Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

Pattern electroretinogram, blue-yellow visual evoked potentials and the risk of developing visual field defects in glaucoma suspects: a longitudinal "survival" analysis with a very long follow-up.

PURPOSE: Estimating glaucoma suspects' risk for visual field defects helps to avoid under- and over-treatment. In this retrospective, longitudinal cohort study with a very long follow-up, we studied whether pattern electroretinograms (PERG) amplitudes and blue-on-yellow visual evoked potential (BY-VEP) latencies can predict visual field defects. METHODS: Participants of the Erlangen Glaucoma Study were examined with PERG and BY-VEP between 9/1991 and 8/2001. Stimuli were created using an optical bench with Maxwellian view and consisted of vertical gratings (0,88 cpd) in a 32° field for both PERG and BY-VEP. Patients were treated according to clinical standards and performed standard automated perimetry (SAP) annually. Retrospectively, patients with normal SAP at baseline were selected. Primary endpoint was conversion to perimetric glaucoma. Predictive value was modeled using Kaplan-Meier analyses and a multivariate cox proportional hazards model with the continuous variables PERG amplitude, BY-VEP peak time and SAP square-root of loss variance (sLV) after stratification for Jonas classification of the optic discs. RESULTS: Of 412 patients (288: Jonas 0, 103: I, and 21: II; baseline age: 20-60 years), 65 converted to perimetric glaucoma during follow-up (0.5-23.3 years; median 5.5 years). Optic disc classification was a strong risk factor for conversion (log rank p < 0.0001), and patients with more advanced changes progressed earlier. In the multivariate analysis (log rank p = 0.005), only PERG amplitude remained an independent risk factor after stratification for optic disc morphology (p = 0.021), with a ~ 30% higher risk per µV amplitude decrease. CONCLUSIONS: PERG helps to estimate glaucoma suspects' risk for visual field defects.

Improving Glaucoma Patients' Quality of Life and Adherence With a Digital Health Application: [RETRACTED].

PRCIES: Empowering glaucoma patients to access their individual glaucoma related health data by using a digital health application leads to a significant improvement in quality of life and adherence. PURPOSE: Evaluate the effectiveness of improvement of glaucoma associated quality of life and adherence in patients using a digital health application. PATIENTS AND METHODS: A prospective randomized monocentric controlled study of 77 patients with primary open angle glaucoma. Patients were recruited at the University Hospital Erlangen. Patients in the intervention group tracked their intraocular pressure, symptoms and therapy using a digital application. Based on the collected data the SmartTonoTracker® gave patients simple statistics and basic recommendations for further treatment. An increasing score on the GlauQol-36 item questionnaire and the MMAS-8 score, conducted at baseline and follow-up by the intervention group, was considered successful. Statistical analysis was conducted using the unpaired t-test, paired t-test, Man-Whitney-U test, frequency analysis, frequency distribution and Pearson-correlation. RESULTS: Significant difference in the patients´ glaucoma-associated quality of life between the intervention group (rate of improvement: 7.6%, P =0.047), and the control group (rate of improvement: 0.17%, P =0.047) was shown. Also, a significant difference in adherence between the intervention group, showing a 9.8% rate of improvement ( P =0.002), and the control group, showing a 3.8% rate of improvement ( P =0.002), was shown. CONCLUSION: Enabling patients to access individual health related glaucoma data by using a digital health application and supporting them with information on their disease led to an improvement in glaucoma-associated quality of life and adherence.

The influence of trace elements on the therapeutic success of suprachoroidal draining devices.

