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Check for Diabetes? Check for Hypothyroidism? Do Diurnal IOP Variations?

Do Postural IOP Variations? Screen VF or Digitized

Imaging-WELL MAYBE? Do Routine Anti-cardiolipin

Antibodies? Do Routine MRIs?

Check for Raynaud’s?

Hemi-Structure and Hemi-Function Sym-Metrix

LOOK FOR BALANCE IN LIFE

THE OPTIC NERVE AND ASYMMETRY

IS OD A MIRROR IMAGE OF OS?

THE OPTIC NERVE AND ASYMMETRY

IS OD A MIRROR IMAGE OF OS?

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DISC SIZE DIFFERENCE IS A GREAT INDICATOR OF A CONGENITAL

VARIATION BUT CAN ALSO INDICATE DISEASE..LOOK AT THE CONTEXT…OS

IS PROPTOTIC

IS OD A MIRROR IMAGE OF OS?

RETINAL SYMMETRY IS A GREAT INDICATOR OF A

CONGENITAL VARIATION OR DYSTROPHY

IS OD A MIRROR IMAGE OF OS?

RETINAL SYMMETRY IS A GREAT INDICATOR OF A CONGENITAL VARIATION..BUT IT MUST BE EVALUATED IN CONTEXT…

IS OD A MIRROR IMAGE OF OS?

GROWTH HORMONE USE

RETINAL ASYMMETRY IS A GREAT INDICATOR OF ACQUIRED DISEASE

OCULAR ISCHEMIC SYNDROME

IS OD A MIRROR IMAGE OF OS?

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RETINAL ASYMMETRY IS A GREAT INDICATOR OF ACQUIRED DISEASE

OCULAR ISCHEMIC SYNDROME

IS OD A MIRROR IMAGE OF OS?

“We tend to see what we expect to see or what we decide we have seen.” Edwards

OPTIC NERVE HEAD SYM-METRIX® IN ACTION®

53 YO

•  ROUTINE P/O FOLLOW-UP •  RECENT PHACO OU, OS LAST •  NO COMPLAINTS EXCEPT THE P/O

GTTS •  IOP UNATTAINABLE BECAUSE OF

BLINK BUT REPORTED AS 15 MM HG AT LAST POST OP

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DO YOU SEE ANYTHING WRONG?

DO YOU SEE ANYTHING WRONG?

NOW DO YOU SEE ANYTHING WRONG?

AASYMMETRY WITH MORE RIM OD THAN OS

SIGNIFICANT ASYMMETRY

RNFL THINNING OS > OD

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GCC THINNING OS > OD

SIGNIFICANT ASYMMETRY

CONCLUSION

NORMAL TENSION GLAUCOMA

NA-AION

MYOPIA AND GLAUCOMA?

IS THERE A RELATIONSHIP BETWEEN

Prevalence of Glaucoma as Related to Axial Length

Surv Ophthalmol 1970;15:1 Axial Length in mm

Total Subjects Total Subjects with Glaucoma

20.0 to 26.4 mm

192 3.125%

26.5 to 33.6 mm

196 11.224%

GLAUCOMA IS MORE PREVALENT IN LONGER EYES

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Responses to Topical Corticosteroids Am J Ophthalmol 1966;62:1039

NOTE 9% -5D HAD IOP OVER 21 MM HG N <20 mm

Hg 20-31 mm Hg

> 31 mm Hg

Volunteers 100 70% 26% 4% POAG 50 0% 8% 92% POAG Offspring

100 10% 68% 22%

POAG Siblings

50 22% 52% 26%

> - 5 D 17 12% 59% 29%

STEROID RESPONSE HIGHER IN HIGHER MYOPES

Pigmentary Glaucoma and Refractive Error Trans Am Acad Ophthalmol Otolaryngol 1970;74:984

Refractive Error % of Eyes with Pigmentary Glaucoma - 78.22 % Myopic

+3 D 0.49% +.5 to +2 D 6.44% -.25 to +.25 D 14.85% -.50 to -2.00 D 31.19% -2.25 to -4.00 D 23.27% -4.25 to -6.75 D 19.80% -7.00 to -9.00 D 1.98% -10.00 to -13.50 D 1.98%

PIGMENTARY GLAUCOMA HIGHER IN MYOPES

POAG LTG and Refractive Error Br J

Ophthalmol 1973;57:499 POAG LTG

Mean Age 71 63

Mean Refract 0.0D -5.1 D

Mean AL 22.9 mm 25.2 mm

Mean Max IOP 34.3 mm Hg 19.8 mm Hg

LTG HIGHER IN MYOPES AND LONG EYES

In longer eyes the sampling location of the RNFL layer is

further away from the center of the ONH yielding artificially thinner

measurements. Rauscher FM, Sekhon N, Feuer WJ et al. Myopia affects retinal nerve fiber layer measurements as determined by optical coherence tomography. J Glacuoma

2009;18:501-505

Signal strength and scan circle placement affects RNFL

measurements. Vizzeri G, Bowd C, Medeiros FA et al. Effect of signal strength and improper alignment

on the variability of stratus optical coherence tomography retinal nerve fiber layer thickness measurements. Am J Ophthalmol 2009;148:249-255

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IMAGES FURTHER OUT FROM THE ONH GIVING THINNER RNFL

AXIAL MYOPIA AND IMAGING THE RNFL

Conclusion???

