Evaluation of Increase in Retinal Thickness as Diagnostic Marker in Central Artery Occlusion.

PURPOSE: To evaluate the increase in retinal thickness as a marker in predicting the onset of central retinal artery occlusions. METHODS: Retrospective clinical study conducted at one Swiss hospital. Electronic records were filtered for patients with artery occlusions. Optical coherence tomography data, including time between the imaging and ischemic event, were reviewed. Increase in relative retinal thickness was measured, defined as an increase in retinal thickness compared to the unaffected partner eye. This was correlated with the time from symptom onset. A cutoff value of relative increase of < 24.5% was applied, as suggested in previous studies. The results were compared to the time gathered from the electronic records, and sensitivity, specificity, positive predictive value as well as negative predictive value were calculated for predicting an ischemia time of < 4.5 h. RESULTS: Forty-two eyes from 41 patients with central artery occlusions were identified. Fourteen were female. Mean age was 66.4 ± 15.8 years. Initial corrected visual acuity was 2.41 ± 0.68 logMAR, and 2.13 ± 0.87 logMAR at the last follow-up (p > 0.05). Of eyes with a visual acuity of counting fingers (n = 38) or worse, 89.5% showed no improvement during follow-up, while eyes with logMAR 1 or better (n = 4) improved. Thirteen eyes (13 patients) presented within 4.5 h of the ischemic event. Four patients received i. v. thrombolysis, with visual recovery in one. In 12 eyes with an ischemia time of < 4.5 h, relative increase was below 24.5%. In the remaining 29 eyes with > 4.5 h, relative increase was below 24.5% in 4 eyes and above 24.5% in 25 eyes. This yielded a sensitivity of 92.3%, a specificity of 86.2%, with a positive predictive value of 75.0% and a negative predictive value of 96.2%. CONCLUSION: Central retinal artery occlusion is associated with severe vision loss. There is no current established therapy. Parameters that objectify the presence of a therapeutic window for thrombolysis are gaining in importance as patient history is often imprecise. Relative retinal thickness increase proved a noninvasive imaging parameter demonstrating adequate performance in detecting patients within the therapeutic window of thrombolysis. Further investigation of this parameter in central retinal occlusion is warranted.

Ophthalmological Outcomes in Patients with Susac Syndrome.

BACKGROUND: To report ophthalmological outcomes and treatment regimen in patients with Susac syndrome. METHODS: This is a retrospective analysis of patients with Susac syndrome treated between November 2015 and March 2023. Multimodal imaging findings, ophthalmic examination data, information on neurological and sensorineural involvement, and therapeutic regimen were reviewed. Visual acuity was recorded as the logarithm of the minimum angle of resolution (logMAR). Ophthalmological manifestations and disease severity were assessed using the previously described clinical activity score (CAS). RESULTS: Ten patients with Susac syndrome m : f = 5 : 5 were identified. The mean follow-up time was 31.2 ± 23.3 months (range 1 to 78 months). The mean age was 41.4 ± 13.8 years (range 21 to 59 years). At baseline, corrected distance visual acuity (CDVA) was 0.03 ± 0.08 logMAR. At the last follow-up, CDVA improved to 0.00 ± 0.03 logMAR (p = 0.029). Three of 20 eyes showed an improvement of 5 letters, while no loss of visual acuity was recorded during the follow-up time. Baseline CAS was 10.65 ± 12.69, and CAS at the last follow-up was 5.15 ± 5.49 (p = 0.068). Except for one patient, all were initially treated with intravenous (i. v.) steroids and subsequent oral tapering. Depending on the treatment response, cyclophosphamide (n = 4), i. v. immunoglobulins (IVIGs) (n = 4), anti-CD20 antibodies (n = 3), or plasmapheresis (n = 1) were applied. All patients under treatment for more than 1 month (n = 9) showed improvement in CAS and CDVA. CONCLUSION: Susac syndrome is a rare autoimmune vascular endotheliopathy. Treatment of Susac syndrome appears to result in improving CAS and CDVA. The majority of patients, in addition to the systemic steroids, required systemic immunosuppressive agents. Interdisciplinary communication is crucial to reduce the time to diagnosis and initiation of therapy in patients with Susac syndrome.

Efficacy of Subthreshold Micropulse Laser for Central Serous Chorioretinopathy.

