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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 2  |  Page : 159-165

Peripapillary retinal nerve fiber layer thickness changes after panretinal photocoagulation and its relation with visual acuity changes in patients with diabetic retinopathy


Department of Ophthalmology, Kannur Medical College, Kannur, Kerala, India

Date of Submission15-Jan-2020
Date of Decision02-Feb-2020
Date of Acceptance15-Feb-2020
Date of Web Publication25-Aug-2020

Correspondence Address:
Dr. Souda Chereyeri
Department of Ophthalmology, Kannur Medical College, Anjarakandy, Kannur - 670 612, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_6_20

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  Abstract 


Background: Panretinal photocoagulation (PRP) is currently the main treatment for proliferative diabetic retinopathy. Optical coherence tomography (OCT) is a noninvasive method of analyzingin vivo retinal architecture. Objectives: The objective was to evaluate the effect of PRP on peripapillary retinal nerve fiber layer thickness (RNFLT) in patients with diabetic retinopathy using OCT and to correlate peripapillary RNFLT changes with the changes in visual acuity (VA). Materials and Methods: This is a prospective study including eighty eyes of eighty patients with proliferative diabetic retinopathy (PDR) and severe non-PDR. PRP was done with frequency-doubled Nd: YAG (532 nm) laser. Peripapillary RNFLT was measured by spectral-domain OCT at baseline and 6 months post-PRP and assessed using paired t-test. The baseline VA and changes in VA 6 months post PRP were recorded. The relationship between RNFL loss and changes in VA was assessed using ANOVA and independent t-test. Results: The mean age of the patients was 60 years, with 65% of males and 35% of females. At 6 months post-PRP, there was a significant reduction in average RNFLT with a reduction in all quadrants, except in the temporal quadrant. According to interval changes of VA, the patients were divided into improved (22.5%), unchanged (48.8%), or worsened (28.7%) groups. Improved VA group showed a significant decrease in peripapillary RNFLT. Conclusion: RNFLT reduction following PRP can be due to axonal loss secondary to the direct or indirect effects of PRP. The extremely mild reduction in the temporal quadrant can be due to the sparing of papillomacular bundle during laser treatment.

Keywords: Diabetic retinopathy, optical coherence tomography, panretinal photocoagulation, peripapillary retinal nerve fiber layer thickness


How to cite this article:
Chereyeri S, Sundaram L. Peripapillary retinal nerve fiber layer thickness changes after panretinal photocoagulation and its relation with visual acuity changes in patients with diabetic retinopathy. Kerala J Ophthalmol 2020;32:159-65

How to cite this URL:
Chereyeri S, Sundaram L. Peripapillary retinal nerve fiber layer thickness changes after panretinal photocoagulation and its relation with visual acuity changes in patients with diabetic retinopathy. Kerala J Ophthalmol [serial online] 2020 [cited 2020 Sep 29];32:159-65. Available from: http://www.kjophthal.com/text.asp?2020/32/2/159/293301




  Introduction Top


Diabetic retinopathy is a disease in response to chronic hyperglycemia involving microangiopathic changes with progressive dysfunction of retinal microvasculature, microvascular occlusion, and leakage.[1] It is the leading cause of blindness with an estimated >141 million adults affected worldwide.[2] Panretinal photocoagulation (PRP) is necessary to inhibit progression and reduce the risk of severe visual loss in proliferative diabetic retinopathy (PDR).[3],[4] Therapeutic effect of PRP depends on the destruction of outer retina, which helps to reduce oxygen demand while maintaining a steady oxygen input.[5] Although PRP primarily affects RPE and photoreceptors, laser burn with higher intensity and longer laser wavelength will result in deeper penetration and cause more destructive changes to the retina.[6] Spectral-domain-optical coherence tomography (SD-OCT) is helpful to assess the status of optic nerve by looking at peripapillary RNFL.[7] As there are only a few studies on peripapillary RNFL thickness postlaser treatment using OCT, especially in South India, with most of them giving variable results, this study is intended to throw light into this area.