PURPOSE: The therapeutic success of minimal invasive glaucoma surgery (MIGS) is challenging due to many factors including fibrotic or occlusive events. Recent clinical data show sudden peaks of intraocular pressure (IOP) in the postoperative care of glaucoma patients after suprachoroidal draining stents. Yet, the reasons for the IOP peaks are speculative. As a link between trace elements and fibrosis had been previously observed in systemic disorders, the present study aimed to investigate the impact of trace elements on the therapeutic success of the suprachoroidal draining stents in patients with open-angle glaucoma (OAG). MATERIAL AND METHODS: An analysis of a prospective single-center study was done: fifty-five eyes of patients with OAG (29 female, 26 male) underwent Cypass Micro-Stent implantation either as a stand-alone procedure or combined with cataract surgery. All patients underwent pre-operatively an ophthalmological examination which included slit lamp biomicroscopy and fundoscopy. IOP was measured by Goldmann applanation tonometry. Functional and morphometric data were assessed by Octopus G1-perimetry, which included measurement of retinal nerve fiber layer thickness (Spectralis OCT). Data of the patients' follow-ups were recorded during 18 months post-operatively. The therapeutic success of CyPass Micro-Stent was classified as 'success' (IOP reduction ≥20% compared to a pre-operative baseline without any medication), 'qualified success' (IOP reduction ≥20 % with same or lower additional eye medication), and 'failure' (IOP reduction ≤20 % or additional surgical treatment necessary). Aqueous humour was extracted once during surgery for analysis of the level of 14 trace elements: Copper (Cu), Cadmium (Cd), Cobalt (Co), Chromium (Cr), Iron (Fe), Lithium (Li), Magnesium (Mg), Manganese (Mn), Phosphorus (P), Lead (Pb), Titanium (Ti), Uranium (U), Vanadium (V), and Zinc (Zn). Analysis of the trace elements was done using an ELEMENT 2, ICP-sf-MS instrument (Thermo-Fisher Scientific, Bremen, Germany). Analysis of levels of trace elements was done across the patients' groups of the three subclasses of therapeutic success. Statistical investigations for substantial differences were conducted using the method of least squares to fit general linear models and mixed models. The last one for the repeated measurements of IOP. RESULTS: Levels of Mg were significantly lower one month postoperatively in the success group (LS-Mean 1.30 mg/L) compared to the qualified success group (LS-Mean 1.22 mg/L; p-value = 0.04). Fe was significantly increased in the failure group (LS-Mean 2.07 µg/L) compared to the qualified success group (LS-Mean 1.64 µg/L; p-value = 0.019) after 3 months of follow-up. Additionally, Fe levels were significantly lower in the success group (LS-Mean 1.47 µg/L) compared to the failure cohort (LS-Mean 2.07 µg/L; p-value = 0.009). After a period of 18 months, significantly higher levels of Mn were observed in the success group (LS-Mean 1.24 µg/L) than in the failure group (LS Mean 0.30 µg/L, p-value = 0.019). CONCLUSION: The present data might suggest that trace elements can influence therapeutic success of suprachoroidal draining devices postoperatively and thus offer first hints for potential novel therapeutic options.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: −4.5; −0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Glaucoma and Alzheimer: Neurodegenerative disorders show an adrenergic dysbalance.

Glaucoma disease is characterized by an increased intraocular pressure (IOP), glaucomatous alterations of the optic disc and corresponding visual field defects. Even lowering the main risk factor IOP until an individual target level does not prevent this neurodegenerative disorder from proceeding. Several autoimmune mechanisms were discovered, partly showing a functionality. One of these autoimmune phenomena targets the ß2-adrenergic receptor (ß2-AR; i.e. agonistic autoantibodies; ß2-agAAb) and is linked to an elevated IOP and an impaired retinal microcirculation. As neurodegenerative disorder, Alzheimer's Disease (AD) is postulated to share a common molecular mechanism with glaucoma. In the present study we investigated autoimmune phenomena targeting the ß2-AR in patients with AD. Sera of the patients were analyzed in a rat cardiomyocyte bioassay for the presence of functional autoantibodies against ß2-AR. In addition, different species of amyloid beta (Aß) monomers were tested (Aß1-14, Aß10-25, Aß10-37 Aß1-40, Aß1-42, Aß28-40, and Aß-[Pyr]3-43). Our results demonstrate that none of the short-chain Aß (Aß1-14, Aß10-25, or Aß28-40) showed any agonistic or inhibitory effect on ß2-AR. Contrary, long-chain Aß-[Pyr]3-43, representing a major neurogenic plaque component, exerted an activation that after blocking by the ß2-AR antagonist ICI118.551, could be identified as that the effect was realized via the ß2-AR. Moreover, the long chain Aß1-40, Aß1-42, and Aß10-37, yet not the short-chain Aß peptides prevented the clenbuterol induced desensitization of the ß2-AR. In addition, we identified functional autoantibodies in the sera of AD patients, activating the ß2-AR, like the ß2-agAAb found in patients with glaucoma. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma and Alzheimer's Disease, we postulate that overstimulation of the ß2-AR pathway can induce an adrenergic overdrive, that may play an important role in the multifactorial interplay of neurodegenerative disorders.

