The impact of impending / onset of vision loss on depression, anxiety, and vision-related quality of life in Birdshot-Retinochoroiditis and Serpiginous Choroiditis

To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its ' subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC

Macular, papillary and peripapillary perfusion densities measured with optical coherence tomography angiography in primary open angle glaucoma and pseudoexfoliation glaucoma

Purpose: To compare the blood flow situation in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using optical coherence tomography angiography (OCTA). Methods: In this prospective study a total of 26 POAG and 23 PXG eyes were included. All patients underwent a complete ophthalmological examination including standard automated perimetry, stereoscopic photographs of the optic disc, peripapillary retinal nerve fibre layer analysis and examination of vascular parameters of the optic nerve head (ONH), the peripapillary region and macula using OCTA. In addition to the vascular parameters recorded by the device, the vascular images were graphically evaluated using Image J. All recorded vascular parameters were compared between both groups and correlated to structural and functional parameters. Results: The mean superficial perifoveal plexus perfusion density (PD) was significantly lower in PXG eyes than compared to POAG eyes using OCTA (32.57% +/- 3.57% vs. 34.92% +/- 2.11%, p = 0.007). The mean PD parameters for the superficial peripapillary plexus (40.98% +/- 3.04% vs. 42.09% +/- 2.29%, p = 0.152) as well as the size of the foveal avascular zone (FAZ) (0.23 mm(2) +/- 0.1 mm(2) vs. 0.23 mm(2) +/- 0.09 mm(2)) did not differ between both groups. Additional graphic evaluation using Image J showed no significant difference for superficial perifoveal plexus PD (32.97% +/- 1.11% vs. 33.35% +/- 0.95%, p = 0.194) and peripapillary plexus PD (46.65% +/- 0.83% vs. 46.95% +/- 0.5%, p = 0.127) between the groups. Retinal nerve fibre layer (RNFL) thickness correlated significantly with peripapillary plexus PD for both OCTA data and Image J data (p < 0.001, p = 0.032). Conclusion: The severity of the glaucoma seems to be crucial for peripapillary and macular perfusion densities, and not the form of glaucoma. An additional graphic evaluation is a possible step that could be implemented to improve the comparability of OCTA scans and to optimize the possibility of quantitative perfusion analysis in the case of deviating quality criteria

Fast and Successful Management of Intraocular Inflammation with a Single Intravitreal Dexamethasone Implant

Purpose: To investigate the efficacy and safety of a single dexamethasone intravitreal implant (Ozurdex®, 700 µg). Methods: In this prospective noncomparative case series, 84 patients (54 females) received a dexamethasone intravitreal implant. At weeks 4, 12 and 24 after the injection, vitreous haze, macular thickness and best corrected visual acuity (BCVA) were assessed and adverse events reported. Results: Clearance of vitreous haze could be achieved after 4 weeks in 61% of all eyes (p < 0.001) and remained significant until week 24 (p < 0.001). This was paralleled by a reduction of central retinal thickness after 4 (p < 0.001), 12 (p < 0.001) and 24 weeks (p < 0.006). Significant and fast improvement of BCVA was already achieved after 4 weeks (p < 0.001) but vanished by week 24. Intraocular pressure reached ≥35 mm Hg in 3 eyes and was significantly more frequent in intermediate uveitis compared to posterior uveitis (p < 0.016). Conclusions: The dexamethasone implant is effective in controlling intraocular posterior segment inflammation and reduces central retinal thickness fast and effectively. © 2014 S. Karger AG, Basel

Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes

Background: To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). Methods: In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. Results: Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p > 0.05). The number of antiglaucoma medications did not change in both groups (p > 0.05) and showed no significant difference between the two groups (p > 0.05). Conclusion: Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation

Virus-associated anterior uveitis and secondary glaucoma: Diagnostics, clinical characteristics, and surgical options