SYSTEMIC DISORDERS AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

NEUROLOGY AND GLAUCOMA

WHEN THE RNFL DIES, THE BRAIN DIES

WHEN THE BRAIN DIES, THE RNFL DIES

THE OPTIC NERVE IS PART OF THE BRAIN

STUFF THAT IS GOOD FOR THE BRAIN IS ALSO GOODFOR THE RNFL

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Degeneration of RGC and axons represent a substantial loss of neural activity in the

brain as 50 % to 60 % of the cerebral cortex spread over 40-45 visual areas represent visual function. This RGC degeneration

entails downstream caspase and mitochondrial dependent apoptotic

cascades resulting in actual loss of cortex. Quigley HA. Neuronal death in glaucoma. Prog Retin Eye Res. 1999;18:39-57.

Nickells RW. From ocular hypertension to ganglion cell death: a theoretical sequence of events leading to glaucoma. Can J Ophthalmol. 2007;42(2):278-287. Van Essen DC. Towards a quantitative, probabilistic neuroanatomy of cerebral cortex. Cortex. 2004;40(1):211-212.

Tatton WG, Chalmers-Redman RM, Tatton NA. Apoptosis and anti-apoptosis signaling in glaucomatous retinopathy. Eur J Ophthalmol. 2001;11(suppl 2):S12-S22. Tahzib NG, Ransom NL, Reitsamer HA, McKinnon SJ. Alpha-fodrin is cleaved by caspase-3 in a chronic ocular hypertensive (COH) rat model of glaucoma. Brain Res Bull. 2004;62:491-495.

Huang W, Dobberfuhl A, Filippopoulos T, et al. Transcriptional up-regulation and activation of initiating caspases in experimental glaucoma. Am J Pathol. 2005;167(3):673-681. Huang W, Fileta JB, Dobberfuhl A, et al. Calcineurin cleavage is triggered by elevated intraocular pressure, and calcineurin inhibition blocks retinal ganglion cell death in experimental

glaucoma. Proc Natl Acad Sci USA. 2005;102(34):12242-12247.

Grey density reduction occurs in the primary visual cortex in patients with advanced glaucoma. Boucard CC, Hernowo AT, Maguire RP, et al. Changes in cortical grey matter density associated with long-standing retinal visual field defects. Brain 2009;132:1898-1906

Measuring the optic nerve diameter at the orbital apex (15 mm behind the eye) shows significant correlation with RNFL loss. Lagreze WA, Gaggi M, Weigel M et al. Retrobulbar optic nerve diameter measured by high-speed magnetic resonance imaging as a biomoarker for axonal loss in glaucomatous optic atrophy. Invest Ophthalmol Vis Sci 2009;50:4223-4228

Progressive visual field loss in NTG is associated with silent cerebral infarcts as defined by CT. Leung DYL, Tham CCY, Li FCH, et al. Silent cerebral infarct and visual field progression in newly diagnosed normal-tension glaucoma. Ophthalmology 2009;116:1250-1256

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CEREBROSPINAL FLUID PRESSURE AND GLAUCOMA

ICP is significantly lower in patients with POAG and NTG and higher in those with OHT without glaucoma. Minor differences of IOP have been

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

Wu SY, Leske MC. Associations with intraocular pressure in the Barbados Eye Study. Arch Ophthalmol. 1997;115:1572-1576. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5):763-768.

Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci. 2008;49(12):5412-5418.

Nemesure B, Honkanen R, Hennis A, et al. Incident open-angle glaucoma and intraocular pressure. Ophthalmology. 2007;114:1810-1815. Suzuki Y, Iwase A, Araie M, et al. Risk factors for open-angle glaucoma in a Japanese population: the Tajimi Study. Ophthalmology. 2006;113:1613-1617.

The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol. 2000;130:429-440.

Sommer A, Tielsch JM. Risk factors for open-angle glaucoma: the Barbados Eye Study. Arch Ophthalmol. 1996;114:235. Magnaes B. Body position and cerebrospinal fluid pressure. Part 1: clinical studies on the effect of rapid postural changes. J Neurosurg. 1976;44:687-697.

Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of body position on intracranial pressure and cerebral perfusion in patients with large hemispheric stroke. Stroke. 2002;33:497-501.

