Current understanding of subclinical diabetic retinopathy informed by histology and high-resolution in vivo imaging.

The escalating incidence of diabetes mellitus has amplified the global impact of diabetic retinopathy. There are known structural and functional changes in the diabetic retina that precede the fundus photography abnormalities which currently are used to diagnose clinical diabetic retinopathy. Understanding these subclinical alterations is important for effective disease management. Histology and high-resolution clinical imaging reveal that the entire neurovascular unit, comprised of retinal vasculature, neurons and glial cells, is affected in subclinical disease. Early functional manifestations are seen in the form of blood flow and electroretinography disturbances. Structurally, there are alterations in the cellular components of vasculature, glia and the neuronal network. On clinical imaging, changes to vessel density and thickness of neuronal layers are observed. How these subclinical disturbances interact and ultimately manifest as clinical disease remains elusive. However, this knowledge reveals potential early therapeutic targets and the need for imaging modalities that can detect subclinical changes in a clinical setting.

INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.

BACKGROUND: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration. METHODS: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes. RESULTS: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells. CONCLUSION: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

Cuticular Drusen in Age-Related Macular Degeneration: Association with Progression and Impact on Visual Sensitivity.

PURPOSE: To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in a cohort with intermediate age-related macular degeneration (AMD). DESIGN: Longitudinal, observational study. PARTICIPANTS: Participants aged 50 years or older, with bilateral large conventional drusen, without late AMD. METHODS: Multimodal imaging (MMI) and microperimetry were performed at baseline and then every 6 months for up to 3 years. Eyes were graded for the MMI-based presence of cuticular drusen at baseline. Color fundus photographs were used to grade for the presence of pigmentary abnormalities. OCT scans were used to calculate drusen volume. The associations between cuticular drusen and progression to MMI-defined late AMD (including OCT signs of atrophy) and the impact on visual sensitivity were examined with and without adjustment for the confounders of baseline age, pigmentary abnormalities, and drusen volume. MAIN OUTCOME MEASURES: Time to develop MMI-defined late AMD and change in mean visual sensitivity. RESULTS: A total of 280 eyes from 140 participants were included, with 70 eyes from 35 individuals (25%) having cuticular drusen at baseline. Cuticular drusen were not significantly associated with an increased rate of progression to late AMD with and without adjustment for confounders (P ≥ 0.784 for both). In an adjusted model, cuticular drusen were not associated with lower baseline visual sensitivity (P = 0.758) or a faster rate of visual sensitivity decline (P = 0.196). CONCLUSIONS: In a cohort with bilateral large conventional drusen, individuals with the cuticular drusen phenotype had neither a higher nor lower risk of developing late AMD over 3 years and were not associated with a difference in rate of visual sensitivity decline compared with those without this phenotype. As such, individuals with this phenotype currently warrant similar monitoring strategies as those with conventional drusen.

Anti-retinal IgG antibodies in patients with early and advanced type 2 macular telangiectasia.

Type 2 idiopathic macular telangiectasia (MacTel-2) is a progressive adult-onset macular disease associated with bilateral perifoveal vascular changes, Muller cell degeneration and increased blood-retinal barrier permeability. The pathophysiological mechanisms of MacTel-2 remain unclear, however it was previously reported that anti-retinal antibodies in MacTel-2 patients are a significant feature of the disease. In this study, we aimed to compare the prevalence of anti-retinal antibodies in patients MacTel-2, healthy controls and patients with other retinal diseases. MacTel-2 patients diagnosed with multimodal imaging were enrolled and their disease severities were graded using spectral-domain optical coherence tomography. For comparison, patients with age-related macular degeneration (AMD), inherited retinal diseases (IRDs) or no retinal disease (healthy controls) were recruited as controls. Blood serum samples were screened for immunoglobulin G anti-retinal antibodies by western blotting, followed by densitometry analysis. Odds ratios (OR) with 95% confidence intervals (CI) were calculated and p < 0.05 considered statistically significant. Overall, anti-retinal antibody-positive cases were older (64 ± 15 vs 53 ± 17 years, p < 0.001) and females were more likely to develop anti-retinal antibodies (OR: 2.41, CI: 1.12-5.18). The frequency of anti-retinal antibody detection in MacTel-2 patients (n = 42, 36%) was not significantly different from healthy controls (n = 52, 25%) or IRD patients (n = 18, 25%) and the majority of MacTel-2 patients had no anti-retinal antibodies. In contrast, the frequency of anti-retinal antibody detection was significantly higher in patients with AMD (n = 15, 73%, p < 0.001). The lack of a greater anti-retinal antibody frequency or specificity in the MacTel-2 cohort suggests that antibody mediated immunological mechanisms may play a less significant role in MacTel-2 disease pathogenesis.

