neuroretinal rim defect and its damage likelihood in poag

8/3/2019 Neuroretinal Rim Defect and Its Damage Likelihood in Poag

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[NEURORETINAL RIM DEFECTS IN RELATIONSHIP TO DISC DAMAGE

LIKELYHOOD SCALE IN PRIMARY OPEN ANGLE GLAUCOMA] October 28, 2011

1 BY: Akpotowho Godwin Ellis | NEUROPATHOLOGY OPT 526 LECTURER: DR. P OMOKHUA

laucoma is defined as multi factorial optic neuropathy which is apotentially blinding disease which affects 66.8 million people worldwide or

Approximately 15% of cases of blindness.

The most common type, primary open-angle glaucoma, having a prevalenceof 1/200 in the general population over 40 years of age.Glaucoma is the second leading cause of blindness. Risk assessment of thedisease goes a long way in diagnosis and management of the disease.Although the raised intra ocular pressure (IOP) is a significant risk factor fordeveloping glaucoma, there is no set threshold for IOP that causesglaucoma. This can result in decreased peripheral vision and eventually leadsto blindness.Glaucoma is associated with a diminution ofoptic nerve fibres leading to a decrease ofneuroretinal rim area. This rim loss occurs inall sectors of the optic disc with regionalpreferences depending on the stage of the

disease. In eyes with modest glaucomatousdamage, rim loss is found predominantly atthe inferotemporal and superotemporaldisc regions.

Early glaucomatous damage can be difficult to detect, requiring carefulobservation of the optic nerve and Retinal Nerve Fiber Layer. The detectionof glaucoma through Optical Coherence Tomography (OCT) and HeidelbergRetinal Tomography (HRT) are very expensive compared to digital

fundus images. With the help of image processing, the features of thefundus images such as optic disc and cup could be localized to suspect the

glaucoma. The detection of OD position and automated feature extraction is

a pre-requisite for the computation of some important diagnostic indexes

like glaucoma.

The most common type of

glaucoma is primary open

angle glaucoma, having a

prevalence of 1,200 in the

general population over 40

years of age.


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NEURORETINAL RIM

It is a term used in describing the area of the optic disc which contains the

neural elements and is located between the edge of the disc and thephysiological cup. When describing the neuroretinal rim, as is often done incases of glaucoma, one must include its colour, size, slope and uniformity.Syn. neural rim.

Characteristics of the normal ONHThe ONH or optic disc is a round/oval plughole, down which more than amillion nerve fibres descend through a sieve-like sheet known as the laminacribrosa. These fibres are then bundled together behind the eye as the opticnerve which continues towards the brain.The retinal nerve fibres are spread unevenly across the surface of the retinain a thin layer which has a feathery appearance, best seen immediatelyabove and below the disc. As the nerve fibres converge on the edge of thedisc they pour over the scleral ring (which marks theedge of the disc) and then down its inner surface. This dense packing ofnerve fibres just inside the scleral ring is visualised as the neuroretinal rim.The cup is the area central to the neuroretinal rim. The cup edge (where it

meets the neuroretinal rim) is best seen by the bend in small and medium-sized blood vessels as they descend into the cup. The neuroretinal rim is usuallybroadest in the Inferior disc region, followed by the Superior disc region, the Nasal discarea, and finally the Temporal disc region (ISNT rule).In normal eyes, the neuroretinal rim is based on the vertically oval shape ofthe optic disc and the horizontally oval shape of the optic cup.


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The optic nerve head can be classified by using direct and indirectophthalmoscopy into six categories:

1. Inferior neuro-retinal rim loss: a disc with tissue loss localised to theinferior/infero-temporal pole, including shelving, or generalised loss ofthe inferior rim, but not focal notching.

2. Superior neuro-retinal rim loss: a disc with tissue loss localised at thesuperior/supero-temporal pole, including shelving and generalised lossof the rim, but not focal notching.

3. Concentric cupping: a disc with generalised enlargement of the opticcup without a localised defect in the neuro-retinal rim.

4. Age-related atrophic (senile sclerotic): a disc with a saucerized,shallow cup and parapapillary atrophy.

5. Myopic glaucomatous disc: a myopic disc with a temporal crescentand additional evidence of glaucomatous damage.

6. Focal ischaemic: a disc with a focal notch.ABNORMAL NEURORETINAL RIM WITH DISC DAMAGEThe characteristic shape of the rim is of utmost importance in the diagnosisof early glaucomatous optic nerve damage. The physiologic shape of theneuroretinal rim is associated with the diameter of the retinal arterioles,which are significantly wider in the inferotemporal arcade than in thesuperotemporal arcade; the visibility of the retinal nerve fiber bundles thatare significantly more often better detectable in the inferotemporal regionthan in the superotempora neuroretinal rim.Neuroretinal rim area can be measured by configuration to suspectglaucoma.

The shape of the neuroretinal rim, the ratio of the inferior to temporal rim

width and the ratio of the superior to temporal rim width were calculated.The photographs were evaluated in a masked fashion without knowledge ofthe clinical diagnosis and the visual field data.


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Fig: Photograph of an abnormally large, otherwise normal optic disc. Optic disc data: area, 5.7 mm 2;

neuroretinal rim width (arrows) inferior, 0.57 mm; superior, 0.35 mm; temporal, 0.18 mm; ratio of inferior

to temporal rim width, 3.17; ratio of superior to temporal rim width, 1.94 . Note physiological shape of the

neuroretinal rim.

