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9/16/2013
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NUTRITION, BEHAVIOR ANDGLAUCOMA
LARRY J ALEXANDER OD FAAO
LETS FIRST ESTABLISH THE “TONE” OF THE DISCUSSION
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 retrolaminartissue 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.
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)
OTHER Neurological ISSUES• EXCESSIVE GLUTAMATE FORMATION ISSUES
INCLUDE:– STROKE– MIGRAINE– CNS TRAUMA– EPILEPSY– PD, AD, HD– HIV DEMENTIA– ALS, MS (Clin Ther 2004;26:615, Curr Alzheimer Res 2004;1:249, Neurochem Res 2007;32:757, Proc Natl Acad Sci USA
2007;104:13444, IGR 2007;9:23)
What About Internal Carotid Stenosis and NTG?
http://www.pillsbury.com/recipes/bacon-cheeseburger-calzones/dd289aa8-a6aa-4528-bb55-1f5057277d83
GLAUCOMA CALZONE
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DEFINITION OF GLAUCOMA
• Vascular Component…Glaucoma is Slow Ischemic Optic Neuropathy
• Neuro-Degenerative Component…Glaucoma is Like Dementia
• Inflammatory Component…Glaucoma is Affected by the Immune System
• Physical Component…Glaucoma can be a Physical Restriction in Aqueous
GLAUCOMA IS OCULAR DEMENTIA, INFLAMMATION, AND ISCHEMIA
LEADING TO GANGLION CELL DEATH WITH SUBSEQUENT RNFL DEATH AND COINCIDENT FUNCTIONAL
LOSS , EVEN COMPROMISE TO THE CORTEX
REPORTED RISK FACTORS and ASSOCIATIONS WITH GLAUCOMA
Modifiable issues highlighted in blue:
• Intraocular pressure• Farsightedness• Nearsightedness• Excessive caffeine• Playing wind instruments• Diabetes• Age• Sex• Trauma• Vascular disease• Hyper and hypotension• Smoking• Obesity
• Family history• Dementia• Erectile dysfunction• Immune system status• Hx ocular surgery• Pigmentary dispersion• Pseudoexfoliation• Ethnicity• Sleep apnea• Low ICP• Hormonal levels• Hyperhomocysteinemia• Oral, topical, inhaled steroids
IS THIS GLAUCOMA?
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SLEEP DEPRIVATION AND GLAUCOMA?
IS THERE A RELATIONSHIPBETWEEN
Nutr Rev. 2007 Dec;65(12 Pt 2):S244-52.Simpson N, Dinges DF.A number of recent studies have reported associations between disrupted sleep/sleep deprivation and inflammatory responses, although the physiological mechanisms underlying these relationships remain unclear. Alterations in sleep due to lifestyle factors, the aging process, and disease states have all been associated with increases in a range of inflammatory markers. Several of these inflammatory processes have been associated with reduced health status (e.g., C-reactive protein and cardiovascular disease).
Altering free radicals with steroids, which paradoxically could increase intraocular pressure, may block lipid peroxidation.. This is primarily achieved through suppression of inflammation.Invest Ophthalmol 1996;37:2744, J Glaucoma 1996;5:427
Immune System influences including antibodies generated by B-cells within the rubric of the general inflammatory process lead to cell death in glaucoma. Protection also occurs through the immune system pointing to the importance of proper modulation of the immune system.Cell Mol Neurobiol 2001;21:617
C-reactive protein (CRP) elevation is also associated with CSVD indicating an inflammatory process, and the elevated CRP levels are also found in NTG patients. The CRP increases endothelin which has been implicated in the proliferation of astrocytes in the nerve head and changes in the trabecular meshwork and has been found to be elevated in glaucoma and NTG after exposure to cold temperatures.Circulation 2005;112:900, J Glaucoma 2005;14:384, Circ Res 2004;95:877, Invest Ophthalmol Vis Sci 2002;43:2704, J Glaucoma 2002;11:259, J Glaucoma 1997;6:83, Br J Ophthalmol 2005;89:60, Invest Ophthalmol Vis Sci 2003;44:2565
Autoimmunity is at the root of most disorders and is defined as an attack on the host cell by activated T cells. It has actually been shown that survival of RGCs after optic nerve injury is facilitated by the autoimmune response via activated T cells. This response can either be by active immunization with a protein or by transfer of activated T cells.Cell Mol Neurobiol 2001;21:617, J Neurosci 2000;20:6421, J Neuroimmunol 2000;106:189, Nat Med 1999;5:49, Am J Ophthalmol2006;141:1105, Surv Ophthalmol 2001;45:S256, Invest Ophthalmol Vis Sci 2003;44:407, Proc Natl Acad Sci USA 2001;98:3398, ProcNatl Acad Sci USA 2000;97:7446
TNF- alpha is a pro-inflammatory cytokine that is present during excitotoxic and ischemic brain injury. Among other functions, it binds to the death receptor and can induce caspase components of the mitochondrial cell death pathway. TNF- alpha has been implicated as a mediator in RGC death.Mol Med 1997;3:765, Stroke 1994;25:1481, Stroke 1997;28:1233, Invest Ophthalmol Vis Sci 2001;42:1787
TNF- α inhibitors (GLC756) are being investigated for the treatment of glaucoma. Exp Eye Res 2006;83:1335, Exp Eye Res 2006;83:1246
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WHAT ARE ISSUES THAT CREATE INFLAMMATION?
• OBESITY• LACK OF EXERCISE• LACK OF SLEEP• POOR DIET • LACK OF ENOUGH OMEGA 3• SMOKING AND AIR POLLUTION• STRESS
THIS IS THE “AMERICAN PROFILE”
SLEEP APNEA AND GLAUCOMA?
IS THERE A RELATIONSHIPBETWEEN
77 YO PO CATARACTMULTIPLE INVESTIGATIONS, MEDICATIONS, AND OPTIC NERVE DECOMPRESSION…
23 INCH NECK WITHSLEEP 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
34% of NFL Lineman Have OSAS.
