Risk Factors and Genetic Markers Associated with the Development and Progression of Glaucoma: A Review

Abstract

Aims

This study aims to systematically evaluate and synthesize current evidence on the environmental risk factors and genetic markers associated with the development and progression of glaucoma, with a focus on primary open-angle (POAG), normal-tension glaucoma (NTG) and angle-closure glaucoma (ACG), in order to clarify their interplay, clinical implications, and potential avenues for personalized risk assessment and therapeutic intervention.

Background

Being one of the major causes of irreversible blindness in the world, glaucoma is a multifactorial optic neuropathy that has a complex interaction between clinical, environmental, and genetic factors. In this literature review, existing evidence on the risk factors and the genetic markers of glaucoma, induced by primary open-angle glaucoma (POAG), NTG, and primary angle-closure glaucoma (PACG), are synthesized.

Methodology

PubMed, Scopus, Web of Science, DOAJ, and Google Scholar have been searched by using key terms (‘Glaucoma,’ ‘POAG,’ ‘ACG,’ ‘Risk Factors,’ ‘Genetic Markers,’ etc.) for peer-reviewed articles, clinical trials, GWAS, and meta-analyses to meet up the study's aim.

Results

Epidemiologic studies reveal significant demographic variations, with POAG prevalent in African populations and PACG in East Asians. Key nonmodifiable risks include age, family history and ethnicity, while modifiable factors comprise elevated IOP, vascular dysregulation and lifestyle. Genetic studies implicate MYOC, OPTN and TBK1 mutations, along with emerging polygenic risk scores, underscoring the importance of personalized management considering gene-environment interactions.

Conclusion

In this review, early screening, genetic screening, and specific interventions have been highlighted to combat the menace of glaucoma that results in a high global burden.

Clinical significance

This comprehensive review enhances clinical practice by identifying high-risk populations for targeted screening and highlighting key genetic markers (e.g., MYOC, OPTN) that enable personalized glaucoma management. It improves diagnostic accuracy by clarifying modifiable (IOP, smoking) and nonmodifiable (age, family history) risk factors while informing therapeutic strategies through mechanistic insights into autophagy and vascular regulation. Additionally, the study addresses healthcare disparities by emphasizing ethnic-specific risk patterns and supports genetic counseling for familial cases, ultimately guiding more effective prevention and treatment approaches to preserve vision.

How to cite this article

Hamid SAT, Abdulmajeed SM, Chowdhury IH, et al. Risk Factors and Genetic Markers Associated with the Development and Progression of Glaucoma: A Review. J Curr Glaucoma Pract 2025;19(4):216–222.

Introduction

Glaucoma is a group of optic neuropathies and a leading cause of irreversible blindness worldwide. Glaucoma can remain asymptomatic until it is severe, resulting in a high likelihood that the number of affected individuals is much higher than the number known to have it. Population-level surveys suggest that only 10 to 50% of people with glaucoma are aware they have it.¹ Primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG) and primary angle-closure glaucoma (PACG), is the most common adult form.² In the United States, more than 80% of cases are open-angle glaucoma; however, angle-closure glaucoma (ACG) is responsible for a disproportionate number of patients with severe vision loss.^3,4

Both have multifactorial etiologies involving clinical, environmental, and genetic risk factors. Over the past decade, numerous human studies have clarified key risk factors for glaucoma development and progression, ranging from demographic and ocular parameters to genetic variants. The most common Mendelian forms of POAG are caused by mutations in the myocilin (MYOC) gene, which have a prevalence of 2–4% in POAG patients.⁵ Genome-wide association studies (GWAS) have identified hundreds of common variants contributing to glaucoma risk, while rare monogenic mutations and emerging polygenic risk scores (PRS) offer insights into high-risk individuals.^6,7

This review synthesizes recent evidence on epidemiological, clinical, and genetic risk factors for POAG (and NTG) and PACG, highlighting how these factors interact to influence disease onset and progression. The focus is exclusively on human studies, with an emphasis on GWAS findings, monogenic glaucoma genes, PRS, and gene–environment interactions.

