Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

PURPOSE: Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. METHODS: We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. RESULTS: There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS: Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

Comparison of Pentacam and Orbscan IIz on posterior curvature topography measurements in keratoconus eyes.

PURPOSE: To compare the measurements of posterior elevation above the best-fit sphere and of pachymetry in established keratoconus patients using 2 different technologies--Scheimpflug imaging with the Pentacam and scanning slit combined with Placido imaging with Orbscan IIz. DESIGN: Retrospective comparative case series. PARTICIPANTS: Patients with confirmed keratoconus by biomicroscopy and Placido topography who had corneal topography scans by the Pentacam and Orbscan IIz on their visit from April 2004 to April 2005. These scans were obtained routinely for patient diagnosis, treatment, and progression. METHODS: The mean difference, standard deviation (SD), and 95% limits of agreement (LOA) were calculated, and Bland-Altman plots were constructed for best-fit sphere radius of curvature, posterior elevation above the best-fit sphere, and pachymetry of the thinnest point. RESULTS: Thirty-six eyes of 29 patients were analyzed. The average radius for posterior best-fit sphere was 5.97 microm (range, 4.69-6.79) for the Pentacam and 6.00 microm (range, 4.97-6.55) for Orbscan IIz. The mean difference (Pentacam - Orbscan IIz) for the radius generated for the best-fit sphere was -0.03+/-0.22 SD with a 95% confidence interval (CI) of -0.11 to 0.04 and a 95% LOA of -0.46 to 0.40 (P = 0.362). The mean posterior elevation by best-fit sphere fixed to the apex was 34.86 microm (range, 3-120) for the Pentacam and 48.50 microm (range, 11-118) for Orbscan IIz. The mean difference was -13.64+/-26.08 SD (95% CI, -22.46 to -4.81; 95% LOA, -64.75 to 37.48; P = 0.003). The average thinnest point for the Pentacam was 443.6 microm (range, 164-587), and that for Orbscan IIz was 445.9 microm (range, 204-597). The mean difference in the thinnest point for the Pentacam and Orbscan IIz was -2.28+/-35.55 (95% CI, -14.31 to 9.75; 95% LOA, -71.95 to 67.39; P = 0.703). CONCLUSION: Both the Pentacam and Orbscan IIz determine similar thinnest points but have a measurable difference in posterior elevations above the best-fit sphere, despite similar radii of curvature. This difference may be important in the screening of patients for refractive surgery to avoid surgery on patients with early keratoconus. This study cannot determine if the Pentacam is underestimating the posterior vault or if Orbscan is overestimating this height, and further studies with a standardized test object are needed.

Topography of long- and middle-wavelength sensitive cone opsin gene expression in human and Old World monkey retina.

The topographical distributions of the relative ratio of long- (L) and middle- (M) wavelength sensitive cone opsin messenger RNA (mRNA) in human and baboon retinas were mapped using real-time polymerase chain reaction. The L:M mRNA ratio increased in a central-to-peripheral gradient in both species, being quite pronounced for humans.

Genetics of corneal disease for the ocular surface clinician.

Advances in the understanding of inherited corneal and external diseases may allow interventions that prevent the substantial vision impairment currently caused by these diseases. The observant clinician may first recognize inherited corneal and external diseases based on clinical examination and a careful family history. Researchers using positional cloning and candidate gene techniques have identified several disease-causing genes. Identification of the genes responsible for inherited corneal and external diseases will lead to more definitive diagnoses and represent the first step in development of effective therapies. Future endeavors are directed toward identifying additional inherited corneal and external diseases, the genes that cause them, and possible gene therapies to improve visual outcomes.

Topographical cone photopigment gene expression in deutan-type red-green color vision defects.

Eye donors were identified who had X-chromosome photopigment gene arrays like those of living deuteranomalous men; the arrays contained two genes encoding long-wavelength sensitive (L) pigments as well as genes to encode middle-wavelength sensitive (M) photopigment. Ultrasensitive methods failed to detect the presence of M photopigment mRNA in the retinas of these deutan donors. This provides direct evidence that deuteranomaly is caused by the complete absence of M pigment mRNA. Additionally, for those eyes with mRNA corresponding to two different L-type photopigments, the ratio of mRNA from the first vs. downstream L genes was analyzed across the retinal topography. Results show that the pattern of first relative to downstream L gene expression in the deuteranomalous retina is similar to the pattern of L vs. M gene expression found in normal retinas.