The therapeutic management of central serous chorioretinopathy (CSC) remains challenging. Although CSC shows a high rate of self-resorption, frequent recurrences or chronification of the disease can result in irreversible loss of vision. Low-dose photodynamic therapy (half-dose or half-fluence PDT) represents the current standard of care for CSC, although regenerative laser procedures may also offer a safe and effective alternative for the treatment of CSC.

The occurrence of secondary choroidal neovascularization (CNV) is a complication in patients with chronic central serous chorioretinopathy. The diagnosis is made using multimodal imaging. The treatment usually includes intravitreal anti-vascular endothelial growth factor (VEGF) injections. A combination with photodynamic therapy can be useful; however, the response to anti-VEGF treatment is significantly reduced compared to other indications for CNV, so that an irreversible decrease of visual acuity often remains.

Zum gegenwärtigen Zeitpunkt steht für die Behandlung der Chorioretinopathia centralis serosa (CCS) keine zugelassene Therapie zur Verfügung. Obwohl die CCS eine hohe Selbstresorptionsrate aufweist, können häufige Rezidive oder eine Chronifizierung der Erkrankung einen permanenten Visusverlust zur Folge haben. Die derzeitige Therapie der ersten Wahl zur Behandlung der chronischen CCS ist die Half-dose- oder Half-fluence-photodynamische Therapie (PDT). Als weitere sichere und effektive Behandlungsverfahren können zudem noch 2 regenerative Laser- und Lichttherapien (RELITE) – die photothermische Therapie mit dem Mikrosekundenpulslaser (MPL) und die photomikrodisruptive Therapie mit der selektiven Retinatherapie (SRT) – diskutiert werden.

Das Auftreten einer sekundären chorioidalen Neovaskularisation ist eine Komplikation im Rahmen einer chronischen Chorioretinopathia centralis serosa. Die Diagnose wird mittels multimodaler Bildgebung gestellt. Die Therapie erfolgt in der Regel mit intravitrealer Anti-VEGF(„vascular endothelial growth factor“)-Injektion. Eine Kombination mit einer photodynamischen Therapie kann sinnvoll sein. Das Ansprechen auf die Anti-VEGF-Therapie ist jedoch im Vergleich zu anderen CNV-Indikationen deutlich reduziert, sodass häufig eine irreversible Visusreduktion bleibt.

Das durchgreifende Makulaforamen stellt eine seltene Erkrankung dar, bei der nicht alle Defekte mittels primärer chirurgischer Intervention verschlossen werden können. Charakterisierung eines umfangreichen Patientenkollektivs dieser seltenen Erkrankung und Detektion möglicher prädiktiver Faktoren für den anatomischen Behandlungserfolg. Retrospektive Analyse aller konsekutiven idiopathischen durchgreifenden Makulaforamina im Zeitraum März 2008 bis Juni 2019 an der Universitätsaugenklinik Köln. Untersucht wurden u. a. epidemiologische Daten, präoperative Parameter (Foramengröße) und Operationstechnik in Bezug auf die Verschlussrate nach primärer Operation. Die anatomische Verschlussrate bei idiopathischen Makulaforamina nach primärer Operation lag bei 83,6

Background To compare real-life anatomical and functional outcomes of half-dose photodynamic therapy (HD-PDT) and 577 nm subthreshold pulse laser therapy (SPL) in treatment-naïve patients with central serous chorioretinopathy (CSC). Methods We retrospectively reviewed consecutive treatment-naïve CSC patients with non-resolving subretinal fluid (SRF) for more than 2 months who received either HD-PDT or SPL treatment. One repetition of the same treatment was allowed in patients with persistent SRF after first treatment. Functional and anatomical outcomes were assessed after first treatment and at final visit. Results We included 95 patients (HD-PDT group, n = 49; SPL group, n = 46). Complete resolution of SRF after a single treatment was observed in 42.9% of HD-PDT-treated patients (n = 21; median time to resolution 7.1 weeks) and in 41.3% of SPL-treated patients (n = 19; median time to resolution 7.0 weeks). In the HD-PDT-group, 44.9% of patients (n = 22) and in the SPL-group, 43.5% (n = 20) of patients, received a second treatment due to persistent SRF, while 12.2% (n = 6) and 15.2% (n = 7), respectively, opted against a second treatment despite persistent SRF. After the final treatment, complete SRF resolution was observed in 61.2% of all HD-PDT-treated patients (n = 30; median time to resolution 8.8 weeks) and 60.9% of all SPL-treated patients (n = 28; median time to resolution 13.7 weeks, p = 0.876). In the final visit, both groups showed significant improvement of BCVA in comparison to baseline ( p < 0.001 for all). The change in BCVA from baseline to final visit was similar for the two groups (HD-PDT, median BCVA change 0.10 logMAR (IQR: 0.0-0.2); in SPL group, median BCVA change 0.10 logMAR (IQR: 0.0-0.2), P = 0.344). The CSC subclassification (simple versus complex) had no influence on the anatomical or functional outcome. Conclusions High-density 577 nm SPL resulted in as good anatomical and functional treatment as HD-PDT and may thus represent a treatment alternative to HD-PDT in CSC.

