Eye diseases of cornea, lens and vitreous 4/9/13 Lecture #19 Eye diseases of cornea, lens and vitreous 4/9/13

Animal wikis Great! Some of my favorites Writing: manatees, hummingbirds Link to eye design: barn owls, panda

Wiki homework Be thinking about your wiki final project topic Email it to me by end of Thursday It is fine if your topic evolves as you gather information May want to focus it down if find lots info May need to expand if not so much

Anterior eye disease Cornea Lens Vitreous Dystrophies Refractive errors Lens Cataracts Vitreous Glaucoma

Function of cornea Performs ≈70% of focusing Protects eye from outside world No blood supply Cleaned and nourished by tears and aqueous humour http://www.eyehub.com/images/eyecyclopedia/cornea.gif

Corneal disease Corneal infections Conjunctiva Mucous membrane lining eyelid and sclera Contains tiny blood vessels Pink eye - conjunctivitis Infection by either bacteria or virus Corneal infections Bacterial or fungal invasion into corneal layers http://64.143.176.9/library/healthguide/en-us/images/media/medical/hw/h9991343_005.jpg Most often caused by virus, same one as causes common cold. If child gets it, you have to remove them from public setting and get them treated for bacterial infection though it can often be the untreatable viral form. Both are pretty contagious.

Dry eye

Tears Basal tears Reflex tears Constantly produced to nourish and moisten eye Mixture of aqueous and oily secretions Reflex tears Made in response to irritation or emotion More watery See for some entertaining http://www.dryeyezone.com/encyclopedia/dryeyesyndrome.html

What are tears? Tears are made of three layers Oily, lipid layer - keeps aqueous layer from evaporating Aqueous layer - keeps eye moist Mucin layer - helps aqueous layer spread

Meibomian gland produces lipid part Discovered by Heinrich Meibom in 1600’s Meibomian gland makes meibum - oily part of tears; 50 glands on upper lid; 25 on lower

Lacrimal glands produce aqueous part Tears drain to naso-lacrimal sac http://eyelearn.med.utoronto.ca/Lectures05-06/Anatomy/images/15Lacr13.jpg If not enough water then truly have dry eye

Goblet cells produce mucus http://www.edinburgh-eyetests.co.uk/tearfilm.jpg Helps watery film wet the eye surface

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 glands Heat treatments Doxycycline Nutritional supplements May be other reasons not enough lipids

Dry eye If there is not enough aqueous part of tears Use artificial tears Plug up drainage holes so stay on eye longer May also be problems with mucin layer which wets the eye and helps aqueous layer to spread Not sure how to improve it

Cornea has 5 layers Epithelium 10% of thickness Blocks foreign matter Absorbs O2 and nutrients from tears Epithelia cells grow and are anchored to basement membrane Many tiny neurons - very sensitive to pain http://www.laservue.net/images/cornea_crosssection_en.jpg See: http://www.nei.nih.gov/health/cornealdisease/#0 for discussion of the 5 layers

Cornea has 5 layers 2. Bowman’s layer Strong layer of fibers composed of collagen If injured it forms scar tissue http://www.eyehub.com/images/eyecyclopedia/cornea.gif

Cornea has 5 layers 3. Stroma Comprises 90% of cornea thickness Composed mostly of collagen (16%) and water (78%) Gives cornea shape and transparency Upper part of stroma repairs itself but lower part does not http://www.eyehub.com/images/eyecyclopedia/cornea.gif

Cornea has 5 layers 4. Descemet’s membrane Thin but strong protective layer Made of collagen (different from stroma) Made by endothelium Can regenerate after injury http://www.eyehub.com/images/eyecyclopedia/cornea.gif Descemet’s membrane

Cornea has 5 layers 5. Endothelium Extremely thin Fluid slowly leaks from inside eye into stroma Endothelium pumps it back out so stroma doesn’t get cloudy!! Endothelium does not regenerate - if damaged, need corneal transplant http://www.eyehub.com/images/eyecyclopedia/cornea.gif

Corneal dystrophies Over 20 kinds Dystrophy - abnormal development Inherited Affect both eyes equally Begin 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 dystrophy Affects 1:2000 Inherited or from wearing hard contacts or eye injury Usually stabilizes and correct with glasses / contacts https://www.eyeconx.com/uploadimages/keratoconusA.jpg

Lattice dystrophy Build up of amyloid (protein) deposits in upper to middle stroma Create a lattice which worsens and makes cornea cloudy Most common occurs in children age 2-7 Treat with corneal transplant though 1/2 of people will get latice formation again

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 http://apps.uwhealth.org/health/adam/graphics/images/en/10226.jpg

