|Year : 2019 | Volume
| Issue : 1 | Page : 10-15
Intraocular pressure negatively correlates with serum brain-derived neurotrophic factor in patients with primary open-angle glaucoma
Isyaku Umar Yarube1, Ahmed Saidu2, Sadiq Hassan3
1 Neuroscience and Pathophysiology Unit, Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Bayero University, Kano, Nigeria
2 Medical Services Branch, Headquarters, Nigerian Air Force, Abuja, Nigeria
3 Department of Ophthalmology, Faculty of Clinical Sciences, College of Health Sciences, Bayero University; Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Web Publication||10-Oct-2019|
Isyaku Umar Yarube
Neuroscience and Pathophysiology Unit, Department of Physiology, Bayero University, Kano
Source of Support: None, Conflict of Interest: None
Introduction: Glaucoma is a blinding eye disease, the hallmark of which is elevation of intraocular pressure (IOP). Glaucoma is nearly impossible to diagnose and treat without expensive equipment and IOP reduction, respectively. Hence, the need for a biomarker is an aid in diagnosis and an alternative treatment option to IOP reduction. Brain-derived neurotrophic factor (BDNF) may serve as both a biomarker and a therapeutic option. However, the exact role of BDNF and its dynamics during glaucoma is not well demonstrated, especially in a Sub-Saharan African population. This study, therefore, examines the serum levels of BDNF and its relationship with IOP. Patients and Methods: Intraocular pressure (IOP) and serum BDNF were measured in 44 glaucoma patients and 41 controls. Results: Glaucoma patients had higher IOP compared to controls. They also had higher BDNF (2.578 ± 0.210) compared to controls (1.745 ± 0.111). Glaucoma patients on medications had higher BDNF (3.086 ± 0.180) compared to those not on medications (0.605 ± 0.116). Serum BDNF significantly correlated with IOP. Conclusion: In conclusion, glaucoma patients have higher IOP and serum BDNF concentrations compared to nonglaucoma controls. IOP negatively correlates with serum BDNF in patients with glaucoma. Untreated glaucoma appears to decrease serum levels of BDNF, whereas treatment of the condition increases it. Serum BDNF may serve as a potential therapeutic target and useful diagnostic and monitoring tool in the management of glaucoma.
Keywords: Brain-derived neurotrophic factor, glaucoma, intraocular pressure (IOP), Kano, Nigeria
|How to cite this article:|
Yarube IU, Saidu A, Hassan S. Intraocular pressure negatively correlates with serum brain-derived neurotrophic factor in patients with primary open-angle glaucoma. Sub-Saharan Afr J Med 2019;6:10-5
|How to cite this URL:|
Yarube IU, Saidu A, Hassan S. Intraocular pressure negatively correlates with serum brain-derived neurotrophic factor in patients with primary open-angle glaucoma. Sub-Saharan Afr J Med [serial online] 2019 [cited 2023 Jan 28];6:10-5. Available from: https://www.ssajm.org/text.asp?2019/6/1/10/268787
| Introduction|| |
Glaucoma is a blinding eye disease that can be broadly classified into “‘open-angle” glaucoma, which is characterized by an open anterior chamber angle and is usually symptomless until it is advanced, and “angle-closure” glaucoma, which manifests as mechanical angle closure of outflow structures presenting with ocular pain and acute visual loss. Glaucoma can also be classified into primary, in which there is no known cause of elevated intraocular pressure (IOP), and secondary, in which the elevation in IOP results from other ocular or systemic diseases. The most common form of the disease is the primary open-angle glaucoma (POAG).
The burden of glaucoma has remained high worldwide despite advances made in diagnosis and treatment. Glaucoma is a leading cause of bilateral blindness worldwide. The number of people who are blind because of glaucoma is projected to hit over 11 million by the year 2020. According to the Nigerian National Blindness survey, glaucoma accounts for 16.7% of blindness in the 40 years age group and over with an estimated glaucoma-related blindness of 0.7% among Nigerian adults.
