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

Stabilization of macular, peripapillary and papillary vascular parameters after XEN and trabeculectomy visualized by the optical coherence tomography angiography

To analyze the effect of filtration in glaucoma surgery, XEN versus trabeculectomy, on the vessel area density (VAD) of the macular, papillary and peripapillary regions using optical coherence tomography angiography (OCT-A). This prospective cohort study analyzes the vascular architecture of 47 eyes of 45 patients after two different filtrating surgery procedures (XEN stent and trabeculectomy (TE)) using the OCT-A. Participants who had an outsourced medical anti-glaucoma therapy received filtrating surgery in a 2:1 (XEN: TE) ratio. The primary outcome measurements were changes in the VAD in various layers of retinal perfusion and the foveal avascular zone (FAZ). Both interventions achieved a significant postoperative reduction in IOP (XEN 17.6 +/- 3.8-13.7 +/- 3.8 mmHg; TE 21.2 +/- 5.4-8.8 +/- 2.6 mmHg). VAD values did not change significantly after filtrating surgery. Comparing both procedures, a significantly higher VAD for patients treated with TE was seen for the superficial vessel complex (SVC) 375 mu m and 750 mu m (p = 0.011, p = 0.017), deep vessel complex (DVC) 375 mu m (p = 0.029) and the optic disc (p = 0.028) after 6 months, while all other parameters did not differ significantly. In conclusion, VAD does not significantly improve after filtrating surgery in preoperative moderately IOP elevated eyes. The IOP lowering effect of filtrating surgery, however, can stabilize vascular parameters in all layers of perfusion

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma

Purpose: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. Design: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or >= 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. Results: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031]). Conclusion: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure

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