Nystagmus Characteristics in Albinism: Unveiling the Link to Foveal Hypoplasia and Visual Acuity.

Purpose: The purpose of this study was to describe the association among nystagmus characteristics, foveal hypoplasia, and visual acuity in patients with albinism. Methods: We studied nystagmus recordings of 50 patients with albinism. The nystagmus waveform was decomposed into two types: dominantly pendular and dominantly jerk. We correlated the nystagmus type, amplitude, frequency, and percentage of low velocity (PLOV) to Snellen visual acuity and foveal hypoplasia grades. Results: The grade of foveal hypoplasia and visual acuity showed a strong correlation (r = 0.87, P < 0.0001). Nystagmus type and PLOV had the strongest significant (P < 0.0001) correlation with visual acuity (r = 0.70 and r = -0.56, respectively) and with foveal hypoplasia (r = 0.76 and r = -0.60, respectively). Patients with pendular nystagmus type had the lowest PLOV, and the highest grade of foveal hypoplasia (P < 0.0001). Severe foveal hypoplasia (grade 4), was almost invariably associated with pendular nystagmus (86%). Conclusions: Foveal hypoplasia grade 4 is associated with pendular nystagmus, lower PLOV, and worse visual acuity. Based on these results, nystagmus recordings at a young age may contribute to predicting visual outcomes.

Display Characterization for Contrast Sensitivity Testing.

SIGNIFICANCE: Contrast sensitivity measurements using a computer display have been reported to lack accuracy when displaying small contrasts. This report investigates if the characterization/calibration of display luminance may contribute substantively to these kinds of described inaccuracies. PURPOSE: This study aimed to investigate what errors in contrast sensitivity may result from characterizing a display by fitting a gamma curve through physical or psychophysical luminance measurement data. METHODS: The luminance functions of four different in-plane switching liquid crystal displays (IPS LCDs) have been measured for all 256 gray levels (the actual luminance function). This has been compared with a gamma-fitted luminance curve (the gamma luminance function). Calculated are the errors in displayed contrast that may arise when assuming the gamma luminance function instead of the actual luminance function. RESULTS: The amount of error differs considerably between the displays. In general, for large contrasts (Michelson log CS <1.2), the error is acceptable (<<0.15 log unit). However, for smaller contrasts (Michelson log CS >1.5), the error may become unacceptably high (>0.15 log unit). CONCLUSIONS: To improve the accuracy of testing contrast sensitivity with an LCD, it is necessary to fully characterize the display, measuring the luminance of each gray level instead of fitting a smooth gamma function through limited luminance data.

The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences.

Purpose: The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism. Subjects and Methods: We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43). Results: Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.6-0.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74. Conclusions: Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features.

Recognizing differentiating clinical signs of CLN3 disease (Batten disease) at presentation.

PURPOSE: To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early-onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation. METHODS: Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early-onset STGD1 (20 patients). RESULTS: Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early-onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5-10 years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p = 0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark-adapted (DA) full-field electroretinogram (ERG) responses were either absent or electronegative. In early-onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG. CONCLUSION: Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease.

Electroretinogram abnormalities in non-infectious uveitis often persist.

PURPOSE: In uveitis, a prolonged implicit time of the cone b-wave is a characteristic electroretinogram (ERG) abnormality. We investigated whether this can improve or deteriorate over time and which clinical factors are associated with change. METHODS: Prospective cohort study. Patients with a non-infectious uveitis were included. An ERG was measured in the first year of uveitis onset and a follow-up ERG one year later. Changes in the implicit time of the cone b-wave were investigated in relation to clinical parameters including the following: demographics, uveitis characteristics, treatment, best-corrected visual acuity, optical coherence tomography parameters and fluorescein angiography scores. RESULTS: Of 98 eyes (63 patients), 40 showed a prolonged cone b-wave on the first ERG, which improved in 10 eyes. Eyes with an improved ERG more often had a panuveitis with initially a higher incidence of cells in the anterior chamber during the first ERG, which resolved at the time of their follow-up ERG. Five of the 58 eyes with a normal first ERG had a deteriorated follow-up ERG. These eyes had more frequently an active uveitis at the time of the follow-up ERG. Of the 78 eyes with a stable cone b-wave, 16 had a quiescent inflammation during follow-up. There were no differences in age or treatment. CONCLUSION: In most patients with non-infectious uveitis, ERG abnormalities appear to be irreversible, even when the inflammation becomes quiescent. However, some ERGs improved, which was associated with reduction in inflammation of the anterior chamber due to panuveitis. In contrast, a worsened ERG was associated with a persistence of inflammation.

