Vascular Response to Sildenafil Citrate in Aging and Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) - the leading cause of vision loss in the elderly - share many risks factors as atherosclerosis, which exhibits loss of vascular compliance resulting from aging and oxidative stress. Here, we attempt to explore choroidal and retinal vascular compliance in patients with AMD by evaluating dynamic vascular changes using live ocular imaging following treatment with oral sildenafil citrate, a phosphodiesterase type 5 (PDE5) inhibitor and potent vasodilator. Enhanced-depth imaging optical coherence tomography (EDI-OCT) and OCT angiography (OCT-A) were performed on 46 eyes of 23 subjects, including 15 patients with non-exudative AMD in one eye and exudative AMD in the fellow eye, and 8 age-matched control subjects. Choroidal thickness, choroidal vascularity, and retinal vessel density were measured across the central macula at 1 and 3 hours after a 100 mg oral dose of sildenafil citrate. Baseline choroidal thickness was 172.1 ± 60.0 µm in non-exudative AMD eyes, 196.4 ± 89.8 µm in exudative AMD eyes, and 207.4 ± 77.7 µm in control eyes, with no difference between the 3 groups (P = 0.116). After sildenafil, choroidal thickness increased by 6.0% to 9.0% at 1 and 3 hours in all groups (P = 0.001-0.014). Eyes from older subjects were associated with choroidal thinning at baseline (P = 0.005) and showed less choroidal expansion at 1 hour and 3 hours after sildenafil (P = 0.001) regardless of AMD status (P = 0.666). The choroidal thickening appeared to be primarily attributed to expansion of the stroma rather than luminal component. Retinal vascular density remained unchanged after sildenafil in all 3 groups (P = 0.281-0.587). Together, our studies suggest that vascular response of the choroid to sildenafil decreases with age, but is not affected by the presence of non-exudative or exudative AMD, providing insight into changes in vessel compliance in aging and AMD.

OUTCOMES OF PNEUMATIC RETINOPEXY PERFORMED BY VITREORETINAL FELLOWS.

PURPOSE: To evaluate the anatomical and visual outcomes of patients who underwent pneumatic retinopexy by vitreoretinal fellows. METHODS: We included 198 eyes (198 patients) that underwent pneumatic retinopexy by vitreoretinal fellows at a single academic institution between November 2002 and June 2016. Main outcomes were single-operation success and final anatomical success in retinal reattachment, as well as visual acuity at 3 months and 6 months after treatment. RESULTS: Single-operation success rate was 63.6% at 3 months and 59.5% at 6 months. Final anatomical reattachment was achieved in 92.9% (n = 184) and 96.6% (n = 143) at 3 months and 6 months, respectively. Logarithm of the minimum angle of resolution visual acuity improved from 0.72 ± 0.1 (∼20/100 Snellen) at baseline to 0.36 ± 0.06 (∼20/40 Snellen) at 6 months (P < 0.001). There was no statistical difference in anatomical success rates or visual outcomes between cases performed by first- or second-year fellows (P > 0.50). Single-operation success was associated only with size of detachment (P = 0.01). Visual outcome was associated with macula status at baseline (P = 0.032) and number of reoperations (P < 0.001). CONCLUSION: Anatomical and visual outcomes of fellow-performed pneumatic retinopexy are comparable with those reported in the previous literature.

Choroidal Changes After Suprachoroidal Injection of Triamcinolone Acetonide in Eyes With Macular Edema Secondary to Retinal Vein Occlusion.

PURPOSE: To evaluate choroidal and suprachoroidal changes following suprachoroidal injection of triamcinolone acetonide injectable suspension (CLS-TA), in eyes with macular edema due to retinal vein occlusion (RVO). DESIGN: Prospective cohort study within a randomized, controlled phase 2 clinical trial. METHODS: Enhanced depth imaging optical coherence tomography (EDI-OCT) images were analyzed from 38 eyes of 38 treatment-naïve patients with macular edema due to RVO, enrolled in the prospective Suprachoroidal Injection of Triamcinolone Acetonide with Intravitreal Aflibercept in Subjects with Macular Edema Due to Retinal Vein Occlusion (TANZANITE) study who received either a suprachoroidal injection of CLS-TA with an intravitreal injection of aflibercept (combination arm) or only an intravitreal injection of aflibercept (monotherapy arm), followed by monthly intravitreal aflibercept injections in both arms based on pro re nata criteria. RESULTS: Macular choroidal thickness measured to the outer choroidal vessel lumen (vascular choroidal thickness, VCT), outer choroid stroma (stromal choroidal thickness, SCT), or inner scleral border (total choroidal thickness, TCT) showed no significant changes over 3 months in both study arms (P = .231-.342). Eyes that received combination therapy showed a trend toward thickening of the suprachoroidal space (SCS) compared with monotherapy alone (13.4 µm vs 5.3 µm at 3 months; P = .077). In the 15 eyes that demonstrated a visible SCS at baseline, the SCS expanded significantly after suprachoroidal CLS-TA injection (16.2 µm to 27.8 µm at 3 months; P = .033). CONCLUSIONS: Suprachoroidal injection of CLS-TA does not alter choroidal thickness in eyes with macular edema due to RVO, but may result in expansion of the SCS.

Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on Enhanced Depth Optical Coherence Tomography.

PURPOSE: To determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective reliability analysis. METHODS: EDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR). RESULTS: Of 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1 µm) and 0.96 (63.9 µm) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend. CONCLUSIONS: The presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1 µm in subfoveal CT or 63.9 µm in average CT may be necessary to detect true clinical change in eyes with macular fluid.

Effect of Uveal Melanocytes on Choroidal Morphology in Rhesus Macaques and Humans on Enhanced-Depth Imaging Optical Coherence Tomography.

PURPOSE: To compare cross-sectional choroidal morphology in rhesus macaque and human eyes using enhanced-depth imaging optical coherence tomography (EDI-OCT) and histologic analysis. METHODS: Enhanced-depth imaging-OCT images from 25 rhesus macaque and 30 human eyes were evaluated for choriocapillaris and choroidal-scleral junction (CSJ) visibility in the central macula based on OCT reflectivity profiles, and compared with age-matched histologic sections. Semiautomated segmentation of the choriocapillaris and CSJ was used to measure choriocapillary and choroidal thickness, respectively. Multivariate regression was performed to determine the association of age, refractive error, and race with choriocapillaris and CSJ visibility. RESULTS: Rhesus macaques exhibit a distinct hyporeflective choriocapillaris layer on EDI-OCT, while the CSJ cannot be visualized. In contrast, humans show variable reflectivities of the choriocapillaris, with a distinct CSJ seen in many subjects. Histologic sections demonstrate large, darkly pigmented melanocytes that are densely distributed in the macaque choroid, while melanocytes in humans are smaller, less pigmented, and variably distributed. Optical coherence tomography reflectivity patterns of the choroid appear to correspond to the density, size, and pigmentation of choroidal melanocytes. Mean choriocapillary thickness was similar between the two species (19.3 ± 3.4 vs. 19.8 ± 3.4 µm, P = 0.615), but choroidal thickness may be lower in macaques than in humans (191.2 ± 43.0 vs. 266.8 ± 78.0 µm, P < 0.001). Racial differences in uveal pigmentation also appear to affect the visibility of the choriocapillaris and CSJ on EDI-OCT. CONCLUSIONS: Pigmented uveal melanocytes affect choroidal morphology on EDI-OCT in rhesus macaque and human eyes. Racial differences in pigmentation may affect choriocapillaris and CSJ visibility, and may influence the accuracy of choroidal thickness measurements.

Repeatability of Choroidal Thickness Measurements on Enhanced Depth Imaging Optical Coherence Tomography Using Different Posterior Boundaries.

PURPOSE: To assess the reliability of manual choroidal thickness measurements by comparing different posterior boundary definitions of the choroidal-scleral junction on enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Reliability analysis. METHODS: Two graders marked the choroidal-scleral junction with segmentation software using different posterior boundaries: (1) the outer border of the choroidal vessel lumen, (2) the outer border of the choroid stroma, and (3) the inner border of the sclera, to measure the vascular choroidal thickness (VCT), stromal choroidal thickness (SCT), and total choroidal thickness (TCT), respectively. Measurements were taken at 0.5-mm intervals from 1.5 mm nasal to 1.5 mm temporal to the fovea, and averaged continuously across the central 3 mm of the macula. Intraclass correlation coefficient (ICC) and coefficient of reliability (CR) were compared to assess intergrader and intragrader reliability. RESULTS: Choroidal thickness measurements varied significantly with different posterior boundaries (P < .001 for all). Intergrader ICCs were greater for SCT (0.959-0.980) than for TCT (0.928-0.963) and VCT (0.750-0.869), even in eyes where choroidal-scleral junction visibility was <75%. Intergrader CRs were lower for SCT (41.40-62.31) than for TCT (61.13-74.24) or VCT (72.44-115.11). ICCs and CRs showed greater reliability for averaged VCT, SCT, or TCT measurements than at individual locations. Intragrader ICCs and CRs were comparable to intergrader values. CONCLUSIONS: Choroidal thickness measurements are more reproducible when measured to the border of the choroid stroma (SCT) than the vascular lumen (VCT) or sclera (TCT).