Comparison of Several Parameters in Two Optical Coherence Tomography Systems for Detecting Glaucomatous Defects in High Myopia

Abstract

Purpose: To compare the diagnostic powers of parameters of the RTVue and Cirrus-HD optical coherence tomography (OCT) systems in detecting glaucoma in highly myopic eyes.

Methods: For this study, 28 glaucoma patients with high myopia (HM-G) and 28 high-myopia controls (HM-C) were enrolled. The circumpapillary retinal nerve fiber layer (cp-RNFL) and ganglion cell complex (GCC) parameters in the RTVue-OCT, and the ganglion cell–inner plexiform layer (GCIPL) and cp-RNFL parameters in the Cirrus HD-OCT, were obtained for each subject. The receiver operating characteristics curve (ROC) was used to assess the diagnostic ability of each parameter, and the areas under the curves (AUROCs) of those parameters were compared.

Results: In both OCTs, the macular parameters showed significantly higher diagnostic power than the cp-RNFL thickness. The minimum GCIPL (0.977), inferotemporal GCIPL (0.947), and vertical cup/disc (C/D) ratio (0.968) showed the best performances among all of the Cirrus HD-OCT parameters. The focal loss volume (FLV) (0.964), global loss volume (GLV) (0.899), and vertical C/D ratio (0.899) showed the best performances among all of the RTVue-OCT parameters. Among the parameters with high diagnostic ability in each protocol of the two OCTs, the superior sector of the cp-RNFL had significantly lower abilities than the FLV and the minimum of the GCIPL (P < 0.05) in detecting glaucoma in high myopia.

Conclusions: The macular measurements had significantly better glaucoma detection abilities than the cpRNFL thickness in the high-myopia subjects in both RTVue-OCT and Cirrus HD-OCT, with no significant differences in the diagnostic ability between the two macular parameters.

Myopia, especially high myopia, was thought to be one of the independent risk factors for glaucoma.¹ Diagnosing glaucoma in high myopia poses great challenges for glaucoma specialists, since many of the optic discs of high-myopia patients are accompanied by tilt/torsional/pale appearances or peripapillary atrophy. This can lead to pseudo-glaucomatous visual field defects and difficulty in distinguishing glaucomatous neuropathy from morphologic optic abnormalities due to high myopia. 

Optical coherence tomography (OCT) is now widely used in aiding clinicians to identify glaucomatous defects at an early stage, and previous studies have shown that a decreased circumpapillary retinal nerve fiber layer (cp-RNFL) in the OCT was a good indicator of glaucoma.² Since the histopathology showed that there was retinal thinning with an enlarged eyeball and increasing axial length in myopia, especially in high myopia, theoretically, it is confusing to differentiate glaucomatous cp-RNFL defects from myopic cp-RNFL thinning. Several studies have indicated that retinal thinning in myopia was found only in the peripheral areas, and that the retinal thickness in the central area is preserved, or even thicker, in high myopia.^1,3 Therefore, it is assumed that macular measurements have advantages over the cp-RNFL in determining whether retinal thickness defects are due to glaucoma or myopia. 

Currently, ganglion cell complex (GCC) measurements using the RTVue-OCT (Optovue, Inc., Fremont, CA, USA) and ganglion cell–inner plexiform layer (GCIPL) measurements using the Cirrus HD-OCT (Cirrus; Carl Zeiss Meditec, Dublin, CA, USA) are the most widely used protocols in macular regions. The GCC thickness includes the inner plexiform layers, ganglion cell and nerve fiber layers, and the Cirrus HD-OCT can measure the GCIPL using a ganglion cell analysis (GCA) algorithm. In non–high-myopia subjects, the macular and cp-RNFL parameters had similar diagnostic abilities in detecting glaucoma.⁴ Although previous work has shown the glaucoma detection ability of the GCC thickness⁵ or GCIPL thickness⁶ in highly myopic subjects, little is known about any differences in the diagnostic power between the two macular measurements in high-myopia patients. Since the GCIPL thickness excludes the cp-RNFL layer when compared to the GCC, there is a theoretical possibility that the macular GCIPL thickness is less influenced by the myopic thinning cp-RNFL, and may have better diagnostic ability for glaucomatous changes in high-myopia eyes.⁶ In the present study, we used Cirrus HD-OCT and RTVue-OCT to compare the diagnostic powers of different macular and cp-RNFL parameters in glaucoma. As we knew, the detecting range of 10-2 visual fields corresponds to macular parameters such as GCC and GCIPL; meanwhile, 30-2 visual fields test a greater area of the field of vision, and these may better reflect global cpRNFL integrity than 10-2 fields, which may show closer correlation to macular thickness measurements as they test the central field. In our study, besides OCT parameters, we also evaluated the ability of 10-2 and 30-2 visual fields to differentiate glaucomatous from healthy eyes. 

