[The Subretinal Implant - Clinical Results]. / Das subretinale Implantat ­ klinische Ergebnisse.

Since the end of the last century, subretinal electronic chips have been used to restore vision in patients blinded by degenerative retinal diseases such as retinitis pigmentosa. Various procedures have been suggested by different international scientific groups. The promising were the retinal-based concepts, for which there are now human data. The two distinct retina-based concepts not only differ in the site of stimulation (epi- or subretinal), but in their physiological concept. Whereas in camera-based systems (epiretinal, transchoroidal), eye movements cannot be used to detect objects, this is possible with subretinal access. It is as yet unclear as to whether this is relevant to restoring some kind of useful visual perception. This and other questions can only be answered by carefully designed human studies with sufficient patient numbers. Comparison of the visual results of the different groups is neither simple nor trivial. The implantations in each project need well trained and skilled retinal surgeons.

[Anti VEGF Therapy Under Real-Life Conditions: Adherance Determines Long Term Outcome in Neovascular AMD]. / Real-Life-Daten zur Anti-VEGF-Therapie: Therapieadhärenz bestimmt den Visuserhalt bei neovaskulärer AMD.

BACKGROUND: Data from real-life studies on neovascular AMD (nvAMD) generally fall significantly behind respective data from interventional prospective trials. This can be attributed at least partially to differences in patient cohorts concerning both stages of AMD (including consecutive scarring or atrophy), as well as adherence to therapy. We have been interested in the question which of the two factors most affects outcome in a real-life setting. PATIENTS AND METHODS: Retrospective study of 1500 cases of nvAMD over a time period of up to 5 years. Inclusion of all cases treated for nvAMD which received at least 3 intravitreal injections, no exclusion of cases. Treatment was according to pro re nata (PRN) scheme. RESULTS: In total, results for gain in visual acuity (letter score + 1,4 and - 0,8 for year 1 and 2, respectively), and number of injections (5,2 and 3,3) are well comparable to data from other German real-life studies. The variance within the dataset, however, is relatively large. Definition of one subgroup characterized by significantly better baseline visual acuity and significantly higher number of injections demonstrates expectedly significantly better outcome. This better performance, however, is outranged by a subgroup defined only by its significantly higher adherence to therapy. In fact, only approx. 30 % of all cases fall into this category and followed the desired PRN intervals reasonably well. This group shows gain in visual acuity of + 3,3 and + 1,6 with number of injections of 7,0 and 5,8 while not being selected according to stages of AMD at baseline. CONCLUSION: In this setting adherence to treatment more than the stage of nvAMD at baseline determined long term outcome of anti-VEGF treatment. This is encouraging for every days work where unfortunately late stages of AMD are not seen rarely. This finding emphases the importance of patient counseling and information to improve adherence to treatment.

A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia.

The constantly recurring epistaxis means a great reduction of quality of life for patients with hereditary haemorrhagic telangiectasia (HHT). As yet, an ideal treatment has not been found. Vascular endothelial growth factor (VEGF) has been described as a possible new therapy. In particular, the success of submucosal doses <100 mg has not been analysed before. We injected bevacizumab (Avastin) submucosally in addition to Nd:YAG laser therapy. Doses <7.5 mg were used. To investigate the effect of these additional injections in comparison to laser therapy alone, a retrospective analysis was done. For this purpose a standardized patient questionnaire was completed, which included recording the patients' Epistaxis Severity Score (ESS) before and after the antibody treatment. Besides, patient files were analysed to collect objective data like haemoglobin levels and the number of blood transfusions needed. Data for eleven patients could be analysed. A significant improvement in the ESS resulting from additional bevacizumab therapy was observed (p < 0.01). In particular, the frequency of epistaxis (p = 0.011), duration of epistaxis (p < 0.01), severity of epistaxis (p < 0.01) and the need for acute medical treatment (p = 0.014) decreased significantly. The haemoglobin levels increased significantly (p = 0.011) and the number of blood transfusions declined. There were no side effects caused by the antibody treatment. Additional injections of a low dose of bevacizumab seem to be superior to Nd:YAG laser therapy alone. These results justify further studies.

