To examine retinal structure and changes in photoreceptor intensity post-dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease.
Prospective observational case series.
We recruited three patients with complete congenital stationary night blindness caused by mutations in GRM6, two brothers with Oguchi disease caused by mutations in GRK1, and one normal control. Retinal thickness was measured from optical coherence tomography (OCT) images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged five of the patients following a period of dark adaptation, and examined layer reflectivity on OCT in a patient with Oguchi disease under light- and dark-adapted conditions.
Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations, as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. Upon removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In one Oguchi patient, the outer segment layer contrast on OCT was fourfold higher under dark-adapted versus light-adapted conditions.
The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar/ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are due to changes within the rods as opposed to changes at a different retinal locus.
Assess outer retinal layer maturation during late gestation and early postnatal life using optical coherence tomography (OCT) and histology.
Thirty-nine subjects ranging from 32 weeks post-menstrual age (PMA) to 4 years were imaged using a hand held OCT (102 imaging sessions). Foveal images from 16 subjects (21 imaging sessions) were normal and evaluated for inner retinal excavation and presence of outer retinal reflective bands. Reflectivity profiles of central, parafoveal, and perifoveal retina were extracted and compared to age-matched histological sections.
Foveal pit morphology in infants was generally distinguishable from adults. Reflectivity profiles showed a single hyper-reflective band at the fovea in all infants less than 42 weeks PMA. Multiple bands were distinguishable in the outer retina at the perifovea by 32 weeks PMA, and at the fovea by 3 months post term. By 17 months postnatal the characteristic appearance of four hyper-reflective bands was evident across the foveal region. These features are consistent with previous results from histology. A ‘temporal divot’ was present in some infants and foveal pit morphology and extent of inner retinal excavation was variable.
Hand-held OCT imaging is a viable technique for evaluating neonatal retinas. In premature infants, who do not develop ROP, the foveal region appears to follow a developmental time course similar to in utero maturation.
As pediatric OCT imaging becomes more common, a better understanding of normal foveal and macular development is needed. Longitudinal imaging offers the opportunity to track postnatal foveal development in preterm infants where poor visual outcomes are anticipated or to track treatment outcomes in this population.
To study retinal structure in choroideremia patients and carriers using high-resolution imaging techniques.
Subjects from four families (six female carriers and five affected males) with choroideremia (CHM) were characterized with best-corrected visual acuity (BCVA), kinetic and static perimetry, full-field electroretinography, and fundus autofluorescence (FAF). High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography (SD-OCT). Coding regions of the CHM gene were sequenced.
Molecular analysis of the CHM gene identified a deletion of exons 9 to 15 in family A, a splice site mutation at position 79+1 of exon 1 in family B, deletion of exons 6 to 8 in family C, and a substitution at position 106 causing a premature stop in family D. BCVA ranged from 20/16 to 20/63 in carriers and from 20/25 to 5/63 in affected males. FAF showed abnormalities in all subjects. SD-OCT showed outer retinal layer loss, outer retinal tubulations at the margin of outer retinal loss, and inner retinal microcysts. Patchy cone loss was present in two symptomatic carriers. In two affected males, cone mosaics were disrupted with increased cone spacing near the fovea but more normal cone spacing near the edge of atrophy.
High-resolution retinal images in CHM carriers and affected males demonstrated RPE and photoreceptor cell degeneration. As both RPE and photoreceptor cells were affected, these cell types may degenerate simultaneously in CHM. These findings provide insight into the effect of CHM mutations on macular retinal structure, with implications for the development of treatments for CHM. (ClinicalTrials.gov number, NCT00254605.)
High-resolution retinal images in choroideremia carriers and affected males demonstrated degeneration of retinal pigment epithelial and photoreceptor cells. The findings illustrate the effect of CHM mutations on macular cone structure, with implications for the development of treatments for CHM.
