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Dr. Aniruddha Agarwal, A15367, Dr. MangaDogra, Dr. Ramandeep Singh, Dr. Vishali Gupta
ABSTRACT
Purpose:Patients with macula-off rhegmatogenous retinal detachments (RRD) may have suboptimal visual recovery despite successful reattachment due to various reasons such as loss of photoreceptors. This study was performed to evaluate the retinal microvasculature in subjects undergoing surgery for RRD using optical coherence tomography angiography (OCTA).
Methods:In a case-control study, analysis of OCTA findings of 18 eyes of 18 patients (12 males) who underwent RRD surgery at a tertiary institute were compared with 20 eyes of 20 age and gender-matched healthy subjects with no known ocular disease. 3×3 mm OCTA scans were obtained in addition to enhanced-depth imaging OCT. The findings on OCTA were compared with normal controls for perfusion indices and additional findings.
Results:Mean age of the patients was 30.1 years and controls was 28.5 years. Six eyes had inferior RD. Seventeen eyes underwent primary scleral buckling and 1 eye underwent vitrectomy-buckle with C3F8tamponade. None of the eyes had re-detachment during the follow-up at 3 months. The best-corrected visual acuity improved from counting fingers to mean of 0.73 ± 0.34 LogMAR. OCTA was performed after 3 months of surgery. Patients with RRD showed evidence of increased intercapillary spacing on en face OCTA. Mean vessel flow density (VFD) among patients was 34.37±0.7% and 35.27±0.2% in the superficial and deep retinal plexus, respectively, compared to 56.12 ± 2.2% and 59.64±1.9% among controls (p<0.001).
Conclusions:OCTA demonstrates significant reduction in mean VFD in patients after surgery for RRD. Decreased VFD may be responsible for suboptimal visual gain in these subjects after retinal re-attachment.
Introduction
Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss requiring early surgical management. The management options forRRD include surgical techniques such as scleral buckling (SB) (external tamponade) and pars planavitrectomy (PPV) with internal tamponade (either gas or silicone oil).1-5Conventionally, the visual prognosis following surgery for RRD is good if the macula is attached preoperatively.6 However, macular detachment preoperatively in cases with subtotal/totalRRD results in guarded visual prognosis. In order to investigate the etiologies of suboptimal visual recovery following successful retinal re-attachment, various studies have been published in the literature.7,8Using a number of advancedtechniques such as optical coherence tomography (OCT), adaptive optics (AO) imaging,9,10microperimetry11 and histopathology, correlation of visual acuity with the recovery of photoreceptors and central retinal microanatomy has been evaluated following repair of RRD.
OCT angiography (OCTA) has revolutionized the field of retinal imaging and analyses of pathophysiology of various vitreoretinal diseases such as diabetic retinopathy, age-related macular degeneration, glaucoma, and other conditions such as uveitis and macular telangiectasia.12 With the help of OCTA, entities such as pachychoroid spectrum disorders have been better studied. With the help of OCTA, it is possible to obtain a detailed depth-resolved reconstruction of the retinochoroidal microvasculature by utilizing endoluminal flow as intrinsic contrast. This property of the OCTA enables improved understanding of the various mechanisms that may be responsible for vision loss in vitreoretinal diseases.
In the index study, we aimed to analyze the retinochoroidal vascular factors involved in the visual recovery following successful retinal reattachment in patients with RRD using OCTA. In addition, the features on OCTA among patients with RRD were compared to normal control subjects in order to understand the pathological mechanisms behind suboptimal visual recovery.
MATERIALS AND METHODS
In the index study, patients with RRD undergoing successful retinal re-attachment surgery at the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India were included. The study was approved by the PGIMER Institutional Ethics Committee (IEC). Written informed consent was obtained from all individual participants included in the study. Those patients with anatomically re-attached retina undergoing OCTA scans were included. The study adhered to the tenets of the Declaration of Helsinki and the rules laid down by Health Insurance Portability and Accountability Act (HIPAA) of 1996.
Study Subjects
Subjects undergoing retinal re-attachment surgery between July 2015 to December 2016 were included in the study. The criteria for inclusion were presence of successful retinal reattachment after single surgical intervention (either primary scleral buckle or primary pars planavitrectomy with gas tamponade), clear ocular media, and absence of macular pathologies such as scars, subfoveal fibrous bands, epiretinal membranes, or residual traction bands. The imaging with OCTA was performed after surgery for all the patients (within 1 year postoperative). Patients undergoing silicone oil tamponade were excluded from the study. Other exclusion criteria were presence of pathologies such as macular holes, optic atrophy, glaucoma, and previous surgical intervention (other than uneventful cataract surgery performed at least 3 months prior to the procedure).