TAKEO SPIKES
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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
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. Ophthalmologica2002;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, Ophthalmologica2002;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???
I Want You to Think and Question.
What if I told you that men with erectile dysfunction have a nearly 3X risk for having
POAG than men with normal erectile function?Ophthalmology 2012:119:289-293
WHY?
There is a clear beneficial effect of the use of glaucoma medication on the likelihood of
death. Patients taking topical PGAs, a-agonists and B-blockers for confirmed POAG
associated with a 74% reduction in death.Arch Ophthalmol 2010;128:235-240
I Want You to Think and Question
WHY?
WHAT ABOUT?
“SHOULD THERE BE MORE CONCERN REGARDING THE UBIQUITOUS USE OF NASAL
AND INHALED CORTICOSTEROIDS”EYELESSONS.COM 2013
Larry’s Story
The lesson from my own experience is “If it’s in the chair, it isn’t rare.”
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STUDIES REPORTING IOP RISE WITH NASAL AND INHALED STEROIDS
• Opatowsky I, Feldman RM, Gross R, Feldman ST. Intraocular pressure elevation associated with inhalation and nasal corticosteroids. Ophthalmology. 1995 Feb;102(2):177-179.
• Garbe E, LeLorier J, Boivin JF, Suissa S. Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angle glaucoma. JAMA. 1997 Mar 5;277(9):722-727.
• Garbe E, Suissa S, LeLorier J. Association of inhaled corticosteroid use with cataract extraction in elderly patients. JAMA.1998 Aug 12;280(6):539-543.
• Sapir-Pichhadze R, Blumenthal EZ. [Steroid induced glaucoma]. Harefuah. 2003 Feb;142(2):137-140, 157.• Clark AF, Wordinger RJ. The role of steroids in outflow resistance. Exp Eye Res. 2009;88:752–759.• Podos SM, Becker B, Morton WR. High myopia and primary open-angle glaucoma. Am J Ophthalmol. 1966 Dec;62(6):1038-
1043.• Mitchell P, Cumming RG, Mackey DA. Inhaled corticosteroids, family history, and risk of glaucoma. Ophthalmology. 1999
Dec;106(12):2301-2306.• Bui CM, Chen H, Shyr Y, Joos KM. Discontinuing nasal steroids might lower intraocular pressure in glaucoma. J Allergy Clin
Immunol. 2005 Nov;116(5):1042-1047. • Peridis S, Hopkins C, Lekakis G, Roberts D. Re: Discontinuing nasal steroids might lower intraocular pressure in glaucoma.
Clin Otolaryngol. 2010 Feb;35(1):72. doi: 10.1111/j.1749-4486.2009.02058.x.• Bollinger KE, Crabb JS, Yuan X, et al. Proteomic similarities in steroid responsiveness in normal and glaucomatous trabecular
meshwork cells. Mol Vis. 2012; 18: 2001–2011. Published online 2012 July 20. • Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye (Lond) 2006;20:407–416.• Jones R, 3rd, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature.
Curr Opin Ophthalmol. 2006;17:163–167.
There is INCR RISK (44% MORE LIKELY) of Glaucoma with High Dose Inhaled Steroids > 3 Months of Use (Ear Nose Throat J 1998;77:846)
More than 20% of Americans suffer from allergic rhinitis and is present in up to 75% of patients with asthma. Blaiss MS. Safety considerations of intranasal corticosteroids for the treatment of allergic rhinitis. Allergy Asthma Proc2007;28;145-152
There is the suggestion that there is a dose-related risk of open-angle glaucoma with inhaled corticosteroids for treating moderate to severe COPD. Gartlehner G, Hansen RA, Carson SS, LohrKN. Efficacy and safety of inhaled corticosteroids in patients with COPD: a systematic review and meta-analysis of health outcomes. Ann Fam Med 2006;4:253-262.
Patients Taking Oral Glucocorticoids Should Have Their IOPs Checked Every 6 Months (Brit Med J 1997;314:695)
With a Strong Family History of Glaucoma Inhaled Steroids Increase the Risk (Ophthalmology 1999;106:2301)
IOP was Reduced With the Discontinuation of Nasal Steroids in Patients with Glaucoma (J Allergy Clin Immunol 2005;116:1042)
STUDIES REPORTING NO IOP RISE WITH NASAL AND INHALED STEROIDS
• Oztürk F, Yücetürk AV, Kurt E, et al. Evaluation of intraocular pressure and cataract formation following the long-term use of nasal corticosteroids. Ear Nose Throat J. 1998 Oct;77(10):846-848, 850-851.
• Duh MS, Walker AM, Lindmark B, Laties AM. Association between intraocular pressure and budesonide inhalation therapy in asthmatic patients. Ann Allergy Asthma Immunol. 2000 Nov;85(5):356-361.
• Marcus MW, Müskens RP, Ramdas WD, et al. Corticosteroids and open-angle glaucoma in the elderly: a population-based cohort study. Drugs Aging. 2012 Dec;29(12):963-970.
• Miller DP, Watkins SE, Sampson T, Davis KJ. Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database. Int J Chron Obstruct Pulmon Dis. 2011;6:467-476.
• Ozkaya E, Ozsutcu M, Mete F. Lack of ocular side effects after 2 years of topical steroids for allergic rhinitis. J Pediatr Ophthalmol Strabismus. 2011 Sep-Oct;48(5):311-317.
• Emin O, Fatih M, Mustafa O, et al. Evaluation impact of long-term usage of inhaled fluticasone propionate on ocular functions in children with asthma. Steroids. 2011 May;76(6):548-552.
• BehbehaniAH, Owayed AF, Hijazi ZM, et al. Cataract and ocular hypertension in children on inhaled corticosteroid therapy. J Pediatr Ophthalmol Strabismus. 2005 Jan-Feb;42(1):23-27.
