Ectasia Detection by Anterior Segment Optical Coherence Tomography in Scheimpflug Tomographically Normal Keratoconus Fellow Eyes.

PURPOSE: The purpose of this study was to determine whether the Scheimpflug tomographically normal fellow eyes of keratoconus patients are also classified as normal using an ectasia screening algorithm based on anterior segment optical coherence tomography (AS-OCT). METHODS: This monocentric cross-sectional study included 22 very asymmetric ectasia patients with tomographically significant keratoconus in 1 eye and normal Scheimpflug tomography in the fellow eye. Twenty-two eyes of 22 healthy subjects served as a control group. We performed corneal tomography using Pentacam AXL (Oculus, Wetzlar, Germany) and used Belin/Ambrósio Enhanced Ectasia total deviation index as well as Belin ABCD keratoconus classification to identify Scheimpflug tomographically normal eyes. We also performed AS-OCT using Anterion (Heidelberg Engineering, Heidelberg, Germany) and analyzed for the presence of ectasia using the Screening Corneal Objective Risk of Ectasia (SCORE) algorithm, with positive values indicating ectasia suspect tomography. RESULTS: The SCORE value was positive in 9.1% (n = 2) of the healthy eyes, in 45.5% (n = 10) of the Scheimpflug tomographically normal eyes of keratoconus patients and in all eyes (n = 22) with tomographically significant keratoconus. The Scheimpflug tomographically normal eyes of keratoconus patients had higher SCORE values compared with healthy controls (P < 0.001). The median (interquartile range) SCORE value was -1.7 (1.3) in healthy controls, -0.5 (2.2) in Scheimpflug tomographically normal eyes of keratoconus patients, and 11.1 (11.0) in tomographically significant keratoconus eyes. CONCLUSIONS: The Scheimpflug tomographically normal fellow eyes of keratoconus patients had higher AS-OCT-based SCORE values than healthy controls, with positive SCORE values found in 46% of the eyes, indicating early tomographic ectatic changes.

Longitudinal Evaluation of Biomechanical Indices in Fellow Eyes of Patients With Keratoconus Classified as Having Very Asymmetric Ectasia With Normal Topography.

PURPOSE: To evaluate the biomechanical longitudinal variability and progression of tomographically normal fellow eyes of patients with keratoconus. METHODS: Of 513 patients with keratoconus, 30 patients with tomographically normal fellow eyes were included in this study. Tomographic and biomechanical parameters of the Pentacam and Corvis ST (Oculus Optikgeräte GmbH) were analyzed in multiple follow-up examinations, including the ABCD grading, Belin/Ambrósio Enhanced Ectasia total deviation index (BAD-D), Corvis Biomechanical Index (CBI), Corvis Biomechanical Factor (CBiF), and Tomographic and Biomechanical Index (TBI). A mixed regression model was applied. The results were compared to a healthy control group (n = 17) and a keratoconus group (n = 20). RESULTS: Within a maximum observation period of 3.3 years, no fellow eye (0%) showed a progression to tomographically evident keratoconus. No significant change in tomographic or biomechanical parameters was detected over the study period. The indices BAD-D, CBI, CbiF, and TBI exhibited a certain variability over time, whereas the tomographic ABC parameters and maximum keratometry barely changed. This was also shown in the control group and for all parameters in the keratoconus group, except the TBI. CONCLUSIONS: During the observation period none of the normal fellow eyes progressed to tomographically detectable keratoconus. However, biomechanical parameters CBI, CbiF, and TBI showed pathological values in 43.3% of eyes and certain variability. Subsequent studies with a longer observation period are warranted to confirm the biomechanical trends seen in this study and to rate the ability of single measurements to diagnose early keratoconus. [J Refract Surg. 2024;40(1):e48-e56.].

Fusarium Keratitis on the Rise - a Clinical Review. / Die Fusarien-Keratitis auf dem Vormarsch ­ eine aktuelle klinische Übersicht.

Fungal keratitis due to Fusarium species is a rare but serious ocular disease. Due to its rapid progression, often late diagnostic confirmation as well as limited topical treatment options, this is potentially sight threatening. Increasing contact lens use and global climate change have been suggested to be factors leading to an increase in cases of fusarium keratitis, even in regions with moderate climate. Early recognition and initiation of antimycotic treatment, as well as early surgical treatment by penetrating keratoplasty are decisive for the outcome.

Biomechanical Analysis of Tomographically Regular Keratoconus Fellow Eyes Using Corvis ST. / Biomechanische Analyse von tomografisch unauffälligen Keratokonus-Partneraugen mit dem Corvis ST.

