Faculty Bibliography

PURPOSE/OBJECTIVE:To inform the interpretation of clinical optical coherence tomography and fundus autofluorescence imaging in geographic atrophy (GA) of age-related macular degeneration by determining the distribution of retinal pigment epithelium (RPE) phenotypes in the transition from health to atrophy in donor eyes. METHODS:In RPE-Bruch membrane flat mounts of two GA eyes, the terminations of organized RPE cytoskeleton and autofluorescent material were compared. In high-resolution histological sections of 13 GA eyes, RPE phenotypes were assessed at ±500 and ±100 μm from the descent of the external limiting membrane (ELM) toward Bruch membrane. The ELM descent was defined as curved, reflected, or oblique in shape. Thicknesses of RPE, basal laminar deposit (BLamD), and RPE plus BLamD were measured. RESULTS:A border of atrophy that can be precisely delimited is the ELM descent, as opposed to the termination of the RPE layer itself, because of dissociated RPE in the atrophic area. Approaching the ELM descent, the percentage of abnormal RPE morphologies increases, the percentage of age-normal cells decreases, overall RPE thickens, and BLamD does not thin. The combination of RPE plus BLamD is 19.7% thicker at -100 μm from the ELM descent than that at -500 μm (23.1 ± 10.7 μm vs. 19.3 ± 8.2 μm; P = 0.05). CONCLUSION/CONCLUSIONS:The distribution of RPE phenotypes at the GA transition supports the idea that these morphologies represent defined stages of a degeneration sequence. The idea that RPE dysmorphia including rounding and stacking helps explain variable autofluorescence patterns in GA is supported. The ELM descent and RPE plus BLamD thickness profile may have utility as spectral domain optical coherence tomography metrics in clinical trials.

PURPOSE/OBJECTIVE:To investigate flow characteristics of the choriocapillaris using optical coherence tomography angiography. DESIGN/METHODS:Retrospective observational case series. METHODS:Visualization of flow in individual choriocapillary vessels is below the current resolution limit of optical coherence tomography angiography instruments, but areas of absent flow signal, called flow voids, are resolvable. The central macula was imaged with the Optovue RTVue XR Avanti using a 10-μm slab thickness in 104 eyes of 80 patients who ranged in age from 24 to 99 years of age. Automatic local thresholding of the resultant raw data with the Phansalkar method was analyzed with generalized estimating equations. RESULTS:The distribution of flow voids vs size of the voids was highly skewed. The data showed a linear log-log plot and goodness-of-fit methods showed the data followed a power law distribution over the relevant range. A slope intercept relationship was also evaluated for the log transform and significant predictors for variables included age, hypertension, pseudodrusen, and the presence of late age-related macular degeneration (AMD) in the fellow eye. CONCLUSIONS:The pattern of flow voids forms a scale invariant pattern in the choriocapillaris starting at a size much smaller than a choroidal lobule. Age and hypertension affect the choriocapillaris, a flat layer of capillaries that may serve as an observable surrogate for the neural or systemic microvasculature. Significant alterations detectable in the flow pattern in eyes with pseudodrusen and in eyes with late AMD in the fellow eye offer diagnostic possibilities and impact theories of disease pathogenesis.

: Retinal vascular disease has the potential to affect hundreds of millions of people, with the inherent risk of vision loss related to cystoid macular edema. Although there have been histologic evaluation of eyes having cystoid macular edema, the most recent paper was published more than 30 years ago. In retinal vascular cystoid macular edema fluorescein angiography, a modality that images the superficial vascular plexus, shows increased leakage. Optical coherence tomography angiography has provided unprecedented resolution of retinal vascular flow in a depth resolved manner and demonstrates areas of decreased or absent flow in the deep vascular plexus colocalizing with the cystoid spaces. There has been a large amount of research on fluid management and edema in the brain, much of which may have analogues in the eye. Interstitial flow of fluid as managed by Müller cells may occur in the retina, comparable in some ways to the bulk flow in brain parenchyma, which is managed by astrocytes. Absent blood flow in the deep retinal plexus may restrict fluid management strategies in the retina, to include transport of excess fluid out of the retina into the blood by Müller cells. Application of this theory may help in increasing understanding of the pathophysiology of retinal vascular cystoid macular edema and may lead to new therapeutic approaches.