• Bergmann J, Witmer MT, Slonim CB. The relationship of intranasal steroids to intraocular pressure. Curr Allergy Asthma Rep. 2009 Jul;9(4):311-315.
• Gonzalez AV, Li G, Suissa S, Ernst P. Risk of glaucoma in elderly patients treated with inhaled corticosteroids for chronic airflow obstruction. Pulm Pharmacol Ther. 2010 Apr;23(2):65-70.
• Peters SP. Safety of inhaled corticosteroids in the treatment of persistent asthma. J Natl Med Assoc. 2006 Jun;98(6):851-861.• Gartlehner G, Hansen RA, Carson SS, Lohr KN. Efficacy and safety of inhaled corticosteroids in patients with COPD: a systematic
review and meta-analysis of health outcomes. Ann Fam Med. 2006 May-Jun;4(3):253-262.• Rossi GA, Cerasoli F, Cazzola M. Safety of inhaled corticosteroids: room for improvement. Pulm Pharmacol Ther. 2007;20(1):23-35. • Buys YM, Yuen D, Jin Y, et al. The Effect of Nasal Steroids on Intraocular Pressure in Ocular Hypertension or Controlled Glaucoma.
AGS 2011. Abstract.ControlNumber:148.
In a large cohort of elderly patients treated for airways disease, it was found that current use and continuous use of high-dose ICS did not result in an increased risk of glaucoma or raised intra-ocular pressure requiring treatment. Gonzalez AV, Li G, Suissa S, Ernst P. Risk of glaucoma in elderly patients treated with inhaled corticosteroids for chronic airflow obstruction. Pulm Phamacol Ther 2010;23:65-70.
There is NO RISK of Glaucoma with Inhaled Steroids (JAMA 1997;277:722)
5-8 % of the General Population are Steroid Responders While 95% of POAG Patients are Steroid Responders (Ann Allergy 1989;62:375, Dermatol Clin 1998;16:277)
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SO WHAT DOES EVIDENCE-BASED MEDICINE SAY TO DO?
Actually….nothing. The studies leave you hanging. But if you read this study…..
“Inhalation steroid therapy can cause ocular hypertension or open angle glaucoma. The authors describe the case of a young girl who presented with raised intraocular pressure and headaches due to the prolonged administration of nasal and inhalation steroids. The ophthalmologist should monitor the intraocular pressure in patients who use inhalation or nasal steroid therapy on a regular base. The physician or paediatricianshould be aware of this complication in children with headaches or diminished visual acuity.” 27
Desnoeck M, Casteels I, Casteels K. Intraocular pressure elevation in a child due to the use of inhalation steroids--a case report. Bull Soc Belge Ophtalmol. 2001;(280):97-100.
WHAT ARE THE AT RISK GROUPS?
WHAT ARE THE TARGET GROUPS?• Patients who currently are being treated for
glaucoma • Patients who have been identified as being at risk for
glaucoma• Patients who are offspring of patients who were
identified with glaucoma• Patients with siblings with glaucoma• Patients with myopia over 5 diopters• Patients who are known steroid responders• Patients who are required to use higher dosages for a
prolonged period of time…
SEE EVERY 6 MONTHS
WHAT ELSE?
• LETTER TO MDS/HEALTH CARE PROVIDERS• LETTER TO PHARMACISTS• EDUCATE PATIENTS
Dr. or Mr./Dr. (pharmacist) or Nurse Practitioner or other ODs in the immediate surround
Dear Dr./Mr. _____________,
I am pleased to announce that our practice is equipped to follow and manage patients who are prescribed nasal and inhaled corticosteroids. These medications have the potential to increase intraocular pressure and create glaucoma in a subgroup of patients. Dr. Rick Wilson in the Wills site http://willsglaucoma.org/steroid-use-and-iop reports in a discussion that 5% of the general population of patients are steroid responders while 95% of Glaucoma patients are steroid responders. He further states that if steroid use is prolonged, 50% or more of the population are steroid responders. What is of most concern is the fact that the majority of the time the steroid responders are asymptomatic until significant damage has occurred.
The characteristics of the patient groups at greatest risk are:
Patients who currently are being treated for glaucoma or Patients who have been identified as being at risk for glaucomaPatients who are offspring of patients who were identified with glaucomaPatients with siblings with glaucomaPatients with nearsightedness over 5 dioptersPatients who are known steroid respondersPatients who are required to use higher dosages for a prolonged period of time…there appeared to be a dosage/duration connection in some of the reports. Note that a number of the studies that report no relationship are short-term studies, even the latest Clinical Trial reported as an AGS abstract.
For those patients outside of these characteristics an intraocular pressure/glaucoma evaluation yearly would be an effective conservative approach. Our office is equipped to perform pre-treatment evaluation and post-treatment follow-up. Additionally we will provide you a report of the patient’s status including spectral domain OCT analysis. Termination of the steroid usually allows the pressure to go back down and structural damage is minimized. Included will be recommendations for appropriate follow-up care. We are delighted to be able to provide these services to your patients.
Sincerely,
Larry J Alexander, OD
Downloadable from eyelessons.com
MYOPIA AND GLAUCOMA?
IS THERE A RELATIONSHIPBETWEEN
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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
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%POAGOffspring
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
0
5
10
15
20
25
30
35
3 0.5 to 2.0 0.25 to 0.25 0.50 to 2.00 2.25 to 4.00 4.25 to 6.75 7.00 to 9.00 10.00 to 13.50
%
pig
mentary
Hyperopia Myopia
78.22% MYOPIC
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
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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
Statistically significant differences in the structure of ONH and peripapillary retina in non
glaucomatous high myopes compared to on glaucomatous emmetropes. OCT measurements
of RNFL thicknesses different in non glaucomatous with tilted discs.
