Aging and eye disease

From Longevity Wiki

Most eye diseases and uncorrectable visual impairments are age-related. A recent US based study demonstrated visual impairment increases as a function of age and is even more prevalent than previous accounts.[1]

The most prevalent eye diseases (glaucoma, macular degeneration, and diabetic retinopathy) all increase with age. Presbyopia and senile cataracts, considered a part of normal aging, are also common contributors to visual impairment that while treatable are not always accessible. Ocular surface disease is a less appreciated condition that also increases with age.[2][1][3][4]

Some of the most common eye diseases related to aging are cataracts, glaucoma, age-related macular degeneration, diabetic retinopathy or blepharitis and dry eyes.


Cataracts refer to cloudiness of the crystalline lens located inside the eye, just behind the iris. Clouding of the crystalline lens essentially is a universal occurrence in all humans with advancing age, but the degree and rate of progression can be highly variable. Often the lens change is gradual; mild lens changes can begin around age 40 with advancing opacity diagnosed as cataract or removed by surgery in greater than 50% of individuals by age 80.[5]


Cataracts increase as a function of aging. Globally they are the leading cause of treatable blindness. According to a recent analysis from the Global Burden of Disease Study caused a worldwide estimated 15.2 million cases of blindness and an aged 50+ years were blind, with an additional 78.8 million cases of moderate to severe vision impairment (MSVI) in individuals 50 years old and up.[6] Although The World Health Assembly Global Action Plan acheived it's target goal of a 25% reduction of avoidable vision impairment from the period of 2010 to 2019 for cataract blindness, the goal was not met for MSVI, and decreases in prevalence "were more than offset by global population growth and aging, leaving more people cataract blind and visually impaired than ever before."[6]


Most cataracts are related to aging, but may rarely also be either congenital, induced by trauma or result from toxicity. Speciallized lens proteins known as crystallins compose the lens lending to its transparency. The process has yet to be fully defined, but generally oxidation accelerates while metabolic activity slows in aged eyes, lending to modification and accumulation of lens proteins.[7] More recent investigations into differentially expressed microRNA (miRNA) in cataractous eyes discovered eight differentially expressed miRNAs that could be involved in the pathogenesis of senile cataract. The miRNA discovered were noted to be related to oxidative stress and autophagy.[8] Metabolic conditions, particularly diabetes, can accelerate cataract formation. Corticosteroids, radiation and heat are also associated with increased cataract formation.


Many patients first complain of night time glare especially from on-coming headlights or glare from the bright sunlight. Cataracts cause a deterioration in visual acuity and contrast.


The primary treatment of cataracts is surgical and cataract surgery is one of the most commonly performed surgeries in developed nations. However, as previously mentioned, there remains a large need for cataract surgery in some parts of the world


Glaucoma is a group of eye diseases and its pathogenesis is multifactorial. Glaucoma causes deterioration of the optic nerve, the nerve that connects the eye to the brain.[9] The most common type of glaucoma is known as primary open angle glaucoma (POAG) and is age-related, but glaucoma can also more rarely be congenital. Generally, risk for glaucoma increases starting around age 40.[10] Association studies have long demonstrated having a family history, especially of a first degree relative with glaucoma, is a risk factor. More recently specific gene associations have also been identified.[11]

Age-related macular degeneration

Age-related macular degeneration (AMD) is a common, age-related condition that affects the central area of the retina, which has the highest density of photoreceptors or light sensing cells. As such, it usually does not lead to blindness, but damage to the area can result in significant loss of central vision. Accumulation in the retina of the autofluorescent pigment lipofuscin leads to retinal pigment epithelium (RPE) apoptosis, and is believed to mediate the visual loss associated to some forms of AMD, such as dry-AMD.[12] Therefore, removal of lipofuscin from RPE cells has been proposed as a therapeutic strategy to treat dry-AMD conditions.[13]

ADORA2A (adenosine receptor 2A) inhibition with a small-molecule KW6002 (Istradefylline) may be a therapeutic approach to treat subretinal fibrosis associated with neovascular age-related macular degeneration (nAMD), the leading cause of vision loss in older adults.[14]


  1. 1.0 1.1 Flaxman, A. D., Wittenborn, J. S., Robalik, T., Gulia, R., Gerzoff, R. B., Lundeen, E. A., ... & Vision and Eye Health Surveillance System study group. (2021). Prevalence of Visual Acuity Loss or Blindness in the US: A Bayesian Meta-analysis. JAMA ophthalmology.
  2. Di Zazzo, A., Micera, A., Coassin, M., Varacalli, G., Foulsham, W., De Piano, M., & Bonini, S. (2019). Inflammaging at ocular surface: clinical and biomolecular analyses in healthy volunteers. Investigative ophthalmology & visual science, 60(5), 1769-1775.
  3. Den, S., Shimizu, K., Ikeda, T., Tsubota, K., Shimmura, S., & Shimazaki, J. (2006). Association between meibomian gland changes and aging, sex, or tear function. Cornea, 25(6), 651-655.
  4. Arita, R., Itoh, K., Inoue, K., Maeda, S., Maeda, K., Furuta, A., ... & Amano, S. (2009). Noncontact Meibography detects changes in meibomian glands in the Aging process in a normal Population and patients with meibomian gland dysfunction. Cornea, 28(11), S75-S79.
  6. 6.0 6.1 Pesudovs, K., Lansingh, V. C., Kempen, J. H., Steinmetz, J. D., Briant, P. S., Varma, R., ... & Bourne, R. R. (2021). Cataract-related blindness and vision impairment in 2020 and trends over time in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Investigative Ophthalmology & Visual Science, 62(8), 3523-3523.
  7. Lam, D., Rao, S. K., Ratra, V., Liu, Y., Mitchell, P., King, J., ... & Chang, D. F. (2015). Cataract. Nature reviews Disease primers, 1(1), 1-15.
  8. Kim, Y. J., Lee, W. J., Ko, B. W., Lim, H. W., Yeon, Y., Ahn, S. J., & Lee, B. R. (2021). Investigation of microRNA expression in anterior lens capsules of senile cataract patients and microRNA differences according to the cataract type. Translational Vision Science & Technology, 10(2), 14-14.
  11. Gramer, G., Weber, B. H., & Gramer, E. (2014). Results of a patient-directed survey on frequency of family history of glaucoma in 2170 patients. Investigative ophthalmology & visual science, 55(1), 259-264.
  12. Wolf G. Lipofuscin and macular degeneration. Nutr Rev. 2003 Oct;61(10):342-6. doi: 10.1301/nr.2003.oct.342-346. PMID: 14604266.
  13. Radu RA, Mata NL, Nusowitz S, et al. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt’s macular de- generation. Proc Nat Acad Sci U S A. 2003;100: 4742–4747.
  14. Qiuhua Yang et al. (Mar 2024). "Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice". SCIENCE TRANSLATIONAL MEDICINE, 16(737) doi:10.1126/scitranslmed.adk3868