Variables that may also be associated with the pattern of glaucomatous,neuroretinal rim loss are:(1) The physiological configuration of the rim being broader at the inferior

and superior disc poles than at the nasal and temporal poles.(2) The morphology of the inner surface of the lamina cribrosa with thelarger pores and the higher ratio of pore to interpore connective tissue areain the inferior and superior regions compared with the temporal and nasalregions; a high ratio of pore area to total area is considered to predispose toglaucomatous nerve fibre loss;(3) The glaucomatous bowing of the lamina cribrosa to the outside mainly inthe inferior and superior disc regions as shown on scanning electronmicroscope photographs of glaucomatous eyes; and

(4) The regional distribution of thin and thick retinal nerve fibres with thinnerve fibres coming from the foveola, passing mainly through the temporalaspect of the optic disc and being less glaucoma susceptible than thicknerve fibres which originate predominantly in the fundus periphery, lead tothe inferior, superior, and nasal disc regions and are more glaucomasensitive than thin retinal ganglion cell axons.The latter parameter may explain why glaucomatous rim loss occurs later inthe temporal horizontal disc sector with predominantly thin nerve fibresthan in the temporal inferior or temporal superior disc sectors containing

thin and thick axons. It is contradictory to the fact that in far advanced


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glaucoma rim remnants are usually located in the nasal disc sector. There,preferentially thick retinal ganglion cell axons leave the eye.As an additional parameter for the pattern of glaucomatous rim loss, the

distance from the central retinal vessel trunk in the lamina cribrosa may beconsidered. In both the normal and glaucomatous eyes of the present study,the retinal vessel trunk was slightly decentred into the nasal upper discquadrant. Similar results have been obtained in a histomorphometric studyof the lamina cribrosa surface. In the latter investigation, the exits of theretinal artery and vein were located 0-15 (O.09) mm and 0 07 (0-14) mm,respectively, nasal to the vertical optic disc axis and 0-02 (0-11) mm and 005(O 09) mm, respectively, superior to the horizontal optic disc axis.Taking into account the vertically oval optic disc shape, one may infer thatthe distance between the retinal vessels in the lamina cribrosa and theneuroretinal rim may be associated with the pattern of glaucomatous rimloss. The sector distant to the retinal vessel trunk is the temporal inferiordisc region followed by the superior temporal and temporal horizontal discregions. The nasal disc sector is the one closest to the retinal vessels withthe nasal upper portion located closer to the retinal vessel trunk than thenasal inferior portion. In the same sequence, the glaucomatous rim loss hasbeen reported to take place: temporal inferior - temporal superior and

temporal horizontal - nasal inferior - nasal superior.Correspondingly, glaucomatous neuroretinal rim notches do not occur on anaverage at the inferior and superior disc poles but at about 13 degreestemporal to the vertical optic disc axis. These locations are more distant tothe retinal vessel trunk than the vertical disc poles at the 6 o'clock and 12o'clock position.For strengthening the hypothesis that the local glaucoma susceptibility iscorrelated with the distance to the retinal vessel trunk, the following factscan be listed:

(1) In glaucomatous eyes with an unusual location of the retinal vessel trunkor an abnormal optic disc shape, the rim had an unusual form.Conversely, in eyes with an unusual glaucomatous rim configuration, theretinal vessel trunk was abnormally positioned (Figs A-C).Also in these glaucomatous eyes, the rim loss was usually most and leastmarked in that sector with the longest and shortest distance to the centralretinal vessel trunk, respectively.


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(2) The location of early glaucomatous visual field defects in the upper nasalor lower nasal field quadrants close to the horizontal line '9-22 indicates a


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ganglion cell loss in the region of the temporal fundus raphe. The axons ofthese ganglion cells lie in the deepest part of the retinal nerve fibre layer.They are closest to the optic disc border.

Within the optic disc, they are more distant to the central retinal vesseltrunk than ganglion cell axons originating in the vicinity of the optic nervehead. These are located more centrally in the optic nerve head and are lostin a later stage of the disease.Diagnostically, it may indicate that in eyes with an abnormal position of thecentral retinal vessels or an unusual optic disc form, early glaucomatous rimchanges should be looked for not only in the temporal inferior disc sectorbut also in that disc sector that is most distant to the central retinal vesseltrunk. It may explain why eyes with open angle glaucoma and a temporalcilioretinal artery retain longer central visual field than open angleglaucomatous eyes without a temporal cilioretinal artery.Pathogenetically, one may infer that the retinal vessel trunk could act as astabilising element. It could render more difficult a mechanical distortionand backward bowing of the lamina cribrosa in glaucoma.

This hypothesis is supported by photographs of a W-shaped lamina cribrosain glaucomatous eyes. The lamina cribrosa is more condensed and bowed

more to the back in the inferior and superior disc regions than close to thelamina cribrosa centre where the retinal vessels emerge. If the vessel trunkis decentred into the superior half of the optic disc, the inferior disc portionwithout vessel trunk support is larger than the superior one. Consequently,it can be deformed to a greater extent than the smaller superior disc part. Itcould explain the greater frequency of neuroretinal rim notches in theinferior temporal disc region compared with the superior temporal area.As a variation to this mechanical theory, one could also speculate that in theclose vicinity of the retinal vessel trunk the vascular supply to the adjacent

tissue is better than in the periphery. A vitally important participation ofbranches of the central retinal vessels in the nourishment of the optic nervefibres in the lamina cribrosa, however, has not yet been demonstrated.As a factor limiting the scope of the present study one can mention that theposition of the central retinal vessel trunk was measured in eyes in whichthe trunk on the lamina cribrosa surface was clearly detectable. This ispossible only in discs showing central cupping. Due to the correlationbetween optic cup and optic disc size it implies that these selected opticdiscs were on average larger than normal optic nerve heads. In anotherhistomorphometric investigation on the lamina cribrosa surface, however,


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the retinal vessel trunk was also located in the upper nasal quadrant.Thatstudy consisted of eyes of varying optic size including also small optic discs.

Characteristics of a glaucomatous ONH generalised/focal enlargement of the cup disc haemorrhage (within 1 disc diameter of ONH) thinning of neuroretinal rim (usually at superior & inferior poles) asymmetryof cupping between patients eyes loss of nerve fibre layer parapapillary atrophy (more common in glaucomatous eyes).

Distinguishing a glaucomatous ONH from a normal ONHLearn the features of a normal and a glaucomatous ONH (above).Strategy:1 Dilate pupils, if possible and safe to do so.2 Identify disc edge and cup edge thereby identifying rim.3 Does the rim thickness obey the ISNT rule?4 Is there a haemorrhage?5 Estimate vertical cup/disc ratio.6 Measure size of ONH.

