Faculty Bibliography

Purpose/UNASSIGNED:To describe features of neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA). Methods/UNASSIGNED:A retrospective case series was performed in 23 eyes from 21 patients who underwent OCTA of neovascular complexes (NVCs) due to PDR. Eyes were imaged with the DRI Triton swept-source OCTA, Avanti RTVue XR or Cirrus HD-OCT 5000 as part of routine clinical examination. Segmentation was adjusted to include vasculature between the vitreous cavity and the internal limiting membrane (ILM). The presence of NVCs was confirmed by clinical examination and multimodal imaging such as color or red-free fundus photography, fluorescein angiography, multicolor imaging or near-infrared reflectance. Results/UNASSIGNED:Thirty-five NVCs were imaged, of which, 34% were neovascularization of the disc (NVD) and 66% were neovascularization elsewhere (NVE). On structural OCT B-scans, NVE appeared as medium to highly reflective tissue that breached the ILM, while NVD showed highly reflective tissue protruding from the disc in a sea fan configuration. Flow signal was seen on OCTA in all cases of NVE and in 67% of NVD lesions. Areas with minimal or absent retinal flow signal identified retinal nonperfusion areas and were found adjacent to 87% of NVE. Intraretinal microvascular abnormalities (IRMAs) were noted next to 70% of NVE. Absent flow signal was seen in 4 NVD cases showing posterior shadowing and were considered inactive. Conclusion/UNASSIGNED:OCTA appears useful for imaging NVCs, IRMAs, and retinal nonperfusion areas in eyes with diabetic retinopathy. This imaging modality enables noninvasive screening and monitoring of PDR and can obviate the need for additional testing in certain clinical settings.

To describe the ocurrence of Bartonella-associated neuroretinitis secondary to non-feline pet exposure, we retrospectively reviewed medical records and imaging from patients with a clinical and serologic diagnosis of Bartonella henselae (BH). Retinal imaging included color fundus photography, optical coherence tomography (OCT) and fluorescein angiography (FA). Four eyes of two patients with cat-scratch disease were included in this study, with a mean age of 35 years. The mean follow-up was 13 months, after presentation of infectious neuroretinitis. Both patients suffered from bilateral neuroretinitis after direct contact with family pets (ferret and guinea pig). All patients were treated with a long-term systemic antimicrobial therapy. Visual acuity in all improved to 20/30 or better at six months. In conclusion, humans may develop cat-scratch disease when they are exposed to Bartonella henselae (BH) in the saliva of infected cats or BH-containing flea feces reaching the systemic circulation through scratches or mucous membranes. As the cat flea (Ctenocephalides felis) may reside on non-feline mammals, Bartonella-associated neuroretinitis may result from contact with other furred family pets.

PURPOSE/OBJECTIVE:To study the early anatomic choroidal alterations in eyes with chronic central serous chorioretinopathy (CSCR) undergoing photodynamic therapy (PDT). DESIGN/METHODS:Multicenter retrospective cohort study. METHODS:A total of 77 patients and 81 eyes with chronic CSCR treated with PDT and 64 untreated fellow eyes were evaluated. Central macular thickness (CMT) and choroidal features including subfoveal choroidal thickness (SFCT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were analyzed. Choroidal vascularity index (CVI) was calculated in all study eyes at baseline and at 1- and 3-months post-PDT. RESULTS:at the 1-month follow-up visit, respectively (P = .01). No significant changes were recorded for SCA and CVI. In the fellow eye group, VA, CMT, and all choroidal parameters showed no differences between baseline and any follow-up visits (all P > .05). CONCLUSIONS:After PDT for chronic CSCR we observed sustained reductions in CMT and SFCT, while reductions in TCA and LCA were only noted at the 1-month follow-up interval. These choroidal parameters may provide additional quantitative biomarkers to evaluate the anatomic response to therapy but await further prospective validation.

PURPOSE/OBJECTIVE:To describe the presence of subretinal lipid globules (SLG), analyze the multimodal imaging features inherent in their optical properties and provide a means to distinguish them from other retinal structures and clinical signs. DESIGN/METHODS:Retrospective cohort study. METHODS:The clinical data and multimodal imaging features of 39 patients (49 eyes) showing SLG were evaluated. Patients underwent color fundus photography, near-infrared reflectance (NIR), spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) and OCT angiography. In vitro phantom models were used to model OCT optical properties of water, mineral oil, and intralipid droplets and to investigate the optical mechanisms producing hypertransmission tails beneath SLG. RESULTS:The SLG were not visible in color fundus photographs or NIR images. With both SD- and SS-OCT B-scans, SLG appeared as 31-157 micron round hyporeflective structures demonstrating a characteristic hypertransmission tail previously described with lipid globules found in the choroid and in neovascular membranes. Similarly, with en face OCT, SLG appeared as small round hyporeflective structures. SLG were encountered most often in eyes with neovascular age-related macular degeneration (AMD) that had type 1 macular neovascularization (MNV) (91.8%). Of these eyes, 93.3% were receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy (median of 15 injections) with a mean follow-up of 52.6 months. The number of prior injections positively correlated with the number of SLG. The detection of MNV preceded the presence of SLG in 66.7% of cases. En face OCT showed that in many eyes (49%) SLG appeared in clusters of >10. In 38.8% of eyes, SLG were found overlying type 1 MNV and in 44.9% of eyes, often those with more numerous SLG, the SLG were located near the lesion border. In 2 eyes with AMD followed for nonexudative type 1 MNV, SLG were detected prior to the detection of other imaging signs of exudation. SLG were observed in several other exudative macular diseases. Phantom models demonstrated that the hypertransmission tail beneath SLG is related to a lensing effect produced by these hyporeflective spherical structures. CONCLUSIONS:SLG are a newly recognized OCT feature frequently seen in eyes receiving intravitreal anti-VEGF therapy for type 1 MNV due to AMD. OCT B-scans show SLG as small, round, hyporeflective structures with a characteristic hypertransmission tail. This OCT signature is influenced by the OCT focal plane and it relates to reduced signal attenuation through oil and a lensing effect created by a higher refractive index compared to surrounding tissue.