PURPOSE: To evaluate the efficacy of a subthreshold micropulse laser (SML) in patients with central serous chorioretinopathy (CSCR). METHODS: Retrospective clinical study conducted at the Departments of Ophthalmology at a university and a municipal hospital in Zurich, Switzerland. We enrolled acute and chronic CSCR patients with persistent subretinal fluid (SRF) treated with SML. Two treatment protocols (fluorescein/indocyanine green angiography or optical coherence tomography guided) were evaluated for efficacy after 3 and 6 months. The primary outcomes of the study were reduction and percentage of eyes with complete resolution of SRF 3 and 6 months after SML treatment. Secondary endpoints included changes in central subfield thickness (CST) and visual acuity (VA) after 3 and 6 months. RESULTS: The study involved 37 eyes (35 patients, 48.6% chronic). A statistically significant reduction in SRF height and CST could be shown, irrespective of SRF duration, type of CSCR, or chosen guidance after 3 and 6 months: SRF - 40 µm (p < 0.01), CST - 52 µm (p < 0.01). Percentage of eyes with complete resolution of fluid at 3 and 6 months after SML were 24.3 and 21.6%, respectively. No statistically significant functional improvement (VA) could be shown. Multivariable regression and linear mixed regression analyses did not identify statistically significant differences in SRF reduction, CMT change, or VA improvement with respect to the type of CSCR or the treatment plan used (p > 0.05). CONCLUSION: The effectiveness of SML in CSCR is under continuous debate. Our study findings demonstrate structural but only little functional changes with SML. In view of the shortage of verteporfin for photodynamic therapy, SML remains an important therapeutic option for CSCR patients.

Natural Course of Solar and Laser-Associated Retinal and Macular Injuries at a Primary Care Hospital in Switzerland.

BACKGROUND: Solar and laser-associated retinopathies are rare occurrences. The two retinopathies are both photo-induced but differ in the involved intensity and duration of exposure. The purpose of this study was to evaluate the clinical features and natural course of these two entities, with a focus on the changes in the outer retina over time. PATIENTS AND METHODS: This retrospective analysis assessed patients with solar or laser maculopathy seen at the Department of Ophthalmology of the University Hospital Zurich in Switzerland over the last 10 years. Visual acuity (VA; Snellen) and optical coherence tomography (OCT) findings were reviewed and analyzed at baseline and last follow-up visit. Areas of damaged outer retina, identified on en face OCT images as hyporeflective areas, were tagged and compared between visits. Descriptive analysis was performed by calculating mean values ± standard deviation (SD). Statistical evaluation was done using the Wilcoxon signed rank test. A p value < 0.05 was considered statistically significant. RESULTS: Five patients with solar retinopathy and six patients with laser-associated retinopathy were identified. In the solar retinopathy group, mean VA at baseline was 0.80 (SD ± 0.37) and improved to 0.90 (SD ± 0.36). This was not statistically significant (p = 0.066). In the laser-associated retinopathy group, mean VA at baseline was 0.89 (SD ± 0.18) and improved to 1.03 (SD ± 0.09), which was not statistically significant either (p = 0.063). At baseline, in OCT cross-sections, initial changes were observed in the interdigitation, myoid, and ellipsoid zone, as well as the outer nuclear layer and the Henle fiber layer. At follow-up, most cases presented an alteration in the residual ellipsoid zone, with the degree of the aforementioned alterations depending on the size of the initial defect. A decrease of the hyporeflective alterations measured in en face OCT scans was observed in both groups but was only statistically significant in the laser-associated retinopathy group (p = 0.018 versus p = 0.172). CONCLUSIONS: OCT can help to detect and monitor solar and laser-associated retinal injuries. Most injuries are minor, with good functional restitution. Minor changes in the ellipsoid zone often persist, even in cases with full visual recovery.

Amiodarone-associated Optic Neuropathy-A Clinical Criteria-based Diagnosis?

Amiodarone-associated optic neuropathy (AAON) is a controversial diagnosis with possible impact on vital cardiac therapy decisions. This retrospective case series aims for application of distinguishing features of AAON versus non-arteritic ischaemic optic neuropathy (NAION): Bilaterality, mode of onset, degree of optic nerve dysfunction, structure of uninvolved disc (unilateral cases), and systemic toxic effects. Applying these criteria to patients with disc swelling under amiodarone, the authors identified four unilateral disc swellings, one with NAION-typical features only and three with one or more NAION-atypical features. All three sequential and six bilateral cases showed one or more NAION-atypical features. The 12 cases highlight the persisting diagnostic dilemma arising from diversity of presentation, lack of plausible pathomechanism, and controversial existence of the entity itself.