7 Examine the retinal nerve fibre layer (using green light).*8 Draw an annotated diagram of the ONH.*may only be possible with slit lamp and posterior pole lens


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Is the glaucomatous optic neuropathy getting worse/ progressing?The appearance of any of the features of a glaucomatous ONH, or theexacerbation of these features compared to a previous record, is indicativeof a progression/worsening of the disease.Disc haemorrhages may be present for two weeks to three months and arean important prognostic sign of progression.

An accurate record requires careful observation and a detailed drawing, atthe very least. Photographic documentation (preferablystereophotography) is highly recommended. Other imaging devices offerprogression analyses, but these are not a surrogate for a detailed clinicalexamination. Progressive worsening of the visual fields should correlatewith structural changes at the ONH.

Pitfalls and pearls


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The hallmark of glaucomatous optic neuropathy is excavation of theneuroretinal rim.Advanced glaucomatous ONH can result in a pale optic disc but disc pallor

should raise a suspicion of another cause such as optic atrophy.A colour difference should not be used to distinguish the cup edge; changein direction of the blood vessels is a more reliable indicator.The optic disc abnormality should correlate with the visual field defect.Where this is not the case, further investigations (e.g., CT/MRI scan) may beindicated.The size of the cup always appears smaller when viewed monoscopicallythan in stereo.A measurement of cup/disc ratio (CDR) alone is insufficient and may bemisleading as small discs will have smaller cups and hence a smaller CDR.

Using a study carried out by S.Kavitha, S.Karthikeyan, Dr.K.Duraiswamy(Asst. Professor, Nandha Engineering College, Erode, India. K.S.R. Collegeof Engineering, Tiruchengode, India. Dean, K.S.Rangasamy College ofTechnology, Tiruchengode, India)on Neuroretinal rim Quantification inFundus Images to Detect Glaucoma, we can also see the relationship

between neuroretinal rim damage and its likelihood in causing primaryopen angle glaucoma.

PRIMARY OPEN-ANGLE GLAUCOMA (POAG)

Primary open angle glaucoma (POAG) encompasses a spectrum ofdisorders, typified by a characteristic optic neuropathy and field loss in eyeswith open drainage angles. It is currently a leading cause of blindnessworldwide, and in the future stands to become more important, aspopulations increasingly age throughout the world. Recently, we havewitnessed a number of exciting advances in glaucoma. Developments haveoccurred regarding diagnosis, treatment, genetics and the relationship ofintraocular pressure (IOP) to disease progression.


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DISEASE DEFINITIONPrimary open-angle glaucoma is a progressive, chronic optic neuropathy inadults in which intraocular pressure (IOP) and other currently unknown

factors contribute to damage and in which, in the absence of otheridentifiable causes, there is a characteristic acquired atrophy of the opticnerve and loss of retinal ganglion cells and their axons. This condition isassociated with an anterior chamber angle that is open by gonioscopicappearance.

CLINICAL FINDINGS CHARACTERISTIC OF PRIMARY OPEN-ANGLEGLAUCOMA

Primary open-angle glaucoma is a chronic ocular disease process that isprogressive, generally bilateral, but often asymmetric. It is associated withthe following characteristics.

Evidence of optic nerve damage from either, or both, of optic disc or retinalnerve fiber layer structural abnormalities.

Diffuse thinning, focal narrowing, or notching of the optic disc rim,especially at the inferior or superior poles.

Documented, progressive thinning of the neuroretinal rim with anassociated increase in cupping of the optic disc. Diffuse or localized abnormalities of the peripapillary retinal nerve fiber

layer, especially at the inferior or superior poles.

Disc rim or peripapillary retinal nerve fiber layer haemorrhages. Optic disc neural rim asymmetry of the two eyes consistent with loss of

neural tissue.

Reliable and reproducible visual field abnormality considered a validrepresentation of the subjects functional status

- Visual field damage consistent with retinal nerve fiber layer damage (e.g.,nasal step, arcuate field defect, or paracentral depression in clusters of testsites)


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- Visual field loss in one hemifield that is different from the other hemifield,i.e., across the horizontal midline (in early/moderate cases)

Pathophysiology:

Even today, much remains unknown about this disease. Elevated IOP almostcertainly plays a significant role, but the process is poorly understood.According to the mechanical theory of POAG, chronically elevated IOPdistorts the lamina cribrosa, crimping the axons of retinal ganglion cells asthey pass through the lamina cribrosa and eventually killing the cells. Thevascular theory suggests that with elevated IOP, reduced blood flow to theoptic nerve starves the cells of oxygen and nutrients.

More recent research suggests anothermechanism of ganglion cell death. Someglaucoma patients exhibit elevated levels of theneurotransmitter glutamate within the vitreous.Ganglion cells contain protein receptors that,when activated by glutamate, increase intracellular calcium to toxic levels, formingdestructive free radicals that kill the cells. Thisplays into the apoptotic theory of glaucoma--a

neurocellular process in which a retinal ganglioncell will commit "suicide." Apoptosis is a normalcellular event designed to ensure a healthyneurological system where non-viable cells are removed. Glaucoma is anabnormal expression of this normal process.

Excess glutamate accumulation--which may result from ischemia--maytrigger apoptosis. Another possible inciting event: the deprivation of vitalneurotrophic nutrients for the retinal ganglion cells from the lateral

geniculate nucleus. The vital nutrient--brain derived neurotrophic factor

Advanced cupping andnerve fiber layer defect in

primary open angleglaucoma.


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(BDNF)--reaches the retinal ganglion cells from the lateral geniculate nucleusvia axoplasmic transport. Elevated IOP and ischemia disrupt axoplasmictransport and deprive the retinal ganglion cells of this vital nutrient.

PATIENT POPULATIONThe patient population consists of adults 18 or older with POAG.ACTIVITYIdentification and management of a patient with POAG.PURPOSETo identify and treat POAG and to preserve visual function while minimizingadverse effects of therapy, thereby enhancing the patients health andquality of life.GOALS Document the status of optic nerve structure and function on

presentation.

Estimate an IOP below which further optic nerve damage is unlikely tooccur.

Attempt to maintain IOP at or below this target level by initiatingappropriate therapeutic intervention(s)

Monitor the structure and function of the optic nerve for further damageand adjust the target IOP to a lower level if deterioration occurs.

Minimize the side effects of treatment and their impact on the patientsvision, general health, and quality of life.