Objectives

  • To evaluate the effect of PRP on peripapillary retinal nerve fiber layer thickness (RNFLT) in patients with diabetic retinopathy using OCT
  • To correlate peripapillary RNFLT changes with changes in visual acuity (VA).



  Materials and Methods Top


  • Study design: Prospective study
  • Study setting: The study was conducted in the department of ophthalmology of a tertiary care center in North Kerala
  • Study population: Patients with PDR or very severe non-PDR (NPDR) who require laser treatment
  • Study period: December 2017 to June 2019 (16 months)
  • Sample size: Eighty patients, with one eye of each patient. If bilateral involvement, only right eye was taken.


Inclusion criteria

  1. Type 2 diabetes mellitus (DM) with PDR or very severe NPDR (ETDRS classification) who require PRP
  2. Clear media without clinically significant cataract
  3. Age of diagnosis of DM >35 years.


Exclusion criteria

  1. Media opacity (which precluded good OCT images)
  2. Eyes with coexisting glaucomatous optic disc changes
  3. Degenerative myopia
  4. Hypertensive retinopathy
  5. Other retinal vascular pathology that may affect RNFL thickness.


Sample size and sampling technique

The sample size was 80, which was calculated using the following formula: n = 4PQ/d2, where P is the prevalence (28.9%), d is the absolute precision (10%), with confidence interval of 95%.

The sampling was done by convenience sampling method.

Data collection

Following approval of the institutional ethics committee, written informed consent was obtained from all patients. Examination involved best-corrected VA (BCVA), anterior segment evaluation, and dilated fundus examination. Baseline peripapillary RNFL thickness was measured in each quadrant (temporal, superior, nasal, and inferior), and 360° average thickness was measured using Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Inc, 5160 Hacienda Drive, Dublin, California, USA). After proper alignment, The optic disc cube 200 X 200 scan was obtained by centering a circle of fixed diameter on the disc. Scans with signal strength below 6 were discarded, and scans with the highest signal strength and the least eye movement were selected. PRP was done with frequency-doubled Nd: YAG (532 nm) laser. The spot size was 500 μm, and the pulse duration was 100 ms. Power was adjusted to attain gray burns, and spots were placed one spot distance apart. Repeated PRP was performed in two or three sessions until the new vessels regressed. Peripapillary RNFLT was measured in each quadrant (temporal, superior, nasal, and inferior), and 360° average thickness was measured by SD-OCT at 6 months post-PRP.

Statistical analysis

Data were entered in Microsoft Excel, and statistical analysis was performed using Statistical Package for Scientific Studies Trial version 17. Paired t-test was used to examine the interval changes in peripapillary RNFLT. P < 0.05 was considered statistically significant. The BCVA was recorded at baseline 6 months post-PRP. Those with advanced media opacities and baseline VA less than counting fingers were excluded from the study. Snellen VA measurements were converted to the logarithm of the minimum angle of resolution to simplify the statistical analysis. The relationship between RNFL loss and changes in VA was assessed using ANOVA and independent t-test.


