OBJECTIVE: To compare the angle of deviation measured from Photo-Hirschberg testing and Krimsky testing, with that from an alternate prism cover test (APCT) in strabismus patients. METHODS: A cross-sectional study was conducted in Songklanagarind Hospital, Thailand. Thirty-three strabismus patients were photographed for analysis by Photo-Hirschberg testing using computer software. The corneal light reflex displacement, converted into prism diopter (PD), was compared to the angle of deviation measured with APCT. Twenty-eight strabismus patients were tested with the Krimsky test. Data were analyzed using Pearson correlation and paired t-tests. The study excluded 4 intermittent exotropia cases, 1 intermittent esotropia case and 2 which cases missing data for krimsky test. RESULTS: The mean±SD of the deviation angle, measured by APCT with a fixation target at 30 cm and 6 m; were 48.09±16.34PD and 47.82±15.73 PD, respectively. At 1 m, the difference in the angle of deviation measured from APCT and the Photo-Hirschberg test within 10 PD were 58.8% and 63.6%, for ET and XT, respectively. The difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 86.7% and 80.0%, respectively. At 4 m, the difference in angle of deviation measured from APCT and Photo-Hirschberg tests within 10 PD in ET and XT were 58.8% and 54.5%, respectively; whereas, the difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 80.0% and 70.0%, respectively. CONCLUSION: The reliability of Krimsky test was better than Photo-Hirschberg test for measuring an angle of deviation.
OBJECTIVE: To compare the angle of deviation measured from Photo-Hirschberg testing and Krimsky testing, with that from an alternate prism cover test (APCT) in strabismus patients. METHODS: A cross-sectional study was conducted in Songklanagarind Hospital, Thailand. Thirty-three strabismus patients were photographed for analysis by Photo-Hirschberg testing using computer software. The corneal light reflex displacement, converted into prism diopter (PD), was compared to the angle of deviation measured with APCT. Twenty-eight strabismus patients were tested with the Krimsky test. Data were analyzed using Pearson correlation and paired t-tests. The study excluded 4 intermittent exotropia cases, 1 intermittent esotropia case and 2 which cases missing data for krimsky test. RESULTS: The mean±SD of the deviation angle, measured by APCT with a fixation target at 30 cm and 6 m; were 48.09±16.34PD and 47.82±15.73 PD, respectively. At 1 m, the difference in the angle of deviation measured from APCT and the Photo-Hirschberg test within 10 PD were 58.8% and 63.6%, for ET and XT, respectively. The difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 86.7% and 80.0%, respectively. At 4 m, the difference in angle of deviation measured from APCT and Photo-Hirschberg tests within 10 PD in ET and XT were 58.8% and 54.5%, respectively; whereas, the difference in the angle of deviation measured from APCT and Krimsky tests within 10 PD in ET and XT were 80.0% and 70.0%, respectively. CONCLUSION: The reliability of Krimsky test was better than Photo-Hirschberg test for measuring an angle of deviation.
Currently, there are various methods for diagnosis of strabismus and measuring the angle of deviation. To date, the alternate prism cover test (APCT) is the gold standard method. However, this method requires professionalism, is time consuming, depends on a special device) prism(, and requires the cooperation of patients in the measurement. In addition, the accuracy of strabismus measurement is often limited; especially when performed by non-experts [1]. Accurate angle measurement is very important for preoperative evaluations, operative procedures and postoperative follow up. Hospitals in developing countries such as Thailand do not have enough specialists or the necessary diagnostic equipment, especially in rural areas. Thus, most eye muscle surgeries are performed in urban hospitals. Additionally, the heavy workload of ophthalmologists hinders them from strabismus examination by APCT. Therefore, cost effective and accurate alternative methods involving simple procedures that can be performed in hospitals within rural areas are required. This study looks at a simple method that uses affordable equipment to reduce that workload. In addition, this method could help reduce the travel burden for patients in rural settings for access to a tertiary care hospital. This study compares the angle of deviation measured from the Photo-Hirschberg test and Krimsky test with that from APCT. It is expected that the results will provide accurate measurement of the angle of deviation; particularly in cases of uncooperative patients.
