Mid-term surgical success after transscleral ab interno glaucoma gel stent implantation.

PURPOSE: To investigate the surgical success and efficacy of XEN45 implantation (XEN45 µm, AbbVie Inc., USA) with and without combined cataract surgery up to the first 5 years. METHODS: In a prospective observational monocentric trial, 192 eyes of 157 patients with open-angle glaucoma received either XEN45 implants only (solo surgery group) or combined surgery/cataract surgeries (combined surgery group). Surgical success (qualified and full success; IOP-limit: ≤12, 15, 18, 21 mmHg), time to secondary IOP-lowering procedure, IOP and number of IOP-lowering medications were analysed for 1, 2, 3, 4 and 5 years. RESULTS: Compared to baseline, IOP (24.1 ± 8.1 to 12.6 ± 2.8 mmHg, -48%, p < 0.001) and the number of IOP-lowering medications (3.0 ± 1.0 to 1.5 ± 1.2, -50%, p < 0.001) decreased significantly at 5 years. Although no differences between IOP and the number of IOP-lowering medication courses between the groups were detected at 5 years (p > 0.11), the combined procedure (63%, 37%) showed better success rates compared to the solo procedure (36%, 13%) in the definition IOP ≤18 and ≤12 mmHg (p = 0.035, 0.028). Solo XEN45 procedures had a higher rate of secondary IOP-lowering procedures compared to combined XEN45 cataract procedures (hazard ratio: 2.02, 95%CI: 1.03-3.97, p = 0.04). Twenty per cent of the eyes, including both procedures, required a secondary IOP-lowering procedure within 5 years. CONCLUSIONS: The XEN45 implant is effective in lowering IOP and the number of IOP-lowering medications in patients with open-angle glaucoma in the mid-term. Comparing XEN45 implant results with the results of trabeculectomy available in current literature, we speculate that there might be a higher surgical success rate without medications in favour of trabeculectomy.

Distribution of the cysteinyl leukotriene system components in the human, rat and mouse eye.

The cysteinyl leukotrienes (CysLTs) have important functions in the regulation of inflammation and cellular stress. Blocking the CysLT receptors (CysLTRs) with specific antagonists is beneficial against progression of retinopathies (e.g. diabetic retinopathy, wet AMD). However, the exact cellular localization of the CysLTRs and their endogenous ligands in the eye have not been elucidated in detail yet. It is also not known whether the expression patterns differ between humans and animal models. Therefore, the present study aimed to describe and compare the distribution of two important enzymes in CysLT biosynthesis, 5-lipoxygenase (5-LOX) and 5-lipoxygenase-activating protein (FLAP), and of CysLTR1 and CysLTR2 in healthy human, rat and mouse eyes. Human donor eyes (n = 10) and eyes from adult Sprague Dawley rats (n = 5) and CD1 mice (n = 8) of both sexes were collected. The eyes were fixed in 4% paraformaldehyde and cross-sections were investigated by immunofluorescence with specific antibodies against 5-LOX, FLAP (human tissue only), CysLTR1 and CysLTR2. Flat-mounts of the human choroid were prepared and processed similarly. Expression patterns were assessed and semiquantitatively evaluated using a confocal fluorescence microscope (LSM710, Zeiss). We observed so far unreported expression sites for CysLT system components in various ocular tissues. Overall, we detected expression of 5-LOX, CysLTR1 and CysLTR2 in the human, rat and mouse cornea, conjunctiva, iris, lens, ciliary body, retina and choroid. Importantly, expression profiles of CysLTR1 and CysLTR2 were highly similar between human and rodent eyes. FLAP was expressed in all human ocular tissues except the lens. Largely weak immunoreactivity of FLAP and 5-LOX was observed in a few, yet unidentified, cells of diverse ocular tissues, indicating low levels of CysLT biosynthesis in healthy eyes. CysLTR1 was predominantly detected in ocular epithelial cells, supporting the involvement of CysLTR1 in stress and immune responses. CysLTR2 was predominantly expressed in neuronal structures, suggesting neuromodulatory roles of CysLTR2 in the eye and revealing disparate functions of CysLTRs in ocular tissues. Taken together, we provide a comprehensive protein expression atlas of CysLT system components in the human and rodent eye. While the current study is purely descriptive and therefore does not allow significant functional conclusions yet, it represents an important basis for future studies in diseased ocular tissues in which distribution patterns or expression levels of the CysLT system might be altered. Furthermore, this is the first comprehensive study to elucidate expression patterns of CysLT system components in human and animal models that will help to identify and understand functions of the system as well as mechanisms of action of potential CysLTR ligands in the eye.

