Abstract
Glaucoma is one of the leading causes of irreversible blindness worldwide and is often referred to as the “silent thief of sight”, because it often progresses without noticeable symptoms until significant vision loss occurs. With an estimated 76 million patients affected in 2020 and a forecast of over 111 million by 2040, the global situation requires urgent attention. Vision loss caused by glaucoma is irreversible but largely preventable, highlighting the importance of early detection and treatment. Diagnosis presents significant challenges, particularly due to the asymptomatic nature of the disease and age-related risk factors. Inequalities in care and access to appropriate treatments are other barriers leading to delayed diagnoses. Early diagnosis and interventions are critical to slow disease progression, protect remaining vision and improve the quality of life of those affected. These measures are particularly important to minimise the psychological impact and impairment in daily activities. The use of innovative technologies and targeted interventions could help improve the early detection and treatment of glaucoma and thus reduce the risk of irreversible vision loss.
Keywords: glaucoma, irreversible blindness, early diagnosis, visual loss
Introduction
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is often referred to as the ‘silent thief of sight’ because it usually progresses without noticeable symptoms until significant vision loss has occurred 1 . Understanding the global status of glaucoma, the challenges of diagnosing it, and the importance of early detection is crucial.
Global Status of Glaucoma
Glaucoma is the second most common cause of blindness worldwide. It is estimated that approximately 76 million people were affected by glaucoma globally in 2020, and this number could rise to more than 111 million by 2040 due to ageing populations 2 , 3 .
A total of 80 million people are currently affected 2 . However, unlike cataracts, vision loss caused by glaucoma is irreversible. It is estimated that over 3 million people are blind due to glaucoma, about 10% of whom have bilateral blindness 4 . The prevalence is higher in certain regions, such as Africa and Asia 5 , 6 , 7 . It was also found that the prevalence of primary angle-closure glaucoma (PACG) and normotensive glaucoma is higher in individuals of Asian origin 3 , 8 .
Glaucoma is also a major cause of blindness in German-speaking countries. In Germany, the prevalence of open-angle glaucoma increases with age: About 0.4% of people aged 40 to 44 years, 2.7% of people aged 70 to 74 years, and up to 10% of people over 90 years are affected 9 . A study from southern Germany estimated the incidence of blindness due to glaucoma at 2.43 per 100,000 person-years, which corresponds to approximately 9,939 new cases of blindness per year in Germany 10 . In Switzerland, awareness and knowledge of glaucoma are relatively low, which can lead to avoidable blindness 11 .
Vision loss caused by glaucoma is irreversible but can be slowed down in most cases, making early detection and treatment critical. Patients with advanced glaucoma require disproportionately more doctorʼs visits and interventions than those in the early stages of the disease 12 . This raises an important question: Why are up to 8.9% of people with primary open-angle glaucoma (POAG) and up to 27% with primary angle-closure glaucoma (PACG) affected by blindness despite screening efforts and effective medical and surgical interventions 13 ?
Understanding the Challenges of Glaucoma Diagnosis: The Scale of the Problem
Diagnosing glaucoma faces significant challenges. As mentioned above, early treatment is crucial to prevent vision loss due to glaucoma. However, this is often complicated by a delayed diagnosis. In countries with better resources, epidemiological studies estimate that about 50 – 80% of glaucoma cases in the population remain undetected, with this figure rising to about 90% in developing countries 14 , 15 , 16 . Individuals with advanced glaucoma at initial diagnosis are often those who have asymptomatic elevated intraocular pressure (IOP) and no family history of glaucoma 17 , 18 , 19 .
Moreover, population-wide screening for glaucoma is impractical due to low community prevalence, lack of cost-effectiveness and other logistical obstacles 20 . The current state of available screening technologies includes measurement of intraocular pressure, functional tests such as perimetry, and structural tests, including assessment of optic nerve and retinal abnormalities (e. g. optic disk excavation by funduscopy, retinal ganglion cell layer, and nerve fibre layer by OCT), gonioscopy and pachymetry. However, there is currently no consensus on the most effective combination of these tests or the optimal thresholds to use in a screening test for glaucoma 21 .
With the screening tools currently available, there are therefore still restrictions on widespread use among the population. However, it is possible that advances in these technologies or the development of new tools in the future could significantly improve the feasibility and effectiveness of glaucoma screening 22 .
Asymptomatic nature of glaucoma
Ironically, an important risk factor for undiagnosed glaucoma is the absence of perceived vision problems. Although early diagnosis and therapeutic intervention are the key to preventing blindness due to glaucoma, detection in the early stages is difficult because of its asymptomatic nature. Glaucoma often does not cause any abnormal symptoms at first, and because its effects are gradual, particularly if only one eye is affected, significant and irreversible damage may occur before the person realises that there is a problem.