Methods
The research was approved by the Human Research Ethics Committee of the Faculty of Medicine, Prince of Songkla University. The study designs were approved as 2 studies: the Photo-Hirschberg test compared to APCT and the Krimsky test compared to APCT. The consent was written by subjects and parents for children younger than 18 years.Subjects were excluded if any of the following were present: cyclovertical strabismus, amblyopia, accommodative ET, paralytic strabismus, previous strabismus surgery and abnormality of the ocular surface; such as, corneal scar or pterygium, which may disturb the CLR and confound interpretation of the study results. This study enrolled 33, horizontal strabismus subjects; 14 males (42.4%) and 19 females, at Songklanagarind Hospital; from 2014 to 2015. The mean age was 16.42±15.64 yr. The pattern of strabismus revealed 18 ET and 11 XT and 1 intermittent ET and 4 intermittent XT. Informed consent was obtained from all subjects who were included in the study, or from their guardians. The subjects received a complete eye examination and measurement of the angle of deviation with an APCT, and Krimsky test by 2 experienced orthoptists. The assistance researcher took 2 photographs with the flash on to perform the Photo-Hirschberg test, which is described later. Times to perform the test in each subject were 30 minutes, 20 minutes, 10 minutes and 20 minutes for eye examination, APCT, photography and Krimsky test, respectively.The Photo-Hirschberg test.Photography was performed using a Canon EOS 650D, digital camera, each subject was recorded 8 times, with a photographic resolution of 5,184 x 3,456 pixel images or 18 megapixels. The camera was placed on a stand 1 meter (m) from the subject at the level of the subject’s eye with the flash on. The subject with a ruler attached to the forehead fixated on a target at 1m for near (N1) and 4 m for distance (D1). At each distance, 4 photographs were taken: occluding the left eye (LE), occluding the right eye (RE), both eyes open with RE fixation and both eyes open with LE fixation, respectively (Fig 1).
Fig 1
The photographic method.
(a) Right eye fixing to a central target, and left eye occluded, A is the distance from the CLR to nasal corneal limbus. (b) Left eye fixing to a central target, and right eye occluded, B is the distance from the CLR to nasal corneal limbus. (c) Both eyes open, and right eye fixating on a central target, C is the distance from the right CLR to nasal corneal limbus. The distance from the left CLR to nasal corneal limbus is D. (d) Both eyes open, and left eye fixating on a central target. (The above illustrations are the original works of the authors).
The photographic method.
(a) Right eye fixing to a central target, and left eye occluded, A is the distance from the CLR to nasal corneal limbus. (b) Left eye fixing to a central target, and right eye occluded, B is the distance from the CLR to nasal corneal limbus. (c) Both eyes open, and right eye fixating on a central target, C is the distance from the right CLR to nasal corneal limbus. The distance from the left CLR to nasal corneal limbus is D. (d) Both eyes open, and left eye fixating on a central target. (The above illustrations are the original works of the authors).The quality of images was checked. The digital images were then transferred to a computer, and the position of the CLR, in relation to the nasal limbus, was recorded using an automated program. Fig 1, A is the distance from the CLR to nasal corneal limbus on the right eye while the right eye is fixing, and B is the distance from the CLR to nasal corneal limbus on the left eye while the left eye is fixing. The sum of A and B was considered to represent virtual orthophoria. In the images with both eyes open, C is the distance from the CLR to nasal corneal limbus on the right eye, and D is the distance from the CLR to nasal corneal limbus on the left eye. The sum of C and D was considered to represent strabismus. The value of [(A + B)–(C + D)] was considered to reflect the magnitude of the angle of horizontal displacement, measured in mm, with negative values representing ET, and positive values representing XT. The magnitude of deviation was related to PD by the Hirschberg coefficients from a previous report [2]. At 1 m (N1), the CLR displacement in mm was converted into PD using a Hirschberg coefficient of 21.31 PD/mm and 17.27 PD/mm for the ET and XT values, respectively. At 4 m (D1) the conversion factors were 20.16 PD/mm and 15.63 PD/mm for the ET and XT values, respectively. The Photo-Hirschberg tests were compared with the angle of deviation obtained from APCT measurements.The Krimsky test was performed by measuring the angles of deviation when the patient fixated on a target at 30 cm (N2) and 6 m (D2). The angles of deviation were compared with the angle of deviation obtained from APCT measurements. The fixation target at near and distance were standard for the Krimsky test and APCT.
Sample size calculation formula for correlation
When Zα/2 = Probability of type I error
The total sample size required for this study was 53.