  Results Top


The study included a total of eighty eyes from eighty patients with a mean age of 60.34 ± 7.83 years (range: 42–82 years) [Figure 1]. There were 52 males (65%) and 28 females (35%) [Figure 2]. The average RNFLT decreased statistically significantly from 84.27 ± 14.8 μm at baseline to 80.42 ± 14.2 μm at 6 months (P = 0.000). In the superior, inferior, and nasal quadrants, the RNFLT decreased from 100.66 ± 21.5 μm, 102.51 ± 23.2 μm, and 64.11 ± 12.3 μm at baseline to 95.39 ± 20.5 μm, 94.99 ± 19.7 μm, and 60.46 ± 11.2 μm, respectively, at 6 months after PRP, and showed statistically significant reduction in all these quadrants (P = 0.000). There was no statistically significant decrease in RNFLT in the temporal quadrant (P = 0.055; baseline RNFLT – 69.2 ± 23.7 μm, RNFLT at 6 months post-PRP – 68.29 ± 23.9 μm) [Table 1] and [Figure 3] and [Figure 4]. The percentage reduction in average RNFLT was 4.5%. Maximum RNFLT reduction was noticed in the inferior quadrant (7.3%), followed by nasal (5.6%) and superior (5.2%) quadrants, and least reduction was noticed in the temporal quadrant (1.3%). The patients were divided into improved (22.5%), unchanged (48.8%), or worsened (28.7%) groups according to interval changes of VA [Figure 5]. There was a statistically significant association between RNFL thinning and difference in VA (P = 0.042 by ANOVA). Independent t-test was done to ascertain which category in VA shows a significant association. For this purpose, VA was further categorized into improved and else (unchanged and worsened). Improved VA group showed a statistically significant decrease in average peripapillary RNFLT (P = 0.012). However, there was no significant association between improved VA and quadrant-wise alterations in RNFLT [Table 2].
Figure 1: Bar chart showing distribution of patients based on age

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Figure 2: Pie chart showing distribution of patients based on gender

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Table 1: Peripapillary retinal nerve fiber layer thickness changes

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Figure 3: Optical coherence tomography optic disc showing normal retinal nerve fiber layer thickness prior to panretinal photocoagulation

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Figure 4: Optical coherence tomography optic disc showing retinal nerve fiber layer thinning at 6 months postpanretinal photocoagulation

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Figure 5: Pie chart showing distribution of patients according to the interval changes of visual acuity

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Table 2: Correlation of peripapillary retinal nerve fiber layer thickness changes with changes in visual acuity

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  Discussion Top


DM is one of the most common metabolic diseases worldwide with well-known microvascular and macrovascular complications. Causes of vision loss in diabetic retinopathy are capillary nonperfusion, diabetic macular edema, vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma.

PRP reduces the risk of severe visual impairment by 50% in diabetic retinopathy patients. In Diabetic Retinopathy Study, PRP has been shown to stabilize and control the proliferative disease and has since become the gold standard treatment.[3],[4],[8] In PRP, melanosomes located within RPE absorb laser energy that causes a thermal injury and coagulates the adjacent photoreceptors and RPE cells. As photoreceptors are metabolically most active cells in the retina with high oxygen consumption, photocoagulation lowers the metabolic load and reduces ischemia and ischemia-driven angiogenic substances. Increased oxygenation and metabolic transport from the choroid to the inner retinal layers are achieved by creating photoreceptor-free glial window defects with laser burns. Although PRP affects RPE and photoreceptors, longer laser wavelength, longer pulse duration, and greater laser intensity may result in deeper penetration and cause more destructive changes to the retina.

OCT is a modern noninvasive biomicroscopic imaging technique used to obtain high-resolution cross-sectional images of the retinal layers. Although PRP has revolutionized how DR patients are treated, the long-term structural and functional effects of PRP on the retina and optic nerve remain unanswered.[9]

Our study was to evaluate the changes in peripapillary RNFL thickness following PRP using SD-OCT. We also evaluated the relationships between changes in peripapillary RNFL thickness with the changes in VA. At 6 months post-PRP, there was a significant reduction in average RNFL thickness with a reduction in all quadrants, except in the temporal quadrant. There was a significant association between peripapillary RNFL thickness change and difference in VA.

