Glaucoma is characterized by progressive changes in the optic nerve head (ONH), retinal nerve fiber layer (RNFL), retinal ganglion cells (RGCs), and the corresponding visual field. Optical coherence tomography (OCT) is a widely used technique for the measurement of ONH parameters, circumpapillary RNFL thickness, and macular RGC thickness. To identify the severity of structural damage, it is important to investigate the dynamic range of ONH parameters, RNFL thickness, and RGC thickness measured by OCT. Previous cross-sectional studies evaluated the dynamic range of OCT parameters by comparing healthy eyes and eyes with glaucoma at various stages [
1-
5]. However, comparison of clinical data in different patients may be affected by various ocular and systemic factors. Thus, the ideal way to assess the dynamic range of OCT parameters according to glaucoma development and progression may be to observe longitudinal changes in OCT parameters within the same eye from nonglaucomatous status to advanced glaucoma. This study was performed to assess the dynamic range of ONH parameters and RNFL thickness in the same eye in a longitudinal manner using OCT.
Results
A total of 15 eyes from 12 participants (two female and 10 male participants) were enrolled. The median age was 53.5 years (interquartile range, 39.3 to 70.5 years), and all participants were Korean. Among the images of the 15 eyes, macular GCIPL thickness analysis was available for only five eyes; the other eyes had segmentation errors in GCIPL thickness determination. Therefore, in the present study, only ONH parameters and RNLF thickness were analyzed. The distribution of glaucoma types was primary open-angle glaucoma in two eyes, neovascular glaucoma in three eyes, uveitic glaucoma in five eyes, steroid-induced glaucoma in two eyes, angle-closure glaucoma in two eyes, and secondary glaucoma after ocular trauma in one eye. To control IOP, trabeculectomy, Ahmed glaucoma valve (New World Medical, CA, USA) implantation, selective laser trabeculoplasty, or cyclophotocoagulation was performed in 14 eyes. The median follow-up period was 52.0 months (interquartile range, 43.0 to 95.0 months). The median baseline IOP was 40.0 mmHg (interquartile range, 27.0 to 52.0 mmHg), the median highest IOP was 42.5 mmHg (interquartile range, 37.5 to 54.5 mmHg), and the final MD of the visual field test was −24.68 dB (interquartile range, −23.93 to −31.13 dB) (
Table 1).
All RNFL thickness parameters showed significant differences between the baseline and final visits (
p < 0.001) (
Fig. 1A-1E and
Table 2). The median average RNFL thickness at the baseline visit was 100.0 μm (interquartile range, 95.0 to 111.0 μm) and decreased to 62.0 μm (interquartile range, 55.0 to 64.0 μm) at the final visit. The median absolute (relative) changes in the average, superior, nasal, inferior, and temporal quadrant RNFL thickness were −36.0 (−40.6%), −67.0 (−51.9%), −18.0 (−21.4%), −61.0 (−51.1%), and −37.0 μm (−41.8%), respectively (
Table 2).
Among the ONH parameters, the rim area, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume significantly changed (
p < 0.01); however, the disc area did not show a significant change (
p = 0.753) (
Fig. 2A-2E and
Table 2). The median relative changes in the rim area, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume were −56.64%, 0.59%, 62.10%, 66.0%, and 337.90%, respectively (
Table 2).
Discussion
In the present study, the dynamic range of RNFL thickness ranged from 40.6% to 51.9%, and the dynamic range of the ONH parameters ranged from 56.64% to 337.90%. During the course of glaucoma progression, the cup volume showed the widest dynamic range. However, the disc area did not show significant changes. To the best of our knowledge, this is the only study to report longitudinal changes in RNFL and ONH parameters measured by OCT from nonglaucomatous status to advanced glaucoma.
To investigate the dynamic range of RNFL thickness, RNFL thickness of healthy eyes and glaucomatous eyes at various stages were analyzed [
1-
5]. For instance, a recent study using Cirrus HD-OCT reported that the average RNFL thickness reached a floor of 60.1 μm thickness at a visual field MD of −17.8 dB and the absolute and relative dynamic range was 28.1 μm and 31.8%, respectively [
4]. The RNFL thickness in conditions with advanced glaucoma (measurement floor) may be explained by residual capillaries, astrocytes, and Müller cells after axonal loss [
8,
9]. Another study using Cirrus HD-OCT reported that the floor of the average, superior, and inferior RNFL thickness was 57.0, 65.0, and 61.2 μm, relatively, with an absolute dynamic range of 35.4, 54.5, and 56.7 μm, respectively, at a visual field MD of −22.2 dB [
3]. In the present study, the average, superior, nasal, inferior, and temporal quadrant RNFL thickness with advanced glaucoma was 62.0, 67.0, 63.0, 65.0, and 48.0 μm, respectively, at a visual field MD of −24.68 dB. The dynamic range presented as an absolute (relative) change in the average, superior, nasal, inferior, and temporal quadrant RNFL thickness was −36.0 (−40.6%), −67.0 (−51.9%), −18.0 (−21.4%), −61.0 (−51.1%), −37.0 μm (−41.8%), respectively. These ranges were similar to those of a previous study with a cross-sectional design [
3,
4].
