Advanced loss of tone and elasticity leads to 'saggy, baggy' eyelids.
Involutional changes in skin, orbicularis and levator muscles, tarsus and canthal tendons cause age-related laxity of the eyelids.
Horizontal laxity of canthal tendons, attenuation or disinsertion of eyelid retractors, and overriding by pre-septal orbicularis oculi muscle cause 'drooping eyelids'.
Commonly involved in age-related eyelid disorders such as lower lid entropion and ectropion.
Involution: shrinkage of an organ in old age or when inactive.
Effects of Eyelid Ageing
Associated problems such as dry eye, redness, irritation, inflammation (related to eyelid ectropion or entropion).
Eyelid 'drooping' may impact vision and visual fields.
Example: Visual field defects caused by lid dermatochalasis, which improve after taping up the upper lid.
Ocular Surface Health and Ageing
Tear Film
Normal tear film thins between blinks.
Tear film volume is small (approximately 8mu unstimulated).
Average tear volume turnover rate: 16% per minute.
Osmolarity: average approximately 300mOsm/L.
pH approximately 7 to 7.4.
Ocular Surface Changes
Ocular surface abnormalities increase with age (Arita et al., 2008).
Ageing leads to changes in meibum composition, resulting in 'opaque' meibum (Sullivan et al., 2006).
Decreased nerve density leads to decreased sensitivity (cornea, conjunctiva?).
Decreased levels of sex hormones affect tear film quality.
Decreased lacrimal gland secretion.
Reduced/changed ocular surface immune responsiveness with ageing (Galleti and de Paiva, The Ocular Surf 2021: 20,139-162).
Possible outcomes: lower eyelid redness and telangiectasia, irregular eyelashes & ocular surface problems, gland openings affected, dry sore eyes.
Major Age-Related Changes: Ocular Surface
Lacrimal gland secretion diminishes, and the composition of secretion changes. Gland inflammation and ductal fibrosis have been reported.
Meibomian glands decrease in number, and their ducts keratinize, causing occlusion. Lipid secretions change in character.
Changes in tear composition and amount occur with age.
Conjunctival wrinkles (conjunctivochalasis) develop nasally and temporally.
Immune Response of Mucosal Ocular Surface
Age-related changes affect immune components of the ocular surface (Galleti and de Paivia, 2021).
Corneal Ageing
Corneal Sensitivity
Corneal sensitivity decreases with age.
Central and peripheral cornea are affected.
Nerve fiber length and density decrease with age (Chin et al., Cornea. 2024 43: 409-418; confocal microscopy).
Ageing Descemet’s Layer
Descemet’s layer: basement membrane produced by endothelial cells.
Thickness increases with age: approximately 5mum at birth, increasing to approximately 20mum in adults.
Anterior lamina = banded zone (prenatal) approximately 3mum.
Posterior lamina = non-banded zone (produced during life).
Peripheral cornea: age-related local thickenings in Descemet’s (Hassall-Henle bodies; 'bumps').
Ageing Cornea: Endothelium
Cell density decreases over life (approximately 4,000 cells/mm2 at birth, approximately 2,000 cells/mm2 at age 80 years).
<1,000 endothelial cells/mm2 results in cornea swelling and cloudiness.
Cell stress manifests as changes in endothelial cell shape (polymegethism) & polymorphism (pleomorphism).
Endothelial cell density decreases with age, disease, trauma, surgery (e.g., IOL), and contact lens wear.
Corneal Shape
Cornea flattens, decreasing refractive power, and decreases astigmatism in the vertical direction.
Corneal diameter increases after birth: average horizontal corneal diameter at birth is approximately 9.5 to 10.5 mm, and in adults approximately 12.0 mm.
Corneal Ageing Summary
Cornea (and ocular) astigmatism changes from with-the-rule to against-the-rule astigmatism (>- approximately 50 years).
Transparency (central) remains normal, dependent on endothelial density.
Decreased corneal sensitivity.
Increased Descemet’s membrane thickness.
Decreased endothelial cell density.
Anterior Chamber Depth and Ageing
Decreased anterior chamber depth with age (Atchison et al. 2010).
Anterior chamber shallows with age, and lens thickness increases.
Ageing of the Iris and Pupil
Functions of the Iris
Control light reaching the retina.
Optical effects (reduce aberrations by limiting ‘peripheral’ light).
Depth of focus at near.
Normal Human Iris Trivia
Size: approximately 2 to 9 mm diameter.
Regulated by sympathetic and parasympathetic systems.
Physiological anisocoria (different pupil sizes): 0.3 to 0.4mm in 50% of the population; > 1.5mm is due to ‘disease’.
Decentered nasally by 0.5mm.
Hippus (physiological tremor).
Ageing and Pupil Size
Pupil size is determined by age, level of retinal illumination (light reflex), emotional factors (e.g., pain, pleasure, fear), and accommodation and/or convergence (near reflex).
With age, pupils:
become smaller and less reactive to light.
are more difficult to dilate.
increase depth of focus/field.
increase diffractive effects.
are smaller, reducing fundus (retinal) illumination and 'view'.
Pupil Size Decrease with Age
Pupil size decreases with age, as shown in a study with n = 1862 participants.
Ageing Human Lens
Lens Features
Ellipsoid shape.
Biconvex: posterior surface with a steeper curve radius (rant approximately 10 mm; rpost approximately 6 mm; radius).
