Glaucoma, a leading cause of irreversible blindness worldwide, poses a significant public health challenge with approximately 80 million individuals affected globally. Alarmingly, half of these cases often go undiagnosed, exacerbating the risk of vision loss. In India alone, nearly 12 million people grapple with this condition, with a staggering 40-50 percent of cases evading detection. With projections indicating a rise in global blindness attributed to glaucoma, it becomes imperative to delve into its intricate mechanisms and risk factors.
While glaucoma manifests as a gradual loss of retinal ganglion cells (RGCs), its etiology remains elusive despite extensive research efforts. Age serves as a prominent risk factor, with individuals over 40 facing heightened susceptibility. Research also indicates a strong genetic predisposition, particularly evident in cases of juvenile-onset and early adult-onset glaucoma linked to specific gene mutations. The pathophysiology of glaucoma is multifaceted, involving an interplay of genetic predisposition, environmental influences, and stochastic factors. This complexity underscores the importance of exploring the delicate balance between nature and nurture in shaping glaucoma risk.
Exploring the Genetic Basis of Glaucoma
In recent years, there has been a notable shift in uncovering the genetic origins of glaucoma, marking a pivotal moment in enhancing our comprehension of this complex condition.
Primary open-angle glaucoma (POAG)
Primary open-angle glaucoma (POAG) is the most common type, characterized by no apparent eye abnormalities. While mutations in genes like myocilin, optineurin, and CYP1B1 contribute to some cases, recent genetic studies found more prevalent risk factors. These include alterations in DNA sequences near genes like CAV1/CAV2, CDKN2B antisense RNA, TMCO1, SIX1/SIX6, and LRP12/ZFPM2, as well as DNA loss in TBK1 and GALC, shedding light on various genetic elements associated with POAG.
Primary angle-closure glaucoma (PACG)
Primary angle-closure glaucoma (PACG) ranks as the second most prevalent type globally, impacting over 16 million individuals. It occurs when the drainage angle closes, hindering fluid outflow and elevating intraocular pressure. A recent extensive genetic investigation pinpointed genetic variations linked to PACG, particularly in or near PLEKHA7, PCMTD1/ST18, and COL11A1 genes. However, the exact role of these genes in PACG remains unclear.
Exfoliation glaucoma (XFG)
Exfoliation glaucoma (XFG), also known as pseudoexfoliation glaucoma, impacts millions globally and stands as the most prevalent identifiable type of open-angle glaucoma. It arises from exfoliation syndrome, a condition marked by the accumulation of white protein-like material on the lens and within the eye’s drainage system, as well as other body tissues. Genetic variations in the LOXL1 and CNTNAP2 genes have been linked to XFG. Ongoing research aims to elucidate how these genes influence the formation of protein deposits and their role in glaucoma development.
Understanding Environmental Factors in Glaucoma Risk
Environmental factors play a crucial role in influencing primary open-angle glaucoma (POAG), impacting both intraocular pressure (IOP) and the rate of retinal ganglion cell apoptosis. While few environmental contributors to POAG are currently identified, certain activities like playing wind instruments, drinking coffee, specific yoga poses, tight necktie wear, and weightlifting can elevate IOP, while general physical exercise tends to lower it. Additionally, nutritional choices like dietary fat and antioxidant intake, along with lifestyle habits such as smoking and postmenopausal hormone use, may influence POAG development. Further research is needed to fully understand their impact on glaucoma onset. Notably, there’s evidence of a gene-environment interaction between hormone replacement therapy and NOS3, a gene associated with nitric oxide synthase 3, as a POAG risk factor.
Residence in northern latitudes emerges as a significant risk factor for exfoliation syndrome (ES) and its related condition, exfoliation glaucoma. ES involves extracellular deposits and stands as the primary cause of secondary open-angle glaucoma. A retrospective study of over 3,300 incident ES cases in northern U.S. residents found an increased risk of ES development, while residing in southern latitudes correlated with reduced ES risk. Furthermore, adjustments for environmental effects revealed associations between climatic factors like high July temperatures and decreased ES risk, alongside increased risk with greater sunshine exposure. These findings suggest that factors like ambient temperature and sunlight exposure serve as environmental triggers for ES, although other elements of northern latitude living, such as altered vitamin D metabolism, could also contribute.
Conclusion
In conclusion, while genetic predispositions play a significant role in glaucoma, environmental factors also exert considerable influence on the risk and progression of the disease. Understanding these environmental risk factors is crucial for developing preventive strategies and personalized treatment approaches. Further research into the interplay between genetics and the environment will deepen our understanding of glaucoma’s complex pathogenesis and pave the way for more effective management and ultimately, improved outcomes for patients. By addressing both genetic and environmental aspects comprehensively, we can move closer to reducing the burden of glaucoma and preserving vision for millions worldwide.
The author is the Director of Sathyan Eye Care Hospital & Coimbatore Glaucoma Foundation.