Effects of DTL electrode position on the amplitude and implicit time of the electroretinogram.

PURPOSE: This study sought to investigate whether there is an optimal position of the Dawson, Trick, and Litzkow (DTL) electrodes when measuring the full-field electroretinogram (ERG) for monitoring purposes. METHODS: In 200 uveitis patients, an extended light-adapted (LA) ERG protocol was measured twice, incorporating the International Society for Clinical Electrophysiology of Vision standards. First, a LA ERG was measured with the DTL in the lower lid position (LLP) and thereafter in the fornix position. Differences in amplitudes and implicit times of a-waves, b-waves, and the 30 Hz peak were investigated. Intraclass correlation coefficients (ICCs) as well as coefficients of variation (CoV) were calculated, to assess both reliability and relative variability between the two DTL positions. RESULTS: Implicit times showed no statistically significant differences between the two DTL positions. As expected, amplitudes at the different stimulus strengths were 1.12-1.19 higher in the LLP, but there were no significant differences in the CoV between the two DTL positions. The ICC was high for the b-wave and 30 Hz flicker response (0.842-0.979), but lower for the a-wave, especially for amplitudes (0.584-0.716). CONCLUSIONS: For monitoring purposes in patients, we conclude that based on relative variability, no position is preferable above the other. However, because in most diseases amplitudes are decreased, the LLP may be chosen because it yields higher amplitudes. Whatever the choice, it is important to ensure that the DTL position remains stable during an ERG recording.

The Detection Of Misrouting In Albinism: Evaluation of Different VEP Procedures in a Heterogeneous Cohort.

Purpose: To investigate the optimal procedures for multichannel visually evoked potentials (VEPs) to detect misrouting in albinism subjects. Methods: Investigations were done in a phenotypically heterogeneous group of 180 albinism subjects and 187 controls with and without ocular pathology. We retrospectively compared standard flash VEP (fVEP), high-frequency fVEP with a handheld device (hh fVEP), pattern-onset VEP (poVEP), and short-onset acuity sweep VEP. The diagnostic power of these stimuli were estimated by calculating the area under the curve (AUC). Subjects were divided in three age groups (<3, 3-6 [toddler], and ≥6 years). Subjects ≥6 years of age were further divided in two visual acuity groups (≤0.3 logMAR and >0.3 logMAR). Results: The optimal stimulus was hh fVEP, standard fVEP, and poVEP 60' for subjects <3, 3-6, and ≥6 years of age, respectively. In subjects ≥6 years old with poor visual acuity, the area under the curve of fVEP was almost equal to that of poVEP 60'. Conclusions: For the optimal detection of misrouting with multichannel VEP recordings, we recommend using a high-frequency hh fVEP in children <3 years of age, standard fVEP in toddlers, and poVEP 60' in subjects ≥6 years of age. fVEP can also be used in the oldest age group for subjects with visual acuity of >0.3 logMAR. Remarkably, some albinism subjects showed misrouting on full-field stimulation but normal routing of the central retina, suggesting that not the whole line of decussation is shifted temporally.

Prolonged Cone b-Wave on Electroretinography Is Associated with Severity of Inflammation in Noninfectious Uveitis.

