GPR143 genotypic and ocular phenotypic characterisation in a Chinese cohort with ocular albinism.

PURPOSE: Ocular albinism type I (OA1) is caused by mutations in the GPR143 gene. The purpose of this study was to describe the clinical and genetic findings in 13 patients from 12 unrelated Chinese pedigrees with a pathogenic variant of the GPR143 gene. METHODS: Most patients underwent clinical examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, spectral domain optical coherence tomography, and full-field electroretinograms (ERG). A combination of molecular screening procedures, consisting of Sanger-DNA sequencing of GPR143 and targeted next-generation sequencing, was performed to identify each mutation. In silico programs were utilized to evaluate the pathogenicity of all the variants. RESULTS: The 13 patients (mean age 21.75 ± 16.63 years, range 1-54 years) all presented with congenital nystagmus, different extents of visual impairment, and severe foveal hypoplasia. Their BCVA was between 0.05 and 0.3 (decimal notation). The patients and obligate carriers exhibited different extents of mild depigmentation of the iris and fundus. We detected 11 distinct mutations in this patient cohort, including 7 novel mutations. Most (82%) were null mutations and included frameshift indel, nonsense, splicing effect, and large genomic DNA deletions, while missense mutations only accounted for 18%. CONCLUSIONS: Patients with GPR143 mutations all have congenital nystagmus, visual impairment, and foveal hypoplasia, whereas hypopigmentation in their iris and fundus is mild. They exhibit no evident genotype-phenotype correlations. GPR143 mutation screening is very important for establishing a precise diagnosis and for providing genetic counseling for patients and their families.

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.

Don't Miss This! Red Flags in the Pediatric Eye Examination: Subnormal Acuity.

Subnormal vision can be a harbinger of threating disease. Recognizing certain "red flags" on history or examination can facilitate early diagnosis in the pediatric patient. These objective tests or subjective complaints may help differentiate true organic causes of vision loss from possible functional overlay, amblyopia or poor results due to an uncooperative child.

X-linked Ocular Albinism.

The prevalence of X-linked ocular albinism (XLOA) is about 1 in 60,000 males. It affects only the eyes; the color of the skin and hairs are normal. Patients usually present with reduced vision, photophobia, nystagmus, and strabismus. Many patients have problem in perceiving depth (stereoscopic vision). The visual loss is permanent, but XLOA is a nonprogressive disorder and visual acuity remains stable throughout life.

Concordance of visual and structural features between siblings with albinism.

PURPOSE: To evaluate similarities and differences in visual function and ocular structure between siblings with albinism. METHODS: The medical records of all siblings diagnosed with albinism were retrospectively reviewed. Comparisons were made using examination at oldest age for younger sibling and examination closest to that age for older siblings. RESULTS: A total of 111 patients from 54 families were studied. Mean age was 12.9 years (range, 2 months to 44.2 years). Mean difference in ages between sibling pair examinations was 11.5 months (range, 0-87 months). Of 45 families, best-corrected visual acuity was equal in 9 (20%), within 1/2 octave in 9 (20%), >1/2 but <1 octave in 21 (47%), and ≥1 octave difference in 6 (13%). Of 27 families, stereoacuity was present in all siblings in 9 (33%), absent in 9 (33%), and present in only 1 sibling in 9 (33%). Of 54 families, grading of iris translucency was equal in 35 (65%) and different by 1 grade in 19 (35%). Of 54 families, foveal grading was equal in 39 (72%), different by 1 grade in 14 (26%), and different by ≥2 grades in 1 (2%). Macular melanin was present in all siblings in 16 of the 54 families (30%), absent in all siblings in 36 (67%), and present in only 1 sibling in 2 (4%) families. CONCLUSIONS: The strong concordance of structural features is contrasted with discordance in visual function. Families of siblings with albinism should be counseled with due caution because visual function is often disparate despite similar structural findings.

Evidence of macular pigment in the central macula in albinism.

