Abstract
Introduction: To compare structural and vascular parameters in the central and peripheral retina and choroid of eyes diagnosed with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) with or without pan-retinal photocoagulation (PRP) using ultrawide-field swept-source optical coherence tomography angiography (SS-OCTA). Methods: All participants underwent SS-OCTA imaging centered on the fovea. Retinal and choroidal thickness, vessel density of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary plexus (CCP), and choroidal Sattler’s and Haller’s layer (CSHL) were analyzed in nine grids using built-in angiography analysis software. Results: A total of 82 eyes from 82 participants were enrolled in this study, including 40 eyes diagnosed with severe NPDR or PDR without PRP and 42 eyes with PRP. Retinal thickness in part grids was higher in eyes with PRP than in eyes without PRP. Vessel density of the SCP in nasal-superior (p = 0.003) grid was lower in eyes with PRP than in eyes without PRP. No significant difference was found in the vessel density of the DCP between the two groups (all p > 0.05). The choroidal thickness and vessel density of the CSHL of all grids were significantly lower in eyes with PRP than in eyes without PRP (all p < 0.05). A statistically significant decrease in vessel density in CCP was found in the superior (p = 0.043), nasal-superior grid (p = 0.003), macular grid (p < 0.001), and optic disc grid (p = 0.001) of eyes with PRP, compared to eyes without PRP. A significant decrease in the vessel density of CSHL was observed in all grids of PDR eyes with PRP compared to PDR eyes without PRP (all p < 0.05). Significant decrease in choroidal thickness was observed in most grids of PDR eyes with PRP, except for macular grid (p = 0.090) and optic disc grid (p = 0.057). Conclusion: Structural and vascular parameters in the central and peripheral retinal and choroidal layers in eyes diagnosed with severe NPDR or PDR with or without PRP could be quantified using a ultrawide-field SS-OCTA. Eyes with PRP showed a significant decrease in choroidal thickness and vessel density of CCP and CSHL, compared with eyes without PRP. This trend was more obvious in eyes with PDR.
Introduction
Diabetic retinopathy (DR) is the leading cause of blindness in working-age people worldwide [1]. Pan-retinal photocoagulation (PRP) is the standard treatment for proliferative diabetic retinopathy (PDR) and severe nonproliferative diabetic retinopathy (NPDR) to reduce the incidence of severe vision loss [2]. PRP destroys the metabolically highly active photoreceptor cells and reduces the oxygen demand of the ischemic retina [3].
Although fundus fluorescein angiography is the gold standard for DR grading and diagnosis, the chorioretinal changes cannot be quantitatively evaluated at different layers by fundus fluorescein angiography. Yoshihisa demonstrated decreases in the retinal blood flow of the optic nerve head, relative flow volume at the first retinal artery, and relative flow volume at the first retinal vein using laser speckle flowgraphy [4]. Savage et al. [5] demonstrated decreased choroidal blood flow after PRP using a pneumotonometer. Emerging as a safe, rapid, and noninvasive technique, optical coherence tomography angiography (OCTA) allows for visualization of the chorioretinal microvasculature and quantification of vessel density or thickness of the macular area [6, 7]. In recent years, there has been a growing investigation of retinal and choroidal changes in the macular area after PRP in severe NPDR and PDR using OCTA [8, 9]. As is well known, laser burns are scattered throughout the retinal tissue away from the macula and optic disc in PRP treatment. Information on peripheral retinal and choroidal changes will offer an opportunity to better understand the role of PRP in the pathophysiology of DR. This study aimed to provide greater insight into the retinal and choroidal differences including thickness and vessel indices in eyes with severe NPDR or PDR undergoing PRP or not using ultrawide-field swept-source (SS)-OCTA with a 24 mm × 20 mm scanning area.
Methods
Study Subjects
This observational and cross-sectional study adhered to the principles of the Declaration of Helsinki and was approved by the Committee on Medical Ethics of the First Affiliated Hospital of the Anhui Medical University. Participants diagnosed with severe NPDR or PDR with or without PRP, as certified by history and ophthalmic examination, were recruited and informed of the purpose of the study. All participants underwent comprehensive ophthalmic examinations including best-corrected visual acuity, slit-lamp biomicroscopy of the anterior segment, fundus examination, and ultrawide-field SS-OCTA. DR grades were based on the Early Treatment Diabetic Retinopathy Study classification endorsed in 2003 by the American Academy of Ophthalmology Guidelines Committee, according to the results of fundus examination and ophthalmic history [10]. All eyes with vitreous hemorrhage due to PDR that underwent pars plana vitrectomy were included in the PDR group, even though retinal neovascularization had disappeared after treatment. The exclusion criteria were opaque media that can influence fundus examinations, glaucoma, high refractive error (more than 3 diopters), uveitis, other retinal diseases, and ocular trauma. Eyes treated with intravitreal anti-vascular endothelial growth factor (VEGF) drugs in the last 3 months or eyes with a scan quality index of <5 OCTA images were also excluded.
Ultrawide-Field SS-OCTA
A 400-kHz SS-OCTA (TowardPi Medical Technology, Beijing, China) was performed with a scan speed of 400,000 A-scans per second and a wavelength of 1060 nm, which yielded a transverse resolution of 10 μm and an in-depth resolution (optical) of 3.8 μm in tissue. Rectangular scans (24 mm × 20 mm) centered on the fovea were acquired by a trained photographer.
Image Analysis
Severe artifacts, where the capillary network could not be easily distinguished from the background signal scan centration or more than 10% of the area of the image contained motion artifacts, were excluded by manually reviewing all images [11]. In some cases, the error in automatic segmentation was manually corrected for the entire scan volume.