Localised relative scotoma in cuticular drusen.

PURPOSE: To investigate retinal sensitivity changes in eyes with pure cuticular drusen. METHODS: Multimodal imaging and microperimetry (37-loci grid) data were examined retrospectively to evaluate functional changes in eyes with pure cuticular drusen. Mean sensitivity in the cuticular drusen cohort was compared to age-matched normals. An age- and loci-specific normative reference was created to analyse localised sensitivity deviation. RESULTS: The mean number loci with relative scotoma in the cuticular drusen cohort (n = 27, mean [SD] age: 48.5 [12.4] years) referenced to normal eyes (n = 80, 53.5 [14.6] years) was 5.5 (95% confidence interval 3.0 to 8.1). However, mean sensitivity was not statistically different to the age-matched normal cohort (95% CI, - 2.3 to + 3.4 dB). The 37-loci grid was stratified into three rings of the approximately same number of loci, and the percentage of cuticular drusen eyes with pointwise deviation was significantly lower in the inner compared to the middle ring (12.3 [5.3]% vs. 17.3 [5.1]%, p < 0.05). CONCLUSIONS: Eyes with cuticular drusen demonstrated relative scotoma, but mean sensitivity was not affected. Pointwise sensitivity provides a more robust measure of retinal sensitivity than mean sensitivity in cuticular drusen and should be assessed both in the clinic and in future clinical trials.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Quantitative analysis of astrocyte and axonal density relationships: Glia to neuron ratio in the optic nerve laminar regions.

Astrocytes are critical for the maintenance of retinal ganglion cell (RGC) axonal function and viability, and form a key component of the functional neurovascular unit. Recently, we described the quantitative properties of astrocytes in relation to the capillary distributions in optic nerve laminar regions. Here, we provide a quantitative analysis of astrocytes and RGC axons in longitudinal sections of optic nerve tissue. Histological and immunocytochemical techniques are used to demonstrate the density of astrocytes, RGC axons and glia-neuron ratios across the pre laminar, lamina cribrosa and post laminar compartments of the optic nerve head (ONH). A study of human, pig, horse and rat optic nerves was performed and comparisons are made between species. This study demonstrates that the distribution of astrocytes correlates closely with the density of axonal processes, in accordance with the functional requirement of different regions of the ganglion cell axon. There was a consistency of glia-neuron ratios in the majority of laminar compartments, except for the human and rat prelaminar regions, which demonstrated lower ratios of astrocyte to axonal processes. The distribution of astrocytes may reflect a functional susceptibility to development of disease in the prelaminar region of the optic nerve. Interspecies comparison at the lamina cribrosa showed strikingly consistent glia-neuron ratios. Collectively, our findings suggest there may be a critical ratio of glia to neuron needed to maintain healthy cellular physiology across different laminar compartments of the optic nerve, with particular importance for the health of the lamina cribrosa region. It is possible that, in disease processes, the glia-neuron relationships across the different laminar compartments may be perturbed and this may be relevant for the development of glaucoma. Emerging technologies may further aid our understanding in how the physiology of optic nerve tissue cellular structure may be affected by changes to ONH characteristics and elevated intraocular pressure induced damage. Such findings may also permit the early identification of RGC axonal injury by identifying quantifiable changes in structural tissue architecture when pathophysiological pathways predominate.

CUTICULAR DRUSEN: Risk of Geographic Atrophy and Macular Neovascularization.

PURPOSE: Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS: A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS: A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION: When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 133 participants (217 eyes) with chronic CSC. METHODS: A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF), and OCT. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1-, 5-, and 10-year follow-up visits; and causes of vision loss at final visit. RESULTS: Data from 6228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years, and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 eye, and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1- or 5-year follow-up visits (both P ≥ 0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (P = 0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the final visit (all P ≤ 0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (P = 0.001). CONCLUSIONS: Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

Cuticular Drusen: Clinical Phenotypes and Natural History Defined Using Multimodal Imaging.

