Purpose Acute central retinal artery occlusion (CRAO) induces ischaemic retinal oedema. The purpose of this study was to define sensitivity and specificity of optical coherence tomography (OCT) based retinal thickness analysis in determining ischaemia onset in CRAO. Methods The relative retinal thickness increase (RRTI) in comparison with the fellow eye was analysed retrospectively in OCT scans of 66 patients diagnosed with CRAO between January 2010 and December 2019 within 48 hr of ischaemia onset. The natural course of RRTI and the sensitivity and specificity of OCT‐based determination of ischaemia onset in identifying CRAO within 4.5 hr using the RRTI were evaluated. Results Relative retinal thickness increase (RRTI) in acute CRAO follows a hyperbolic curve with a steep incline within the early phase after which it reaches a plateau. Optical coherence tomography (OCT)‐based retinal thickness analysis in CRAO allows to differentiate patients with ischaemia onset within the past 4.5 hr or thereafter with a sensitivity of 100% and a specificity of 94.3%. Conclusion Relative retinal thickness increase (RRTI) allows to identify CRAO patients that are eligible for a potentially beneficial reperfusion therapy within a therapeutic window of 4.5 hr with a high accuracy. Especially in patients with unknown ischaemia onset, this diagnostic tool could be of major importance in the future clinical management.
Human corneas usually are not available for research, as they are used for transplantation only. At the same time, scientific studies on cultured human endothelial cells can produce misleading results due to inevitable dedifferentiation. Therefore, an organ-culture model of porcine corneas-displaying endothelial cell death rates comparable to those of cultured human corneas-would be very desirable. Fresh pig eyes were prepared under sterile conditions to obtain corneoscleral buttons, corneal buttons and so called "split corneal buttons" (new preparation method) and cultivated for 15 days. Morphology of the endothelial cell layer was observed by light microscopy on day 1, 8 and 15. On day 15 staining with trypan blue and alizarin red S was performed. Photographs were evaluated in a randomized, blinded manner. Here, the morphology of the corneal endothelium and the number of endothelial cells per mm were analyzed. After 15 days of cultivation the endothelial cell layer was maintained only in corneal buttons and split corneal buttons. Alizarin red S stained areas and the existence of polymorphisms like rosette figures and reformation figures were significantly less frequent in split corneal buttons than in corneal buttons. Loss of endothelial cells was significantly greater in corneal buttons [575 ± 25/250 cells/mm (median ± 25%/75%-quantile); 14.8%] than in split corneal buttons [417 ± 138/179 cells/mm (median ± 25%/75%-quantile); 10.2%]. The new preparation method of split corneal buttons allows the cultivation of porcine corneas for 2 weeks with cell death rates comparable to those of the corresponding human tissue in cornea banks without the need to add de-swelling additives to the media. This is therefore a simple and highly reliable method model to be applied in intervention studies on corneal endothelial cells in their natural compound.
Purpose The purpose of this study was to establish a standardized in vitro phacoemulsification damage model for future investigations of the effects of phacoemulsification, surgical devices, protective ophthalmic viscoelastic devices (OVDs), irrigation solutions and other aspects related to cataract phacoemulsification surgery on the corneal endothelium using porcine eyes. Methods Thirty‐four porcine eyes were randomly assigned to three groups (phacoemulsification (n = 13), irrigation (n = 9), control (n = 12)). A total of 5 min of ultrasound energy with intermittent irrigation/aspiration was applied in the eyes of the phacoemulsification group. The eyes of the irrigation group received the identical treatment, but without the application of ultrasound energy. The control group was left untreated. All eyes were then prepared to split corneal buttons followed by 15 days of cultivation. Endothelial cell density (ECD) was assessed blinded on day 15. Results Endothelial cell density declined significantly more until day 15 in the phacoemulsification group (2567 ± 317/267 cells/mm² (median ± 25%/75%‐quartiles), −32.5 ± 7.0/6.4%) compared to the irrigation (3450 ± 350/383 cells/mm², −11.8 ± 5.3/2.6%; p < 0.001) and the control group (3650 ± 288/258 cells/mm², −10.2 ± 3.2/4.6%; p < 0.001). Conclusion The phacoemulsification damage model presented in this study is sensitive to phacoemulsification energy and may reliably be used to investigate various factors involved in phacoemulsification with regard to their influence on corneal endothelial cells. This method is able to replace animal experiments or in vitro cell culture experiments that often do not translate well to the in vivo situation in humans.
PurposeTime is the key criterion in the management of non‐arteritic central retinal artery occlusion (NA‐CRAO). However, the precise onset of vision loss is often difficult to determine. This study aimed to evaluate the temporal changes of retinal thickness in acute NA‐CRAO and the potential of this parameter to be used as a surrogate marker to estimate the onset of retinal ischaemia.MethodsOptical coherence tomography was used to continuously assess retinal thickness and oedema progression rate in six porcine eyes. Additionally, a retrospective analysis of 12 patients with acute NA‐CRAO was performed to determine association strength and progression rate between retinal thickness and onset of ischaemia. All Optical coherence tomography (OCT) scans (pigs and NA‐CRAO patients) were performed within an ischaemic time frame of up to 9 hr.ResultsRetinal oedema progression rate in pigs was 25.32 µm/hr [CI 95%: 24.24–26.40 µm/hr]. Retrospective analysis of the patients revealed a strong correlation between retinal oedema and duration of ischaemia (Spearman's rho = 0.77, p = 0.004) with an estimated progression rate of 10.02 µm/hr [CI 95%: 3.30–16.74 µm/hr].ConclusionRetinal thickness increases with oedema formation, and ischaemia onset is strongly correlated with this structural biomarker in both, pigs and NA‐CRAO patients. Prospective clinical trials will have to determine the clinical feasibility of retinal thickness measurements as a biomarker to support clinical management of NA‐CRAO.
Acute central retinal artery occlusion (CRAO) induces a time-dependent increase in retinal thickness. By manually measuring the relative retinal thickness increase (RRTI) in comparison to the contralateral eye based on optical coherence tomography (OCT), ischemia onset within the past 4.5 hours could be determined with 100% sensitivity and 94.3% specificity. To enable examiner-independent and quicker diagnostics, we analyzed the RRTI using the automatic retinal thickness measurement. In this retrospective study, 28 eyes were evaluated with an acute CRAO (<46 hours). All patients received a Spectralis SD-OCT image of both eyes. The RRTI was calculated for the ETDRS sectors using the Segmentation Module for Single Retinal Layer Analysis. Receiver operating characteristic (ROC) analysis was performed to determine patients ≤4.5 hours by RRTI. In all sectors, time to OCT (TTO) and RRTI correlated positively. The optimal cutoff point to detect CRAOs ≤4.5 hours was between 18.7% nasally and 22.9% RRTI temporally. Sensitivity and specificity varied between the sectors with 90–95% sensitivity and 89–100% specificity. In conclusion, the automatic measurement of RRTI also allows the differentiation of CRAOs within a possible therapeutic time window ≤4.5 hours and CRAOs ≥4.5 hours with a high sensitivity and specificity. Additionally, it offers quicker, easier, and a user-independent assessment of ischemia onset, helping to set a base for establishing automatic indices generated by the OCT machines.
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