Carlson GD, Oliff HS, Gorden C, et al. Cerebral spinal fluid pressure: effects of body position and lumbar subarachnoid drainage in a canine model. Spine. 2003;28:119-122. Carlson KH, McLaren JW, Topper JE, Brubaker RF. Effect of body position on intraocular pressure and aqueous flow. Invest Ophthalmol Vis Sci. 1987;28:1346-1352.

Kiuchi T, Motoyama Y, Oshika T. Relationship of progression of visual field damage to postural changes in intraocular pressure in patients with normal-tension glaucoma. Ophthalmology. 2006;113:2150-2155.

Ozcan MS, Praetel C, Bhatti MT, et al. The effect of body inclination during prone positioning on intraocular pressure in awake volunteers: a comparison of two operating tables. Anesth Analg. 2004;99:1152-1158, table of contents.

Lamina separates two distinctive pressurized zones, IOP 10-21 mm Hg and ICP 5-15 mm Hg. Average IOP is

16 and Average ICP is 12 and the

IOP-ICP is called the Trans-laminar pressure.

Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol.

2002;120:701-713; discussion 829-730. Morgan WH, Yu DY, Alder VA, et al. The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure. Invest

Ophthalmol Vis Sci. 1998;39:1419-1428. Goetz C, ed. Textbook of Clinical Neurology. Philadelphia: Saunders; 2003:511-529.

Both IOP and ICP affected by BP. ??? Systemic Hypotension ??? CAI use for glaucoma

??? Positional Effects

CSFP

IOP

BLOOD PRESSURE

SLEEP AND POSITION

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Alteration of Trans-laminar pressure may bow the lamina creating a

pinching of axons. Both intraocular fluid and intracranial fluid are created by carbonic anhydrase reactions and

ultrafiltration.

Anderson DR, Hendrickson AE. Failure of increased intracranial pressure to affect rapid axonal transport at the optic nerve head. Invest Ophthalmol Vis Sci. 1977;16:423-426.

Quigley HA, Guy J, Anderson DR. Blockade of rapid axonal transport. Effect of intraocular pressure elevation in primate optic nerve. Arch Ophthalmol. 1979;97:525-531. Quigley H, Anderson DR. The dynamics and location of axonal transport blockade by acute intraocular pressure elevation in primate optic nerve. Invest Ophthalmol.

1976;15:606-616. Levy NS. The effects of elevated intraocular pressure on slow axonal protein flow. Invest Ophthalmol. 1974;13:691-695.

Minckler DS, Tso MO, Zimmerman LE. A light microscopic, autoradiographic study of axoplasmic transport in the optic nerve head during ocular hypotony, increased intraocular pressure, and papilledema. Am J Ophthalmol. 1976;82:741-757.

Jonas JB, Berenshtein E, Holbach L. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci. 2003;44:5189-5195.

Jonas JB, Mardin CY, Schlotzer-Schrehardt U, Naumann GO. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci. 1991;32:401-405. Jonas JB, Berenshtein E, Holbach L. Lamina cribrosa thickness and spatial relationships between intraocular space and cerebrospinal fluid space in highly myopic eyes.

Invest Ophthalmol Vis Sci. 2004;45:2660-2665.

MIGRAINE OCCURS IN 43% OF WOMEN AND 18% OF MEN. AURA IN 25%. CNTGS STATES MIGRAINE WAS RISK FACTOR FOR PROGRESSION OF GLAUCOMA.

OTHER STUDIES REPORT NO STATISTICAL RELATIONSHIP.

Stewart W, Wood C, Reed M, et al. Cumulative lifetime migraine incidence in women and men. [published online ahead of print July 15, 2008]. Cephalagia. Stewart WF, Linet MS, Celentano DD, et al. Age- and sex-specific rates of migraine with and without visual aura. Am J Epidemiol. 1991;134:1111-1120.

Phelps CD, Corbett JJ. Migraine and low-tension glaucoma. A case control study. Invest Ophthalmol Vis Sci. 1985;26:1105-1108. Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group. Risk factors for progression of visual field abnormalities in normal-tension

glaucoma. Am J Ophthalmol. 2001;131(6):699-708. Anderson DR, Drance S, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group. Factors that predict the benefit of lowering intraocular pressure in normal

tension glaucoma. Am J Ophthalmol. 2003;136:821-829. Klein BE, Klein R, Meuer SM, Goetz LA. Migraine headache and its association with open-angle glaucoma: The Beaver Dam Eye Study. Invest Ophthalmol Vis Sci.

1993;34(10):3024-3027. Wang JJ, Mitchell P, Smith W. Is there an association between migraine headache and open-angle glaucoma? Findings from the Blue Mountains Eye Study. Ophthalmology.

1997;104:1714-1719. Leske MC, Heijl A, Hussein M, et al. Factors for glaucoma progression and the effect of treatment: the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2003;121:48-56. Canadian Glaucoma Study Group. Canadian Glaucoma Study: 1. Study design, baseline characteristics, and preliminary analyses. Can J Ophthalmol. 2006;41:566-575.