PURPOSE: To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. DESIGN: Retrospective, observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1). METHODS: We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy. MAIN OUTCOME MEASURES: Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. RESULTS: The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen. CONCLUSIONS: Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.

Quantitative comparisons between optical coherence tomography angiography and matched histology in the human eye.

The aim was to quantitatively compare retinal vascular detail as seen on optical coherence tomography angiography (OCTA) and matched histology in the human eye. 13 normal human donor eyes were used. The central retinal artery was cannulated after which human packed red blood cells were perfused through the retinal vasculature. Retinal vessels were imaged using a custom-built OCTA device during red blood cell perfusion. The eye was subsequently perfused with endothelial cell antibodies and the flat-mounted retina studied histologically using a confocal scanning laser microscope. Qualitative and quantitative comparisons of retinal vascular information as seen on OCTA and histology from the same region of interest were performed. Gradable OCTA images were acquired from 4 of 13 eyes with mean postmortem-to-OCTA imaging time of 4.5 ±â€¯1.3 h 23 pairs of OCTA-histology matched images were evaluated. The retinal arteries and veins had similar pixel intensity on OCTA images. The diameter of retinal veins was significantly greater than its paired artery on OCTA (P < 0.001). The density of vascular structures on OCTA (40.2% ±â€¯10.1%) was significantly less than matched histology (52.1% ±â€¯9.3%, P < 0.001). Mean capillary diameter on OCTA (10.2 ±â€¯2.4 µm) was significantly greater than histology (8.2 ±â€¯2.4 µm; P < 0.001). This is the first study to directly compare OCTA against histology from the same human eye. OCTA visualizes many of the vascular structures in the human retinal circulation but does not exactly match what is seen on histologic examination.

IMAGING OF PIGMENT EPITHELIAL DETACHMENTS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate the utility of optical coherence tomography angiography (OCTA) for detecting pathologic vascularization within pigment epithelial detachments (PEDs). METHODS: This was a retrospective, cross-sectional, consecutive case series. Multimodal imaging (structural OCT, fluorescein, and indocyanine green angiography) was used as the gold standard to classify PEDs as nonvascularized or vascularized. Optical coherence tomography angiography imaging of the PED was subsequently and independently evaluated to classify PEDs as vascularized or nonvascularized. Specifically, OCTA images were evaluated for the presence of abnormal flow on cross-sectional OCTA and the presence of a vascular complex on en face OCTA. Comparisons between OCTA and the gold standard were determined. RESULTS: Sixty-four eyes of 49 patients were evaluated. A total of 18 eyes were classified as nonvascularized PED, and 46 eyes were classified as vascularized PED using the gold standard. Optical coherence tomography angiography was found to have a sensitivity of 76%, specificity of 61%, positive predictive value of 83%, and negative predictive value of 50% for detecting vascularized PEDs. False positive cases in the nonvascularized PED group were due to projection or flow artifacts from hyperreflective material overlying the PED. False negative cases were seen in eyes with minimal exudation on structural OCT and also those manifesting retinal pigment epithelial tears. CONCLUSION: Our proposed two-step approach of OCTA interpretation, first using cross-sectional OCTA and then en face OCTA, may allow the detection of vascularization within PEDs and, in some cases, reduce the need for conventional angiography. Increased awareness about potential artifacts and limitations of OCTA may help clinicians interpret OCTA more accurately.

Histologic and Optical Coherence Tomographic Correlates in Drusenoid Pigment Epithelium Detachment in Age-Related Macular Degeneration.

