Search

Pharmacologic vitreolysis with ocriplasmin has emerged as a new option for the treatment of symptomatic vitreomacular traction syndrome (VMT). Not all cases of VMT require therapy. Knowledge of the natural history of VMT is essential for patient counselling and for deciding between observation and treatment. Ocriplasmin treatment for VMT may provide very good results if used with the correct candidates. On the other hand, observation might be the best option in cases of VMT with high chances of spontaneous resolution. The purpose of this review is to report on the natural course of VMT based on the current literature, present briefly the author’s experience with the use of ocriplasmin in cases of VMT, and provide practical hints for the implementation of this treatment modality in the clinical setting.

Micro computed tomography (µCT) scanners are used to create high-resolution images and to quantify properties of the scanned objects. While modern µCT scanners benefit from the cone beam geometry, they are compromised by scatter radiation. This work aims to develop a Monte Carlo (MC) model of a µCT scanner in order to characterize the scatter radiation in the detector plane. The EGS++ framework with the MC code EGSnrc was used to simulate the particle transport through the main components of the XtremeCT (SCANCO Medical AG, Switzerland). The developed MC model was based on specific information of the manufacturer and was validated against measurements. The primary and the scatter radiation were analyzed and by implementing a dedicated tracing method, the scatter radiation was subdivided into different scatter components. The comparisons of measured and simulated transmission values for different absorber and filter combinations result in a mean difference of 0.2% ± 1.4%, with a maximal local difference of 3.4%. The reconstructed image of the phantom based on measurements agrees well with the image reconstructed using the MC model. The local contribution of scattered radiation is up to 10% of the total radiation in the detector plane and most of the scattered particles result from interactions in the scanned object. The MC simulations show that scatter radiation contains information about the structure of the object. In conclusion, a MC model for a µCT scanner was successfully validated and applied to analyze the characteristics of the scatter radiation for a µCT scanner.

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.

To evaluate the efficacy of intravitreal ocriplasmin for the resolution of vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) in the clinical setting and to assess whether the indication spectrum of this treatment modality can be expanded beyond that of the MIVI-TRUST trials. The records of patients with VMT with or without FTMH, who were treated with intravitreal ocriplasmin were reviewed. Patients were divided in two groups. In the first group, VMT with or without FTMH was present without any other macular pathology. In the second group, VMT with or without FTMH occurred alongside of other macular disease including age-related macular degeneration, diabetic maculopathy and post-operative pseudophakic cystoid macular edema. Release of the VMT was achieved in 12/20 patients (12/20 eyes) of the first group. 16 eyes in this group met 3 or more criteria known to be associated with favorable prognosis after intravitreal ocriplasmin treatment. No cases of release of the VMT were observed in the second group, which included 15 patients (15 eyes). Significant improvement of visual acuity and reduction of the central macular thickness was observed only in the subgroup of eyes which responded to treatment. Concomitant macular pathology was a significant factor for treatment failure and we suggest that ocriplasmin should be regarded with caution in these cases. Careful patient selection for treatment with ocriplasmin using specific criteria in the clinical setting can provide superior results to those reported in the MIVI-TRUST trials.

A 24-year-old patient with Friedreich's ataxia presented with advanced visual loss due to optic nerve atrophy. After interdisciplinary consultation and after obtaining informed consent, an off-label therapy with the N-methyl-D-aspartate (NMDA) antagonist memantine was initiated. In a 1-year follow-up no further loss of the nerve fiber layer could be detected by optical coherence tomography (OCT) and visual acuity remained stable. Despite the limitations of this single and time limited case observational study, memantine should be discussed as an option for treatment of acute optic nerve atrophy in Friedreich's ataxia.