PURPOSE:The purposes of this study were to describe choroidal findings observed using optical coherence tomography with enhanced depth imaging (EDI-OCT) in eyes with birdshot chorioretinitis (BSCR) and to test the hypothesis that these findings are related to participant demographics, clinical characteristics, and treatment. METHODS:In a multicenter, cross-sectional study, 172 eyes of 86 individuals with BSCR underwent a standardized clinical evaluation, including defined protocols for EDI-OCT imaging, with macular and peripapillary volume scans. Choroidal findings were compared to demographic information, ophthalmic examination findings, and treatment history, using logistic regression models. EDI-OCT images were evaluated by two independent, masked graders. RESULTS:Median age was 56 years old; 54 participants (62.8%) were female. One or more choroidal lesions (a predefined hyporeflective zone) were identified in 105 eyes (63.6%). Median choroidal thickness was 293 μm. Choroidal lesions were associated with longer disease durations (odds ratio [OR]: 1.08; P = 0.03), increased vitreous haze (>0.5+; OR: 4.43; P = 0.02), presence of macular edema (OR: 3.00; P = 0.02), and thick choroids (OR: 3.89; P = 0.001). Use of immunomodulatory therapy was associated with lower risk of thin choroids (lower 25th percentile, OR: 0.17; P = 0.001) or thick choroids (upper 25th percentile, OR: 0.22; P = 0.002). At least some choroidal lesions did not have corresponding, clinically apparent "birdshot lesions" on fundus examination. CONCLUSIONS:Choroidal abnormalities identified by EDI-OCT imaging are common in the macular and peripapillary regions of eyes with BSCR. Choroidal lesions were associated with clinical signs of inflammation, suggesting that they represent foci of disease activity. EDI-OCT may provide useful information about disease mechanisms and response to treatment in future, longitudinal studies of BSCR.

PURPOSE/OBJECTIVE:Patchy atrophy is a type of chorioretinal atrophy located outside of the fovea in eyes with myopic retinopathy. Bruch membrane defects have previously been described to occur in highly myopic eyes in foveal chorioretinal atrophy associated with choroidal neovascularization (CNV). We examined whether Bruch membrane defects can be found also in patchy atrophy. DESIGN/METHODS:Retrospective observational case series. METHODS:The study included all patients who were consecutively examined for high axial myopia (axial length ≥26.5 mm) and patchy atrophy in the study period from September to November 2015. The patients underwent a comprehensive ophthalmologic examination including swept-source optical coherence tomography (OCT) of the macula. Main outcome measures were macular Bruch membrane defects. RESULTS:Out of 22 eyes (17 patients) with patchy atrophy, 21 eyes (96%) showed macular Bruch membrane defects, which were characterized by a lack of Bruch membrane, retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris. At the edges of the macular Bruch membrane defects, the ends of the Bruch membrane were folded and the RPE was upturned. The inner retina overlying the area of the Bruch membrane defect was markedly thinned. CONCLUSIONS:Macular Bruch membrane defects belong to the hallmarks of a type of myopic chorioretinal atrophy not associated with CNV (ie, patchy atrophy). Considering that Bruch membrane defects were also observed in myopic CNV-related foveal atrophy, macular Bruch membrane defect might be a common finding in fundus lesions related to pathologic myopia.

