Lecture #19

Eye diseases of cornea, lens and vitreous4/9/13

Animal wikis

• Great!• Some of my favorites

Writing: manatees, hummingbirdsLink to eye design: barn owls, panda

Wiki homework

• Be thinking about your wiki final project topicEmail it to me by end of Thursday

• It is fine if your topic evolves as you gather informationMay want to focus it down if find lots infoMay need to expand if not so much

Anterior eye disease

• CorneaDystrophiesRefractive errors

• LensCataracts

• Vitreous Glaucoma

Function of cornea

• Performs ≈70% of focusing

• Protects eye from outside world

• No blood supplyCleaned and nourished by tears and aqueous humour

Corneal disease• Conjunctiva

Mucous membrane lining eyelid and sclera Contains tiny blood vessels

• Pink eye - conjunctivitisInfection by either bacteria or virus

• Corneal infectionsBacterial or fungal invasion into corneal layers

Dry eye

Tears

• Basal tearsConstantly produced to nourish and moisten eyeMixture of aqueous and oily secretions

• Reflex tearsMade in response to irritation or emotionMore watery

What are tears?

• Tears are made of three layersOily, lipid layer - keeps aqueous layer from evaporatingAqueous layer - keeps eye moistMucin layer - helps aqueous layer spread

Meibomian gland produces lipid part

Lacrimal glands produce aqueous partTears drain to naso-lacrimal sac

Goblet cells produce mucus

Tears then need to drain

Tears then drain out through holes in eyelid

If drain too quickly, eyes become dry

Plug these holes

Dry eye

• If meibomian glands get blocked, there will not be enough lipids and tears will evaporate too quickly

• To unclog glandsHeat treatmentsDoxycyclineNutritional supplements

• May be other reasons not enough lipids

Dry eye

• If there is not enough aqueous part of tearsUse artificial tearsPlug up drainage holes so stay on eye longer

• May also be problems with mucin layer which wets the eye and helps aqueous layer to spreadNot sure how to improve it

Cornea has 5 layers

1. Epithelium10% of thicknessBlocks foreign matterAbsorbs O2 and nutrients

from tearsEpithelia cells grow and

are anchored to basement membrane

Many tiny neurons - very sensitive to pain

Cornea has 5 layers

2. Bowman’s layerStrong layer of fibers composed of collagen

If injured it forms scar tissue

Cornea has 5 layers3. Stroma

Comprises 90% of cornea thickness

Composed mostly of collagen (16%) and water (78%)

Gives cornea shape and transparencyUpper part of stroma repairs itself but lower part does not

Cornea has 5 layers4. Descemet’s membrane

Thin but strong protective layer

Made of collagen (different from stroma)

Made by endothelium

Can regenerate after injury

Descemet’s membrane

Cornea has 5 layers5. Endothelium

Extremely thin

Fluid slowly leaks from inside eye into stromaEndothelium pumps it back out so stroma doesn’t get cloudy!!

Endothelium does not regenerate - if damaged, need corneal transplant

Corneal dystrophies

• Over 20 kindsDystrophy - abnormal developmentInheritedAffect both eyes equallyBegin in one of 5 layers and spread to others

Layers become cloudy - so can’t see

Keratoconus• Thinning of middle of

cornea (stroma) causes cornea to change shape- cone like

• Most common corneal dystrophyAffects 1:2000

• Inherited or from wearing hard contacts or eye injuryUsually stabilizes and correct with glasses / contacts

Lattice dystrophy

• Build up of amyloid (protein) deposits in upper to middle stroma

• Create a lattice which worsens and makes cornea cloudy

Fuchs dystrophy

• Endothelial layer deteriorates

Can’t pump out aqueous humour so cornea swells

Vision becomes blurry

Treatments for corneal dystrophies

• Corneal transplants Match by blood type 20% rejection rate

Treatment for corneal scars

• Phototherapeutic keratectemy Laser ablationRemove scarred or damaged tissue

Use UV excimer laser under computer control

Refractive error

• If cornea has wrong curvature, image on retina is out of focus

Myopia - image focused in front of retina : 25% of people

Hyperopia - image focused behind retina

Refractive error• Astigmatism

Cornea is more curved in one direction than the other (like spoon or football)

Multiple focal lengths so multiple images

Always blurry

Treatments for refractive errors - reshaping the cornea

• RK - Radial keratotomy• PTK - Phototherapeutic keratectemy• LASEK - Laser assisted sub-epithelial

keritectomy • LASIK - Laser Assisted In Situ Keratomileusis

Radial keratotomy• Modify cornea shape

by cutting slits• Developed in Russia in

1970s• Unpredictable healing• Vision may change

through day or over time

• Not recommended

Treatment for refractive errors• Phototherapeutic

keratectomy Can also be used to reshape cornea - correct myopia

Remove epithelial layer and reshape upper part of cornea

Epithelial layer regenerates

Keratectomy - remove part of cornea

LASEK surgery• Laser assisted sub-

epithelial keratectomy• Cut and peel back

epithelial layer• Re-shape upper

stroma just below epithelium with laser

• Replace epithelial layer

LASIK refractive surgery

• Laser Assisted In Situ KeratomileusisCut a flap in cornea with blade or laser (this cuts more than just epithelium)Laser vaporizes stroma to reshape itFlap is folded back though doesn’t seal

