[Intraoperative Optical Coherence Tomography - an Overview of Current Clinical Data for the Application in the Anterior and Posterior Segments]. / Intraoperative optische Kohärenztomografie ­ eine aktuelle Übersicht klinischer Studien zur Anwendung im Vorder- und Hinterabschnitt.

Intraoperative optical coherence tomography (iOCT) represents another milestone in ocular imaging technologies. Now, for the first time, high resolution OCT images are available not only pre- or postoperatively, but also intraoperatively. In recent years, there have been significant advances in iOCT technology - from hand-held probes and mounted systems towards iOCT systems which are fully integrated into the surgical microscope and which provide seamless integration into the workflow. These systems offer high-resolution, intraoperative OCT scans in real-time and provide additional information on microstructures of the retina or the cornea. These findings may even lead to a modification of surgical strategies. Like any other new technology, iOCT technology still has some limitations, such as shadowing from instruments and the lack of eye tracking systems. Therefore, the current state of iOCT technology still requires some skill to track surgical maneuvers in real time. Further research and development will help to solve these limitations in the future. However, even if not required for all surgical procedures, iOCT imaging can already improve safety and control in many surgical procedures on the anterior and posterior segments. This has already been shown in several studies and case series. Particularly in the surgery of vitreomacular traction, peeling of epiretinal membranes (ERM peeling) and macular hole surgery, iOCT offers significant added value. It improves the visualisation of transparent structures and helps to avoid the usage of dyes. In addition the success of the surgical maneuvers can be investigated intraoperatively. In lamellar keratoplasty and glaucoma surgery too, iOCT improves precision and safety. Moreover, iOCT technology may help to achieve further insight into ocular pathologies and a better understanding of the impact of surgical maneuvers on visual rehabilitation. Further prospective studies are however required to evaluate the usefulness of iOCT in various surgical procedures on both, the anterior and posterior segments.

Efficacy of 0.2 µg/day fluocinolone acetonide implant (ILUVIEN) in eyes with diabetic macular edema and prior vitrectomy.

PurposeLimited data are available on the efficacy of the 0.2 µg/day fluocinolone acetonide (FAc) implant in eyes with prior vitrectomy. Here, we present a collection of 26 vitrectomized eyes treated with the 0.2 µg/day FAc implant.MethodsRetrospective study involving six centers from four European countries analyzing the safety and efficacy data from patients (26 eyes from 25 patients) with DME and a prior vitrectomy that had been treated with one 0.2 µg/day FAc implant.ResultsPrior intravitreal therapies included anti-VEGF (mean, 3.8 injections) and steroids (mean, 1.9 injections). Pars plana vitrectomy (PPV) was performed in these eyes primarily for abnormalities of vitreoretinal interface, followed by proliferative diabetic retinopathy and vitreous hemorrhage. The 0.2 µg/day FAc implant was injected 24.2 months, on average, after PPV and the mean duration of follow-up after injection was 255 days (range, 90 to 759 days). The mean change in BCVA was +11.7 ETDRS letters (range, -19 to +40 letters; P<0.0004) and the mean change in central foveal thickness (CFT) was -233.5 µm (range, -678 to 274 µm; P<0.0001). The mean change in IOP from baseline at the last visit was +1.4 mm Hg (range, -9 to +8 mm Hg; P=0.0090). Eight eyes initiated or continued IOP lowering medications.ConclusionsThese data suggest the 0.2 µg/day FAc implant is effective in vitrectomized patients with an acceptable safety profile. Further studies are still required to confirm the current findings and to assess the effect of the 0.2 µg/day FAc implant over a longer period of follow-up.

[Placenta Growth Factor (PlGF) and Retinal Vascular Diseases--Current Knowledge from Experimental and Clinical Studies]. / Plazenta-Wachstumsfaktor (PlGF) und retinale Gefäßerkrankungen--experimentelle und klinische Datenlage.