The adaptive optics scanning light ophthalmoscope (AOSLO) allows visualization of microscopic structures of the human retina in vivo. In this work, we demonstrate its application in combination with oral and intravenous (IV) fluorescein angiography (FA) to the in vivo visualization of the human retinal microvasculature. Ten healthy subjects ages 20 to 38 years were imaged using oral (7 and/or 20 mg/kg) and/or IV (500 mg) fluorescein. In agreement with current literature, there were no adverse effects among the patients receiving oral fluorescein while one patient receiving IV fluorescein experienced some nausea and heaving. We determined that all retinal capillary beds can be imaged using clinically accepted fluorescein dosages and safe light levels according to the ANSI Z136.1-2000 maximum permissible exposure. As expected, the 20 mg/kg oral dose showed higher image intensity for a longer period of time than did the 7 mg/kg oral and the 500 mg IV doses. The increased resolution of AOSLO FA, compared to conventional FA, offers great opportunity for studying physiological and pathological vascular processes.
(110.1080) Active or adaptive optics; (330.5380) Physiology; (170.1610) Clinical applications; (170.3880) Medical and biological imaging; (170.4470) Ophthalmology
To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations.
Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array.
While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with “L/M interchange” mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic.
The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy.
Subjects with OPN1LW and OPN1MW mutations showed a spectrum of retinal phenotypes with genotype-specific differences. This has implications for restoration of visual function in these subjects and highlights high-resolution retinal imaging as a complementary tool for emerging therapeutic efforts.
Geometrical analysis of the photoreceptor mosaic can reveal subclinical ocular pathologies. In this paper, we describe a fully automatic algorithm to identify and segment photoreceptors in adaptive optics ophthalmoscope images of the photoreceptor mosaic. This method is an extension of our previously described closed contour segmentation framework based on graph theory and dynamic programming (GTDP). We validated the performance of the proposed algorithm by comparing it to the state-of-the-art technique on a large data set consisting of over 200,000 cones and posted the results online. We found that the GTDP method achieved a higher detection rate, decreasing the cone miss rate by over a factor of five.
(100.0100) Image processing; (170.4470) Ophthalmology; (110.1080) Active or adaptive optics
To assess the repeatability and measurement error associated with cone density and nearest neighbor distance (NND) estimates in images of the parafoveal cone mosaic obtained with an adaptive optics scanning light ophthalmoscope (AOSLO).
Twenty-one participants with no known ocular pathology were recruited. Four retinal locations, approximately 0.65° eccentricity from the center of fixation were imaged 10 times in randomized order with an AOSLO. Cone coordinates in each image were identified using an automated algorithm (with or without manual correction), from which cone density and NND were calculated. Owing to naturally occurring fixational instability, the 10 images recorded from a given location did not overlap entirely. We thus analyzed each image set both before and after alignment.
Automated estimates of cone density on the unaligned image sets showed a coefficient of repeatability of 11,769 cones/mm2 (17.1%). The primary reason for this variability appears to be fixational instability, as aligning the 10 images to include the exact same retinal area, results in an improved repeatability of 4,358 cones/mm2 (6.4%) using completely automated cone identification software. Repeatability improved further by manually identifying cones missed by the automated algorithm, with a coefficient of repeatability of 1,967 cones/mm2 (2.7%). NND showed improved repeatability, and was generally insensitive to the undersampling by the automated algorithm.
As our data were collected in a young, healthy population, this likely represents a best-case estimate for corresponding measurements in patients with retinal disease. Similar studies need to be carried out on other imaging systems (including those using different imaging modalities, wavefront correction technology, and/or cone identification software), as repeatability would be expected to be highly sensitive to initial image quality and the performance of cone identification algorithms. Separate studies addressing inter-session repeatability and inter-observer reliability are also needed.
retina; cones; adaptive optics; repeatability; photoreceptors
To ascertain the potential pathogenicity of a retinitis pigmentosa (RP)-causing RHO F45L allele in a family affected by congenital achromatopsia (ACHM).
Case series/observational study that included two patients with ACHM and 24 extended family members. Molecular genetic analysis was performed to identify RHO F45L carrier status in the family and a control population. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Comprehensive clinical testing included acuity, color vision, and dilated fundus examination. Electroretinography was used to assess rod and cone function.
Five carriers of the RHO F45L allele alone (24–80 years) and three carriers in combination with a heterozygous CNGA3 mutant allele (10–64 years) were all free of the classic symptoms and signs of RP. In heterozygous carriers of both mutations, SD-OCT showed normal retinal thickness and intact outer retinal layers; rod and cone densities were within normal limits on AOSLO. The phenotype in two individuals affected with ACHM and harboring the RHO F45L allele was indistinguishable from that previously reported for ACHM.