Treatment for corneal scars Phototherapeutic keratectemy Laser ablation Remove scarred or damaged tissue Use UV excimer laser under computer control http://www.gutsehen.de/gfx/prk.jpg

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 Multiple focal lengths so multiple images Cornea is more curved in one direction than the other (like spoon or football) http://www.cullomeyecenter.com/index.cfm/conditions/astigmatism 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 http://www.gutsehen.de/gfx/prk.jpg 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 http://www.lasereyesite.com/index.html

LASIK refractive surgery Laser Assisted In Situ Keratomileusis Cut a flap in cornea with blade or laser (this cuts more than just epithelium) Laser vaporizes stroma to reshape it Flap is folded back though doesn’t seal Epi-LASIK cuts thinner flap so does reseal http://www.internationalmedicalcentre.com/images/lasik01.jpg

What happens during LASIK surgery http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/SurgeryandLifeSupport/LASIK/ucm133329.htm

Reshaping of cornea Near sighted Far sighted Near sighted focuses too much. Need to make less rounded / more flat Far sighted focuses not enough. Need to make more rounded / less flat

Comparisons suggest LASEK and LASIK produce equivalent results

Some reasons NOT to do LASIK You may not be suited for procedure: Eye disease Thin corneas Unstable vision Vision may get worse Unstable cornea No long term data LASIK corneal flap may be deep in cornea These tissues do not regenerate Flap is permanent

Possible complications - starbursts LASIKdisaster.com

Possible complications - halos LASIKdisaster.com

Ghosting

Near sighted problems - PRK http://www.fda.gov/cdrh/pdf/P930016S012d.pdf

Far sighted problems

Possible problems http://www.lasikdisaster.com/

NEI - cataracts

Lens Lens Transparent so light is efficiently transmitted High index so light is focused onto the retina http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/8785.jpg

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 transparent http://www.cryst.bbk.ac.uk/research/crystallin/Cortical%20cataract.html Eye lens fiber cells filled with crystallins

Crystallins α-crystallins β and γ crystallins Related to heat shock proteins β and γ crystallins http://www.cryst.bbk.ac.uk/research/crystallin/2domaingamcryst.jpg γ crystallins are symmetric

Other proteins can be co-opted to form part of lens Taxon specific crystallins which have in addition to alpha, beta and gamma 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 refraction Insensitive to UV damage

Crystallin structure Crystallins are present from birth Processes which damage protein are bad Oxidation, deamidation, cleavage Result in protein unfolding Normally α crystallins are chaperones keeping other proteins folded As lens proteins unfold, α crystallins used up Unfolded proteins form precipitates Loss of lens transparency Deamidation - removal of NH2 group - damages certain amino acids which would impact protein stability

Cataracts Clouding of lens Typically occurs with age 50% of people > 80 have cataracts Cataracts affect 5.5 million people in US ftp://ftp.nei.nih.gov/eyedis/EDA12_72.tif

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 http://www.eyesite.org/cataractvideo.html

Treatment #2 Replacement lens Made of plastic Blocks UV Is flexible so can attach to eye focusing muscles Focus near and far! http://www.eyesite.org/cataractvideo.html

Treatment #2 Introduce replacement lens into lens capsule May only replace part of lens Can improve spectral transmission (more blue) http://www.eyesite.org/cataractvideo.html

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 eye Aqueous 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 tonometry Measure air pressure needed to deflect cornea http://www.glaukooma.com/content_images/tonometry.jpg

Caveats High intraoccular pressure (IOP) is highest risk factor but: Majority of people with high IOP do not get glaucoma Optic nerve damage can occur even without high pressure -Low tension or normal tension glaucoma

Risk factors Affects 70 million people Age Family history of glaucoma 2 % over age 40; 7% over age 80 Over age 40 - African Americans 5x more likely Over age 60 - Mexican Americans more likely Family history of glaucoma Though not Mendelian trait

Symptoms Gradual loss of peripheral vision Can be slow loss over years No pain Difficult to notice effects

Kinds of glaucoma Open angle glaucoma Developmental glaucoma Fluid seems to keep flowing Developmental glaucoma Anterior portion of eye doesn’t develop correctly Pigmentary glaucoma Iris pigment epithelium atrophies and pigment clogs drainage of fluid

Open angle glaucoma The thing to note is that there are multiple factors on many different chromosomes

Genetics 9 loci identified so far that initiate primary open angle glaucoma Explain only small % of cases Two genes which cause early onset glaucoma Myocilin (3% of cases) Optineurin Not obvious how genes cause the disease Expressed in both retinal ganglion cells and trabecular meshwork May cause problems if protein misfolding

Treatments Eye drops or pills Laser trabeculoplasty Decrease fluid production or increase drainage Laser trabeculoplasty Laser 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 therapy How do you replace a faulty gene?