PURPOSE: Albinism represents a spectrum of disorders with diminished to absent amounts of melanin pigmentation including the posterior segment of the eye. Macular pigment (MP) consists of two main carotenoids, lutein and zeaxanthin, concentrated in the macula. MP serves as blue light absorbent, antioxidant, and may reduce chromatic aberration and glare. It remains unclear if albinos have detectable MP. The purpose was to investigate the distribution of MP in albino patients with psychophysical and imaging techniques. METHODS: MP was measured at the eccentricity of 0.5° by heterochromatic flicker perimetry (QuantifEye(®); Tinsley Precision Instruments Ltd.) or by scanning laser ophthalmoscopy (MPOD module, MultiColor Spectralis(®), Heidelberg Engineering, Heidelberg, Germany) in four albino patients, who were also investigated with multimodal ophthalmic imaging. RESULTS: Visual acuity ranged from 20/32 to 20/125, nystagmus was present in three patients, and all patients showed typical foveal hypoplasia on fundus exam and optical coherence tomography. Fundus autofluorescence (FAF) demonstrated various degrees of central FAF signal attenuation. Genetic testing was available in three patients and confirmed the diagnosis. Measurable amounts of MP were detected in all four patients and ranged from 0.05 to 0.24, which is below the normal range. CONCLUSIONS: We conclude that MP can be demonstrated and measured in albinos. Further studies are needed to investigate MP accumulation following carotenoid supplementation and its impact on visual performance.

Clinical Insights Into Foveal Morphology in Albinism.

PURPOSE: A hallmark of albinism is foveal hypoplasia. However, literature suggests variable foveal development. This study evaluates the association between ocular phenotype and foveal morphology to demonstrate the broad structural and functional spectrum. METHODS: Best-corrected visual acuity (BCVA), nystagmus, angle kappa, stereoacuity, iris transillumination, macular melanin presence, foveal avascular zone, and annular reflex were recorded in 14 patients with albinism. Spectral-domain optical coherence tomography provided macular images. RESULTS: The clinical phenotype was broad, with BCVA varying from 20/20 to 20/100. Better BCVA was associated with a preserved foveal avascular zone, annular macular reflex, stereoacuity, and macular melanin. Imaging demonstrated a continuum of foveal development correlating with BCVA. Individuals with a rudimentary pit had normal inner and outer segment lengthening and better BCVA. CONCLUSIONS: The spectrum of ocular structure and visual function in albinism is broad, suggesting a possible diagnosis of albinism in a patient with an even more normal clinical presentation.

Technical brief: Constant intense light exposure to lesion and initiate regeneration in normally pigmented zebrafish.

Zebrafish are capable of robust and spontaneous regeneration of injured retina. Constant intense light exposure to adult albino zebrafish specifically causes apoptosis of rod and cone photoreceptor cells and is an excellent model to study the molecular mechanisms underlying photoreceptor regeneration. However, this paradigm has only been applied to lesion zebrafish of the nonpigmented albino genetic background, which precludes the use of numerous transgenic reporter lines that are widely used to study regeneration. Here, we explored the effectiveness of constant intense light exposure in causing photoreceptor apoptosis and stimulating regeneration in normally pigmented zebrafish retinas. We show that constant intense light exposure causes widespread photoreceptor damage in the dorsal-central retinas of pigmented zebrafish. Photoreceptor loss triggers dedifferentiation and proliferation of Müller glia as well as progenitor cell proliferation. We also demonstrate that the timeline of regeneration response is comparable between the albino and the pigmented retinas.

Albinism: particular attention to the ocular motor system.

The purpose of this report is to summarize an understanding of the ocular motor system in patients with albinism. Other than the association of vertical eccentric gaze null positions and asymmetric, (a) periodic alternating nystagmus in a large percentage of patients, the ocular motor system in human albinism does not contain unique pathology, rather has "typical" types of infantile ocular oscillations and binocular disorders. Both the ocular motor and afferent visual system are affected to varying degrees in patients with albinism, thus, combined treatment of both systems will maximize visual function.

Diagnostic potential of iris cross-sectional imaging in albinism using optical coherence tomography.

