[Treated cases of retinopathy of prematurity in Germany : 5-year data from the Retina.net ROP registry]. / Behandelte Frühgeborenenretinopathie in Deutschland : 5-Jahres-Daten des Retina.net ROP-Registers.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the main reasons for childhood blindness. The number of infants requiring treatment, however, is low for individual centers. The Retina.net ROP registry has been founded to allow a joint analysis of treatment patterns and courses post treatment. OBJECTIVE: This paper reports treatment patterns over 5 years. MATERIAL AND METHODS: All infants born between January 2011 and December 2015 who were entered into the treatment registry by one of the 12 participating centers were analyzed. RESULTS: The data of 150 infants (292 eyes) were analyzed and ROP 3+ in zone II was the most prevalent treatment indication. Gestational age and birth weight remained stable over the years. The treatment patterns, however, changed with anti-VEGF treatment (bevacizumab or ranibizumab) accounting for only 10% of treated eyes in 2011 but for 56% and 30% in 2014 and 2015, respectively. Almost all eyes with AP-ROP or zone I disease received anti-VEGF treatment. Zone II disease was predominantly treated with laser photocoagulation. Recurrences were more common and appeared later in the anti-VEGF group compared to the laser group (23%/interval 60 days vs. 17%/interval 23 days). Perioperative complications were evenly distributed across treatment groups. CONCLUSION: The data in this analysis represent about 10-15% of treated infants in Germany. The results provide evidence for an increasing use of anti-VEGF agents for ROP. The data reflect a selection bias for anti-VEGF treatment in eyes with a more aggressive disease. This needs to be considered when interpreting data such as disease recurrence rates. The risk for late recurrences after anti-VEGF treatment is of particular clinical significance.

[Influence of the donor age on graft survival : Is the demographic change also important for corneal tissue donation?] / Einfluss des Donoralters auf das Transplantatüberleben : Ist der demografische Wandel auch von Bedeutung für die Augenhornhautgewebespende?

The success of corneal transplantation highly depends on the quality of the used graft. Various factors play a crucial role such as a perfect stroma without optically relevant, centrally located cloudiness or changes (e. g. scars) or an adherent Descemet membrane. One of the most important parameters is the quality of the endothelial cell layer with a sufficiently large endothelial cell count. An open question is so far whether the donor age affects corneal quality and therefore has an impact on the success of transplantation. A comprehensive review of the available literature revealed that a large amount of scientific data on the influence of donor age exist to answer this question. In a variety of studies, no significant dependence of graft quality of donor age could be detected. Rather the studies prove that graft survival depends primarily on the state of the endothelial cell layer, and postoperative endothelial cell loss must be considered as a major cause of graft failure. Extensive quality assurance procedures in tissue preparation and cornea processing in the eye banks in Germany (Europe) ensures that only corneas with tested high quality are allocated for transplantation regardless of the donor age. Against the background of an aging population, the use of grafts from older donors should not be waived.

Serum and Plasma Levels of Vascular Endothelial Growth Factors in Relation to Quality of Glucose Control, Biomarkers of Inflammation, and Diabetic Nephropathy.

Levels of vascular endothelial growth factors (VEGF) are regulated in a complex network of adipokines, glucose control, and low grade inflammation together with activated platelets, leucocytes, and endothelial dysfunction. Increased levels of VEGF are associated with enhanced angiogenesis and impaired repair mechanisms of vascular lesions in endorgans. Little is known about the interaction of systemic VEGF levels with quality of diabetes control, biomarkers of inflammation, and diabetic nephropathy. Moreover, it is unclear, whether serum and plasma VEGF levels are similarly suited to reflect risk associated with VEGF.In this case control study, we analyzed these parameters in serum and plasma of age and sex matched controls without diabetes (n=99) and type 2 diabetes (n=302). Serum VEGF-A was significantly increased in patients with T2DM while plasma levels were in the same range as for controls. Individual levels varied in a wide range. Serum levels were 4.9 times higher in controls and 7.3 times higher in T2DM as compared to plasma levels. T2DM was associated with significantly higher levels of hsCRP, ALAT, and albumin/creatinine ratio. When calculated for tertiles of HbA1c, we observed a highly significant increase from tertile one to the upper tertile for serum VEGF-A but not for plasma VEGF-A. Correlation analysis revealed a significant relationship between VEGF-A, HbA1c, inflammation, and diabetic nephropathy. Our results indicate that increased VEGF-A levels in T2DM significantly depend on quality of HbA1c control. Serum levels of VEGF-A, with a strong contribution of platelet derived VEGF, better reflect the glycemic burden than plasma levels of VEGF-A. Mechanistic studies are needed to explore links to inflammation and diabetic nephropathy.