Pericyte-derived cells participate in optic nerve scar formation.

Introduction: Pericytes (PCs) are specialized cells located abluminal of endothelial cells on capillaries, fulfilling numerous important functions. Their potential involvement in wound healing and scar formation is achieving increasing attention since years. Thus, many studies investigated the participation of PCs following brain and spinal cord (SC) injury, however, lacking in-depth analysis of lesioned optic nerve (ON) tissue. Further, due to the lack of a unique PC marker and uniform definition of PCs, contradicting results are published. Methods: In the present study the inducible PDGFRß-P2A-CreERT2-tdTomato lineage tracing reporter mouse was used to investigate the participation and trans-differentiation of endogenous PC-derived cells in an ON crush (ONC) injury model, analyzing five different post lesion time points up to 8 weeks post lesion. Results: PC-specific labeling of the reporter was evaluated and confirmed in the unlesioned ON of the reporter mouse. After ONC, we detected PC-derived tdTomato+ cells in the lesion, whereof the majority is not associated with vascular structures. The number of PC-derived tdTomato+ cells within the lesion increased over time, accounting for 60-90% of all PDGFRß+ cells in the lesion. The presence of PDGFRß+tdTomato- cells in the ON scar suggests the existence of fibrotic cell subpopulations of different origins. Discussion: Our results clearly demonstrate the presence of non-vascular associated tdTomato+ cells in the lesion core, indicating the participation of PC-derived cells in fibrotic scar formation following ONC. Thus, these PC-derived cells represent promising target cells for therapeutic treatment strategies to modulate fibrotic scar formation to improve axonal regeneration.

Radius-Maumenee syndrome: A case series with a long-term follow-up.

The aim of the case series is to highlight the surgical challenges experienced like failed intervention, choroidal effusion, a postoperative cystoid macular oedema, and describe treatment options for Radius-Maumenee syndrome. Authors reported on 3 bilateral cases of Radius-Maumenee syndrome which underwent medical treatment, trabeculectomy with Mitomycin C, implantation with XEN45, Ahmed glaucoma valve, Baerveldt glaucoma implant, and cyclophotocoagulation.

Five-year follow-up of corneal endothelial cell density after transscleral ab interno glaucoma gel stent implantation.

PURPOSE: This study investigates the course of the endothelial cell density over a period of 5 years after XEN45 implantation (XEN45µm, Allergan Plc., USA) with or without combined cataract surgery. METHODS: This is a prospective, cross-sectional, monocentric, non-randomized clinical trial with the intention to treat a population of the University Eye Clinic Glaucoma Service Salzburg. One hundred and fifty-five eyes with preoperative central corneal endothelial cell counts were subjected to XEN45 implantation with (combined surgery group) or without (solo surgery group) combined cataract surgery. Endothelial cell density was measured at 3 corneal positions. XEN45 location parameters were determined with anterior segment OCT and gonioscopy. RESULTS: In the combined surgery group, a significant reduction of central endothelial cell count was found at years 2 and 4 when compared to baseline (p = 0.001 and p = 0.02, n = 86), whereas at years 1, 3, and 5, no change was detected (all p > 0.09). The median reduction of endothelial cell count was - 79 (95% CI: - 183 to - 9) and - 93 (95% CI: - 220 to 23) cells at years 2 and 4, respectively. In the solo surgery group (n = 69), no significant change in endothelial cell counts was detected at any time during the 5-year evaluation period (all p > 0.07). Explorative data analyses revealed that XEN45 location parameters did not significantly influence the course of endothelial cell count over time. CONCLUSIONS: Endothelial cell loss after XEN45 implantation seems to be low. The present data suggest no impact on the position of the implant with regard to central endothelial cell counts in this study.