Statistical analyses
The relation between the angles of deviation measured by the Photo-Hirschberg test and the APCT, and that between the angle of deviation measured by the Krimsky test and APCT, were evaluated using two-way scatter plots and Pearson’ Correlation (r) to describe the direction, form and strength of the relationship. The strength of linear relationship was interpreted from poor to very strong [3]. The zone between the dotted lines in Figs 3–6 represents range within ±10 PD of the APCT values. Acceptable and unacceptable areas were designated a, b, c, and d. The acceptable areas were b; representing the angle of deviation derived from the Photo-Hirschberg test or Krimsky test, as more than 10 PD higher than that from APCT, and c, representing the angle of deviation derived from the Photo-Hirschberg test or Krimsky test lower than that from APCT of less than 10 PD. The unacceptable areas were a, representing the angle of deviation derived from the Photo-Hirschberg test or Krimsky test of more than 10 PD higher than that from APCT; whereas, area d, the angle of deviation derived from the Photo-Hirschberg test or Krimsky test of more than 10 PD lower than that from APCT.
Results
The angle of deviation from the Photo-Hirschberg test and APCT were measured from 33 strabismus subjects. The 1 intermittent ET case and 4 intermittent XT cases were excluded before analysis. The Krimsky test was performed on 31 subjects; 2 subjects having variable angles were omitted from analysis (Fig 2).
Fig 2
Flow diagram of strabismus subjects.
Using APCT, The ET group showed mean angle deviations of 47.06±13.09 and 46.72±12.42 at N and D, respectively. The XT group showed mean angle deviations of 49.33±19.98 and 49.13±19.36 at N and D, respectively.With the Photo-Hirschberg test, the ET group showed mean angle deviations of 50.87±19.58 and 48.71±16.10 at N1 and D1, respectively; whereas, the XT group showed mean angle deviations of 33.15±18.68 and 38.20±21.56 at N1 and at D1, respectively.The ET group for the Krimsky test, showed mean angle deviations of 46.67±12.05 and 45.33±13.02 at N2 and at D2, respectively, and the XT group showed mean angle deviations of 50.36±14.07 and 51.43±12.32 at N2 and at D2, respectively.
Correlation analysis
At N, the correlation coefficients(r) of the angle of deviation measured by the Photo-Hirschberg test and APCT, for ET and XT, were 0.443 and 0.637, respectively. This indicated a fair to moderately strong correlation (Fig 3). The number of subjects with differences in angle of deviation within 10 PD were 17 (60.7%), 10 (58.8%) and 7 (63.6%), for total, ET and XT, respectively (Table 1). The correlation coefficients(r) of the angle of deviation measured by the Krimsky test and APCT, for ET and XT, were 0.717 and 0.812, respectively; indicating a moderately strong correlation (Fig 4). The number of subjects with differences in angle of deviation within 10 PD were 21 (84.0%), 13 (86.7%) and 8 (80.0%), for total, ET and XT, respectively (Table 2).
Fig 3
The relationship between angle of deviation from the Photo-Hirschberg test with APCT at N.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia;XT = exotropia).
Table 1
Summary results of correlation between angle of deviation from the Photo-Hirschberg test with the APCT.
Variable
At N, n(%)
At D, n(%)
Total
ET
XT
Total
ET
XT
Absolute difference within acceptable range
17 (60.7)
10 (58.8)
7 (63.6)
16 (57.1)
10 (58.8)
6 (54.5)
Area b
6 (21.4)
3 (17.6)
3 (27.3)
8 (28.6)
4 (23.5)
4 (36.4)
Area c
11 (39.3)
7 (41.2)
4 (36.4)
8 (28.6)
6 (35.3)
2 (18.2)
Absolute difference within unacceptable range
11 (39.3)
7 (41.2)
4 (36.4)
12 (42.9)
7 (41.2)
5 (45.5)
Area a
5 (17.9)
5 (29.4)
0 (0)
4 (14.3)
4 (25.5)
0 (0)
Area d
6 (21.4)
2 (11.8)
4 (36.4)
8 (28.6)
3 (17.6)
5 (45.5)
APCT = alternate prism cover test, ET = Esotropia, XT = Exotropia, PD = prism diopter, = n number of subjects, N = near fixation, D = distance fixation.
Fig 4
The relationship between angle of deviation from the Krimsky test with APCT at N.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).
Table 2
Summary results of correlation between angle of deviation from the Krimsky with the APCT.