PURPOSE: This study sought to investigate retinal function in patients with noninfectious uveitis by using full-field electroretinography (ERG) and correlate the ERG to disease duration and severity of inflammation. DESIGN: Prospective cohort study. METHODS: Patients (n = 200) with noninfectious uveitis and a disease duration of <1 year (group A [n = 80]) and those with a disease duration of >5 years (group B [n = 120]) were included. ERGs of the total 355 uveitis eyes were measured according to an extended International Society for Clinical Electrophysiology of Vision protocol. ERG abnormalities were related to demographics and uveitis characteristics, including anatomical classification, duration of uveitis, severity of inflammation, best corrected visual acuity (BCVA), cystoid macular edema (CME), and the highest fluorescein angiography (FA) score during the course of the disease. RESULTS: ERGs showed abnormalities in 235 eyes (66.2%). The most frequent and pronounced ERG abnormality was a prolonged implicit time of the cone b-wave (151 eyes [42.5%]), which was associated with vitritis (P = .005); cells in the anterior chamber (P = .007); the highest fluorescein angiography score (P = .011); age (P < 0.001); and pupil diameter (P < 0.001). BCVA was relatively good (0.05 logMAR [interquartile range {IQR}, 0.011, 0.22]) and not associated with this ERG abnormality. There were no differences between the ERG abnormalities in group A and those in group B and no significant associations between ERG abnormalities and anatomical classification or specific diagnoses. CONCLUSIONS: ERG results are frequently affected in cases of noninfectious uveitis of all anatomic subtypes, including anterior uveitis without apparent inflammation of the posterior segment. ERG abnormalities appear to be associated with the severity of inflammation from both the present and the past and therefore may be seen even when signs of retinal inflammation have disappeared.

Electroretinogram abnormalities in nonanterior childhood uveitis.

PURPOSE: A major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full-field electroretinography (ERG). METHODS: Cross-sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score. RESULTS: The ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b-wave (37%; n = 23/63) and an abnormal 30-Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00-0.15 LogMAR). CONCLUSION: The ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long-term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies.

The Phenotypic Spectrum of Albinism.

PURPOSE: To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity (VA), and to define diagnostic criteria for the white population. We also estimated the prevalence of albinism in The Netherlands. DESIGN: Retrospective cohort study. PARTICIPANTS: We investigated the phenotype of 522 patients with albinism from the databases of Bartiméus (452 patients), Leiden University Medical Center (44 patients), and the Academic Medical Center Amsterdam (26 patients). METHODS: We collected clinical, genetic, and electrophysiologic data of patients with albinism. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia. MAIN OUTCOME MEASURES: Visual acuity, nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia, and misrouting. RESULTS: Nystagmus was absent in 7.7% (40/521), iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496) had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia, and misrouting was not established in 16.1% (49/304). The VA varied from -0.1 to 1.3 logarithm of the minimum of angle of resolution (logMAR). The foveal hypoplasia grading correlated best with the VA (r = 0.69, P < 0.001), whereas iris translucency, fundus pigmentation, and misrouting did not predict the VA significantly. We estimated a prevalence of albinism in The Netherlands of at least 1:12 000. CONCLUSIONS: None of the characteristics of albinism were consistently present in our cohort. To be able to distinguish albinism from other conditions with similar ocular features, especially in northern and western European countries, we propose major and minor clinical criteria. Major criteria would be (1) foveal hypoplasia grade 2 or more, (2) misrouting, and (3) ocular hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or more. Minor criteria would be (1) nystagmus, (2) hypopigmentation of skin and hair, (3) grade 1 fundus hypopigmentation, and (4) foveal hypoplasia grade 1. We propose that 3 major criteria or 2 major and 2 minor criteria are necessary for the diagnosis. In the presence of a molecular diagnosis, 1 major criterion or 2 minor criteria will be sufficient.

Quantification of visual function assessment using remote eye tracking in children: validity and applicability.

PURPOSE: Measurements of visual and oculomotor functions are essential for providing tailored support to visually impaired children. In young or intellectually disabled children these measurements can be difficult or even impossible to perform. Recordings of orienting gaze in response to specific visual information, made with eye tracking, may offer a solution. The aim of this study was to observe and quantify eye tracking (ET)-based gaze responses to provide information about visual and oculomotor functioning, and to compare this information with standard visual function assessments (VFA). METHODS: One hundred and twenty-six visually impaired children from 1-14 years underwent a VFA. Next they underwent a remote ET test. Four aspects of oculomotor control (nystagmus, fixation, saccades, pursuit) and three visual functions (visual field, contrast, colour) were selected to compare both methods. Performance was assessed (1) during VFA using standard behavioural observation and test scores and (2) after ET by observing and scoring the eye movement recordings. Validity, in terms of agreement between results, was measured by correlation analyses. From the orienting gaze responses, quantitative parameters (gain, fixation duration and directional saccades) were calculated to characterize visual performance. RESULTS: Good agreement between the two test methods was found for observational assessment of oculomotor control and visual functions (correlations ranging from rs  = 0.39 to rs  = 0.69). The quantitative parameters of visual performance showed distinct results between children with and without specific functional impairments, both in children aged 1-6 and 7-14 years. CONCLUSION: Eye tracking-based gaze recordings are a promising tool to assess oculomotor and visual performance in a communication-free manner. Calculating quantitative parameters from specific gaze responses could assist in the characterization of functional visual performance in children, independent of age. Gaze responses are a useful addition to standard VFA in clinical practice.

