Evaluation of Serum Myelin Basic Protein in POAG Patients at a Tertiary Institution in Lagos, Nigeria

Evaluation of Serum Myelin Basic Protein in POAG Patients at a Tertiary Institution in Lagos, Nigeria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of Serum Myelin Basic Protein in POAG Patients at a Tertiary Institution in Lagos, Nigeria Judith Ogechi Anikwenwa, Adetunji Olusesan Adenekan, Adegboyega Sunday Alabi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8264197/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose Glaucoma, a neurodegenerative disorder, causes retinal ganglion cell damage and loss of neurons in the visual system up to the visual cortex. The loss of myelin sheath leads to the release of myelin sheath components, including the myelin basic protein (MBP), into the bloodstream. While MBP has shown promise as a biomarker for glaucoma in some Asian populations, data among individuals of African descent remain limited. This study evaluated the serum levels of MBP in primary open-angle glaucoma (POAG) patients compared to non-glaucoma controls, with the aim of reporting its usefulness as a biomarker for glaucoma detection in an African population. Methods This cross-sectional study compared serum MBP levels in treatment-naive primary open-angle glaucoma (POAG) patients and non-glaucoma controls. Blood samples were collected from 83 treatment-naive POAG participants and 83 age and sex matched non-glaucoma participants and analyzed using enzyme-linked immunosorbent assay (ELISA). Results The mean age of POAG participants was 50.78 ± 17.3 years, with a male predilection. The mean intraocular pressure (IOP) was significantly higher in POAG patients (18.22 ± 6.8 mmHg) than in controls (13.89 ± 2.5 mmHg). Serum MBP levels were significantly elevated in POAG patients (1128.75 ng/L) compared to controls (963.75 ng/L; p < 0.001). There was no significant correlation between MBP levels and disease severity. MBP levels were higher in high-tension glaucoma and females; however, the difference was not statistically significant. Conclusion Findings supported the neurodegenerative state of POAG and the use of serum MBP levels as a potential biomarker for early POAG detection. Glaucoma POAG Neurodegenerative disease Myelin Basic Protein ELISA Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Glaucoma is a multifactorial progressive neurodegenerative disorder with characteristic acquired death of the retinal ganglion cells and loss of their axons, as well as the deformation of the optic nerve, leading to the loss of neurons in the lateral geniculate nucleus and the visual cortex, with corresponding visual field defects, having intraocular pressure as the only modifiable risk factor [ 1 ] The severity of glaucoma can be defined functionally, via the Hodapp, Parish and Anderson method, into mild, moderate and advanced glaucoma. However, there is a newer severity grading system, the disc damage likelihood scale (DDLS) score, which is based on the circumferential extent of the absent rim [ 2 , 3 ] The neuro-inflammation in glaucoma is akin to those found in other neurodegenerative and demyelinating diseases, like Alzheimer’s disease, Parkinson’s disease, and Multiple sclerosis, where myelin loss precedes axonal loss, so that myelin basic protein (MBP) diffuses into the bloodstream from the cerebrospinal fluid (CSF) and can be detected in the serum. [ 4 ] The optic nerve, which is myelinated by oligodendrocytes posterior to the lamina cribosa, is destroyed from the inflammatory cascade, including stimulation of matrix metalloproteinases, interleukin 6, tumor necrosis factor (TNF), and complement factors that are released through the different pathways responsible for the pathogenesis of glaucoma. The destruction of the retrolaminar myelin sheaths leads to the release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF). [ 5 , 6 , 7 ] Myelin basic protein (MBP), the second most common protein in the myelin sheath, can cause the disruption of the blood-brain barrier (BBB), by inciting inflammation and reducing the integrity of the tight junctions, which in turn lead to increase permeability and leakage into the CSF and the bloodstream. [ 8 , 9 , 10 ] Since the invention of the Catalyst for Cure for glaucoma, different biomarkers for the detection of glaucoma have been discovered. One of these is serum MBP, which has been studied amongst Koreans and has been discovered to be a good biomarker for the detection of glaucoma, however, there is paucity of study of this serum MBP in the black race. [ 11 , 12 ] This study aimed to further establish that glaucoma is a neurodegenerative disease and also investigate the possibility of having serum MBP as a biomarker for primary open angle-glaucoma (POAG) in Nigerian patients, thereby addressing the gap in biomarker research among African populations. Methods This cross-sectional study compared serum MBP levels in treatment naïve primary open- angle glaucoma (POAG) patients and non-glaucoma controls at the Lagos University Teaching Hospital, Lagos, Nigeria, and was conducted from October 2023 to February 2024. This comparative study enrolled 83 newly diagnosed, treatment-naïve POAG patients and 83 age- and sex-matched non-glaucoma controls aged 18 years and above. Eligibility criteria included adults ≥ 18 years who provided written informed consent. Exclusion criteria included glaucoma patients already on medications/who have had glaucoma surgery, secondary glaucoma, narrow angles or angle-closure, signs or symptoms suggestive of neurodegenerative diseases, other causes of optic neuropathy or retinal degenerative diseases. Ocular examinations, including visual acuity, anterior and posterior segment examination using slit lamp, ultrasound pachymetry, gonioscopy, and perimetry were performed on all participants. Primary Open Angle Glaucoma was defined as glaucomatous optic neuropathy as evidenced by vertical cup-disc ratio of ≥ 0.5, optic disc notching, neuroretinal rim thinning, increased disc damage likelihood scale (DDLS) score usually of 5 or higher barring of circumlinear vessels, lamina dot sign, and corresponding visual field defects on perimetry +/- elevated intraocular pressure (> 21mmHg), in an eye without gonioscopic evidence of angle closure and without an identifiable secondary cause. Minimum criteria for diagnosis of glaucoma using the visual field include a Glaucoma Hemifield Test outside normal limits on at least two fields or a cluster of three or more non-edge points in a location typical for glaucoma all of which are depressed on a pattern deviation plot at a p < 5% level and one of which is depressed at a p < 1% level on two consecutive fields or corrected pattern standard deviation that occurs in < 5% of normal fields on two consecutive fields.