Lejla Vajzovic

Purpose: To present the management and outcomes of a case of an acute submacular hemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: A single case was retrospectively evaluated. Results: A 79-year-old man with a history of submacular hemorrhage from nAMD and persistent disease activity in the left eye presented with an acute submacular hemorrhage in his better-seeing right eye, which was previously closely monitored for an extrafoveal serous pigment epithelial detachment without exudation. The patient received intravitreal antivascular endothelial growth factor (anti-VEGF) and subsequently had pars plana vitrectomy with subretinal tissue plasminogen activator and gas tamponade. After 5 days of face-down positioning, the hemorrhage was successfully displaced from the fovea. Recurrent disease activity 2 weeks postoperatively prompted intensive biweekly anti-VEGF therapy. By postoperative month 5, the patient’s visual acuity improved from 20/400 to 20/70 OD. Conclusions: This case highlights the importance of close monitoring of patients with nAMD who exhibit aggressive disease as well as the efficacy of prompt surgical intervention and increased anti-VEGF frequency for large submacular hemorrhages.

Retinal diseases such as age-related macular degeneration, diabetic retinopathy, and uveitic macular edema are leading causes of visual impairment.^{1 – 3} Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents and/or steroids have been effective in controlling vascular leakage and often restoring visual acuity but require repeated injections. Novel treatments such as intravitreal reservoirs or subretinal injections of gene therapies can be effective over a longer period but may cause glaucoma and cataract (in the case of steroids) or incur the cost and complexity of delivery in a microsurgical setting (in the case of subretinal gene therapy).⁴ This has led to the development of ocular therapeutics that can be delivered by transscleral injection into the suprachoroidal space in an office-based procedure.⁵ Triamcinolone suspension via suprachoroidal injection was approved in 2021 by the U.S. Food and Drug Administration for the treatment of uveitic macular edema, and clinical trials are underway using this delivery route for other posterior segment diseases. A limitation of this procedure is that clinicians are unable to obtain real-time feedback on the location and spread of the delivered product; rather, heat map imaging is used to estimate this.⁵

Significance Imaging deep structures with optical coherence tomography (OCT) is difficult in highly scattering biological tissue, such as the sclera. There is a need to visualize the suprachoroidal space and choroid through the sclera to study suprachoroidal drug delivery. Aim We aim to develop optical methods to image through the highly scattering sclera with a custom-built OCT system to visualize the suprachoroidal space and drug delivery within. Approach We developed a custom handheld OCT scanner to image the anterior segment and suprachoroidal space in ex vivo eye models. Tartrazine (Yellow 5) solution, which has been shown to optically clear biological tissue in the visible regime, was tested as a clearing agent to optimize near infrared OCT imaging through the sclera. Results Tartrazine dramatically increased OCT signal return from the deeper sclera and choroid and thus enabled visualization of the suprachoroidal drug delivery after transscleral injection. Conclusions We demonstrated successful optical clearing of the thick, porcine sclera with a compact handheld OCT system to image the suprachoroidal space. We believe there is broader potential to use optical clearing with handheld OCT for a variety of previously inaccessible, highly scattering tissue samples.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT–measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm² in Patient 1, 55 mm² in Patient 2, and 106 mm² in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image–based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT–obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.