3 × 3 grids (comprising nine rectangles: tempo-superior, tempo, tempo-inferior, superior, macular grid, nasal-superior, inferior, optic disc grid, and nasal-inferior) with a total area of 17 × 17 mm2 were chosen to analyze the parameters of the retina and choroid (Fig. 1a). All images were manually reviewed to confirm proper placement of the grids, with the optic disc placed in the nasal grid and the macular fovea placed centrally. Images of the superficial capillary plexus (SCP) (Fig. 1b), deep capillary plexus (DCP) (Fig. 1c), choroidal capillary plexus (CCP) (Fig. 1d), and choroidal Sattler’s and Haller’s layers (CSHL) (Fig. 1e) were automatically generated using built-in software. The instrument outlined the boundaries of the SCP extending from the internal limiting membrane to 9 µm below the inner plexiform layer (Fig. 1f), the DCP extending from 6 µm below the inner plexiform layer to 9 µm below the outer plexiform layer (Fig. 1g), the CCP extending from the Bruch’s membrane to 29 µm below Bruch’s membrane (Fig. 1h), and the CSHL extending from 29 µm below Bruch’s membrane to the choroid-sclera interface (Fig. 1i). The thickness of the retina and choroid, and the vessel density of the SCP, DCP, CCP, and CSHL in the nine rectangles were obtained using the built-in software algorithm.
Statistical Analysis
Data are reported as mean ± standard deviations or percentages, as appropriate. The studied parameters were compared between the groups using the t test or χ2 tests, depending on their distribution. Pearson’s correlation analysis was used to estimate for relationships between the studied parameters. Statistical significance was set at p < 0.05. All analyses were performed using SPSS (version 21.0; IBM, Armonk, NY, USA).
Results
Demographics and Clinical Characteristics
We analyzed 40 eyes of 40 participants (29 with severe NPDR and 11 with PDR) without PRP and 42 eyes of 42 participants (17 with severe NPDR and 25 with PDR) with PRP. The overall demographic data, clinical characteristics of the participants, and scan quality index of the images are shown in Table 1. No significant difference was observed in age, diabetic duration, prevalence of hypertension, best-corrected visual acuity, or scan quality index between eyes with and without PRP.
Parameter . | PRP . | p value . | |
---|---|---|---|
(−) . | (+) . | ||
Patients, n | 40 | 42 | |
Eyes, n | 40 | 42 | |
Sex | |||
Female, n | 17 | 22 | |
Male, n | 23 | 20 | |
Age, mean±SD, years | 52.48±8.77 | 55.83±12.18 | 0.096 |
Diabetic duration, mean±SD, years | 9.15±5.85 | 11.93±7.09 | 0.168 |
Diagnosis, n (%) | |||
Severe NPDR | 29 (72.5) | 17 (40.5) | 0.003 |
PDR | 11 (27.5) | 25 (59.5) | |
Time after PRP, months | − | 1–30 | − |
History of PPV, n (%) | − | 25 (59.5) | − |
History of anti-VEGF drug, n (%) | 12 (30) | 27 (64.3) | 0.002 |
Hypertension, n (%) | 21 (52.5) | 25 (59.5) | 0.522 |
BCVA, logMAR, mean±SD | 0.36±0.31 | 0.48±0.37 | 0.956 |
Scan quality index, mean±SD | 6.70±0.99 | 7.00±1.08 | 0.833 |
Parameter . | PRP . | p value . | |
---|---|---|---|
(−) . | (+) . | ||
Patients, n | 40 | 42 | |
Eyes, n | 40 | 42 | |
Sex | |||
Female, n | 17 | 22 | |
Male, n | 23 | 20 | |
Age, mean±SD, years | 52.48±8.77 | 55.83±12.18 | 0.096 |
Diabetic duration, mean±SD, years | 9.15±5.85 | 11.93±7.09 | 0.168 |
Diagnosis, n (%) | |||
Severe NPDR | 29 (72.5) | 17 (40.5) | 0.003 |
PDR | 11 (27.5) | 25 (59.5) | |
Time after PRP, months | − | 1–30 | − |
History of PPV, n (%) | − | 25 (59.5) | − |
History of anti-VEGF drug, n (%) | 12 (30) | 27 (64.3) | 0.002 |
Hypertension, n (%) | 21 (52.5) | 25 (59.5) | 0.522 |
BCVA, logMAR, mean±SD | 0.36±0.31 | 0.48±0.37 | 0.956 |
Scan quality index, mean±SD | 6.70±0.99 | 7.00±1.08 | 0.833 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation; PPV, pars plana vitrectomy; VEGF, vascular endothelial growth factor; BCVA, best-corrected visual acuity; NPDR, non-proliferative diabetic retinopathy, PDR, proliferative diabetic retinopathy; SD, standard deviation.
Comparison of Retinal Thickness and Vessel Metrics in Eyes with or without PRP
Figure 2a–c shows a representative sample of retinal thickness and vessel density in the SCP and DCP in eyes without PRP. Figure 2d–f shows a representative sample of retinal thickness and vessel density in the SCP and DCP in the eye after PRP. The mean retinal thickness at all grids in eyes with or without PRP is shown in Table 2. We found that retinal thickness in the superior (p = 0.012), nasal-superior (p = 0.037), tempo (p = 0.001), macular (p = 0.031), and inferior (p = 0.012) grids in eyes with PRP was slightly higher than that in eyes without PRP (Table 2). No significant difference in vessel density of the SCP was observed between eyes with and without PRP in most grids, except for the nasal-superior grid (Table 2). The vessel density of the nasal-superior SCP grid (p = 0.003) in eyes with PRP was lower than that in eyes without PRP (Table 2). No significant difference was found in the vessel density of the DCP between eyes with and without PRP in all grids (all p > 0.05) (Table 2).
