Influence of Post-radiation Ocular Surface Disorder on Ocular Surgery: A Case Report and Review of the Literature.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions. CASE PRESENTATION: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed. CONCLUSION: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient's complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.

Analysis of Suspected Achromatopsia by Multimodal Diagnostic Testing.

BACKGROUND: Achromatopsia (ACHM) as a hereditary cone disease might manifest in a stationary and progressive manner. The proper clinical and genetic diagnosis may allow an individual prognosis, accurate genetic counselling, and the optimal choice of low vision aids. The primary aim of the study was to determine the spectrum of clinical and genetic diagnostics required to characterize the ACHM. METHODS: A retrospective analysis was performed in 8 patients from non-related families (5 ♀,3 ♂); age at diagnosis: 3 - 56 y, mean 18.13 (SD ± 18.22). Clinical phenotyping, supported by colour vision test, fundus photography-, autofluorescence- (FAF), infra-red- (IR), OCT imaging and electroretinography provided information on the current status and the course of the disease over the years. In addition, genetic examinations were performed with ACHM relevant testing (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H and the transcription factor ATF6). RESULTS: All patients suffered photophobia and reduced visual acuity (mean: 0.16 [SD ± 0.08]). Nystagmus was identified in 7 from 8 subjects and in one patient a head-turn right helped to reduce the nystagmus amplitude. Colour vision testing confirmed complete achromatopsia in 7 out of 8 patients. Electrophysiology found severely reduced photopic- but also scotopic responses. Thinning and interruption of the inner segment ellipsoid (ISe) line within the macula but also FAF- and IR abnormalities in the fovea and/or parafovea were characteristic in all ACHM patients. Identification of pathogenic mutations in 7 patients helped to confirm the diagnosis of ACHM (3 adults, 4 children; 3 ♀ and 4 ♂). Achromatopsia was linked to CNGA3 (2 ♀, 1 ♂) and CNGB3 variants (2 ♀, 3 ♂). The youngest patient (♀, 10 y) had 3 different CNGB3 variants on different alleles. In a patient (♂, 29 y) carrying 2 pathogenic digenic-triallelic CNGA3- and CNGB3-mutations, a severe progression of ISe discontinuity to coloboma-like macular atrophy was observed during the 12-year follow-up. The oldest female (67 y) showed a compound homozygous CNGA3- and heterozygous CNGB3-, as well as a heterozygous GUCY2D variants. The destruction of her ISe line was significantly enlarged and represented a progressive cone-rod phenotype in comparison to other ACHM patients. In a patient (♂, 45 y) carrying a pathogenic CNGB3 and USH2 mutation, a severe macular oedema and a rod-cone phenotype was observed. In addition, two variants in C2ORF71 considered as VOS were found. One patient showed the rare ATF6 mutation, where a severe coloboma-like macular atrophy was observed on the left eye as early as at the age of three years. CONCLUSION: Combining multimodal ophthalmological diagnostics and molecular genetics when evaluating patients with ACHM helps in characterizing the disease and associated modifiers, and is therefore strongly recommended for such patients.

Morphology of Serous Retinal Detachment in Morning Glory Optic Disc Anomaly in a Patient before and after Treatment with Systemic Carboanhydrase Inhibitors.