Glaucoma is a silent blinder − by the time an individual is symptomatic, the disease must have reached an advanced stage. Early diagnosis and treatment is the only way of effectively preventing blindness in glaucoma. This far, the most effective way of diagnosing glaucoma is the assessment of the optic nerve head and the visual field changes. Assessment of the optic nerve and the visual field changes requires the availability of costly equipment and the expertise of trained ophthalmologists. These resources are hard to come by in resource-limited settings. A biomarker of glaucoma, if available, could allow general practitioners to screen for or even diagnose glaucoma at early stage. It is likely that brain-derived neurotrophic factor (BDNF) may potentially serve as such a biomarker, but there is the need to establish the relationship between BDNF and intraocular pressure (IOP) (the hallmark of glaucoma), which has hitherto not been done and which this study seeks to explore.
Furthermore, IOP control has remained the only evidence-based treatment option in glaucoma, hence the need to explore other treatment modalities. Studies have shown that the levels of some neurotrophic agents are depleted in many neurological disorders including glaucoma. With the fact that neurotrophic agents, including BDNF, are important for the growth and survival of neurons in the central and peripheral nervous systems, it is worthwhile to look into neuroprotection for the prevention and treatment of progressive loss of vision in glaucoma. Neuroprotection using neurotrophins such as the BDNF can offer a viable treatment option. However, the exact role of BDNF and its dynamics during glaucoma is not well demonstrated, especially in a Sub-Saharan African population. This study, therefore, examines the serum levels of BDNF and its relationship with IOP in glaucoma patients in Kano.
| Methods|| |
Study setting and sampling
The study was carried out at Murtala Mohammed Specialist Hospital (MMSH), located in Kano, north-west Nigeria. MMSH is a 250-bed hospital with 20 departments and units, among which is the Eye Clinic that serves a population of about 360 glaucoma patients every month. Fourty-four patients with POAG were recruited for the study. Patients with ocular conditions other than POAG, those with history or evidence of diabetes mellitus, drug abuse, smoking, and alcohol dependence, and those with any neuropsychiatric illness or treatment were excluded. Apparently healthy first-degree relatives of the glaucoma patients and other nonglaucoma volunteers served as controls.
Sample size was determined using computer software for power and sample size determination according to Lenth. Systematic sampling was employed in selecting patients for this cross-sectional study.
The diagnosis of POAG was made by a trained personnel based on optic disc abnormalities, reproducible visual field defects typical of glaucoma, as determined by the Humphrey field analyzer (Carl Zeiss, Germany), S1TA full-threshold program 30-2, and open anterior chamber angles on gonioscopy. IOP was measured in both the eyes using the Goldman applanation tonometer (Type-AT 900, Part No.: 1001371, SN: 25933, HAAG-STREIT AG, Koeniz, Switzerland). A drop of a local anesthetic, amethocaine (ECWA Central Pharmacy Ltd, Jos, Nigeria), was instilled in each eye and the tonometer was cleaned with isopropyl alcohol. The eye was stained with a fluorescein strip and the Goldman applanation tonometer mounted on a slit lamp (Type-AT 900, Part No.: 1001371, SN: 25933, HAAG-STREIT AG) was used to measure the IOP. Blood pressure was measured using a digital sphygmomanometer (OMRON, San Ramon, CA, USA). Sociodemographic data, past medical/ocular history, and other clinical characteristics were obtained and documented using semistructured interviewer-administered data capture form specially designed for the study.
Samples of venous blood were collected from all patients between 9 a.m. and 11 a.m. to minimize the possible effects of circadian rhythms on BDNF concentrations. Samples were allowed to clot for 2 h at room temperature before centrifugation for 15 min at 1000g. BDNF concentrations were determined from the harvested sera using the BDNF Human Elisa Kit (E-EL-H0010; Elabscience Biotechnology Co. Ltd, Atlanta, GA, USA) according to the manufacturer’s directions.
Ethical approval was obtained from the Kano State Ministry of Health, with Ref.: MOH/Off/797/T. I./97, dated May 3, 2016. Signed informed consent was obtained from each participant before commencement of data collection. The study complied with to the provisions of the declaration of Helsinki 1995 (as reviewed in Tokyo in 2004).
Data was processed using IBM SPSS Statistics version 20.0 (SPSS Inc., Chicago, IL, USA). Summary of data were expressed as frequency and mean ± standard deviation. Mean IOP values of glaucoma and control groups, and mean BDNF values of any two categories were compared for differences using t-test. Categorized IOP values were analyzed for differences between glaucoma and control groups, and between glaucoma patients on medication and those not on medication using Mann–Whitney test. Mean BDNF values were compared based on sociodemographic and clinical features using analysis of variance and Tukey post hoc test. Chi-square and Kendall’s tau b tests were used to determine the relationship of IOP with categorical and continuous variables, respectively. Significant values of P were those <0.05.
| Results|| |
Fourty-four glaucoma patients and 41 nonglaucoma controls were recruited for the study. Mean age of the glaucoma patients and controls were 51.9 ± 15.3 (with 95% confidence interval, CI, of 47.2–56.5) and 52.6 ± 14.2 (48.1–58.1) years, respectively. There was no significant difference between the glaucoma patients and controls in terms of age (t = −0.226, P = 0.822). Among the glaucoma patients, there were 25 (57%) males and 19 (43%) females, whereas there were 21 (51%) males and 20 (49%) females among the controls. There was no difference in sex composition of the two groups (Mann–Whitney U = 851.5, P = 0.607).
Mean IOP values were significantly higher in the glaucoma patients (18.21 ± 3.39 mmHg right eye and 18.93± 3.70 mmHg left eye) compared to the controls (13.20 ± 2.0 mmHg right eye and 13.27 ± 2.11 mmHg left eye) (t = 7.749, P = 0.001 and t = 8.119 and P = 0.001, respectively). Furthermore, the values of IOP in the clinical categories were significantly higher in the glaucoma patients than in the controls (Mann–Whitney U = 512.5, P = 0.001) [Table 1]. The IOP values were significantly lower among patients on glaucoma medications compared to those yet to be placed on medications [Table 2]. There were 93% males and 78% females on glaucoma medication.
|Table 1 Distribution of intraocular pressure among glaucoma patients and controls|
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|Table 2 Intraocular pressure among glaucoma patients on and not on medications|
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Serum BDNF level among the glaucoma patients was 2.578 ± 0.210 (95% CI 2.154–3.002), whereas that of the controls was 1.745 ± 0.111 (95% CI 1.522–1.968), and the difference between the two was statistically significant (t = 3.436, P = 0.001). Among the glaucoma patients, 35 were on glaucoma medications and had BDNF level of 3.086 ± 0.180, whereas nine were not on medications and had BDNF level of 0.605 ± 0.116, and the difference was statistically significant (t = 6.841, P = 0.001). Serum BDNF did not differ based on sociodemographic features [Table 3] but varied significantly according to some clinical features such as mean arterial blood pressure (MAP) (P = 0.001) and IOP in the right eye (P = 0.018) [Table 4].
|Table 3 Variations of serum BDNF level of glaucoma patients according to sociodemographicfeatures|
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|Table 4 Variations of serum BDNF level of glaucoma patients according to clinical features|
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Serum BDNF was significantly associated with diastolic blood pressure (P = 0.006), MAP (P = 0.019), and IOP (right eye) (P = 0.027) [Table 5]. There was significant correlation between BDNF and IOP of the glaucoma patients (R2 = 0.5436, P = 0.033), whether on medication (R2 = 0.4321, P = 0.021) or not (R2 = 0.9979, P = 0.042) [Figure 1].
|Table 5 Relationship between serum BDNF level and selected features of glaucoma patients|
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|Figure 1 Correlation between BDNF and intraocular pressure of glaucoma patients who are on or not on medication. BDNF: brain-derived neurotrophic factor.|
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| Discussion|| |
This study examined the relationship between BDNF and IOP in 44 glaucoma patients and 41 nonglaucoma controls, matched for age and sex and several sociodemographic characteristics. Furthermore, majority of the respondents were Hausa/Fulani, which was in conformity with the ethnic composition of the study area. Although most of the glaucoma patients in this study were on glaucoma medications, males being more than females. This disparity may have to do with the fact that females are usually less economically empowered than males in the study area and hence more likely to get access to healthcare.
From the obtained results, the glaucoma patients had elevated IOP in contrast to the nonglaucoma patients who had normal values of IOP. Increased IOP is a common finding in POAG, and usually the main cause of the characteristic optic nerve damage. This supports the assertion that elevated IOP is the most important risk factor for the development and progression of POAG. In the population-based Barbados Eye Study, participants with IOP >21 mmHg had more than 11 times the likelihood of having POAG than those with IOP of 21 mmHg or less. This study also reports no significant difference in IOP between the males and females respondents in both the groups, and also between relatives or nonrelatives of glaucoma patients.
This study reports higher mean values of BDNF among the glaucoma patients compared to the nonglaucoma controls. Interestingly, the glaucoma patients on medication had very high (higher than the average for the glaucoma group) serum BDNF, whereas those not on medication had very low values (lower than the values seen among the controls) of BDNF. It appears that without treatment, patients on glaucoma have very low levels of serum BDNF (lower than healthy nonglaucoma patients), and placing these patients on treatment increases their serum BDNF levels in a rebound manner. Further studies are needed to confirm this phenomenon. This result contradicts that of Ghaffariyeh et al., who found lower serum BDNF levels of glaucoma patients compared to those of the apparently healthy controls. The difference could be because of the proportion of glaucoma patients on glaucoma medication against that of patients not on medication. MAP and IOP could also contribute to this difference as these parameters affect BDNF based on our findings. However, it is unlikely that sociodemographic features, including family history of glaucoma, could contribute to the difference as BDNF did not differ based on such characteristics in our findings.
The absence of relationship between serum BDNF levels with age observed in this study is in conflict with the findings of the study by Lommatzsch et al., which reported that BDNF levels in plasma decreased significantly with increasing age. In addition, advanced age is a recognized risk factor for POAG and the decreased level of BDNF with increasing age might be connected to the increased prevalence of POAG in people older than 40 years. Relatively younger average age and narrow age range of patients in our study compared to those in other studies may have limited the chance of observing significant relationships between age and serum BDNF.The primary factors responsible for apoptotic cell death in glaucoma are elevated IOP and vascular dysregulation, especially in people with normal tension glaucoma. Our data demonstrates the moderate correlation between IOP and BDNF, wherein serum BDNF decreases with increasing IOP. Interestingly, the correlation is observed in glaucoma patients on treatment and those who have not started any treatment. This suggests that decrease in BDNF may be involved in the mechanism through which IOP damages the retina, and further emphasizes the importance of lowering IOP as a treatment modality for POAG. BDNF, a polypeptide responsible for growth and preservation of neurons, is transported to the retinal ganglion cell bodies through a retrograde axonal transportation system and the synaptic connections within. The current therapy for glaucoma mainly focuses on IOP reduction; it is possible that by reducing the IOP, the level of BDNF might rise, thereby improving the neuroprotective effect induced by BDNF. This correlation is supported by the rebound increase in BDNF in patients initiated on treatment reported in this study and points to the therapeutic potentials of BDNF in glaucoma.
Conclusion and recommendations
Glaucoma patients have higher values of IOP and serum BDNF compared to nonglaucoma controls. IOP negatively correlates with serum BDNF in patients with glaucoma. Untreated glaucoma appears to decrease serum levels of BDNF, whereas treatment of the condition increases it. Serum BDNF may serve as a potential therapeutic target and useful diagnostic and monitoring tool in the management of glaucoma.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]