Educate and involve the patient and appropriate familymembers/caregivers in the management of the disease.

PATIENT OUTCOME CRITERIA

Preservation of visual function Maintenance of quality of life

DIAGNOSISThe comprehensive initial glaucoma evaluation (history and physicalexamination) includes all components of the comprehensive adult medicaleye evaluation102 in addition to, and with special attention to, those factorsthat specifically bear upon the diagnosis, course, and treatment of POAG.The examination may require more than one visit. For instance, an individualmight be suspected of having glaucoma on one visit but may return for

further evaluation to confirm the diagnosis, including additional IOP


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measurements, gonioscopy, CCT determination, visual field assessment, andoptic nerve head and retinal nerve fiber layer evaluation anddocumentation.

Evaluation of Visual FunctionPatients with glaucoma may have sufficient visual field loss to impair nightdriving, near vision, and outdoor mobility.Ophthalmic EvaluationIn completing the elements in the comprehensive adult medical eyeevaluation, the ophthalmic evaluation specifically focuses on the followingelements:

History

Visual acuity measurement Pupil examination Anterior segment examination Intraocular pressure measurement Gonioscopy Optic nerve head and retinal nerve fiber layer examination Fundus examination

History

Ocular, family, and systemic history (e.g., asthma). The severity and outcome of glaucoma in family members, including

history of visual loss from glaucoma, should be obtained during initialevaluation.

Review of pertinent records, with particular reference to the past IOPlevels, status of the optic nerve, and visual field.

Current ocular and systemic medications (e.g., corticosteroids) andknown local or systemic intolerance to ocular or systemic medications.

Ocular surgery: A history of LASIK or photorefractive keratectomy isassociated with a falsely low IOP measurement due to thinning of thecornea. Cataract surgery may also lower the IOP compared with thepresurgical baseline. A history of prior glaucoma laser or incisionalsurgical procedures should be elicited.

Visual acuity measurementVisual acuity with current correction (the power of the present correctionrecorded) at distance and, when appropriate, at near should be measured.Refraction may be indicated to obtain the best-corrected visual acuity.


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Pupil examinationThe pupils are examined for reactivity and an afferent pupillary defect.

Anterior segment examinationA slit-lamp biomicroscopic examination of the anterior segment can provideevidence of physical findings associated with narrow angles, such as shallowperipheral anterior chamber depth and crowded anterior chamber angleanatomy, corneal pathology, or a secondary mechanism for elevated IOPsuch as pseudoexfoliation (exfoliation syndrome), pigment dispersion withKrukenberg spindle and/or iris transillumination defects, iris and angleneovascularization, or inflammation.

Intraocular pressure measurementIntraocular pressure (IOP) remains the single most important risk factor forthe development of glaucomatous optic neuropathy, and its measurementis vital in the initial diagnosis and management of the glaucomas. It is alsothe only major risk factor that can be treated. There has been much recentinterest in the ability to monitor continuous, 24 hour IOP, in order toevaluate sleep IOP profiles and potentially to combine such data withmeasures of diurnal blood pressure. Such technology is not yet available but

promises to be a significant advance of great clinical potential.Intraocular pressure is measured in each eye, preferably by Goldmannapplanation tonometry, before gonioscopy or dilation of the pupil.Recording time of day of IOP measurements may be helpful to assessdiurnal variation. Unrecognized fluctuations in IOP may lead to progressionof POAG. Therefore, additional measurements may be indicated, either atdifferent hours of the day on the same day or on different days.

Gonioscopy

The diagnosis of POAG requires careful evaluation of the anterior chamberangle to exclude angle closure or secondary causes of IOP elevation, such asangle recession, pigment dispersion, peripheral anterior synechiae, angleneovascularization, and inflammatory precipitates.The careful examination of the anterior chamber angle is essential inevaluating glaucoma suspects and diagnosing glaucoma. Gonioscopyenables the visualization of the anterior angle and its assessment permitsthe exclusion of angle closure, angle recession, plateau iris or secondaryangle block as the cause of raised IOP. Gonioscopy is most commonlyperformed indirectly by using a contact lens with a mirror system that


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overcomes the inherent total internal reflection of the angle anatomy. Theangle is graded to relate information of its visible anatomical features.Several non-contact OCT devices can be used to evaluate the angle; these

include the stand alone Visante (Carl Zeiss Meditec) and Slit Lamp (SL)-OCT(Heidelberg Engineering), and the analysis modules available on some of thenew generation spectral domain (SD) OCTs including the RTVue (OptovueInc.), Cirrus HD-OCT (Carl Zeiss Meditec) and Spectralis (HeidelbergEngineering)1). Although considerably more expensive than a classic contact goniolens,they have the advantage of being objective and quantitative. In addition,these devices can accurately measure and map corneal thickness. They canalso image bleb quality following trabeculectomy and the integrity ofperipheral iridotomies. However, due to the nature of OCT its is often notpossible to see the complete angle due to the signal being blocked andtherefore assumptions need to be made for the positioning of the scleraspur when measuring the angle.

Optic nerve head and retinal nerve fiber layer examinationExamination of the optic nerve head and retinal nerve fiber layer providesvaluable structural information about glaucomatous optic nerve damage.

Visible structural alterations of the optic nerve head or retinal nerve fiberlayer and development of peripapillary choroidal atrophy frequently occurbefore visual field defects can be detected.Careful study of the optic disc neural rim for small hemorrhages isimportant, since these hemorrhages often precede visual field loss andfurther optic nerve damage in patients with glaucoma.In the Ocular Hypertension Treatment Study, the incidence of POAG in eyeswith disc hemorrhage was 13.6% compared with 5.2% in eyes without dischemorrhage over 8 years.146 In the Early Manifest Glaucoma Trial, 13% of

patients had disc hemorrhages at baseline examination, and hemorrhageswere associated with progression.The preferred technique for optic nerve head and retinal nerve fiber layerevaluation involves magnified stereoscopic visualization (as with the slit-lamp biomicroscope), preferably through a dilated pupil.In some cases, direct ophthalmoscopy complements magnified stereoscopicvisualization, providing additional information of optic nerve detail due tothe greater magnification of the direct ophthalmoscope. Red-freeillumination of the posterior pole by stereo-biomicroscopy with an indirect


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lens at the slit lamp, the direct ophthalmoscope, or with digital red-freephotography may aid in evaluating the retinal nerve fiber layer.