PURPOSE: To characterize in vivo anatomic abnormalities of the iris in albinism compared with healthy controls using anterior segment optical coherence tomography (AS-OCT) and to explore the diagnostic potential of this technique for albinism. We also investigated the relationship between iris abnormalities and other phenotypical features of albinism. DESIGN: Prospective cross-sectional study. PARTICIPANTS: A total of 55 individuals with albinism and 45 healthy controls. METHODS: We acquired 4.37×4.37-mm volumetric scans (743 A-scans, 50 B-scans) of the nasal and temporal iris in both eyes using AS-OCT (3-µm axial resolution). Iris layers were segmented and thicknesses were measured using ImageJ software. Iris transillumination grading was graded using Summers and colleagues' classification. Retinal OCT, eye movement recordings, best-corrected visual acuity (BCVA), visual evoked potential (VEP), and grading of skin and hair pigmentation were used to quantify other phenotypical features associated with albinism. MAIN OUTCOME MEASURES: Iris AS-OCT measurements included (1) total iris thickness, (2) stroma/anterior border (SAB) layer thickness, and (3) posterior epithelial layer (PEL) thickness. Correlation with other phenotypical measurements, including (1) iris transillumination grading, (2) retinal layer measurements at the fovea, (3) nystagmus intensity, (4) BCVA, (5) VEP asymmetry, (6) skin pigmentation, and (7) hair pigmentation (of head hair, lashes, and brows). RESULTS: The mean iris thickness was 10.7% thicker in controls (379.3 ± 44.0 µm) compared with the albinism group (342.5 ± 52.6 µm; P>0.001), SAB layers were 5.8% thicker in controls (315.1 ± 43.8 µm) compared with the albinism group (297.7 ± 50.0 µm; P=0.044), and PEL was 44.0% thicker in controls (64.1 ± 11.7 µm) compared with the albinism group (44.5 ± 13.9 µm; P<0.0001). The most ciliary quartile of the PEL yielded a sensitivity of 85% and specificity of 78% for detecting albinism. Phenotypic features of albinism, such as skin and hair pigmentation, BCVA, and nystagmus intensity, were significantly correlated to AS-OCT iris thickness measurements. CONCLUSIONS: We have characterized in vivo abnormalities of the iris associated with albinism for the first time and show that PEL thickness is particularly affected. We demonstrate that PEL thickness has diagnostic potential for detecting iris abnormalities in albinism. Anterior segment OCT iris measurements are significantly correlated to BCVA and nystagmus intensity in contrast to iris transillumination grading measurements that were not. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Reading performance in infantile nystagmus.

OBJECTIVE: To characterize reading deficits in infantile nystagmus (IN), to determine optimal font sizes for reading in IN, and to investigate whether visual acuity (VA) and severity of nystagmus are good indicators of reading performance in IN. DESIGN: Prospective cross-sectional study. PARTICIPANTS AND CONTROLS: Seventy-one participants with IN (37 idiopathic, 34 with albinism) and 20 age-matched controls. METHODS: Reading performance was assessed using Radner reading charts and was compared with near logarithm of the minimum angle of resolution (logMAR) VA, nystagmus intensity, and foveation characteristics as quantified using eye movement recordings. MAIN OUTCOME MEASURES: Reading acuity (smallest readable font size), maximum reading speed, critical print size (font size below which reading is suboptimal), near logMAR VA, nystagmus intensity, and foveation characteristics (using the eXpanded Nystagmus Acuity Function). RESULTS: Using optimal reading conditions, maximum reading speeds were 18.8% slower in albinism and 14.7% slower in idiopathic IN patients compared with controls. Reading acuities were significantly worse (P<0.001) in IN patients compared with controls. Also, the range of font sizes over which reading speeds were less than the optimum were much larger in IN patients compared with controls (P<0.001). Reading acuity was correlated strongly to near VA (r(2) = 0.74 albinism, r(2) = 0.55 idiopathic), but was better than near VA in participants with poor VA. Near VA was a poor predictor of maximum reading speed. Nystagmus intensity and foveation were poor indicators of both reading acuity and maximum reading speed. CONCLUSIONS: Maximum reading speeds can be near normal in IN when optimal font sizes are provided, even in individuals with poor VA or intense nystagmus. However, reading performance in IN is acutely sensitive to font size limitations. Font sizes for optimal reading speeds in IN may be as much as 6 logMAR lines worse than the near VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

VEP characteristics in children with achiasmia, in comparison to albino and healthy children.

