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

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

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

Abnormal foveal morphology in carriers of oculocutaneous albinism

To investigate the foveal morphology in carriers of oculocutaneous albinism (OCA) using spectral domain optical coherence tomography (SD-OCT). A cross-sectional, observational study.Handheld SD-OCT (Envisu C2300) was used to acquire horizontal scans through the centre of the fovea in biological parents of patients with OCA (n=28; mean age±SD=40.43±8.07 years) and age-matched and ethnicity-matched controls (n=28; mean age±SD=38.04±10.27 years). Sequence analysis was performed for variants in known genes associated with OCA. Best-corrected visual acuity (BCVA), presence of foveal hypoplasia and grade, foveal, parafoveal and perifoveal thickness measurements of total retinal layers (TRL), inner retinal layers (IRL) and outer retinal layers (ORL) thickness were measured.Foveal hypoplasia was identified in 32.14% of OCA carriers; grade 1 in all cases. OCA carriers demonstrated significant thicker TRL thickness (median difference: 13.46 µm, p=0.009) and IRL thickness (mean difference: 8.98 µm, pTYR, OCA2 and SLC45A2, novel OCA2 variants (n=3) and heterozygosity of the pathogenic TYR haplotype.We have, for the first time, identified foveal abnormalities in OCA carriers. This provides clinical value, particularly in cases where limited phenotype data are available. Our findings raise the possibility that previously reported mild cases of foveal hypoplasia or isolated foveal hypoplasia could correspond to OCA carrier status.</p

Characterisation of Abnormal Optic Nerve Head Morphology in Albinism Using Optical Coherence Tomography

Purpose: To characterise abnormalities in three-dimensional optic nerve head (ONH) morphology in people with albinism (PWA) using spectral domain optical coherence tomography (SD-OCT) and to determine whether ONH abnormalities relate to other retinal and clinical abnormalities. Methods: SD-OCT was used to obtain 3-dimensional images from 56 PWA and 60 age- and gender-matched control subjects. B-scans were corrected for nystagmus associated motion artefacts. Disc, cup and rim ONH dimensions and peripapillary retinal nerve fibre layer (ppRNFL) thickness were calculated using Copernicus and ImageJ software. Results: Median disc areas were similar in PWA (median=1.65mm2) and controls (1.71mm2, p=0.128) although discs were significantly elongated horizontally in PWA (p<0.001). In contrast, median optic cup area in PWA (0.088mm2) was 23.7% of that in controls (0.373mm2, p<0.001) with 39.4% of eyes in PWA not demonstrating a measurable optic cup. This led to significantly smaller cup: disc ratios in PWA (p<0.001). Median rim volume in PWA (0.273mm3) was 136.6% of that in controls (0.200mm3). ppRNFL was significantly thinner in PWA compared to controls (p<0.001), especially in the temporal quadrant. In PWA ppRNFL thickness was correlated to ganglion cell thickness at the central fovea (p=0.007). Several ONH abnormalities such as cup/disc ratio were related to higher refractive errors in PWA. Conclusions: In PWA ocular maldevelopment is not just limited to the retina but also involves the ONH. Reduced ppRNFL thickness is consistent with previous reports of reduced ganglion cell numbers in PWA. The thicker rim volumes may be a result of incomplete maturation of the ONH

Retinal and optic nerve changes in microcephaly: An optical coherence tomography study.

