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Biomedical subjects

Dorothea Besch

Publications and source records attributed to Dorothea Besch.

At least 19 recordsLinked to original sources
PubMed2007

Full macular translocation versus photodynamic therapy with verteporfin in the treatment of neovascular age-related macular degeneration: 1-year results of a prospective, controlled, randomised pilot trial (FMT-PDT).

BACKGROUND: The purpose of this study was to compare full macular translocation (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective, randomised, non-masked, mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or PDT. Baseline and control examinations in 3-monthly intervals over a 12-month period included standardized protocol refraction, visual acuity testing and fluorescein angiography. Primary outcome measurements were made to establish the change in distant visual acuity from the baseline to the 12-month examination. The statistical analyses were carried out on the intent-to-treat principle. RESULTS: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five patients) were recorded in the FMT group. None of the eyes treated in the FMT group had phtysis. CONCLUSION: This pilot study showed that no statistically significant difference existed between the FMT and PDT in terms of the vision loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of vision improvement was significantly higher for the patients in the FMT group. However, in the era of promising therapy with anti-vascular endothelial growth factor for neovascular AMD, FMT should not be offered as a standard primary procedure for neovascular AMD.

Aged↗
PubMed2006

Dose, timing and frequency of subconjunctival 5-fluorouracil injections after glaucoma filtering surgery.

BACKGROUND: Although adjunctive postoperative 5-fluorouracil (5-FU) injections are known to improve the success rate of glaucoma surgery, it is still unknown what dose, timing and frequency of application will give the best results with respect to the inhibition of postoperative scarring and intraocular pressure regulation. We therefore designed the following retrospective investigation. METHODS: We studied 172 eyes from 172 patients who had undergone trabeculectomy with adjuvant 5-FU-therapy. Variations of dosage, timing and frequency were analysed retrospectively. Surgery was defined as a complete success when the patient reached an intraocular pressure under 21 mmHg and a reduction of 20% 12 months after the operation. A relative success was achieved with these criteria under additional local medication. Not reaching these postoperative criteria for a complete success was classified as failure. RESULTS: On average, adjunctive 5-FU-treatment was started 4.6+/-5.85 days postoperatively. The injections contained between 2 mg and 5 mg FU, and the mean total dose was 26.6+/-13.2 mg (range 5-65 mg). Surgery on 94 patients (54.65%) was classified as "complete success", that on 25 patients (14.53%) was classified as "relative success" and that on 53 eyes (30.81%) was classified as "failure" 12 months (+/-3 months) postoperatively. The best results were obtained when the treatment started on or before the first postoperative day (68.0-71.4% complete success; P<0.05). In contrast, an increase in 5-FU dosage did not result in an increased success rate of trabeculectomy. None of the 172 patients suffered from vision-threatening complications such as endophthalmitis or hypotony maculopathy. CONCLUSION: Early treatment with 5-FU significantly increases the success rates of filtering surgery.

Adult↗
PubMed2005

Neuroprotective effects of cardiotrophin-like cytokine on retinal ganglion cells.

BACKGROUND: Premature neuronal cell death is a feature of numerous central nervous system and eye diseases, including glaucoma. Neurons (including retinal ganglion cells, RGCs) are protected by several neurotrophic factors, among those the IL-6 family of cytokines. Lately, a novel member of the IL-6 family of cytokines has been identified and cloned. This cytokine is known as novel neurotrophin-1/B-cell-stimulating factor-3 (NNT-1/BSF-3) or cardiotrophin-like cytokine (CLC). It shows neurotrophic as well as B-cell stimulatory effects. METHODS: In this study, the neuroprotective properties of CLC on RGC loss in vivo were investigated. RESULTS: CLC significantly protected RGCs from degeneration in both chosen models of retinal neuronal damage: optic nerve crush (P<0.01) and N-methyl-D-aspartate (NMDA) injection (P<0.001). CONCLUSIONS: CLC shows neuroprotective effects on RGCs in vivo and might be a treatment option for chronic neurodegenerative eye diseases such as glaucoma. Clinical feasibility for the substance requires further investigation since the immunomodulatory and possible adverse effects have not yet been thoroughly characterized.

Animals↗
PubMed2005

Progressive cone dystrophy with deutan genotype and phenotype.

