Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model.

OBJECTIVE: This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS: Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS: A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS: The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Multi-system neurological disease is common in patients with OPA1 mutations.

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal 'dominant optic atrophy plus' variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Republished review: cataract and cognitive impairment: a review of the literature.

Acquired cataract and cognitive impairment are both common age-related problems, and ophthalmologists are increasingly likely to encounter patients who have both. Patients with dementia types who display early visuoperceptual impairment may present first to ophthalmology services. When these patients have coexisting cataract, it may be difficult to distinguish visual complaints due to cataract from those due to dementia. The interaction between visual impairment due to cataract and neurodegenerative disorders affecting the central visual pathways, is not fully understood. Visual impairment due to cataract may stress impaired attentional mechanisms and cataract extraction may improve cognitive performance in some patients with early cognitive impairment; however, the benefits of cataract surgery in established dementia are less clear. In this study, the literature on this subject was reviewed and the implications for practice were considered.

Distance stereoacuity in intermittent exotropia.

BACKGROUND: Studies of distance stereoacuity in intermittent exotropia suggest that normal stereoacuity corresponds to good control of the deviation and that reduced or negative stereoacuity signifies poorer control. AIM: : To evaluate distance stereoacuity in intermittent exotropia using the Frisby Davis Distance stereo test (FD2). METHODS: Children with intermittent exotropia where the near angle was less than or equal to distance were eligible for recruitment. Standardised prospective data collection included FD2 distance stereoacuity. This was a longitudinal study in which outcomes are reported for baseline, last follow-up (> or =6 months before any surgery) or preoperative and last postoperative visits for those undergoing surgery. RESULTS: 110 children with intermittent exotropia had FD2 stereoacuity tested at baseline: 70 comprehended the test. Mean (standard deviation (SD)) age was 4.6 (1.7) years (range 2-10 years). 41/70 (59%) showed positive responses: mean (SD) stereoacuity 30 (12) s of arc. The mean follow-up period before any surgery was 13 months (range 6-27 months). At follow-up, mean (SD) stereoacuity was 24 (11) s of arc. Preoperative and postoperative stereoacuity were not significantly different from those not undergoing surgery. CONCLUSION: This study was the first to report distance stereoacuity in intermittent exotropia using the FD2 stereo test: patients with intermittent exotropia can achieve normal levels of distance stereoacuity, but a considerable proportion, despite comprehending, showed a negative response. This suggests that using the FD2, distance stereoacuity in intermittent exotropia is either absent or normal rather than reduced. Possible reasons for this and its implications are discussed.

Unilateral visual impairment and neurodevelopmental performance in preschool children.

BACKGROUND: Unilateral visual impairment (UVI) as a result of amblyopia or refractive error is common in childhood, but its functional significance remains largely unexplored. AIM: To investigate the influence of visual acuity and stereoacuity on the performance of preschool children on tasks requiring visuomotor skills and visuospatial ability. METHODS: Children with normal (6/6) visual acuity (VA) in both eyes and children with UVI ranging from 6/9 to 6/60, with no strabismus and normal vision in the fellow eye, were assessed on a neurodevelopmental test battery of visually guided tasks. RESULTS: 50 children (mean age (SD): 52.4 (5.7) months; median (range) VA: 6/9 (6/6 to 6/60); median (range) stereoacuity: 70 seconds arc (40-absent)) completed the test battery. UVI and stereoacuity correlated moderately (Pearson's r = 0.537, p < 0.001) but seven of 28 children with impaired VA had normal stereoacuity (< 70 seconds arc) while five of 22 with normal VA had abnormal stereoacuity. Stereoacuity correlated with performance on a task requiring fine hand-eye coordination and a task measuring visuomotor integration. UVI did not correlate with performance on any test battery items. CONCLUSIONS: UVI itself does not appear to relate to visuomotor actions, except when associated with reduced stereoacuity. Stereoacuity appears to have an influential role in fine visuomotor actions and spatial representation in preschool children.

Frisby Davis distance stereoacuity values in visually normal children.