Chauhan BC, Mikelberg FS, Balaszi G, et al. Canadian Glaucoma Study. 2. Risk factors for the progression of open angle glaucoma. Arch Ophthalmol. 2008;126:1030-1036.

What About Internal Carotid Stenosis and NTG?

Conclusion???

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HORMONES AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

IOP was significantly lower in women taking HT than in those who had never taken HT, even after removing other possible influences on IOP. Tint NL, Alexander P, Tint KM, et al. Hormone therapy and intraocular pressure in nonglaucomatous eyes. Menopause 2010;17:157-160���

������Data in a recent study suggest a possible role for declining sex hormone levels in the genesis of primary open angle glaucoma. This study also found that current use of estrogen with progestin was associated with a reduced risk of POAG. Pasquale LR, Rosner BA, hankinson SE, Kang JH. Attributes of female reproductive aging and their relationship to primary open-angle glaucoma:a prospective study. J

Glaucoma 2007;16:598-605.������

Suggestions that estrogens are neuroprotective in degenerative disorders and possibly within the retina and in glaucoma. Kumar DM, Simpkins JW, Agarwal N. Estrogens and neuroprotection in retinal diseases. Mol Vis 2008;14:1480-1486. Nakazawa T, Takahashi H, Shimura M. Estrogen has a neuroprotective effect on axotomized RGCs through ERK signal transduction pathway. Brain Res 2006;1093:141-149.

ESTROGEN LEVELS MAY HAVE SOME EFFECT ON GLAUCOMA GEORGIAN MEDICAL NEWS 2005; 9: 33

ESTRADIOL LEVELS 1/2 IN GLAUCOMA VERSUS NORMALS IGR 2007;9:13

ESTRADIOL POTENTIATES FLOW, TESTOSTERONE INHIBITS FLOW ACTA OPHTHALMOLOGICA SCANDINAVICA 2003; 81: 617, J GLAUCOMA 2007;16:598

RIM STRUCTURE ALTERED DURING MENSTRUAL CYCLE ACTA OPHTHALMOLOGICA SCANDINAVICA 2004; 82:741

SUGGESTION THAT FEMALE SEX HORMONES MAY BE PROTECTIVE OF THE OPTIC NERVE. VAJARANANT TS, NAYAK S, WILENSKY JT, JOSLIN CE. GENDER AND GLAUCOMA: WHAT WE KNOW AND WHAT WE NEED TO KNOW. CURR OPIN OPHTHALMOL 2010;21:91-99.

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There are suggestions that “Topical estrogen drops may be a new alternative treatment of glaucoma.” Ozcura F, Aydin S. Med Hypotheses 2007;69:456. Conclusion???

SLEEP APNEA AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

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77 YO PO CATARACT MULTIPLE INVESTIGATIONS, MEDICATIONS, AND OPTIC NERVE DECOMPRESSION…

23 INCH NECK WITH SLEEP STUDY CONFIRMED OBSTRUCTIVE SLEEP APNEA

…the odds of an individual diagnosed with sleep apnea having glaucoma is 1.736 times the odds of individuals without sleep apnea (73.6 % MORE LIKELY ) having glaucoma in this patient population. We recommend that questions concerning sleep-disturbed breathing be included for patients suspected of having glaucoma. Similarly, we recommend that patients diagnosed with glaucoma be questioned about the risk factor of sleep-disturbed breathing. Boyle M, Semes L, Fuhr P, Clay O. AAO Poster Session

Obstructive sleep apnea leads to reduced sensitivity in the visual field. Steindel A, Lautenschlager C, Struck HG. Ocular risks in obstructive sleep apnea syndrome. Ophthalmologe 2010 epub June 9 ahead of print.

Oxygen desaturation was not found to be statistically related to glaucoma or sleep disorder. Roberts TV, Hodge C, Graham SL, et al. Prevalence of nocturnal oxygen desaturation and self-reported sleep-disordered breathing in glaucoma. J Glaucoma 2009;18:114-118.

