John Bradbury

Reading speed test for potential central vision measurement

This study examines the validity and reliability of a reading speed test as a measure of potential central vision. Reading speed was calculated in words per minute (wpm) from the time taken to read 30 words of 1.20 logMAR size text. Scores were obtained from subjects with cataract (n = 48), macular disease (n = 35), peripheral vision loss (n = 14) and normal eyes (n = 10). Subjects with macular disease (27.0 ± 13.2 wpm) read much slower than subjects with cataract (91.9 ± 13.6 wpm). Little difference was found between subjects with cataract, peripheral vision loss (91.5 ± 14.7 wpm) and normal eyes (103.8 ± 15.5 wpm). Repeat testing gave values within ± 16% of reading speed. These results suggest that a reading speed test using large text could be useful as a potential central vision test in cataract patients.

Micro syndrome in Muslim Pakistan children

OBJECTIVE To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families. DESIGN Retrospective case series. PARTICIPANTS Fourteen children from 11 families attending one of five British hospitals. MAIN OUTCOME MEASURES The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family. RESULTS We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive. CONCLUSIONS Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.

Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5

Background/aims: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. Methods: All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). Results: The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. Conclusion: Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

Recessive Mutations in SLC38A8 Cause Foveal Hypoplasia and Optic Nerve Misrouting without Albinism

Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.

Bilateral Changes in Foveal Structure in Individuals with Amblyopia

PURPOSE To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 × 6-mm area with a resolution of 256 × 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 μm; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 μm; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.

A randomised placebo-controlled trial of topical cysteamine therapy in patients with nephropathic cystinosis

Five patients with nephropathic cystinosis were evaluated to assess the ability of topical cysteamine to clear corneal cystine crystals. All patients were randomised to receive topical cysteamine 0.2% six times a day in one eye with normal saline in the other eye as a control.All five patients showed some improvement in visual symptoms (photophobia, ble-pharospasm and visual acuity) together with an improvement in corneal crystal density. Three of these also had an improvement in Snellen visual acuity and contrast sensitivity.

Simultaneous administration of hepatitis B and polio vaccines associated with bilateral optic neuritis

Editor,—Immunisation against hepatitis B is recommended when there is an increased risk of contracting the virus because of lifestyle, occupation, or factors such as close contact with a case. Immunisation against poliomyelitis is routinely given to infants in the UK with reinforcement during childhood and then again in the teenage years. For those individuals at continued risk of infection, further reinforcing doses are given every 10 years. Both are commonly used vaccines and serious adverse reactions are extremely rare. We describe a case of severe bilateral, progressive optic neuritis occurring 1 week after vaccination against hepatitis B and poliomyelitis. ### CASE REPORT A 44 year old female health worker presented with gradual reduction of vision in both eyes associated with retrobulbar discomfort exacerbated by ocular movement, 7 days …

Variable expression of neurological phenotype in autosomal recessive oculodentodigital dysplasia of two sibs and review of the literature

Individuals with oculodentodigital dysplasia (ODDD) have a characteristic facial appearance and variable involvement of the eyes, teeth and fingers. Gutmann et al. (Am J Med Genet 41:18, 1990) drew attention to neurological symptoms as a feature in a proportion of individuals with ODDD and demonstrated white matter changes on cranial magnetic resonance imaging. The majority of cases described previously have family histories compatible with autosomal dominant inheritance. Until now, five families have been reported where autosomal recessive inheritance is more likely. Neurological symptoms were described in only one of these families but cerebral imaging was not performed. We describe clinical, including neurological and radiological findings, in two sisters with autosomal recessive ODDD.

A new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis maps to a locus on chromosome 16q23.2–24.2.

he phrase anterior segment dysgenesis (ASD), also sometimes known as anterior segment ocular or mesenchymal dysgenesis (ASOD or ASMD, OMIM #107250), was first used in 1981 by Hittner and colleagues to describe a range of developmental defects in structures at the front of the eye. 1 These defects are thought to result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to the cornea, iris, and other components of the anterior chamber during eye development. 23 Conditions falling within the ASD spectrum include aniridia, posterior embryotoxon, Axenfeld’s anomaly, Reiger’s anomaly/syndrome, Peters’ anomaly, and iridogoniodysgenesis. Aniridia (OMIM #106210) ranges from almost complete absence of the iris, through enlargement and irregularity of the pupil mimicking a coloboma, to small slit-like defects in the anterior layer visible only with a slit lamp. In Axenfeld’s anomaly (OMIM #109120), the Schwalbe’s line is prominent and centrally displaced (posterior embryotoxon) with peripheral iris strands fused to it. Eye signs in Rieger’s anomaly (OMIM #109120) patients may include malformations of the anterior chamber angle and aqueous drainage structures (iridogoniodysgenesis), microcornea, iris hypoplasia, eccentric pupil (corectopia), iris tears (polycoria), and iridocorneal tissue adhesions traversing the anterior chamber angle. 45 In Reiger’s syndrome (OMIM #180500), patients have ASD in association with underdeveloped or misshapen teeth (hypodontia) and may also have hearing loss, heart defects and skeletal abnormalities. Peters’ anomaly (OMIM #604229) consists of a central corneal leucoma, absence of the posterior corneal stroma and Descemet membrane, and varying degrees of iris and lenticular attachment to the posterior cornea. All of these conditions carry with them an increased risk of glaucoma owing to abnormalities in the Schlemm’s canal and trabecular meshwork. Human ASD phenotypes are genetically heterogeneous, 6

Strabismus Surgical Skills Assessment Tool: Development of a Surgical Assessment Tool for Strabismus Surgery Training

PURPOSE To develop a structured tool to assess strabismus surgical skills and to determine the face and content validity of this tool. DESIGN Development of a surgical assessment tool and its validation by an expert panel. METHODS A structured subjective evaluation form was developed to evaluate a trainees technique and skill in strabismus surgery. The tool consists of strabismus surgery-specific components, such as conjunctival incision, muscle exposure, and suture placement, and global indices, such as hemostasis, tissue control, and knowledge of instruments. Each of these components was evaluated on a 5-point Likert scale. A survey of experienced strabismus surgeons was performed to establish the face and content validity of the tool. The results of the survey were used to amend the tool. RESULTS The final tool comprises 10 strabismus surgery-specific competencies and 7 global indices. The final version of the tool was deemed to address the vital aspects of a strabismus surgical procedure (face validity), and the components of the assessment tool were deemed to assess appropriate competencies and skills associated with the procedure (content validity). CONCLUSIONS The strabismus surgery skill assessment tool is a structured quantitative instrument designed to aid surgical evaluation and training of ophthalmic surgical trainees. The Strabismus Surgical Skill Assessment Tool is a paper-based tool that is easy to use, provides the trainee with detailed feedback and a measure of progression of their surgical skills, and stimulates discussion between trainee and trainer to direct further training.