The Evolution of Fibrosis and Atrophy and Their Relationship with Visual Outcomes in Asian Persons with Neovascular Age-Related Macular Degeneration.

PURPOSE: To describe the rate of development and progression of fibrosis and macular atrophy (MA) and their relationship with 1-year visual outcomes in Asian participants with neovascular age-related macular degeneration (nAMD). DESIGN: Review of images collected from a prospectively recruited observational cohort. PARTICIPANTS: Participants with treatment-naïve nAMD. METHODS: All participants underwent multimodality imaging at baseline and month 12 and were treated according to standard of care. Retinal specialists evaluated color fundus photographs fluorescein and indocyanine green angiography images to determine the subtypes according polypoidal choroidal vasculopathy (PCV) and non-PCV subtypes. An independent reading center graded qualitative and quantitative morphologic features on spectral-domain OCT. Fibrosis and MA were determined based on multimodal imaging. MAIN OUTCOME MEASURES: Incidence of fibrosis and MA and their impact on visual outcome at 1 year. RESULTS: We included 93 eyes (48.4% PCV). Between baseline and month 12, visual acuity (VA) improved from 0.81±0.56 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/126) to 0.71±0.61 logMAR (Snellen equivalent, approximately 20/100; P = 0.007), and mean retinal thickness decreased from 471.1 µm to 343.4 µm (P < 0.001). Between baseline and month 12, prevalence of fibrosis and MA increased from 13.0% to 37.8% (P < 0.001) and 9.7% to 17.2% (P = 0.008), respectively. Worse baseline VA and presence of subretinal hyperreflective material (SHRM) at month 12 were associated with worse VA at month 12 after adjusting for multiple factors, whereas PCV subtype was associated with better VA at month 12. At month 12, the predominant composition of SHRM was fibrosis (82.5%). CONCLUSIONS: We describe significant development of fibrosis and MA in Asian nAMD eyes and show that fibrosis is the most important predictor of outcomes. These results highlight the need for therapy beyond anti-vascular endothelial growth factor inhibition to address fibrosis in Asian nAMD.

Incidence of Fellow Eye Involvement in Patients With Unilateral Exudative Age-Related Macular Degeneration.

Importance: Since the advent of optical coherence tomography angiography (OCT-A), nonexudative neovascularization has been described in the fellow eyes of unilateral exudative age-related macular degeneration (AMD). However, there is limited literature describing the natural course and optimal management of these lesions. Objective: To determine the incidence of fellow eye involvement in patients presenting with unilateral typical AMD or polypoidal choroidal vasculopathy and to evaluate the patterns of OCT-A changes within 6 months before the onset of exudative changes, especially focusing on nonexudative neovascularization. Design, Setting, and Participants: Data for this study were taken from a prospective, observational cohort study involving Asian patients with exudative AMD in the Asian AMD Phenotyping Study between October 2015 and March 2016. Analyses began in June 2017. Only patients who had gradable OCT-A and indocyanine green angiography (ICGA) scans of the fellow eye at baseline and follow-up at least 6 months apart were included for the analysis. The contralateral eye was evaluated for presence of nonexudative neovascularization based on multimodal imaging, which included ICGA, spectral domain optical coherence tomography, and OCT-A. Main Outcomes and Measures: The difference between the incidence of those with nonexudative choroidal neovascularization and those without as analyzed using log-rank test and qualitative analysis of OCT-A images. Results: We included 95 fellow eyes of 95 patients who presented with unilateral exudative AMD with a mean (SD) age of 68.6 (8.6) years. Nonexudative neovascularization was present in 18 eyes (19%) (8 [22.9%] and 10 [19.0%] fellow eyes with typical AMD and polypoidal choroidal vasculopathy, respectively; 8 [44.4%] on OCT-A; 5 [27.8%] on ICGA; and 5 [27.8%] on both OCT-A and ICGA). Development of exudative changes was noted in 6 fellow eyes (6.3%). Four eyes developed exudation from previously noted nonexudative neovascularization, and 2 eyes arose exudative changes from de novo. The probability of developing exudation within 6 months was significantly higher in eyes with baseline nonexudative neovascularization (0.087; 95% CI, 0.0033-0.210) compared with eyes without (0.010; 95% CI, 0.0026-0.041) (P = .008). In all eyes whose OCT-A images were available immediately before the onset of exudative changes, there was an increase in the size of network vessels compared with baseline. Conclusions and Relevance: The presence of nonexudative neovascularization may predispose to the development of exudative changes.

Glaucoma related retinal oximetry: a technology update.

There are two long-standing theories about the pathogenesis of glaucoma - barotrauma and the effect of vascular hypoxia. Currently, it is still unknown whether diminished blood flow is the cause or result of glaucomatous atrophy of ganglion cells and the optic nerve. Though many other imaging techniques used to directly assess ocular blood flow have been well studied, they are limited by their inability to directly assess metabolism in the ocular tissues or measure the oxygen carrying capacity in the vessels. Retinal oximetry is a relatively novel, noninvasive imaging technique that reliably measures oxygen saturation levels in the retinal vessels, offering surrogate markers for the metabolic demands of the eye. The clinical significance of these measurements has not been well established. Thus, this review gives an overview of ocular imaging and current retinal oximetry techniques, while contextualizing the important oximetry studies that have investigated the vascular theory behind glaucoma.