To compare the anatomical and visual outcomes of 20 gauge (g) pars plana vitrectomy (PPV) with indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling and 23 g PPV with brilliant blue G (BBG)-assisted ILM peeling for idiopathic epiretinal membrane (ERM). 38 eyes of 38 patients with idiopathic ERM were included. They were divided in two groups: group 1 (18 eyes) underwent 20 g PPV with ICG-assisted ILM peeling and group 2 (20 eyes) 23 g PPV with BBG-assisted ILM peeling. Postoperative best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared. Average BCVA in group 1 improved significantly from 0.60 logarithm of the minimal angle of resolution (log MAR) at baseline to 0.3 log MAR postoperatively. Average BCVA in group 2 improved significantly from 0.60 log MAR at baseline to 0.3 log MAR postoperatively. Mean CMT reduced significantly from 473 to 375 μm in group 1 and from 486 to 396 μm in group 2. There were no significant differences in the BCVA and CMT between the groups. Both surgical methods appeared to be safe and provided similar anatomical and visual outcomes.

To investigate the accuracy of x-ray grating interferometry phase-contrast (PC) imaging for the characterization of human coronary artery plaque.PC and conventional absorption computed tomographic (CT) imaging was performed ex vivo in this institutional review board-approved study in 40 human coronary artery segments by using a synchrotron radiation source. Qualitative analyses and calculations of image quality (McNemar test), plaque components (McNemar test), and plaque classification (Cohen κ test) according to the American Heart Association classification were performed in 38 plaques detected at histopathologic examination (reference standard). Quantitative measurements of plaque components (ie, collagen, lipids, smooth muscle, and calcifications) were compared among PC and absorption images by using analysis of variance for repeated measures with post hoc Bonferroni correction.Image quality was superior in PC (median image score, 1) in all cases (100%) compared with absorption imaging (median image score, 3) (P.001). Plaque components were detected by means of PC without significant differences (seven of seven calcifications, 22 of 22 plaques with collagen and smooth muscle cells, P.99; 29 of 29 plaques with lipids, P = .10) with histopathologic findings, whereas absorption imaging was used to detect calcifications (seven of seven, P.99) without statistical differences only (nine of 29 plaques with lipids, 0 of 22 plaques with collagen and smooth muscle cells, P.001). Accuracy for plaque stage assessment with PC (early vs advanced) was 100%, and characterization was correct in 33 of 38 plaques (87%), while conventional absorption imaging allowed correct characterization of seven plaques only (18%, P.001). PC CT numbers were significantly different (P.05) for all plaque components (mean for calcifications, 1236 HU ± 69; collagen, 78 HU ± 24; lipids, -18 HU ± 23; and smooth muscle cells, 34 HU ± 12), whereas absorption images showed significant differences (P.001) between calcifications (1336 HU ± 241) and other plaque components, but not for collagen (22 HU ± 13), lipids (-15 HU ± 14), and smooth muscle (13 HU ± 9) (P.99).PC imaging allows accurate characterization of human coronary artery plaques and quantitative assessment of plaque components, thereby outperforming absorption imaging.

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) invitro. 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. © 2013 Elsevier Ltd.

Interventional closure of intracardiac wall defects using occluder devices has evolved as a highly attractive treatment option. However incomplete and delayed healing reactions often result in a major risk of residual defects thromboembolism or device fractures. Biodegradable living tissue engineered occluder membranes (TEOMs) could provide autologous thromboresistant implants with growth and remodeling capacities. PGA P4HB composite matrices were seeded with human umbilical cord derived cells or vascular derived control cells and exposed to static (n ¼ 19) or dynamic (n ¼ 13) conditioning. Harvested TEOMs were integrated into occluder frameworks exposed to crimping and delivered into pre formed defects of juvenile porcine hearts. Dynamically conditioned TEOM constructs showed higher collagen formation in histology than static constructs with significantly higher stiffness moduli in uniaxial tensile testing. Grating interferometry revealed substantial but inhomogeneous cone like degradation of the composite matrices in dynamic conditioning. The crimping and delivery procedures resulted in no significant changes in macroscopy histo morphology cellular viability DNA or hydroxyproline content and scanning electron microscopy findings. Here we present the in vitro fabrication crimping and experimental delivery of living human umbilical cord cell derived TEOMs based on composite matrices as a potential future autologous therapy of intracardiac wall defects.

Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence-based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels of evidence for the efficacy of various treatment approaches such as laser photocoagulation, PDT, subretinal surgery or novel anti-angiogenic drugs [Arch Ophthalmol 2006;124:597–599]. The high evidence shown by these studies supported the rationale to use PDT also in additional, less frequent, vasoproliferative diseases. Although these ‘case series’ and ‘individual case control studies’ have a low level of evidence, they give us important information for treatment decisions in these rare conditions. The goal of this survey is to review the current literature regarding PDT in vasoproliferative and exudative ocular diseases outside AMD. Many studies modified the treatment parameters of PDT to address the specific pathology of the underlying disease. Table 1 summarizes the diseases and treatment parameters that are described in this part 2, the entire table of this review is included in part 1 (www.karger.com/doi/10.1159/ 000101922).

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.

Background: The use of vital dyes in "chromovitrectomy" allows the easier removal of less recognizable structures like epiretinal membranes (EM) or the inner limiting membrane (ILM). In recent years numerous studies demonstrated the use of indocyanine green (ICG), trypan blue (TB) and patent blue (PB) for this indication. Reports of the possible risk of these dyes, i. e. especially ICG, in respect of reduced visual acuity results, possible visual field defects or alterations of the retinal pigment epithelium (RPE) resulted in limitations in their application. Material and methods: Human RPE cells and choroidal endothelial cells were cultured in monolayers on semipermeable membranes representing an in vitro model of the outer blood-retinal barrier. By measurement of the transepithelial electrical resistance (TER) the stable barrier function was determined. Two different models representing an air-filled and a fluid-filled eye were tested on the one hand by addition of the dye to the culture medium and, on the other, by direct application on the cell monolayer. In these two models ICG (5 mg/ml, 0.5 mg/ml, 0.125 mg/ml), TB (1.5 mg/ml, 0.15 mg/ml) and PB (2.4 mg/ml, 0.24 mg/ml) were applied for three minutes and the influence on the barrier function was determined. RPE cell growth was also tested in these two models after the application of ICG, TB and PB. Finally, monolayers of RPE cells were evaluated by transmission electron microscopy (TEM). Results: After application of TB, PB and the lowest concentration of ICG of 0.125 mg/ml, the TER remained stable in both models. In contrast, ICG in a concentration of 5 mg/ml and 0.5 mg/ml caused a significant TER decrease in the model of the air-filled eye, whereas no influence on the function of the outer blood-retinal barrier was noted in the model of the fluid-filled eye. RPE cell growth rates were not influenced by the addition of the vital dyes, with the exception of ICG in a concentration of 5 mg/ml in the model of the air-filled eye, resulting in a temporary reduction of the cell count. In good correspondence to these results also in TEM intercellular blisters were noted after application of 5 mg/mL ICG for 3 minutes in the model of the air-filled eye. However, damage to the RPE cells themselves was not obvious. No pathological changes in the TEM were noted after application of TB and PB. Conclusions: The use of PB and TB at the posterior eye segment seems to be safe concerning damage to the PRE and its barrier function. In contrast, ICG in higher concentrations and with longer application times may cause a toxic effect on RPE morphology and function.

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.