Methods

The glaucoma participants were recruited from the Glaucoma Clinic of the Eye and Ear Nose and Throat Hospital of Fudan University (Shanghai, China). The research followed the tenets of the Declaration of Helsinki, and all of the procedures and protocols were approved by the human subjects review committee of the Eye and Ear Nose and Throat Hospital of Fudan University in Shanghai, China. 

The diagnosis of primary open-angle glaucoma (POAG) depended on glaucomatous optic neuropathy (GON) and previous high IOP (21 mm Hg or higher). The GON was identified by any of the following signs: neuroretinal rim thinning, notching, excavation, retinal nerve fiber layer defects or asymmetry, or a vertical cup to disc ≥ 0.2 between the two eyes. The GON was judged by two glaucoma experts independently, and inconsistencies between these two doctors were decided by a third glaucoma expert. The exclusion criteria for all of the subjects were pathologic myopia, media opacities, other ocular diseases, a history of ocular or laser surgery, systemic diseases, and medications that could possibly induce optic neuropathy. If both eyes in one patient conformed to the inclusion criteria, one eye was enrolled in the study randomly. The axial lengths of the subjects were greater than 26 mm, and the best-corrected visual acuity (BCVA) was at least 20/25. During the data collection phase, the IOPs of the glaucoma patients were all controlled below 21 mm Hg by antiglaucoma medication. Inclusion criteria for the high-myopia group comprised the following: The axial lengths of the subjects were greater than 26 mm; BCVA was at least 20/25; funduscopic examination showed that the structure of macular and optic disc was normal; vertical cup to disc was ≤0.4 or was <0.2 between the two eyes; IOP (Goldmann) was <21 mm Hg; Humphrey perimetry (30-2 Swedish Interactive Thresholding Algorithm) was normal. 

All of the participants gave written informed consent before the experiments. In addition, all of the subjects received comprehensive ophthalmologic examinations: BCVA, applanation tonometry, digital fundus photography, and IOL Master measurements (Carl Zeiss, Jena, Germany). Each glaucoma patient underwent Humphrey perimetry testing using the 10-2 and 30-2 programs. Reliable visual field results were defined as ≤ 33% false positive, false negative, reliable factor ≤ 15%, and pupil diameter ≥ 3 mm. Each subject underwent the RTVue-100 Fourier domain-OCT and Cirrus HD-OCT. The standard glaucoma protocol of the RTVue-100 was used, including a three-dimensional optic disc scan for the definition of the disc margin, an optic nerve head (ONH) scan, and a standard GCC scan. The thickness of cp-RNFL was measured by ONH scan, which included nearly all the axons of the ganglion cells, while the GCC scan measured the summation of three layers in the macula: the inner plexiform layer, the ganglion cell layer and the nerve fiber layer, which were on behalf of the ganglion cell dendrites, ganglion cell bodies, and ganglion cell axons, respectively. The parameters of the ONH scan were composed of average, superior, and inferior cp-RNFL thicknesses, and the parameters of the GCC scan were composed of the average, superior, and inferior GCC thicknesses and the focal loss volume (FLV), global loss volume (GLV), and vertical cup/disc (C/D) ratio, which were included in further analyses. 

Using the Cirrus HD-OCT, each eye underwent a peripapillary scan to measure cp-RNFL thickness and a macular scan to measure the GCIPL thickness by using the GCA algorithm. Different from the GCC, the GCIPL thickness measures the GCC without the cp-RNFL. Only those scans with signal strengths of 6 or more, and without motion artifacts, were kept for analysis. The parameters of the cp-RNFL scan included the average, sectoral (superior, nasal, inferior, and temporal), and symmetry thicknesses, while the parameters of the GCIPL scan included the minimum, average, and sectoral (superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal) thicknesses, which were included in further analyses. 

