A novel iris transillumination grading scale allowing flexible assessment with quantitative image analysis and visual matching.

PURPOSE: To develop a sensitive scale of iris transillumination suitable for clinical and research use, with the capability of either quantitative analysis or visual matching of images. METHODS: Iris transillumination photographic images were used from 70 study subjects with ocular or oculocutaneous albinism. Subjects represented a broad range of ocular pigmentation. A subset of images was subjected to image analysis and ranking by both expert and nonexpert reviewers. Quantitative ordering of images was compared with ordering by visual inspection. Images were binned to establish an 8-point scale. Ranking consistency was evaluated using the Kendall rank correlation coefficient (Kendall's tau). Visual ranking results were assessed using Kendall's coefficient of concordance (Kendall's W) analysis. RESULTS: There was a high degree of correlation among the image analysis, expert-based and non-expert-based image rankings. Pairwise comparisons of the quantitative ranking with each reviewer generated an average Kendall's tau of 0.83 ± 0.04 (SD). Inter-rater correlation was also high with Kendall's W of 0.96, 0.95, and 0.95 for nonexpert, expert, and all reviewers, respectively. CONCLUSIONS: The current standard for assessing iris transillumination is expert assessment of clinical exam findings. We adapted an image-analysis technique to generate quantitative transillumination values. Quantitative ranking was shown to be highly similar to a ranking produced by both expert and nonexpert reviewers. This finding suggests that the image characteristics used to quantify iris transillumination do not require expert interpretation. Inter-rater rankings were also highly similar, suggesting that varied methods of transillumination ranking are robust in terms of producing reproducible results.

[Oculocutaneous and ocular albinism]. / Okulokutaner und okulärer Albinismus.

Albinism can be divided into oculocutaneous albinism (OCA) and ocular albinism (OA). In the differential diagnostics these can be distinguished from rarer syndromes with partial albinism, which are frequently associated with susceptibility to infections and neurological symptoms. The OCA is an autosomal recessive inherited disease of melanin biosynthesis, which leads to complete or partial loss of melanin in the skin, hair follicles and eyes. Of the seven currently known subtypes (OCA 1-7), four are well-characterized (OCA 1-4). These are based on gene mutations, which code for tyrosinase, a key enzyme in melanin synthesis and for further proteins. These play an important role in the catalytic activity of tyrosinase and the structure and function of melanosomes. In the presence of these subtypes, the clinical symptoms and the course of the disease show a pronounced variability, especially in the type and extent of pigmentation of the skin and hair as well as the severity of eye involvement, which makes the phenotypic classification difficult. Treatment priorities are a consistent protection from UV light for prophylaxis against skin cancer and regular preventive investigations. The ocular alterations typical for albinism necessitate timely diagnostics and care by institutions specialized in ophthalmology. Novel strategies for systemic treatment of subtypes of albinism are in preclinical testing. The OA without skin involvement shows X­linked inheritance, is much rarer and is characterized by reduced pigmentation of the retina and iris, nystagmus and macular hypoplasia, sometimes with substantial loss of visual acuity. The typical ocular symptoms of OA can be manifested to a varying extent in all forms of OCA.

[Phenotype of the visual system in oculocutaneous and ocular albinism]. / Phänotyp des visuellen Systems bei okulokutanem und okulärem Albinismus.

In spite of albinism being one of the visual impairments which has been known for over a century, it has only been known for a few decades that albinism is correlated to severe cerebral morphological developmental alterations. The increasing knowledge about the role of melanin in the development and orientation of cerebral neurons not only renders more insight into albinism, but also a greater insight in the physiological neuronal and cerebral development in man. Concerning the morphological and visual phenotype there are new clinical findings which enlarge the known spectrum of albinism. In a representative group of 506 persons with oculocutaneous and ocular albinism who are in care at the Department of Ophthalmology at the University of Saarland (UKS), we present a staging of morphological findings of the iris, retinal pigment epithelium and macula, and of the optic nerve head which has been in use for 10 years. Albinism may present with a remarkably mild ocular phenotype and a near to normal functional phenotype. We present correlations between molecular genetic types of albinism, ocular phenotype and visual function. Of great importance concerning later visual acuity is the dysplasia of the optic nerve head (ONH), which is a frequent finding in albinism. The appearance of the ONH should always be included in any clinical description of an albinism patient. It is highly possible that due to a moderate phenotype there are still many patients who have not been diagnosed yet. Visual acuity of 30/20 to 20/20 and no nystagmus do not rule out albinism. In addition, when performing albino VEPs in phenotypically normal children with infantile strabismus, small ONHs, but normal visual acuity and no nystagmus, the classical atypical chiasmal crossing is sometimes found. Therefore, the number of persons having undiagnosed albinism is probably quite high, perhaps there even is a very broad transition zone from normal to albinotic.

The genes for X-linked ocular albinism (OA1) and microphthalmia with linear skin defects (MLS): cloning and characterization of the critical regions.

We have used cell lines from patients with deletions and translocations involving the Xp22 region to map the genes for two X-linked disorders, ocular albinism type 1 (OA1) and microphthalmia with linear skin defects (MLS). Using existing and newly isolated DNA markers, the map position within Xp22 of key patient breakpoints, defining the boundaries of the genomic regions involved in these disorders (the critical regions), has been precisely determined. A 2.6 Mb yeast artificial chromosome (YAC) contig, spanning the critical regions for these two disorders, was assembled. Detailed long-range restriction analysis of the contig established the sizes of the critical regions to be 200 kb for OA1 and 800 - 925 kb for MLS. Ten potential CpG-islands, representing candidate sites for genes, have been mapped within the 2.6 Mb region. Our data should greatly facilitate efforts aimed at cloning the genes for these developmental defects.