Achiasmia is a rare disorder of visual pathway maldevelopment that can show diverse clinical and magnetic resonance imaging spectra. The aim of this study was to define the characteristics of visual evoked potentials (VEPs) that differentiate abnormal optic-nerve-fibre decussation in children with achiasmia versus children with albinism and healthy children. In four children with achiasmia, the following VEP characteristics were studied and compared to children with ocular albinism and with healthy control children: (a) flash and pattern onset VEP interhemispheric asymmetry; (b) flash N2, P2 and onset C1 amplitudes and latencies; (c) interocular polarity differences in interhemisphere potentials; and (d) chiasm coefficients (CCs). In the children with achiasmia, VEPs were related to an absence of or reduced optic-nerve-fibre decussation at the chiasm and showed: ipsilateral asymmetry, significantly higher VEP amplitudes over the ipsilateral hemisphere (p < 0.05), interocular inverse polarity and negative CC. Other VEP features (uncrossed asymmetry and positive CC) were also seen if additional visual pathway maldevelopment (such as severe optic nerve hypoplasia and/or absence of the optic tractus on one side) were associated with achiasmia. In the children with albinism, the VEPs were related to excess optic-nerve-fibre decussation at the chiasm and showed: contralateral asymmetry, significantly higher VEP amplitudes over the contralateral hemisphere (p < 0.001), interocular inverse polarity and negative CC. In achiasmia and albinism, the VEPs to flash stimulation were more robust and more clearly distinguished between the conditions compared with the VEPs to pattern onset stimulation. VEPs in achiasmia are associated with absent or reduced optic-nerve-fibre decussation, where ipsilateral interhemispheric asymmetry is associated with interocular inverse polarity and a negative CC.

Change in visual acuity in albinism in the early school years.

PURPOSE: To determine whether binocular best-corrected visual acuity (B-BCVA) improves in the early school years in patients with albinism and whether this is related to type of albinism, ocular pigment, or appearance of the macula. METHODS: Patients with albinism seen between 5.5 and 9 years (Visit A) and 9.5 and 14 years of age (Visit B), with visits separated by at least 2.5 years, were included. Type of albinism, B-BCVA, glasses wear, iris pigment and macular transparency grade, and presence or absence of an annular reflex and melanin in the macula were recorded. RESULTS: Mean B-BCVA was 20/84 at Visit A and 20/61 at Visit B (P < .001). B-BCVA improved in 80%. Improvement in B-BCVA and glasses wear, iris grade, macular grade, macular melanin, and annular reflex were weakly correlated. However, a moderate correlation was found between measured B-BCVA and iris grade at Visit A (r = 0.485, P < .001) and Visit B (r = 0.467, P < .001), and the presence of macular melanin at Visit A (r = 0.436, P < .001) and Visit B (r = 0.482, P < .001). CONCLUSIONS: B-BCVA often improves in albinism in the early school years and this observation should be included in counseling. The etiology is unknown but may be related to change in nystagmus, use of precise null point, developmental maturation, and/or some of the ocular characteristics evaluated in this study.

Foveal development and nystagmus.

The combination of optical coherence tomography (OCT) and genetic methods along with other clinical diagnostic tools permit the discrimination of infantile nystagmus subtypes with a precision that has not previously been possible. Analysis of specific diseases, such as albinism and achromatopsia as well as known genetic abnormalities, such as FRMD7 and PAX6 mutations, shows subtle but significant differences between nystagmus subtypes using eye movement recordings. In addition, OCT can be used to chart the progression of retinal diseases with age, for example, as has been shown in achromatopsia. OCT can also be used to predict the level of visual deficit due to retinal abnormalities, as demonstrated for albinism. These findings suggest that the classification of all infantile nystagmus into one single entity is premature.

The functional significance of foveal abnormalities in albinism measured using spectral-domain optical coherence tomography.

