Kathleen M. Brockie
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Glaucoma is a degenerative diseasewhich can be caused by high intraocular pressure (IOP)(Glaucoma,2002). This IOP arises in theaqueous humor, the area between the cornea and the iris, where adrainage system allows the aqueous to drain from this area andrecycle (Learnabout Glaucoma, 2002). Aspecific balance of the production and removal of aqueous determinesthe IOP. Either malfunction or malformation of this drainage systemcan cause a rise in pressure. The elevated pressure causesirrevocable damage to the optic nerve and retinal fibers as well asdamage to the other areas of the visual system, which leads to agradual and permanent loss of vision if not treated (Glaucoma,2002). Damage to the opticnerve causes loss of vision because this nerve, or group of ganglionaxons, is responsible for transporting images to the brain from theeye. While there are other possible causes of glaucoma, such asvariations of the myocilin gene, IOP is thought to be the main cause(Learnabout Glaucoma, 2002).Treatment, especially with early detection, can slow or ceasecontinued damage.
Types of Glaucoma
There are several types of glaucoma,the most prominent types being Open Angle, and Acute Angle Closureand the more infrequent types including Secondary Glaucoma,Congenital Glaucoma, Normal Tension Glaucoma (NTG), and PigmentaryGlaucoma. Open Angle Glaucoma (OAG), the most prevalent form ofglaucoma (Glaucoma,2002), is painless, and can gounnoticed without the help of an optometrist or ophthalmologist.Obstructed drainage channels, which develop over a period of time,characterize this type of glaucoma. These obstructions are notpresent at the openings of the channels, rather they occur inside thechannels. The aqueous cannot recycle because of these obstructedchannels, the IOP rises, and damage results (Learnabout Glaucoma, 2002). AcuteAngle Closure Glaucoma, however, is much more painful and results inrapid vision loss. In this case, the iris and cornea are not wideenough apart which can cause the edge of the iris to block thedrainage channels (Learnabout Glaucoma; andGlaucoma,2002). Secondary Glaucomaresults from other eye diseases or problems, such as diabetes,trauma, and tumors . Congenital Glaucoma is a rare glaucoma found ininfants (Glaucoma,2002). Normal Tension Glaucomaoccurs in those with normal IOPs but have damage to the opticnerve. Pigmentary Glaucoma results from parts of the pigment in theiris breaking off and slowly clogging the drainagechannels.
The continued discussion is focused onthe use of Electroretinograms (ERGs) in early detection for OpenAngle Glaucoma (OAG). Currently, the most common tests for OAG arethe measurement of the IOP, assessment of the optic nerve healthusing ophthalmoscopy, measurement of peripheral vision using a visualfield test, and inspection of the structures in the front of the eyewith a gonioscopy (Glaucoma, 2002). Recently, however, studies havebeen investigating the use of an ERG as a way to test for glaucoma aswell. There are several types of ERGs including Flash or ConeMediated ERG (ERG) (Viswanathan, Frishman, Robson, Harwerth, andSmith, 1999; Colotto, Falsini, Salgarello, Iarossi, Galan, andScullica, 2000), Pattern ERG (PERG) (Maddess, James, Goldberg,Wine, and Dobinson, 2000; Voswamatjam. Frosj,am. and Robsom, 2000)and the Multifocal ERG (mERG) (Hood, Greenstien, Holopigian,Bauer, Firoz, and Liebmann, 2000). In general, an ERG is anoninvasive measure used to clinically diagnose diseases of theretinal area (Viswanathan et al., 1999). The visual field test showssigns of degeneration of the ganglion cells already in progress whilethe benefit to ERGs is early detection. (Hood et al., 2000). However,scientists are still debating which is the most useful type ofERG.