In this retrospective, single-center, observational study, we compared the clinical characteristics, analyzed the glaucoma development, and the glaucoma surgery requirement mediators in patients with different virus-associated anterior uveitis (VAU). In total, 270 patients (= eyes) with VAU confirmed by positive Goldmann-Witmer coefficients (GWC) for cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV), rubella virus (RV), and multiple virus (MV) were included. Clinical records of these patients were analyzed. Demographic constitution, clinical findings, glaucoma development, and surgeries were recorded. The concentrations of 27 immune mediators were measured in 150 samples of aqueous humor. The GWC analysis demonstrated positive results for CMV in 57 (21%), HSV in 77 (29%), VZV in 45 (17%), RV in 77 (29%), and MV in 14 (5%) patients. CMV and RV AU occurred predominantly in younger and male patients, while VZV and HSV AU appeared mainly with the elderly and females (P<0.0001). The clinical features of all viruses revealed many similarities. In total, 52 patients (19%) showed glaucomatous damage and of these, 27 patients (10%) needed a glaucoma surgery. Minimal-invasive glaucoma surgery (MIGS) showed a reliable IOP reduction in the short-term period. In 10 patients (37%), the first surgical intervention failed and a follow-up surgery was required. We conclude that different virus entities in anterior uveitis present specific risks for the development of glaucoma as well as necessary surgery. MIGS can be suggested as first-line-treatment in individual cases, however, the device needs to be carefully chosen by experienced specialists based on the individual needs of the patient. Filtrating glaucoma surgery can be recommended in VAU as an effective therapy to reduce the IOP over a longer period of time

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant

Background Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. Methods Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. Results Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 μm (1 month; p = 0.003,) to 361 μm (2 months; p = 0,002) and to 415 μm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 μm (1 month; p < 0,001) and to 343 μm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. Conclusions In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity

Efficacy and safety of intravitreal dexamethasone implants in different indications

