Diane M. Tait

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.

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin

Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin. Here, we used high-resolution retinal imaging to examine the cone mosaic in two individuals with genes encoding a middle-wavelength sensitive (M) pigment with the C203R mutation. We found a significant reduction in cone density compared to normal and color-deficient controls, accompanying disruption in the cone mosaic in both individuals, and thinning of the outer nuclear layer. The C203R mosaics were different from that produced by another mutation (LIAVA) previously shown to disrupt the cone mosaic. Comparison of these mosaics provides insight into the timing and degree of cone disruption and has implications for the prospects for restoration of vision loss associated with various cone opsin mutations.

Retinal Imaging Using Commercial Broadband Optical Coherence Tomography

Aims To examine the practical improvement in image quality afforded by a broadband light source in a clinical setting and to define image quality metrics for future use in evaluating spectral domain optical coherence tomography (SD-OCT) images. Methods A commercially available SD-OCT system, configured with a standard source as well as an external broadband light source, was used to acquire 4 mm horizontal line scans of the right eye of 10 normal subjects. Scans were averaged to reduce speckling and multiple retinal layers were analysed in the resulting images. Results For all layers there was a significant improvement in the mean local contrast (average improvement by a factor of 1.66) when using the broadband light source. Intersession variability was shown not to be a major contributing factor to the observed improvement in image quality obtained with the broadband light source. We report the first observation of sublamination within the inner plexiform layer visible with SD-OCT. Conclusion The practical improvement with the broadband light source was significant, although it remains to be seen what the utility will be for diagnostic pathology. The approach presented here serves as a model for a more quantitative analysis of SD-OCT images, allowing for more meaningful comparisons between subjects, clinics and SD-OCT systems.

Spectral Domain Optical Coherence Tomography and Adaptive Optics: Imaging Photoreceptor Layer Morphology to Interpret Preclinical Phenotypes

Recent years have seen the emergence of advances in imaging technology that enable in vivo evaluation of the living retina. Two of the more promising techniques, spectral domain optical coherence tomography (SD-OCT) and adaptive optics (AO) fundus imaging provide complementary views of the retinal tissue. SD-OCT devices have high axial resolution, allowing assessment of retinal lamination, while the high lateral resolution of AO allows visualization of individual cells. The potential exists to use one modality to interpret results from the other. As a proof of concept, we examined the retina of a 32 year-old male, previously diagnosed with a red-green color vision defect. Previous AO imaging revealed numerous gaps throughout his cone mosaic, indicating that the structure of a subset of cones had been compromised. Whether the affected cells had completely degenerated or were simply morphologically deviant was not clear. Here an AO fundus camera was used to re-examine the retina (~6 years after initial exam) and SD-OCT to examine retinal lamination. The static nature of the cone mosaic disruption combined with the normal lamination on SD-OCT suggests that the affected cones are likely still present.

Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram.

The topographical distribution of relative sensitivity to red and green lights across the retina was assayed using a custom-made wide-field color multifocal electroretinogram apparatus. There were increases in the relative sensitivity to red compared to green light in the periphery that correlate with observed increases in the relative amount of long (L) compared to middle (M) wavelength sensitive opsin mRNA. These results provide electrophysiological evidence that there is a dramatic increase in the ratio of L to M cones in the far periphery of the human retina. The central to far peripheral homogeneity in cone proportions has implications for understanding the developmental mechanisms that determine the identity of a cone as L or M and for understanding the circuitry for color vision in the peripheral retina.

Unusual Adaptive Optics Findings in a Patient With Bilateral Maculopathy

Over the past decade there has been a rapid evolution in our ability to noninvasively image the living human retina. Of particular interest is adaptive optics (AO), a technique that corrects for the eye’s monochromatic aberrations and allows nearly diffraction-limited imaging of the retina.1 There is increasing clinical application of AO imaging2–5 owing to the ability to resolve retinal pathological changes on a cellular level, although the future of AO imaging for clinical diagnosis is not clear. Of particular value in determining the potential diagnostic role of AO are cases in which the standard clinical picture is unclear. Here we describe a patient with bilateral progressive vision loss where AO imaging and optical coherence tomography (OCT) contributed to our understanding of the structural abnormalities associated with the visual dysfunction.

Normality of colour vision in a compound heterozygous female carrying protan and deutan defects.

Background:  Inherited red‐green colour vision defects are quite common, affecting one in 12 males, but are less common in women, affecting about one in 250. Because red‐green defects are X‐linked, nearly 15 per cent of females are heterozygous carriers of red‐green colour deficiency. In addition, about one in 150 females are ‘double carriers’, where both of their X chromosomes have L/M gene arrays encoding a red‐green defect. If a woman carries the same type of colour vision defect on each X‐chromosome, she will be red‐green colour deficient, whereas if she carries opposing defects (protan versus deutan) on each X chromosome, she will have normal colour vision, owing to the process of X‐inactivation. These women are referred to as compound heterozygotes, though very few have been reported. Questions remain about whether the colour vision capacity of these women is comparable to that of ‘normal’ trichromats.

Color Blindness: Inherited

The term color vision refers to our ability to discriminate objects based on their color – in fact, humans can differentiate among millions of hues. However, over 8% of the population experiences an inherited deficiency in color discrimination. Actually, the majority of color-vision defects is inherited. The defects vary based on the type and number of photoreceptors affected, and correspondingly can have differing perceptual consequences. The genetic mechanisms and perceptual losses of the various forms of inherited color-vision deficiencies are discussed in this article.

Color Blindness: Acquired

Human color vision is normally trichromatic, allowing the discrimination of nearly 2 million hues. From the photoreceptors that initiate the process of transforming light into a neural signal, to the cortical machinery that provides the basis for our perceptual experience, the human color-vision system is extremely complex. As a result, there are multiple situations where the system can be damaged or disrupted. In this article, we review the myriad of conditions that result in the acquisition of a color-vision defect.