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

Differences between Mycobacterium chimaera and tuberculosis Using Ocular Multimodal Imaging: A Systematic Review

Due to their non-specific diagnostic patterns of ocular infection, differential diagnosis between Mycobacterium (M.) chimaera and tuberculosis can be challenging. In both disorders, ocular manifestation can be the first sign of a systemic infection, and a delayed diagnosis might reduce the response to treatment leading to negative outcomes. Thus, it becomes imperative to distinguish chorioretinal lesions associated with M. chimaera, from lesions due to M. tuberculosis and other infectious disorders. To date, multimodal non-invasive imaging modalities that include ultra-wide field fundus photography, fluorescein and indocyanine green angiography, optical coherence tomography and optical coherence tomography angiography, facilitate in vivo examination of retinal and choroidal tissues, enabling early diagnosis, monitoring treatment response, and relapse detection. This approach is crucial to differentiate between active and inactive ocular disease, and guides clinicians in their decisional-tree during the patients' follow-up. In this review, we summarized and compared the available literature on multimodal imaging data of M. chimaera infection and tuberculosis, emphasizing similarities and differences in imaging patterns between these two entities and highlighting the relevance of multimodal imaging in the management of the infections

Long-Term Clinical and Multimodal Imaging Findings in Patients with Disseminated Mycobacterium Chimaera Infection

BACKGROUND To analyze long-term ophthalmic clinical and multimodal imaging findings of disseminated Mycobacterium (M.) chimaera infection after cardiothoracic surgery among the Swiss Cohort. METHODS Systemic and multimodal ophthalmic imaging and clinical findings including rate of recurrence were reviewed and correlated to a previously proposed classification system of choroidal lesions and classification of ocular disease. MAIN OUTCOMES MEASURES long-term clinical and multimodal ocular imaging findings of M. chimaera. RESULTS Twelve patients suffering from systemic infection from M. chimaera were included. Mean age at the first ophthalmic examination was 59 years (range from 48 to 66 years). Mean duration of the follow-up was 22.63 ± 17.8 months. All patients presented with bilateral chorioretinal lesions at baseline; 5 patients had additional signs, including optic disc swelling (2), choroidal neovascularization (1), retinal neovascularization (1) and cilioretinal vascular occlusion (1). Four recurrence events after discontinuation or adjustment of the antibiotic treatment were observed. Progressive choroiditis was seen in 5 patients under treatment, 4 of them deceased. CONCLUSIONS Expertise from ophthalmologists is not only relevant but also critical for the assessment of the adverse drug effect of antimycobacterial treatment along with monitoring therapeutic response and identifying recurrences

Assessing Choroidal Nevi, Melanomas and Indeterminate Melanocytic Lesions Using Multimodal Imaging—A Retrospective Chart Review

Using multimodal imaging, the literature proposed the following risk factors for choroidal nevus growth into melanoma: increased tumor thickness, subretinal fluid, decreased visual acuity, presence of orange pigment, ultrasound acoustic hollowness, and increased tumor diameter. This study investigated the presence of the mentioned risk factors in choroidal nevi, choroidal melanomas, and indeterminate choroidal melanocytic lesions. This retrospective, single-center chart review assessed choroidal melanocytic tumors with multimodal imaging. We defined our primary outcome as the cumulative presence of mentioned risk factors. Further, we evaluated various optical coherence tomography (OCT), ultrasound, and autofluorescence findings. We analyzed 51 tumors from 49 patients during the period from April 2008 to June 2021. The median (IQR) age was 64.0 (56.0 to 70.5) years, with 23 of 49 (46.9%) patients being female. The follow-up time for all tumors was median (IQR) 25.0 (12.0 to 39.0) months. The choroidal nevi had a median (range) risk score of 0.0 (0.0 to 3.0), and the choroidal melanoma of 5.0 (3.0 to 6.0), with statistically significant different ratings (p < 0.001). Multimodal imaging creates a score that may help to distinguish choroidal nevi from choroidal melanomas objectively

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

Severe Complications after Corneal Collagen Cross-Linking (CXL)

