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. 2025 Sep 15;20(9):e0332590. doi: 10.1371/journal.pone.0332590

Comparison of angle-closure detection between automated gonioscopy and anterior-segment optical coherence tomography

Yuki Takagi 1,2,*, Ryo Asano 1,3, Yui Morioka 2, Yukihiro Sakai 2, Sho Yokoyama 1,2, Kei Ichikawa 2, Kazuo Ichikawa 2
Editor: Jiro Kogo,4
PMCID: PMC12435641  PMID: 40953048

Abstract

Purpose

To investigate the concordance between angle-closure assessments based on GS-1 gonioscope images and those obtained with anterior-segment optical coherence tomography.

Study design

Retrospective clinical study.

Methods

We included 33 patients (53 eyes) who visited Chukyo Eye Clinic during 2020–2024, were suspected of having angle closure, and underwent anterior-segment optical coherence tomography (CASIA2 Advance STAR Analyzer) and GS-1 examinations. The 16-directional images captured with the GS-1 were divided into two halves, creating 32 directions, which were rearranged to correspond with those obtained via anterior-segment optical coherence tomography. Agreement between evaluations was analyzed using Cohen’s κ, and the area under the receiver operating characteristic curve was evaluated. Anterior-segment optical coherence tomography images were manually corrected, and eyes with areas classified as “narrow” or “closed” were categorized as angle closure. With the GS-1, two glaucoma specialists independently reviewed the images. Areas in which the posterior trabecular meshwork was obscured in more than half of the image (Scheie classification grades III–IV) were judged indicative of angle closure.

Results

We included 1,660 directions from 53 eyes in the agreement analysis. The proportion of directions judged as angle closure was 57.0% with anterior-segment optical coherence tomography and 46.1% with the GS-1. Cohen’s κ for inter-test agreement was 0.173 (95% confidence interval: 0.128–0.218), and the area under the receiver operating characteristic curve was 0.588 (95% confidence interval: 0.561–0.615).

Conclusion

Analyses using anterior-segment optical coherence tomography yielded more frequent classifications of angle closure than evaluations based on GS-1 gonioscopic images.

Introduction

Gonioscopy, developed in the 1800s [1], is essential for the diagnosis of certain types of glaucoma, particularly angle-closure glaucoma [2,3]. Angle-closure glaucoma is especially important in Asian countries, where it is more common, including in Japan, and less common among Caucasians [4].

Gonioscopy enables angle assessment via color imaging and facilitates static and dynamic examinations, making it useful for evaluating angle structures [5]. However, owing to the complexity of the procedure and the required proficiency, it is not commonly performed in clinical practice [5,6]. Moreover, the evaluation of gonioscopic features reportedly varies depending on examiner expertise [7]. Furthermore, capturing and storing numerous detailed gonioscopic images of the entire angle is difficult. These factors highlight the need for relatively noninvasive devices that can replace or supplement gonioscopy and can be operated by examiners such as orthoptists.

As alternatives to gonioscopy, anterior-segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) can be performed noninvasively and are reportedly useful for evaluating the anterior chamber and iridocorneal angle structures [811]. In particular, AS-OCT is highly useful because of its short examination time. However, AS-OCT and UBM cannot assess trabecular meshwork pigmentation or distinguish between organic and functional angle closure. Therefore, these tests have not yet replaced gonioscopy.

The GS-1 Gonioscope (GS-1; NIDEK, Gamagori, Japan) is a device capable of automatically capturing color photographs of the entire angle (16 directions) (Fig 1). Reportedly, it enables rapid examinations with relatively low invasiveness [1215]. Therefore, it is considered useful for monitoring temporal changes in angle structures, and its application in evaluating peripheral anterior synechiae formation following outflow reconstruction surgery has been reported [16]. As such, it has the potential to complement conventional gonioscopy.

Fig 1. Gonioscopic Images Captured by Automated Gonioscopy (GS-1).

Fig 1

Gonioscopic photographs of the left (L) eye, with 16 directional angle images captured. Similar to traditional gonioscopy, the displayed image is inverted vertically and horizontally. However, the specific anatomical locations of each angle are indicated next to the corresponding gonioscopic images. I: inferior, N: nasal, S: superior, T: temporal.

In comparative studies of device performance for angle-closure assessment, angle closure has been more frequently diagnosed than gonioscopy using AS-OCT [1721]. Gonioscopy has also been compared with EyeCam imaging [22,23], revealing high concordance between them. However, no studies have compared GS-1 with AS-OCT, nor have reports evaluated the diagnostic value of GS-1 images for angle closure. Therefore, in this study, we examined the concordance between angle-closure assessments based on GS-1 and AS-OCT, both of which can be performed by orthoptists. AS-OCT yielded more frequent classifications of angle closure than GS-1.

Materials and methods

Patients and study design

Patients who visited Chukyo Eye Clinic from 2020 to 2024, suspected of having angle closure based on a Van Herick grade ≤2 on slit-lamp microscopy, and underwent AS-OCT (CASIA2 Advance; TOMEY, Nagoya, Japan) and GS-1 examinations were included. Exclusion criteria included a history of peripheral iridotomy, intraocular surgeries such as cataract extraction, or ocular diseases other than cataracts.

This study was conducted retrospectively and was reviewed for research purposes on March 3, 2024. It was performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Chukyo Eye Clinic (approval number: 20240227075). An opt-out approach was used for informed consent owing to the retrospective nature of the study.

AS-OCT imaging

In this study, AS-OCT imaging was performed using the CASIA2 Advance device in a dark room by an orthoptist. To assess angle closure, we used the STAR Analyzer program installed on the device. This program automatically classifies the 32 directions of the anterior chamber angle as open, narrow, or closed based on the angle-opening distance (AOD) at 500 μm anterior to the scleral spur (AOD500) (Fig 2). Cutoff values for the AOD500 in each direction are predefined in the program (ranging from 0.098 to 0.198 mm). If the AOD500 value is equal to or greater than the cutoff, the angle is classified as open. If it is below the cutoff, the angle is classified as narrow; if it is 0 mm, it is classified as closed. Automatic segmentation was first performed for the scleral spur, iris, and other structures. The same examiner then reviewed each image and manually corrected the segmentation before reanalysis of the data. For the final classification, each of the 32-directional results was categorized as “angle closure present” if classified as narrow or closed, and as “angle closure absent” if classified as open.

Fig 2. Example of CASIA2 Advance STAR Analyzer Results.

Fig 2

In the center of the image, the classification results for each of the 32 directions are displayed, with narrow areas shown in yellow, closed areas in red, and open areas in green. In the top left corner, the Narrow Angle Index, a measurement of the degree of angle closure, is displayed. AOD500: angle-opening distance at 500 μm anterior to the scleral spur. I: inferior, N: nasal, S: superior, T: temporal.

Automated gonioscopy imaging

GS-1 imaging was performed by orthoptists in a bright room. Images were captured from 16 directions, divided into halves, and independently reviewed by two glaucoma specialists (R.A. and Y.T.). Areas in which the posterior trabecular meshwork was obscured in more than half of the image (Scheie classification grades III–IV) were judged as indicative of angle closure. In case of disagreements between the two reviewers, a consensus was reached through discussion.