Hintergrund: Dexamethasonimplantate (DEX-Implantate) wurden 2010 zur Behandlung des Makulaödems nach retinalem Venenverschluss (RVO) und 2011 zur Behandlung der nicht infektiösen Uveitis des hinteren Augensegmentes zugelassen. Hierdurch haben sich die therapeutischen Optionen für diese Patienten erheblich verbessert. Allerdings können die Ergebnisse unter klinischen Alltagsbedingungen erheblich von den Ergebnissen von Zulassungsstudien abweichen. Zusätzlich werden durch die strengen Ein- und Ausschlusskriterien von Zulassungsstudien bestimmte Patientengruppen ausgeschlossen, für die jedoch ebenfalls Daten benötigt werden. Material und Methoden: Alle Arbeiten dieser kumulativen Habilitationsschrift sollen unser Wissen über Effektivität und Sicherheit von DEX-Implantaten in den zugelassenen Indikationen und darüber hinaus unter klinischen Bedingungen sowie im Langzeitverlauf erweitern, um unsere Patienten optimaler behandeln zu können. Ergebnisse: Unsere Originalarbeiten 1 bis 5 belegen eine gute Wirksamkeit von DEX-Implantaten bei der Behandlung des Makulaödems aufgrund eines RVO’s sowie bei Uveitispatienten, sofern keine makuläre Ischämie vorliegt. Dabei zeigt Originalarbeit 1 im Wesentlichen gemessen anhand der Mikroperimetrie (MP), dass DEX-Implantate eine deutlich kürzere Wirksamkeit als 6 Monate beim RVO aufweisen als in der Zulassungsstudie gefunden wurde. Die MP war dabei sehr hilfreich Patienten mit frühem Wiederbehandlungsbedarf zu identifizieren. Trotzdem stellen DEX-Implantate aufgrund ihrer guten Wirksamkeit über 3 bis 4 Monate eine attraktive therapeutische Alternative zu vascular endothelial growth factor (VEGF)-Inhibitoren, die in deutlich kürzeren Abständen appliziert werden müssen, dar. Originalarbeit 2 geht auf Patienten mit niedrigem Ausgangsvisus beim Zentralvenenverschluss ein, die von der Zulassungsstudie ausgeschlossen wurden und zeigt, dass einige Patienten in Abhängigkeit von der makulären Ischämie gering von der Therapie profitieren. In Originalarbeit 3 werden die Ergebnisse von Patienten mit RVO unter Alltagsbedingungen nach Behandlung mit DEX-Implantaten oder Ranibizumab betrachtet und es zeigt sich ein Angleichen der Ergebnisse aufgrund einer deutlichen Untertherapie. Originalarbeit 4 weist die größte bisher publizierte Langzeitserie von Entzündungspatienten auf, die mit bis zu 6 DEX-Implantaten behandelt wurden. Dabei ließen sich erstmals Aussagen zur Effektivität von DEX-Implantaten bei unterschiedlichen, der Entzündung zu Grunde liegenden Erkrankungen, sowie Begleitmedikationen treffen. Patienten mit idiopathischer Augenentzündung gefolgt von Sarkoidosepatienten profitierten besonders von der Behandlung mit DEX-Implantaten, so dass eine alleinige Therapie ohne Basistherapie gerechtfertigt zu sein scheint. Zusätzlich zeigte sich interessanterweise, dass insbesondere Patienten unter Ciclosporin A-Basistherapie von einer verlängerten Wirksamkeit der DEX-Implantate zu profitieren schienen. Originalarbeit 5 berichtet über die Therapie mit DEX-Implantaten bei pädiatrischen Uveitispatienten für die bisher keine Zulassung besteht. Natürlich muss bei DEX-Implantaten auch das Nebenwirkungsspektrum betrachtet werden. Hier wäre die Steroid induzierte Augeninnendruck (IOP) Steigerung sowie die Steroid induzierte Katarakt zu nennen. Bezüglich des Nebenwirkungsspektrum zeigten unsere Ergebnisse, dass die durch DEX- Implantate erzeugten IOP-Steigerungen generell transient und gut zu regulieren waren. Allerdings sollte die Indikation für DEX-Implantate bei Kindern und Glaukompatienten mit antiglaukomatöser 2-3fach Therapie vorsichtig gestellt werden. Hinsichtlich Kataraktinduktion zeigte sich dagegen ein kumulativer Effekt von DEX-Implantaten, so dass nach Mehrfachinjektionen mit einer Katarakt gerechnet werden muss. Dieses sollte bei der Patientenauswahl, insbesondere pädiatrischen und jungen Patienten, berücksichtigt werden. Schlussfolgerungen: DEX-Implantate stellen eine wirksame Therapie zur Behandlung des Makulaödems nach RVO und bei der nicht infektiösen Uveitis unter klinischen Bedingungen und über die Zulassungsstudien hinaus dar. Bei der Wahl der Therapie sollten Faktoren wie Alter der Patienten sowie ein vorbestehendes Glaukom berücksichtigt werden. Eine Untertherapie sollte unbedingt vermieden werden, da hierdurch mögliche Visusgewinne erheblich reduziert werden können.Background: Therapeutic options have increased considerably since approval of Dexamethasone implants (DEX) for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) in 2010 and for the treatment of non infectious uveitis of the posterior segment in 2011. However, all prospective randomized studies do not reflect real life issues so that real life results may differ significantly. In addition several groups of patients were excluded by approval studies through strict in and exclusion criteria. But data for these patients are needed as well. Material and methods: The aim of this work was to increase our understanding of efficacy and safety of DEX-implants for the approved indications and furthermore under real ife issues and in a long term clinical course. Results: DEX-implants show a good efficacy in the treatment of ME caused by RVO or uveitis, if macular ischemia is absent. Research article 1 indicates that DEX-implants have a shorter efficacy than 6 months in RVO than found in the approval studies. MP was very helpful to identify patients with a need for early retreatment. Despite this DEX-implants are an attractive alternative to vascular endothelial growth factor (VEGF)- inhibitors because treatment has not to be performed that often. Research article 2 shows that patients with central retinal vein occlusion and low visual acuity, who were excluded from the approval studies, had a benefit of DEX therapy in dependence on macular ischemia. Research article 3 reports on RVO patients, who were treated with DEX-implants or ranibizumab in a real life clinical setting. Undertreatment led to similar results. Research article 4 contains the largest long term series of uveitis patients, who were treated with up to 6 DEX-implants. For the first time it could be shown that the efficacy of DEX-implants is dependent on the underlying disease and systemic medication. Especially patients with idiopathic uveitis and sarcoidosis benefited well of the DEX treatment. Therefore a single therapy with DEX-implants may be justified. In addition patients with ciclosporine A therapy seemed to profit of a longer efficacy of DEX-implants. Finally research article 5 reports on the off label treatment with DEX-implants in pediatric patients. Adverse events of DEX-implants may include steroid induced intraocular pressure (IOP) elevation or cataract. Our results indicate that IOP elevation was generally transient and good to control. But a cummulative risk for cataract induction exists after several DEX-implants. Therefore DEX-implants should be used with caution in pediatric patients and glaucoma patients with an IOP lowering therapy consisting of 2-3 components. Conclusion: Therapy with DEX-implants is very effective in the treatment of ME after RVO and in cases of non infectious uveitis in a real life clincal setting and furthermore. Patient characteristics like age and preexisting glaucoma have to be considered. Undertherapy may severely reduce possible visual acuity gains and should be prevented in every case

Dexamethasone implants in paediatric patients with noninfectious intermediate or posterior uveitis: first prospective exploratory case series

