As a more complete picture of the clinical phenotype of Parkinson's disease emerges, non-motor symptoms have become increasingly studied. Prominent among these non-motor phenomena are mood disturbance, cognitive decline and dementia, sleep disorders, hyposmia and autonomic failure. In addition, visual symptoms are common, ranging from complaints of dry eyes and reading difficulties, through to perceptual disturbances (feelings of presence and passage) and complex visual hallucinations. Such visual symptoms are a considerable cause of morbidity in Parkinson's disease and, with respect to visual hallucinations, are an important predictor of cognitive decline as well as institutional care and mortality. Evidence exists of visual dysfunction at several levels of the visual pathway in Parkinson's disease. This includes psychophysical, electrophysiological and morphological evidence of disruption of retinal structure and function, in addition to disorders of 'higher' (cortical) visual processing. In this review, we will draw together work from animal and human studies in an attempt to provide an insight into how Parkinson's disease affects the retina and how these changes might contribute to the visual symptoms experienced by patients.

Results from recent randomised clinical trials in amblyopia should change our approach to screening for and treatment of amblyopia. Based on the current evidence, if one screening session is used, screening at school entry could be the most reasonable time. Clinicians should preferably use age-appropriate LogMAR acuity tests, and treatment should only be considered for children who are clearly not in the typical range for their age. Any substantial refractive error should be corrected before further treatment is considered and the child should be followed in spectacles until no further improvement is recorded, which can take up to 6 months. Parents and carers should then be offered an informed choice between patching and atropine drops. Successful patching regimens can last as little as 1 h or 2 h a day, and successful atropine regimens as little as one drop twice a week. Intense and extended regimens might not be needed in initial therapy.

Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling.

Purpose-Autosomal dominant optic atrophy (DOA) is a major cause of visual impairment in young adults and it is characterized by selective retinal ganglion cell loss. In order to define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiological and molecular study of presumed DOA cases in the north of England. Design-Case seriesParticipants-Seventy-six affected probands with a clinical diagnosis of DOA were identified from our neuro-ophthalmology and neurogenetics database.Methods-OPA1 genetic testing was performed using a PCR-based sequencing strategy. OPA1 negative cases were then screened for large-scale OPA1 re-arrangements and OPA3 mutations. Additional affected family members identified through contact tracing were examined and longitudinal visual data was analyzed.Main Outcome Measures-The prevalence and molecular characteristics of DOA in the north of England. Visual function and disease progression among patients with OPA1 positive mutations. Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsResults-The detection rate of OPA1 mutations was 57.6% among probands with a positive family history of optic atrophy (19/33) and 14.0% among singleton cases (6/43). About two-thirds of our DOA families harbored OPA1 mutations (14/22, 63.6%), and five novel OPA1 mutations were identified. Only one family carried a large-scale OPA1 rearrangement and no OPA3 mutations were found in our optic atrophy cohort. The minimum point prevalence of DOA in the north of England was 2.87 per 100,000 (95% CI 2.54-3.20), or 2.09 per 100,000 (95% CI 1.95-2.23) when only OPA1 positive cases were considered. Snellen visual acuity varied markedly between OPA1 positive cases with a mean of 20/173 (Range 20/20-hand movement), and visual function worsened in 67.4% of patients during follow-up. The mean rate of visual loss was 0.032 LogMAR/years but some patients experienced much faster visual decline (Range = 0-0.171 LogMAR/years). OPA1 missense mutations were associated with a significantly worse visual outcome compared to other mutational subtypes (P = 0.0001).Conclusions-DOA causes significant visual morbidity and affects at least 1 in 35,000 of the general population.

Objectives To test the efficacy of treatment for unilateral visual loss detected by preschool vision screening and the extent to which effectiveness varies with initial severity. Design Randomised controlled trial of full treatment with glasses and patching, if required, compared with glasses only or no treatment. Masked assessment of best corrected acuity after one year of follow up. Setting Eight UK eye departments. Participants 177 children aged 3-5 years with mild to moderate unilateral impairment of acuity (6/9 to 6/36) detected by screening. Results Children in the full and glasses treatment groups had incrementally better visual acuity at follow up than children who received no treatment, but the mean treatment effect between full and no treatment was equivalent to only one line on a Snellen chart (0.11 log units; 95% confidence interval 0.050 to 0.171; P < 0.0001). The effects of treatment depended on initial acuity: full treatment showed a substantial effect in the moderate acuity group (6/36 to 6/18 at recruitment) and no significant effect in the mild acuity group (6/9 to 6/12 at recruitment) (P = 0.006 for linear regression interaction term). For 64 children with moderate acuity loss the treatment effect was 0.20 log units, equivalent to one to two lines on a Snellen chart. When all children had received treatment, six months after the end of the trial, there was no significant difference in acuity between the groups. Conclusions Treatment is worth while in children with the poorest acuity, but in children with mild (6/9 to 6/12) unilateral acuity loss there was little benefit. Delay in treatment until the age of 5 did not seem to influence effectiveness.

Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.

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