What’sthePressureinGlaucoma,1or2?

MitchIbachOD,FAAOVanceThompsonVisionFinancialDisclosures:Glaukos (honorarium)Equinox(invested)

Glaucomaisa

1PressureDisease

Common Belief:

Glaucomaisa

2PressureDisease

Likely Truth:Problem#1

• Whatisglaucoma?

Answer#1

• Wedon’tknow Whatwedoknowü Opticneuropathyü Cuppingü Visualfieldloss

Problem#2

• Whatcausescuppingandfieldloss?

Answer#2

• Wedon’tknow Whatwedoknowü IOPmatters

WhatWeDoKnow

• MeanIOP=20mmHG,Treatmentgroupreducedto15mmHG(25%)

• VFprogression:62%controlvs.45%treatment

• RiskofVFprogressiondecreased10%forevery1mmHG IOPlowering.IOPMATTERS

Leske, C., Heijl, A., Hyman, L., & Bengtsson, B. (1999, November). Early Manifest Glaucoma Trial. Ophthalmology, 106(11), 2144-2153.

Problem#3

• WhydoesIOPmatter?

Answer#3

• Wedon’tknow Whatwedoknowü IOPisthepressure

insidetheeye

WhatWeDoKnow

OcularHypertensionTreatmentStudy

4.4%9.5%5 years

Gordon, M., Beiser, J., Brandt, J., Heuer, D., Higginbotham, E., Johnson, C., & Keltner, J. (2002, June). The Ocular Hypertension Treatment Study. Archives of Ophthalmology, 120, 714-720.

WhatWeDoKnow- OHTS

Coleman, A., Gordon, M., Kass, M., & Beiser, J. (2004, October). Baseline Risk Factors for the Development of Primary Open-Angle Glaucoma in The Ocular Hypertension Treatment Study. American Journal of Ophthalmology, 138(4), 684-685.

WhatWeDoKnow- OCTHelps!

Radcliffe, N., & Hussnain, S. (2014, September). Optical Coherence Tomography in Glaucoma. Glaucoma Today, 59-60.

Marco, Y., Lin, C., Weinreb, R., Lai, G., Chiu, V., & Leung, C. (2016, June). Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinnging. Ophthalmology, 123(6), 1201-1210.

WhatWeDoKnow- HysteresisMatters

(Low) CH has been consistently shown to be independently and strongly associated with or

predictive of glaucoma progression Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness andcorneal hysteresis associated with glaucoma damage. Am J Ophthalmol2006;141:868

CornealHysteresisfoundtobeassociatedwithprogression

OR LCL UCL P-value

Ageperyear<65 1.12 1.01 1.24 .03

Ageperyear>65 1.08 1.01 1.15 .02

GATIOPpermmHg 1.22 0.95 1.58 .12

Treatment 1847.6 3.16 106 .02

IOPbytreatmentinteraction 0.79 0.61 1.03 .08

CCTper100microns 1.65 0.66 0.98 .30

Yearswithglaucoma 1.00 0.96 1.04 .98

BaselineIOP 0.99 0.93 1.06 .79

CHpermmHg 0.81 0.66 0.98 .03

IOP- TheGreatMisnomerHowoftenmisusedwordsgeneratemisleadingthoughts.

-HerbertSpencer

• Intra-ocularpressure– Intra- “within” e.g.intrastate– Inter- “between” e.g.interstate– Trans- “across” e.g.transatlantic

– TranscornealPressureDifference

620+15=635mmHG

760+15=775mmHG

1520+15=1535mmHG

775mmHG

1535mmHG

635mmHG

•Pressureinsidetheeyedoesn’tMatter•PressureacrosstheCornea(IOP)does

•Why?

Why? …is it true

Anatomy&Physiology

PhysicsData

Jonas JB, Berenshtein E, Holbach L.Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci. 2003 Dec;44(12):5189-95.

IOP

CSF

BasicPhysics

Force1(IOP) Force2(ICP)

Corneal Hysteresis May play a role

ICPeffectstheNerve

Pseudotumor Glaucoma

Normal – IOP slightly greater than ICP

Glaucoma– IOP greater than ICP

Normal – IOP lower than ICP

ICPchangeswithAge

0

2

4

6

8

10

12

14

0-5

6-10

11

-15

16-20

21-25

26-30

31-35

36-40

41-45

46-50

51-55

56-60

61-65

66-70

71-75

76-80

81-85

86-90

91-95

CSFpmmHg

mmHg

Fleischman, D. et al presented at ARVO 2011

CSFPressureinGlaucoma

Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normaltension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmology Vis Sci. 2008;49:5412-5418.

Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology.2010;117:259-266.

