Faculty Bibliography

The choroid provides nutritional support for the retinal pigment epithelium and photoreceptors. Choroidal dysfunction plays a major role in several of the most important causes of vision loss including age-related macular degeneration, myopic degeneration, and pachychoroid diseases such as central serous chorioretinopathy and polypoidal choroidal vasculopathy. We describe an imaging technique using depth-resolved swept-source optical coherence tomography (SS-OCT) that provides full-thickness three-dimensional (3D) visualization of choroidal anatomy including topographical features of individual vessels. Enrolled subjects with different clinical manifestations within the pachychoroid disease spectrum underwent 15 mm × 9 mm volume scans centered on the fovea. A fully automated method segmented the choroidal vessels using their hyporeflective lumens. Binarized choroidal vessels were rendered in a 3D viewer as a vascular network within a choroidal slab. The network of choroidal vessels was color depth-encoded with a reference to the Bruch's membrane segmentation. Topographical features of the choroidal vasculature were characterized and compared with choroidal imaging obtained with indocyanine green angiography (ICGA) from the same subject. The en face SS-OCT projections of the larger choroid vessels closely resembled to that obtained with ICGA, with the automated SS-OCT approach proving additional depth-encoded 3D information. In 16 eyes with pachychoroid disease, the SS-OCT approach added clinically relevant structural details, including choroidal thickness and vessel depth, which the ICGA studies could not provide. Our technique appears to advance the in vivo visualization of the full-thickness choroid, successfully reveals the topographical features of choroidal vasculature, and shows potential for further quantitative analysis when compared with other choroidal imaging techniques. This improved visualization of choroidal vasculature and its 3D structure should provide an insight into choroid-related disease mechanisms as well as their responses to treatment.

PURPOSE/OBJECTIVE:To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of current literature and an analysis of retinal imaging. METHODS:We reviewed the literature for previous reports of BALAD. An analysis of retinal images was performed to support anatomic conclusions. RESULTS:A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Further, detachment of the entire layer of inner segments is a common postmortem artefact. We propose that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION/CONCLUSIONS:Our review serves to strengthen the OCT nomenclature "bacillary layer detachment", based on specific reflectance information obtained by OCT and previously published histologic observations.

The retinal capillary vasculature serves the formidable role of supplying the metabolically active inner and middle retina. In the parafoveal region, the retinal capillary plexuses (RCP) are organized in a system of three capillary layers of varying retinal depths: the superficial capillary plexus (SCP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). While the dynamic flow through these plexuses is complex and not completely understood, current research points to a hybrid model that includes both parallel and in series components in which blood flows in a predominantly serial direction between the superficial vascular complex (SVC) and deep vascular complex (DVC). Each capillary plexus autoregulates independently, so that under most conditions the retinal vasculature supplies adequate blood flow and oxygen saturation at varying depths despite diverse environmental stressors. When the flow in the deep vascular complex (i.e. ICP and DCP) fails, an ischemic lesion referred to as Paracentral Acute Middle Maculopathy (PAMM) can be identified. PAMM is an optical coherence tomography (OCT) finding defined by the presence of a hyperreflective band at the level of the inner nuclear layer (INL) that indicates INL infarction caused by globally impaired perfusion through the retinal capillary system leading to hypoperfusion of the DVC or specifically the DCP. Patients present with an acute onset paracentral scotoma and typically experience a permanent visual defect. Lesions can be caused by a diverse set of local retinal vascular diseases and systemic disorders. PAMM is a manifestation of the retinal ischemic cascade in which the mildest forms of ischemia develop at the venular end of the DCP, i.e. perivenular PAMM, while more severe forms progress horizontally to diffusely involve the INL, and the most severe forms progress vertically to infarct the inner retina. Management is targeted toward the identification and treatment of related vasculopathic and systemic risk factors.