Development of sensitivity to tetrodotoxin in beating chick embryo hearts, single cells, and aggregates.

The spontaneous activity of intact embryonic heart becomes progressively more sensitive to tetrodotoxin block with increasing age of the embryo. The activity of isolated single heart cells in culture was relatively insensitive, independent of embryo age. Aggregates formed from single cells responded to tetrodotoxin in the same manner as intact hearts; aggregated cells from older hearts were sensitive.

Long-term evaluation of anatomic and functional results after complicated retinal detachment treated with pars plana vitrectomy and heavy silicone oil tamponade.

BACKGROUND: Heavier than water tamponades offer the possibility to support the inferior part of the fundus after retinal detachment. The aim of this study was to evaluate the anatomic and functional outcome of complicated retinal detachment treated with vitreous surgery and heavy silicone oil (HSO) tamponade. Surgery was performed in eyes with rhegmatogenous retinal detachment (RD) predominantly in the lower hemisphere or with penetrating injury (either as primary intervention or after development of proliferative vitreoretinopathy [PVR]). MATERIALS AND METHODS: Sixty-one eyes of 61 patients with RD - mostly complicated by PVR - and a minimum follow-up of 12 months were included in this study. Vitreoretinal surgery with HSO (Oxane HD) tamponade was performed in all patients. In 52 patients, heavy silicone oil was used in the management of complicated RD. 9 patients had surgery for complicated RD after penetrating eye injury.The mean follow-up period was 30.3 +/- 10.2 months. RESULTS: The overall final anatomic success rate was 79 %. In 39 % of the cases the retina remained attached during the entire follow-up period. CONCLUSIONS: The anatomic success rate after surgery with HSO (Oxane HD) was relatively low; however, only complex cases bearing a higher risk of retinal re-detachment received HSO in this study. Oxane HD does not appear to have major advantages compared to conventional silicone oil or other new-generation heavy silicone oils in these cases.

[Cost calculations for treating penetrating eye injuries within the DRG C01Z at a university eye hospital]. / Kostenkalkulation für die Behandlung von offenen Augenverletzungen in der DRG C01Z an einer Universitäts-Augenklinik.

BACKGROUND: Since 2004, inpatient health care for penetrating eye injuries in Germany had been paid according to the calculated DRG C01Z. Because the extent of treatment mainly derives from the extent of eye damage, this DRG economically summarises very heterogeneous cases. It was the aim to check the cost recovery for the surgical treatment of penetrating eye injuries at a university eye hospital. MATERIAL AND METHODS: Performance data for the DRG C01Z were collected for the years 2005 and 2006 using the E1 sheets according to section sign21 KHEntG. Costs for single operations were calculated from fixed and variable costs for the operating theatre and the ward, including costs for personnel and supplies. RESULTS: In the 2-year period, out of 4,721 inpatient procedures, 180 perforating eye injuries were surgically treated. In 80 cases, a pure corneal/scleral suture (plus cataract surgery, n=10; mean operating time 67.81 min) was performed. In the other 100 cases, a pars plana vitrectomy (ppV) with adjuvant measures (mean operating time 124.69 min) was needed. Each operation had fixed surgical costs of EUR 130.60; variable costs, including personnel and supplies, varied between EUR 570 for corneal/scleral suture (+/-EUR 250 for combined cataract surgery (n=10) and EUR 1230 (mean) for a ppV. Cost-effective additional adjuncts such as cerclage, perfluorocarbon, gas, silicone oil, or cataract surgery led to extra costs of between EUR 51 and EUR 250 per adjunct (mean EUR 182). At least two of these adjuncts were used in 50% of ppVs, and at least one was used in 90% of ppVs. Hospitalisation costs were about EUR 2184 (EUR 273 per day), with a mean stay of 8 days. The overall costs of an operation for penetrating eye injuries differed significantly in terms of the procedure (corneal/scleral suture: EUR 2662, mean length of stay 7.06 days; ppV: EUR 3712, mean length of stay 8.62 days). Additional costs for multiple surgeries, as occurred in 11.1% of all cases, were not compensated by the DRG system. CONCLUSION: In consideration of a relative DRG weight of 1,177 and a base rate of EUR 2723.79 in Bavaria for 2005 and 2006, perforating eye injuries were compensated within the C01Z DRG at EUR 3205,96. Thus, for ppVs no costs are recovered, whereas "pure suture" procedures are overweighted. Due to this inhomogeneity, a split in the C01Z DRG is necessary.

