Choriocapillaris Flow Deficits Research Articles

Differences in choroidal responses to near work between myopic children and young adults.

Near work is generally considered as a risk factor for myopia onset and progression. This study aimed to investigate the choroidal responses to a brief-period of near work in children and young adults. Thirty myopic medical students (aged 18-28years) and 30 myopic children (aged 8-12years) participated in this study. The submacular total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI) and choriocapillaris flow deficit (CcFD), as well as subfoveal choroidal thickness (SFCT) were measured with swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) before and immediately after 20min, 40min, 60min of near work at a distance of 33cm. In adults, 20min of near work induced a significant reduction in SFCT (- 5.1 ± 6.5μm), LA [(- 19.2 ± 18.6) × 103 μm2], SA [(- 8.2 ± 12.6) × 103 μm2] and TCA [(- 27.4 ± 24.9) × 103 μm2] (all P < 0.01). After 40min of near work, LA was still reduced [(- 9.4 ± 18.3) × 103 μm2], accompanied with a decreased CVI (- 0.39% ± 0.70%) and an increased CcFD (0.30% ± 0.78%) (all P < 0.05). After 60min of near work, CVI was still reduced (- 0.28% ± 0.59%), and CcFD was still increased (0.37% ± 0.75%) (all P < 0.05). In children, 20min of near work induced a significant increase in CcFD (0.55% ± 0.64%), while 60min of near work induced increases in SA [(7.2 ± 13.0) × 103 μm2] and TCA [(9.7 ± 25.3) × 103 μm2] and a reduction in CVI (- 0.28% ± 0.72%) (all P < 0.05). Children exhibited lower near work-induced LA and TCA reduction than adults, with a mean difference of - 0.86% and - 0.82%, respectively (all P < 0.05). The temporal characteristics and magnitude of changes of choroidal vascularity and choriocapillaris perfusion during near work was not identical between children and adults. The initial response to near work was observed in choriocapillaris in children, whereas it was observed in the medium- and large-sized vessels in adults. Clinical Trial Registry (ChiCTR), ChiCTR2000040205. Registered on 25 November 2020, https://www.chictr.org.cn/bin/project/edit?pid=64501 .

Prediction of Functional and Anatomic Progression in Lamellar Macular Holes

PurposeTo use artificial intelligence to identify imaging biomarkers for anatomical and functional progression of lamellar macular hole (LMH) and to elaborate a deep learning (DL) model based on optical coherence tomography (OCT) and OCT angiography (OCTA) for prediction of visual acuity (VA) loss in untreated LMHs. DesignMulticentric retrospective observational study ParticipantsPatients >18 years old diagnosed with idiopathic LMHs with availability of good quality OCT and OCTA acquisitions at baseline and a follow up>2 years were recruited. MethodsA DL model based on soft voting of two separate models (OCT and OCTA-based respectively) was trained for identification of cases with VA loss> 5 ETDRS letters (attributable to LMH progression only) during a 2-years follow-up. Biomarkers of anatomical and functional progression of LMH were evaluated with regression analysis, feature learning(support vector machine(SVM) model) and visualization maps. Main Outcome measuresEllipsoid zone(EZ) damage, volumetric tissue loss (TL), vitreopapillary adhesion (VPA), epiretinal proliferation, central macular thickness (CMT), parafoveal vessel density (VD) and vessel length density (VLD) of retinal capillary plexa, choriocapillaris (CC) flow deficit density (FDD). ResultsFunctionally progressing LMHs (VA-PROG group, 41/139 eyes (29.5%)) showed higher prevalence of EZ damage, higher volumetric TL, higher prevalence of VPA, lower superficial capillary plexus(SCP) VD and VLD and higher CC FDD compared to functionally stable LMHs (VA-STABLE group,98/139 eyes (70.5%)). The DL and SVM models showed 92.5% and 90.5% accuracy respectively. The best performing features in the SVM were EZ damage, TL, CC FDD and parafoveal SCP VD. Epiretinal proliferation and lower CMT were risk factors for anatomical progression only. ConclusionsDL can accurately predict functional progression of untreated LMHs over 2 years. The use of AI might improve our understanding of the natural course of retinal diseases. Integrity of CC and SCP might play an important role in the progression of LMHs.

