PubMed Health⌕ Search

Biomedical subjects

F Ziemssen

Publications and source records attributed to F Ziemssen.

At least 19 recordsLinked to original sources

Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age-related macular degeneration.

BACKGROUND: The purpose of the study is to report data on short-term safety of intravitreal bevacizumab treatment and its effect on visual function, central retinal thickness, and angiographical changes of occult choroidal neovascularization due to age-related macular degeneration. METHODS: A consecutive interventional case series of 30 patients with active subfoveal occult choroidal neovascularization secondary to age-related macular degeneration was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline and subsequent injections following standardized criteria. At baseline and follow-up visits patients had visual acuity assessment, intraocular pressure measurement, fluorescein angiography, and optical coherence tomography imaging. RESULTS: No serious ocular or systemic adverse events were identified. A significant increase of intraocular pressure or signs of retinal toxicity or endophthalmitis were not detected in any patient. Optical coherence tomography revealed significant decrease (p < 0.001) in central retinal thickness after 1 week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1 week and improvement was maintained at week 12 in the majority of patients. Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3 or more lines was seen in 14 of 30 patients; one patients showed improvement of 6 lines. No patient had severe vision loss of 6 lines or more; moderate vision loss of 3 lines was seen in one patient. Re-injections of bevacizumab according to standard criteria were performed one to two times during the follow-up period of 12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks). CONCLUSIONS: Short-term results suggest that intravitreal injection of bevacizumab is well tolerated and for the majority of patients with occult choroidal neovascularization in AMD results in improvement of visual acuity, decrease in central retina thickness, and reduction of angiographic leakage of the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic option for selected patients with exudative AMD. Randomized prospective multicenter trials seem justified to further evaluate long term effects and impact of intravitreal bevacizumab on different subtypes of AMD compared to established therapies.

Aged↗

Effects of bevacizumab on retinal function in isolated vertebrate retina.

BACKGROUND: Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. METHODS: Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. RESULTS: During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. CONCLUSION: The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.

Angiogenesis Inhibitors↗

Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular membranes.

AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age related macular degeneration. METHODS: Retrospective review of 22 surgically excised CNV. 12 of these patients had been treated with PDT 3-146 days previously. Apoptotic cells were detected with the TUNEL technique and compared to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised both by collapsed and patent vessels. The EC displayed a statistical significant positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001) and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV excised 1-5 months after PDT displayed a patent vascularisation and high proliferative activity. All membranes either treated or untreated disclosed only sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS: Verteporfin PDT leads to selective and effective damage of EC within CNV. Both patent and occluded vessels were lined by apoptotic EC. This finding and the increased expression of proliferation marker at later time points suggest that revascularisation after PDT is caused by angiogenesis rather than recanalisation.

Aged↗

[Intravitreal bevacizumab for neovascular age-related macular degeneration].

The efficacy and safety of the therapeutic anti-VEGF concept has already been demonstrated for pegaptanib and ranibizumab. Bevacizumab acts as an antibody against all VEGF-A isoforms and has been developed for oncological indications with intravenous application. Initial reports on intravitreal administration in patients with neovascular age-related macular disease (AMD) have shown beneficial morphological and functional effects. In the meantime, bevacizumab has been used off-label in thousands of patients with AMD. However, data from prospective, controlled, randomized trials on both safety and efficacy are lacking. Herein recent experiences with bevacizumab are summarized and discussed. Furthermore, a web-based platform for online data registration and pooled analyses is presented.

Angiogenesis Inhibitors↗

[(Side) effects of VEGF inhibition].

Vascular endothelial growth factor (VEGF) plays a pivotal role for embryo- and organogenesis. By regulating haemodynamics, (lymphoid) vessel architecture, haematopoiesis and immune system, endocrinology and reparative processes in adults, inhibited VEGF can cause multiple adverse events. Although the intravitreal administration of smaller doses can drastically reduce the systemic exposure, possible local side effects on retinal perfusion and survival of neuronal tissue must be taken into consideration. Before experience has been gained with VEGF inhibitors for longer than several years, individual discussion before the use, extensive informed consent and careful follow-up are necessary. From the ethical point of view, the available drugs should not be used without hesitation despite the clear benefit. First experiences with bevacizumab (Avastin), the first available (off-label) drug in Germany, are reported. In future, direct comparison of the different available drugs has to assess possible differences in the risk-benefit profile.

Angiogenesis Inhibitors↗

[Bevacizumab for treatment of macular edema secondary to retinal vein occlusion].

