Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the vascular characteristics of the choriocapillaris in eyes with pachychoroid as compared with normal controls. METHODS:Eyes with pachychoroid disease were defined as those with a history of central serous chorioretinopathy or peripapillary pachychoroid syndrome. Pachychoroid without disease was defined as eyes with no history of disease with a subfoveal choroidal thickness ≥ the age-adjusted 95 percentile thickness. Frame averaged optical coherence tomography angiography images of the choriocapillaris obtained with a Zeiss Plex Elite were binarized, skeletonized, and evaluated for vascular branching parameters. RESULTS:There were 7 normal controls, 10 pachychoroid without disease, and 17 pachychoroid disease subjects. Mean choriocapillaris vessel segment length was 12.19 µm in eyes with pachychoroid disease as compared with 11.48 µm for normal controls and 11.62 µm for pachychoroid without disease (P=.003 and P=.006, respectively). The branches per mm were fewer in pachychoroid disease, 1215, as compared to normal controls, 1471, or pachychoroid without disease, 1384, (P<.001, and P = .002, respectively). The choriocapillaris vessel diameter was larger, but the fractal dimension was smaller in pachychoroid disease eyes as compared to normal or pachychoroid without disease eyes. There was no statistically significant difference between normal controls and pachychoroid without disease for any measured vascular parameter of the choriocapillaris. CONCLUSIONS:Choriocapillaris vascular parameters suggest that pachychoroid is not necessarily pathologic. It is possible choroidal thickening is an epiphenomenon and there are more significant vascular parameters that are related to disease. These concepts may help guide future prospective studies.

PURPOSE/OBJECTIVE:To longitudinally characterize structural/angiographic findings of retinal-choroidal anastomosis (RCA) in macular telangiectasia type 2 (MacTel2). METHODS:Combined retrospective/prospective review of MacTel2 patients with >2 visits and >2 months follow-up, including examination, fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and projection-resolved OCT angiography. RESULTS:There were 24 eyes of 12 patients with mean age 61.1 (±7.3 [SD]) years and median follow-up 447 (range 81-1511) days. There were 5 eyes diagnosed with new RCA after not having any previously. RCA was diagnosed in 8 (33%) eyes initially and eventually 13 (54%). In the 8 eyes initially diagnosed with RCA, the number of RCAs and outer retinal hyperrflective lesions increased over the follow-up. The RCAs were found in clusters, generally temporal to the fovea. RCA was uniformly associated with complete retinal subsidence, defined as the loss of outer nuclear layer substance such that the middle retinal layers sank down toward retinal pigment epithelium (RPE), was also present in each case. Each RCA colocalized with a region of hyperreflectivity, previously termed outer retinal hyperreflective lesion (ORHL). There was a lack of fluorescein leakage, lipid, hemorrhage, or any structural correlates to fluid exudation, and no signs of subretinal/sub-RPE neovascularization. CONCLUSION/CONCLUSIONS:De novo RCA development appears to be associated with retinal subsidence, and after RCAs form, they increase in number and topographic distribution over time. Initially after formation, there was no sign of exudation. These data suggest descent of the deep capillary plexus occurs with RCA, devoid subretinal/sub-RPE neovascularization in MacTel2.

PURPOSE/OBJECTIVE:To survey the pachychoroid spectrum literature to determine how the component diseases are defined. METHODS:English language articles mentioning pachychoroid, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, peripapillary pachychoroid syndrome, and pachyvessels from 1 January 2013 until 31 March 2020 were included. The disease definitions from the Methods sections were evaluated. Definitions were then grouped, if possible, by shared traits. Two definitions were considered similar if the traits mandated or excluded completely satisfy each. RESULTS:This study found there were 18 unique definitions for pachychoroid, 6 for pachychoroid pigment epitheliopathy, 12 for pachychoroid neovasculopathy, and 8 for pachyvessels. There were 39 papers that had no definition of the pachychoroid disease entity being studied. Even when the disease was defined, the criteria were often nebulous, such as "dilated vessels" or "thickened choroid". When parameters were listed, as when thresholds were established for choroidal thickness, they were set at levels below average values for choroidal thickness in the general population. CONCLUSIONS:The variation and ambiguity in disease definitions would make comparisons between publications difficult and hinder precise communication. In addition, the current definitions would classify a significant proportion of the general population as being in the pachychoroid spectrum of diseases.

BACKGROUND:A consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed. METHODS:The panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions. RESULTS:The panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness. CONCLUSIONS:The use of the proposed definitions may provide uniform language for clinicians and future research.

PURPOSE/OBJECTIVE:To develop a method of averaging optical coherence tomography (OCT) angiography to improve visualization of choriocapillaris structure. METHODS:A stack of OCT angiographic data from vascular layers were placed into the red-green-blue channels of a conventional digital color image. The superficial plexus was placed in the blue channel, choriocapillaris in the green, and deep vascular plexus in the red channel. The red-green-blue images derived from nine separate OCT angiographic scans were registered using an automatic registration sequence and the images were averaged. The averaged red-green-blue image was then split into the three averaged component layers. The technique is flexible and any vascular layer, such as macular neovascularization, can be used as well. RESULTS:The utility of the imaging method was demonstrated by showing the imaging of two different diseases. A patient with a history of familial amyloidosis, hypertension, kidney failure, kidney transplantation, and prednisone use, followed by central serous chorioretinopathy treated by photodynamic therapy. She had alterations in retinal pigment epithelial pigmentation and widespread abnormalities of autofluorescence. She showed remarkably decreased vascular density and vessel configuration of her choriocapillaris. A patient with pseudoxanthoma elasticum with subretinal drusenoid deposits at an early age also showed marked decreased choriocapillaris density and vascular configuration. These findings were compared with healthy controls of similar age with no abnormalities. CONCLUSION/CONCLUSIONS:The detailed method is capable of averaging choriocapillaris OCT angiographic images using a simple automatic method. Image averaging offers opportunity to improve the noisy OCT angiographic images such that actual vascular structure is visible.

To describe patterns of reperfusion in the superficial vascular plexus (SVP), deep capillary plexus (DCP) and choriocapillaris (CC) as detected on optical coherence tomography (OCTA) in cynomogulus macaque monkey model following increase in intraocular pressure by an intravitreal injection. Animal imaging study. Two cynomogulus macaque monkeys. A 100 µL intravitreal injection (IVI) of saline was given in one eye of each monkey. Serial OCTA using a Zeiss Plex Elite 9000 was used to evaluate reperfusion patterns within the SCP, DCP, and CC. OCTA evidence of perfusion. Pulsation of the central retinal artery was detected after the intraocular pressure was elevated to 98 and ≥ 99 mmHg from IVI. Episodic flow within the SVP arterioles and venules and poor visualization of flow in capillaries was noted during the initial phase of elevated pressure. As the pressure declined, the flow signal within the DCP appeared initially as dots, which progressed laterally to loops which form capillary vortex configuration. Recovery of flow within the SVP and CC appeared sooner than in the DCP. At 40 min after the injection, well after the intraocular pressure normalized, the retinal and choriocapillaris vascular perfusion showed focal defects in every layer. Compared with pre-injection images, vessel density in the DCP was 68.8% and 78.6% of baseline in monkey 1 and monkey 2, respectively. In contrast vessel density in the SVP recovered to 84.2% and 88.9% of baseline. Increases in intraocular pressure from IVI have the potential to affect every layer of blood flow in the fundus. After nominal return of intraocular pressure, focal defects in flow persisted, which may result in longer term damage to the retina.

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.