Tsutsumi T, Tomidokoro A, Saito H et al. Confocal scanning laser ophthalmoscopy in high myopic eyes in a population-based setting. Invest Ophthalmol Vis Sci 2009;50:5281-5287
Law SK, Tamboli DA, Giaconi J, Caprioli J. Characterization of retinal nerve fiber layer in nonglaucomatous eyes with tilted discs. Arch Ophthalmol. 2010 Jan;128(1):141-2.
IMAGES FURTHER OUTFROM THE ONH GIVINGTHINNER RNFL
AXIAL MYOPIA AND IMAGING THE RNFL • Patients who are offspring of patients who were identified with glaucoma• Patients with siblings with glaucoma• Patients with axial length over 25 mm• Patients with myopia over 5 diopters—Be on the alert for normotensive
glaucoma as well• Patients who are known steroid responders• For diagnosis
• Use all available modalities realizing that data acquisition will be difficult because of fixation issues and optic nerve head architecture
• Remember to perform gonioscopy and look for pigmentary glaucoma• Rely on newer technologies such as Ganglion Cell Complex assessment
that is less dependent on optic nerve head architecture and easier to acquire because of fixation advantages.
• For treatment• Realize that the patient with higher myopia and axial length will be
potentially more difficult to manage with therapeutic intervention and will be more difficult to follow because of testing issues.
SMOKING AND GLAUCOMA
IS THERE ABSOLUTE PROOF?
http://www.eyelessons.com/articles/item/is-there-a-significant-relationship-of-smoking-and-obesity-to-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 Zhi2008;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 (METABOLIC SYNDROME), SLEEP APNEA AND GLAUCOMA
IS THERE ABSOLUTE PROOF?http://www.eyelessons.com/articles/item/is-there-a-significant-relationship-of-smoking-and-obesity-to-glaucoma
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 pressure2. elevated serum triglycerides
3. low HDL4. 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 Obes2010;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
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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
IS THERE ABSOLUTE PROOF?
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 intraocularpressure 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
IS THERE ABSOLUTE PROOF?
= CONTROLLED IOP
http://www.eyelessons.com/articles/item/marijuana-and-glaucoma
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?
?
IS THERE ABSOLUTE PROOF?
NUTRITION AND GLAUCOMA Is There More to Glaucoma Treatment Than Lowering IOP? Maneli Mozaffarieh, MD, and Josef Flammer, MD University Eye Clinic, Basel, Switzerland Abstract. Classic glaucoma treatment focuses on intraocular pressure (IOP) reduction. Better knowledge of the pathogenesis of the disease has opened up new therapeutical approaches. Whereas most of these new avenues of treatment are still in the experimental phase, others, such as magnesium, gingko, salt and fludrocortisone, are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved locally by carbonic anhydrase inhibitors, and systemically with magnesium or with low doses of calcium channel blockers. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Inhibition of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodeling. Upregulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head. Reduction of oxidative stress especially at the level of mitochondria also seems to be protective. This can be achieved by gingko; dark chocolate; polyphenolicflavonoids occurring in tea, coffee, or red wine; anthocyanosides found in bilberries; as well as by ubiquinone and melatonin. (Surv Ophthalmol 52:S174--S179, 2007. 2007 Elsevier Inc. All rights reserved.)
Evidence for the use of nutritional supplements and herbal medicines in common eye diseases. West AL, Oren GA, Moroi SE. The available evidence does support the use of certain vitamins and minerals in patients with certain forms of age-related macular degeneration. For cataracts, the available evidence does not support these supplements to prevent or treat cataracts in healthy individuals. For diabetic retinopathy and glaucoma, the available evidence does not support the use of these supplements. In the category of herbal medicines, the available evidence does not support the use of herbal medicines for any of these ocular diseases. (Am J Ophthalmol. 2006 Jan;141(1):157-66.)
Use of herbal medicines and nutritional supplements in ocular disorders: an evidence-based review. Wilkinson JT, Fraunfelder FW. Current data does not support the use of antioxidants or herbal medications in the prevention or treatment of cataracts, glaucoma or diabetic retinopathy. It is important for providers to be aware of the benefits and the significant potential adverse effects that have been associated with nutritional supplements and herbal medications, and to properly inform their patients when making decisions about supplementation.(Drugs. 2011 Dec 24;71(18):2421-34)
Positive Actions Supported in the Literature
• Minimizing inflammation• Normalizing ocular collagen and protecting ocular
tissue against the neurotoxicity of glutamate.• Address nutrients that exert specific influences on
Glycosaminoglycans (GAGs)• Increasing ocular antioxidant defenses and scavenging
harmful free radical molecules.• Increasing the ocular level of glutathione to improve
outflow and minimize antioxidant activity• Preventing inappropriate release and actions of nitric
oxide (NO) and vasoconstrictors from vascular endothelium.
Positive Actions Supported in the Literature
• Improving ocular blood flow• Minimizing inflammation and modulating the immune
system• Protecting the mitochondria before the process of
apoptosis is unstoppable…Neuroprotection• Control excessive glutamate• CONSIDER THE GENETICS RELATED TO THE PROBLEM.
NEW DATA INDICATE THAT THERE ARE GENETIC INFLUENCES ON THE ABILITY TO ASSIMILATE AND UTILIZE KEY NUTRITIONAL COMPONENTS.
The Eye on Fire
Modulating The Morbidity of Inflammation
IS THERE ABSOLUTE PROOF?
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WHAT KIND OF BEHAVIOR MODIFICATION AND SUPPLEMENTS MODULATE INFLAMMATION?
• Employ an Anti-Inflammatory Diet• Stop smoking• Lose Weight• Exercise• Balance Omega 6 Intake With Omega 3
Supplementation• Check Vitamin D Levels and Consider
Supplementation• Consider the Benefits of a High Quality Vitamin
Supplement• Consider Curcumin Supplementation• Consider Other Immune System Modulators Like
Colostrum
THE POTENTIAL EFFECTS OF SUPPLEMENTS??? WHICH ONES???