PURPOSE: The relationship between foveal abnormalities in albinism and best-corrected visual acuity (BCVA) is unclear. High-resolution spectral-domain optical coherence tomography (SD OCT) was used to quantify foveal retinal layer thicknesses and to assess the functional significance of foveal morphologic features in patients with albinism. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-seven patients with albinism and 20 healthy control volunteers were recruited to the study. METHODS: Using high-resolution SD OCT, 7×7×2-mm volumetric scans of the fovea were acquired (3-µm axial resolution). The B scan nearest the center of the fovea was identified using signs of foveal development. The thickness of each retinal layer at the fovea and foveal pit depth were quantified manually using ImageJ software and were compared with BCVA. MAIN OUTCOME MEASURES: Total retinal thickness, foveal pit depth, photoreceptor layer thickness, and processing layer thickness in relation to BCVA. RESULTS: Total photoreceptor layer thickness at the fovea was correlated highly to BCVA (P = 0.0008; r = -0.501). Of the photoreceptor layers, the outer segment length was correlated most strongly to BCVA (P<0.0001; r = -0.641). In contrast, there was no significant correlation between either total retinal thickness or pit depth and BCVA (P>0.05). This was because of an inverse correlation between total photoreceptor layer thickness and total processing layer thickness (P<0.0001; r = -0.696). CONCLUSIONS: Neither the total retinal thickness nor the pit depth are reliable indicators of visual deficit, because patients with similar overall retinal thickness had widely varying foveal morphologic features. In albinism, the size of the photoreceptor outer segment was found to be the strongest predictor of BCVA. These results suggest that detailed SD OCT images of photoreceptor anatomic features provide a useful tool in assessing the visual potential in patients with albinism. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Relationship of slow-phase velocity to visual acuity in infantile nystagmus associated with albinism.

PURPOSE: To investigate the relationship between slow-phase velocity of nystagmus and visual acuity in children with albinism. METHODS: Twelve children with infantile nystagmus associated with albinism had eye movements recorded by binocular video-oculography (10 patients) or by scleral search coil (2 patients). In children younger than 3 years of age visual acuities was assessed by means of Teller acuity cards and corrected for age. Histograms of horizontal eye velocities were fit by a gamma distribution in all patients (r2>0.85). The velocity at the peak of the gamma distribution was compared with the limiting velocity predicted by the dynamic visual acuity (DVA) model. RESULTS: All histograms of slow-phase eye velocity were skewed toward lower velocities, with the peak distribution ranging from 5 to 20 degrees/second. The velocity at the peak of the gamma distribution for each subject was uniformly equal to or below the limiting velocity predicted by the DVA model. The average of the gamma distribution across all subjects corresponded to an upper limit to eye velocity of 17 degrees/second. At this velocity the DVA model predicted visual acuity of 20/50, which is lower than the average visual acuity reported in albinism. The distributions of eye velocity were lower than the limiting eye velocity predicted on the basis of DVA almost 50% of the time. CONCLUSIONS: Visual acuity in albinism is limited by macular hypoplasia rather than by slow-phase eye velocity of nystagmus.

Reading acuity in albinism: evaluation with MNREAD charts.

INTRODUCTION: The MNREAD reading acuity (RA) charts use continuous-text reading to measure (1) RA, ie, the smallest size of print that the patient can resolve; (2) maximum reading speed (MRS); and (3) critical print size (CPS), ie, the smallest print that the patient can read with maximum speed. This project used the MNREAD charts to evaluate reading performance in children and adults with albinism to determine the smallest print size recommended to facilitate effortless reading. METHODS: A total of 63 subjects with albinism were administered the MNREAD test to determine the critical print size for effortless reading. The subjects read continuous, high-contrast text print until they could no longer discern the words. The MRS and CPS were determined with the MNREAD protocol. Presence or absence of nystagmus and strabismus was recorded. Distance visual acuity was measured with ETDRS charts. RESULTS: The sample included 25 male and 38 female subjects with a median age of 16 years. Median MRS was 150 words per minute. The mean CPS was 0.84 logMAR, notably larger than the mean RA of 0.53 logMAR. CONCLUSIONS: The MNREAD acuity charts can be used to determine functional reading ability and critical print size for effortless reading in individuals with albinism. The amount of enlargement in print size can be used in educational and vocational recommendations to facilitate reading.

