[Marginal protection of retinal cells by bisperoxovanadium : Appropriate therapy in the model of retinal ischemia?] / Marginale Protektion retinaler Zellen durch Bisperoxovanadium : Geeignete Therapie im Modell der retinalen Ischämie?

BACKGROUND: Ischemic processes usually lead to the destruction of retinal cells and therefore play a key role in a multitude of eye diseases. OBJECTIVE: The aim of this study was to investigate whether bisperoxovanadium has a potential neuroprotective effect in an ischemia/reperfusion animal model. MATERIAL AND METHODS: Initially, ischemia was induced in one eye of an ischemia/reperfusion model and 3 days later, a 14-day medication-based treatment was initiated. Bisperoxovanadium was administered intraperitoneally every 3 days. Subsequently, the number of ganglion cells, the rate of apoptosis, amacrine cells, macroglia, microglia, and their activation state, as well as photoreceptors were determined by histological and immunohistochemical analyses. RESULTS: In comparison to the control group, a significant retinal ganglion cell loss, a significant reduction of the inner layers as well as a decrease in photoreceptor and amacrine cell numbers could be determined in the ischemic eyes. In addition, there was an increase in the number of microglia in these animals. The rats treated with bisperoxovanadium did not exhibit a significant neuroprotective effect regarding the number of ganglion cells, the rate of apoptosis, macroglia, amacrine cells, or photoreceptors; however, a low structural degeneration of photoreceptors could be observed as an effect of the treatment. Additionally, fewer microglia and activated microglia were observed after bisperoxovanadium treatment. CONCLUSION: Bisperoxovanadium seems to have only a marginal neuroprotective effect on ischemic retinae. It needs to be examined whether earlier therapy onset, higher dose or different route of administration would significantly improve the results or whether this therapeutic approach is unsuitable.

[Early onset of fingolimod-associated macular edema]. / Frühzeitiges Auftreten eines Fingolimod-assoziierten Makulaödems.

BACKGROUND: Fingolimod, a disease-modifying sphingosine 1­phosphate receptor modulator, which was approved in Germany in 2011, decreases the relapse rate and reduces neuroinflammation in patients with relapsing-remitting multiple sclerosis. Macular edema is a well-known ocular side effect of fingolimod therapy. Specific intervals for ophthalmologic check-ups after starting fingolimod and definite treatment schedules for fingolimod-associated macular edema are, however, still lacking. CASE REPORT: We present a case of early fingolimod-associated macular edema in a 45-year-old female patient with relapsing-remitting multiple sclerosis. The patient complained about visual impairment 1 month after the start of fingolimod and visited an eye specialist. Funduscopic examination and imaging diagnostics revealed macular edema in both eyes. The treatment with fingolimod was immediately stopped. For therapy of macular edema topical application of nepafenac and oral acetazolamide were given. During the 6 months of treatment the macular edema completely disappeared and visual function recovered completely. DISCUSSION: At the time of diagnosis, it is fundamentally important to discuss the continuation of fingolimod administration with the attending neurologist and if necessary to discontinue the drug. Regular ophthalmologic check-ups at 4­week intervals over a period of 3 months are meaningful after beginning fingolimod treatment. As before, it is still a key aspect to determine predictive opthalmologic and neurological factors before beginning treatment to evaluate which patients are at risk of fingolimod-associated macular edema.

[New Developments in Cataract Surgery]. / Interessantes aus der Kataraktchirurgie.

Recent technological innovations in cataract surgery have made the procedure even more precise and safe and the odds of having a highly satisfied patient even higher. These innovations include visualisation systems - such as intraoperative aberrometry - which are particularly helpful when it comes to implanting toric IOLs, where even a slight rotation or misalignment can significantly reduce the postoperative visual quality. Another way to ensure the exact positioning of a toric IOL is to create a mark by making an intrastromal incision using the femtosecond laser. The latter technology has increased the precision of capsulotomy and other steps of the operation and has been successfully employed in patients with a challenging clinical profile, including paediatric and hypermature cataracts. The femtosecond laser, however, induces an increase in intraocular prostaglandins, which can lead to miosis. Applying topical NSAIDs before starting surgery has proved to be effective in coping with the consequences of the increase in prostaglandins. Good vision without using glasses for near, intermediate and far distances remains a goal for many patients. IOLs with extended depths of focus (EDOF) technology can provide this comfort - to some but not all patients. An intraocular sensor, Eyemate, that is implanted during cataract surgery, enables the glaucoma patient to check his or her IOP at any time and improves the management of glaucoma and its main risk factor, elevated IOP. Several methods - drugs or nutritive agents - are said to prevent cataractogenesis. These studies have probably to be taken with the proverbial grain of salt.

