Diabetes mellitus is an important risk factor for developing primary open angle glaucoma. Although persons with diabetes or diabetic retinopathy have been found to have thinner retinal nerve fiber layer (RNFL). Panretinal photocoagulation (PRP) is an important treatment strategy for the treatment of proliferative diabetic retinopathy as it reduces the risk of severe visual loss by destroying the retinal ganglion cells whose axons form the optic nerve of the eye. PRP also causes a decrease in the RNFL thickness, leading to an effect on visual field testing. Heidelberg retinal tomography (HRT) is an important instrument that obtains a layer by layer imaging within the optic nerve head (ONH) and peripapillary nerve fiber layer. This instrument provides true and real-time quantitative information with high reproducibility for the measurement data about the optic disc and RNFL. The purpose of the study is to determine the impact of PRP on the ONH. To determine this the ONH parameters of participants with PDR undergoing PRP were compared with NPDR participants not undergoing PRP using HRT.
Subjects and Methods
A total of 90 eyes of 90 consecutive newly diagnosed patients with diabetic retinopathy (nonproliferative, NPDR, Group I and proliferative, PDR, Group II) were included in this prospective, longitudinal, noninterventional observational case series. Participants with high-risk characteristics in the form of tractional retinal detachment (TRD) or vitreous hemorrhage were excluded from the study, and those who developed the same in the course of the 3-year observation period were also excluded from the final analysis. Any patients with glaucoma, iris neovascularization, angle closure, ocular hypertension, or suspicious discs were also excluded from the study.
The study was conducted between April 2012 and December 2016. The study was approved by the institutional ethics board and conformed to the ethical standards stated in the 1964 Declaration of Helsinki. Informed consent was obtained from all participants before enrollment.
Enrolled patients were followed in the retina department of the tertiary hospital. Initially, there were 50 eyes in the NPDR group and 40 eyes in the PDR group, but only 34 eyes in the NPDR group and 22 eyes in the PDR group were used for final analysis. Twenty-six participants with NPDR were lost to follow-up and did not show any interest for ophthalmic examination even on repeated telephonic requests as they did not have any visual complaints. Of the 40 PDR patients, 10 eyes were lost due to deaths related to diabetic complications, while eight developed TRD, vitreous hemorrhage, or neovascular glaucoma. All the participants were followed at 1 and 3 years of the baseline.
All the 22 eyes in Group II underwent PRP. They underwent an HRT test at baseline and then after 1 and 4 years of PRP. PRP was performed using a frequency-doubled Nd: YAG-532 nm laser (532 nm; VISULAS 532; Zeiss, Carl Zeiss Meditec, Jena, Germany) by a single surgeon with the help of a widefield Mainster PRP lens (Ocular Instruments, Inc, Bellevue, WA, USA) with a spot size of 300 μm and a total of 1800 spots. The power was set enough to cause grayish white burns with the duration of 0.1 seconds/spot laser, completed in three sessions, each session 1 week apart. New vessels at disc and new vessels elsewhere were not treated directly. The temporal border of the fovea was delineated with three or four rows of laser burns placed two disc diameters away from the fovea. Throughout the course of treatment, the optic disc and fovea were visualized repeatedly. Laser spots were placed approximately one burn width apart.
All the participants underwent detailed assessment involving medical and family history; ophthalmic examination including visual acuity testing with refraction, slit-lamp biomicroscopy, ocular tonometry with Goldmann applanation tonometer, dilated stereoscopic and indirect ophthalmoscopic fundus examination. ONH-related RNFL assessments were performed with HRT.
ONH topography was analyzed with the HRT III. Heidelberg retinal tomography used confocal scanning principles, A 15° angle view was used in the dim room light. After generating a mean topographic image, contour lines were drawn by the same experienced technician. The accuracy in defining ONH circumference was confirmed with a minimum of 6 points for drawing the contour line. Keratometric values were used for the correction of magnification errors. The same contour line was transferred to HRT III at 1 and 4 years of follow-up. Participants with SD <30μ were included in the study. The reference plane was automatically set at the standard value of 50μ below the contour line at the temporal sector of the disc margin between 350 and 356 degrees.
For the global analysis, the following topographic parameters calculated by HRT III were evaluated among both the groups of patients at baseline and at 1 and 4 years of follow-up after PRP completion in Group II: cup area, rim area, cup/disc area ratio, linear cup/disc area ratio, cup volume, rim volume, mean cup depth, maximum cup depth, and mean RNFL thickness.
Statistical analysis was performed using the Statistical Package for Social Sciences II software (version 13.0, SSPS Inc, Chicago, III, USA). Normality was tested using the Kolmogorov–Smirnov test. Student t-test was to evaluate the continuous variables such as age, IOP, and visual acuity. HRT parameters were compared using Friedmann, followed by Wilcoxon signed-rank test for nonnormal parameters and repeated measure ANOVA, followed by Bonferroni correction for normal parameters. The statistical significance level was P < 0.05.