AIMS: To establish the range of normal distance stereoacuity in young children using the Frisby Davis distance stereo test (FD2). METHODS: Children passing preschool vision screening assessments underwent measurement of distance stereoacuity with the FD2 using a standard testing protocol. RESULTS: 59 visually normal children aged between 36 months and 68 months were recruited to this study. All 59 were able to understand the test requirements and were examined with the FD2 stereo test. Four (6.8%) had no measurable stereoacuity; 13 (24%) had stereoacuity measurable only at a 3 metre testing distance (mean 92.3 seconds of arc; SD 52.6). These children were significantly younger than the remaining 42 (76%) who demonstrated a stereoacuity response at a 6 metre testing distance (mean 29.6 seconds of arc; SD 13.1, p=0.008). CONCLUSION: The FD2 stereo test enables the measurement of distance stereoacuity in young children. There appears to be a maturational effect with distance stereoacuity improving between 36 months and 68 months. The data on age related normal values will provide a baseline from which to compare outcomes in clinical populations.

Mitochondrial abnormalities in ageing macular photoreceptors.

PURPOSE: To evaluate somatic mitochondrial (mt)DNA mutations in the macula during ageing. METHODS: Ten 30-microm cryostat sections from the macula (foveal and perifoveal regions) and peripheral retina of 14 donors (aged 14-94 years) were cut for cytochrome c oxidase cytochemistry. The photoreceptor layer was microdissected and DNA extracted for 4977-bp mtDNA (mtDNA(4977)) quantification using PCR. Dual cytochemistry for cytochrome c oxidase and succinate dehydrogenase allowed the detection of cytochrome c oxidase-deficient cones. RESULTS: Findings showed a progressive accumulation of mtDNA(4977) from ages 14 to 94 years. From ages 14 to 60 years there was an increase from 0.006% to 0.25%, and from ages 60 to 94 years there was a steeper increase from 0.25% to 5.39%. Counts of cones in the dual-reacted preparations showed more cytochrome c oxidase-deficient cones in the foveal region than elsewhere. CONCLUSIONS: The results show that mitochondrial DNA deletions and cytochrome c oxidase-deficient cones accumulate in the ageing retina, particularly in the foveal region. These defects may contribute to the changes in macular function observed in ageing and age-related maculopathy.

Using the eye-movement system to control the head.

We tested the hypothesis that A.I., a subject who has total ophthalmoplegia, resulting in a lack of eye movements, used her head to orientate in a qualitatively similar way to eye-based orientating of control subjects. We used four classic eye-movement paradigms and measured A.I.'s head movements while she performed the tasks. These paradigms were (i) the gap paradigm, (ii) the remote-distractor effect, (iii) the anti-saccade paradigm, and (iv) tests of saccadic suppression. In all cases, A.I.'s head saccades were qualitatively similar to previously reported eye-movement data. We conclude that A.I.'s head movements are probably controlled by the same neural mechanisms that control eye movements in unimpaired subjects.

Iris sector heterochromia as a marker for neural crest disease.

A 6-month-old female infant with biopsy-proved Hirschsprung's disease had associated sector heterochromia of the irides. The association between sector heterochromia and Hirschsprung's disease has been previously reported and both conditions have been ascribed to neural crest defects. Histologic characteristics of the ocular involvement have not previously been reported, to our knowledge. Histopathologic examination of the globes revealed decreased iris stroma, decreased pigmentation in the anterior stroma, and reduced numbers of pigment-producing cells in the affected areas. Both the ocular and gastrointestinal findings reflect abnormalities in tissues of neural crest origin.

Prospective comparison of preoperative imaging and intraoperative ultrasonography in the detection of liver tumors.

A prospective evaluation of the accuracy of preoperative computed tomography (CT), ultrasonography (US), and angiography was performed in 54 patients undergoing resection of hepatic neoplasms. The results were compared with surgical findings and intraoperative ultrasonography (IOUS). A total of 167 lesions was seen by means of IOUS, of which preoperative US enabled detection of 127 (76%). In 48 patients CT allowed detection of 91 of 150 lesions (61%), and in 35 patients angiography showed 56 of 107 lesions (52%). When the detection rate is analyzed according to hepatic segment, the greater overall accuracy of preoperative US may be attributed to a markedly better detection rate in lateral segment of the left lobe of the liver. Lesion size also represented a factor, with preoperative US allowing detection of a greater number of small (less than 2 cm) lesions compared with CT. In patients studied with both CT and US, the combined lesion-detection rate increased to 81% in the right lobe and 76% in the left lobe. Because of this we recommend that preoperative assessment include both CT and US evaluation of the liver. IOUS showed 25% to 35% additional lesions compared with preoperative US and CT. More importantly, 40% of the lesions demonstrated by IOUS were neither visible nor palpable at surgery. We recommend that IOUS be considered in all patients in whom resection of hepatic neoplasm is planned.