Participants for ERG studies are mainlymacaque monkeys and cats for invasive measures, and humans for thenon-invasive measures. Glaucoma is experimentally induced in thenon-humans by laser, which jeopardizes the ganglion cell performanceto represent actual optic nerve damage (Viswanatha et al., 2000). Anintraocular injection of tetrodotoxin (TTX) is also used to subduethe sodium action potentials of the ganglion cells and amacrine cells(Colotto et al., 2000). This lessening of the action potentialsreduces spiking in the ERG of the amacrine cells, the ganglion cellsand perhaps the interplexiform cells. Once the participants areprepared, through either experimental glaucoma or actual glaucoma,there are a variety of ERGs that can be performed.
Flash or Cone-MediatedERG
Viswanathan et al. and Colotto et al.used the flash or cone-mediated ERG. One used macaque monkeys andnormal human participants, and then generalized the results to theglaucomatous human population based on the idea that the anatomy andphysiology of the eye, as well as visual capabilities, are similarbetween the two species (Viswanathan et al., 1999). The other studyused glaucoma patients and ocular hypertension patients specifically(Colotto et al., 2000). The general purpose of the two studies was touse this ERG to measure glaucoma damage in either the monkeys(Viswanathan et al., 1999) or in an actual human glaucoma sample(Colotto et al., 2000). A photopic, or light adapted, ERG measuredelectrical activity to take advantage of the photopic state so thatrods are saturated. This results in the cone receptors producinga-wave responses while bipolar and possibly Muller cells produceb-wave responses. Monkey ERG information was measured at the cornea,while the human ERG information was measured by an electrode placedon the lower eyelid (Viswanathan et al., 1999; Colotto et al., 2000).The ERG measured electrical activity originating from differentgroups of retinal cells using different stimuli for the separatepopulations. The illumination of a table-tennis ball with a red lightflashing was the stimulus for the monkeys (Viswanathan, et al.,1999), whereas the human sample fixated on a green light in thecenter of a stimulating field, or specific area producing high neuralactivity for a particular group of cells, on a computer (Colotto etal. 2000). Early stages in retinal processing create the initialwaves of activity recorded in the ERG, so damage to these areas wouldbe easy to detect with this method. These responses are normally"negative-going", or PhNR (Photopic Negative Response) as theresearchers simply referred to them, in both normal and glaucomaticeyes. Results show that in eyes with experimental and actual glaucomathe PhNR's were significantly reduced, indicating that the measuredcells produced less activity (Viswanathan et al., 1999).
These studies found that using theflash ERG, which stimulates a larger area of the retina than that ofnormal perimetric testing, shows damage to the ganglion cells outsidethe central area measured by perimetry (Viswanathan et al., 1999).This is beneficial because damage due to glaucoma starts in theperiphery. So, the further in the periphery tests can assess damage,the sooner glaucoma can be detected and subsequently treated. It isimportant to note, however, that PhNR was not as affected byglaucoma damage as responses on the pattern electroretinogram(Colotto et al., 2000).
In a follow up study to Viswanathan's1999 study, comparisons were made between the Patternelectroretinogram (PERG) and the uniform field ERG, done perhapsbecause of the evidence that the PERG is the most prominent andsensitive electrodiagnostic test used for glaucoma detection(Viswanathan, 1999). The PERG measures voltage changes in response to"contrast reversals of pattern stimuli" at the cornea (Viswanathan etal., 2000). Again, macaque monkeys with experimental glaucoma and TTXinjections were the participants, and a contact placed on the corneameasures retinal activity. The PERG manipulates grating patterns ofuniform field or contrast reversal with square-wave luminancemodulations to activate inner-retinal areas. The PERG measure foundthat the summation of responses is similar to that of the PhNR's inViswanathan's previous study. However, these results also show thatafter there is a light-increment in the stimulus pattern there is aslow PhNR, but after the light-decrement the normal PhNR was positiveindicating that the threshold was not met for an action potential.These results are equally true of eyes with actual glaucoma, but aresignificantly reduced. These results also show that glaucoma, orexperimental glaucoma in this case, can be detected early due toeffects on retinal ganglion cells.