BACKGROUND: Morning glory optic disc anomaly (MGODA) is a rare congenital defect of the optic nerve head. The optic nerve is enlarged, and its conical excavation is filled with glial tissue. It may be associated with cerebral malformations and ocular complications, whereas serous retinal detachment occurs in 38% of affected patients. Surgical treatment of detachment showed poor visual outcome in the past and conservative treatment options are scarce. CASE: A woman with MGODA presented in our clinic with sudden vision loss due to serous retinal detachment. She denied any previous ophthalmological problems and her past medical history was unremarkable. Vision testing showed normal visual acuity in her left eye and finger counting in her right eye. Slit lamp examination was unremarkable. Fundus examination of the right eye showed retinal detachment without holes or traction membranes and an enlarged optic disc with raised peripapillary tissue and glial tissue in the center of the optic disc. Due to the pathognomonic otpic disc finding, we diagnosed MGODA complicated by a serous retinal detachment. We treated the patient with systemic carboanhydrase inhibitors and documented the initial clinical findings as well as the course of disease under treatment by optical coherent tomography (OCT), fundus autofluorescence imaging (FAF), and visual field testing. During follow-up, we detected noticeable subretinal fluid regression and improvement in visual acuity. CONCLUSION: The application of oral carboanhydrase inhibitors appears to be a valid therapeutic option in patients with MGODA-associated serous macular detachment. OCT and FAF imaging are useful modalities for documentation of subretinal fluid regression and structural changes in the peripapillary region.

Postoperative Results in the Treatment of Retinal Detachment with Scleral Buckling Surgery.

BACKGROUND: The course after scleral buckling surgery is investigated in patients with rhegmatogenous retinal detachment. PATIENTS AND METHODS: The Ethics Committee of Eastern Switzerland approved the retrospective single-center study (EKOS19/152, Project ID: 2019-02034). The primary endpoint is the anatomical reattachment of the retina 3 months after surgery. Secondary endpoints are visual acuity and the occurrence of intra- and postoperative complications. The patient files of all patients treated for rhegmatogenous retinal detachment with scleral buckling surgery between January 2005 and December 2014 at the Cantonal Hospital of St. Gallen were included. RESULTS: In 165 of 184 patients (89.7%), reattachment of the retina 3 months postoperatively was achieved by single scleral buckling surgery. Treatment of rhegmatogenous retinal detachment improved patients' visual acuity by an average of 4.8 ETDRS letters. Intraoperatively, subretinal hemorrhage occurred in one patient. Postoperatively, interfering buckling material was removed in 24 patients (13.1%). A pars plana vitrectomy was performed in six patients (3.2%) due to epiretinal membrane, in two patients (1.1%) due to a macular hole, and in three patients (1.6%) due to disturbing vitreous opacities. CONCLUSIONS: Scleral buckling surgery is an effective and relatively low complication method for the treatment of selected patients with rhegmatogenous retinal detachment.

"Treat-and-Extend" Regimen for Exudative Age-Related Macular Degeneration: A Two-Year Retrospective Follow-up Study.

BACKGROUND: After the introduction of a "treat-and-extend" regimen (T&E) with aflibercept for exudative age-related macular degeneration, naive eyes were compared with eyes pretreated with a "pro re nata" scheme (PRN). PATIENTS AND METHODS: The Ethics Committee of Eastern Switzerland approved the retrospective single-centre study (EKOS20/084, project ID: 2020-01193). The study included 342 eyes of 303 patients newly treated with or switched to T&E between January 2018 and March 2018 at the Eye Clinic of the Cantonal Hospital St. Gallen. The gender distribution of the treated eyes was 63.5% (n = 217) female and 36.5% (n = 125) male. The mean age was 81.6 years (SD = 8.6 years). The collective was divided into three groups: 1) naive, untreated eyes (n = 92), 2) eyes with ≤ 6 previous treatments with PRN (n = 37), 3) eyes with > 6 previous treatments with PRN (n = 213). The following parameters were analysed up to December 2019: the evolution of visual acuity, the number of intravitreal injections, the number of recurrences, the duration of the follow-up, the dropout rate, and the duration of the last treatment interval. RESULTS: During the observation period, group 1 showed a statistically significant improvement in visual acuity of + 1.5 ETDRS, while groups 2 and 3 showed a decrease in visual acuity of - 2.9 and - 3.7 ETDRS, respectively. Group 1 had better development of visual acuity than groups 2 and 3 (p = 0.005), while groups 2 and 3 were not significantly different (p = 0.92). The other parameters examined in the three groups did not differ significantly between groups. CONCLUSIONS: Treatment with aflibercept in T&E shows significantly better visual acuity in naive eyes than in eyes pretreated with PRN.