Degenerative effects of cobalt-chloride treatment on neurons and microglia in a porcine retina organ culture model.

In order to understand the pathological processes of retinal diseases, experimental models are necessary. Cobalt, as part of the vitamin B12 complex, is important for neuronal integrity. However, it is known that high quantities of cobalt induce cytotoxic mechanisms via hypoxia mimicry. Therefore, we tested the degenerative effect of cobalt chloride (CoCl2) on neurons and microglia in a porcine retina organ culture model. Organotypic cultures of porcine retinas were cultured and treated with different concentrations of CoCl2 (0, 100, 300 and 500 µM) for 48 h. After four and eight days, CoCl2 induced a strong degeneration of the porcine retina, starting at 300 µM. A loss of retinal ganglion cells (RGCs, Brn-3a), amacrine cells (calretinin) and bipolar cells (PKCα) was observed. Additionally, a high expression of hypoxia induced factor-1a (HIF-1a) and heat shock protein 70 (HSP70) was noted at both points in time. Also, the Caspase 3 protein was activated and P21 expression was induced. However, only at day four, the Bax/Bcl-2 ratio was increased. The effect of CoCl2 was not restricted to neurons. CoCl2 concentrations reduced the microglia amount (Iba1) and activity (Iba1 + Fcγ-Receptor) at both points in time. These damaging effects on microglia were surprising, since CoCl2 causes hypoxia and a pro-inflammatory environment. However, high concentrations of CoCl2 also seem to be toxic to these cells. Similar degenerative mechanisms as in comparison to retinal ischemia animal models were observed. In summary, an effective and reproducible hypoxia-mimicking organotypic model for retinal degeneration was established, which is easy to handle and ready for drug studies.

[Unusual masquerade of an ocular carcinoma metastasis]. / Untypische Masquerade einer okulären Karzinommetastase.

BACKGROUND: Idiopathic and therapy resistant uveitis especially of unclear origin, is a diagnostic challenge for ophthalmologists. Metastases to the anterior chamber or vitreous body can occasionally mimic the clinical picture of uveitis, a variant on the usual lymphomatous masquerade syndrome. The underlying pathological pathways leading to the metastatic spread of tumor cells within the fluid compartments of the eye remain unclear. CASE REPORT: We present an unusual case of vitreous metastases to the right eye of a patient in whom an underlying primary malignancy was unknown. After recurrent episodes of cortisone-refractive panuveitis with pseudohypopyon, a diagnostic vitreous biopsy was performed. Cytopathological examination of the vitreous sample revealed carcinoma cells with an immune profile suggestive of lung cancer metastasis. Subsequent staging investigations revealed a primary lung adenocarcinoma as well as cerebral, adrenal and osseous metastases. THERAPY: Due to the extent of dissemination of this non-small cell lung cancer (NSCLC), only palliative treatment including external beam irradiation and systemic chemotherapy was possible to reduce pain and to maintain vision as well as an attempt at systemic control of the disease.

[Femtosecond laser in cataract surgery. A critical appraisal]. / Femtosekundenlaser in der Kataraktchirurgie. Eine kritische Betrachtung.

