Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial.

BACKGROUND: Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. METHODS: EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3-8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. FINDINGS: Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. INTERPRETATION: The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. FUNDING: Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation.

USE OF HAND-HELD OPTICAL COHERENCE TOMOGRAPHY DURING RETINOPATHY OF PREMATURITY SCREENING DEMONSTRATES AN INCREASED OUTER RETINA FROM EARLY POSTMENSTRUAL AGE IN PRETERM INFANTS WITH RETINOPATHY OF PREMATURITY.

PURPOSE: To identify structural markers of active retinopathy of prematurity (ROP) in foveal and parafoveal retinal layers using hand-held optical coherence tomography. METHODS: Hand-held optical coherence tomography images (n = 278) were acquired from a prospective mixed cross-sectional longitudinal observational study of 87 participants (23-36 weeks gestational age; n = 30 with ROP, n = 57 without ROP) between 31 and 44 weeks postmenstrual age excluding treated ROP and features of cystoid macular edema. Six retinal layer thicknesses from the fovea to the parafovea were analyzed at five locations up to 1,000 µ m, temporally and nasally. RESULTS: The mean outer retinal thickness during active ROP increased at the fovea and parafovea from postmenstrual age 33 weeks to 39 weeks ( P < 0.001), whereas the parafoveal inner nuclear layer and retinal nerve fiber layer reduced ( P < 0.001). Outer retinal thickness at the fovea from 33 weeks to 39 weeks postmenstrual age was consistently thicker in infants with ROP across all levels of prematurity (gestational age). CONCLUSION: Increased foveal and parafoveal outer retina measured using hand-held optical coherence tomography shows potential as a marker for ROP screening.

Eye tracking: empirical foundations for a minimal reporting guideline.

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

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.

Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study.

PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH). DESIGN: Multicenter, observational study. PARTICIPANTS: 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). METHODS: 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. MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA). RESULTS: 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. CONCLUSIONS: 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.

Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles.

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p < 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.

Can Structural Grading of Foveal Hypoplasia Predict Future Vision in Infantile Nystagmus?: A Longitudinal Study.

PURPOSE: To evaluate structural grading and quantitative segmentation of foveal hypoplasia using handheld OCT, versus preferential looking (PL), as predictors of future vision in preverbal children with infantile nystagmus. DESIGN: Longitudinal cohort study. PARTICIPANTS: Forty-two patients with infantile nystagmus (19 with albinism, 17 with idiopathic infantile nystagmus, and 6 with achromatopsia) were examined. METHODS: Spectral-domain handheld OCT was performed in preverbal children up to 36 months of age. Foveal tomograms were graded using our 6-point grading system for foveal hypoplasia and were segmented for quantitative analysis: photoreceptor length, outer segment (OS) length, and foveal developmental index (FDI; a ratio of inner layers versus total foveal thickness). Patients were followed up until they could perform chart visual acuity (VA) testing. Data were analyzed using linear mixed regression models. Visual acuity predicted by foveal grading was compared with prediction by PL, the current gold standard for visual assessment in infants and young children. MAIN OUTCOME MEASURES: Grade of foveal hypoplasia, quantitative parameters (photoreceptor length, OS length, FDI), and PL VA were obtained in preverbal children for comparison with future chart VA outcomes. RESULTS: We imaged 81 eyes from 42 patients with infantile nystagmus of mean age 19.8 months (range, 0.9-33.4 months; standard deviation [SD], 9.4 months) at the first handheld OCT scan. Mean follow-up was 44.1 months (range, 18.4-63.2 months; SD, 12.0 months). Structural grading was the strongest predictor of future VA (grading: r = 0.80, F = 67.49, P < 0.0001) compared with quantitative measures (FDI: r = 0.74, F = 28.81, P < 0.001; OS length: r = 0.65; F = 7.94, P < 0.008; photoreceptor length: r = 0.65; F = 7.94, P < 0.008). Preferential looking was inferior to VA prediction by foveal grading (PL: r = 0.42, F = 3.12, P < 0.03). CONCLUSIONS: Handheld OCT can predict future VA in infantile nystagmus. Structural grading is a better predictor of future VA than quantitative segmentation and PL testing. Predicting future vision may avert parental anxiety and may optimize childhood development.

POTENTIAL UTILITY OF FOVEAL MORPHOLOGY IN PRETERM INFANTS MEASURED USING HAND-HELD OPTICAL COHERENCE TOMOGRAPHY IN RETINOPATHY OF PREMATURITY SCREENING.