Variable
At N2, n(%)
At D2, n(%)
Total
ET
XT
Total
ET
XT
Equality
5 (20)
4 (26.7)
1 (10)
5 (20)
4 (26.7)
1 (10)
Absolute difference within acceptable range
16 (64)
9 (60)
7 (70)
14 (56)
8 (53.3)
6 (60)
Area b
5 (20)
2 (13.3)
3 (30)
5 (20)
2 (13.3)
3 (30)
Area c
11 (44)
7 (46.7)
4 (40)
9 (36)
6 (40)
3 (30)
Absolute difference within unacceptable range
4 (16)
2 (13.3)
2 (20)
6 (24)
3 (20)
3 (30)
Area a
2 (8)
1 (6.7)
1 (10)
2 (8)
1 (6.7)
1 (10)
Area d
2 (8)
1 (6.7)
1 (10)
4 (16)
2 (13.3)
2 (20)
APCT = alternate prism cover test, ET = Esotropia, XT = Exotropia, PD = prism diopter, n = number of subjects, N2 = near fixation at 30 cm, D2 = distance fixation at 6 m.
The relationship between angle of deviation from the Photo-Hirschberg test with APCT at N.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia;XT = exotropia).
The relationship between angle of deviation from the Krimsky test with APCT at N.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).APCT = alternate prism cover test, ET = Esotropia, XT = Exotropia, PD = prism diopter, = n number of subjects, N = near fixation, D = distance fixation.APCT = alternate prism cover test, ET = Esotropia, XT = Exotropia, PD = prism diopter, n = number of subjects, N2 = near fixation at 30 cm, D2 = distance fixation at 6 m.At D, the correlation coefficients(r) for angle of deviation measured by the Photo-Hirschberg test and APCT were 0.501 and 0.778, for ET and XT, respectively; indicating a moderately strong correlation (Fig 5). The number of subjects with difference in angle of deviation within 10 PD were 16 (57.1%), 10 (58.8%) and 6 (54.5%), for total, ET and XT, respectively (Table 1). The correlation coefficients(r) of the angle of deviation measured by the Krimsky test and APCT were 0.696 and 0.798, for ET and XT, respectively; indicating a moderately strong correlation (Fig 6). The number of subjects with differences in angle of deviation within 10 PD were 19 (76.0%), 12 (80.0%) and 7 (70.0%), for total, ET and XT, respectively (Table 2).
Fig 5
The relationship between angle of deviation from the Photo-Hirschberg test with APCT at D.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).
Fig 6
The relationship between angle of deviation from the Krimsky test with APCT at D.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).
The relationship between angle of deviation from the Photo-Hirschberg test with APCT at D.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).
The relationship between angle of deviation from the Krimsky test with APCT at D.
The solid line is the line of equality and the zone between dotted lines represents range ±10 PD of the APCT values. The acceptable area were b and c. The unacceptable area were a and d. (ET = esotropia; XT = exotropia).This study excluded 1 intermittent ET, 4 intermittent XT patients, with angles of deviation of 27.7, 0.17, 5.01, 16.2 and 25.2 PD, determined from the Photo-Hirschberg test and angles of deviation of 20, 40, 40, 35 and 40 PD measured using APCT.
Discussion
The accuracy of the angle of deviation depends on the measurement method, experience of the personnel as well as cooperation of the patient. The Hirschberg’s test, which uses the position of corneal light reflex (CLR) related to pupillary or corneal limbus for estimation of angle of deviation, is a simple and easy test. However, the test precision is poor, because it uses the measurement of position of CLR, which is prone to human error; especially when performed by inexperienced personnel [1, 4]. The Hirschberg coefficients varies between 13 and 21 prism diopter (PD) per mm, due to variations of research methodology, techniques and subjects [5-12]. Recently, investigators [2] have used digital cameras and computers to detect the position of CLR, so as to improve the accuracy of the Hirschberg’s test. This present study aimed to use conversion factors from our previous study. We defined this method as: a Photo-Hirschberg test. The past, a method using CLR combined with photographs, videos, and computer software was reported that could possibly improve diagnosis and measurement of angle of deviation [13, 14].The Krimsky test, employed for measuring the angle of deviation using deviated light from a prism and the position of CLR, is simple, but depends on experienced personnel and a cooperative patient. Choi [15] observed accuracy within 10 PD in angle of deviation measurement using Hirschberg and Krimsky tests by experienced strabismologists. Holmes [16] observed that the 95% limits of agreement for inter observer for APCT at near (N) and distance (D) were 9.2 PD and 10.2 PD, respectively. Therefore, we defined the acceptable range of difference in angle of deviation between methods as within±10 PD.Basmak [17] showed the angle Kappa was higher in XT patients than in ET patients, resulting in a biased angle measurement when performed by the Hirschberg test or Krimsky tests. The angle Kappa is the angle between the optical axis and the visual axis of the eye, which affects the position of the CLR in non-strabismus people.This study compared the degree of angle of deviation from APCT and Photo-Hirschberg tests, with values of the Hirschberg coefficients from photographs and using specific software. This study also compared the degree of angle of deviation from APCT and Krimsky tests. Previous studies modified the Hirschberg test to improve the accuracy for measuring angle of deviation. The Photo-Hirschberg is one of such modifications, with moderately strong correlation with APCT for near and distance fixations (r = 0.415, 0.620). Half of the subjects had values within the acceptance range, but the correlation was lower compared with other studies. Yang [18] studied the efficacy of the 3D strabismus photo analyzer, computerized software for measuring angle of deviation from photographs. The results showed moderately strong correlation between an APCT and 3D strabismus photo analyzer (r = 0.772). Hasebe [12] studied an automated strabismus analysis from corneal light reflex using a video refractor. The results showed strong correlation(r = 0.956) between Hirschberg and APCT. This study defined an acceptance with discrepancy of deviation ±13.7 PD that differed from our study. Yoo [19], using infrared photographs, with a specific filter, measured the angle of deviation in small angle ET, and reported strong correlation(r = 0.815) with both APCT and Krimsky tests.Sousa de Almeida [20], using a computer-aided methodology, based on detection of strabismus from a video, showed that the 95% limits of agreement were ±13.7 PD. The data from photographs may vary, because of intermittent XT patients, accommodative ET or error of dimension-distance [20, 21]. In intermittent XT patients, the value of deviation angle was less than that using APCT. We assumed that patients still had fusion while being photographed. Now, we suggest to improve the method of photographing to reduce accommodation, such as the use of an infrared filter.The correlation between the Krimsky test and the APCT, for near fixation and distance fixation, were 0.773 and 0.738, respectively; indicating moderately strong correlation. The difference of the angle of deviation was within the acceptable range in three quarters of the subjects. Previous studies have reported similar correlation. Yang [18] showed strong correlation between APCT and Krimsky (r = 0.809), while Joo [22] showed moderately strong correlation between APCT and Krimsky in ET and XT(r = 0.738, 0.651) and very strong correlation between APCT and Distance Krimsky tests in ET and XT(r = 0.981, 0.919).The angle of deviation measured by the Photo-Hirschberg test, Krimsky test, and APCT showed positive correlation, suggesting that the Photo-Hirschberg method can be used as an alternative to APCT; especially in uncooperative patients. Additionally, it can be used as a follow up option for measuring the angle of deviation in strabismus subjects.Limitations of this study, the number of study patients was quite small. However, the findings of this study can serve as a preliminary foundation for further study.
Conclusion
The reliability of Krimsky test was better than Photo-Hirschberg test for measuring an angle of deviation.
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We note that Figure 2 includes an image of a patient / participant in the study.As per the PLOS ONE policy (http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research) on papers that include identifying, or potentially identifying, information, the individual(s) or parent(s)/guardian(s) must be informed of the terms of the PLOS open-access (CC-BY) license and provide specific permission for publication of these details under the terms of this license. Please download the Consent Form for Publication in a PLOS Journal (http://journals.plos.org/plosone/s/file?id=8ce6/plos-consent-form-english.pdf). The signed consent form should not be submitted with the manuscript, but should be securely filed in the individual's case notes. Please amend the methods section and ethics statement of the manuscript to explicitly state that the patient/participant has provided consent for publication: “The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish these case details”.If you are unable to obtain consent from the subject of the photograph, you will need to remove the figure and any other textual identifying information or case descriptions for this individual.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.Reviewer #1: YesReviewer #2: Partly**********2. Has the statistical analysis been performed appropriately and rigorously?Reviewer #1: YesReviewer #2: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.Reviewer #1: YesReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)Reviewer #1: This study addresses an important issue and worked on a technique that may be useful in areas with no strabismus specialist. Although the idea is good yet the study is limited by the small number of cases and major exclusion criteria. The manuscript needs a lot of work to be suitable for publication. Below are the details.Line 58: “Many studies have tried… “ What are those studies? No references mentioned.Lines 55 to 82: This part should be moved to the discussion. The details of previous investigators’ approach can be included briefly in introduction only if needed to explain the purpose of the study. This section should be reduced in introduction and moved mostly to discussion.Line 89: “Four subjects in the XT group were intermittent XT”: The authors described the diagnosis of four subjects out of the total cohort only. It is unclear why this diagnosis was singled out specifically here. Why not mention the breakdown of the diagnosis of all the test subjects?Line 87-94: Inclusion criteria were mentioned, then diagnosis of 4 subjects, then the consent, then back to exclusion criteria. This order is not usual. I recommend keeping the exclusion criteria right after the inclusion criteria.Lines 91-94: Why was accommodative ET excluded? Why were cases with amblyopia or pervious surgery excluded? These subgroups are very common diagnoses, especially in the difficult cases that will need to be sent to an expert for opinion. By such exclusions authors are suggesting that the test is no useful on these subgroups and hence not useful for a big chunk of the cases in the strabismus clinic. Cause of such exclusions should be discussed.Lines 94-96: Revise sentence structure and avoid repetition (subjects received eye examination)Line 96: I was expecting detailed description of how to Photo-Hirschberg test was done. This is mentioned later lines 108 onwards. I think this should be moved to be in the right place. It is confusing to have to go back and forth in the manuscript. As such it lacks the smoothness that readers expect.Lines 99-100: “Time span..” It is not clear what the authors mean by time span. Time span between what and what? And why is that? This “time span” needs detailed description.Lines 101 -106: The consent is repeated again here. It is mentioned earlier in line 90! I would recommend starting the methodology by stating the approval by the IRB and the consent and then proceeding with the rest of the methodology. Line 105: “and showed.. “ till the end should be deleted. At this point of reading the study didn’t show anything yet. We are still in the methods.Line 117: “limbuson”: seems a spelling mistakeLine 118: “When the right eye is fixated”: I think the authors mean when the right eye “is fixing”. Please correct this throughout the text.Line 108: How did the photographer deal with cases of intermittent exotropia to show the deviation?Lines 170-187: All this data should be in detailed in the table and deleted from the text. It is very confusing to read or compare these number in paragraph format. A table only without text is enough to show results like this.Lines 189-198: the first paragraph of the discussion is almost all a repetition from the introduction.Lines 213-215: The angles of the cases should be in the results section. The analysis as to why this might have happened goes into the discussion section.Lines 217: Do authors want to implicate that their method is not useful in intermittent exotropia cases? Need clarifications as to what is the authors conclusions about the use in intermittent exotropia cases.Line 234: Conclusion should be in relation to the title and objective of the study. The study is testing “the reliability of Photo-Hirschberg and Krimsky”. The objective as per the abstract “to compare photo-H, Krimsky and APCT”. therefore this should be mentioned in the conclusion. This sentence “ Photo-Hirschberg test could be used to examine and monitor” is not informative. Any test could be used to measure and monitor! Same for saying “Krimsky can be used in uncooperative patients”: this is again basic knowledge and not the conclusion of this study.Reviewer #2: The assessment of measurement reliability should not be done by Pearson's correlation but use the Intrasclass Correlation (ICC). Please refer to the recent comments on measurement reliability and its importance for individual differences research (https://www.nature.com/articles/s41562-019-0655-x). In https://www.sciencedirect.com/science/article/pii/S2095927318305784, the anatomy of ICC is introduced. Please update all the reliability analyses in terms of the basic requirement by the two references abovementioned.