Pathological angiogenesis is a major characteristic of many diseases, such as cancer and retinal vascular disorders. Vascular diseases of the eye, such as diabetic retinopathy (DR) and neo-vascular age-related macular degeneration (nAMD), are the main cause of severe vision loss. The specific role of the cytokine VEGF-A in these pathologies has been proven in many ways. Thus, VEGF-A is still the major target for antiangiogenic therapy. Recently, another angiogenic factor, the placental growth factor (PlGF), has become a focal point for clinical research. This interest is based on the fact that the expression of PlGF is limited to embryonic development and PlGF can hardly be found in healthy tissues. During pathological angiogenetic processes, such as retinal vascular diseases, however, PlGF is increasingly expressed. Substances which inhibit the effect of PlGF and thus pathological angiogenesis, without simultaneously affecting healthy tissues, could significantly extend the therapeutic options for the treatment of retinal vascular diseases. Convincing results have recently been published from clinical trials in oncology, as well as preclinical investigations in animal models of retinal vascular diseases. The aim of this review is to summarise the role of PlGF in retinal vascular diseases and the available experimental data on the therapeutic potential of PlGF inhibitors.

[Reliable UV-light protection in intraocular lenses--scientific rationale and quality requirements]. / Zuverlässiger UV-Schutz durch Intraokularlinsen--Rationale und Qualitätsanforderungen.

Since the late 1980s implantation of UV-blocker intraocular lenses during cataract surgery has become an internationally accepted standard. Last year the Kassenärztliche Vereinigung Bayern (KVB) and statutory health insurance organisations proposed for the first time quality criteria for intraocular lenses (IOL), thereby including exact parameters for the amount of UV light transmission (≤10% at 400 nm). Since then, the discussion has been raised again as to what extent IOLs should filter or block UV light. In this article, exact definitions of spectral subbands within the optical radiation band are given. Today, 400 nm is the internationally accepted standard to distinguish UV light and visible light. Moreover, exposure of the eye to UV radiation is described as well as mechanisms of photooxidative damage to the retina. Comprehensive laboratory and animal experimental studies show that light of short wave lengths, i.e., above all UV light but also blue light, may induce photochemical damage to the retina. Primary sites of such damage are both the outer segments of the photoreceptors and the retinal pigment epithelium (RPE). Physiological protective mechanisms of the eye, such as filtering properties of different ocular media are described in detail. Cornea, aqueous and vitreous absorb UV radiation below 300 nm, while the natural adult lens absorbs UV radiation between 300 and 400 nm. This protection is lost when the lens is removed by cataract surgery and thus should be restored. UV light does not contribute to vision but damages retinal structures. Therefore, UV-blocking intraocular lenses with a 10% cut-off near 400 nm should be implanted during cataract surgery. This ensures sufficient retinal protection after surgery. These theoretical considerations are supported by results from animal and clinical studies.

[Blue Light-Filtering IOLs - Currently available data]. / Blaufilter-Intraokularlinsen - derzeitige Datenlage.

Data from both experimental and epidemiological trials have suggested a potential correlation between extraction of the natural lens associated with exposure to photo-oxidative stress to the retina and a progression of diseases such as AMD. A fundamental factor could be the unchecked exposure to blue light. This is why in the past years so-called blue light-filtering intraocular lenses have been implanted to serve as a protection to the retina. The following contribution is based on a data base research (Pub Med, National Library of Medicine, USA) and summarises information currently available on the use of blue light-filtering lenses. Experimental modeling has shown that, compared to regular UV lenses, blue light-filtering lenses block a considerable part of blue light transmission to the retina and reduce damage to retinal cells and production of inflammatory markers such as VEGF. The majority of the clinical data demonstrate that blue light-filtering lenses are compatible in terms of visual acuity, contrast sensitivity and colour perception as well as patient-rated quality of vision. But a few additional studies report reduced contrast sensitivity and limitations in mesopic vision.This is also true for the circadian rhythm. However, the evaluation of this parameter in connection with blue light-filtering lenses has only been done on a theoretical basis. Long-term data showing that blue light-filtering lenses actually do reduce the incidence of retinal diseases such as AMD are currently not available.

Antivascular endothelial growth factor as an approach for macular edema.

Macular edema is an abnormal thickening of the macula associated with the accumulation of excess fluid in the extracellular space of the neurosensory retina. The following chapter looks at the basic pathomechanisms of macular edema as well as major pathologic conditions leading to it: special focus is on diabetic retinopathy, retinal venous occlusions and a number of inflammatory disorders. Currently available data on up-to-date pharmacologic treatment options such as steroids and anti-VEGF compounds is presented and discussed.