Tetrodotoxin desensitization in aggregates of embryonic chick heart cells.

Spontaneous beating of heart-cell aggregates from 4-day chick embryos was initially blocked by 10(-5) g/ml tetrodotoxin (TTX). With continued exposure to the drug, the fraction of blocked aggregates decreased from about 80% at 15 min to about 25% at 2-3 h, at which time, beating aggregates had become desensitized to the toxin, showing no response to a fresh dose. Aggregates from 5-day hearts were more sensitive to TTX, but fewer became desensitized in its presence. Desensitization to TTX was not seen in 6- and 7-day aggregates. Inhibition of protein synthesis by cycloheximide did not affect beating or initial sensitivity to TTX of 4-day aggregates, but desensitization failed to occur. Before TTX, the mean value of maximal upstroke velocity (V(max)) of the action potentials in 4-day aggregates was 33 V/s. After desensitization V(max) was 12 V/s. Activity of desensitized aggregates in the presence of TTX was augmented by elevated calcium levels, and suppressed by presumed inhibitors of slow inward current (manganese, D600). Desensitization was reversible; upon removal of TTX 10(-5) g/ml, aggregates regained their responsiveness to a fresh dose of the drug with a 2-3 h time-course similar to that of desensitization. This was prevented by continued exposure to TTX at concentrations as low as 10(-8) g/ml. These data suggest that (a) desensitization involves a change in the mode of action-potential generating from one involving Na-specific, TTX-sensitive channels to one utilizing slower Mn-sensitive channels; (b) the process of desensitization occurs over a period of 2-3 h and is dependent upon the products of protein synthesis; and (c) desensitization is reversible after removal of TTX over a 2-3 h time-course similar to its onset.

Macular function and morphology after peeling of idiopathic epiretinal membrane with and without the assistance of indocyanine green.

AIM: To investigate macular function and morphology after surgical removal of idiopathic epiretinal membrane (IEM) with and without assistance of indocyanine green (ICG). METHODS: A retrospective study as a consecutive case series, of 39 patients with IEM. 39 patients, 23 female, 16 male, mean age 67 years, underwent standard three port pars plana vitrectomy with removal of epiretinal membrane. Two groups of patients were consecutively operated: in 20 patients ICG 0.1% in glucose 5% was used to stain the epiretinal membrane. 19 patients underwent the identical procedure but without use of ICG. Postoperative follow up was 1-92 months (mean 15.5 months). Functional outcome was assessed with subjective improvement, best corrected visual acuity (BCVA), Amsler grid test, 10 degrees and 30 degrees automated perimetry (Heidelberg visual field analyser) (HFA), and Goldmann kinetic perimetry. Macular morphology was assessed with stereoscopic biomicroscopy and optical coherence tomography (OCT). The main outcome measures were macular function as determined by BCVA, presence of visual field defects, and metamorphopsia as determined by Amsler grid test, macular morphology as determined by slit lamp biomicroscopy, and OCT. RESULTS: BCVA improved in 28 patients, remained unchanged in eight patients, and decreased in three patients. Improvement of BCVA was statistically significant in both groups (p = 0.003). Mean BCVA in patients operated with ICG improved from 0.33 preoperatively to 0.53 postoperatively. Mean BCVA in patients operated without ICG improved from 0.32 preoperatively to 0.54 postoperatively. Reduction of macular oedema as measured by OCT was statistically significant in both groups (p<0.01). There was no statistically significant difference in postoperative BCVA, macular oedema as measured by OCT, postoperative Amsler grid test, and subjective improvement between the two groups. The incidence of residual or recurrent epiretinal membrane was greater in the group operated without ICG (p = 0.014). Visual field defects were detected in one patient operated with ICG and in three patients operated without ICG. CONCLUSIONS: Removal of epiretinal tissue with or without assistance of ICG improved visual function and reduced macular oedema in most patients. Adverse effects clearly attributable to the use of ICG were not observed but further investigation is warranted.

Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development.

PURPOSE: During the course of the development of visual prostheses, subretinal stimulation films were implanted in micropigs in order to prove the feasibility of subretinal electrical stimulation with subsequent cortical response. One aim was to demonstrate that epidural recording of visual evoked potentials is possible in the micropig. METHODS: Film-bound stimulation electrode arrays were placed in the subretinal space of micropigs. This enabled the retina to be stimulated subretinally. Since conventional visual evoked potential (VEP) measuring is virtually impossible in the pig from the neurosurgical point of view, epidural recording electrode arrays were positioned over the visual cortex as permanent electrodes. RESULTS: The feasibility of temporary implantation of film-bound stimulation electrode arrays was successfully demonstrated in the micropig model. On stimulation with monopolar voltage pulses (1000 to 3000 mV), reproducible epidural VEP measurements (5 to 10 micronV) were detected. CONCLUSIONS: The feasibility of subretinal stimulation of the retina was demonstrated in a retinal model that is similar to the human retina. This animal model therefore offers a suitable means of studying the tolerability of stimulation situations in the course of visual prosthesis development.

Electrophysiological study of Syrian hamster hereditary cardiomyopathy.

This study was performed to determine if the intracellular electrical activity of adult cardiac papillary muscle from a strain of Syrian hamster (B10 14.6) with a genetically determined cardiomyopathy was different from that of a control strain (B10 RB). Muscles driven at rates from 1 Hz through the physiological range. Resting potentials of muscle from the two strains were not significantly different, except in increased [C2+]0, where the control was slightly hyperpolarised. Action potential overshoot was significantly greater in the myopathic at all frequencies, while the upstroke velocity was not significantly different, except at 8 Hz where the myopathic value was depressed. Action potential durations at 20, 50 and 95% repolarisation were significantly greater in the myopathic, at all rates and with increased [C2+]0. Response of the muscles to verapamil and D600 were complex, with a decrease seen in duration at 20% repolarisation and an increase in 50% duration at 1 Hz rate. No strain-related difference in sensitivity to the drugs was seen. The results supporty the hypothesis that a sarcolemmal defect is intimately related to the genesis of the cardiomyopathy.

Age-dependent alterations in rat ventricular myocardium: a quantitative analysis.

A quantitative electron microscopic examination of the ventricular myocardium of the male Fischer 344 rat was undertaken to determine the extent of age-dependent changes in ultrastructure. Rats of 6, 16 and 30 months of age were examined using a non-biased stereological test system. Volume fractions of mitochondria, myofibrillar mass and lipid remained unchanged during aging. Dense body volume fraction increased four-fold over the period studied, while the sarcoplasmic reticulum volume increased only from 6 months to 16 months and did not change thereafter. Biochemical analysis of the specific activities of the two lysosomal enzymes, acid phosphatase and beta-glucuronidase demonstrated a differential response to aging, with acid phosphatase remaining constant and beta-glucuronidase increasing slightly. Neither enzyme activity correlated with the pronounced change in dense body volume fraction. This study provides clear evidence that the previously observed changes in cardiac performance associated with aging are not readily explicable on the basis of a degradation of cardiac ultrastructure.

Lymphocyte requirement for the functional development of follicle-associated epithelium.

Follicular development in the bursa of Fabricius was disrupted by testosterone treatment and chorioallantoic membrane grafting. Analysis by a quantitative histological technique demonstrated that testosterone treatment causes a dose dependent delay in development by inhibiting lymphoid proliferation. Inhibition of lymphoid development prevented the development of carbon transport ability by follicle associated epithelium. Reconstitution of follicular development by grafting treated bursae to the chorioallantoic membrane of untreated hosts results in the development of functional follicle associated epithelium. These results establish the lymphoid requirement for the development of transport ability by the follicle-associated epithelium.

Antibody production in organ culture by bursae of mature chickens and the development of immunological compentence.

Antibody responsiveness of bursal lymphocytes was studied in vitro. Organ culture of bursal tissue in the presence of antigen, either sheep erythrocytes or bovine serum albumin, results in significant numbers of plaque-forming cells (PFC) compared to controls. The response in organ culture is age-dependent in that only bursae from chickens at least three weeks of age contained significantly increased numbers of secreting cells. Prolonged culture of normally unresponsive bursae from newly hatched birds results in a PFC response to antigen, suggesting that in vitro maturation occurs.

The influence of embryonic testosterone treatment on bursal epithelial pinocytotic activity.

Developing White Leghorn chicks were treated with testosterone propionate in ovo to effect a partial chemical bursectomy. After hatching, birds were administered carbon particles or horseradish peroxidase via the cloaca, and the transport of these tracers by the bursal epithelium was examined. Uptake of both tracers was inhibited in the treated when compared to untreated birds. The degree of development of interaction between bursal epithelium and underlying lymphoid tissue appeared to play a major role in determining ability of the epithelium to transport these tracers. Epithelium associated with follicles possessing medullary and cortical divisions was able to transport, while intraepithelial follicles or regions of the epithelium overlying diffuse lymphoid tissue did not transport either carbon or horseradish peroxidase. Bursal function in regional defense of the gut may depend on a local interaction of bursal epithelium with lymphoid, and perhaps other cell types.

[Invasive aspergillosis of the orbit in immunocompetence]. / Invasive Aspergillose mit Orbitabefall unter Immunkompetenz.

BACKGROUND: An isolated aspergillosis of the sphenoidal sinus is a difficult diagnosis because the often misleading clinical symptoms of this rare disease can develop late and first be presented to the ophthalmologist. Because of this even life-threatening disease in normally immunodeficient patients, fast diagnostics and treatment is indicated. CASE REPORT: We report about an immunocompetent man to suffer from an invasive aspergillosis involving the sphenoidal sinus after external operation of a mucocele. Aspergillus infiltrated the right orbit by bone erosion and led to an acute loss of vision on his right eye and a pathological visual field (visual acuity 0.1). A systemical antimycotic therapy was performed and the right orbit and the optical channel were operated to remove the mycosis. During operation the optical nerve was found to be completely surrounded by the mycosis. After surgery visual acuity recovered slowly but completely in about two weeks (visual acuity 1.0) and visual field examination revealed normal findings. These findings were stable now for one year. CONCLUSION: The main findings of unilateral acute visual loss and pre-operations of the paranasal sinuses in combination with persistent headache can lead to the suspect of an aspergillosis infection. It is important to establish correct diagnosis--especially in immunocompetent patients--early to prevent a probably irreversible visual loss and in an advanced stage to handle the life-threatening risk of this disease.

[Intraocular pressure in sections with 2 microkeratomes in vitro]. / Intraokularer Druckverlauf bei Schnitten mit 2 Mikrokeratomen in vitro.

BACKGROUND: The rapid integration of new technology into ophthalmologic practice, e.g. LASIK (laser in situ keratomileusis), is associated with new complications. The limitations of the new technology cannot be precisely determined. During lamellar cuts with microkeratomes intraocular pressure (IOP) elevations occur. The IOP elevation during the lamellar cut cannot be determined by conventional tonometry. MATERIALS AND METHOD: We examined the IOP rise during the complete microkeratome treatment. Fresh enucleated porcine eyes were cannulated and direct IOP measurement with a Statham manometer was carried out. Thus we evaluated the IOP during the complete treatment for two differently constructed microkeratome systems. RESULTS: IOP elevations (mean values) between 77 mm Hg for the Corneal Shaper and 229 mm Hg for the Keratek during the vacuum phase and 140 mm Hg for the Corneal Shaper and 360 mm Hg for the Keratek during the lamellar cut were monitored. A sudden IOP decrease to-5 mm Hg was registered for the post-vacuum phase. CONCLUSIONS: In our opinion unphysiologic high IOP values could be dangerous for risk eyes.

