by visual fields.11 The most common neurodegenerative ... When visual field loss is due to .... Randolph C, Karantzoulis S, Guskiewicz K: Prevalence and.
C A L I F O R N I A
O P T O M E T RY JANUARY/FEBRUARY 2014
VOLUME 41, NUMBER 1
A comprehensive view of professional optometry in California today
OPTOMETRY IN FOCUS
No brain to spare
Brain trauma’s role in glaucoma & Alzheimer’s disease GOVERNMENT AFFAIRS
Educate your dual eligible patients CE@HOME
Ischemic optic neuropathy
No brain to spare Denise A. Valenti, OD, FAAO
With three National Football League (NFL) teams within the state, California health care providers cannot help but be aware of the controversy over head injury, concussion and the increased vulnerability to Alzheimer’s disease (AD) due to traumatic brain injury. This fall, the San Diego Chargers sidelined Johnny Patrick, King Dunlap, D.J. Fluker and Ryan Mathews for concussions. The San Francisco 49ers pulled Eric Reid and Vernon Davis when they experienced concussive events. The Oakland Raiders players Terelle Pryer, Tracy Porter and Rashad Jennings experienced concussions as well. While the NFL has settled for $765 million with concussion victims, the league is still taking preventative measures. Precautions such as rest, pull from play in future games and treatment when concussive injury occurs may prevent permanent damage to the brain’s neurons.
Optometry in Focus
Dr. Denise A. Valenti (DeSylvia) is a graduate of Oregon State University where she also received a certificate in gerontology. Dr. Valenti was the first OSU student member of her family not to play Beaver Football. She attended the Southern California College of Optometry and did a Low Vision Residency at the University of Houston College of Optometry. Dr. Valenti provided direct clinical care for over twenty-five years. Her research includes the study of neurodegenerative diseases in the visual system, Alzheimer’s disease, Parkinson’s disease, brain injury and glaucoma. She collaborates with Dr. Marc Pomplun, eye movement specialist, and athletic trainer Ed Perkins at the University of Massachusetts Boston on visual assessments in sports concussive injury. Dr. Valenti serves on numerous journal review panels related to vision and neurology and currently sits on a National Institutes of Health Study Section. She lectures on neurodegenerative diseases in the visual system both nationally and abroad.
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The greater the extent of brain cell loss, the more likely there is to be functional loss from other diseases like AD due to a reduced neural reserve, if cell loss does occur as a consequence to stress on axons and cells. The diagnosis of AD in Ronald Regan, former US president, is illustrative of how wide reaching the neurodegenerative disease AD can be. Reduced neural reserves along the visual pathways can result in more significant expression of neurodegenerative disease such as glaucoma. It is thought that one of the reasons for increased vulnerability to neurodegenerative diseases in NFL players is repeated head injury that can occur with football — causing more neural cell loss and, therefore, a diminished cerebral reserve.1 Other patients at risk for long-term degenerative processes secondary to traumatic brain injury are armed forces personnel, who are exposed to blasts from improvised explosive devices. NFL football players, soldiers, President Regan and glaucoma patients all have the same thing in common — no brain to spare.
NFL football players, soldiers, President Regan and glaucoma patients all have the same thing in common — no brain to spare. A significant portion of the brain pathways are involved in visual processing. As much as 20 percent related to direct sight tasks and 50 percent in vision-related neuroprocessing. The retina is a direct extension of the brain. Developmentally, the tissue of the retina and optic nerve extend from the diencephalon and are retained as part of the central nervous system. Neurodegenerative diseases of the brain impact the retina and age-related diseases originating in the eye result in measureable structural losses of brain structure. The visual association area, the part of the brain that processes motion, contrast and speed along the magnocellular visual pathway, was found to be the very first region in the brain that was affected by AD deposits in the study of donated brains from normal and AD donors. It was not unusual for there to be deposits in the vision area, but not in the memory areas of the brain.2 This had not been previously investigated as the vision dysfunctions are not ones usually offered in patient complaints and are not routinely measured as part of an eye exam. The same group identifying the visual association area as being the early brain region involved in AD is studying the neurodegenerative processes in football brain injury.3 Visual field tests measuring the temporal response of the magnocellular pathway with a flicker target, such as Frequency Doubling Technology, currently in use for glaucoma, have been found to identify deficits specific to AD.4-6 The deficits identified with FDT most likely to involve the visual association area were found to have the early signs of AD.
