001 in group 1 and p = 0.020 in group 2. A logarithmic curve best fitted the correlation in the regression analysis, where y = 1.731 - 1.569x (R(2) = 0.611, p < 0.0001) in group 1 and y = 2.413 - 2.169x (R(2) = 0.531, p < 0.0001) in group 2 [x: log(Amp50'), y: PVEP-VA (logMAR)]. By using the relations and ROC curve, we determined a variance value of 0.4041 (logMAR) with 100% sensitivity and 94.0% specificity in group 1 and 0.3658 with 70.6% sensitivity and 50.5% specificity in group 2 to discriminate malingerers. CONCLUSIONS: The pattern VEP amplitude of 50' checkerboard size was useful to assess VA and can be helpful in discriminating malingering from real disability.

Experience and number of patients as associated factors toward clinical confidence among nursing students in caring for tuberculosis patients in Indonesia.

BACKGROUND: Nurses and nursing students are at greater risk of tuberculosis (TB) exposure due to their higher intensity contact with patients. In Indonesia, a country with high TB incidence, it is crucial to assess undergraduate nursing students' clinical confidence during their clinical practicums. PURPOSE: This study aimed to explore factors associated with nursing students' clinical confidence in caring for TB patients. METHODS: This cross-sectional study utilized an internet survey based on the United States National TB Curriculum Consortium (NTCC) in September and November 2020. The survey questions focused on TB knowledge, beliefs about the value of TB instruction, and clinical confidence in caring for TB patients. Descriptive statistics, t-test, ANOVA, Pearson's correlation coefficient, and hierarchical regression were used for data analysis. The Indonesian version of the original NTCC survey was used. RESULTS: The study found that nursing students' knowledge about TB increased with their year of study (r = 0.290, p < .001). However, students perceived TB instruction as less valuable as they neared graduation (r = -0.233, p < .001) and with more frequent practice in the TB unit (r = -0.162, p < .001). Students who spent more time learning about TB outside of class perceived the TB instruction in the nursing curriculum more positively (r = 0.181, p < .004). The study also found a significant difference between nursing students' belief in the value of TB education and their clinical confidence in caring for TB patients (F = 5.711, p < .001). Furthermore, experience caring for TB patients and the number of TB patients cared for predicted clinical confidence. CONCLUSIONS/IMPLICATIONS: This study highlights the need for improved curriculum content and teaching methods regarding TB for nursing students. It also suggests that experience caring for TB patients and the number of TB patients cared for can improve clinical confidence in nursing students. Given the high incidence of TB in Indonesia, this study's findings could have important implications for the country's healthcare system.

Taiwanese fathers' experiences of caring for their children during childhood cancer treatment.

PURPOSE: Parents must manage their own stress and help their child with cancer during the treatment process, both physically and emotionally. With the increased involvement of fathers in caring for the family, how fathers adjust to the stress and play a role in care responsibilities is unknown. This study aimed to explore the fathers' experiences of caring for their ill child during the cancer diagnosis and treatment process. METHOD: This study adopted a qualitative descriptive design and conducted in-depth interviews with 21 fathers with a diagnosed child recruited from a northern Taiwan medical center. Data were managed and analysed using content analysis. RESULTS: Two main categories in the Taiwanese fathers' experiences of caring for their ill child during the cancer diagnosis and treatment process emerged: 1) the maintainer of family stability, and 2) thoughts and value adjustment. Each main category consists of 3-4 generic categories. They make the necessary adjustments between work and family, actively participate in caring for the entire family, and redefine family values. They convey information about the illness to their children, pay attention to the physical and psychological development of the child with cancer, and cherish the time spent together as a family. CONCLUSIONS: During the cancer treatment process, fathers play the roles of the protector and maintainer of family stability and adjust their attitudes and thoughts toward the family members and family life. Healthcare professionals can offer the fathers comprehensive support and improve the family's overall well-being during this demanding period.

ω-3 PUFAs Ameliorated the Maternal High-Fructose Diet-Induced Early-Onset Retinopathy in Offspring via Inhibiting NLRP3-Associated Neuroinflammation.

SCOPE: Maternal high fructose diet (HFD) during pregnancy and lactation can initiate retinal dysfunction. However, the underlying mechanism remains largely unknown. METHODS AND RESULTS: By using the rodent model of maternal HFD in this study, the results from electroretinography (ERG) indicate that b-wave amplitude, an index of inner retinal function, is significantly reduced as early as 3 months old and the deteriorated effect can be detected at 15 months old. Further, the protein expressions of CD11b (a marker of active microglia), p40phox subunit of NADPH oxidase, GFAP (a marker of active astrocytes), and NLPR3 examined by western blot and immunofluorescence are significantly increased in the retina of the male HFD offspring at 3 months old. Treatment with omega-3 polyunsaturated fatty acids (ω-3 PUFAs) for 2 weeks (from 2.5 to 3 months old) effectively reverses the aforementioned changes. CONCLUSION: Together, these results indicate that the early onset and extensive retinal dysfunction may be a result of glial activation which is induced by maternal HFD to initiate an inflammatory microenvironment leading to a long-term progression of retinopathy. Short-term administration of ω-3 PUFA at a young age may be a feasible strategy to intervene in the maternal HFD-programmed retinal impairment in male offspring.