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation.

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT-angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic ß2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.

Blue-Yellow VEP with Projector-Stimulation in Glaucoma.

BACKGROUND AND AIM: In the past, increased latencies of the blue-on-yellow pattern visually evoked potentials (BY-VEP), which predominantly originate in the koniocellular pathway, have proven to be a sensitive biomarker for early glaucoma. However, a complex experimental setup based on an optical bench was necessary to obtain these measurements because computer screens lack sufficient temporal, spatial, spectral, and luminance resolution. Here, we evaluated the diagnostic value of a novel setup based on a commercially available video projector. METHODS: BY-VEPs were recorded in 126 participants (42 healthy control participants, 12 patients with ocular hypertension, 17 with "preperimetric" glaucoma, and 55 with perimetric glaucoma). Stimuli were created with a video projector (DLP technology) by rear projection of a blue checkerboard pattern (460 nm) for 200 ms (onset) superimposed on a bright yellow background (574 nm), followed by an offset interval where only the background was active. Thus, predominantly S-cones were stimulated while L- and M-cone responses were suppressed by light adaptation. Times of stimulus onset to VEP onset-trough (N-peak time) and offset-peak (P-peak time) were analyzed after age-correction based on linear regression in the normal participants. RESULTS: The resulting BY-VEPs were quite similar to those obtained in the past with the optical bench: pattern-onset generated a negative deflection of the VEP, whereas the offset-response was dominated by a positive component. N-peak times were significantly increased in glaucoma patients (preperimetric 136.1 ± 10 ms, p < 0.05; perimetric 153.1 ± 17.8 ms, p < 0.001) compared with normal participants (123.6 ± 7.7 ms). Furthermore, they were significantly correlated with disease severity as determined by visual field losses retinal nerve fiber thinning (Spearman R = -0.7, p < 0.001). CONCLUSIONS: Video projectors can be used to create optical stimuli with high temporal and spatial resolution, thus potentially enabling sophisticated electrophysiological measurements in clinical practice. BY-VEPs based on such a projector had a high diagnostic value for detection of early glaucoma. Registration of study Registration site: www. CLINICALTRIALS: gov Trial registration number: NCT00494923.

Case Report: Neutralization of Autoantibodies Targeting G-Protein-Coupled Receptors Improves Capillary Impairment and Fatigue Symptoms After COVID-19 Infection.

Clinical features of Coronavirus disease 2019 (COVID-19) are caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Acute infection management is a substantial healthcare issue, and the development of long-Covid syndrome (LCS) is extremely challenging for patients and physicians. It is associated with a variety of characteristics as impaired capillary microcirculation, chronic fatigue syndrome (CFS), proinflammatory cytokines, and functional autoantibodies targeting G-protein-coupled receptors (GPCR-AAbs). Here, we present a case report of successful healing of LCS with BC 007 (Berlin Cures, Berlin, Germany), a DNA aptamer drug with a high affinity to GPCR-AAbs that neutralizes these AAbs. A patient with a documented history of glaucoma, recovered from mild COVID-19, but still suffered from CFS, loss of taste, and impaired capillary microcirculation in the macula and peripapillary region. He was positively tested for various targeting GPCR-AAbs. Within 48 h after a single BC 007 treatment, GPCR-AAbs were functionally inactivated and remained inactive during the observation period of 4 weeks. This observation was accompanied by constant improvement of the fatigue symptoms of the patient, taste, and retinal capillary microcirculation. Therefore, the removal of GPCR-AAb might ameliorate the characteristics of the LCD, such as capillary impairment, loss of taste, and CFS.

Inhibitory and Agonistic Autoantibodies Directed Against the ß2-Adrenergic Receptor in Pseudoexfoliation Syndrome and Glaucoma.

Pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG) are assumed to be caused by a generalized elastosis leading to the accumulation of PEX material in ocular as well as in extraocular tissues. The exact pathophysiology of PEXS is still elusive. PEXG, the most common type of secondary open-angle glaucoma (OAG), is characterized by large peaks of intraocular pressure (IOP) with a progressive loss of the visual field. Agonistic autoantibodies (agAAbs) against the ß2-adrenergic receptor (AR) have been shown to be present in sera of patients with primary and secondary OAG and ocular hypertension and are seemingly linked to IOP. In the present study, we investigated the autoantibodies directed against the ß2-AR in sera of patients with PEXS and PEXG. We recruited 15, 10, and 15 patients with PEXG, PEXS, and primary OAG, respectively. Ten healthy individuals served as controls. All patients underwent standard ophthalmological examination with Octopus G1 perimetry. agAAbs prepared from serum samples were analyzed in a rat cardiomyocyte-based bioassay for the presence of agAAbs. We identified the interacting loop of the ß2-AR and the immunoglobulin G (IgG) subclasses using synthetic peptides corresponding to the extracellular loops of the receptors and enzyme-linked immunosorbent assay, respectively. None of the controls were ß2-agAAb-positive (0.2 ± 0.5 U). No ß2-agAAbs (0.2 ± 0.4 U), but inhibitory ß2-AAbs were observed in 80% of the patients that partially blocked the drug-induced ß2-adrenergic stimulation; 5.8 ± 1.7 U vs. 11.1 ± 0.9 U for clenbuterol in the absence and the presence of sera from patients with PEXS, respectively. Epitope analyses identified the third extracellular loop of the ß2-AR as the target of the inhibitory ß2-AAbs, being of IgG3 subtype in PEXS patients. In contrast, patients with PEXG showed ß2-agAAbs (5.6 ± 0.9 U), but no inhibitory ones. The ß2-agAAbs levels of patients with PEXG and primary OAG patients (3.9 ± 2.8 U; p > 0.05) were at a similar level. In two cases of PEXG, the ß2-agAAbs exert synergistic effects with clenbuterol. The activity increased from 11.5 ± 0.3 (clenbuterol only) to 16.3 ± 0.9 U. As autoimmune mechanisms were reportedly involved in the pathogenesis of glaucoma, agonistic and inhibitory ß2-AAbs seem to be a part of this multifactorial interplay.

Responses of Postreceptoral Pathways Elicited by L- and M-Cone Isolating ON- and OFF-Electroretinograms in Glaucoma Patients.

Purpose: To compare the electroretinographical (ERG) responses elicited by L- and M-cone isolating ON- and OFF-sawtooth stimuli in normal subjects and glaucoma patients. Methods: Twenty-one normal subjects and 44 primary open-angle glaucoma patients participated in the study. L- and M-cone isolating (18% cone contrast; 284 cd/m2) rapid ON- and rapid OFF-sawtooth (4 Hz) stimuli with two stimulus sizes (full-field (FF) and central 70° diameter) were generated using the triple silent substitution technique. ON- and OFF-response asymmetries were studied by adding the two (to obtain L-add and M-add responses). The initial positive (P) and subsequent late negative (LN) components of the L-add and M-add ERGs were compared between the subject groups and correlated with retinal nerve fiber layer thickness (RNFLT) and pattern ERG responses. Results: The responses to L-ON and to M-OFF stimuli and vice versa resembled each other particularly with 70° stimuli. The PL-add amplitudes were not significantly different between the normal subjects and glaucoma patients, whereas the LNL-add amplitude was significantly (P < 0.01) smaller in the glaucoma patients. Both PM-add and LNM-add were not significantly different between the subject groups. The PERG amplitude with 0.8° check sizes and the 0.8°/16° amplitude ratio (PERG ratio) were significantly (P < 0.05) different between the subject groups. The 70° LNL-add amplitude and the 0.8° PERG amplitude were significantly correlated with RNFLT. Conclusions: The ERGs to 70° cone isolating sawtooth stimuli reflect cone opponency. The cone opponent ERG responses were not significantly different between glaucoma patients and normal subjects. Luminance driven L-add responses were significantly different, indicating that central luminance signals are mainly affected in glaucoma.