Image Acquisition
Patients who fulfilled the above diagnostic criteria were imaged using OCTA device (OptovueRTVue XR 100 Avanti, Optovue Inc., Fremont, CA, USA)at their month 3 postoperative visit. Optovue OCTA utilizes split-spectrum amplitude decorrelation algorithm (SSADA) for the acquisition of the en face and cross-sectional retinal images. The A-scan rate of the device is 70,000 per second and it uses a light source centered on 840nm to obtain images of different sizes (3 × 3 mm, 6 × 6 mm, or 8 × 8 mm). The structuralen face images allow recognition of artifacts such as shadowing and loss of signal. The OCTA images were analyzed using the RTVue software. Pre-defined automatic segmentation algorithms are available for the superficial and deep retinal vascular plexus, outer retina and choriocapillaris layer. In addition to the automatic segmentation slabs, the OCTA and OCT B-scans were manually segmented to identify additional features on the en face images.
In addition to the OCTA images, OCT images were also acquired for all the patients enrolled in the study. The SD-OCT images were acquired using Spectralis®, Heidelberg Engineering, Germany. The scans were performed using the high-resolution mode with 7-line raster scan and a minimum of 25 frames per second. Preoperative and postoperative color fundus photography was performed using ultra-wide field retinal camera (Optos P200Tx, Optos Inc., Scotland, UK) and/or conventional fundus camera (Carl Zeiss FF450, Zeiss Meditec, La Jolla, CA, USA) for thepatients included in the study.
Image Analyses
The image analyses were performed to assess the retinal vasculature after successful retinal re-attachment.A custom semi-automated algorithm was developed and used to quantify the capillary density index (CDI) and fractal dimension (FD).13,14 For capillary density index, all OCTA images were analyzed using a public domain software ImageJ (National Institutes of Health, USA).A circle with a radius of 1.5mm is centered at the subfoveal region and it is divided into 4 quadrants – superonasal, superotemporal, inferonasal and inferotemporal quadrants. Using the Niblackthresholding and ROI manager, all images werebinarized and converted to 8-bits with a mean pixel value and standard deviation of all points. Subsequently, the luminal area (LA) was highlighted within the circle with the brightness set to 0 and 254. The LA in the individual quadrant was merged with the corresponding threshold area and measured using ROI manager. The CDI of each quadrant was defined as the percentage of capillary density over the stromal area at the macula region. The global CDI is the average CDI value within the 1.5mm-radius circle centering on the subfoveal region.
In addition to the vascularity indices, the centralfull retinal thickness (FRT) was measured by two independent graders vertically from the inner border of the retinal nerve fiber layer to the outer border of the retinal pigment epithelium on the SD-OCT scans (at the fovea). The average of the two graders’ measurements was used for analysis.
Any disagreements between the graders were resolved with open adjudication. En face OCTA and structural en face images were analyzed to assess alterations in the retinal vasculature. Statistical analysis was performed using GraphPad Prism® (GraphPad Software Inc., La Jolla, CA) version 6.0. The quantitative data was expressed in mean along with standard deviations. Non-parametric tests were used to analyze the data from the study. Mann-Whitney U test was used to assess differences in TRA, LA, SA, CDI and FRT between the study and healthy eyes.All the p values were 2-sided and considered statistically significant when the values were <0.05.
RESULTS
In this study, 19 eyes of 19 patients undergoing surgery for RRD were included based upon the inclusion criteria previously mentioned. All the patients had macula “off” retinal detachment. The mean age of the patients was 40.21± 16.81 years. There were 15 males and 4 females in the study. All mean preoperative BCVA was 1.56± 1.07LogMAR units. At the time of imaging, the mean BCVA was 0.70 ± 0.37 units (p=0.007). The mean preoperative IOP was 13.94 ± 5.8 mm Hg which increased to 20.68± 5.37 mm Hg postoperatively. OCTA imaging was performed after a mean of 4.86± 2.66 months following retinal detachment surgery. The mean duration of visual symptoms (i.e. the duration of RRD prior to surgery) was 1.76 ± 2.84 months (range: 10 days to 6 months).