Leukotriene Signaling as a Target in α-Synucleinopathies.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are two common types of α-synucleinopathies and represent a high unmet medical need. Despite diverging clinical manifestations, both neurodegenerative diseases share several facets of their complex pathophysiology. Apart from α-synuclein aggregation, an impairment of mitochondrial functions, defective protein clearance systems and excessive inflammatory responses are consistently observed in the brains of PD as well as DLB patients. Leukotrienes are lipid mediators of inflammatory signaling traditionally known for their role in asthma. However, recent research advances highlight a possible contribution of leukotrienes, along with their rate-limiting synthesis enzyme 5-lipoxygenase, in the pathogenesis of central nervous system disorders. This review provides an overview of in vitro as well as in vivo studies, in summary suggesting that dysregulated leukotriene signaling is involved in the pathological processes underlying PD and DLB. In addition, we discuss how the leukotriene signaling pathway could serve as a future drug target for the therapy of PD and DLB.

Characterization of the Two Inducible Cre Recombinase-Based Mouse Models NG2-CreER™ and PDGFRb-P2A-CreERT2 for Pericyte Labeling in the Retina.

PURPOSE: Pericytes (PCs), located abluminal of endothelial cells on capillaries, are essential for vascular development and stability. They display a heterogeneous morphology depending on organ localization, differentiation state, and function. Consequently, PCs show a diverse gene expression profile, impeding the usage of a unique PC marker and therefore the distinct identification of PCs. Inducible reporter mouse models represent an important tool for investigating the fate of PCs under physiological and pathophysiological conditions. PC-specific expression efficiency of the fluorescence reporter tdTomato following tamoxifen induction was analyzed and compared in two inducible Cre recombinase-expressing mouse models under control of the NG2 and PDGFRb promotor. METHODS: The NG2-CreER™-tdTomato and the PDGFRb-P2A-CreERT2-tdTomato mice were treated with tamoxifen at three defining time points of retinal vascular development: post-natal days (P)5, P10/11/12, and P48/49/50/51. TdTomato reporter induction efficiency was determined by analyzing retinal whole mounts utilizing confocal microscopy, using the antibodies Anti-neural/glial antigen 2 (PCs), Anti-Collagen IV (basement membrane), and Anti-Glutamine Synthetase (Müller glial cells). RESULTS: Tamoxifen induction at the three different time points resulted in PC-specific expression of tdTomato in both reporter models. In the NG2-CreER™-tdTomato mouse, the induction efficiency ranged from 21.9 to 35.5%. In the PDGFRb-P2A-CreERT2-tdTomato mouse, an induction efficiency between 78.9 and 94.1% was achieved. TdTomato expression in the retina was restricted to PCs and vascular smooth muscle cells in the NG2-CreER™-tdTomato mouse, however, in the PDGFRb-P2A-CreERT2-tdTomato mouse, tdTomato was also expressed in Müller glial cells. CONCLUSION: Both reporter mouse models represent promising tools for fate-mapping studies of PCs. While the NG2-CreER™-tdTomato mouse reveals very specific labeling of PCs in the retina, its induction efficiency is lower compared to the PDGFRb-P2A-CreERT2-tdTomato mouse. Although the latter revealed a high percentage of tdTomato-positive PCs in the retina, additional labeling of Müller cells potentially hampers analysis of reporter-positive PCs.

Episcleral venous pressure response to brain stem stimulation: Effect of topical lidocaine.