[The German Acanthamoeba keratitis register: Initial results of a multicenter study]. / Das Deutsche Akanthamöbenkeratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. PATIENTS AND METHODS: Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. RESULTS: Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 ± 4.0 months (range 0-23 months). A triple therapy with Brolene® Lavasept® and antibiotic eye drops at least 5 ×/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 ± 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 ± 5/25) and without (5/32 ± 5/25) keratoplasty. CONCLUSION: Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases (berthold.seitz@uks.eu), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease.

[Suture-free amniotic membrane transplantation]. / Nahtlose Amnionmembrantransplantation.

Amniotic membrane transplantation has been used very successfully in ophthalmology since the 1940s for treatment of surface disorders. Over the course of the years the indications for use have been continuously extended. In contrast the operative technique is predominantly invasive, i.e. the amniotic membrane is surgically sutured onto the surface of the eye. In order to avoid surgical trauma the authors have developed a device which allows the amniotic membrane to be stretched in a ring and the amniotic ring can then be placed suture-free on the eye surface. The authors are hopeful that the biological principle of the amniotic membrane can be better utilized by uncomplicated repetitive application.

Human corneal endothelial cell sheets for transplantation: thermo-responsive cell culture carriers to meet cell-specific requirements.

Corneal endothelial diseases lead to severe vision impairment, motivating the transplantation of donor corneae or corneal endothelial lamellae, which is, however, impeded by endothelial cell loss during processing. Therefore, one prioritized aim in corneal tissue engineering is the generation of transplantable human corneal endothelial cell (HCEC) layers. Thermo-responsive cell culture carriers are widely used for non-enzymatic harvest of cell sheets. The current study presents a novel thermo-responsive carrier based on simultaneous electron beam immobilization and cross-linking of poly(vinyl methyl ether) (PVME) on polymeric surfaces, which allows one to adjust layer thickness, stiffness, switching amplitude and functionalization with bioactive molecules to meet cell type specific requirements. The efficacy of this approach for HCEC, which require elaborate cell culture conditions and are strongly adherent to the substratum, is demonstrated. The developed method may pave the way to tissue engineering of corneal endothelium and significantly improve therapeutic options.

[Transplantation of corneal endothelium--chances and challenges]. / Die Transplantation des kornealen Endothels--Möglichkeiten und Grenzen.

BACKGROUND: Endothelial keratoplasty is a promising surgical procedure which may replace penetrating keratoplasty in cases of endothelial cell diseases of the cornea. This method may thereby help to prevent postoperative astigmatism and transplant rejection. METHODS AND RESULTS: A survey of publications reporting about results after endothelial keratoplasty shows that the main problem of this transplantation technique is a postoperative endothelial cell loss which is comparable to or even higher than that observed in penetrating keratoplasty. Improving surgical techniques led to a reduction of the endothelial cell loss, however, cell-based strategies to prevent postoperative cell loss or to enhance the cell densities of donor corneas or endothelial lamellae are rare. DISCUSSION: This review presents an overview of clinical results after endothelial keratoplasty. Current strategies in the field of cell biology and tissue cultivation of corneal endothelial cells, genetic manipulation of the corneal endothelium and tissue engineering strategies aiming at the production of transplantable endothelial cell sheets are described. CONCLUSION: The limited availability of donor corneas makes it mandatory to develop methods in the field of tissue engineering in order to improve corneal endothelial cell survival or to increase corneal endothelial cell density, using interdisciplinary approaches.

[Heavy silicone oil endotamponade--a useful alternative to conventional endotamponade]. / Schwere Silikonölendotamponade - eine gute Ergänzung zur konventionellen Endotamponade.

Retinal surgery of retinal detachment in the inferior part of the eye is often complicated by the development of proliferative vitreoretinopathy. Therefore the heavier-than-water concept using heavy silicone oils is a logical consequence for treatment of otherwise unsuccessful retinal surgery in such cases. While some surgeons already use heavy silicone oils in the clinical routine, others are carefully following complication rates. Even good anatomical and functional results are published as critical case reports. In this report we describe the advantages of the heavy silicone oil endotamponade and our own clinical experiences with Densiron(R) 68. The use of heavy silicone oils turned out to be quite convenient, leading for example to shorter tamponade times, easy handling of the oil, no need for uncomfortable prone-position of the patients. On the other hand one has to consider that Densiron(R) 68 is a mixture which contains 70 % PDMS and 30 % F 6 H8, a heavy fluid that was associated with multiple complications if used as sole long-term endotamponade. Based on these experiences we recommend all users bear in mind possible complications. However, such complications can be prevented.