Add-on perceptual learning on refractive amblyopia in children.

AIM: To evaluate the visual outcomes of standard amblyopic treatment add-on training via perceptual learning in refractive amblyopic children and to identify the risk factors for treatment failure. METHODS: Retrospective charts were reviewed in children with refractive amblyopia who received standard treatment and add-on Cambridge Visual Stimulator (CAM) training. The add-on CAM group that was enrolled had worn full-corrected glasses for at least 2mo before training. A control group received only the standard treatment. Treatment success was defined as best-corrected visual acuity (BCVA) ≥20/25. The age, sex, initial BCVA, refractive errors, sessions and duration of training, and final BCVA were recorded. RESULTS: A total of 209 children (129 children in add-on CAM group and 80 children in control group) were enrolled. Seventy-six percent of unilateral and 87% of bilateral amblyopic children achieved treatment success. In children with unilateral or bilateral moderate amblyopia, the duration to reach BCVA ≥20/25 was significantly shorter in add-on CAM group than in control group. Poor initial BCVA (P<0.001) and high astigmatism (P=0.007) were risk factors for treatment failure after add-on CAM training. Age, sex, and types of refractive error were not associated with treatment success. CONCLUSION: Add-on CAM training is an effective strategy for visual improvement and can shorten the treatment course when the effect of standard treatment is limited in amblyopic children.

Butyrate reduction and HDAC4 increase underlie maternal high fructose-induced metabolic dysfunction in hippocampal astrocytes in female rats.

Maternal nutrient intake influences the health of the offspring via microenvironmental systems in digestion and absorption. Maternal high fructose diet (HFD) impairs hippocampus-dependent memory in adult female rat offspring. However, the underlying mechanisms remain largely unclear. Maternal HFD causes microbiota dysbiosis. In this study, we find that the plasma level of butyrate, a major metabolite of microbiota, is significantly decreased in the adult female maternal HFD offspring. In these rats, GPR43, a butyrate receptor was downregulated in the hippocampus. Moreover, the expressions of mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) were downregulated in the hippocampus. The decreases of these functional proteins were reversed by fructooligosaccharides (FOS, a probiotic) treatment in adulthood. Astrocytes are critical for energy metabolism in the brain. Primary astrocyte culture from female maternal HFD offspring indicated that GPR43 and the mitochondrial biogenesis were significantly suppressed, which was reversed by supplemental butyrate incubation. The oxygen consumption rate (OCR) was reduced in the HFD group and rescued by butyrate. Intriguingly, the nuclear histone deacetylase 4 (HDAC4) was enhanced in the HFD group, suggesting an inhibitory role of butyrate on histone deacetylase activity. Inhibition of HDAC4 effectively restored the OCR, bioenergetics, and biogenesis of mitochondria. Together, these results suggested that the impaired butyrate signaling by maternal HFD could underlie the reduced mitochondrial functions in the hippocampus via HDAC4-mediated epigenetic changes.

Thyroxin treatment protects against white matter injury in the immature brain via brain-derived neurotrophic factor.

BACKGROUND AND PURPOSE: Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. METHODS: Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. RESULTS: On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. CONCLUSIONS: T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

Hypoxic-ischemic retinal injury in rat pups.

BACKGROUND: Visual loss associated with brain damage, especially hypoxic-ischemic (HI) encephalopathy, is the most common cause of visual impairment in children in developed countries. We hypothesized that HI insults can cause long-term damage in immature eyes. METHODS: In postnatal day 7 rat pups, HI was induced by unilateral common carotid artery ligation followed by hypoxia. Retina damage was assessed by electroretinography (ERG) and cell counting. Neuronal injury and astrogliosis were evaluated by terminal deoxynucleotidyl transferase nick-end labeling, cleaved caspase 3, ED1, and glial fibrillary acidic protein immunostaining. RESULTS: We observed rapid and persistently extensive injuries in the ganglia cell layer (GCL), inner plexiform layer, and inner nuclear layer (INL) in ipsilateral retinas after HI injury, corresponding to the marked alteration in ERG. HI insult caused prominent microglial and Muller cell activation in ipsilateral inner retinas. Neuronal death in the GCL and INL after HI injury was mainly apoptotic, involving caspase-dependent pathways. CONCLUSION: Our study demonstrated the first evidence of HI retinal damage at both the pathological and functional level using the Vannucci model in neonatal rats. Because retinal damage is often associated with HI injury, it is important to demonstrate that a particular neuroprotective strategy effectively preserves the retina in addition to the brain.

Combination Therapy with Intravitreal Triamcinolone Acetonide and Oral Levodopa for the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Pilot Study.