• Epi-LASIK cuts thinner flap so does reseal

What happens during LASIK surgery

Reshaping of cornea

• Near sighted

• Far sighted

Comparisons suggest LASEK and LASIK produce equivalent results

Some reasons NOT to do LASIK• You may not be suited for procedure:

Eye diseaseThin corneasUnstable vision

• Vision may get worseUnstable cornea

• No long term data• LASIK corneal flap may be deep in cornea

These tissues do not regenerateFlap is permanent

Possible complications - starbursts

LASIKdisaster.com

Possible complications - halos

LASIKdisaster.com

Ghosting

Near sighted problems - PRK

Far sighted problems

Possible problems

NEI - cataracts

Lens

• LensTransparent so light is efficiently transmitted

High index so light is focused onto the retina

Lens composition• Composed of water

and lens crystallins (90% of protein)

• Crystallins made once and then stored in lens for rest of life

• Must remain soluble to be transparentEye lens fiber cells filled

with crystallins

Crystallins• α-crystallins

Related to heat shock proteins

• β and γ crystallins

γ crystallins are symmetric

Other proteins can be co-opted to form part of lens

Many are active metabolic enzymes elsewhere in body!!!

Recruitment of proteins

• Recruited to lens by changing gene expression• May be result of gene duplication followed by

new expression• Proteins selected which highly stable

Contribute to index of refractionInsensitive to UV damage

Crystallin structure

• Crystallins are present from birth • Processes which damage protein are bad

Oxidation, deamidation, cleavageResult in protein unfolding

• Normally α crystallins are chaperones keeping other proteins folded

• As lens proteins unfold, α crystallins used upUnfolded proteins form precipitatesLoss of lens transparency

Cataracts• Clouding of lens• Typically occurs with

age• 50% of people > 80

have cataracts• Cataracts affect 5.5

million people in US

Cateract symptoms• Blurry vision• Poor night vision• Problems with glare

Cataracts

• Congenital

• Age related

Age related cataract prevention

• Decrease sun exposure• Increase antioxidants• Stop smoking• Get eye exam

Treatment #1• Cut small incision (3

mm)• Remove front of lens to

expose cataract• Use ultrasound to

fragment cataract• Remove fragments

Treatment #2

• Replacement lensMade of plasticBlocks UV

Is flexible so can attach to eye focusing musclesFocus near and far!

Treatment #2• Introduce

replacement lens into lens capsule

• May only replace part of lens

• Can improve spectral transmission (more blue)

Glaucoma

Glaucoma

• Variety of diseases that result in loss of retinal ganglion cells

• Loss begins in periphery• 50% of people have glaucoma and don’t

realize it

Fluid flow at front of eyeAqueous humor is generated by ciliary body and flows into anterior chamber to nourish eye

Flows out where cornea and iris meet Iridocorneal angle

Trabecular and uveoscleral drainage Spongy tissues

Fluid flow at front of eye

If fluid does not drain: Pressure in eye builds up

This damages retinal ganglion cells and vision is lost

Measuring eye pressure• Applanation tonometry

Measure applied pressure necessary to deflect cornea

• Noncontact tonometryMeasure air pressure needed to deflect cornea

Caveats

• High intraoccular pressure (IOP) is highest risk factor but:Majority of people with high IOP do not get glaucomaOptic nerve damage can occur even without high pressure

-Low tension or normal tension glaucoma

Risk factors

• Affects 70 million people

• Age2 % over age 40; 7% over age 80Over age 40 - African Americans 5x more likelyOver age 60 - Mexican Americans more likely

• Family history of glaucomaThough not Mendelian trait

Symptoms

Gradual loss of peripheral visionCan be slow loss over years No painDifficult to notice effects

Kinds of glaucoma

• Open angle glaucomaFluid seems to keep flowing

• Developmental glaucomaAnterior portion of eye doesn’t develop correctly

• Pigmentary glaucomaIris pigment epithelium atrophies and pigment clogs drainage of fluid

Open angle glaucoma

Genetics

• 9 loci identified so far that initiate primary open angle glaucomaExplain only small % of cases

• Two genes which cause early onset glaucomaMyocilin (3% of cases)Optineurin

• Not obvious how genes cause the diseaseExpressed in both retinal ganglion cells and trabecular meshworkMay cause problems if protein misfolding

Treatments

• Eye drops or pillsDecrease fluid production or increase drainage

• Laser trabeculoplastyLaser widens holes in drainage meshwork

• Conventional surgery Create new exit pathways

Open fluid flow in meshwork or sclera

Use of marijuana to treat glaucoma

Next time

• Gene therapyHow do you replace a faulty gene?