Structural, Microvascular, and Functional Findings Associated with Fovea Plana.

PURPOSE: To analyse structural (OCT), microvascular (OCTA), and functional changes (BCVA, mfERG) associated with fovea plana and to compare it to healthy controls. METHODS: A retrospective observational study was performed on 13 patients (26 eyes; aged 34.46 y ± 20.26) with a clinical picture of fovea plana and 15 controls (30 eyes; aged: 41.47 y ± 14.03). RESULTS: In fovea plana, BCVA ranged from 0.25 to 1.0, with a spherical error of - 5.5 to + 18.0 dpt. Posterior segment changes included elevated papillomacular retinal fold, uveal effusion syndrome, crowded optic discs, and hypopigmented fundus. OCTA imaging of the superficial (FAZ-S), intermediate (FAZ-I), and deep foveal avascular zone (FAZ-D) confirmed absence of foveal avascular zone (FAZ-S in 13 eyes, FAZ-I in 21 eyes, and FAZ-D in 10 eyes). Fovea plana patients had a significantly smaller FAZ-S, FAZ-I, and FAZ-D than controls (p < 0.001). Within the fovea plana group, a smaller FAZ-S correlated with reduced BCVA (p = 0.004) and with reduced mfERGs in zones 1 and 2 (p = 0.001 and p = 0.017). Also, a smaller FAZ-D showed positive correlations with the mfERG, with statistically significant values in zones 1 and 2 (p = 0.003 and p = 0.017). CONCLUSION: In conclusion, our results confirm an altered structural, microvascular, and functional pattern in patients with a clinical picture of fovea plana. As documented by the functional microvascular interactions in our study, the developmental arrest in foveation reflects the functional maturation by means of visual acuity and central retinal function.

Patients with central serous chorioretinopathy not only have pachychoroidal disorders but also altered retinal metabolic function.

PURPOSE: The aim of our study was to compare metabolic (oxygen saturation; %) and anatomical (diameter; µm) retinal vessel parameters of patients with central serous chorioretinopathy (CSC) to those of controls. METHODS: In this prospective cross-sectional cohort study, 72 eyes of patients with CSC were compared with 21 eyes of healthy controls. Of the 72 patients, 52 had chronic, nonactive CSC (subgroup nCSC) and 20 had active CSC (subgroup aCSC), according to activity on fluorescein angiography. Retinal vessel oximetry (RO) was performed using the Oxymap T1 oximeter. Oxygen saturation in all major peripapillary retinal arterioles (A-SO2 ) and venules (V-SO2 ) was measured, and their difference (A-V SO2 ) was calculated. In addition, we evaluated the corresponding diameter in retinal arterioles (D-A) and venules (D-V). For statistical evaluation, ANOVA-based linear mixed-effects models were calculated (SPSS®; p < 0.05). RESULTS: Central serous chorioretinopathy (CSC) patients had significantly higher A-SO2 and V-SO2 compared to that of controls (p = 0.031 and p = 0.018 respectively). Especially, the subgroup of aCSC patients showed significantly higher A-SO2 and V-SO2 values (p = 0.027 and p = 0.034, respectively). In addition, superotemporal and superonasal quadrant location showed significant interactions with A-SO2 and V-SO2 (p ≤ 0.03). Diameter in retinal arterioles (D-A), an venules (D-V) and A-V SO2 findings showed no significant differences (p > 0.096). CONCLUSION: These data indicate that patients with CSC have altered metabolic function. The presence of disease activity showed the greatest influence on RO measurement, both compared to controls and to those with inactive chronic CSC disease.

The artificial iris - Analysis of various implantation techniques after ocular trauma.

