Spectrum of Foveal Development in Albinism Detected with Optical Coherence Tomography

doi:10.1016/j.jaapos.2006.01.008

Journal of American Association for Pediatric Ophthalmology and Strabismus

Volume 10, Issue 3, June 2006, Pages 237-242

Presented, in part, at the 31st Meeting of AAPOS, Orlando, FL, March 10-13, 2005.

https://doi.org/10.1016/j.jaapos.2006.01.008 Get rights and content

Background: Optical coherence tomography (OCT) has shown the absence of a foveal depression in an individual with oculocutaneous albinism, type 1 (OCA1) and best-corrected visual acuity (BCVA) of 20/400. However, the presence of an annular light reflex in the macula has been noted with indirect ophthalmoscopy in other patients with albinism who have better vision. We studied macular architecture in albinism with OCT when binocular BCVA was ≥20/60 and compared this to detection of foveal development with binocular indirect ophthalmoscopy. Methods: Eleven patients with albinism and BCVA ≥20/60 were recruited for OCT. Average central macular thickness was recorded. Presence of an oval annular reflex was determined with binocular indirect ophthalmoscopy. Results: Mean binocular BCVA was 20/39 (range: 20/20 to 20/50). Twelve eyes had a rudimentary annular reflex detected with ophthalmoscopy. OCT was reliable in 20 of 22 eyes. A foveal depression was identified with OCT in four eyes. Mean macular thickness for these four eyes was 233 μm (±22.5 μm). We found a weak inverse correlation between BCVA (logMAR) and thickness (r = −0.21). Conclusions: OCT shows the spectrum of foveal development in albinism, from complete absence of development to a central depression corresponding to a rudimentary annular reflex detected with ophthalmoscopy. The reduced rate of detection of foveal development with OCT compared with ophthalmoscopy is likely related to poor fixation in patients with nystagmus.

Section snippets

Methods

Eleven patients with a diagnosis of albinism and binocular best-corrected visual acuity (BCVA) measuring at least 20/60 were recruited for this prospective study between April and August in 2004. We selected this criterion for BCVA to include a group of patients who were more likely to have foveal development. We excluded uncooperative patients and those who refused to participate. Diagnosis of albinism was made with clinical phenotype determined by a pediatric ophthalmologist (C.G.S.) and

Results

Patient demographics are summarized in Table 1. Patients 3 and 4 are brother and sister, as are patients 10 and 11. Although entry criterion for the study was binocular BCVA ≥20/60, all subjects had BCVA of 20/50 or better. Mean binocular BCVA was 20/39. Two patients in this study (no. 4, no. 11) did not have nystagmus detected with clinical examination. Neither of these patients had indication of foveal development with ophthalmoscopy or OCT. All patients except one (no. 8) had a grade 3

Discussion

The spectrum of foveal hypoplasia in albinism can be detected with binocular indirect ophthalmoscopy.2, 3 To our knowledge, this is the first study to show objective, in vivo evidence of foveal development in albinism with OCT. Both ophthalmoscopy and OCT are limited due to the often associated nystagmus and photosensitivity in persons with albinism. While indirect ophthalmoscopy is subjective, it seems to be more sensitive to detection of rudimentary foveal development by permitting detection

References (22)

K.A. Lee et al.
Stereopsis in patients with albinismclinical correlates
J Aapos.
(2001)
M.R. Hee et al.
Topographic of diabetic macular edema with optical coherence tomography
Ophthalmology
(1998)
V. Guedes et al.
Optical coherence tomography measurement of macular and nerve fiber layer thickness in normal and glaucomatous human eyes
Ophthalmology
(2003)
A. Chan et al.
Stage 0 macular holesobservations by optical coherence tomography
Ophthalmology
(2004)
N.N. Markomichelakis et al.
Patterns of macular edema in patients with uveitisqualitative and quantitative assessment using optical coherence tomography
Ophthalmology
(2004)
M.A. Apushkin et al.
Correlation of optical coherence tomography findings with visual acuity and macular lesions in patients with X-linked retinoschisis
Ophthalmology
(2005)
C.H. Meyer et al.
Foveal hypoplasia in oculocutaneous albinism demonstrated by optical coherence tomography
Am J Ophthalmol
(2002)
D.E. McGuire et al.
Foveal hypoplasia demonstrated in vivo with optical coherence tomography
Am J Ophthalmol
(2003)
C.K. Patel et al.
Optical coherence tomography under general anesthesia in a child with nystagmus
Am J Ophthalmol
(2004)
R.A. King et al.
Albinism