PURPOSE/OBJECTIVE:To evaluate and compare para- and perilesional choriocapillaris vascular impairment in eyes with geographic atrophy (GA) with and without outer retinal tubulations (ORT). METHODS:Using swept source optical coherence tomography angiography (OCTA), 6x6mm scans of eyes with GA with and without ORT were acquired. Choriocapillaris en face flow and structural images were binarized, prior to flow signal deficit (FD) analysis in the para-atrophy zone (a 500 µm wide band adjacent to the GA) and the peri-atrophy zone (a 500 µm wide band adjacent to the latter). RESULTS:Twenty-four eyes of 19 patients with ORT and 18 eyes of 15 patients without ORT were analyzed. With and without ORT, mean percental area of FD (%FD) was greater in para- than in peri-atrophy zone. The difference of %FD between para- and peri-atrophy zone (deltaFD) was lower in eyes with ORT (mean 1.8477%, 95% CI 0.8607 to 2.8346) than without ORT (mean 4.0018%, 95% CI 2.8622 to 5.1414). CONCLUSION/CONCLUSIONS:In eyes with GA due to non-neovascular AMD, smaller reductions in FDs were found between the para- and peri-atrophy zone in eyes with ORT. In both cohorts, the para-atrophy zone had more FD than the peri-atrophy zone.

PURPOSE/OBJECTIVE:To describe the clinical and multimodal imaging (MMI) features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, in eyes with macular neovascularization (MNV). DESIGN/METHODS:Retrospective, observational case series. METHODS:Fourteen eyes (14 patients, 7 male) were imaged with spectral-domain optical coherence tomography (OCT), and either fluorescein angiography or OCT angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity (BCVA) assessments. RESULTS:Mean age was 75±13 (range: 45-96) years, with mean follow-up duration of 27±21 (range: 1-56) months. Neovascular age-related macular degeneration (nAMD) was found in 71% (10/14) eyes. Type 2 MNV lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved following intravitreal anti-VEGF therapy in all eyes. Baseline BCVA improved from LogMar 0.84±0.32 (Snellen equivalent 20/138) to LogMar 0.48±0.31 (Snellen equivalent 20/60) at last follow-up, with treatment of the MNV. CONCLUSIONS:Type 2 MNV and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal anti-VEGF therapy results in rapid resolution of BDs and visual improvement in most eyes.

PURPOSE/OBJECTIVE:Macular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with anti-angiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histological analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD. DESIGN/METHODS:Case study and clinicopathologic correlation. SUBJECT/METHODS:A white woman in whom AMD findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and optical coherence tomography (OCT), with no detectable subretinal fluid or other recurrent exudation, and no intravitreal injections before death at age 90 years. METHODS:The right eye was preserved 6.25 hours after death, post-fixed in osmium tannic acid paraphenylenediamine, and prepared for sub-micrometer epoxy resin sections (n=115), with 19 matched to clinical OCT B-scans. MAIN OUTCOME MEASURES/METHODS:Light microscopic morphology of a hyperautofluorescent (hyperFAF) area attributed to prior exudation ("floodplain" hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF. RESULTS:Floodplain hyperFAF was visible throughout the 9 years follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer. CONCLUSION/CONCLUSIONS:This direct clinicopathologic correlation for FAF imaging is the first for nAMD. FAF is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. HyperFAF attributed to an exudative floodplain signifies loss of photoreceptors over continuous RPE. HypoFAF in MA signifies loss of both cell layers. FAF imaging should be interpreted with the multilayer perspective provided by OCT for maximal value. Prevention of exudation in nAMD may preserve photoreceptors.

PURPOSE/OBJECTIVE:To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age. DESIGN/METHODS:Retrospective study. SUBJECTS/METHODS:There were 50 eyes of 49 patients (age range 1-74 years) with CHRRPE studied at nine tertiary vitreoretinal institutions. METHODS:We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the optical coherence tomography (OCT) findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption and retinal pigment epithelium/Bruch's membrane complex involvement of CHRRPE. MAIN OUTCOMES/RESULTS:Clinical and imaging findings of CHRRPE at different ages. RESULTS:Analysis of 50 CHRRPE revealed younger patients were more likely to have partial thickness involvement of the retina (p = 0.009) with predominantly inner retinal layer involvement (p = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to have an increase in central macular thickness independently of tumor location. CONCLUSION/CONCLUSIONS:Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues towards the outer retina over time, with increase in central macular thickness, despite the location of the tumor.