Efficacy of oral manganese and D-galactose therapy in a patient bearing a novel TMEM165 variant.

TMEM165-CDG has first been reported in 2012 and manganese supplementation was shown highly efficient in rescuing glycosylation in isogenic KO cells. The unreported homozygous missense c.928G>C; p.Ala310Pro variant leading to a functional but unstable protein was identified. This patient was diagnosed at 2 months and displays a predominant bone phenotype and combined defects in N-, O- and GAG glycosylation. We administered for the first time a combined D-Gal and Mn2+ therapy to the patient. This fully suppressed the N-; O- and GAG hypoglycosylation. There was also striking improvement in biochemical parameters and in gastrointestinal symptoms. This study offers exciting therapeutic perspectives for TMEM165-CDG.

Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1.

Purpose: Retinal and choroidal abnormalities in neurofibromatosis type 1 (NF1) remain poorly studied. It has been reported, however, that the function of the retinal pigment epithelium (RPE) in NF1 was abnormal, with a supra-normal Arden ratio of the electro-oculogram (EOG). This study aims to evaluate the function of the RPE, using EOG, first in patients with NF1 compared to controls and second in patients with NF1 with choroidal abnormalities compared to patients with NF1 without choroidal abnormalities. Methods: This prospective case-control study included 20 patients with NF1 (10 patients with choroidal abnormalities and 10 patients without) and 10 healthy patients, matched for age. A complete ophthalmologic assessment with multimodal imaging, an EOG, and a full-field electroretinogram were performed for each included patient. The main outcome measured was the EOG light peak (LP)/dark trough (DT) ratio. Results: The LP/DT ratio was 3.02 ± 0.52 in patients with NF1 and 2.63 ± 0.31 in controls (P = 0.02). DT values were significantly lower in patients with NF1 than in controls (240 vs. 325 µV, P = 0.02), while light peak values were not significantly different (P = 0.26). No difference was found for peak latencies. No significant correlation between the surface and number of choroidal abnormalities and EOG parameters was demonstrated. Conclusions: This study confirms the dysfunction of the RPE in patients with NF1, involving a lower DT and a corresponding higher LP/DT ratio. We hypothesize that this pattern may be due to a dysregulation of the melanocytogenesis, inducing a disruption in Ca2+ ion flux and an abnormal polarization of the RPE.

Congenital cataract surgery: long-term refractive outcomes of a new intraocular lens power correction formula.

PURPOSE: The final refraction after intraocular lens (IOL) implantation remains a challenge in the management of paediatric cataracts. No consensual guidelines exist for the choice of IOL power. The aim of this study was to validate a method of IOL power calculation by evaluating the final refractive error in all patients with IOL implantation operated at our institution. METHODS: We retrospectively studied all children under 7 years of age who underwent cataract surgery with IOL implantation at our institution between 2010 and 2015. Intraocular lens (IOL) power was calculated as follows: After B-scan determination of the emmetropic IOL power, a reduction of 40%, 35%, 30%, 25%, 20%, 15%, 10% and 5% was applied to children 0-3, 3-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-48 months, respectively. The following data were collected: follow-up, age at surgery, uni- or bilaterality, implanted IOL power and final refraction. RESULTS: During this period, 81 children (125 eyes) met the inclusion criteria with a median follow-up of 60 months (36-97). The median age at surgery was 6.61 months (0.76-48). We included 52 children with bilateral cataract (96 eyes) and 29 children with unilateral cataract (29 eyes). The mean implanted IOL power was 23.3 ± 4.6 diopters (D). The mean spherical equivalent at last follow-up was 0.07 ± 3.5 D. CONCLUSION: Our undercorrection formula for IOL implantation after congenital cataract surgery leads to long-term refractive results globally close to emmetropia.

Ophthalmological findings in children with unicoronal craniosynostosis.