Application of VEGF inhibitors represents a treatment option for macular edema secondary to retinal vein occlusion that targets the disease at the causal molecular level. First reports on intravitreal injections of bevacizumab show promising morphological and functional effects and demonstrate that bevacizumab is a potent antiedematous agent in this context. A significant reduction of the central retinal thickness followed by a rapid improvement of visual acuity may be achieved within days. In a pilot study with a review period of 3 months, we found a significant improvement of one or more lines in 93% and four or more lines in 27% of eyes. This was associated with a concomitant significant reduction in central retinal thickness, which, however, was not sustained by a single injection (64% reduction after 1 month and 28% after 3 months). No relevant adverse events were noted. The duration of action after intravitreal bevacizumab administration is currently unknown. Reinjections will be necessary to maintain a lasting beneficial effect. Prospective, controlled long-term studies are mandatory to develop standardized treatment protocols that allow a safe and effective application of this off-label therapy.

Angiogenesis Inhibitors↗

[Early antiexudative response--OCT monitoring after intravitreal bevacizumab injection].

VEGF is more potent than histamine by a factor of 50,000 for inducing increased vessel permeability. Already in the first few minutes, hydraulic conductivity and diffusive permeability are significantly increased, followed by a longer-lasting, marked leakage over 20 h. Specific inhibition of the angiogenic, vasoactive, and permeability-inducing protein VEGF is now possible by new drugs, one of which is the first available (off-label) treatment in Germany for routine clinical use (Avastin). Retinal edema is composed of increased outflow of water and low molecular substances in the interstitial environment and is an important determinate of functional development in different ocular diseases. First experiences with the anti-hyperpermeability effect show early response and high potential in pathologic leakage. Future examinations have to assess when a permanent benefit can be achieved in respect to the other antiproliferative capabilities of the drug.

Angiogenesis Inhibitors↗

[Multiple sclerosis. An update with practical guidelines for ophthalmologists].

Multiple sclerosis (MS) is the most frequent chronic inflammatory disease of the central nervous system. Mostly young adults present with a variety of different symptoms due to the multiple localisations of the inflammatory lesions. Up to one-third of MS patients experience symptoms of optic neuritis as the initial symptom. That is the reason why the ophthalmologist often is the first physician contacted by patients later on diagnosed with MS. Today, it is known that there is already a significant irreversible axonal loss in MS patients progressing from the beginning of the disease. Therefore early, diagnosis and application of available therapeutic options are necessary for the patient's benefit. The therapeutic aim in early immunomodulatory treatment is to decrease the number of relapses and to slow down the development of clinical disability. This interdisciplinary overview presents guidelines for the clinical routine: how to assess the individual risk of each patient and how to treat the patient in accordance with current pathogenic, diagnostic and therapeutic knowledge.

Germany↗

[Blinking activity during visual display terminal work. Part 1: Ocular discomfort and pathophysiological principles].

Up to three-fourths of visual display operators complain about ocular discomfort after lengthy work at a monitor. The increase of displays at work has resulted in a problem area with growing impact for the economy and healthcare. Symptoms overlapping the complaints of dry eye disease point to the joint pathophysiological origin. In numerous studies the drastic decrease in blinking frequency was shown to be an essential cause of dry eye symptoms. Lid movements not only have the purpose of smoothing the precorneal tear film ("windshield effect"), but also affect the composition and stability of the different layers. Unfortunately, previous work has often been limited by the heterogeneity of measurement settings, leading to inconsistent results.

Blinking↗

[Blinking activity during visual display terminal work. 2: reduced blinking and therapeutic approaches].

New findings based on a noninvasive, automated long-term measurement method revealed interindividual differences in lid movement behavior, existence of blinking patterns, and the dominance of cognitive influence in the regulation of blinking frequency during increased concentration and especially visual attention. The development of an individual blinking animation promises long-lasting increase and harmonization of lid movements during visual display work. Maintenance of the integrity of the ocular surface by preventing surface evaporation and providing sufficient precorneal environment eradicates important pathogenic factors of ocular discomfort. An animation program for stimulation of blinking has been developed. First results showed that an increase in blinking rate initiated by the computer itself is feasible in principle during work at a visual display terminal. Further improvement of this new approach is promising.

Blinking↗

["Do you have a remedy for macular degeneration?" A field study about the advice given on dietary supplementation in 60 German pharmacies].

