Development and co-construction of a therapeutic patient education program for albinism.

BACKGROUND: Long-term and ongoing support in accordance with the changing needs of patients and their families is one of the main components of patient care, including therapeutic patient education (TPE). OBJECTIVE: To co-construct a TPE program for albinism with all those involved in the management of albinism patients. METHODS: Eight steps have been defined for the co-construction process: 1) identify all the relevant experts and invite them to participate in the construction of a TPE program to improve care for and support of patients with albinism, 2) review and analyse all publications regarding TPE for albinism, 3) conduct semi-structured interviews with the patients' parents, 4) conduct brainstorming meetings with the participating experts for an exchange of experience and expertise, 5) elaborate the program's concrete content with the experts, 6) draw up a TPE skills checklist, 7) create TPE educational tools to facilitate learning, 8) review and summarize each step of the co-construction protocol. RESULTS: Co-construction of a TPE program for children, adolescents, and young adults with albinism, and their parents. CONCLUSION: Strengths and advantages of the co-construction process include: i) highlighting of the experiential knowledge mentioned in the repository, ii) multiplicity of points of view and perspectives, iii) rapid improvement in TPE training both for the association and the patients, iv) awareness of the shift caregivers' position with regards to TPE and recognition of the polysemy of their discourse. The TPE program for albinism has been authorized since 2018.

Multidisciplinary consensus recommendations from a European network for the diagnosis and practical management of patients with incontinentia pigmenti.

BACKGROUND: Incontinentia pigmenti (IP) is a rare multisystemic X-linked dominant genetic disorder characterized by highly diagnostic skin lesions. The disease can be misdiagnosed in infants, and complications affecting the eyes and/or the brain can be severe. Our objective was to highlight the urgency of an appropriate diagnosis and management strategy, as soon as the first symptoms appear, and the need for a well-codified monitoring strategy for each child. METHODS: An in-depth literature review using a large number of databases was conducted. The selection criteria for articles were literature review articles on the disease, case series and retrospective studies based on the disease, clinical studies (randomized or not) on treatment, articles discussing patient care and management (treatment, diagnosis, care pathways), and recommendations. The research period was from 2000 until 2018. A group of multidisciplinary experts in IP management was involved, issued from different healthcare providers of the European Network for Rare Skin Diseases (ERN-Skin). The final recommendations have been submitted to two patient representative associations and to a general practitioner and a neonatal specialist prior to their finalization. RESULTS AND CONCLUSION: The diagnosis of IP must be promptly performed to detect potential extracutaneous manifestations, thus allowing the timely implementation of specific therapeutic and monitoring strategies. Eye involvement can be a therapeutic urgency, and central nervous system (CNS) involvement requires a very rigorous long-term follow-up. Assessments and patient support should take into account the possible co-occurrence of various symptoms (including motor, visual and cognitive symptoms).

[Pediatric myasthenia with ocular involvement]. / Myasthénie chez l'enfant avec atteinte oculaire.

PURPOSE: Myasthenia is a rare disease in children, with an estimated incidence of 1 to 5 per million children. However, the potential severity of its consequences and the existence of specific treatments require prompt diagnosis by pediatric ophthalmologists. METHODS: Retrospective review of patient records. Patients were identified from a rare disease database. Patients under the age of 18 years with confirmed diagnosis of myasthenia and ocular symptoms seen in a specialized clinic between 2005 and 2021 were included. RESULTS: Twenty-six (16 girls) with confirmed myasthenia and ocular symptoms were included. Ten patients had definite autoimmune myasthenia gravis (AIMG); 6 had suspected AIMG with negative antibody testing. Six patients had definite congenital myasthenic syndrome (CMS); 4 had suspected CMS with no evidence of mutation. Mean age at diagnosis of myasthenia was 5 years-3 years and 5 months for CMS and 6 years and 3 months for AIMG. Male to female (M:F) ratio was 6/10 for autoimmune myasthenia gravis and 4/6 for CMS. Ptosis was present in all cases; strabismus in 21 patients (68%). The clinical forms of myasthenia were ocular myasthenia in 12 patients (10 AIMG and 2 CMS), generalized in 12 patients (7 CMS and 5 AIMG) and secondary generalization of ocular myasthenia in 2 patients (2 AIMG). DISCUSSION: These results are based on only 26 cases, which can be explained by the rarity of this diagnosis in children. As in adults, the first signs are often ophthalmologic - ptosis alone or associated with strabismus. Diagnosis is difficult because of the absence of clinical signs, laboratory tests or electrophysiological signs with high sensitivity. Thus, the work-up may remain completely negative in secondarily proven forms. In addition, electroneuromyograms and oculomotor recordings in small children are more difficult to perform than in adults. For these reasons, the clinical examination is essential. In the case of strong suspicion, all additional medical examinations are carried out in a day unit, in order to reach a positive diagnosis of myasthenia. The so-called "congenital" forms, which are genetic, are proportionately higher than in adults, and diagnosis and treatment are often more difficult than in the classic autoimmune forms. CONCLUSION: Myasthenia can affect children from a very young age and can present as ptosis, initially isolated or associated with strabismus. Diagnosis and treatment may be difficult and should be organized in specialized centers.