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of retina | Tempo-superior | 238.73±20.25 | 260.02±74.87 | 0.086 |
Superior | 276.95±25.16 | 296.83±41.97 | 0.012 | |
Nasal-superior | 270.25±22.66 | 283.88±34.16 | 0.037 | |
Tempo | 249.13±19.13 | 272.19±39.16 | 0.001 | |
Macular grid | 346.10±36.67 | 367.60±50.42 | 0.031 | |
Optic disc grid | 328.30±43.81 | 335.88±53.48 | 0.486 | |
Tempo-inferior | 226.80±14.46 | 241.71±52.63 | 0.087 | |
Inferior | 253.75±21.63 | 271.83±39.17 | 0.012 | |
Nasal-inferior | 240.40±22.74 | 255.52±63.13 | 0.157 | |
Vessel density of SCP | Tempo-superior | 34.50±5.12 | 33.14±4.40 | 0.201 |
Superior | 40.60±4.57 | 38.71±5.42 | 0.093 | |
Nasal-superior | 40.50±4.14 | 37.21±5.49 | 0.003 | |
Tempo | 35.65±2.91 | 34.19±4.46 | 0.085 | |
Macular grid | 37.55±3.41 | 38.33±4.99 | 0.411 | |
Optic disc grid | 43.68±3.28 | 41.90±6.20 | 0.113 | |
Tempo-inferior | 29.40±6.79 | 29.02±6.74 | 0.802 | |
Inferior | 33.90±5.37 | 34.29±4.87 | 0.734 | |
Nasal-inferior | 29.83±6.75 | 30.48±5.35 | 0.629 | |
Vessel density of DCP | Tempo-superior | 32.30±5.58 | 31.24±5.26 | 0.378 |
Superior | 31.13±5.30 | 29.95±5.88 | 0.346 | |
Nasal-superior | 31.75±4.81 | 29.74±5.33 | 0.077 | |
Tempo | 33.78±4.22 | 32.26±5.27 | 0.156 | |
Macular grid | 30.00±6.86 | 30.69±7.25 | 0.659 | |
Optic disc grid | 26.88±5.03 | 28.02±6.03 | 0.353 | |
Tempo-inferior | 27.38±7.50 | 27.24±6.83 | 0.931 | |
Inferior | 25.70±6.54 | 26.74±6.26 | 0.465 | |
Nasal-inferior | 25.65±6.83 | 27.26±0.88 | 0.249 |
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of retina | Tempo-superior | 238.73±20.25 | 260.02±74.87 | 0.086 |
Superior | 276.95±25.16 | 296.83±41.97 | 0.012 | |
Nasal-superior | 270.25±22.66 | 283.88±34.16 | 0.037 | |
Tempo | 249.13±19.13 | 272.19±39.16 | 0.001 | |
Macular grid | 346.10±36.67 | 367.60±50.42 | 0.031 | |
Optic disc grid | 328.30±43.81 | 335.88±53.48 | 0.486 | |
Tempo-inferior | 226.80±14.46 | 241.71±52.63 | 0.087 | |
Inferior | 253.75±21.63 | 271.83±39.17 | 0.012 | |
Nasal-inferior | 240.40±22.74 | 255.52±63.13 | 0.157 | |
Vessel density of SCP | Tempo-superior | 34.50±5.12 | 33.14±4.40 | 0.201 |
Superior | 40.60±4.57 | 38.71±5.42 | 0.093 | |
Nasal-superior | 40.50±4.14 | 37.21±5.49 | 0.003 | |
Tempo | 35.65±2.91 | 34.19±4.46 | 0.085 | |
Macular grid | 37.55±3.41 | 38.33±4.99 | 0.411 | |
Optic disc grid | 43.68±3.28 | 41.90±6.20 | 0.113 | |
Tempo-inferior | 29.40±6.79 | 29.02±6.74 | 0.802 | |
Inferior | 33.90±5.37 | 34.29±4.87 | 0.734 | |
Nasal-inferior | 29.83±6.75 | 30.48±5.35 | 0.629 | |
Vessel density of DCP | Tempo-superior | 32.30±5.58 | 31.24±5.26 | 0.378 |
Superior | 31.13±5.30 | 29.95±5.88 | 0.346 | |
Nasal-superior | 31.75±4.81 | 29.74±5.33 | 0.077 | |
Tempo | 33.78±4.22 | 32.26±5.27 | 0.156 | |
Macular grid | 30.00±6.86 | 30.69±7.25 | 0.659 | |
Optic disc grid | 26.88±5.03 | 28.02±6.03 | 0.353 | |
Tempo-inferior | 27.38±7.50 | 27.24±6.83 | 0.931 | |
Inferior | 25.70±6.54 | 26.74±6.26 | 0.465 | |
Nasal-inferior | 25.65±6.83 | 27.26±0.88 | 0.249 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation.