Nach photodynamischer Therapie (PDT) berichten Patienten wiederholt von einer vorubergehenden Sehverschlechterung in der ersten postoperativen Woche. Vor, 2 Tage und eine Woche nach PDT wurden der Visus (mit bestkorrigierter Refraktion) und die Refraktionsanderung untersucht und eine A-Scan-Ultraschallbiometrie durchgefuhrt. Insgesamt 53 PDT-Behandlungen bei 24 Augen konnten in diese prospektive Studie aufgenommen werden. In 3 Fallen erfolgten zusatzlich lineare und dreidimensionale optische Koharenztomographien der Makula. Der Refraktionsvergleich aller 53 Behandlungen wies bei 43% (n=23) am zweiten postoperativen Tag eine Hyperopisierung von durchschnittlich +0,35 dpt nach, welche sich bis zur Untersuchung eine Woche nach PDT auf +0,07 dpt reduzierte. Der Visusverlauf zeigte nach 2 Tagen mit der jeweils besten Korrektur bei 68% der Falle (36/53) einen konstanten oder besseren Visus. Zu einer Visusreduktion kam es in 32% (17/53), eine Woche spater konnte eine solche nur noch bei 23% (12/53) dokumentiert werden. Die Biometrie zeigte am 2. postoperativen Tag eine Verkurzung der Hornhaut-Retina-Distanz von durchschnittlich 0,13 mm. Dies entsprach der gemessenen Hyperopisierung von durchschnittlich 0,35 dpt. Das OCT zeigte ein transientes postoperatives Odem im Bereich des behandelten Areals. Eine Hyperopisierung am zweiten postoperativen Tag nach PDT trat bei 43% auf. Die subjektive postoperative Visusminderung konnte meist durch Korrektur der Hyperopisierung ausgeglichen werden. Ein Odem im behandelten Netzhautareal scheint kausal fur diese verantwortlich zu sein.

Objective A procollagen α2(I) messenger RNA (mRNA) variant, with a 115-bp band and an expected band of 180 bp, was found to be increased during early, acute scleroderma-like disease in UCD-200 chickens. The present study investigated the influence of cytokines on the expression of these 2 proα2(I) mRNA variants. Methods Embryonic fibroblasts of UCD-200 chickens (UCD-200-CEF) and normal white leghorns (NWL-CEF) were grown in 3-dimensional collagen gels. Procollagen mRNA expression was analyzed by RNase protection assay, and proliferation was determined by 3H-thymidine incorporation. Transforming growth factor β1 (TGFβ1) and TGFβ2 were measured in culture supernatants by enzyme-linked immunosorbent assay. Results Compared with NWL-CEF, UCD-200-CEF expressed 7.2 times more of the smaller profibrotic proα2(I) mRNA variant. TGFβ1 stimulated the proliferation of UCD-200-CEF, but not NWL-CEF. The 115 bp:180 bp ratio was increased by TGFβ1 in both NWL-CEF and UCD-CEF. TGFβ2 and TGFβ3 reduced the expression of the profibrotic proα2(I) mRNA in UCD-200-CEF to the same levels observed in healthy control NWL-CEF. In culture supernatants, NWL-CEF produced 4.1 times more TGFβ2 than that produced by UCD-CEF. Inhibition of endogenous TGFβ2 in NWL-CEF resulted in the same 115 bp:180 bp ratio as seen in untreated UCD-CEF. Conclusion TGFβ2 reduces the expression of a profibrotic proα2(I) mRNA variant in UCD-200-CEF. The constitutive overproduction of this proα2(I) mRNA variant and the diminished synthesis of TGFβ2 in untreated UCD-200-CEF suggest that TGFβ2 can act as an antifibrotic cytokine and might be a key player during fibrosis onset. These results shed light on the contradictory observations regarding the role of TGFβ2 in human systemic sclerosis.

Purpose: To describe photodynamic therapy (PDT) and additional indocyanine green (ICG) guided feeder vessel photocoagulation as a treatment of choroidal neovascularization (CNV) secondary to choroidal rupture in case of blunt head trauma. Design: Interventional case report. Methods: A 61-year-old woman developed subfoveal CNV originating from a choroid tear 8 years after blunt head trauma. Four sessions of PDT were applied and an additional two consecutive sessions of selective ICG-guided feeder vessel photocoagulation conducted. Results: Transient reduction of leakage and closure of feeder vessels could not prevent further growth of the CNV. Conclusions: PDT reduced leakage temporarily and additional ICG-guided feeder vessel photocoagulation closed treated feeder vessel and CNV. New feeder vessel formation and growth of CNV in case of traumatic choroid rupture could not be treated effectively by these two laser treatment modalities to prevent severe deterioration of visual acuity.

