Chi-Chao Chan, M.D. Immunopathology Section Laboratory of Immunology National Eye Institute National Institutes of Health

1. Cornea and Lens
Histopathology
Refractive Surgery
Cataracts
High Myopia
Chi-Chao Chan, M.D.
Immunopathology Section
Laboratory of Immunology
National Eye Institute
National Institutes of Health

2. Classification
Ocular Tissue (a
z)
cornea
Trabecular meshwork
Conjunctiva
conjunctiva
Cornea
sclera
Lens
Optic Nerve
retina
Orbit/Extraocular Muscles
Retina
vitreous
Sclera
Trabecular meshwork
Uvea (Iris, Ciliary body, Choroid)
Vitreous
iris
Ciliary body
lens
retina
choroid
sclera
optic nerve
 The average size of a normal adult eye: 25 mm (h) x 24.5 mm (v) x 24 mm (AP)

3. Conjunctiva
Gross (Macroscopic structure):
» Palpebral (Tarsal) Conjunctiva
» Fornical Conjunctiva
» Bulbar Conjunctiva
epithelium
Microscopic Structure:
» Epithelium (two or more layers)
– Stratified epithelia, goblet cells
» Substantia propria (fibrovascular tissue including
nerves and lymphatics)
Substantia propria

4. Cornea
Cornea
Epithelium
Bowman
layer
Stroma
Keratocyte
Descement
membrane
Endothelium

5. Cornea
Diameter: 11.5 x 10.5 mm (adult)
Layers (520-540 mm centrally):
» Epithelium (5-6 layers)
» Bowman’s Layer (8 -14 nm)
» Stroma (90% thickness)
» Descemet’s Membrane (10-12 mm)
» Endothelium (single layer)
Nerve: unmyelinated nerves
Avascular tissue

6. Refractive Surgery
An eye surgery used to improve the refractive
state of the eye and decrease or eliminate
dependency on glasses or contact lenses
Remodeling of the cornea
The most common methods today use excimer
lasers to reshape curvature of the cornea
Successful refractive eye surgery can reduce or
cure common vision disorders such as myopia
(near sight), hyperopia (far sight) and astigmatism
(non-perfected spherical cornea).

7. Refractive Surgery
Radial Keratotomy (RK)
Astigmatic Keratotomy (AK)
Automated Lamellar Keratoplasty (ALK)
Laser Refractive Surgery
– Phototherapeutic Keratotomy (PTK)
– Photorefractive Keratectomy (PRK)
– Laser In Situ Keratomileusis (LASIK)
– EPI-LASIK
– Customized Transepithelial No-touch (C-TEN)
Intrastromal Corneal Ring (Intacs)

8. LASIK
Photorefractive Keratectomy (PRK)
LASIK
LASIK: Laser Assisted In Situ Keratomileusis
A type of refractive surgery
Wound healing only at the periphery of micotome incision
Stromal reaction less after LASIK than PRK
Requires a long time for wound healing
Perz-Santonja, et al. Refract Surg 1998;14:601-9.
Park, et al. Cataract Refract Surg 1999;25:842-50.
Wachtlin, et al. Refract Surg 1999;15:451-8.
Kato. Br J Ophthalmol 1999;83:1302-5.

9. LASIK

10. LASIK
Intralamellar scar
• Origin of lamellar binding:
• Binding of collagen fibrils
• Interweaving of lamellae
• Stabilization by ground substance
(extracellular matrix)
Maurice & Monroe. Exp Eye Res 1990;50:59-63.

11. LASIK
Microkeratome
Courtesy of J. Douglas Cameron, MD

12. LASIK
Microkeratome
Courtesy of J. Douglas Cameron, MD

13. LASIK
Femtosecond Microkeratome: Flap Hinge
Courtesy of J. Douglas Cameron, MD

14. LASIK
Microkeratome:
Flap hinge
Courtesy of J. Douglas Cameron, MD

15. LASIK
Microkeratome:
Flap hinge
Courtesy of J. Douglas Cameron, MD

16. INTACS
• A 47-yr-old man with a
history of keratoconus
and failure of using a
Rigid Gas Permeable
(RGP) contact lens, O.S.
• Implantation of Intacs,
O.U.
• 10 mons later: Multiple,
whitish, small crystalline
deposits around the
edges and the border of
the superior Intacs
segment nasally
• Penetrating keratoplasty,
O.S.
Cao, et al. J Med Case Rep 2011, 5:398.