Episcleral venous pressure (EVP) is important for steady state intraocular pressure (IOP), as it has to be overcome by aqueous humor in order to leave the eye. Recent evidence suggests a neuronal tone being present, as topical anesthesia lowered EVP. The superior salivatory nucleus in the brainstem could be identified to elicit increases in EVP during electrical stimulation. In the present study the effect of topical anesthesia on the stimulation effect was investigated. 8 Spraque Dawley rats were anesthetized, artificially ventilated with CO2 monitoring and continuous blood pressure monitoring. Intraocular pressure was measured continuously through a cannula in the vitreous body. Episcleral venous pressure was measured by direct cannulation of an episcleral vein via a custom made glass pipette connected to a servonull micropressure system. Electrical stimulation of the superior salivatory nucleus (9 µA, 200 pulses of 1 ms duration) increased EVP from 8.51 ± 1.82 mmHg to 10.97 ± 1.93 mmHg (p = 0.004). After application of topical lidocaine EVP increased from 7.42 ± 1.59 mmHg to 9.77 ± 1.65 mmHg (p = 0.007). The EVP response to stimulation before and after lidocaine application was not statistically significantly different (2.45 ± 0.5 vs 2.35 ± 0.49 mmHg, p = 0.69), while the decrease in baseline EVP was (8.51 vs. 7.42 mmHg, p = 0.045). The present data suggest that distinct neuronal mechanisms controlling the episcleral circulation of rats exist. This is in keeping with previous reports of two distinct arterio-venous anastomoses, one in the limbal circulation and one in the conjunctival/episcleral circulation.

Two-year efficacy after first transscleral controlled cyclophotocoagulation in patients with and without pseudoexfoliation.

PURPOSE: Transscleral controlled cyclophotocoagulation (COCO) is a transscleral 810-nm diode laser cyclophotocoagulation that automatically adjusts the applied laser energy utilizing an optical feedback loop. The present study investigates the influence of pseudoexfoliation (PEX) on the efficacy of COCO in a Caucasian study population. METHODS: Retrospective data from 130 consecutive eyes were analyzed during a 2-year follow-up. Baseline characteristics, intraocular pressure (IOP), number of IOP-lowering medications, visual field, best-corrected visual acuity (BCVA), and secondary surgical interventions (SSI) were analyzed. The primary endpoint was IOP reduction at M24 compared to baseline, and the secondary endpoints were IOP course, reduction of IOP-lowering medications, surgical success, and IOP-lowering SSIs stratified by PEX and baseline IOP. RESULTS: IOP reductions of -35, -39, -25, -25, -23, -34, and -36% could be achieved from baseline to D1, W1, M1, M3, M6, M12, and M24 (all p < 0.001), respectively, while there was a significant overall reduction over time (p < 0.001) in the number of topical IOP-lowering medications postoperatively. The proportion of eyes requiring additional systemic IOP-lowering medication reduced from 31 to 0% at M24 (p = 0.025). Eyes without PEX and IOP < 30 mmHg at baseline had the lowest risk for IOP-lowering SSIs (p < 0.03). BCVA dropped at M12 (0.25 [95% CI: 0.12-0.38]), and the drop persisted during the following 12 months. CONCLUSION: The present study demonstrates a midterm IOP-lowering effect after COCO while reducing the burden for topical and systemic IOP-lowering medications. Patients without PEX and IOP < 30 mmHg have a lower risk of SSI. The procedure per se cannot be excluded as causative for the decreased postoperative BCVA. Further prospective investigations are suggested.

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial.

The aim of the HYLAN M study was to investigate if symptoms and/or signs of patients suffering from severe dry eye disease (DED) can be improved by substituting individually optimized artificial tear therapy by high molecular weight hyaluronan (HMWHA) eye drops. In this international, multicenter study, patients with symptoms of at least ocular surface disease index (OSDI) 33 and corneal fluorescein staining (CFS) of at least Oxford grade 3 were included. A total of 84 per-protocol patients were randomized in two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the week 8 visit, the average OSDI of the verum group had improved by 13.5 as compared to the control group (p = 0.001). The best corrected visual acuity (BCVA) had improved by 0.04 logMAR (p = 0.033). CFS, tear film break-up time (TBUT), Schirmer I, lid wiper epitheliopathy (LWE), mucocutaneous junction (Yamaguchi score), and tear osmolarity were not significantly different between the verum and control groups (p > 0.050). We conclude that for most patients with severe DED, 0.15% HMWHA eye drops provide excellent improvement of symptoms without impairment of dry eye signs.

Change in visual acuity 12 and 24 months after transscleral ab interno glaucoma gel stent implantation with adjunctive Mitomycin C.