Statistical analysis

The 16-directional images captured via GS-1 were divided into halves, creating 32 directions, which were rearranged to correspond with the 32 directions of the manually corrected AS-OCT results. GS-1 images in which angle structures could not be identified and AS-OCT images in which the scleral spur could not be identified were excluded from the analysis. Cohen’s κ was used to evaluate the agreement between the assessments. Additionally, cases in which more than 50% of the images were indicative of angle closure were categorized as angle-closure cases, and the agreement between the manually corrected AS-OCT results and GS-1 results was also evaluated using Cohen’s κ.

Furthermore, the images were divided into quadrants (superior, inferior, temporal, and nasal), and the agreement between the methods was assessed for each quadrant using Cohen’s κ. Receiver operating characteristic (ROC) analysis was performed, with AS-OCT as the reference standard and GS-1 classification results as the test variables. The area under the ROC curve (AUC) and its 95% confidence interval (CI) were calculated. The agreement of angle closure between the automatic and manually corrected AS-OCT results was also examined for each image and each case.

To evaluate the repeatability of the manual correction process in AS-OCT post-processing, approximately 30% of the total cases were randomly selected for intra-examiner reliability analysis. The same examiner performed a second round of segmentation corrections on a different day under masked conditions (blinded to the first assessment results). Agreement between the two assessments was evaluated using Cohen’s κ on a per-image and per-case basis.

All statistical analyses were performed using SPSS (version 29.0; IBM Corp., Armonk, NY, USA), and statistical significance was set at P < 0.05.

An a priori power analysis was conducted using G*Power version 3.1.9.7 [24] to determine the required sample size for Cohen’s κ analysis. Assuming a medium effect size (κ = 0.4), an alpha level of 0.05, and a desired power of 0.80, the minimum required sample size was calculated as 45 eyes.

Results

A total of 33 patients (53 eyes; 6 males and 27 females; mean ± standard deviation age, 71.3 ± 9.3 years) were included in the study. The analysis covered 1,696 directions across the 53 eyes; however, 8 directions with poor angle visualization upon AS-OCT and 28 directions with unclear images on GS-1 examination were excluded from the agreement analysis. The clinical characteristics of the study population are summarized in Table 1.

Table 1. Demographic Information of Patients.

Characteristics Total (n = 53)
Age, years 71.3 ± 9.3
Sex, female, number (%) 42 (79.2%)
Number of right eyes (%) 28 (52.8%)
Best-corrected visual acuity (logMAR) −0.053 ± 0.19
Spherical equivalent (D) 0.77 ± 2.07
Angle opening distance temporal (mm) 0.16 ± 0.68
Angle recess area temporal (mm2) 0.076 ± 0.30
Trabecular iris space area temporal (mm2) 0.70 ± 0.29
Trabecular iris angle (degree) 14.44 ± 7.07
Anterior chamber distance (mm) 2.22 ± 0.18
Lens vault (mm) 0.76 ± 0.20

Values are presented as means ± standard deviations, unless otherwise indicated. logMAR: logarithm of the minimum angle of resolution; D: diopter.

The comparison of the two methods is presented in Table 2. The proportion of images judged as angle closure was 57.0% with AS-OCT and 46.1% with the GS-1. Cohen’s κ for inter-test agreement was 0.173 (95% CI: 0.128–0.218). When analyzed by eye, the proportion of eyes judged as angle closure was 60.4% with AS-OCT and 33.9% with GS-1. Cohen’s κ was 0.151 (95% CI: −0.076–0.378).

Table 2. Comparison of GS-1 and AS-OCT Assessment of Angle Closure.

n Angle closure determined via GS-1 (%) Angle closure determined via AS-OCT (%) κ (95% CI) AUC (95% CI)
Per image 1,660 46.1 57.0 0.173 (0.128, 0.218) 0.589 (0.562, 0.617)
Per eye 53 33.9 60.4 0.151 (−0.076, 0.378) 0.584 (0.428, 0.740)

AS-OCT: anterior-segment optical coherence tomography, AUC: area under the receiver operating characteristic curve, CI: confidence interval, GS-1: GS-1 Gonioscope.

The quadrant-specific comparison results are shown in Table 3. Cohen’s κ and the AUC for the superior quadrant were 0.260 (95% CI: 0.168–0.352) and 0.631 (95% CI: 0.578–0.685), respectively; those for the inferior quadrant were 0.203 (95% CI: 0.109–0.297) and 0.605 (95% CI: 0.548–0.661), respectively; those for the nasal quadrant were 0.206 (95% CI: 0.140–0.271) and 0.619 (95% CI: 0.565–0.672), respectively; and those for the temporal quadrant were 0.036 (95% CI: −0.060–0.130) and 0.518 (95% CI: 0.462–0.574), respectively. In the comparison before and after manual correction of AS-OCT measurements, Cohen’s κ by image was 0.806 (95% CI: 0.777–0.835), and that by case was 0.763 (95% CI: 0.585–0.941).

Table 3. Comparison of GS-1 and AS-OCT Assessment of Angle Closure by Quadrant.

Angle closure determined via GS-1 (%) Angle closure determined via AS-OCT (%) κ (95% CI) AUC (95% CI)
Temporal 60.0 53.75 0.036 (−0.060, 0.130) 0.518 (0.462, 0.574)
Nasal 22.0 59.81 0.206 (0.140, 0.271) 0.619 (0.565, 0.672)
Superior 46.06 53.7 0.260 (0.168, 0.352) 0.631 (0.578, 0.685)
Inferior 56.35 62.35 0.203 (0.109, 0.297) 0.605 (0.548, 0.661)

AS-OCT: anterior-segment optical coherence tomography, AUC: area under the receiver operating characteristic curve, CI: confidence interval, GS-1: GS-1 Gonioscope.

In total, 19 eyes were re-evaluated for intra-examiner reliability. The per-image analysis yielded a Cohen’s κ of 0.895 (P < 0.001), and the per-case analysis demonstrated perfect agreement with a κ of 1.000 (P < 0.001). These results indicate high repeatability and consistency of the examiner’s manual corrections in this study.

Representative images illustrating discrepancies between GS-1- and AS-OCT-based assessments are provided in Fig 3. In one case, a 73-year-old female patient was judged to have angle closure in 93.8% of directions via AS-OCT but in only 46.8% via GS-1. The inferonasal angle (240°–270°) was deemed closed on AS-OCT; however, the scleral spur was visible in the corresponding GS-1 image, leading to a judgment of an open angle.

Fig 3. Example of a Case with Disagreement between AS-OCT and Automated Gonioscopy.

Fig 3

A) Result obtained using the CASIA2 Advance STAR Analyzer, showing “narrow” and “closed” angles in 93.8% of directions. The superior quadrant appears wide, whereas the inferior quadrant exhibits closure in the 240°–270° range. B) Corresponding GS-1 image of the inferior quadrant (240°–270°). In the left half of the image, the trabecular meshwork and scleral spur are visible (white brace). I: inferior, N: nasal, S: superior, T: temporal.

