Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas

Nerve growth factor improves visual loss in childhood optic gliomas: a randomized, double-blind, phase II clinical trial.

Paediatric optic pathway gliomas are low-grade brain tumours characterized by slow progression and invalidating visual loss. Presently there is no strategy to prevent visual loss in this kind of tumour. This study evaluated the effects of nerve growth factor administration in protecting visual function in patients with optic pathway glioma-related visual impairment. A prospective randomized double-blind phase II clinical trial was conducted in 18 optic pathway glioma patients, aged from 2 to 23 years, with stable disease and severe visual loss. Ten patients were randomly assigned to receive a single 10-day course of 0.5 mg murine nerve growth factor as eye drops, while eight patients received placebo. All patients were evaluated before and after treatment, testing visual acuity, visual field, visual-evoked potentials, optic coherence tomography, electroretinographic photopic negative response, and magnetic resonance imaging. Post-treatment evaluations were repeated at 15, 30, 90, and 180 days Brain magnetic resonance imaging was performed at baseline and at 180 days. Treatment with nerve growth factor led to statistically significant improvements in objective electrophysiological parameters (electroretinographic photopic negative response amplitude at 180 days and visual-evoked potentials at 30 days), which were not observed in placebo-treated patients. Furthermore, in patients in whom visual fields could still be measured, visual field worsening was only observed in placebo-treated cases, while three of four nerve growth factor-treated subjects showed significant visual field enlargement. This corresponded to improved visually guided behaviour, as reported by the patients and/or the caregivers. There was no evidence of side effects related to nerve growth factor treatment. Nerve growth factor eye drop administration appears a safe, easy and effective strategy for the treatment of visual loss associated with optic pathway gliomas

Prevalence of neurological involvement and malformative/systemic syndromes in A- and V-pattern strabismus.

PURPOSE: To evaluate the prevalence of neurological involvement and malformative/systemic syndromes in A- and V-patterns with respect to other kinds of infantile concomitant strabismus. METHODS: A retrospective comparative study of 14,006 consecutive patients examined in the Pediatric Ophthalmology and Strabismus Unit at the Catholic University of Rome between January 2002 and February 2010 was carried out. A total of 2.72% (385) of patients presented with concomitant constant infantile strabismus associated with A- and V- patterns (study group; mean age 8 years; range: 8 months - 37 years; male 211, female 174). Another 377 consecutive patients affected by infantile concomitant strabismus without A- or V- patterns were used as controls (control group; mean age 9 years, range: 1-34 years; male 194, female 183). All patients underwent a complete ophthalmologic and orthoptic examination with ocular motility evaluation and prism cover test or the Hirschberg test in primary, up and down gaze positions, as well as cycloplegic retinoscopy. The angle of deviation was evaluated at near (33 cm) and distance fixation (6 m) with full correction of refraction. RESULTS: Neurological involvement and malformative/systemic syndromes were observed in 30.4% of the study group and in 19.8% of patients in the control group (P < 0.001). Patients with A-pattern showed a greater prevalence of neurological impairment, hydrocephalus and meningomyelocele, while those affected by V-pattern exhibited a greater prevalence of craniosynostosis and malformative syndromes. CONCLUSIONS: Neurological involvement and malformative/systemic syndromes seem to be more evident in patients presenting with A- and V-pattern strabismus

Visual Function and Ophthalmological Findings in CHARGE Syndrome: Revision of Literature, Definition of a New Clinical Spectrum and Genotype Phenotype Correlation

CHARGE syndrome (CS) is a rare genetic disease causing multiple anatomical defects and sensory impairment. Visual function is usually reported by caregivers and has never been described with a structured behavioral assessment. Our primary objective was to describe ocular abnormalities, visual function and genotype–ocular-phenotype correlation in CS. A prospective monocentric cohort study was performed on 14 children with CS carrying pathogenic CHD7 variants. All children underwent ophthalmological evaluation and structured behavioral assessment of visual function. The VISIOCHARGE questionnaire was administered to parents. Colobomas were present in 93% of patients. Genotype–phenotype correlation documented mitigated features in a subset of patients with intronic pathogenic variants predicted to affect transcript processing, and severe features in patients with frameshift/nonsense variants predicting protein truncation at the N-terminus. Abnormal visual function was present in all subjects, with different degrees of impairment. A significant correlation was found between visual function and age at assessment (p-value = 0.025). The present data are the first to characterize visual function in CS patients. They suggest that hypomorphic variants might be associated with milder features, and that visual function appears to be related to age. While studies with larger cohorts are required for confirmation, our data indicate that experience appears to influence everyday use of visual function more than ocular abnormalities do

OCT-Angiography Findings in Patients with Amblyopia: Comparison between Healthy Controls, Treatment-Responsive, and Treatment-Unresponsive Amblyopic Patients

