Swaantje Grisanti

Early postoperative safety and surgical outcomes after implantation of a suprachoroidal micro-stent for the treatment of open-angle glaucoma concomitant with cataract surgery

Purpose To evaluate the safety of a new suprachoroidal device, the Cypass micro‐stent, for the surgical treatment of open‐angle glaucoma (OAG) implanted in conjunction with cataract surgery. Setting Multicenter clinical study. Design Prospective interventional case series. Methods This is an interim report of an ongoing safety study. Patients with OAG glaucoma (Shaffer grade 3 and 4) who were also candidates for cataract surgery in the affected eye had standard phacoemulsification followed by micro‐stent implantation in the supraciliary space. Included were patients with uncontrolled (≥21 mm Hg, Cohort 1) or controlled (<21 mm Hg, Cohort 2) medicated intraocular pressure (IOP) at baseline. Glaucoma medications were discontinued at surgery and resumed at the discretion of each investigator. Measures included adverse events/complications and postoperative changes in IOP or medication. Results The mean baseline medicated IOP was 21.1 mm Hg ± 5.91 (SD); the mean number of IOP‐lowering medications was 2.1 ± 1.1 (N = 184). There were no major events such as retinal or choroidal detachment or endophthalmitis. The most common complications were transient early hypotony (13.8%) and transient IOP increase (10.5%). Uncontrolled patients (n = 57) had a 37% IOP reduction (P<.001), with more than a 50% reduction in glaucoma medications at 6 months (P<.001). Intraocular pressure–controlled patients (n = 41) had a 71.4% reduction in glaucoma medications (P<.001). Conclusion Initial clinical experience with the new micro‐stent showed a low rate of surgical complications with concomitant decreases in IOP and/or glaucoma medications. Financial Disclosure Drs. Hoeh, Ahmed, Swaantje Grisanti, Salvatore Grisanti, Grabner, Nguyen, Rau, and Yoo are clinical investigators for Transcend Medical; Dr. Ahmed is a consultant to Transcend Medical; Dr. Ianchulev is an employee of Transcend Medical.

A TGF-β receptor 1 inhibitor for prevention of proliferative vitreoretinopathy.

This study evaluates the use of the TGF-β receptor 1 inhibitor LY-364947 (LY) to prevent proliferative vitreoretinopathy (PVR). For the in vitro experiments Human Tenons Fibroblasts (HTFs) and retinal pigment epithelial (RPE) cells were treated with different concentrations of LY to determine HTF proliferation and RPE transdifferentiation. For in vivo testing 30 rabbits underwent a PVR trauma model. The animals received different concentrations of intravitreally injected LY, with or without vitrectomy. LY treatment reduced HTF proliferation and RPE transdifferentiation in vitro. In vivo intravitreal injection of LY prevented PVR development significantly. This positive effect was also present when LY injection was combined with vitrectomy. Intravitreal injection of LY prevented tractional retinal detachment in 14 out of 15 animals. In conclusion, treatment with the TGF-β receptor 1 inhibitor LY reduces HTF proliferation and RPE transdifferentiation in vitro and prevents proliferative vitreoretinopathy and subsequent tractional retinal detachment in vivo.

Differential expression of vascular endothelial growth factor-a isoforms in neovascular age-related macular degeneration.

Purpose: To investigate the role of vascular endothelial growth factor-A (VEGF-A) isoforms in neovascular age-related macular degeneration. Methods: Choroidal neovascular membranes (CNV) were excised in 24 patients, 8 of them underwent previous photodynamic therapy. All procedures were performed before anti-VEGF therapies were implemented in Germany. Normal human donor eyes served as controls. Messenger RNA expression of total VEGF-A and VEGF-A isoforms was measured. Results: Vascular endothelial growth factor-A121 is the most abundant isoform in CNV and control tissues. In controls, VEGF-A121 is lowest in neural retina and highest in choroids. For total VEGF-A and VEGF-A165, this is vice versa. VEGF-A165 and VEGF-A189 are significantly higher in CNV than in control choroids, the opposite is found for VEGF-A121. After photodynamic therapy, total VEGF-A and VEGF-A121 are increased, VEGF-A165 and VEGF-A189 are decreased. Age-dependently, there is an increase in VEGF-A165 and a decrease in VEGF-A121. Conclusion: Vascular endothelial growth factor-A isoforms are differentially distributed, suggesting that tissue-specific regulation of various isoforms is physiologically important. The disruption of this homeostasis in CNV membranes may be significant in the onset and progression of neovascular age-related macular degeneration. Our findings support the dominant role of VEGF-A121 in neovascular age-related macular degeneration but hint that VEGF-A165 may have an equivalent role in other neovascular retinal pathology.