Discussion

In this study, we examined the concordance of angle-closure evaluations between GS-1 and AS-OCT. A higher proportion of AS-OCT images were judged as angle closure compared with GS-1 images. Consequently, in certain cases, AS-OCT indicated notably narrow angles, whereas GS-1 enabled visualization of the trabecular meshwork.

AS-OCT and gonioscopy have been compared in several previous studies [1721]. Although the AS-OCT devices used in those studies varied, the criteria for angle closure were similar. Angle closure was defined as contact between the scleral spur and the iris with AS-OCT, whereas it was defined as Scheie classification grade III–IV with gonioscopy. In all of those reports, angle closure was more frequently judged with AS-OCT than with gonioscopy [1721], with κ-values reported as moderate [20].

In this study, the criteria for angle closure differed from those in the abovementioned reports [1721], and automated rather than manual gonioscopy was used. However, AS-OCT still resulted in a higher proportion of angle-closure judgments. Conversely, Cohen’s κ was lower than the moderate agreement reported in previous studies, a notable difference.

Several factors may explain this discrepancy. One potential factor is the use of GS-1 instead of manual gonioscopy. During GS-1 imaging, the device emits light, which enters the pupil and may induce constriction. Angles reportedly appear wider under bright conditions than under dark conditions [25,26]. Therefore, although GS-1 examinations performed under bright conditions allow 360° color imaging that is useful for documenting features such as pigmentation, they may not be suitable for screening or diagnosing angle closure. A similar influence has been suggested in a previous report using devices such as the EyeCam [22]. However, that report demonstrated moderate agreement, differing from the results of this study.

Another possible explanation is the variation in the criteria used to determine angle closure with AS-OCT between previous reports and this study. In prior studies [1721], angle closure was defined as contact between the scleral spur and the iris. In contrast, this study used the CASIA2 Advance scanner setting of AOD500 as the threshold. Further research is required to standardize the criteria for angle closure across methods.

For gonioscopy, manual and automated, the criteria in previous reports and in this study were based on the visibility of the posterior trabecular meshwork. Anatomically, the visibility of the posterior trabecular meshwork and scleral spur–iris contact are considered relatively comparable criteria. In contrast, AOD500 and posterior trabecular meshwork visibility are structurally different measures. This discrepancy likely accounts for the lower concordance observed in this study compared with previous reports [20,22].

In the quadrant-specific comparison, the superior quadrant had the highest κ-value. A previous report using UBM indicated that the angle width in the superior quadrant does not significantly differ between dark and bright conditions [26], suggesting that the superior quadrant is the least influenced by illumination among all the quadrants, as also implied by the results of this study.

In the inferior quadrant, AS-OCT yielded more frequent judgments of angle closure than did gonioscopic evaluations with the GS-1. The abovementioned report [26] indicated that the inferior quadrant has the narrowest angle in dark conditions. Thus, the inferior quadrant may be most prone to narrowing in dark environments, and since AS-OCT in this study was performed under dark conditions, the results align with those of the previous report.

That prior study [26] also revealed that the difference in angle width between dark and bright conditions was greatest in the nasal quadrant. Consistently, in this study, the nasal quadrant exhibited the largest disparity in angle-closure assessments between GS-1 and AS-OCT.

Furthermore, the previous study [26] reported that the angle in the temporal quadrant was generally wider than in the other quadrants under bright and dark conditions, with smaller differences between lighting conditions compared with the inferior and nasal quadrants. However, in this study, GS-1 identified angle closure more frequently in the temporal quadrant than in the other quadrants, suggesting a deviation from previous findings. A potential explanation for this discrepancy is that GS-1 imaging involves a degree of ocular compression. However, the temporal quadrant may be the least affected by such compression during GS-1 imaging among all four quadrants. Therefore, larger studies incorporating comparisons with manual gonioscopy are warranted to determine whether these tendencies are consistent.

In this study, AS-OCT evaluations were performed using the CASIA2 Advance STAR Analyzer, with manual segmentation corrections and AOD500 employed to assess angle closure. The segmentation corrections involved not only adjusting the position of the scleral spur but also revising the iris segmentation, which is essential for AOD500. In most cases, manual corrections of the iris segmentation were necessary. The primary reason was that, in cases with narrow angles, the segmentation often did not extend to the iris root. Consequently, much of the manual work involved extending the segmentation to the iris root. Despite this, the agreement of angle closure between the automatic analysis of the CASIA2 Advance STAR Analyzer and the manually corrected results was high. This likely reflects the fact that cases requiring segmentation corrections predominantly consisted of those with narrow angles. Therefore, the high agreement can be attributed to the narrower angles that necessitated corrections. Given this observation, the automatic analysis of the CASIA2 Advance STAR Analyzer may still be useful for screening angle closure. However, we did not analyze the extent of the required corrections in this study, nor the proportion of cases requiring correction based on the presence or severity of angle closure. These aspects warrant further investigation.

This study has some limitations. The number of cases was limited, and larger investigations are necessary. Comparisons with manual gonioscopy were not performed, and uncertainty remains regarding the extent to which the GS-1 captures the angle in a more open configuration compared with manual gonioscopy. In addition, because AS-OCT was used as a relative reference standard, verification bias is possible. Therefore, future studies are needed that include three-way comparisons among GS-1, manual gonioscopy, and AS-OCT. The concordance between angle-closure determination using the CASIA2 Advance STAR Analyzer, which employs AOD500 as a criterion, and manual gonioscopy features remains unclear and warrants future investigation. In this study, angles classified as either “narrow” or “closed” via AS-OCT were collectively considered closed angles in comparison with GS-1 results. This approach was taken to ensure consistency and fairness in the comparison, given that GS-1 provides only qualitative, static images under bright conditions without dynamic or indentation assessment, complicating the discernment of true appositional closure and a merely narrow angle. Although AS-OCT measurements are more sensitive and quantitative, no standardized grading system for GS-1 results has been established, and subjective judgments can easily influence interpretation. Therefore, we adopted a binary classification of “open” versus “non-open” in this study. However, more detailed comparisons, in which “narrow” and “closed” categories are separated, should be considered in future research. Another limitation of this study is that we did not formally evaluate intra- and inter-observer agreement in the interpretation of GS-1 images. Although all images were independently assessed by two glaucoma specialists and final decisions were made through consensus in cases of disagreement, we did not calculate numerical agreement rates or have the same examiner perform repeat evaluations. In future studies, the incorporation of reliability analyses, using statistics such as Cohen’s κ or the intraclass correlation coefficient, may enhance the validity and reproducibility of the evaluation methods.

In conclusion, the analysis results for angle closure via the CASIA2 Advance STAR Analyzer yielded more frequent judgments of angle closure than the evaluations based on gonioscopic images captured with the GS-1. As AS-OCT can be performed in a dark room, it may be more useful than the GS-1 for the diagnosis of angle closure. However, for evaluating findings such as angle pigmentation, the GS-1’s capability to capture and archive 360° color images of the entire angle may be useful.