Intraocular pressure during lamellar cuts with two different microkeratomes.

BACKGROUND: The rapid integration of new technology into ophthalmologic practice, e. g. LASIK (laser in situ keratomileusis), is associated with new complications. The limitations of the new technology cannot be precisely determined. During lamellar cuts with microkeratomes intraocular pressure (IOP) elevations occur. The IOP elevation during the lamellar cut cannot be determined by conventional tonometry. MATERIALS AND METHOD: We examined the IOP rise during the complete microkeratome treatment. Fresh enucleated porcine eyes were cannulated and direct IOP measurement with a Statham manometer was carried out. Thus we evaluated the IOP during the complete treatment for two differently constructed microkeratome systems. RESULTS: IOP elevations (mean values) between 77 mm Hg for the Corneal Shaper and 229 mm Hg for the Keratek during the vacuum phase and 140 mm Hg for the Corneal Shaper and 360 mm Hg for the Keratek during the lamellar cut were monitored. A sudden IOP decrease to -5 mm Hg was registered for the post-vacuum phase. CONCLUSIONS: In our opinion unphysiologic high IOP values could be dangerous for risk eyes.

[Central retinal artery occlusion. Importance of selective intra-arterial fibrinolysis]. / Zentralarterienverschluss. Stellenwert der selektiven intraarteriellen Fibrinolyse.

BACKGROUND: Conventional treatment of a central retinal artery occlusion usually has a poor prognosis but intra-arterial fibrinolysis (IF) of the ophthalmic artery is an invasive treatment option. The importance of IF was evaluated in 62 patients with central retinal artery occlusion and in addition the risk spectrum for this disease was considered. MATERIAL AND METHODS: Data from charts of 62 patients were retrospectively analysed. Visual recovery after IF (n = 17) was compared to conventional treatment (e.g. decrease of IOP, improvement of rheological conditions, n = 45). Patients were excluded from IF if the occlusion was present for more than 8 h, if there was a history of bleeding and previous operations, or if they were older than 85 years. IF was performed using either urokinase (n = 7) or tPA (n = 10). RESULTS: Out of 62 patients, 22 (35%) with central retinal artery occlusion underwent catheterisation. Stenosis of the carotid artery excluded IF in 5 out of these 22 cases, therefore only 17 patients were treated by IF. Of the patients, 40 (65%) were excluded from IF for various reasons: 47% (19/40) arrived later than 8 h after occlusion, 17% (7/40) did not consent to IF, 15% (6/40) had medical contraindications and 13% (5/40) were over 85 years of age. Two patients required no IF because of a cilioretinal anastomosis with moderate visual acuity and another patient showed spontaneous visual recovery during ophthalmic examination. Of the 17 patients treated with IF, 4 achieved an improvement of visual acuity by more than 2 lines, no change of visual acuity was observed in 12/17 patients and 1/17 lost more than 2 lines after treatment. Of the 45 conservatively treated patients, 16 achieved improvement by more than 2 lines and no change occurred in 29/45 patients. Three patients treated with IF suffered from a stroke during treatment. The main risk factor for central retinal artery occlusion was high blood pressure in 32% of all cases and nicotine abuse in 16%. CONCLUSIONS: Many patients presented too late for IF. However, there was no statistical difference between patients with IF and conventional treatment with regards to the improvement of visual acuity. Additionally there is an increased risk of a stroke from IF, therefore a prospective study is necessary to evaluate the importance of IF. Stabilisation of high blood pressure may be the best prophylaxis for preventing a central retinal artery occlusion.