Faculty Bibliography

INTRODUCTION/BACKGROUND:Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option. MATERIALS AND METHODS/METHODS:A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage. RESULTS:Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries. CONCLUSION/CONCLUSIONS:The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships.

PURPOSE/OBJECTIVE:To present a clinicopathologic correlation of indolent, non-progressive multifocal choroidal lesions, clinically presumed to be lymphoid in nature, using multimodal imaging and histopathological analysis of a donor eye. DESIGN/METHODS:Case study and clinicopathologic correlation. PARTICIPANT/METHODS:A 77-year-old man of Caucasian ancestry was followed for nineteen years with indolent non-progressive multifocal choroidal infiltration of his right eye, presumed to be lymphocytic in nature based on the appearance of the lesions. METHODS:Multimodal imaging including fundus photography, B-scan ultrasonography, optical coherence tomography, fluorescein angiography, and indocyanine green angiography were performed throughout 19 years of follow up prior to the patient's death. The involved eye was preserved 21 hours postmortem and analyzed using standard histopathological and immunohistochemical techniques. MAIN OUTCOME MEASURES/METHODS:Correlation of findings on multimodal imaging with histopathological and immunohistochemical findings in the involved eye. RESULTS:Clinical examination over the course of 19 years showed no deterioration in visual acuity of the involved eye. Multimodal imaging revealed yellow-orange choroidal lesions that showed no appreciable progression during the 19 year follow up. These areas stained minimally on fluorescein angiography. Indocyanine green angiography revealed tortuous choroidal vessels and fluorescence blockage. Enhanced-depth imaging optical coherence tomography revealed hyporeflective homogenous choroidal thickening. Light microscopy, histopathology, and immunohistochemistry showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were most consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). CONCLUSIONS:Indolent non-progressive multifocal choroidal lymphoid lesions in this patient remained confined to the choroid on clinical examination and imaging for almost two decades, with no clinical evidence of extension into the retina. Light microscopy, histopathology, and immunohistochemistry postmortem showed that the lesions were composed of small, mature-appearing B-cells that spared the choriocapillaris. The findings were consistent with an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). This entity is distinct from more aggressive uveal and choroidal lymphoma and is expected to remain relatively stationary on long-term clinical follow-up, with a good visual prognosis.

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/OBJECTIVE:To develop a consensus nomenclature for reporting optical coherence tomography angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN/METHODS:Delphi-based survey SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising two rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The four main areas of consensus were: definition of parameters of "widefield (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study endpoint was defined by the degree of consensus for each question: "strong consensus" was defined as ≥ 85% agreement, "consensus" as 80-84% and "near consensus" as 70-79%. MAIN OUTCOME MEASURES/METHODS:Consensus and near-consensus on OCTA nomenclature in retinal vascular disease RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥ 30% of absolute imaged area. The presence of new vessels (NV) and intra-retinal microvascular abnormalities (IRMAs), the foveal avascular zone (FAZ) parameters, the presence and amount of "no flow" area and the assessment of vessel density in various retinal layers should be added for the staging and classification of DR. Decreased flow ≥ 30% of the absolute imaged area should define an ischemic central retinal vein occlusion (CRVO). Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS:This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

Non-exudative macular and choroidal neovascularization (MNV and CNV) usually refers to the entity of treatment-naïve type 1 neovascularization in the absence of associated signs of exudation. Histopathological studies, dating back in the early 70s, identified the presence of non-exudative MNV, but the first clinical report of this finding was in the late 90s using indocyanine green angiography in eyes with age-related macular degeneration (AMD). With more advanced retinal imaging, there has been an ever increasing appreciation of non-exudative MNV associated with AMD and CNV with other macular disorders. However, consensus regarding the exact definition and the clinical management of this entity is lacking. Furthermore, there may be variation in the imaging features and clinical course suggesting that a spectrum of disease may exist. Herein, we review the large body of published work that has provided a better understanding of non-exudative MNV and CNV in the last decade. The prevalence, multimodal imaging features, clinical course, and response to treatment are discussed to elucidate further key insights about this entity. Based on these observations, this review also proposes a new theory about the origin and course of different sub-types of non-exudative MNV/CNV which can have different etiologies and pathways according to the clinical context of disease.

PURPOSE/OBJECTIVE:To characterize relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization (MNV) and visual responses to ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS:This was a post hoc analysis of the phase 3 HARBOR trial of ranibizumab in nAMD. Analyses included ranibizumab-treated eyes with baseline multimodal imaging data; baseline MNV; subretinal and/or intraretinal fluid at screening, baseline, or week 1; and spectral-domain optical coherence tomography images through month 24 (n = 700). Mean best-corrected visual acuity (BCVA) over time and mean BCVA change at months 12 and 24 were compared between eyes with type 1, type 2/mixed type 1 and 2 (type 2/M), and any type 3 MNV at baseline. RESULTS:At baseline, 263 (37.6%), 287 (41.0%), and 150 (21.4%) eyes had type 1, type 2/M, and any type 3 lesions, respectively. Type 1 eyes had the best mean BCVA at baseline (59.0 [95% CI: 57.7-60.3] letters) and month 24 (67.7 [65.8-69.6] letters), whereas type 2/M eyes had the worst (50.0 [48.6-51.4] letters and 60.8 [58.7-62.9] letters, respectively). Mean BCVA gains at month 24 were most pronounced for type 2/M eyes (10.8 [8.9-12.7] letters) and similar for type 1 (8.7 [6.9-10.5] letters) and any type 3 eyes (8.3 [6.3-10.3] letters). CONCLUSION/CONCLUSIONS:Differences in BCVA outcomes between CONAN lesion type subgroups support the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier: NCT00891735. Date of registration: April 29, 2009.

Imaging is an integral part of the evaluation and management of retinal disorders. Each imaging modality has its own unique capabilities and can show a different aspect or perspective of disease. Multimodal retinal imaging provides a wealth of substantive and insightful information; however, the integration of all this complex data can be overwhelming. We discuss the applications and the strengths and limitations of the many different retinal imaging tools that are approved for clinical use. These modalities include color fundus photography, widefield imaging, fundus autofluorescence, near infrared reflectance, optical coherence tomography angiography, and en face optical coherence tomography. We also cover the advantages and disadvantages of a multimodal approach.

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.