Comparison of retinal nerve fiber layer thickness changes with other studies

Lim et al.[10] in a cross-sectional study and Cankaya et al.[11] reported that RNFLs in the PRP group were thinner than those in the diabetic group who did not undergo PRP, which implied that PRP might cause RNFL thinning beyond the effect of diabetes alone. They found a significant reduction in inferior and nasal RNFLT in the period between 1 and 6 months after PRP. Similar findings were reported by Lee et al. in their prospective longitudinal study conducted over 2 years.[12]

Wadhwani et al. in their long-term study concluded that the PRP causes RNFL thickness reduction until 3 years after the procedure.[13]

Wagdy et al. reported that the major reduction in RNFL thickness occurred at the time interval between 1 and 6 months following laser treatment. More significant reduction was seen in both the nasal and the inferior quadrants.[14]

Soliman et al. found 19.4% reduction in average RNFLT after 6 months of laser treatment compared with normal values of the same age group. RNFLT reduction was most severe in the nasal quadrant (32.5%) and least in the temporal quadrant (14.5%).[15]

Abhishekh and Monika concluded significant RNFL thinning 1-year post-PRP.[16] Hsu and Chung suggested that decrease in RNFL thickness may be due to direct damage from glycosylation end products of diabetes and thermal damage from photocoagulation.[17]

Conversely, a retrospective study by Kim and Cho in the Korean Journal of Ophthalmology documented that after 6 months, even though the RNFL thickness decreased in the treatment and control groups, the changes between the two groups were not statistically significant.[6] In another study by Kim et al., the RNFL thickness gradually reduced but was not less than baseline values.[18]

In our study, more significant reduction in RNFL thickness was noticed at the superior and inferior quadrants. Researchers have suggested the possible explanation for the reduction in superior RNFL thickness that superior retina has more microaneurysms and acellular capillaries and greater alterations in the retinal blood flow, possibly accounting for the change. However, there is no satisfactory explanation for the reduction in the inferior quadrant.[10] In our study, there was no statistically significant decrease in RNFLT in the temporal quadrant. The extremely mild reduction in temporal-quadrant RNFL thickness can be attributed to the sparing of the papillomacular bundle during the application of laser treatment.[14]

In the present study, the VA of majority of patients (48.8%) was unchanged; however, VA was decreased in 28.7% of patients; improvement was achieved in 22.5% of the patients at 6 months post-PRP compared to baseline. ETDRS revealed diminished vision in 26% of the patients who did not undergo PRP and in 11% of the patients who underwent PRP.[19] McDonald and Schatz in their study reported two or more lines of decrease in vision due to PRP-induced macular edema.[20] In our study, statistically significant association was seen between RNFL loss and difference in VA (P = 0.042). Improved VA group showed a statistically significant decrease in peripapillary RNFLT (P = 0.012). Similarly, Kim and Cho reported that improved cases in the treatment group showed statistically significant decreases in peripapillary RNFL thickness. However, there was no significant reduction between the two groups.[6]


  Conclusion Top


PRP is considered a gold standard treatment of PDR. In most PDR cases, following PRP, regression of new vessels is observed. VA is maintained or even improved after PRP. RNFLT decrease at 6 months can be due to axonal loss secondary to the direct or indirect effects of PRP. SD-OCT is a very valuable tool to document the RNFLT changes following PRP.

Limitations of the study

  1. The sample size was small to fully represent a difference in peripapillary RNFLT
  2. Our maximum follow-up period was 6 months. Future studies should examine long-term results to determine if a similar pattern exists with longer follow-up
  3. There is no concurrent control group of diabetics with PDR who did not undergo PRP, as creating this control group would raise ethical issues.


Acknowledgment

We would like to thank the management of Kannur Medical College, Anjarakandy, for providing me facilities to conduct the study in their institution and the entire team of our department for their valuable support. I express my heartfelt gratitude to Dr. Lalith Sundaram, Professor and Head of Department, Kannur Medical College, Anjarakandy, for his constant supervision, invaluable guidance, and inspiration. Furthermore, special thanks to Dr. Namitha for helping me out with the statistical part of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Yanoff M, Duker JS. Ophthalmology. 4th ed. Oxford: Saunders; 2014. p. 542.  Back to cited text no. 1
    
2.
Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond) 2015;2:17.  Back to cited text no. 2
    
3.
Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology 1981;88:583-600.  Back to cited text no. 3
    
