About OJO | Search | Ahead of print | Current Issue | Archives | Author Instructions | Reviewer Guidelines | Online submissionLogin 
Oman Journal of Ophthalmology Oman Journal of Ophthalmology
  Editorial Board | Subscribe | Advertise | Contact
https://www.omanophthalmicsociety.org/ Users Online: 588  Wide layoutNarrow layoutFull screen layout Home Print this page  Email this page Small font size Default font size Increase font size

Previous Article  Table of Contents  Next Article  
ORIGINAL ARTICLE
Year :   |  Volume :   |  Issue :   |  Page :  

Evaluation of macular perfusion in eyes with proliferative diabetic retinopathy using optical coherence tomography - Angiography following panretinal photocoagulation


1 Department of Vitreo-retina, Sankara Eye Hospital, Coimbatore, Tamil Nadu, India
2 Department of Medical Electronics, BMS College of Engineering, Bengaluru, Karnataka, India

Date of Submission18-Jun-2021
Date of Decision29-Aug-2021
Date of Acceptance19-Sep-2021
Date of Web Publication22-Jul-2022

Correspondence Address:
Shraddha Shah,
Sankara Eye Hospital, Coimbatore- 641 035, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ojo.ojo_191_21

   Abstract 


AIM: The aim of this study is to evaluate the effect of panretinal photocoagulation (PRP) on macular perfusion using optical coherence tomography–angiography (OCT-A) in eyes with proliferative diabetic retinopathy (PDR) by assessing the vessel density (VD) and the size of the foveal avascular zone (FAZ) of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), before and after PRP.
SETTINGS AND DESIGN: Prospective interventional study.
SUBJECTS AND METHODS: Twenty-nine eyes of 17 patients with PDR underwent a measurement of best-corrected visual acuity (BCVA) and were imaged using OCT and OCT-A at baseline and 6-months of follow-up. Patients received three sittings of PRP using frequency-doubled neodymium-doped yttrium aluminum garnet laser.
STATISTICAL ANALYSIS USED: The OCT-A variables were analyzed using generalized estimating equations.
RESULTS: BCVA was unchanged at 6-months follow-up (P = 0.09). FAZ of SCP and DCP (P = 0.28 and 0.89, respectively), VD at foveal SCP (P = 0.08), foveal DCP (P = 0.05), parafoveal SCP (P = 0.13), and parafoveal DCP (P = 0.07) showed no statistically significant difference at 6 months post PRP.
CONCLUSIONS: OCT-A parameters were not significantly affected by PRP at 6-months follow-up indicating no alteration in macular perfusion. Further analyses with larger samples and longer duration are warranted to confirm our results.

Keywords: Macular perfusion, optical coherence tomography-angiography, panretinal photocoagulation, proliferative diabetic retinopathy



How to cite this URL:
Shah S, Venkataraman A, Appaji A, Prabhushanker M, Ganesan G. Evaluation of macular perfusion in eyes with proliferative diabetic retinopathy using optical coherence tomography - Angiography following panretinal photocoagulation. Oman J Ophthalmol [Epub ahead of print] [cited 2022 Aug 10]. Available from: https://www.ojoonline.org/preprintarticle.asp?id=351706




   Introduction Top


Optical coherence tomography–angiography (OCT-A), a novel technique, visualizes the foveal avascular zone (FAZ), alterations in its size and shape, areas of capillary nonperfusion, retinal neovascularization, and microvascular density of superficial and deep capillary plexus (DCP) in cases of diabetic retinopathy (DR).[1]

Panretinal photocoagulation (PRP) performed for severe nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) has been reported to cause alteration of blood-retinal barrier, ocular blood flow, and choroidal vasculature.[2],[3],[4] Studies have shown that PRP tends to increase the levels of cytokines and interleukins altering the macular perfusion.[5]

Thus, in our study, we aim to evaluate the effect of PRP on macular perfusion in eyes with PDR by comparing the vessel density (VD) and size of the FAZ in the superficial capillary plexus (SCP) and the DCP, before and after PRP.


