Purpose: To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). Methods: A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. Results: Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 μm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 μm vs. 257 ± 57 μm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). Conclusion: An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR.

Purpose: To analyse in depth the associations between objectively measured corneal higher‐order aberrations (HOAs) and subjectively perceived visual quality after small incision lenticule extraction (SMILE) as quantified with the standardized and clinically validated quality of vision (QOV) questionnaire.Methods: This cross‐sectional study included patients after bilateral simultaneous SMILE for the treatment of myopia and/or myopic astigmatism with plano target refraction. Scheimpflug imaging (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was used to objectively quantify corneal HOAs. The standardized and validated QOV questionnaire was employed to gauge patients’ subjectively perceived visual quality regarding frequency, severity and bothering effect of visual disturbances.Results: A total of 394 eyes of 197 patients with a mean age of 32.4 ± 7.7 years and a mean postoperative follow‐up of 24.3 ± 14.1 months were included. SMILE induced a statistically significant (p < 0.001) increase in spherical aberration (0.074 ± 0.131 µm), coma (0.142 ± 0.179 µm), trefoil (0.018 ± 0.067 µm) as well as in total HOAs (0.191 ± 0.176 µm). Surgically induced and postoperative levels of HOA showed no correlation with the three QOV scores representative of overall visual symptom frequency, severity and bothering effect (all R² values ≤ 0.016). In addition, the associations between specific visual symptoms (e.g. starburst) and singular HOA terms (e.g. haloes) were very weak (all Rho values ≤ 0.164).Conclusions: Small incision lenticule extraction induced significant amounts of corneal HOAs that, however, showed no clear relationships to patient‐reported QOV or specific long‐term visual symptoms.

To describe the progression of pachychoroid neovasculopathy (PNV) into pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)/polypoidal choroidal vasculopathy (PCV). Retrospective longitudinal cohort study. Patients diagnosed with PNV with a follow-up of ≥2 years. Multimodal imaging, including OCT and fluorescein and indocyanine green angiography, was reviewed for the presence of choroidal neovascularization (CNV), aneurysms within/at the margins of the CNV, and subfoveal choroidal thickness (SFCT). Rate of PNV to PAT1/PCV conversion and risk factors thereof. In total, 37 eyes of 32 patients with PNV with a mean follow-up of 3.3 ± 1.1 years (range, 2.0-5.2) were included in the study. At PNV diagnosis, the mean age was 59.7 ± 8.7 years (range, 38.5-78.0 years) and mean SFCT was 357 ± 92 μm (185-589). During the follow-up, 5 (13.5%) eyes developed aneurysms after a mean 3.4 ± 0.8 years (2.3-4.2), defining PAT1/PCV. The risk of PAT1/PCV conversion was 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. A mean of 5.2 ± 4.0 to 7.9 ± 3.6 intravitreal anti-VEGF injections were given per year, resulting in a significant reduction of SFCT to 317 ± 104 μm (122-589) (P = 0.0007). The age at diagnosis of PNV was significantly lower in eyes that later went on to develop PAT1/PCV (54.0 ± 5.6 [45.9-60.5] vs. 61.2 ± 8.4 [38.5-78.0] years; P = 0.025). At the end of the follow-up, SFCT had on average decreased by -14.0% ± 17.6% (-55.9% to 23.1%) in the PNV group, whereas it had increased by mean 6.9% ± 4.4% (0.00%-10.8%) in the PAT1/PCV conversion group (P = 0.0025). PNV can develop aneurysms within its type 1 CNV, defining the conversion to PAT1/PCV. In this study, the conversion to PAT1/PCV was seen in 13.5% of eyes, resulting in Kaplan-Meier estimates of risk for conversion of 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. Younger age at diagnosis of PNV and sustained choroidal thickening despite anti-VEGF therapy might be risk factors for PNV to progress into PAT1/PCV.

Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis.Methods: In line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants.Results: Here, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives.Discussion: The identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.

Purpose: There is an ongoing controversial debate about the effectiveness of laser treatments in chronic central serous chorioretinopathy (cCSC). We performed a prospective non-randomized interventional study to learn about the effects of a subthreshold laser treatment (Topcon Endpoint Management™, Topcon Healthcare Inc., Tokyo, Japan) in patients with cCSC. Methods: Patients with cCSC and a minimum symptom duration of 4 months were included and treated with a standardized laser pattern covering the macular area. Retreatment was performed every 3 months if persistent subretinal fluid was observed. The primary endpoint was resolution of subretinal fluid at 6 months. Further outcome parameters included best corrected visual acuity, microperimetry, central macular and subfoveal choroidal thickness. Results: A total of 42 eyes of 39 patients were included. Mean patient age was 48 ± 10.6 years (range 25–67). Mean symptomatic time before inclusion into the study was 134 ± 133.4 weeks (16–518). Before inclusion, 78.6% of the patients had failed to resolve subretinal fluid under mineralocorticoid receptor antagonists and 14.3% had a recurrence after half-dose photodynamic therapy. Complete resolution of subretinal fluid was observed in 42.9% at 6 months and in 53.8% at 12 months after baseline. Central retinal thickness decreased from 398 ± 135 µm to 291 ± 68 µm (p < 0.001), subfoveal choroidal thickness changed slightly (430 ± 116 µm to 419 ± 113 µm, p = 0.026), microperimetry-derived macular function improved by 19.1 ± 4.7 dB to 21.3 ± 4.8 dB (p = 0.008) and mean BCVA improved by 4.9 ± 8.6 ETDRS letters (p < 0.001). Conclusion: The results show that the investigated laser treatment is effective in reducing subretinal fluid and leads to an improvement of functional parameters.

Non-response to intravitreal ranibizumab represents a frequent problem in pachychoroid neovasculopathy (PNV). To investigate the effectivity of switching to aflibercept, the database of the Ludwig Maximilians University, Munich, was screened for patients fulfilling the following inclusion criteria: (i) diagnosis of PNV; (ii) inadequate response to ≥ 3 ranibizumab injections, in spite of monthly dosing, defined as persistence of subretinal-fluid four weeks after the last ranibizumab injection; (iii) resulting switch to aflibercept administered as three monthly injections. Primary outcome measure was percentage of eyes with a dry macula four weeks after the third aflibercept injection. Secondary outcome measures included changes in maximum subretinal fluid (SRF), central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). In total, 14 eyes of 14 patients were included. Mean age was 64.1 ± 7.5 (range: 51–78) years. Switching to aflibercept was performed after mean 8.4 ± 4.1 (3–15) ranibizumab injections. While no eye (0%) achieved a dry macula status during ranibizumab treatment, switching to aflibercept achieved a dry macula status in eight eyes (57.1%) after three injections. While both ranibizumab and aflibercept showed an effect on CST (p = 0.027, p = 0.003), only aflibercept showed a significant effect on SRF (p = 0.0009) and SFCT (p = 0.044). In cases of PNV not responding to intravitreal ranibizumab, switching treatment to aflibercept induces a favorable short-term response resolving persistent fluid and achieving a dry macula. Further studies with longer follow-up are warranted.