Development and evaluation of a novel device to standardise intravitreal injections in rabbits
Creators: name: Williams, Ruth
name: Cook, Fiona
name: Fulleylove, Michael
name: Campbell, Simon
name: Pearson, Allen
Publisher: name: F1000 Research Limited
Year: 2019

description: Rabbits are frequently used for ocular pharmacokinetic studies owing to clinical translatability. High levels of expertise and dexterity are required to inject into the rabbit eye with consistency and precision. Acquisition and maintenance of skills can be challenging if the technique is carried out infrequently or if it is a new technique for a research group.<br><br> The location of drug deposition within the vitreous influences the pharmacokinetics (PK) of compounds injected into the eye. Standardisation of this location across various operators with various degrees of skills and dexterity is likely to lead to reduced variability and increased reproducibility of PK data. We therefore developed a device which fixates the needle penetration point, needle angle and depth of injection.<br> We hypothesised that the device will increase the precision of injection (reduced variability) compared to freehand injection and that this would be true for experienced operators as well as novices.<br><br> In order to design the device anatomical data of the rabbit eye was collected and used to generate a computer model. Prototype devices were produced using 3D printing. These were tested on a 3D model of the rabbit eye before selecting the final design which was produced by injection moulding. The device was tested on fresh rabbit cadavers with in situ eyes. Contrast agent deposition within the vitreous was analysed using magnetic resonance imaging (MRI).The needle penetration point was analysed using histopathology.<br><br> Results comparing the location of contrast agent within the vitreous using MRI demonstrated that both freehand and device-guided injections achieved acceptable mid-vitreal locations. While over half (6/9) of the free-hand injections resulted in contrast agent being deposited in direct proximity of the lens, none of the device-guided injections (0/11) were deposited in this location. This finding can be interpreted as a safety benefit of the device, as injections which are close to the lens might cause damage to the lens which would inevitably lead to loss of data from the affected animal.<br><br> Results evaluating the needle penetration point using histopathology showed that the experienced operator achieved precise results both using the device and free-hand injections. Contrary to our hypothesis novice operators achieved less precise results using the device compared to free-hand injections. This finding indicates that the device cannot replace dexterity and experience. Novices might be able to achieve better results with further hands-on training and the 3D model of the rabbit eye produced during this study might be a beneficial tool for this training.<br><br> The current study describes the development of a device which aims to standardise intravitreal injections in rabbits. While the device does not seem to have a clear benefit with regards to reducing variability and increasing reproducibility of needle penetration site, the device is likely to offer a safety benefit over free-hand injections by depositing the injected compound further away from the lens.<br><br> Further in vivo studies will be required to assess the device with regards to safety and its effect on reproducibility of pharmacokinetic data.