   Subjects and Methods Top


Participants

This prospective interventional study was conducted at a tertiary eye care center in Southern India. The study was approved by the Institutional ethics committee. The study adhered to the tenets of the Declaration of Helsinki and patients signed a written informed consent before being included in the study. Treatment-naïve patients with Type II diabetes mellitus with clinical and angiographic evidence of PDR and who were willing to participate were included in the study from July 2019 to September 2019. Exclusion criteria were (a) eyes with diabetic macular edema (DME), defined as the central retinal thickness of >300 μ on spectral-domain-OCT (b) High-risk PDR defined as per the early treatment diabetic retinopathy study (ETDRS) protocol (c) hazy media due to cataract or vitreous hemorrhage impeding acceptable image quality (d) history of the previous treatment for DR including anti-vascular endothelial growth factors (VEGF), lasers, and vitrectomy (e) patients requiring fill-in PRP.

Clinical assessment

All patients underwent a detailed ophthalmic evaluation which included best-corrected visual acuity (BCVA) using Snellen's chart recorded in the logarithm of the minimum angle of resolution units, intraocular pressure measurement using noncontact tonometer (Topcon CT-800), and fundus examination using indirect ophthalmoscope. Fundus fluorescein angiography (FFA) (Topcon TRC-50DX) was done to confirm and document the diagnosis of PDR in all the patients at baseline. Angiographic images were obtained using the Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Inc., Dublin, CA) with AngioPlex software. To optimize image quality, patients were fully dilated and low-quality scans (due to blinking or significant motion artifact) were excluded and repeated until an acceptable image quality (signal strength >6) was achieved. In each eye, the inner retina was subdivided into two distinct layers: The superficial retinal capillary layer, located between the inner limiting membrane and the posterior boundary of the inner plexiform layer (IPL), and the deep retinal capillary layer, which comprises blood vessels between the posterior boundary of the IPL and the outer plexiform layer. A standard scan of 6 mm × 6 mm of the affected eyes was captured. The foveal region was outlined as a central circle with a 1 mm diameter and the parafoveal region, an annulus of 2.5 mm diameter surrounding it, according to ETDRS circles.[6] The parafoveal region was further segmented into superior, inferior, nasal, and temporal quadrants for both SCP and DCP in accordance with the ETDRS grid.[6] The VD defined as the percentage of the area occupied by vessels in the foveal and parafoveal region of SCP and DCP along with the FAZ of the DCP, were calculated using a customized algorithm in Matlab 2019a software (MathWorks, Inc., Natick, MA, USA) [Figure 1]. The FAZ for SCP, measured in mm2 was calculated by the built-in software present in the Cirrus HD-OCT AngioPlex. The central retinal thickness foveal (CRT-F) and central retinal thickness parafoveal (CRT-PF) divided into four quadrants of superior, inferior, temporal, and nasal were measured using the existing algorithm available on the Cirrus HD-OCT.
Figure 1: Extraction of values using customized algorithm in Matlab 2019a software. (a) Optical coherence tomography – angiography of 6 mm × 6 mm scan showing vessel density of deep capillary plexus (b) vessel density of the foveal zone (c) vessel density of temporal parafoveal zone (d) vessel density of the inferior parafoveal zone (e) vessel density of the nasal parafoveal zone (f) vessel density of the superior parafoveal zone

Click here to view


Procedure

All patients underwent three sittings of PRP at an interval of 7 days, with the help of a wide field QuadrAspheric lens (Volk Instruments, Bellevue, CA, USA) using double-frequency neodymium-doped yttrium aluminum garnet (Nd: YAG) laser (532 nm; VISULAS 532; Zeiss, Carl Zeiss Meditec, Jena, Germany). A spot size of 200 μ, laser duration of 0.1–0.2 s with an intensity of 200 mW–400 mW was titrated till a grey burn spot was noticed. The distance between two burns was kept at one burn width apart. An average total of 2000–3000 spots were placed in all four quadrants sparing the central macula and the disc.