Glycemic Control and Retinal Microvascular Changes in Type 2 Diabetes Mellitus Patients without Clinical Retinopathy.

To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P<0.05). The IC group had lower vessel density in the superficial retinal layer and deep retinal layer than the controls (all P<0.05). The choriocapillaris (CC) flow deficit (FD) was significantly greater in the MC group than in the IC and control groups (18.2%, 16.7%, and 14.2%, respectively; all P<0.01). In multivariate regression analysis, CC-FD was associated with the mean HbA1c level (P=0.008). There were no significant differences in OCT parameters among the groups. OCTA revealed that early CC impairment is associated with HbA1c levels; the CC changes precede clinically apparent DR. The OCTA parameters differed among the groups according to the degree of glycemic control. Our results suggest that microvascular changes precede DR and are closely related to glycemic control.

Quantitative Analysis of the Vasculature and Cone Photoreceptors in Subjects With Diabetes Without Diabetic Retinopathy

Purpose To characterize any differences in the vasculature and cone photoreceptor packing geometry (CPG) between subjects with diabetes without/no diabetic retinopathy (NDR) and healthy controls. Methods Eight NDR and five controls were enrolled. Optical coherence tomography angiography (OCTA) taken at the macula was used to measure vessel density, vessel length density, and vessel density index (VDI) in three vascular plexuses, namely, the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus (DCP). The choriocapillaris (CC) flow deficit (FD) was also measured. OCTA images were binarized and processed to extrapolate the parafovea and parafoveal quadrants and the OCTA indices mentioned above. The CC was processed with six different radii to quantify FD. Adaptive optics - scanning laser ophthalmoscopy images were acquired and processed to extract CPG indices, i.e., cone density (CD), cone-to-cone spacing (CS), linear dispersion index, heterogeneity packing index and percent of cells with six neighbors at 3.6° in the temporal retina. Results In all eyes, statistically significant differences were found (i) in parafoveal FD across the six radii (p < 0.001) and (ii) in the correlation between the parafoveal temporal quadrant (PTQ) DCP VDI and CS (r = 0.606, p = 0.048). No other significant correlations were found. For OCTA or CPG indices, no significant differences were found between the cohorts in the parafovea or parafoveal quadrants. Conclusions CS is the most sensitive CPG index for detecting alterations in the cone mosaic. The DCP and the cone photoreceptors are significantly correlated, indicating that alterations in the DCP can affect the cones. Future work elucidating the vascular alterations and neurodegeneration present in diabetic eyes should focus on the DCP and multiple CPG indices, not solely CD. Moreover, such alterations are highly localized, hence using larger regions e.g. parafovea versus smaller areas, such as the PTQ, will potentially mask significant correlations.

Choriocapillaris and Retinal Vascular Alterations in Presymptomatic Alzheimer's Disease.

To compare optical coherence tomography angiography (OCTA) retina metrics between cognitively healthy subjects with pathological versus normal cerebrospinal fluid (CSF) Aβ42/tau ratios. Swept-source OCTA scans were collected using the Zeiss PLEX Elite 9000 and analyzed on 23 cognitively healthy (CH) subjects who had previously undergone CSF analysis. Thirteen subjects had a pathological Aβ42/tau (PAT) ratio of <2.7132, indicative of presymptomatic Alzheimer's disease (AD), and 10 had a normal Aβ42/tau (NAT) ratio of ≥2.7132. OCTA en face images of the superficial vascular complex (SVC) and deep vascular complex were binarized and skeletonized to quantify the perfusion density (PD), vessel length density (VLD), and fractal dimension (FrD). The foveal avascular zone (FAZ) area was calculated using the SVC slab. Choriocapillaris flow deficits (CCFDs) were computed from the en face OCTA slab of the CC. The above parameters were compared between CH-PATs and CH-NATs. Compared to CH-NATs, CH-PATs showed significantly decreased PD, VLD, and FrD in the SVC, with a significantly increased FAZ area and CCFDs. Swept-source OCTA analysis of the SVC and CC suggests a significant vascular loss at the CH stage of pre-AD that might be an indicator of a neurodegenerative process initiated by the impaired clearance of Aβ42 in the blood vessel wall and by phosphorylated tau accumulation in the perivascular spaces, a process that most likely mirrors that in the brain. If confirmed in larger longitudinal studies, OCTA retinal and inner choroidal metrics may be important biomarkers for assessing presymptomatic AD.