Comparison of Choroidal Thickness and Vessel Metrics in Eyes with or without PRP
Figure 3a–c shows a representative sample of choroidal thickness and vessel density in the CCP and CSHL in eyes without PRP. Figure 3d–f shows a representative sample of choroidal thickness and vessel density in eyes with CCP and CSHL in eyes after PRP. A significant decrease in choroidal thickness of all grids was found in eyes with PRP compared to eyes without PRP (all p < 0.05) (Table 3). No significant difference was found in the vessel density of CCP between eyes with and without PRP in part of grids (Table 3). A statistically significant decrease in vessel density in CCP was found in the superior (p = 0.043), nasal-superior grid (p = 0.003), macular grid (p < 0.001), and optic disc grid (p = 0.001) of eyes with PRP, compared to eyes without PRP (Table 3). A significant decrease in the vessel density of CSHL was observed in all grids of eyes with PRP compared to eyes without PRP (all p < 0.05) (Table 3).
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid | Tempo-superior | 267.63±67.81 | 217.69±53.55 | <0.001 |
Superior | 277.25±70.54 | 228.67±57.66 | 0.001 | |
Nasal-superior | 230.75±73.36 | 191.52±56.54 | 0.008 | |
Tempo | 245.30±67.90 | 202.95±52.46 | 0.002 | |
Macular grid | 287.58±69.00 | 248.33±65.71 | 0.010 | |
Optic disc grid | 203.55±79.38 | 161.71±66.41 | 0.011 | |
Tempo-inferior | 235.78±80.71 | 179.11±51.30 | <0.001 | |
Inferior | 222.55±87.42 | 164.98±51.85 | <0.001 | |
Nasal-inferior | 155.43±72.55 | 109.21±38.99 | 0.001 | |
Vessel density of CCP | Tempo-superior | 48.23±2.20 | 47.52±3.55 | 0.288 |
Superior | 48.60±1.69 | 47.29±3.70 | 0.043 | |
Nasal-superior | 49.35±1.42 | 47.62±3.34 | 0.003 | |
Tempo | 47.90±1.75 | 46.93±3.28 | 0.101 | |
Macular grid | 46.40±2.23 | 43.10±4.02 | <0.001 | |
Optic disc grid | 47.00±1.77 | 44.02±5.07 | 0.001 | |
Tempo-inferior | 47.10±2.63 | 46.05±3.77 | 0.149 | |
Inferior | 47.85±2.28 | 47.31±3.33 | 0.396 | |
Nasal-inferior | 48.10±1.52 | 47.64±4.05 | 0.504 | |
Vessel density of CSHL | Tempo-superior | 71.70±1.71 | 70.29±2.11 | 0.001 |
Superior | 70.93±2.12 | 69.69±1.66 | 0.004 | |
Nasal-superior | 70.68±2.07 | 69.33±1.80 | 0.002 | |
Tempo | 70.88±2.61 | 69.48±2.38 | 0.013 | |
Macular grid | 72.45±2.28 | 70.55±1.94 | <0.001 | |
Optic disc grid | 69.93±3.42 | 66.24±7.30 | 0.005 | |
Tempo-inferior | 71.43±3.03 | 69.74±2.71 | 0.009 | |
Inferior | 70.50±2.79 | 67.81±3.60 | <0.001 | |
Nasal-inferior | 68.88±3.44 | 61.90±9.26 | <0.001 |
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid | Tempo-superior | 267.63±67.81 | 217.69±53.55 | <0.001 |
Superior | 277.25±70.54 | 228.67±57.66 | 0.001 | |
Nasal-superior | 230.75±73.36 | 191.52±56.54 | 0.008 | |
Tempo | 245.30±67.90 | 202.95±52.46 | 0.002 | |
Macular grid | 287.58±69.00 | 248.33±65.71 | 0.010 | |
Optic disc grid | 203.55±79.38 | 161.71±66.41 | 0.011 | |
Tempo-inferior | 235.78±80.71 | 179.11±51.30 | <0.001 | |
Inferior | 222.55±87.42 | 164.98±51.85 | <0.001 | |
Nasal-inferior | 155.43±72.55 | 109.21±38.99 | 0.001 | |
Vessel density of CCP | Tempo-superior | 48.23±2.20 | 47.52±3.55 | 0.288 |
Superior | 48.60±1.69 | 47.29±3.70 | 0.043 | |
Nasal-superior | 49.35±1.42 | 47.62±3.34 | 0.003 | |
Tempo | 47.90±1.75 | 46.93±3.28 | 0.101 | |
Macular grid | 46.40±2.23 | 43.10±4.02 | <0.001 | |
Optic disc grid | 47.00±1.77 | 44.02±5.07 | 0.001 | |
Tempo-inferior | 47.10±2.63 | 46.05±3.77 | 0.149 | |
Inferior | 47.85±2.28 | 47.31±3.33 | 0.396 | |
Nasal-inferior | 48.10±1.52 | 47.64±4.05 | 0.504 | |
Vessel density of CSHL | Tempo-superior | 71.70±1.71 | 70.29±2.11 | 0.001 |
Superior | 70.93±2.12 | 69.69±1.66 | 0.004 | |
Nasal-superior | 70.68±2.07 | 69.33±1.80 | 0.002 | |
Tempo | 70.88±2.61 | 69.48±2.38 | 0.013 | |
Macular grid | 72.45±2.28 | 70.55±1.94 | <0.001 | |
Optic disc grid | 69.93±3.42 | 66.24±7.30 | 0.005 | |
Tempo-inferior | 71.43±3.03 | 69.74±2.71 | 0.009 | |
Inferior | 70.50±2.79 | 67.81±3.60 | <0.001 | |
Nasal-inferior | 68.88±3.44 | 61.90±9.26 | <0.001 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation.