The use of CPAP actually causes an additional IOP increase in OSA. Invest Ophthalmol Vis Sci 2008;49:934, Eye 2007; Advance online publication 4, Br J Ophthalmol 2007;91:1524

Report a high prevalence of glaucoma in OSAS. Visual field defects in glaucoma patients with OSAS may be due to ON perfusion defects. Karakucuk S, Goktas S,

Aksu M, et al. Graifes Arch Clin Exp Ophthalmol 2008;246:129-134 Sleep apnea patients should be referred for assessment of associated eye disorders. McNab AA. The eye and sleep apnea. Sleep Med Rev 2007;11:269-276

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The prevalence of glaucoma in patients with obstructive sleep apnoea is an estimated 27%. Sex, age, body mass index or apnoea plus hypopnoea index are not factors influencing the presence of glaucoma in this population of patients. Bendel RE, Kaplan J, Heckman M, et al. Prevalence of glaucoma in patients with obstructive sleep apnoea-a cross-sectional case-series. Eye (Lond) 2008;22:1105-1109

Report of prevalence of NTG in OSAS at 5.9%. Emphasize importance of sleep history in glaucoma patients. Sergi M, Salerno DE, Rizzi M, et al. Prevalence of normal tension glaucoma in obstructive sleep apnea syndrome patients. J Glaucoma 2007;16:42-46

There is not a strong support of the impact of sleep apnea on the eventual development of glaucoma relative to other putative factors. Girkin CA, McGwin G, McNeal SF, Owsley C. Is there an association between pre-existing sleep apnea and the development of glaucoma? Br J Ophthalmol 2006;90:679-681

The prevalence of glaucoma in sleep apnea patients is similar to that of the general Caucasian population. Geyer O, Cohen N, Segev E, et al The prevalence of glaucoma in patients with sleep apnea syndrome: same as in the general population. Am J Ophthalmol 2003;136:1093-1096

Prevalence of sleep apnea in NTG 0% under 45, (AGE RELATED) 50% ages 45-64, 63% over 64. NTG patients should be checked for sleep apnea. Mojon DS, Hess CW, Goldbulu D, et al. Normal-tension glaucoma is associated with sleep apnea syndrome. Ophthalmologica 2002;216:180-184.

Link to NTG is controversial. Thorax 1982;37:845, Eur

JOphthalmol 1997;7:211, Ophthalmology 1999;106:1009, Acta Ophthalmol Scand 2000;78:638, Ophthalmologica 2000;214:115, Ophthalmologica 2002;216:180

There is also an association to ION and ODE Br J Ophthalmol 2007;91:1524, Am J Ophthalmol 2007;144:953

Moderate to severe OSA is associated with a higher incidence of VF defect and glaucomatous optic nerve changes. Tsang CS, Chong SL, Ho CK, Li MF. Moderate to severe obstructive sleep apnoea patients is associated with a higher incidence of visual field defect. Eye (LOND) 2006;20:38-42.

The sleep apnoea syndrome is correlated with a proportional decrease in the RNFL. Decreased ocular perfusion related to hypoxia and vasospasm associated with OSAS may cause RNFL thinning, which may precede clinically detectable glaucoma. Kargi SH, Altin R, Koksal M, et al Retinal nerve fibre layer measurements are reduced in patients with obstructive sleep apnea syndrome. Eye (Lond) 2005;19:575-579

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SO SHOULD PATIENTS WITH SLEEP APNEA BE

WORKED UP FOR GLAUCOMA AND SHOULD GLAUCOMA PATIENTS BE UNDER SUSPICION FOR

SLEEP APNEA???

BEHAVIORAL ISSUES AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

SMOKING AND GLAUCOMA

Smoking increases the risk for virtually every human affliction including glaucoma (often defined by increased IOP in studies) because of the interference with the oxygenation of the blood and the increase in oxidative stress. Arch Ophthalmol 1987;105(8):1066-1071, Surv Ophthalmol 1998;42(6):535-547, Hong

Kong Med J 2000;6(2):195-202, J Glaucoma 2003;12(3):209-212, Przegl Lek 2008;65(10):724-727, Przegl Lek 2005;62(10):1167-1170, Chin Med J (ENGL) 2004:117(5):706-710, Public Health 2004;118(4):256-261

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The direct relationship to glaucoma, however, appears to be controversial as studies and reviews fail to establish a firm link between either smoking or environmental smoke and glaucoma development. Yet the same studies recommend that cessation of smoking is important in the management of glaucoma patients. Arch Ophthalmol 2003;121(12):1762-1768, J

Glaucoma 2008;17(7):558-566, Br J Ophthalmol 2008;92(10):1304-1310

The issue of smoking is proven to be a risk factor for the presence of glaucoma. Open Ophthalmol J 2009;3:38-42, J Glaucoma 2009;18(6):423-428

The most critical risk factors associated with blindness in high tension glaucoma, however, were elevated initial IOP, fluctuation, poor control, noncompliance and late detection Clin Ophthalmol 2008;2(4):757-762 while the for angle-closure the risks include hypertension, family history, shallow anterior chamber and large CD. Zhonghua Yan

Ke Za Zhi 2008;44(6):503-506

In one large collaborative study it was shown that surgically treated patients with glaucoma had lower IOPs if they were non-smokers. Ophthalmology 2008;15(6):927-933

From a functional standpoint, cigarette smoking is associated with reductions in retinal sensitivity. Acta Ophthalmol

