30 research outputs found
Cerebral malaria: insight into pathology from optical coherence tomography
AbstractWe aimed to investigate structural retinal changes in malarial retinopathy (MR) using hand-held optical coherence tomography (HH-OCT) to assess its diagnostic potential. Children with MR (n = 43) underwent ophthalmoscopy, fluorescein angiography and HH-OCT during admission, 1-month (n = 31) and 1-year (n = 8) post-discharge. Controls were comatose patients without malaria (n = 6) and age/sex-matched healthy children (n = 43). OCT changes and retinal layer thicknesses were compared. On HH-OCT, hyper-reflective areas (HRAs) were seen in the inner retina of 81% of MR patients, corresponding to ischaemic retinal whitening on fundus photography. Cotton wool spots were present in 37% and abnormal hyper-reflective dots, co-localized to capillary plexus, in 93%. Hyper-reflective vessel walls were present in 84%, and intra-retinal cysts in 9%. Vascular changes and cysts resolved within 48 h. HRAs developed into retinal thinning at 1 month (p = 0.027) which was more pronounced after 1 year (p = 0.009). Ischaemic retinal whitening is located within inner retinal layers, distinguishing it from cotton wool spots. Vascular hyper-reflectivity may represent the sequestration of parasitized erythrocytes in vessels, a key CM feature. The mechanisms of post-ischemic retinal atrophy and cerebral atrophy with cognitive impairment may be similar in CM survivors. HH-OCT has the potential for monitoring patients, treatment response and predicting neurological deficits.</jats:p
Congenital monocular elevation deficiency associated with a novel TUBB3 gene variant
Background The genetic basis of monocular elevation deficiency (MED) is unclear. It has previously been considered to arise due to a supranuclear abnormality.Methods Two brothers with MED were referred to Leicester Royal Infirmary, UK from the local opticians. Their father had bilateral ptosis and was unable to elevate both eyes, consistent with the diagnosis of congenital fibrosis of extraocular muscles (CFEOM). Candidate sequencing was performed in all family members.Results Both affected siblings (aged 7 and 12 years) were unable to elevate the right eye. Their father had bilateral ptosis, left esotropia and bilateral limitation of elevation. Chin up head posture was present in the older sibling and the father. Bell’s phenomenon and vertical rotational vestibulo-ocular reflex were absent in the right eye for both children. Mild bilateral facial nerve palsy was present in the older sibling and the father. Both siblings had slight difficulty with tandem gait. MRI revealed hypoplastic oculomotor nerve. Left anterior insular focal cortical dysplasia was seen in the older sibling. Sequencing of TUBB3 revealed a novel heterozygous variant (c.1263G>C, p.E421D) segregating with the phenotype. This residue is in the C-terminal H12 α-helix of β-tubulin and is one of three putative kinesin binding sites.Conclusion We show that familial MED can arise from a TUBB3 variant and could be considered a limited form of CFEOM. Neurological features such as mild facial palsy and cortical malformations can be present in patients with MED. Thus, in individuals with congenital MED, consideration may be made for TUBB3 mutation screening
Management of nystagmus in children : a review of the literature and current practice in UK specialist services
Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management
SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization
Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype
Ophthalmology
To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). Multicenter, observational study. A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384). Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans. Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH. We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value
Phenotypic Features of the Visual System in Albinism
Purpose: The main aims were to: 1) characterise the morphology of the iris structures and investigate the diagnostic potential of changes in albinism, 2) investigate visual field changes in albinism and 3) to analyse the relationship between refractive error/iris pigmentation and foveal hypoplasia in infantile nystagmus.
Methodology: The iris was imaged in 55 individuals with albinism and 45 controls using anterior segment optical coherence tomography (OCT) and segmented using ImageJ software. Visual field assessment using Humphrey field analyser was carried out on 61 individuals with albinism and 32 individuals with idiopathic infantile nystagmus (IIN), and were compared to posterior OCT parameters. Refractive measures were compared to foveal hypoplasia in different groups with nystagmus (albinism=33, IIN=18, PAX6=9 and achromatopsia=12) and iris posterior epithelial layer (PEL) thickness in albinism.
Results: The iris posterior epithelial layer (PEL) in albinism demonstrates significant thinning compared to controls, especially at the ciliary end (P<0.001). Ciliary PEL thickness demonstrated 85% sensitivity and 78% specificity in aiding the diagnosis of albinism.
Visual field measurements showed that detection thresholds in albinism were significantly worse than in IIN (P<0.001). In albinism the upper nasal visual field quadrant demonstrated poorer detection thresholds compared to other quadrants (P<0.05 for all comparisons). Left eyes had lower detection thresholds than right eyes (P<0.0001). Changes in peripapillary retinal nerve fibre layer were not associated with these changes in detection thresholds.