PURPOSE: To investigate dynamic foveal morphology with postmenstrual age, in preterm infants with and without retinopathy of prematurity using hand-held optical coherence tomography, adjusting for gestational age (GA) and birthweight (BW). METHODS: Prospective mixed cross-sectional/longitudinal observational study of 87 participants (23-36 weeks GA; n = 30 with, n = 57 without retinopathy of prematurity) using hand-held optical coherence tomography images (n = 278) acquired between 31 weeks and 44 weeks postmenstrual age excluding treated retinopathy of prematurity. Measurements included foveal width, area, depth, central foveal thickness, maximum slope, and parafoveal retinal thickness at 1,000 µm nasal and temporal to the central fovea. RESULTS: Retinopathy of prematurity was significantly correlated with only foveal width in either GA or BW adjusted statistical models. In contrast, severity of prematurity (GA, BW) correlated with foveal area (P < 0.005), depth (P ≤ 0.001), and slope (P < 0.01), although central foveal thickness (P = 0.007) and parafoveal retinal thickness (P < 0.001) correlated with GA, but not with BW. CONCLUSION: Foveal width is independent of GA and BW with potential in retinopathy of prematurity screening assessment using hand-held optical coherence tomography. Foveal morphology could be graded in prematurity during development, with possible implications for future management of preterm infants.

Aberrant visual pathway development in albinism: From retina to cortex.

Albinism refers to a group of genetic abnormalities in melanogenesis that are associated neuronal misrouting through the optic chiasm. We perform quantitative assessment of visual pathway structure and function in 23 persons with albinism (PWA) and 20 matched controls using optical coherence tomography (OCT), volumetric magnetic resonance imaging (MRI), diffusion tensor imaging and visual evoked potentials (VEP). PWA had a higher streamline decussation index (percentage of total tractography streamlines decussating at the chiasm) compared with controls (Z = -2.24, p = .025), and streamline decussation index correlated weakly with inter-hemispheric asymmetry measured using VEP (r = .484, p = .042). For PWA, a significant correlation was found between foveal development index and total number of streamlines (r = .662, p < .001). Significant positive correlations were found between peri-papillary retinal nerve fibre layer thickness and optic nerve (r = .642, p < .001) and tract (r = .663, p < .001) width. Occipital pole cortical thickness was 6.88% higher (Z = -4.10, p < .001) in PWA and was related to anterior visual pathway structures including foveal retinal pigment epithelium complex thickness (r = -.579, p = .005), optic disc (r = .478, p = .021) and rim areas (r = .597, p = .003). We were unable to demonstrate a significant relationship between OCT-derived foveal or optic nerve measures and MRI-derived chiasm size or streamline decussation index. Our novel tractographic demonstration of altered chiasmatic decussation in PWA corresponds to VEP measured cortical asymmetry and is consistent with chiasmatic misrouting in albinism. We also demonstrate a significant relationship between retinal pigment epithelium and visual cortex thickness indicating that retinal pigmentation defects in albinism lead to downstream structural reorganisation of the visual cortex.

Altered whole-brain connectivity in albinism.

Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc.

Retinal development in albinism: a prospective study using optical coherence tomography in infants and young children.

BACKGROUND: Retinal development normally involves migration of the inner retinal layers away from the fovea, migration of the cone photoreceptors into the fovea, and elongation of the photoreceptors over time. This process is arrested prematurely in albinism. However, because retinal development continues at least until the age of 4 years, when development arrests in albinism is uncertain. In this study we outlined the time course of retinal development in children with albinism. METHODS: We studied 44 children with a diagnosis of albinism and 223 control participants. All participants were aged between 0 and 6 years. We obtained 219 mixed cross-sectional and longitudinal optical coherence tomography examinations in the albinism group and compared them with 558 control examinations. Retinal layer segmentation was performed with ImageJ software. Generalised linear mixed regression modelling was used to analyse group differences in retinal development. FINDINGS: In the albinism group, inner retinal layer migration from the fovea was delayed and arrested prematurely, resulting in a significantly thicker central macular thickness than in the control group (p<0·0001). Whereas the central macular thickness increased with age in the control group, in the albinism group it initially decreased with age as a result of continuing regression of the inner retinal layers (p=0·041). The perifoveal retinal thickness was significantly decreased in albinism from a reduction of both inner (p<0·0001) and outer (p<0·0001) retinal layer thicknesses. There was evidence that the photoreceptor layers across the fovea were elongating in albinism, albeit at a reduced rate, compared with the control group. This difference was most apparent for the foveal photoreceptor inner segment (p=0·001). INTERPRETATION: Our findings show that perturbations exist in several aspects of retinal development including the migration and differentiation of the neuronal cells within the retina. We showed continuing regression of the inner retinal layers and elongation of the photoreceptor layers suggesting residual plasticity of the developing albino retina. This finding is important because treatment at the earliest stages of the condition might normalise retinal development and optimise vision. FUNDING: UK Medical Research Council (grant number MR/J004189/1), Ulverscroft Foundation, National Eye Research Centre, Nystagmus Network UK.