Scand 2004;82(4):432-435

In an interesting study on the effects of smoking on normotensive patients it was found that both IOP and BP increased secondary to the nicotine in cigarettes. Niger J Physiol Sci 2007;22(1-2):33-36

OBESITY AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

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Presence of metabolic syndrome increases risk of OHTN in males 2X

and females 5X. Metabolic syndrome defined as having three or more of the

following: 1. high blood pressure

2. elevated serum triglycerides 3. low HDL

4. elevated fasting glucose levels 5. large waist circumferance

Imai K, Hamaguchi M, Mori K et al. Metabolic syndrome as a risk factor for high-ocular

tension. Int J Obes 2010;34:1209-1217

There is certainly a suggestion that there is an association of insulin resistance and the metabolic syndrome to increased intraocular pressure. Diabetes Metab Res Rev. 2005;21:434 Body Mass Index appears to have an association with elevated intraocular pressure. Jpn J Ophthalmol. 2003; 47;191, Int J Epidemiol. 2000;29:661, Clin Experiment

Ophthalmol. 2002;30:237, Am J Ophthalmol. 2008;146:69

Certainly initial reaction to this fact among clinicians would be to point to neck size and positive pressure as a related factor with sleep apnea falling into the picture. Sleep Med Rev. 2007;11:269, Can J. Ophthalmol.

2007;42;238 The relationship of cerebrospinal fluid pressure elevation, Idiopathic Intracranial Hypertension, serum cortisol, and sleep apnea also create an interesting scenario for elevated intraocular pressure. Am J Ophthalmol. 2007;143:635

EXERCISE AND GLAUCOMA

Caution: Pigmentary Dispersion

IS THERE A RELATIONSHIP BETWEEN

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Exercise reduces IOP and the reduction is sustainable. Int J Neurosci 2006;116:1207

In another study it was shown that in persons with increased IOP, regular, moderately intense aerobic exercise rather than short-lived intense exercise is more useful. Int J Neurosci 2006;116:351

Another study showed that exercise changes Ocular Perfusion Pressure and produces increased tissue blood flow in the retina in the immediate post-exercise period, while blood flow increases more persistently in the choroid-retina. Eye 2006;20:796

It is further confirmed the ocular hypotensive effect of strenuous exercise on the IOP and demonstrates that Pulsitile Ocular Blood Flow increases significantly after exercise. Optom Vis Sci 2003;80:460

Suggestion that running distances (25 miles/week) may be of benefit in minimizing the risk for the development of glaucoma. Williams PT. Relationship of incident glaucoma versus physical activity and fitness in male runners. Medicine and Science in Sports and Exercise 2009;41:1566-1572

Exercise has an additive effect of lowing intraocular

pressure regardless of the class of IOP medication or the number of medications. There is a 2-3 mm Hg reduction after just 5 minutes of aerobic activity. CAUTION

WITH PIGMENTARY DISPERSION. Natsis K, Asouhidou I, Nousios G et al. Airobic exercise and intraocular pressure in normotensive and

glaucoma patients. BMC Ophthalmology 2009:6

VASCULAR SYSTEM AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

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OHTS study photo review 84% detection of disc heme, observation gave 16%. Disc heme related

to age, CCT, family history and smoking. Presence of heme increased risk of progression

by 6 X and 13.6% in eyes with previous heme 5.2% without previous heme.

BUT!!!

87% of eyes with disc hem did not progress in the 31 month follow-up.

Kass MA, Heuer DK, Higgenbotham EJ et al. The ocular hypertension treatment study: a

randomized trial determines that topical ocular hypertensive medication delays the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:701-713.

Gordon MO, Beiser JA, Brandt JD et al. The ocular hypertension treatment study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:714-720

Simvastatin significantly protected against the

development of progression of visual fields in a cohort of

121 patients with normal tension glauoma.

Leung DY, Li FC, Kwong YY et al. Simvastatin and disease stabilization in normal tension

glaucoma: a cohort study. Ophtahlmology 2010;117:471-476. WHY?

VASCULAR PERFUSION IS AN ISSUE. DIFFERENCE OF SYSTOLIC AND

DIASTOLIC IOP IS OCULAR PULSE AMPLITUDE (OPA) AND IS LOWER IN

PATIENTS WITH POAG AND NTG. AVE OPA IS 2.09 TO 2.8 MM HG

OPTOMETRY 2010;81:408-413 ARCH OPHTHALMOL 2002;120:954-959 OPHTHALMOLOGY 2007;114:1965-1972

OPHTHALMOLOGY 2008;115:85-93 OPHTAHLMOLOGY 2000;107:1287-1293 ARCH OPHTHALMOL 1995;113:216-221 ARCH OPHTHALMOL 2007;125:805-812

BR J OPHTHALMOL 1996;80:864-867 J GLAUCOMA 1997;6:23-32

AM J OPHTHALMOL 1998;126:42-51 ACTA OPHTHALMOLOGICA 2009;87:323-328

CURR EYE RES 2006;31:851-862 BR J OPHTHALMOL 2001;85:678-682

EYE 1997;11:485-488 BR J OPHTHALMOL 2000;84:1282-1284

CURR EYE RES 1981;1:19-23 J GLAUCOMA 2008;17:403-407

GRAEFS ARCH CLIN EXP OPHTHALMOL 2008;246:559-565 J GLAUCOMA 2007;16:700-703 OPTOMETRY 2009;80:169-174

This Vascular Perfusion Stuff is All over the Place.