The RHO F45L allele is not pathogenic in this large family; hence, the two ACHM patients would unlikely develop RP in the future.
The combined approach of comprehensive molecular analysis of individual genomes and noninvasive cellular resolution retinal imaging enhances the current repertoire of clinical diagnostic tools, giving a substantial impetus to personalized medicine.
exome sequencing; adaptive optics; rhodopsin mutations; retinitis pigmentosa; retinal degeneration
Spectral-Domain Optical Coherence Tomography; Ocular Trauma; Commotio Retinae; Adaptive Optics; Photoreceptors; Retina
Carriers of blue cone monochromacy have fewer cone photoreceptors than normal. Here we examine how this disruption at the level of the retina affects visual function and cortical organization in these individuals. Visual resolution and contrast sensitivity was measured at the preferred retinal locus of fixation and visual resolution was tested at two eccentric locations (2.5° and 8°) with spectacle correction only. Adaptive optics corrected resolution acuity and cone spacing were simultaneously measured at several locations within the central fovea with adaptive optics scanning laser ophthalmoscopy (AOSLO). Fixation stability was assessed by extracting eye motion data from AOSLO videos. Retinotopic mapping using fMRI was carried out to estimate the area of early cortical regions, including that of the foveal confluence. Without adaptive optics correction, BCM carriers appeared to have normal visual function, with normal contrast sensitivity and visual resolution, but with AO-correction, visual resolution was significantly worse than normal. This resolution deficit is not explained by cone loss alone and is suggestive of an associated loss of retinal ganglion cells. However, despite evidence suggesting a reduction in the number of retinal ganglion cells, retinotopic mapping showed no reduction in the cortical area of the foveal confluence. These results suggest that ganglion cell density may not govern the foveal overrepresentation in the cortex. We propose that it is not the number of afferents, but rather the content of the information relayed to the cortex from the retina across the visual field that governs cortical magnification, as under normal viewing conditions this information is similar in both BCM carriers and normal controls.
We recently completed a strategic planning process to better understand the development of our five-year-old PBRN and to identify gaps between our original vision and current progress. While many of our experiences are not new to the PBRN community, our reflections may be valuable for those developing or re-shaping PBRNs in a changing health care environment.
We learned about the importance of: (1) Shared vision and commitment to a unique patient population; (2) Strong leadership, mentorship, and collaboration; (3) Creative approaches to engaging busy clinicians and bridging the worlds of academia and community practice; (4) Harnessing data from electronic health records and navigating processes related to data protection, sharing, and ownership.
We must emphasize research that is timely, relevant, and integrated into practice. One model supporting this goal involves a broader partnership than was initially envisioned for our PBRN, one which includes clinicians, researchers, information architects and quality improvement experts partnering to develop an Innovation Center. This Center could facilitate development of relevant research questions while also addressing ‘quick-turnaround’ needs.
Gaps remain between our PBRN’s initial vision and current reality. Closing these gaps may require future creativity in partnership building and nontraditional funding sources.
practice-based research; community health; primary care; electronic health records; health care safety net
Recent years have seen an explosion in the development of novel ophthalmic imaging devices, delivering non-invasive views of the living retina. Adaptive optics (AO) imaging systems enable resolution of individual cells in the living retina. Analysis of these images has been limited to measures of cone density and regularity. Here we introduce a small case series where the information in the high-resolution image extends beyond these standard metrics. These images should serve as the basis for evolving discussion as to how best to interpret AO retinal images.
It has been shown that after a visible stimulus, optical oscillations of nearly all cone photoreceptors can be observed using long coherence length light and in a few cones using short coherence length light. Here, we show that after exposure to a visible stimulus, a short coherence length imaging source reveals light-evoked oscillation signals in a large number of cones. More than 80% of cones in a given retinal area are activated (modulation in the reflectance signal) after stimulation, and the pattern of their activation can be subjectively classified into one of four categories. The application of light-evoked signal detection techniques for in vivo retinal imaging may prove useful for assessing the functional status of cones in normal and diseased retinae.