A p38 MAPK inhibitor improves outcome after glaucoma filtration surgery.

Purpose:The aim of this study is to explore the effects of SB 202190, a highly selective p38 MAPK inhibitor, on bleb survival following glaucoma filtering surgery. Materials and Methods:Human Tenon’s fibroblasts were treated with SB 202190 (0 to 100 &mgr;M) to determine IC50, and cell proliferation and migration. Twenty rabbits were divided into 4 groups (G1-G4): G1 animals received only a trabeculectomy. G2-G4 animals had trabeculectomy plus one of the following subconjunctival adjuvants, given intraoperatively and postoperatively: G2=sham, G3=20 &mgr;M SB 202190, and G4=50 &mgr;M SB 202190. The blebs were assessed using the Indiana Bleb Appearance Grading Scale. The intraocular pressure (IOP) was expressed as the right to left eye ratio (R/L ratio). For morphometric bleb analysis the JMicrovision software was used. Results:SB 202190 inhibits human Tenon’s fibroblasts proliferation and migration in vitro (IC50=17.2 &mgr;M). In vivo subconjunctival application of SB 202190 after glaucoma filtration surgery significantly increases bleb height, bleb extension, and bleb survival time compared with the control. In all groups, the IOP ratio correlates with the fibrotic process. G3 shows a significantly reduced IOP ratio at day 14 compared with the control. Analysis of the bleb histology shows that G3 has a significant smaller fibrosis area compared with G1 and G2. Application of the highest dose (50 &mgr;M SB 202190) is associated with hyphema in 2 of 5 animals (40%). Conclusion:Application of SB 202190 significantly improves bleb characteristics and IOP control after filtering glaucoma surgery in a rabbit model.

Antiangiogenic treatment for neovascular glaucoma and after filtering surgery

ZusammenfassungBevacizumab (Avastin®) wird derzeit als begleitendes Adjuvanz in der Behandlung der Rubeosis iridis und des Neovaskularisationsglaukoms diskutiert. Bei einer beginnenden Rubeosis scheint Bevacizumab präventiv zu wirken und verhindert die Progression der Erkrankung. Mit zunehmender Beteiligung des Kammerwinkels scheint die Einbindung von Bevacizumab in ein komplexeres, stadienabhängiges Therapieschema zur erfolgreichen intraokularen Druckkontrolle sinnvoll. Die Behandlung der ursächlichen Grunderkrankung, die zu der Rubeosis iridis geführt hat, ist in allen Stadien als Basisbehandlung indiziert. Ein weiteres mögliches Einsatzgebiet für Bevacizumab könnte in der postoperativen Angiogeneseinhibition während oder nach filtrierender Glaukomchirurgie bestehen. Mögliche Applikationsformen, die momentan Anwendung finden, sind die subkonjunktivale Gabe während eines filtrierenden Eingriffs, im Zuge eines postoperativen Needlings oder als intravitreale Gabe zeitgleich mit einer drucksenkenden Operation bei einem Neovaskularisationsglaukom. Der folgende Übersichtsartikel fasst bisherige Studienergebnisse über die Anwendung von Bevacizumab bei einer Rubeosis iridis, einem Neovaskularisationsglaukom und in der Filtrationschirurgie zusammen und gibt einen Ausblick auf mögliche zukünftige Therapieschemata.AbstractBevacizumab is increasingly discussed as adjuvant treatment for rubeosis and for all stages of neovascular glaucoma. In incipient rubeosis bevacizumab has a preventive effect and arrests the progression of disease. In the case of increasing involvement of the anterior chamber angle, bevacizumab should be integrated into stage-adapted treatment to achieve successful control of intraocular pressure. The treatment of the causative ischemic stimulus is necessary in every stage of disease. One further indication for bevacizumab is the postoperative inhibition of angiogenesis after glaucoma surgery. Possible routes of administration are subconjunctival application during trabeculectomy, postoperative needling, or intravitreal injection during a filtrating operation. This review summarizes results of current studies about bevacizumab for rubeosis, neovascular glaucoma, or filtrating surgery and adds future perspectives for possible therapeutic schemes.Bevacizumab is increasingly discussed as adjuvant treatment for rubeosis and for all stages of neovascular glaucoma. In incipient rubeosis bevacizumab has a preventive effect and arrests the progression of disease. In the case of increasing involvement of the anterior chamber angle, bevacizumab should be integrated into stage-adapted treatment to achieve successful control of intraocular pressure. The treatment of the causative ischemic stimulus is necessary in every stage of disease. One further indication for bevacizumab is the postoperative inhibition of angiogenesis after glaucoma surgery. Possible routes of administration are subconjunctival application during trabeculectomy, postoperative needling, or intravitreal injection during a filtrating operation. This review summarizes results of current studies about bevacizumab for rubeosis, neovascular glaucoma, or filtrating surgery and adds future perspectives for possible therapeutic schemes.

Antiangiogene Therapie bei neovaskulärem Glaukom und nach Filterkissenchirurgie

ZusammenfassungBevacizumab (Avastin®) wird derzeit als begleitendes Adjuvanz in der Behandlung der Rubeosis iridis und des Neovaskularisationsglaukoms diskutiert. Bei einer beginnenden Rubeosis scheint Bevacizumab präventiv zu wirken und verhindert die Progression der Erkrankung. Mit zunehmender Beteiligung des Kammerwinkels scheint die Einbindung von Bevacizumab in ein komplexeres, stadienabhängiges Therapieschema zur erfolgreichen intraokularen Druckkontrolle sinnvoll. Die Behandlung der ursächlichen Grunderkrankung, die zu der Rubeosis iridis geführt hat, ist in allen Stadien als Basisbehandlung indiziert. Ein weiteres mögliches Einsatzgebiet für Bevacizumab könnte in der postoperativen Angiogeneseinhibition während oder nach filtrierender Glaukomchirurgie bestehen. Mögliche Applikationsformen, die momentan Anwendung finden, sind die subkonjunktivale Gabe während eines filtrierenden Eingriffs, im Zuge eines postoperativen Needlings oder als intravitreale Gabe zeitgleich mit einer drucksenkenden Operation bei einem Neovaskularisationsglaukom. Der folgende Übersichtsartikel fasst bisherige Studienergebnisse über die Anwendung von Bevacizumab bei einer Rubeosis iridis, einem Neovaskularisationsglaukom und in der Filtrationschirurgie zusammen und gibt einen Ausblick auf mögliche zukünftige Therapieschemata.AbstractBevacizumab is increasingly discussed as adjuvant treatment for rubeosis and for all stages of neovascular glaucoma. In incipient rubeosis bevacizumab has a preventive effect and arrests the progression of disease. In the case of increasing involvement of the anterior chamber angle, bevacizumab should be integrated into stage-adapted treatment to achieve successful control of intraocular pressure. The treatment of the causative ischemic stimulus is necessary in every stage of disease. One further indication for bevacizumab is the postoperative inhibition of angiogenesis after glaucoma surgery. Possible routes of administration are subconjunctival application during trabeculectomy, postoperative needling, or intravitreal injection during a filtrating operation. This review summarizes results of current studies about bevacizumab for rubeosis, neovascular glaucoma, or filtrating surgery and adds future perspectives for possible therapeutic schemes.Bevacizumab is increasingly discussed as adjuvant treatment for rubeosis and for all stages of neovascular glaucoma. In incipient rubeosis bevacizumab has a preventive effect and arrests the progression of disease. In the case of increasing involvement of the anterior chamber angle, bevacizumab should be integrated into stage-adapted treatment to achieve successful control of intraocular pressure. The treatment of the causative ischemic stimulus is necessary in every stage of disease. One further indication for bevacizumab is the postoperative inhibition of angiogenesis after glaucoma surgery. Possible routes of administration are subconjunctival application during trabeculectomy, postoperative needling, or intravitreal injection during a filtrating operation. This review summarizes results of current studies about bevacizumab for rubeosis, neovascular glaucoma, or filtrating surgery and adds future perspectives for possible therapeutic schemes.

Entwicklung einer serösen Retinopathie unter Behandlung eines metastasierten kutanen Melanoms

Inhibitors of the mitogen-activated protein kinase (MAPK) signal pathway have decisively improved the prognosis of metastatic cutaneous melanoma in patients with an activating mutation in position V600 of the BRAF gene. We report on a patient who was regularly examined in our clinic while participating in a randomized blinded clinical trial. The aim of this trial was to examine the effectiveness and tolerability of a combination of the BRAF inhibitor dabrafenib and the MAPK kinase (MEK) inhibitor trametinib compared with a monotherapy with dabrafenib (plus placebo). During therapy the patient developed a diffuse neuroretinal detachment which could not be completely reversed after discontinuation of the study medication.

Development of serous retinopathy during therapy of a metastatic cutaneous melanoma

Inhibitors of the mitogen-activated protein kinase (MAPK) signal pathway have decisively improved the prognosis of metastatic cutaneous melanoma in patients with an activating mutation in position V600 of the BRAF gene. We report on a patient who was regularly examined in our clinic while participating in a randomized blinded clinical trial. The aim of this trial was to examine the effectiveness and tolerability of a combination of the BRAF inhibitor dabrafenib and the MAPK kinase (MEK) inhibitor trametinib compared with a monotherapy with dabrafenib (plus placebo). During therapy the patient developed a diffuse neuroretinal detachment which could not be completely reversed after discontinuation of the study medication.

The Pathophysiology of Subretinal Hemorrhage

Subretinal hemorrhage (SRH), the accumulation of blood between the neurosensory retina and the retinal pigment epithelium (RPE), may arise from the choroidal or retinal circulation or both. Different pathological entities affecting these circulatory systems as well as trauma may be the cause of SRH. Independently from the underlying trigger, SRH damages tissue through a variety of mechanisms: The presence of iron, hemosiderin, and fibrin in the blood has toxic effects on the overlying photoreceptors; clot retraction can sheer and damage the photoreceptors; and, finally, physical separation of the photoreceptors from the RPE may impair nutrient exchange and can result in atrophy of both the neurosensory part and the RPE. Finally, the development of a disciform scar associated with an uninterrupted exudative process will lead to further anatomical and functional deterioration. As the mechanisms of damage are time-dependent, the goal of the following outline is to provide a review on the underlying mechanisms with an emphasis on how changes are shaped through time.

Use of Machine Learning on Contact Lens Sensor–Derived Parameters for the Diagnosis of Primary Open-angle Glaucoma

PURPOSE To test the hypothesis that contact lens sensor (CLS)-based 24-hour profiles of ocular volume changes contain information complementary to intraocular pressure (IOP) to discriminate between primary open-angle glaucoma (POAG) and healthy (H) eyes. DESIGN Development and evaluation of a diagnostic test with machine learning. METHODS Subjects: From 435 subjects (193 healthy and 242 POAG), 136 POAG and 136 age-matched healthy subjects were selected. Subjects with contraindications for CLS wear were excluded. PROCEDURE This is a pooled analysis of data from 24 prospective clinical studies and a registry. All subjects underwent 24-hour CLS recording on 1 eye. Statistical and physiological CLS parameters were derived from the signal recorded. CLS parameters frequently associated with the presence of POAG were identified using a random forest modeling approach. MAIN OUTCOME MEASURES Area under the receiver operating characteristic curve (ROC AUC) for feature sets including CLS parameters and Start IOP, as well as a feature set with CLS parameters and Start IOP combined. RESULTS The CLS parameters feature set discriminated POAG from H eyes with mean ROC AUCs of 0.611, confidence interval (CI) 0.493-0.722. Larger values of a given CLS parameter were in general associated with a diagnosis of POAG. The Start IOP feature set discriminated between POAG and H eyes with a mean ROC AUC of 0.681, CI 0.603-0.765. The combined feature set was the best indicator of POAG with an ROC AUC of 0.759, CI 0.654-0.855. This ROC AUC was statistically higher than for CLS parameters or Start IOP feature sets alone (both P < .0001). CONCLUSIONS CLS recordings contain information complementary to IOP that enable discrimination between H and POAG. The feature set combining CLS parameters and Start IOP provide a better indication of the presence of POAG than each of the feature sets separately. As such, the CLS may be a new biomarker for POAG.