Fundus examinationExamination of the fundus, through a dilated pupil whenever feasible,includes a search for other abnormalities that may account for optic nervechanges and/or visual field defects (e.g., optic nerve pallor, disc drusen,optic nerve pits, disc edema from central nervous system disease, maculardegeneration, retinovascular occlusion, and other retinal disease).Supplemental Ophthalmic TestingSupplemental ophthalmic testing includes the following components:

Central corneal thickness measurement

Visual field evaluation. Optic nerve head and retinal nerve fiber layer analysis

MEASUREMENT OF VISUAL FUNCTIONVisual function is generally evaluated by measuring the visual field viastandard automated perimetry. In glaucoma, the central vision is notaffected until late in the disease process. Consequently there is littlediagnostic value in evaluating only central visual function by way of visual

acuity.Clinical evaluation of automated perimetry charts remains a standard for thedetection of glaucoma.Typical glaucomatous visual field defects were first described by von Graefein 1869 and result from apoptotic death of the retinal ganglion cells. Thefield defects reflect damage to the NFL bundles as they track from the opticnerve, although the primary site of damage is thought to be at the level ofthe lamina cribrosa within the optic nerve. Classic defects include early

isolated paracentral, arcuate, nasal step and occasional temporal wedgedefects.It is likely that a generalized defect due to diffuse loss of axons is present inmany glaucomatous visual fields, but such defects have limited diagnosticvalue as they are difficult to distinguish from the effects of media opacityand pupil size.The standard clinical application of static threshold automated perimetryentails the assessment of the central 30 degrees. A variety of thresholdestimation algorithms are available, with the faster strategies based on

Baysian methodsfor example the SITA strategy found on the Humphrey


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Field Analyzer (HFA). It is important to re-test abnormal looking visual fieldsto ensure repeatability, particularly in the nave patient, as there is a clearlydefined learning curve that can mimic early defects. Interpretation can be

aided by statistical packages that analyze the data relative to age matchednormal values (Total Deviation), and scan for focal defects by removing theinfluence of diffuse loss (Pattern Deviation). There are also analyses thatjudge subjects intra-test reliability and the symmetry between the upperand lower field, such as the glaucoma hemifield test. It is essential toestablish good quality baseline data for both the early diagnosis and themanagement of manifest disease. Indeed, recent recommendations havestated the need for six fields in the first two years in order to appropriatelymanage patients with glaucoma. To successfully identify those patients witha -2dB/year change, leading to profound loss within seven to eight years, it isnecessary to have multiple fields to confidently interpret the measurementwithin the noise. This was inspired by the important findings of studies suchas the EMGT, within which a small but significant percentage of patientsexhibited dramatic and rapid progression even at the earliest manifestationof their glaucoma. This is also the thinking behind the excellent new VisualField Index available for interpretation of rate of progression on theHumphrey Field Analyzer (HFA).

There are several standard analyses for glaucomatous progression, themost common being the Humphrey Field Analyzers Glaucoma ProgressionAnalysis (GPA). The analysis empirically compares serial fields to resultscollected in a group of patients with stable glaucoma. The originalapplication used age-matched normal data to perform the analysis (TotalDeviation), but the EMGT found results to be more accurate when based onthe Pattern Deviation analysis, by reducing the influence of diffuse loss.

Figure: New glaucoma progression analysis printout for the HFA, incorporating the Visual Field Index,which quantifies the rate of progression and illustrates the projected loss. The left printout shows a


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relatively stable patient with a slow rate of progression, whereas the right printout shows a rapid rate ofprogression in a patient who underwent a change in therapy before the rate of progression reduced asseen in the last 6 fields plotted in the VFI.

Central corneal thickness measurementMeasurement of CCT aids the interpretation of IOP readings and helps tostratify patient risk for ocular damage. An overestimation of the real IOPmay occur in eyes with corneas that are thicker than average, while anunderestimation of the real IOP tends to occur in eyes with corneas that arethinner than average. Several studies have sought to quantify therelationship between measured IOP level and CCT, but there is no generallyaccepted correction formula. There is a controversy over whether CCT

represents a risk factor for glaucoma due to its effect on IOP measurementor whether CCT is a risk factor itself, unrelated to IOP. While it is clear thatthinner CCT is a risk factor for the development of POAG, studies ofprogression have had variable findings.

Visual field evaluationAutomated static threshold perimetry is the preferred technique forevaluating the visual field. The frequency doubling technology (FDT)method with the central 20-degree test program (C-20) and short-

wavelength automated perimetry (SWAP) with the central 24-degree testprogram (24-2) are two of several alternative testing methods to screen fora defect before conducting more definitive threshold testing. Visual fieldtesting based on SWAP and FDT may detect defects or progression ofdefects earlier than conventional white-on-white perimetry in somepatients. Careful manual combined kinetic and static threshold testing (e.g.,Goldmann visual fields) is an acceptable alternative when patients cannotperform automated perimetry reliably or if it is not available. Repeat,confirmatory visual field examinations may be required for test results that

are unreliable or show a new glaucomatous defect before changingmanagement. It is best to use a consistent examination strategy for visualfield testing.

MANAGEMENTGoalsThe goals of managing patients with POAG are to achieve the following:

Controlled IOP in the target range

Stable optic nerve/retinal nerve fiber layer status


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Stable visual fieldsBecause elevated IOP is a treatable cause of POAG damage, one can expectto reduce the risk of disease progression in many patients by lowering the

IOP by means of medication, laser therapy, or incisional glaucoma surgery.Management is a challenge for the patient and the doctor, because POAG isa chronic, often asymptomatic, condition that may require frequent use ofmultiple and expensive medications that may cause side effects or mayrequire laser or incisional surgery. The effects of treatment, the patientsquality of life, and the patients life expectancy are important to considerwhen choosing therapy. The diagnosis, severity of the disease, prognosisand management plan, and likelihood of long-term therapy should be

discussed with the patient.Substantial field loss in glaucoma is associatedwith a decrease in quality of life measures.

