Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital. Case-control study.

INTRODUCTION: Glaucoma is a disease which causes optic nerve damage and remains a major public health concern worldwide. Late presentation is a major risk factor for glaucoma induced blindness. The aim of this study was to assess determinants for late presentation of glaucoma among adult glaucomatous patients.
METHODS: A hospital-based case-control study was conducted among 452 adult glaucomatous patients. Late presenters were glaucoma patients diagnosed with cup to disc ratio (CDR) > 0.8 and mean deviation of greater than -14 decibel in either of the eyes at their first presentation. Study participants were selected among glaucomatous follow-up patients by using systematic random sampling. Data were entered into EPI Info version 7 and exported to SPSS version 22 for analysis. Bivariable and multivariable logistic regression analysis was done to identify determinants. Variables with P-value < 0.05 were considered as statistically significant. RESULT: The mean age of participants were 55.1 ± 13.2 years. Being > 60 years of age, 4.51 times (AOR: 4.51; 95% CI: 1.74, 11.67), resided > 53 km away from the hospital 6.02 times (AOR: 6.02; 2.76, 13.14), Presenting IOP > 30 mmHg, 4.49 times (AOR: 4.49, 95% CI: 2.10, 9.12), poor knowledge of glaucoma, 4.46 times (AOR: 4.46, CI: 2.62, 7.58) and absence of regular eye checkup, 2.35 times (AOR: 2.35, 95% CI: 1.09, 5.47) higher odds of being late presenter.
CONCLUSION: Increasing age, high IOP, poor knowledge of glaucoma, residing far away from the hospital and absence of regular eye checkups were significantly associated with late presentation.

Introduction

Globally, glaucoma causes irreversible blindness in 4.6–6.7 million people [1] with a prevalence of 3.54% for the population aged 40 to 80 years. In 2013, the number of people aged 40 to 80 years with glaucoma was 64.3 million which was predicted to increase to 76.0 million in 2020 and 111.8 million in 2040 [2]. Glaucoma mainly affects developing nations, and Africa accounts for 15% of the world’s blindness due to glaucoma [2]. Population-based studies in Asian countries showed a higher prevalence of glaucoma [3] and Primary Open Angle Glaucoma (POAG) is the most commonly reported [4-6]. The prevalence of previously undiagnosed glaucoma in South Africa was 87.0% [7]. In Ethiopia, glaucoma results an irreversible vision loss in 62,000 individuals, becoming the fifth common cause of blindness in the country [8]. In a study done in 2002 in North Shoa of Ethiopia, glaucoma accounted 11.4% of blindness [9].

Several studies estimated that 10–33% of people with glaucoma had advanced disease and visually impaired at the first diagnosis due to their late presentation [10-12]. The reason for the late presentation was due to lack of early symptoms [13,14], slowly progressive and asymptomatic of nature of glaucoma [15]. Previous studies showed age, sex, educational level, occupational group, poor socioeconomic status, high intraocular pressure (IOP) at presentation, pseudo-exfoliation, awareness and knowledge about glaucoma, absence of a positive family history of glaucoma as determinants for late presentation of glaucoma [16-19]. Other studies also showed that late presentation is a major risk factor for blindness due to glaucoma [17,19,20-22]. It has been estimated that in Africa, half of patients with glaucoma are blind in at least one of their eyes at presentation [23]. Glaucoma was one of the leading cause of irreversible blindness in Ethiopia [8], thus this study has an immense importance to salvage the community from glaucoma induced blindness. Previous published evidences in Ethiopia didn’t have enough information to explore the determinant factors for the late presentation of glaucoma. Most of these studies were done to assess and the prevalence of blindness due to glaucoma [8,9] and the associated factors of glaucoma [24]. Because of this, it needs explicit in situ study to identify the determinants for late presentation of glaucoma. In addition, the result of this study will provide base line information for the health care workers, researchers, health care planers, policy makers and other stakeholders accordingly. Therefore, this study was aimed to assess determinants for late presentation of glaucoma among adult glaucomatous patients in Ethiopia.

Materials and methods

Study design, setting and sampling

A hospital-based case-control study was conducted in the University of Gondar, Comprehensive Specialized Hospital, tertiary eye care and training center (UoG CSH TECTC) Northwest Ethiopia, 2020. Gondar city is located 738 kilometers away from Addis Ababa, the capital city of Ethiopia. UoG CSH TECTC is the only tertiary eye care center in the city providing comprehensive eye care for the Northwest Ethiopia which provides services for glaucoma patients from early diagnosis to frequent follow-up.

All adult glaucomatous patients aged ≥ 18 years, diagnosed within the last two years and on follow-up were included in the study. Whereas, glaucomatous patients who were diagnosed with glaucoma or a glaucoma follow-up in another health institution before their first presentation, glaucomatous patients diagnosed with acute angle-closure glaucoma, patients who are unable to communicate and patients with an incomplete medical record were excluded from the study.

The sample size was calculated using the double population proportion formula using EPI Info version 7 software. n = (2 x P (1-P) (Zβ +Zα/2)2 / (P1—P2)2

Where, n = sample size, P = P1+P2; P1 = Proportion of controls with exposure was 19.51%, P2 = Proportion of cases with exposure was 9.67%. Z = the value of z statistic at 95% confidence level = 1.96, β power 80% = 0.80, Zβ = 0.84, control to case ratio = 1:1 [17], assuming a non-response rate of 10% for cases and controls, the overall sample size was estimated at 492 (246 cases and 246 controls). The study participants for both cases and controls were selected among glaucomatous patients on follow-up who visited the glaucoma clinic during the data collection period using systematic random sampling. The cases were recruited from late glaucoma presenters while the controls were selected among those without late glaucoma. The projected numbers in two months follow-up for cases and controls were 495 and 540 respectively. So, Kcase = 495/246 = 2.012 approximately 2 and Kcontrol = 540/246 = 2.19 approximately 2. Both controls and cases were selected by systemic random sampling with a fraction of k = 2 form their medical record numbers. Then, each selected patient was accessed in the waiting area. If the patient was not available the next immediate medical record number of the same group was selected and a sampling fraction was added to get the next patient. An identification number was given for each medical record number to avoid duplication.

Operational definitions

Cases (Late presenters): Any chronic glaucoma patients diagnosed with cup to disc ratio (CDR) > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes at their first presentation [16,18].

Controls: Chronic glaucoma patients diagnosed with cup to disc ratio (CDR) < 0.8 and typical glaucomatous field loss with a mean deviation of < -14 decibel in both of the eyes at their first presentation [16,18].

Late glaucoma diagnosis: Glaucomatous disc cupping of CDR > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes [18].

Knowledge: A standard knowledge questionnaire including seventeen (17) questions was used to assess respondents’ knowledge about glaucoma. One point (1) was allocated for each correct response, otherwise, zero (0) was given. Respondents who scored the median (≥7.0) and above of 17 knowledge questions were considered to have good knowledge; while those who scored below the median were considered as having poor knowledge about glaucoma [23].

Regular eye checkup: Those individuals who check up their eyes in every two years [17,24].

Data collection tool and procedure

A semi-structured questionnaire having five parts related to sociodemographic & economic factors, ocular factors, behavioral factors, knowledge-related factors, and systemic disease-related information of the participant was prepared by reviewing different literatures.

A data extraction format was developed to review the chart of each eligible patient to assess the type and stage of glaucoma, IOP, and visual acuity (VA) of study participants. The diagnosis of glaucoma was made by a senior ophthalmologist. The questionnaire was initially prepared in English, translated into Amharic (local language) by language experts for data collection, and re-translated to English to check consistency in meaning of words and concepts. The questionnaire was pre-tested for reliability and validity in 25 glaucomatous patients in another hospital (Bahir Dar Felege Hiwot referral eye Hospital) with the same methods and the content of the questionnaire was assessed for its clarity, completeness and modified accordingly. It was also checked for its reliability using a reliability test and has a Cronbach alpha value of 0.77.

A data collection procedure involving a patient interview and reviewing patients’ medical records. The data was collected by trained ophthalmic nurses and supervision was done by a senior optometrist. Data collectors first introduced themselves and the purpose of the study. After obtaining consent from the subjects, data was collected from the participants with face-to face interview. Necessary information was obtained from the patients’ medical record that was recorded on their first visit to the glaucoma clinic.

Supervision has been made during the data collection and appropriate feedback had been provided. Training was given to the data collectors before the data collection. Regular check-up for completeness and consistency of the collected data has been made by the principal investigator on daily basis.

Statistical analysis

Data were coded, entered into EPI Info version 7 (https://www.cdc.gov/epiinfo/pc.html) and exported to SPSS version 22 (https://www.ibm.com/analytics/spss-statistics-softw) for analysis. The descriptive statistics were presented with tables, percentages, mean, and standard deviations. Hosmer- Lemeshow goodness of fit was done to check the model assumption of logistic regression. Multicollinearity between the independent variables was checked using the Variance Inflation Factor and the mean value was less than three. Both bi-variable and multivariable logistic regression analysis was done and variables with p-value < 0.2 under bi-variable logistic regression considered for multivariable logistic regression. In the multivariable logistic regression analysis, variables with a p-value of less than 0.05 were declared as statistically significant. Odds ratio with 95% confidence interval and the corresponding p-value was used to identify determinants of late presentation among glaucoma patients.

Ethical consideration

Ethical approval was obtained from the Institutional Review Board (IRB) of University of Gondar, College of Medicine and health sciences in accordance with the Declaration of Helsinki. Written letter of permission was obtained from the medical registration office to access the patients’ medical record. Written informed consent was obtained from the study participants after a brief explanation of the objective of the study. Any involvement in the study was after their complete consent was obtained. All the study participants were informed about the purpose of the study and their right to refuse and withdraw from the study at any time. Confidentiality was also maintained through an anonymous questionnaire by excluding identifiers and using codes.

Results

Socio-demographic characteristics of study participants

From the total of 492 study participants, 452 (226 cases and 226 controls) with a response rate of 91.87% were involved in the study. From the study participants, 277 (61.3%) were males. The mean age of the study participants at the diagnosis of glaucoma was 55.1 years with a standard deviation (SD) ±13.2 (Table 1).

Table 1

Socio-demographic characteristics of study participants in University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2020.

Variable	Controls, n (%)	Cases, n (%)
Sex Male Female	142 (62.8)84 (37.2)	135 (59.7)91(40.3)
Age at diagnosis 18–40 41–50 51–60 >60	38 (16.8)72 (31.9)65 (28.8)51 (22.5)	16 (7.1)48 (21.2)67 (29.6)95 (42.1)
Educational status No formal education Primary Secondary College and above	81 (35.8)31 (13.7)54 (23.9)60 (26.6)	102 (45.1)37(16.4)52 (23.0)35 (15.5)
Occupation Governmental employee Non-governmental employee Merchant Farmer Housewife Others*	38 (16.8)14 (6.2)67 (29.7)47 (20.8)36 (15.9)24 (10.6)	20 (8.9)10 (4.4)65 (28.8)69 (30.5)45 (19.9)17 (7.5)
Monthly income (US$) ≤ 19 20–33 34–50 >50	60 (26.5)46 (20.4)39 (17.3)81 (35.8)	81 (35.8)55 (24.4)38 (16.8)52 (23.0)
Distance from the hospital in Km ≤ 3 4–24 25–53 > 53	86 (38.1)74 (32.7)35 (15.5)31 (13.7)	32 (14.2)34 (15.1)81 (35.8)79 (35.0)
Positive family history of glaucoma Yes No I don’t know	30 (13.3)173 (76.5)23 (10.2)	21 (9.3)182 (80.5)23 (10.2)

Others* = retired (11), driver (3), daily laborer (9), religious leaders (13), students (5).

Ocular related factors of study participants

The median IOP of the overall study participants was 25.80 mmHg and inter-quartile range (IQR) 9.97 mmHg, while it was 29.00 mmHg and 24.10 mmHg for cases and controls respectively. The most common diagnosis of glaucoma was primary open-angle glaucoma, 255 (56.4%). Of those patients who had IOP > 30 mmHg, 71.53% were cases. Only 71 (15.7%) of the total study participants had habit of regular eye checkup. Among the study participants, 288 (50.44%) had good knowledge about glaucoma (Table 2).

Table 2

Ocular related factors among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2020.

Variable	Controls, n (%)	Cases, n (%)
Presenting IOP <21.00 21.00–25.00 25.01–30.00 >30.00	70 (31.0)62 (27.4)57 (25.2)37 (16.4)	33 (14.6)41 (18.1)59 (26.1)93 (41.2)
Type of glaucoma POAG CACG PxG Others*	139 (74.3)32 (3.1)41 (19.9)14 (2.7)	116 (51.8)16 (35.4)87 (9.7)7 (3.1)
Systemic diseases Diabetes mellitus  Yes  No Hypertension  Yes  No Asthma  Yes  No	59 (26.1)167 (73.9)22 (9.7)204 (90.3)7 (3.1)219 (96.9)	15 (6.6)211 (93.4)18 (8.0)208 (92.0)11 (4.9)215 (95.1)
Previous ocular trauma Yes No	18 (8.0)208 (92)	8 (3.5)218 (96.5)
Regular eye check up Yes No	56 (24.8)170 (75.2)	15 (6.6)211 (93.4)
Ocular comorbidity No Yes	165 (73.0)61 (27.0)	159 (70.4)67 (29.6)
Knowledge about glaucoma Poor Good	67 (29.6)159 (70.4)	157 (69.5)69 (30.5)

Others* = Normal tension glaucoma, Neovascular glaucoma, Steroid induced glaucoma, Phacomorphic glaucoma, POAG = primary open angle glaucoma, CACG = Chronic angle closure glaucoma, PxG = pseudo-exfoliative glaucoma.

Determinants of late presentation of glaucoma of study participants

In multivariable logistic regression analysis; age, the distance of residence from UoG TETC, regular eye checkup, high IOP at presentation, knowledge about glaucoma, and history of diabetes mellitus remained significantly associated with late presentation of glaucoma. Accordingly, being 51–60 and >60 years old had 2.36 times (AOR: 2.36; 95% CI: 1.18, 4.65) and 4.51 times (AOR: 4.51; 95% CI: 1.74, 11.67) higher odds of being late presenter respectively than those ≤ 40 years of age. Participants who resided 24–53 km and > 53 km away from UoG TECTC had the odds of 4.50 times (AOR: 4.50; 2.15, 9.40) and 6.02 times (AOR: 6.02; 2.76, 13.14) more likely being late presenter respectively compared to those who resided <3km away from the UoG TECTC. Similarly, this study revealed that those patients with presenting IOP of 25.01–30.00 mmHg and > 30 mmHg had 2.17 times (AOR: 2.17, 95% CI: 1.23, 5.09) and 4.49 times (AOR: 4.49, 95% CI: 2.10, 9.12) higher odds of presenting late respectively compared to those whose presenting IOP were < 21.00 mmHg. Besides, the odds of late presentation among participants who had poor knowledge of glaucoma was 4.46 times (AOR: 4.46, 95% CI: 2.62, 7.58) higher compared to those who had good knowledge. In the same way, the odds of late presentation for those patients who didn’t regularly checkup their eyes was 2.35 times (AOR: 2.35, 95% CI: 1.09, 5.47) more likely to present late compared to those who had regular eye checkup. On the other hand, those who had history of diabetes mellitus had 84% lesser odds of being late presenter (AOR = 0.16, 95% CI: 0.68, 0.38) compared to those who didn’t have diabetes (Table 3).

Table 3

Determinant factors associated with late presentation among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2020.

Study factor	Control	Case	COR (95%CI)	AOR (95% CI)	P value
Age ≤ 40 41–50 51–60 >60	38726550	16486796	1.001.58 (0.79, 3.15)2.44 (1.20, 4.67)4.56 (2.318, 8.97)	1.001.55 (0.60, 3.13)2.36 (1.18, 4.65)4.51 (1.74, 11.67)	0.0860.025<0.001
Educational status No formal education Primary Secondary College & above	81315460	102375235	2.16 (1.30, 3.60)2.04 (1.08, 3.85)1.65 (0.94, 2.90)1.00	0.52 (0.17,1.56)0.66 (0.21, 2.05)1.10 (0.41, 2.93)1.00	0.2410.4700.852
Occupation Governmental Non-governmental Merchant Farmer House wife Others	381467473624	201065694517	1.001.36 (0.51, 3.60)1.84 (0.97, 3.50)2.79 (1.46, 5.38)2.38 (1.18, 4.77)1.35 (0.59, 3.07)	1.001.30 (0.36, 4.80)1.46 (0.47, 4.59)0.52 (0.13, 2.12)0.74 (0.19, 2.94)1.82 (0.45, 7.30)	0.6850.5130.3670.6660.400
Monthly income (US$) ≤ 19 20–33 34–50 > 50	60463981	81553852	2.10 (1.30, 3.40)1.87 (1.10, 3.14)1.52 (0.86, 2.67)1.00	2.29 (0.86, 5.90)1.30 (0.50, 3.39)1.13 (0.491, 2.60)1.00	0.1060.5910.774
Distance in Km ≤3 km 4–24 km 25–53 > 53	86743531	32348179	1.001.23 (0.69, 2.19)6.22 (3.52, 10.96)6.85 (3.83, 12.24)	1.001.06 (0.52, 2.18)4.50 (2.15, 9.40)6.02 (2.76, 13.14)	0.871<0.001<0.001
Regular eye checkup Yes No	56170	15211	1.004.63 (2.53,8.48)	1.002.35 (1.09, 5.47)	0.044
Diabetes mellitus Yes No	59167	15211	0.20 (0.11, 0.37)1.00	0.16 (0.68, 0.38)1.00	<0.001
Ocular injury Yes No	18208	8218	0.42 (0.18, 0.99)1.00	0.45 (0.15, 1.32)1.00	0.146
Knowledge about glaucoma Poor Good	67159	15769	5.40 (3.61, 8.07)1.00	4.46 (2.62, 7.58)1.00	<0.001
Pseudo-exfoliation No Yes	18541	13294	1.003.21 (2.10, 4.93)	1.000.36 (0.12, 1.07)	0.066
IOP <21.00 21.00–25.00 25.01–30.00 >30.00	70625737	33415993	1.001.40 (0.80, 2.48)2.19 (1.26, 3.81)5.33 (3.04, 9.36)	1.001.33 (0.77, 3.86)2.17 (1.23, 5.09)4.49 (2.10, 9.12)	0.1110.011<0.001
Type of glaucoma POAG CACG PxG Others	139324114	11616877	1.000.60 (0.31, 1.15)2.54 (1.63, 3.97)0.60 (0.23, 1.53)	1.000.50 (0.21, 1.18)0.71 (0.23, 2.14)0.65 (0.21, 1.97)	0.1130.5430.440

COR = Crudes Odds Ratio, AOR = Adjusted Odds Ratio, CI = Confidence Interval, Bolded figures = statistically significant, POAG = Primary Open Angle Glaucoma, CACG = Chronic Angle ClosureGglaucoma, PxG = Pseudo-exfoliative Glaucoma.

Discussion

This study attempts to elucidate determinants for late presentation of glaucoma among glaucomatous patients.

In this study, age was an independent factor for the late presentation of glaucoma. A strong positive relationship between increasing age and risk of the late presentation was seen. By which those > 60 years of age were 4.51 times more likely to present late. Similar results were reported from different studies [17,19,20-21,25,26]. This might be because the prevalence and incidence of glaucoma increase with age [4] and it might also be explained by the low healthcare-seeking behavior of elderly individuals [27].

This study also revealed high IOP at presentation as a determinant for late presentation of glaucoma. By which those who presented with IOP between 25.01–30.00 mmHg and >30.00 mmHg became 2.17 times and 4.49 times more likely to present late respectively than those who presented with IOP ≤ 21.00mmHg. The result is in line with other studies which showed higher IOPs result in more rapid visual field damage and increased risk of late presentation [16,18,19]. This might be due to the evidence that higher IOPs lead to more rapid visual field loss [28].

The distance of residency from the hospital was also found to be significantly associated with the late presentation of patients. This might be due to the reason that the geographic proximity of the health care center has a substantial impact on the health-seeking behavior of patients [29].

Another significant association with the late presentation of glaucoma in this study was poor knowledge about glaucoma. Those individuals with poor knowledge about the disease were late presenters compared to those with good knowledge about the disease. Similar findings were also reported from other studies [21,26]. This could be due to the reason that having good knowledge about glaucoma as a blinding and irreversible disease influences the eye care service-seeking behavior of people and their uptake of services [30]. However, a study done in South Africa [18] revealed no significant association between knowledge of glaucoma and late presentation. In the South African study, knowledge of glaucoma as a blinding disease was assessed using only a single question, which is not standardized. While the present study used seventeen standard questions which were relatively more detailed to assess every dimension of patients’ knowledge on glaucoma, which might explain the discrepancy. Moreover, the smaller sample size (66 cases and 66 controls) recruited in the South African study might mask the association.

This study sought a significant association between regular eye check-ups and late presentation of glaucoma. This is comparable with another study done in the United Kingdom and Iran [16,17]. This might be since those who attend regular eye check-ups are more likely to seek medical attention earlier in their eye disease. These results lend weight to the concept that those who did not regularly check their sight tests are at greater risk of late presentation.

The present study also revealed that patients who had a history of diabetes mellitus are less likely to present late compared to those who didn’t have diabetes mellitus. The result is comparable with a study done in South Africa [18]. This might be due to the reason that; diabetic patients are more likely to have regular medical and ocular examinations for diabetic retinopathy screening and follow-up, hence the opportunity to spot glaucoma at an earlier stage. This can be supported by the evidence of opportunistic detection of glaucomatous optic discs within a diabetic retinopathy screening [31].

This study might have inherited limitation of recall bias due to the study design. When knowledge of participants on glaucoma was assessed, it was their current knowledge that was assessed, and this might have an impact on the participant’s knowledge report. The history of diabetes mellitus was self-reported by the study participants.

Conclusion

Increasing age and high IOP have substantial positive association with late presentation of glaucoma. Moreover, having poor knowledge about glaucoma, absence of regular eye check-up and being resided at far distance were positively associated with late presentation. Nevertheless, having history of diabetes mellitus was associated negatively with late presentation of glaucoma.

Questionnaire in English Language.

(PDF)

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Questionnaire in Amharic language.

(PDF)

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Sample data for determinants and late presentation of glaucoma.

(XLSX)

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17 Nov 2021

2 Feb 2022

Authors’ response for the Editorials and reviewers’ comment

Manuscript number: PONE-D-21-27844

Manuscript title: Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital: Case-control study

Responses to the Editorials

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• We accepted the comment,

• We checked and corrected based on the journal requirements point-by-point.

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• We accepted the comment,

• All files were uploaded based on the requirement accordingly.

• All of the authors are participated and reviewed the manuscript for the language usage, spelling, and grammar.

• Specially, the authors listed below (The higher institutional employs who had “English language proficiency”) reviewed the manuscript in-depth.

• Mr. Natnael Lakachew Assefa (Assistant Professor of Optometry): Reviewed the document, responded the editors and reviewers comment, checked the language usage, spelling error, and grammar correction.

• Mr. Abel Sinshaw Assem (Lecturer of Clinical Optometry): Reviewed the manuscript, checked the language usage, spelling error, and grammar correction.

3. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information

Authors’ Response: Thank you for your information!

• We accepted the comment and submitted the data collection tool (Questionnaire) as supporting Information.

• “S1 Questionnaire in English Language” and “S2 Questionnaire in Amharic (Local Language)”.

4. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified whether consent was written or verbal/oral. If consent was verbal/oral, please specify: 1) whether the ethics committee approved the verbal/oral consent procedure, 2) why written consent could not be obtained, and 3) how verbal/oral consent was recorded. If your study included minors, please state whether you obtained consent from parents or guardians in these cases. If the need for consent was waived by the ethics committee, please include this information

Authors’ Response: Thank you for your comment!

• We accepted the comment and described in detail

• “Ethical requirement: Page 9, line 2-10” and “Consent form: S1, Page 1”

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• We accepted the comment and authorization accessed with this link https://orcid.org/0000-0002-4998-6128

6. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. Authors’ Response: Thank you for your comment!

• We accepted the comment and uploaded sample data with this submission as a supporting Information: “S3- Sample data”

Responses to the Reviewer #1

1. The results section of the abstract is not precise and they needs to be refocused.

Authors’ Response: Thank you for your comment!

• We accepted the comment and revised the abstract section including the result section.

• “Abstract result section: Page 2, line 13-17”

2. The glaucoma diagnosis criteria should be clearly stated to provide context for the glaucoma diagnosis to provide a basis for comparison with other studies.

Authors’ Response: Thank you for your comment!

• We accepted the comment and corrected.

• “Methods section: page 6, line 18-20”: “Late glaucoma diagnosis: Glaucomatous disc cupping of CDR > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes.”

3. The classification of age is arbitrary i.e 18-40 then 41-50. Please use standard age classification such as 18-35 youth, 36-59 adult, 60 and older.

Authors’ Response: Thank you for your comment!

• Age classification was done by SPSS software analysis based on the participant’s age range with interquartile method.

• The study participants included in our study were aged ≥ 18 years.

• Due to study subjects age variation and limited studies with same population characteristics in the study area, we classified based on statistics.

• If we used the suggested classification, most of the subjects would be in the same age group and difficult for analysis.

4. Was only eye involved in the analysis where the glaucoma was bilateral? was there a correlation between the 2 eyes? if so then stick the use of one eye in the analysis.

Authors’ Response: Thank you for your comment!

• All patients who fulfill the Late glaucoma diagnosis criteria of CDR > 0.8 and MD > -14 decibel in either eye (Either both eyes or one eye) were included in the analysis.

• “Described in Methods section: page 6, line 11-17”:

• Cases (Late presenters): Any chronic glaucoma patients diagnosed with cup to disc ratio (CDR) > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes at their first presentation [16, 18].

• Controls: Chronic glaucoma patients diagnosed with cup to disc ratio (CDR) < 0.8 and typical glaucomatous field loss with a mean deviation of < -14 decibel in both of the eyes at their first presentation [16, 18].

5. How was Normal Tension Glaucoma diagnosed? Please explicitly outline

Authors’ Response: Thank you for your comment!

• Since the diagnosis of all chronic glaucoma types were done by CDR and MD, Normal Tension Glaucoma was diagnosed with same criteria.

• “Described in Methods section: page 6, line 18-20”: “Late glaucoma diagnosis: Glaucomatous disc cupping of CDR > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes.”

6. The table headings are to laborious. Authors should relook at them:

Authors’ Response: Thank you for your comment!

• We accepted the comment and revised table headings:

• “Result section: page 10, line 7-8; page 12, line 9-10; page 15, line 4-5”

Responses to the Reviewer #2

Major comments:

1. The experimental design is not rigorous and solid enough, also the results are not strong enough to support conclusion

Authors’ Response: Thank you for your comment!

• We accepted the comment and we appreciated your suggestion:

• But the study design employed was cross-sectional not experimental: “Methods section: page 5, line 3”.

• This study might have an inheritance limitation of the cross-sectional study design for the conclusion of cause and effects due to this we included this as a limitation of our study at the end of the discussion section: “Discussion section: page 20, line 5-8”.

2. Page 6. Methods: the definition of late presentation of glaucoma and controls are not clear, please add more detailed information about the selection of cases and controls (Please reference to Fraser S, Bunce C, Wormald R, Brunner E. Deprivation and late presentation of glaucoma: case-control study. BMJ. 2001 Mar 17;322(7287):639-43. doi: 10.1136/bmj.322.7287.639. PMID: 11250847; PMCID: PMC26542; Motlagh BF, Pirbazari TJ. Risk factors for late presentation of chronic glaucoma in an Iranian population. Oman J Ophthalmol. 2016 May-Aug;9(2):97-100. doi: 10.4103/0974-620X.184527. PMID: 27433036; PMCID: PMC4932803.).

Authors’ Response: Thank you for your comment!

• We accepted the comment and revised the definitions of cases and controls based on your suggestion in the corrected manuscript operational definition section.

• “Described in Methods section: page 6, line 11-17”:

• Cases (Late presenters): Any chronic glaucoma patients diagnosed with cup to disc ratio (CDR) > 0.8, in which there is no suggestion of other optic nerve pathology and typical glaucomatous field loss with a mean deviation of greater than -14 decibel in either of the eyes at their first presentation [16, 18].

• Controls: Chronic glaucoma patients diagnosed with cup to disc ratio (CDR) < 0.8 and typical glaucomatous field loss with a mean deviation of < -14 decibel in both of the eyes at their first presentation [16, 18].

3. Page 10. Table 1. The classification of patients’ occupation is not logical enough. The standard occupational classification categorized into three groups: professional and technical occupations (I and II); manual and nonmanual skilled occupations (III and IV) and partly skilled and nonskilled occupations (V and VI). Please explain the reason about the classification in your manuscript.

Authors’ Response: Thank you for your comment!

• We classified occupations based on the study participants’ occupational statues and considering the general population occupation classification of the study setting/area.

• Those suggested classification is not familiar classification in our settings.

• The study population occupations are categorized in one of the listed occupations in our study area,

• That was the reason and used these classifications to be consistent with other studies.

Miner comments:

1. Page 3, introduction: “In 2013, the number of people aged 40 to 80 years with glaucoma was 64.3 million which was predicted to increase to 76.0 million in 2020 and 111.8 million in 2040”. Reference should be added.

Authors’ Response: Thank you for your comment!

• We accepted the comment and reference is added in the corrected manuscript.

• “Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 2014, 121(11):2081-2090.”

2. Page 3, introduction: “In Africa and South Asia, the prevalence of undiagnosed glaucoma in the population has been reported to be more than 90%”. Please modify the sentence, current one is hard to understand.

Authors’ Response: Thank you for your comment!

• We accepted the comment and rewritten the sentence clearly in the corrected manuscript.

• “Introduction section: page 3, line 7-10”: “Population-based studies in Asian countries showed a higher prevalence of glaucoma [3] and Primary Open Angle Glaucoma (POAG) is the most commonly reported [4-6]. The prevalence of previously undiagnosed glaucoma in South Africa was 87.0% [7].”

3. Page 4, introduction: More information should be added to describe the significant of this study?

Authors’ Response: Thank you for your comment!

• We accepted the comment and included more descriptive sentences for the significance of the study in the corrected manuscript.

• “Introduction section: page 4, line 1-3 and line 7-9”

4. Page 6: Methods: typo, it should be “systematic random sampling” but not “systemic random sampling”.

Authors’ Response: Thank you for your comment!

• It was systematic random sampling method and described in the corrected manuscript methods section:

• “Methods section: page 5, line 21-23 and page 6, line 1-6”: “The study participants for both cases and controls were selected among glaucomatous patients on follow-up who visited the glaucoma clinic during the data collection period using systematic random sampling. The cases were recruited from late glaucoma presenters while the controls were selected among those without late glaucoma. The projected numbers in two months follow-up for cases and controls were 495 and 540 respectively. So, Kcase = 495/246= 2.012 approximately 2 and Kcontrol = 540/246 = 2.19 approximately 2. Both controls and cases were selected by systemic random sampling with a fraction of k=2 form their medical record numbers.”

5. Page 6: Methods: Please provide more information about the questioner of knowledge-related factors in supplementary material.

Authors’ Response: Thank you for your comment!

• We accepted the comment and provided the questionnaire as supplementary document in English language and Amharic (Local language|).

• “S1 Questionnaire in English Language and S2 Questionnaire in Amharic (Local Language)”

6. Page 7: Methods: Definition about “Regular eye checkup”, dose it means eye checkup for every two years or only once in past two years? If so, it should not be defined as “regular” eye check-up but “frequency of ophthalmic examination in the last 2 years”.

Authors’ Response: Thank you for your comment!

E We accepted the comment and corrected in the revised manuscript as “Those individuals who check up their eyes every two years”.

E “Methods section: page 7, line 4-5”: “Regular eye checkup: Those individuals who check up their eyes in every two years [17, 24].”

7. Page 8: Methods: Software information (EPI Info, SPSS) should be provided, for example, the company name or website link.

Authors’ Response: Thank you for your comment!

• We accepted the comment and indicted the company name in the revised manuscript.

• “Methods section: page 8, line 9-10” :

• “EPI INFO Version 7: https://www.cdc.gov/epiinfo”

• “SPSS Version 20: https://www.ibm.com/analytics/spss-statistics-software”

8. Page 10. Results, table 1. Are there any patients under 18 years old? And please clarify the unit for monthly income?

Authors’ Response: Thank you for your comment!

• No: The study participants included in the study were adults aged equally or greater than 18 years which is described in the revised manuscript methods section.

• “Methods section: page 5, line 9-10”: All adult glaucomatous patients aged ≥, diagnosed within the last two years and on follow-up were included in the study.

• Unit monthly income was “US dollars (US$)” and corrected in the revised manuscript. “Result section: page 11, table 1 and page 16, table 2”

9. Page 15. Results, table 3. Monthly income in table 3 is not consistent with table1. Please keep it consistent in the whole manuscript.

Authors’ Response: Thank you for your comment!

• We accepted the comment and corrected in the revised manuscript.

10. Page 16. Results, table 3. Please define " POAG, CACG, PxG" in table 3 legend.

Authors’ Response: Thank you for your comment!

• We accepted the comment and corrected in the revised manuscript.

Responses to the Reviewer #3

1. A main suggestion is to interpret the results in the public health context, i.e. to discuss what can be done from a public health perspective on timely glaucoma diagnosis based the observed results. The current Conclusion basically repeats the data results after a literature review, but what is really more important (and why the study was done in the first place) is how the study results and knowledge can inform potential interventions to prevent late glaucoma diagnosis in a typic resource limited setting in Africa, e.g. community based educational campaigns, information brochure in diabetes clinics etc.

Authors’ Response: Thank you for your comment!

• We accepted the comment and suggestions:

• We added the significant of the study in the introduction section, conclusions were revised based on the objective of the study: “Introduction section: page 4, line 1-3 and line 7-9”

• We revised the introduction section (the state of knowledge, significance of the study for the population and others): “Introduction section: page 3, line 21-23 and page 4, line 1-6”.

• We revised the discussions and conclusions based on your comment and suggestions.

2. Page 3, "In Africa and South Asia, the prevalence of undiagnosed glaucoma in the population has been reported to be more than 90%", this seems unbelievably high: >90% in the population have glaucoma. Glaucoma prevalence can't be this high.

Authors’ Response: Thank you for your comment!

• We accepted the comment and revised the references and modified accordingly.

• “Introduction section: page 3, line 7-10”: “Population-based studies in Asian countries showed a higher prevalence of glaucoma [3] and Primary Open Angle Glaucoma (POAG) is the most commonly reported [4-6]. The prevalence of previously undiagnosed glaucoma in South Africa was 87.0% [7].”

3. Page 11, the middle, "The median IOP of the over study participants was 25.80 mmHg and ...". Is this reporting the IOP at diagnosis time, or the IOP at time of this study's visit?

Authors’ Response: Thank you for your comment!

• The data for IOP was taken from the patients’ medical record card at thier first diagnosis time not during the data collection time of the study.

• Described in the manuscript methods section: page 7, line 22-23 and in the uploaded supporting information S1 and S2 data collection tool.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

24 Feb 2022

1 Mar 2022

Authors’ response for the Editorials and reviewers’ comment

Manuscript number: PONE-D-21-27844

Manuscript title: Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital: Case-control study

Responses to the Editorials

1. Journal Requirements:

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.

Authors’ Response: Thank you for your comment!

• We checked each references and corrected based on the journal reference guidelines.

• We reviewed and checked the document point by point based on the comments and suggestions of the editor’s and reviewers’.

Responses to the Reviewer #1

1. Reviewer #1: The correction indicated by the reviewer have been addressed and the now the paper reads more coherently and structurally conforms to the format of the journal.

Authors’ Response: Thank you in advance for your constructive comment and sharing your profound experience throughout the manuscript revision process.

Responses to the Reviewer #4

1. Reviewer #4: This is an interesting study, although could be improved by a clearer argument for why previous literature from the area is limited and/or inappropriate, and so why this specific study is required. There are some grammatical slips throughout the manuscript, although these are minor. Specific comments are outlined, below.

Authors’ Response: Thank you in advance for your constructive comment and suggestions.

Abstract

1. two decimal places for age is probably excessive (similarly elsewhere in the manuscript)

Authors’ Response: we accepted and corrected with one decimal places in the new manuscript.

2. the abstract doesn’t give a definition of “late presenter”

Authors’ Response: we accepted and definition included in the new manuscript:

• Page 2, line 7-9: “Late presenters were glaucoma patients diagnosed with cup to disc ratio (CDR) > 0.8 and mean deviation of greater than -14 decibel in either of the eyes at their first presentation.”

3. “residing far away from the hospital” mention in the Conclusion is not listed in the results

Authors’ Response: These are resided > 53 km (the farthest km) away from the hospital which was described in:

• Abstract results section: page 2, line 15: “resided > 53 km away from the hospital 6.02 times (AOR: 6.02; 2.76, 13.14”

• Results section: page 14, line 10-13: “Participants who resided 24 – 53 km and > 53 km away from UoG TECTC had the odds of 4.50 times (AOR: 4.50; 2.15, 9.40) and 6.02 times (AOR: 6.02; 2.76, 13.14) more likely being late presenter respectively compared to those who resided <3km away from the UoG TECTC.”

Introduction

1. Pg 3, line 14: grammar

Authors’ Response: we accepted and rewritten in the new manuscript.

• Page 3, line 13-14: “Several studies estimated that 10 – 33% of people with glaucoma were visually impaired at their first diagnosis [10-12].”

2. The introduction could make a more clearly argued case for why the study is important: in particular, it cites three studies regarding what are the determinants of late presentation (including one from Africa), but then goes on to say “there is little published evidences [sic] for why some… have advanced disease at first diagnosis”.What are the gaps and/or conflicts in previous work that into this area, and how does the current study hope to address these? in particular, if the authors feel that the previous work from elsewhere in Africa is not applicable to Ethiopia, they should probably state so more explicitly: even better if they can cite supporting demographic / other evidence to support why this is the case. Some of the arguments made in the Discussion regarding weaknesses in previous studies from Africa (e.g. regarding sample size) could be mentioned explicitly in the Introduction.

Authors’ Response: we accepted and rewritten in the new manuscript.

• Page 3, line 22-23 and page 4, line 1-6: “Glaucoma was one of the leading cause of irreversible blindness in Ethiopia, thus this study has an immense importance to salvage the community from glaucoma induced blindness. Ethiopian glaucoma patients have different socio-cultural, genetic, environmental and other population related factors compared to European, Asian and other African countries. Previous published evidences done in Ethiopia doesn’t explore the determinant factors for the severity of glaucoma at the first presentation. Thus, it needs explicit in situ study to identify the determinants for late presentation of glaucoma.”

Materials and Methods

1. pg 5, Line 9: age criterion is missing

Authors’ Response: we accepted and “aged ≥ 18 years” is added in the new manuscript.

2. pg 6, line 21: questionnaire

Authors’ Response: we accepted and spelling is corrected in the new manuscript.

3. pg 7, line 15: “expertise”: experts?

Authors’ Response: we accepted and spelling is corrected as “experts” in the new manuscript.

4. pg 7, line 16: a bit more detail about the reliability check would be useful (assuming it involved retesting, how many people were retested, and what was the interval between testing?): or is this the information that is partly provided on page 8, line 1?

Authors’ Response: we accepted and corrected in the new manuscript.

• Page 7, line 16-20: “The questionnaire was pre-tested for reliability and validity in 25 glaucomatous patients in another hospital (Bahir Dar Felege Hiwot referral eye Hospital) with the same methods and the content of the questionnaire was assessed for its clarity, completeness and modified accordingly. It was also checked for its reliability using a reliability test and has a Cronbach alpha value of 0.77.”

Results

1. It is stated that a history of diabetes was significantly associated with late presentation: isn’t it the ABSENCE of a history of diabetes that is associated?

Authors’ Response: Having of history of diabetes was significantly associated, but “it is protective against late presentation” and we described it in the corrected manuscript:

• Result section: page 15, line 3-5: “On the other hand, those who had history of diabetes mellitus had 84% lesser odds of being late presenter (AOR = 0.16, 95% CI: 0.68, 0.38) compared to those who didn’t have diabetes.”

• We discussed this issues in discussion section: page 19, line 21-23 and page 20, line 1-4: “The present study also revealed that patients who had a history of diabetes mellitus are less likely to present late compared to those who didn’t have diabetes mellitus. The result is comparable with a study done in South Africa [18]. This might be due to the reason that diabetic patients are more likely to have regular medical and ocular examinations for diabetic retinopathy screening and follow-up, hence the opportunity to spot glaucoma at an earlier stage. This can be supported by the evidence of opportunistic detection of glaucomatous optic discs within a diabetic retinopathy screening [31].”

Discussion

1. pg 18, line 20: grammar (sentence fragment)

Authors’ Response: We accepted and rewritten in the new manuscript.

• Page 18, 20: we corrected and rewritten the sentences.

2. pg 18, line 23: these cited reasons are rather generic: a much better job otargetingspecific reasons is done in the following paragraph when differences between the current study, and the previous South African study, are discussed.

Authors’ Response: We accepted and edited in the new manuscript: Page 18, line 23.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

11 Mar 2022

17 Mar 2022

Authors’ response for the Editorials and reviewers’ comment

Manuscript number: PONE-D-21-27844

Manuscript title: Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital: Case-control study

Responses to the Editorials

1. Journal Requirements:

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.

Authors’ Response: Thank you for your comment!

• We checked each references and corrected based on the journal reference guidelines.

• We revised the manuscript based on the comments and suggestions of the editor’s and reviewers’.

Responses to the Reviewer #4

1. Reviewer #4: The manuscript has improved in several areas as a result of the authors’ revisions.

However, I find the revision to the Introduction disappointing; it is a superficial rewording, and hasn’t engaged with the criticisms made in my original review appended below:

“The introduction could make a more clearly argued case for why the study is important: in particular, it cites three studies regarding what are the determinants of late presentation (including one from Africa), but then goes on to say “there is little published evidences [sic] for why some… have advanced disease at first diagnosis”.

What are the gaps and/or conflicts in previous work that into this area, and how does the current study hope to address these? in particular, if the authors feel that the previous work from elsewhere in Africa is not applicable to Ethiopia, they should probably state so more explicitly: even better if they can cite supporting demographic / other evidence to support why this is the case. Some of the arguments made in the Discussion regarding weaknesses in previous studies from Africa (e.g. regarding sample size) could be mentioned explicitly in the Introduction.”

Several sentences cry out for appropriate references: “Glaucoma is one of the leading causes… [ref?]; Ethiopian patients have [various differences…] [ref?]; previous published evidences done in Ethiopia (sic).. [what evidence? references? Also, “evidence” is already plural - please correct].” At the moment, the modified paragraph is a list of unsupported assertions which weakens the paper substantially, particularly as it is this paragraph that is the one that is supposed to convince the reader there is a need for the current study.

Authors’ Response: Thank you very much for your constrictive comment and suggestions.

• We accepted your comment and revised each of the points you raised in the corrected manuscript.

• We revised the references and cited statements appropriately.

• We revised the significance of this study, the gaps of the previous studies and the justifications to conduct this research.

• We addressed the comments as follows:

• “……….for why some… have advanced disease at first diagnosis”

Corrected in page 3, line 13-16: “Several studies estimated that 10 – 33% of people with glaucoma had advanced disease and visually impaired at the first diagnosis due to their late presentation [10-12]. The reason for the late presentation was due to lack of early symptoms [13, 14], slowly progressive and asymptomatic of nature of glaucoma [15].

• “What are the gaps and/or conflicts in previous work that into this area, and how does the current study hope to address these? ..............could be mentioned explicitly in the Introduction.”

Corrected in page 4, line 2-10: “Previous published evidences in Ethiopia didn’t have enough information to explore the determinant factors for the late presentation of glaucoma. Most of these studies were done to assess and the prevalence of blindness due to glaucoma [8, 9] and the associated factors of glaucoma [24]. Because of this, it needs explicit in situ study to identify the determinants for late presentation of glaucoma. In addition, the result of this study will provide base line information for the health care workers, researchers, health care planers, policy makers and other stakeholders accordingly.”

• “Several sentences cry out for appropriate references”

Corrected and cited appropriately, page 4, line 1 and 5: …..Glaucoma was one of the leading cause of irreversible blindness in Ethiopia [8]……... Most of these studies were done to assess and the prevalence of blindness due to glaucoma [8, 9] and the associated factors of glaucoma [24].

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

12 Apr 2022

Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital. Case-control study

PONE-D-21-27844R3

Dear Dr. Assefa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication, pending for some grammatical errors, 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,

David Chau

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

there are still grammatical errors need correction

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #2: (No Response)

Reviewer #4: All comments have been addressed

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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 #2: (No Response)

Reviewer #4: Yes

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Reviewer #2: (No Response)

Reviewer #4: Yes

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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 #2: (No Response)

Reviewer #4: Yes

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Reviewer #2: (No Response)

Reviewer #4: Yes

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Please 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 #2: (No Response)

Reviewer #4: (No Response)

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Reviewer #2: Yes: Bing Jiang

Reviewer #4: No

22 Apr 2022

PONE-D-21-27844R3

Determinants for late presentation of glaucoma among adult glaucomatous patients in University of Gondar Comprehensive Specialized Hospital. Case-control study

Dear Dr. Assefa:

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.

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on behalf of

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