Follow-up

All patients were followed up for 6 months. BCVA, OCT, and OCT-A scans were taken at baseline and 6-month follow-up. Patients did not undergo any other additional treatment for PDR such as anti-VEGF injections or fill-in lasers.

Statistical analysis

All statistical analyses were conducted with the SPSS 23 software (SPSS, Inc., Chicago, IL, USA). Shapiro–Wilk test was applied to test the normality of the variables. Generalized estimating equation model was applied to assess the effect of intervention. P < 0.05 was considered significant.


   Results Top


Twenty-nine eyes of 17 patients with PDR consisting of 13 males (76.4%) and four females were recruited in this study. The mean age was found to be 54.55 ± 6.13 years. The baseline BCVA was 0.11 ± 0.18. No significant difference in BCVA (0.22 ± 0.29) was noted at 6 months (P = 0.09).

The CRT-F was 272 ± 41 μm at baseline and 267 ± 40 μm at 6 months suggesting no significant change (P = 0.52). Furthermore, no significant change was noticed in the retinal thickness of all the parafoveal quadrants, pre-and post-PRP at 6-months follow-up (P = 0.46) [Table 1].
Table 1: Mean optical coherence tomography parameters taken at baseline and at 6 months post panretinal photocoagulation in proliferative diabetic retinopathy

Click here to view


The VD (measured in percentage) was statistically unchanged for SCP (4.55 ± 7.4 at baseline and 2.45 ± 3.0 at 6 months, P = 0.08) as well as for DCP (1.53 ± 2.9 at baseline and 1.04 ± 2 at 6 months, P = 0.05) in the foveal region. Similar trends were seen in the parafoveal regions of SCP (13.7 ± 5.3 at baseline and 11.9 ± 5.3 at 6 months, P = 0.13) and DCP (7.87 ± 3.4 at baseline and 6.5 ± 3.7 at 6 months, P = 0.07). The FAZ of SCP and DCP at baseline were 0.38 mm ± 0.06 mm and 1.26 mm ± 0.19 mm, respectively. At 6 months, the values recorded were 0.39 mm ± 0.09 mm (P = 0.28) and 1.26 mm ± 0.26 mm (P = 0.89), respectively, thus indicating no significant change [Table 2].
Table 2: Mean optical coherence tomography-angiography parameters of superficial capillary plexus and deep capillary plexus, in eyes with proliferative diabetic retinopathy, shown at baseline and at 6 months post panretinal photocoagulation

Click here to view



   Discussion Top


The mean age of patients with PDR was 54.55 years. The age group of 50–80 years being the most common age for PDR to develop in an Indian population has been supported by a study conducted by Gadkari et al.[7]

Alterations in the microcirculation may precede clinically distinguishable retinopathy in diabetic patients. The VD of the superficial and deep layers which acts as an objective marker for this microvascular alteration is known to decrease in DR.[8] PRP is the standard treatment for PDR. However, its destructive nature could result in complications such as DME or worsening of preexisting macular edema leading to moderate visual loss, visual field restriction, and retinal nerve fiber layer thinning, among others.[5],[9] PRP is known to cause an inflammatory response with an upregulation of cytokines and interleukins resulting in capillary dropouts further decreasing macular perfusion.[5] The primary aim of our study was to assess the effect of PRP on the macular perfusion. It was however found in our study that, PRP had no short-term effect on the macular perfusion, the VD of SCP and DCP showing no statistical difference at 6 months following PRP [Figure 2]. Furthermore, a stabilization of BCVA was noted with no significant change in the macular thickness of the foveal and parafoveal zone (P = 0.52 and 0.46, respectively) at the end of 6-months follow-up. This suggests that PRP is a safe treatment modality for PDR and does not necessarily contribute to DME on a short-term follow-up.
Figure 2: Vessel density as captured on optical coherence tomography–angiography scans of 6 mm × 6 mm (a) Shows the percentage of vessel density of the superficial capillary plexus at baseline and at (b) Six months postlaser

