Matthias Becker

Normal values for fundus perimetry with the scanning laser ophthalmoscope

PURPOSE To evaluate the normal light sensitivity values for fundus perimetry and their short time fluctuation (reliability) in normal volunteers of different ages. After the development of full-threshold static fundus perimetry, age-corrected sensitivity values for normal subjects are required to interpret results and to compare them with conventional computerized perimetry. METHOD Full-threshold fundus perimetry of the central field (33 x 21 degrees) by means of the scanning laser ophthalmoscope was performed on 152 eyes of 99 healthy persons aged 16 to 77 years with normal vision and no eye disease. Fixation was simultaneously documented. Light sensitivity values were evaluated according to each subjects age and test point location. RESULTS Linear regression analysis disclosed a significant (P < .0001) decrease of the mean sensitivity of 0.275 dB per decade of increasing age, starting with 16.6 dB at age 10 years. Standard deviation around the center of fixation was 0.287 degrees in the first decade, and it increased by 2.82 minutes of arc per decade (P < .0001). Variation in triple examinations of subjects did not differ from short time fluctuation. CONCLUSION Visual fields examined with fundus perimetry show reliable measurements in a range comparable to conventional computerized perimetry. There is a significant correlation between increase of age and decrease of light sensitivity in fundus perimetry. Visual fields obtained with fundus perimetry seem to correlate well with known data from computerized static threshold perimetry. It should be recognized that even in normal subjects, the stability of fixation decreases with increasing age.

Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization

PURPOSE To assess the role of bevacizumab in inflammatory ocular neovascularization. DESIGN Retrospective, multicenter, consecutive case series of inflammatory ocular neovascularization. METHODS Patients with inflammatory ocular neovascularization of varying causes for whom standard therapy failed were treated with intravitreal injection of bevacizumab. Main outcome measures included improvement of best-corrected visual acuity (BCVA) expressed in logarithm of minimum angle of resolution units, response of inflammatory ocular neovascularization by funduscopy and angiography, and decrease in central foveal thickness as measured by optical coherence tomography at the three-month follow-up. RESULTS At the three-month follow-up, 84 eyes of 79 patients had been treated with a mean of 1.3 injections (range, one to three). Thirty-four eyes showed juxtafoveal choroidal neovascularization (CNV), 34 eyes showed subfoveal CNV, eight eyes showed peripapillary CNV, and 11 eyes showed neovascularization of the disc (NVD) or neovascularization elsewhere (NVE). BCVA improved 2.4 lines from 0.68 (6/28 or 20/94) to 0.44 (6/17 or 20/55) (P < .001). BCVA improved by one to three lines in 34.5% of the eyes, by four to six lines in 16.7% of the eyes, and by more than six lines in 14.2% of the eyes. Function was unchanged in 23.8% of the eyes. BCVA worsened in 10.7% (zero to three lines in 7.1%, more than four lines in 3.6%). Central foveal thickness decreased from baseline 346 to 252 microm (P < .001). For CNV, 32 eyes (43.2%) had complete regression after the injection, 27 (36.5%) had partial regression, five (6.8%) had no response, and 10 eyes (13.5%) were not evaluated by the contributors. For NVD or NVE, seven eyes (63.6%) had complete regression of new vessels and four eyes (36.4%) had partial regression after the injection. CONCLUSIONS Intravitreal bevacizumab led to short-term significant visual improvement and regression of inflammatory ocular neovascularization in a wide variety of inflammatory ocular diseases.

Scanning laser fundus perimetry before laser photocoagulation of well defined choroidal neovascularisation

AIM To assess the centre of fixation before laser photocoagulation of well defined juxtafoveal or extrafoveal choroidal neovascularisation (CNV) secondary to age related macular degeneration (AMD), and to better predict visual function after treatment using scanning laser ophthalmoscope (SLO) fundus perimetry. METHODS 19 consecutive eyes with juxtafoveal or extrafoveal CNV were examined by fundus perimetry before and after laser treatment with documentation of the fixation point using the SLO. The stability of fixation was defined as standard deviation around the mean fixation point. Overlays of fluorescein angiographic pictures and fundus perimetry were obtained using image analysis software. RESULTS Fundus perimetry allowed accurate determination of the centre of fixation. Overlays demonstrated the precise geographic relation of the angiographically detectable foveal margin of the CNV and the centre of fixation. Thereby, prediction of the visual outcome with regard to reading ability was facilitated. Stability of fixation did not change significantly after treatment. CONCLUSIONS Fundus perimetry using the SLO was helpful in patients who underwent laser treatment for juxtafoveal or extrafoveal CNV secondary to AMD and may aid the pretreatment counselling of such patients.