Worse foveal hypoplasia was associated with myopia in achromatopsia but with hypermetropia in albinism. Increasing hypermetropia in albinism was associated with PEL thinning (P<0.01).
Conclusion: The PEL demonstrates significant thinning in albinism which may be used as a diagnostic aid. The cause of lower detection thresholds within the upper nasal visual field and left eyes in albinism is unclear. Hyperillumination appears more important than foveal hypoplasia in the development of refractive error in albinism
Phenotypic Features Determining Visual Acuity in Albinism and the Role of Amblyogenic Factors
Albinism is a spectrum disorder causing foveal hypoplasia, nystagmus, and hypopigmentation of the iris and fundus along with other visual deficits, which can all impact vision. Albinism is also associated with amblyogenic factors which could affect monocular visual acuity. The foveal appearance in albinism can range from mild foveal hypoplasia to that which is indistinguishable from the peripheral retina. The appearance can be quickly and easily graded using the Leicester Grading System in the clinic. However, interquartile ranges of 0.3 logMAR for the grades associated with albinism limit the accuracy of the grading system in predicting vision. Here, we discuss the potential role of nystagmus presenting evidence that it may not be a major source of variability in the prediction of visual acuity. We also show that interocular differences in visual acuity are low in albinism despite high levels of amblyogenic factors indicating that active suppression of vision in one eye in albinism is uncommon.</p
In vivo morphology of the optic nerve and retina in patients with Parkinson’s disease
PURPOSE. To investigate optic nerve (ON) and macular morphology in patients with Parkinson’s disease (PD) using spectral-domain optical coherence tomography (SD-OCT). SUBJECTS. Twenty-five participants with PD (19 males and 6 females; mean age 60.79; SD 6 9.24) and 25 sex-, age-, ethnicity-, and refraction-matched healthy controls. METHODS. A high-resolution SD-OCT device was used to acquire scans in 25 participants with PD (mean age 60.79; 6 SD 9.24) and 25 sex-, age-, ethnicity-, and refraction-matched healthy controls. Main outcome measures included optic nerve head parameters (disc/cup diameters/ areas, cup/rim volumes, cup depth, cup/disc ratio; peripapillary retinal nerve fiber layer [ppRNFL] thickness), retinal thickness (in inner and outer annuli around the foveal center) and thickness of individual retinal layers. RESULTS. Our study showed significant ppRNFL thinning in PD patients in all quadrants (P <0.05) associated with a shallower optic cup (P = 0.03) as compared with controls. Foveal remodelling with retinal thinning (nasal and temporal segments in both annuli; and superior segment in outer annulus; P <0.05), foveal pit widening (P = 0.05), central outer plexiform layer (OPL) thickening (P <0.001), and nasal RPE thinning (P <0.001) was also found in PD. The differences were more obvious in hemiretinae related to the predominantly affected cerebral hemisphere. Changes were more pronounced in advanced stages and longer PD duration. CONCLUSIONS. Optic nerve changes in PD are likely to be caused by primary neurodegeneration. Central retinal thinning, pit widening, central OPL thickening, and RPE thinning indicate foveal remodelling. Specific changes of the fovea and thinning of individual retinal layers, correlating with disease severity and duration, indicate that ON and retinal changes have potential to be used as biomarkers for PD
Visual Field Deficits in Albinism in Comparison to Idiopathic Infantile Nystagmus
Purpose: This is the first systematic comparison of visual field (VF) deficits in people with albinism (PwA) and idiopathic infantile nystagmus (PwIIN) using static perimetry. We also compare best-corrected visual acuity (BCVA) and optical coherence tomography measures of the fovea, parafovea, and circumpapillary retinal nerve fiber layer in PwA.
Methods: VF testing was performed on 62 PwA and 36 PwIIN using a Humphrey Field Analyzer (SITA FAST 24-2). Mean detection thresholds for each eye were calculated, along with quadrants and central measures. Retinal layers were manually segmented in the macular region.
Results: Mean detection thresholds were significantly lower than normative values for PwA (−3.10 ± 1.67 dB, P
Conclusions: Clear peripheral and central VF deficits exist in PwA and PwIIN, and static VF results need to be interpreted with caution clinically. Since PwA exhibit considerably lower detection thresholds compared to PwIIN, VF defects are unlikely to be due to nystagmus in PwA. In addition to horizontal VF asymmetry, PwA exhibit both vertical and interocular asymmetries, which needs further exploration.</p
Hand-held optical coherence tomography imaging in children with anterior segment dysgenesis
In this study, we investigated the
potential of hand-held optical
coherence tomography to improve diagnosis in anterior
segments (AS) by visualizing the ante-
rior and posterior eye structures with-
out general anaesthetic (GA) or
sedation