Methodology

The paper titled “Risk Factors and Genetic Markers Associated with the Development and Progression of Glaucoma” is a narrative as well as a systematic literature review, which summarizes the modern-day evidence based on peer-reviewed articles, clinical trials, GWAS, and meta-analysis, available in indexed journals over the past few years. In order to gather the most relevant literature on the subject, a thorough literature search was conducted in few, but highly important databases, including, but not limited to PubMed, Scopus, Web of Science, DOAJ, and Google Scholar, using the following key search terms: Glaucoma, POAG, ACG, Risk factors, Disease progression, Genetic markers, and GWAS.

This review is a systematic integration of the existing data on environmental and genetic factors affecting the pathogenesis and development of glaucoma, in particular POAG and ACG. It takes an organized manner by dividing risk factors into modifiable (e.g., intraocular pressure (IOP), vascular dysregulation) and nonmodifiable (e.g., age, ethnicity, family predisposition) aspects, besides outlining genetic loci that are involved in disease predisposition and progression as well.

Results were presented under thematic categories in order to have a clear insight toward the complexity of glaucoma causal etiology. The information was summarized in the form of narratives, which were accompanied by tabular structures that highlight important risk factors, important genetic variants, and their clinical implication. The recognized limitations, such as bias in publication, heterogeneity of the population, and variability of procedures among studies, are vital explanations for the evidence at hand.

Through the use of this impeccable, evidence-based study, the review will provide an insightful, extensive perspective on the dichotomous relationship between genetic predisposition and the influence of the environment in glaucoma. Not only does this synthesis help to explain extant paradigms, but it also accentuates future research and clinical practice.

Results

Glaucoma represents a complex, multifactorial optic neuropathy that progressively damages retinal ganglion cells and the optic nerve, leading to irreversible vision loss. This literature review systematically examines three critical aspects of glaucoma: its fundamental nature and classification, underlying pathophysiological mechanisms, and global epidemiological burden. First, we analyze how leading ophthalmological organizations (AAO, EGS, APGS) define and categorize glaucoma, highlighting key differences between primary open-angle (POAG) and angle-closure (PACG) forms, as well as variations across ethnic populations. The review then delves into the intricate pathophysiology, exploring how elevated IOP, vascular dysfunction, oxidative stress, and neuroinflammation collectively contribute to optic nerve damage. We subsequently present compelling global data showing glaucoma's disproportionate burden across different regions, with particular emphasis on its growing prevalence (projected to affect 111.8 million by 2040) and substantial economic impact. The analysis further investigates both nonmodifiable (age, genetics, ethnicity) and modifiable (IOP, vascular factors, lifestyle) risk factors, while also examining significant genetic markers such as MYOC, OPTN, and TBK1 that influence disease susceptibility and progression. By synthesizing these interconnected dimensions, this review aims to provide a comprehensive understanding of glaucoma's complexities by which professionals such as ophthalmologist, vision and gene scientist, policy makers and health professionals can apply effective prevention and management strategies for this leading cause of global blindness.

Definition and Classification of Glaucoma

Glaucoma is an optic neuropathy, as indicated by the American Academy of Ophthalmology (AAO)-2024, since it is a disease that occurs gradually, and a cup-shaped hole is developed on the optic disk, accompanied by thinning of the retinal nerve fiber layer (RNFL), leading to an abnormality in the visual field.⁸ The AAO-2024 informs the participants about how NTG functions as a form of glaucoma that affects individuals with normal IOP. European Glaucoma Society (EGS) describes glaucoma as optic nerve neuropathy of progressive character: it entails contiguous impacts on the optic nerve and retinal nerve fiber layer by means of distinctive anatomical alterations that effectuates loss of vision. In this case, the IOP is not the only factor in the development of risk, although it contributes significantly.⁹ The EGS states that early detection is essential since it promotes prevention of permanent impairment of vision (1) because of vascular dysregulation and (2) because of genetic predisposition.⁹

In its turn, Glaucoma is a heterogeneous group of disorders in the Asia-Pacific Glaucoma Society (APGS) and is the progressive damage of the optic nerve, but also acknowledges the higher rates of ACG in Asian populations and the disease pattern of each individual ethnicity.¹⁰ Three key points in the definitions are related to the idea that glaucoma is an optic neuropathy that develops in a progressive way, and which needs to be assessed in terms of both functionality as well as structural abnormality, including taking the high IOP as a significant but not absolute risk that must be prevented early in order to avert blindness. Such professional bodies also differ regarding their principal areas of interest because the AAO is focused on IOP control, whereas the EGS is oriented to different glaucoma causes, and the APGS is concerned with local epidemiological data.^8–10

Glaucoma can be split into different optic neuropathies that destroy retinal ganglion cells gradually and lead to a decrease in the perception of the visual field as a result of anatomical, etiological, and clinical types. The initial classifications divide the term glaucoma into primary and secondary, then further classification is divided into anterior chamber angle conditions. POAG is the most widespread type of glaucoma that brings forth degenerative optic neuropathy in individuals with open anterior chambers, but increased IOP only qualifies as a diagnostic criterion, whereas NTG brings about glaucomatous tissue damage at pressure levels below 21 mm Hg.^8,9 On the other hand, PACG is caused by the blockade of the course of opening angles at the trabecular meshwork, resulting in the formation of acute (episode IOP increase > 40 mm Hg) and chronic groups (continuously progressive damage, absent acute signs).^8,9

The factors that can be identified as causing glaucoma give rise to secondary glaucoma, such as open-angle glaucoma and pseudoexfoliative and pigmentary glaucoma types.⁸ Also, neovascular and uveitic glaucoma are members of the group of ACG.⁸ The glaucomatous condition should progress in two ways, which involve primary congenital glaucoma at the level of infants below the age of 3 years and juvenile open-angle glaucoma that occurs between 3 and 45 years.⁹ Other systems of classification focus on high or normal concentrations of IOP or advanced levels of the disease.⁸ It is the support of the AAO, EGS, and APGS by the framework since glaucoma diversity is discussed systematically in making the diagnostic and clinical processes more improved.

Pathophysiology and Mechanisms of Optic Nerve Damage in Glaucoma

Pathophysiology of glaucoma involves several pathways, which are interconnected, and include raised IOP, vascular dysfunction, oxidative stress, and neuroinflammation.¹¹ Increase of IOP is a strong risk factor of glaucomatous optic neuropathy, which causes mechanical stress on the optic nerve head (ONH).¹² There is increased deformation of the lamina cribrosa, a sieve-perforated structure embedded in the ONH, when presented with enlarged IOP, which subsequently causes axonal compressions and blockage of axoplasmic job flow.¹³ Research indicates that the prolonged mechanical stress transforms the content of the extracellular matrix, so it decreases the compliance of the tissue and aggravates the apoptosis of RGCs.¹⁴ Moreover, astrocytes and microglia strain generated by IOP in ONH leads to pro-inflammatory reactions, which also add to the neurodegeneration.¹⁵

Although IOP is at the center stage, vascular insufficiency is another determinant of glaucomatous damage. Ischemic injury and oxidative stress appear due to reduced ocular blood flow and alteration of autoregulation in the ONH.¹⁶ Systemic vascular disorder is one of the frequent parameters in patients with NTG, which implies that perfusion deficits play a role in optic neuropathy independent of IOP.¹⁷ Additional damage to blood supply could be endothelial dysfunction, vasospasm, and thrombosis aggravating the loss of RGCs.¹⁸

Oxidative injury is a characteristic of glaucoma, and the reactive oxygen species (ROS) become excessive in such a way that the endogenous systems of antioxidants are overwhelmed.¹⁹ Dysfunction of mitochondria in RGC elevates ROS to cause lipid peroxidation, damage of DNA, and the activation of apoptosis pathways.²⁰ What is more, glutamate excitotoxic mechanism also causes neurodegeneration because of excess extracellular glutamate saturating N-methyl-D-aspartate (NMDA) receptors, which causes calcium influx and cell death.²¹

The new evidence has shown the involvement of neuroinflammation in the development of glaucoma. Microglia and astrocyte activation stimulate the secretion of proinflammatory cytokines (e.g., TNF-alpha, IL-6) that prevent further RGC loss.²² Chronic inflammatory changes violate the blood–retinal barrier and lead to the occurrence of additional oxidative damage.²³ Heat shock proteins and other antigens present within the neuronal cells have also been posed to play a role in the annihilating effects due to autoimmune responses to glaucoma.²⁴

Global Epidemiology and Burden of Glaucoma

Glaucoma is differentially prevalent all over the world with respect to age, ethnicity, and region. According to a thorough meta-analysis by a group of researchers,²⁵ 64.3 million individuals between the ages of 40–80 years old were affected by glaucoma in 2013, and this amount is projected to increase to 111.8 million by 2040. POAG and PACG are the two major forms of glaucoma that have dissimilar distribution patterns. The type of POAG that is common among the population of African origins is as high as 6–8% in West Africa, whereas in Caucasians it is 1–3%.²⁶ Conversely, PACG is contributing to almost half the number of glaucoma difficulties in East Asia, especially in China and Mongolia, because of the anatomical inclinations of shallow anterior chambers.²⁷

The disparities in the glaucoma burden at the regional level are magnanimous. The late diagnosis of glaucoma in sub-Saharan Africa and a greater level of vision impairment at the onset of the condition are explained by the reduced availability of eye care services.²⁸ Conversely, the countries that have developed screening programs, i.e., the UK and the USA, report earlier measured detection and treatment results, but the results are still disparate in minority populations. Research indicates not only that persons of African origin are more prevalent but also that they develop glaucoma earlier and in a more rapid manner.²⁹

The cost of glaucoma is great. It comprises the direct medical expenses, drugs, tests, surgical procedures, and even includes indirect costs, the loss of productivity, necessity to have caregivers, and decrease in quality of life. In the United States, an economic analysis indicated that the total expenditure in caring conditions associated with glaucoma totaled above 2.9 billion dollars annually.³⁰ It is projected to rise exponentially in coming years with ageing populations, especially in LMICs, where the availability of eye care resources is meager and glaucoma awareness is lacking.

The fact that the disability-adjusted life years (DALYs) relating to glaucoma are also on the increase demonstrates its increasing trend. The Global Burden of Disease Study 2019 showed that glaucoma caused more than 400,000 years lived with disability in the world with immoderate results in Asia and Africa.³⁰ This highlights the importance of early detection tools and genetic risk profiling to avert the development and manifestation of diseases.

Risk Factors Associated with Glaucoma Development and Progression

The following Table 1 groups the major risk factors of glaucoma into nonmodifiable (age, race, family history, corneal thickness) and modifiable (IOP control, hypertension, smoking, medication adherence) determinants, and ocular and systemic comorbidities, which increase the prevalence of the condition in a systemic way. Specific attention is paid to the population-specific risks, i.e., the prevalence of POAG among the representatives of the African descent and ACG among Asian people, and the significance of vascular and lifestyle risks on the development of the disease. This table synthesizes the data in seminal reports to make a uniform, evidence-based tool that a clinician can use to stratify the risk and best manage early detection and possible personalization of management approaches in glaucoma.

Table 1:

Distribution of risk factors related to the glaucoma development and progression

Category	Risk factor	Explanation
Nonmodifiable	Age	Risk increases significantly after age 40 years, especially over 60 years. Associated with age-related diseases such as macular degeneration, vascular diseases, and obstructive sleep apnea.31–33
	Gender	Male: More prevalent to develop POAG by univariate analysis and Bayesian meta-analysis.34,35 Female: Higher risk for angle-closure glaucoma.36
	Family history	Strong genetic link; first-degree relatives have a higher risk, e.g., 22% lifetime risk of glaucoma among first-degree relatives of glaucoma patients in comparison to 2.3% in relatives of normal controls.37
	Race/ethnicity	African descent: Higher POAG risk.35 Whites: steepest Increase in OAG prevalence with age.35 Asian descent: Higher angle-closure risk compared to whites.38
	Thin central corneal thickness	Underestimates true IOP and is linked to optic nerve susceptibility.
	Myopia (nearsightedness)	Higher prevalence among Asian patients.38 High myopia increases POAG risk due to optic nerve structural vulnerability.35
	Hyperopia (farsightedness)	Increases angle-closure glaucoma risk due to shallow anterior chambers.
Modifiable	Elevated intraocular pressure (IOP)	Exposure to IOP elevations and fluctuations, which occur during a variety of regular or occasional activities, may increase the risk for the development or progression of glaucoma.37
	Systemic hypertension/hypotension	Vascular dysregulation may compromise optic nerve perfusion.
	Diabetes mellitus	May contribute to optic nerve damage; evidence is mixed. Increase the risk of POAG, especially as hyperglycemia results in heightened sensitivity to IOP and risk of neuronal injury.39
	Corticosteroid use	Prolonged use can elevate IOP, especially topical forms.
	Sleep apnea	Associated with optic nerve ischemia and progression.
	Smoking	Linked to vascular compromise and oxidative stress. The risk of glaucoma in smokers may be higher in men.40
	Migraine/vasospasm	May indicate poor optic nerve perfusion, increasing risk. The association between OAG and migraine was found to be significant only for subjects aged 70–79 years.41
Ocular/other	Low ocular perfusion pressure	Reduced blood flow to the optic nerve increases susceptibility to damage.
	Optic nerve structural factors	A large or asymmetric cup-to-disk ratio can indicate early or increased risk.
	Nocturnal hypotension	Excessive drop in blood pressure at night may reduce optic nerve perfusion.
Progression factors	Uncontrolled IOP	Persistent high IOP accelerates optic nerve damage.
	Advanced initial optic nerve damage	Greater risk of rapid visual field loss.
	Poor treatment adherence	Missed medications or appointments worsen disease control.
	IOP fluctuations	Significant variations in IOP contribute to nerve damage.
	Vascular dysregulation	Poor blood flow dynamics may hasten progression.

Genetic Markers Associated with Glaucoma

Glaucoma, the heterogeneous set of optic neuropathies, is a condition with high genetic determination factors that affect the susceptibility to this disease, as well as the phenotypic variation and responsiveness to treatment. Increasing numbers of genome-wide association study (GWAS) and candidate gene studies have highlighted several loci implicated in POAG, NTG, and developmental glaucomas and have discovered key pathways in the dynamics of aqueous humor, optic nerve homeostasis, and anterior segment development.^7,42Table 2 summarizes the most important genetic markers such as MYOC (juvenile-onset POAG), OPTN (NTG), and CYP1B1 (primary congenital glaucoma) and their inheritance, functional relationships, and clinically relevant mutations (MYOC Gln368Ter, OPTN E50K). Interestingly, structural defects in TBK1 gene and SIX6, accentuate the connection between autophagy deficits and predisposition to retinal ganglion cell susceptibility, and FOXC1/PITX2 and LMX1B emphasize the developmental origins of syndromic glaucoma. Through the description of these molecular pathways, this table presents a roadmap for risk stratification, early genetic testing, and upcoming precision medicine in glaucoma care.

Table 2:

Distribution of genetic markers associated with glaucoma

Genetic markers	Associated with	Inheritance pattern	Study design and role	Common mutations
MYOC (myocilin)	Primary open-angle glaucoma (POAG), especially juvenile-onset POAG		Mutations can lead to protein misfolding and accumulation in the trabecular meshwork, affecting aqueous humor outflow and increasing intraocular pressure.	Gln368Ter, Pro370Leu
OPTN (optineurin)	Normal-tension glaucoma (NTG), a subtype of POAG		Involved in cellular protection against oxidative stress and autophagy.	E50K
WDR36 (WD repeat domain 36)	Some forms of adult-onset POAG		It may be involved in ribosomal RNA processing and cellular stress response.	–
CYP1B1 (cytochrome P450 family one subfamily B member 1)	Primary congenital glaucoma (PCG)	Autosomal recessive, sporadic	Genetic linkage analysis, involved in the development of the trabecular meshwork and anterior chamber angle.	R368H, E387K
LMX1B (LIM homeobox transcription factor 1 beta)	Nail-patella syndrome and open-angle glaucoma		Regulates genes necessary for eye development and function.	–
TBK1 (TANK-binding kinase 1)	Normal-tension glaucoma		Related to autophagy and optic nerve survival.	–
FOXC1 and PITX2	Axenfeld–Rieger syndrome, which includes glaucoma	Autosomal dominant	Genetic linkage analysis These transcription factors are critical for anterior segment development.
TMCO1 (transmembrane and coiled-coil domains 1)	POAG
CAV1/CAV2 (caveolin 1 and 2)	POAG		Involved in intraocular pressure regulation and endothelial function.
SIX6 (SIX homeobox 6)	POAG		Implicated in retinal ganglion cell development.	rs33912345

Discussion

This literature review sought to explore the responsible epidemiological, clinical, and genetic factors for the causation of glaucoma and also tried to represent their interrelationship in a systematic way.

Epidemiological Factors

There are significant geographic, racial, and demographic differences uncovered in the epidemiology of glaucoma. It was estimated that in 2013, over 64.3 million people between the ages of 40 and 80 years were affected by glaucoma, and this number is set to increase to 111.8 million in 2040.²⁵ POAG is more common in people of African descent, where incidences are as high as 668. Known as POAG, African Americans ages between 40 and 50 years old are more prone to this disease, and it can progress even faster than in other races.^26,28 Conversely, East Asian populations (China and Mongolia included) are more prone to primary angle-closure glaucoma (PACG), the reason being elements that are anatomical, such as shallow anterior chambers.²⁷ The nonmodifiable risk factor that is long-proven is age, and the risk starts increasing quickly after age 40 years. Also, PACG is more prevalent in women, whereas POAG seems to affect more men.²⁶ The unevenness is also reflected in the diagnosis and access to treatment, especially in low- and middle-income nations, intensifying the burden of diseases and vision impairment.³⁰

Clinical and Environmental Risk Factors

There is a diverse range of clinical risk factors that affect the cause and perception of glaucoma and are either modifiable or nonmodifiable. Increased IOP is the main modifiable risk factor, which has been shown to be directly linked to the mechanical strain on the ONH, which leads to axonal compression and retinal ganglion cell (RGC) apoptosis in combination with extracellular matrix remodeling.^12,14 Thin central cornea thickness (CCT) leads to the underestimated IOP and becomes linked to the ONH susceptibility; refractive error consisting of high myopia or hyperopia affects the probability of POAG or PACG, respectively.¹⁸ Other systemic manifestations of comorbidity to complicate the optic nerve perfusion include diabetes, systemic hypertension or hypotension, obstructive sleep apnea, sleep-related nocturnal hypotension, and enhance oxidative and ischemic insults.^19,21 Inadequate compliance to treatment, changes in IOP, and the extensive damage to the optic nerve at the time of diagnosis are crucial factors in the fast progression of the disease and permanent visual loss.