Arterial Spin-Labeling in the Assessment of Pediatric Nontraumatic Orbital Lesions.

Benign and malignant pediatric orbital lesions can sometimes have overlapping features on conventional MR imaging sequences. MR imaging of 27 children was retrospectively reviewed to describe the signal of some common pediatric extraocular orbital lesions on arterial spin-labeling and to evaluate whether this sequence helps to discriminate malignant from benign masses, with or without ADC value measurements. Qualitative and quantitative assessments of arterial spin-labeling CBF and ADC were performed. All lesions were classified into 3 arterial spin-labeling perfusion patterns: homogeneous hypoperfusion (pattern 1, n = 15; benign lesions), heterogeneous hyperperfusion (pattern 2, n = 9; cellulitis, histiocytosis, malignant tumors), and homogeneous intense hyperperfusion (pattern 3, n = 3; infantile hemangiomas). Arterial spin-labeling can be a valuable tool to improve the diagnostic confidence of some orbital lesions, including infantile hemangioma. An algorithm is proposed.

Prevalence of radiographic changes in forelimb digits and metacarpophalangeal joints of South African endurance racehorses.

Background: If the number of events alone is considered, endurance riding is the fastest growing and the second-most popular Fédération Equestre Internationale (FEI) discipline. Lameness is the most common cause of elimination from endurance races worldwide. To the authors' knowledge, no studies have been published investigating the prevalence of radiographic changes in the forelimb digits and metacarpophalangeal joints (MCP) of endurance racehorses in South Africa. Objective: Investigate the prevalence of radiographic changes in the forelimb digits and MCP joints of South African endurance racehorses. Method: One hundred endurance racehorses registered with ERASA were volunteered by their owners to partake in the current study. Radiographs were obtained from horses competing in endurance races during the 2018-2019 endurance racing season. Radiographs included seven standard views of each distal forelimb. Radiographic images were independently evaluated by three observers, point prevalence and inter-rater reliability (IRR) was calculated. Results: Data analysis of the forelimb digits revealed a large proportion of horses with bilateral signs of dorsopalmar hoof imbalance (95%); a diversion from a straight digital axis (91%), with an extended (broken back) proximal interphalangeal joint (67%) being the most common abnormality. Osteoarthritis of the proximal (16%) and distal (7%) interphalangeal joints was only observed in a low percentage of horses. Interestingly, the hoof-distal-phalanx-ratio of the majority (86%) of horses was more than 25% but none of these horses showed any other signs of chronic laminitis, indicating that hoof-distal-phalanx-ratio might not be a reliable indicator of chronic laminitis in this population of horses. Ossification of the ungular cartilages was observed in the majority (69%) of horses, either affecting one or both distal phalanges. Descriptive data analysis of the MCP joints showed that a large proportion of horses displayed radiological signs of MCP joint osteoarthritis (28%), with 10% being bilateral. Conclusions and clinical relevance: The current study provides insight into radiographic changes and their prevalence in the distal front limbs of South African endurance racehorses. Knowledge about the prevalence of specific radiographic changes would enable equine practitioners to better evaluate and manage horses that are affected. Although no correlations were made with age, speed or number of competitive kilometres competed, the current study may serve as a basis for future research.

[Screening and prevention of toxic optic neuropathies due to anti-mycobacterium therapies: proposal of recommendations]. / Dépistage et prévention des neuropathies optiques toxiques aux anti-mycobactériens : proposition de recommandations.