Click here to view


In diabetics, irrespective of the status of retinopathy, the FAZ is distorted with gaps, holes, along with loss of integrity of the surrounding vascular arcades with capillary dropouts resulting in its enlargement.[10] This enlargement correlates with the progression of DR, indicating the larger the area of FAZ the greater the area of ischemia. Although FFA is the gold standard for assessing retinal vasculature, OCT-A has proved superiority over FFA in delineating the FAZ and the central and paracentral macular vasculature, since FFA does not allow visualization of FAZ at different levels of the retina as the vessels are obscured by leakage of the dye.[11] The normal FAZ seen on an OCT-A is a round or oval area of regular borders with a center void of vessels. The enlargement of FAZ in DR occurs at both the levels of SCP as well as DCP.[12] A study by Samara et al. done in healthy eyes, showed the FAZ of DCP to be significantly larger than SCP (0.495 mm2 ±0.227 mm2 and 0.266 mm2 ±0.097 mm2, respectively).[13] Nesper et al. suggested that DCP is susceptible to greater damage than SCP in an event of a retinal vascular disorder or macular insult.[14] This could probably be due to the higher prevalence of retinal microaneurysm at the level of DCP.[15] In our study, it was observed that in these eyes with PDR, at baseline, the FAZ of DCP (1.26 mm ± 0.19 mm) was enlarged by 231.45% in comparison to that of SCP (0.38 mm ± 0.06 mm). A significant difference (P < 0.001) was noted, indicating that DCP could be an early predictor of disease severity in DR. The FAZ of SCP and DCP at baseline and at 6 months after PRP did not show any significant change (P = 0.28, 0.89 of SCP and DCP, respectively) [Figure 3]. This steady state of FAZ suggests that the damage done to the capillaries by hyperglycemia before treatment is irreversible and laser photocoagulation, by creating an anoxic state and reducing the VEGF production, may help in preventing further enlargement of the FAZ.
Figure 3: Foveal avascular zone as seen on optical coherence tomography–angiography in eye with proliferative diabetic retinopathy. (a) Foveal avascular zone of 0.38 mm2 of superficial capillary plexus at baseline as seen in yellow. (b) Foveal avascular zone of 0.36 mm2 of superficial capillary plexus of the same eye at 6 months following panretinal photocoagulation as seen in yellow showing no significant change

Click here to view


The results of our study are in concurrence with another study by Lorusso et al.[5] with respect to the VD and FAZ of SCP and DCP. The authors, however, used Pattern Scanning Laser as compared to a single-spot double frequency Nd: YAG laser delivery system that was used in our study suggesting a comparable safety and efficacy profile between the two laser delivery systems in the treatment of PDR. Another similar study by Mirshahi et al.[16] investigated the alteration of OCT-A parameters following PRP, where they observed changes in the vascular density of the foveal zone at the SCP and DCP level but not in the FAZ. However, this could be due to the inclusion of patients with both very severe NPDR and PDR in their study.

To the best of our knowledge, this is the first study conducted in an Indian population, to elaborate the changes occurring at the macula and its perfusion status in eyes with PDR treated with PRP, using the novel noninvasive Angioplex platform and single-spot double frequency Nd: YAG laser delivery system. This study also highlights the differences in the FAZ of the SCP and DCP in eyes with PDR suggesting that the FAZ of DCP could be a marker of disease severity. In conclusion, OCT-A is promising alternative to OCT and FFA in quantifying vascular changes occurring in eyes with PDR. Our study demonstrated that in eyes with PDR, CRT, FAZ, and VD at SCP and DCP are not significantly affected by PRP at 6-months follow-up suggesting no alteration in the macular perfusion. Further studies with larger sample size and longer duration are needed to validate our results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Hagag AM, Gao SS, Jia Y, Huang D. Optical coherence tomography angiography: Technical principles and clinical applications in ophthalmology. Taiwan J Ophthalmol 2017;7:115-29.  Back to cited text no. 1
[PUBMED]  [Full text]  
2.
Moriarty AP, Spalton DJ, Shilling JS, Ffytche TJ, Bulsara M. Breakdown of the blood-aqueous barrier after argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 1996;103:833-8.  Back to cited text no. 2
    