Background: Full-thickness macular hole (FTMH) is a rare disease. Not all FTMHs can be closed by primary surgical intervention. ObjectiveThis work aims to characterize a large patient population with FTMHs and to detect possible predictive factors for anatomical treatment success. Materials and methods: The study comprises a retrospective analysis of all consecutive idiopathic macular holes between March 2008 and June 2019 at the University Eye Hospital Cologne. Epidemiologic data, preoperative parameters (size of the FTMH), and surgical technique were examined in relation to the closure rate following primary surgery. Results: The anatomical closure rate for idiopathic FTMH after primary surgery was 83.6%. No association between age, gender, and lens status and closure rate could be shown. Regarding anatomical surgical success, the favorable prognostic factors identified were a small FTMH size, short symptom duration, performance of transconjunctival 23-gauge vitrectomy, and application of the inverted flap technique of the internal limiting membrane (ILM). Conclusion: Surgical treatment represents a valuable treatment option for patients with macular holes due to good prospects of success. Prompt intervention after diagnosis using 23-gauge vitrectomy and an ILM flap with gas tamponade seems to result in the most favorable outcomes.

Purpose: To assess the impact of ocular confounding factors on aqueous humor (AH) proteomic and metabolomic analyses for retinal disease characterization. Methods: This study recruited 138 subjects (eyes): 102 with neovascular age-related macular degeneration (nAMD), 18 with diabetic macular edema (DME), and 18 with cataract (control group). AH samples underwent analysis using Olink Target 96 proteomics and Metabolon's metabolomics platform Data analysis included correlation, differential abundance, and gene-set analysis. Results: In total, 756 proteins and 408 metabolites were quantified in AH. Total AH protein concentration was notably higher in nAMD (3.2-fold) and DME (4.1-fold) compared to controls. Pseudophakic eyes showed higher total AH protein concentrations than phakic eyes (e.g., 1.6-fold in nAMD) and a specific protein signature indicative of matrix remodeling. Unexpectedly, pupil-dilating drugs containing phenylephrine/tropicamide increased several AH proteins, notably interleukin-6 (5.4-fold in nAMD). Correcting for these factors revealed functionally relevant protein correlation clusters and disease-relevant, differentially abundant proteins across the groups. Metabolomics analysis, for which the relevance of confounder adjustment was less apparent, suggested insufficiently controlled diabetes and chronic hyperglycemia in the DME group. Conclusions: AH protein concentration, pseudophakia, and pupil dilation with phenylephrine/tropicamide are important confounding factors for AH protein analyses. When these factors are considered, AH analyses can more clearly reveal disease-relevant factors. Translational Relevance: Considering AH protein concentration, lens status, and phenylephrine/tropicamide administration as confounders is crucial for accurate interpretation of AH protein data

Age-related macular degeneration (AMD) is a multifactorial retinal disease with a large genetic risk contribution. Reticular pseudodrusen (RPD) is a sub-phenotype of AMD with a high risk of progression to late vision threatening AMD. In a genome-wide association study of 2,165 AMD+/RPD+ and 4,181 AMD+/RPD-compared to 7,660 control participants, both chromosomes 1 ( CFH ) and 10 ( ARMS2/HTRA1 ) major AMD risk loci were reidentified. However association was only detected for the chromosome 10 locus when comparing AMD+/RPD+ to AMD+/RPD-cases. The chromosome 1 locus was notably absent. The chromosome 10 RPD risk region contains a long non-coding RNA (ENSG00000285955/BX842242.1) which colocalizes with genetic markers of retinal thickness. BX842242.1 has a strong retinal eQTL signal, pinpointing the parafoveal photoreceptor outer segment layer. Whole genome sequencing of phenotypically extreme RPD cases identified even stronger enrichment for the chromosome 10 risk genotype.