For statistical analysis, age, refractive errors, BCVA, IOP, axial length (AL), and C/D ratio were compared between the groups using an independent t-test. The area under the receiver operating characteristic curve (AUROC) was used to compare the powers to detect glaucoma in the parameters of the Humphrey perimetry, Cirrus HD-OCT, and RTVue-OCT. The differences in the AUROCs among these parameters were compared by the method of Delong et al.⁷ An independent t-test was performed with SPSS statistics software (Chicago, IL, USA), and the ROC analysis was performed using MedCalc software (Ostend, Belgium). A P value < 0.05 was defined as statistically significant. 

Results

In the present study, 28 glaucoma patients with high myopia (HM-G) and 28 high-myopia controls (HM-C) were enrolled. The mean age was 32.86 ± 7.39 years (mean ± SD) for the HM-G group and 29.18 ± 6.69 years (mean ± SD) for the HM-C group (Table 1). No significant differences were found between the HM-G group and HM-C group with regard to age, degree of myopia, AL, and central corneal thickness (CCT) (P > 0.05) (Table 1). The C/D ratio of the HM-G group was significantly larger than that of HM-C group (P < 0.0001). 

When compared to the HM-C group, the HM-G patients had statistically significant damage in the mean deviation (MD) and pattern standard deviation (PSD) in the 30-2 and 10-2 Humphrey perimetry programs (Table 2). The AUROCs in the ROC analysis of the perimetry parameters in the HM-G and HM-C groups are shown in Table 3. The AUROC of the PSD in the 10-2 program (0.924 ± 0.0417, mean ± SE) was significantly higher than the MD in the 10-2 program and the PSD in the 30-2 program (P < 0.05). However, there were no significant differences among the other three parameters (P > 0.05) (Table 4). 

Table 1

 

Characteristics of the Two Groups

 

Table 2

 

Perimetry Parameters of the Two Groups

 

Table 3

 

AUC of Perimetry Parameters

 

Table 4

 

Comparison of AUCs of Perimetry Parameters

 

The structural measurements of the Cirrus HD-OCT for the HM-G and HM-C groups are shown in Table 5. The HM-G patients had significantly thinner cp-RNFL than the HM-C subjects in all of the sectors (P < 0.001) except the nasal sector. Moreover, the HM-G patients had significantly thinner GCIPLs than the HM-C subjects in all of the macular sectors (P < 0.001). The AUROCs in the ROC analysis of the parameters of the Cirrus-OCT for the HM-G and HM-C groups are shown in Table 6. The minimum GCIPL (0.977), inferotemporal GCIPL (0.947), and vertical C/D (0.968) showed the best performances in all of the Cirrus-OCT parameters, and the comparisons of AUROCs of the GCIPL parameters in Cirrus HD-OCT are shown in Table 7. The AUROC of the minimum, among all the GCIPL parameters, was significantly higher than for the other GCIPL parameters (P < 0.05) except the inferotemporal sector GCIPL. In addition, the AUROCs of the inferotemporal sector, inferior sector, and average of the GCIPL were significantly higher than for the inferonasal, superior, and superonasal sectors (all P < 0.05). The comparisons of the AUROCs of the cp-RNFL parameters in the Cirrus HD-OCT are shown in Table 8. Furthermore, the AUROCs of the nasal sector of the cp-RNFL were significantly lower than the average and for any of the other sectors (P < 0.05), while the vertical C/D ratio boasted the best abilities among all of the cp-RNFL parameters in detecting glaucoma in high myopes (P < 0.05). No significant differences could be found among the other cp-RNFL parameters except the nasal sector cp-RNFL (P > 0.05). 

Table 5

 

Measurements of Cirrus OCT Parameters

 

Table 6

 

The AUCs of Cirrus OCT Parameters

 

Table 7

 

Comparison of AUCs of GCIPL Parameters in Cirrus OCT

 

Table 8

 

Comparison of AUCs of RNFL Parameters in Cirrus OCT

 

The structural measurements of the RTVue-OCT for the HM-G and HM-C groups are shown in Table 9. The HM-G group had significantly thinner cp-RNFL and GCC thicknesses than the HM-C subjects in all of the sectors (P < 0.001), while the FLV (0.964), GLV (0.899), and vertical C/D ratio (0.899) showed the best performances of all of the RTVue-OCT parameters as seen in Table 10. The comparisons of the AUROCs of the GCC parameters in the RTVue-OCT are shown in Table 11. Overall, the AUROC of the FLV GCC was significantly higher than the average and for the superior sector of the GCC (P < 0.05), and the AUROC of the GLV was significantly larger than for the superior sector of the GCC (P < 0.05). There are no significant differences that could be found between vertical C/D ration and cp-RNFL parameters in RTVue-OCT (Table 12). 