**********6. PLOS authors have the option to publish the peer review history of their article (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 #1: Yes: Amr ElKamshoushyReviewer #2: No[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]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. Please note that Supporting Information files do not need this step.8 Aug 2021The idea of the manuscript is interesting However, the manuscript needs some justification for the exclusion of some patients, and explanation of how patients were intermittent exotropia were photpgraphed..ANS: We need to set the research protocol in real world, so intermittent exotropia was not in the exclusion criteria. After we included all subjects and analyzed, we try to explain for someone who needs to use the data in clinical practice. After your recommend we reanalyzed after excluded intermittent strabismus cases.Please submit your revised manuscript by Aug 19 2021 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.Please include the following items when submitting your revised manuscript:• 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.ANS: I changed my financial disclosure and include in cover letter.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: http://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,Ahmed Awadein, MD, Ph.D, FRCSAcademic EditorPLOS ONEJournal Requirements:When submitting your revision, we need you to address these additional requirements.1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found athttps://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf andhttps://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf2. Thank you for submitting your clinical trial to PLOS ONE and for providing the name of the registry and the registration number. The information in the registry entry suggests that your trial *TCTR20141201001* was registered after patient recruitment began. PLOS ONE strongly encourages authors to register all trials before recruiting the first participant in a study.As per the journal’s editorial policy, please include in the Methods section of your paper:1) your reasons for your delay in registering this study (after enrolment of participants started);ANS: The ethics committee was approved the research protocol then we made registration of the protocol to TCTR before we started to recruit subjects. However, we did not check for completion of registration.2) confirmation that all related trials are registered by stating: “The authors confirm that all ongoing and related trials for this drug/intervention are registered”.ANS: We confirmed that all related trials are registered by stating: “The authors confirm that all ongoing and related trials for this drug/intervention are registered”.3. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables should remain uploaded as separate "supporting information" files.ANS: Changed4. Thank you for stating the following in the Acknowledgments Section of your manuscript:"This research was partially supported by a grant from the Faculty of Medicine, Prince of Songkla University."-ANS: I rewrite it from the manuscript.We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:"No"Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now. Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.Please include your amended statements within your cover letter; we will change the online submission form on your behalf.ANS: I include the statement “There was no additional external funding received for this study.” in my updated Funding Statement and put it in my cover letter5. Thank you for stating the following in your Competing Interests section:"No"Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state "The authors have declared that no competing interests exist.", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-nowThis information should be included in your cover letter; we will change the online submission form on your behalf.ANS: On behalf of all authors the corresponding author declares that no competing interests exist and put it in cover letter.Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests6. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.ANS: no other supporting information files7. We note that Figure 2 includes an image of a patient / participant in the study.As per the PLOS ONE policy (http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research) on papers that include identifying, or potentially identifying, information, the individual(s) or parent(s)/guardian(s) must be informed of the terms of the PLOS open-access (CC-BY) license and provide specific permission for publication of these details under the terms of this license. Please download the Consent Form for Publication in a PLOS Journal (http://journals.plos.org/plosone/s/file?id=8ce6/plos-consent-form-english.pdf). The signed consent form should not be submitted with the manuscript, but should be securely filed in the individual's case notes. Please amend the methods section and ethics statement of the manuscript to explicitly state that the patient/participant has provided consent for publication: “The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish these case details”.If you are unable to obtain consent from the subject of the photograph, you will need to remove the figure and any other textual identifying information or case descriptions for this individual.ANS: I changed the Figure 2 and no longer a photograph.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.Reviewer #1: YesReviewer #2: Partly________________________________________2. Has the statistical analysis been performed appropriately and rigorously?Reviewer #1: YesReviewer #2: NoANS: We reanalyze the manuscript.