Predictors of disease course and long-term outcomes of idiopathic intracranial hypertension in children and adolescents.

This study aimed to identify predictors for unfavorable disease course and clinical and visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH). Employing a multi-tiered approach, we retrospectively analyzed clinical, ophthalmic, and neuroimaging data from patients diagnosed with IIH between 2003 and 2021. Of the 97 patients included, 56 (58%) were females. The median age was 12 years [Interquartile range (IQR) 9, 14], and the median follow-up time was 39.0 months (IQR 14.8, 90.9). Forty-two (43%) patients had an unfavorable disease course, 28 (29%) had persistence of headache at last follow-up, and 16 (18%) had a poor visual outcome, most of them with mild visual disturbances. Poor visual outcome was more common in females compared to males [16/47 (34%) vs. 0/39, p < 0.001)]. On multivariate regression analysis, female sex and disease recurrence were significantly associated with poor visual outcomes (OR: 18.5, CI:1.3-270, P = 0.03, and OR: 5.1, CI: 1.2-22.5, P = 0.03, respectively). Patients with persistent headaches exhibited lower incidence of papilledema, lower opening pressure, and fewer neuroimaging markers indicating elevated intracranial pressure. CONCLUSIONS: This study provides insights into predictive factors for an unfavorable disease course, persistent headaches, and poor visual outcomes in patients with childhood IIH. Patients with persistent headaches may have a variant of a chronic pain syndrome warranting a different therapeutic approach. WHAT IS KNOWN: • Childhood-onset Idiopathic Intracranial hypertension (IIH) is a heterogenous disease. The knowledge on disease trajectory and long-term outcomes and its predictors is limited. WHAT IS NEW: • A higher opening pressure and factors suggestive of the metabolic syndrome predict an unfavorable disease course whereas female sex and disease recurrence are significantly associated with poor visual outcomes • A third of the patients diagnosed with IIH experience ongoing headaches despite achieving favorable visual outcomes. This subset, characterized by lower disease-severity indicators at onset may represent a distinct subgroup warranting a different therapeutic approach.

Sleep Disturbances in Adolescents With Idiopathic Intracranial Hypertension.

BACKGROUND: We aimed to assess the presence of sleep disturbances in adolescents with idiopathic intracranial hypertension (IIH) and to determine whether demographic, anthropometric, and clinical factors are associated with disrupted sleep. METHODS: Sleep disturbances and patterns were evaluated in a cohort of adolescents (aged 12 to 18 years) with ongoing IIH and compared with a healthy age- and sex-matched control group. All participants responded to three self-rating questionnaires: the School Sleep Habits Survey (SSHS), the Pediatric Sleep Questionnaire (PSQ), and the Depression, Anxiety, and Stress Scale. The study group's demographic, clinical, laboratory, and radiological data were documented, and their association with sleep patterns was examined. RESULTS: Thirty-three adolescents with ongoing IIH and 71 healthy controls were included. There was a significantly higher prevalence of sleep disturbances in the IIH group compared with the controls (SSHS, P < 0.001 and PSQ, P < 0.001), as well as of their independent subscales: sleep-related breathing disorders (P = 0.006), daytime sleepiness (P = 0.04), sleep/wake disruptions (P < 0.001), and sleep-related depressive tendencies (P < 0.001). According to subgroup analyses, these differences were also present between the normal-weight adolescents but not between the overweight IIH and control adolescents. No differences were found in the demographic, anthropometric, and IIH disease-related clinical measures between individuals with IIH with disrupted and normal sleep patterns. CONCLUSIONS: Sleep disturbances are common among adolescents with ongoing IIH, irrespective of their weight and disease-related characteristics. Screening adolescents with IIH for sleep disturbances is recommended as part of their multidisciplinary management.

Regenerative Effect of Adipose Derived Mesenchymal Stem Cells on Ganglion Cells in the Hypoxic Organotypic Retina Culture.