3.
Mendivil A. Ocular blood flow velocities in patients with proliferative diabetic retinopathy after panretinal photocoagulation. Surv Ophthalmol 1997;42 Suppl 1:S89-95.  Back to cited text no. 3
    
4.
Savage HI, Hendrix JW, Peterson DC, Young H, Wilkinson CP. Differences in pulsatile ocular blood flow among three classifications of diabetic retinopathy. Invest Ophthalmol Vis Sci 2004;45:4504-9.  Back to cited text no. 4
    
5.
Lorusso M, Milano V, Nikolopoulou E, Ferrari LM, Cicinelli MV, Querques G, et al. Panretinal photocoagulation does not change macular perfusion in eyes with proliferative diabetic retinopathy. Ophthalmic Surg Lasers Imaging Retina 2019;50:174-8.  Back to cited text no. 5
    
6.
Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs--An extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:786-806.  Back to cited text no. 6
    
7.
Gadkari SS, Maskati QB, Nayak BK. Prevalence of diabetic retinopathy in India: The all India ophthalmological society diabetic retinopathy eye screening study 2014. Indian J Ophthalmol 2016;64:38-44.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Khadamy J, Abri Aghdam K, Falavarjani KG. An update on optical coherence tomography angiography in diabetic retinopathy. J Ophthalmic Vis Res 2018;13:487-97.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Soman M, Ganekal S, Nair U, Nair K. Effect of panretinal photocoagulation on macular morphology and thickness in eyes with proliferative diabetic retinopathy without clinically significant macular edema. Clin Ophthalmol 2012;6:2013-7.  Back to cited text no. 9
    
10.
Freiberg FJ, Pfau M, Wons J, Wirth MA, Becker MD, Michels S. Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2016;254:1051-8.  Back to cited text no. 10
    
11.
Soares M, Neves C, Marques IP, Pires I, Schwartz C, Costa MÂ, et al. Comparison of diabetic retinopathy classification using fluorescein angiography and optical coherence tomography angiography. Br J Ophthalmol 2017;101:62-8.  Back to cited text no. 11
    
12.
Takase N, Nozaki M, Kato A, Ozeki H, Yoshida M, Ogura Y. Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical coherence tomography angiography. Retina 2015;35:2377-83.  Back to cited text no. 12
    
13.
Samara WA, Say EA, Khoo CT, Higgins TP, Magrath G, Ferenczy S, et al. Correlation of foveal avascular zone size with foveal morphology in normal eyes using optical coherence tomography angiography. Retina 2015;35:2188-95.  Back to cited text no. 13
    
14.
Nesper PL, Roberts PK, Onishi AC, Chai H, Liu L, Jampol LM, et al. Quantifying microvascular abnormalities with increasing severity of diabetic retinopathy using optical coherence tomography angiography. Invest Ophthalmol Vis Sci 2017;58:O307-15.  Back to cited text no. 14
    
15.
Moore J, Bagley S, Ireland G, McLeod D, Boulton ME. Three dimensional analysis of microaneurysms in the human diabetic retina. J Anat 1999;194:89-100.  Back to cited text no. 15
    
16.
Mirshahi A, Ghassemi F, Fadakar K, Mirshahi R, Bazvand F, Riazi-Esfahani H. Effects of panretinal photocoagulation on retinal vasculature and foveal avascular zone in diabetic retinopathy using optical coherence tomography angiography: A pilot study. J Curr Ophthalmol 2019;31:287-91.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Previous Article    Next Article
 
  Search
 
  
     Search Pubmed for
 
    -  Shah S
    -  Venkataraman A
    -  Appaji A
    -  Prabhushanker M
    -  Ganesan G
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Subjects and Methods
   Results
   Discussion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed91    
    PDF Downloaded6    

Recommend this journal