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What is Really Going on in Glaucoma? 25 years of experience Richard R Dubielzig

What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

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Page 1: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

What is Really Going on in Glaucoma?25 years of experience

Richard R Dubielzig

Page 2: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Canine Primary Glaucoma

• Goniodysgenesis• Pectinate ligament dysplasia• Mesodermal dysgenesis• Open-angle, closed-cleft glaucoma (Peiffer)• Acute angle-closure glaucoma (Miller)• Who knows what else

Page 3: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina
Page 4: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Primary Glaucoma in Dogs• 28% of Cocker Spaniels in the COPLOW

collection are affected• 35% of Bassett Hounds • 62% Female

Page 5: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

The Normal Canine Angle

Dr Kerry Ketring

Page 6: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

The Normal Canine Angle

Primary Pectinate Ligament

Page 7: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

The Normal Canine Angle

Ciliary Cleft

Corneoscleral TrabecularMeshwork

Page 8: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

GoniodysgenesisNormal Pressure

Dr Kerry Ketring

Page 9: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

What is Canine Primary Glaucoma?• Sudden onset of painful, red, often blind eye with very

high pressures– In this study the time of disease is measured from when the

owner first notices a painful red eye (Hour 0)• The response to treatment is variable, but severe cases

are blind from the start

• Enucleation is a common outcome – When dealing with the second eye, enucleation is often

chosen very early (24 hours from the first signs of disease)

Page 10: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Pigment Dispersionand

Neutrophilic Inflammation

Chris Reilly

Page 11: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Pigment Dispersion in Primary Glaucoma

• Distinguish superior from inferior angle by pigment alone– 1 to 3 Days: 92%– 4 to 7 Days: 95%– Chronic: 79%

• Cells Stripped from Iris– 1 to 3 Days: 43%– 4 to 7 Days: 75%– Chronic: 55%

• Pigmented Cells in the Angle– 1 to 3 Days: 64%– 4 to 7 Days: 95%– Chronic: 50%

Reilly CM et al. (2005) Canine goniodysgenesis-related glaucoma: a morphologic reviewof 100 cases looking atinflammation and pigment

dispersion. Vet. Ophthal.

Page 12: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Neutrophilic Inflammation

• 1 to 3 Days: 86%• 4 to 7 Days: 50%• Chronic: 15%

Page 13: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Upper Angle

Lower Angle

Pigment Dispersion

Page 14: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

30 hour Glaucoma

Early Changes in the Iridocorneal Angle

Neutrophils and Spindle Cell Proliferation

Page 15: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

One Day Trabecular Meshwork

Evidence of Gradual Atrophy of the Corneoscleral Trabecular Meshwork

Normal Atrophic

Page 16: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Pre-Glaucoma: The Second Eye

The Up Side The Down Side

Page 17: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

The Second EyeAtrophy of the trabecular meshwork

Up Down

Page 18: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Case Study 34 hour glaucoma

5 year-old spayed Laborador

Page 19: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Case Study 34 hour glaucoma

5 year-old spayed Laborador

Radiating bands of retinalnecrosis

Page 20: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Case Study 34 hour glaucoma

Goniodysgenesis

Page 21: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Case Study 34 hour glaucoma

Page 22: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Case Study 34 hour glaucoma

“Red-Dead” Ganglion Cells

Page 23: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Effects of Primary Glaucoma on the Optic Nerve and the Retina

Two Day Glaucoma, Canine 24 Hour Glaucoma, Canine

Page 24: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

30 hour Glaucoma

Page 25: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Optic Nerve 2 to 4 Days

Necrosis of the neuropil

Page 26: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Three day Glaucoma

Page 27: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

4 Day Optic Nerve HeadPhagocytosis/Malacia

Page 28: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Five day Canine Glaucoma

Stained for phagocytes

Page 29: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

5 day Canine Glaucoma

Gitter cell macrophages

Page 30: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

By seven days the opticnerve head is end-stagewith deep cupping andgliosis

Page 31: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Schnabel's cavernous optic atrophy

Entrappedvitreous

Page 32: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Early Progression of Retinal Disease

Kerry Ketring images

Page 33: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

2 to 4 Day Glaucoma (Canine)

Page 34: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

2 to 4 Day Glaucoma (Canine)

Sampled forHistopathology

Page 35: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Four Day Glaucoma

Page 36: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

One Day GlaucomaRed-Dead Ganglion Cells

Page 37: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Proptosis, 3 days

Page 38: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Electronmicrograph of 4-Day GlaucomaApoptosis

Page 39: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

BuphthalmosScleral Thickness

NormalCanine

4 DayGlaucoma

7 Day Glaucoma

Page 40: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

BuphthalmosScleral Thickness

NormalCanine

4 DayGlaucoma

7 Day Glaucoma

Page 41: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Average Ganglion Cell CountsThis count includes “Red Dead” cells

Page 42: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

“Red Dead” Ganglion Cells

Page 43: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Average Retinal Thickness, μ

Page 44: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Average Scleral Thickness, μ

Page 45: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Phagocytes in the Retina and Optic Nerve

Page 46: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Retinal MHC-2 Phagocytes

Page 47: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Optic Nerve MHC-2 Phagocytes

Page 48: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

MHC-2 on 4-5 Day Glaucoma Optic Nerve

Page 49: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Retinal GFAP

Page 50: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Suggested TimelineBefore the Owner Detects Pain

1. Young normotensive dog with goniodysgenesisa) Ciliary cleft open at first

2. Gradual loss of ganglion cellsa) Likely bouts of pressure spikesb) Pigment dispersion?

3. Gradual atrophy of the corneoscleral trabecular meshwork4. Collapse of the ciliary cleft

a) Detected with ultrasound biomicroscopy

Page 51: What is Really Going on in Glaucoma? 25 years of experience · Case Study 34 hour glaucoma “Red-Dead” Ganglion Cells. Effects of Primary Glaucoma on the Optic Nerve and the Retina

Suggested TimelineAfter the Owner Detects Pain

1. Sudden painful crisisa) Pathology suggests an event 2-3 days before owner

detects2. Stepwise rapid necrosis of the optic nerve and retina

a) Neutrophils, dead ganglion cells, apoptosis, and finally phagocytosis

3. The second eye progresses through the same cycle