Real-World Weekly Efficacy Analysis of Faricimab in Patients with Age-Related Macular Degeneration.

Objectives: This study entailed a weekly analysis of real-world data (RWD) on the safety and efficacy of intravitreal (IVT) faricimab in neovascular age-related macular degeneration (nAMD). Methods: A retrospective, single-centre clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland, approved by the Cantonal Ethics Committee of Zurich, Switzerland. Patients with nAMD were included. Data from patient charts and imaging were analysed. The safety and efficacy of the first faricimab injection were evaluated weekly until 4 weeks after injection. Results: Sixty-three eyes with a complete 4-week follow-up were enrolled. Six eyes were treatment-naïve; fifty-seven eyes were switched to faricimab from another treatment. Neither group showed signs of retinal vasculitis during the 4 weeks after injection. Central subfield thickness (CST) and volume (CSV) showed a statistically significant decrease compared to the baseline in the switched group (CST: p = 0.00383; CSV: p = 0.00702) after 4 weeks. The corrected visual acuity returned to the baseline level in both groups. The macular neovascularization area decreased in both groups, but this was not statistically significant. A complete resolution of sub- and intraretinal fluid after 4 weeks was found in 40% (switched) and 75% (naïve) of the treated patients. Conclusions: The weekly follow-ups reflect the structure-function relationship beginning with a fast functional improvement within two weeks after injection followed by a return to near-baseline levels after week 3. The first faricimab injection in our cohort showed a high safety profile and a statistically significant reduction in macular oedema in switched nAMD patients.

Human selection bias drives the linear nature of the more ground truth effect in explainable deep learning optical coherence tomography image segmentation.

Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect.

Impact of a stress coping strategy on perceived stress levels and performance during a simulated cardiopulmonary resuscitation: a randomized controlled trial.

BACKGROUND: Cardiopulmonary resuscitation (CPR) causes significant stress for the rescuers which may cause deficiencies in attention and increase distractibility. This may lead to misjudgements of priorities and delays in CPR performance, which may further increase mental stress (vicious cycle). This study assessed the impact of a task-focusing strategy on perceived stress levels and performance during a simulated CPR scenario. METHODS: This prospective, randomized-controlled trial was conducted at the simulator-center of the University Hospital Basel, Switzerland. A total of 124 volunteer medical students were randomized to receive a 10 minute instruction to cope with stress by loudly posing two task-focusing questions ("what is the patient's condition?", "what immediate action is needed?") when feeling overwhelmed by stress (intervention group) or a control group. The primary outcome was the perceived levels of stress and feeling overwhelmed (stress/overload); secondary outcomes were hands-on time, time to start CPR and number of leadership statements. RESULTS: Participants in the intervention group reported significantly less stress/overload levels compared to the control group (mean difference: -0.6 (95% CI -1.3, -0.1), p=0.04). Higher stress/overload was associated with less hands-on time. Leadership statements did not differ between groups, but the number of leadership statements did relate to performance. Hands-on time was longer in the intervention- group, but the difference was not statistically significant (difference 5.5 (95% CI -3.1, 14.2), p=0.2); there were no differences in time to start CPR (difference -1.4 (95% CI -8.4, 5.7), p=0.71). CONCLUSIONS: A brief stress-coping strategy moderately decreased perceived stress without significantly affecting performance in a simulated CPR. Further studies should investigate more intense interventions for reducing stress. TRIAL REGISTRATION: NCT01645566.

Vitamin A deficiency retinopathy related to medical interventions in a Swiss cohort: a case series.