PURPOSE: The aim of this study is to analyze the outcome of various techniques for a custom-made iris prosthesis implantation as part of reconstructive anterior segment surgery following traumatic aniridia. METHODS: This retrospective interventional study was done for 6 eyes that received an artificial iris as secondary reconstructive measure for photophobia and unsatisfactory vision following initial globe repair. Different implantation techniques were employed. These included simple sulcus implantation, implantation of a composite (iris prosthesis with attached intraocular lens) implant, and combinations with phacoemulsification, vitrectomy, and penetrating keratoplasty. RESULTS: In all cases, the artificial iris was implanted successfully. In the follow-up period (1-48 months), postoperative complications included rhegmatogenous retinal detachment, prolonged intraocular inflammation, and corneal transplant decompensation due to graft rejection. There was no case of secondary glaucoma. Complications could be managed successfully. All patients showed improved best-corrected visual acuity and were satisfied with functional and cosmetic results. CONCLUSION: This case series highlights the different implantation techniques for reconstruction of the anterior segment after ocular trauma. The versatility of the custom-made iris implant accounts for a wide range of applications and the foldable material reduces the need for large incisions in the already traumatized eye.

Thermal Laser Monotherapy for Extrafoveal Polypoidal Choroidal Vasculopathy.

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid. Diagnosis is mainly based on polypoidal aneurysm-like lesions seen in indocyanine green (ICG) angiography. Various therapeutic options have been proposed. METHODS: Outcomes of 10 cases with extrafoveal PCV and consecutive macular edema treated with thermal laser are reported. Diagnosis of PCV was confirmed by ICG angiography. RESULTS: Upon successful occlusion of the polyps in 10 eyes after thermal laser treatment demonstrated in ICG angiography, a regression of central foveal edema was seen in optical coherence tomography and color fundus photography. Visual acuity improved from logMAR 0.8 to logMAR 0.3. Follow-up ranged from 4 months to 15 years, with a median of 1 year. Two eyes had a recurrence of exudative maculopathy 5 and 7 years after laser treatment, respectively. CONCLUSION: A careful differentiation between various subforms of exudative maculopathy using fluorescein and ICG angiography can identify certain selected patients with extrafoveal PCV, for whom thermal laser monotherapy can be a therapeutic option.

Indications and outcomes for intravitreal injection of C3F8 gas for symptomatic vitreomacular traction.

To evaluate the indications and outcomes of perfluoropropane (C3F8) gas injection for symptomatic vitreomacular traction (VMT). A retrospective analysis of eyes with VMT treated with 0.3 mL of C3F8 gas was performed. Patients were not asked to posture after gas injection. In phakic patients, cataract surgery was performed simultaneously. Patients were examined after one week and one month postoperatively. Twenty-nine consecutive eyes of 26 patients with symptomatic VMT who underwent pneumatic vitreolysis were included. A complete posterior vitreous detachment was achieved in 18 eyes (62.1%) after a single gas injection at the final visit. The rate of posterior vitreous detachment was reduced significantly with the presence of epiretinal membrane (ERM) (p = 0.003). Three eyes formed a macular hole (MH) postoperatively and another eye developed a retinal detachment. Mean visual acuity increased significantly after one month (p < 0.008). Pneumatic vitreolysis is a viable option for treating VMT with few adverse events. Patient with concomitant ERM had a significantly lower success rate.

Linking the Presence of Macular Oedema to Structural and Functional Alterations in Retinitis Pigmentosa.