Crowding ratio in young normally sighted children.

PURPOSE: To determine normal values of the crowding ratio (CR) in children. METHODS: Of 62 normally sighted primary school children aged 4-12 years old the CR was determined both for distance and near vision. The examinations were performed using commonly available test charts based on the LEA symbols. RESULTS: At near, the CR was significantly better than at distance and for all ages <2.0. The upper limit of the CR at distance was <2.0 from age six. CONCLUSION: With commonly available tests the CR can easily be determined in school age children. For children >6 years of age, a CR > 2.0 (i.e. at least 3 lines difference between the result of a single optotype acuity test and a line acuity test) is suspicious and warrants further investigation. It may, for example, be a sign of cerebral visual impairment (CVI).

The effect of zirconia and titanium implant abutments on light reflection of the supporting soft tissues.

OBJECTIVES: To determine the difference in light reflection of oral mucosa covering titanium (Ti) or zirconia (ZrO(2)) abutments as it relates to the thickness of the covering mucosa. MATERIAL AND METHODS: Fifteen anterior implants (Astra Osseo speed(®)) in 11 patients were fitted with a Ti or a ZrO(2) abutment (cross-over, within-subject comparison). Hyper-spectral images were taken with a camera fitted on a surgical microscope. High-resolution images with 70 nm interval between 440 and 720 nm were obtained within 30 s (1392 × 1024 pixels). Black- and white-point reference was used for spatial and spectral normalization as well as correction for motion during exposure. Reflection spectra were extracted from the image on a line mid-buccal of the implant, starting 1 mm above the soft tissue continuing up to 3 mm apically. RESULTS: Median soft tissue height is 2.3 mm (min: 1.2 mm and max: 3.1 mm). The buccal mucosa rapidly increases in the thickness, when moving apically. At 2.2 mm, thickness is 3 mm. No perceivable difference between the Ti and ZrO(2) abutment can be observed when the thickness of the mucosa is 2±0.1 mm (95% confidence interval) or more. CONCLUSION: It is expected that the difference in light reflection of soft tissue covering Ti or ZrO(2) abutments is no longer noticeable for the human eye when the mucosa thickness exceeds 2 mm. Haemoglobin peaks in the reflection spectrum can be observed and make hyper-spectral imaging a practical and useful tool for measuring soft tissue health.

Simulating the straylight effects of cataracts.

PURPOSE: To study the additional straylight falling on the retina (retinal straylight) caused by cataract and find commercially available filters to simulate the cataract straylight effects. SETTING: Research laboratory. METHODS: The retinal straylight addition of cataract was derived from straylight parameter data in the literature. The scattering characteristics of cataract-simulating filters were measured using a scatterometer. RESULTS: The straylight addition due to cataract follows a power law as a function of angle with power of -2.12 and straylight parameter log values of up to 1.6 for relatively mild cataract cases. Of the commercial filters that were tested, the Tiffen Black Pro Mist (BPM) filters resembled the straylight characteristics of cataracts fairly well. The filters had a limited effect on visual acuity and contrast sensitivity, which was also found for early cataracts. The BPM 2 followed a power law as a function of angle with power of approximately -2.21 and straylight log values of 1.12. CONCLUSIONS: The BPM 2 filter is a good early-cataract-simulating filter. Stacking such filters is a good way to increase the cataract density. A drawback is that the BPM 2 filter has a transmission of 66% so stacking filters reduces the overall transmission significantly.