4.
Rema M, Sujatha P, Pradeepa R. Visual outcomes of pan-retinal photocoagulation in diabetic retinopathy at one-year follow-up and associated risk factors. Indian J Ophthalmol 2005;53:93-9.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Goh SY, Ropilah AR, Othmaliza O, Mushawiahti M. Retinal nerve fiber layer and retinal photocoagulation. J Surg Acad 2016;6:4-9.  Back to cited text no. 5
    
6.
Kim HY, Cho HK. Peripapillary retinal nerve fiber layer thickness change after panretinal photocoagulation in patients with diabetic retinopathy. Korean J Ophthalmol 2009;23:23-6.  Back to cited text no. 6
    
7.
Yang Z, Tatham AJ, Zangwill LM, Weinreb RN, Zhang C, Medeiros FA. Diagnostic ability of retinal nerve fiber layer imaging by swept-source optical coherence tomography in glaucoma. Am J Ophthalmol 2015;159:193-201.  Back to cited text no. 7
    
8.
Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, et al. Panretinal photocoagulation vs. intravitreous ranibizumab for proliferative diabetic retinopathy: A randomized clinical trial. JAMA 2015;314:2137-46.  Back to cited text no. 8
    
9.
Filek R, Hooper P, Sheidow T, Gonder J, Varma DK, Heckler L, et al. Structural and functional changes to the retina and optic nerve following panretinal photocoagulation over a 2-year time period. Eye (Lond) 2017;31:1237-44.  Back to cited text no. 9
    
10.
Lim MC, Tanimoto SA, Furlani BA, Lum B, Pinto LM, Eliason D, et al. Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance. Arch Ophthalmol 2009;127:857-62.  Back to cited text no. 10
    
11.
Cankaya AB, Ozdamar Y, Ozalp S, Ozkan SS. Impact of panretinal photocoagulation on optic nerve head parameters. Ophthalmologica 2011;225:193-9.  Back to cited text no. 11
    
12.
Lee SB, Kwag JY, Lee HJ, Jo YJ, Kim JY. The longitudinal changes of retinal nerve fiber layer thickness after panretinal photocoagulation in diabetic retinopathy patients. Retina 2013;33:188-93.  Back to cited text no. 12
    
13.
Wadhwani M, Bali S, Bhartiya S, Mahabir M, Upadhaya A, Dada T, et al. Long term effect of panretinal photocoagulation on retinal nerve fiber layer parameters in patients with proliferative diabetic retinopathy. Oman J Ophthalmol 2019;12:181-5.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Wagdy FM, El Sobky HM, Sarhan AR, Hafez MA. Evaluation of retinal nerve fiber layer thickness in diabetic retinopathy by optical coherence tomography after full scatter panretinal argon laser photocoagulation. J Egypt Ophthalmol Soc 2013;106:153-8.  Back to cited text no. 14
  [Full text]  
15.
Soliman M, Osman L, Hassan N. Optical coherence tomography in evaluating the nerve fiber layer following pan-retinal photocoagulation. Bull Ophthalmol Soc Egypt 1999;92:5-8.  Back to cited text no. 15
    
16.
Abhishekh A, Monika G. Effect of panretinal photocoagulation on retinal nerve fiber layer thickness, comparison with patients of NPDR and correlation with number of laser spots. International Journal of Sciences and Applied Research2016;3:10-5.  Back to cited text no. 16
    
17.
Hsu SY, Chung CP. Evaluation of retinal nerve fiber layer thickness in diabetic retinopathy after panretinal photocoagulation. Kaohsiung J Med Sci 2002;18:397-400.  Back to cited text no. 17
    
18.
Kim JJ, Im JC, Shin JP, Kim IT, Park DH. One-year follow-up of macular ganglion cell layer and peripapillary retinal nerve fibre layer thickness changes after panretinal photocoagulation. Br J Ophthalmol 2014;98:213-7.  Back to cited text no. 18
    
19.
Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98:766-85.  Back to cited text no. 19
    
20.
McDonald HR, Schatz H. Macular edema following panretinal photocoagulation. Retina 1985;5:5-10.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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