Ocular abnormalities in a patient with partial deletion of chromosome 6p. A case report.

We report on a patient with a de-novo deletion of chromosome 6p. This male infant presented with multiple systemic congenital defects together with an unusual ocular phenotype. Slit-lamp examination revealed thin, opaque, rectilinear bands within the anterior segment partially connecting iris to corneal endothelium. These were associated with bilateral hyperopia and optic nerve hypoplasia. Ocular abnormalities in such patients have been documented although the number of individuals is small and identical cytogenetic defects are rarely encountered. We compare the clinical findings in this case with previously described phenotypes. Characterisation of such cases is important as it is becoming apparent that deletion of genetic information encoded on chromosome 6p has implications for ocular embryogenesis.

Stickler's syndrome associated with congenital glaucoma.

A case report of Stickler's syndrome associated with congenital glaucoma is presented. Stickler's syndrome is an autosomal dominant disorder characterised by progressive arthropathy, midfacial flattening, Pierre Robin anomaly or cleft palate, sensorineural hearing loss, progressive myopia, vitreoretinal degeneration, and retinal detachment. Congenital glaucoma and Stickler's syndrome are two diagnoses frequently considered in high myopia in infancy. The case report described presents a case of Stickler's syndrome in association with congenital glaucoma. This association is unusual, but important to recognise in the neonatal period. The possibility of coexistence of these clinical entities, should be considered in the future.

Superior oblique tendon expansion in the management of superior oblique dysfunction.

Traditional superior oblique weakening procedures may be unpredictable and lead to superior oblique underaction. The use of 240 retinal band as a spacer to lengthen the superior oblique tendon has been proposed as a more controlled approach than superior oblique tenotomy and related procedures. The use of this technique is reported in a patient with diplopia following an orbital floor blow out fracture, and in a child with Brown's superior oblique tendon sheath syndrome.

The Newcastle Control Score: a new method of grading the severity of intermittent distance exotropia.

AIM: To describe the development and application of a novel scoring system for grading the severity of intermittent distance exotropia (IDEX) and its potential application as an intervention criterion for surgical intervention. METHODS: The Newcastle Control Score (NCS) for IDEX was developed by incorporating both subjective (home control) and objective (clinic control) criteria into a scale to grade severity. The score structure described was evaluated for interobserver and test-retest reliability. To determine an optimal score threshold for surgical intervention, 170 cases of IDEX were scored retrospectively. Cure rates for surgical and non-surgical cases were then compared according to preoperative or presenting scores. RESULTS: Interobserver and test-test reliability were good (r = 0.82 and r = 0.89 respectively). Total cure rate with surgery was 54% and without surgery 18% (chi(2) = 23.093, df = 1, p<0.001). Significantly fewer patients with NCS >/=3 achieved cure without surgery than those with NCS 2 (chi(2) = 3.362, df = 1, p<0.047). CONCLUSIONS: The NCS is a reliable method for grading the severity of IDEX and aids decisions regarding intervention. Patients with a score of 3 or more are unlikely to attain a cure without surgery.

Senior-Loken syndrome. Case reports of two siblings and association with sensorineural deafness.

Two siblings with Senior-Loken syndrome are described. The need for a full evaluation of renal function and hearing in children with a retinal dystrophy is emphasised.

Bias due to incomplete follow up in a cohort study.

AIM: To investigate the bias introduced by incomplete follow up in a cohort study of ocular outcome after premature birth. METHODS: A geographically defined cohort of children born before 32 weeks' gestation was prospectively recruited at birth to study the ocular outcome at 2 years. On the basis of attendance at 2 years, the children's families were allocated to one of three groups: group 1 attended for follow up, group 2 were difficult to trace, and group 3 were very reluctant for assessment. All children were examined by a single ophthalmologist, masked to these groupings. RESULTS: 558 children (98.8% of study group) were examined, of whom 505 were in group 1, 20 in group 2, and 33 in group 3. The groups which were more difficult to study (groups 2 and 3) showed a significantly higher prevalence of ocular abnormalities, including strabismus (p=0. 02) and cicatricial retinopathy of prematurity (p=0.002) compared with those attending for follow up. Further, not all of these cases could have been identified by review of the children's previous records. Ocular abnormalities would be underestimated by 16% (11.3% in group 1 compared with 13.4% in the total cohort, p=0.77). CONCLUSIONS: This study suggests that the prevalence of abnormalities would be underestimated by incomplete follow up, as those subjects who were most difficult to obtain for study had a significantly higher prevalence of abnormalities.