BACKGROUND: The use of femtosecond lasers (FSL) is increasingly spreading in cataract surgery. Potential advantages over standard manual cataract surgery are the superior precision of corneal incisions and capsular openings as well as the reduction of ultrasound energy for lens nucleus work-up. Exact positioning and dimensioning of the anterior capsular opening should help reduce decentration and tilt of the intraocular lens (IOL) optics and thus achieve better target refraction. Together with the possibility to correct low-grade corneal astigmatism by precise arcuate incision, FSL technology is expected to convert cataract surgery from a purely curative into a refractive procedure. METHODS: Apart from own experiences this review article critically analyses the pertinent literature published so far as well as congress presentations and personal reports of other FSL surgeons. The advantages and disadvantages are scrutinized with regard to their impact on the surgical and refractive results and compared with those experienced by the authors with manual cataract surgery over several decades. Economic and healthcare political aspects are also addressed. RESULTS: The use of FSL surgery improves the precision and reproducibility of corneal incisions and the capsular opening and reduces the amount of ultrasound energy required for lens nucleus work-up. However, the clinical benefits must be put into perspective due to the subsequent surgical manipulation of the incisions (during lens emulsification, aspiration and IOL injection), the lacking possibility to visualize the crystalline lens equator as the reference for correct capsulotomy centration and the relativity of ultrasound energy consumption on the corneal endothelial trauma. This is of particular relevance against the background of the significantly higher costs. Conversely, tears of the anterior capsule edge which, apart from interfering with correct IOL positioning, may entail serious complications presently occur more frequently with all FSL instruments. From the economic and healthcare political viewpoint, thought should be given to the possible acquisition of the cataract surgical business by the industry or investors, as cataract surgery is a high-volume standardized procedure with enormous future potential. This could fundamentally change our currently decentralized and individualized structures and subsequently the steam of patient and make surgeons largely dependent or superfluous.

[Femtosecond laser-assisted cataract surgery]. / Femtosekundenlaser-assistierte Kataraktchirurgie.

Employing a femtosecond laser as an initial step in cataract surgery has the clear potential to provide more precise capsulotomies and full lens fragmentation in cases of pre-existing astigmatism in conjunction with relaxing corneal incisions. In the long run femtosecond laser-assisted cataract surgery might replace phacoemulsification which has been the standard in cataract surgery over the last 20 years. Besides precision and predictability, the low rate of complications impresses surgeons working with the technology, particularly those employing a laser with a fluid-filled interface which seems to prevent major complications including increases in intraocular pressure.

[Supraciliary microstent for open-angle glaucoma: clinical results of a prospective multicenter study]. / Supraziliarer Mikrostent bei Offenwinkelglaukom: Klinische Ergebnisse einer prospektiven Multicenterstudie.

PURPOSE: The suprachoroidal CyPass micro-stent is designed to be implanted into the supraciliary space to facilitate aqueous outflow along the uveoscleral pathway in patients with open-angle glaucoma (OAG). This study assessed the safety of micro-stent implantation in patients undergoing cataract surgery. METHODS: In this multicenter study the CyPass microstent was implanted in patients with OAG undergoing cataract surgery. The implantation was performed using a minimally invasive, conjunctiva-sparing, ab interno intervention. Primary endpoints were safety aspects of the implant, secondary endpoints were the reduction of intraocular pressure (IOP) and topical medication. RESULTS: There were no severe adverse events during or after surgery in any of the patients. In patients with controlled glaucoma (IOP < 21 mmHg) the average IOP remained constant throughout the 24 month follow-up period but mean medication use decreased from 2.0 at baseline to 1.1 postoperative. In patients with IOP of ≥ 21 mmHg the pressure was reduced by 37 % postoperatively and mean medication decreased from 2.2 at baseline to 1.0. CONCLUSIONS: The safety profile of combined cataract surgery and CyPass microstent implantation is acceptable and patients also showed a decrease in IOP and medication use.

[The light-adjustable lens. Principles and clinical application]. / Die lichtadjustierbare Linse. Grundlagen und klinische Anwendung.

Despite improvements in preoperative lens power calculations many patients are in need of spectacle correction to achieve emmetropia and/or optimal distance vision after cataract surgery. A method to adjust residual spherical and astigmatic errors postoperatively in a predictable and non-invasive way is the implantation of the light-adjustable lens (LAL). Selective irradiation of the LAL with UV light (365 nm) using a digital light delivery device enables a customized light pattern for each patient which produces modifications in the lens curvature and lens power by polymerization of silicon monomers in the lens matrix. In Europe this therapeutic option is currently only available in Spain and Germany, therefore, the number of patients treated is limited. In the future this technique will be available for correction of higher order aberrations and to design individual multifocality.

[Toric phakic intraocular lenses]. / Torische phake Intraokularlinsen.