Background and Objectives: To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model. Methods and Results: Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold＞1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs. Conclusions: These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.

Acinar Atrophy, Fibrosis and Fatty Changes Are Significantly More Common than Sjogren's Syndrome in Minor Salivary Gland Biopsies.

Background and Objective: Hyposalivation and xerostomia can result from a variety of conditions. Diagnosis is based on a combination of medical history, clinical and serological parameters, imaging, and minor salivary gland biopsy when indicated. The Objective was to characterize microscopic changes in minor salivary gland biopsies taken in patients with xerostomia. Materials and Methods: 10-year retrospective analysis of minor salivary gland biopsies, 2007-2017. Histomorphometric analysis included gland architecture, fibrosis, fat replacement, inflammation and stains for IgG/IgG4, when relevant. Results: 64 consecutive biopsies, of which 54 had sufficient tissue for diagnosis of Sjogren's Syndrome (SS) were included (18 males, 46 females, average age 56 (±12.5) years). Only 12 (22.2%) were microscopically consistent with SS, none stained for IgG4. Medical conditions were recorded in 40 (63%), most frequently hypertension and hyperlipidemia (28% each). Medications were used by 45 (70%), of which in 50% more than one. Xerostomia in non-SS cases was supported by abnormal gland morphology, including acinar atrophy, fibrosis and fatty replacement. All morphological abnormalities are correlated with age, while fatty replacement correlated with abnormal lipid metabolism. Multiple medications correlated with microscopic features which did not correspond with SS. Conclusions: SS was confirmed in a minority of cases, while in the majority fatty replacement, fibrosis and multiple medications can explain xerostomia, and are related to aging and medical conditions. Medical history and auxiliary tests could lead to correct diagnosis in non-SS patients, avoiding biopsy. The necessity of a diagnostic biopsy should be given serious consideration only after all other diagnostic modalities have been employed.

Visual function tests including the role of optical coherence tomography in neurofibromatosis 1.

Optic pathway glioma (OPG) is a common and significant complication of neurofibromatosis 1 (NF-1) that might lead to vision loss. The main reason to treat OPG is to preserve vision. Tumor location along the visual pathway largely dictates the presenting signs and symptoms. Clinical ophthalmic evaluation is focused on optic nerve functions including evaluation of pupils' reaction to light, visual acuity, color vision, and visual field, as well as optic nerve appearance. An important relatively new ancillary test is optic coherence tomography (OCT) that measures the volume of retinal nerve fiber layer around the optic nerve and the ganglion cell layer-inner plexiform layer (GCL-IPL) of the macula, both proved to be strongly associated with losing vision in OPG. Accurate evaluation of vision functions plays a critical role in the decision of treatment. In this review, we describe the ophthalmological assessment including new biomarkers in clinical use. We also outline prognostic factors and current recommendations for surveillance and indications for treatment.

Reduced Suprathreshold Odor Identification in Patients with Pseudotumor Cerebri: A Non-Randomized Prospective Study.

BACKGROUND: Recent evidence suggests that olfaction is impaired in patients with pseudotumor cerebri (PTC). OBJECTIVES: To measure suprathreshold olfactory function by using the University of Pennsylvania Smell Identification Test (UPSIT), assessing its usefulness for routine clinical use. METHODS: Forty PTC patients underwent USPIT olfactory testing. RESULTS: Twenty-nine out of 40 (73%) PTC patients (36 women, 4 men; mean age 34 years) had reduced suprathreshold smell sensation according to UPSIT scores: 19 (47%) had mild microsmia, 9 (23%) had moderate microsmia, and one (3%) was classified as having severe microsmia. The mean UPSIT score of all patients was 32.4 (95% confidence interval 31.4-33.4). Multivariate regression analysis found that UPSIT scores were not related to disease activity, disease duration, initial intracranial pressure (ICP), or visual function. CONCLUSIONS: Many PTC patients have reduced suprathreshold olfactory dysfunction that can be discovered by UPSIT, a rapidly administered smell test, which is suitable for clinical office use.