Therapeutic ChoicesThe IOP can be lowered by medical treatment, laser therapy, or incisionalglaucoma surgery (alone or in combination). The choice of initial therapydepends on numerous considerations, and discussion of treatment with thepatient should include the relative risks and benefits of the three options.

Medical treatment

Management: Significant advances have been made in recent years indiagnostic devices for glaucoma. A scanning laser ophthalmoscope(Heidelberg Retinal Tomograph II) can identify abnormalities in optic discmorphology and compare them against a normative database, documentingchanges to the optic disc topography over time. A scanning laserpolarimeter (GDx Nerve Fiber Analyzer by Laser Diagnostic Technologies)can accurately identify changes in the retinal nerve fiber layer. Here again, a

normative database assigns statistical significance and can identifyabnormalities in the nerve fibers. Genetic testing (Ocugene) can identifypatients with genetic characteristics of glaucoma and possibly predict thecourse of the disease.

Despite advances in diagnostic technology and new research intoneuroprotection, the mainstay of glaucoma treatment remains IOPreduction. Beta-blockers are still very popular medications and used in manycases of POAG. Timoptic (timolol maleate, Merck) is the most commonly

prescribed beta-blocker, but others are also noteworthy.


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Betoptic S (betaxolol 0.25% suspension, Alcon)selectively blocks beta-1 receptors, largely sparingbeta-2 receptors in the lungs (making it a safer

option for patients with certain pulmonaryconditions, though other classes of medicationmay ultimately be safer for these patients). Otherunique beta-blockers include Ocupress (carteolol,Novartis)--which has less propensity than otherbeta-blockers to elevate total cholesterol levelsand reduce HDL cholesterol levels--and Timoptic-XE (timolol maleate, Merck), which allows for once-a-day therapy.

Alpha-adrenergic medications advanced with the development of Alphagan(brimonidine 0.2%, Allergan), a selective alpha-2 adrenergic agonist. Thismedication has an excellent safety profile and IOP-lowering potential similarto beta-blockers. While clinicians have frequently prescribed Alphagan bid,clinical studies show that it should be prescribed tid, especially when used asmonotherapy. Otherwise, IOP control could be lost at times throughout theday. The most common adverse effect has been allergic reactions. A newformulation, Alphagan P (brimonidine 0.15% in Purite), has reduced the

incidence of local allergic reactions by 41%.

1

Topical carbonic anhydrase inhibitors such as Trusopt (dorzolamide, Merck)and Azopt (brinzolamide, Alcon) have been successful in lowering the IOP inmany patients. However, few clinicians use these medications as first-linetherapy. Cosopt (Merck), which combines timolol 0.5% with dorzolamide,can be effective when a single agent fails to control IOP.

IOP control was revolutionized with the development of prostaglandinanalogs and prostaglandin-like medications. Xalatan (latanoprost,Pharmacia) has enjoyed considerable success, offering outstanding IOPlowering, long-term control, and minimal local and systemic effects. Rescula(unoprostone, Novartis), actually a docosanoid, has a similar safety profileto Xalatan, though its IOP-lowering is not as great and it requires bid dosing.

More recently developed is Lumigan (bimatoprost, Allergan). Like Xalatan,this medication increases uveoscleral outflow of aqueous and has

Endstage primary open-angle glaucoma.


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outstanding IOP-lowering ability. The medication is well toleratedsystemically, hyperemia being the main adverse effect.

Another new prostaglandin analog, Travatan (travoprost, Alcon) apparentlyhas a greater IOP-lowering potential in patients of African descent. It, too, iswell tolerated systemically and ocularly. Travatan has been shown to bemore effective than Timoptic in IOP reduction.

The ophthalmologist should consider the balance between side effects andeffectiveness in choosing a regimen of maximal effectiveness and toleranceto achieve the desired IOP reduction for each patient. Frequent dosing andside effects (such as depression, exercise intolerance, and impotence with

topical beta-blockers) may affect adherence to therapy.

To determine the effectiveness of topical therapy, it is necessary todistinguish between the therapeutic impact of an agent on IOP and ordinarybackground fluctuations of IOP. It may be useful to begin by treating onlyone eye and comparing the relative change of the IOP in the two eyes atfollow-up visits.However, because the two eyes of an individual may not respond equally tothe same medication, and because of the possibility of asymmetricspontaneous fluctuations and the potential for contralateral effect ofmonocular topical medications, it is acceptable to compare the effect in oneeye relative to multiple baseline measurements. Additional studies areneeded to compare directly monocular and binocular drug trials to find outwhether a monocular trial is better at determining a nonresponder than abinocular trial. If a drug fails to reduce IOP sufficiently despite goodadherence to therapy, it can be replaced with an alternate agent untileffective medical treatment is established. If a single medication is effective

in lowering IOP but the target pressure is not reached, combination therapyor switching to an alternative therapy may be appropriate.The patient and ophthalmologist together decide on a practical and feasibleregimen to follow in terms of dosing, cost, and adherence in the context ofthe patients age and preferences. The ophthalmologist should assess thepatient who is being treated with glaucoma medication for local ocular andsystemic side effects; toxicity, including interactions with other medications;and potential life-threatening adverse reactions.To reduce systemic absorption, patients should be educated about eyelid

closure or nasolacrimal duct occlusion when applying topical medications.


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New Technologies in the Diagnosis and Management of Glaucoma

The last decade has seen an explosion of new technologies that have begunto challenge our understanding of the structural and functional relationships


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in early glaucoma, while at the same time introducing potentially newstandards of care.There are several of the latest technologies and developments. Methods for

the non-invasive, objective, quantitative, structural assessment include: Scanning laser tomography. Optical coherence tomography for the optic nerve (ON) and retinal

nerve fiber layer (RNFL); and Scanning laser polarimetry for exclusive RNFL analysis.

All three technologies are reported to have excellent diagnosticperformance in the detection of early glaucoma. These instruments are notmeant for stand-alone use but rather support the clinical evaluation of the

ON/RNFL. They may provide corroboration of a working diagnosis or requirethe clinician to re-evaluate his or her assessment of the ON/RNFL. They mayalso be used to follow for change over time.