Diabetic choriocapillaris flow deficits affect the outer retina and are related to hemoglobin A1c and systolic blood pressure levels

Patient systemic and ocular data based on optical coherence tomography (OCT) and OCT angiography images were analyzed (n = 45; control and diabetic eyes with or without diabetic retinopathy [DR]; mean age, 49.6 ± 8.1 years). All participants had best-corrected visual acuity < 0.05 in logMAR. The choriocapillaris flow area (CCFA) ratio was lower and the coefficient of variation (CV) of CCFA ratio was higher in diabetic eyes with or without DR than in control eyes. CCFA ratio of DR eyes was lower than that of diabetic eyes without DR. Superficial retinal vessel length density (VLD) was reduced only in DR eyes. CCFA ratio correlated with retinal VLD, photoreceptor outer segment (PROS) length, and retinal pigment epithelium (RPE) volume in the study population; mean PROS decreased in diabetic eyes with or without DR, and RPE volume increased in DR eyes. CCFA ratio < 65.9% and CV of CCFA ratio ≥ 0.140 were more frequently found in diabetic eyes (odds ratio [OR], 13.333; P = 0.001), and related to HbA1c ≥ 7.0% (OR, 4.992; 95% confidence interval [CI] 1.164–21.412; P = 0.030) or systolic blood pressure ≥ 135 mmHg (OR, 5.572; 95% CI 1.156–26.863; P = 0.032). These findings could help understand diabetic pathogenesis in the choriocapillaris and outer retina, and remind clinicians to manage both diabetes and hypertension.

Impact of slab selection on the relationship between choriocapillaris flow deficits and enlargement rate of geographic atrophy

ObjectiveTo evaluate the effect of changing slab position on the correlation between choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) and yearly enlargement rate (yER) of GA.MethodsOCT and OCTA images obtained on Cirrus HD-OCT device were collected from patients with GA. Each patient underwent OCTA scan at baseline and two OCT scans, one at baseline and one after at least 12 months. GA was delineated on en-face fundus image to calculate yER. OCTA images were generated from three 10 µm thick slabs 11, 21 and 31 µm posterior to RPE-fit line. 100 µm-wide concentric rings were generated around GA to calculate FD% in each ring which was correlated with yER.ResultsFor the 11–21 µm slab, FD% was not significantly correlated with yER for any of the rings (p > 0.05). For the 21–31 and 31–41 µm slab, FD% of rings located in the 600 µm region around GA was significantly correlated with yER (p < 0.05). However, in all slab locations, there was no significant correlation between yER and CC FD% of rings located beyond the 600 µm region (p > 0.05).ConclusionsSlab selection for quantification of CC FD% may have a significant impact on quantitative results in eyes with GA.

LONGITUDINAL MICROVASCULAR AND NEURONAL RETINAL EVALUATION IN PATIENTS WITH DIABETES MELLITUS TYPES 1 AND 2 AND GOOD GLYCEMIC CONTROL.

To evaluate microvascular and neuronal changes over 3 years in patients with Type 1/2 diabetes mellitus (DM1/DM2), good metabolic control, and no signs of diabetic retinopathy. In this prospective, longitudinal study, 20 DM1, 48 DM2, and 24 controls underwent macular optical coherence tomography and optical coherence tomography angiography at baseline and after 3 years. Following parameters were considered: thickness of the central macula, retinal nerve fiber layer, ganglion cell (GCL+/GCL++) complex; perfusion and vessel density and fractal dimension at the superficial and deep capillary plexuses; choriocapillaris flow deficits; and foveal avascular zone metrics. MATLAB and ImageJ were used for optical coherence tomography angiography scans analyses. The mean HbA1c was 7.4 ± 0.8% in DM1 and 7.2 ± 0.8% in DM2 at baseline, with no change at 3 years. No eye developed diabetic retinopathy. In longitudinal analyses, perfusion density at superficial capillary plexuses ( P = 0.03) and foveal avascular zone area and perimeter ( P < 0.0001) significantly increased in DM2 compared with other groups. No longitudinal changes occurred in optical coherence tomography parameters. In comparisons within groups, DM2 had a significant thinning of GCL++ in the outer ring, decreased perfusion density at deep capillary plexuses and choriocapillaris flow deficits, and increase in foveal avascular zone perimeter and area in deep capillary plexuses; DM1 had an increase in foveal avascular zone perimeter in deep capillary plexuses ( P < 0.001 for all comparisons). Longitudinal data showed significant microvascular retinal changes in DM2. No changes were detected in neuronal parameters and in DM1. Longer and larger studies are needed to confirm these preliminary data.