Erlanger Glaucoma Registry: Effect of a Long-Term Therapy with Statins and Acetyl Salicylic Acid on Glaucoma Conversion and Progression.

Purpose: Drugs with cardiovascular protective properties (statins, acetylsalicylic acid (ASS)) were assumed to have positive effects on patients suffering from glaucoma disease. The present retrospective study aimed to investigate the influence of statins, ASS or a combination of both on the glaucoma conversion and progression rate in glaucoma suspects and glaucoma patients with a 20-year follow-up period. Methods: A retrospective analysis of 199 eyes of 120 patients (63 male, 57 female) of the Erlanger Glaucoma Registry (EGR; ClinicalTrials.gov Identifier: NCT00494923; ISSN 2191-5008, CS-2011) was performed considering systemic therapy with statins, ASS or a combination of both: 107 eyes with ocular hypertension (OHT) and 92 eyes with pre-perimetric primary open-angle glaucoma (pre-POAG). All patients received an ophthalmological examination including morphometric and functional glaucoma diagnostics. Glaucoma conversion was defined as the conversion of OHT to pre-POAG. Glaucoma progression was defined as confirmed visual field loss. Data were shown as percentages. Statistical analysis was performed by Chi-Quadrat tests. Results: 1. Glaucoma conversion/progression was observed in 46.7% of the subjects, additionally in combination with hypercholesterinemia in 76.8%. 2. Statins: 27.3% of eyes under systemic statin therapy showed a conversion/progression. Patients taking statins ≥ 10 years yielded a reduced conversion/progression rate (p = 0.028, non-significant after Bonferroni-Holm). 3. ASS: 34.7% of eyes under systemic ASS therapy showed a conversion/progression. A significantly lower conversion/progression rate was observed after ASS therapy ≥ 12 years (p = 0.017, significant after Bonferroni-Holm). 4. ASS and statins: 25.0% of eyes under combined therapy showed a conversion/progression. A significantly reduced conversion/progression rate was reached after 8 years of combined therapy (p = 0.049, non-significant after Bonferroni-Holm). Conclusions: Patients with ocular hypertension and early glaucoma seem to benefit from adjuvant cardiovascular protective therapy. However, the benefits and disadvantages of treatment with statins and/or ASS should be kept in mind. Thus, a thorough risk-benefit evaluation has to be performed for each patient individually to avoid unwanted side effects.

Extended Ganglion Cell Layer Thickness Deviation Maps With OCT in Glaucoma Diagnosis.

Purpose: The aim of the present study was to investigate the diagnostic power of RGCL in the macula quantitatively and qualitatively by using a conventional and extended elliptic grid with deviation maps. Subjects and Methods: Thickness of RGCL was measured using SPECTRALIS® OCT (Heidelberg Engineering, Heidelberg, Germany) in 150 eyes of 150 subjects of the Erlangen Glaucoma Registry (EGR; NTC00494923): 26 ocular hypertension (OHT), 39 pre-perimetric open-angle glaucoma (pre-OAG), 19 normal tension glaucoma (NTG), 34 primary open-angle glaucoma (POAG), 16 secondary open-angle glaucoma (SOAG), and 16 controls. Analysis of RGCL was done quantitatively (global value, GV) and qualitatively (qualitative total value, QTV) by using a color-coded point score for data of the common elliptic macular grid of deviation maps. Furthermore, qualitative analysis of RGCL was done for an extended elliptic macula grid (extended qualitative total value, eQTV). Receiver operating characteristic (ROC) curves were calculated for the conventional and the enlarged macular grid for all subjects' groups. Results: GV of RGCL thickness differed significantly between pre-OAG (p < 0.05), NTG (p < 0.001), POAG (p < 0.001), SOAG (p < 0.001), yet not OHT (p > 0.05) and controls, respectively. Quantitative ROC analysis of GV showed AUC of 0.965 (SOAG), 0.942 (POAG), 0.916 (NTG), 0.772 (pre-OAG), and 0.526 (OHT). QTV differed significantly between pre-POAG (p < 0.05), NTG (p < 0.001), POAG (p < 0.001), SOAG (p < 0.001), yet not OHT (p > 0.05) and controls, respectively. Qualitative ROC analysis of QTV showed AUCs of 0.908 (NTG) 0.914 (POAG), 0.930 (SOAG), 0.734 (pre-POAG), and 0.519 (OHT). Implementation of eQTV yielded even higher AUCs for NTG (0.919), POAG (0.969), and SOAG (0.973) compared to GV. Similar AUCs of eQTV and GV were observed for OHT (0.514) and pre-OAG (0.770). Conclusion: The results of the present study showed that quantitative and qualitative analysis of RGCL thickness yielded similar diagnostic impacts compared to RNFL. Qualitative analysis might be a quick and easy useable tool for clinical all-day life. The present data suggest that analysis of an extended macula region might improve its diagnostic impact.