Supporting information

S1 File. Clinical data of all included patients.

(XLSX)

pone.0332590.s001.xlsx (37.2KB, xlsx)

Acknowledgments

The authors would like to thank Editage for their English language review.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Dellaporta A. Historical notes on gonioscopy. Surv Ophthalmol. 1975;20(2):137–49. doi: 10.1016/0039-6257(75)90021-1 [DOI] [PubMed] [Google Scholar]
  • 2.Prum BE Jr, Rosenberg LF, Gedde SJ, Mansberger SL, Stein JD, Moroi SE, et al. Primary Open-Angle Glaucoma Preferred Practice Pattern(®) Guidelines. Ophthalmology. 2016;123(1):P41–111. doi: 10.1016/j.ophtha.2015.10.053 [DOI] [PubMed] [Google Scholar]
  • 3.Prum BE Jr, Herndon LW Jr, Moroi SE, Mansberger SL, Stein JD, Lim MC, et al. Primary Angle Closure Preferred Practice Pattern(®) Guidelines. Ophthalmology. 2016;123(1):P1–40. doi: 10.1016/j.ophtha.2015.10.049 [DOI] [PubMed] [Google Scholar]
  • 4.Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7. doi: 10.1136/bjo.2005.081224 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Friedman DS, He M. Anterior chamber angle assessment techniques. Surv Ophthalmol. 2008;53(3):250–73. doi: 10.1016/j.survophthal.2007.10.012 [DOI] [PubMed] [Google Scholar]
  • 6.Campbell P, Redmond T, Agarwal R, Marshall LR, Evans BJW. Repeatability and comparison of clinical techniques for anterior chamber angle assessment. Ophthalmic Physiol Opt. 2015;35(2):170–8. doi: 10.1111/opo.12200 [DOI] [PubMed] [Google Scholar]
  • 7.Esporcatte BL, Vessani RM, Melo LA Jr, Yanagimori NS, Bufarah GH, Allemann N, et al. Diagnostic Performance of Optical Coherence Tomography and Nonspecialist Gonioscopy to Detect Angle Closure. J Curr Glaucoma Pract. 2022;16(1):53–8. doi: 10.5005/jp-journals-10078-1354 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Baskaran M, Ho S-W, Tun TA, How AC, Perera SA, Friedman DS, et al. Assessment of circumferential angle-closure by the iris-trabecular contact index with swept-source optical coherence tomography. Ophthalmology. 2013;120(11):2226–31. doi: 10.1016/j.ophtha.2013.04.020 [DOI] [PubMed] [Google Scholar]
  • 9.Grewal DS, Brar GS, Jain R, Grewal SPS. Comparison of Scheimpflug imaging and spectral domain anterior segment optical coherence tomography for detection of narrow anterior chamber angles. Eye (Lond). 2011;25(5):603–11. doi: 10.1038/eye.2011.14 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Radhakrishnan S, Goldsmith J, Huang D, Westphal V, Dueker DK, Rollins AM, et al. Comparison of optical coherence tomography and ultrasound biomicroscopy for detection of narrow anterior chamber angles. Arch Ophthalmol. 2005;123(8):1053–9. doi: 10.1001/archopht.123.8.1053 [DOI] [PubMed] [Google Scholar]
  • 11.See JLS. Imaging of the anterior segment in glaucoma. Clin Exp Ophthalmol. 2009;37(5):506–13. doi: 10.1111/j.1442-9071.2009.02081.x [DOI] [PubMed] [Google Scholar]
  • 12.Teixeira F, Sousa DC, Leal I, Barata A, Neves CM, Pinto LA. Automated gonioscopy photography for iridocorneal angle grading. Eur J Ophthalmol. 2020;30(1):112–8. doi: 10.1177/1120672118806436 [DOI] [PubMed] [Google Scholar]
  • 13.Shi Y, Yang X, Marion KM, Francis BA, Sadda SR, Chopra V. Novel and Semiautomated 360-Degree Gonioscopic Anterior Chamber Angle Imaging in Under 60 Seconds. Ophthalmol Glaucoma. 2019;2(4):215–23. doi: 10.1016/j.ogla.2019.04.002 [DOI] [PubMed] [Google Scholar]
  • 14.Matsuo M, Pajaro S, De Giusti A, Tanito M. Automated anterior chamber angle pigmentation analyses using 360° gonioscopy. Br J Ophthalmol. 2020;104(5):636–41. doi: 10.1136/bjophthalmol-2019-314320 [DOI] [PubMed] [Google Scholar]
  • 15.Takagi Y, Watanabe M, Kojima T, Sakai Y, Asano R, Ichikawa K. Comparison of the efficacy and invasiveness of manual and automated gonioscopy. PLoS One. 2023;18(4):e0284098. doi: 10.1371/journal.pone.0284098 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Matsuo M, Inomata Y, Kozuki N, Tanito M. Characterization of Peripheral Anterior Synechiae Formation After Microhook Ab-interno Trabeculotomy Using a 360-Degree Gonio-Camera. Clin Ophthalmol. 2021;15:1629–38. doi: 10.2147/OPTH.S306834 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Rigi M, Bell NP, Lee DA, Baker LA, Chuang AZ, Nguyen D, et al. Agreement between Gonioscopic Examination and Swept Source Fourier Domain Anterior Segment Optical Coherence Tomography Imaging. J Ophthalmol. 2016;2016:1727039. doi: 10.1155/2016/1727039 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Sakata LM, Lavanya R, Friedman DS, Aung HT, Gao H, Kumar RS, et al. Comparison of gonioscopy and anterior segment ocular coherence tomography in detecting angle closure in different quadrants of the anterior chamber angle. Ophthalmology. 2008;115(5):769–74. doi: 10.1016/j.ophtha.2007.06.030 [DOI] [PubMed] [Google Scholar]
  • 19.Porporato N, Baskaran M, Tun TA, Sultana R, Tan M, Quah JH, et al. Understanding diagnostic disagreement in angle closure assessment between anterior segment optical coherence tomography and gonioscopy. Br J Ophthalmol. 2020;104(6):795–9. doi: 10.1136/bjophthalmol-2019-314672 [DOI] [PubMed] [Google Scholar]
  • 20.Tun TA, Baskaran M, Tan SS, Perera SA, Aung T, Husain R. Evaluation of the Anterior Segment Angle-to-Angle Scan of Cirrus High-Definition Optical Coherence Tomography and Comparison With Gonioscopy and With the Visante OCT. Invest Ophthalmol Vis Sci. 2017;58(1):59–64. doi: 10.1167/iovs.16-20886 [DOI] [PubMed] [Google Scholar]
  • 21.Nolan WP, See JL, Chew PTK, Friedman DS, Smith SD, Radhakrishnan S, et al. Detection of primary angle closure using anterior segment optical coherence tomography in Asian eyes. Ophthalmology. 2007;114(1):33–9. doi: 10.1016/j.ophtha.2006.05.073 [DOI] [PubMed] [Google Scholar]
  • 22.Baskaran M, Aung T, Friedman DS, Tun TA, Perera SA. Comparison of EyeCam and anterior segment optical coherence tomography in detecting angle closure. Acta Ophthalmol. 2012;90(8):e621-5. doi: 10.1111/j.1755-3768.2012.02510.x [DOI] [PubMed] [Google Scholar]
  • 23.Perera SA, Baskaran M, Friedman DS, Tun TA, Htoon HM, Kumar RS, et al. Use of EyeCam for imaging the anterior chamber angle. Invest Ophthalmol Vis Sci. 2010;51(6):2993–7. doi: 10.1167/iovs.09-4418 [DOI] [PubMed] [Google Scholar]
  • 24.Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91. doi: 10.3758/bf03193146 [DOI] [PubMed] [Google Scholar]
  • 25.Leung CK, Cheung CYL, Li H, Dorairaj S, Yiu CKF, Wong AL, et al. Dynamic analysis of dark-light changes of the anterior chamber angle with anterior segment OCT. Invest Ophthalmol Vis Sci. 2007;48(9):4116–22. doi: 10.1167/iovs.07-0010 [DOI] [PubMed] [Google Scholar]
  • 26.Kunimatsu S, Tomidokoro A, Mishima K, Takamoto H, Tomita G, Iwase A, et al. Prevalence of appositional angle closure determined by ultrasonic biomicroscopy in eyes with shallow anterior chambers. Ophthalmology. 2005;112(3):407–12. doi: 10.1016/j.ophtha.2004.10.026 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Jiro Kogo

