Faculty Bibliography

PURPOSE/OBJECTIVE:To describe the long-term findings of a patient with Sorsby fundus dystrophy treated with corticosteroids and propose a mechanism by which the results were obtained. METHODS:Comprehensive ophthalmologic examination with multimodal imaging to include optical coherence tomography and optical coherence tomography angiography was used to evaluate a patient with Sorsby fundus dystrophy treated with intravitreal triamcinolone. RESULTS:A 35-year-old woman presented in 2003 with aggressive macular neovascularization in both eyes; her visual acuity was 20/25 in the right and 20/400 in the left eye. She previously had photodynamic therapy without apparent benefit. She was then treated with photodynamic therapy and an intravitreal injection of 4 mg of triamcinolone, which caused the neovascularization to become inactive. She was eventually switched to an intravitreal injection of triamcinolone 4 mg every 3 to 4 months in the right eye. She had no further treatment in the left eye because of extensive scarring. After 15 1/2 years of treatment, her visual acuity in the right eye was 20/20. Optical coherence tomography showed a large, low-level, irregular elevation of the retinal pigment epithelium. optical coherence tomography angiography revealed widespread macular neovascularization, and the choriocapillaris showed extensive loss. The patient had a TIMP-3 mutation, c.610A>T (p.Ser204Cys). CONCLUSION/CONCLUSIONS:TIMP3 has numerous effects including controlling vascular endothelial growth factor signaling and tumor necrosis factor alpha production. Corticosteroids have the potential to modulate both cytokines. This is the longest reported treatment follow-up of Sorsby fundus dystrophy with macular neovascularization, and the patient retained excellent visual acuity.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.

PURPOSE/OBJECTIVE:To describe imaging produced by machine learning-based segmentation of high-resolution optical coherence tomography imaging of the intermediate capillary plexus and deep capillary plexus, layers of vessels not imaged well by dye-based angiography. METHODS:Three healthy subjects with no ocular problems were imaged with spectral domain optical coherence tomography using an instrument with a scanning speed of 85,000 A-scans per second and 3 µm axial optical resolution. A random forest segmentation strategy was used to segment the intermediate capillary plexus and deep capillary plexus. The depth-resolved imaging data was visualized with the help of volume rendering. RESULTS:The high-resolution optical coherence tomography showed the intermediate capillary plexus and deep capillary plexus at the outer borders of the inner nuclear layer. These vessels could be visualized with unprecedented detail in three dimensions. There were multiple bridging vessels connecting to the whorl-like patterns of capillary mesh of the deep capillary plexus, a feature only previously imaged in histologic evaluation of excised eyes. CONCLUSION/CONCLUSIONS:High-resolution optical coherence tomography, machine learning, and advanced image display techniques have wide relevancy in studying the retina in health and disease. Application of this approach has provided images of the deeper vascular layers of the eye that approximate histologic imaging, but noninvasively.

PURPOSE/OBJECTIVE:To determine the dose-response characteristics of the anti-vascular endothelial growth factor agents ranibizumab and aflibercept in neovascular age-related macular degeneration (NAMD) using published randomized trials and observational series. METHODS:Literature review of published series from 2006 - 2018 as determined from electronic searches of PubMed and the Cochrane Library. Data extracted included treatment strategy, frequency and first year visual acuity response. Monthly or bimonthly treatment schedules were classified as Fixed, pro re nata studies as PRN, treat and extend as TE, and when no strategy was listed, as Variable. RESULTS:Of 2062 citations retrieved, 96 were deemed eligible; these 96 citations provided 120 data points of dose frequency versus visual acuity change in year 1 of treatment. The dose response curve was nonlinear, but a log transform of the number of injections per year yielded a linear relationship defined by the expression, Letters of Improvement = -6.66 + 15.7*log (Number of Injections Year 1). After accounting for the number of injections neither the drug used (ranibizumab or aflibercept) nor the strategy employed (Fixed, PRN, TE, or Variable) were significant predictors of acuity change. As a group, studies using the PRN approach had the lowest number of injections and the worst acuity improvements as a treatment strategy. CONCLUSIONS:There appears to be a predictable, mathematically defined relationship between dose frequency and visual acuity change at 1 year in NAMD. The performance of current treatment efforts, as suggested by reported series and Medicare claims data, appears to be substandard.

PURPOSE/OBJECTIVE:To quantify retinal vasculature changes in Stargardt disease1 with volume-rendered optical coherence tomography angiography (OCTA). METHODS:OCTA volumes from heathy subjects and two subgroups of STGD1 patients with the presence/absence of definitely decreased autofluorescence (DDAF) areas were compared. OCTA vessel surface area (VSA) and vessel volume (VV) were measured in central zones (Z) of 1, 2 and 3mm diameter. RESULTS:29 eyes of 15 STGD1 patients (20/9 eyes with/without DDAF) and 30 eyes of 15 controls contributed data. An enlarged foveal avascular zone was found in STGD1 patients without and even more with DDAF associated with a vessel rarefication in central and also paracentral zones with unnoticeable autofluorescence. VSA and VV were reduced in both STGD1 subgroups for all zones (P<0.0001). STGD1 eyes with compared to without DDAF showed reduced VSA and VV in Z2+3 (both P<0.05). CONCLUSION/CONCLUSIONS:Volume-rendering of OCTA in STGD1 shows a reduced retinal flow in the central macula. This is most likely secondary to loss of neurosensory tissue with disease progression and therefore not likely be favorably influenced by gene transfer and retinal pigment epithelial transplantation. Retinal blood flow assessed by 3D-volume rendered OCTA could serve as surrogate marker for vascular changes of the central retina.

PURPOSE/OBJECTIVE:To analyze swept source optical coherence angiography (SS-OCTA) images acquired at different depths above and below the default location of the Zeiss PLEX Elite 9000. METHODS:Normal eyes of subjects in their 20s and 30s were evaluated. Angiographic slab images were taken at the default location of 29-49 µm below the retinal pigment epithelium (RPE) as well as 21-41 µm through 52-72 µm below in steps. The images were processed using the projection removal function from the device´s software. Raw images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer. RESULTS:11 eyes of 11 subjects were evaluated for the uncompensated and the compensated sets with the projection removal function turned off and on. The default location, 29-49 µm below the RPE, showed a granular choriocapillaris appearance. This appearance remained in all slabs from each group, differing slightly throughout depth. The projection removal function modified the grayscale values and diminished projection from overlaying retinal vessels. The compensation technique altered the appearance of flow deficits and the changes induced by it were more evident on the images were the projection removal function was turned on. CONCLUSION/CONCLUSIONS:Flow images in SS-OCTA of the choriocapillaris from varying levels are similar in appearance, suggesting projection from the choriocapillaris is important in image formation, although layers of vessels in the inner choroid may contribute by various amounts. A model explaining the prominent projection artifacts observed in the choroid with SS-OCTA imaging is presented.