PURPOSE: Since completion of the AREDS study, evidence has accumulated to suggest that some form of dietary supplementation may be of value in special individuals who are at risk of progressive age-related macular degeneration (ARMD). We wanted to find out which of the many supplements available are recommended in practice and which instructions, promises, and purchasing arguments are used by German pharmacies. METHODS: A blinded consultation following a standardized protocol was carried out in 60 pharmacies. RESULTS: In 36 pharmacies specific products for dietary supplementation were recommended, but the dosage never complied with the AREDS study, and in 24 pharmacies, the necessity for a medical examination or consultation with an ophthalmologist was not mentioned. Possible interactions with other drugs or side effects were generally excluded. CONCLUSIONS: Potential risks of supplement intake were underestimated. Medical knowledge of the most frequent cause of blindness in the Western world was insufficient. A clear policy of recommendations according to evidence-based criteria is needed.

Attitude of Health Personnel↗

[Vitrectomy with or without cerclage in the treatment of retinal detachment].

In the beginning, pars plana vitrectomy was often combined with encircling elements in the treatment of complicated retinal detachments. Initial considerations were the limited control of the vitreous base due to the restricted view of the fundus periphery and the prevention of redetachment by anterior tears or traction. Today, additional encircling is justified in specified conditions of retinal surgery, e.g., retinal shortening by long-lasting detachments, anterior PVR, or choroidal injuries. Despite several synergistic effects in surgical management, severe complications have to be taken into account for scleral buckling in vitreoretinal surgery. Nevertheless, primary vitrectomy in combination with scleral buckling has led to a marked decrease of primary failure rate and improvement of functional results in retinal detachment surgery.

Combined Modality Therapy↗

[Angle closure glaucoma in association with relative anterior microphthalmus (RAM) after premature birth-retinopathy (ROP)].

BACKGROUND: The infantile angle-closure glaucoma is a common and well characterized complication of retinopathy of prematurity (ROP). Progressive shallowing of the anterior chamber by retrolental fibrous masses is mostly responsible for the pressure elevation during the first years of life. Apart of this pathogenesis, ROP-associated glaucoma is totally different in cases that do not manifest until adulthood. Only few cases are described in the literature. CASE REPORT: A 36-year-old female patient presented with symptoms of acute intraocular pressure (IOP) elevation and fundus results of a cicatricial ROP stadium II. Control of IOP was not achieved by systemic and topical drug treatment. The biometry showed a relative anterior microphthalmus (RAM) in myopia. After peripheral iridectomy, the IOP normalized and remained stable over a long-time period. CONCLUSION: Myopia induction after ROP and ROP treatment often lead to special anatomical conditions corresponding to the classical relative anterior microphthalmus. Shallowing of the anterior chamber and development of angle-closure glaucoma increase with age. Thus, a manifestation not before the third decade of life was a typical finding in the literature review. A detailed recording of history and consideration of the biometric data are of importance for diagnosis. Peripheral iridectomy was found to be the therapy with the highest success rate. The increase of a pupillary block mechanism can prevent further visual loss to the often pre-damaged eyes. Consideration of this entity is crucial in unilateral IOP elevation, because an increasing prevalence of these patients can be expected due to the increase of premature babies since 1970.

Adult↗

Adult polyglucosan body disease: a postmortem correlation study.

Autopsy of a 50-year-old woman with adult polyglucosan body disease and missense mutations (Arg515His, Arg524Gln) in the glycogen branching enzyme gene (GBE) revealed accumulation of polyglucosan bodies in the heart, brain, and nerve. GBE activity was decreased in the morphologically affected tissues but was normal in unaffected tissues. GBE mRNA transcripts were similar in all tissues and in controls, which confirms the lack of tissue-specific GBE isoforms.

1,4-alpha-Glucan Branching Enzyme↗

A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.

OBJECTIVE: To determine the cause of sporadic rippling muscle disease (RMD) in a 24-year-old patient. BACKGROUND: RMD is a rare myopathy characterized by percussion-induced rapid muscle contractions (PIRC), muscle mounding, and rippling waves. We have recently found that autosomal dominant RMD is caused by mutations in the caveolin-3 gene (CAV3) on chromosome 3p25. Possibly, increased activity of neuronal nitric oxide synthase (nNOS) contributes to the clinical characteristics of increased mechanical muscle hyperexcitability. METHODS: Clinical examination, mutational analysis, and immunohistochemistry of muscle tissue were performed in a patient with sporadic RMD. RESULTS: The authors observed a de novo CAV3 missense mutation Arg26Gln. Immunohistochemistry showed reduced caveolin-3 surface expression in a muscle biopsy. In addition, the authors found normal sarcolemmal nNOS expression and a reduced expression of alpha-dystroglycan in muscle fibers. CONCLUSIONS: These data confirm that RMD is caused by CAV3 mutations. Moreover, there is evidence that CAV3 mutations may also be found in patients without a positive family history of RMD.

Adult↗