PURPOSE: To analyze changes in best-corrected visual acuity (BCVA) after implantation of the transscleral ab interno glaucoma gel stent (XEN Gel Stent; Allergan, Dublin) in patients with open-angle glaucoma. METHODS: In a single-center, prospective, non-randomized study of 137 eyes with open-angle glaucoma which underwent implantation with XEN, 69 eyes underwent XEN implantation alone (group 1) and 68 eyes underwent XEN implantation and cataract surgery (group 2). BCVA (Bailey-Lovie chart, logMAR scale) was evaluated at baseline, postoperative day 1, weeks 1 and 2, and months 1, 3, 6, 12, and 24. Risk factors for decline in BCVA were analyzed in multivariate models. RESULTS: Baseline BCVA in group 1 was 0.21 ± 031; the group's mean BCVA did not change at any postoperative visit, although a ≥ 2-line loss of BCVA was detected in 15% (95% CI 7-29%) and 4% (95% CI 0-20%) after months 12 and 24, respectively. Baseline BCVA in group 2 was 0.33 ± 031; vision increased significantly at months 3 (0.22 ± 0.29, p = 0.015), 6 (0.20 ± 0.26, p = 0.006), 12 (0.18 ± 0.29, p = 0.001), and 24 (0.18 ± 0.29, p = 0.005). A ≥ 2-line loss of BCVA was reported in 4% (95% CI 1-15%) and 7% (95% CI 1-24%) after months 12 and 24, respectively. CONCLUSIONS: There was no deterioration of BCVA in group 1; those in group 2 had an overall significant increase in BCVA. BCVA decrease was lower than is typically reported in the literature post-trabeculectomy.

Femtosecond laser in refractive corneal surgery.

The introduction of the femtosecond (fs) laser has revolutionized ophthalmic surgery. With the worldwide application of fs-lasers, clinical outcomes and safety in corneal procedures have improved significantly and they have become an ideal tool for ultra-precise corneal refractive surgery. Flap creation in laser in situ keratomileusis (LASIK) is the most common use of this laser. It can also be used for other corneal refractive procedures including channel creation for the insertion of intrastromal corneal ring segments (ICRS), performing astigmatic keratotomies (AK), femtosecond lenticule extraction including small incision lenticule extraction (SMILE), and the insertion of corneal inlays. This article summarizes recent advanced applications of fs laser technology in corneal refractive surgery.

Effect of the outer stent position on efficacy after minimally invasive transscleral glaucoma gel stent implantation.

PURPOSE: The outer stent lumen can be located either deeper (in or under Tenon's layer) or more superficially in the conjunctival stroma after the transscleral XEN Glaucoma Gel Microstent (XEN-GGM; Allergan Plc., USA) implantation. The present study aimed to investigate the effect of the postoperative conjunctival implant position on surgical success and intraocular pressure (IOP) after XEN-GGM. METHODS: Prospective data from 66 consecutive open-angle glaucoma eyes of 54 patients were collected preoperatively and 1 and 2 weeks, and 1, 6 and 12 months postoperatively. The layer of implantation was determined in the first month postoperatively as intra- and subtenon or intraconjunctival depending on the location of the outer lumen of the stent in OCT (Visante OCT; Zeiss, Germany). Primary outcome measures were differences in relative IOP reduction at 12 months between the two groups. Further, complete and qualified surgical success, number of secondary needlings and number of IOP-lowering medications and absolute IOP were assessed. RESULTS: Relative IOP reduction was higher in intra- and subtenon group (n = 37/66, 56%) at week 1 (-54% versus -19%, p < 0.001), week 2 (-39% versus -21%, p = 0.02), month 1 (-42% versus -28%, p = 0.035) and month 12 (-39% versus -24%, p = 0.024). The mean absolute IOP was lower in intra- and subtenon group at week 1 (10.8 [95%CI, 8.8-14.1] versus 16.6 [95%CI, 14.1-19.0] mmHg, p < 0.001) and months 12 (13.9 [95%CI, 12.4-15.4] versus 16.7 [95%CI, 14.6-18.8] mmHg, p = 0.041). At month 6, a lower burden for IOP-lowering medication was shown for the intra- and subtenon group (0.2 ± 0.5 versus 1.0 ± 1.1, p = 0.034). The mean number of secondary needlings, which were done in 47/66 (71%) of the eyes, was lower in the intra- and subtenon group in the first year (1.9 ± 1.7 versus 1.2 ± 1.2, p = 0.03). Qualified surgical success was higher in the intra- and subtenon group (90% versus 61%, p = 0.01) after 1 year. CONCLUSION: The present study demonstrates a higher efficacy achieved with lower secondary needling rates in deeper implant positions in conjunctiva after XEN-GGM.

