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

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

3. Wiki homework Be thinking about your wiki final project topic
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

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

5. Function of cornea Performs ≈70% of focusing
Protects eye from outside world
No blood supply
Cleaned and nourished by tears and aqueous humour

6. 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
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.

7. Dry eye

8. 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

9. 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

10. 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

11. Lacrimal glands produce aqueous part Tears drain to naso-lacrimal sac
If not enough water then truly have dry eye

12. Goblet cells produce mucus
Helps watery film wet the eye surface

13. Tears then need to drain
Tears then drain out through holes in eyelid
If drain too quickly, eyes become dry
Plug these holes

14. 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

15. 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

16. 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
See: for discussion of the 5 layers

17. Cornea has 5 layers 2. Bowman’s layer
Strong layer of fibers composed of collagen
If injured it forms scar tissue

18. 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

19. 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
Descemet’s membrane

20. 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

21. 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

22. 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

23. 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

24. Fuchs dystrophy Endothelial layer deteriorates
Can’t pump out aqueous humour so cornea swells
Vision becomes blurry

25. Treatments for corneal dystrophies
Corneal transplants
Match by blood type
20% rejection rate

26. Treatment for corneal scars
Phototherapeutic keratectemy
Laser ablation
Remove scarred or damaged tissue
Use UV excimer laser under computer control

27. 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

28. Refractive error Astigmatism Multiple focal lengths so multiple images
Cornea is more curved in one direction than the other (like spoon or football)
Multiple focal lengths so multiple images
Always blurry

29. 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

30. 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

31. 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

32. 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

33. 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

34. What happens during LASIK surgery

35. 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

36. Comparisons suggest LASEK and LASIK produce equivalent results

37. 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

38. Possible complications - starbursts
LASIKdisaster.com

39. Possible complications - halos
LASIKdisaster.com

40. Ghosting

41. Near sighted problems - PRK

42. Far sighted problems

43. Possible problems

44. NEI - cataracts

46. Lens Lens Transparent so light is efficiently transmitted
High index so light is focused onto the retina

48. 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
Eye lens fiber cells filled with crystallins

49. Crystallins α-crystallins β and γ crystallins
Related to heat shock proteins
β and γ crystallins
γ crystallins are symmetric

50. 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!!!

51. 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

52. 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

53. 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

54. Cateract symptoms
Blurry vision
Poor night vision
Problems with glare

55. Cataracts
Congenital
Age related

56. Age related cataract prevention
Decrease sun exposure
Increase antioxidants
Stop smoking
Get eye exam

57. Treatment #1 Cut small incision (3 mm)
Remove front of lens to expose cataract
Use ultrasound to fragment cataract
Remove fragments

58. Treatment #2 Replacement lens Made of plastic Blocks UV
Is flexible so can attach to eye focusing muscles
Focus near and far!

59. Treatment #2 Introduce replacement lens into lens capsule
May only replace part of lens
Can improve spectral transmission (more blue)

60. Glaucoma

62. 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

63. 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

64. 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

65. Measuring eye pressure
Applanation tonometry
Measure applied pressure necessary to deflect cornea
Noncontact tonometry
Measure air pressure needed to deflect cornea

66. 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

67. 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

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

69. 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

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

71. 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

72. 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

73. Open fluid flow in meshwork or sclera

74. Use of marijuana to treat glaucoma

77. Next time
Gene therapy
How do you replace a faulty gene?