Systemic and Ophthalmic Manifestations in Different Types of Refractive Errors in Patients with Down Syndrome.

Background and Objective: This study aims to investigate the prevalence of systemic and ophthalmic manifestations in different refractive groups in children and young adults with Down syndrome (DS). Materials and Methods: The study was a population-based, cross-sectional study that included 141 Caucasian children and young adults with DS. They were classified into the following three groups: myopia DS group (37 subjects, mean age 15.8 years), emmetropia DS group (41 subjects, mean age 11.7 years) and hyperopia DS group (63 subjects, mean age 10.9 years). The participants underwent inspection, slit-lamp examination, cycloplegic refraction, ocular alignment and ocular motility examination. Ten systemic manifestations were analyzed. Results: There was no difference in the prevalence of any systemic manifestations between the groups. Considering the ophthalmic manifestations, there was statistical difference in the distribution of proportions among the three groups for nystagmus (p = 0.011), iris-stromal atrophy (p = 0.048) and strabismus (p = 0.031). The prevalence of strabismus in our DS myopia group was 35.1%, and in DS hyperopia group 38.1%. Conclusions: The results of our study suggest that DS children and young adults with any refractive error do not have a higher chance of additional systemic manifestations. Myopia in DS was associated with a higher prevalence of nystagmus and iris stromal atrophy, whereas astigmatism was found to be more frequent in hyperopia.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus.

Periodic alternating nystagmus consists of involuntary oscillations of the eyes with cyclical changes of nystagmus direction. It can occur during infancy (e.g. idiopathic infantile periodic alternating nystagmus) or later in life. Acquired forms are often associated with cerebellar dysfunction arising due to instability of the optokinetic-vestibular systems. Idiopathic infantile periodic alternating nystagmus can be familial or occur in isolation; however, very little is known about the clinical characteristics, genetic aetiology and neural substrates involved. Five loci (NYS1-5) have been identified for idiopathic infantile nystagmus; three are autosomal (NYS2, NYS3 and NYS4) and two are X-chromosomal (NYS1 and NYS5). We previously identified the FRMD7 gene on chromosome Xq26 (NYS1 locus); mutations of FRMD7 are causative of idiopathic infantile nystagmus influencing neuronal outgrowth and development. It is unclear whether the periodic alternating nystagmus phenotype is linked to NYS1, NYS5 (Xp11.4-p11.3) or a separate locus. From a cohort of 31 X-linked families and 14 singletons (70 patients) with idiopathic infantile nystagmus we identified 10 families and one singleton (21 patients) with periodic alternating nystagmus of which we describe clinical phenotype, genetic aetiology and neural substrates involved. Periodic alternating nystagmus was not detected clinically but only on eye movement recordings. The cycle duration varied from 90 to 280 s. Optokinetic reflex was not detectable horizontally. Mutations of the FRMD7 gene were found in all 10 families and the singleton (including three novel mutations). Periodic alternating nystagmus was predominantly associated with missense mutations within the FERM domain. There was significant sibship clustering of the phenotype although in some families not all affected members had periodic alternating nystagmus. In situ hybridization studies during mid-late human embryonic stages in normal tissue showed restricted FRMD7 expression in neuronal tissue with strong hybridization signals within the afferent arms of the vestibulo-ocular reflex consisting of the otic vesicle, cranial nerve VIII and vestibular ganglia. Similarly within the afferent arm of the optokinetic reflex we showed expression in the developing neural retina and ventricular zone of the optic stalk. Strong FRMD7 expression was seen in rhombomeres 1 to 4, which give rise to the cerebellum and the common integrator site for both these reflexes (vestibular nuclei). Based on the expression and phenotypic data, we hypothesize that periodic alternating nystagmus arises from instability of the optokinetic-vestibular systems. This study shows for the first time that mutations in FRMD7 can cause idiopathic infantile periodic alternating nystagmus and may affect neuronal circuits that have been implicated in acquired forms.

Phenotypical characteristics of idiopathic infantile nystagmus with and without mutations in FRMD7.