Choriocapillaris Reperfusion in Resolved Chronic Central Serous Chorioretinopathy Treated with Eplerenone: Long-Term Effects on the Fellow Eye.

The aim of this work is to utilize swept-source optical coherence tomography angiography (SS-OCTA) to assess the long-term changes in the choroidal and choriocapillaris (CC) layers of the fellow unaffected eye of patients with unilateral resolved chronic central serous chorioretinopathy (cCSC) following treatment with continuous oral eplerenone (EPL). The study included 35 patients with cCSC and subretinal fluid (SRF) in one eye. SS-OCTA imaging was performed on the fellow cCSC eyes at baseline, 6months, and 12months during eplerenone therapy. CC OCT angiography was analyzed to determine the percentage of choriocapillaris flow deficits (FD%), the number of flow deficits (FDn), and the average area of flow deficits (FDa). The results demonstrated significant changes in CC flow deficits from baseline to follow-up visits. Specifically, there was a significant decrease in FD% from 28.9 ± 2.2% at baseline to 26.4 ± 1.9% at 6months (p = 0.023), and further to 24.9 ± 1.7% at 12months (p = 0.001). Additionally, the FD area gradually contracted over the follow-up period (p < 0.05). Conversely, there was a significant increase in the number of flow deficits compared to baseline (p < 0.05). No statistically significant changes were observed in best-corrected visual acuity (BCVA) at the follow-up visits (p > 0.05). The findings of this study demonstrated long-term reperfusion of the choriocapillaris in unaffected fellow cCSC eyes during continuous oral eplerenone therapy. The beneficial effects of eplerenone therapy were observed after 6months and maintained at 1year. These results suggest that specific mineralocorticoid receptor (MR) antagonists may be effective in promoting choriocapillaris recovery in the unaffected eyes of patients with cCSC.

Continuous Eplerenone Treatment in Chronic Central Serous Chorioretinopathy: Long-Term Results from a Pilot Study.

To assess the long-term morpho-functional retinal and choroidal changes in chronic central serous chorioretinopathy (cCSC) pachychoroid eyes in response to continuous oral eplerenone (EPL) treatment. This pilot study was conducted on patients with unilateral exudative cCSC. We enrolled a total of 17 exudative cCSC and 17 non-exudative fellow eyes of 17 patients. Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography [OCT] and OCT angiography) parameters in both eyes were collected at baseline. Follow-up data were collected at 6, 12, and 48 months after initiation of EPL treatment. (i) Exudative cCSC eyes: Compared with baseline (0.34±0.13 LogMAR), BCVA significantly improved at follow-up examinations (6 months: 0.28±0.13 LogMAR, p=0.039; 12 months: 0.22±0.11 LogMAR, p=0.025; 48 months: 0.21±0.08 LogMAR, p=0.028). Furthermore, there was a significant reduction from baseline in all structural OCT parameters (subretinal fluid and subfoveal choroidal thickness [SFCT]; p<0.05). (ii) Non-exudative fellow eyes: There was no significant change in BCVA. There was a significant reduction from baseline in SFCT and choriocapillaris flow deficit percentage (p<0.05). In this pilot study, continuous oral EPL therapy in cCSC pachychoroid eyes resulted in long-term morpho-functional improvement. The beneficial effect of EPL occurred within the first year and was maintained after four years. Based on these preliminary observations, EPL may be effective in the exudative forms of CSC.

The Impact of Cataracts on the Measurement of Macular Choriocapillaris Flow Deficits Using Swept-Source OCT Angiography.