20 Jun 2025

Dear Dr. Takagi,

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We look forward to receiving your revised manuscript.

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Jiro Kogo

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1:  I appreciate the authors’ effort to evaluate concordance between AS-OCT and GS-1 gonioscopic photography for angle-closure assessment. However, I have identified several critical methodological limitations that, in the present design and with available data, cannot be adequately addressed:

1. Sample size and power calculation

You acknowledge in the Limitations section that the study’s sample size is small. However, no formal sample size or power calculation is reported. Without evidence that your study was sufficiently powered to detect clinically meaningful differences in concordance, the validity of your findings remains uncertain.

2. Choice of comparison standard

Gonioscopy is rightly considered the gold standard for assessing angle closure. Yet your study compares AS-OCT and GS-1 images to one another, rather than directly to gonioscopic grading. Logically, to evaluate whether GS-1 photography can serve as a less invasive alternative, its results should be compared against gonioscopic examination, not AS-OCT.

3. Inconsistent lighting conditions

AS-OCT examinations were performed under dark-room conditions, whereas GS-1 photographs were acquired in ambient light. These differing illumination environments can substantially affect angle appearance, rendering direct comparison inappropriate.

4. Intra-examiner reliability during manual correction

During the AS-OCT post-processing stage, an examiner manually corrected the automated segmentation. It is unclear whether intra-examiner consistency of these corrections was assessed, and no reliability statistics are provided.

5. Undefined reference standard in ROC analysis

In your ROC curve analysis, you do not specify which modality serves as the reference (gold standard). Without this clarification, the results cannot be interpreted.

Given these fundamental methodological flaws, we believe the manuscript is not suitable for further consideration in its present form. We encourage you to address these issues—particularly defining an appropriate gold standard, standardizing imaging conditions, and performing rigorous reliability and power analyses—before resubmitting, either to this journal or elsewhere.

Reviewer #2:  The paper conducted an agreement analysis of angle-closure assessments between GS-1 and AS-OCT. While the experiments and analysis are clearly presented, a few issues remain in the explanations, such as unclear comparison restrictions and limitations in the dataset. The following concerns are raised:

1.Definition of angle closure in AS-OCT and GS-1: In AS-OCT, angles classified as “narrow” or “closed” are considered as angle closure, while GS-1 defines angle closure as the obscuration of the posterior trabecular meshwork for more than half of the eye. Could you clarify how the terms “narrow” or “closed” are specifically defined in AS-OCT?

2.Comparison between AS-OCT slices and GS-1 areas: The comparison between AS-OCT slices and GS-1 areas using directional pairs is presented. However, both the Cohen’s Kappa and AUC are relatively low. When using AOD 500 as a threshold, why is a narrow angle also considered as angle closure, given that AS-OCT was originally found to have higher sensitivity for assessing angle closure severity?

3.Lighting conditions and the comparison with dark-room AS-OCT: As mentioned in the discussion, GS-1 sheds light during the examination, which could be considered a light-examination condition. It is commonly agreed that the anterior angle appears narrower under dark-room conditions. Given this assumption, is the comparison with dark-room AS-OCT results truly valid? Could this lighting difference be a factor influencing the disagreement between the two measurements?

4. Limitations in dataset: Although the statistical analysis has been conducted and the sample size exceeds the minimum required, the number of participants is relatively small, and the distribution of participants is unclear.

Reviewer #3:  Thank you for submitting this interesting and clinically relevant study comparing automated gonioscopy (GS-1) with AS-OCT for angle-closure detection. The study design is appropriate, and the topic is important for glaucoma diagnostics.

However, I recommend addressing the following key points before the manuscript is suitable for publication:

Low agreement between methods

• The observed inter-modality agreement is minimal (κ ≈ 0.17). Please provide a more critical discussion of the clinical implications of this low concordance. Should clinicians rely more on one modality?

Inclusion/exclusion criteria and clinical parameters

• Please clarify whether patients were included consecutively or selectively, and provide more detail on patient characteristics such as lens status (phakic/pseudophakic), presence of other eye diseases (e.g., plateau iris), and axial length.

Observer variability

• The manuscript would benefit from reporting intra- and interobserver variability, and from explaining whether repeat assessments were performed or whether consensus procedures were used to resolve discrepancies.

Reproducibility

• It's unclear if repeat measurements or quality control thresholds were applied during imaging or analysis.

Minor points

• Address minor formatting issues (e.g., font size inconsistencies between lines 53–60; spacing issues in Table 1).

• Typo in line 215: “mat” → “may”.

Recommendation:

The manuscript addresses an important clinical topic, but revision is needed to improve methodological clarity and the interpretation of findings, particularly regarding the limitations of GS-1 and the impact of environmental and definitional differences.

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

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Attachment

Submitted filename: Comments2025-5-20.docx

pone.0332590.s002.docx (14.2KB, docx)
PLoS One. 2025 Sep 15;20(9):e0332590. doi: 10.1371/journal.pone.0332590.r002

Author response to Decision Letter 1


14 Jul 2025

July 11, 2025

Dr. Jiro Kogo

Academic Editor

PLOS ONE

Revised manuscript: PONE-D-25-17859

Title: “Comparison of angle-closure detection between automated gonioscopy and anterior-segment optical coherence tomography”

Dear Dr. Kogo:

We are pleased to correspond with you again regarding the revision of our aforementioned manuscript, which has benefited from a review that has contributed to improving its academic value.

We are grateful to the reviewers and to you for the thorough review of our revised manuscript. We also appreciate the insightful comments provided by the reviewers, which have significantly helped to improve the quality of our manuscript.