Pericytes in the Retina.

Pericytes (PCs) are specialized cells located abluminal of endothelial cells (ECs) on capillaries, embedded within the same basement membrane. They are essential regulators of vascular development, remodeling, and blood-retina-barrier (BRB) tightness and are therefore important components to maintain tissue homeostasis. The perivascular localization and expression of contractile proteins suggest that PCs participate in capillary blood flow regulation and neurovascular coupling. Due to their ability to differentiate into various cell types in vitro, they are regarded as potential cells for tissue repair and therapeutic approaches in regenerative medicine. Altered function or loss of PCs is associated with a multitude of CNS diseases, including diabetic retinopathy (DR). In this chapter, we will provide a short overview of retinal vascular development, the origin of PCs, and focus on PCs in retinopathy of prematurity (ROP) and in the diabetic retina. Further, animal models to study the fate of PCs and the potential role of (retinal) PCs in regeneration and wound healing will be discussed.

Longitudinal bleb morphology in anterior segment OCT after minimally invasive transscleral ab interno Glaucoma Gel Microstent implantation.

PURPOSE: Like the classic trabeculectomy, the minimally invasive, ab interno XEN Glaucoma Gel Microstent (XEN-GGM) creates a filtration bleb in the conjunctiva. The goal of this study was to investigate internal bleb morphology over time with anterior segment optical coherence tomography (AS-OCT) after XEN-GGM implantation. METHODS: In a prospective, single-centre, single-armed cohort study, blebs were characterized using AS-OCT in 78 eyes of 60 patients at day 1, at weeks 1 and 2 and at months 1, 3, 6, 9 and 12 after XEN-GGM implantation in patients with open-angle glaucoma. Morphological bleb characteristics were correlated with IOP and surgical success. RESULTS: Anterior segment optical coherence tomography data indicate early and late bleb changes in the course of 12 months. Uniform blebs in AS-OCTs showed higher IOPs at all examinations between week 1 (17.7 ± 4.8 mmHg versus 11.3 ± 7.1 mmHg, p = 0.001) and month 3 (16.4 ± 6.1 versus 13.4 ± 6.1, p = 0.04). Subconjunctival tissue separation bleb morphology was associated with lower mean IOPs during the course of 12 months (r = -0.75, p = 0.031). Predictors for surgical failure at month 12 were microcystic multiform bleb morphology in AS-OCT at month 3 (60% versus 15%, relative risk 4.0, p = 0.043) and uniform bleb morphology at month 9 (33% versus 23%, relative risk 1.4, p = 0.015). CONCLUSION: Bleb appearance after XEN surgery seems to be different to classic trabeculectomy literature. The present data suggest correlation of IOP and surgical long-term success with bleb morphology in AS-OCT. Prevalence of small diffuse cysts is directly associated with lower IOPs, while cystic encapsulation at 3 months predicts higher surgical failure.

Four-year results of a minimally invasive transscleral glaucoma gel stent implantation in a prospective multi-centre study.