IS THERE ABSOLUTE PROOF?
ISSUES OF COST AND BIOAVAILABILITYREMEMBER IF THIS DOESN’T WORK
SUPPLEMENTATION WON’T WORK
IS THE CAUSE
MIRTOGENOL AND GLAUCOMA
+
http://www.eyelessons.com/articles/item/mirtogenol-is-it-the-real-deal
http://www.eyelessons.com/articles/item/pycnogenol-for-diabetes-mellitus
Mirtogenol-bilberries + pycnogenol significantly increased velocity of blood flow through
ophthalmic arteries, central retinal arteries, and posterior ciliary arteries while lowering IOP in ocular hypertension. The lowering of IOP was
synergistic with latanoprost but took 6X as long to occur.
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
In a study of ocular hypertensives without symptoms
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Mechanism of Action
• Anthocyanins and procyanidins phenolic extracts-Any of a class of organic compounds with a hydroxyl group attached to a carbon atom in a ring of an aromatic compound.
• Previous investigation in control of capillary leakage in diabetic retinopathy. Schönlau F, Rohdewald P. Pycnogenol® for diabetic retinopathy. A review. Int Ophthal. 2002;24:161–171. Perossini M, Guidi G, Chiellini S, Siravo D. Diabetic and hypertensive retinopathy therapy with Vacciniummyrtillus anthocyanosides (Tegens®):Double blind placebo-controlled clinical trial. Ann Ottal Clin Ocul. 1987;113:1173–1190. Repossi P, Malagola R, De Cadilhac C. The role of anthocyanosideson vascular permeability in diabetic retinopathy. Ann Ottal Clin Ocul.1987;113:357–361.
• IOP lowering attributable to “significant ocular blood flow increase.” Steigerwalt RD, Belcaro G, Paolo M, Bombardelli E, Burki C, SchönlauF. Effects of Mirtogenol on ocular blood flow and intraocular hypertensionin asymptomatic subjects. Mol Vis. 2008;14:1288–1292.
Mechanism of Action
• Pycnogenol improves endothelial function which is altered in POAG. REDUCES PLASMA ENDOTHELIN-1 AND ENHANCES NITRIC OXIDEEhrlich R, Kheradiya NS, Winston DM, Moore DB, Wirostko B, Harris A. Age-related ocular vascular changes. Graefes Arch Clin Exp Ophthalmol. 2009;247:583–591.Nishioka K, Hidaka T, Takemoto H, et al. Pycnogenol®, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res 2007;30:775–780.
• Mirtoselect counteracts hyperpermeability of ciliary capillaries…acting on aqueous secretionVirno M, Pecori Giraldi J, Auriemma L, Antocianosidi di mirtilloe permeabilità dei vasi del corpo ciliare. Boll Ocul. 1986;65:789–795.
2008 Controlled Study. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447819/
• 160 mg Mirtoselect• 80 mg Pycnogenol
2010 Controlled Study. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447819/
• 80 mg Mirtoselect• 40 mg Pycnogenol• 1gtt Latanoprost
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The Results-IOP
0
5
10
15
20
25
30
35
40
0 5 10 15 20 25
MirtogenolLatanoprostBoth
40 % Decrease
Weeks of Treatment
IOP
The Results-Diastolic Blood Flow
Weeks of Treatment
0
1
2
3
4
5
6
7
8
0 4 6 12 16 20 24
MirtrogenolLatanoprostBoth
CM/S
192 % Increase
The Results-Systolic Blood Flow
Weeks of Treatment
0
5
10
15
20
25
30
0 4 6 12 16 20 24
MirtrogenolLatanoprostBoth
CM/S
39 % Increase
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Schönlau F, Rohdewald P. Pycnogenol® for diabetic retinopathy. A review. Int Ophthal. 2001;24:161–171.
Perossini M, Guidi G, Chiellini S, Siravo D. Diabetic and hypertensive retinopathy therapy with Vaccinium myrtillusanthocyanosides (Tegens®):Double blind placebo-controlled clinical trial. Ann Ottalmol Clin Ocul. 1987;113:1173–1190.
Repossi P, Malagola R, De Cadilhac C. The role of anthocyanosides on vascular permeability in diabetic retinopathy. Ann OttalmollClin Ocul.1987;113:357–361.
Ehrlich R, Kheradiya NS, Winston DM, Moore DB, Wirostko B, Harris A. Age-related ocular vascular changes. Graefes Arch Clin ExpOphthalmol. 2009;247:583–591.
Nishioka K, Hidaka T, Takemoto H, et al. Pycnogenol® ®, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans. Hypertens Res 2007;30:775–780.
Virno M, Pecori Giraldi J, Auriemma L, Antocianosidi di mirtillo e permeabilità dei vasi del corpo ciliare. Boll Ocul. 1986;65:789–795.
Steigerwalt RDJr., Gianni B, Paolo M, et al. Effects of Mirtogenol™on ocular blood flow and intraocular hypertension in asymptomatic subjects. Mol Vis. 2008; 14: 1288–1292.
Cellini M, Versura P, Zamparini E, et al. Effects of endothelin-1 and flunarizine on human trabecular meshwork cell contraction. Exp Biol Med (Maywood) 2006;231:1081–1084.
Schmetterer L, Krejcy K, Kastner J, et al. The effect of systemic nitric oxide-synthase inhibition on ocular fundus pulsations in man. Exp Eye Res. 1997;64:305–312.
Liu X, Wei J, Tan F, et al. Antidiabetic Effect of Pycnogenol® French Maritime Pine Bark Extract in patients with diabetes type II. Life Sci. 2004;75:2505–2513.
Colantuoni A, Bertuglia S, Magistretti MJ, Donato L. Effects of Vaccinium Myrtillus anthocyanosides on arterial vasomotion. Arzneimittelforschung. 1991;41:905–909.