We have revised the manuscript in accordance with both the specific and general requests, with the modified text highlighted in yellow in the revised manuscript. Below, please find our point-by-point responses to the reviewers’ comments and concerns. Our responses are provided in blue text. 

RESPONSE TO REVIEWER’S COMMENTS

REVIEWER EVALUATION

We would like to thank the reviewers for their time and efforts in reviewing our manuscript and for providing comments that have considerably helped us to improve our manuscript.

Reviewer #1: I appreciate the authors’ effort to evaluate concordance between AS-OCT and GS-1 gonioscopic photography for angle-closure assessment. However, I have identified several critical methodological limitations that, in the present design and with available data, cannot be adequately addressed:

1. Sample size and power calculation

You acknowledge in the Limitations section that the study’s sample size is small. However, no formal sample size or power calculation is reported. Without evidence that your study was sufficiently powered to detect clinically meaningful differences in concordance, the validity of your findings remains uncertain.

Thank you for your valuable comment. We agree that conducting an a priori power analysis and determining the required sample size are essential aspects in clinical research. In this study, we performed an a priori power analysis based on Cohen’s kappa by using G*Power version 3.1.9.7 (Faul et al., 2007) to calculate the necessary sample size. Specifically, assuming a medium effect size (κ = 0.4), an alpha level of 0.05, and a desired power of 0.80, the minimum required sample size was calculated to be 45 eyes. This information has been clearly stated in the Methods section, as follows:

“An a priori power analysis was conducted using GPower version 3.1.9.7 [24] to determine the required sample size for Cohen’s κ analysis. Assuming a medium effect size (κ = 0.4), an alpha level of 0.05, and a desired power of 0.80, the minimum required sample size was calculated as 45 eyes.” (Page 10, lines 158-161)

24. Faul F, Erdfelder E, Lang AG, Buchner A. G *Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Meth 2007;39:175-91. doi: 10.3758/bf03193146.

2. Choice of comparison standard

Gonioscopy is rightly considered the gold standard for assessing angle closure. Yet your study compares AS-OCT and GS-1 images to one another, rather than directly to gonioscopic grading. Logically, to evaluate whether GS-1 photography can serve as a less invasive alternative, its results should be compared against gonioscopic examination, not AS-OCT.

Thank you for your comment. We fully understand that gonioscopy is the gold standard to diagnose angle closure, and that a comparison of GS-1 results with gonioscopic examination is essential to validate the accuracy of the GS-1. However, in clinical practice, reports have indicated that gonioscopy is often underutilized owing to time and technical constraints. Therefore, alternative or complementary methods that can be performed by examiners other than physicians, such as orthoptists, are needed to screen for angle closure.

AS-OCT has already been demonstrated in several previous studies to be useful for the diagnosis of angle closure. Moreover, AS-OCT can be performed by orthoptists, and with practical clinical implementation in mind, we prioritized a comparison between the GS-1 and AS-OCT in this study.

We also recognize the importance of directly comparing the GS-1 with manual gonioscopy, and we have clearly stated this limitation in the Discussion section, as follows:

“Additionally, comparisons with manual gonioscopy were not performed, leaving uncertainty about the extent to which the GS-1 captures images of the angle in a more open state compared with manual gonioscopy. Therefore, future studies are needed for comparisons between the GS-1 and manual gonioscopy.” (Page 19, lines 300-303)

I also added a statement in the Introduction to emphasize the need for alternative or complementary examinations to gonioscopy that can be performed by examiners such as orthoptists, as follows:

“Gonioscopy allows for angle assessment via color imaging and facilitates both static and dynamic examinations, rendering it useful for the understanding of angle structures [5]. However, owing to the complexity of the procedure and the need for proficiency, it is not always performed in practice [5,6]. Moreover, the evaluation of gonioscopic features reportedly varies depending on the degree of proficiency [7]. Furthermore, capturing and storing numerous detailed gonioscopic images of the entire angle is difficult. These factors reveal a need for relatively non-invasive devices that can replace or supplement gonioscopes and can be operated by examiners such as orthoptists.” (Page 4, lines 46-53)

3. Inconsistent lighting conditions

AS-OCT examinations were performed under dark-room conditions, whereas GS-1 photographs were acquired in ambient light. These differing illumination environments can substantially affect angle appearance, rendering direct comparison inappropriate.

Thank you for your insightful comments. We consider this a very important point. In principle, the standard approach for the diagnosis of angle closure is to perform examinations under dark-room conditions, as the anterior chamber angle reportedly appears wider under bright conditions. Therefore, GS-1 examinations should ideally also be performed in a dark room. However, as the GS-1 device itself emits light during imaging, we judged that the room conditions would not make a difference. Consequently, we performed the GS-1 examinations under normal, light conditions. We acknowledge that this might have significantly influenced the results of our study, and we have described this point in the Discussion section, as follows:

“During GS-1 imaging, the device emits light, causing light to enter the participant’s pupil and potentially induce pupil constriction. Angles reportedly appear wider under bright conditions than they do under dark conditions [25,26]. Therefore, GS-1-based examinations, which are performed under bright conditions, may not be useful for screening or diagnosis of angle closure.” (Page 16, lines 232-236)

As mentioned earlier, the objective of this study was to evaluate the diagnostic capability of GS-1 gonioscopy to detect angle closure, specifically as a modality that can be performed by orthoptists. Similarly, AS-OCT can be operated by orthoptists and its utility in the diagnosis of angle closure has already been reported. Therefore, considering the feasibility of examinations performed by orthoptists, we prioritized a comparison between GS-1 gonioscopy and AS-OCT in this study; clinical implementation was our foremost concern.

4. Intra-examiner reliability during manual correction

During the AS-OCT post-processing stage, an examiner manually corrected the automated segmentation. It is unclear whether intra-examiner consistency of these corrections was assessed, and no reliability statistics are provided.

Thank you for your helpful comments. We agree that intra-examiner reproducibility of AS-OCT is an important factor to ensure its reliability. In this study, approximately 30% of the cases (19 eyes) were randomly selected to assess intra-examiner reproducibility of AS-OCT evaluations. The analysis demonstrated high agreement, with a per-image Cohen’s kappa of 0.895 (P<0.001) and a per-case kappa of 1.000 (P<0.001), indicating excellent intra-examiner consistency in this study.

We have added the following sentences to the Methods and Results sections:

“To evaluate the repeatability of the manual correction process in AS-OCT post-processing, approximately 30% of the total cases were randomly selected for intra-examiner reliability analysis. The same examiner performed a second round of segmentation corrections on a different day under masked conditions (the examiner was blinded to the first assessment results). Agreement between the two assessments was evaluated using Cohen’s κ statistics on both a per-image and per-case basis.” (Pages 9-10, lines 149-154)

“In total, 19 eyes were re-evaluated for intra-examiner reliability. The per-image analysis yielded a Cohen’s κ of 0.895 (P<0.001), and the per-case analysis revealed perfect agreement with a kappa of 1.000 (P<0.001). These results indicate high repeatability and consistency of the examiner’s manual corrections in this study.” (Page 14, lines 193-196)

5. Undefined reference standard in ROC analysis

In your ROC curve analysis, you do not specify which modality serves as the reference (gold standard). Without this clarification, the results cannot be interpreted.