After more than 3 years of follow-up, the satisfactory results achieved with the toric iris-fixated phakic intraocular lens (IOL) mean we can regard implantation of this lens as a procedure with the potential to provide safe, predictable, effective and stable correction of astigmatic errors, providing patients are carefully selected and receive adequate preparation for surgery. The iris-fixated toric phakic IOL (Verisyse, Advanced Medical Optics; Artisan, Ophtec) is a PMMA lens with a total diameter of 8.5 mm and an optic diameter of 5 mm. It has a spherical anterior and a toric posterior surface. Its refractive power ranges from -2 dpt to -21 dpt for myopia and from +2 dpt to +12.5 dpt for the correction of hyperopia. Cylindrical correction is available from 2 dpt to 7.5 dpt. The Visian toric implantable Collamer lens (Staar) differs in that it is foldable and can be inserted through a very small incision of about 2.8 mm. It is placed in front of the natural lens in the ciliary sulcus. The aim of implanting these phakic IOLs is to correct the entire refractive error, meaning both the spherical and the astigmatic error, in a single step. Different lens models are available, and the selection depends on the direction of the cylinder axis and the anatomical situation, among other things.

[Complications after laser in situ keratomileusis (LASIK): results of a meta-analysis on incidences and expectable costs]. / Komplikationen nach Laser-in-Situ-Keratomileusis (LASIK): Ergebnisse einer Metaanalyse zu Inzidenzen und Folgekosten.

PURPOSE: Laser in situ Keratomileusis (LASIK) is considered to be safe and effective for the treatment of moderate myopia. Nevertheless, the treatment can result in complications, associated with additional costs for treatment of the latter and an associated reduction of the primary treatment's overall cost efficiency. METHODS: To both identify clinically relevant LASIK-associated complications and to estimate their expectable incidence and treatment cost-profile, a quantitative meta-analysis of trial publications between 1995 - 2004 was implemented. Inclusion criteria were a minimum sample size of 25 eyes, a reported preoperative patient refraction between - 1 und - 14 dioptres and the documentation of an at least 6 months recall period. For each reported complication its "meta incidence" (point estimate and 95 % confidence interval) was estimated. Furthermore, for each complication a clinical pathway for its treatment was modelled assuming a worst case scenario; the treatment costs for this pathway were simulated. The resulting costs for the treatment of one complication were then averaged by the expectable incidence of the respective complication; the maximum "expectable" costs for the respective complication's treatment were then summed up to correct the overall LASIK direct costs. RESULTS: A total of 30 trial reports was included into the meta-analysis; in total, 21 clinically relevant complications were identified (31 % intraoperative complications, among which 19 % were microkeratome-associated, versus 69 % postoperative complications, among which 87 % were classified as long-term postoperative). The most frequent complication was "light sensations" with a meta incidence of 46 % (95 % confidence interval 42 - 50 %), the most cost intensive complications were those requiring clinical re-treatment (overall meta incidence 24 % and expectable cost increase of 449 euro per primary LASIK procedure). In summary the total direct costs of 2426 euro per eye for the initial LASIK procedure may be increased by a total of maximum 648.30 euro, according to a maximum "expectable" cost increase of 27 % per primary LASIK due to complications. CONCLUSION: At least the worst case scenario introduced into this investigation demonstrated an economically relevant order for the expectable LASIK complications and the associated additional costs for complication treatment.

[Cataract surgery in childhood uveitis]. / Kataraktchirurgie bei Uveitis im Kindesalter.

The development of cataract is the most frequent vision-threatening complication of uveitis in children. In such cases cataract surgery is associated with a particular risk of intra- and postoperative complications and requires an intensive perioperative immunosuppression, an essentially atraumatic operation in a quiscient eye, and aggressive amblyopia treatment. When these factors are taken into consideration, a timely cataract operation can result in a sustained visual rehabilitation even for children with uveitis.

[Incremental cost effectiveness of multifocal cataract surgery]. / Inkrementelle Kosteneffektivität der multifokalen Kataraktchirurgie.