Visual outcomes of laser vision correction in eyes with preoperative amblyopia.

PURPOSE: To evaluate the visual outcomes of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in amblyopic eyes. SETTING: Care Vision Refractive Clinic, Tel Aviv, Israel. DESIGN: Retrospective case series. METHODS: Amblyopic eyes of patients with a preoperative corrected distance visual acuity (CDVA) of 20/33 or worse had PRK or LASIK. Postoperative visual outcomes (uncorrected distance visual acuity, CDVA) and correlations with age, preoperative CDVA, refractive error type, astigmatism grade, procedure type, laser suite model, amblyopia grade, and amblyopia type were analyzed. RESULTS: This study evaluated 327 eyes (327 patients). The CDVA improved more than 1, 2, and 3 Snellen lines in 147 eyes (45.0%), 75 eyes (22.9%), and 32 eyes (9.8%), respectively. Age (P = .007, B = 0.002), and preoperative CDVA (P < .001, B = -0.405) were significantly associated with CDVA improvement. The outcome in eyes with lower myopia was significantly better than in eyes with hyperopia (0.054 logMAR difference; P = .016) or high myopia (0.036 logMAR difference; P = .002). Moderately amblyopic eyes had significantly better visual outcomes than mildly amblyopic eyes (0.038 logMAR difference; P = .001). No significant difference was found between PRK and LASIK (P = .262). CONCLUSIONS: Laser vision correction, regardless of the type of procedure (LASIK or PRK) might improve CDVA in a large portion of amblyopic patients. Improvement was greater in younger patients, eyes with lower initial CDVA, and eyes with lower myopia.

Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. METHODS: Retrospective database analysis of adult patients with IIH from 4 different neuro-ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. RESULTS: The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. CONCLUSIONS: There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder.

Therapeutic Monoclonal Antibodies and Fragments: Bevacizumab.

Bevacizumab (Avastin) is a recombinant humanized monoclonal immunoglobulin antibody that has two antigen-binding domains and blocks all active forms of vascular endothelial growth factor-A. It was originally designed and is still in use as antitumor agent (for colorectal and non-small cell lung cancers). Besides inhibiting vessel growth and neovascularization, the drug promotes the regression of existing microvessels and induces 'normalization' of surviving mature vasculature, stabilizes vessels and prevents leakage. Its molecular weight is 149 kDa and its estimated terminal half-life is approximately 20 days for both men and women. The effectiveness and safety of bevacizumab was proven in retrospective and prospective controlled clinical trials for the treatment of neovascular age-related macular degeneration, neovascularization in proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusion and retinopathy of prematurity, especially for zone I. Uncontrolled trials have shown its effectiveness in various other conditions as myopic and uveitic choroidal neovascularization and neovascular glaucoma. There are no absolute contraindications to intravitreal injection though it is recommended to withhold treatment in patients who have recently suffered from a cardiovascular or cerebrovascular event and during pregnancy. Ocular complications from intravitreal use are usually mild and transient (corneal abrasion, chemosis, subconjunctival hemorrhage and vitreous hemorrhage). Bacterial endophthalmitis is rare (about 0.1%). New or progressive subretinal hemorrhages, tears of the retinal pigment epithelium and an increased incidence of geographic atrophy have also been reported.

Hyperandrogenism is associated with earlier age of onset of idiopathic intracranial hypertension in women.