To explore the effect of DR severity on the choroid in eyes with and without PRP, we compared the vessel density of CSHL and choroidal thickness in eyes with NPDR and PDR with or without PRP. We found a slight decrease in choroidal thickness and vessel density of CCP and CSHL in several grids in NPDR eyes with PRP, compared with NDPR eyes without PRP (Table 4). However, a significant decrease in the vessel density of CSHL was observed in all grids of eyes with PDR with PRP compared with those without PRP (all p < 0.05) (Table 5). We found significantly decreased choroidal thickness in most grids of eyes with PDR with PRP, except for the macular grid (p = 0.090) and optic disc grid (p = 0.057) (Table 5). A significant decrease in the vessel density of CCP was observed only in the nasal-superior (p = 0.016) and macular (p = 0.001) grids of PDR eyes with PRP, compared to PDR eyes without PRP (Table 5).
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid in NPDR eyes | Tempo-superior | 269.34±73.37 | 237.71±56.08 | 0.133 |
Superior | 280.76±77.96 | 235.59±49.62 | 0.038 | |
Nasal-superior | 233.07±78.78 | 205.29±57.04 | 0.211 | |
Tempo | 245.70±60.71 | 225.59±53.42 | 0.264 | |
Macular grid | 286.07±72.29 | 249.47±56.70 | 0.081 | |
Optic disc grid | 201.10±84.38 | 162.88±64.10 | 0.114 | |
Tempo-inferior | 231.66±81.50 | 193.18±56.69 | 0.093 | |
Inferior | 219.90±90.34 | 169.71±60.88 | 0.048 | |
Nasal-inferior | 156.17±77.69 | 120.94±44.17 | 0.094 | |
Vessel density of CCP in NPDR eyes | Tempo-superior | 48.38±2.16 | 48.47±2.67 | 0.900 |
Superior | 48.55±1.76 | 48.76±1.86 | 0.700 | |
Nasal-superior | 49.31±1.54 | 48.88±2.87 | 0.512 | |
Tempo | 48.00±1.39 | 47.94±1.92 | 0.905 | |
Macular grid | 46.48±2.32 | 45.18±2.94 | 0.103 | |
Optic disc grid | 47.21±1.59 | 45.47±2.76 | 0.009 | |
Tempo-inferior | 46.97±2.68 | 46.41±3.54 | 0.551 | |
Inferior | 47.86±2.50 | 48.00±2.55 | 0.859 | |
Nasal-inferior | 48.17±1.39 | 47.24±4.40 | 0.291 | |
Vessel density of CSHL in NPDR eyes | Tempo-superior | 71.66±1.95 | 70.88±2.34 | 0.235 |
Superior | 70.86±2.34 | 70.35±1.22 | 0.411 | |
Nasal-superior | 70.62±2.27 | 70.06±1.60 | 0.376 | |
Tempo | 70.72±2.93 | 70.65±1.27 | 0.919 | |
Macular grid | 72.48±2.49 | 71.29±1.69 | 0.088 | |
Optic disc grid | 69.72±3.80 | 67.47±6.17 | 0.131 | |
Tempo-inferior | 71.28±3.45 | 70.00±1.73 | 0.163 | |
Inferior | 70.48±2.79 | 69.00±2.52 | 0.078 | |
Nasal-inferior | 68.86±3.57 | 64.82±3.57 | 0.016 |
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid in NPDR eyes | Tempo-superior | 269.34±73.37 | 237.71±56.08 | 0.133 |
Superior | 280.76±77.96 | 235.59±49.62 | 0.038 | |
Nasal-superior | 233.07±78.78 | 205.29±57.04 | 0.211 | |
Tempo | 245.70±60.71 | 225.59±53.42 | 0.264 | |
Macular grid | 286.07±72.29 | 249.47±56.70 | 0.081 | |
Optic disc grid | 201.10±84.38 | 162.88±64.10 | 0.114 | |
Tempo-inferior | 231.66±81.50 | 193.18±56.69 | 0.093 | |
Inferior | 219.90±90.34 | 169.71±60.88 | 0.048 | |
Nasal-inferior | 156.17±77.69 | 120.94±44.17 | 0.094 | |
Vessel density of CCP in NPDR eyes | Tempo-superior | 48.38±2.16 | 48.47±2.67 | 0.900 |
Superior | 48.55±1.76 | 48.76±1.86 | 0.700 | |
Nasal-superior | 49.31±1.54 | 48.88±2.87 | 0.512 | |
Tempo | 48.00±1.39 | 47.94±1.92 | 0.905 | |
Macular grid | 46.48±2.32 | 45.18±2.94 | 0.103 | |
Optic disc grid | 47.21±1.59 | 45.47±2.76 | 0.009 | |
Tempo-inferior | 46.97±2.68 | 46.41±3.54 | 0.551 | |
Inferior | 47.86±2.50 | 48.00±2.55 | 0.859 | |
Nasal-inferior | 48.17±1.39 | 47.24±4.40 | 0.291 | |
Vessel density of CSHL in NPDR eyes | Tempo-superior | 71.66±1.95 | 70.88±2.34 | 0.235 |
Superior | 70.86±2.34 | 70.35±1.22 | 0.411 | |
Nasal-superior | 70.62±2.27 | 70.06±1.60 | 0.376 | |
Tempo | 70.72±2.93 | 70.65±1.27 | 0.919 | |
Macular grid | 72.48±2.49 | 71.29±1.69 | 0.088 | |
Optic disc grid | 69.72±3.80 | 67.47±6.17 | 0.131 | |
Tempo-inferior | 71.28±3.45 | 70.00±1.73 | 0.163 | |
Inferior | 70.48±2.79 | 69.00±2.52 | 0.078 | |
Nasal-inferior | 68.86±3.57 | 64.82±3.57 | 0.016 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation; NPDR, non-proliferative diabetic retinopathy.