Table 9

 

The Measurements of RTVue-OCT Parameters

 

Table 10

 

The AUC of RTVue-OCT Parameters

 

Table 11

 

Comparison of AUCs of RTVue-OCT Parameters

 

When comparing the parameters with the best performance in the Humphrey perimetry, with regard to the RTVue-OCT and Cirrus HD-OCT (Table 13), we found that the superior sector of the cp-RNFL in the RTVue-OCT and the superior sector of the cp-RNFL in the Cirrus HD-OCT had significantly lower abilities than the FLV and the minimum of the GCIPL (P < 0.05) in detecting glaucoma in high myopia. No significant differences were found among the other parameters listed in Table 13. 

Table 12

 

Comparison of AUCs of RNFL Parameters in RTVue-OCT

 

Table 13

 

Comparison of ROC Curves of Parameters of Humphrey Perimetry, RTVue-OCT, and Cirrus OCT

 

Discussion

In the present study, we aimed to compare the diagnostic ability of several parameters for glaucoma in high myopia via the RTVue-OCT and Cirrus HD-OCT. To the best of our knowledge, few studies have used OCT to compare the retinal structures between glaucoma with myopia and nonglaucoma myopia in order to discriminate retinal thinning as a result of glaucoma from that due to myopia. In our study, we found that the macular measurements (GCC and GCIPL) had significantly better glaucoma detection abilities than the cp-RNFL thickness in the high-myopia subjects in both the RTVue-OCT and Cirrus HD-OCT. A previous study examined the ability of RTVue and Cirrus in detecting glaucoma in high myopia. However, the study came to a different conclusion; the researchers found a similar performance between cpRNFL and macular measurements. One likely reason for the difference is the age of the patients. The patients in our study were young, with a mean age of 33 years, compared to a mean age of 45 years in that study. It is known that axons decrease over time in healthy people.⁸ 

Among the GCC parameters in RTVue-OCT, the FLV had the best diagnostic power, while among the GCIPL parameters of the Cirrus HD-OCT, the minimum GCIPL had the best diagnostic power. Previous studies have shown consistent results, in which the minimum GCIPL in the Cirrus HD-OCT had the highest AUROC for detecting glaucoma,^4,9–11 and the inferotemporal and average GCIPLs were secondary to the minimum GCIPL in the diagnostic values for glaucoma detection.⁹ Several studies have also indicated that the GCC analysis in the RTVue-OCT had an advantage over the other parameters for diagnosing glaucoma in high myopia.^5,12 Since both the minimum GCIPL thickness and the FLV of the GCC were supposed to represent a focal loss of RGC volume, our results implied that the focal macular defects were more specific to glaucomatous retinal ganglion cell (RGC) loss than the general defects. 

In our study, the AUROCs for the FLV of the GCC and superior cp-RNFL in the RTVue-OCT were 0.964 and 0.808, respectively, while the AUROCs for the minimum GCIPL and superior cp-RNFL in the Cirrus HD-OCT were 0.97764 and 0.845, respectively, implying that the diagnostic power of the macular parameters (GCC or GCIPL) significantly overwhelmed the cp-RNFL measurements in high myopia, which was consistent with one previous study.¹³ We suspect that there are two main reasons for the superiority of the macular parameters. Firstly, several studies showed that the retinal thinning in myopia was found only in the peripheral areas, and that the retinal thickness in the central area is preserved or even thicker in high myopia.^3,14 The thinning of the GCC and GCIPL thicknesses are supposed to be due to glaucomatous RGC loss, rather than high myopia, since the central areas may be less influenced by elongated ALs. Secondly, the diameters of the scan circles used in the optic disc protocols are fixed, and the peripapillary disc margins are not that reliable, since most of the optic discs in highly myopic eyes displayed tilted, torsional, and peripapillary atrophic appearances. 

Although the AUROC of the minimum GCIPL is higher than that of the FLV of the GCC, no significant difference could be found between them, indicating similar diagnostic values of the macular measurements of the different OCTs in detecting glaucomatous defects in high myopia. Previous studies have shown that the advantages of the GCIPL over the GCC are that the GCIPL is less influenced by the cp-RNFL thickness variation than the GCC, and the GCIPL measurement has good reproducibility. 