________________________________________3. Have the authors made all data underlying the findings in their manuscript fully available?The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.Reviewer #1: YesReviewer #2: Yes________________________________________4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes________________________________________5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)Reviewer #1: This study addresses an important issue and worked on a technique that may be useful in areas with no strabismus specialist. Although the idea is good yet the study is limited by the small number of cases and major exclusion criteria. The manuscript needs a lot of work to be suitable for publication. Below are the details.Line 58: “Many studies have tried… “ What are those studies? No references mentioned.Ans: ChangedLines 55 to 82: This part should be moved to the discussion. The details of previous investigators’ approach can be included briefly in introduction only if needed to explain the purpose of the study. This section should be reduced in introduction and moved mostly to discussion.ANS: ChangedLine 89: “Four subjects in the XT group were intermittent XT”: The authors described the diagnosis of four subjects out of the total cohort only. It is unclear why this diagnosis was singled out specifically here. Why not mention the breakdown of the diagnosis of all the test subjects? –ANS: We reanalyze and rewrite the manuscript after excluded intermittent strabismus cases.Line 87-94: Inclusion criteria were mentioned, then diagnosis of 4 subjects, then the consent, then back to exclusion criteria. This order is not usual. I recommend keeping the exclusion criteria right after the inclusion criteria.ANS: changedLines 91-94: Why was accommodative ET excluded? Why were cases with amblyopia or pervious surgery excluded? These subgroups are very common diagnoses, especially in the difficult cases that will need to be sent to an expert for opinion. By such exclusions authors are suggesting that the test is no useful on these subgroups and hence not useful for a big chunk of the cases in the strabismus clinic. Cause of such exclusions should be discussed.ANS: Accmmodation ET showed variation of angle and depend on accommodation power and glasses correction so it may confound the interpretation.Amblyopia case will have some problem for fixation when we measure angle of deviationfrom alternate prism cover test (APCT).Previous surgery may disturb the action of the eye muscle.Lines 94-96: Revise sentence structure and avoid repetition (subjects received eye examination)ANS: ChangedLine 96: I was expecting detailed description of how to Photo-Hirschberg test was done. This is mentioned later lines 108 onwards. I think this should be moved to be in the right place. It is confusing to have to go back and forth in the manuscript. As such it lacks the smoothness that readers expect.ANS: ChangedLines 99-100: “Time span..” It is not clear what the authors mean by time span. Time span between what and what? And why is that? This “time span” needs detailed description.ANS: ChangedLines 101 -106: The consent is repeated again here. It is mentioned earlier in line 90! I would recommend starting the methodology by stating the approval by the IRB and the consent and then proceeding with the rest of the methodology. Line 105: “and showed.. “ till the end should be deleted. At this point of reading the study didn’t show anything yet. We are still in the methods.ANS: ChangedLine 117: “limbuson”: seems a spelling mistakeANS: ChangedLine 118: “When the right eye is fixated”: I think the authors mean when the right eye “is fixing”. Please correct this throughout the text.ANS: ChangedLine 108: How did the photographer deal with cases of intermittent exotropia to show the deviation?ANS: We reanalyzed and rewrite the manuscript after excluded intermittent strabismus cases. We suggest to improve the method with using an infrared filter.Lines 170-187: All this data should be in detailed in the table and deleted from the text. It is very confusing to read or compare these number in paragraph format. A table only without text is enough to show results like this.ANS: ChangedLines 189-198: the first paragraph of the discussion is almost all a repetition from the introduction.ANS: ChangedLines 213-215: The angles of the cases should be in the results section. The analysis as to why this might have happened goes into the discussion section.ANS: ChangedLines 217: Do authors want to implicate that their method is not useful in intermittent exotropia cases? Need clarifications as to what is the authors conclusions about the use in intermittent exotropia cases.ANS: ChangedLine 234: Conclusion should be in relation to the title and objective of the study. The study is testing “the reliability of Photo-Hirschberg and Krimsky”. The objective as per the abstract “to compare photo-H, Krimsky and APCT”. therefore this should be mentioned in the conclusion. This sentence “ Photo-Hirschberg test could be used to examine and monitor” is not informative. Any test could be used to measure and monitor! Same for saying “Krimsky can be used in uncooperative patients”: this is again basic knowledge and not the conclusion of this study.ANS: We changed conclusion.Reviewer #2: The assessment of measurement reliability should not be done by Pearson's correlation but use the Intrasclass Correlation (ICC). Please refer to the recent comments on measurement reliability and its importance for individual differences research (https://www.nature.com/articles/s41562-019-0655-x). In https://www.sciencedirect.com/science/article/pii/S2095927318305784, the anatomy of ICC is introduced. Please update all the reliability analyses in terms of the basic requirement by the two references abovementioned.ANS: the reliability done by number of subjected within acceptable ranges ( within +/-10 PD of the APCT values). I study ICC from previous references but, I am not quite sure that its fit for our paper.________________________________________6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.Submitted filename: response to reviewers.docxClick here for additional data file.5 Oct 2021The reliability of the angle of deviation measurement from Photo-Hirschberg tests and Krimsky testsPONE-D-21-11420R1Dear Dr. tengtrisorn,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.Kind regards,Ahmed Awadein, MD, Ph.D, FRCSAcademic EditorPLOS ONEAdditional Editor Comments (optional):Reviewers' comments:19 Nov 2021PONE-D-21-11420R1The reliability of the angle of deviation measurement from the Photo-Hirschberg tests and Krimsky testsDear Dr. Tengtrisorn:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.If we can help with anything else, please email us at plosone@plos.org.Thank you for submitting your work to PLOS ONE and supporting open access.Kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Ahmed AwadeinAcademic EditorPLOS ONE