ICPchangeswithBMI

Berdahl, J. P., Fleischman, D., Zaydlarova, J., Stinnett, S., Allingham, R. R., & Fautsch, M. P. (2012). Body mass index has a linear relationship with cerebrospinal fluid pressure. Investigative ophthalmology & visual science, 53(3), 1422–1427. doi:10.1167/iovs.11-8220

DiurnalVariations

Fleischman, D. et al presented at ARVO 2011

Why? …does it matter

DOES CSF Pressure Matter in Glaucoma

CSFPressureinGlaucoma

Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normaltension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmology Vis Sci. 2008;49:5412-5418.

Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology.2010;117:259-266.

Fanelli, J. (2012, December). Can Pressure Be Helpful. Review of Optometry.Allingham, R. (2015, August). Cerebrospinal Fluid a Major Player in Glaucoma? Ophthalmology Times.

http://www.vittamed.com/

Why? …does it matter

Decouple IOP from ICP

NormalNormalIOPNormalCSFp

Atmospheric

Abso

lute

Pres

sure

Rela

tive

Pres

sure

Rela

tive

Pres

sure

Abso

lute

Pres

sure

Intraocular Intracranial

760mmHg 776mmHg 772mmHg

0mmHg 16mmHg 12mmHg

Trans-Corneal Pressure Difference16mmHg

Trans-Laminar Pressure Difference4mmHg

GlaucomaHighIOPMildLowCSFp

Atmospheric

Abso

lute

Pres

sure

Rela

tive

Pres

sure

Rela

tive

Pres

sure

Abso

lute

Pres

sure

Intraocular Intracranial

760mmHg 782mmHg 769mmHg

0mmHg 22mmHg 9mmHg

Trans-Corneal Pressure Difference22mmHg

Trans-Laminar Pressure Difference13mmHg

TreatmentinGlaucomaLoweredlocalatmosphericpressureLoweredabsoluteIOPMildLowCSFp

Atmospheric

Abso

lute

Pres

sure

Rela

tive

Pres

sure

Rela

tive

Pres

sure

Abso

lute

Pres

sure

Intraocular Intracranial

760mmHg(ambient) 782mmHg 769mmHg

-10mmHg(locally applied) 12mmHg 9mmHg

Trans-Corneal Pressure Difference22mmHg

Trans-Laminar Pressure Difference3mmHg

Note that TCPD is same but TLPD is normalized

Pressureexertedanywhereinaconfinedincompressiblefluidistransmittedequallyinalldirectionsthroughoutthefluid

Pascal'slawIIH/VIIP

NormalIOPHighCSFp

Atmospheric

Abso

lute

Pres

sure

Rela

tive

Pres

sure

Rela

tive

Pres

sure

Abso

lute

Pres

sure

Intraocular Subarachnoid

760mmHg 776mmHg 780mmHg

0mmHg 16mmHg 20mmHg

Trans-Corneal Pressure Difference16mmHg

Trans-Laminar Pressure Difference-4mmHg

VIIP1. Globe Flattening2. Hyperopic Shift3. Choroidal Folds4. Optic Disk Edema

Space Need

Increased ICP is evidenced by swelling around the optic nerve

MRI of eye in an Astronaut with VIIP

Might all be treated by

increasing IOP to balance TLPG

Mader et al 2011

MostlyLongTermSpaceFlight

Kramer et. al. Orbital and Intracranial Effects of Microgravity: Findings at 3-T MR Imaging. Radiology: Vol 263:3 2012

50% of Astronauts experience VIIP

IIH/VIIPRaisedlocalatmosphericpressureNormalIOPHighCSFp

Atmospheric

Abso

lute

Pres

sure

Rela

tive

Pres

sure

Rela

tive

Pres

sure

Abso

lute

Pres

sure

Intraocular Subarachnoid

760mmHg(ambient) 776mmHg 780mmHg

+10mmHg(locally applied) 26mmHg 20mmHg

Trans-Corneal Pressure Difference16mmHg

Trans-Laminar Pressure Difference6mmHg

Note that TCPD is same but TLPD is normalized

Why? …should you care

Glaucomaisthe2nd LeadingcauseofBlindnessworldwide

Summary

• IntracranialpressureislowerinGlaucoma

ØICPislowerinPOAG Yes

ØICPisevenlowerinNTG Yes

ØICPishigherinOHT Yes

Problem#3

• WhydoesIOPmatter?

Answer#3

• IOP(transcornealpressuredifference)isasurrogateforthetranslaminarpressuredifference

Problem#2

• Whatcausescuppingandfieldloss?

Answer#2• Cupping- Posteriorlydirectedforce

generatedbytheTranslaminarPressureDifference

• Fieldloss- Ganglioncelldeathcausedbyinadequateaxonaltransport HighPressure

LowPressure

Problem#1

• Whatisglaucoma?

Answer#1

Glaucoma= xtime

……andmaybesomeotherthings

IOP– ICPlaminacribrosathickness

THANKYOU