Optic Nerve Head Development in Healthy Infants and Children Using Handheld Spectral-Domain Optical Coherence Tomography.

PURPOSE: To determine feasibility of optic nerve head (ONH) imaging and to characterize ONH development in full-term infants without sedation using handheld spectral-domain optical coherence tomography (SD OCT). DESIGN: Prospective cross-sectional study. PARTICIPANTS: Three hundred fifty-two children aged between 1 day and 13 years. METHODS: All participants were imaged using handheld SD OCT without sedation during a single scan session. The percentage of successful scans was calculated. Interexaminer reproducibility and differences between right and left eyes were assessed using intraclass correlation coefficients (ICCs). Images were analyzed using ImageJ software. The developmental trajectories over time for ONH parameters were calculated using fractional polynomial modelling. MAIN OUTCOME MEASURES: Disc and cup diameter (expressed as distance in micrometers and visual angle in degrees), cup depth, Bruch's membrane opening-minimum rim width (BMO-MRW), retinal thickness, and retinal nerve fiber layer (RNFL; 1700 µm and 6° from the disc center). RESULTS: On average, 70% of participants were imaged successfully. Interexaminer reliability was excellent (ICC, >0.89) for diametric and retinal thickness parameters. Right and left eyes were similar for diametric measurements (ICC, >0.79), but more variable for nasal BMO-MRW, RNFL, and retinal thickness. The mean disc and cup diameter increase by 30% and 40%, respectively, between birth and 13 years of age when expressed as a distance measure, but remained constant (at 5°-5.5° and 2°, respectively) when expressed as a visual angle with reference to the eye nodal point. The peripapillary temporal RNFL demonstrated a marked initial decrease of nearly 35% between birth and approximately 18 months of age. This was followed by a slow increase up to 12 years of age when measured at 1700 µm from the disc center, although there was little change when measured at 6° from the disc center. CONCLUSIONS: We demonstrated feasibility of handheld SD OCT imaging of the ONH in full-term infants and children without anaesthesia or sedation. This is the first in vivo handheld SD OCT study to describe the development of ONH parameters during the critical early years of visual maturation. Our results provide a normative database for use in routine practice and further studies of ONH pathologic features.

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia.

PURPOSE: To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). DESIGN: Prospective, cross-sectional, observational study. SUBJECTS: A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. METHODS: High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 µm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 µm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. MAIN OUTCOME MEASURES: Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. RESULTS: Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. CONCLUSIONS: Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis.

Aetiology of infantile nystagmus.

PURPOSE OF REVIEW: Mechanisms underlying infantile nystagmus are unclear. The aim of this review is to outline recent developments in understanding the aetiology of infantile nystagmus. RECENT FINDINGS: There have been advances in understanding mechanisms underlying idiopathic infantile nystagmus, which has progressed through determining the role of the FRMD7 gene in controlling neurite outgrowth, and albinism, in which recent models have investigated the possibility of retinal miswiring leading to nystagmus. We also briefly review aetiology of infantile nystagmus in afferent visual deficits caused by ocular disease, and PAX6 mutations. Improved phenotypical characterization of all these infantile nystagmus subtypes has been achieved recently through high-resolution retinal imaging using optical coherence tomography. Several new hypotheses proposing common mechanisms that could underlie various infantile nystagmus subtypes are also highlighted. SUMMARY: Although there is still no consensus of opinion regarding the mechanisms causing infantile nystagmus, identification of new genes and determining their cellular function, phenotypical characterization of genetic subtypes, and improvements in animal models have significantly advanced our understanding of infantile nystagmus. These recent developments pave the way to achieving a much clearer picture of infantile nystagmus aetiology in the future.

A randomized controlled trial comparing soft contact lens and rigid gas-permeable lens wearing in infantile nystagmus.