PURPOSE: To study the electroretinographic signals originating in the long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cone pathways by means of large-field and multifocal cone type-specific electroretinograms (ERGs) in a patient with progressive cone dystrophy. METHODS: A 65-year-old male patient with colour vision disturbances (age at onset 10 years), loss of visual acuity (14 years), and central visual field defects (40 years) was investigated. Large-field flicker-ERG responses to stimuli that exclusively modulated the L-cones or the M-cones, or the two simultaneously (both in-phase and in counter-phase), were measured. Short-wavelength-sensitive (S) cones were not modulated. Multifocal ERGs (mfERGs) were also recorded, with a pattern-reversing display that modulated only the L- or the M-cones at equal cone contrasts and average quantal catches. Genetic analysis of L- and M-pigment genes was performed on genomic DNA isolated from peripheral venous blood. RESULTS: The patient showed a normal rod-driven ERG but reduced cone-driven electroretinographic amplitudes with normal implicit times in the International Society for Clinical Electrophysiology of Vision (ISCEV) standard ERG. The large-field flicker-ERG responses to pure L-cone modulation were significantly above noise level but were substantially reduced in comparison with both normal trichromatic subjects and (otherwise normal) deuteranopes. The L-cone driven electroretinographic implicit times and phases were within normal limits. The M-cone driven electroretinographic responses were not detectable. A model fit of all the L- and M-cone driven flicker-ERG data revealed that the responses were exclusively driven by the L-cones. Consistently, the cone type-specific mfERGs showed severely reduced but detectable responses to L-cone-isolating stimuli. The M-cone driven multifocal-ERG responses were undistinguishable from noise. The L- and M-pigment gene array consisted of only a single L-pigment gene. The complete coding sequence of this gene was determined and showed no abnormality. CONCLUSIONS: This patient exhibits a coincidence of progressive cone dystrophy and deuteranopia. The molecular genetic data of the L/M-pigment gene array is consistent with the deutan phenotype. It cannot be excluded that the rearrangement of the X-chromosome pigment gene array is responsible for the cone dystrophy in this patient. It is, however, suggested that the dichromacy and the cone dystrophy have different and independent genetic origins.

Aged↗
PubMed2005

Delayed otogenic hydrocephalus after acute otitis media in pediatric patients: the changing presentation of a serious otologic complication.

CONCLUSIONS: The clinical presentation of otogenic dural sinus thrombosis (DST) as a complication of acute otitis media (AOM) can be masked by antibiotic treatment. Morning episodes of vomiting and/or headache, visual impairment and a history of AOM seem to be indicative of otogenic hydrocephalus. We therefore advocate that the MRI scans of patients with similar symptoms should be carefully studied to facilitate the early diagnosis of a potentially life-threatening complication. OBJECTIVE: To describe the frequency, pathognomonic signs, clinical course and outcome of otogenic hydrocephalus and DST as complications of AOM in pediatric patients. MATERIAL AND METHODS: We undertook a retrospective chart review of all pediatric patients (age 1-14 years) treated for otitis media and its complications at an academic medical center between 1999 and 2003. The main outcome measures were otologic and ophthalmologic findings and CT and MRI scans at the beginning of treatment and 3 months later. RESULTS: We report on five cases with otogenic DST following AOM. All but one of them presented initially with diplopia caused by otogenic hydrocephalus. In four cases the otologic complaints had already disappeared by the time of MRI confirmation of the diagnosis. Only one child was referred with severe otologic symptoms. Management included systemic antibiotics, short-term heparin anticoagulation and surgical decompression. In our cases, even after intensive i.v. antibiotic treatment, only surgery led to a significant improvement in the clinical condition.

Acute Disease↗
PubMed2005

Glare sensitivity and professional drivers' safety: a case of rod-cone dystrophy with negative electroretinogram.

BACKGROUND: To obtain a driver's licence certain requirements for visual acuity and visual field have to be fulfilled. Mesopic contrast and glare sensitivity are not regularly tested and are not crucial to passing the driving test. CASE REPORT: We report a case of a 39-year-old professional bus driver whose only complaint was increased glare sensitivity. After he had been involved in four traffic accidents, ophthalmological investigations revealed binocular annular scotomata and night blindness, leading to the diagnosis of rod-cone dystrophy. DISCUSSION: Enhanced glare sensitivity is a common complaint in elderly people or people with the beginnings of cataract but may also represent an initial symptom of a retinal disorder. It is therefore advisable for traffic safety if drivers with such complaints undergo a complete ophthalmological investigation including visual field testing.

Accidents, Traffic↗
PubMed2004

Visual short-term effects of Viagra: double-blind study in healthy young subjects.