Purpose To present a case series of rare and severe complications after corneal collagen cross-linking (CXL) of keratoconus patients. Methods Single-center descriptive case series covering the period of 2012 to 2022 at the Department of Ophthalmology at the University Hospital, Zurich, Switzerland. Results We present four eyes of four patients that showed severe unusual complications within the first month after CXL. Three patients had been treated with the classical epithelium-off “Dresden” protocol. One patient had been treated with the accelerated epithelium-off protocol. One patient presented with extensive corneal edema due to rubbing the eye after treatment. Two patients showed a bacterial infectious keratitis: one due to Streptococcus pneumoniae and the other due to Staphylococcus hominis, Micrococcus luteus, and Streptococcus epidermidis. The latter of the two patients exhibited extensive infectious crystalline keratopathy. The fourth patient showed a severe ulcerative lesion where no infectious cause could be found. Therefore, an autoimmune keratolytic process had to be suspected. Apart from the corneal edema, which resolved ad integrum, the other complications resulted in permanent corneal scarring and thinning. One patient needed an emergency amniotic transplant. Conclusion Severe complications after CXL remain rare. Most common causes are complications that are not directly associated with the treatment as such. Those indirect complications occur after the treatment during the healing course of the epithelium. Associations with bandage contact lenses, topical steroids, atopic disease, and inappropriate patient behavior are often suspected. Correctly performed corneal scrapings with repeated microbiological analysis and a detailed patient history are essential for establishing the correct diagnosis, especially in complicated cases that do not respond to a standard therapeutic regimen. This case series supports the efforts that are currently taken to improve the CXL technique in a way that postoperative complications are further reduced. A more efficient epithelium-on technique might be a step in that direction. // Ziel Darstellung einer Fallserie von seltenen, schwerwiegenden Komplikationen nach kornealem Kollagen-Crosslinking (CXL) von Patienten mit Keratokonus. Methoden Monozentrische, beschreibende Fallserie über einen Zeitraum von 2012 bis 2022 an der Augenklinik des Universitätsspitals Zürich, Schweiz. Ergebnisse Wir zeigen 4 Augen von 4 Patienten, die mit ungewöhnlichen, schwerwiegenden Komplikationen innerhalb des 1. Monats nach CXL an unserer Klinik vorstellten. Drei der Patienten waren mit dem klassischen Epithelium-off-„Dresden“-Protokoll behandelt worden, ein Patient mit einem beschleunigten Epithelium-off-Protokoll. Ein Patient stellte sich mit einem ausgeprägten Hornhautstromaödem aufgrund von Reiben des Auges vor. Zwei Patienten zeigten eine infektiöse, bakterielle Keratitis mit Streptococcus pneumoniae bzw. Staphylococcus hominis, Micrococcus luteus, Streptococcus epidermidis. Der 4. Patient zeigte eine schwere ulzerative Läsion ohne nachweisbare infektiöse Genese, weshalb ein autoimmuner, keratolytischer Prozess vermutet wurde. Außer dem Hornhautödem, das sich vollständig zurückbildete, resultierten die anderen Komplikationen in einer bleibenden Vernarbung und Ausdünnung der Hornhaut. Ein Patient benötigte eine notfallmäßige Amnionmembrantransplantation. Schlussfolgerung Schwerwiegende Komplikationen nach CXL bleiben selten. Die häufigsten Ursachen hierfür sind Komplikationen, die nicht direkt mit der eigentlichen Prozedur zusammenhängen, sondern erst im postoperativen Heilungsverlauf des Hornhautepithels auftreten. Ein Zusammenhang mit therapeutischen Kontaktlinsen und unangemessenem Patientenverhalten wird in vielen Fällen angenommen. Korrekt durchgeführte Hornhaut-Scrapings mit wiederholter mikrobiologischer Aufarbeitung und eine detaillierte Patientenanamnese sind unerlässlich für eine korrekte Diagnosestellung, insbesondere in komplizierten Fällen, die nicht auf die üblichen Therapieregime ansprechen. Diese Fallserie unterstützt die aktuellen Bemühungen, die CXL-Technik dahingehend zu verbessern, sodass postoperative Komplikationen weiter reduziert werden. Eine effizientere Epithelium-on-Technik wäre ein Schritt in diese Richtung

Analysis of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) Parameters in Young Adults after SARS-CoV-2 Infection (COVID-19) Compared with Healthy Young Controls