OBJECTIVE: To investigate the association between the central retinal thickness (CRT), the retinal nerve fibre layer thickness (RNFL), and the functional alterations in retinitis pigmentosa (RP) patients. METHODS: Forty-three patients with typical RP and nineteen age-matched controls, who underwent SD-OCT (macular and optic disc OCT protocols) and electrophysiology, were included. The RP group was divided into two subgroups: with clinical appearance of macular oedema (ME-RP; 30 eyes) and without macular oedema (no-ME; 44 eyes). Central retinal thickness OCT data were averaged in three zones (zone 1 [0°-3°], zone 2 [3°-8°], and zone 3 [8°-15°]) and were evaluated in relation to the RNFL thickness and electrophysiological data. RESULTS: The ME-RP group showed increased CRT (zone 1) and RNFL thickness compared to the controls and no-ME-RP (p ≤ 0.002). The no-ME-RP group had reduced CRT thickness (all zones; p ≤ 0.018) compared to the controls and ME-RP, whereas the RNFL thickness in the no-ME-RP group was reduced only compared to the ME-RP group (p < 0.001). The ME-RP group showed significantly more attenuated functional responses than the no-ME-RP patients. A significant positive interaction was found between the CRT (zones 1 and 2) and the RNFL thickness within ME-RP (p ≤ 0.010). Significant negative interactions were found between CRT, RNFL thickness, and functional findings within ME-RP (p ≤ 0.049). CONCLUSION: The presence of macular oedema correlated well with increased RNFL thickness and residual function in RP patients. Such association provides evidence of an underlying transneuronal mechanism of retinal degeneration. Simultaneous monitoring of CRT and RNFL thickness may help in the future to evaluate the progression of the disease and the efficacy of treatments in RP patients.

Optic Disc Features in Familial Retinal Arteriolar Tortuosity.

PURPOSE: Describing optic disc appearance in familial retinal arteriolar tortuosity (fRAT) using multimodal imaging and raising awareness of peripapillary arterial changes due to this disorder. METHODS: A cross-sectional study was performed in four consecutive patients of two non-related families. Detailed ophthalmological examination was performed and supported by medical and family history and multimodal imaging. RESULTS: In all subjects, increased tortuosity of second- and third-order retinal arteries in superior and deeper vascular plexus was documented. Furthermore, tortuosity in the peripapillary circle of Zinn-Haller was found. In addition, retinal vessel oximetry confirmed tortuosity only of the arterial vessels. CONCLUSION: The present data suggests that a blurry bordered, hyperemic optic disc in the presence of abnormally tortuous arteriolar vessels and asymptomatically or oligosymptomatically spontaneously resolved hemorrhages could be associated with a fRAT. This finding could be linked to peripapillary arterial vessel tortuosity.

Visual Outcomes after Anti-VEGF Therapy for Exudative Age-Related Macular Degeneration in a Real-Life Setting.

BACKGROUND: To report visual outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for exudative age-related macular degeneration (AMD) in a real-life setting. PATIENTS AND METHODS: Retrospective case series of consecutive patients treated with either ranibizumab and/or aflibercept for monolateral or bilateral exudative AMD. A physician established the indication for treatment and administered the injections. An independent physician confirmed the indication for primary treatment. A Pro Re Nata and a Treat and Extend regimen were used. Assessment of subretinal and/or intraretinal fluid, retinal hemorrhage and increase in pigment epithelial detachment served as criteria for further treatment decisions. Visual acuity (VA) was measured in ETDRS letters at each examination and then analyzed using a specialized software. Evolution of mean VA was considered for all study eyes and subgroups of eyes with an initial VA ≥ 70 ETDRS letters (subgroup 1) and ≤ 69 ETDRS letters (subgroup 2). RESULTS: A total of 102 eyes of 76 patients (30 men, mean age 75.9 years; 46 women, mean age 81.5 years) were included. Subgroup 1 consisted of 47 eyes, and subgroup 2 of 55 eyes. Mean follow-up was 55 months (range 6 to 150 months). For the entire collective as for subgroups 1 and 2, the mean VA was 64, 77, or 51 ETDRS letters at baseline. Mean VA improved at month 12 (68, 80, or 58 ETDRES letters) and then slowly decreased over time until month 150 (62, 72, or 54 ETDRS letters). Maximum improvement of + 5, + 3, or, + 9 ETDRS letters occurred after 9, 8, or 10 months of follow-up. Atrophy and fibrosis were mainly responsible for VA decrease. Ten serious adverse events were reported to Swissmedic: two cases of cardiovascular events and eight cases of intraocular inflammation. CONCLUSIONS: Anti-VEGF therapy carried out in a real-life setting shows good VA outcomes with a favorable safety profile.