Gradient refractive index: increases from the surface inwards to the center.
Refractive index: cortex = 1.38 vs nucleus = 1.41.
Anterior pole; Lens thickness approximately 4mm; Equatorial diameter ~10mm; Equator and Posterior pole.
Physical Features of Lens Ageing
Lens thickness increases and lens equatorial diameter increases with age.
Lens Equivalent Refractive Index and Power
Lens equivalent refractive index and lens equivalent power decrease with age (Atchison et al., 2008).
Lens Stiffness
Lens stiffness increases with age.
Lens Spectral Transmission
Age-related loss in retinal illumination: decreasing light transmission + smaller pupil area.
Reasonably uniform % loss per decade.
Most impact on shorter violet (400-440 nm) and blue (440-500 nm) wavelengths.
Redox Biology of the Eye Lens
Young age: lens glutathione mostly in reduced form.
GSH levels are maintained by an active glutathione redox cycle that ensures a high GSH:GSSG ratio.
Aged and cataractous lenses have altered GSH/GSSG ratios.
Lens Chemical Barrier
A 'chemical lens barrier' forms at the cortex/nucleus interface around ~40 years ('middle-age'); it is an internal 'chemical barrier' to the diffusion of small molecules (Sweeney and Truscott, 1998; Moffat et al.,1999).
Consequences:
Impedes the flow of molecules such as antioxidants (e.g., GSH) into the nucleus, predisposing the lens nucleus to oxidation.
Unstable molecules, once inside the barrier, are present much longer in the lens nucleus.
Location of Active Metabolism in the Lens
Arrows indicate the direction of diffusion of glutathione (GSH) from active cells to metabolically inactive lens nucleus cells.
When glutathione is oxidized to GSSG in the lens nucleus, it diffuses down the concentration gradient in the opposite direction, towards the lens surface.
Synthesis and recycling of GSH decreases with age, leading to progressive loss of nuclear GSH and a rise in GSSG.
Lens UV-Filter Proteins
UV-filter proteins in the lens: low-molecular weight compounds that absorb UV radiation from 300 to 400 nm.
Can protect the lens (and the retina) from UVR-induced damage, but proteins degrade over time and with age.
With age, the ratio of primary to secondary UV filter proteins reduces from approximately 10:1 to 2:1.
Ageing of the Lens Summary
Physical and biomechanical changes:
Central thickness and equatorial lens diameter increase (lens fibers added over life).
Lens power decreases.
Anterior capsule thickness increases.
Lens stiffness increases.
Colour changes (yellowing related to changes in UV-barrier properties).
Refractive index across the lens changes; equivalent refractive index decreases.
Molecular changes:
Life-long protein changes: post-translational modifications accumulate in the human lens with age (from birth - not easy to quantify).
Lens proteins become progressively insoluble over time.
Lens ‘barrier’ forms around ~40 years, limiting GSH (reduced) moving into the nucleus, increasing nucleus oxidative stress (GSH -> GSSG).
UV-barrier proteins 'change’ with age and lens yellows; filters out shorter wavelengths of light.
Optical effects: light scattering + light absorption and transmission effects change with age (wavelength-related).
Ciliary Muscle and Ageing
Ciliary muscle maximum width increases significantly with age (Sheppard and Davies, 2011).
During accommodation, changes to ciliary muscle thickness and length remained constant throughout life (Sheppard and Davies, 2011).
During accommodation in the aged eye, ciliary muscle sectors behave similarly, suggesting accommodation is equal for the different sectors (Dominguez-Vincent et al., 2019).
Accommodative change in ciliary muscle diameter seems unaffected by ageing or IOL (intraocular lens) implantation.
Morphological changes do not seem to affect ciliary muscle contracting during accommodation, even for presbyopes, supporting a lenticular model of presbyopia development.
Ageing and Presbyopia
Presbyopia = loss of ability to focus light directly onto the retina at near.
Caused by age-related changes in the lens, lens capsules, lens zonules, ciliary muscle, and choroid.
Presbyopia Aetiologies or Causes?
Ageing lens is harder to deform or change shape (mechanical) + changes in lens size and shape that affect forces generated by zonules (geometrical).
Ciliary muscle theory: changes in tissue with ciliary muscle replaced by connective tissue, but the force of contraction is likely maintained with age.
Zonule theory: seems to change little with age.
Lens capsule theory: the anterior capsule thickens with age, less elastic, and does not change curvature so easily.
Lens nucleus stiffness: central lens power independent of ageing nucleus stiffness (Schachar et al., 2025 PLoS One) – unlikely presbyopia aetiology.
A combination of the various ‘theories’?
Ageing: Ciliary Body and Aqueous Humour Dynamics
Aqueous humour: age-related decrease in the rate of production by 15 to 35% between 20 to 70 years (Gabelt et al., 2005) + increase in trabecular meshwork (TM) outflow resistance with age.
Progressive decrease in human TM cell count with age (Alvarado et al. 1984; Grierson et al., 1982; Gabelt et al. 2005).
Increase in cells detaching from TM, 20 years (1.2 million cells), 80 years (~500,000 cells); decrease of 12,000 cells/year (Gabelt et al. 2005); 0.56% per year (Alvarado et al. 1984).
Grierson et al. (1982) reported a decline from 763,000 TM cells at 20 years to 403,000 at 80 years; loss of 6000 cells/year. (VISN2111)