Given these fundamental methodological flaws, we believe the manuscript is not suitable for further consideration in its present form. We encourage you to address these issues—particularly defining an appropriate gold standard, standardizing imaging conditions, and performing rigorous reliability and power analyses—before resubmitting, either to this journal or elsewhere.

Thank you for your comment. We apologize for not clearly stating that AS-OCT was used as the reference standard in the ROC analysis to evaluate concordance with GS-1 gonioscopy. In response to your suggestion, we have now clarified this fact in the Methods section.

“Receiver operating characteristic (ROC) analysis was performed, using AS-OCT as the reference standard and the GS-1 classification results as the test variables. The area under the ROC curve (AUC) and its 95% confidence interval were calculated.” (Page 9, lines 143-145)

Furthermore, upon recalculating and reviewing the analyses, we discovered that the ROC curves had been calculated using GS-1 gonioscopy as the reference standard instead of AS-OCT in some cases. We re-confirmed that AS-OCT is the correct reference standard, and we have repeated the ROC analyses. The corrected results have been updated in Tables 2 and 3 and the related text (page 12, lines 183-187).

Table 2. Comparison of GS-1 and AS-OCT Assessment of Angle Closure.

n Angle closure determined via GS-1 (%) Angle closure determined via AS-OCT (%) κ (95% CI) AUC (95%CI)

Per image 1660 46.1 57.0 0.173 (0.128, 0.218) 0.589 (0.562, 0.617)

Per eye 53 33.9 60.4 0.151 (-0.076, 0.378) 0.584 (0.428, 0.740)

AS-OCT: anterior-segment optical coherence tomography, AUC: area under the receiver operating characteristic curve, CI: confidence interval, GS-1: GS-1 Gonioscope.

Table 3. Comparison of GS-1 and AS-OCT Assessment of Angle Closure by Quadrant.

Angle closure determined via GS-1 (%) Angle closure determined via AS-OCT (%) κ (95% CI) AUC (95% CI)

Temporal 60.0 53.75 0.036 (-0.060, 0.130) 0.518 (0.462, 0.574)

Nasal 22.0 59.81 0.206 (0.140, 0.271) 0.619 (0.565, 0.672)

Superior 46.06 53.7 0.260 (0.168, 0.352) 0.631 (0.578, 0.685)

Inferior 56.35 62.35 0.203 (0.109, 0.297) 0.605 (0.548, 0.661)

AS-OCT: anterior-segment optical coherence tomography, AUC: area under the receiver operating characteristic curve, CI: confidence interval, GS-1: GS-1 Gonioscope.

Reviewer #2: The paper conducted an agreement analysis of angle-closure assessments between GS-1 and AS-OCT. While the experiments and analysis are clearly presented, a few issues remain in the explanations, such as unclear comparison restrictions and limitations in the dataset. The following concerns are raised:

1.Definition of angle closure in AS-OCT and GS-1: In AS-OCT, angles classified as “narrow” or “closed” are considered as angle closure, while GS-1 defines angle closure as the obscuration of the posterior trabecular meshwork for more than half of the eye. Could you clarify how the terms “narrow” or “closed” are specifically defined in AS-OCT?

Thank you for your insightful comments. The criteria for angle closure are indeed a critical aspect of this study. Although the criteria to determine angle closure upon AS-OCT were described in the Methods section, the specific numerical thresholds were not included. We have now added these detailed values.

“To assess angle closure, we used the STAR Analyzer program installed on the device. This program automatically classifies the 32 directions of the anterior chamber angle as open, narrow, or closed based on the angle-opening distance (AOD) at 500 μm anterior to the scleral spur (AOD500) (Fig 2). Cutoff values for the AOD500 in each direction are predefined in the program (ranging from 0.087 to 0.198 mm). If the AOD500 value is equal to or greater than the cutoff, the angle is classified as open. If it is below the cutoff, the angle is classified as narrow, and if it is 0 mm, it is classified as closed.” (Page 7, lines 103-110)

2.Comparison between AS-OCT slices and GS-1 areas: The comparison between AS-OCT slices and GS-1 areas using directional pairs is presented. However, both the Cohen’s Kappa and AUC are relatively low. When using AOD 500 as a threshold, why is a narrow angle also considered as angle closure, given that AS-OCT was originally found to have higher sensitivity for assessing angle closure severity?

Thank you for your comment. In this study, the definition of angle closure via GS-1 gonioscopy, based on previous reports, was the inability to observe the posterior trabecular meshwork. However, this definition relies on qualitative assessment, and since indentation gonioscopy cannot be performed with the GS-1 device, discerning whether the angle is simply narrow or actually appositional (closed) from the images alone is challenging.

Given this background, we determined that GS-1 gonioscopy can only provide a binary classification into “open” and “non-open” (including both narrow and closed angles). Therefore, in this study, we also combined “narrow” and “closed” classifications made via AS-OCT as “angle closure present” to maintain consistency and fairness in the comparison.

However, as AS-OCT allows for more sensitive and quantitative evaluation, we recognize that if standardized evaluation methods for GS-1 become established in the future, separately analyzing “narrow” and “closed” angles would be meaning ful. We have added this point as a supplementary note in the Discussion section, as follows:

“In this study, angles classified as either “narrow” or “closed” via AS-OCT were collectively considered as closed angles in comparison with GS-1 results. This approach was taken to ensure consistency and fairness in the comparison, given that GS-1 provides only qualitative, static images under bright conditions without dynamic or indentation assessment, complicating the discernment of true appositional closure and a merely narrow angle. Although AS-OCT measurements are more sensitive and quantitative, no standardized grading system for GS-1 results has been established, and subjective judgments can easily influence the interpretation. Therefore, we adopted a binary classification of “open” versus “non-open” in this study. However, more detailed comparisons, in which “narrow” and “closed” categories are separated should be considered in future research.” (Page 19-20, lines 306-316)

3.Lighting conditions and the comparison with dark-room AS-OCT: As mentioned in the discussion, GS-1 sheds light during the examination, which could be considered a light-examination condition. It is commonly agreed that the anterior angle appears narrower under dark-room conditions. Given this assumption, is the comparison with dark-room AS-OCT results truly valid? Could this lighting difference be a

Attachment

Submitted filename: Response to Reviewers.docx

pone.0332590.s004.docx (44.7KB, docx)

Decision Letter 1

Jiro Kogo

26 Aug 2025

Dear Dr. Takagi,

Please submit your revised manuscript by Oct 10 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Jiro Kogo

Academic Editor

PLOS ONE

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

**********

Reviewer #2: We appreciate the authors’ thorough responses to the previous reviews. However, a few minor concerns remain, and we would appreciate further clarification within the manuscript.