There is no consensus on whether amblyopia affects the retinal vascular plexus and morphology. Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy, OCTA was used. All patients underwent a comprehensive ophthalmological examination, including visual acuity, refraction, ocular motility tests, and anterior and posterior segment examination. OCTA was performed by an expert physician using the Zeiss Cirrus 5000-HD-OCT Angioplex (Carl Zeiss, Meditec, Inc., Dublin, OH, USA). OCTA scans were performed using a 3 × 3 mm2 and 6 × 6 mm2 fovea-centered image setting. The mean outer macular vessel density in the previously amblyopic group was 19.15 ± 0.51%. This was statistically significantly higher than in both the amblyopic group (18.70 ± 1.14%) and the normal controls (18.18 ± 1.40%) (p = 0.014). The previously amblyopic group also significantly differed from both normal controls and amblyopic eyes with regards to the inner (p = 0.011), outer (p = 0.006), and full (p = 0.003) macular perfusion. Finally, linear regression analysis revealed that BCVA was linearly correlated to outer perfusion in amblyopic (p = 0.003) and ex amblyopic eyes (p &lt; 0.001). Considering the cross-sectional nature of our study, from our results, we can only hypothesize a possible correlation between light stimulation and retinal vasculature development. However, further longitudinal studies are needed to support this hypothesis

Improved sensory status and quality-of-life measures in adult patients after strabismus surgery

PURPOSE: To evaluate the change in sensory status and quality-of-life measures in adults with long-standing childhood-onset constant strabismus. METHODS: Consecutive patients with childhood-onset, long-term constant strabismus were enrolled. Sensory status was examined with Bagolini striated glasses test and Worth 4-dot test. Stereopsis was tested with the Lang and TNO stereopsis tests. Quality of life was studied with 2 different questionnaires (Short Form Health Survey [SF-36] and the Amblyopia and Strabismus Questionnaire [A&SQ]), which patients completed before and 3 months after strabismus surgery. RESULTS: A total of 20 patients (age range, 18-63 years) were included, 10 of whom were esotropic and 10 of whom were exotropic. Of these, 13 obtained a satisfactory postoperative alignment and demonstrated an increase of sensory status with Bagolini striated glasses. Six patients who demonstrated suppression preoperatively achieved fusion and stereopsis postoperatively. The mean score in all domains of the A&SQ improved significantly, particularly with regard to social contact and cosmesis (P = 0.00067), distance estimation (P = 0.000312), and visual disorientation (P = 0.004777). Similarly, the mean score in 7 of 8 areas in the SF-36 improved significantly, particularly with regard to physical function (P = 0.000564), general health (P = 0.002296), vitality (P = 0.002891), social function (P = 0.004234), and mental health (P = 0.000334). The overall mean score of both questionnaires improved in all patients with a satisfactory postoperative alignment and increase of sensory status. CONCLUSIONS: Surgical treatment of strabismus in adults with long-standing childhood-onset constant strabismus can result in patients feeling that their quality of life has improved and can restore binocular sensory function

Effect of vertical transposition of the medial rectus muscle on primary position alignment in infantile esotropia wuth A- or V- pattern strabismus.

PURPOSE: To determine the effect of vertical displacement of muscle insertions on the surgical dose-response relationship in patients undergoing bilateral medial rectus recessions. METHODS: Retrospective chart review of patients undergoing bilateral medial rectus recessions for correction of congenital esotropia with or without vertical displacement for A or V patterns. Patients were clustered into A pattern, V pattern, and "simple" (no pattern) groups. Strabismus angle at distance and near before and after surgery was recorded. Surgical dose-response relationships (in prism diopters/mm) were determined at the 6-month follow-up visit and compared. RESULTS: A total of 55 patients (28 male and 27 female patients; mean age, 6.9 years; range, 2-17 years) were included. Of these, 28 had either A pattern (18) or V pattern (10), and 27 were in the simple group. Mean preoperative angle of deviation was 34\u394 at distance and 40\u394 at near. The surgical dose-response relationship was significantly greater (at both distance and near) in the A pattern group (2.43\u394/mm, distance [p=0.005]; 2.76\u394/mm, near [p=0.04]) than in the simple group (1.56\u394/mm, distance; 2.03\u394/mm, near). The surgical response in the V pattern group (1.96\u394/mm, distance [p=0.34]; 2.03\u394/mm, near [p=0.94]) was not significantly different from the simple group. CONCLUSIONS: Upward displacement of the medial rectus muscles increased the surgical dose/response relationship in patients with A-pattern esotropia. A similar effect was not observed with downward displacement in patients with V-pattern strabismus. Surgeons should be aware of this enhanced response when planning surgery for A-pattern esotropia