This paper presents a successful combination of ultra-high speed (120,000 depth scans/s), ultra-high resolution optical coherence tomography with adaptive optics and an achromatizing lens for compensation of monochromatic and longitudinal chromatic ocular aberrations, respectively, allowing for non-invasive volumetric imaging in normal and pathologic human retinas at cellular resolution. The capability of this imaging system is demonstrated here through preliminary studies by probing cellular intraretinal structures that have not been accessible so far with in vivo, non-invasive, label-free imaging techniques, including pigment epithelial cells, micro-vasculature of the choriocapillaris, single nerve fibre bundles and collagenous plates of the lamina cribrosa in the optic nerve head. In addition, the volumetric extent of cone loss in two colour-blinds could be quantified for the first time. This novel technique provides opportunities to enhance the understanding of retinal pathogenesis and early diagnosis of retinal diseases.
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.
Using a combination of in vivo retinal imaging tools, the authors found extensive variation in the size of the foveal pit and the foveal avascular zone, with larger foveal pits associated with larger foveal avascular zones.
To assess the relationship between foveal pit morphology and size of the foveal avascular zone (FAZ).
Forty-two subjects were recruited. Volumetric images of the macula were obtained using spectral domain optical coherence tomography. Images of the FAZ were obtained using either a modified fundus camera or an adaptive optics scanning light ophthalmoscope. Foveal pit metrics (depth, diameter, slope, volume, and area) were automatically extracted from retinal thickness data, whereas the FAZ was manually segmented by two observers to extract estimates of FAZ diameter and area.
Consistent with previous reports, the authors observed significant variation in foveal pit morphology. The average foveal pit volume was 0.081 mm3 (range, 0.022 to 0.190 mm3). The size of the FAZ was also highly variable between persons, with FAZ area ranging from 0.05 to 1.05 mm2 and FAZ diameter ranging from 0.20 to 1.08 mm. FAZ area was significantly correlated with foveal pit area, depth, and volume; deeper and broader foveal pits were associated with larger FAZs.
Although these results are consistent with predictions from existing models of foveal development, more work is needed to confirm the developmental link between the size of the FAZ and the degree of foveal pit excavation. In addition, more work is needed to understand the relationship between these and other anatomic features of the human foveal region, including peak cone density, rod-free zone diameter, and Henle fiber layer.
Inherited red-green colour vision defects are quite common, affecting nearly 1 in 10 males, but are less common in women, affecting about 1 in 250. However because red-green defects are X-linked, nearly 15% of females are heterozygous carriers of red-green colour deficiency. In addition, about 1 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 herself will be red-green colour deficient, whereas if she carries opposing defects (protan vs. deutan) on each X chromosome she will be trichromatic, owing to the process of X-inactivation. These women are referred to as compound heterozygotes, though very few have been reported. Moreover, questions remain as to whether the colour vision capacity of these women is comparable to that of “normal” trichromats.
We examined a compound heterozygote carrier of both protanopia and deuteranomaly. We also examined male members of her family representing both forms of red-green defect carried by the female proband. Complete colour vision testing was done, including Rayleigh matches, pseudoichromatic plates, unique hue measurements, and 100-Hue tests. Flicker-photometric ERG estimates of L:M cone ratio were obtained, as were Medmont C100 settings.
Genetic analyses provided direct confirmation of compound heterozygosity. The compound heterozygote showed Schmidt’s sign, consistent with an extreme skew in her L:M cone ratio, and usually associated with protan carrier status.
Apart from Schmidt’s sign, we found the colour vision of the compound heterozygote to be indistinguishable from that of a normal trichromat.
Color Vision; Retina; Protan; Deutan
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.
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.
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.
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.
Assessment of retinal structure and function in achromatopsia may be useful for the selection of patients for future therapeutic trials and for monitoring therapeutic efficacy.
To assess photoreceptor structure and function in patients with congenital achromatopsia.
Twelve patients were enrolled. All patients underwent a complete ocular examination, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinographic (ERG), and color vision testing. Macular microperimetry (MP; in four patients) and adaptive optics (AO) imaging (in nine patients) were also performed. Blood was drawn for screening of disease-causing genetic mutations.