Pharmacological agents known to stimulate monoamine systems improve memory, and destruction of the dopaminergic systems or dopamine depletion lead to impairments in various learning-related tasks. These reported effects of the central dopaminergic system imply the involvement of D2 receptors. The aim of the present study was to investigate changes in [3H]spiroperidol binding in seven areas of rat brain following informal and active avoidance learning. Littermate male and female rats were reared until 3 months of age in standard colony conditions and treated as active controls or in enriched environmental conditions and exposed to pole-jump active avoidance trials. Female rats acquired avoidance behavior more rapidly than males. Among the brain regions, only the hippocampus showed significant variations in D2 receptor binding between the groups; sex differences and learning-sex interaction were observed in the corpus striatum. There was an inverse correlation between learning performance and hippocampal D2 receptor binding. Our results show that learning affects hippocampal D2 receptors in a sexually dimorphic pattern.

Objective: The visual system often is affected in patients with preeclampsia and even more in cases of eclampsia, a life-threatening pregnancy complication. Symptoms include blurred vision and deterioration of visual acuity. Pregnancy can also affect pre-existing conditions, such as diabetic retinopathy. In this case series, we describe three patients with the same underlying condition, i.e. (pre)eclampsia who experienced acute visual disturbance whereas the final diagnosis was different: disseminated intravascular coagulopathy (DIC), posterior reversible encephalopathy syndrome (PRES), and diabetic retinopathy. Methods and results: All patients underwent a thorough slit lamp examination and ocular coherence tomography (OCT). All patients presented with acute impaired vision and subretinal fluid and-/or fibrin. Conclusions: These cases highlight the importance of early involvement of ophthalmologists when pregnant women complain about visual disorders.

Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.

PURPOSE:The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD).METHODS:This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined.RESULTS:RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886.CONCLUSIONS:RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.

Purpose: To investigate and compare the salivary alpha-amylase (sAA) activity as an indicator of the sympathetic activity and stress response in patients with central serous chorioretinopathy (CSC) and healthy control subjects. Methods: Prospective multicenter case series, including 80 CSC patients and 88 healthy control subjects. Central serous chorioretinopathy status was classified as either active or inactive, depending on the presence of subretinal fluid on optical coherence tomography. Salivary samples were collected in the morning from patients and control subjects of the main cohort and at midnight for the additional cohort. Salivary alpha-amylase activity was determined in all patients and control subjects. Results: Morning sAA activity was significantly higher in patients with active CSC compared with inactive CSC ( P = 0.049) and to healthy control subjects ( P = 0.012). There was no significant difference in sAA activity between patients with inactive CSC and control subjects ( P = 1.0). Nocturnal sAA activity did not show any significant difference between patients with active CSC and either inactive CSC or control subjects ( P = 0.139). Conclusion: Morning sAA activity is increased in patients with active CSC, although diurnal rhythmicity is preserved. Measurement of sAA is easy to perform and might be an eligible tool to further investigate the relation between stress and CSC.

Purpose: The aim of this study was to investigate the influence of dietary supplementation using Age-Related Eye Disease Study 2 (AREDS2) on complement activation in patients with neovascular age-related macular degeneration (nAMD) under ongoing treatment. Methods: In this prospective, single-center, controlled, open-label investigator-initiated trial, eligible nAMD patients were randomized at a ratio of 1:1 in 2 groups: those with and without dietary AREDS2 supplementation for 4 weeks. Zinc, plasma, and aqueous humor (AH) complement levels were quantified via enzyme-linked immunosorbent assays. Results: Fifty of 62 enrolled patients completed the trial (AREDS2 n = 27, controls n = 23). Systemic zinc and complement levels were not different at baseline between the 2 groups (p > 0.1). At the final visit, systemic zinc levels were significantly higher in the AREDS2 group (10.16 ± 2.08 μmol/L; 8.66 ± 1.17 μmol/L; p = 0.007), whereas systemic and AH complement levels were not different (p > 0.1). In both groups, no significant change was observed in systemic levels of C3, C3a, FH, FI, and sC5b-9 (p > 0.1). Only systemic complement component Ba showed an increase from baseline to the end visit (p = 0.01). This increase was higher in the control group (p = 0.02) than in the AREDS2 group (p = 0.23). Conclusions: Short-term dietary AREDS2 supplementation leads to a significant increase in systemic zinc levels without any influence on complement activation levels.