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.
Highlights
Subretinal injections of therapeutics currently are being investigated as potential treatments for major causes
Stargardt's macular dystrophy is being studied as a therapy to prevent
as evidence suggests that dysfunction and loss of the retinal pigment epithelium (RPE) leads to photoreceptor damage
Summary
Subretinal injections of therapeutics currently are being investigated as potential treatments for major causes of blindness. Injection of healthy retinal pigment epithelium (RPE) cells into the subretinal space of eyes with age-related macular degeneration (AMD) and Stargardt’s macular dystrophy is being studied as a therapy to prevent or reverse photoreceptor injury, as evidence suggests that dysfunction and loss of the RPE leads to photoreceptor damage and vision loss in these diseases.[1,2,3,4] More recently, clinical trials involving subretinal injections of viral vectors as gene therapy for retinitis pigmentosa,[5] Leber’s congenital amaurosis.[6,7] and Leber’s hereditary optic neuropathy[8] have been conducted. RPE cells or other therapeutics from the needle.[11] This may lead to insufficient delivery of stem cells into the subretinal space or leakage of viral vectors into the vitreous body, and increase the risk of postoperative vitritis
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