17. INTACS
A. A space containing residue
plastic (Intacs) material is
surrounded by a dense
acellular/ hypocellular
collagen scar. The channel
haze is observed at the inner
edge of Intacs.
B. The severely attenuated
corneal endothelial cells.
C. The acidophilic densification
and mild inflammatory cell
infiltration at the inner edge of
Intacs.
D. Immunochemistry of CD68
shows macrophage (CD68+)
infiltration at the inner edge of
Intacs.
Cao, et al. J Med Case Rep 2011, 5:398.

18. Neovascularization
• Corneal neovascularization is an unwanted
vascular growth into the avascular cornea.
Contact lens causing
»
Soft contact lens wearers - micropannus
Inflammation
»
»
Vascularized pannus
Stromal keratitis – e.g., Cogan syndrome
Stem cell deficiency
Poor wound healing
»
Corneal transplantation under 2 yr.

19. Neovascularization
Stem cell deficiency due to graft vs host disease

20. Neovascularization
Cogan Keratopathy
Courtesy of. David G. Cogan, MD

21. Lens
Cornea
Lens
Cornea
Lens

22. Lens
Gross (Macroscopic structure):
- Soft, elastic, avascular, transparent, highly refractile, biconvex
structure composed of mainly crystallins
- Anterioposterior: 3.5 - 5 mm (birth-adult) Equatorial: 6.4-9.0 mm
(birth-adult)
Microscopic Structure:
- Capsule
- Zonules
- Lens Cells: Epithelium
- Anterior
- Equatorial
- Cortex and Nucleus
capsule
epithelium
cortex
nucleus

23. Lens
Microscopic Structure:
capsule
Capsule
Zonules
Lens Cells: Epithelium
-
epithelium
cortex
Anterior
Equatorial
nucleus
Cortex and Nucleus
Zonules
C.B.
Posterior
lens

24. Transparent tissues:
• Cornea
• Lens
Photographs using a fish-eye lens

25. Lens
Lens Equator:
• Capsule
• Epithelia
• Lens fiber
Bow region
Lens epithelial cell

26. Lens

27. Lens: Congenital Cataracts
• Congenital cataract: opacity present at birth
• Infantile cataract: opacity during 1st year life
• Spherophakic
• Lamellar, Polar, Sutural,
Coronary, Cerulean,
Nuclear, Capsular;
Complete,
Membranous
• Rubella

28. Lens: Congenital Cataracts
Trisomy 13
Pierre Robin
Trisomy 18
PHPV
*

29. Lens: Adult Cataracts
Aging
–
Nuclear, Cortical, Posterior Subcapsular
–
In theory, everyone would get cataract if one lives long enough
Drug-induced
–
Corticosteroids, Phenothiazines, Miotics, Aminodarone, etc.
Trauma
–
Contusion, Injury: mechanical, chemical, radiation, etc.
Metabolic
–
Diabetes Mellitus, Galactosemia, Wilson Disease, etc.
Nutritional

30. Lens: Adult Cataracts
Exfoliation Syndrome
–
–
True Exfoliation
Exfoliation Syndrome (Pseudoexfoliation)
Cataract Associated with Uveitis
Cataract & Skin Diseases
–
Atopic Dermatitis
Glaukomflecken
Cataract Associated with Degenerative
Disorders
–
Retinitis Pigmentosa, Essential Iris Atrophy, etc.