PURPOSE: Previous reports have connected between Idiopathic intracranial hypertension (IIH), obesity and different hormonal states. The aim of this study was to characterize the endocrine profile in women with IIH. METHODS: This is a data-based study of 51 IIH patients. We measured anthropometric parameters and assessed hormonal profile including cortisol, testosterone, bioavailable testosterone (BT), prolactin, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, insulin, aldosterone, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Pearson or Spearman rank correlation for non-normally distributed variables were calculated to evaluate the relation among the anthropometric measurements: age, body mass index (BMI), waist and hip circumference and waist to hip ratio (WHR) with hormones levels. RESULTS: Seventy-eight percent of the cohort had WHR < 0.85 and 21.6% had a WHR > 0.85. Increased levels of testosterone, BT and androstenedione were all positively related to younger age of diagnosis in patient who are diagnosed after the age of 25 (R = -1.066, -0.845, -0.735, p < 0.001, =0.024, 0.019, respectively). No correlation was found between any of the analyzed hormones and the duration of the disease, WHR or BMI, except insulin, which was positively related to BMI (R = 0.461, p = 0.001). CONCLUSIONS: Increased levels of circulating androgens are associated with earlier age of onset of IIH in women.

The efficacy of asymmetric bilateral medial rectus muscle recession surgery in unilateral, esotropic, type 1 Duane syndrome.

BACKGROUND: Many patients with esotropic, type 1 Duane syndrome adopt a head turn to gain binocular vision. Numerous surgical procedures have been performed to correct this condition, including asymmetric bilateral medial rectus muscle recession, first proposed by Jampolsky. However, few publications reported on the efficacy of this procedure. METHODS: The medical records of patients with unilateral, esotropic Duane syndrome who had asymmetric medial rectus muscle recession for correction of their abnormal head turn were retrospectively reviewed with attention to head turn, ductions, and motor alignment at near and distance fixation. Surgery was considered successful when preoperative head turn was completely eliminated. RESULTS: A total of 28 patients (18 females; mean age, 8 years) were included. In 24 patients (86%), the left eye was involved. Medial rectus recession averaged 4.7 mm (range, 3.25-6.0 mm) in the affected eye, with a recession larger by 1.0 mm in the unaffected eye. Average esotropia in the forced primary position improved from 32(Δ) preoperatively to 6(Δ) postoperatively, with a mean 22° improvement in head position (24°-2°). Twenty-four patients (86%) achieved complete resolution of their head turn postoperatively; the other 4 patients experienced partial improvement, with a residual head turn of 10°; a second re-recession of the medial rectus muscle in the affected eye of 1 patient resulted in complete resolution of head turn. CONCLUSIONS: Our study showed that asymmetric bilateral medial rectus recession eliminated the head turn in most of our patients with unilateral esotropic Duane syndrome.

Intraocular pressure measurements in relation to head position and through soft contact lenses: comparison of three portable instruments.

BACKGROUND AND OBJECTIVE: to compare the reproducibility of three portable instruments-the Tono-Pen tonometer (Reichert Ophthalmic Instruments, Depew, NY), the Phosphene tonometer (Bausch & Lomb, Rochester, NY), and the TERT (Through Eyelid Russian Tonometer; Rjazan State Instrument Making, Rjazan, Russia)-in the measurement of intraocular pressure (IOP) with and without soft contact lenses and in different head positions. PATIENTS AND METHODS: twenty-six eyes of healthy volunteers were examined by the three instruments while the subjects were sitting, recumbent, and hyperextending their heads, and with and without contact lenses. IOP measurements were compared and the effects of head position and presence of contact lenses on the resultant values were analyzed. RESULTS: the average difference between the recumbent and sitting positions was 3.56, 2.68, and 2.62 mm Hg for the Tono-Pen tonometer, Phosphene tonometer, and TERT, respectively. There was an increase of 5.60, 2.78, and 2.63 mm Hg in hyperextension compared to sitting for the Tono-Pen tonometer, Phosphene tonometer, and TERT, respectively. The difference in the IOP values obtained in the presence and absence of therapeutic contact lens for the three instruments in the three positions was between -1.23 and +1.47 mm Hg. CONCLUSION: IOP measurements of bedridden patients are only slightly higher than those of sitting patients except for the Tono-Pen tonometer in the hyperextension position. The presence of contact lenses does not affect IOP values obtained by the three evaluated instruments.