Surgical for Glaucoma ManagementSurgical intervention becomes an option in the management of open-angleglaucoma when the intraocular pressure (IOP) cannot be sufficientlyreduced with medical or laser therapy to prevent progressive optic nervedamage and/or visual field loss. Surgery should also be considered when

medical treatment is unavailable, the patient cannot adhere to thetreatment regimen or the cost of medical therapy exceeds their means.Consideration for surgical intervention should include disease severity,advanced optic nerve damage or visual field defects with threat to centralvision, and the age and systemic status of the patient.

Adequate treatment of glaucoma requires a high level of adherence totherapy. Frequently this is not achieved; studies indicate relatively pooradherence to therapy. Even with instruction, free medication, once-daily

administration, use of a dosing aid, and electronic monitoring of adherence,nearly 45% of patients in one study took fewer than 75% of their prescribeddoses. Instilling eyedrops correctly is difficult for patients, and their ability todo so may worsen as glaucoma progresses.Repeated instruction and counselling in proper techniques for usingmedication as well as a clearly written medication regimen and follow-uptelephone calls may improve adherence to therapy. At each examination,medication dosage and frequency of use should be recorded.


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Reviewing the time medication was taken may be useful. Adherence to thetherapeutic regimen and recommendations for therapeutic alternatives ordiagnostic procedures should be discussed. Cost may be a factor in

adherence, especially when multiple medications are used. Patienteducation and informed participation in treatment decisions may improveadherence and overall effectiveness of glaucoma management.

Laser trabeculoplastyLaser trabeculoplasty can be considered as initial therapy in selectedpatients or an alternative for patients who cannot or will not usemedications reliably due to cost, memory problems, difficulty withinstillation, or intolerance to the medication. Laser trabeculoplasty lowersIOP by improving aqueous outflow and can be performed using argon,diode, and frequency-doubled YAG lasers.

Argon and diode laser trabeculoplasty

Studies using continuous-wave argon laser with a wavelength spectrum thatpeaks at 488 nm (argon laser trabeculoplasty [ALT]) found that treatmentincreases aqueous outflow and provides a clinically significant reduction ofIOP in more than 75% of initial treatments of previously unoperated eyes.

Since these initial studies, more compact solid-state diode lasers havemostly replaced the original argon laser with equal IOP lowering efficacy.

Follow-up EvaluationGuidelines for follow-up of patients with POAG are summarized in Tablebelow. These recommendations apply to ongoing glaucoma managementand not to visits for other purposes. Follow-up evaluation includesexamination as well as optic nerve head and visual field assessment asindicated.


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History

The following interval history can be elicited at POAG follow-up visits:

Interval ocular history Interval systemic medical history Side effects of ocular medications Frequency and time of last IOP-lowering medications and review of

use of medications.Ophthalmic examinationThe following components of the ophthalmic examination should beperformed at POAG follow-up visits: Visual acuity measurement Slit-lamp biomicroscopy Intraocular pressure measurement

Based on the understanding of the effect of CCT on IOP measurements,

measurement of CCT should be repeated after any event (e.g., refractivesurgery) that may alter CCT.

GonioscopyGonioscopy is indicated when there is a suspicion of an angle-closurecomponent, anterior chamber shallowing or anterior chamber angleabnormalities, or if there is an unexplained change in IOP. Gonioscopy mayalso be performed periodically (e.g., 1 to 5 years).


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Optic nerve head and visual field evaluationOptic nerve head evaluation and documentation by imaging, photography,or drawing and visual field evaluation should be performed at the

recommended intervals.

Within each of the recommended intervals, factors that determinefrequency of evaluations include the severity of damage (mild, moderate,severe, with more frequent evaluations for more severe disease), the rate ofprogression, the extent to which the IOP exceeds the target pressure, andthe number and significance of other risk factors for damage to the opticnerve.[A:III] In certain cases, follow-up visual field testing may be requiredmore frequently than the recommended intervals (e.g., a second test toestablish a baseline for future comparisons, to clarify a suspicious test result,or to overcome an apparent testing artifact). For example, a patient withglaucomatous damage who has shown long-term stability can be followedevery 6 to 12 months, depending on how severe the damage is, while apatient with evidence of glaucomatous progression may receive a change incare plan with more frequent follow-up.

Risk Factors for ProgressionThe risk factors for progression in eyes already diagnosed with OAG arerelated to the level of IOP and factors independent of IOP:Intraocular pressure: Several multicenter randomized clinical trials haveinvestigated the relationship between IOP and risk of glaucomatousprogression. Higher baseline IOP, higher mean IOP during follow-up, andhigher yearly average IOP were associated with greater progression ofglaucoma as measured by visual field or optic nerve changes. Greater IOPfluctuation in some, but not all studies, has also been shown to be related tovisual field progression, but this strongly correlated with absolute IOP level

and may not be an independent risk factor.Beta-zone peripapillary atrophy: Either the baseline presence or the size ofperipapillary atrophy adjacent to the optic nerve (beta zone) has beenrelated to visual field or optic nerve progression in several large prospectiveand retrospective studies.Disc hemorrhage: Either presence of a disc hemorrhage or percentage ofvisits with disc hemorrhage have been associated with progression of visualfield defect or optic nerve damage. The association has been reported inboth normal-tension and in high-pressure glaucoma.

Larger cup-to-disc ratio or small optic nerve rim area


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Thinner central cornea: Strong evidence exists for thinner central cornea asa risk factor for progression from ocular hypertension to POAG, butevidence is mixed for thinner central cornea as a risk factor for progression

in glaucoma.Damage in one eye is associated with an increased risk of future damage inthe other eye. A retrospective study in eyes with OAG and severe visual fielddamage in one eye showed a risk of progression in the other eye (KaplanMeier estimate of visual field progression = 12.1%). Risk factors forprogression were larger initial cup-to-disc ratio and lower calculated ocularperfusion pressure. In a separate retrospective study, progression in visualfield damage between eyes showed a significant correlation. In a largeretrospective study of eyes with normal-tension glaucoma and unilateralvisual field damage, the risk factors for progression in the normal eye weregreater visual field damage in the eye with glaucoma and smallerneuroretinal rim area.

PROVIDER AND SETTINGThe performance of certain diagnostic procedures (e.g., tonometry,pachymetry, perimetry, optic disc imaging, and photography) may bedelegated to appropriately trained and supervised personnel.

However, the interpretation of results and medical and surgicalmanagement of the disease require the medical training, clinical judgment,and experience of the ophthalmologist.

Most diagnostic and therapeutic procedures can be safely undertaken on anoutpatient basis. In some instances, however, hospitalization may berequired. This includes, for example, patients who have special medical orsocial needs.

COUNSELING/REFERRALIt is important to educate and engage patients in the management of theircondition. Patients should be educated about the disease process, therationale and goals of intervention, the status of their condition, and therelative benefits and risks of alternative interventions so that they canparticipate meaningfully in developing an appropriate plan of action.Patients should be encouraged to alert their ophthalmologists to physical oremotional changes that occur when taking glaucoma medications. Thediagnosis of glaucoma can itself lead to negative psychological effects and

to fear of blindness.


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Numerous studies have been performed to characterize the psychologicalprofile of the glaucoma patient, and some have shown the prevalence ofanxiety to be higher in this population. It has been much harder to

demonstrate a consistent presence of depression in glaucoma patients;numerous studies have been unable to do soand only a minority do.Glaucoma affects the patients visual and health-related quality of life inmany ways,this includes employment issues (e.g., fear of loss of job andinsurance from diminished ability to read and drive), social issues (e.g., fearof negative impact on relationships and sexuality), and loss of independenceand activities that require good visual acuity (e.g., sports and otherhobbies). The ophthalmologist should be sensitive to these problems andprovide support and encouragement. Some patients may find peer-supportgroups or counseling helpful.Patients considering keratorefractive surgery should be informed about thepossible impact laser vision correction has on reducing contrast sensitivity,altering visual field testing results, and decreasing the accuracy of IOPmeasurements.During the conduct of LASIK the IOP will briefly increasefrom the effect of the suction ring to make the eye rigid during creation ofthe superficial flap. This effect may cause additional damage in patientswhose optic nerves already have advanced damage. Therefore, LASIK may

be relatively contraindicated in such individuals, but photorefractivekeratectomy may be possible. In addition, postoperative fluid may developin the corneal flap-stromal interface and lead to temporary underestimationof the applanation IOP in patients treated aggressively with topicalcorticosteroids to resolve interface inflammation, who may actually have anundetected, corticosteroid-induced elevation of IOP. Conversely,corticosteroid-induced IOP elevation may cause interface fluid that mimicsinterface inflammation and leads to IOP underestimation. Patients withglaucomatous optic neuropathy considering implantation of a multifocal

intraocular lens should be informed of the risk of reduced contrastsensitivity. It is important to establish preoperative and baselinedocumentation of optic nerve head status and visual field to facilitatesubsequent glaucoma management.

If the diagnosis or management of POAG is in question or if the condition isrefractory to treatment, consultation with or referral to an ophthalmologistwith special training or experience in managing glaucoma should beconsidered. Patients with substantial visual impairment or blindness can be


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referred for and encouraged to use appropriate vision rehabilitation andsocial services.

Clinical Pearls:

Glaucoma is a long-term disease. Accumulate the necessaryinformation so that you can diagnose with confidence. Do not to rushto a diagnosis. It typically is not necessary to diagnose the disease andstart treatment at the patient's initial presentation.

A single IOP measurement does not accurately represent the patient'strue status, but is merely a snapshot pressure at that moment. Beforemaking a diagnosis or initiating treatment, take repeated IOP

measurements at different times on different days so that you have amore accurate picture of the patient's IOP "baseline range."

While scanning lasers have not supplanted visual fields in thediagnosis and management of glaucoma, they provide usefulinformation on optic nerve head and nerve fiber layer structure.

Prostaglandins and prostaglandin-like medications are not FDA-approved as first-line therapy due to the possibility of inducing ocularinflammation and iris color changes. Yet many clinicians use them asfirst-line therapy.

CONCLUSION

Early detection of structural damage to the optic nerve head is critical indiagnosis of glaucoma, because such glaucomatous damage precedes

clinically identifiable visual loss. Glaucoma is the second leading ocular


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disease and early detection of glaucoma can prevent progression of thedisease and consequent loss of vision. Segmentation of optic disc cup andneuroretinal rim can provide important parameters for detecting and

tracking this disease.

REFERENCES

1. Community Eye Health Journal | Vol 19 No. 59 | SEPTEMBER 2006.2. Review of optometry supplement, the handbook of glaucoma,

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3. Kirsch RE, Anderson DR. Clinical recognition of glaucomatous cupping.Am J Ophthalmol. 1973 Mar;75(3):442454.

4. Pederson JE, Anderson DR. The mode of progressive disc cupping inocular hypertension and glaucoma. Arch Ophthalmol. 1980

Mar;98(3):490495.

5. Tuulonen A, Airaksinen PJ. Initial glaucomatous optic disk and retinalnerve fiber layer abnormalities and their progression. Am J Ophthalmol.

1991 Apr 15;111(4):485490.

6. Jonas JB, Fernndez MC, Strmer J. Pattern of glaucomatousneuroretinal rim loss. Ophthalmology. 1993 Jan;100(1):6368. [PubMed].

7. Jonas JB, Fernandez MC. Shape of the neuroretinal rim and position ofthe central retinal vessels in glaucoma. Br J Ophthalmol. 1994;78:99102.

8. Jonas JB, Budde WM, Nemeth J, Grundler AE, Mistlberger A, Hayler JK.Central retinal vessel trunk exit and location of glaucomatousparapapillary atrophy in glaucoma. Ophthalmology. 2001;108: 10591064.

9. Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of theoptic nerve head. Surv Ophthalmol. 1999;43:293320.

10.Littmann H. Zur Bestimmung der wahren Grosse eines Objektes auf demHintergrund des lebenden Auges. Klin Monatsbl Augenheilkd.

1982;180:286289.11.Jonas JB, Fernandez MC, Naumann GOH. Glaucomatous parapapillary

chorioretinal atrophy: occurrence and correlations. Arch Ophthalmol.1992;110:214222.
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neuroretinal rim defect and its damage likelihood in poag

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