While treatment of pulmonary infections by Mycobacterium tuberculosis is currently only rarely the cause of iatrogenic complications, treatment of atypical mycobacterial infections often requires prolonged treatment duration, which can lead to toxic optic neuropathies. This review summarizes the indications for such prolonged treatment and risk factors for toxic optic neuropathies when using ethambutol, isoniazid and/or linezolid and proposes customized screening recommendations.

Foveal hypoplasia in parents of patients with albinism.

BACKGROUND: Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal hypoplasia (FH) is one of the main criteria for the diagnosis of albinism. The aim of this study was to analyze the macular profile of the parents of patients with albinism. METHODS: This study included a case series of 27 patients with albinism seen in Rothschild Foundation between April 2017 and February 2020. Spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) were performed in every patient when possible and in every available parents. FH was graded according to Thomas' classification based on OCT. Next generation sequencing-based gene panel testing was performed in parents and children when a FH was detected on OCT in a parent. RESULTS: Twenty-seven patients with albinism were examined. Nine parents had FH based on the OCT B-scan (33%). In parents without FH based on the SD-OCT B-scan (67%), OCT-A showed a reduced avascular zone in the deep vascular plexus in 4 parents. Six parents carried variants that could explain their phenotype, including TYR R402Q hypomorphic alleles. CONCLUSION: This study showed the presence of FH in parents of patients with albinism, and aimed to genetically explain this phenotype.

[Chiasmatic syndrome]. / Syndrome chiasmatique.

The optic chiasm is an essential anatomical structure in neuro-ophthalmology. The systematization of the visual pathways results from the arrangement of the retinal ganglion cell fibers. It explains the signs of chiasmal syndrome. A good knowledge of the anatomy permits to correlate visual field defects with imaging results. It is now possible to map the organization of the ganglion cell fibers within the chiasm. Their hemidecussation allows for stereoscopic vision in humans. The causes of chiasmal syndrome are multiple, but tumors and compressive causes predominate. The proximity of the pituitary region to the chiasm accounts for the frequency of chiasmal syndrome, which involves ophthalmologists not only through dysfunction of the visual pathway, which may be the presenting sign, but also through possible complications throughout the course of the disease. This review aims to synthesize the embryology, anatomy and principles of work-up for chiasmal syndrome as well as its many possible causes.

[Implementation of a new gene therapy in ophthalmology: Regulatory and organizational issues]. / Mise en place d'une nouvelle thérapie génique en ophtalmologie : aspects réglementaires et organisationnels.

Voretigene neparvovec (VN) is the first gene therapy in ophthalmology for patients with RPE65-mediated hereditary retinal dystrophy. It has recently obtained European market approval, which is subject to strict regulatory and organizational conditions for its use. Here, we analyze the main studies supporting the authorization of this new therapy and describe the necessary steps to take at a hospital level for optimal administration to patients following current regulations.

Focal Areas of High Signal Intensity in Children with Neurofibromatosis Type 1: Expected Evolution on MRI.

BACKGROUND AND PURPOSE: Focal areas of high signal intensity are T2WI/T2-FLAIR hyperintensities frequently found on MR imaging of children diagnosed with neurofibromatosis type 1, often thought to regress spontaneously during adolescence or puberty. Due to the risk of tumor in this population, some focal areas of high signal intensity may pose diagnostic problems. The objective of this study was to assess the characteristics and temporal evolution of focal areas of high signal intensity in children with neurofibromatosis type 1 using long-term follow-up with MR imaging. MATERIALS AND METHODS: We retrospectively examined the MRIs of children diagnosed with neurofibromatosis type 1 using the National Institutes of Health Consensus Criteria (1987), with imaging follow-up of at least 4 years. We recorded the number, size, and surface area of focal areas of high signal intensity according to their anatomic distribution on T2WI/T2-FLAIR sequences. A generalized mixed model was used to analyze the evolution of focal areas of high signal intensity according to age, and separate analyses were performed for girls and boys. RESULTS: Thirty-nine patients (ie, 285 MR images) with a median follow-up of 7 years were analyzed. Focal areas of high signal intensity were found in 100% of patients, preferentially in the infratentorial white matter (35% cerebellum, 30% brain stem) and in the capsular lenticular region (22%). They measured 15 mm in 95% of cases. They appeared from the age of 1 year; increased in number, size, and surface area to a peak at the age of 7; and then spontaneously regressed by 17 years of age, similarly in girls and boys. CONCLUSIONS: Focal areas of high signal intensity are mostly small (<15 mm) abnormalities in the posterior fossa or capsular lenticular region. Our results suggest that the evolution of focal areas of high signal intensity is not related to puberty with a peak at the age of 7 years. Knowledge of the predictive evolution of focal areas of high signal intensity is essential in the follow-up of children with neurofibromatosis type 1.

Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: french national audit of practices, literature review, and consensus agreement.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) can lead to severe ophthalmologic sequelae. The main risk factor is the severity of the initial ocular involvement. There are no recommendations for ocular management during acute phase.We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. We sent a questionnaire on ocular management practices in SJS/ TEN during acute phase to ophthalmologists and dermatologists. The survey focused on ophthalmologist opinion, pseudomembrane removal, topical ocular treatment (i.e. corticosteroids, antibiotics, antiseptics, artificial tear eye drops, vitamin A ointment application), amniotic membrane transplantation, symblepharon ring use, and systemic corticosteroid therapy for ophthalmologic indication. Nine of 11 centers responded. All requested prompt ophthalmologist consultation. The majority performed pseudomembrane removal, used artificial tears, and vitamin A ointment (8/9, 90%). Combined antibiotic-corticosteroid or corticosteroid eye drops were used in 6 centers (67%), antibiotics alone and antiseptics in 3 centers (33%). Symblepharon ring was used in 5 centers (55%) if necessary. Amniotic membrane transplantation was never performed systematically and only according to the clinical course. Systemic corticosteroid therapy was occasionally used (3/9, 33%) and discussed on a case-by-case basis.The literature about ocular management practice in SJS/ TEN during acute phase is relatively poor. The role of specific treatments such as local or systemic corticosteroid therapy is not consensual. The use of preservatives, often present in eye drops and deleterious to the ocular surface, is to be restricted. Early amniotic membrane transplantation seems to be promising.

Ophthalmological management in craniosynostosis.

INTRODUCTION: In published series, a large proportion of patients with craniosynostosis show impaired vision. MATERIALS AND METHODS: A literature review was performed, using the PubMed and Google Scholar databases, to identify original and review articles on the consequences of craniosynostosis on the eyes and visual pathways, and on the ophthalmological management of craniosynostosis. RESULTS AND DISCUSSION: Many ophthalmic, potentially sight-threatening, complications, can occur in patients with craniosynostosis, especially when syndromic. Optic neuropathy, mostly resulting from the papilledema-optic atrophy sequence, secondary to raised intracranial pressure (ICP), should be diagnosed early, in order to promptly lower the ICP. Cyclovertical and horizontal strabismus and refractive errors are frequent in unicoronal synostosis (anterior plagiocephaly) and syndromic craniosynostosis. Exorbitism, encountered in some cases of syndromic craniofacial synostosis, leads to exposure keratopathy, which requires aggressive management to avoid severe irremediable corneal complications. Amblyopia can result from optic neuropathy, corneal opacities, strabismus, or refractive errors. If undiagnosed and untreated at a young age, it results in permanent visual impairment. CONCLUSION: Children with craniosynostosis require a multidisciplinary care network including a pediatric ophthalmologist. Systematic ophthalmological follow-up enables papilledema to be diagnosed and amblyopia to be diagnosed and treated, in order to avoid visual impairment.

[Ocular manifestations in Ehlers-Danlos Syndromes: Clinical study of 21 patients]. / Manifestations ophtalmologiques des syndromes d'Ehlers­Danlos : à propos d'une cohorte de 21 patients.

