Abstract Heart valve tissue engineering based on decellularized xenogenic or allogenic starter matrices has shown promising first clinical results. However, the availability of healthy homologous ...donor valves is limited and xenogenic materials are associated with infectious and immunologic risks. To address such limitations, biodegradable synthetic materials have been successfully used for the creation of living autologous tissue-engineered heart valves (TEHVs) in vitro. Since these classical tissue engineering technologies necessitate substantial infrastructure and logistics, we recently introduced decellularized TEHVs (dTEHVs), based on biodegradable synthetic materials and vascular-derived cells, and successfully created a potential off-the-shelf starter matrix for guided tissue regeneration. Here, we investigate the host repopulation capacity of such dTEHVs in a non-human primate model with up to 8 weeks follow-up. After minimally invasive delivery into the orthotopic pulmonary position, dTEHVs revealed mobile and thin leaflets after 8 weeks of follow-up. Furthermore, mild-moderate valvular insufficiency and relative leaflet shortening were detected. However, in comparison to the decellularized human native heart valve control – representing currently used homografts – dTEHVs showed remarkable rapid cellular repopulation. Given this substantial in situ remodeling capacity, these results suggest that human cell-derived bioengineered decellularized materials represent a promising and clinically relevant starter matrix for heart valve tissue engineering. These biomaterials may ultimately overcome the limitations of currently used valve replacements by providing homologous, non-immunogenic, off-the-shelf replacement constructs.
Ocular photodynamic therapy (PDT) was introduced as a novel treatment for neovascular forms of age-related macular degeneration and choroidal neovascularization (CNV) secondary to pathologic myopia ...in the mid/end 1990s. The current treatment recommendations are based on the results of two large, prospective, multicenter, randomized clinical trials (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Studies) and thousands of patients have been treated worldwide over the last years. Meanwhile, PDT has been performed in several other ocular pathologies with some remarkable results, however, with most reports being case reports and small case series without statistical significance. These extended applications include CNV secondary to choroiditis and retinochoroiditis, angioid streaks, central serous chorioretinopathy, retinal angiomatous proliferation, parafoveal telangiectasia or CNV associated with macular dystrophy and idiopathic CNV, as well as diseases without CNV, such as choroidal hemangioma, retinal hamartoma, choroidal melanoma, chronic central serous chorioretinopathy, angiomatous lesions secondary to systemic diseases, rubeosis iridis or neovascular glaucoma. To date, with the introduction of anti-VEGF therapy, the role of PDT will certainly change. However, it is reasonable to believe that it will maintain an important role in combination therapy due to its unique properties of selective vascular targeting. Therefore, it is essential for the ophthalmologist to be familiar with the extended applications and their modifications of treatment parameters. This review will summarize the standard and experimental applications of PDT based on our own results and the literature.
The authors report a retinal branch artery occlusion occurring after facial injection of a dermal filler. The superior temporal artery showed occlusion due to a clearly visible long and fragmented ...embolus suggestive of gel and clearly distinguishable from calcific or cholesterol emboli. The authors suppose that hyaluronic acid gel was embolized in the patient. The embolized material is supposed to enter the ocular circulation through retrograde arteriolar flow after intra‐arterial injection into one of the peripheral branches of the ophthalmic artery. If there is any evidence of a visual problem after facial injection of a dermal filler, prompt consultation of an ophthalmologist is recommended.
To describe fundus autofluorescence (AF), fluorescein angiography (FA) and indocyanine green angiography (ICGA) in different types of retinal astrocytic hamartomas in tuberous sclerosis (Morbus ...Bourneville-Pringle).
Two eyes with 8 lesions, i.e. type 1 (n = 7) and type 3 (n = 1), were examined. AF pictures were taken prior to injection, FA and ICGA images were obtained in the early and the late phase. To achieve additional cases, a systematic literature review with exten- sive Internet and library search was performed.
Strong AF was seen in type 2 and type 3 retinal astrocytic hamartomas, whereas type 1 lesions blocked the physiologic fundus AF. Fluorescence angiography of all types of lesions revealed hypofluorescence in early frames and hyperfluorescence originating from leakage in late frames. ICGA showed a subtle blockade in type 1, a total blockade in type 2 and in the central part and a partial blockade in the peripheral part in type 3 lesions.
Retinal astrocytic hamartomas in tuberous sclerosis can be easily detected by angiography, especially type 1 lesions which are difficult to visualize by funduscopy. Early- and late-phase fluorescein angiography and ICGA are helpful to differentiate the three lesion types.
Photodynamic therapy (PDT) is a well established clinical treatment for age-related macular degeneration (AMD), and comprises intravenous injection of verteporfin and subsequent application of a ...non-thermal laser beam to the area of AMD to induce selective vascular occlusion. Since there is evidence that PDT may cause outer blood-retinal barrier (BRB) breakdown and possibly RPE cell alteration, we investigated the effect of PDT on the BRB function of the RPE in an in vitro model.
