Milena Pahlitzsch

Introduction To evaluate the long-term effect on intraocular pressure (IOP) and glaucoma medication of selective laser trabeculoplasty (SLT) compared to minimally invasive glaucoma surgery (MIGS) in primary open-angle glaucoma (POAG) and its potential in clinical practice. Methods A total of 342 consecutive patients (stand-alone procedures) were included. One hundred and five patients underwent SLT treatment (360° SLT, 95–105 spots, Trabeculas SLT ARCLaser, Nürnberg, DE), 107 patients had an ab interno-derived trabeculotomy (Trabectome^®, NeoMedix, Tustin, USA), and 130 patients received iStent inject^® implantation (2 implants-Glaukos, CA, USA). IOP and glaucoma therapy were evaluated preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1, 2, and 3 years postoperatively. Statistical analysis was performed using a regression model and propensity matching score (reduced cohort number) using SPSS v20.0. Kaplan–Meier analysis was included using the following six criteria: criterion A (IOP ≤ 21 mmHg with or without medication, qualified success), criterion B (IOP ≤ 18 mmHg with or without medication, qualified success), criterion C (IOP ≤ 21 mmHg without medication, complete success), criterion D (IOP ≤ 18 mmHg without medication, complete success), criterion E (IOP ≤ 21 mmHg and IOP reduction > 20% after therapy), and criterion F (IOP ≤ 18 mmHg and IOP reduction > 20% after therapy). Results In the matched cohort, the SLT cohort showed an IOP reduction of 31.2% from 19.9 ± 2.3 to 13.7 ± 2.7 mmHg (p < 0.001) 3 years postoperatively; in Trabectome^® IOP decreased by 31.4% from 20.5 ± 1.3 to 13.8 ± 2.0 mmHg (p < 0.001) and in iStent inject^® by 29.9% from 19.5 ± 2.0 to 13.8 ± 2.7 mmHg (p < 0.001). Trabectome^® and iStent inject^® could not demonstrate a significant reduction in glaucoma therapy (Trabectome^® p = 0.138, iStent inject^® p = 0.612); a significant drop was noted in SLT (2.2 ± 1.2 to 1.7 ± 1.2, p = 0.046). SLT and MIGS achieved good to moderate survival rates using criterion A (93.3% SLT, 79.7% Trabectome^®, 77.6% iStent inject^®) and criterion B (74.5% SLT, 48.0% Trabectome^®, 56.2% iStent inject^®). As expected, low survival rates were obtained with non-filtering procedures: criterion C 11.1% in SLT, 6.5% in Trabectome^®, 7.0% in iStent inject^® and criterion D 3.0% in SLT, 4.3% in Trabectome^®, 3.7% in iStent inject^® in 3-year follow-up. Conclusion The SLT is a low-complication and effective method for reducing pressure in mild to moderate POAG. SLT is suitable as an initial procedure when setting up a step scheme; MIGS is the treatment of choice as a follow-up for mild to moderate forms of glaucoma and accepted topical therapy. Ethic approval had been given by the Ethikkommission Charité – Universitätsmedizin Berlin, EA4/047/20—retrospectively registered.

Purpose: Nesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development. Methods: In this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9 +/- 3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3 +/- 2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors. Results: Sex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-gamma, Interleukin-1 beta, IL-2, 4, 5, 6, 7, 10, 12 and TNF-alpha) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05). Conclusion: As a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.

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.

Zusammenfassung: Die Möglichkeit, primäre neuroprotektive Wirkstoffe einsetzen und kontrolliert überwachen zu können, ist ein vielversprechender Ansatz für die künftige Therapiegestaltung in neurodegenerativen Erkrankungen, insbesondere im Glaukom. Bisherige medikamentöse und chirurgische Therapieansätze zielen auf die sekundäre Neuroprotektion durch Augeninnendrucksenkung ab. Bildgebende Verfahren bilden eine essenzielle Grundlage in der Diagnostik und Therapiekontrolle. Die potenzielle Bedeutung der DARC-Technologie (Detection of apoptosing retinal Cells: Visualisierung von retinalen Ganglienzellen durch fluoreszenzmarkiertes Annexin V = ANX776 mithilfe der cSLO-Technologie) im klinischen Alltag liegt in der leichten Umsetzbarkeit. Das notwendige HRT-Gerät steht in vielen großen Augenzentren zur Verfügung und die Untersuchung mit i. v. Gabe des fluoreszierenden Markers ähnelt dem Ablauf einer konventionellen Fluoreszenzangiografie. Eine Limitation stellt vor allem die individuell stark schwankende physiologische Apoptose der humanen retinalen Ganglienzellen dar, die es vor Einsatz im klinischen Alltag in einem Normkollektiv zu standardisieren gilt.

