Christopher J. Lyons

Orbital Decompression for Disfiguring Exophthalmos in Thyroid Orbitopathy

Background: Progressive exophthalmos from dysthyroid orbitopathy may result in marked disfigurement. Commonly affecting middle-aged women, it can be a significant social and psychologic handicap. Cosmesis is increasingly recognized as an indication for orbital decompression. Many argue, however, that decompression carries risks of operative complications which are only warranted where vision is threatened. Methods: Between 1984 and 1990, the authors performed orbital decompression for cosmetic indications on 34 patients (65 orbits) with thyroid orbitopathy. The charts of these patients were reviewed to assess the results of surgery and the nature and incidence of complications. Results: The mean retroplacement achieved was 4 mm (range, -1.0 to 10 mm). In 29 (85%) of the 34 patients, there was a difference of 1 mm or less in the proptosis of the two eyes postoperatively. Diplopia arose de novo in five (18%) previously asymptomatic patients. Postdecompression strabismus was managed successfully with adjustable surgery (mean, 1.3 operations per patient). With the exception of transient infraorbital nerve hypoesthesia, there were no surgical complications. Conclusion: Decompression surgery is effective in reducing exophthalmos in dysthyroid orbitopathy. In this series of operations, complications were rare and treatable. Decompression is often the first of a series of operations that may be necessary to correct the cosmetic sequelae of this condition. It should be considered by experienced surgeons in carefully selected and counseled patients who have disfiguring thyroid orbitopathy.

Deficient motion perception in the fellow eye of amblyopic children

The extent of motion processing deficits and M/dorsal pathway involvement in amblyopia is unclear. Fellow eye performance was assessed in amblyopic children for motion-defined (MD) form, global motion, and maximum displacement (Dmax) tasks. Group performance on MD form was significantly worse in amblyopic children than in control children. Global motion deficits were significantly related to residual binocular function. Abnormally elevated Dmax thresholds were most prevalent in children with anisometropia. Our findings from these three uncorrelated tasks implicate involvement of binocular motion-sensitive mechanisms in the neural deficits of amblyopic children with strabismic, anisometropic, and aniso-strabismic etiologies.

Psychophysical Indexes of Temporal Processing Abnormalities in Children With Developmental Dyslexia

Children with dyslexia and children progressing normally in reading performed several perceptual tasks to determine (a) the psychophysical measures that best differentiate children with dyslexia from children with average reading abilities; (b) the extent of temporal processing deficits in a single, well-defined group of children with dyslexia; and (c) the co-occurrence of visual and auditory temporal processing deficits in children with dyslexia. 4 of our 12 psychophysical tasks indicated differences in temporal processing ability between children with dyslexia and children with good reading skills. These included 2 auditory tasks (dichotic pitch perception and FM tone discrimination) and 2 visual tasks (global motion perception and contrast sensitivity). The battery of 12 tasks successfully classified 80% of the children into their respective reading-level groups. Within the group of children with dyslexia who had temporal processing deficits, most were affected in either audition or vision; few children were affected in both modalities. The observed deficits suggest that impaired temporal processing in dyslexia is most evident on tasks that require the ability to synthesize local, temporally modulated inputs into a global percept and the ability to extract the resultant global percept from a noisy environment.

Three novel mutations in KIF21A highlight the importance of the third coiled-coil stalk domain in the etiology of CFEOM1

BackgroundCongenital fibrosis of the extraocular muscles types 1 and 3 (CFEOM1/CFEOM3) are autosomal dominant strabismus disorders that appear to result from maldevelopment of ocular nuclei and nerves. We previously reported that most individuals with CFEOM1 and rare individuals with CFEOM3 harbor heterozygous mutations in KIF21A. KIF21A encodes a kinesin motor involved in anterograde axonal transport, and the familial and de novo mutations reported to date predictably alter one of only a few KIF21A amino acids – three within the third coiled-coil region of the stalk and one in the distal motor domain, suggesting they result in altered KIF21A function. To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A.ResultsSixteen CFEOM1 and 29 CFEOM3 probands were studied. Three previously unreported de novo KIF21A mutations were identified in three CFEOM1 probands, all located in the same coiled-coil region of the stalk that contains all but one of the previously reported mutations. Eight additional CFEOM1 probands harbored three of the mutations previously reported in KIF21A; seven had one of the two most common mutations, while one harbored the mutation in the distal motor domain. No mutation was detected in 5 CFEOM1 or any CFEOM3 probands.ConclusionAnalysis of sixteen CFEOM1 probands revealed three novel KIF21A mutations and confirmed three reported mutations, bringing the total number of reported KIF21A mutations in CFEOM1 to 11 mutations among 70 mutation positive probands. All three new mutations alter amino acids in heptad repeats within the third coiled-coil region of the KIF21A stalk, further highlighting the importance of alterations in this domain in the etiology of CFEOM1.