Influence of Mitomycin C on the Therapeutic Success of Stand-Alone Xen45 Gel Stents and Its Combination with Cataract Surgery in Open-Angle Glaucoma Patients.

PURPOSE: Minimally invasive glaucoma surgery (MIGS), like Xen45 gel stents, is known as effective therapy in lowering intraocular pressure (IOP); however, fibrotic reactions are a common problem in postoperative management. It was the aim of this study to investigate the therapeutic success of Xen45 gel stents as a stand-alone technique (Xen) and combined with cataract surgery (XenPhaco), and with antimetabolites (mitomycin C, MMC) in open-angle glaucoma patients. METHODS: Retrospective analysis was performed of 199 eyes of 177 glaucoma patients of the Department of Ophthalmology, University of Erlangen Nürnberg, and from the Erlangen Glaucoma Registry (NCT00494923; ISSN 2191-5008, CS-2011) who underwent implantation of a Xen45 gel stent. Therapeutic success was defined as IOP reduction of ≥ 20% on the same or less anti-glaucomatous medication after 12 months compared to preoperative and without any additional glaucoma-related surgery (except bleb needling). IOP reduction, reduction in local anti-glaucomatous eye drops, and intra- and postoperative complications were monitored. RESULTS: Stand-alone Xen45 gel stent: therapeutic success was reached in 39% (-MMC) and 55% (+MMC). Failure rate was 61% (-MMC) and 45% (+MMC). XenPhaco: therapeutic success was achieved in 57% (-MMC) and 46% (+MMC). Failure rate was 43% (-MMC) and 54% (+MMC). Data were not different for group and subgroup analyses (p > 0.05). CONCLUSIONS: The use of MMC seemed to increase the therapeutic success rate after stand-alone Xen45 gel stent implantation and combined with cataract surgery, yet statistical significant was not reached.

Agonistic ß2-Adrenergic Receptor Autoantibodies Characterize the Aqueous Humor of Patients With Primary and Secondary Open-Angle Glaucoma.

Purpose: Agonistic ß2-adrenergic receptor autoantibodies (ß2-agAAbs) were recently observed in sera of patients with ocular hypertension (OHT), primary (POAG), and secondary open-angle glaucoma (SOAG), yet not in healthy controls (HCs). It was the aim of the present study to investigate the presence of ß2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding ß2-agAAb serum data. Material and Methods: Thirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for ß2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U). Results: Thirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a ß2-agAAb in their sera and AH samples, respectively. All ß2-agAAb AH-positive OAG patients were also seropositive. We also observed a ß2-agAAb seropositivity in 95 and 89% of patients with POAG and SOAG, respectively. Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of AH samples. The ß2-agAAb adrenergic activity was increased in the AH of patients with POAG (6.5 ± 1.5 U) when compared with those with SOAG (4.1 ± 1.1 U; p = 0.004). Serum ß2-agAAb adrenergic activity did not differ between the cohorts [POAG (4.5 ± 1.5 U); SOAG (4.6 ± 2.1 U; p=0.458)]. No correlation of the beating rates were observed between serum and AH samples for group and subgroup analyses. Conclusion: The detection of ß2-agAAb in systemic and local circulations supports the hypothesis of a direct functional impact of these agAAbs on ocular G-protein coupled receptors. The high prevalence of ß2-agAAb in serum and AH samples of patients with POAG or SOAG suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype.

Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients.