Optometry in Focus
Glaucoma cell loss in the retina and damage to the axons ultimately result in measurable cell loss in the visual association area also7, 8 and this part of the brain is vulnerable to damage in NFL players from direct hits to the side of the helmet and the contra coupe effect on both sides of the brain.9, 10 Injury secondary to blasts such as seen in the military with improvised explosive devises can impact all parts of the visual neuropathways. Neurodegenerative diseases starting in the eye can destroy 25 percent of retinal ganglion cells before there are measureable functional losses, most often quantified by visual fields.11 The most common neurodegenerative disease of the eye is glaucoma. When visual field loss is due to glaucoma, the functional loss that is manifest does not linearly represent the much larger magnitude of measured retinal ganglion cell loss.12 Neuronal cells that are lost due to the age-related amyloid deposits in the brain that occur in Alzheimer’s disease result in degeneration of brain axons13 and subsequently the endpoint retinal ganglion cells within the eye.14 Much like with glaucoma, significant numbers of neuronal cells are lost before the symptoms of memory dysfunction of Alzheimer’s disease is expressed. Concussive injury may not result in the loss of neuronal cells, but may create axonal dysfunction that can be repaired over time. However, if it is a repeat injury and there is enough axonal damage, it can result in local cell apoptic death and distal apoptic cell death. Glaucoma, AD and brain injury are diseases that impact central nervous system tissue and all three can result in damage to the neuropathways processing vision. All three diseases place stress locally on neuronal tissue. Glaucoma does this in the form of the elevated pressure damaging local cells and axons. AD stresses the visual pathways by causing local neuronal death and eventually axon loss by the mechanical stress of amyloid deposits and stress chemically by the toxic impact of the amyloid. Concussive injury creates damage by the sheering force and stress on cells and axons. Approximately 2.2 million people in the United States have been diagnosed with glaucoma and it is expected that by 2020 3 million will be impacted by the disease. Glaucoma is responsible for 9-12 percent of blindness in the United States and it is the leading cause of blindness among African Americans and Hispanics. AD is the sixth leading cause of death in the United States and it is expected one in three seniors will die with AD. There were an estimated 5.2 million Americans of all ages suffering with AD in 2013.15 Surveys of retired NFL players
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indicate that 24 percent had more than three concussive events during their careers16 and these players were five times more likely to have been diagnosed with mild cognitive impairment (the precursor diagnosis to AD), however, only 1.3 percent surveyed were diagnosed as having AD. A study of the death records of 3,500 NFL players with five or more seasons from 1959 to 1988 showed that these players overall lived longer than the general population but had AD four times more frequently.17
Surveys of retired NFL players indicate that 24 percent had more than three concussive events during their careers and these players were five times more likely to have been diagnosed with mild cognitive impairment... Glaucoma does not have its origin in the retina but the optic nerve, and is rapidly being considered a disease of neurodegeneration rather than simply an eye disease.18 Its disease process is painless and insidious and often goes undetected, particularly among vulnerable populations. Furthermore, patients with age-related neurodegenerative diseases impacting cognitive functioning such as Alzheimer’s and Parkinson’s diseases have been shown to have a higher rate of glaucoma, in some reports up to 25 percent compared to the average of 4-8 percent in the absence of Alzheimer’s and Parkinson’s disease.19-21 There is a diminution of cerebral reserves when you have one single neurologic disease, which makes an additional neurologic disease more severe. Newer imaging studies indicate that glaucoma may impact neural structures involved
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Optometry in Focus
If there are two or even three neurodegenerative processes such as glaucoma, injury and AD that affect one of the major relay centers for visual function, it is easy to appreciate that the loss in function can be substantial given the probable compromise in cerebral cellular reserves. in visual-cognitive processing. Gupta and colleagues demonstrated, using magnetic resonance imaging (MRI) post mortem, structural grey matter changes in the lateral geniculate nucleus (LGN) that were attributed to glaucoma.22 The LGN is the first major brain region in the vision pathway, and over 90 percent of retinal axons synapse there. In vivo MRI has revealed further changes secondary to glaucoma,23 particularly that LGN neurons change early in the glaucoma disease process and show significant shrinkage, which is observed even before nerve fiber loss in the optic nerve with conventional direct viewing methods.24, 25 In their study of glaucoma, Michelson and colleagues found that the spatiotemporal contrast sensitivity test, frequency doubling technology (FDT) — correlated significantly with DTI in addition to the retinal imaging.26 Severe brain injury can create significant pressure changes within the brain, brain stem, meninges, retrobulbar space and eye. There is a correlation between intraocular pressure and intracranial pressure such as the drop in pressures with open wound and skull fracture, but