[Oxidative tissue damage]. / Was ist oxidativer Stress?

Oxidative stress is defined as an overflow of oxidative metabolites either in the human body or in a compartment of the body. Today this chemical definition has been slightly modified and encompasses an elevation of oxidative metabolites or a relative deficiency of anti-oxidants. Molecular oxygen is the basis of many highly reactive oxidative species which are able to directly damage or lead to the generation of secondary reactions which then initiate oxidative processes. The cell has established numerous mechanisms and strategies to antagonise those oxidative processes at different steps. Many diseases have been shown to be either related to or even be initiated by oxidative processes. The eye is at high risk to be damaged by oxidative mechanisms. One major reason is its permanent exposition to oxidative stimuli. The biochemical composition of ocular structures, especially that of the retina (unsaturated fatty acids), is an important factor making the eye more susceptible as compared to other organs. Ocular ischaemia, ischaemia or hypoxia of the retina, diabetic retinopathy and glaucoma are important disease entities that are initiated or propagated by oxidative processes. Ischaemic processes lead to classical reactions of the oxidative pathway. This is no longer believed to be the case in diabetic retinopathy. Here, advanced glycation end products (AGE's) and related species are able to induce oxidative reactions and the expression of growth factors. In age-related macular degeneration, photodynamic processes that already occur in childhood are believed to be a major factor contributing to the pathogenesis of the disease process. In addition, the expression of growth factors and new vessel growth can be initiated via inflammatory reactions or oxidative metabolites.

[Is there a drug therapy for age-related macular degeneration?--current status and new therapeutic approaches]. / Gibt es eine medikamentöse Therapie der altersbedingten Makuladegeneration?--Derzeitiger Stand und neue therapeutische Ansätze.

Age-related macular degeneration (AMD) is the major cause of legal blindness in society today. In dry AMD age-related changes in Bruch's membrane and RPE result in the accumulation of cell debris with consequent degeneration. In the less common but more aggressive form, wet AMD, hypoxia and inflammation lead to an up-regulation of different growth factors such as VEGF resulting in formation of choroidal neovascularisation. Different therapeutic modalities have evolved to address this problem. Examples are photodynamic therapy to eradicate choroidal neovascularisation (CNV) via a physiochemical reaction or intravitreal application of anti-VEGF agents to stop leakage of fluid from the same CNV. The overall results have been either disappointing or not practical because of the necessity of chronic treatment. The treatment goal continues to evolve to that already realised in oncology which is for a cure. This mandates the investigation of combination strategies. Combination strategies should focus on utilising the differing mechanisms of action on the pathogenesis of the disease all the while minimising the side effects of the individual therapeutic agents.

[Scope and limititions of innovative vitrectomy systems]. / Möglichkeiten und Grenzen der innovativen Vitrektomiesysteme.

PURPOSE: The aim of the present article is to review the methodical and technological development of pars plana vitrectomy. Special attention is drawn to safety, efficiency and functionality of the innovative 25-gauge und 23-gauge vitrectomy systems which are compared to the standard 20-gauge vitrectomy system. This was done based on clinical studies and case reports. METHODS: A literature search was conducted in a cluster of different medical databases (XMedall; XPharmall). Focus of the research was the "development" and "status quo" of pars plana vitrectomy. In particular, clinical studies and case reports dealing with safety and efficiency of 20-, 23- and 25-gauge vitrectomy systems have been evaluated. Only peer-reviewed articles from 1966 until today were investigated. Finally, a descriptive analysis of the relevant studies was made. RESULTS: Both innovative vitrectomy systems are safe and effective and help to reduce operating time. There was no significant difference in postoperative complications following 25-gauge vitrectomy and 20-gauge vitrectomy. 25-gauge instruments, however, show a greater flexibility. For this reason a certain learning curve is required and the range of application is limited. Due to its greater stiffness and larger diameter, the 23-gauge system - while still allowing a transconjunctival access - may overcome the disadvantages of the 25-gauge system. However, the use of silicone oil may lead to leakage of the sclerotomies and thus necessitate additional suturing. CONCLUSION: The use of both innovative vitrectomy systems offers the advantage of a faster and less invasive surgical procedure. However, there are disadvantages which limit the indications for 25-gauge vitrectomy. The 23-gauge vitrectomy may overcome these disadvantages and - due to its wider range of application - may be used instead of conventional 20-gauge vitrectomy in most cases. It may therefore become the new standard for vitrectomy.

