[Clinical findings in a patient with Lowe syndrome and a splice site mutation in the OCRL1 gene]. / Klinische Befunde eines Patienten mit Lowe-Syndrom und einer Splice Site Mutation im OCRL1-Gen.

The oculo-cerebro-renal syndrome of Lowe (OCRL) is a rare X-chromosomal disorder characterised by the triad of congenital cataracts, renal tubular dysfunction, and mental retardation. Typically complete opacification and discoid deformation of the lenses are seen, indicating a developmental defect in early embryogenesis. We report on a 35-year-old patient with a mild Lowe syndrome phenotype including incomplete lenticular opacities. Clinical findings suggest that the gene product of the mutated allele (IVS19 + 1G > A) identified in the patient exhibits some residual function.

[Photodynamic therapy in classic chorioidal neovascularisation in patients with angioid streaks]. / Photodynamische Therapie mit Verteporfin bei klassischer chorioidaler Neovaskularisation bei Patienten mit Angioid Streaks.

BACKGROUND: The development of subfoveal or juxtafoveal choroidal neovascularisation (CNV) secondary to angioid streaks poses a great therapeutic challenge. The relevance of the photodynamic therapy (PDT) with verteporfin is still unclear. We present the functional and anatomic outcome of 5 patients with CNV due to angioid streaks treated by PDT. METHODS: We reviewed 4 eyes with subfoveal and 1 eye with juxtafoveal CNV in angioid streaks of 5 patients (4 male, 1 female) treated by PDT between 2000 and 2005. The age ranged from 20 to 74 years (median 63 years). PDT was performed according to the TAP criteria. Best corrected visual acuity was measured using ETDRS charts. RESULTS: Visual acuity (VA) ranged between 20/63 and 20/32 (median 20/32) at first presentation and between 20/2000 (counting fingers) and 20/20 (median 20/400) at last presentation. Median follow-up time was 13 months with a range of 5 to 45 months. The visual acuity in one patient decreased by 1 line, in 3 patients by more than 6 lines whereas VA of one patient (juxtafoveal CNV) increased by 2 lines. PDT was repeated in 4 patients once because of persistent leakage and in one patient twice. At the end of the follow-up period a fibrous disciform lesion was seen in 4 patients, in one patient subfoveal membranectomy was performed due to a recurrence. CONCLUSIONS: In general, PDT of CNV is less favourable in angioid streaks than in AMD. However, in the natural course final VA is counting fingers. Therefore the good results of individual cases justify the PDT under a critical indication.

Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration.

AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment. RESULTS: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.

Imaging of retinal autofluorescence in patients with age-related macular degeneration.

BACKGROUND: Several studies have demonstrated an accumulation of autofluorescent materials in the retinal pigment epithelium (RPE) with increasing age. Histologic analysis revealed that lipofuscin is the most potential fluorescent substance in the aging RPE. Therefore, it has been speculated that lipofuscin precedes the presence of drusen and the development of age-related macular degeneration (ARMD). METHOD: A scanning laser ophthalmoscope was used to visualize autofluorescence in the fundus of patients with early ARMD. The digital recordings were analyzed offline with a digital image analyzing system. RESULTS: In 85 of 103 patients, focal areas of increased autofluorescence were visible. Areas of hyperpigmentation at the level of the RPE showed increased autofluorescence in all cases, whereas areas of depigmentation demonstrated decreased autofluorescence. CONCLUSION: Patients with ARMD demonstrated focal accumulation of fluorescent material most likely lipofuscin. Thus, the scanning laser technique combined with an image analyzing system may help to identify eyes at risk for developing exudative ARMD.

Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon.

Acetohydroxy acid synthase (AHAS) and isomeroreductase (IR) catalyze subsequent reactions in the flux of metabolites towards isoleucine, valine, leucine, and pantothenate. A 4,705-bp DNA fragment from Corynebacterium glutamicum known to code for AHAS and IR was sequenced and analyzed by Northern (RNA blot) analysis. As in other bacteria, the AHAS of this gram-positive organism is encoded by two genes, ilvB and ilvN. Gene disruption verified that these genes encode the single AHAS activity in C. glutamicum. The start of ilvB was determined by amino-terminal sequencing of a fusion peptide. By Northern analysis of the ilvBNC cluster, three in vivo transcripts of 3.9, 2.3, and 1.1 kb were identified, corresponding to ilvBNC, ilvNC, and ilvC messages, respectively. The ilvC transcript (encoding IR) was by far the most abundant one. With a clone from which the ilvB upstream regions had been deleted, only the ilvNC and ilvC transcripts were synthesized, and with a clone from which the ilvN upstream regions had been deleted, only the smallest ilvC transcript was formed. It is therefore concluded that in the ilv operon of C. glutamicum, three promoters are active. The amounts of the ilvBNC and ilvNC transcripts increased in response to the addition of alpha-ketobutyrate to the growth medium. This was correlated to an increase in specific AHAS activity, whereas IR activity was not increased because of the relatively large amount of the ilvC transcript present under all conditions assayed. Therefore, the steady-state level of the ilvBNC and ilvNC messages contributes significantly to the total activity of the single AHAS. The ilvC transcript of this operon, however, is regulated independently and present in a large excess, which is in accord with the constant IR activities determined.