C.G. Summers

Vision in albinism

Trans Am Ophthalmol Soc

(1996)

Cited by (54)

Microperimetry assessment in foveal hypoplasia: functional results in a series of pediatric patients
2024, Canadian Journal of Ophthalmology
Citation Excerpt :
FH has been associated with poor vision and nystagmus for a long time, but a direct correlation between macular thickness and visual acuity was not confirmed in every study. Holmstrom et al.23 did not find any correlation between foveal thickness and visual acuity in a group of patients with albinism and aniridia, whereas a weak correlation was found by Harvey et al.24 in a group of albinos. However, in this study, we found poor correlations between the degree of FH, BCVA, and nystagmus.
To study the relationships of functional and morphologic retinal parameters in a series of pediatric patients with varying degrees of foveal hypoplasia (FH).
Monocentric observational retrospective study.
Among 21 pediatric patients, 16 met inclusion criteria, having FH confirmed with spectral-domain optical coherence tomography (SD-OCT) scan
Data were analyzed retrospectively. Patients able to undergo macular microperimetry (MP) and SD-OCT examinations were included in the analysis. MP and SD-OCT outcomes were compared with FH grading and best-corrected visual acuity (BCVA) using Pearson's correlation.
Thirty-one eyes from 16 patients (mean age 12.4 years) with different degrees of FH were analyzed. Two patients had grade 1, 7 had grade 2, 5 had grade 3, and 2 had grade 4 FH. Clinical nystagmus was present in 8 patients. The correlation between BCVA and SD-OCT data (–0.31) was lower than that found between BCVA and nystagmus (0.64), that for fixation index P1 (–0.60), as well as that for macular sensitivity (–0.63).
Although limited by the small sample, our study confirms the feasibility of automated MP evaluation in pediatric patients with FH. The added value of this work is the provision of data on relationships between anatomic and functional macular measurements acquired with SD-OCT, MP, and BCVA in eyes with various degrees of FH. Larger prospective studies are necessary to confirm these results.
Étudier le lien entre les paramètres fonctionnels et morphologiques de la rétine chez des enfants présentant différents degrés d'hypoplasie fovéale (HF).
Étude d'observation rétrospective réalisée dans un seul centre.
Sur les 21 enfants, 16 répondaient aux critères d'inclusion et présentaient une HF confirmée par tomographie par cohérence optique en domaine spectral (SD-OCT).
Les données ont été analysées de manière rétrospective. Les patients qui étaient en mesure de subir une micropérimétrie maculaire (MPM) et une SD-OCT ont été inclus dans l'analyse. La corrélation de Pearson a servi à comparer les résultats de la MPM et de la SD-OCT en fonction du degré d'HF et de la meilleure acuité visuelle corrigée (MAVC).
Ont été analysés 31 yeux de 16 patients (âge moyen : 12,4 ans) présentant différents degrés d'HF : grade 1 chez 2 patients; grade 2 chez 7 patients; grade 3 chez 5 patients et grade 4 chez 2 patients. De ce nombre, 8 patients présentaient un nystagmus clinique. La corrélation entre la MAVC et les données obtenues à la SD-OCT (–0,31) était plus faible que celle entre la MAVC et le nystagmus (0,64), l'indice de fixation P1 (–0,60) et la sensibilité maculaire (–0,63).
Malgré les limites que présente notre petit échantillonnage, notre étude confirme la faisabilité de l’évaluation par MPM automatisée chez des enfants qui présentent une HF. Elle est d'autant plus intéressante qu'elle fournit des données sur les liens entre les mesures maculaires anatomiques et fonctionnelles obtenues grâce à la SD-OCT et à la MPM, d'une part, et la MAVC, d'autre part, dans des yeux qui présentent différents degrés d'HF. Des études prospectives de plus grande envergure permettront de confirmer nos résultats.
Investigating Determinants and Evaluating Deep Learning Training Approaches for Visual Acuity in Foveal Hypoplasia
2023, Ophthalmology Science
To describe the relationships between foveal structure and visual function in a cohort of individuals with foveal hypoplasia (FH) and to estimate FH grade and visual acuity using a deep learning classifier.
Retrospective cohort study and experimental study.
A total of 201 patients with FH were evaluated at the National Eye Institute from 2004 to 2018.
Structural components of foveal OCT scans and corresponding clinical data were analyzed to assess their contributions to visual acuity. To automate FH scoring and visual acuity correlations, we evaluated the following 3 inputs for training a neural network predictor: (1) OCT scans, (2) OCT scans and metadata, and (3) real OCT scans and fake OCT scans created from a generative adversarial network.