Verteporfin therapy and triamcinolone acetonide: convergent modes of action for treatment of neovascular age-related macular degeneration.

PURPOSE: Choroidal neovascularization associated with age-related macular degeneration is the primary cause of blindness in the elderly in developed countries, due to a number of pathogenic effects, including angiogenesis, cell-mediated inflammation, leukocyte adhesion and extravasation, and matrix remodeling. METHODS: By producing photochemical effects at the site of target tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS: PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective in reducing the risk of vision loss in patients with classic containing subfoveal CNV and occult with no classic CNV. However, in predominantly occult CNV, the treatment may be most effective in smaller lesions, and less in larger lesions. Most important, visual acuity rarely is improved. CONCLUSIONS: Pilot studies and large case series suggest that a combination of PDT and intravitreal triamcinolone acetonide has the potential to improve visual outcomes and reduce the need for additional treatments. Randomized, prospective clinical trials are underway to confirm the efficacy and safety of this novel treatment modality.

Endotoxins in ophthalmic viscosurgical devices.

PURPOSE: To measure the endotoxin concentration (EC) of 25 commercially available, hyaluronic acid- and hydroxypropylmethylcellulose-based (HPMC) ophthalmic viscosurgical devices (OVDs). METHODS: The in vitro Limulus amebocyte lysate (LAL) assay, which indicates the presence of endotoxins originating from gram-negative bacteria, was used to determine the EC. The procedure was performed according to the European Pharmacopoeia/USP. EC including duplicate determinations, negative controls, dilution series with control standard endotoxin, dilution series with sample extract and positive sample control. RESULTS: 16 OVDs (Amvisc, Amvisc Plus, Biolon, Coatel, Healon, Healon GV, Healon, HPMC Ophtal L, Microvisc, Microvisc Plus, Ocucoat, Provisc, Rayvisc, Viscoat, Visco Shield 2%, Visko 1.4%) had an EC under 1.2 endotoxin units/mL, five (Adatocel, HPMC Ophtal H, LA Gel, Viscorneal, Viscorneal Plus) had an EC > or = 1.2 and < or = 24 EU/ml, and four (Biocorneal, Dispasan also named Ophthalin, Dispasan Plus, Visko 1%) had an EC of > 24 EU/ml. DISCUSSION: To avoid viscoelastic-related inflammatory or immunological reactions, the use of pure OVDs is recommended, especially for surgical procedures with an inherent possibility of leaving viscoelastic remnants in the eye (e.g., cataract surgery, visco-canalostomy or penetrating keratoplasty).

Immunological effects of allopurinol in the treatment of experimental autoimmune uveitis (EAU) after onset of the disease.

PURPOSE: Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known. METHODS: Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis of retinal proteins. Based on digital image analysis, analysis of discriminance was done. RESULTS: There were significant immunomodulating effects in both therapy groups (Wilks' lambda 0.001, P < 0.008) compared to controls. However, the effects were more pronounced in the AL7 group, where peak intensities and the number of peaks were markedly more reduced. CONCLUSIONS: Immunomodulating effects of allopurinol can be detected even if the therapy starts after the onset of the disease. Thus allopurinol strongly influences the immunologic mechanism in this model of autoimmune disease. In view of its minimal side effects, the drug could be a promising alternative for the therapy and prophylaxis of uveitis and other autoimmune diseases.

[Is a cataract avoidable? Current status with special emphasis on the pathophysiology of oxidative lens damage, nutritional factors, and the ARED study]. / Ist die Katarakt vermeidbar? Eine aktuelle Bestandsaufnahme unter besonderer Berücksichtigung der Pathophysiologie oxidativer Linsenschäden, nutritiver Einflussfaktoren und der ARED-Studie.