Maddess et al. also conducted a studyalso utilizing the PERG, but tested a new visual stimulus rather thantesting the ability of the ERG. The researchers found that previousstudies failed to accurately represent the different ganglion cellsizes and density. It is important to note that "parasol cellsproject information onto the magnocellular layers of the dorsallateral geniculate nucleus (dLGN) and so are frequently referred toas M cells." (Maddess et al., 2000). Additionally, in the M pathwaythere are two distinct parts, which in cats are the X and the Ycells, resulting in Mx and My cells. TheMy cells are much larger than the Mx, so damageto one My cell produces much more vision loss at thatparticular retinal location. The visual stimuli needed to be alteredin the PERG to accurately measure My cells. Theseparticular researchers found that an applicable stimulus to use is aspatial frequency-doubling (FD) illusion, where there were ninesections of stripes of gratings that alternate in coarseness anddirection. This study found that responses to the FD illusioncorresponded to My cell responses in the retinal area,thus also correlating with damage incurred by glaucoma in the retinalarea. Since these My cells cover a large area, thesensitivity to glaucoma rises and early detection is also possiblewith this PERG stimulus relationship.
The PERG however also has someproblems, such as having small amplitudes, not correlating withvisual field measures, and needing a large stimulus. Thus, theMulitifocal ERG (mERG) was developed, which records multiple localretinal responses in a relatively short amount of time. Glaucomablocks inner retinal activity so the action seen is solely fromganglion and amacrine cells. While the differences between normaleyes and glaucoma eyes is significant, and the mERG is able todistinguish between the two eyes in one participant, it has problemsas well. For example, changes that appear in one participant may notappear in other participants, and in order for a measure to bereliable it has to be generalizable across populations. Thus, theconditions used for this particular experiment did not appear toproduce enough change, due to damage in the ganglion cells, andtherefore may not be useful in early detection ofglaucoma.
Ultimately these studies have foundthat the ERG is useful in the early detection of glaucoma. However,there is still a need for more research. Alterations in the ERGfunctions need to be made since each one has problems whichcompromises their reliability. This summary has also shown thatresearchers need to continue to look for different stimuli for theactual research setting. Each study used different stimuli whichshows that at this point that one stimulus is not necessarily betterthan another. Thus far, studies investigating the different types ofERGs useful in the detection of glaucoma have been limited, howevertheir findings have been important in the study ofglaucoma.
Colotto, A., Falsini, B, Salgarello,T., Iarossi, G., Galan, M.E., Scullica, L. (2000). Photopic negativersponse of the human ERG: losses associated with glaucomatous damage.Investigative Ophthalmology and Visual Science, 41 (8),2205-2211.
Hood, D.C., Greenstein, V.C.,Holopigian, K., Bauer, R., Firoz, B., Liebmann, J.M., Odel, J.G.,Ritch, R. (May, 2000). An attempt to detect glaucomatous damage tothe inner retina with the multifocal ERG. InvestigativeOphthalmology and Visual Science, 41 (6), 1570-1579.
Maddess, T., James, A.C., Goldberg, I.,Wine, S., Dobinson, J. (November, 2000). A spatial frequency-doublingillusion-based pattern electroretinogram for glaucoma.Investigative Ophthalmology and Visual Science, 41 (12),3818-3826.
Viswanathan, S, Frishman, L.J., Robson,J.G., Harwerth, R.S., Smith III, E.L. (May, 1999). The photopicnegative response of the macaque electroretinogram: reduction byexperimental glaucoma. Investigative Ophthalmology and VisualScience, 40 (6), 1124-1136.
Viswanathan, S., Frishman, L.J.,Robson, J.G. (August, 2000). The uniform field and pattern ERG inmacaques with experimental glaucoma: removal of spiking activity.Investigative Ophthalmology and Visual Science, 41 (9),2797-2810.
Glaucoma, (n.d.). RetrievedFebruary 8, 2002, fromhttp://www.stlukeseye.com/Conditions/Glaucoma.asp
Learn about glaucoma, (n.d.).Retrieved February 8, 2002, fromhttp://www.glaucoma.org/learn/