Faculty Bibliography

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 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.

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 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.

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.