INTRODUCTION: Among non-syndromic, single-suture craniosynostoses, unicoronal craniosynostosis (UCS) presents the highest rate of ophthalmic manifestations requiring a visual follow-up, due to the high risk of amblyopia. After birth or during childhood, children with UCS have a high risk to present an aniso-astigmatism and a strabismus. The aim of this study was to characterize clinical ophthalmologic findings associated with UCS in a paediatric cohort. METHODS: This retrospective study included children admitted in our unit between 2015 and 2021, with isolated UCS treated in our institution and complete ophthalmological assessment comprising visual assessment, refractive status and oculomotor examination. Children with associated craniofacial disorders were excluded. RESULTS: A total of 28 children met the inclusion criteria. Median age was 62 [13-192] months with a large proportion of girls (86%) and 71% of right-sided UCS. The mean best corrected visual acuity was 0.07 (±0.13) LogMAR, including 10 (36%) children with an amblyopia or history of amblyopia. Astigmatism was significantly higher on the contralateral side of the UCS than on the ipsilateral side, with a refractive cylinder error of 0.97 (±1.06) vs 0.56 (±0.68) diopters, respectively (p = 0.03). Strabismus was observed in 20 patients (71%) with a main pattern of esotropia with a vertical component. A pseudo-superior oblique palsy was found in 13 children (65%) with a median cyclodeviation of 8.7° [-5,4°-20.6°]. CONCLUSION: Children with UCS experience a high rate of various visual manifestations. This study highlights their need for a strict ophthalmological follow-up, in order to early diagnose and prevent visual complications.

RETINAL VASCULAR ABNORMALITIES IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1.

PURPOSE: Retinal vascular abnormalities (RVAs) have been recently described in patients with neurofibromatosis Type 1 (NF1) as vascular tortuosity, best visible on infrared imaging. This study assessed clinical RVA's characteristics in a large series of children with NF1. METHODS: This retrospective observational study was conducted in children (0-18 years) with an NF1 diagnosis. Using near-infrared imaging, RVAs were classified according to the nature of vessels involvement and their degree of tortuosity. RESULTS: Retinal imaging from 140 children, with a median age of 8.8 years (1.5-18), was included; 52 patients (37.1%) (81 eyes) exhibited RVAs. These RVAs comprised 96% (50/52) of simple vascular tortuosity and 17% (9/52) of a corkscrew pattern. A corkscrew pattern involved only small veins, whereas simple vascular tortuosity could affect both arteries and veins. No statistically significant age correlation was observed, but evolution of RVAs from simple vascular tortuosity to corkscrew pattern was observed in 5 cases. CONCLUSION: Retinal vascular abnormalities occurred in 37.1% of children with NF1. These abnormalities may result from NF1 promoting localized tortuosity in both small arteries and veins, whereas only small second-order or tertiary-order venules evolve to a highly tortuous pattern.

Long-term Kinetic Papilledema Improvement After Venous Sinus Stenting in Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: The aim of this study was to assess the safety and effectiveness of lateral sinus stenosis (LSS) stenting in patients with idiopathic intracranial hypertension (IIH) who are refractory to medical treatment, particularly focusing on visual outcomes including papilledema. MATERIAL AND METHODS: Retrospective study of consecutive patients with IIH refractory to medical treatment who underwent LSS stenting. Clinical features, visual fields and optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thicknesses were assessed before stenting, at 1 month poststenting and at last follow-up. Complications were also recorded. RESULTS: A total of 16 women were included, with a mean age of 39 ± 11 years. All patients had papilledema while 15/16 (94%) had headaches. Mean visual acuity was 0.036 logMAR, range (+0.4 to +0.0 logMAR). The mean RNFL thickness prior to stenting was 121.7 µm (±34.7 µm) and mean GCL thickness was 80.2 µm (±8.9 µm). Mean follow-up was 19.7 months (±11.8 months). After stenting, acetazolamide was discontinued in 15/16 (94%) patients. Papilledema improved in 14/16 (88%) of patients. The mean RNFL thickness was significantly decreased 1 month after stenting (96.3 ± 15.6 µm; p < 0.001) and at last visit (93.4 ± 15.3 µm; p < 0.001). The GCL thickness after LSS stenting was moderately decreased at the last visit examination: 80.2 ± 8.9 µm vs. 78.0 ± 10.7 µm; (p < 0.01). No stent-related complication occurred, while there was one case of restenosis. CONCLUSION: Improvement of papilledema appears to occur relatively rapidly after the LSS stenting. The results further support the role of LSS stenting in the treatment of IIH, especially with respect to visual symptoms.

Occlusion Rate and Visual Complications With Flow-Diverter Stent Placed Across the Ophthalmic Artery's Origin for Carotid-Ophthalmic Aneurysms: A Meta-Analysis.

