# En-Face Optical Coherence Tomography Angiography for Longitudinal Monitoring of Retinal Injury
## 5 Conclusions and Perspectives  
In this study, we demonstrated the potential utilities of combined en-face OCTA and the high-resolution B-Scans for non-invasive longitudinal assessment of progression of laser-induced injury in the retina in the small animal model. The orthographic analysis of lesion and OCTA detects features that are indicative of phases of the inflammatory response of retina. We utilized differential analysis of the lesion measurements to quantify the changes over time, detecting the phases with differential analysis. The image-based features offer desirable capability needed to investigate the transition from the early transient swelling (\(\geq\) 200 \(\upmu\)m) with a previously unidentified capillary non-perfusion (localized in the IVP/DVP microvasculature), to the later edema formation that leads to scaring and CNV. The acute injury model demonstrated that the photoreceptor ablation occurred without inducing microvascular changes. The vascular non-perfusion and remodeling in the CNV model is a new finding identified in the L-CNV injury. The non-perfusion is not a direct impact of laser damage disrupting the inner retinal vasculature as it is not present in the acute injury lesions with an equivalent total energy (fluence = intensity \(\times\) time). Furthermore, the orthographic/OCTA methodology was able to confirm that in the acute model, the microvasculature was not disrupted, and the injury was predominantly photoreceptor damage. Therefore, the depth-resolved visualization of the vascular network with OCTA is a label-free imaging technique allowing for developing an improved understanding of the vascular layer involvement retinal pathology. Vascular remodeling is a crucial component of inflammation which could not be both non-invasively and volumetrically assessed using conventional angiography techniques. However, orthographic/OCTA can track pathology and resolve the capillary alterations over time, further enabling the identification of key phases of the inflammatory progression. The two models separated the acute inflammatory response and the chronic response, highlighting days 3-7 as a critical transition phase. While this study focused on the assessment and monitoring of laser-induced damage, the methodology applies to many other retinal diseases with angiogenic components. The assessment of subtle microvascular remodeling is important for monitoring retina health due to the high oxidative demand and avascular inner layers, such as those exhibited in diabetic retinopathy and glaucoma. J.L. : Performed experiments and developed image analysis methodologies. First author on the paper. W.L. : Validated and interpreted imaging of the pathology in FA and fundus images so they could be correlated to changes in the OCTA imaging. W.Z. : Interpretation of retinal vascular biology and pathology to direct and develop animal models. M.M. : Corresponding author and Principle Investigator of the experiments. This work was supported by UT Brain grant 366611 and the Seymour Fisher Endowment (M.M. ), NIH grant EY022694 and EY026629(W.Z. ), and NEHS T32 ES007254 (J.L.) **Conflicts of Interest:** There are no competing interests to disclose. Figure 17: The OCT volume was sequentially re-sliced for en-face views with 60 \(\upmu\)m thick optical slabs. The OCTA projections (**a**–**g**) track the lesion marked with yellow crosshairs and circled in the Fluorescence Angiography (**h**). The same optical slabs are presented as traditional en-face views (**i**–**o**) however the edge gradients of the lesions are not well defined, and the boundaries are difficult to determine. (**p**) is the three-dimensional visualization of the orthographic views cutting through the center of the lesion. The bottom B-scan is the horizontal slice through the center of the lesion marked. The Superficial Vascular Plexus is highlighted in A, The Intermediate Vascular Plexus in (**b**), and the Deep Vascular Plexus in C. The Retinal pigment epithelial layer is ruptured as evidenced by the altered structure (**e**–**f**).