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid in PDR eyes | Tempo-superior | 263.09±53.17 | 204.08±48.23 | 0.002 |
Superior | 268.00±47.51 | 223.96±63.09 | 0.047 | |
Nasal-superior | 224.64±59.60 | 182.16±55.37 | 0.046 | |
Tempo | 244.27±87.51 | 187.56±46.78 | 0.016 | |
Macular grid | 291.55±62.57 | 247.56±72.34 | 0.090 | |
Optic disc grid | 210.00±67.65 | 160.92±69.23 | 0.057 | |
Tempo-inferior | 246.64±81.42 | 169.56±46.03 | 0.001 | |
Inferior | 229.55±82.92 | 161.76±45.77 | 0.003 | |
Nasal-inferior | 153.45±60.17 | 101.24±33.66 | 0.002 | |
Vessel density of CCP in PDR eyes | Tempo-superior | 47.82±2.36 | 46.88±3.96 | 0.472 |
Superior | 48.73±1.55 | 46.28±4.30 | 0.077 | |
Nasal-superior | 49.45±1.13 | 46.76±3.42 | 0.016 | |
Tempo | 47.64±2.54 | 46.24±3.83 | 0.278 | |
Macular grid | 46.18±2.04 | 41.68±4.08 | 0.001 | |
Optic disc grid | 46.45±2.16 | 43.04±6.03 | 0.078 | |
Tempo-inferior | 47.45±2.58 | 45.80±3.98 | 0.216 | |
Inferior | 47.82±1.66 | 46.84±3.75 | 0.415 | |
Nasal-inferior | 47.91±1.87 | 47.92±3.86 | 0.993 | |
Vessel density of CSHL in PDR eyes | Tempo-superior | 71.81±0.87 | 69.88±1.88 | 0.003 |
Superior | 71.09±1.45 | 69.24±1.79 | 0.005 | |
Nasal-superior | 70.82±1.47 | 68.84±1.80 | 0.003 | |
Tempo | 71.27±1.56 | 68.68±2.64 | 0.005 | |
Macular grid | 72.36±1.69 | 70.04±1.97 | 0.002 | |
Optic disc grid | 70.45±2.21 | 65.40±8.00 | 0.049 | |
Tempo-inferior | 71.82±1.47 | 69.56±3.23 | 0.034 | |
Inferior | 70.55±2.94 | 67.00±4.03 | 0.013 | |
Nasal-inferior | 68.91±3.21 | 59.92±9.99 | 0.007 |
Parameter . | PRP . | p value . | ||
---|---|---|---|---|
(−) . | (+) . | |||
Thickness of choroid in PDR eyes | Tempo-superior | 263.09±53.17 | 204.08±48.23 | 0.002 |
Superior | 268.00±47.51 | 223.96±63.09 | 0.047 | |
Nasal-superior | 224.64±59.60 | 182.16±55.37 | 0.046 | |
Tempo | 244.27±87.51 | 187.56±46.78 | 0.016 | |
Macular grid | 291.55±62.57 | 247.56±72.34 | 0.090 | |
Optic disc grid | 210.00±67.65 | 160.92±69.23 | 0.057 | |
Tempo-inferior | 246.64±81.42 | 169.56±46.03 | 0.001 | |
Inferior | 229.55±82.92 | 161.76±45.77 | 0.003 | |
Nasal-inferior | 153.45±60.17 | 101.24±33.66 | 0.002 | |
Vessel density of CCP in PDR eyes | Tempo-superior | 47.82±2.36 | 46.88±3.96 | 0.472 |
Superior | 48.73±1.55 | 46.28±4.30 | 0.077 | |
Nasal-superior | 49.45±1.13 | 46.76±3.42 | 0.016 | |
Tempo | 47.64±2.54 | 46.24±3.83 | 0.278 | |
Macular grid | 46.18±2.04 | 41.68±4.08 | 0.001 | |
Optic disc grid | 46.45±2.16 | 43.04±6.03 | 0.078 | |
Tempo-inferior | 47.45±2.58 | 45.80±3.98 | 0.216 | |
Inferior | 47.82±1.66 | 46.84±3.75 | 0.415 | |
Nasal-inferior | 47.91±1.87 | 47.92±3.86 | 0.993 | |
Vessel density of CSHL in PDR eyes | Tempo-superior | 71.81±0.87 | 69.88±1.88 | 0.003 |
Superior | 71.09±1.45 | 69.24±1.79 | 0.005 | |
Nasal-superior | 70.82±1.47 | 68.84±1.80 | 0.003 | |
Tempo | 71.27±1.56 | 68.68±2.64 | 0.005 | |
Macular grid | 72.36±1.69 | 70.04±1.97 | 0.002 | |
Optic disc grid | 70.45±2.21 | 65.40±8.00 | 0.049 | |
Tempo-inferior | 71.82±1.47 | 69.56±3.23 | 0.034 | |
Inferior | 70.55±2.94 | 67.00±4.03 | 0.013 | |
Nasal-inferior | 68.91±3.21 | 59.92±9.99 | 0.007 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation; PDR, proliferative diabetic retinopathy.
Correlations between the Choroidal Thickness and Vessel Density of CSHL with the Time after PRP
No association between choroidal thickness and time after PRP was found in all grids (all p > 0.05) (Table 6). No association between the vessel density of CCP and the time after PRP was found in all grids (all p > 0.05) (Table 6). No association between the vessel density of CSHL and the time after PRP was found in all grids (all p > 0.05) (Table 6).
. | Thickness of choroid, µm . | Vessel density of CCP, % . | Vessel density of CSHL, % . | |||||
---|---|---|---|---|---|---|---|---|
Correlationcoefficient . | p value . | . | Correlationcoefficient . | p value . | . | Correlationcoefficient . | p value . | |
Tempo-superior | 0.052 | 0.742 | 0.130 | 0.411 | 0.061 | 0.703 | ||
Superior | 0.017 | 0.913 | 0.171 | 0.278 | −0.099 | 0.533 | ||
Nasal-superior | −0.101 | 0.526 | 0.116 | 0.466 | −0.217 | 0.167 | ||
Tempo | −0.161 | 0.307 | 0.093 | 0.560 | −0.165 | 0.296 | ||
Macular grid | 0.025 | 0.877 | 0.214 | 0.173 | −0.061 | 0.702 | ||
Optic disc grid | −0.133 | 0.402 | 0.081 | 0.608 | −0.027 | 0.864 | ||
Tempo-inferior | −0.052 | 0.743 | 0.194 | 0.218 | 0.061 | 0.700 | ||
Inferior | −0.186 | 0.237 | 0.137 | 0.386 | −0.194 | 0.217 | ||
Nasal-inferior | −0.178 | 0.261 | 0.168 | 0.287 | −0.056 | 0.727 |
. | Thickness of choroid, µm . | Vessel density of CCP, % . | Vessel density of CSHL, % . | |||||
---|---|---|---|---|---|---|---|---|
Correlationcoefficient . | p value . | . | Correlationcoefficient . | p value . | . | Correlationcoefficient . | p value . | |
Tempo-superior | 0.052 | 0.742 | 0.130 | 0.411 | 0.061 | 0.703 | ||
Superior | 0.017 | 0.913 | 0.171 | 0.278 | −0.099 | 0.533 | ||
Nasal-superior | −0.101 | 0.526 | 0.116 | 0.466 | −0.217 | 0.167 | ||
Tempo | −0.161 | 0.307 | 0.093 | 0.560 | −0.165 | 0.296 | ||
Macular grid | 0.025 | 0.877 | 0.214 | 0.173 | −0.061 | 0.702 | ||
Optic disc grid | −0.133 | 0.402 | 0.081 | 0.608 | −0.027 | 0.864 | ||
Tempo-inferior | −0.052 | 0.743 | 0.194 | 0.218 | 0.061 | 0.700 | ||
Inferior | −0.186 | 0.237 | 0.137 | 0.386 | −0.194 | 0.217 | ||
Nasal-inferior | −0.178 | 0.261 | 0.168 | 0.287 | −0.056 | 0.727 |
Significant p values (<0.05) are highlighted as bold.
PRP, pan-retinal photocoagulation.
Changes in Retinal and Choroidal Morphology in the Eyes with PRP in B-Scans
Figure 4 shows representative en face images and B-scans of the retina and choroid in the eyes at different times after PRP. We observed destruction of the photoreceptors, outer retina, retinal pigment epithelium, and choriocapillaris in the laser spots of the eye 1 month after PRP (Fig. 4a, b). We also found a hyperreflexic protuberance at the retinal pigment epithelium layer in laser spots of the eye 1 month after PRP (Fig. 4a, b). However, depression of the inner retinal surface was observed in the laser spots of the eye 2 years after PRP (Fig. 4c, d). Destruction of the photoreceptors, outer retina, retinal pigment epithelium, and choriocapillaris was also observed (Fig. 4c, d). However, a hyperreflexic protuberance in the retinal pigment epithelium layer was not observed (Fig. 4d). Blood flow signals were not observed at the level of the choriocapillaris layer beneath the retinal laser lesions at some laser spots (Fig. 4d).
Discussion
In this study, we quantified structural and vascular parameters in the central and peripheral retinal and choroidal layers in eyes diagnosed with severe NPDR or PDR with and without PRP using ultrawide-field SS-OCTA, which made it possible to obtain an image with a 24 mm × 20 mm rectangular scan, while still maintaining a lateral resolution of 10 µm [12‒15]. No significant difference was found in retinal thickness and vessel density of SCP or DCP between eyes with and without PRP. A significant decrease in choroidal thickness and vessel density in CSHL was found in eyes with PRP, compared with eyes without PRP. A statistical decrease in vessel density in CCP was found in the superior, nasal-superior grid, macular grid, or optic disc grid of eyes with PRP compared to eyes without PRP. A significant decrease in the vessel density of CSHL was observed in all grids of eyes with PDR with PRP compared to eyes with PDR without PRP. A significant decrease in choroidal thickness was observed in most grids of eyes with PDR with PRP, except for the macular grid and optic disc grid.
The development of macular edema following PRP has been well documented. The Manchester study found a significant increase in central subfield retinal thickness after PRP through follow-up [16]. Gabrielle et al. found that central subfield retinal thickness increased slightly with time effect during the follow-up [17]. In this study, we also found a slight increase in retinal thickness at the macular grid in eyes with PRP compared to eyes without PRP. Differences in the observational results from this study can be attributed to the differences in the stages of DR, age, and anti-VEGF treatment. Our study included larger scan areas compared with those in previous studies and provided insight into the periphery of the retina. We did not observe a severe reduction of retinal thickness in the peripheral area of the laser-induced tissue scarring.
