Hannah M. Kersten

Ophthalmic manifestations of inherited neurodegenerative disorders

Ophthalmic findings are common features of neurodegenerative disorders and, in addition to being clinically important, have emerged as potentially useful biomarkers of disease progression in several conditions. Clinically, these visual system abnormalities can be a clue to diagnosis, as well as being a prominent cause of disability in affected patients. In this Review, we describe the various afferent visual system and other ophthalmic features of inherited neurodegenerative disorders, including the muscular dystrophies, Friedreich ataxia, the spinocerebellar ataxias, hereditary spastic paraplegia, Charcot–Marie–Tooth disease, and other conditions. We focus on the expanding role of optical coherence tomography in diagnostic imaging of the retina and optic nerve head, and the possible use of ophthalmic findings as biomarkers of disease severity in hereditary neurodegenerative disorders. In addition, we discuss the ophthalmic manifestations and treatment implications of mitochondrial dysfunction, which is a feature of many inherited neurodegenerative diseases.

Corneal nerve microstructure in Parkinson's disease.

Ocular surface changes and blink abnormalities are well-established in Parkinsons disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinsons disease. This case-control study examined the ocular surface in patients with moderately severe Parkinsons disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinsons disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinsons disease, ten were male and the mean age was 65.5±8.6years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinsons disease (7.56±2.4mm/mm2) compared with controls (15.91±2.6mm/mm2) (p<0.0001). Corneal sensitivity did not differ significantly between the patients with Parkinsons disease (0.79±1.2mBAR) and the control group (0.26±0.35mBAR), p=0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R2=0.66, p=0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinsons disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinsons disease, previously thought to be a central nervous system disorder.

Ophthalmic findings in myotonic dystrophy type 2: a case series.

In 2014, we published in the Journal of Neurology the finding that epiretinal membranes (ERM) are a common feature of myotonic dystrophy type 1 (DM1), affecting approximately half of the patients in our cohort [1]. Recently, Choi et al. [2] noted ERMs in 5 of 24 (21%) Korean patients with DM1. The lower rate is likely to be due to a difference in examination methodology. Our paper was based on optical coherence tomography (OCT) findings. OCT allows for non-invasive cross-sectional imaging and quantitative analysis of the posterior structures of the eye including the retina and optic nerve [3]. In this letter we describe our ophthalmic findings, applying the same systematic approach, in a case series of patients with myotonic dystrophy type 2 (DM2). DM2 is caused by a dominantly inherited CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZFN9) gene on chromosome 3q21 [4]. The prevalence of DM2 is not known, although in most populations it is thought to be rarer than DM1 [5]. The clinical presentation of DM2 is similar to, but generally milder than, DM1, although as in DM1, there is significant phenotypic variability [5]. There is not the severe central nervous system involvement that may be seen in individuals with DM1 [4]. The following case series outlines the ophthalmic presentation, including OCT findings, of five patients with DM2. All patients had the diagnosis of DM2 confirmed with genetic testing. None of the patients were related. Three women and two men, aged between 52 and 68 years, were included in the case series.As expected, themost frequent findingwas ahistory of bilateral cataract surgery with intraocular lens insertion, in four of the five patients. The remaining patient had bilateral early polychromatic and posterior subcapsular cataract. The characteristic cataracts observed in patients with DM2 are the same as those found in DM1 [6]. OCT examination findings were variable in this small group. The average peripapillary (around the circumference of the optic nerve head) retinal nerve fibre layer (RNFL) thickness ranged from 76 lm in a 52-year-old male patient (with optic nerve features suspicious of glaucoma) to 111 lm in a 55-year-old female. By comparison, average RNFL thickness amongst control participants examined for our DM1 study was 99 ± 9 lm [1]. The thickness of the RNFL in individual quadrants was also highly variable. The total macular volume ranged from 7.81 to 9.8 mm (8.72 ± 0.33 mm in control participants) [1]. The patient with the lowest macular volume was a 68-year-old female with a history of central serous retinopathy. The greatest macular volume measurement was found in the 55-year-old female with a large macular ERM. The patient’s visual acuity was mildly reduced at 6/7.5. ERM was found in four eyes of three DM2 patients. Of these, two eyes had cellophane macular reflex and two had pre-retinal fibrosis (Fig. 1). Cellophane macular reflex & Richard H. Roxburgh RichardR@adhb.govt.nz

D7 Optical coherence tomography findings in huntington’s disease: a potential biomarker of disease progression

Background Previous reports of ocular abnormalities in Huntington’s disease (HD) have detailed eye movement disorders but not whether the nerve fibre layer at the back of the eye is affected. This layer has been shown to be thinned in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Aims The objective of this case-control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). Methods A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Results Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 μm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R (2) = −0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R (2) = −0.71, p = 0.002), and motor scores (R (2) = −0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Conclusions Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber’s hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.

Optical coherence tomography findings in a patient with type 1 sialidosis

Type 1 sialidosis is a metabolic storage disorder characterised by the accumulation of sialylated oligosaccharides. The condition is also known as macular cherry-red spot and myoclonus syndrome due to the characteristic macular appearance in affected individuals. This case outlines the presentation of a patient with type 1 sialidosis, including ophthalmological assessment with retinal photography and spectral domain optical coherence tomography (OCT). OCT scans showed thickening of the perimacular and peripapillary retinal nerve fibre layer, thought to be due to the abnormal accumulation of metabolic products. The cherry-red spot appearance is due to the normal appearing macula being seen in contrast to the abnormally pale surrounding, thickened retinal nerve fibre layer.