Idiopathic infantile nystagmus (IIN) consists of involuntary oscillations of the eyes. The familial form is most commonly X-linked. We recently found mutations in a novel gene FRMD7 (Xq26.2), which provided an opportunity to investigate a genetically defined and homogeneous group of patients with nystagmus. We compared clinical features and eye movement recordings of 90 subjects with mutation in the gene (FRMD7 group) to 48 subjects without mutations but with clinical IIN (non-FRMD7 group). Fifty-eight female obligate carriers of the mutation were also investigated. The median visual acuity (VA) was 0.2 logMAR (Snellen equivalent 6/9) in both groups and most patients had good stereopsis. The prevalence of strabismus was also similar (FRMD7: 7.8%, non-FRMD7: 10%). The presence of anomalous head posture (AHP) was significantly higher in the non-FRMD7 group (P < 0.0001). The amplitude of nystagmus was more strongly dependent on the direction of gaze in the FRMD7 group being lower at primary position (P < 0.0001), compared to non-FRMD7 group (P = 0.83). Pendular nystagmus waveforms were also more frequent in the FRMD7 group (P = 0.003). Fifty-three percent of the obligate female carriers of an FRMD7 mutation were clinically affected. The VA's in affected females were slightly better compared to affected males (P = 0.014). Subnormal optokinetic responses were found in a subgroup of obligate unaffected carriers, which may be interpreted as a sub-clinical manifestation. FRMD7 is a major cause of X-linked IIN. Most clinical and eye movement characteristics were similar in the FRMD7 group and non-FRMD7 group with most patients having good VA and stereopsis and low incidence of strabismus. Fewer patients in the FRMD7 group had AHPs, their amplitude of nystagmus being lower in primary position. Our findings are helpful in the clinical identification of IIN and genetic counselling of nystagmus patients.

The Relation between Reading Skills and Eye Movement Patterns in Adolescent Readers: Evidence from a Regular Orthography.

Over the past decades, the relation between reading skills and eye movement behavior has been well documented in English-speaking cohorts. As English and German differ substantially with regard to orthographic complexity (i.e. grapheme-phoneme correspondence), we aimed to delineate specific characteristics of how reading speed and reading comprehension interact with eye movements in typically developing German-speaking (Austrian) adolescents. Eye movements of 22 participants (14 females; mean age = 13;6 years;months) were tracked while they were performing three tasks, namely silently reading words, texts, and pseudowords. Their reading skills were determined by means of a standardized German reading speed and reading comprehension assessment (Lesegeschwindigkeits- und -verständnistest für Klassen 6-12). We found that (a) reading skills were associated with various eye movement parameters in each of the three reading tasks; (b) better reading skills were associated with an increased efficiency of eye movements, but were primarily linked to spatial reading parameters, such as the number of fixations per word, the total number of saccades and saccadic amplitudes; (c) reading speed was a more reliable predictor for eye movement parameters than reading comprehension; (d) eye movements were highly correlated across reading tasks, which indicates consistent reading performances. Contrary to findings in English-speaking cohorts, the reading skills neither consistently correlated with temporal eye movement parameters nor with the number or percentage of regressions made while performing any of the three reading tasks. These results indicate that, although reading skills are associated with eye movement patterns irrespective of language, the temporal and spatial characteristics of this association may vary with orthographic consistency.

Biomechanical analysis of x-pattern exotropia.

PURPOSE: To simulate and check the plausibility of the proposed mechanisms of X-pattern exotropia and to determine the least invasive surgical method that can be used to treat the disorder. DESIGN: Computational supported analysis and retrospective study. METHODS: The oculomotor model SEE++ was used to simulate the effects of the different causes that have been proposed for the X-phenomenon. In addition, a retrospective study was conducted using preoperative and postoperative measurements of 10 patients with X-pattern exotropia. Eye movements and surgery of these patients were simulated and analyzed statistically. RESULTS: Our computer-based simulations showed that only 1 of the 4 proposed theories can account successfully for the observed X-patterns: an overaction of all 4 oblique muscles can induce divergent exotropia in upgaze and downgaze, and an alteration of horizontal muscles can cause the additional divergence in all gaze positions. The simulation of eye muscle surgery confirmed that a sufficient correction of the divergent deviation in all gazes already can be achieved by a recession and resection of 2 horizontal eye muscles. CONCLUSIONS: In case of X-pattern exotropia, recession and resection of 2 horizontal muscles can be used as a first-line therapy, leading to a simplification of the therapy.

Women underrepresented on editorial boards of 60 major medical journals.

BACKGROUND: Although there has been a continuous increase in the number of women working in the field of medicine, women rarely reach the highest academic positions as full professors or editorial board members. OBJECTIVE: We aimed to determine the proportion of women on the editorial boards of top-ranked medical journals in different medical specialties. METHODS: We analyzed the gender of editorial board members of 60 top-ranked journals of 12 Thomson Reuters Web of Knowledge Journal Citation Reports categories. A total of 4175 editors were included in our analysis. RESULTS: Only 15.9% (10 of 63) editors-in-chief were female. In the 5 categories, critical care, anesthesiology, orthopedics, ophthalmology and radiology, nuclear medicine and medical imaging, currently not 1 woman holds the position of editor-in-chief. Less than one fifth (17.5%, 719 of 4112) of all editorial board members were women. There were significant differences among the evaluated categories, with the highest percentage of women in the category of medicine, general and internal and the lowest in the category critical care, followed by orthopedics. In every category, the proportion of women as editorial board members was substantially lower than that of men. CONCLUSIONS: Women are underrepresented on the editorial boards of major medical journals, although there is a great variability among the journals and categories analyzed. If more women are nominated to serve on editorial boards, they will be a visible sign of continuing progress and serve as important role models for young women contemplating a career in academic medicine.

Polytetrafluoroethylene (Goretex) for muscle elongation in the surgical treatment of strabismus with restricted motility.

PURPOSE: Repeated strabismus surgery as well as eye muscle fibrosis in various forms of strabismus, can be followed by restriction of the motility of the eye. Tendon elongation may be necessary if further improvement of the deviation and duction of the eye muscle is to be achieved. We used polytetrafluoroethylene (Goretex) and looked at its user comfort, compatibility and dose-rate relationship. METHOD: Three patients with consecutive exotropia after repeated operations for congenital esotropia, two patients with VI nerve palsy and residual head turn after combined convergence operation and one child with congenital fibrosis syndrome underwent muscle tendon elongation with Goretex (7-15 mm) of either the medial or the lateral rectus muscle, which had already been resected and/or recessed in former surgeries. Forced duction under general anaesthesia was restricted in all patients. RESULTS: The correction of the deviation in primary position (deviation at distance + 3 degrees to - 4 degrees and at near - 1 degrees to - 8 degrees ) and in side gaze was satisfactory and motility was clearly improved. There were no postoperative complications (infection, shrinkage, scarring) and the postoperative results in terms of the angle of deviation and the improvement in motility remained stable for 1-6 years. CONCLUSION: Polytetrafluoroethylene (Goretex) is a good material with which to resolve complicated cases of strabismus in which muscle tendon elongation for bulbus restriction is necessary.

[Ocular myasthenia: a diagnostic and management challenge--a review]. / Okuläre Myasthenie: eine diagnostische und therapeutische Herausforderung--eine Ubersicht.

BACKGROUND: Ocular myasthenia is a localised form of myasthenia clinically involving the extraocular muscles, the m. levator palpebrae superioris and the m. orbicularis oculi. Various symptoms can masquerade peripheral and supranuclear eye muscle palsies and ptosis. MATERIALS AND METHOD: This literature review of recent years focuses on the diagnostic tests that may be helpful to confirm myasthenia especially in patients without acetylcholine receptor antibodies. CONCLUSIONS: Ocular dysfunction accounts for 50-80% of the initial manifestation of myasthenia gravis. Clinical manifestations, diagnostic tests and treatment assessment are reviewed. Early recognition of the disease is important for better prognosis.

[Diagnosis and therapy of Graves' ophthalmopathy--consensus guidelines]. / Diagnostik und Therapie der endokrinen Orbitopathie--Konsensusrichtlinien.

On 22-09-2001 the VIth Grazer Hormonsymposion took place. Diagnosis and therapy of Graves' Ophthalmopathy was discussed in an interdisciplinary way by endocrinologists, surgeons and ophthalmologists. The results of the round-table discussion and the consensus talk are presented.