1. In the conclusion section, the authors state that AS-OCT may be more useful than the GS-1 because it can be performed in a dark room. However, traditional gonioscopy is also performed under dark-room conditions, and the GS-1 is introduced as “having the potential to complement conventional gonioscopy”. Could the authors further clarify the rational and intended clinical role of the GS-1 in this context aside from being non-contact (since it was not mentioned after introduction section)? Specifically, what is the motivation for selecting the GS-1 as the comparison method against AS-OCT, rather than manual gonioscopy, given that both AS-OCT and GS-1 differ in imaging principles and lighting conditions?

2. Although being frequently questioned in recent years, manual gonioscopy is still considered as a golden standard for angle closure examination, please justify how AS-OCT results in this case replace manual gonioscopy and be considered as a relative ‘true value’ in the current comparison.

3. The manuscript is generally well-written, though minor grammatical refinements could help with better understanding.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: No

**********

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

PLoS One. 2025 Sep 15;20(9):e0332590. doi: 10.1371/journal.pone.0332590.r004

Author response to Decision Letter 2


1 Sep 2025

September 1, 2025

Dr. Jiro Kogo

Academic Editor

PLOS One

Revised manuscript: PONE-D-25-17859R1

Title: “Comparison of angle-closure detection between automated gonioscopy and anterior-segment optical coherence tomography”

Dear Dr. Jiro Kogo:

It is a pleasure to correspond with you again regarding the revision of our aforementioned manuscript, which received a favorable review.

We are grateful to the reviewers and the editor for their thorough evaluation of our revised manuscript. We also appreciate the insightful comments provided by the reviewer, which have greatly improved the quality of the work.

We have revised the manuscript in accordance with the specific and general requests, with the modified text highlighted in yellow in the revised manuscript. Below, please find our point-by-point responses to the reviewers’ comments and concerns. Our responses are provided in blue text. 

RESPONSE TO REVIEWER’S COMMENTS

REVIEWER EVALUATION

We would like to thank the reviewers for their time and effort in reviewing our manuscript and for providing comments that have considerably helped us improve it.

Reviewer #2: We appreciate the authors’ thorough responses to the previous reviews. However, a few minor concerns remain, and we would appreciate further clarification within the manuscript.

1. In the conclusion section, the authors state that AS-OCT may be more useful than the GS-1 because it can be performed in a dark room. However, traditional gonioscopy is also performed under dark-room conditions, and the GS-1 is introduced as “having the potential to complement conventional gonioscopy”. Could the authors further clarify the rational and intended clinical role of the GS-1 in this context aside from being non-contact (since it was not mentioned after introduction section)? Specifically, what is the motivation for selecting the GS-1 as the comparison method against AS-OCT, rather than manual gonioscopy, given that both AS-OCT and GS-1 differ in imaging principles and lighting conditions?

Thank you for your valuable comments. We fully understand that gonioscopy is the gold standard for diagnosing angle closure and that comparing GS-1 findings with gonioscopic examination is essential to validate the accuracy of the GS-1. However, in real-world clinical practice, reports indicate that gonioscopy is often underutilized because of time and technical constraints. Therefore, there is a need for alternative or complementary methods that can be performed by examiners other than physicians, such as orthoptists, to screen for angle closure. The primary aim of the present study was to compare AS-OCT and GS-1, both of which can be performed by orthoptists. The need for equipment that can be operated by orthoptists as a potential alternative to manual gonioscopy is described in the Introduction as follows:

“Gonioscopy enables angle assessment via color imaging and facilitates static and dynamic examinations, making it useful for evaluating angle structures [5]. However, owing to the complexity of the procedure and the required proficiency, it is not always performed in clinical practice [5,6]. Moreover, the evaluation of gonioscopic features reportedly varies depending on examiner expertise [7]. Furthermore, capturing and storing numerous detailed gonioscopic images of the entire angle is difficult. These factors highlight the need for relatively noninvasive devices that can replace or supplement gonioscopy and can be operated by examiners such as orthoptists.” (page 4, lines 47-54)

Furthermore, to clarify the study objective, we have revised and expanded the Introduction with the following sentence:

“Therefore, in this study, we examined the concordance between angle-closure assessments based on GS-1 and AS-OCT, both of which can be performed by orthoptists.” (page 6, lines 80-82)

Regarding the clinical role of the GS-1, based on our findings, we consider it unsuitable for screening for angle closure. However, because it captures 360° color images of the entire angle, we believe it is useful for evaluating features such as pigmentation. Accordingly, we have revised and expanded the Discussion section as follows:

“Therefore, although GS-1 examinations performed under bright conditions allow 360° color imaging that is useful for documenting features such as pigmentation, they may not be suitable for screening or diagnosing angle closure.” (page 16, lines 231-233)

“However, for evaluating findings such as angle pigmentation, the GS-1’s capability to capture and archive 360° color images of the entire angle may be useful.” (page 20, line 324 to page 21, line 326)

Finally, we apologize if our wording caused confusion; the GS-1 is not a non-contact device—it is a contact device.

2. Although being frequently questioned in recent years, manual gonioscopy is still considered as a golden standard for angle closure examination, please justify how AS-OCT results in this case replace manual gonioscopy and be considered as a relative ‘true value’ in the current comparison.

Thank you for your comments. As noted above, we likewise consider manual gonioscopy to be the current gold standard. However, given that the aim of the present study was to compare AS-OCT and GS-1—both of which can be performed by orthoptists—we focused our analyses on these two modalities. We treated AS-OCT as a relative “true value” because prior reports have shown good sensitivity relative to manual gonioscopy and because GS-1 imaging is performed under bright conditions, which may underestimate angle closure. Nevertheless, since AS-OCT is not the true gold standard, we have revised and expanded the Discussion to acknowledge this limitation with the following statement:

“Comparisons with manual gonioscopy were not performed, and uncertainty remains regarding the extent to which the GS-1 captures the angle in a more open configuration compared with manual gonioscopy. In addition, because AS-OCT was used as a relative reference standard, verification bias is possible. Therefore, future studies are needed that include three-way comparisons among GS-1, manual gonioscopy, and AS-OCT.” (page 19, lines 296-300)

3. The manuscript is generally well-written, though minor grammatical refinements could help with better understanding.

Thank you for your helpful comments. We have carefully revised the manuscript for clarity and grammar.

We sincerely thank the academic editor, editors, and reviewers for their thorough and insightful review, which has greatly improved the quality of our paper. We remain open to any further revision requests and look forward to your response.

Sincerely,

Yuki Takagi, MD

Department of Ophthalmology

Japan Community Healthcare Organization Chukyo Hospital

1-1-10 Sanjo Minami-ku Nagoya-city, Aichi Prefecture, Japan

Telephone: +81-52-691-7151

Fax: +81-52-692-5220

Email: ytakagi@sanjogroup.jp

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Decision Letter 2

Jiro Kogo

3 Sep 2025

Comparison of angle-closure detection between automated gonioscopy and anterior-segment optical coherence tomography

PONE-D-25-17859R2

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Acceptance letter

Jiro Kogo

PONE-D-25-17859R2

PLOS ONE

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Associated Data

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    S1 File. Clinical data of all included patients.

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