[Cataract extraction and blue light--impact on the retina]. / Kataraktextraktion und Blaulicht--Wirkung auf die Netzhaut.

This review focuses on the scientific background for the use of "yellow artificial lenses". We will address the fact that numerous basic scientific publications point to a rationale for this practice although it is often difficult to derive clear-cut evidence from clinical epidemiological studies for the preventive use of yellow artificial lenses. In the first part we refer to studies showing that especially the shortwave part of the visible spectrum of light can be harmful for the retina and optic nerve. For this, we have screened the literature for the major sources of radical production and for the targets of oxidative stress after impingement of "blue light" on the retina. Furthermore, we can show that many studies in cell and molecular biology, animal experiments and first clinical trials point to a preferential use of yellow-tinted lenses especially in the elderly and AMD patients.

Mycophenolate mofetil (MMF) following penetrating high-risk keratoplasty: long-term results of a prospective, randomised, multicentre study.

BACKGROUND: The purpose of this prospective, randomised, multicentre study was to prove the efficacy and safety of mycophenolate mofetil (MMF) in preventing graft rejection and in improving clear graft survival following high-risk keratoplasty. METHODS: In all, 98 of 140 scheduled patients were included in this study (57 MMF, 41 control). Recruitment was stopped prematurely due to a statistically significant result. The patients in the MMF group received MMF orally 2 x 1 g daily for 6 months. All of the patients received fluocortolone 1 mg/kg/day tapered over 3 weeks and topical prednisolone acetate 5 x /day tapered over 5 months. Main criteria were immune reaction-free and clear graft survival, and the occurrence of side effects. RESULTS: The mean follow-up time was 34.9+/-16.3 (mean+/-SD) months. Eleven patients withdrew from the study (nine patients due to protocol deviation, two because of side effects). Six reversible and two irreversible graft rejections occurred in the MMF group, and five reversible and seven irreversible rejections in the control group. The Kaplan-Meier analysis revealed an immune reaction-free graft survival after the mean follow-up time of 83% in the MMF group and 64.5% in the control group (P=0.044). Graft failure occurred in 10 MMF-treated patients (two due to rejection) and in nine patients in the control group (seven due to rejection). A total of 36 of 57 MMF-treated patients experienced mostly reversible adverse events. CONCLUSIONS: Systemic immunosuppression with MMF over 6 months is relatively well tolerated and improves rejection-free graft survival following high-risk keratoplasty statistically significant, even in the long run.

[Different endotamponade agents and their clinical indications]. / Indikation zum Einsatz verschiedener Endotamponaden.

The use of polydimethylsiloxane (PDMS) as silicone oil endotamponade has become a gold standard in retinal surgery. In cases of complicated retinal detachment with inferior and posterior retinal detachment this tamponade may be insufficient, and heavy silicone oils may be superior in such cases. Monocentric studies about use of the heavy silicone oil Densiron 68, a mixture of PDMS with perfluorohexyloctane (F6 H8), are reviewed. Meanwhile, F 6 H8 is approved as sole endotamponade, but complications such as emulsification and inflammation associated with the use of only F 6 H8 as endotamponade are reported and will also be reviewed. An advantage of heavy silicone oils is the relatively short residence time of the endotamponade. An uncomfortable "head down" position of the patients after surgery is not necessary. Current research focuses on developing new heavy silicone oils with a lower tendency to emulsify.

[Uveitis intermedia in childhood]. / Uveitis intermedia im Kindesalter.

Round 10-12% of all children who present with signs of uveitis suffer from intermediate uveitis. Compared to uveitis anterior in children, the association of intermediate uveitis to a systemic disease is much more complicated. Most cases of uveitis intermedia are idiopathic and show the signs of a pars planitis. Post-infectious and immunological causes are difficult to detect. In cases of uveitis in children, it is necessary to know the specific symptoms of possible underlying systemic diseases. On this basis, an adequate and specific diagnosis will most probably be successful. This paper presents the different causes of uveitis intermedia in childhood and compares the incidence of the disease in comparison with adults as far as this is mentioned in the literature.

[Intraocular epithelial downgrowth - report on 14 cases from 1986 to 2000]. / Intraokulare Epithelimplantation - Bericht über 14 Patienten 1986 - 2000.