Risk factors for strabismus in children born before 32 weeks' gestation.

AIM: To investigate risk factors associated with strabismus in children born prematurely. METHODS: Prospective study of all children born before 32 weeks' gestation between 1 January 1990 and 31 December 1991 in a geographically defined population of approximately 3 million in the Northern Region of the United Kingdom. All children were examined aged 2 years by the same ophthalmologist and paediatrician. RESULTS: 558 children (98.6% of study group) were examined. Logistic regression showed an increased risk of strabismus in children with cicatricial retinopathy of prematurity (p=0.02), refractive error (p=0.003), family history of strabismus (p<0.0001), and poor neurodevelopmental outcome (p<0.0001), in particular impaired locomotor skills (p=0.008) and hand-eye coordination (p=0. 001). Gestational age and regressed acute ROP were not independent risk factors for strabismus (p=0.92 and 0.85 respectively). CONCLUSIONS: This study has identified factors which are independently related to strabismus (although not necessarily causative) and others which are related only indirectly. This may contribute both to the management of children born prematurely and to future studies of the aetiology of strabismus.

Retinopathy of prematurity in a controlled trial of prophylactic surfactant treatment.

AIMS: To investigate the incidence of acute and cicatricial retinopathy of prematurity (ROP) in a cohort of premature neonates entered into a randomised, multicentre trial of prophylactic exogenous surfactant for respiratory distress syndrome (RDS) compared with controls receiving surfactant only if severe RDS developed. METHODS: The incidence of acute and cicatricial ROP was assessed in 304 neonates born at less than 30 weeks' gestation in a geographically defined population of approximately three million. RESULTS: There was a trend towards improved survival in the group receiving prophylactic surfactant with 102/151 (67.5%) surviving compared with 82/141 controls (58.2%, p = 0.12). The prophylactic surfactant group would be expected to have an increased risk of ROP due to improved survival, particularly of the most premature infants. However, there was no statistically significant difference in the incidence of acute ROP between the two groups and the incidence of cicatricial ROP was lower in the group receiving prophylactic surfactant (4/100 survivors, 4.0%) compared with neonates receiving rescue surfactant as required (6/81, 7.4%). This difference did not reach statistical significance (p = 0.35). CONCLUSION: The trend for a lower incidence of cicatricial ROP in those neonates treated with prophylactic surfactant compared with the rescue surfactant group, despite improved survival, suggests that the use of prophylactic surfactant also had a beneficial effect on the development of cicatricial ROP.

Influence of pupil size on measurements made with the Lens Opacity Meter 701.

The Lens Opacity Meter 701 (Interzeag, Switzerland) is a recently developed instrument for assessing cataract. It measures the degree of scatter of a red light beam by the lens. Fifty patients prior to cataract surgery had measurements made before and after dilatation of the pupil. Inconsistent results were found at pupil diameters of less than 4 mm. It is postulated that this was due to absorption of scattered light by the iris.

Regionalisation of retinopathy of prematurity (ROP) screening improves compliance with guidelines: an audit of ROP screening in the Northern Region of England.

AIMS: This project was designed to determine whether a coordinated regional strategy can improve the implementation of national guidelines for screening for retinopathy of prematurity (ROP), and to identify causes for failure of compliance. METHODS: Retrospective case note audit relating to two periods, 1990-1 and 1994, involving all 17 neonatal intensive care units in the Northern Region of England. Between the two periods, a regional strategy was instituted in an endeavour to improve compliance. Babies born in or admitted to the units during the study periods who were eligible for ROP screening were included. Screening performance was assessed against a standard of 100% compliance with the guidelines. In the second audit period compliance with subsidiary standards was also measured, and reasons for failure were identified. RESULTS: Compliance improved from 47% (262/558) in the first audit cycle to 73% (264/360) in the second. Subgroup analysis in this second cycle indicated better compliance (93.3%) in higher risk babies (< or = 29 weeks' gestational age). Babies transferred between units, discharged home before screening, or who failed to qualify for screening on one of the two defined criteria, were more likely to be missed. CONCLUSION: A carefully implemented regional approach to screening resulted in a higher uptake for babies most at risk. Simple recommendations are made to achieve further improvement in compliance with the guidelines. The wider implications for screening in other conditions and in other areas and specialties are highlighted.