Vessel density at the macular grid did not change significantly, although there was a trend of increasing vessel density in the SCP and DCP groups. Fawzi et al. [8], Faghihi et al. [18], and Lorusso et al. [19] did not find significant alterations in vessel density parameters following PRP in similar studies. Amani et al. [8] found no significant difference in vessel density following PRP, but an increase in the flow metrics of all capillary layers in the macular area following PRP. Retinal blood flow of the optic nerve head, the first retinal artery, and vein was reduced after PRP treatment and measured using laser speckle flowgraphy [6]. Retinal blood flow and shear rate measured by Doppler Fourier-domain optical coherence tomography did not decrease following PRP [20].
In this study, the vessel density of the SCP in the superior and nasal-superior grids in eyes with PRP was lower than that in eyes without PRP. No significant difference was found in the vessel density of the SCP between eyes with and without PRP in other grids. No significant difference was found in the vessel density of the DCP between the eyes with and without PRP in all grids.
A series of studies have shown a significant decrease in subfoveal choroidal thickness after PRP using enhanced-depth OCT [9, 21‒23]. Our results were consistent with those of previous studies. We observed a significantly thinner choroid not only at the macular grid but also at the peripheral grids in eyes with PRP than in eyes without PRP. The changes in vessel density of CSHL in our study indicated a significant decreasing tendency in all grids of eyes with PRP compared with eyes without PRP. Few studies have investigated the effects of PRP on the CSHL owing to the limitations of OCTA on scanning range and depth. Savage et al. [5] found decreased choroidal blood flow after PRP using a pneumotonometer. Jee et al. [22] reported that the luminal area of the choroid significantly decreased after PRP in a B-scan with a width of 1500 µm centered on the fovea using SS-OCT. All these findings indicated decreased blood flow to the choroid following PRP. Interestingly, a significant decrease in the vessel density of CSHL and choroidal thickness was observed in PDR eyes with PRP compared to those without PRP. However, this decrease in choroidal parameters was not obvious in the eyes with NPDR. A longitudinal study found that eyes diagnosed with severe NPDR and early PDR showed a reverse pattern of choroidal vascular parameters after PRP [24]. Studies have shown that the choroidal layer is affected in more advanced stages of DR [25, 26]. More serious choroidopathy may affect vascular expansion and flow redistribution after PRP in eyes with PDR [27].
Histological studies reported the destruction of the photoreceptor layer, outer retina, retinal pigment epithelium, and choriocapillaris in the laser treated area [28]. Large choroidal vessels are intact in photocoagulated areas [29]. We observed similar changes in en face and B-scan OCTA images of eyes with PRP. We also found an evident hyperreflexic protuberance at the retinal pigment epithelium layer in laser spots of the eye 1 month after PRP, but not 2 years after PRP. A possible explanation for the hyperreflexic protuberance at retinal pigment epithelium layer following short-time laser treatment may be PRP-induced inflammation [30]. The destruction of the choriocapillaris and lack of recovery were reported in a histopathologic study of laser scars in humans [31]. But Perry et al. [32] demonstrated a recovery of the capillary integrity in feline eyes after laser photocoagulation. A study of laser lesions of OCTA also showed that recovery continued with time in some lasered spots [33]. In this study, no significant difference was found in vessel density of CCP between eyes with and without PRP in part of grids. A statistical decrease in vessel density in CCP was found in the superior, nasal-superior, macular, or optic disc grids of eyes with PRP, compared with those in eyes without PRP. We do not believe that this regional difference in vessel density in CCP is specific. The difference in vessel density in the choriocapillaris induced by laser photocoagulation can be attributed to the laser parameters such as wavelength, power, exposure time, and spot size in different regions.
This study has several limitations. First, this was an observational and cross-sectional study. We will make a profound longitudinal study to assess how the severity of DR affects the vascular density and structural changes in patients with or without PRP. Second, systemic factors were not fully considered in this study. The effect of systemic factors on choroidal parameters has been reported in a previous study [34]. Finally, the effect of intravitreal anti-VEGF drugs has not been fully considered. However, despite these limitations, this study compared chorioretinal parameters in DR with and without PRP in a wider field of view than currently available. Further prospective investigations are required to confirm the findings of this study.
Conclusion
In summary, structural and vascular parameters in the central and peripheral retinal and choroidal layers in eyes diagnosed with severe NPDR or PDR with and without PRP can be quantified using a ultrawide-field SS-OCTA. Eyes with PRP showed a significant decrease in choroidal thickness and vessel density of CCP and CSHL, compared with those in eyes without PRP. Further longitudinal investigations may help elucidate the role of PRP in the retina and choroid in DR, and this trend was more obvious in eyes with PDR.
Statement of Ethics
This observational and cross-sectional study adhered to the principles of the Declaration of Helsinki. This study protocol was reviewed and approved by the Committee on Medical Ethics of the First Affiliated Hospital of Anhui Medical University (approval number: Quick-PJ 2022-14-30). Written informed consent was obtained for participation.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This research was supported by grants from the National Natural Science Foundation of China (No. 81700856) and the Natural Science Foundation of Anhui Province, China (No. 1808085QH280) and (No.1908085QH381).
Author Contributions
Fang Li and Jian Gao had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Fang Li, Jian Gao, Cai-hua Rao, and Lun Liu contributed to the design, acquisition, and analysis of data. Jian Gao, Fang Li, and Lun Liu contributed to the drafting and critical revision of the manuscript for important intellectual content.
Additional Information
Fang Li and Lun Liu contributed equally to this work and should be considered as co-first authors.
Data Availability Statement
All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.