Faculty Bibliography

PURPOSE/OBJECTIVE:To review controls mechanism for blood flow in the choroid and to propose a system by which venous outflow is controlled by a Starling resistor. To propose an explanation for the choroidal venous architectural anatomy. METHODS:The main blood flow control mechanisms were reviewed including autoregulation, neurovascular coupling, myogenic regulation were reviewed. Applicable blood flow control mechanisms in the brain, a high flow organ in a low compliance outer shell, were used to examine analogous processes that may be occurring in the choroid. RESULTS:There does not appear to be effective autoregulation in the choroid, although myogenic mechanisms may be present. There is a sophisticated neural innervation that provides partial control. Like the brain, the eye has a high pulsatile blood flow rate and is encased in a non-compliant casing. As part of modulating pulsatile pressure in the cranium, the brain uses venous storage and a Starling resistor effect, to modulate venous outflow. An analogous function in the eye could be provided by the choroid, which contains fascicles of large veins that converge in vortices to drain out of the eye. This vortex area appears to be where the Starling resistor effect is possible. This mechanism would have important impact on theories of many ocular diseases including central serous chorioretinopathy and spaceflight associated neuro-ocular syndrome. CONCLUSIONS:Control of blood flow is critical in the choroid, and this control appears to extend to the venous outflow system. Abnormalities in venous outflow may critically affect function in predictable pathogenic mechanisms.

PURPOSE/OBJECTIVE:To evaluate the features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6mg/0.05ml for treatment of neovascular age-related macular degeneration (AMD). DESIGN/METHODS:Retrospective case series. PARTICIPANTS/METHODS:Fifteen eyes from 12 patients identified from 10 centers in the United States. METHODS:Review of patient demographics, ophthalmologic examination and retinal imaging. MAIN OUTCOME MEASURES/METHODS:Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography and treatment strategies RESULTS: The number of previous anti-VEGF IVIs ranged between 2 to 80 in the affected eye prior to the switch to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days following brolucizumab IVI. Mean visual acuity prior to brolucizumab IVI was logMAR 0.426 (Snellen equivalent 20/53) and at diagnosis of retinal vasculitis was logMAR 0.981 (Snellen equivalent 20/191, range 20/25 to 20/1600) (P= 0.008). All affected eyes showed intraocular inflammation with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular non-perfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular non-perfusion and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients and 3 patients had negative evaluation for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, topical) and two eyes had vitrectomy without improvement in vision. After mean follow-up of 25 days, mean visual acuity was logMAR 0.833 (Snellen equivalent 20/136), which was reduced compared to baseline (P=.033). CONCLUSIONS:Retinal vasculitis and IOI after brolucizumab IVI is characterized by variable occlusion of large and /or small retinal arteries and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required as vitreous cells may obscure visualization of retinal details.

PURPOSE/OBJECTIVE:To analyze swept-source optical coherence angiography slab images acquired at the default level for the choriocapillaris from the Zeiss PLEX Elite 9000 before and after using a previously described imaging compensation technique. METHODS:Eyes of normal subjects, in their 20 seconds and 30 seconds, were evaluated. Angiographic slab images, 20 µm in thickness, were taken at the default location of 29 to 49 µm below the retinal pigment epithelium. These images were evaluated, as were images that underwent a published compensation technique that adjusts for light penetration to the sampled layer. Each set of images was threshold at 1 SD below the mean. Visual comparison of the swept-source optical coherence angiography images along with a quantitative analysis using a novel parameter known as multiscale structural similarity index, a measure of image similarity, was performed. RESULTS:Eleven eyes of 11 subjects were evaluated. The default location, 29 µm to 49 µm below the retinal pigment epithelium, showed the granular choriocapillaris appearance. Visual comparison showed that the compensation technique altered the appearance of the thresholded images, creating the appearance of new deficits while causing others to disappear. The mean multiscale structural similarity index for the original versus thresholded images and original versus thresholded compensated was 0.49 and 0.34, respectively, representing a statistically significant difference. CONCLUSION/CONCLUSIONS:The findings of this study show that the use of a commonly used imaging compensation technique can have undesired effects on the image, and its use should be carefully considered. A model explaining the cause of such changes in the choriocapillaris swept-source optical coherence angiography images is presented.