Purpose: To compare retinal changes in young adults with previous SARS-CoV-2 infection with healthy young controls using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). Methods: This prospective single-center study was conducted at the University Hospital of Zurich, Zurich, Switzerland. Participants were imaged from May to November 2021 using the SOLIX device (Visionix International SAS, Pont-de-l’Arche, France). We performed 12 mm × 12 mm, 6.4 mm × 6.4 mm, 6 mm × 6 mm and 3 mm × 3 mm OCT and OCTA scans, as well as fundus photography of each participant’s eyes. Results: In total, 466 participants were imaged. Of these, 233 were healthy controls with negative RT-PCR tests for SARS-CoV-2, 168 were young adults who had a SARS-CoV-2 infection at least 180 days previously, 19 were participants who had a SARS-CoV-2 infection < 180 days previously, and 46 were participants with asymptomatic SARS-CoV-2 infection (i.e., serologically positive but with no symptoms). Compared with healthy controls, statistically significant differences were found for OCTA recordings of the optic disc for the whole image (WI) and WI capillary vessel density, with both being higher in the SARS-CoV-2 group. Conclusion: Statistically significant results were only observed for selected variables, and in parts, only unilaterally, with relatively large p values (p = 0.02–0.03). Thus, we did not interpret these as clinically significant, leading to the conclusion that young and otherwise healthy individuals (mainly men) seem to recover from mild COVID-19 infections with no ophthalmological residues

Assessment of Patients' Confidence Regarding a New Triage Concept in a Medical Retina Clinic during the First COVID-19 Outbreak

BACKGROUND During the first COVID-19 pandemic outbreak, a new triage concept had to be implemented for patients with retinal diseases having a scheduled appointment at the medical retina clinic. In this study, we aimed to assess patients' confidence in this triage concept and patients' satisfaction regarding the received treatment during the outbreak. METHODS This retrospective study included all patients with a diagnosed retinal disease, triaged into three priority groups based on their condition's urgency during lockdown. After restrictions were eased, a subset of previously triaged patients was interviewed to assess their confidence in the triage and their satisfaction regarding the received treatment during the pandemic. RESULTS In total, 743 patients were triaged during the lockdown. Over 80% received an urgent appointment (priority 1). Among all priority 1 patients, over 84% attended their appointment and 77% received an intravitreal injection (IVI), while 7% cancelled their appointment due to COVID-19. In post-lockdown interviews of 254 patients, 90% trusted the emergency regimen and received treatment. CONCLUSIONS Our triage seemed to be useful in optimizing access to treatment for patients with retinal diseases. An excellent rating of patients' confidence in the triage and satisfaction regarding the received treatment during the first COVID-19 outbreak could be achieved

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

Differences in Mean Values and Variance in Quantitative Analyses of Foveal OCTA Imaging

PURPOSE Multiple approaches for quantifying parameters such as vessel density (VD) and vessel length density (VLD) in optical coherence tomography angiography (OCTA) en-face segmentations are currently available. While it is common knowledge that data gathered from different methods should not be directly compared to each other, a comparison of the different methods can help to further the understanding of differences between different methods of measurement. Here we compare a common method of semiautomatically quantifying VD and VLD with an automated method supplied by the manufacturer of an OCTA device and report on differences in performance in order to probe for and highlight differences in values gathered by both methods. METHODS OCTA was performed using the swept source PLEX Elite 9000 device, software version 2.0.1.47652 (Carl Zeiss Meditec Inc., Dublin, CA, USA). Scans of 3 mm × 3 mm from healthy volunteers centred on the fovea were acquired by a well-trained certified ophthalmologist. Scans with a signal strength of 8 out of 10 or higher were included. Quantitative parameters of the 3 mm × 3 mm cube scans were automatically generated and segmented into superficial capillary plexus (SCP) and deep capillary plexus (DCP) layers using layer segmentation produced by the instrument software and prototype analysis VD quantification software (Macular Density v.0.7.1, ARI Network Hub, Carl Zeiss Meditec Inc., Dublin, CA, USA) supplied by the manufacturer. An alternative approach of quantitative analysis of VD and VLD was performed manually with ImageJ (National Institutes of Health, Bethesda, Maryland, USA), as previously reported. VD was assessed as the ratio of the retinal area occupied by vessels. VDL was measured as the total length of the skeletonised vessels using 1-pixel centre line extraction of the blood vessels. RESULTS We report differences in standard deviation (SD) in OCTA parameters obtained using different methods. The standard deviation of VD and VLD measurements was statistically significantly different in VD of 3 mm × 3 mm DCP (p = 0.009), VLD of 3 mm × 3 mm SCP (p = 0.000), and VLD of 3 mm × 3 mm DCP (p = 0.021). No statistically significant differences were found in VD of 3 mm × 3 mm SCP (p = 0.128) or VLD of 3 mm × 3 mm SCP (p = 0.107). CONCLUSIONS As expected, we were able to demonstrate significant differences in quantitative OCTA parameters gathered from the same images using different methods of quantification. Values gathered using different methods are not interchangeable. In scientific studies and in situations where long-term follow-up is necessary, the same device and the same method of quantification should be used to maintain retrospective comparability of measurements