BACKGROUND: Keratoconus is a bilateral, yet asymmetric disease. In rare cases, the second eye may show no signs of tomographic changes. The purpose of this study was to analyze the biomechanical characteristics in tomographically regular keratoconus fellow eyes. MATERIALS AND METHODS: This retrospective, consecutive case series analyzed 916 eyes of 458 patients who presented to our keratoconus clinic between November 2020 and October 2022. Primary outcome measures included best-corrected visual acuity (BCVA), tomographic Scheimpflug analysis using Pentacam AXL (Oculus, Wetzlar, Germany), and biomechanical assessment using Corvis ST (Oculus, Wetzlar, Germany). Tomographic changes were assessed via analysis of the anterior and posterior curvature, K-max, thinnest corneal thickness (TCT), the Belin/Ambrosio Deviation Display (BAD-D), and the ABCD-Grading. Biomechanical changes were analyzed using Corvis Biomechanical Index (CBI) and Tomographic Biomechanical Index (TBI). RESULTS: Of 916 eyes, 34 tomographically regular fellow eyes (7.4%) were identified and included in the analysis. Overall, the mean BCVA was - 0.02 ± 0.13 logMAR. Tomographic analysis showed mean K-max of 43.87 ± 1.21 D, mean TCT of 532 ± 23 µm, and mean BAD-D of 1.02 ± 0.43. Biomechanical analysis demonstrated mean CBI of 0.28 ± 0.26 and mean TBI of 0.34 ± 0.30. While normal CBI-values were observed in 16 (47%) of 34 eyes, only 13 eyes (38%) showed a regular TBI and only 7 eyes (21%) showed regular TBI and CBI. The sensitivity of CBI and TBI to detect a tomographically normal keratoconus fellow eye was 53% and 62%, respectively. CONCLUSION: A highly asymmetric corneal ectasia with regular tomographic finding in a fellow eye is rare among keratoconus patients. In such cases, a biomechanical analysis may be useful in detecting early signs of corneal ectasia. In our analysis, the TBI showed high sensitivity for detecting a biomechanical abnormality in tomographically regular fellow eyes.

[Fusarium Keratitis-an upcoming threat in Germany?] / Keratitis durch Fusarien ­ eine zunehmende Bedrohung in Deutschland?

BACKGROUND: Fungal keratitis due to Fusarium species is known to be typical of developing countries; however, with the increasing use of contact lenses a rise of Fusarium keratitis has been observed in Germany. METHODS: In a monocentric retrospective study, we analyzed all patients who presented to our university eye hospital with infectious keratitis between January 2011 and December 2021 and had a proof of Fusarium species in either microscopy, culture or PCR. RESULTS: We could identify 13 patients with a proof of Fusarium species. A significant increase of cases in 2021 was observed. In 76.9% of our cases the patients were female and in 76.9% the patients had a history of prior contact lens use. In only 4 cases the initial corneal sample gave a positive result for Fusarium. On average the suspicion of fungal keratitis arose 13.1 days after onset of symptoms, correct diagnosis was achieved after 14.6 days. All isolated specimens showed resistance against at least one of the common fungicides. In 70% of our cases treatment with penetrating keratoplasty was necessary. The patients showed a 57.1% recurrence rate after penetrating keratoplasty. In 80% of our cases best documented visual acuity after Fusarium keratitis was ≤ 0.4. CONCLUSION: Due to difficult detection and a high resistance rate to common antifungals, Fusarium keratitis is prone to delayed diagnosis and limited treatment outcomes. Whenever risk factors are present and infectious keratitis does not respond to antibiotics, antimycotic treatment must be initiated. Early keratoplasty may be necessary.

Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model.

Clinically relevant brain metastases (BMs) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors in this process are not well understood. Here, in vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-term arrest. An extensive clot embedded ∼20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, the generation of tissue factor-mediated thrombin by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and the formation of brain macrometastases. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall formation of BMs. In conclusion, our data show that plasmatic coagulation is activated early by intravascular tumor cells in the brain with subsequent clot formation, which led us to discover a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for trials on prevention of BMs.

Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells.

Brain metastases (BM) are an ever-increasing challenge in oncology, threatening quality of life and survival of many cancer patients. The majority of BM originate from lung adenocarcinoma, and stage III patients have a risk of 40-50% to develop BM in the first years of disease onset. As therapeutic options are limited, prevention of their occurrence is an attractive concept. Here we investigated whether Nintedanib (BIBF 1120), a tyrosine kinase inhibitor (TKI) targeting the VEGF pathway approved for lung adenocarcinoma, and the dual anti-VEGF-A/Ang2 nanobody BI836880 have the potential to prevent BM formation. A mouse model of brain metastasis from lung adenocarcinoma was used in which tumor cells were injected intracardially. Metastases formation occurred inside and outside of the brain and was followed by MRI, IVIS, and immunohistochemistry. BM were reduced in volume and number by both Nintedanib and the dual anti-VEGF-A/Ang2 nanobody, which translated into improved survival. Both compounds were able to normalize cerebral blood vessels at the site of brain metastatic lesions. Extracranial metastases, however, were not reduced, and meningeal metastases only partially. Interestingly, unspecific control IgG also lead to brain vessel normalization and reduction of brain and meningeal metastases. This data indicates a brain-specific group effect of antiangiogenic compounds with respect to metastasis prevention, most likely by preventing an early angiogenic switch. Thus, Nintedanib and BI836880 are promising candidates for future BM preventive study concepts in lung adenocarcinoma patients.