Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography

Abstract

PurposeWe advance studies of subretinal treatments by developing a microscope-integrated optical coherence tomography (MIOCT) image-based method for measuring the volume of therapeutics delivered into the subretinal space.MethodsA MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging an object of known size in model eyes. This method then was applied to subretinal blebs created by injection of diluted triamcinolone. Bleb volumes obtained from MIOCT were compared to the intended injection volume and the surgeon's estimation of leakage.ResultsValidation of the image-based volume measurement method showed accuracy to ±1.0 μL (6.0% of measured volume) with no statistically significant variation under different imaging settings. When this method was applied to subretinal blebs, four of 11 blebs without surgeon-observed leakage yielded a mean volume of 32 ± 12.5 μL, in contrast to the intended 50 μL volume injected from the delivery device. This constituted a mean difference of −18 μL (mean percent error, 36 ± 25%). For all 11 blebs, the surgeon's estimations of leakage were significantly different from and showed no correlation with the volume loss based on image-based volume measurements (P < 0.001, paired t-test; intraclass correlation = 0).ConclusionsWe validated an accurate and reproducible method for measuring subretinal volumes using MIOCT. Use of this method revealed that the intended volume might not be delivered into the subretinal space. MIOCT can allow for accurate assessment of subretinal dose delivered, which may have therapeutic implications in evaluating the efficacy and toxicity of subretinal therapies.Translational RelevanceUse of MIOCT can provide feedback on the accuracy of subretinal injection volumes delivered.

Intraoperative optical coherence tomographic findings in patients undergoing subretinal gene therapy surgery

“…The iOCT detection of contrast created by the medication in the vitreous helped to reveal medication reflux in the first case. This hyper-reflective image is similar to that found in the study with triamcinolone and porcine eyes performed by Hsu et al [17].…”

“…During subfoveal medication delivery, careful real-time iOCT examination for foveal inversion was found to be important for safer medication delivery. It is felt that avoiding excessive retinal stretching may prevent complications such as macular holes in patients with very atrophic retina as noted in previous studies [17,21,22]. Identification of important dynamic real-time iOCT findings such as intraretinal fluid/schisis, suprachoroidal fluid, RPE separation and retinal folds can be helpful during the procedures (Fig.…”

“…International Journal of Retina and Vitreous *Correspondence: lauera@ohsu.edu 1 studies, iOCT was used to evaluate subretinal delivery of retinal pigment epithelial cells in animals [16]. Newer iOCT methods in porcine eyes have measured subretinal bleb volume, pointed air bubble shadowing and described other findings such as triamcinolone leakage [17]. Early studies in patients examined surgical techniques and utility of the iOCT for gene therapy by evaluating the ability to identify foveal detachment, the degree of retinal stretch, the presence of air bubbles, incidence of injection into the suprachoroidal space, patency of retinotomies, the impact of shadowing by intraocular instruments and others surgical techniques aspects [18][19][20][21][22][23].…”

What Is the Impact of Intraoperative Microscope-Integrated OCT in Ophthalmic Surgery? Relevant Applications and Outcomes. A Systematic Review

“…It is capable of recording live 3D images, which can be visualized directly into the surgeon’s oculars, providing a truly three-dimensional visualization of volumes in real-time using a novel dual-channel stereoscopic heads-up display. Some recent applications of 4D-MI-OCT are visualization of suture depth in strabismus surgery, evaluation of big-bubble formation in DALK, subretinal delivery of stem cells, and assessment of fibrovascular membranes and residual tractions in vitrectomy for proliferative diabetic retinopathy, especially in the cases of tractional retinal detachment, combined tractional-rhegmatogenous retinal detachment, and vitreous haemorrhage [ 122 , 123 , 124 , 125 , 126 , 127 ]. Moreover, 4D-MI-OCT has been used to perform transvitreal vitrectomy-assisted retinochoroidal biopsy in the case of uveal melanoma.…”

Four-Dimensional Microscope-Integrated Optical Coherence Tomography Guidance in a Model Eye Subretinal Surgery

“…Intraoperative 4D MIOCT allows for precise administration of therapeutics and accurate control over instrument location. In subretinal fluid injection maneuver, it allows for visualization of primary subretinal bleb, accurate quantity delivery 5 and secondary injection of cells. It helps to identify and thus avoid fluid escape to sub-RPE space, and fluid or cell reflux into vitreous cavity.…”