Abstract Background To evaluate the efficacy and safety of dexamethasone (DEX) implants in paediatric patients with noninfectious intermediate or posterior uveitis. Methods Prospective single center exploratory case series. Children and adolescents, 6 to 17 years old, with a vitreous haze score of ≥1.5+ or cystoid macular edema (CME) of >300 μm were enrolled. Vitreous haze score at month 2 was chosen as primary endpoint. Best corrected visual acuity (BCVA), central retinal thickness (CRT) and concomitant medication at month 6 were defined as secondary endpoints. Intraocular pressure (IOP) and cataract formation were determined as safety endpoints. Results Three out of 6 eligible patients participated in the case series. At month 2, vitreous haze was reduced from a score of 1.5+ to 0.5+ and 0 and BCVA improved by ≥3 lines, ≥4 lines and ≥2 lines of Early Treatment of Diabetic Retinopathy (ETDRS)-letters, respectively. Visual acuity gain was accompanied by a CRT reduction of −186 μm and −83 μm in the first and third patient, in whom CME was the indication for DEX implantation. A reduction of concomitant medication was achieved in 1 patient. IOP increase was seen in all 3 patients, but could be treated sufficiently with primarily IOP lowering medications and without need for glaucoma surgery. Cataract progression did not occur. Conclusions DEX implants led to an improvement in all endpoints, especially BCVA. This study confirms that IOP rises may also occur in the paediatric population and should be monitored and treated appropriately. Trial registration European Union Drug Regulating Authorities Clinical Trials (EudraCT)- nr: 2013–000541-39

Optical coherence tomography angiography (OCTA) findings in Serpiginous Choroiditis

Background: To describe changes in the retina/choroid in patients with Serpiginous Choroiditis (SC) by Optical Coherence Tomography Angiography (OCTA) in a multimodal imaging approach. Methods: Prospective, monocentric study of 24 eyes of 12 consenting patients diagnosed with SC, who underwent OCTA, which was analyzed and compared to other methods such as enhanced depth imaging-OCT, fluorescein angiography, indocyanine green angiography, and fundus autofluorescence. Results: The study group consisted of 9 patients with peripapillary SC, 1 macular SC, and 2 atypical cases. All eyes presented an inactive SC confirmed by standard imaging. OCTA demonstrated the lesions tridimensionally in great detail. There was no difference in the angioarchitecture among the 3 forms of SC. A loss of the choriocapillaris/retinal pigment epithelium left a “window-defect”, where the vessels of larger caliber of the choroid became recognizable and their appearance inverted (“white-on-black”). A relationship between the presence of segmentation errors (SE) in the slabs and low visual acuity was established with a one-way ANOVA. Conclusions: OCTA was able to non-invasively assess vascular lesions of the choroid/retina in patients with SC with a high degree of correlation to other diagnostic modalities. Consequent long-term assessments could lead to a better understanding of disease progression

In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain

[Rationale]: Aripiprazole is an atypical antipsychotic drug with high in vitro affinity for 5-HT1A, 5-HT2A and dopamine (DA) D2 receptors. However, its in vivo actions in the brain are still poorly characterized.[Objective]: The aim was to study the in vivo actions of aripiprazole in the rat and mouse brain.[Methods]: Brain microdialysis and single-unit extracellular recordings were performed.[Results]: The systemic administration of aripiprazole reduced 5-HT output in the medial prefrontal cortex (mPFC) and dorsal raphe nucleus of the rat. Aripiprazole also reduced extracellular 5-HT in the mPFC of wild-type (WT) but not of 5-HT1A (−/−) knockout (KO) mice. Aripiprazole reversed the elevation in extracellular 5-HT output produced by the local application of the 5-HT2A/2C receptor agonist DOI in mPFC. Aripiprazole also increased the DA output in mPFC of WT but not of 5-HT1A KO mice, as observed for atypical antipsychotic drugs, in contrast to haloperidol. Contrary to haloperidol, which increases the firing rate of DA neurons in the ventral tegmental area (VTA), aripiprazole induced a very moderate reduction in dopaminergic activity. Haloperidol fully reversed the inhibition in dopaminergic firing rate induced by apomorphine, whereas aripiprazole evoked a partial reversal that was significantly different from that evoked by haloperidol and from the spontaneous reversal of dopaminergic activity in rats treated with apomorphine.[Conclusions]: These results indicate that aripiprazole modulates the in vivo 5-HT and DA release in mPFC through the activation of 5-HT1A receptors. Moreover, aripiprazole behaves as a partial agonist at DA D2 autoreceptors in vivo, an action which clearly distinguishes it from haloperidol.This work was supported by grants from the Spanish Ministry of Education and Science (SAF 2004-05525) and Bristol Myers Squibb. PC and AB are recipients of a Ramón y Cajal contract from the Ministry of Science and Technology. LDM is recipient of a predoctoral fellowship from IDIBAPS. Support from the Spanish Ministry of Health, Instituto de Salud Carlos III, Red de Enfermedades Mentales (REM-TAP Network) is also acknowledged.Peer reviewe