INTRODUCTION: The goal of this study was to describe and analyze the ophthalmological manifestations found in 21 patients followed for Ehlers-Danlos Syndrome in our department. METHODS: This retrospective study analyzed 21 consecutive patients (17 women and 4 men) with Ehlers-Danlos syndrome seen in the Necker hospital, Paris, between April 2016 and November 2017. The mean age was 25.95 years (12-47). A complete evaluation was performed searching for symptoms, orthoptic evaluation and complete ophthalmologic examination with slit lamp examination of the anterior segment, pachymetry and fundus examination with fundus photography and OCT. RESULTS: Nineteen patients presented ophthalmological signs (90.5%). The most frequent ophthalmological signs were: ocular motility disorders in 15 patients (71.4%), with convergence insufficiency in 13 of them, blue sclera in 8 patients (38%) and dry eye syndrome in 7 patients (33%, with 2 patients with reduced Break-Up Time<10seconds and 5 with very reduced Break-Up Time<5seconds). Mean pachymetry was 539.25µm (365-612). One patient presented with bilateral keratoglobus (4.8%). High myopia was present in 2 patients (9.5%) and associated with retinal tears in one patient (4.8%). No patients presented with angioid streaks. DISCUSSION: In this study, the main ophthalmological sign was convergence insufficiency present in more than 60% of the patients. This highlights the importance of an orthoptic examination in patients with Ehlers-Danlos syndrome. Dry eye syndrome with tear film instability was frequent, even though the patients were young. Blue sclera was seen in 38% of the patients. We reported two patients with high myopia and one patient with keratoglobus in our cohort. No patients presented with angioid streaks, and mean pachymetry was normal in our series. CONCLUSION: An ophthalmological and orthoptic evaluation should be performed in all patients with Ehlers-Danlos syndrome to detect and treat ocular manifestations. If Ehlers-Danlos syndrome is suspected, ophthalmological examination can also provide support for the diagnosis.

[Hereditary optic neuropathies in pediatric ophthalmology]. / Neuropathies optiques héréditaires en ophtalmo-pédiatrie.

INTRODUCTION: Hereditary optic neuropathies (HON) often begin in adulthood. However, some of them can have an early onset. These may have specific clinical features and natural histories. PATIENTS AND METHODS: Retrospective study of HON patients with onset before the age of 14 years seen in a referral center. In addition to the age of onset, we evaluated the genetic etiology, visual acuity at 15 years, last best corrected visual acuity, optic disc appearance, visual field and extra-ophthalmological manifestations. RESULTS: Forty-four patients (16 women) were included; i.e. 27.8% of all patients followed for HON. The mean age of onset was 8.5±3.3 years, with an onset earlier than 3 years in 5 patients. An etiology was not found in 8 patients. Of the remaining 36 patients, 12 had Leber's hereditary optic neuropathy (LHON), 11 had dominant optic atrophy, 12 had WS/WS-like syndrome, 2 had recessive optic atrophy and 1 had spastic paraplegia type 7. For 78 eyes of 40 patients (mean age 26.9±14.5 years), the mean last visual acuity was 0.80±0.33 LogMAR, with differences according to genetic forms. Visual acuity was less than or equal to counting fingers for 7 eyes (29.1%) of 4 WS/WS-like patients and one LHON patient. CONCLUSION: Early onset NOH are not unusual. Their visual prognosis is as severe as adult onset NOH, with variations depending on the underlying genetic causes.

[The visual snow phenomenon.] / Le phénomène de neige visuelle.

INTRODUCTION: Visual snow is a symptom described by some patients and poorly recognized by ophthalmologists. It consists in the permanent perception of a textured or a snowy vision, sometimes associated with palinopsia, exaggerated perception of the blue field entoptic phenomenon and photophobia. We report a group of patients suffering from visual snow in order to precise its characteristics and discuss its pathophysiology. MATERIALS AND METHODS: Prospective study of patients diagnosed between September 2010 and December 2012 with a visual snow phenomenon. For each patient, a formal ophthalmologic examination, an Amsler grid test, an automated visual field (central 20°), a color vision test (15 Hue), a full field, a pattern and a multifocal electroretinogram as well as flash and pattern visual evoked potentials (Métrovision©) were performed. A brain imaging was not systematically performed. RESULTS: Twelve patients aged 9-48old were included (six men and six women, 85 % of students). Several signs were variably associated with the visual snow phenomenon: palinopsia (50 %), constant blue field entoptic phenomenon (40 %), photophobia (30 %), migraine (30 %); in 20 % of cases, an initial toxic intake was found (20 %). DISCUSSION: This study highlights the reproducibility of typical symptoms described by patients reporting the visual snow phenomenon. This feature strongly supports the organic origin of the phenomenon. The pathophysiology of this phenomenon, however, remains unclear; the hypothesis of a lower threshold for perception of entoptic images cannot entirely account for the reported symptoms.