it is poorly understood.27 In a study of 102 patients with traumatic brain injury, the IOP was measured and was found to be low in grade I trauma the first five days and by day 30 returned to normal ranges. In more significant trauma, grade II and grade III, the IOP was even lower and also increased to normal during recovery and in the worst trauma the IOP was similar to the drops that occur before brain death.28 Children suffering a traumatic brain injury were measured to determine the relationship to IOP and brain pressures and there also was a relationship with elevated IOP as the brain pressures elevated.29 A chronic state of depressed cerebral spinal fluid pressure (CSFP) resulted in a glaucoma type optic nerve damage in an animal model and this was also found in human patients in that those with abnormal tension glaucoma had lower CSFP and a higher trans lamina cribosa pressure.30 In glaucoma with an abnormal elevation of IOP, the lamina cribrosa and the intraocular space
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relative to the CSF region differ from those without glaucoma, indicating a dynamic relationship between eye health and the dynamics of brain pressure and structure.31 With severe AD there is shrinkage of the entire brain and this can create changes in the pressure dynamics within the brain.32 Advanced AD may result in a lower than normal CSFP.33 Mean CSFP is lower in patients with primary open angle glaucoma. A newly proposed risk factor for glaucoma is a decreased CSFP.34, 35 When there is a lower pressure on the posterior nerve, there is a higher rate of damage similar to glaucoma.36 In a study of those diagnosed with glaucoma, it was found that the CSFP was 33 percent lower.37 It is hypothesized that there is an influence on subarachnoid space. Posterior to the globe, the pressure relationship to intracranial, retrolaminar and translaminar tissue creates damage much like would occur if the elevation were inside the eye. The opposite influence and elevated CSFP may be protective for glaucoma damage and this may be the mechanism in ocular hypertension.34, 38 The impact of brain injury and brain disease can influence the course of eye disease. The vulnerability of those suffering repetitive brain injuries, such as NFL football players or military personnel, can create greater risk for AD in that there is a diminution of cerebral cellular reserves. If the cells impacted are part of the visual pathway, this results in fewer reserves if there is a glaucoma risk. The cellular deficit as well as anatomic changes may be the reason for an increased rate of glaucoma among those with AD. One study found a glaucoma rate of 25.9 percent for AD patients and 5.2 percent for the control patients.39 A review of records in a large glaucoma clinic identified seven patients with an elevated IOP with initial normal visual fields and normal optic disc and having a diagnosis of AD and found that these patients had a more rapid progression of glaucomatous
Optometry in Focus
neuropathy than expected.40 In a study of patients with AD in Japan, a glaucoma rate of 23.8 percent was found in those with AD compared to a rate of 9.9 percent in those not diagnosed with AD. 21 If there are two or even three neurodegenerative processes such as glaucoma, injury and AD that affect one of the major relay centers for visual function, it is easy to appreciate that the loss in function can be substantial given the probable compromise in cerebral cellular reserves.35 Further drug treatments for those diagnosed with AD impact the visual system and can potentially mask a subtle glaucoma. Donepezil (Aricept) and rivastigmine (Exelon) have been shown to lower the IOP as much as 10 percent41, 42 and rivastigmine was demonstrated to increase the cerebral blood flow at the optic nerve while stabilizing visual field loss in patients diagnosed with normal tension glaucoma.43 Memantine (Namenda), a neuroprotective drug used in the treatment of AD, was demonstrated to prevent glaucomatous-induced cell loss in brain structures.44 The brain does not have an infinite set of cells in reserve. Damage along the visual pathways for any reason can eventually impact function and disease state. Repetitive head injury sustained by NFL football players can result in cell damage within the brain. The greater the damage, the greater the risk of earlier expression of an age-related neurodegenerative disease. If that disease is AD, which impacts the visual system, the risk for a complex expression of glaucoma is there. We do not yet fully understand how these diseases interact. What is clear is that the protection of brain tissue in the form of healthy lifestyle and allowing recovery from injury so axonal stress does not progress to cell death is important. Optometrists, as they provide a continuum of care while taking into consideration the health and the lifestyle of each patient, are in an excellent position to protect brain health. — REFERENCES 1. Randolph C, Karantzoulis S, Guskiewicz K: Prevalence and characterization of mild cognitive impairment in retired national football league players. J Int Neuropsychol Soc 2013, 19(8):873-880. 2. McKee AC, AU R, Cabral HJ, Kowall NW, Seshadri S, Kubilus CA, Drake J, Wolf PA: Visual association pathology in preclinical Alzheimer disease. Journal Neuropathology Experimental Neurology 2006, 65:621-630. 3. McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, Lee HS, Wojtowicz SM, Hall G, Baugh CM et al: The spectrum of disease in chronic traumatic encephalopathy. Brain 2013, 136:43-64. 4. Valenti DA: Alzheimer’s disease: Using frequencydoubling technology to identify potential visual system
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