Age as the main risk factor
Age is a major risk factor for eye disorders such as glaucoma, with the prevalence increasing from 0.6% in people aged 40 – 49 years to 8.3% in people aged 80 years and older. This age-related increase is evident in both men and women and in almost all ethnic groups 23 . Older adults often have an impaired understanding of ophthalmology and frequently do not consider their visual health a priority. Many older people mistakenly assume that poor vision is an inevitable part of ageing 24 , 25 . In addition, there are significant mental, physical and perceptual challenges for patients undergoing visual field testing, especially in the elderly population with glaucoma 26 .
This mindset, combined with age-related physiological changes and overlapping health conditions, complicates early diagnosis and management of glaucoma in older adults.
The challenges of glaucoma diagnosis from the perspective of the ophthalmologist
A delayed diagnosis of glaucoma is either due to patients not presenting to an ophthalmologist at all or doing so too late, or because ophthalmologists fail to detect the condition. A definitive diagnosis of glaucoma often depends on long-term observations and progressive changes in the characteristics of the optic disc over time – essential information that cannot be captured by cross-sectional imaging alone 20 . Experienced clinicians agree that an accurate diagnosis of glaucoma requires a holistic assessment that integrates structural and functional testing, a detailed history, and clinical examination of the optic nerve and peripapillary retina.
From the perspective of the ophthalmologist, a comprehensive approach is essential to overcome the challenges of diagnosing glaucoma. This includes detailed eye examinations – such as slit lamp examination, intraocular pressure (IOP) measurement, pachymetry, gonioscopy, and extended fundus examination – the development of appropriate infrastructure, and the accurate interpretation of published scientific literature. However, different ophthalmologists interpret the various diagnostic parameters in different ways. Although glaucoma experts are expected to provide the most accurate basis for assessment of glaucoma, the lack of reliable diagnostic indicators or biomarkers for evaluating the optic disc, especially in the early stages of glaucoma, adds to the overall complexity. In addition, significant physiological variations in the visual appearance of the optic disc make subjective interpretation of changes in fundus images more difficult, making the diagnostic process even more challenging. To meet these challenges, German ophthalmological societies recommend regular screening from the age of 40. In patients with additional risk factors, a shorter examination interval is recommended to ensure early diagnosis and treatment. Key risk factors for open-angle glaucoma in Caucasians include pseudoexfoliatio lentis and ocular hypertension, which are associated with the highest risk estimates. Further risk factors, such as first-degree familial history, myopia of 4 or more diopters, abnormal papillary excavation, or prolonged steroid therapy, also require adjustment of screening intervals. Regular examinations allow for early detection and timely interventions, which are essential for effective management of glaucoma and to reduce the risk of irreversible vision loss.
Inequalities in glaucoma care – another barrier to timely diagnosis
Despite advances in medical technology and treatment, one of the most pressing challenges in the fight against this disease remains unequal access to diagnosis and care. Socio-economic, ethnic and geographical inequalities create a landscape in which certain population groups face greater obstacles to timely and effective treatment.
These inequalities not only delay diagnosis, but also lead to poorer treatment outcomes for vulnerable groups, underscoring the urgent need for action. For many patients, the problem is rooted in a lack of awareness. Preventive eye care is often underused because patients may not understand the importance of regular screening or may not be aware of their own risk factors for glaucoma. Financial constraints, lack of insurance cover and transport problems further restrict access to professional eye care, especially in underserved communities 27 , 28 .
Social epidemiological research emphasises the link between socioeconomic status (SES) and health outcomes. People with lower socioeconomic status (SES) often experience more significant health problems, have shorter life expectancies, and are diagnosed with conditions such as glaucoma much later than those with higher SES. In Germany, for example, people from the highest socioeconomic groups live on average five to ten years longer than people from the lowest groups 29 , 30 .
Low SES is directly associated with delayed diagnosis of glaucoma, exacerbating inequalities in treatment and outcomes 31 .
Ethnic and social inequalities make early detection even more difficult. Research shows that African-Americans are more likely to be blind than non-Hispanic white Americans at the initial diagnosis of glaucoma 32 . Lower health literacy has been associated with lower use of preventive services, delayed diagnoses, higher hospitalisation rates, and increased mortality 33 , 34 . In addition, geographical barriers – such as living in rural areas with limited access to specialised eye care – make access particularly difficult for communities that include historically disadvantaged groups 35 , 36 . In addition, patients from historically disadvantaged groups have lower rates of use of health services, further exacerbating inequalities in visual health outcomes.
Targeted interventions that prioritise early detection and access to care are needed to address these inequalities. Solutions such as tele-glaucoma and community-based screening initiatives offer promising opportunities to improve early diagnosis, especially in underserved areas. In addition, AI technologies offer potential for more accessible and affordable glaucoma detection, although distortions in AI systems need to be carefully monitored. Moreover, closing the gap in early diagnosis of glaucoma will depend on a mix of patient-centred care, improved health education, and stronger patient-doctor relationships. Policymakers, healthcare providers, and community stakeholders must work together to reduce these inequalities and ensure that all population groups have equitable access to early detection and effective glaucoma care.