Genetic Factors

In modern genetic studies, there are several glaucoma-related genes identified, explaining the inheritance of the risk factor of the disease. Point mutations in MYOC (myocilin) have a significant relation to juvenile and adult-onset POAG in which malformation of proteins in the trabecular pathway task results in hindrance of the drainage of aqueous humor and prevents IOP (Gln368Ter, Pro370Leu). The mutations of OPTN and specifically E50K are associated with NTG, which affect neuroprotective and autophagic processes.⁴³ Other implicating genes are WDR36, which is involved in stress responses, CYP1B1 a major cause of primary congenital glaucoma through developmental defects in the anterior chamber (R368H, E387K), and TBK1, FOXC1, and PITX2, which influence ocular development, and are the cause of syndromic and nonsyndromic glaucoma.⁴⁴ As well, GWAS suggest that among the variants with high potential to contribute to POAG are SIX6 (retinal ganglion cell development) and CAV1/CAV2 (IOP regulation and vascular activity).⁴⁵

Interplay between Risk Factors and Genetic Markers

The pathogenesis and the development of glaucoma is the incidence of an interactive relationship between hereditable tendencies and potentially changeable clinical or environmental riskfulness factors. As an example, carriers of MYOC mutations are predisposed to the development of increased IOP, which, in combination with environmental hazards, such as oxidative stress or exposure to corticosteroids, promotes an accelerated ONH-destructive process.¹² Also, systemic vascular dysregulation, which is evident among TBK1 or OPTN mutated patients, is likely to predispose them to ischemic optic neuropathy, especially in cases where conditions such as migraine, nocturnal hypotension, or diabetes even recur.¹⁷ Ethnic differences in genetic markers prevalence e.g., CYP1B1 in Asians or OPTN in the NTG cases, also conform to epidemiological tendencies.^25,27 Thus, learning the interaction of these genetic variations with IOP, vascular health, and the inflammatory pathways gives us a very valuable route of risk stratification, early detection, and precision-based interventions toward glaucoma treatment.

Conclusion

Glaucoma is still one of the significant public health issues, where the multifactorial nature of the disease is characterized by the complex interplay between genetics and the environment. The epidemiological research points out the disproportionate distribution of the disease and its development between the various ethnic and demographic groups and implies the necessity of specific screening and intervention modes. Clinically, the pathogenesis of the disease focuses on elevated IOP, vascular dysregulation, and susceptibility to optic nerve damage, and gene-based studies have already defined the key markers of predisposition and disease severity (MYOC, OPTN, TBK1, CYP1B1). The availability of GWAS as well as polygenic risk scores (PRS) provides hope and prospects toward the identification of individuals with high risks at an early stage.

In the future, the multidisciplinary collaborative efforts involving genetic profiling, high-level imaging, and the core use of precision medicine will play a key role in enhancing glaucoma treatment. Awareness, detection at an early stage, and equal access to care, especially in underserved communities, should be targeted by the public health initiatives. Future studies on gene-environment relationships and other potential treatment targets are the key to establishing successful treatment regimes. Healthcare providers can take a step further in limiting the progression and spread of glaucoma by considering both the changeable risk factors as well as genetic susceptibility in reducing the burden of glaucoma, causing irreversible blindness in the entire global population.

Clinical Significance

This comprehensive review enhances clinical practice by identifying high-risk populations for targeted screening and highlighting key genetic markers (e.g., MYOC, OPTN) that enable personalized glaucoma management. It improves diagnostic accuracy by clarifying modifiable (IOP, smoking) and nonmodifiable (age, family history) risk factors while informing therapeutic strategies through mechanistic insights into autophagy and vascular regulation. Additionally, the study addresses healthcare disparities by emphasizing ethnic-specific risk patterns and supports genetic counseling for familial cases, ultimately guiding more effective prevention and treatment approaches to preserve vision.

Acknowledgments

The authors would like to show their gratitude to the authority of Al-Noor Eye Hospital, Dhaka, an Al Basar International Foundation project, for providing consent and logistics support to complete this study on time.

Orcid

Salman Ahmed Taher Hamid https://orcid.org/0009-0007-9872-0928

Saeema M Abdulmajeed https://orcid.org/0009-0004-5682-1833

Imtiaj H Chowdhury https://orcid.org/0000-0002-4637-1363

Md Mahmudul Hasan https://orcid.org/0000-0001-9873-0471