31. Cataract: Anterior

32. Cataract: Equator

33. Cataract: Nucleus

34. Cataract: Posterior

35. Cataract: Soemmering’s Ring
• Dumbbell shape
• Congenital
• IOL

36. Cataract: Periphery

37. Cataract: IOL
• Cortical cleanup
• IOL material
• Optic edge
design
• Anterior capsule

38. Cataract: Exfoliation
•
•
•
•
Age related disease
Accumulation of abnormal fibrillar extracellular material
Anterior segment involvement
Cause cataract and glaucoma
SEM
a. SEM: lens capsule
b. TEM: lens capsule
c. TEM: lens epithelium
Z: zonular fiber/lamella
Ritch, Schlotzer-Schrehardt.
Surv Ophthalmol 2001;45:265315.

39. Axial Myopia
Average axial length of normal eye is
23.5-24.0 mm

40. Fundus Manifestations
Tilted optic nerve
Peripapillary chorioretinal atrophy
Peripheral retinal changes
Myopic Maculopathy
Posterior staphyloma
Macular schisis
Atrophic changes in the RPE and choroid
Lacquer cracks
Choroidal neovascularization
Macular atrophy

41. Tilted Optic Nerve Head
•
•
•
Because of the elongated eye, the nerve inserts obliquely
Most commonly, the nerve head is tilted toward the temporal side
This can make the assessment of the cup:disc ratio difficult and OCT nerve may be unreliable

42. Peripapillary
Chorioretinal Atrophy
• Due to tangential tractional forces of the elongating globe, the RPE, Bruch’s
membrane, and choroid fall short of reaching the entrance of the nerve into
the eye, and bare sclera is seen

43. Peripheral Retinal Changes








Lattice degeneration
Paving-stone degeneration
Pigmentary degeneration
Chorioretinal atrophy
White without pressure
Retinal holes
Retinal tears
Retinal detachments

44. Lattice Degeneration
•
•
Can develop retinal tear, breaks/holes
May progress to retinal detachment

45. Paving-stone Degeneration
Cobblestone degeneration

46. Posterior Staphyloma
• Abnormal elongation of the globe and the attenuation of
the sclera are accompanied by a localized ectasia
involving the sclera, choroid, and RPE (outward bowing)
• Histologically, staphylomas contain decreased amounts of
scleral collagen bundles and decrease in caliber
• Axial length elongation and/or posterior staphyloma may
generate inward tractional force which is opposed by the
residual posterior vitreous cortex, ILM, and/or retinal
vessels
• Detected in 9-35% of highly myopic eyes with posterior
staphylomas
• Majority remain stable
• Can lead to foveal detachment and/or macular hole

47. Posterior Staphyloma
• The prevalence and severity of staphylomas are found to increase with greater age, eye
length, and myopic refraction
• Most commonly involves the posterior pole, extending from 2 to 5 disc diameters nasal to the
optic nerve to an area involving the macula
• Best seen on B-scan ultrasound

48. Macular Foveoschisis
Detected in 9-35% of highly myopic eyes with posterior
staphylomas
• Majority remain stable
• Can lead to foveal detachment and/or macular hole
•

49. Macular Foveoschisis
Tnag, et al. J Ophthalmol 2010, 2010:1-4.
• interbridging strands in the outer plexiform layer of the
macular region
• located mainly in the outer plexiform layer

50. Atrophic Changes in the
RPE and Choroid
Early degenerative changes affect the
choriocapillaris and RPE
– Loss of choroidal melanocytes and RPE atrophy
 'tessellated/tigroid' fundus

51. Atrophic Changes in the
RPE and Choroid
In later stages, the neuroretina also
becomes atrophic leading to generalized
and/or patchy atrophy
– Vision may begin to be affected at this stage

52. Lacquer Cracks
• Yellow-white linear or stellate lesions that are typically horizontal oriented and branched
• Represent mechanical breaks of the RPE, Bruch’s membrane, and choriocapillaris from
elongation of the globe
• Usually occur in eyes >26.5 mm in length and more common in males
• Macular hemorrhages can sometime occur in the crack in the absence of CNV
• Number usually increase over time and can be associated with the development of atrophy
• Important prognostic factor for the development of CNV

53. Thank you!