Twenty-one monolayers of human RPE cells were cultured on semipermeable membranes until a stable barrier function was achieved as determined by transepithelial electrical resistance (TER) and sodium fluorescein permeability. To test the effect of PDT on the outer BRB function, non-thermal laser (692 nm), verteporfin or a combination of both were applied. TER assessment prior to and after PDT was utilized to identify changes in barrier function of the RPE in this in vitro model. Finally, monolayers of RPE cells were evaluated by transmission electron microscopy (TEM).
No significant TER decrease was observed after application of non-thermal laser alone or after administration of verteporfin in therapeutic concentrations, but combination of these modalities resulted in significantly decreased TER within 4 h. Except for intercellular blisters, no damage to the RPE was evident in TEM. Verteporfin added at concentrations higher than therapeutic doses (2 mg/ml) resulted in an immediate decrease in TER and damage to the RPE cells.
The combination of a therapeutic concentration of verteporfin and application of non-thermal laser resulted in a morphologically and functionally detectable breakdown of the outer BRB function of the RPE without any damage to the RPE cells themselves in vitro. However, increasing the concentration of verteporfin can result in RPE cell damage.
To quantify transient serous retinal detachment in classic and occult choroidal neovascularization (CNV) after photodynamic therapy (PDT).
Prospective consecutive case series.
Consecutive patients ...with classic and occult CNV were examined by optical coherence tomography before PDT and at 2 and 7 days after PDT.
In classic CNV (n = 6), retinal elevations increased from 217 (SD 42) μm before PDT to 626 (SD 157) μm 2 days after PDT and decreased to 240 (SD 36) μm 7 days after treatment. In occult CNV (n = 4), the mean retinal elevation of 266 (SD 41) μm before PDT increased to 544 (SD 94) μm 2 days after PDT and decreased to 259 (SD 40) μm 7 days after treatment.
Cross-sectional optical coherence tomography imaging revealed transient subretinal fluid accumulation in classic as well as in occult CNV after PDT. The subretinal location possibly relates to an outer blood-retinal barrier breakdown after PDT.
To assess the effect of intravitreal dexamethasone implant (Ozurdex) for the treatment of macular edema secondary to retinal vein occlusion (RVO) resistant to repeated intravitreal ranibizumab ...injection. Retrospective review of 11 patients (11 eyes) with ranibizumab-resistant macular edema secondary to RVO. Macular edema was considered refractory to ranibizumab if no change of the pattern of macular fluid on optical coherence tomography and no change of best-corrected visual acuity (BCVA) was observed after at least three consecutive monthly injections, excluding the loading dose. A single Ozurdex injection was performed and BCVA and central foveal thickness (CFT) were reviewed 2, 3, and 6 months after treatment. Mean BCVA improved significantly from 0.51 logarithm of the minimal angle of resolution (log MAR) at baseline to 0.3 log MAR (
p
= 0.03) at 2 months and 0.29 log MAR (
p
= 0.003) at 3 months. There was no significant difference in the BCVA between baseline at 6 months (
p
= 0.62). Mean CFT reduced significantly from 538 µm at baseline to 281 µm at 2 months (
p
= 0.00003), 281 µm at 3 months (
p
= 0.00003), and 445 µm at 6 months (
p
= 0.03). Treatment with Ozurdex results in improvement of BCVA and reduction of CFT in patients with ranibizumab refractory macular edema due to RVO at 3 months. However, it seems that the visual acuity gain may not last up to 6 months, so that a re-injection before this time point could be considered.
This volume focuses on the highly debated topic of theatrical translation, one brought on by a renewed interest in the idea of performance and translation as a cooperative effort on the part of the ...translator, the director, and the actors. Exploring the role and function of the translator as co-subject of the performance, it addresses current issues concerning the role of the translator for the stage, as opposed to the one for the editorial market, within a multifarious cultural context. The current debate has shown a growing tendency to downplay and challenge the notion of translational accuracy in favor of a recreational and post-dramatic attitude, underlying the role of the director and playwright instead. This book discusses the delicate balance between translating and directing from an intercultural, semiotic, aesthetic, and interlingual perspective, taking a critical stance on approaches that belittle translation for the theatre or equate it to an editorial practice focused on literality. Chapters emphasize the idea of dramatic translation as a particular and extremely challenging type of performance, while consistently exploring its various textual, intertextual, intertranslational, contextual, cultural, and intercultural facets. The notion of performance is applied to textual interpretation as performance, interlingual versus intersemiotic performance, and (inter)cultural performance in the adaptation of translated texts for the stage, providing a wide-ranging discussion from an international group of contributors, directors, and translators.
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