Field-dependent aniseikonia associated with an epiretinal membrane a case study.

PURPOSE: Aniseikonia is a binocular anomaly in which the two eyes perceive images of different sizes and/or shapes. It is usually assumed to be constant as a function of visual field angle (VFA) (i.e., angular distance from the line of sight). This is correct for optically induced aniseikonia, such as the aniseikonia that is associated with anisometropia and probably also pseudophakia. The purpose of this article is to show that if the aniseikonia is of retinal origin, then the aniseikonia may no longer be constant as a function of VFA (i.e., field-dependent aniseikonia). DESIGN: Case report, with the patient having a unilateral epiretinal membrane. METHODS: The aniseikonia was measured in vertical and horizontal directions with a customized version of the Aniseikonia Inspector software. The VFA was made variable by changing the dimensions of the comparison targets in the direct comparison procedure. MAIN OUTCOME MEASURE: Aniseikonia as a function of VFA. RESULTS: The patient exhibited good repeatable aniseikonia, ranging from 23% to 2.5% for VFAs ranging from 0.36 degrees to 5.7 degrees . Higher angles had lower aniseikonia. A control subject did not show this field-dependent aniseikonia. CONCLUSIONS: Aniseikonia may vary with VFA due to a retinal cause such as an epiretinal membrane. The problem with field-dependent aniseikonia is that it cannot be corrected fully with conventional optics, which exhibit an approximately constant magnification as a function of VFA. Nevertheless, by correcting 5% to 10% aniseikonia, which showed up in the VFA measurement range at 2 degrees to 3 degrees , our patient had improved visual comfort, especially for reading.

Evaluation of a new direct-comparison aniseikonia test.

BACKGROUND AND PURPOSE: Aniseikonia is a condition in which the two eyes perceive images of different size or shape, causing a variety of visual symptoms including asthenopia. Besides anisometropes (with a prevalence of 5-10% in the population above age 20 years), also pseudophakes and refractive surgery patients are at risk. For example, 40% of the pseudophakes seem to suffer from aniseikonia. Reliable measurement and management of aniseikonia is therefore important. The "Aniseikonia Inspector" is a new, commercially available, software product to measure and manage aniseikonia. The purpose of this study is to evaluate this aniseikonia test of the Aniseikonia Inspector. METHODS: Aniseikonia was induced in four subjects, with normal vision, by means of afocal size lenses. Using the Aniseikonia Inspector, the resulting aniseikonia was measured in vertical, horizontal and diagonal directions. RESULTS: The average ratio between the measured aniseikonia and the induced aniseikonia was 0.98, 0.89 and 0.93 respectively for the vertical, horizontal and diagonal directions. For two consecutive measurements of the same aniseikonic state, the difference in measurement value was 97%, 75% and 94% of the time within one resolution step size (0.5% horizontally and vertically, and 0.7% diagonally). CONCLUSION: Aniseikonia was measured accurately. Measurements in the vertical direction were more accurate than in the diagonal or horizontal directions, which is probably due to fixation disparities. The Aniseikonia Inspector is a very useful new tool in treating the growing number of aniseikonia patients.

Stray light of spectacle lenses compared with stray light in the eye.

Stray light in spectacle lenses may affect the overall vision. It may also affect the measurement of ocular stray light, contrast sensitivity, or glare sensitivity. This article describes common stray light characteristics for glass and plastic spectacle lenses and compares this to the stray light characteristics of the eye, which are well known from the literature. Stray light is described by the skirts of the point-spread function (PSF), which were measured for angles from 4 degrees to 30 degrees. The PSF of spectacle lenses appears to follow the equation PSF = a(10). (theta/10)b, with a(10) and b representing fitting parameters and theta representing the stray light angle. The slope b is on average -2, which similar to that of the eye. For clean spectacle lenses, the PSF is usually at least an order of magnitude lower than that of the eye, whereas "as worn" (uncleaned) spectacle lenses may approach the PSF of the eye. To reach the PSF of the eye, the spectacle lens needs to be contaminated by as much as one or two fingerprints. The article also shows that plastic spectacle lenses degrade much faster than glass spectacle lenses when looking at the amount of stray light.