AIMS OF THE STUDY: Vitamin A deficiency retinopathy is a potentially blinding disease. In developed countries, vitamin A deficiency due to malnutrition is rare. However, vitamin A deficiency can be caused by malabsorption resulting from bowel resection or medication. In this retrospective study, we present five cases of vitamin A deficiency retinopathy related to malabsorption secondary to medical interventions. METHODS: Electronic charts over a ten-year period (2012-2022) were screened for vitamin A deficiency retinopathy. Only patients with vitamin A deficiency confirmed by laboratory tests were included. Symptoms, medical history, visual acuity, optical coherence tomography, fundus autofluorescence, electrophysiological examination, and vitamin A levels were reviewed. RESULTS: Five eligible cases were identified. Median age was 44.7 years (range 22.2-88.9), median duration of ocular symptoms prior to diagnosis was 14 months, and median visual acuity was 1.0 (range 0.5-1.0, Snellen, decimal). Three patients had a history of bariatric surgery, one patient had a small bowel resection and was on octreotide treatment, and one patient suffered from cystic fibrosis and had a history of small bowel resection and severe hepatopathy. Optical coherence tomography showed various abnormalities, including a reduced interdigitation zone, subretinal drusenoid deposits, and a thinned outer nuclear layer. Electroretinogram findings ranged from abnormal oscillatory potentials to non-recordable rod responses. CONCLUSIONS: Vitamin A deficiency retinopathy can occur following medical interventions associated with malabsorption. In cases of night blindness, vitamin A levels should be measured.

Relationship of Vessel Density to Vessel Length Density in Patients with Treated Fabry Disease.

BACKGROUND: Fabry disease (FD) is a potentially lethal lysosomal disorder with systemic vascular changes. Previous studies demonstrated retinal vascular involvement using optical coherence tomography angiography (OCTA) in affected patients; Aim: To analyze and quantify the retinal vasculature measuring vessel density (VD), vessel length density (VLD), and the ratio of VD to VLD (VD/VLD) in superficial capillary plexuses (SCP) and deep capillary plexuses (DCP) using OCTA in patients with FD and to show whether they differ from healthy controls (HC); Patients and methods: Single-center, retrospective, consecutive cohort study of patients with genetically proven FD. Patients underwent an ophthalmological examination including OCTA. VD, VLD, foveal avascular zone (FAZ), and the VD/VLD were compared to an HC group using a linear mixed model; Results: A statistically significant difference in the VLD and VD/VLD of DCP was observed between the two groups (p < 0.001). Using ROC curves with AUC and Youden's Index, a cut-off value for differentiating both groups using VD/VLD in DCP FD with high specificity and high sensitivity was established; Conclusions: FD and HC groups seem to be separable using the VD/VLD ratio in DCP. This new biomarker might differentiate changes in the retinal microvasculature that are not detectable by VD or VLD alone.

Characterizing Flow and Structure of Diabetic Retinal Neovascularization after Intravitreal Anti-VEGF Using Optical Coherence Tomography Angiography: A Pilot Study.

Background/Aims. This study evaluates changes of flow and structure of diabetic retinal neovascularization (NV) treated with intravitreal antivascular endothelial growth factor (VEGF) agents using optical coherence tomography angiography (OCTA). With OCTA, retinal blood vessels are visualized at high resolution to separately look at flow and structure information without the need for dye injection. We introduce a new measurement method including and combining information of flow and structure. Methods. Retrospective observational case series. Patients with proliferative diabetic retinopathy (PDR) were treated with intravitreal antiVEGF injections. Retinal NV were repeatedly imaged using swept-source OCTA (Zeiss PlexElite 9000) at baseline, after initial treatment block with 3-4 monthly injections, and during a follow-up period of up to 51 weeks. Change of size and flow density of the structural and angio area of NV was assessed. Results. Nine NV in eight eyes of five patients were analyzed with a median follow-up time of 45 weeks. After the initial treatment block, en face structural area regressed, 18.7% ± 39.0% (95% CI 44.2-6.8%, p=0.26), and en face angio area regressed, 51.9% ± 29.5% (95% CI 32.6 to 71.2%, p=0.007). Flow density within the en face structural area decreased by 33% ± 19.2% (95% CI 20.5-45.5%, p=0.0077). Flow density within the en face angio area decreased by mean 17.9% ± 25.2% (95% CI 1.4-34.4%, p=0.066). In two fellow eyes, NV recurrence could be observed before the onset of vitreous bleeding in one. Conclusion. Our study introduces a new quantitative measurement for NV in PDR, combining structure and flow measurement. The structure area remained after treatment, while its flow density and angio area regressed. We propose this measurement method as a more physiological and possibly more comparable metrics.

Routine Clinical Practice Treatment Outcomes of Eplerenone in Acute and Chronic Central Serous Chorioretinopathy.