PURPOSE: To investigate short-term visual effects of a single 100-mg dose of Viagra (sildenafil citrate) in healthy men. DESIGN: Randomized, double-blind, placebo-controlled clinical trial of drug effects on normal volunteers conducted by a single center. METHODS: Twenty men, aged 20 to 40 years, were treated with either a placebo or 100 mg sildenafil. Visual function tests included electroretinogram (ERG) recordings, on-/off- and 3.3 Hz-flicker-ERG recordings, anomaloscope matches, and measurements of cone contrast sensitivities and transient tritanopia. RESULTS: Most visual tests did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave, and 3.3 Hz-flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sidenafil plasma concentration. Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant. There were no reports of visual side effects, and all electrophysiologic and psychophysical measurements returned to the normal range within 24 hours. CONCLUSIONS: A single oral dose of 100-mg sildenafil given to healthy young men led to small but statistically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods. Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other PDE5 and PDE6 inhibitors.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Inherited multifocal RPE-diseases: mechanisms for local dysfunction in global retinoid cycle gene defects.

Alterations of retinoid cycle genes are known to cause retinal diseases characterized by focal white dot fundus lesions. Fundus appearances reveal circumscribed RPE-changes, although generalized metabolic defects and global functional abnormalities are present. As a possible explanation, topographic inhomogeneities of the human photoreceptor mosaic and the role of a cone specific visual cycle will be discussed. Due to particular characteristics of photoreceptor subtypes as well as different pathways for photopigment regeneration the metabolic demand of individual RPE cells might differ. In "flecked retina diseases" heterogeneity of metabolic demand in individual RPE cells could therefore be responsible for their multifocal appearance.

Fundus Oculi↗
PubMed2003

Prevention and therapy in hereditary retinal degenerations.

A survey of the present state of developments concerning prevention and therapy of hereditary retinal diseases is given. In recent years the techniques of molecular genetics have led to a rapid identification of a great number of cloned or mapped genes responsible for such diseases. Moreover, further progress has been made in the understanding of disease mechanisms by describing the defective proteins and their altered metabolism. The most recent preventive and therapeutic strategies including gene therapy, dietary regimens, anti-apoptotic agents, transplantation and retinal prosthesis are discussed.

Diet Therapy↗
PubMed2003

MfERG waveform characteristics in the RS1h mouse model featuring a 'negative' ERG.

Several retinal disorders lead to a relatively greater attenuation of the b-wave compared to the a-wave of the electroretinogram (ERG), a constellation called 'negative' ERG. To determine the waveform characteristics of multifocal ERGs (mfERGs) and their dependence on recording parameters in such a case, we studied the Rs1h(-/Y) mouse, the model for x-linked juvenile retinoschisis. mfERGs were recorded with a VERIS 4 system connected to a piggyback stimulator prototype that added the stimulus to the optical pathway of a HRA scanning-laser ophthalmoscope (SLO) by means of a wavelength-sensitive mirror. Real-time fundus visualization was achieved with the infrared laser of the SLO (835 nm). High-pass filter settings and the time interval used by the 'artefact removal' feature were varied to study their influence on the waveform. The mfERG in the Rs1h(-/Y) mouse had a 'negative' shape. However, the high-pass filter setting had to be lowered from the usual 10 Hz down to about 2 Hz in order to obtain that result, otherwise the negative shape was lost and mainly a positive peak remained. Similarly, a short time interval used by the 'artefact removal' feature also removed the negative shape. The Rs1h(-/Y) mouse was found to be a valuable model of diseases with a 'negative' waveform shape also in mfERG. Our results underline the importance of a lower high-pass filter cutoff frequency when recording mfERGs in such disorders. In addition, if the 'artefact removal' feature is used, it should be verified that it doesn't distort the waveform shape.

Animals↗
PubMed2002

Leber's hereditary optic neuropathy: clinical and molecular genetic results in a patient with a point mutation at np T11253C (isoleucine to threonine) in the ND4 gene and spontaneous recovery.

BACKGROUND: Mitochondrial DNA mutations at nucleotide position (np) 3460 in the ND1 gene, np 11778 in the ND4 gene, and np 14484 in the ND6 gene are commonly considered to be associated with the clinical features of LHON and account for the majority of LHON cases. Here we report the clinical and molecular genetic findings of a LHON patient with a new mitochondrial DNA mutation at np 11253 in the ND4 gene and spontaneous recovery. METHODS: The clinical examination consisted of visual acuity measurements, visual field testing, and ophthalmoscopy over a period of 14 years. Total lymphocyte DNA was analyzed for all common LHON mutations. Because the LHON patient did not harbor any of the common or recently described rare LHON mutations, we performed a sequence analysis of the whole mitochondrial genome. RESULTS: The patient exhibited typical clinical features of LHON. Molecular genetic analysis did not reveal any of the common LHON mutations. Sequence analysis of the mtDNA of the patient and his unaffected sister and niece was performed and showed a T to C missense mutation at np 11253 in the ND4 gene, leading to a replacement of an evolutionary highly conserved isoleucine by a threonine residue. This mutation introduces a polar group into a hydrophobic domain of the protein and induces a significant change in hydrophobicity of the peptide sequence. The mutation was not found among 100 controls. CONCLUSION: The fact that the new mutation at np 11253 is found within a highly conserved region and was not present in any controls implies that this mutation is responsible for LHON in this patient. Interestingly, this point mutation has formerly been reported in the mitochondria of the substantia nigra in an unrelated patient with proven Parkinson's disease.