[ 2 ] The severity of glaucoma was done using to Hodapp, Anderson and Parish classification [ 2 ]. Blood samples were withdrawn from cubital vein into BD vacutainer® EDTA tubes and analyzed for serum MBP levels using enzyme-linked immunosorbent assay kits (Eastbiopharm human myelin basic protein enzyme-linked immunosorbent assay kits: Reference number: CK-E11682, Hangzhou, China) according to the protocol for the kit. Data were statistically analyzed using SPSS) version 26.0 (IBM Corp: Armonk, NY). Categorical data was presented as proportion and percentages. Continuous data were presented with mean and standard deviation when normally distributed while median and interquartile range were used for the skewed data. Test for normal distribution assumption was done using Kolmogorov-Smirnov test. Test for significant association between the two groups (POAG and non-glaucoma group) and other categorical variables was carried out using Pearson’s Chi-square and Fischer exact test. Difference in or median values of the serum levels of myelin basic protein of the two groups was assessed using or Man-Whitney U respectively. Independent student t-test was used to compare ocular characteristics between the two groups. Kruskal Wallis was used to compare median of serum levels of MBP according to glaucoma severity and other categorical variables with more than two groups. Linear relationship between MBP and other numeric variables was assessed using Spearman correlation. Receiver operating characteristic (ROC) curve analysis was done in order to evaluate the diagnostic ability of MBP to discriminate between the POAG group and non-glaucoma groups. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. The area under the curve (AUC) was used to assess the discriminating ability accuracy. The optimal cut-point value was determined using the Youden index (J) which is calculated as: Maximum sensitivity + specificity – 1 Significant level was set at p-value of < 0.05. Box plot were used for data presentation where necessary. Results The socio-demographic data showed the age group with the highest percentage of newly diagnosed POAG was between the ages 40–59 where there were 36 participants, 18 participants in the age group 40–49 and 50–59 each, so that almost half (43.4%) of the POAG participants are within the age range of 40–59 years, with the mean age being 50.78 ± 17.3 years. There were more males with POAG than females, where 32 participants (38.6%) were female and 51 (61.4%) were males so that the female: male ratio was 1:1.6. (Table 1) The overall mean IOP for the POAG group was slightly higher than that of the non-glaucoma group though both were within the normal range of between 10-21mmHg (18.22 ± 6.8mmHg and 13.89 ± 2.5mmHg respectively). The POAG group had thinner corneas as the mean central corneal thickness (CCT) of participants in this group was 519.5 ± 39.6µm while that of the non-glaucoma group was 527.66 ± 26.5µm (Table II). It was noticed that thin corneas (CCT < 520µm) were more in the POAG group where 39 out of the 83 participants (47.0%) had CCT < 520µm compared to the non-glaucoma group where 29 participants (34.9%) had CCT < 520µm. The average vertical cup-to-disc ratio (VCDR) seen in the POAG group was 0.75 ± 0.1 while that of the non-glaucoma group was 0.33 ± 0.1 (Table II). The BCVA (with pinhole or spectacle correction) was noticed to be better (≥ 6/18) in the non-glaucoma participants than the POAG participants in both eyes; right- 82(98.8%) vs 65(78.3%) and left eye- 83(100.0%) vs 67(80.7%) with p-value < 0.001. There was more visual impairment (< 6/18) recorded in the POAG group than the non-glaucoma group; right- 18(21.7%) vs 1(1.2%) and left- 16(19.3%) vs 0(0.0%) The serum MBP range in the POAG group was 513.75ng/L to 3518.00ng/L while in the non-glaucoma group it was 83.75ng/L to 2046.00. The median serum MBP level for the POAG group was 1128.75ng/L (966.3–1377.0) while that of the non-glaucoma group was 963.75ng/L (657.5-1271.1), giving a p-value of < 0.001, Mann-Whitney U test of 4.016 and Confidence interval (CI) as 165 (103.1-491.56) (Fig. 1, Fig. 2 and Table III). In this study, it was found that the age group of the POAG participants with the highest levels of serum MBP was the 30–39 years group, having a median value of 1434.0ng/L and the lowest was seen in age group ≥ 70years, having value of 1031.0ng/L (p-value 0.727). Males had slightly lower serum MBP compared to females (1116.25ng/L and 1210.0ng/L, respectively) with a p-value of 0.727. Those with a family history of glaucoma had a median serum MBP level of 1202ng/L while those with no known family history of glaucoma had 1127.88ng/L (p-value 0.733) (Table IV). Using the HAP classification system, the level for the mild group was 1072.19ng/L, moderate was 1224.69ng/L while the advanced was 1130.00ng/L and p-value 0.314. Using the DDLS, the median serum level for MBP in the early stage was 1135.63ng/L, moderate was 1127.00ng/L and advanced was 1176.50ng/L (Table V, Fig. 3). Evaluation of the serum MBP levels for discrimination between NTG and HTG was done (Fig. 4). It showed a slightly higher level in the HTG compared to the NTG (median 1209.69ng/L vs 1073.75ng/L, p = 0.448, CI = 135.94); however, the difference was statistically insignificant. The sensitivity and specificity of the serum MBP level in discriminating between POAG and non-glaucoma participants at optimal cut-off point of 801.88ng/L were 92% and 40% respectively. The area under curve (AUC) was 0.681 (0.600-0.761). The positive predictive value (PPV) was 82.8% while the negative predictive value (NPV) was 61.4%. (Table VI) Discussion In this study, the mean age at presentation was 50.78(SD = 17.3) years with higher percentage of participants within the age group of 40–59 years. This is similar to findings by Adekoya et al where 79.8% of POAG patients were > 40 years of age and another study by Olawoye et al which showed there was a higher percentage among the age group 60–69 followed by 50–59 years. [ 13 , 14 ] In a sub-Saharan study, conducted by the African Glaucoma Consortium, the overall mean age at presentation was 58.9(SD = 17.1) years, with participants from West African countries being the youngest at diagnosis, with mean age of 55.8(SD = 16.4) years. The reason for the higher mean age in this study, in comparison to ours, may be the difference in patients’ inclusion criteria. [ 15 ] Our study, like the sub-Saharan study where 58.9% of the participants were males, reported more male participants and is similar to the findings in the study by Olawoye. [ 14 ] The result is also consistent with a systematic review and meta-analysis of glaucoma prevalence and projection globally, which found that males are more likely to suffer from glaucoma than females. [ 16 ] Our study showed that participants with POAG had a higher known family history of glaucoma in at least one relative (23 participants; 27.7%) than the non-glaucoma group (14 participants; 16.9%). This is close to what was reported by Adekoya et al and in the sub-Saharan study where a positive family history of 26.4% and 21.6%, respectively, were recorded. [ 13 ] The best corrected visual acuity (BCVA) was better in the non-glaucoma group, as a higher percentage of the POAG had visual impairment (VA < 6/18) compared to the non-glaucoma group. Overall however, more participants in the POAG group (78.3% right eye; 80.7% left eye) had normal VA (≥ 6/18) than visual impairment (< 6/18). This is close to what was found in a study by Adegbehinde et al in South-west Nigeria where 80.5% of the POAG participants had BCVA of ≥ 6/18 in better eye.[ 17 ] The mean corrected IOP gotten in both groups was significantly different as the POAG group had a mean IOP of 18.22 ± 6.8mmHg while the non-glaucoma group was 13.89 ± 2.5mmHg. This is similar to the study by Adegbeingbe et al that found their POAG group to have a mean IOP of 18.3 ± 9.0mmHg while the non-glaucoma group had a mean IOP of 13.1 ± 2.8mmHg.Based on the corrected IOP of the POAG participants in this study, majority had normal tension glaucoma (≤ 21mmHg) in 47 participants (56.6%) while less than half of the participants had high tension glaucoma (≥ 22mmHg) in 36 participants (43.4%). A study by Siesky showed that POAG patients of African descent have significantly lower retrobulbar blood flow and ocular perfusion hence more vascular dysregulation when compared to POAG patients of European decent. [ 18 ] It is possible that this has contributed to why there were more of NTG participants than HTG in this study as vascular dysregulation has been linked mostly to NTG. [ 19 ] This may also explain why in the Nigerian National Blindness and Visual Impairment Survey (NNBVIS) 56% of the POAG patients in Nigeria had NTG. [ 20 ] The serum MBP level in participants with POAG in this study was higher than the non-glaucoma group and the difference was statistically significant. Higher levels of serum MBP in POAG participants compared to the non-glaucoma group was also noted in the landmark study done amongst Koreans by Shin et al. [ 12 ] The values however were substantially different in both races as the POAG group in Korea had average serum MBP levels of 318.12 ± 146.91ng/L and non-glaucoma group 61.91 ± 100.02ng/L while this study found that the value for POAG was 1128.75ng/L and non-glaucoma 963.75ng/L. There are various possible reasons for the disparity in the values gotten from the Koreans and Nigerians. Difference in race could be a major factor, as a study by Langer-Gould et al showed that blacks have more demyelination process in neurodegenerative diseases.[ 21 ] It has been postulated that it could be due to the reduced Vitamin D levels in blacks as a result of the dark skin which hinders the cutaneous penetration of ultraviolet-B radiation needed for the biosynthesis of Vitamin D. Vitamin D plays a role in axon growth as well as myelination hence a relative deficiency of it would predispose to some instability and loss of myelin leading to increased level of its breakdown materials in the bloodstream. [ 22 ] This could explain why both the POAG group and the non-glaucoma group in this study have higher values of serum MBP compared to those gotten from the Asian study. It is worthy of note that the study done in Korea only enrolled 38 participants, where 21 of them were POAG ages 37-61years and 17 were non-glaucoma participants aged 25–57 years as against our larger number of 83 participants aged 18–88 years of age in each group. This could be responsible for the lower values in Korea as our study had a wider range in terms of number of participants as well as the age group. Another important factor to consider is the fact that the Korean study used convenient sampling method to select participants which may have shifted the study outcome whereas this current study randomized the participants recruited in the POAG group thereby preventing any form of bias. The disparity in the serum MBP kits in both studies could possibly also contribute to the marked difference in the values. The Koreans used human MBP ELISA kit (E-EL-H0161, Elabscience) with an assay range of 15.63-1000ng/L while in this study human MBP ELISA kit (CK-E11682, Eastbiopharm) with an assay range of 50-6000ng/L. [ 12 ] In this study, there was no correlation between serum MBP levels and clinical severity of POAG and this is similar to the findings in the Korean study. This is possibly due to the fact that serum MBP has been observed to remain high for only two weeks after demyelination or brain injury hence there is a steady clearance of this protein from the CSF and blood and no buildup of the MBP in the serum over time but rather a constant clearing of the MBP from the serum so that there is no significant difference between the mild, moderate and advanced glaucoma eventually. [ 9 ] To ascertain whether serum levels of MBP can be utilized to as a diagnostic test for POAG, the receiver operating characteristic (ROC) curve was used. The sensitivity and specificity at optimal cut-off point of 801.88ng/L were 92% and 40% respectively with an area under curve (AUC) of 0.681 and this was low in comparison to another study by Shin et al that had an excellent diagnostic ability with an AUC of 0.924. [ 12 ] The positive predictive value (PPV) was 82.8%, and the negative predictive value (NPV) was low (61.4%), meaning 82.8% of participants with serum MBP levels above 801.88ng/L actually had POAG. In comparison, 61.4% of participants with serum MBP levels below 801.88ng/L did not have POAG and a serum MBP below the cut-off value does not rule out POAG entirely. This would mean serum MBP cannot be used as a stand-alone test for diagnosis of POAG however it could possibly be used as a complementary tool for detection when done alongside other tests for glaucoma and could be used for monitoring of progression or response to treatment when done serially. The study’s limitations include the comparison of small sample sizes of POAG and non-POAG participants. A larger-scale survey could give a more comprehensive analysis of the diagnostic and prognostic properties of serum MBP as a biomarker in POAG. Although this study attempted to minimize confounders by excluding participants with other conditions that influence MBP levels, residual confounders may still affect MBP levels. An example is the considerable number of non-glaucoma participants who had a family history of glaucoma, hence this could be a confounder. The paucity of similar studies in journals limited the ability to compare this research's findings with those of many others. Conclusion Elevated serum MBP levels in POAG patients indicate neurodegeneration in POAG and may potentially serve as a biomarker for early glaucoma detection. Further longitudinal and larger studies are needed to validate these findings and integrate MBP with other biomarkers to enhance diagnostic accuracy. The serum MBP test could also be helpful in monitoring patients on treatment to detect a reduction in neurodegeneration or progression after treatment initiation. Declarations Competing Interests The authors declare that they do not have any conflict of interest. The authors had no financial obligation to any of the products or equipment used in this study. Ethical approval Study approval (ADM/DSCST/HREC/APP/5705) was obtained from the Health Research Ethics Committee of the Lagos University Teaching Hospital, LUTH, Lagos, Nigeria. The study adhered strictly to the tenets of the Declaration of Helsinki. Consent to participate Written informed consent was obtained from all participants after a detailed explanation of the study. Previous presentation This paper is part of a dissertation submitted to the National Postgraduate Medical College of Nigeria in partial fulfillment of the requirements for the award of Fellowship of the Medical College (Ophthalmology), November 2024. It was delivered as a poster presentation at the Association of Nigerian Physicians in America (ANPA) Conference, April 10th, 2025, in Lagos, Nigeria Funding The authors declare that no funds, grants, or other support were received during the preparation of the study or manuscript. Author Contribution All authors contributed to the conception and design of the study. Material preparation, data collection, and analysis were performed by Judith Ogechi Anikwenwa and Oladapo Rotimi. The manuscript draft was written by Judith Ogechi Anikwenwa, Adetunji Olusesan Adenekan and Sunday Adegeboyega Alabi. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Data Availability The authors intend to grant access to the datasets used and/or analysed in the study upon reasonable request from the corresponding author References Shahsuvaryan LM. Glaucomatous optic neuropathy management: the role of neuroprotective agents. Med hypothesis, Discov Innov Ophthalmol. 2013;2:41–46. Susanna Jr. R, Vessani RM. Staging glaucoma patient: why and how? Open Ophthalmol J. 2009;3:59–64. Spaeth GL. The disc damage likelihood scale. Glaucoma Today. 2005;1:19–21. You Y, Joseph C, Wang C, et al. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease. Brain. 2019;142:426–442. Freddi TA, Ottaiano AC. The optic nerve: anatomy and pathology.In: Gayer G, 1st ed Seminars in Ultrasound, CT and MRI. Philadelphia: Elsiever; 2022.378–388. James CT, 1st ed.Ocular disease mechanisms and management. Philadelphia: Elsevier; 2010. 180–183. Soto I, Howell GR. The complex role of neuroinflammation in glaucoma. 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Vascular and Autonomic Dysregulation in Primary Open-Angle Glaucoma. Curr Opin Ophthalmol. 2016;27:94–101. Kyari F, Entekume G, Rabiu M, et al. A population-based survey of the prevalence and types of glaucoma in Nigeria: Results from the Nigeria National Blindness and Visual Impairment Survey. BMC Ophthalmol. 2015;15:1–15. Langer-Gould A, Brara SM, Beaber BE, et al. Incidence of multiple sclerosis in multiple racial and ethnic groups. Neurology. 2013;80:1734–1739. Rodney C, Rodney S, Millis RM. Vitamin D and demyelinating diseases: Neuromyelitis optica (NMO) and multiple sclerosis (MS). Autoimmune Dis. 2020;2020:1–9. Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 22 Jan, 2026 Reviews received at journal 19 Dec, 2025 Reviews received at journal 16 Dec, 2025 Reviewers agreed at journal 12 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviewers invited by journal 10 Dec, 2025 Editor assigned by journal 03 Dec, 2025 Submission checks completed at journal 03 Dec, 2025 First submitted to journal 02 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":93600,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMedian serum myelin basic protein levels among POAG participants\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/9308c54689703d860e621c28.jpeg"},{"id":98376168,"identity":"51322c1e-34e1-4bff-9728-ab016d94114d","added_by":"auto","created_at":"2025-12-17 07:04:39","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":98421,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMedian serum myelin basic protein levels among non-glaucoma participants\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/d2ff90777bbf6300611a343a.jpeg"},{"id":98376167,"identity":"cf3023ec-369e-4650-a617-dc43c4cf7052","added_by":"auto","created_at":"2025-12-17 07:04:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15234,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMedian comparison of serum myelin basic protein according to the severity of glaucoma using the HAP classification\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/94ac503d88d0dd16dc67b316.png"},{"id":98376169,"identity":"386f1def-48fa-4df5-8b80-54184f607aaf","added_by":"auto","created_at":"2025-12-17 07:04:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":12309,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMedian comparison of serum myelin basic protein according to types of glaucoma\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/602c52f12f2c817437466e12.png"},{"id":98445767,"identity":"af788651-f38e-4aa4-8f85-177706b25529","added_by":"auto","created_at":"2025-12-17 17:21:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":820081,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/b6651a03-5d0c-49b0-9d14-14348a0a6367.pdf"},{"id":98376166,"identity":"771a4dce-6fbf-4537-a8c1-1107c5cdaea0","added_by":"auto","created_at":"2025-12-17 07:04:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25187,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8264197/v1/80d688bbe68f6d442c4e60d5.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of Serum Myelin Basic Protein in POAG Patients at a Tertiary Institution in Lagos, Nigeria","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlaucoma is a multifactorial progressive neurodegenerative disorder with characteristic acquired death of the retinal ganglion cells and loss of their axons, as well as the deformation of the optic nerve, leading to the loss of neurons in the lateral geniculate nucleus and the visual cortex, with corresponding visual field defects, having intraocular pressure as the only modifiable risk factor [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The severity of glaucoma can be defined functionally, via the Hodapp, Parish and Anderson method, into mild, moderate and advanced glaucoma. However, there is a newer severity grading system, the disc damage likelihood scale (DDLS) score, which is based on the circumferential extent of the absent rim [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe neuro-inflammation in glaucoma is akin to those found in other neurodegenerative and demyelinating diseases, like Alzheimer\u0026rsquo;s disease, Parkinson\u0026rsquo;s disease, and Multiple sclerosis, where myelin loss precedes axonal loss, so that myelin basic protein (MBP) diffuses into the bloodstream from the cerebrospinal fluid (CSF) and can be detected in the serum. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe optic nerve, which is myelinated by oligodendrocytes posterior to the lamina cribosa, is destroyed from the inflammatory cascade, including stimulation of matrix metalloproteinases, interleukin 6, tumor necrosis factor (TNF), and complement factors that are released through the different pathways responsible for the pathogenesis of glaucoma. The destruction of the retrolaminar myelin sheaths leads to the release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF). [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMyelin basic protein (MBP), the second most common protein in the myelin sheath, can cause the disruption of the blood-brain barrier (BBB), by inciting inflammation and reducing the integrity of the tight junctions, which in turn lead to increase permeability and leakage into the CSF and the bloodstream. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSince the invention of the Catalyst for Cure for glaucoma, different biomarkers for the detection of glaucoma have been discovered. One of these is serum MBP, which has been studied amongst Koreans and has been discovered to be a good biomarker for the detection of glaucoma, however, there is paucity of study of this serum MBP in the black race. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThis study aimed to further establish that glaucoma is a neurodegenerative disease and also investigate the possibility of having serum MBP as a biomarker for primary open angle-glaucoma (POAG) in Nigerian patients, thereby addressing the gap in biomarker research among African populations.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis cross-sectional study compared serum MBP levels in treatment na\u0026iuml;ve primary open- angle glaucoma (POAG) patients and non-glaucoma controls at the Lagos University Teaching Hospital, Lagos, Nigeria, and was conducted from October 2023 to February 2024. This comparative study enrolled 83 newly diagnosed, treatment-na\u0026iuml;ve POAG patients and 83 age- and sex-matched non-glaucoma controls aged 18 years and above. Eligibility criteria included adults\u0026thinsp;\u0026ge;\u0026thinsp;18 years who provided written informed consent. Exclusion criteria included glaucoma patients already on medications/who have had glaucoma surgery, secondary glaucoma, narrow angles or angle-closure, signs or symptoms suggestive of neurodegenerative diseases, other causes of optic neuropathy or retinal degenerative diseases.\u003c/p\u003e \u003cp\u003eOcular examinations, including visual acuity, anterior and posterior segment examination using slit lamp, ultrasound pachymetry, gonioscopy, and perimetry were performed on all participants.\u003c/p\u003e \u003cp\u003ePrimary Open Angle Glaucoma was defined as glaucomatous optic neuropathy as evidenced by vertical cup-disc ratio of \u0026ge;\u0026thinsp;0.5, optic disc notching, neuroretinal rim thinning, increased disc damage likelihood scale (DDLS) score usually of 5 or higher barring of circumlinear vessels, lamina dot sign, and corresponding visual field defects on perimetry +/- elevated intraocular pressure (\u0026gt;\u0026thinsp;21mmHg), in an eye without gonioscopic evidence of angle closure and without an identifiable secondary cause.\u003c/p\u003e \u003cp\u003eMinimum criteria for diagnosis of glaucoma using the visual field include a Glaucoma Hemifield Test outside normal limits on at least two fields or a cluster of three or more non-edge points in a location typical for glaucoma all of which are depressed on a pattern deviation plot at a p\u0026thinsp;\u0026lt;\u0026thinsp;5% level and one of which is depressed at a p\u0026thinsp;\u0026lt;\u0026thinsp;1% level on two consecutive fields or corrected pattern standard deviation that occurs in \u0026lt;\u0026thinsp;5% of normal fields on two consecutive fields.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] The severity of glaucoma was done using to Hodapp, Anderson and Parish classification [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBlood samples were withdrawn from cubital vein into BD vacutainer\u0026reg; EDTA tubes and analyzed for serum MBP levels using enzyme-linked immunosorbent assay kits (Eastbiopharm human myelin basic protein enzyme-linked immunosorbent assay kits: Reference number: CK-E11682, Hangzhou, China) according to the protocol for the kit.\u003c/p\u003e \u003cp\u003eData were statistically analyzed using SPSS) version 26.0 (IBM Corp: Armonk, NY). Categorical data was presented as proportion and percentages. Continuous data were presented with mean and standard deviation when normally distributed while median and interquartile range were used for the skewed data. Test for normal distribution assumption was done using Kolmogorov-Smirnov test. Test for significant association between the two groups (POAG and non-glaucoma group) and other categorical variables was carried out using Pearson\u0026rsquo;s Chi-square and Fischer exact test. Difference in or median values of the serum levels of myelin basic protein of the two groups was assessed using or Man-Whitney U respectively. Independent student t-test was used to compare ocular characteristics between the two groups. Kruskal Wallis was used to compare median of serum levels of MBP according to glaucoma severity and other categorical variables with more than two groups. Linear relationship between MBP and other numeric variables was assessed using Spearman correlation. Receiver operating characteristic (ROC) curve analysis was done in order to evaluate the diagnostic ability of MBP to discriminate between the POAG group and non-glaucoma groups. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. The area under the curve (AUC) was used to assess the discriminating ability accuracy. The optimal cut-point value was determined using the Youden index (J) which is calculated as: Maximum sensitivity\u0026thinsp;+\u0026thinsp;specificity \u0026ndash; 1\u003c/p\u003e \u003cp\u003eSignificant level was set at p-value of \u0026lt;\u0026thinsp;0.05. Box plot were used for data presentation where necessary.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe socio-demographic data showed the age group with the highest percentage of newly diagnosed POAG was between the ages 40\u0026ndash;59 where there were 36 participants, 18 participants in the age group 40\u0026ndash;49 and 50\u0026ndash;59 each, so that almost half (43.4%) of the POAG participants are within the age range of 40\u0026ndash;59 years, with the mean age being 50.78\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3 years. There were more males with POAG than females, where 32 participants (38.6%) were female and 51 (61.4%) were males so that the female: male ratio was 1:1.6. (Table 1)\u003c/p\u003e\n\u003cp\u003eThe overall mean IOP for the POAG group was slightly higher than that of the non-glaucoma group though both were within the normal range of between 10-21mmHg (18.22\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8mmHg and 13.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5mmHg respectively). The POAG group had thinner corneas as the mean central corneal thickness (CCT) of participants in this group was 519.5\u0026thinsp;\u0026plusmn;\u0026thinsp;39.6\u0026micro;m while that of the non-glaucoma group was 527.66\u0026thinsp;\u0026plusmn;\u0026thinsp;26.5\u0026micro;m (Table II). It was noticed that thin corneas (CCT\u0026thinsp;\u0026lt;\u0026thinsp;520\u0026micro;m) were more in the POAG group where 39 out of the 83 participants (47.0%) had CCT\u0026thinsp;\u0026lt;\u0026thinsp;520\u0026micro;m compared to the non-glaucoma group where 29 participants (34.9%) had CCT\u0026thinsp;\u0026lt;\u0026thinsp;520\u0026micro;m. The average vertical cup-to-disc ratio (VCDR) seen in the POAG group was 0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 while that of the non-glaucoma group was 0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1 (Table II).\u003c/p\u003e\n\u003cp\u003eThe BCVA (with pinhole or spectacle correction) was noticed to be better (\u0026ge;\u0026thinsp;6/18) in the non-glaucoma participants than the POAG participants in both eyes; right- 82(98.8%) vs 65(78.3%) and left eye- 83(100.0%) vs 67(80.7%) with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001. There was more visual impairment (\u0026lt;\u0026thinsp;6/18) recorded in the POAG group than the non-glaucoma group; right- 18(21.7%) vs 1(1.2%) and left- 16(19.3%) vs 0(0.0%) The serum MBP range in the POAG group was 513.75ng/L to 3518.00ng/L while in the non-glaucoma group it was 83.75ng/L to 2046.00. The median serum MBP level for the POAG group was 1128.75ng/L (966.3\u0026ndash;1377.0) while that of the non-glaucoma group was 963.75ng/L (657.5-1271.1), giving a p-value of \u0026lt;\u0026thinsp;0.001, Mann-Whitney U test of 4.016 and Confidence interval (CI) as 165 (103.1-491.56) (Fig. 1, Fig. 2 and Table III).\u003c/p\u003e\n\u003cp\u003eIn this study, it was found that the age group of the POAG participants with the highest levels of serum MBP was the 30\u0026ndash;39 years group, having a median value of 1434.0ng/L and the lowest was seen in age group\u0026thinsp;\u0026ge;\u0026thinsp;70years, having value of 1031.0ng/L (p-value 0.727). Males had slightly lower serum MBP compared to females (1116.25ng/L and 1210.0ng/L, respectively) with a p-value of 0.727. Those with a family history of glaucoma had a median serum MBP level of 1202ng/L while those with no known family history of glaucoma had 1127.88ng/L (p-value 0.733) (Table IV).\u003c/p\u003e\n\u003cp\u003eUsing the HAP classification system, the level for the mild group was 1072.19ng/L, moderate was 1224.69ng/L while the advanced was 1130.00ng/L and p-value 0.314. Using the DDLS, the median serum level for MBP in the early stage was 1135.63ng/L, moderate was 1127.00ng/L and advanced was 1176.50ng/L (Table V, Fig. 3).\u003c/p\u003e\n\u003cp\u003eEvaluation of the serum MBP levels for discrimination between NTG and HTG was done (Fig. 4). It showed a slightly higher level in the HTG compared to the NTG (median 1209.69ng/L vs 1073.75ng/L, p\u0026thinsp;=\u0026thinsp;0.448, CI\u0026thinsp;=\u0026thinsp;135.94); however, the difference was statistically insignificant.\u003c/p\u003e\n\u003cp\u003eThe sensitivity and specificity of the serum MBP level in discriminating between POAG and non-glaucoma participants at optimal cut-off point of 801.88ng/L were 92% and 40% respectively. The area under curve (AUC) was 0.681 (0.600-0.761). The positive predictive value (PPV) was 82.8% while the negative predictive value (NPV) was 61.4%. (Table VI)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the mean age at presentation was 50.78(SD\u0026thinsp;=\u0026thinsp;17.3) years with higher percentage of participants within the age group of 40\u0026ndash;59 years. This is similar to findings by Adekoya et al where 79.8% of POAG patients were \u0026gt;\u0026thinsp;40 years of age and another study by Olawoye et al which showed there was a higher percentage among the age group 60\u0026ndash;69 followed by 50\u0026ndash;59 years. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] In a sub-Saharan study, conducted by the African Glaucoma Consortium, the overall mean age at presentation was 58.9(SD\u0026thinsp;=\u0026thinsp;17.1) years, with participants from West African countries being the youngest at diagnosis, with mean age of 55.8(SD\u0026thinsp;=\u0026thinsp;16.4) years. The reason for the higher mean age in this study, in comparison to ours, may be the difference in patients\u0026rsquo; inclusion criteria. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur study, like the sub-Saharan study where 58.9% of the participants were males, reported more male participants and is similar to the findings in the study by Olawoye. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] The result is also consistent with a systematic review and meta-analysis of glaucoma prevalence and projection globally, which found that males are more likely to suffer from glaucoma than females. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur study showed that participants with POAG had a higher known family history of glaucoma in at least one relative (23 participants; 27.7%) than the non-glaucoma group (14 participants; 16.9%). This is close to what was reported by Adekoya et al and in the sub-Saharan study where a positive family history of 26.4% and 21.6%, respectively, were recorded. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe best corrected visual acuity (BCVA) was better in the non-glaucoma group, as a higher percentage of the POAG had visual impairment (VA\u0026thinsp;\u0026lt;\u0026thinsp;6/18) compared to the non-glaucoma group. Overall however, more participants in the POAG group (78.3% right eye; 80.7% left eye) had normal VA (\u0026ge;\u0026thinsp;6/18) than visual impairment (\u0026lt;\u0026thinsp;6/18). This is close to what was found in a study by Adegbehinde et al in South-west Nigeria where 80.5% of the POAG participants had BCVA of \u0026ge;\u0026thinsp;6/18 in better eye.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] The mean corrected IOP gotten in both groups was significantly different as the POAG group had a mean IOP of 18.22\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8mmHg while the non-glaucoma group was 13.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5mmHg. This is similar to the study by Adegbeingbe et al that found their POAG group to have a mean IOP of 18.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0mmHg while the non-glaucoma group had a mean IOP of 13.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8mmHg.Based on the corrected IOP of the POAG participants in this study, majority had normal tension glaucoma (\u0026le;\u0026thinsp;21mmHg) in 47 participants (56.6%) while less than half of the participants had high tension glaucoma (\u0026ge;\u0026thinsp;22mmHg) in 36 participants (43.4%). A study by Siesky showed that POAG patients of African descent have significantly lower retrobulbar blood flow and ocular perfusion hence more vascular dysregulation when compared to POAG patients of European decent. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] It is possible that this has contributed to why there were more of NTG participants than HTG in this study as vascular dysregulation has been linked mostly to NTG. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] This may also explain why in the Nigerian National Blindness and Visual Impairment Survey (NNBVIS) 56% of the POAG patients in Nigeria had NTG. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe serum MBP level in participants with POAG in this study was higher than the non-glaucoma group and the difference was statistically significant. Higher levels of serum MBP in POAG participants compared to the non-glaucoma group was also noted in the landmark study done amongst Koreans by Shin et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] The values however were substantially different in both races as the POAG group in Korea had average serum MBP levels of 318.12\u0026thinsp;\u0026plusmn;\u0026thinsp;146.91ng/L and non-glaucoma group 61.91\u0026thinsp;\u0026plusmn;\u0026thinsp;100.02ng/L while this study found that the value for POAG was 1128.75ng/L and non-glaucoma 963.75ng/L. There are various possible reasons for the disparity in the values gotten from the Koreans and Nigerians. Difference in race could be a major factor, as a study by Langer-Gould et al showed that blacks have more demyelination process in neurodegenerative diseases.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] It has been postulated that it could be due to the reduced Vitamin D levels in blacks as a result of the dark skin which hinders the cutaneous penetration of ultraviolet-B radiation needed for the biosynthesis of Vitamin D. Vitamin D plays a role in axon growth as well as myelination hence a relative deficiency of it would predispose to some instability and loss of myelin leading to increased level of its breakdown materials in the bloodstream. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] This could explain why both the POAG group and the non-glaucoma group in this study have higher values of serum MBP compared to those gotten from the Asian study. It is worthy of note that the study done in Korea only enrolled 38 participants, where 21 of them were POAG ages 37-61years and 17 were non-glaucoma participants aged 25\u0026ndash;57 years as against our larger number of 83 participants aged 18\u0026ndash;88 years of age in each group. This could be responsible for the lower values in Korea as our study had a wider range in terms of number of participants as well as the age group. Another important factor to consider is the fact that the Korean study used convenient sampling method to select participants which may have shifted the study outcome whereas this current study randomized the participants recruited in the POAG group thereby preventing any form of bias. The disparity in the serum MBP kits in both studies could possibly also contribute to the marked difference in the values. The Koreans used human MBP ELISA kit (E-EL-H0161, Elabscience) with an assay range of 15.63-1000ng/L while in this study human MBP ELISA kit (CK-E11682, Eastbiopharm) with an assay range of 50-6000ng/L. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] In this study, there was no correlation between serum MBP levels and clinical severity of POAG and this is similar to the findings in the Korean study. This is possibly due to the fact that serum MBP has been observed to remain high for only two weeks after demyelination or brain injury hence there is a steady clearance of this protein from the CSF and blood and no buildup of the MBP in the serum over time but rather a constant clearing of the MBP from the serum so that there is no significant difference between the mild, moderate and advanced glaucoma eventually. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTo ascertain whether serum levels of MBP can be utilized to as a diagnostic test for POAG, the receiver operating characteristic (ROC) curve was used. The sensitivity and specificity at optimal cut-off point of 801.88ng/L were 92% and 40% respectively with an area under curve (AUC) of 0.681 and this was low in comparison to another study by Shin et al that had an excellent diagnostic ability with an AUC of 0.924. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] The positive predictive value (PPV) was 82.8%, and the negative predictive value (NPV) was low (61.4%), meaning 82.8% of participants with serum MBP levels above 801.88ng/L actually had POAG. In comparison, 61.4% of participants with serum MBP levels below 801.88ng/L did not have POAG and a serum MBP below the cut-off value does not rule out POAG entirely. This would mean serum MBP cannot be used as a stand-alone test for diagnosis of POAG however it could possibly be used as a complementary tool for detection when done alongside other tests for glaucoma and could be used for monitoring of progression or response to treatment when done serially.\u003c/p\u003e \u003cp\u003eThe study\u0026rsquo;s limitations include the comparison of small sample sizes of POAG and non-POAG participants. A larger-scale survey could give a more comprehensive analysis of the diagnostic and prognostic properties of serum MBP as a biomarker in POAG. Although this study attempted to minimize confounders by excluding participants with other conditions that influence MBP levels, residual confounders may still affect MBP levels. An example is the considerable number of non-glaucoma participants who had a family history of glaucoma, hence this could be a confounder. The paucity of similar studies in journals limited the ability to compare this research's findings with those of many others.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eElevated serum MBP levels in POAG patients indicate neurodegeneration in POAG and may potentially serve as a biomarker for early glaucoma detection. Further longitudinal and larger studies are needed to validate these findings and integrate MBP with other biomarkers to enhance diagnostic accuracy. The serum MBP test could also be helpful in monitoring patients on treatment to detect a reduction in neurodegeneration or progression after treatment initiation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they do not have any conflict of interest. The authors had no financial obligation to any of the products or equipment used in this study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e Study approval (ADM/DSCST/HREC/APP/5705) was obtained from the Health Research Ethics Committee of the Lagos University Teaching Hospital, LUTH, Lagos, Nigeria. The study adhered strictly to the tenets of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate\u003c/strong\u003e \u003cp\u003e Written informed consent was obtained from all participants after a detailed explanation of the study.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003ePrevious presentation\u003c/h2\u003e \u003cp\u003eThis paper is part of a dissertation submitted to the National Postgraduate Medical College of Nigeria in partial fulfillment of the requirements for the award of Fellowship of the Medical College (Ophthalmology), November 2024. It was delivered as a poster presentation at the Association of Nigerian Physicians in America (ANPA) Conference, April 10th, 2025, in Lagos, Nigeria\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of the study or manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the conception and design of the study. Material preparation, data collection, and analysis were performed by Judith Ogechi Anikwenwa and Oladapo Rotimi. The manuscript draft was written by Judith Ogechi Anikwenwa, Adetunji Olusesan Adenekan and Sunday Adegeboyega Alabi. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe authors intend to grant access to the datasets used and/or analysed in the study upon reasonable request from the corresponding author\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShahsuvaryan LM. Glaucomatous optic neuropathy management: the role of neuroprotective agents. Med hypothesis, Discov Innov Ophthalmol. 2013;2:41\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSusanna Jr. R, Vessani RM. Staging glaucoma patient: why and how? Open Ophthalmol J. 2009;3:59\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpaeth GL. The disc damage likelihood scale. Glaucoma Today. 2005;1:19\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYou Y, Joseph C, Wang C, et al. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease. Brain. 2019;142:426\u0026ndash;442.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreddi TA, Ottaiano AC. The optic nerve: anatomy and pathology.In: Gayer G, 1st ed Seminars in Ultrasound, CT and MRI. Philadelphia: Elsiever; 2022.378\u0026ndash;388.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJames CT, 1st ed.Ocular disease mechanisms and management. Philadelphia: Elsevier; 2010. 180\u0026ndash;183.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoto I, Howell GR. The complex role of neuroinflammation in glaucoma. Cold Spring Harb Perspect Med. 2014;4:1\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWąsik N, Sok\u0026oacute;ł B, Hołysz M, et al. Serum myelin basic protein as a marker of brain injury in aneurysmal subarachnoid haemorrhage. ActaNeurochir (Wien). 2020;162:545\u0026ndash;552.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith R, Chepisheva M, Cronin T, et al. Diagnostic approaches techniques in concussion/mild traumatic brain injury: Where are we? In:Michael E, 1st ed. Neurosensory disorders in mild traumatic brain Injury. Florida: Academic press; 2019.247\u0026ndash;277.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026rsquo;Aversa TG, Eugenin EA, Lopez L, et al. Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain-barrier disruption: implications for the pathogenesis of multiple sclerosis. Neuropathol Appl Neurobiol. 2013;39:270.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTorre A. Catalyst for a cure. Glaucoma Research Foundation. 2023;1:1\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShin YJ, Kim E, Han BK, et al. Serum biomarkers for the diagnosis of glaucoma. Diagnostics. 2021;11:1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdekoya BJ, Shah SP, Onakoya AO, et al. Glaucoma in southwest Nigeria: clinical presentation, family history and perceptions. Int Ophthalmol. 2014;34:1027\u0026ndash;1036.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlawoye O, Tarella S. Spectrum of glaucoma presentation in a Nigerian tertiary hospital. Niger J Ophthalmol. 2014;22:11\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlawoye O, Kizor-Akaraiwe N, Pons J, et al. STAGE Research Group. Clinical Characteristics and Stage at Presentation of Glaucoma Patients in Sub-Saharan Africa. J Glaucoma. 2022;31(9):717\u0026ndash;723.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014;121:2081\u0026ndash;2090.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdegbehingbe S, Olusanya B, Ajayi B, et al. Central Cornea Thickness in Glaucoma and Non-Glaucoma African Population. Ophthalmol Res An Int J. 2016;6:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiesky B, Harris A, Racette L, et al. Differences in ocular blood flow in glaucoma between patients of African and European descent. J Glaucoma2015;24:117\u0026ndash;121.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLouis P. Vascular and Autonomic Dysregulation in Primary Open-Angle Glaucoma. Curr Opin Ophthalmol. 2016;27:94\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKyari F, Entekume G, Rabiu M, et al. A population-based survey of the prevalence and types of glaucoma in Nigeria: Results from the Nigeria National Blindness and Visual Impairment Survey. BMC Ophthalmol. 2015;15:1\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanger-Gould A, Brara SM, Beaber BE, et al. Incidence of multiple sclerosis in multiple racial and ethnic groups. Neurology. 2013;80:1734\u0026ndash;1739.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodney C, Rodney S, Millis RM. Vitamin D and demyelinating diseases: Neuromyelitis optica (NMO) and multiple sclerosis (MS). Autoimmune Dis. 2020;2020:1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Glaucoma, POAG, Neurodegenerative disease, Myelin Basic Protein, ELISA","lastPublishedDoi":"10.21203/rs.3.rs-8264197/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8264197/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eGlaucoma, a neurodegenerative disorder, causes retinal ganglion cell damage and loss of neurons in the visual system up to the visual cortex. The loss of myelin sheath leads to the release of myelin sheath components, including the myelin basic protein (MBP), into the bloodstream. While MBP has shown promise as a biomarker for glaucoma in some Asian populations, data among individuals of African descent remain limited. This study evaluated the serum levels of MBP in primary open-angle glaucoma (POAG) patients compared to non-glaucoma controls, with the aim of reporting its usefulness as a biomarker for glaucoma detection in an African population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study compared serum MBP levels in treatment-naive primary open-angle glaucoma (POAG) patients and non-glaucoma controls. Blood samples were collected from 83 treatment-naive POAG participants and 83 age and sex matched non-glaucoma participants and analyzed using enzyme-linked immunosorbent assay (ELISA).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean age of POAG participants was 50.78\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3 years, with a male predilection. The mean intraocular pressure (IOP) was significantly higher in POAG patients (18.22\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 mmHg) than in controls (13.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 mmHg). Serum MBP levels were significantly elevated in POAG patients (1128.75 ng/L) compared to controls (963.75 ng/L; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant correlation between MBP levels and disease severity. MBP levels were higher in high-tension glaucoma and females; however, the difference was not statistically significant.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eFindings supported the neurodegenerative state of POAG and the use of serum MBP levels as a potential biomarker for early POAG detection.\u003c/p\u003e","manuscriptTitle":"Evaluation of Serum Myelin Basic Protein in POAG Patients at a Tertiary Institution in Lagos, Nigeria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-17 07:04:34","doi":"10.21203/rs.3.rs-8264197/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-22T13:06:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-19T05:35:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-16T08:52:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"173316727702539971665930422569685549736","date":"2025-12-12T17:58:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118731582182058373972677169256205754099","date":"2025-12-11T03:08:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-10T17:48:36+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-03T11:15:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-03T11:13:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2025-12-02T21:20:01+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9b510104-b17e-4852-ac49-60e4e53ec49b","owner":[],"postedDate":"December 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-14T14:23:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-17 07:04:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8264197","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8264197","identity":"rs-8264197","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}