Drug-Induced Pseudo-Central Serous Chorioretinopathy in Carcinoma Patients.

PURPOSE: Patients with carcinomas often share symptoms of vision deterioration as part of paraneoplastic retinopathy (PNR), based on a cross-reaction between antigens expressed by the underlying tumor and retinal proteins. However, some of the underlying symptoms may be explained by a drug-induced toxicity. The application of new therapeutic strategies with mitogen-activated protein kinase (MEK) and fibroblast growth factor receptor (FGFR) inhibitors in advanced cancers are still under evaluation for safety and tolerability, but also for dose-limiting toxicities. In the presented data, we identified a drug-induced pseudo-central serous chorioretinopathy (pCSC) to be the reason for central vision deterioration. METHODS: A retrospective, observational, case-controlled study included seven patients receiving MEK and six patients receiving FGFR inhibitor treatment for bronchopulmonal cancer. We compared the clinical and diagnostic pictures of pCSC patients with that of 50 CSC patients (100 eyes) and 7 patients (14 eyes) with PNR. The activity of pCSC was assessed by clinical examination, supported by multimodal imaging. The relationships between clinical symptomatology and systemic disease activity were evaluated. RESULTS: Three out of thirteen patients (23.1%) showed signs of pCSC (one FGFR and two MEK inhibitor patients). All three pCSC patients showed central bilateral detachment of the neurosensory retina on OCT imaging, but also paracentral multifocal lesions in the second subject. Compared to our CSC and PNR patients, the lesions in pCSC patients showed no lipofuscin irregularities on FAF. With reduction of the MEK treatment, the lesions on one MEK subject disappeared and BCVA restored to 0.8. In one MEK- and the FGFR subject, the lesions reduced in size without therapy discontinuation. CONCLUSION: Based on our data, MEK and FGFR inhibitor-associated pCSC is a mild, self-limited retinopathy that seems to disappear simultaneously or shortly after discontinuation of medication, with subsequent restoration of the central visual function.

Comparative study of combined vitrectomy with phacoemulsification versus vitrectomy alone for primary full-thickness macular hole repair.

BACKGROUND: To assess the effectiveness and safety of 23-gauge pars plana vitrectomy combined with phacoemulsification versus vitrectomy alone in patients over 50 years with primary full-thickness macular holes (FTMH). METHODS: We retrospectively reviewed the medical records related to 406 consecutive vitrectomies performed for primary FTMH. Phacovitrectomy was performed in 294 phakic eyes whereas vitrectomy alone in 112 pseudophakic eyes. The cases were divided into three groups according to the stage of the FTMH: stage 2 (n = 93), stage 3 (n = 270), or stage 4 (n = 43). The primary outcome measure was the closure of the FTMH. The secondary outcome measures were the evolution of visual acuity as well as intraoperative and postoperative complications. RESULTS: Neither the primary nor the secondary outcomes differed between phacovitrectomy and vitrectomy alone for all three stages. The FTMH were closed in 375 eyes (92.4 %) after a first operation. The closure rate was higher for stage 2 (96.8 %) than for stages 3 (91.1 %) or 4 (90.75 %), but not significantly (P = 0.189). The mean visual acuity increased significantly from preoperatively LogMAR 0.68 (± SD 0.2) to LogMAR 0.43 (± SD 0.24) at the end of the follow-up (p < 0.001). CONCLUSIONS: Combined 23-gauge pars plana vitrectomy with phacoemulsification for primary FTMH repair in patients over 50 years is as efficient and safe when compared with vitrectomy only. TRIAL REGISTRATION: The study was approved on 30th April 2020 by the local ethics committee (Ethikkommission Ostschweiz, EKOS 20/074; BASEC Nr. 2020-01033 ).