Purpose : Age-related macular degeneration (AMD), a leading cause of blindness, is characterized by the formation of drusen. Subretinal drusenoid deposits (SDD) sit over the retinal pigment epithelium, are a proven risk factor for AMD, and can be visualized on cross-sectional spectral domain optical coherence tomography (SD-OCT). We are evaluating the relationship between SDD and serum risk factors for cardiovascular disease (CVD) in AMD. Methods : 58 subjects (ages of 50-90), diagnosed with AMD on two successive examinations, were recruited prospectively, provided blood samples and underwent SDOCT. The presence of SDD was determined on SD-OCT by an experienced examiner, and a panel of serum risk factors performed: Total Cholesterol (TC), Triglycerides (TG), HDL, VLDL, LDL Direct and high sensitivity C-reactive protein (hs-CRP). Independent t-tests were performed on these results. Results : 25 of 58 subjects were found to have SDD present on SD-OCT. Independent ttests demonstrated a significant association (p<0.05) of high TC (>149 mg/dL) (p=0.01) and low HDL (<39mg/dL) (p=0.02) in subjects with SDD compared to subjects without SDD. Post hoc analysis showed that of patients with high TC, 52% had SDD and 22% did not have SDD present (p=0.02); of patients with low HDL, 4% had SDD, 12% did not (p=0.04); of patients with high LDL-direct, 72% had SDD and 55% did not have SDD (p=0.05). Results for TG and hsCRP were inconclusive. Conclusions : The relationship of TC and AMD is inconsistently reported in the literature, with no demonstrated difference between the phenotypes of AMD. Our results demonstrate that high TC is a specific and significant risk factor for AMD with SDD compared to AMD without SDD. High TC is also a strong risk factor for CVD. Therefore, the leading cause of blindness (AMD) can now be connected to the leading cause of death (CVD) through its SDD phenotype, which may be an effective ophthalmic predictor for future CVD. High LDL is a strong risk for CVD as well, and the risk for SDD also approached significance. High HDL is a known risk for AMD, and per our study, may confer even greater risk for SDD. One limitation of our study is that the groups were not matched for other independent CVD risk factors such as hypertension and smoking history, which

Purpose/UNASSIGNED:We explored via multimodal imaging and histology an eye with mixed-types 1 and 2 macular neovascularization (MNV) and complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in age-related macular degeneration. Methods/UNASSIGNED:An 82-year-old white man was followed 7 years by optical coherence tomography and treated with intravitreal anti-vascular endothelial growth factor for 3 years. At the last clinic visit, visual acuity was stable at 20/50. Two months later the patient died, and eyes were preserved at 8.33 hours after death. Submicrometer epoxy resin sections of osmicated tissue were stained with toluidine blue and evaluated by oil immersion microscopy. Results/UNASSIGNED:A shallow irregular RPE elevation on optical coherence tomography correlated with type 1 MNV with fibrocellular scar and neocapillaries (close to RPE), at a density similar to underlying native choriocapillaris (0.37 vs. 0.42). Type 2 MNV covered the native RPE and was enveloped at the margins by RPE, without neocapillaries. Native RPE cells transdifferentiated from age-normal to melanotic and entered type 1 MNV and choroid. Some photoreceptors persisted over MNV. The cRORA initiated at a collapsed druse, expanded during follow-up, and exhibited low choriocapillaris density (0.05). Conclusions/UNASSIGNED:An eye with maintained vision on 3 years of anti-vascular endothelial growth factor therapy had type 1 MNV sustaining RPE. Type 2 MNV enveloped by RPE was visible in optical coherence tomography and histology. Persistence of photoreceptors and RPE over MNV contrasted with drusen-associated cRORA. Translational Relevance/UNASSIGNED:Vision during long-term anti-vascular endothelial growth factor treatment persists by MNV partially preserving outer retinal cells and by RPE enveloping type 2 MNV.

Purpose/UNASSIGNED:To use structural criteria to reconcile the three-dimensional organization and connectivity of the parafoveal microvasculature. Methods/UNASSIGNED:The parafoveal microvasculature was perfused and labeled in 16 normal human donor eyes for lectin, alpha smooth muscle actin, and filamentous actin. Established structural criteria gathered using confocal microscopy, including vessel diameter, endothelial cell morphology, and presence/density of smooth muscle cells, were used to differentiate arteries, arterioles, capillaries, venules, and veins. Three-dimensional visualization strategies were used to define the connections between retinal arteries and veins within the superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Results/UNASSIGNED:The parafoveal microvasculature has two different inflow patterns and seven different outflow patterns. The SVP and ICP were connected to retinal arteries by arterioles. Inflow into the DCP occurred only via small arterioles (a1; mean diameter, 8.3 µm) that originated from the ICP. Direct connections between the DCP and retinal arteries were not identified. Each capillary plexus formed its own venule that drained independently or in conjunction with venules from other plexuses into a retinal vein at the level of the ganglion cell layer. For the DCP, a1 was significantly smaller than its draining venule (mean diameter, 18.8 µm; P < 0.001). Conclusions/UNASSIGNED:The SVP and ICP of the parafoveal microvasculature have both in series and in parallel arterial and venous connections. Arterial supply to the DCP originates from the ICP, but with direct drainage to the retinal vein. These findings may help to develop an understanding of the pattern of retinal lesions characterizing a myriad of retinal vascular diseases.