PURPOSE: Supplementation of cataract patients with multifocal intraocular lenses involves an additional financial investment when compared to the corresponding monofocal supplementation, which usually is not funded by German health care insurers. In the context of recent resource allocation discussions, however, the cost effectiveness of multifocal cataract surgery could become an important rationale. Therefore an evidence-based estimation of its cost effectiveness was carried out. METHODS: Three independent meta-analyses were implemented to estimate the gain in uncorrected near visual acuity and best corrected visual acuity (vision lines) as well as the predictability (fraction of patients without need for reading aids) of multifocal supplementation. Study reports published between 1995 and 2004 (English or German language) were screened for appropriate key words. Meta effects in visual gain and predictability were estimated by means and standard deviations of the reported effect measures. Cost data were estimated by German DRG rates and individual lens costs; the cost effectiveness of multifocal cataract surgery was then computed in terms of its marginal cost effectiveness ratio (MCER) for each clinical benefit endpoint; the incremental costs of multifocal versus monofocal cataract surgery were further estimated by means of their respective incremental cost effectiveness ratio (ICER). An independent meta-analysis estimated the complication profiles to be expected after monofocal and multifocal cataract surgery in order to evaluate expectable complication-associated additional costs of both procedures; the marginal and incremental cost effectiveness estimates were adjusted accordingly. A sensitivity analysis comprised cost variations of +/- 10 % and utility variations alongside the meta effect estimate's 95 % confidence intervals. RESULTS: Total direct costs from the health care insurer's perspective were estimated 3363 euro, associated with a visual meta benefit in best corrected visual acuity and near visual acuity of 5.1 lines (95 % confidence interval 3.8 - 6.4 lines) and 6.1 lines (4.7 - 7.5 lines), respectively, and a meta predictability estimate of 81 % (72 - 89 %). The mean MCER for best corrected visual acuity results became 659 euro per gained visual acuity line (sensitivity range 473 - 973 euro). For near visual acuity, a mean MCER of 555 euro (sensitivity range 404 - 787 euro) per gained visual line was found. In terms of incremental costs, multifocal cataract surgery implied an additional mean investment of 63 euro (sensitivity range 0 - 234 euro) per additionally gained near visual acuity line, and 5 euro (0 - 18 euro) per additionally gained percentage point in predictability, when compared to monofocal cataract surgery as the standard treatment. The meta-analysis on complication profiles revealed posterior capsule opacification (meta incidence 20 %) and vitreous loss (meta incidence 2 %) as the complications to be expected most frequently. The cost adjustment for expectable complication patterns after multifocal cataract surgery implied total direct costs of 3491 euro, resulting in marginal costs of 576 euro per line (sensitivity range 419 - 817 euro per line) gained in near visual acuity and 684 euro per line (491 - 1011 euro per line) gained in best corrected visual acuity. CONCLUSION: Bearing incremental costs of 63 euro per additionally gained vision line (near visual acuity) in mind, multifocal cataract surgery comprises a cost effective alternative to the monofocal standard treatment.

[Presbyopia treatment using a femtosecond laser]. / Presbyopietherapie mit Femtosekundenlaser.

Presbyopia is by far the most common refractive error worldwide, with no permanent therapeutic option available. All efforts to restore accommodation by the use of surgery have not led to a generally accepted therapy. However, there is evidence from an animal model that the use of a femtosecond (fs) laser might influence the modulus of elasticity in the lens. Fs-laser impulses can create intralenticular disruption in animal eyes as well as human cadaver lenses and improve elasticity. The concept of treating presbyopia with fs-laser requires a new, complex theory combining the optical and the mechanical aspects of accommodation in the eye. Diagnostic tools for measuring optical change in power and geometrical modification as the eye views from far to near are needed to obtain objective clinical data. A non-invasive treatment of presbyopia to restore accommodation might be possible in the future.

[Compensation of corneal astigmatism with toric intraocular lens: results of a multicentre study]. / Ausgleich des kornealen Astigmatismus mit torischer Intraokularlinse: Ergebnisse der Multicenterstudie.

UNLABELLED: This clinical trial was conducted to evaluate visual acuity, refraction and rotation after implantation of the foldable toric intraocular lens (IOL) MicroSil Toric. PATIENTS AND METHODS: 68 eyes of 48 patients from four different surgical departments were examined over a follow-up of three months after cataract surgery. RESULTS: An individually produced IOL with cylindrical correction between 2.0 and 12.0 D was implanted in all eyes. Postoperatively, 68 % of the eyes achieved an uncorrected visual acuity (VA) of 0.5 or better, 12 % achieved 1.0 or better. A corrected VA of 0.5 or better was achieved by 85 %, 31 % achieved a corrected VA of 1.0 or better. Corrected VA improved by 3 (+/- 2) lines. The uncorrected VA improved by 6.0 lines in the mean. The increases in uncorrected and corrected VA were statistically significant (p < 0.001). The efficacy index amounted to 1.1 in the median and 1.3 (+/- 1.5) in the mean. Residual refraction (spherical equivalent) was 0.89 D (+/- 0.7 D) in the mean and was reduced by 5.14 D (+/- 4.78 D) in the mean. The total astigmatic error was reduced both in a statistically as well as in a clinically significant manner from 4.6 D (+/- 2.3 D) to 1.12 D (+/- 0.9 D) in the mean. 75 % of eyes needed a postoperative cylindrical correction of less than 1.5 D, 95 % less than 2.25 D. Corneal astigmatism was not changed significantly (p = 0,435). The surgically induced astigmatism (Naeser) amounted to 0.7 D in the median. In 85 % of the cases IOL rotation was less than 5 degrees. 15 % of the IOLs rotated more than 5 degrees, one IOL more than 10 degrees (max. 28 degrees). Patients ranked their surgical outcome on a scale from 1 (very good) to 6 (poor) which resulted in a mean score of 1.9 (+/- 1.0; min. 1.0; max. 5.0). No clinically relevant correlations of clinical parameters and satisfaction were detected. CONCLUSION: Implantation of the foldable, toric IOL with Z-haptics decreased the refractive error and improved postoperative visual outcome. This IOL was suitable for low as well as for high astigmatism. IOL rotation was low during the follow-up of three months resulting in sufficient correction of the pre-existing astigmatism.

Clinical benefit, complication patterns and cost effectiveness of laser in situ keratomileusis (LASIK) in moderate myopia: results of independent meta analyses on clinical outcome and postoperative complication profiles.

PURPOSE: Laser in situ keratomileusis (LASIK) means a patient investment of 2426 Euro per eye, which usually cannot be funded by European health care insurers. In the context of recent resource allocation discussions, however, the cost effectiveness of LASIK could become an important indication of allocation decisions. Therefore an evidence based estimation of its incremental cost effectiveness was intended. METHODS: Three independent meta analyses were implemented to estimate the refractive gain (dpt) due to conventional LASIK procedures as well as the predictability of the latter (%) (fraction of eyes achieving a postoperative refraction with maximum deviation of +/- 0.5 dpt from the target refraction). Study reports of 1995 - 2004 (English or German language) were screened for appropriate key words. Meta effects in refractive gain and predictability were estimated by means and standard deviations of reported effect measures. Cost data were estimated by German DRG rates and individual clinical pathway calculations; cost effectiveness was then computed in terms of the incremental cost effectiveness ratio (ICER) for both clinical benefit endpoints. A sensitivity analysis comprised cost variations of +/- 10 % and utility variations alongside the meta effects' 95% confidence intervals. RESULTS: Total direct costs from the patients' perspective were estimated at 2426 Euro per eye, associated with a refractive meta benefit of 5.93 dpt (95% meta confidence interval 5.32 - 6.54 dpt) and a meta predictability of 67% (43% - 91%). In terms of incremental costs, the unilateral LASIK implied a patient investion of 409 Euro (sensitivity range 351 - 473 Euro) per gained refractive unit or 36 Euro (27 - 56 Euro) per gained percentage point in predictability. When LASIK associated complication patterns were considered, the total direct costs amounted up to 3075 Euro, resulting in incremental costs of 519 Euro / dpt (sensitivity range 445 - 600 Euro / dpt) or 46 Euro / % (34 - 72 Euro / %). Most frequently reported LASIK complications were "central islands / over- / undercorrection / regression" (meta incidence estimate 24%) and "haze" (15%), which were identified by means of an independent meta analysis. CONCLUSION: Bearing incremental costs of 519 Euro per gained refractive unit in mind, the conventional LASIK procedures showed an encouraging cost effectiveness range; the latter estimate may serve as a rationale for future allocation discussions in ophthalmology.