OBJECTIVE: To perform the first randomized controlled trial comparing soft contact lens (SCL) with rigid gas-permeable lens (RGPL) wearing in infantile nystagmus (IN), using spectacle wear as a baseline. DESIGN: Randomized, controlled cross-over trial with an intention-to-treat design. PARTICIPANTS AND CONTROLS: A total of 24 participants with IN (12 idiopathic, 12 with albinism). METHODS: Participants were randomized into 1 of 2 treatment arms receiving the following sequence of treatments (2-3 weeks for each treatment): (A) spectacles, SCL, RGPL, and spectacle wear; or (B) spectacles, RGPL, SCL, and spectacle wear. MAIN OUTCOME MEASURES: The main outcome measure was mean intensity of nystagmus at the null region viewing at 1.2 m. Secondary outcome measures included the same measure at 0.4 m viewing and across the horizontal meridian (measured over a ±30° range at 3° intervals) for distance and near. The nystagmus foveation characteristics were similarly assessed over ±30° and at the null region at 1.2 m and 0.4 m viewing. Visual outcome measures included best-corrected visual acuity (BCVA) at 4 m and 0.4 m, gaze-dependent visual acuity (GDVA) (i.e., visual acuity when maintaining gaze angles over a ±30° range at 10° intervals) at 4 m, and reading performance at 0.4 m derived from the Radner reading chart. RESULTS: There were no significant differences between SCL and RGPL wearing for any nystagmus characteristics or compared with spectacle wearing. The BCVA, reading acuity, and critical print size were significantly worse for SCL wearing compared with RGPL and baseline spectacle wear (P<0.05), although mean differences were less than 1 logarithm of the minimum angle of resolution (logMAR) line. CONCLUSIONS: Nystagmus was not significantly different during SCL and RGPL wearing in IN, and contact lens wearing does not significantly reduce nystagmus compared with baseline spectacle wearing. The wearing of SCL leads to a small but statistically significant deterioration in visual function compared with both RGPL and spectacle wearing at baseline, although mean effect sizes were not clinically relevant.

Macular morphology in patients with optic nerve head drusen and optic disc edema.

PURPOSE: In this study we investigated macular morphology, including individual retinal layers, in patients with optic nerve head drusen (ONHD) and optic disc edema (ODE) compared with healthy participants, using high-resolution spectral domain optical coherence tomography (OCT). DESIGN: Prospective, cross-sectional, observational study. PARTICIPANTS: A total of 67 patients with ONHD, 36 patients with ODE, and 57 healthy participants. METHODS: High-resolution spectral domain OCT (Copernicus [OPTOPOL Technology S.A., Zawiercie, Poland] 3-µm resolution, 7 × 7 × 2-mm volumetric scans) was used to image macula morphology. Average retinal nerve fiber layer (RNFL) thickness was measured using a semiautomated method with manual correction of the internal limiting membrane, RNFL, and retinal pigment epithelium (RPE). Retinal and RNFL thicknesses were measured and analyzed in 3 circular zones (Early Treatment Diabetic Retinopathy Study protocol). Individual retinal layers at the macula were quantified by analyzing tomograms using ImageJ (http://rsbweb.nih.gov/ij/; Accessed June 1, 2013). MAIN OUTCOME MEASURES: Average retinal and individual retinal layer thickness in patients with ODE or ONHD, and healthy controls. RESULTS: Patients with ONHD had thicker retinae in the inner annulus compared with patients with ODE and controls (significant in the temporal segment compared with those with ODE [P = 0.013] and in the superior segment compared with controls [P = 0.05]). Patients with ONHD had a significantly thinner inner plexiform layer (IPL) (P = 0.02), nerve fiber layer (P = 0.05), and RPE (P = 0.0001), and thicker ganglion cell layer (P = 0.003) and outer plexiform layer (OPL) (P < 0.001) compared with controls. Patients with ODE demonstrated the thickest retina and RNFL in the outer annulus (significant in the inferior segment compared with controls, P = 0.02 for both) with significant thickening in the IPL (P = 0.004), OPL (P < 0.003), and outer segment layer (P ≤ 0.02), and severe ganglion cell loss (P = 0.004) and RPE (P = 0.0001) thinning compared with healthy volunteers. CONCLUSIONS: Our study shows that optic nerve diseases are associated with selective changes in different retinal layers in patients with ODE and ONHD. These findings may be of diagnostic value and could be taken into consideration in assessing patients and studying the pathogenesis of these conditions.

Gender- and Ethnicity-Related Differences in Optic Nerve Head Topography in Healthy Indian and Caucasian Participants.

We investigated the effect of ethnicity and gender on optic nerve head morphology in healthy subjects using spectral-domain optical coherence tomography (SD-OCT). Thirty-five Indian (i.e. Indian subcontinent) females, 34 Caucasian females, 32 Indian males, and 32 Caucasian males were examined using SD-OCT (Copernicus, Optopol Technology). Disc and rim areas were larger in Caucasian males compared with females but smaller in Indians males compared with females. Indian participants had significantly larger cup areas and volumes without significant differences in retinal nerve fibre layer (RNFL) thicknesses between groups. Gender and ethnicity differences should be considered in assessment of patients.

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.

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 << 0.0001) and PwIIN (-1.70 ± 1.54 dB, P < 0.0001). Mean detection thresholds were significantly lower in PwA compared to PwIIN (P < 0.0001) and significantly worse for left compared to right eyes in PwA (P = 0.0002) but not in PwIIN (P = 0.37). In PwA, the superior nasal VF was significantly worse than other quadrants (P < 0.05). PwIIN appeared to show a mild relative arcuate scotoma. In PwA, central detection thresholds were correlated with foveal changes in the inner and outer retina. VF was strongly correlated to BCVA in both groups. 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.