Faculty Bibliography

To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD).

Purpose/UNASSIGNED:To develop a machine-learning image processing model for three-dimensional (3D) reconstruction of vitreous anatomy visualized with swept-source optical coherence tomography (SS-OCT). Methods/UNASSIGNED:Healthy subjects were imaged with SS-OCT. Scans of sufficient quality were transferred into the Fiji is just ImageJ image processing toolkit, and proportions of the resulting stacks were adjusted to form cubic voxels. Image-averaging and Trainable Weka Segmentation using Sobel and variance edge detection and directional membrane projections filters were used to enhance and interpret the signals from vitreous gel, liquid spaces within the vitreous, and interfaces between the former. Two classes were defined: "Septa" and "Other." Pixels were selected and added to each class to train the classifier. Results were generated as a probability map. Thresholding was performed to remove pixels that were classified with low confidence. Volume rendering was performed with TomViz. Results/UNASSIGNED:Forty-seven eyes of 34 healthy subjects were imaged with SS-OCT. Thirty-four cube scans from 25 subjects were of sufficient quality for volume rendering. Clinically relevant vitreous features including the premacular bursa, area of Martegiani, and prevascular vitreous fissures and cisterns, as well as varying degrees of vitreous degeneration were visualized in 3D. Conclusions/UNASSIGNED:A machine-learning model for 3D vitreous reconstruction of SS-OCT cube scans was developed. The resultant high-resolution 3D movies illustrated vitreous anatomy in a manner like triamcinolone-assisted vitrectomy or postmortem dye injection. Translational Relevance/UNASSIGNED:This machine learning model now allows for comprehensive examination of the vitreous structure beyond the vitreoretinal interface in 3D with potential applications for common disease states such as the vitreomacular traction and Macular Hole spectrum of diseases or proliferative diabetic retinopathy.

INTRODUCTION/UNASSIGNED:Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. AREAS COVERED/UNASSIGNED:imaging of human hyalocytes. EXPERT OPINION/UNASSIGNED:Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

PURPOSE/OBJECTIVE:To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging. METHODS:We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions. RESULTS:A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION/CONCLUSIONS:Our review serves to strengthen the OCT nomenclature "bacillary layer detachment", based on specific reflectance information obtained by OCT and previously published histologic observations.

Proliferative diabetic retinopathy (PDR) is a major cause of blindness in diabetic individuals. Optical coherence tomography (OCT) and OCT-angiography (OCTA) are noninvasive imaging techniques useful for the diagnosis and assessment of PDR. We aim to review several recent developments using OCT and discuss their present and potential future applications in the clinical setting. An electronic database search was performed so as to include all studies assessing OCT and/or OCTA findings in PDR patients published from 1 January 2020 to 31 May 2021. Thirty studies were included, and the most recently published data essentially focused on the higher detection rate of neovascularization obtained with widefield-OCT and/or OCTA (WF-OCT/OCTA) and on the increasing quality of retinal imaging with quality levels non-inferior to widefield-fluorescein angiography (WF-FA). There were also significant developments in the study of retinal nonperfusion areas (NPAs) using these techniques and research on the impact of PDR treatment on NPAs and on vascular density. It is becoming increasingly clear that it is critical to use adequate imaging protocols focused on optimized segmentation and maximized imaged retinal area, with ongoing technological development through artificial intelligence and deep learning. These latest findings emphasize the growing applicability and role of noninvasive imaging in managing PDR with the added benefit of avoiding the repetition of invasive conventional FA.

BACKGROUND:Blood is one of the main absorbers in the near-infrared spectrum and thus retinal vessels appear dark in near-infrared reflectance (NIR) images. Proliferative diabetic retinopathy (PDR) is characterized by abnormal neovascularization which also absorbs light and appears dark against a lighter fundus background. We analyzed neovascularization in PDR using NIR imaging, by observing changes in the neovascular complexes (NVCs) contrast and reflectivity over time. METHODS:Retrospective case series of 20 eyes of 17 patients with PDR who underwent NIR imaging with optical coherence tomography (OCT) using the Spectralis System. NVCs presence and activity was determined using clinical, tomographic and angiographic criteria. At baseline, all NVCs were qualitatively graded in the NIR image into 3 groups (absent, present and inactive and present and active) and their evolution over time was registered as progression, regression or same status. RESULTS:Twenty-seven NVCs were imaged, of which, 52% were neovascularization of the disc (NVD) and 48% were elsewhere (NVE). Consecutive NIR images were obtained from baseline to up to 5 time-points with a mean follow-up of 3.2 ± 1.7 years. All eyes underwent laser treatment and 30% had additional intravitreal therapy. Using NIR imaging, NVCs were classified at baseline as absent, present and inactive and present and active, respectively in 11, 4 and 85% of cases. NIR identified active neovascularization as hyporeflective irregular dark vessels originating from the retinal venules in NVE or from the disc in NVD. In all groups during follow-up, progression was identified as the development of new vascular hyporeflective dark fronds while regression was shown by reduced dark perfusion. Five eyes developed a wolf's jaw configuration with vascular hyporeflective new vessels and hyperreflective tissue from extensive fibrosis. Fibrosis was more apparent in later images, reaching 86%. In 3 cases (11%), the NVC was no longer seen in NIR, although was still identifiable on OCT over the NVC area. CONCLUSIONS:NIR is a non-invasive imaging modality commonly performed alongside OCT and frequently overlooked which can be useful to evaluate NVCs in PDR. Changes in NVC contrast and reflectivity due to blood perfusion can help in the detection and monitoring of diabetic proliferative disease and aid clinicians in daily practice.

PURPOSE/OBJECTIVE:Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN/METHODS:Multicenter, retrospective cohort study. PARTICIPANTS/METHODS:Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS:Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES/METHODS:Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS:The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS:The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.