Among the 56 eyes, 34 (60.7%) eyes in NPDR (30 males and four females) group had a mean age of 61.29 ± 10.48 (range 45 to 82) years and 22 (39.3%) eyes (20 males and two females) in PDR group had a mean age of 57.63 ± 9.76 (range 38 to 71) years.
Using Wilcoxon sign-rank test, it was observed that in group II (PDR) participants undergoing PRP, there was a significant difference in cup area (P = 0.023) [Table 1], cup volume (P = 0.001) [Table 2], mean cup depth (P = 0.015) [Table 3], maximum cup depth (P < 0.001) [Table 4], mean RNFL thickness (P < 0.001) at 1 year of follow up, and remained significant in all at 4 years of follow-up except for cup area in PDR patients, [Figure 1 and Table 5], whereas there was no significant difference in any of the optic disc parameters in the participants of Group I belonging to NPDR group, but the difference in both the groups was not significant for any of the parameters at the interval of 4 years except for maximum cup depth [Tables 1-8].
On using, the Wilcoxin sign-rank test to determine the P values between the two groups, it was observed there was a significant difference between the groups for maximum cup depth (P = 0.021) and mean RNFL thickness (P = 0.020) at the interval of 1 year, but this difference did not remain significant after 4 years of follow-up for any of the abovementioned parameters except for maximum cup depth (P = 0.031) [Tables 1-8].
ONH topography and quantitative measurements of nerve fiber layer thickness are increasingly used in the detection and management of glaucoma and other optic neuropathies. There are a number of technologies to measure ONH parameters these include scanning laser polarimetry, optical coherence tomography, and confocal scanning laser ophthalmoscope.[6,7,8,9,10,11,12,13,14]
Our results showed a significant difference in various parameters in PRP patients in the PDR group, our results are in agreement with the various studies done in post-PRP PDR patients, observed by Cankaya et al. they observed a significant difference between rim area, cup depth, and cup-to-disc ratio in between the DR patients treated with and without PRP; in a study done bySingh et al. they also reported significant changes at 6 months post-PRP in rim area, cup depth and cup disc ratio in the DR patients undergoing PRP, this is in contrast to the findings observed by Ritenour et al. they also observed no significant change in RNFL thickness at 2 and 6 months of PRP in DR patients.
PRP is an ablative procedure that destroys retinal tissue by decreasing the number of functional cells. The high-density laser beam is reported to cause the destruction of the entire retinal layer, including ganglion cells. This thermal damage leads to the loss of RNFL.[10,11,12] Amano et al. detected the presence of abnormal appearing ONH in diabetes and proposed the glycation end products of diabetes lead to damage of the optic nerve. As per the findings of Singh et al., reported, PRP induces significant changes in the ONH in patients with diabetic retinopathy as measured with HRT. This is an important consideration in the diagnosis and evaluation of progression in glaucoma patients with diabetic retinopathy who have undergone PRP, in the short term (measured changes over 3 and 6 months). Lim et al. also reported a tendency for increased cup disc ratio that was a significant difference in the RNFL thickness in peripapillary regions among healthy subjects, diabetic patients without PRP, and diabetic patients with PRP. This is contrary to a study conducted by Kim et al. on peripapillary thickness before and after 6 months after PRP which concluded that retinal laser photocoagulation does not damage the RNFL if the laser burn is only of a moderate degree. In patients with concurrent glaucoma or without, and diabetes or diabetic retinopathy, small changes in topography must, therefore, be interpreted with caution and not necessarily attributed to glaucoma progression. It may therefore stand to reason that any progression is seen on HRT in patients having PRP be repeated after 1 year to document progression as against RNFL changes due to PRP.[18,19,20,21,22,23]
This study is the first study, in which a long-term follow-up of DR patients has been done for a period of 4 years. A lot of these observations and variations between study groups might be explained by fluctuations in RNFL due to the effect of diabetes, diabetic control, diabetic retinopathy, and PRP on retinal microvasculature. It is, therefore, a major lacuna in our study that we did not have any records of HbA1c at time points corresponding to the RNFL measurements.
Although there is a significant difference in ONH parameters in diabetic retinopathy patients undergoing PRP. RNFL and ONH morphology in eyes treated with PRP must be interpreted with caution. This trend in PDR patients in ONH parameters is maintained even at 4 years, but no significant difference with NPDR patients.
This may require setting a new baseline for RNFL measurements using the HRT when documenting RNFL loss or glaucoma progression in patients who have had PRP.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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