Mean (±SD) age was 30.8 (±16.6) years. Mean best-corrected visual acuity was 0.85 (±0.14) logarithm of the minimal angle of resolution (logMAR) units. Seven patients (58.3%) showed either an absent foveal reflex or nonspecific retinal pigment epithelium mottling to mild hypopigmentary changes on fundus examination. Two patients showed an atrophic-appearing macular lesion. On anomaloscopy, only 5 patients matched over the entire range from 0 to 73. SD-OCT examination showed a disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors in 10 patients (83.3%). Seven of these patients showed an optically empty space at the level of the photoreceptors in the fovea. AO images of the photoreceptor mosaic were highly variable but significantly disrupted from normal. On ERG testing, 10 patients (83.3%) showed evidence of residual cone responses to a single-flash stimulus response. The macular MP testing showed that the overall mean retinal sensitivity was significantly lower than normal (12.0 vs. 16.9 dB, P < 0.0001).
The current approach of using high-resolution techniques to assess photoreceptor structure and function in patients with achromatopsia should be useful in guiding selection of patients for future therapeutic trials as well as monitoring therapeutic response in these trials.
The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy (SLO) and spectral domain optical coherence tomography (SD-OCT) provide clinicians with remarkably clear pictures of the living retina. While the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, these same optics induce significant aberrations that in most cases obviate cellular-resolution imaging. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. Applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, RPE cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here we review some of the advances made possible with AO imaging of the human retina, and discuss applications and future prospects for clinical imaging.
imaging; adaptive optics; retina; pathology; photoreceptors
Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome associated with normal or near-normal color vision. In this paper, the authors describe novel observations on the underlying structural basis of OT at the level of the cone mosaic.
Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT.
Retinal images were obtained from two brothers (13 and 15 years) and two unrelated subjects, one male (47 years) and one female (24 years). High-resolution images of the cone mosaic were obtained using high-speed adaptive optics (AO) fundus cameras. Visible structures were analyzed for density using custom software. Additional retinal images were obtained using spectral domain optical coherence tomography (SD-OCT), and the four layers of the photoreceptor-retinal pigment epithelium complex (ELM, IS/OS, RPE1, RPE2) were evaluated. Cone photoreceptor length and the thickness of intraretinal layers were measured and compared to previously published normative data.
The adult male subject had infantile onset nystagmus while the three other patients did not. In the adult male patient, a normal appearing cone mosaic was observed. However, the three other subjects had a sparse mosaic of cones remaining at the fovea, with no structure visible outside the central fovea. On SD-OCT, the adult male subject had a very shallow foveal pit, with all major retinal layers being visible, and both inner segment (IS) and outer segment (OS) length were within normal limits. In the other three patients, while all four layers were visible in the central fovea and IS length was within normal limits, the OS length was significantly decreased. Peripherally the IS/OS layer decreased in intensity, and the RPE1 layer was no longer discernable, in keeping with the lack of cone structure observed on AO imaging outside the central fovea.
Findings are consistent with the visual deficits being caused by a reduced number of healthy cones in the two brothers and the adult female. In the unrelated adult subject, no structural basis for the disorder was found. These data suggest two distinct groups on the basis of structural imaging. It is proposed that the former group with evidence of a reduction in cone numbers is more in keeping with typical OT, with the latter group representing an OT-like phenotype. These two groups may be difficult to readily discern on the basis of phenotypic features alone, and high-resolution imaging may be an effective way to distinguish between these phenotypes.
Our understanding of the etiology of red-green color vision defects is evolving. While missense mutations within the long- (L-) and middle-wavelength sensitive (M-) photopigments and gross rearrangements within the L/M-opsin gene array are commonly associated with red-green defects, recent work using adaptive optics retinal imaging has shown that different genotypes can have distinct consequences for the cone mosaic. Here we examined the cone mosaic in red-green color deficient individuals with multiple X-chromosome opsin genes that encode L opsin, as well as individuals with a single X-chromosome opsin gene that encodes L opsin and a single patient with a novel premature termination codon in his M-opsin gene and a normal L-opsin gene. We observed no difference in cone density between normal trichomats and multiple or single gene dichromats. In addition, we demonstrate different phenotypic effects of a nonsense mutation versus the previously described deleterious polymorphism, (LIAVA), both of which differ from multiple and single gene dichromats. Our results help refine the relationship between opsin genotype and cone photoreceptor mosaic phenotype.
adaptive optics; color vision; cones; deutan; opsin gene