Oculomotor nerve palsy in childhood

BACKGROUND The management of children with oculomotor nerve palsy is complicated by their variable presentation, amblyopia, potential loss of binocularity, and associated neurological disease. Our purpose was to evaluate the causes, neurological associations, treatment, and sensorimotor outcomes of a group of children who developed oculomotor nerve palsy. METHODS We identified 18 children aged 14 years or younger, of whom 13 (72%) were less than 8 years old, through a retrospective record review of all children with oculomotor nerve palsy seen between January 1995 and January 2001 by one of the authors (C.J.L.). RESULTS Congenital-onset oculomotor nerve palsy was the most frequent presentation, followed by traumatic, neoplastic, vascular, and migrainous or para-infectious etiologies. Pupil sparing was seen in 1 patient with neoplastic etiology. Primary aberrant regeneration was the presenting sign in a child with neurofibromatosis type 2. Amblyopia developed in 7 (39%) children and was successfully treated in 5 of the 7 (71%). Stereopsis was maintained in 6 (33%) children of whom 2 were within the amblyogenic age group. Six (33%) patients underwent strabismus surgery, and 3 of them (50%) achieved orthotropia and maintained stereopsis. INTERPRETATION Children with oculomotor nerve palsy require neuroimaging. Their pupillary signs, unlike those of adults, are not helpful in differentiating compressive etiologies from other causes. Good visual acuity was obtained in children within the amblyogenic age group with appropriate occlusion therapy. Stereopsis was uncommon in children who developed third nerve palsy during the amblyogenic period; preservation of stereopsis was dependent either on rapid and complete recovery, or on the childs adoption of a compensatory head position.

Acute acquired comitant esotropia: A prospective study

Purpose To define the clinical characteristics of patients presenting with acute onset esotropia and features suggestive of possible underlying central nervous system pathology. To assess the prognosis for the return of binocular function and to consider the most appropriate management.Methods A prospective clinical study was carried out of all patients presenting to the department of paediatric ophthalmology at a university teaching hospital over the period January 1994 to April 1997. Each patient underwent a full ophthalmological examination (including assessment of sensory status). All patients were referred to a paediatric neurologist for examination and CT and/or MRI scan.Results Ten patients presented during the study period. Uncorrected hypermetropia and/ or decompensated monofixation syndrome were the commonest aetiological factors. One patient was found to have a cerebellar tumour. In 5 patients prescription of the full hypermetropic correction alone was sufficient to restore binocularity. Five patients required bilateral medial rectus recession. Binocular function was restored in all cases in 5 cases with bifoveal fusion.Conclusion Decompensation of a pre-existing phoria or monofixation syndrome appears the commonest aetiology. Prescription of the full hypermetropic correction found at cycloplegic refraction forms an essential part of initial management. No single clinical sign can reliably indicate the rare patient harbouring a tumour. A high index of suspicion should be maintained and neuro-imaging considered in the absence of expected findings such as hypermetropia or fusion potential or in the presence of atypical features or neurological signs.

Renal-coloboma syndrome: Prenatal detection and clinical spectrum in a large family

Renal-coloboma syndrome includes abnormalities in the urogenital and ocular systems as its primary manifestations, although it can be associated with abnormalities in other systems as well. This syndrome is caused by mutations in the PAX2 gene and is transmitted as an autosomal dominant trait. We report a family in which at least 7 members have manifestations of renal-coloboma syndrome, including two in whom renal disease was diagnosed prenatally by ultrasound examination. A pathogenic frame-shift mutation (619insG) was found in the PAX2 gene in affected family members, who show remarkable variability in both the ocular and renal manifestations of the syndrome.

Visual impairment due to a dyskinetic eye movement disorder in children with dyskinetic cerebral palsy

Neurological lesions that cause dyskinetic cerebral palsy (CP) commonly involve ocular movements. This report describes a group of 14 children (nine males, five females) whose CP is associated with severe dyskinetic eye movements. Ages ranged from 4 months to 13 years (mean 6.9 years). Clinical features of this eye movement disorder are discussed and defined. The visual function of these children is slow, variable, and highly inefficient. They are often misdiagnosed as blind, due to cortical visual impairment. Early recognition of dyskinetic eye moment disorder and appropriate developmental and educational management are important.

Cortical visual impairment in children with infantile spasms

BACKGROUND Infantile spasms are often associated with cortical visual impairment. METHOD We report a series of 10 patients with infantile spasms, hypsarrhythmic electroencephalograms, and developmental delay, (ie, West syndrome), who presented with severe visual inattention despite a normal ocular examination. RESULTS At follow-up (14 months to 6 years), 5 patients (50%) had no improvement in their visual behaviour. Although some degree of improvement was observed in the others, their visual function remained abnormal. All patients had moderate or severe mental retardation. CONCLUSIONS The clinical features of West syndrome are reviewed, and the cause of the associated cortical visual impairment is discussed. Cortical visual impairment with infantile spasms is an important association, which pediatric ophthalmologists should recognize.

The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease

Aim The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease. Methods Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype–phenotype correlations. Results 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were identified. Six of these mutations are novel, and none were found in 346 control chromosomes. In 16 cases of Coats disease, one polymorphism combination was found in two samples: no mutations were detected. No genotype–phenotype correlation emerged. Three severely affected cases with FZD4 mutations failed to show additional mutations in the three other FEVR genes. Conclusion The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease.