Treatment of age-related macular degeneration: focus on ranibizumab

Ranibizumab, a humanized antigen-binding fragment (Fab) that binds all isoforms of VEGF-A, significantly slows down loss of vision and causes significant visual improvement in many patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD). These benefits of intravitreal ranibizumab apply to all angiographic subtypes of neovascular AMD and across all lesion sizes when the drug is injected at monthly intervals as shown in two pivotal phase III trials (ANCHOR and MARINA). The results from the PrONTO study suggest that less frequent treatment with ranibizumab through a variable dosing regimen dependent on optical coherence tomography (OCT) findings is a treatment option that results in comparably favorable visual outcomes. Currently, it is unclear whether combination therapy of ranibizumab with photodynamic therapy (PDT) provides any significant advantage over ranibizumab monotherapy (FOCUS trial); however, the combination of PDT and ranibizumab may decrease the need for frequent retreatment. This question will be addressed in the SUMMIT trial. Therapy with ranibizumab is generally very well tolerated with a low rate of seriously adverse ocular events or systemic side-effects. The advent of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the therapy of neovascular AMD. Ranibizumab at the moment appears to be the most effective approved treatment for neovascular AMD

Recurrent corneal erosions related to an ocular injury 15 years before presentation

Purpose: To report the case of a patient who presented with recurrent corneal erosions caused by an undetected plastic foreign body in the upper eyelid, which had remained asymptomatic for nearly 15 years following an ocular injury. Observations: A 39-year-old patient presented with recurrent corneal erosions and frontal headaches of unknown aetiology over the preceding eight months. The patient had previously been seen by twelve different ophthalmologists and had been treated over a 6-month period with a bandage contact lens, and therapeutic corneal scraping had been performed twice. However, the corneal erosion had repeatedly reappeared after removal of the bandage contact lens. On clinical examination prior to a planned phototherapeutic keratectomy, we extracted a 1.5 cm plastic foreign body, localised in the subtarsal area of the upper conjunctival fornix. Upon specific questioning, the patient denied any recent trauma, but reported a work-related accident with an accompanying eye injury 15 years before presentation. Conclusions and importance: Posttraumatic foreign bodies in the eye may remain asymptomatic for prolonged periods before giving rise to clinical signs such as recurrent corneal erosions. Hence, a thorough clinical examination with meticulous eyelid eversion should always be performed in such patients

Effects of small-scale turbulence on the growth of two diatoms of different size in a phosphorus-limited medium

15 pages, 7 figures, 5 tables, 1 appendix.-- Issue title: "Workshop on Future Directions in Modelling Physical-Biological Interactions (WKFDPBI)"The effect of turbulence on the nutrient flux towards osmotrophic cells is predicted to be size dependent. This should translate into growth. We experimentally followed and modelled the growth of two marine diatoms of different size (Thalassiosira pseudonana, 6 μm in diameter and Coscinodiscus sp., ca. 109 μm in diameter) under still water and turbulent conditions, using a shaker table. Experiments were done with phosphorus-limited cultures and lasted for ca. 5 days. Turbulence enhanced the growth of Coscinodiscus sp. in agreement with theory but not the growth of T. pseudonana, which was actually slightly lower under turbulence. At the end of the experiments there were about 1.7 times as many Coscinodiscus sp. cells in the turbulent treatment than in the still treatment, while for T. pseudonana almost the same cell concentration was found in both conditions. In addition, the Coscinodiscus sp. cells growing under still conditions presented a higher specific alkaline phosphatase activity than those growing in turbulence which indicates a higher need for phosphorus in the still cultures. A simple dynamic model, based on Michaelis Menten nutrient uptake kinetics, needed nearly no optimisation other than using observed initial conditions of phosphate and cell concentrations. The model showed how an increased nutrient flux towards the cells translates non-linearly into cell growth, most likely by affecting the half-saturation constant (KM). However, since Coscinodiscus sp. experienced significant mortality and cells partially settled to the bottom of the containers, unequivocal support for the size-dependent effect of turbulence on nutrient uptake will require further experiments and more sophisticated modelling. The mechanisms to connect an increased nutrient flux towards cells with population growth and whether this process is size dependent are important in parameterizing the effects of turbulence on marine plankton in coupled physical biological modelsThis work was supported by Spanish Projects TURFI (REN2002-01591/MAR) and VARITEC (CTM2004-04442-C02) and by European Union projects MEDEA (MAS3-CT95-0016) and NTAP (EVK3-CT-2000-00022). This is European Land Ocean Interaction Studies contribution 523/40Peer reviewe

Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy

Purpose: Cell therapy is a promising treatment for retinal pigment epithelium (RPE)- associated eye diseases such as age-related macular degeneration. Herein, selective microsecond laser irradiation targeting RPE cells was used for minimally invasive, large- area RPE removal in preparation for delivery of retinal cell therapeutics. Methods: Ten rabbit eyes were exposed to laser pulses 8, 12, 16, and 20 μs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 μm2). Post-irradiation retinal changes were assessed with fluorescein angiography (FA), indocyanine green angiogra- phy (ICGA), and optical coherence tomography (OCT). RPE viability was evaluated with an angiographic probit model. Following vitrectomy, a subretinal injection of balanced salt solution was performed over a lasered (maximum 13.6 mm2) and untreated control area. Bleb retinal detachment (bRD) morphology was then evaluated by intraoperative OCT. Results: Within 1 hour after irradiation, laser lesions showed FA and ICGA leakage. OCT revealed that large-area laser damagewas limited to the RPE. The angiographic median effective dose irradiation thresholds (ED50)were45μJ(90 mJ/cm2)at8μs,52μJ(104 mJ/cm2) at 12 μs, 59 μJ (118 mJ/cm2)at16μs,and71μJ(142mJ/cm2) at 20 μs. Subretinal injection over the lasered area resulted in a controlled, shallowbRD rise, whereas control blebs were convex in shape, with less predictable spread. Conclusions: Large-area, laser-based removal ofhost RPEwithout visible photoreceptor damage is possible and facilitates surgical retinal detachment. Translational Relevance: Selective microsecond laser-based, large-area RPE removal prior to retinal cell therapy may reduce iatrogenic trauma. Introductio

Способы и методы нормирования труда на предприятии

Статья посвящена анализу процесса нормирования труда на предприятиях различных форм собственности, определению способов нормирования труда, регулированию пропорций между различными видами труда, учету количественных и качественных затрат труда, установлению соотношения между усилиями сотрудника и их оплатой

Sulcus anatomy and diameter in pseudophakic eyes and correlation with biometric data: Evaluation with a 50 MHz ultrasound biomicroscope

PURPOSE: To evaluate the sulcus anatomy and possible correlations between sulcus diameter and white-to-white (WTW) diameter in pseudophakic eyes, data that may be important in the stability of add-on intraocular lenses (IOLs). SETTING: University Eye Hospital, Tuebingen, Germany. DESIGN: Case series. METHODS: In pseudophakic eyes, the axial length (AL) and horizontal WTW were measured by the IOLMaster device. Cross-sectional images were obtained with a 50 MHz ultrasound biomicroscope on the 4 meridians: vertical, horizontal (180 degrees), temporal oblique, and nasal oblique. Sulcus-to-sulcus (STS), angle-to-angle (ATA), and sclera-to-sclera (ScTSc) diameters were measured. The IOL optic diameter (6.0 mm) served as a control. To test reliability, optic measurements were repeated 5 times in a subset of eyes. RESULTS: The vertical ATA and STS diameters were statistically significantly larger than the horizontal diameter (P=.0328 and P=.0216, respectively). There was no statistically significant difference in ScTSc diameters. A weak correlation was found between WTW and horizontal ATA (r = 0.5766, P<.0001) and between WTW and horizontal STS (r = 0.5040, P=.0002). No correlation was found between WTW and horizontal ScTSc (r = 0.2217, P=.1217). CONCLUSIONS: The sulcus anatomy had a vertical oval shape with the vertical meridian being the largest, but it also had variation in the direction of the largest meridian. The WTW measurements showed a weak correlation with STS. In pseudophakic eyes, Soemmerring ring or a bulky haptic may affect the ciliary sulcus anatomy

Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE transplantation

Cell therapeutics for AMD were often implanted regardless of RPE status in the target zone. This may result in RPE multilayering. Here we study a novel laser to remove RPE without collateral damage prior to RPE implantation to encourage better subretinal integration. Pigment rabbits (n=24) were immunosuppressed with Sirolimus, Doxycyclin and Minocyclin. Using a SLO/ OCT (Heidelberg Engineering) extended with a prototype laser (Meridian Medical; wavelength: 532 nm; pulse duration, 8 µs), a large area of RPE was selectively removed in 19 rabbits. Animals without laser lesions served as controls (n=5). A 25 gauge vitrectomy (Geuder) with removal of posterior hyaloid membrane was performed thereafter. Human iPS-RPE (1000 cells/ µl) were manually injected using a 100 µl syringe (Hamilton) connected to a 38G cannula (MedOne) into the RPE laser lesion, or over healthy RPE in controls, monitored by intraoperative OCT imaging (RESCAN 700, Zeiss). In vivo follow up/ retinal imaging was up to 12 weeks including fluorescein and indocyanine angiography, as well as SD-OCT (Spectralis ®, Heidelberg Engineering). Representative RPE laser wounds exhibited mild late phase FA& ICGA leakage, without abnormal outer retinal or choroidal hyperreflectivity on OCT. By contrast, lesions with earlier leakage on FA/ ICGA showed beam-sized outer retinal hyperreflectivity on OCT, suggesting coagulation. The size of the RPE wounds was typically 10-12mm2.iOCT demonstrated in an immediate and directed spread of the bleb retinal detachment (bRD) within the lasered zone. By contrast, bRDs performed over non-lasered RPE raised slower with a circular spread. Subretinal injection ranged from 5-70µl, with lesser volumes/ larger bRDs areas over lasered regions.At 6 and 12 weeks, none of implanted regions showed FA/ICGA leakage, some lesions had blockage due to hyperpigmentation; on OCT, representative areas showed preserved ellipsoid bands, with some RPE undulations. Lasered/implanted areas with a peripheral hyperpigmentation showed central outer retinal atrophy along with irregular RPE. Control implantation sites showed retinal atrophy and a variably thickened RPE band. Large-area RPE removal with laser disruption is feasible in healthy rabbits and appears to facilitate superior integration of RPE suspension grafts, compared to subretinal injection alone. Future work aims to correlate histology with in vivo imaging. This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually

Short-term follow up after Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE suspension transplantation in rabbits

Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases. Herein, microsecond laser irradiation targeting RPE cells was used for large-area RPE removal followed by subretinal injection of human induced pluripotent stem cell derived RPE (hiPS-RPE). 19 immunosuppressed pigmented rabbits (Chinchilla bastard hybrid) underwent a large area RPE removal using an infrared reflectance (IR) confocal scanning laser ophthalmoscope (cSLO) with spectral-domain optical coherence tomography (SD-OCT) system (Heidelberg Engineering ) extended with a prototype laser (modified Merilas 532 shortpulse ophthalmic laser photocoagulator, Meridian Medical) (wavelength, 532 nm; pulse duration, 8 µs), followed by a 25G vitrectomy. Subsequently, a suspension of hiPS-RPE (1000 cells/ µl) was grafted subretinally into the RPE laser lesion under real-time intraoperative OCT imaging (RESCAN 700, Zeiss) by manual injection via a 25/38G cannula connected to a 100µl Hamilton syringe. 5 rabbits served as a control with hiPS-RPE injected subretinally over healthy RPE. The rabbits were followed with in vivo multimodal retinal imaging at baseline after laser and then for 7 days including fluorescein (FA) and indocyanine angiography (ICGA), aw well as SD-OCT (Spectralis ®, Heidelberg Engineering). Baseline imaging of RPE laser wounds showed mild late phase FA/ICGA leakage, with normal outer retinal and choroidal reflectivity on OCT, without signs of coagulation. The size of the RPE wounds was typically 10-12mm2. Real time iOCT showed a directed spread of the bleb retinal detachment (bRD) within the lasered zone, in contrast to a circular spread in controls. Subretinal injection ranged from 5-20µl, with lesser volumes/ larger bRD areas over lasered regions. At 7 days, implanted regions showed FA/ICGA leakage, blockage due to hyperpigmentation was observed mostly at the edges of the lasered zone; OCT showed hyperreflectivity of the outer retina with RPE irregularities. Control implantation sites showed hyperreflectivity in all retinal layers and a variably thickened RPE band suggesting clumping. Microsecond laser irradiation to the RPE seems to accelerate the subretinal integration of hiPS-RPE, when compared to subretinal injection over intact RPE. Future work will address correlation of multimodal imaging and histology. This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually

Study of the dynamics of the accumulation of chemical elements by moss-transplants

Artificial retinal detachment is increasingly used in submacular surgery. However, overcoming physiological retinal adhesiveness by subretinal fluid injection is suspected to cause cellular damage and thus to limit visual rehabilitation. This experimental study was designed to examine the ultrastructural changes induced by retinal detachment under vitrectomy conditions and to evaluate factors that reduce adhesiveness and minimize cellular damage

Subretinal electronic chips allow blind patients to read letters and combine them to words

A light-sensitive, externally powered microchip was surgically implanted subretinally near the macular region of volunteers blind from hereditary retinal dystrophy. The implant contains an array of 1500 active microphotodiodes (‘chip’), each with its own amplifier and local stimulation electrode. At the implant's tip, another array of 16 wire-connected electrodes allows light-independent direct stimulation and testing of the neuron–electrode interface. Visual scenes are projected naturally through the eye's lens onto the chip under the transparent retina. The chip generates a corresponding pattern of 38 × 40 pixels, each releasing light-intensity-dependent electric stimulation pulses. Subsequently, three previously blind persons could locate bright objects on a dark table, two of whom could discern grating patterns. One of these patients was able to correctly describe and name objects like a fork or knife on a table, geometric patterns, different kinds of fruit and discern shades of grey with only 15 per cent contrast. Without a training period, the regained visual functions enabled him to localize and approach persons in a room freely and to read large letters as complete words after several years of blindness. These results demonstrate for the first time that subretinal micro-electrode arrays with 1500 photodiodes can create detailed meaningful visual perception in previously blind individuals