Logic Dictates it is an Issue, But the Issue is Yet to Be

Defined.

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ASSOCIATIONS WITH POAG AND NTG

•  TREATED SYSTEMIC HTN ESPECIALLY WITH Ca BLOCKERS (Current Eye Research 2007;32:153, Ophthalmology 2007;114:2221)

•  DIAS PERFUSION PRESSURE = DIAS BP - IOP SHOULD BE > 30 (Memarzadeh et al at The 18th Annual AGS Meeting, March 2008, Ophthalmology 2008;115:85, Glaucoma Today 2008;6:31, Ophthalmology 2000;107:1287, Int Ophthalmol 1998;22:19, Invest Ophthalmol Vis Sci 2005;46:561, N Engl J Med 1973;288:392, Surv Ophthalmol 1999;43:S10, Am J Ophthalmol 1994;117:603, Arch Ophthalmol 1995;113:216, Arch Ophthalmol 1995:113:918 )

•  ADD NIGHT-TIME, BETA BLOCKER ISSUES, CV RELATIONSHIP TO AD (Ophthalmology 2007;114:1965, American Geriatrics Society 2008 Annual Scientific Meeting: Abstract P10. Presented May 1, 2008)

BLOOD FLOW •  SVP GONE 46% GLAUCOMA AND

PRESENT 98% CONTROLS. (Br J Ophthalmol 2007;91:405, ARVO 2007 Abstract 2879)

•  CCT AND INCR IN RVO (ARVO 2007 Abstract 3080/B587)

•  GLAUCOMA HAS LOWER OCULAR SURFACE TEMP (Br J Ophthalmol. 2007;91:878)

DORZOLAMIDE AS A VASOREGULATOR

•  MAY INCREASE BLOOD VELOCITY AND FLOW (Microvasc Res 2006;72:101)

•  DOES THIS ALSO LOWER ICP AND ALTER THE TRANS-LAMINAR PRESSURE GRADIENT?

•  SHOULD NOT USE IN PATIENTS WITH A DEFECTIVE CORNEAL PUMP (Arch Ophthalmol 2007;125:1345)

Conclusion???

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ANATOMICAL ISSUES AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

CENTRAL CORNEAL THICKNESS

????

Patients with Normal Tension Glaucoma have Thinner Corneas.

Kurtz S, Haber I, Kesler A. Corneal thickness measurements in normal-

tension glaucoma workups: is it worth the effort? J Glaucoma 2010;19:58-60.

WHY?

NUTRITIONAL ISSUES AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

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Natural and synthetic compounds have been reported to have neuro-protective capabilities including all antioxidants, inhibitors of glutamate release, calcium channel blockers, polyamine antagonists, nitric oxide synthase inhibitors, cannabinoids, aspirin, melatonin and vitamin B-12. (Curr Opin Ophthalmol

2000;11:78)

It has also been suggested that metabolic inhibition-EATING LESS- is also neuroprotective. (Ann NY Acad Sci 1999;890:240)

Mitrogenol-bilberries + pycnogenol significantly increased velocity of

blood flow through ophthalmic arteries, central retinal arteries, and

posterior ciliary arteries while lowering IOP in ocular hypertension.

Steigerwalt Jr RD, Belcaro G, Morazzoni P, et al. Mirtogenol potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects. Clin Ophthalmol 2010; 4: 471-476

Ascorbate and glutathione concentrations decreased in exfoliation syndrome while reactive oxygen species are

increased. Antioxidant potential (ROS) plays some role in the pathogenesis of glaucoma.

Ferreira SM, Lerner SF, Brunzini R et al. Antioxidant status in the aqueous humour of patients with glaucoma associated with exfoliation syndrome. Eye 2009;23:1691-1697.

HYPERHOMOCYSTEINEMIA AND GLAUCOMA

IS THERE A RELATIONSHIP BETWEEN

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The plasma level of Hcy was found to be increased only in PXG patients and the plasma levels of vit-B6 were found to increase in the NTG and POAG sample groups. Using homocysteine and vit-B6 levels as the determinants of hyperhomocysteinemia still needs further research. Turgut B, Kaya M, Arslan S, et al. Levels of circulating homocysteine, vitamin B6, vitamin B12, and folate in different typers of open-angle glaucoma. Clin Interv Aging 2010;26:133-139.