In the non–high-myopia population, previous studies have shown that the diagnostic ability of the disc rim measurement (for instance, the C/D ratio) in the glaucomatous changes was inferior to that of the cp-RNFL parameters.^13,15 However, in our study, the index of the C/D ratio in the two OCTs showed a consistently higher diagnostic ability (AUROC = 0.968 and 0.899, respectively) than the cp-RNFL parameters. The results (the P value) are shown in the first line in Table 8 and Table 12. The vertical C/D ratio showed significantly higher diagnostic power than the cp-RNFL in Cirrus-OCT. Although the vertical C/D ratio showed the best abilities among all of the cp-RNFL parameters in RTVue-OCT, no significant differences could be found between vertical C/D ratio and cp-RNFL parameters. We speculated that the main cause of the discordance was that the research subjects in our study consisted of a high-myopia population, while those in the previous studies were not. Histopathologic and in vivo imaging studies¹ showed that there was retinal thinning with an enlarged eyeball and increasing AL in myopia. Since the cp-RNFL thinning was due to the glaucomatous RGC loss, long AL, or both, it is difficult to diagnose glaucoma in high-myopia eyes based on cp-RNFL. 

In our study, we found that 10-2 visual fields seemed to perform better than 30-2 visual fields. There are two possible causes for this result. First, the eyes included in this study had a preponderance of paracentral defects, creating bias in favor of macular parameters. Second, 10-2 fields may show closer correlation to macular thickness measurements as they test the central field while 30-2 visual fields test a greater area of the field of vision, which may better reflect global cpRNFL integrity. Eyes included in this study were highly myopic, and peripapillary atrophy might exist, which could affect the thickness of RNFL and further influence the 30-2 visual field diagnosis ability. 

As peripapillary atrophy (PPA) is common in eyes with high myopia, these eyes were not excluded from the study. The total cpRNFL thickness was measured in a 3.4-mm-diameter scan circle centered on the ONH in Cirrus HD-OCT and RTVue-OCT. The measuring range was fixed, so we cannot ensure that it did not pass through PPA. Most PPA appeared at the temporal side, and it might influence the diagnostic power of temporal RNFL. This could also be a reason that the macular parameters had better diagnostic powers than RNFL for glaucoma in high-myopia eyes. The HM-G patients had significantly thinner temporal RNFLs than the HM-C subjects (P < 0.001). So we inferred that retinal thickness defects are due to glaucoma rather than myopia. The current results showed that the diagnostic power of temporal RNFL was not very great. If those eyes with PPA were excluded, we could actually better evaluate the diagnostic performance of temporal RNFL. This is one limitation of this study. 

A previous study reported that humans have 1.2 million axons per optic nerve on average,¹⁶ and age-related thinning in humans has been estimated at an average of 4000 to 5000 axons lost per year.^16–19 The study showed that normal aging may account for a loss of 400,000 RGC axons during a 70-year life span, with a loss of 2500 axons per year in those younger than 50 years and 7500 axons per year in those older than 50 years.¹⁷ In this study, the patients with glaucoma were young, with a mean age of 33 years. As RNFL thickness decreases with age, further study is needed to see if the results in older individuals are the same as in younger individuals. 

The limitation of the study is that the sample size is relatively small, and large cohort investigations need to be performed in the future. Since the normative database in the RTVue-OCT and Cirrus HD-OCT databases does not take into account the retinal thickness variations in myopia, clinicians should be aware of reassessing the results when diagnosing high-myopia glaucoma. There has been some research on improving the software to increase GCC segmentation; however, this did not significantly improve the software-provided classification for glaucoma with high myopia.²⁰ A previous study showed that the cp-RNFL led to false-positive high detection for glaucoma with high myopia. A more accurate diagnosis for HM-G could be made if a normative database in highly myopic eyes were created.²¹ 

Acknowledgments

Supported by the National Nature Science Foundation of China grants (81020108017, 81500752), the State Key Program of National Natural Science Foundation of China (81430007), the National Health and Family Planning Commission of China (201302015), the New Technology Research Project Shanghai Municipal Commission of Health and Family Planning (SHDC12014114 and 2013SY058), and the National Major Scientific Equipment Program (2012YQ12008003). 

The sponsors or funding organizations had no role in the design or conduct of this research. 

Disclosure: Y. Zhang, None; W. Wen, None; X. Sun, None