Purpose: To evaluate efficacy of eplerenone therapy vs. observation on resolution of subretinal fluid (SRF) in patients with acute and chronic central serous chorioretinopathy (CSCR) in routine clinical practice. Methods: Retrospective comparative case series of eyes diagnosed with CSCR treated with eplerenone or observation. Primary outcome measure was maximum height of SRF at 12 months. Secondary outcome was percentage of eyes with complete resolution of SRF, percentage of eyes with reduction of SRF ≥50%, and best corrected visual acuity (VA) at 12 months. Separate analysis was conducted for eyes with acute and chronic CSCR. Results: Sixty-eight eyes of 60 patients (82% male) were included. Eleven of the 38 eyes with acute CSCR, and seven of the 30 eyes with chronic CSCR, received eplerenone. Subretinal fluid decreased from baseline to 12 months in acute (287 ± 221 to 31 ± 63 µm) and chronic (148 ± 134 to 40 ± 42 µm) CSCR. Kaplan-Meier curves were similar for treated and observed eyes and COX regression analysis did not show a significant difference in SRF resolution in treated vs. observed eyes (p = 0.6 for acute, p = 0.2 for chronic CSCR). Conclusion: This routine clinical practice outcome study did not show evidence of efficacy of eplerenone on resolution of SRF in acute nor chronic CSCR.

Acute and subacute macular and peripapillary angiographic changes in choroidal and retinal blood flow post-intravitreal injections.

Whether post injectional acute intraocular pressure (IOP) increase is associated with decreased peripapillary and macular perfusion is still under debate. Here, we investigated early changes in the choroidal and retinal blood flow using OCTA imaging in a cohort of patients undergoing anti-VEGF intravitreal injections (IVI) for macular edema following retinal vein occlusion and diabetic retinopathy. In this prospective single-center, observational study, the pre- and post-IVI changes in retinal perfusion were examined via assessment of vessel length density (VLD) and vessel density (VD) in deep and superficial capillary segmentations (DCP and SCP), foveal avascular zone (FAZ) in SCP, as well as flow signal deficits in the choriocapillaris segmentation. Mean IOP significantly changed over the study course (p = 0.000; ANOVA). Measurements at 5 min post-IVI (33.48 ± 10.84 mmHg) differed significantly from baseline (17.26 ± 2.41 mmHg, p = 0.000), while measurements from one day, one week, and one-month post-IVI did not (p = 0.907, p = 1.000 and p = 1.000 respectively). In comparison to baseline, no changes in OCTA parameters, including FAZ, VD, VLD, and FV, were detected 5 min post-IVI. No significant alterations in OCTA parameters were observed during study course. Increased IOP spikes were detected post-IVI; however, no potential permanent ischemic retinal damage was suspected.

Globotrioasylsphingosine Levels and Optical Coherence Tomography Angiography in Fabry Disease Patients.

BACKGROUND: To date, there are no studies associating the dried blood spot (DBS) levels of globotrioasylsphingosine (lysoGb3) with quantitative optical coherence tomography angiography (OCTA) parameters in Fabry disease (FD) patients. Here, we aimed to investigate the association between OCTA vessel density (VD), vessel length density (VLD) with DBS lysoGb3. METHODS: A retrospective, single center analysis of all consecutive FD patients enrolled at the Department of Ophthalmology of the University Hospital of Zurich from 1 December 2017 to 9 September 2020. An association between VD and VLD detected by OCTA and lysoGb3 was investigated using a linear mixed model. RESULTS: A total of 57 FD patients (23 male, 34 female; 109 eyes) were included. Forty-one patients suffered from the classic phenotype and 16 from the later-onset phenotype. LysoGb3 inversely correlated with VD and VLD in both the superficial (VD: p = 0.034; VLD: p = 0.02) and deep capillary plexus (VD: p = 0.017; VLD: p = 0.018) in the overall FD cohort. CONCLUSIONS: Our study shows an association between lysoGb3 and OCTA VD and VLD. This supports the hypothesis that quantitative OCTA parameters might be useful as diagnostic biomarkers for evaluating systemic involvement in FD, and possibly other diseases.

Ten-year survival trends of neovascular age-related macular degeneration at first presentation.

BACKGROUND: To describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: Retrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections. RESULTS: For our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient's better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes). CONCLUSIONS: The chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes.