To compare retinal layer thickness and chorioretinal vascular density (VD) between acute and chronic branch retinal vein occlusion (BRVO).
This study included patients with BRVO. The VD of the superficial capillary plexus (VDs), the VD of the deep capillary plexus (VDd), and VD of the choriocapillaris were obtained using optical coherence tomography angiography. Acute and chronic BRVO data were compared to assess differences between the involved and uninvolved areas.
We included 17 eyes with acute BRVO and 23 eyes with chronic BRVO. The VDs in the involved area were not significantly different between the involved area and in the uninvolved area in acute BRVO (
Vascular impaired patterns in the retinal layer differed between acute and chronic BRVO. These results may suggest that vascular change and remodeling develops differently in acute and chronic phases in BRVO.
Optical coherence tomography angiography (OCTA) is an imaging technique that has been recently studied and used to visualize blood vessels with depth resolution [
Branch retinal vein occlusion (BRVO) is a common disease that affects visual acuity [
This study was approved by the institutional review board of Korea University (2016AN0285). Informed consent was waived due to the retrospective nature of the study. The research and data collection were conducted in accordance with the tenets of the Declaration of Helsinki from the World Medical Association.
We reviewed the medical records of consecutive patients who had been diagnosed with BRVO, and who underwent OCTA between March 2016 and February 2018 at Korea University Medical Center. Patients were included if they had a diagnosis of BRVO that was made by retinal specialists. The exclusion criteria were as follows: (1) superonasal or inferonasal BRVO not affecting the macula; (2) the presence of macular edema on optical coherence tomography (OCT) imaging; (3) BRVO due to other causes such as uveitis or vasculitis; (4) BRVO accompanied by arterial occlusion or ocular ischemic syndrome; (5) other ocular diseases such as diabetic retinopathy or epiretinal membrane; (6) a history of intraocular treatment, such as intravitreal injection, laser photocoagulation or intraocular surgery within 6 months; (7) an axial length >26.5 mm; (8) OCTA images with artifacts that affected VD measurement, such as masking artifacts, blinking artifacts, or motion artifacts and (9) poor quality OCTA images (with a signal strength index of <50).
We defined acute BRVO when patients had fundus findings such as intraretinal hemorrhages, cotton wool spots, and vascular congestion [
The OCT instrument (DRI OCT Triton) used in this study had a central wavelength of 1,050 nm, speed of 100,000 A-scans/second, horizontal resolution of 20 µm, and an axial resolution of 7 µm. The volume scan was performed in a 12 × 9 mm area that covered the macula and optic disc, and each scan consisted of 1024 A-scans centered between the fovea and optic disc. The retinal thickness was measured at the central 1 mm (foveal) and 3 mm (parafoveal) areas in the early treatment of diabetic retinopathy study chart [
The OCTA images were obtained when the OCT images were acquired. The OCTA scans were taken in a 3 × 3-mm area centered on the macula. Each cube consisted of 320 A-scans of four repeated B-scans centered on the fovea. En face OCTA images of the SCP, DCP, and CC were generated based on automated layer segmentation. This segmentation was performed using image viewer software as follows: (1) SCP, from 2.6 µm posterior to the internal limiting membrane to 15.6 µm posterior to the junction of the inner plexiform layer and inner nuclear layer; (2) DCP, an 54.6-µm-thick slab from the 15.6 µm posterior to the junction of the inner plexiform layer and inner nuclear layer; and (3) CC, a 10.4-µm-thick slab from Bruch's membrane. The software provided a VD of the SCP at the foveal and parafoveal areas. The VD of the DCP (VDd) and CC were obtained by changing the reference layers (
The mean ocular perfusion pressure (OPP) was calculated using the following formula:
Continuous variables were expressed as means ± standard deviations, and categorical variables as counts (%). The Kolmogorov-Smirnov test was used to test the variables' normality. The general characteristics and parameters of patients with acute and chronic BRVO were compared using Pearson's chi-squared test or Fisher's exact test for categorical variables. The independent
Univariate linear regression or multiple linear regression analyses were used to assess the relationships among variables. The backward variable elimination method was used to select for important variables in multiple linear regression models. These variables only included covariates with
Forty-seven patients with BRVO, including 21 patients with acute BRVO and 26 patients with chronic BRVO, were included. A total of seven patients, including four with acute BRVO and three with chronic BRVO, had high stromal decorrelation signals in the OCTA images (
In 17 patients with acute BRVO, the retinal thickness, GC-IPL thickness, ORL thickness, and choroidal thickness did not differ between the involved and uninvolved areas (
In 23 patients with chronic BRVO, the retinal thickness and GC-IPL thickness in the involved area (280.36 ± 39.83, 96.82 ± 24.34 µm, respectively) were thinner than in the uninvolved area (293.83 ± 32.01 µm, p = 0.008; 106.78 ± 24.02 µm,
The retinal thickness in the involved area of chronic BRVO (280.36 ± 39.83 µm) was thinner than in acute BRVO (309.12 ± 39.16 µm,
The VDs in the involved area of chronic BRVO (44.04 ± 4.48%) was lower than for acute BRVO (46.78 ± 3.71%,
Univariate linear regression analysis indicated that visual acuity was correlated with the following parameters: age (
Univariate linear regression analysis indicated that symptom duration was correlated with retinal thickness in the involved area (β = −0.379,
In this study, we showed that structural and vascular changes did not differ between acute and chronic BRVO. Retinal layer thickness did not differ between involved and uninvolved layers in acute BRVO, however, VDd was significantly different between involved and uninvolved layers. Meanwhile, in chronic BRVO, inner retinal layer thickness was significantly thinner in the involved layers than in uninvolved layers. In addition, VD was also significantly lower in the involved layers in both SCP and DCP. These results may suggest that the mechanism of vascular change in DCP was different from SCP. In this study, the VDd was lower in the involved area than in the uninvolved area, in both acute and chronic BRVO. There was no significant difference between acute and chronic BRVO, and it has been hypothesized that BRVO mainly affects the DCP. This result is consistent with results from previous studies [
We also investigated CC, which is not typically reported in studies on BRVO. The VDc did not differ between cases of acute and chronic BRVO. Although this result was not statistically significant, the VDc was lower in the involved area than in the uninvolved area in both acute and chronic BRVO. In particular, the low VDc value was well observed in patients with high stromal decorrelation signals (
In multivariate linear regression analysis, the factors that affected visual acuity were age and VDd. These findings were consistent with those from previous studies, which found that VDd was an important factor for visual acuity during OCTA [
The OCT parameters in this study were similar to those reported in a previous study [
Previous OCT studies have employed spectral domain OCT, however spectral domain OCT has limited penetration. In addition, it is difficult to automatically measure choroidal thickness. Therefore, the studies only used the choroidal thickness of the subfoveal area, or of specific points. The swept source OCT used in this study clearly demonstrates the choroidoscleral junction without an averaging process. This allowed accurate automated measurement of choroidal thickness by specific region. The CC measurement using OCTA may also be advantageous because of swept source OCT, compared to the spectral domain OCT, for the same reason.
The OPP was determined using blood pressure and intraocular pressure. Hypertension is a risk factor for BRVO. Several prior studies have shown that the OPP affects choroidal disease [
In the OCTA images, there was a high stromal decorrelation signal observed in wide capillary nonperfusion. This phenomenon leads to overestimation of the VD by automated measurement. Therefore, human judgment is required when using the automatically measured VD. This is one of the limitations of this study. Although it is more accurate to use the method of measuring VD through binarization, this approach is difficult to assess quickly in a clinical environment. This study confirms the utility of automated VD measurements in OCTA images.
There were some other limitations to this study. The first is the retrospective and cross-sectional design, which makes it vulnerable to inherent biases. The second is incorrect symptom duration. The symptom duration was based on the patient's statement; therefore, this could differ from the actual time of the disease progression. However, in patients with chronic BRVO, the symptom duration was longer than in patients with acute BRVO. The result indicated that the symptom duration experienced by the patient was related to the timing of actual disease. Third, the OCTA software provides a parafoveal area with a diameter of 2.5 mm, while the OCT software provides a diameter of 3 mm. Therefore, there is a discrepancy in the area of measurement. Finally, the OCTA software used in this study does not provide data on the foveal avascular zone, or the flow void area of the CC. The foveal avascular zone is known to be affected by BRVO and is provided by other OCTA software. The flow void area of the CC is a region where blood flow is depressed. This area provides additional information about the status of CC. Therefore, additional studies are needed to investigate the automatically measured foveal avascular zone and flow void area of the CC.
In conclusion, neuronal structural and vascular impaired patterns in the retinal layer differed between acute and chronic BRVO. These results suggest that neuronal structural and vascular change and remodeling develop differently in acute and chronic phases in BRVO, and that changes in the acute phase, such as the deep vascular layer could be important factors for visual prognosis.
This manuscript is based upon work supported by the Ministry of Trade, Industry & Energy (MOTIE, Korea) under Industrial Technology Innovation (10063364).
Univariate linear regression analysis of ocular perfusion pressure factors in branch retinal vein occlusion
Values are presented as mean ± standard deviation, number (%), or mean ± standard deviation (range).
BRVO = branch retinal vein occlusion; logMAR = logarithm of the minimum angle of resolution.
*Independent
Values are as mean ± standard deviation.
BRVO = branch retinal vein occlusion; GC-IPL = ganglion cell layer to inner plexiform layer; ORL = outer retina layer; SCP = superficial capillary plexus; DCP = deep capillary plexus; CC = choriocapillaris.
*Wilcoxon signed-rank test; †Paired
Values are as mean ± standard deviation.
BRVO = branch retinal vein occlusion; GC-IPL = ganglion cell layer to inner plexiform layer; ORL = outer retina layer; SCP = superficial capillary plexus; DCP = deep capillary plexus; CC = choriocapillaris.
*Mann-Whitney
logMAR = logarithm of the minimum angle of resolution; GC-IPLT = thickness between ganglion cell layer to inner plexiform layer.
*