IMPORTANCE: The transscleral XEN Glaucoma Gel Microstent (XEN-GGM, Allergan Plc., Parsippany, New Jersey) is implanted by a minimally invasive ab interno technique. BACKGROUND: The present study aims to assess the long-term clinical outcomes in patients after XEN-GGM implantation. DESIGN: This prospective, non-randomized, multi-centred study was conducted in three countries (Austria, Canada and Germany). PARTICIPANTS: Sixty-four consecutive eyes of 64 patients with open angle glaucoma received the XEN-GGM (63 µm) without Mitomycin C. Thirty-five (55%) were solo procedures, and 29 (45%) were combined with cataract surgery. METHODS: Visits were planned at baseline, 6 months, 1, 2, 3 and 4 years postoperatively. MAIN OUTCOME MEASURES: The main outcome measures were mean intraocular pressure (IOP), mean number of IOP lowering medication. Secondary outcome parameters were: visual acuity, visual fields and complete surgical failure (defined as presence of a secondary IOP lowering procedure or loss of light perception) at 4 years, postoperatively. RESULTS: Mean best-medicated baseline IOP was 22.5 ± 4.2 mmHg and decreased significantly to 13.4 ± 3.1 mmHg 4 years postoperatively (-40%, n = 34, P < 0.001). Mean number of IOP lowering medication decreased significantly from 2.4 ± 1.3 preoperatively to 1.2 ± 1.3 (-50%, n = 34, P < 0.001) postoperatively. Visual field mean deviation showed no significant change between preoperative and postoperative examinations. Complete surgical failure rate per year was 10%. CONCLUSIONS AND RELEVANCE: The XEN-GGM resulted in lower IOP and a reduction in medications from baseline over 4 years of follow-up. There was no detectable decrease in visual fields over the study. The surgical failure rate is comparable to other filtration surgeries.

Retinal Pericytes: Characterization of Vascular Development-Dependent Induction Time Points in an Inducible NG2 Reporter Mouse Model.

Purpose/aim of the study: In the retina, defects in pericytes (PCs) function/loss are associated with various complications; however, the exact pathological mechanisms are still not fully elucidated. Following the behavior of retina-resident PCs during health and disease will reveal new insights for both the understanding of pathological mechanisms and the development of new regenerative therapies for the treatment of retinopathies. The main goal of this study is to determine whether the NG2-reporter mouse (NG2CreERTM-eGFP) is a suitable model to study the fate of retina-resident PCs. MATERIAL AND METHODS: Vascular development-dependent reporter induction in retinal PCs was evaluated at different time points [(a) > P21, (b) < P21, and (c) P1 to > P21)] and additionally four different modes of application were tested. Reporter expression was evaluated by enhanced green fluorescent protein (eGFP) immunofluorescence by confocal microscopy and induction efficiency was calculated by analyzing NG2-expressing PCs in comparison to eGFP-labeled PCs in the three capillary layers. RESULTS: eGFP-positive PCs were detected in the three retinal capillary layers at all time points and administration routes tested. Multiple tamoxifen (TAM) applications in adult (> P21) NG2CreERTM-eGFP mice resulted in 3.59% eGFP-positive PCs. 2.37% eGFP-labeled PCs were detected after single intraperitoneal TAM injections at early postnatal days (P2/P5); however, just 1.61% PCs revealed reporter expression upon activation via the lactating mother (P4-P7). The highest number of eGFP-labeled PCs (7.09%) was detected following triple TAM administrations (P10-P12). The number of reporter-positive PCs doubled using homozygous animals. CONCLUSION: Despite low recombination efficiency in the used PC-specific fate mapping mouse model, changes in NG2 promoter activity of PCs during vascular development are indicated by single and multiple TAM inductions at different developmental time points. Nevertheless, these findings need further confirmation in up-coming studies by using homozygous NG2CreERTM-eGFP mice and additionally by mating the NG2CreERTM with a different reporter mouse to increase the low recombination efficiency.

Lack of Galanin Receptor 3 Alleviates Psoriasis by Altering Vascularization, Immune Cell Infiltration, and Cytokine Expression.