The relationships between visual acuity outcomes and determinants, such as foveal morphology, nystagmus, and refractive error.
The mean subject age was 24.4 years (range, 1–73 years; standard deviation = 18.25 years) at the time of OCT imaging. The mean best-corrected visual acuity (n = 398 eyes) was equivalent to a logarithm of the minimal angle of resolution (LogMAR) value of 0.75 (Snellen 20/115). Spherical equivalent refractive error (SER) ranged from −20.25 diopters (D) to +13.63 D with a median of +0.50 D. The presence of nystagmus and a high-LogMAR value showed a statistically significant relationship (P < 0.0001). The participants whose SER values were farther from plano demonstrated higher LogMAR values (n = 382 eyes). The proportion of patients with nystagmus increased with a higher FH grade. Variability in SER with grade 4 (range, −20.25 D to +13.00 D) compared with grade 1 (range, −8.88 D to +8.50 D) was statistically significant (P < 0.0001). Our neural network predictors reliably estimated the FH grading and visual acuity (correlation to true value > 0.85 and > 0.70, respectively) for a test cohort of 37 individuals (98 OCT scans). Training the predictor on real OCT scans with metadata and fake OCT scans improved the accuracy over the model trained on real OCT scans alone.
Nystagmus and foveal anatomy impact visual outcomes in patients with FH, and computational algorithms reliably estimate FH grading and visual acuity.
Promises and pitfalls of evaluating photoreceptor-based retinal disease with adaptive optics scanning light ophthalmoscopy (AOSLO)
2021, Progress in Retinal and Eye Research
Adaptive optics scanning light ophthalmoscopy (AOSLO) allows visualization of the living human retina with exquisite single-cell resolution. This technology has improved our understanding of normal retinal structure and revealed pathophysiological details of a number of retinal diseases. Despite the remarkable capabilities of AOSLO, it has not seen the widespread commercial adoption and mainstream clinical success of other modalities developed in a similar time frame. Nevertheless, continued advancements in AOSLO hardware and software have expanded use to a broader range of patients. Current devices enable imaging of a number of different retinal cell types, with recent improvements in stimulus and detection schemes enabling monitoring of retinal function, microscopic structural changes, and even subcellular activity. This has positioned AOSLO for use in clinical trials, primarily as exploratory outcome measures or biomarkers that can be used to monitor disease progression or therapeutic response. AOSLO metrics could facilitate patient selection for such trials, to refine inclusion criteria or to guide the choice of therapy, depending on the presence, absence, or functional viability of specific cell types. Here we explore the potential of AOSLO retinal imaging by reviewing clinical applications as well as some of the pitfalls and barriers to more widespread clinical adoption.
The emerging roles of the macular pigment carotenoids throughout the lifespan and in prenatal supplementation
2021, Journal of Lipid Research
Since the publication of the Age-Related Eye Disease Study 2 (AREDS2) in 2013, the macular pigment carotenoids lutein (L) and zeaxanthin (Z) have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration. More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of L and Z supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for L and Z supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with L and Z might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.
Etiological assessment of a nystagmus in childhood
2018, Journal Francais d'Ophtalmologie
En dehors du nystagmus latent témoin d’un trouble de développement de la vision binoculaire, tout nystagmus de l’enfant nécessite un bilan étiologique. La connaissance de la physiopathogénie des nystagmus permet d’orienter le bilan en fonction principalement de ses caractéristiques morphologiques. L’examen ophtalmologique clinique est complété par un OCT et un bilan électrophysiologique (ERG, PEV). En cas de normalité, une IRM est systématiquement demandée, ainsi qu’une analyse génétique.
Apart from the latent nystagmus, which arises as a consequence of failure to develop binocular vision, every case of childhood nystagmus needs an etiological assessment. Knowledge of the pathogenesis of the various types of nystagmus guides this assessment, particularly considering the morphological characteristics of the nystagmus. The clinical ophthalmologic examination is complemented by OCT and electrophysiologic testing (ERG, VEP). If this testing is normal, an MRI and genetic assessment are required.