The relative dynamic ranges of the nasal (−21.4%) and the temporal quadrant RNFL (−41.8%) were lower than those of the superior (−51.9%) and the inferior quadrants (−51.1%). This finding may be explained by the preferential occurrence of RNFL loss in the superior and inferior quadrants. Therefore, RNFL thickness changes in the nasal and temporal quadrants may have a lower ability to detect progression than the superior or inferior RNFL thickness.
Previous studies evaluating the dynamic range of OCT parameters have focused on the circumpapillary RNFL or macular RGC thickness [
1-
5]. Little is known about the dynamic range of ONH parameters. In the present study, the median rim area, cup to disc ratio, and cup volume at final visit was 0.58 mm
2, 0.82, and 0.579 mm
3, respectively. Previous studies assessing ONH parameters in advanced glaucoma showed similar results [
10,
11]. For instance, in a study by Lavinsky et al. [
10], the mean rim area, cup to disc ratio, and cup volume of eyes with advanced glaucoma was 0.65 mm
2, 0.78, and 0.50 mm
3, respectively. When longitudinal change was evaluated, the median relative dynamic range of the rim area, cup to disc ratio, and cup volume was −56.64%, 64.10%, and 337.90%, respectively. These ranges were greater than those of the RNFL thickness. In particular, cup volume showed the widest dynamic range. The RNFL mainly consists of axons of RGCs. In contrast, large retinal vessels, including the trunk and prelaminar tissue, are present in the optic cup, in addition to the neuroretinal rim. Thus, in addition to axonal changes in RGCs (RNFL, rim), changes in vascular and connective tissues may coexist in the optic cup. This may contribute to a wider dynamic range of cup volumes than the other parameters.
In contrast to the other ONH parameters, the disc area did not show a significant change during the course of glaucoma development and progression. Belghith et al. [
12] investigated longitudinal changes in the location of Bruch’s membrane opening (BMO), which corresponds to the disc area automatically determined by the Cirrus HD-OCT algorithm from healthy status to an early glaucoma stage, and also reported that the BMO location was stable. Sharma et al. [
13] reported that the BMO area did not change with acute IOP elevation. Thus, BMO may be considered as an anatomic reference for the measurement of various ONH parameters, such as ONH surface depth, anterior lamina cribrosa surface depth, and prelaminar tissue thickness [
14]. Our study results further suggest that disc area determined by BMO location may be less affected than other parameters, even in an advanced stage of glaucoma.
Macular RGCs have been reported to have a wider dynamic range than RNFL thickness, especially in advanced glaucoma [
4,
5]. Therefore, the assessment of the dynamic range of macular RGC thickness may provide useful information. Unfortunately, in the present study, RGC thickness analysis of sufficient quality was available in only five eyes. In the majority of cases, artifacts and segmentation errors related to various retinopathies or abnormal thickening caused by macular edema were found. Among the 15 eyes, three had diabetic retinopathy with a history of panretinal photocoagulation. This might have contributed to the visual field test results. However, all of these eyes exhibited visual field losses of less than 10°, which may be mainly explained by glaucoma. Therefore, eyes with diabetic retinopathy were not excluded.
In the present study, 14 of 15 eyes underwent glaucoma surgery or laser treatment. A sudden drastic IOP decrease due to glaucoma surgery may affect the OCT parameters, especially in the early postoperative period. Therefore, the results of the present study may show different OCT change patterns compared with the conditions without surgical intervention. The median follow-up period showed a wide range of 20 to 109 months. Moreover, the number and intervals between visits were variable and 14 of 15 eyes underwent surgical intervention during the follow-up period, which might have affected OCT parameters, especially in the early postoperative period. Unfortunately, the present study enrolled only 15 eyes, which would hinder adjusting various affecting factors (i.e., number of tests, interval of tests, intervals between the operation and OCT test, and intereye correlation). Therefore, only data from the initial and final visits were analyzed using nonparametric statistical analyses. Further studies investigating longitudinal changes in OCT parameters, including RGC thickness, with a greater number of patients from nonglaucomatous status to advanced glaucoma may be needed. Recent studies have reported that OCT angiography parameters showed different dynamic range patterns in the RNFL or RGC [
4,
5]. We hope that further studies examining the longitudinal changes in OCT angiography parameters will be performed.
In conclusion, the dynamic range of RNFL thickness from a nonglaucomatous status to advanced glaucoma by longitudinal observation showed results similar to those of previous cross-sectional studies. When the dynamic range of the ONH parameters was evaluated, cup volume showed the widest range, and disc area showed the smallest change. These findings may be helpful for the assessment of glaucoma in clinical practice.