Ocular straylight in albinism.

PURPOSE: Albinism is an inherited disorder that affects the melanin biosynthesis pathway, which results in reduced or absent pigment formation. This may lead to increased light transmission through the iris and more reflected light from the fundus. Both these effects contribute to the occurrence of ocular straylight. One aim of this study is to determine whether and how increased iris transmission and fundus reflection in subjects with albinism contributes to the occurrence of ocular straylight. The other aim is to determine the effect that an iris print-contact lens (CL) could have in terms of reducing the occurrence of ocular straylight. METHODS: Ocular straylight was quantified by means of the straylight parameter s and measured as a function of angle and wavelength in 17 subjects with different types of albinism, none of whom wore an iris print-CL. The measurements were then repeated with the subjects wearing an iris print-CL to reduce the iris transmission component and thus the occurrence of ocular straylight. The contributions of transmission and reflectance components were estimated for each individual. RESULT: Straylight level increase varied from normal (s ≈9) to severe (8x). In 15 cases, the reflectance component contributed s >3 to up to s = 17. In eight cases, the transmission component contributed s >3 to up to s = 101. A significant reduction in straylight was observed using an iris print-CL in six subjects with elevated straylight values. In the other 11 subjects with albinism, the iris print-CL had no significant effect on straylight because of the low values of the transmission component. CONCLUSIONS: This study gives insight into the effects of transmission and reflectance on the total measured straylight occurrence in subjects with albinism. Subjects experiencing increased ocular straylight values may benefit significantly from wearing iris print-CLs because transmission of light through the natural iris may cause a significant increase in straylight.

Clinical and oculomotor characteristics of albinism compared to FRMD7 associated infantile nystagmus.

PURPOSE: Previous studies have found no difference between nystagmus characteristics associated with idiopathic infantile nystagmus (IIN) and that associated with albinism. The present aim is to compare the oculomotor characteristics and other associated clinical features of albinism and a genetically homogenous group of IIN volunteers where the nystagmus is associated with FRMD7 mutations. METHODS: Oculomotor characteristics and related clinical features between albinism (n = 52) and idiopathic nystagmus associated with FRMD7 mutations (FRMD7-IIN, n = 83) were compared. The nystagmus characteristics compared included amplitude, frequency, intensity of nystagmus, foveation characteristics, and waveform type. Other clinical features compared were strabismus, stereopsis and anomalous head posture. RESULTS: The FRMD7-IIN group contained a higher proportion of pendular waveform types compared with the albinism group (P < 0.0001). Nystagmus frequency was significantly lower in albinos (mean = 3.3 Hz, SD = 0.13 Hz) compared with the FRMD7-IIN group (mean = 4.3 Hz, SD = 0.18 Hz) (F = 14.5, P < 0.0001). Strabismus and anomalous head posture was seen in higher proportions in the albinism group, and stereopsis was worse compared with the FRMD7-IIN group (P ≪ 0.0001). CONCLUSIONS: Differences in nystagmus characteristics associated with albinism and those associated with FRMD7 mutations leading to IIN are described for the first-time. These findings may provide useful information in the future elucidation of mechanisms underlying the nystagmus associated with albinism and idiopathic infantile nystagmus.

Arrested development: high-resolution imaging of foveal morphology in albinism.

Albinism, an inherited disorder of melanin biosynthesis, disrupts normal retinal development, with foveal hypoplasia as one of the more commonly associated ocular phenotypes. However the cellular integrity of the fovea in albinism is not well understood - there likely exist important anatomical differences that underlie phenotypic variability within the disease and that also may affect responsiveness to therapeutic intervention. Here, using spectral-domain optical coherence tomography (SD-OCT) and adaptive optics (AO) retinal imaging, we obtained high-resolution images of the foveal region in six individuals with albinism. We provide a quantitative analysis of cone density and outer segment elongation demonstrating that foveal cone specialization is variable in albinism. In addition, our data reveal a continuum of foveal pit morphology, roughly aligning with schematics of normal foveal development based on post-mortem analyses. Different albinism subtypes, genetic mutations, and constitutional pigment background likely play a role in determining the degree of foveal maturation.