Stability of liposomes containing bio-enhancers and tetraether lipids in simulated gastro-intestinal fluids.

The stability of egg phosphatidylcholine (EPC) and cholesterol (Chol) based liposomes and liposomes with the addition of the tetraether lipid glycerylcaldityl tetraether (GCTE) and the bio-enhancers cholylsarcosine, octadecanethiol and TPGS 1000 in Tris buffer pH 2, sodium taurocholate 10mM and pancreatin was compared. At pH 2 all formulations released nearly 100% of the small hydrophilic fluorescent marker carboxyfluorescein (CF) within the first 10min, whereas they were mostly stable in size as confirmed by dynamic light scattering (DLS) measurements. Also leakage of the macromolecule FITC-dextran 70kDa over 60min at pH 2 was at most 23.9%. After 20min in 10mM sodium taurocholate vesicles without GCTE showed a release of CF between 84.0% and 89.5%. In contrast, GCTE-stabilised formulations after 90min in sodium taurocholate exhibited a CF release between 36.6% and 69.0% depending on the addition of bio-enhancers. Pancreatin had a minor influence on liposome stability in all assays. It is possible to form EPC/Chol vesicles containing different types of bio-enhancers and to stabilise them with GCTE against bile salts. This type of liposomes could be a versatile tool for the oral delivery of drug substances with poor stability in the GI tract and low permeability.

Characterisation of uveitis in association with multiple sclerosis

Purpose To characterise uveitis in association with multiple sclerosis (MS). Methods We conducted a retrospective chart review of patients with uveitis and MS at two uveitis centres (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patients first and last visits. Additionally, neurological records were obtained when possible. Results We identified 113 patients (196 eyes) with uveitis and MS. Of these, 53 had a diagnosis of MS confirmed by review of neurological records, 50 additional patients fulfilled the Poser criteria for MS and 10 with MS were referred by an outside neurologist. Among them, 83 (73%) were women and the mean age of presentation was 40.6 years (range 13–64 years). The average visual acuity in affected eyes at presentation was 20/39. There were 90 patients (80%) who presented with intermediate uveitis and 24 patients (15%) with anterior uveitis. Posterior and pan-uveitis were found in four patients (3%) and two patients (2%), respectively. During a median follow-up of 3.2 years (range 0.04–21 years), visual acuity improved –0.09 logMar/year. Compared with our location-matched controls with idiopathic intermediate uveitis (n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis (p=0.027) and more likely to be female (p=0.01). There was no statistical difference in visual acuity or rate of vision change between our cases and controls (p=0.58 and p=0.36, respectively). Conclusions Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be women than patients with idiopathic intermediate uveitis. The visual prognosis is generally favourable.

Lack of Consensus in the Diagnosis and Treatment for Ocular Tuberculosis among Uveitis Specialists

Abstract Purpose: To assess the approach of specialists to ocular tuberculosis (TB). Methods: The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Results: Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1–75%) or that a patient with a risk factor for TB had ocular TB (range 0–90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Conclusions: Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Change in choroidal thickness after intravitreal aflibercept in pretreated and treatment-naive eyes for neovascular age-related macular degeneration

Aim Evaluation of effects of intravitreal aflibercept therapy on choroidal thickness (CT) in neovascular age-related macular degeneration. Methods Retrospective cohort study evaluating the change in CT following a loading dose of three intravitreal aflibercept injections at 4 weeks interval. Pretreated and treatment-naive eyes as well as untreated fellow eyes were evaluated at five retinal locations (subfoveal, 300 and 2500 µm nasal and temporal to the fovea) using spectral domain optical coherence tomography prior to and 4 weeks after a loading dose of three intravitreal aflibercept injections. Results A total of 84 treated eyes (61 pretreated, 23 treatment naive) and 48 fellow eyes were enrolled into the study. Treatment-naive and pretreated eyes showed a significant reduction in CT at all retinal locations. The effect was more pronounced in treatment-naive eyes. In the pretreated group, the mean reduction in CT was greatest at 2500 µm temporal to the fovea at 10.7 µm compared with 22.4 at 300 µm nasal to the fovea in the treatment-naive group. Only the fellow eyes in the treatment-naive group showed a significant CT reduction 12 weeks after initiation of therapy to the partner eye. Conclusions Aflibercept induces a reduction in CT in treatment-naive and pretreated eyes with neovascular age-related macular degeneration. There is some evidence of a systemic effect of aflibercept reflected by CT reduction in untreated fellow eyes.

Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction

Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP. The SRP72-PBD is a tetratricopeptide repeat, which binds an extended linear motif of SRP68 with high affinity. The SRP72-RBD is a flexible peptide crawling along the 5e- and 5f-loops of SRP RNA. A conserved tryptophan inserts into the 5e-loop forming a novel type of RNA kink-turn stabilized by a potassium ion, which we define as K+-turn. In addition, SRP72-RBD remodels the 5f-loop involved in ribosome binding and visualizes SRP RNA plasticity. Docking of the S domain structure into cryo-electron microscopy density maps reveals multiple contact sites between SRP68/72 and the ribosome, and explains the role of SRP72 in the SRP pathway.

Familial juvenile macular dystrophy with congenital hypotrichosis capitis

SummaryBackground: Our knowledge about the pathogenesis of hereditary macular diseases is still very circumscript. For genetic determination, a knowledge of the coincidence of eye symptoms and other defined common symptoms is helpful. The purpose of this paper was to present two sisters of a family of consanguineous parents with the combination of hypotrichosis of the head and macular dystrophy in the context of a tricho-ocular malformation of an ectodermal dysplasia. A review of the recent literature is included. Patients and methods: Two 13- and 17-year-old sisters presented at our hospital with reduced visual acuity because of symmetrical central changes of the retinal pigment epithelium and chorioatrophic scars according to macular dystrophy combined with hypotrichosis capitis. We performed fundus perimetry and histological examinations of the hair. Results: The 13-year-old patient exhibited central changes of the retinal pigment epithelium leading to a relative central scotoma for Goldmann I/4 during fundus perimetry in both eyes (visual acuity 0.125 and 0.4). We found central chorioatrophic scars, followed by absolute central scotomas, with unstable fixation in the upper retinal hemisphere in her 17-year-old sister with reduced visual acuity (0.16 and 0.2). Conclusion: There are few descriptions of the association of macular dystrophy and hypotrichosis. The combination of hypotrichosis and macular dystrophy could make genetical analysis easier. Mutational analysis of the TIMP-3 gene that has previously been associated with Sorsby fundus dystrophy did not reveal any disease-causing mutations in our patients.Fragestellung: Die Pathogenese von erblichen Makulaerkrankungen ist weitgehend ungeklärt. Das Zusammentreffen von Augenbefunden mit anderen definierten Symptomen kann eine genetische Determination vereinfachen. Ziel dieser Arbeit war die Vorstellung von 2 Schwestern einer Familie konsanguiner Eltern mit der Befundkombination aus einer Hypotrichose des Kopfhaars im Sinn einer ektodermalen Dysplasie und einer Makuladystrophie. Diese Fälle werden im Kontext mit den Literaturberichten dargestellt. Patienten und Methode: Zwei 13- und 17 jährige Schwestern stellten sich mit beidseitig herabgesetzter Sehschärfe bei jeweils symmetrisch ausgeprägten zentralen Depigmentierungen bzw. chorioatrophischen Narben im Sinn einer Makuladystrophie in Kombination mit einer Hypotrichose des Kopfhaars in unserer Klinik vor. Wir führten fundusperimetrische Untersuchungen sowie dermatologischerseits histologische Untersuchungen der Haare durch. Ergebnisse: Bei der 13 jährigen Patientin bestanden bei ringförmigen Depigmentierungen beidseits relative Zentralskotome für die Marke I/4 in der Fundusperimetrie (Visus 0,125 und 0,4). Die 17 jährige Schwester zeigte beidseits zentrale, chorioatrophische Narben, denen absolute Zentralskotome mit instabiler, in die obere Netzhauthemisphäre verlagerter Fixation entsprachen (Visus 0,16 und 0,2). Schlußfolgerung:Über eine Assoziation von Makuladystrophie und Hypotrichose gibt es bisher wenige Beschreibungen, von denen nur das fundoskopische Bild der von Ludvig 1963 beschriebenen Familie dem Befund unserer Patientinnen vergleichbar ist. Das kombinierte Auftreten von Hypotrichose und Makuladystrophie könnte eine genetische Analyse erleichtern. Eine molekulargenetische Untersuchung unserer Patientinnen im TIMP3-Gen, das für die Sorsby-Fundusdystrophie verantwortlich zeichnet, ergab keine krankheitsassoziierten Veränderungen.

The Treatment of Uveitic Cataract

Cataract formation is an especially common complication resulting from uveitis. It is rare in posterior uveitis, but occurs in up to 50% of patients with anterior and intermediate uveitis (21), and in nearly 80% of patients with Fuchs heterochromic iridocyclitis (FHC). Duration and intensity of inflammation, and treatment, e.g. corticosteroids and previous vitrectomy, are critical determinants for cataract formation. Compared with the general population, cataract formation occurs at an earlier age in uveitis patients (36).