Prevalence and Risk Factors for Nonexudative Neovascularization in Fellow Eyes of Patients With Unilateral Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

Purpose: To determine the prevalence of subclinical nonexudative neovascularization and associated choroidal vascular changes in the fellow eyes of patients presenting with unilateral typical exudative AMD (tAMD) or polypoidal choroidal vasculopathy (PCV) using indocyanine green angiography (ICGA) and swept-source (SS) optical coherence tomography angiography (OCT-A). Methods: We recruited patients presenting with tAMD or PCV in a prospective clinical study. The diagnosis in the presenting eye was determined based on clinical, fluorescein angiography (FA), and ICGA findings. We evaluated the contralateral eye for presence of nonexudative neovascularization, choroidal hyperpermeability, and pachyvessels in the outer choroid, based on multimodal imaging which included ICGA, spectral-domain (SD) OCT and OCT-A. We measured subfoveal choroidal thickness in both eyes for each patient. Results: We included 76 fellow eyes of 76 patients who presented with unilateral tAMD (n = 33) or PCV (n = 43). Nonexudative neovascularization was present in 18% eyes (14 eyes, 8 in tAMD group, 6 in PCV group; 7 on ICGA, 4 on OCT-A, 3 on both ICGA and OCT-A). Pachychoroid pigment epitheliopathy was present in 13 eyes with nonexudative neovascularization, and was the only risk factor associated with nonexudative neovascularization. Conclusions: Approximately one in five fellow eyes with unilateral tAMD and PCV have features of nonexudative neovascularization. The use of multimodal imaging including ICGA and OCT-A can identify these features. The presence of pachychoroid epitheliopathy should alert clinicians to the possibility of underlying neovascularization.

CHARACTERIZATION AND DIFFERENTIATION OF POLYPOIDAL CHOROIDAL VASCULOPATHY USING SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To determine the correlation and agreement between swept-source optical coherence tomography angiography (SS-OCT-A) with fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral domain OCT (SD-OCT) in characterizing polypoidal choroidal vasculopathy (PCV) and in differentiating eyes with typical age-related macular degeneration (t-AMD). METHODS: This study included 32 and 54 eyes with t-AMD and PCV, respectively, who underwent SS-OCT-A, SD-OCT, fluorescein angiography, and indocyanine green angiography. The images from these four techniques were compared. RESULTS: On SS-OCT-A, flow signals with vascular network configuration were detected in 81.2% and 77.8% of eyes with t-AMD and PCV, respectively. 40.4% of polyps were detected as flow signals with polypoidal configuration. Compared with indocyanine green angiography, SS-OCT-A had sensitivity and specificity of 83.0% and 57.1%, respectively, for vascular network, and 40.5% and 66.7% for polyps. Longitudinal changes were in agreement between SS-OCT-A and SD-OCT in 90% of eyes. 88.2% of eyes with dry retina on SD-OCT had persistent vascular net on SS-OCT-A. In two cases with reactivation of PCV, SS-OCT-A was more sensitive at detecting recurrence than SD-OCT. CONCLUSION: Swept-source optical coherence tomography angiography is effective at detecting vascular network that correlate to conventional angiography in eyes with t-AMD and PCV. Swept-source optical coherence tomography angiography is inferior to indocyanine green angiography in detecting polyps and cannot replace indocyanine green angiography for differentiating PCV from t-AMD; however, SS-OCT-A may be more sensitive than SD-OCT in detecting early recurrence.

OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy.

We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography.

Inter-eye comparison of retinal oximetry and vessel caliber between eyes with asymmetrical glaucoma severity in different glaucoma subtypes.

BACKGROUND: To compare retinal vessel oxygenation and vessel caliber in primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal controls, as well as between eyes of asymmetrical glaucoma severity. METHODS: This was a prospective, cross-sectional study. The 159 subjects (PACG, n=39; POAG, n=41; NTG, n=41; normal controls, n=38) underwent retinal oxygen saturation measurements using the Oxymap T1 Retinal Oximeter, optical coherence tomography, and Humphrey visual field testing. Retinal oxygen saturation and vessel diameter were compared between the glaucoma groups and normal controls, as well as between eyes of asymmetrical glaucoma severity. Kruskal-Wallis test was performed for comparison among different subtypes of glaucoma. Wilcoxon signed-rank test was used to compare the inter-eye differences. RESULTS: Compared to normal controls, arteriolar oxygen saturation was increased in PACG eyes (P=0.048) but not in POAG or NTG eyes. There were no significant differences in oxygen saturation in venules or arteriovenous (AV) difference in all three glaucoma groups. Venular diameter was significantly reduced in all glaucoma groups compared to normal controls (P<0.001), but no such change was observed in arteriolar diameter (P=0.10). When comparing between eyes of asymmetrical glaucoma severity, arteriolar oxygen saturation (P=0.03) and AV difference (P=0.04) were significantly higher, while arteriolar diameter was significantly lower (P=0.001) in the worse eye in PACG group. There were no significant differences in oximetric parameters or vessel calibers between the worse and the better eyes in POAG and NTG groups. CONCLUSION: Eyes with PACG showed increased arteriolar oxygen saturation and increased AV difference. This was not observed in POAG and NTG eyes. Arteriolar diameter in PACG and venular diameter in all three glaucoma groups were reduced. The difference observed in PACG eyes may be due to an increased metabolic demand in the disease process compared to open-angle glaucoma.