Correlation of novel PAX6 gene abnormalities in aniridia and clinical presentation
2017, Canadian Journal of Ophthalmology
To describe the clinical presentation and genotype of subjects with aniridia with a particular focus on foveal hypoplasia.
Prospective cohort study.
Thirty-three Canadian participants with aniridia and of various ethnic backgrounds residing in British Columbia.
Full ophthalmic examinations and posterior segment spectral domain-optical coherence tomography (SD-OCT) imaging were performed. Foveal hypoplasia was graded independently by 2 staff ophthalmologists. PAX6 sequencing was performed and chromosomal 11p anomalies investigated. Candidate gene and single-nucleotide polymorphism sequencing in genes functionally related to PAX6 were also studied.
Best corrected visual acuities in the cohort ranged from 0.0 logMAR to no light perception. Total absence of iris tissue was seen in the majority (42 of 66 eyes). In those in whom SD-OCT was possible, foveal hypoplasia was seen in the majority (45 of 56 eyes, 80%). Molecular genetic defects involving PAX6 were identified in 30 participants (91%), including 4 novel PAX6 mutations (Gly18Val; Ser65ProfsX14; Met337ArgfsX18; Ser321CysfsX34) and 4 novel chromosome 11p deletions inclusive of PAX6 or a known PAX6 regulatory region.
The number of PAX6 mutations associated with aniridia continues to increase. Variable foveal architecture despite nearly identical anterior segment disease in 4 participants with an Ex9 ELP4-Ex4 DCDC1 deletion suggested that molecular cues causing variation in disease in the posterior segment differ from those at play in the anterior segment. Results in 3 patients without identifiable PAX6 mutations and a review of the literature suggest that such cases be described as phenocopies rather than actual cases of the syndrome of aniridia.
Décrire la présentation clinique et le génotype de sujets porteurs d’une aniridie en accordant une importance particulière à l’hypoplasie fovéale.
Étude de cohorte prospective
33 Canadiens de différentes origines ethniques résidant en Colombie-Britannique et porteurs d’une aniridie.
Les patients ont subi un examen ophtalmologique complet de même qu’une tomographie par cohérence optique en domaine spectral (SD-OCT) du segment postérieur. L’hypoplasie fovéale a été classée indépendamment par deux ophtalmologistes membres du personnel. Un séquençage du gène PAX6 a été réalisé, et l’on a procédé à un examen des anomalies du chromosome 11p. On a aussi effectué le séquençage du gène candidat et du polymorphisme d’un seul nucléotide dans les gènes liés au gène PAX6 sur le plan fonctionnel.
La meilleure acuité visuelle corrigée dans la cohorte s’échelonnait de 0,0 logMAR à l’absence de perception de la lumière. L’absence totale de tissu iridien a été observée chez la majorité des sujets (42 yeux sur 66). Lorsqu’il a été possible de réaliser une SD-OCT, l’examen a mis au jour une hypoplasie fovéale dans la majorité des cas (45 yeux sur 56, soit 80 %). Trente participants (91 %) étaient porteurs de défauts génétiques moléculaires du gène PAX6. Par ailleurs, on a découvert 4 nouvelles mutations du gène PAX6 (Gly18Val, Ser65ProfsX14, Met337ArgfsX18 et Ser321CysfsX34) et 4 nouvelles délétions chromosomiques 11p du gène PAX6 ou d’une région régulatrice connue du gène PAX6.
Le nombre de mutations du gène PAX6 en lien avec l’aniridie ne cesse d’augmenter. Les variations de l’architecture fovéale chez 4 participants qui présentaient une délétion en Ex9 du gène ELP4 et en Ex4 du gène DCDC1, malgré la présence d’une atteinte presque identique du segment antérieur, permettent de croire que les signaux moléculaires qui influent sur l’atteinte du segment postérieur diffèrent de ceux qui touchent le segment antérieur. Enfin, 3 patients ne présentaient aucune mutation identifiable du gène PAX6. Selon une revue de la littérature, ces cas constitueraient des phénocopies plutôt que de véritables aniridies.

View all citing articles on Scopus

: Supported by an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.

View full text

Major articleSpectrum of Foveal Development in Albinism Detected with Optical Coherence Tomography

Section snippets

Methods

Results

Discussion

J Aapos.

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Albinism

Vision in albinism

Trans Am Ophthalmol Soc

Major article
Spectrum of Foveal Development in Albinism Detected with Optical Coherence Tomography