The benefit of long-term nutrient intake to reduce the risk of age-related ocular disease such as cataract or macular degeneration is subject to controversy. Conclusions about the benefits and risks of antioxidant supplements can be expected after reviewing the current literature concerning oxidative-induced lens damage and nutritional effects. Identification of influenceable risk factors for senile cataracts could achieve immense economical relevance. In contrast to former longitudinal epidemiological studies, the AREDS report failed to verify protective properties of highly concentrated vitamin supplements on cataract formation. Although there are enough epidemiological indications for reducing the risk of cataracts by the intake of antioxidants, a general recommendation for the use of supplements is untimely or even wrong until stringent evidence of efficacy is provided. The usefulness of cataract prevention is discussed.

Topical allopurinol or corticosteroids and acetylcysteine in the early treatment of experimental corneal alkali burns: a pilot study.

PURPOSE: To investigate the effect of topical allopurinol on experimental corneal burns and to compare this to established treatment modalities such as topical prednisolone and acetylcysteine. METHODS: Twenty Wistar rats were randomly assigned to four groups (n=5 each). The groups were controls (normal saline), allopurinol 0.4% eye drops, prednisolone acetate 1% eye drops and acetylcysteine 8% eyedrops. Corneal burn was induced using a 3 mm paper disc soaked in 1N NaOH for 60 seconds. Drops were instilled 6 times per day. In addition, one drop/day ofloxacine was given to prevent secondary infections. Eyes were enucleated 50 hours later and fixed in 4.5% formaldehyde. Three histological levels of each globe were stained with hematoxylin-eosin and examined by two independent masked investigators using a 0 to 4+ inflammatory score. All pair-wise multiple comparison procedures (Student-Newman-Keuls method) were applied for statistical work-up. RESULTS: All three substances significantly reduced the number of histologically visible inflammatory cells compared to the control group (p<0.05). CONCLUSIONS: In the present study, topical allopurinol was as effective as established drugs, namely steroids and acetylcysteine, in the early treatment of experimental alkali corneal burns.

Changes in the tear proteins of diabetic patients.

BACKGROUND: Previous studies have shown a significant increase in tear protein peaks in the tears of diabetic patients suffering from dry eye. The aim of this study was to analyze the tear protein patterns from patients with diabetes mellitus who do not suffer from ocular surface diseases (DIA). METHODS: A total of 515 patients were examined in this study (255 healthy subjects (controls) and 260 patients suffering from diabetes mellitus). Tear proteins were separated by sodium-dodecyl-sulfate polyacrylamide gel electrophoresis. After digital image analysis densitometric data files were created and subsequently used for multivariate statistical procedures. RESULTS: A significant increase in the number of peaks was detected in diabetic patients compared to controls (P < 0.0003). The analysis of discriminance revealed a highly significant discrimination between diabetic patients and controls (Wilks lambda: 0.27; P < 0.000001). Furthermore, a significant difference in the protein pattern of diabetic patients could be detected between those suffering from dry eye or not (P < 0.002). The changes in protein patterns of diabetic patients increased with the duration of the diabetic disease. In diabetic patients with a disease duration longer than 10 years the changes were significantly more expressed than in patients with a shorter diabetic history (P < 0.003) and in healthy subjects (P < 0.0001). CONCLUSIONS: The tear protein patterns of diabetic patients are very different in the number and intensity of spots from those of healthy subjects. Furthermore, it could be demonstrated that the differences found in the tear patterns of diabetic patients are not equal to those found in previous studies in patients suffering from dry-eye disease. The alterations in the diabetic tears were correlated with the duration of the diabetic disease. With longer disease, history changes in the tear protein patterns increased. With the course of the disease some protein peaks appeared that are not present in healthy persons. Our study shows that the analysis of electrophoretic tear protein patterns is a new non-invasive approach in the early diagnosis and analysis of the pathogenesis of diabetes induced ocular surface disease.

[Macular holes. Review of the current status of knowledge of pathogenesis and treatment methods]. / Makulaforamina. Ubersicht über den aktuellen Kenntnisstand zu Pathogenese und Behandlungsstrategien.

This article is based on the author's personal views and clinical experience and offers an overview of the current state of knowledge on the pathogenesis of macular holes including currently available therapy strategies. Special attention is paid to the prevailing controversial issues regarding treatment concepts for macular holes.