Adult↗
PubMed2002

Sequence analysis of the complete mitochondrial genome in patients with Leber's hereditary optic neuropathy lacking the three most common pathogenic DNA mutations.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by central vision loss in young adults. The majority of LHON cases around the world are associated with mutations in the mitochondrial genome at nucleotide positions (np) 3460, 11,778, and 14,484. Usually, these three mutations are screened in suspected LHON patients. The result is important not only in respect to the diagnosis but also as different LHON mutations lead to variations in expression, severity, and recovery of the disease. There are, however, a significant number of patients without any of these primary mutations. In these situations, genetic counselling of a patient and his family can be difficult. We sequenced the complete mitochondrial DNA (mtDNA) in 14 LHON patients with the typical clinical features but without a primary mtDNA mutation to evaluate the potential of extensive mutation screening for clinical purposes. Our results suggest to include the mutation at np 15,257 in a routine screening as well as the ND6 gene, a hot spot for LHON mutations. Screening for the secondary LHON mutations at np 4216 and np 13,708 may also help in making the diagnosis of LHON as these seem to modify the expression of LHON mutations. Although they do not allow to prove the clinical diagnosis, their presence increases the probability of LHON. Sequencing the complete mitochondrial genome can reveal novel and known rare disease causing mutations. However, considering the effort it adds little value for routine screening.

Adolescent↗
PubMed2002

Ten novel ORF15 mutations confirm mutational hot spot in the RPGR gene in European patients with X-linked retinitis pigmentosa.

RGPR was the first gene found to be mutated in XLRP, the subtype of RP displaying the most severe form of retinal degeneration with partial or complete blindness in the third or fourth decade of life. Despite the RP3 locus on Xp21.1 accounting for 60-90% of XLRP, only 10-20% of identified RPGR mutations were reported in earlier analyses. This discrepancy appeared to be resolved when Vervoort et al. identified a mutational hot spot in a new purine-rich 3' exon (ORF15) that accounted for 60% of their XLRP patients [Vervoort et al., 2000]. In our mutation screening of 37 unrelated European XLRP patients we identified two recently described deletions and 10 novel mutations in exon ORF15 of RPGR, 4 of which were nonsense and 6 frameshift mutations. The latter included one duplication and 5 deletion mutations, all of which lead to a downstream premature termination. No mutations were detected in the additionally screened new exon ORF14. The data reported here, together with previous findings, document a significant clustering of mutations as well as polymorphisms in ORF15 of RPGR. In our unselected XLRP patient population, ORF15 mutations constitute 32% of cases, a finding that contradicts the results of Vervoort and coworkers [Vervoort et al., 2000] but is in agreement with a more recent study on North American XLRP patients [Breuer et al., 2002]. The observed prevalence is sufficient to justify an initial mutation screening of ORF15 in the genetically heterogeneous group of XLRP.

Carrier Proteins↗
PubMed2002

A mutational hot spot in the mitochondrial ND6 gene in patients with Leber's hereditary optic neuropathy.

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by rapid bilateral loss of central vision. Most patients harbor one of three mutations in the mitochondrial DNA. In order to identify the genetic cause of the disease in one LHON patient without any of the three primary mutations, we sequenced the mitochondrial genome. METHODS: Ophthalmological examination was performed in the affected person and his unaffected relatives. The complete mitochondrial protein coding region was sequenced in the patient. RESULTS: Clinical examination of the affected 10-year-old Turkish boy showed typical features of LHON. Peripapillary microangiopathy was also seen in relatives of the maternal line. Sequence analysis revealed a point mutation at position 14482 in the mitochondrial ND6 gene that changes a conserved methionine residue to isoleucine. A mutation at this nucleotide position has been previously suggested to be of pathogenic significance and has not been detected in any controls. CONCLUSIONS: We have identified that the mutation at nucleotide position 14482 which is the eight mutation in the ND6 gene that causes LHON, making this gene a hot spot for the disease. All eight identified mutations in the ND6 gene lie within the evolutionarily most conserved region of the ND6 gene in a hydrophobic pocket. This may help in understanding the pathomechanism of LHON.

Child↗
PubMed2002

Abnormalities of the long flash ERG in congenital stationary night blindness of the Schubert-Bornschein type.

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.

Adolescent↗