To assess the long-term outcome of Trabectome surgery in the treatment of primary open angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEX): 3-year results.

Importance: Different tip designs in modern cataract surgery have not been studied between the reported systems.Background: Aim of this study is to assess the efficacy of two tip designs, Intrepid® balanced tip (BT) and Kelman tapered tip (TT), in femtosecond laser assisted cataract surgery (FLACS) and the microcoaxial torsional phacoemulsification.Design: Prospective randomized unmasked cohort outcome study (hospital setting).Participants: Threehundert‐forty‐three eyes of 343 patientes underwent cataract surgery.Methods: Data of n = 196 FLACS and n = 147 manual phacoemulsification were analysed. Intrepid® balanced tip and Kelman tapered tip, Alcon, USA, were tested in FLACS (LenSx Alcon, USA) und manual phaco (Alcon Centurion System, USA). Four study cohorts were formed; FLACS BT (n = 90, 70.2 years), FLACS TT (n = 106, 68.1years), Manual BT (n = 70, 71.3 years), Manual TT (n = 77, 71.8 years). The nuclei were graded in Lens Opacities Classification System (LOCS) II,III and IV.Main Outcome Measures: Cumulative dissipated energy (CDE%s), balanced salt solution volume (BSSml), total longitudinal energy (%s) and torsional amplitude (%s).Results: Lower CDE values were seen in FLACS compared to manual phacoemulsification (CDE %s median FLACS BT 3.28, FLACS TT 4.07, Manual BT 5.57, Manual TT 6.27). There was a significant difference between CDE FLACS BT and FLACS TT (p = 0.038), and between FLACS BT and Manual TT (p = 0.001).Conclusions and Relevance: The right choice of tip designs in advanced phacoemulsification systems is a key factor in increasing efficacy in cataract surgery. The balanced tip showed a considerable energy‐saving advantage in FLACS and manual phacoemulsification compared to the tapered tip.

Purpose: To assess the correlation between the disc damage likelihood scale (DDLS) objectively measured by a nonmydriatic fundus camera, confocal laser scanning ophthalmoscopy (HRT3), and spectral-domain optical coherence tomography (SD-OCT) in uveitic glaucoma. Methods: A total of 59 patients with uveitic glaucoma (21 female, 38 male; mean age 56.8 ± 18.7 years) were included in this prospective cross-sectional study. All patients were measured by the Kowa Nonmyd WX 3D camera (2D/3D nonmydriatic retinal camera, Kowa Company), the HRT3 (Heidelberg Engineering), and SD-OCT (Carl Zeiss Meditec) by one examiner on the same day. All 3 devices graded the optic disc topography. Statistical data were calculated using SPSS (v 20.0, SPSS). Results: In patients showing borderline results in one of the modalities (n = 45), the DDLS showed a significant correlation with the retinal nerve fiber layer (p = 0.016), while Moorfields regression analysis (p = 0.550) and glaucoma probability score (p = 0.629) did not correlate significantly. The highest predictive power was demonstrated by the objectively measured DDLS (area under the receiver operating characteristic curve 0.445-0.588), compared to R. Burk (0.149-0.375) and F.S. Mikelberg (0.033-0.450) coefficients considering HRT and optical coherence tomography. Conclusions: In this study cohort, the objective DDLS showed the highest predictive power and thus is a reliable tool in diagnosing uveitic glaucoma. These 3 devices cannot be used interchangeably. As diagnosis and follow-ups are challenging in uveitis patients, the stereophotography is additionally a valuable tool.

To compare IOPen and ICare rebound tonometry to Goldmann applanation tonometry (GAT) according to International Standards Organization (ISO) 8612 criteria. Totally 191 eyes (n=107 individuals) were included. Criteria of ISO 8612 were fulfilled: 3 clusters of IOP, measured by GAT, were formed. The GAT results were given as mean±standard deviation. GAT (19.7±0.5 mm Hg) showed a significant correlation to ICare (19.8±0.5 mm Hg) (r=0.547, P<0.001) and IOPen (19.5±0.5 mm Hg) (r=0.526, P<0.001). According to ISO 8612 criteria in all 3 IOP groups the number of outliers (of the 95% limits of agreement) exceeded 5% for ICare and IOPen vs GAT: No.1 (n=68) 29.4% and 22.1%, No.2 (n=62) 35.5% and 37.1%, No.3 (n=61) 26.2% and 42.6%, respectively. The strict requirements of the ISO 8612 are not fulfilled in a glaucoma collective by ICare and IOPen at present. As long as the Goldmann tonometry is applicable it should be used first of all for reproducible IOP readings. ICare and IOPen tonometry should be considered as an alternative tool, if application of Goldmann tonometry is not possible.