PURPOSE: Drusenoid pigment epithelium detachment (DPED) is a known precursor to geographic atrophy in age-related macular degeneration (AMD). We sought histologic correlates for spectral-domain (SD) optical coherence tomography (OCT) signatures in DPED and determined the frequency and origin of these OCT signatures in a clinical cohort of DPED eyes. DESIGN: Laboratory imaging and histologic comparison, and retrospective, observational cohort study. PARTICIPANTS: Four donor eyes with histopathologic diagnosis of AMD (2 with nonneovascular DPED and 2 with neovascular pigment epithelium detachment [PED]) and 49 eyes of 33 clinic patients with nonneovascular DPED more than 2 mm in diameter. METHODS: Donor eyes underwent multimodal ex vivo imaging, including SD OCT, then processing for high-resolution histologic analysis. All clinic patients underwent SD OCT, near-infrared reflectance, and color photography. MAIN OUTCOME MEASURES: Histologic correlates for SD OCT signatures in DPED, estimate of coverage by different retinal pigment epithelium (RPE) phenotypes in the DPED surface; frequency and origin of histologically verified SD OCT signatures in a clinical cohort of DPED eyes, and comparisons of histologic features between neovascular PED and DPED resulting from AMD. RESULTS: Intraretinal and subretinal hyperreflective foci as seen on SD OCT correlated to RPE cells on histologic examination. Hypertransmission of light below the RPE-basal lamina band correlated with dissociated RPE. Subretinal hyperreflective material resulting from acquired vitelliform lesions corresponded to regions of apically expelled RPE organelles. In the clinical cohort, all histologically verified reflectivity signatures were visible and quantifiable. The appearance of intraretinal hyperreflective foci was preceded by thickening of the RPE-basal lamina band. Compared with PEDs associated with neovascular AMD, DPEDs had different crystallization patterns, no lipid-filled cells, and thinner basal laminar deposits. CONCLUSIONS: Multiple RPE fates in AMD, including intraretinal cells that are highly prognostic for progression, can be followed and quantified reliably using eye-tracked serial SD OCT. This information may be particularly useful for obtaining an accurate timeline of incipient geographic atrophy in clinic populations and for quantifying anatomic end points and response to therapy in AMD clinical trials.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CHORIORETINAL LESIONS DUE TO IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow. METHODS: This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti-vascular endothelial growth factor therapy. RESULTS: Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti-vascular endothelial growth factor therapy (all tested variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.

Visual Acuity Is Correlated with the Area of the Foveal Avascular Zone in Diabetic Retinopathy and Retinal Vein Occlusion.

PURPOSE: To determine if the area of the foveal avascular zone (FAZ) is correlated with visual acuity (VA) in diabetic retinopathy (DR) and retinal vein occlusion (RVO). DESIGN: Cross-sectional study. PARTICIPANTS: Ninety-five eyes of 66 subjects with DR (65 eyes), branch retinal vein occlusion (19 eyes), and central retinal vein occlusion (11 eyes). METHODS: Structural optical coherence tomography (OCT; Spectralis, Heidelberg Engineering) and OCT angiography (OCTA; Avanti, Optovue RTVue XR) data from a single visit were analyzed. FAZ area, point thickness of central fovea, central 1-mm subfield thickness, the occurrence of intraretinal cysts, ellipsoid zone disruption, and disorganization of retinal inner layers (DRIL) length were measured. VA was also recorded. Correlations between FAZ area and VA were explored using regression models. Main outcome measure was VA. RESULTS: Mean age was 62.9±13.2 years. There was no difference in demographic and OCT-derived anatomic measurements between branch retinal vein occlusion and central retinal vein occlusion groups (all P ≥ 0.058); therefore, data from the 2 groups were pooled together to a single RVO group for further statistical comparisons. Univariate and multiple regression analysis showed that the area of the FAZ was significantly correlated with VA in DR and RVO (all P ≤ 0.003). The relationship between FAZ area and VA varied with age (P = 0.026) such that for a constant FAZ area, an increase in patient age was associated with poorer vision (rise in logarithm of the minimum angle of resolution visual acuity). Disruption of the ellipsoid zone was significantly correlated with VA in univariate and multiple regression analysis (both P < 0.001). Occurrence of intraretinal cysts, DRIL length, and lens status were significantly correlated with VA in the univariate regression analysis (P ≤ 0.018) but not the multiple regression analysis (P ≥ 0.210). Remaining variables evaluated in this study were not predictive of VA (all P ≥ 0.225). CONCLUSIONS: The area of the FAZ is significantly correlated with VA in DR and RVO and this relationship is modulated by patient age. Further study about FAZ area and VA correlations during the natural course of retinal vascular diseases and following treatment is warranted.

Bullous Variant of Central Serous Chorioretinopathy: Expansion of Phenotypic Features Using Multimethod Imaging.

PURPOSE: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). METHODS: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. RESULTS: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1±83.1 µm) was not different compared with that of the nonbullous CSC group (400.6±100.6 µm; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). CONCLUSIONS: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features.