The Heidelberg retina angiograph ( HRA) classic enables fluorescein angiography (FA) and indocyanine green angiography (ICG-A) of the retina and choroid. The goal of this study was to design an accessory device to adapt the HRA classic for application on structures anterior to the retina. The optical device consisted of a cylindrical two-piece plastic frame holding a magnifying lens commonly used with the indirect ophthalmoscope. A 60-diopters lens was inserted in this frame to enable the angiography of the anterior segment. A less strong lens of 30 diopters was used for the visualization of pathologic findings in the vitreous cavity. We designed an easy-to-use and low-cost device to adapt the HRA classic for angiography of the fundus, vitreous cavity and anterior segment in the same session and without delay. FA and ICG-A images of two patients with rubeosis iridis and of one patient with choroidal melanoma are described.

The aim of this study was to describe skew deviation and vertical nystagmus as the initial signs for basilar artery thrombosis, a life-threatening disease. A 51-year-old woman complained of vertical diplopia for more than 20 h. A computed tomography of the brain was normal, but subsequently the patient developed additional symptoms including nausea, ventilation problems (dyspnoea) and somnolence. Neuro-ophthalmological evaluation revealed a skew deviation and a vertical nystagmus. Magnetic resonance imaging allowed the diagnosis of basilar artery occlusion. An emergency intervention with cerebral catheter angiography and local intra-arterial thrombolysis was performed. Total recanalization of the basilar artery was achieved resulting in a complete neurological recovery, including the skew deviation and nystagmus. This rare case of skew deviation associated with basilar artery occlusion was a diagnostic challenge and highlights adequate differential diagnosis. Skew deviation is an important clinical sign. In this patient it was the key to a correct diagnosis enabling an immediate and successful intervention.

Background: Chronic venous insufficiency (CVI) represents a major global health problem with increasing prevalence and morbidity. CVI is due to an incompetence of the venous valves, which causes venous reflux and distal venous hypertension. Several studies have focused on the replacement of diseased venous valves using xeno- and allogenic transplants, so far with moderate success due to immunologic and thromboembolic complications. Autologous cell-derived tissue-engineered venous valves (TEVVs) based on fully biodegradable scaffolds could overcome these limitations by providing non-immunogenic, non-thrombogenic constructs with remodeling and growth potential. Methods: Tri- and bicuspid venous valves (n=27) based on polyglycolic acid-poly-4-hydroxybutyrate composite scaffolds, integrated into self-expandable nitinol stents, were engineered from autologous ovine bone-marrow-derived mesenchymal stem cells (BM-MSCs) and endothelialized. After in vitro conditioning in a (flow) pulse duplicator system, the TEVVs were crimped (n=18) and experimentally delivered (n=7). The effects of crimping on the tissue-engineered constructs were investigated using histology, immunohistochemistry, scanning electron microscopy, grating interferometry (GI), and planar fluorescence reflectance imaging. Results: The generated TEVVs showed layered tissue formation with increasing collagen and glycosaminoglycan levels dependent on the duration of in vitro conditioning. After crimping no effects were found on the MSC level in scanning electron microscopy analysis, GI, histology, and extracellular matrix analysis. However, substantial endothelial cell loss was detected after the crimping procedure, which could be reduced by increasing the static conditioning phase. Conclusions: Autologous living small-diameter TEVVs can be successfully fabricated from ovine BM-MSCs using a (flow) pulse duplicator conditioning approach. These constructs hold the potential to overcome the limitations of currently used non-autologous replacement materials and may open new therapeutic concepts for the treatment of CVI in the future.

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.

Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence-based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels of evidence for the efficacy of various treatment approaches such as laser photocoagulation, PDT, subretinal surgery or novel anti-angiogenic drugs [Arch Ophthalmol 2006;124:597-599]. The high evidence shown by these studies supported the rationale to use PDT also in additional, less frequent, vasoproliferative diseases. Although these 'case series' and 'individual case control studies' have a low level of evidence, they give us important information for treatment decisions in these rare conditions. The goal of this survey is to review the current literature regarding PDT in vasoproliferative and exudative ocular diseases outside AMD. Many studies modified the treatment parameters of PDT to address the specific pathology of the underlying disease. Table 1 summarizes the diseases and treatment parameters that are described in this part 2, the entire table of this review is included in part 1 (www.karger.com/doi/10.1159/ 000101922).

Purpose To quantify transient serous retinal detachment in classic and occult choroidal neovascularization (CNV) after photodynamic therapy (PDT). Design Prospective consecutive case series. Methods Consecutive patients with classic and occult CNV were examined by optical coherence tomography before PDT and at 2 and 7 days after PDT. Results 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. Conclusion 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.

Objective: 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). Methods: 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. Results: 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. Conclusions: 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.

Systemic Sclerosis (SSc) is a connective tissue disease affecting the skin and internal organs. Retinopathy has been described in patients with SSc, but cannot be distinguished from secondary changes due to concomitant hypertension. UCD 200 chickens, a well-established animal model for SSc, were used in this study to investigate the posterior ocular segment for manifestations of SSc. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling was applied to detect endothelial cell (EC) apoptosis, a condition previously shown to represent the first step in SSc pathogenesis in humans and to be present in the skin and the involved internal organs of UCD 200 chickens in the acute stage. Our study showed a complete absence of EC apoptosis in the pecten and choroidal vessels of UCD 200 chickens in the acute stage. Ophthalmoscopy, biomicroscopy and histology revealed normal structures of the pecten, retina and choroid in the chronic stage. In summary, we showed that there is no primary involvement of the posterior ocular segment in avian SSc. SSc of UCD 200 chickens closely mimics human SSc, presenting all the clinical, serological and histological disease manifestations seen in the human counterpart. Therefore, our data raise serious doubts about primary posterior ocular involvement in human SSc. However, fundal examinations in patients with SSc may have their justification for assessment of hypertensive retinopathy.

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.

Purpose: Due to its high sensitivity towards electron density variations phase‐sensitive X‐ray imaging is well suited for imaging soft tissue matter. A recently established method is grating interferometry (GI) which produces three complementary types of contrast: absorption, phase and dark‐field. However, there are still open questions, for instance about details of the dark‐field contrast formation process. This work develops a numerical simulation framework in order to investigate the contrast formation process. Methods: The framework combines Monte Carlo methods (MC) with wave‐optics, since in realistic simulations of phase sensitive X‐ray imaging both particle‐and wave‐like properties of X‐rays have to be considered. The source and sample part of the simulation was implemented using the MC transport code egs++. To account for wave‐like properties the transport code was expanded to include refraction at surfaces and the optical path length. The gratings and the detector are implemented using wave‐optics. The MC part of the framework is connected to the wave‐optics part by treating each photon as a plane wave with the same propagation direction. Thus, the data from the MC part can be transformed into a complex amplitude by coherently summing up all plane‐waves. The framework is validated by comparing reconstructed image data sets from measured and calculated projections of known phantoms. Results: The combination of MC and wave‐optics has been successfully implemented. The validation of the framework showed very good agreement between simulations and experimental results for all three contrast types. Image correlation coefficients above 0.92 have been found, establishing the framework as a reliable method to model GI. Conclusion: The developed comprehensive simulation framework, taking refraction and scattering such as Compton and Rayleigh into account, can now be used for detailed investigations of the phase contrast imaging formation process and is particularly suited to study the scattering/dark‐field contribution of such processes.

This 5-year-old boy activated an air-pressure pistol directly toward his right eye. Visual acuity was reduced to 20/80. Computed tomography disclosed intraorbital and extraocular air, but no fractures.

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging., Journal of Synchrotron Radiation, 21 (3), ISSN:0909-0495, ISSN:1600-5775

Multiple scattering represents a challenge for numerous modern tomographic imaging techniques. In this Letter, we derive an appropriate line integral that allows for the tomographic reconstruction of angular resolved scattering distributions, even in the presence of multiple scattering. The line integral is applicable to a wide range of imaging techniques utilizing various kinds of probes. Here, we use x-ray grating interferometry to experimentally validate the framework and to demonstrate additional structural sensitivity, which exemplifies the impact of multiple scattering tomography.