Steigerwalt RD Jr, Belcar G, Morazzoni P, et al. Mirtogenol® potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects. Clinical Ophthalmology 2010; 4: 471–476.
Summary of Facts
• At around 4-6 weeks the synergistic effects of a Prostaglandin and Mirtrogenol (120 mg )– Increases systolic blood flow – Increases diastolic blood flow – Decreases intraocular pressure
• 120 mg of Mirtrogenol costs about $1
192 % Increase
39 % Increase
40 % Decrease
SOME STANDARDS
VITAMIN A
• Involvement in Immune System• Potential Risk• A recent study points to the fact that neither
supplementary consumption nor serum levels of vitamins A and E were associated with glaucoma prevalence. (Eye (Lond). 2013 Apr;27(4):487-940)
• Obtain From Diet and Good Multivitamin
LYCOPENE
• Carotenoid• Safe• There is no strong evidence to recommend
supplementation of any form of Lycopene beyond that obtained in the normal diet for minimizing the risk of glaucoma damage.
• Obtain From Diet
LUTEIN AND ZEAXANTHIN
• Carotenoids• Safe and effective in ARM• While it has been suggested, there is no
strong evidence to recommend supplementation of any form of Lutein and Zeaxanthin beyond that obtained in the normal diet for minimizing the risk of glaucoma damage.
• Obtain From Diet
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VITAMIN C• Anti-oxidant That Functions in Immune System• Recent work has elucidated the fact that normal
tension glaucoma patients have lower levels of serum vitamin C (Graefes Arch Clin Exp Ophthalmol. 2010 Feb;248(2):243-8)and that ascorbic acid levels are reduced in the aqueous of patients with glaucoma. (Eye (Lond). 2009 Aug;23(8):1691-7,Clin Experiment Ophthalmol. 2009 May;37(4):402-6)
• Recent work found that vitamin C supplementation was associated with decreased odds of glaucoma but the serum levels did not correlate. (Eye (Lond). 2013 Apr;27(4):487-940)
• Obtain From Diet and Consider for Supplementation in Poor Diets
VITAMIN D3• FAT SOLUBLE • The link of Vitamin D3 to glaucoma is associated with
vascular perfusion issues as well as neuroprotectionand the immune system
• There is even recent work suggesting topical vitamin D3 is of benefit lowering the IOP by increasing drainage in a primate model. (Arch Biochem Biophys. 2012 Feb 1;518(1):53-60)
• Obtain From Diet, Sunlight• There is evidence to recommend supplementation of
vitamin D3 beyond that obtained in the normal diet for minimizing the risk of glaucoma damage.
VITAMIN E• Fat Soluble Anti-Oxidant that is controversial• Vitamin E is known to affect the expression and
activity of immune and inflammatory cells, to enhance vasodilation and to inhibit the activity of the cell signaling molecule protein kinase C (PKC)
• It is estimated that more than 90% of Americans do not meet daily dietary recommendations for vitamin E. (J Am Diet Assoc. 2004;104(:567)
• Obtain From Diet and a Good Multivitamin• There is some evidence to recommend
supplementation of vitamin E beyond that obtained in the normal diet for minimizing the risk of glaucoma damage. .
Hyperhomocysteinemia, Normal Tension Glaucoma, Blood Flow Anomalies and Optic Neuropathy have a lot in common and are often related to supplementation with Vitamins B6, B12 and Folic Acid. Recent publications have defined a relationship between plasma total homocysteine and POAG but there was no defined relationship to serum folic acid, B12 or B6. (Ophthalmology. 2012
Dec;119(12):2493-9, Curr Eye Res. 2012 Aug;37(8):712-8.) To further complicate the conclusions two years prior to this report there was found to be no association of elevated homocysteine levels in normal tension glaucoma. (J Glaucoma. 2010 Dec;19(9):576-80) Yet other findings demonstrated a relationship of elevated homocysteine only in pseudoexfoliative glaucoma and not normal tension or open angle glaucoma. (Clin Interv Aging. 2010 Apr 26;5:133-9, Graefes Arch Clin Exp Ophthalmol.2012 Jul;250(7):1067-74, Graefes Arch Clin Exp Ophthalmol. 2011 Mar;249(3):443-8)
VITAMIN B6• Very important in enzymatic activity and immune
function
• Works in concert with B12 and Folic Acid• Obtain From Diet and Good
Multivitamin…Malabsorption Issues• Consider for Supplementation in Poor Diets or
Patients with Hyperhomocysteinemia
VITAMIN B12• Very important in enzymatic activity, neuroprotection and
immune function….Alzheimer Disease • Vitamin B12 deficiency is estimated to affect 10%-15% of
individuals over the age of 60
• Works in concert with B6 and Folic Acid• Obtain From Diet and Good Multivitamin…Malabsorption
Issues• Consider for Supplementation in Poor Diets or Patients
with Defined or Suspected Hyperhomocysteinemia
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FOLIC ACID• Very important metabolism of nucleic and
amino acids as well as DNA metabolism• Works in concert with B6 and B12• Obtain From Diet (Folate) and Good
Multivitamin (Folic Acid)…MalabsorptionIssues
• Consider for Supplementation in Poor Diets or Patients with Defined or Suspected Hyperhomocysteinemia
ZINC• CRITICAL ENZYME• WATCH TOXICITY• WORKS IN CONCERT WITH B6 AND B12• OBTAIN FROM DIET (FOLATE) AND GOOD
MULTIVITAMIN (FOLIC ACID)…MALABSORPTION ISSUES
• CONSIDER FOR SUPPLEMENTATION IN POOR DIETS OR PATIENTS WITH ASSOCIATED ARM
MAGNESIUM• VERY SHORT ACTING• MAGNESIUM SEEMS TO HAVE A BENEFICIAL
EFFECT ON THE VISUAL FIELD IN GLAUCOMA PATIENTS WITH BOTH INCREASED AND NORMAL IOP--POSSIBLY BY ALLEVIATING VASOSPASM AT 300 MG/DAY. MAGNESIUM ALSO WORKS TO ACTIVATE ENZYMATIC SYSTEMS. (Ophthalmologica1995;209(1):11-3) (Surv Ophthalmol 1995;209(1):83-4)
• OBTAIN FROM DIET AND GOOD MULTIVITAMIN
SELENIUM
• CRITICAL IN GLUTATHIONE PRODUCTION• WATCH TOXICITY• OBTAIN FROM DIET AND GOOD
MULTIVITAMIN
OMEGA 3• SOURCE OF TREMENDOUS CONTROVERSY• EAT NON-CONTAMINATED FISH IF YOU CAN
AFFORD IT• TRIGLYCERIDE BASE MORE BIOAVAILABLE AND
MORE STABLE• BALANCE WITH OMEGA 6 IS CRITICAL• SUPPORT OF DRY EYE FROM GLAUCOMA GTTS• DEFINED RESULTS IN CARDIOVASCULAR• KNOWN ANTI-INFLAMMATORY EFFECTS• SOME EVIDENCE TO RECOMMEND
SUPPLEMENTATION ESPECIALLY IN CHALLENGED DIETS.