The impact of cataracts on the measurement of macular choriocapillaris flow deficits (CC FDs) was assessed by comparing the quantitative results before and after cataract surgery using an image quality algorithm developed for swept-source optical coherence tomography angiography (SS-OCTA) scans and a validated strategy for quantifying the CC FDs. SS-OCTA image quality scores and CC FDs measurements within the fovea-centered 1-mm, 3-mm, and 5-mm diameter circles were compared before and after cataract surgery. CC FDs changes in a modified Early Treatment Diabetic Retinopathy Study (ETDRS) grid were further investigated. Twenty-four eyes were studied. Overall image quality in all three circles was observed to improve significantly following the removal of cataracts (all P < 0.05). Although there was good repeatability in the measurements of CC FDs at both visits (intraclass correlation coefficients were over 0.95), significant decreases in CC FD measurements were observed after surgery within the 1-mm circle (P < 0.001) and the 3-mm circle (P = 0.011), but no changes were observed within the 5-mm circle (P = 0.509) or any of the quadrant sectors of the modified ETDRS grid (all P > 0.05). The presence of cataracts resulted in worse image quality and increased CC FD measurements within the fovea-centered 1-mm and 3-mm circles, with the 1-mm circle being impacted the most. The impaired detection of CC perfusion deficits within the central macula of cataract eyes needs to be appreciated when imaging the CC in phakic eyes, especially in clinical trials.

Choroidal vasculature act as predictive biomarkers of long-term ocular elongation in myopic children treated with orthokeratology: a prospective cohort study

BackgroundDespite receiving orthokeratology (ortho-k), the efficacy of retarding ocular elongation during myopia varies among myopic children. The current study aimed to investigate the early changes of choroidal vasculature at one month after ortho-k treatment and its association with one-year ocular elongation, as well as the role of such choroidal responses in predicting the one-year control efficacy of ortho-k treatment.MethodsA prospective cohort study was conducted in myopic children treated with ortho-k. Myopic children aged between 8 and 12 years who were willing to wear ortho-k lenses were recruited consecutively from the Eye Hospital of Wenzhou Medical University. Subfoveal choroidal thickness (SFCT), submacular total choroidal luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow deficit (CcFD) were evaluated by optical coherence tomography (OCT) and OCT angiography over a one-year period.ResultsFifty eyes from 50 participants (24 males) who finished one-year follow-ups as scheduled were included, with a mean age of 10.31 ± 1.45 years. The one-year ocular elongation was 0.19 ± 0.17 mm. The LA (0.03 ± 0.07 mm2), SA (0.02 ± 0.05 mm2) increased proportionally after one-month of ortho-k wear (both P < 0.01), as did the SFCT (10.62 ± 19.98 μm, P < 0.001). Multivariable linear regression analyses showed that baseline CVI (β = − 0.023 mm/1%, 95% CI: − 0.036 to − 0.010), one-month LA change (β = − 0.009 mm/0.01 mm2, 95% CI: − 0.014 to − 0.003), one-month SFCT change (β = − 0.035 mm/10 µm, 95% CI: − 0.053 to − 0.017) were independently associated with one-year ocular elongation during ortho-k treatment after adjusting with age and sex (all P < 0.01). The area under the receiver operating characteristic curve of prediction model including baseline CVI, one-month SFCT change, age, and sex achieved 0.872 (95% CI: 0.771 to 0.973) for discriminating children with slow or fast ocular elongation.ConclusionsChoroidal vasculature is associated with ocular elongation during ortho-k treatment. Ortho-k treatment induces increases in choroidal vascularity and choroidal thickness as early as one month. Such early changes can act as predictive biomarkers of myopia control efficacy over a long term. The utilization of these biomarkers may help clinicians identify children who can benefit from ortho-k treatment, and thus has critical implications for the management strategies towards myopia control.

Choroidal Circulation in 8- to 30-Year-Old Chinese, Measured by SS-OCT/OCTA: Relations to Age, Axial Length, and Choroidal Thickness.

The purpose of this study was to evaluate and explore the determinants of choroidal vascularity and choriocapillaris perfusion in a Chinese population aged 8 to 30 years old. Three hundred eighty eyes from 380 subjects aged 8 to 30 years were included in this cross-sectional study. Submacular choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), and choriocapillaris flow deficit (CcFD) were estimated using images obtained from optical coherence tomography (OCT). In this population, the mean ChT was 260.4 ± 63.3 µm, TCA was 1.56 ± 0.38 mm2, LA was 0.94 ± 0.25 mm2, and SA was 0.62 ± 0.15 mm2. The mean CVI was 60.25 ± 3.21% and CcFD was 11.95 ± 1.98%. Multivariable analyses showed that higher CVI and LA was associated with older age, thicker ChT, and shorter AL; and lower CcFD was associated with shorter AL. However, the associations were not uniformly rectilinear between CcFD and age. Specifically, CcFD was positively associated with age in subjects ≤19 years old and negatively associated with age in subjects >19 years old. Development of the choroidal medium- and large-sized vascular layers and choriocapillaris was different across patients aged 8 to 30 years old. Greater axial length was associated with attenuated choroidal circulation. Choroidal thickness correlated well with choroidal vascularity, but not with choriocapillaris perfusion. Further comprehensive and longitudinal assessment of choroidal vasculature and choriocapillaris perfusion will help greatly to understand the physiological and pathological mechanisms responsible for myopia.

Quantitative assessment of choriocapillaris flow deficits and type 1 macular neovascularization growth in age-related macular degeneration

During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [− 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [− 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

Progression Biomarkers of Microvascular and Photoreceptor Changes Upon Long-Term Evaluation in Type 1 Diabetes.

To assess demographic, metabolic, and imaging predictors influencing microvasculature and photoreceptors changes over a 4-year follow-up in type 1 diabetes mellitus (DM1). This prospective cohort study enrolled patients with DM1 with mild non-proliferative diabetic retinopathy. Complete medical records, glycosylated hemoglobin (HbA1c), optical coherence tomography angiography, and adaptive optics were collected for the 4 years of follow-up. The main outcome measures included perfusion density at the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris (CC) flow deficits (FDs, %), cone density, linear dispersion index (LDi), and heterogeneity packing index (HPi). The SCP presented a dichotomic perfusion trend, with increasing PD at 1 and 2 years and a subsequent decline (P < 0.001). DCP presented a similar trend in the first 2 years (P < 0.01) but not at the following time points, whereas CC FDs constantly increased over time (P < 0.01). The best-fitted model for the microvascular parameters demonstrated that the main factors affecting SCP included time (P < 0.001), duration of diabetes (P = 0.007), and HbA1c (P = 0.03), whereas the DCP was influenced by LDi modifications (P = 0.006). The LDi and HPi were mainly influenced by SCP and CC perfusion in the parafovea (P = 0.02). This study demonstrated an initial vasodilatory phenomenon resulting from a compensatory mechanism from the superficial vasculature, followed by capillary dropout. Initially, it would seem that there was an adaptive response by the DCP to the needs of the photoreceptors. Although the SCP may initially support the DCP, when the microvascular damage becomes diffuse and involves the SCP and CC it directly affects photoreceptor integrity.

Decreased Central Macular Choriocapillaris Perfusion Correlates With Increased Low Luminance Visual Acuity Deficits

Correlations between low luminance visual acuity deficits (LLVADs) and central choriocapillaris perfusion deficits were investigated to help explain how increases in LLVAD scores at baseline predict annual growth rates of geographic atrophy (GA). Prospective cross-sectional study. Photopic luminance best-corrected visual acuity (PL-BCVA) and low luminance BCVA (LL-BCVA) were measured using the Early Treatment Diabetic Retinopathy Study chart. LL-BCVA was measured using a 2.0-log unit neutral density filter. LLVADs were calculated as the difference between PL-BCVA and LL-BCVA. Within a fovea-centered 1-mm circle, the percentage of choriocapillaris flow deficits (CC FD%), drusen volume, optical attenuation coefficient (OAC) elevation volume, and outer retinal layer (ORL) thickness were assessed. In all 90 eyes (30 normal eyes; 31 drusen-only eyes; 29 non-foveal GA eyes), significant correlations were found between the central CC FD% and PL-BCVA (r=-0.393, P < .001), LL-BCVA (r=-0.534, P < .001), and the LLVAD (r=0.439, P < .001). Central cube root (cubrt) drusen volume, cubrt OAC elevation volume, and ORL thickness were correlated with PL-BCVA, LL-BCVA, and LLVADs (all P < .05). Stepwise regression models showed that central cubrt OAC elevation volume and ORL thickness were associated with PL-BCVA (R2=0.24, P < .05); central CC FD%, cubrt OAC elevation volume, and ORL thickness were associated with LL-BCVA (R2=0.44, P < .01); and central CC FD% and ORL thickness were associated with LLVAD (R2=0.24, P < .01). The significant correlations between central CC FD% and LLVAD support the hypothesis that the ability of LLVAD to predict the growth of GA is mediated through a decrease in macular choriocapillaris perfusion.