Ethnic and social inequalities are also evident in scientific research, where the under-representation of ethnic minorities in glaucoma studies limits the understanding of how these populations experience the disease. A meta-analysis of 105 studies of POAG conducted between 1994 and 2019 found that 98% of the participants were non-Hispanic whites, while African and Hispanic populations exposed to higher risk were significantly under-represented 32 . The lack of ethnic minority representation in glaucoma research limits our understanding of how the disease develops in these often high-risk groups. This under-representation can lead to diagnostic tools and screening protocols that fail to account for significant variations and potentially delay early diagnosis in African and Hispanic communities.
Genome-wide association studies (GWAS) have identified thousands of genetic loci and phenotypes relevant for clinical use in glaucoma in recent years. However, ethnic groups are unevenly represented in these studies: 95.6% of respondents are European, while people of Asian origin (3.1%) are significantly underrepresented 37 . Genetic testing has used ancestry-informative markers (AIMs), i. e., single nucleotide polymorphisms (SNPs), which exhibit significant differences in allele frequency between populations from different geographic regions. Studies have shown that biogeographical origin, based on AIMs, is correlated with features such as central corneal thickness and cup-to-disk ratio – two factors considered as risk factors for developing glaucoma 38 .
The study of mitochondrial DNA haplogroups has shown that differences in metabolism can play an important role in the development of diseases such as POAG and pseudoexfoliation glaucoma. One study identified certain African mitochondrial DNA haplogroups such as L1c2, L1c2b and L2, which occur in about 25% of the African-American population, as risk factors for the development of POAG 39 .
Such genetic factors may help explain why ‘people of colour’ – particularly individuals of African descent – have an increased risk of developing glaucoma or progressing from ocular hypertension (OHT) to glaucoma 40 . These findings demonstrate that sociological factors alone are not sufficient to explain differences in glaucoma prevalence and progression. Rather, they emphasise the importance of genomics and the need for balanced representation of patients from different ethnic groups in normative databases used for glaucoma diagnosis. At the same time, they open up new perspectives for the development of innovative therapies targeting mitochondrial functions and emphasise the urgency of taking greater ethnic diversity into account in future clinical trials 41 .
Why are Early Diagnosis and Treatment Important?
Prevention of irreversible vision loss
Unlike some other eye disorders, the damage caused by glaucoma is irreversible. Once vision is lost, it cannot be restored. This underlines the need for an early diagnosis that allows timely interventions to protect what vision remains. Prompt detection and treatment are essential to prevent or slow the progression of glaucoma. Approaches such as medications, laser therapy, or surgery can effectively lower intraocular pressure and prevent further damage to the optic nerve. By addressing the problem early, patients can significantly reduce their risk for permanent vision loss.
Improved quality of life
Vision loss due to glaucoma has a significant impact on daily life, from performing basic tasks to work and social interactions. Early diagnosis and treatment slow disease progression, preserve vision, and thus quality of life. Recently, increasing attention has been paid to integrating patientsʼ perspectives into the assessment of diseases. Beyond traditional measurement variables such as visual field loss and intraocular pressure, increasing consideration is being given to patient-relevant factors such as quality of life, symptoms, and treatment convenience 42 . Glaucoma affects daily life in many ways, including balance, mobility, and ambulation 43 . Studies show that glaucoma patients often walk more slowly and are at a higher risk of tripping or colliding with objects 44 , 45 , 46 , 47 . In addition, the risk of falls among glaucoma patients, especially at home, is significant, increasing the likelihood of fractures and other injuries 48 49 50 51 52 53 . Early diagnosis and intervention can reduce the progress of visual field loss, maintain mobility, and reduce the risk of falls.
Extended driving ability
Glaucoma also interferes with driving. Patients with glaucoma are more susceptible to traffic accidents 54 , 55 and many have to stop driving either voluntarily or are forced to because of their condition 56 , 57 . For those who continue to drive, there are often limitations such as avoiding driving at night or in bad weather conditions 56 . Losing a driving licence is a significant concern for many glaucoma sufferers 58 . Early diagnosis and consistent treatment can prolong years of driving safely, maintain autonomy, and reduce the emotional stress of losing a driverʼs license.
Psychological effects
The psychological effects of glaucoma are profound. Studies show that glaucoma patients are 10.6 times more likely to suffer from depression and 12.3 times more likely to experience anxiety than the general population 59 , 60 , possibly due to the limitations their condition places on independence and social interactions. By diagnosing and treating glaucoma early, patients can reduce the progression of visual impairment, potentially alleviating some of the psychological stress and sustaining a better quality of life for longer.
Conclusion
Glaucoma remains one of the leading causes of blindness worldwide and poses a significant challenge due to the difficulty of early diagnosis. Public awareness, regular eye examinations and advances in diagnostic technology are essential to address this problem. Early detection is particularly important because the damage caused by glaucoma is irreversible, but timely interventions can slow or stop the progression of the disease, preserving vision and improving quality of life.
Footnotes
Conflict of Interest The authors declare that they have no conflict of interest.
Interessenkonflikt Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.
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