BACKGROUND: Flow-diverter stents (FDSs) have recently gained acceptance for the treatment of intracranial aneurysms, especially for carotid-ophthalmic aneurysms (COAs). However, complications have been reported after coverage of side branches, especially the ophthalmic artery (OA). OBJECTIVE: To evaluate, through a meta-analysis, the occlusion rate, and the ophthalmic complications after treatment of COA by FDS. METHODS: We reviewed on MEDLINE via PubMed, Embase via Ovid, and Cochrane central database via CENTRAL. We included all case series with at least 15 patients and clinical trials about flow diversion of aneurysms close to the OA's origin. Among these studies, we only included articles with aneurysm occlusion rate and rate of new ophthalmic symptoms. RESULTS: We included 16 studies with 913 COA treated by FDSs and covering the OA with a mean follow-up of 16.4 mo. The random-effect modeling analysis concerning the overall rate of new ophthalmic complications, after FDS deployment covering the OA, was 3.0% (CI95% 1.0-6.0). There was medium-high heterogeneity in the study reports P < .01, I2 = 70.2% [50.4%; 82.1%]. We were not able to statistically explain this heterogeneity with the performed analysis, which could be related to the design of the included studies. We found an overall aneurysm occlusion rate of 85.0% (95% CI 80.0-89.0). CONCLUSION: Our meta-analysis found a high aneurysm occlusion rate (85%) and low rate of iatrogenic visual complications, with only 3.0% of new visual symptoms, after treatment of COA by FDS.

Extraocular muscle positions in anterior plagiocephaly: V-pattern strabismus explained using geometric mophometrics.

INTRODUCTION: Ophthalmological involvement in anterior plagiocephaly (AP) due to unicoronal synostosis (UCS) raises management challenges. Two abnormalities of the extraocular muscles (EOM) are commonly reported in UCS without objective quantification: (1) excyclorotation of the eye and (2) malposition of the trochlea of the superior oblique muscle. Here we aimed to assess the positions of the EOM in AP, using geometric morphometrics based on MRI data. MATERIALS AND METHODS: Patient files were listed using Dr WareHouse, a dedicated big data search engine. We included all patients with AP managed between 2013 and 2018, with an available digital preoperative MRI. MRIs from age-matched controls without craniofacial conditions were also included. We defined 13 orbital and skull base landmarks in order to model the 3D position of the EOM. Cephalometric analyses and geometric morphometrics with Procrustes superimposition and principal component analysis were used with the aim of defining specific EOM anomalies in UCS. RESULTS: We included 15 preoperative and 7 postoperative MRIs from patients with UCS and 24 MRIs from age-matched controls. Cephalometric analyses, Procrustes superimposition and distance computations showed a significant shape difference for the position of the trochlea of the superior oblique muscle and an excyclorotation of the EOM. CONCLUSIONS: Our results confirm that UCS-associated anomalies of the superior oblique muscle function are associated with malposition of its trochlea in the roof of the orbit. This clinical anomaly supports the importance of MRI imaging in the surgical management of strabismus in patients with UCS.

Long-term visual outcome in patients treated by flow diversion for carotid-ophthalmic aneurysms.

BACKGROUND: Flow-diverter stents (FDSs) are an upgrade in the treatment of intracranial aneurysms. However, complications concerning covered branches have been reported, especially the ophthalmic artery (OA). The purpose of our study was to evaluate the long-term ophthalmic complication rate of carotid-ophthalmic aneurysms (COA) without visual pathways compression, treated by a FDS covering the OA by performing an exhaustive ophthalmic examination. MATERIAL AND METHODS: Retrospective analysis of a single-center database screening the patients treated from October 2009 to April 2015 for an intracranial aneurysm with a FDS. The patients treated for a non-compressive COA with coverage of the OA by the device were studied (n=30). Among these patients, 15 (50%) were excluded. The remaining 15 patients underwent a systematic and extensive ophthalmic examination at least 2 years after the stent placement by two ophthalmologists. RESULTS: Fifteen patients with 16 COAs treated with a FDS were included. Mean follow-up was 4.1±2 years. Six patients (40%), presented ophthalmic complications, including three fugax amauroses (18.8%) and four significant visual field defects (25%). After comparing each eye's visual field's patients, we observed a significant difference between the eye on the FDS side compared with the contralateral eye, with a mean deviation of -1.58 dB versus -0.67 dB respectively (P=0.003). Visual acuity was preserved in all patients. CONCLUSION: Patients treated by FDS for COA have a good long-term clinical ophthalmic outcome. However, extensive ophthalmic examination shows a high percentage of minor ophthalmic modifications. Interventional neuroradiologists should be aware of these possible complications when choosing to treat these aneurysms with FDS.