We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.

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PURPOSE:To compare different methods for the assessment of disability glare sensitivity in the elderly, to arrive at an objective assessment of the condition of the eye. To delineate the importance of straylight values in vision. METHODS: Three groups of subjects were studied: 1) Young subjects without any eye disease, 2) elderly subjects without any eye disease and 3) elderly subjects with (early) cataract in at least one eye. All subjects underwent 2 glare tests, 2 straylight tests, ETDRS visual acuity test, Pelli Robson contrast sensitivity test, refraction, LOCS III cataract classification. Straylight was quantified by means of the straylight parameter s. RESULTS: Repeatability, discriminative ability, and added value as compared to visual acuity were low for the glare tests and good for the straylight measurements. For young normal subjects, with log(s)=0.9, the standard glare situation with low beams gives a contrast reduction of 1.3, whereas for the healthy 77 year olds this increases to 2. With cataract hardly affecting visual acuity, log(s) can be as high as 1.8, resulting in a contrast reduction of 3.4. CONCLUSION: Straylight measurement is of relevance for the assessment of the glare-related hindrance during driving, and can be used to objectify complaints and aid in the decision-making regarding cataract surgery. (J Optom 2009;2:112-118 ©2009 Spanish Council of Optometry) KEY WORDS: straylight; glare sensitivity; disability glare; CIE; aging; driving. RESUMEN OBJETIVO:Comparar diferentes métodos para medir la sensibilidad al deslumbramiento perturbador en sujetos de edades avanzadas, con el fin además de lograr una valoración objetiva de las afecciones oculares. Definir la importancia que tiene la luz dispersa (parásita) sobre la visión. MÉTODOS: Se estudiaron tres grupos de sujetos: 1) Sujetos jóvenes sin ningún tipo de afección ocular, 2) sujetos de edad avanzada sin ningún tipo de afección ocular y 3) sujetos de edad avanzada con cataratas (incipientes) en, al menos, uno de los ojos. A todos los sujetos se les realizaron, entre otras, 2 pruebas de deslumbramiento y 2 pruebas de luz dispersa, se les midió la agudeza visual mediante optotipos ETDRS (siglas en inglés del Estudio sobre el tratamiento temprano de la retinopatía diabética), la sensibilidad al contraste con el test de Pelli-Robson, la refracción, y se clasificó la catarata (para sujetos del tercer grupo) utilizando el Sistema de Clasificación de Opacidades del Cristalino( o sus siglas en inglés, LOCS III). La luz dispersa (parásita) se cuantificó por medio del parámetro de luz dispersa s. RESULTADOS: La repetibilidad, la capacidad discriminativa, y el valor añadido, resultaron ser bajos para los tests de deslumbramiento pero buenos para las medidas de la luz dispersa (en comparación con los valores que proporciona la medida de la agudeza visual). Para los sujetos jóvenes sin patologías oculares, con log(s)=0,9, la situación habitual de deslumbramiento con haces bajos causa una reducción del contraste del 1,3, mientras que para l...

We investigated abnormalities of the retinal cone ON- and OFF-pathways in 24 males with Schubert-Bornschein congenital stationary night blindness (CSNB). Substantial differences were found between both CSNB types. In incomplete type, a-, b- and d-waves were reduced and delayed, whereas in complete type only the b-wave showed significant changes. Oscillatory potentials (OPs) were not discernible from noise in incomplete CSNB and showed significant peak alterations of the ON-OPs only in complete CSNB. In the complete CSNB type, the ON pathway appeared to be mainly affected. In the incomplete CSNB form marked involvement of both the ON and the OFF pathways was noted.

Murex hybrid capture DNA assay (HCS) is a solution hybridization antibody capture assay for detection and quantitation of cytomegalovirus (CMV) DNA in leukocytes. To determine whether CMV HCS is sensitive enough to initiate and monitor antiviral therapy after allogeneic stem cell transplantation (SCT), 51 consecutive SCT recipients were prospectively screened for the appearance of CMV infection by HCS, PCR, and culture assays from blood samples. Preemptive antiviral therapy was initiated after the second positive PCR result in all patients, as previously reported, and HCS was not considered for clinical decision making. A total of 417 samples were analyzed. Of these, 21 samples were found to be positive by PCR and HCS, 88 samples were PCR positive but HCS negative, and 308 were negative by both assays. Concordance of results between PCR and HCS and between HCS and blood culture was observed in 78.9 and 95.9% of the samples assayed, respectively. PCR was found to be more sensitive than HCS, and HCS was more sensitive than the blood culture assay (P < 0.0001). Four patients with symptomatic CMV infection were PCR positive prior to the onset of CMV-related symptoms, whereas HCS detected CMV DNA in three patients prior to and one at onset of CMV disease. The numbers of genomes per milliliter of blood were higher in patients with symptomatic CMV infection than in those with asymptomatic CMV infection (P = 0.06). None of the HCS-negative patients developed CMV disease. Thus, all patients with CMV disease were correctly identified by HCS; however, the lower sensitivity limit of the HCS assay may still be insufficient to allow diagnosis of CMV infection early enough to prevent CMV disease in patients following allogeneic SCT.