The neuropeptide galanin is distributed in the central and peripheral nervous systems and in non-neuronal peripheral organs, including the skin. Galanin acts via three G protein-coupled receptors which, except galanin receptor 1, are expressed in various skin structures. The galanin system has been associated with inflammatory processes of the skin and of several other organs. Psoriasis is an inflammatory skin disease with increased neovascularization, keratinocyte hyperproliferation, a proinflammatory cytokine milieu, and immune cell infiltration. In this study, we showed that galanin receptor 3 is present in endothelial cells in human and murine dermal vessels and is co-expressed with nestin in neo-vessels of psoriatic patients. Moreover, in a murine psoriasis model, we showed that C57/BL6 mice lacking galanin receptor 3 display a milder course of psoriasis upon imiquimod treatment, leading to decreased disease severity, delayed neo-vascularization, reduced infiltration of neutrophils, and significantly lower levels of proinflammatory cytokines compared with wild-type mice. In contrast, galanin receptor 2-knockout animals did not differ significantly from wild type mice at both the macroscopic and molecular levels in their inflammatory response to imiquimod treatment. Our data indicate that galanin receptor 3, but not galanin receptor 2, plays an important role in psoriasis-like skin inflammation.

Intraocular Pressure Course During the Femtosecond Laser-Assisted Cataract Surgery in Porcine Cadaver Eyes.

Purpose: Femtosecond laser-assisted cataract surgery (FLACS) is an increasingly common procedure. Most laser systems require corneal applanation and thereby increase intraocular pressure (IOP). The purpose of the present study was to evaluate the IOP changes that occur during the FLACS procedure performed using the Catalys femtosecond laser system. Methods: IOP was measured by direct cannulation of the vitreous body of porcine cadaver eyes (N = 20). By inserting a second cannula connected to a water column, all the eyes were set to a baseline IOP of 20 mm Hg. The eyes were lifted by custom-made stands to achieve the appropriate height and position under the Catalys system. The standard FLACS procedure was performed using varying fragmentation times to assess the influence of tissue fragmentation times on IOP peaks. Results: We identified significant IOP elevations from baseline IOP levels during all steps of the FLACS procedure (baseline: 20.28 ± 1.32 mm Hg; vacuum: 34.48 ± 4.21 mm Hg; capture: 47.90 ± 13.02 mm Hg; lock: 48.41 ± 9.04 mm Hg; analysis: 47.15 ± 5.97 mm Hg; capsulotomy: 45.74 ± 6.52 mm Hg; fragmentation: 48.41 ± 6.80 mm Hg; end: 17.81 ± 1.61 mm Hg; all P < 0.001). Furthermore, the tissue fragmentation time had a significant effect on the peak IOP values detected (R = 0.62, P = 0.04, n = 9). Conclusions: The present study reveals significant IOP increases during FLACS procedures carried out using the Catalys system.

[Mid- and Longterm Experiences with the Boston-Keratoprosthesis. The Cologne and Salzburg Perspective]. / Mittel- und langfristige Erfahrungen mit der Boston-Keratoprothese. Die Kölner und Salzburger Perspektive.

Background Eyes with severe corneal opacifications and insufficient prognosis for high-risk corneal transplantation can be considered for the implantation of a Boston-keratoprosthesis. Since 2013, this technique of "artificial" corneal replacement is provided to high-risk eyes at the Department of Ophthalmology, University of Cologne and for 9 years at the University of Salzburg. In the meantime, a type I Boston keratoprosthesis (BI-KPro) has been implanted in 24 eyes in Cologne and in 28 eyes in Salzburg. Methods In this article, results and complications according to BI-KPro are discussed, both from the literature in PubMed, as well as from our own experiences. Results Twenty-four eyes of 22 patients had been provided with a BI-KPro since September 2013, of which only one keratoprosthesis could not be obtained thus far, and an increase in visual acuity could be achieved in 23 eyes (96%). On average, 1.5 revisions per eye were required during the postoperative course. Since 2007, a BI-KPro has been implanted in 28 eyes in Salzburg. In 62% (16 of 26 eyes), visual acuity increased postoperatively, with a complication rate of 81% in a longer follow-up period. In both cohorts, the spectrum of complications ranged from retroprosthetic membrane formation, to secondary glaucoma, to infectious keratitis with or without graft melting, to vitritis, to endophthalmitis. Conclusion The range of possible complications according to BI-KPro is broad, but the BI-KPro represents currently the most widely used form of artificial corneal replacement in high-risk eyes and leads to visual improvement in most patients.