PURPOSE: Agonistic ß2-adrenergic receptor autoantibodies (ß2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the ß2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to ß2-agAAb status in patients with OAG. MATERIAL AND METHODS: Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of ß2-agAAb. RESULTS: (I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the ß2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028). CONCLUSION: FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of ß2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that ß2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.

Summation of Temporal L-Cone- and M-Cone-Contrast in the Magno- and Parvocellular Retino-Geniculate Systems in Glaucoma.

Purpose: The purpose of this study was to characterize summation of temporal L- and M-cone contrasts in the parvo- (P-) and magnocellular (M-) pathways in glaucoma and the relationship between the respective temporal contrast sensitivities (tCS) and clinical parameters. Methods: Perifoveal tCS to isolated or combined L- and M-cone contrasts (with different contrast ratios, and therefore different luminance and chromatic components) were measured at different temporal frequencies (at 1 or 2 Hz and at 20 Hz) using triple silent substitution in 73 subjects (13 healthy, 25 with glaucoma, and 35 with perimetric glaucoma). A vector summation model was used to analyze whether perception was driven by the P-pathway, the M-pathway, or both. Using this model, L- and M-cone input strengths (AL, AM) and phase differences between L- and M-cone inputs were estimated. Results: Perception was always mediated by the P-pathway at low frequencies, as indicated by a median phase angle of 179.84 degrees (cone opponency) and a median AL/AM ratio of 1.04 (balanced L- and M-cone input strengths). In contrast, perception was exclusively mediated by the M-pathway at higher frequencies (input strength not balanced: AL/AM = 2.94, median phase angles = 130.17 degrees). Differences in phase were not significant between diagnosis groups (Kruskal-Wallis = 0.092 for P- and 0.35 for M-pathway). We found differences between groups only for the M-pathway (L-cone tCS deviations at 20 Hz were significantly lower in the patients with glaucoma P = 0.014, with a strong tendency in M-cones P = 0.049). L-cone driven tCS deviations at 20 Hz were linearly correlated with perimetric mean defect (MD) and quadratically correlated with retinal nerve fiber layer (RNFL) thickness. Conclusions: Unaltered phase angles between L- and M-cone inputs in glaucoma indicated intact temporal processing. Only in the M-pathway, contrast sensitivity deviations were closely related to diagnosis group, MD, and RNFL thickness, indicating M-pathway involvement.

Glaucoma classification in 3 x 3 mm en face macular scans using deep learning in a different plexus.

Glaucoma is among the leading causes of irreversible blindness worldwide. If diagnosed and treated early enough, the disease progression can be stopped or slowed down. Therefore, it would be very valuable to detect early stages of glaucoma, which are mostly asymptomatic, by broad screening. This study examines different computational features that can be automatically deduced from images and their performance on the classification task of differentiating glaucoma patients and healthy controls. Data used for this study are 3 x 3 mm en face optical coherence tomography angiography (OCTA) images of different retinal projections (of the whole retina, the superficial vascular plexus (SVP), the intermediate capillary plexus (ICP) and the deep capillary plexus (DCP)) centered around the fovea. Our results show quantitatively that the automatically extracted features from convolutional neural networks (CNNs) perform similarly well or better than handcrafted ones when used to distinguish glaucoma patients from healthy controls. On the whole retina projection and the SVP projection, CNNs outperform the handcrafted features presented in the literature. Area under receiver operating characteristics (AUROC) on the SVP projection is 0.967, which is comparable to the best reported values in the literature. This is achieved despite using the small 3 × 3 mm field of view, which has been reported as disadvantageous for handcrafted vessel density features in previous works. A detailed analysis of our CNN method, using attention maps, suggests that this performance increase can be partially explained by the CNN automatically relying more on areas of higher relevance for feature extraction.

[MIGS-off-label option for treatment-refractory steroid-induced ocular hypertension]. / MIGS ­ eine Off-label-Option für eine therapierefraktäre, steroidinduzierte okuläre Hypertension.

Steroid-induced ocular hypertension (SIOH), which cannot be regulated by topical antiglaucoma agents, is a rare complication after intravitreal implantation of diverse cortisone derivatives. This case report presents a therapeutic approach for treatment-refractory SIOH after intravitreal implantation of fluocinolone acetonide using various minimally invasive glaucoma surgery (MIGS) techniques.