OBJECTIVE: To investigate the morphology of the retina and optic nerve (ON) in microcephaly. METHODS: This was a prospective case-control study including 27 patients with microcephaly and 27 healthy controls. All participants underwent ophthalmologic examination and handheld optical coherence tomography (OCT) of the macula and ON head. The thickness of individual retinal layers was quantified at the foveal center and the parafovea (1,000 μm nasal and temporal to the fovea). For the ON head, disc diameter, cup diameter, cup-to-disc ratio, cup depth, horizontal rim diameter, rim area, peripapillary retinal thickness, and retinal nerve fiber layer thickness were measured. RESULTS: Seventy-eight percent of patients had ophthalmologic abnormalities, mainly nystagmus (56%) and strabismus (52%). OCT abnormalities were found in 85% of patients. OCT revealed disruption of the ellipsoid zone, persistent inner retinal layers, and irregular foveal pits. Parafoveal retinal thickness was significantly reduced in patients with microcephaly compared to controls, nasally (307 ± 44 vs 342 ± 19 μm, p = 0.001) and temporally (279 ± 56 vs 325 ± 16 μm, p < 0.001). There was thinning of the ganglion cell layer and the inner segments of the photoreceptors in microcephaly. Total peripapillary retinal thickness was smaller in patients with microcephaly compared to controls for both temporal (275 vs 318 μm, p < 0.001) and nasal sides (239 vs 268 μm, p = 0.013). CONCLUSIONS: Retinal and ON anomalies in microcephaly likely reflect retinal cell reduction and lamination alteration due to impaired neurogenic mitosis. OCT allows diagnosis and quantification of retinal and ON changes in microcephaly even if they are not detected on ophthalmoscopy

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

Longitudinal Evaluation of Changes in Retinal Architecture Using Optical Coherence Tomography in Achromatopsia

PURPOSE. This prospective study investigates longitudinal changes in retinal structure in patients with achromatopsia (ACHM) using optical coherence tomography (OCT).  METHODS. Seventeen patients (five adults, 12 children) with genetically confirmed CNGA3- or CNGB3-associated ACHM underwent ocular examination and OCT over a follow-up period of between 2 and 9.33 years (mean = 5.7 years). Foveal tomograms were qualitatively graded and were segmented for quantitative analysis: central macular thickness (CMt), outer nuclear layer thickness (ONLt), and size of the foveal hyporeflective zone (vertical HRZ thickness: HRZt and horizontal HRZ width: HRZw) were measured. Data were analyzed using linear mixed regression models. Both age and visit were included into the models, to explore the possibility that the rate of disease progression depends on patient age. RESULTS. Fifteen of 17 patients (88%) showed longitudinal changes in retinal structure over the follow-up period. The most common patterns of progression was development of ellipsoid zone (EZ) disruption and HRZ. There was a significant increase in HRZt (P = 0.01) and HRZw (P = 0.001) between visits and no significant change in CMt and ONLt. Retinal parameters showed no difference in changes by genetic mutation (CNGA3 (n = 11), CNGB3 (n = 6)).  CONCLUSIONS. This study demonstrates clear longitudinal changes in foveal structure mainly in children, but also in adults with ACHM, over a long follow-up period. The longitudinal foveal changes suggest that treatment at an earlier age should be favored.</p

ERG Responses in Albinism, Idiopathic Infantile Nystagmus, and Controls

PurposeOur primary aim was to compare adult full-field ERG (ffERG) responses in albinism, idiopathic infantile nystagmus (IIN), and controls. A secondary aim was to investigate the effect of within-subject changes in nystagmus eye movements on ffERG responses.MethodsDilated Ganzfeld flash ffERG responses were recorded using DTL electrodes under conditions of dark (standard and dim flash) and light adaptation in 68 participants with albinism, 43 with IIN, and 24 controls. For the primary aim, the effect of group and age on ffERG responses was investigated. For the secondary aim, null region characteristics were determined using eye movements recorded prior to ffERG recordings. ffERG responses were recorded near and away from the null regions of 18 participants also measuring the success rate of recordings.ResultsFor the primary aim, age-adjusted photopic a- and b-wave amplitudes were consistently smaller in IIN compared with controls (P ConclusionsAge-adjusted photopic ffERG responses are significantly reduced in IIN adding to the growing body of evidence of retinal abnormalities in IIN. Differences between photopic responses in albinism and controls depend on age. Success at obtaining ffERG responses could be improved by recording responses at the null region