Among the 19 patients included in the study, primary pars planavitrectomy withC3F8tamponade was performed in 11 eyes. 8 eyes of 8 patients underwent primary scleral buckling. All the patients included in the study had anatomically attached retinae at the time of imaging. None of the patients required re-intervention after primary surgery. There were 20 healthy subjects (control subjects) (7 females) with no known ocular disease included in the study. The mean age of these subjects was 43.73 ± 13 years.The demographic characteristics of the subjects is listed in Table 1.
| Table 1: Demographic details of patients included in the study | |
| Feature | Value |
| Mean Age (years ± SD) | 40.5 ± 16.42 |
| Male: Female | 12:8 |
| Mean BCVA (LogMAR) | 1.58 ± 1.05 |
| Mean IOP (mm Hg) | 13.65 ± 5.8 |
En face OCTA images of the patients with RRD showed increased intercapillary spacing, reduced capillary density and decreased vascularization in the superficial and deep retinal plexuses compared to healthy control subjects. Quantitative analyses of the superficial and deep retinal plexuses were performed for the following parameters listed in the methods: TRA, LA, SA and CDI. The mean values of TRA, LA, SA and CDI for the patients and control subjects is provided in Table 2 (superficial retinal plexus) and Table 3 (deep retinal plexus). The global CDI values among patients was 33.5% and 33.69% in the superficial and deep retinal plexus, respectively, compared to 58.46% and 62.49% among healthy control subjects (p<0.001).The mean TCA, LA, SA and CDI were significantly lower among patients undergoing surgery for RRD compared to healthy controls. In addition, the mean central retinal thickness was also significantly lower among subjects than healthy controls.
| Table 2: Vascularity Indices in the Retinal Superficial Vessels | |||
| Region | Vascularity Index (%)
Patients |
Vascularity Index (%)
Controls |
P value* |
| Superior Parafovea | 33.55 ± 1.4 | 56.90 ± 2 | <0.01 |
| Inferior Parafovea | 33.33 ± 1.28 | 59.82 ± 2 | <0.01 |
| Nasal Parafovea | 33.25 ± 1.2 | 57.71 ± 2 | <0.01 |
| Temporal Parafovea | 33.89 ± 2.68 | 59.43 ± 2 | <0.01 |
| Global | 33.5 ± 1.04 | 58.46 ± 1 | <0.01 |
| *Mann-Whitney U Test | |||
| Table 3: Vascularity Indices in the Retinal Deep Vessels | |||
| Region | Vascularity Index (%)
Patients |
Vascularity Index (%)
Controls |
P value* |
| Superior Parafovea | 34.0 ± 1.95 | 60.45 ± 2 | <0.01 |
| Inferior Parafovea | 33.1 ± 2.9 | 63.83 ± 2 | <0.01 |
| Nasal Parafovea | 33.53 ± 2.27 | 61.74 ± 3 | <0.01 |
| Temporal Parafovea | 34.04 ± 1.81 | 63.94 ± 2 | <0.01 |
| Global | 34.0 ± 1.95 | 62.49 ± 2 | <0.01 |
| *Mann-Whitney U Test | |||
DISCUSSION
It is known that patients with macula-off rhegmatogenous RDs may have suboptimal visual recovery despite successful reattachment due to various reasons such as loss of photoreceptors.7,8,10 However, microvascular changes in the macula following reattachment have not been adequately studied. Using OCTA, we evaluated the retinal microvasculature in subjects who underwent surgery for RRD.
In our study, we found that there was decreased vascularity and increased intercapillary spacing of the superficial and deep retinal layers after retinal re-attachment. The results showed that patients with RRD had evidence of increased intercapillary spacing on en face OCTA. Mean vascularity index among patients was 33.5% and 33.69% in the superficial and deep retinal plexus, respectively, compared to 58.46% and 62.49% among controls (p<0.001).
OCTA provides non-invasive high-resolution imaging of retinochoroidal vascular network in subjects undergoing RRD.12Our findings suggest that retino-vascular changes may lead to photoreceptor damage that occurs in patients with retinal detachment. This may lead to poorer surgical outcome. Post-surgical photoreceptor degeneration and vascular alterations may also be related to the inflammation that occurs due to RRD.
The limitation of the index study is its modest sample size. Future studies with larger sample size and more structured methodology may help us improve our understanding further. In summary, patients with successful retinal re-attachment may have retino-vascular changes affecting the retinal plexuses, especially the deep retinal plexus leading to photoreceptor damage and suboptimal visual recovery.
1. Funding/Support
This work was partly supported by a grant from Department of Biotechnology, India for the development of Centre of Excellence at the Advanced Eye Centre, PGIMER Chandigarh.
2. Financial Disclosures
The authors have no financial disclosure/proprietary interest. The authors report no conflicts of interest. The authors alone are responsible for the content and preparation of this manuscript.
3. Other Acknowledgements
None
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