Hyperhomocysteinemia was found in 27.1% of PXFG patients, 30.6% of POAG patients, and 29.4% of NTG patients. Clement CL, Goldberg I, Healey PR, Graham SL. Plasma homocysteine, MTHFR

gene mutation, and open-angle glaucoma. J Glaucoma 2009;18:73-78

PEXG and Alzheimer's disease share common associations such as the higher prevalence of hyperhomocysteinemia in both disorders. Folate, vitamin B12 and B6 levels were significantly decreased and associated with elevated Hcy levels in PEXG. Roedl JB, Bleich S, Reulbach U, et al. Vitamin deficiency and

hyperhomocysteinemia n pseudoexfoliation glaucoma. J Neural Transm 2007;114:571-575.

Hyperhomocysteinemia is a risk factor for thromboembolic vasculopathy in patients with PEXS and PEXG. Therefore, vitamin B supplementation should be considered in these patients when hyperhomocysteinemia is detected. Saricaoglu MS, Karakurt A, Sengun A, Hasiripi H. Plasma homocsteine levels and vitamin B status in patients with pseudoexfoliation syndrome. Saudi Med J 2006;27:833-837.

Elevated plasma homocysteine, a risk factor for cardiovascular disease, is more common in exfoliation syndrome and exfoliative glaucoma patients than healthy controls. Patients with exfoliation syndrome may benefit from measurement of homocysteine levels. Vessani RM, Ritch R, Liebmann JM, Jofe M. Plasma homocysteine is elevated in patients with exfoliation syndrome. Am J Ophthalmol 2003;136:41-46. Leibovitch I, Kurtz S, Shemesh G, et al. Hyperhomocysteinemia in pseudoexfoliation glaucoma. J Glaucoma 2003;12:36-39.

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…postulated that chronic beta-amyloid in AD along with caspase activation and excitotoxicity are all implicated in RGC death. (Metab Pediatr Syst Ophthalmol 1989;12:64, Font Biosci 2003;8:1140 Eur Neurol 2002;47:165, Semin Ophthalmol 2003;18:50)

Elevated homocysteine levels have also been associated with WMLs. (IGR 2007;9:15)

Nutrition. 2006 Apr;22(4):441-3. continued

•  Serum vitamin E, serum alpha-carotene, and dietary intake of antioxidants and vitamin B6 were associated with lower levels of plasma HCY, whereas hypertension was associated with increased HCY.

•  C-reactive protein and HCY levels are related to traditional dietary and behavioral factors associated with age-related macular degeneration.

400 to 1000 mcg of folic acid per day, 10 to 50 mg of vitamin B6, and 50-300 mcg of vitamin B12 per day + N-ACETYL-CYSTEINE (Acta Cardiol. 2007;62:579)

TREATMENT

SO THEN

HOW DO YOU MANAGE

GLAUCOMA?

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GET THE PRESSURE DOWN WITH MINIMAL FLUCTUATION

HOPE THAT THE PATIENT COMPLIES

HOPE THAT THE PATIENT DOES NOT

RUN OUT OF MONEY

HOPE THE PATIENT GOES TO A BETTER PLACE BEFORE THEY GO

BLIND

What is the overall recommendation for patients with glaucoma?

Do Not Smoke

Get Quality Sleep Maintain the Ideal Weight

Exercise Daily Control Hypertension and Cholesterol

Control Diabetes Eliminate Stress

Control Inflammation Maintain an Anti-Inflammatory Diet

Use Nutritional Supplementation if

Needed (Conservative)

Minimal Supplement Beneficial Action Dosage 1000 mg Triglyceride Backbone Omega 3

Immune System Modulation

b.i.d. but no recommended RDA

500 IU Vitamin D3 Neuroprotection, Immune System Modulation

b.i.d. with RDA in flux as measurement of blood levels becoming more important

High Quality Multivitamin with 400 mcg Folic Acid, 2 mg B6 6 mcg B12, Vit E, based on AHA recommendations.

Anti-Oxidation, Balance and Control of Homocysteine

q.d. or b.i.d. based on brand. Folic acid competes with methotrexate.

100 mg CoEnzyme Q10 Anti-Oxidation q.d. but more needed if on Statins or Red Yeast Rice. There is no established RDA

Desirable Optional Supplements For Mitochondrial Protection

500 mg Alpha Lipoic Acid and 400 mg Acetyl L Carnitine

Anti-Oxidant Crossing Blood Brain Barrier, Raises Glutathione, Together Maximize Lipid Metabolism

q.d. to b.i.d. but there is no established RDA

500 mg Curcumin Neuroprotection, Immune System Modulation

q.d. but there is no established RDA

60 mg Ginkgo biloba Anti-Oxidant, Facilitates Blood Flow

q.d. to b.i.d. with caution as it can thin blood

Roll Tide