Stimulus investigative range in the perimetry of retinitis pigmentosa: some preliminary findings

The manipulation of perimetric stimulus parameters over a given dynamic range has been reported to provide diagnostic information additional to that of changes in differential sensitivity. Preliminary studies (Flanagan et al., 1984a) have indicated that the perimetric response in retinitis pigmentosa behaves atypically over a range of stimulus combinations and strategies. The current study investigated the perimetric response of 17 retinitis pigmentosa patients of various genetic types over a range of stimulus parameters (target size, presentation time and background luminance) and test strategies (kinetic and threshold static) using the Octopus automated perimeter, the Goldmann and Tubinger bowl perimeters and the Dicon Autoperimeter 3000. Statokinetic dissociation was found to be present with large target sizes at 10 asb and 31.5 asb bowl luminances. Some patients demonstrated enhanced sensitivity to shorter stimulus presentations.     

Parallel visual processes in symmetry perception: Normality and pathology

Mirror symmetry is one of those regularities for which the visual system seems to have developed a special sensitivity. It is detected robustly and efficiently in a single glance, suggesting that the basic processes do not perform a serial, pointwise comparison of structural elements but rather operate in parallel. Psychophysical evidence relating to the processing mechanisms will be reviewed. Although the focus will be on symmetry perception in normal vision, interesting findings on symmetry perception in observers with deficient vision (e.g., retinitis pigmentosa, visual hemineglect) will also be touched upon briefly. This revised version was published online in July 2006 with corrections to the Cover Date.     

Accumulation of tissue inhibitor of metalloproteinases-3 in human eyes with Sorsby's fundus dystrophy or retinitis pigmentosa

BACKGROUND/AIMS—Tissue inhibitor of metalloproteinases-3 (TIMP-3) is normally synthesised by the retinal pigment epithelium (RPE) and deposited in Bruch's membrane. Mutations in the TIMP3 gene cause Sorsby's fundus dystrophy (SFD), which is characterised by thickening of Bruch's membrane, choroidal neovascularisation, and photoreceptor degeneration. To elucidate the role of TIMP-3 in human retinal degenerative diseases, we immunolocalised TIMP-3 in eyes with SFD caused by the Ser-181-Cys TIMP3 gene mutation or retinitis pigmentosa (RP; not caused by TIMP3 mutations).
METHODS—Standard light microscopic immunocytochemistry, including antigen retrieval, was used to localise TIMP-3 in paraffin sections of human eyes: two with SFD, three with different genetic forms of RP, and two normal.
RESULTS—In the SFD eyes, the thickened Bruch's membrane was strongly TIMP-3 positive except where RPE cells had degenerated. Similarly, in the RP eyes, Bruch's membrane was TIMP-3 positive except where RPE cells were lost, consistent with ongoing RPE mediated turnover of TIMP-3 in this region. In areas of total photoreceptor loss, migrated RPE cells formed cuffs around blood vessels in the RP retinas. Thick, TIMP-3 positive extracellular matrix (ECM) deposits associated with the migrated RPE cells occluded some vascular lumina, correlating with the observed loss of inner retinal neurons in RP.
CONCLUSIONS—TIMP-3 is a component of the increased ECM sequestered in Bruch's membrane in SFD. Further information is needed on normal TIMP-3/ECM interactions in Bruch's membrane and the effect of mutant TIMP-3 on this process. The finding of TIMP-3 accumulations in retinas with RP not caused by TIMP-3 mutations emphasises the importance of ECM remodelling in normal and diseased human eyes.

Keywords: tissue inhibitor of metalloproteinases-3; Sorsby's fundus dystrophy; retinitis pigmentosa; inherited retinal diseases     

Usher syndrome: increasing awareness in Scotland

Summary In July 1993, professionals from a number of European countries met at the 7th European Usher Syndrome Study Group. The purpose of the Study Group (which meets on a biannual basis) is to give professionals working in this specialized field the opportunity to share ideas and examples of their work. People attending included medical practitioners, social service workers, representatives from voluntary bodies and individuals with Usher. The following article is an expanded version of a paper presented at the Study Group. It describes the development of a 3 hour workshop for the wide range of practitioners a child or young person with Usher syndrome may meet. Through group work, positive approaches to working through the personal and practical implications of Usher syndrome are explored.     

A diagnostic approach to syndromic retinal dystrophies with intellectual disability

Inherited retinal dystrophies are a group of monogenic disorders that, as a whole, contribute significantly to the burden of ocular disease in both pediatric and adult patients. In their syndromic forms, retinal dystrophies can be observed in association with intellectual disability, frequently alongside other systemic manifestations. There are now over 80 genes implicated in syndromic retinal dystrophies with intellectual disability. Identifying and accurately characterizing these disorders allows the clinician to narrow the differential diagnosis, evaluate for relevant associated features, arrive at a timely and accurate diagnosis, and address both sight‐threatening ocular manifestations and morbidity‐causing systemic manifestations. The co‐occurrence of retinal dystrophy and intellectual disability in an individual can be challenging to investigate, diagnose, and counsel given the considerable phenotypic and genotypic heterogeneity that exists within this broad group of disorders. We performed a review of the current literature and propose an algorithm to facilitate the evaluation, and clinical and mechanistic classification, of these individuals.     

Mastocytosis

Variants of mastocytosis can present with puzzling cutaneous and systemic symptoms and signs that can result in an erroneous diagnosis of idiopathic urticaria or idiopathic anayphylaxis. The molecular basis of mastocytosis is now better understood, with updated classification based on distinct growth factor and oncogene abnormalities. Elicitation of a full history and careful attention to the skin examination will usually provide the clinician enough information to deduce that the condition is not simply chronic idiopathic urticaria. This article was presented at the American College of Asthma, Allergy, and Immunology Annual Meeting in Anaheim, CA, November 6, 2005.     

A patient homozygous for the SCA6 gene with retinitis pigmentosa

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.     

Pigmentary degeneration indwed by N-methyl-N-nitrosourea and the fate of pigment epithelial cells in the rat retina

Pigmentary degeneration of the retina was induced by a single intraperitoneal Injection of 75mgkg of N-methyl-N-nitrosourea (MNU) In female Brown-Norway colored rats at 50 days of age, which were then observed at 24, 48 and 72 h and 7, 21,35 and 150 days after the treatment. MNU-treated rats showed selective destruction of the photoreceptor cells by an apoptotic mechanlsm 24 h after the treatment, and the destruction was completed by day 7. During the photoreceptor cell degeneration, proliferation of Miller cells and infiltratlon of macrophages was prominent 72h and 21 days aRttr the treatment, respectively. Müller cell proliferation and macrophage infiltratbn corresponded to degenerative photo-receptor cell phagocytosis, and prollferating Müller cell processes responded to stabilize the damaged retina. Pigment epithelial cell detachment from the Bruch's membrane was seen 72 h after the treatment, and migration within all layers of the retina was seen at day 7 when photoreceptor Cells were lost. At 21, 35 and 150 days after the treatment, lack of photoreceptor cells and deposition of pigment epithelial cells within the retina but not in contact to vascular endothe-lial cells were characteristic. MNU-induced photoreceptor apoptosis followed by Miiller cell and macrophage reaction then pigment epithellal cells deposition withln the retina partially resembles retinitis pigmentosa in humans.