CURCUMIN
• POTENT IMMUNOMODULATOR• TEN KNOWN NEUROPROTECTIVE ACTIONS• KNOWN TO DOWN REGULATE PRO-
ANGIOGENIC PROTEINS• UNLESS HIGH CONSUMPTION OF CURRY
MUST SUPPLEMENT TO OBTAIN EFFECT AND MAY BE OF VALUE IN GLAUCOMA
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CURCUMIN• DECREASES ROS AND RNS• REDUCES MICROGLIAL ACTIVATION• DECREASES IL-12• INITIATES TH1 TO TH2 SHIFT• PREVENTS ACTIVATION OF NFKB• REGULATES T CELLS, B CELLS, MACROPHAGES,
NEUTROPHILS, NK CELLS• DOWN-REGULATES PROINFLAMMATORY
CYTOKINES AND CHEMOKINES• RECOMMEND 500 TO 1000 MG/DAY BUT
BIOAVAILABILITY MAY BE AN ISSUE
COLOSTRUM• From Wikipedia
http://en.wikipedia.org/wiki/Colostrum “Colostrum …..is a form of milk produced by the mammary glands of mammals (including humans) in late pregnancy. Most species will generate colostrum just prior to giving birth.
• Bovine colostrum contains powerful, neutralizing agents called immunoglobulins for protection against a host of pathogens. Colostrum is also a source of other immune and growth factor components including antibodies, specific growth factors, proline-rich polypeptides, lactoferrin, leukocytes, and lactoperoxidases. It has been found that colostrum can have therapeutic effects against a variety of infections of bacterial, viral, and parasitic origin.
COMPONENTS OF COLOSTRUM• IMMUNOGLOBULINS
– IgG– IgA– IgM– IgE– IgD
• Cytokines• Lactoferrin• Lysozyme • Lactalbumin• Lacotperoxidase
COMPONENTS OF COLOSTRUM• Proline Rich Polypeptides• Growth Factors
– Epidermal Growth Factors– Fibroblast Growth Factors– Insulin-like Growth Factor– Platelet-derived Growth Factor– Transforming Growth Factors
• Vitamins– A, B2, B9, B12, D
COMPONENTS OF COLOSTRUM• Essential Nutrients
– Carbohydrates, Lipids, Protein
• Minerals– Ca, CL, Fe, Mg, P, K, Na, Zn
• Amino Acids
SCIENCE OF COLOSTRUM• Isolation of HIV-1-Neutralizing Mucosal Monoclonal Antibodies from Human
Colostrum 2012• Hyperimmune Bovine Colostrum as a Low-Cost, Large-Scale Source of Antibodies
with Broad Neutralizing Activity for HIV-1 Envelope with Potential Use in Microbicides 2012
• Randomized control trials using a tablet formulation of hyperimmune bovine colostrum to prevent diarrhea caused by enterotoxigenic Escherichia coli in volunteers 2011
• Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells 2012
• Colostrum supplementation protects against exercise - induced oxidative stress in skeletal muscle in mice 2012
• Prevention of Influenza Episodes With Colostrum Compared With Vaccination in Healthy and High-Risk Cardiovascular Subjects: The Epidemiologic Study in San Valentino. 2007
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What Else May Impact and Can Be Obtained From Diet or Multivitamin?
• Magnesium seems to have a beneficial effect on the visual field in glaucoma patients with both increased and normal IOP--possibly by alleviating vasospasm at 300 mg/day. Magnesium also works to activate enzymatic systems. (Ophthalmologica1995;209(1):11-3) (Surv Ophthalmol 1995;209(1):83-4)
• Zinc• Selenium
WHAT ABOUT MAINTENANCE OF MITOCHONDRIAL HEALTH?
Bruce Ames, the undisputed leader in the field of micronutrient impact on mitochondria, posits a new theory about homeostasis during micronutrient shortage, which, if confirmed, will radically change thinking about requirements for micronutrients and public health. His triage hypothesis offers that the risk of degenerative diseases associated with aging, including cancer, cognitive decline, and immune dysfunction, can be decreased by ensuring adequate intake of micronutrients (the 40 essential vitamins, minerals, amino acids, and fatty acids) earlier in life, a simple and inexpensive solution to a potentially large public health problem. The triage hypothesis predicts that insidious changes may indeed be occurring, providing a unifying rationale for diverse observations in the literature that suggest links between micronutrient availability, aging, and the diseases of aging. (Proc Natl Acad Sciences USA 2006;103:17589)
ALPHA-LIPOIC ACID• FAT AND WATER SOLUBLE AND CROSSES THE BLOOD-BRAIN
BARRIER• RAISES GLUTATHIONE LEVELS• REGENERATES ANTI-OXIDANTS AND REMOVES IRON• ACETYL CARNITINE AND LIPOIC ACID, IMPROVES
MITOCHONDRIAL FUNCTION IN THE LIVER AND BRAIN AND INCREASES ACTIVITY LEVELS AND SCORES ON COGNITION TESTS. (Proc. Natl. Acad. Sci. USA 2002;99:2356, Proc. Natl. Acad. Sci. USA 2002;99:1870, Proc. Natl. Acad. Sci. USA 2002;99:1876).