Purpose: To determine the clinical effectiveness of combination therapy with intravitreal injection of triamcinolone acetonide (IVITA) and oral levodopa in eyes affected by nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Longitudinal study involving 45 eyes of 45 patients with NAION who were evaluated within 14 days of NAION onset. The treatment group received an IVITA 4 mg/0.1 mL followed by 25 mg carbidopa/100 mg levodopa (Sinemet 25-100) 3 times daily for 12 weeks and the control group was untreated. Best-corrected visual acuity (BCVA) converted to logarithmic minimum angle of resolution (logMAR), visual field (VF) grades based on automated or Goldman perimetry, and mean retinal nerve fiber layer (RNFL) thickness measured on optical coherence tomography were assessed at the initial visit, 1, 3, and 6 months after NAION attack. Results: At the first visit and 6 months after NAION onset, the mean logMAR BCVA in the treatment group was significantly better than the control group (P < 0.05). BCVA was not significantly different between onset and the 6-month visit for both the control and the treatment group; however, the change in BCVA after 6 months was significantly greater in the treatment group compared with the control group (P = 0.007). Concomitant systemic disease, the changes in VF grades, and RNFL thickness from initial to 6 months after NAION onset were not significantly different between 2 groups. Conclusions: Combination therapy with IVITA and oral levodopa/carbidopa appears to be effective in the treatment of recent-onset NAION.

Retinopathy of Prematurity Is a Biomarker for Pathological Processes in the Immature Brain.

INTRODUCTION: Retinopathy of prematurity (ROP) is considered a neurovascular disease. We investigated whether ROP, mild or severe, is associated with neurodevelopmental impairment (NDI) in extremely preterm children. METHODS: We conducted a multicenter retrospective cohort study in southern Taiwan. A total of 394 children <28 weeks of gestation who survived to discharge from 2011 to 2018 received neurodevelopmental assessment at corrected age of 24 months. Severe ROP was defined as ROP of stages 2 plus or worse, or recipients of retinal therapy, and mild ROP as stage 1 or 2 in at least one eye. NDI was defined as cognitive or motor impairment using the Bayley Scales of Infant and Toddler Development, moderate to severe cerebral palsy, or profound hearing loss. RESULTS: Among the 374 children validated for analysis, 157 children (42%) had non-ROP, 145 (39%) mild ROP, and 72 (19%) severe ROP. As ROP severity increased progressively from non-ROP, to mild ROP, and to severe ROP, the rates of NDI increased from 25%, to 46%, and to 61%. The multivariable logistic regression showed that the model included three levels of ROP, and neonatal morbidities achieved better overall performance for NDI than the model that included neonatal morbidities alone. Compared with non-ROP, mild ROP and severe ROP had adjusted odds ratios of 1.90 (95% CI: 1.10-3.28) and 2.75 (95% CI: 1.33-5.67) for NDI, respectively. CONCLUSION: Mild ROP and severe ROP are independent neonatal morbidities associated with NDI. Neurodevelopmental follow-up of extremely preterm children with any stage of ROP is needed.

Artemin Is Upregulated by TrkB Agonist and Protects the Immature Retina Against Hypoxic-Ischemic Injury by Suppressing Neuroinflammation and Astrogliosis.

Hypoxic-ischemia (HI) is a major cause of acquired visual impairment in children from developed countries. Previous studies have shown that systemic administration of 7,8-dihydroxyavone (DHF), a selective tropomyosin receptor kinase B (TrkB) agonist, provides long-term neuroprotection against HI injury in an immature retina. However, the target genes and the mechanisms of the neuroprotective effects of TrkB signaling are not known. In the present study, we induced an HI retinal injury through unilateral common carotid artery ligation followed by 8% oxygen for 2 h in P7 rat pups. DHF was administered intraperitoneally 2 h before and 18 h after the HI injury. A polymerase chain reaction (PCR) array was used to identify the target genes upregulated after the DHF treatment, which was then confirmed with quantitative real-time reverse transcriptase PCR and a western blot. Effects of the downstream mediator of DHF were assessed using an intravitreal injection of neutralizing antibody 4 h after DHF administration (24 h after HI). Meanwhile, the target protein was injected into the vitreous 24 h after HI to validate its protective effect when exogenously supplemented. We found that systemic DHF treatment after HI significantly increased the expression of the artemin (ARTN) gene and protein at P8 and P10, respectively. The neuroprotective effects of DHF were inhibited after the ARTN protein blockade, with an increase in neuroinflammation and astrogliosis. ARTN treatment showed long-term protection against HI injury at both the histopathological and functional levels. The neuroprotective effects of ARTN were related to a decrease in microglial activation at P17 and attenuation of astrogliosis at P29. ARTN enhances phosphorylation of RET, ERK, and JNK, but not AKT or p38 in the immature retina. Altogether, these results suggest that the neuroprotective effect of a TrkB agonist is partially exerted through a mechanism that involves ARTN because the protective effect is ameliorated by ARTN sequestration. ARTN treatment after HI injury protects the immature retina by attenuating late neuroinflammation and astrogliosis in the immature retina relating to the ARTN/RET/JNK/ERK signaling pathway. ARTN may be a strategy by which to provide long-term protection in the immature retina against HI injury.