Fundus autofluorescence (FAF) imaging is an in vivo imaging method that allows for topographic mapping of naturally or pathologically occurring intrinsic fluorophores of the ocular fundus. The dominant sources are fluorophores accumulating as lipofuscin in lysosomal storage bodies in postmitotic retinal pigment epithelium cells as well as other fluorophores that may occur with disease in the outer retina and subretinal space. Photopigments of the photoreceptor outer segments as well as macular pigment and melanin at the fovea and parafovea may act as filters of the excitation light. FAF imaging has been shown to be useful with regard to understanding of pathophysiological mechanisms, diagnostics, phenotype-genotype correlation, identification of prognostic markers for disease progression, and novel outcome parameters to assess efficacy of interventional strategies in chorio-retinal diseases. More recently, the spectrum of FAF imaging has been expanded with increasing use of green in addition to blue FAF, introduction of spectrally-resolved FAF, near-infrared FAF, quantitative FAF imaging and fluorescence life time imaging (FLIO). This article gives an overview of basic principles, FAF findings in various retinal diseases and an update on recent developments.

PURPOSE/OBJECTIVE:To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN/METHODS:Consensus meeting. PARTICIPANTS/METHODS:An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS:During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES/METHODS:A consensus classification of neovascular AMD. RESULTS:The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS:The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

PURPOSE/OBJECTIVE:Preliminary to evaluate geometric indices (vessel sphericity and cylindricity) for volume-rendered optical coherence tomography angiography (OCTA) in healthy and diabetic eyes. METHODS:Twenty-six eyes of 13 healthy subjects and 12 eyes of patients with central ischemic, non-proliferative diabetic retinopathy were included. OCTA volume and surface area of the foveal vessels were measured and compared to determine OCTA sphericity and cylindricity indices and surface efficiency (SE). RESULTS:, p = 0.021). In relation to total foveolar tissue volume, the proportion of blood vessels was 22% in healthy individuals and only 20% in diabetics. The difference between the groups was more pronounced with respect to the total OCTA surface area, with a decrease of 13% in diabetics. A diabetic eye was most likely using geometric vessel indices analysis if the sphericity value was ≥ 0.190, with a cylindricity factor of ≥ 0.001. Reproducibility of the method was good. CONCLUSIONS:A method for OCTA surface area and volume measurements was developed. The application of the novel OCTA sphericity and cylindricity indices could be suitable as temporal biomarker to characterize stable disease or disease progression and may contribute to a better understanding in the evolution of diabetic retinopathy.

PURPOSE/OBJECTIVE:To evaluate the subfoveal choroidal thickness (SFCT) and vascular architecture in the fellow eyes of patients with circumscribed choroidal hemangioma (CCH). METHODS:In this retrospective observational study, patients were selected from outpatient ophthalmology clinics at the Memorial Sloan Kettering Cancer Center and Vitreous Retina Macula Consultants of New York. Subfoveal choroidal thickness was measured using enhanced depth imaging spectral domain optical coherence tomography from the outer portion of Bruch membrane to the choroidal-scleral interface. Choroidal vascular architecture was qualitatively examined. The main outcome measure was SFCT in fellow eyes of patients with CCH, which was compared with an age- and gender-matched control group. RESULTS:Thirty-one fellow eyes (15 right eyes and 16 left eyes) of patients with CCH (23 males and 8 females) were examined. The fellow eye had a mean SFCT of 361.2 ± 99.9 μm compared with 252.0 ± 77.6 μm in the control group (P < 0.0001). Vascular architecture was disorganized in 13 (42%) fellow eyes and 1 (3%) control eye (P < 0.0001), with no apparent gradient of vessel sizes or discrete choroidal layers. The normal association between older age and a thinner choroid existed in control eyes but not in fellow eyes. Hemangioma thickness measured by ultrasound and the presence of subfoveal fluid in the CCH eye did not correlate with the fellow-eye SFCT. CONCLUSION/CONCLUSIONS:In patients with CCH, fellow eyes had thicker SFCT when compared with age- and gender-matched control eyes. Choroidal architecture was often irregular, without segmented vascular layers. These findings suggest that inherent choroidal changes may exist in patients with CCH.