• OTHER STUDIES POINT TO THE FACT THAT ALPHA-LIPOIC ACID PROTECTS AND RESCUES THE RETINAL NEURONS UNDER STRESS (PLoS One. 2013 Jun 5;8(6):e65389., J Neurosci 2010,30: 5644–5652, Neuropharmacology 2002;43:1015, Neuroscience 2007;145:1120) EVEN WHEN CHALLENGED BY TOXINS IN CIGARETTE SMOKE. (Invest Ophthalmol Vis Sci 2007;48:339)
• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF VALUE IN GLAUCOMA
ACETYL-L-CARNITINE• IMPORTANT IN COVERTING FATTY ACIDS TO ENERGY• MAXIMIZES MITOCONDRIAL FUNCTIONS• NEUROPROTECTIVE• PROTECTS AGAINST GLUTAMATE• OBTAIN FROM DIET AND MANUFACTURED BY BODY BUT
SUPPLEMENTATION MAY BE OF VALUE IN GLAUCOMA
GINGKO BILOBA• ENHANCES PERIPHERAL BLOOD FLOW WHILE INHIBITING
PLATELET ACTIVATION• ANTI-OXIDATION• POTENTIAL SIDE EFFECTS• MAXIMIZES MITOCONDRIAL FUNCTIONS…ENTERS
MITOCHONDRIA• NEUROPROTECTIVE• PROTECTS AGAINST GLUTAMATE• DIFFICULT TO OBTAIN FROM DIET BUT
SUPPLEMENTATION MAY BE OF VALUE IN GLAUCOMA
COENZYME Q10• FAT-SLUBLE ANTIOXIDANT • HEART CENTRIC• POTENTIAL SIDE EFFECTS• MAXIMIZES MITOCONDRIAL FUNCTIONS…WORKS AT
MEMBRANE• NEUROPROTECTIVE• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF
VALUE IN GLAUCOMA ESPECIALLY IN CASES OF CARDIOVASCULAR COMPROMISE
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MELATONIN• HORMONE ACTING AS AN ANTI-OXIDANT• CURRENT EVIDENCE SUGGESTS THAT MELATONIN MAY ACT AS A
PROTECTIVE AGENT IN OCULAR CONDITIONS SUCH AS PHOTO-KERATITIS, CATARACT, GLAUCOMA, RETINOPATHY OF PREMATURITY AND ISCHEMIA/REPERFUSION INJURY. (J Pineal Res 2006;40:101)
• “BUT MODERATE AND SEVERE GLAUCOMA DOES NOT APPEAR TO BE ASSOCIATED WITH ABNORMAL MELATONIN CONCENTRATIONS IN AQUEOUS HUMOR.” (Am J Ophthalmol 2006;142:325)
• POTENTIAL SIDE EFFECTS• POSITIVELY EFFECTS MITOCHONDRIAL HEALTH• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF
VALUE IN GLAUCOMA ESPECIALLY IN CASES OF TREMENDOUS DIURNAL VARIATION
TAURINE• 50% OF FREE AMINO ACID CONTENT OF RETINA• POTENT ANTI-OXIDANT• COUNTERBALANCES GLUTAMATE• NEUROPROTECTANT• POSITIVELY EFFECTS MITOCHONDRIAL HEALTH• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF
VALUE IN GLAUCOMA
XXX N-ACETYL CYSTEINE• AMINO ACID ULTIMATELY CONVERTED TO GLUTATHIONE• POTENT ANTI-OXIDANT• ASSISTS IN REGENERATION OF VITAMINS C AND E• ACTS AS A CHELATING AGENT..ZINC COPPER ISSUES• NEED EXTRA VITAMIN C• POSITIVELY EFFECTS MITOCHONDRIAL HEALTH• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF
VALUE IN GLAUCOMA BUT SIDE EFFECTS MAY OUTWEIGH POTENTIAL BENEFITS
RESVERATROL• POLYPHENOL • POTENT ANTI-OXIDANT• NEUROPROTECTANT• POSSIBLE EFFECT ON CLOTTING• POSITIVELY EFFECTS MITOCHONDRIAL HEALTH• OBTAIN FROM DIET BUT SUPPLEMENTATION MAY BE OF
VALUE IN GLAUCOMA BUT SIDE EFFECTS MAY OUTWEIGH POTENTIAL BENEFITS
Now Lets Get Real From a Cost and Compliance Standpoint THERE IS NEITHER A MAGIC PILL NOR A MAGIC
NUTRICEUTICAL, BUT RATHER A MENTAL SET AND LIFESTYLE THAT SET THE TONE FOR MAXIMIZING
HEALTH.
9/16/2013
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REQUISITES FOR SUCCESS
• EASY TO TAKE…SMALL AND SLICK• MINIMAL SIDE EFFECTS• TAKE WITH FOOD• COSTS LESS THAN $1.00/DAY
BEHAVIOR, NUTRITION, AND GLAUCOMA…ADVICE
• CONTROL YOUR WEIGHT• EXERCISE• DON’T SMOKE…NOT EVEN• WATCH INTAKE OF INFLAMMATORY
FOODS…HEALTHY DIET• CONTROL HYPERTENSION, GLYCEMIC LEVELS AND
CHOLESTEROL• ELIMINATE STRESS
• SUPPLEMENTATION WHEN NECESSARY