PURPOSE/OBJECTIVE:To investigate the retinal vascular findings and associated cystoid edema in the central macula of eyes with retinal vein occlusion using volume-rendered angiographic and structural optical coherence tomography. STUDY DESIGN/METHODS:Observational case series. METHODS:In this retrospective study 12 eyes of 12 consecutive patients, 3 with branch and 9 with central retinal vein occlusion, were imaged in 27 sessions with optical coherence tomography (OCT) using split-spectrum amplitude decorrelation. The structural OCT data were segmented for cystoid spaces and integrated into the angiographic data for subsequent volume rendering. The inner and deep vascular plexus were analyzed in relation to cystoid macular edema with retention of depth information. RESULTS:Retinal vascular flow abnormalities were demonstrated by flow voids with abnormal vascular morphology in the inner vascular layer and varying flow loss in the deep vascular plexus. Areas of cystoid edema were associated with topographically co-localizing flow voids in the deep vascular layer. Treatment with intravitreous anti-vascular endothelial growth factor injections resulted in resolution of edema but no change in flow patterns in either the inner or deep plexus. Recurrence of edema happened in the same areas of altered inner and absent deep vascular plexus flow signal. CONCLUSIONS:Cystoid macular edema in retinal vein occlusion occurred in relation to altered inner plexus and absent deep vascular plexus flow. This pattern of cystoid fluid accumulation is similar to that seen in diabetic retinopathy and may represent an important underlying pathophysiologic foundation for cystoid macular edema in retinal vascular diseases.

PURPOSE/OBJECTIVE:To determine frequency and associations of macular Bruch membrane defects in the region of macular atrophy developing after the onset of myopic choroidal neovascularization (CNV). DESIGN/METHODS:Retrospective observational case series. METHODS:The study included all patients who were consecutively examined for high myopia (axial length ≥26.5mm) and CNV-related macular atrophy in the study period from June to July 2015. The patients underwent a comprehensive ophthalmologic examination including swept-source optical coherence tomography (OCT) of the macula. Main outcome measures were macular Bruch membrane defects. RESULTS:Out of 33 eyes (28 patients) with myopic CNV-related macular atrophy, 25 eyes (76%) showed macular Bruch membrane defects, which were characterized by a lack of Bruch membrane, retinal pigment epithelium, photoreceptors, and choriocapillaris. At the edges of the macular Bruch membrane defects, the ends of the Bruch membrane were upturned, and an inward protrusion of large choroidal vessels could be detected. In the center of macular Bruch membrane defects, remnants of Bruch membrane could be crumpled. In multivariate analysis, higher prevalence of secondary macular Bruch membrane defects was significantly associated with a lower prevalence of intravitreal medical therapy (P < .001) after adjusting for larger macular atrophy area size (P < .001) and longer interval between development of the CNV and final examination (P = .42). CONCLUSIONS:Macular Bruch membrane defects belong to the hallmarks of myopic CNV-related macular atrophy. Since macular Bruch membrane defects lack photoreceptors and thus represent psychophysically an absolute scotoma, they are of profound importance for visual prognosis. As incidentally observed at study end, the prevalence of macular Bruch membrane defects may be lower if a previous myopic CNV was treated by intravitreal medical therapy.

PURPOSE: To evaluate potential accumulation of fluid in the outer choroid in eyes with central serous chorioretinopathy. DESIGN: Retrospective observational case series. METHODS: Patients in two community-based retinal practices were evaluated for hyporeflective areas in the outer choroid consistent with collections of fluid using enhanced depth imaging optical coherence tomography. Eligible patients were examined over the preceding 2 years, had a history of central serous chorioretinopathy, and did not have a history of choroidal neovascularization or photodynamic therapy. RESULTS: In the New York group there were 131 eyes of 70 patients who had a mean age of 56.3 (+/- 12.5) years, and 88 (67.2%) had hyporeflective regions consistent with posterior loculation of fluid in the macular region. In the Minnesota data set there were 91 eyes of 48 patients who had a mean age of 47.9 (+/-9.9) years and hyporeflective regions consistent with posterior loculation of fluid was present in 59 (64.8%). In the entire group the mean subfoveal choroidal thickness of those without loculated fluid was 344 microns as compared with 498 microns with loculated fluid (P<.001). The areas of loculated fluid were hyporeflective, were larger topographically than the large choroidal vessels, had an angular inner border, and did not have a bounding vascular wall. CONCLUSIONS: Posterior loculation of fluid is a common finding in central serous chorioretinopathy, but it has a different pattern and distribution than does collections of fluid in the outer choroid and suprachoroidal space as seen in other forms of choroidal effusion.