Decreased Macular Choriocapillaris Perfusion in Eyes With Macular Reticular Pseudodrusen Imaged With Swept-Source OCT Angiography.

To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen. Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 × 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle. Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05). Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.

Imaging Biomarkers of Mesopic and Dark-Adapted Macular Functions in Eyes With Treatment-Naïve Mild Diabetic Retinopathy

To investigate the relationship between imaging biomarkers and mesopic and dark-adapted (i.e. scotopic) functions in patients with firstly detected treatment-naïve mild diabetic retinopathy (DR) and normal visual acuity. Prospective cross-sectional study. In this study, 60 patients with treatment-naïve mild DR (ETDRS 20-35) and 30 healthy controls underwent microperimetry, structural optical coherence tomography (OCT) and OCT angiography (OCTA). The foveal mesopic (22.4±4.5 dB and 25.8±2.0 dB, p=0.005), parafoveal mesopic (23.2±3.8 and 25.8±1.9, p<0.0001), and parafoveal dark-adapted (21.1±2.8 dB and 23.2±1.9 dB, p=0.003) sensitivities were reduced in DR eyes. For the foveal mesopic sensitivity, the regression analysis showed a significant topographical association with choriocapillaris flow deficits percentage (CC FD%; β: -0.234, p=0.046) and ellipsoid zone (EZ) "normalized" reflectivity (β: 0.282, p=0.048). The parafoveal mesopic sensitivity was significantly topographically associated with inner retinal thickness (β: 0.253, p=0.035), deep capillary plexus (DCP) vessel length density (VLD; β: 0.542, p=0.016), CC FD% (β: -0.312, p=0.032), and EZ "normalized" reflectivity (β: 0.328, p=0.031). Similarly, the parafoveal dark-adapted sensitivity was topographically associated with inner retinal thickness (β: 0.453, p=0.021), DCP VLD (β: 0.370, p=0.030), CC FD% (β: -0.282, p=0.048), and EZ "normalized" reflectivity (β: 0.295, p=0.042). In treatment-naïve mild DR eyes, both rod and cone functions are affected and they are associated with both DCP and CC flow impairment, which suggests that a macular hypoperfusion at these levels might implicate a reduction in photoreceptor function. The "normalized" EZ reflectivity may be a valuable structural biomarker for assessing the photoreceptor function in DR.

Diurnal changes in choroidal optical coherence tomography angiography indices over 24 hours in healthy young adults

This prospective study investigated the magnitude and pattern of variation in choroidal optical coherence tomography angiography (OCT-A) indices every 4 h over 24 h in healthy young myopic (n = 24) and non-myopic (n = 20) adults. Choriocapillaris and deep choroid en-face images from macular OCT-A scans were analysed from each session to extract magnification-corrected vascular indices including choriocapillaris flow deficit number, size and density and deep choroid perfusion density in the sub-foveal, sub-parafoveal, and sub-perifoveal regions. Choroidal thickness was also obtained from structural OCT scans. Significant variations over 24 h (P < 0.05) were observed in most of the choroidal OCT-A indices excluding sub-perifoveal flow deficit number, with peaks observed between 2 to 6 AM. For myopes, peaks occurred significantly earlier (3–5 h), and the diurnal amplitude was significantly greater for sub-foveal flow deficit density (P = 0.02) and deep choroidal perfusion density (P = 0.03) compared with non-myopes. Choroidal thickness also showed significant diurnal changes (P < 0.05) with peaks between 2 to 4 AM. Significant correlations were found between diurnal amplitudes or acrophases of choroidal OCT-A indices and choroidal thickness, intraocular pressure, and systemic blood pressure. This provides the first comprehensive diurnal assessment of choroidal OCT-A indices over 24 h.

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117-21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262-214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057-16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.