BACKGROUND: Diffuse and cystic epithelial downgrowth occur rarely, but they represent a mostly preventable potential cause of blindness as sequels to trauma and surgery. The aim of this study is to report on the etiology and course of disease in patients with histologically verified epithelial downgrowth. PATIENTS AND METHODS: From 1986 until 2000 the ophthalmopathological laboratory of the University Eye Hospital Hamburg-Eppendorf received 13 (4 external) referrals. Ten patients with cystic of diffuse intraocular epithelial downgrowth were treated and 9 eyes were operated on in the Hospital. RESULTS: At presentation 4/10 patients had a visual acuity of < or = 0.1, and 2/10 had no light perception. A cystic epithelial downgrowth was verified histologically in 9/13, and a diffuse form in 4/13 patients. Mucin production was proven histochemically in 1/9 intraocular epithelial downgrowth sections. In one case a spontaneous iris cyst was detected by the immunohistological examinations. Trauma (10/14) and surgery (3/14) were the most frequent causes and were symptomatic on average 17 years after the primary event. A curative surgery was done in 13/14 patients (5 x en bloc excision, 2 x penetrating keratoplasty, 1 x iridectomy, 2 x enucleations, 3 x external) resulting in no recurrences during the follow-up of 4(1/2) years (1 - 12 years). The postoperative visual acuity was ameliorated in 5/9, worsened in 2 patients, and 2 were enucleated. CONCLUSIONS: Epithelial downgrowth is a rare but preventable cause of blindness. The most important prophylaxis is meticulous primary surgery including a sufficient wound closure. The visual outcome depends on the preoperative conditions.

[Interstitial photodynamic laser therapy for liver metastases: first results of a clinical phase I-study]. / Interstitielle Photodynamische Lasertherapie zur Behandlung von Lebermetastasen: Erste Ergebnisse einer in vivo Phase I-Studie.

PURPOSE: Development and evaluation of a new photodynamic treatment technique for the laser therapy of liver malignancies MATERIAL AND METHODS: The combination with new catheter systems enables the use of the photodynamic therapy (PDT) to treat also tumors in parenchymal organs. So far it is mainly used to treat superficial or endoluminal tumors. The presented study is part of a multicenter phase I-study. We treated 5 patients with colorectal liver metastases with the new photosensitizer SQN 400 and following interstitial photodynamic laser treatment. Evaluation of tumors were performed by contrast-enhanced CT scans. RESULTS: In the contrast enhanced CT scans the development of a complete necrosis within a radius of 1 cm around every single fibre could be shown. Additional the ablation of tumors with the combined use of several fibres is possible. Severe complications or toxicities were not observed. CONCLUSION: The photodynamic laser therapy of liver malignancies is a minimal invasive procedure with little side effects which produces sharply defined yet small volumes of necrosis.

[MR-guided biopsies of undetermined liver lesions: technique and results]. / MRT-gezielte perkutane Biopsie bei unklaren fokalen Leberläsionen: Technik und Ergebnisse.

PURPOSE: To evaluate safety and precision of liver tumor biopsies performed in an open low field system using different sequence techniques. MATERIALS AND METHODS: In 47 patients with liver tumors, MR-guided biopsies were performed in a low field system (0.2 Tesla, Magnetom Open, Siemens) using two different sequences. The procedure was monitored with T1-weighted FLASH sequences (TR/TE = 100/9; 70(3)) in all patients and with FISP-Rotated-Keyhole-sequence (TR/TE = 18/8; 90(3)) in additional 20 patients. After positioning of the needle tip in the tumors, 166 biopsy specimens were acquired with 16 G cutting needles (Somatex*). The diameter of the biopsied lesions ranged from 1 to 10 cm (mean diameter 3.2 cm). Visibility of the needles and precision of the biopsies were evaluated. RESULTS: All interventional biopsies were performed without vascular or organ injuries. Adequate specimens for histologic interpretation were obtained in 42 cases (89.3%). The biopsy results were non-specific in 2 patients (4.2%) and the lesions missed in 3 patients (6.3%). Mean in-room time was 35 minutes and the intervention time was 8.3 minutes. T1-weighted FLASH images proved optimal for confirming needle-tip placement during the biopsies or punctures. Organs, tumors and vessels were easily identified. The FISP sequence proved to be inferior in visualizing vessels and tumors. CONCLUSION: MR-guided liver biopsies are safely and precisely performed using T1-weighted FLASH-sequences with sufficient visualization of the lesions and might be complementary to US- or CT-guided biopsies.

[Pathogenesis of choroidal neovascularization. Old concepts, new questions]. / Pathogenese der choroidalen Neovaskularisation. Alte Konzepte, neue Fragen.

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world but the pathogenesis remains poorly understood. Malfunction of the retinal pigment epithelium (RPE) plays a central role in the disease and leads to either choriodal atrophy or proliferation. This article reviews the current concepts of the development of choriodal atrophy and neovascularisation. Furthermore, available animal models and potential therapeutical targets are discussed.

Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma.

PURPOSE: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured < or = 7 cm, total tumor volume < or = 200 cm(3)). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. RESULTS: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. CONCLUSION: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.