OBJECTIVE PERIMETRY IN GLAUCOMA: PART 2, PRACTICAL ISSUES

A 45 year-old white female was seen originally in 2000 as a contact-lens patient and recommended for glaucoma evaluation due to the suspicious appearance of her optic nerves. She has since been followed at our clinic for seven years. This case chronicles her progress over that period of time.

Medical and ocular histories are non-contributory for glaucoma risk. Her best corrected visual acuity was 20/20 in each eye at all visits, with refraction of -4.50 -0.75 X 176 (OD) and -2.50 - 1.25 X 147 (OS).

The IOP readings by applanation have been within a relatively narrow range from 17 mm Hg to 22 mm Hg in each eye with one exception of a 28 mm Hg reading in each eye in 2000. IOP measurements have been made at a variety of times over the seven year period, including both mornings and afternoons.

Pachymetry was first measured in 2002 and was right 594 µM, left: 621 µM. These values indicate possible IOP overestimation due to presence of "thick" corneas.

By gonioscopy, the anterior chamber angles have always been wide open with visibility of the ciliary body in four quadrants. There is no pigment in the angles.

Visual fields

1. SITA-Fast 5/2000. Baseline visual field. Both eyes have reliable results. Although there are some test locations with depressed sensitivity identified by both total and pattern deviation probability in the right eye, these did not appear to follow a nerve fibre layer pattern and so were disregarded in the context of glaucoma. However, in the left eye there is a cluster of 4 test locations with depressed sensitivity values in the inferior field of the left eye according to pattern deviation probability (Figures 1a and b.) For this reason, repeat testing was arranged in one month.

Figure 1a.

Figure 1b.

2. Repeat visual field 6/2000 (SITA Standard). Reliable results in left eye did not confirm left eye depressions observed at the previous visit. A high proportion of fixation losses in the right eye suggested that this eye’s test was unreliable (Figure 2a and b).

Figure 2a.

Figure 2b.

3. Screening FDT N30-5. 5/2001 Reliable, no test locations were missed with this suprathreshold screening test in either eye (not shown).

4. Screening FDT N30-5 5/2003. Reliable, test locations were missed with this suprathreshold screening test in either eye (not shown).

5. Matrix 30-2 8/2005. Unreliable due to fixation losses in each eye (not shown).

6. 24-2 SITA-Fast 11/2005. Reliable with no glaucomatous depressions in either eye (not shown).

7. 24-2 SITA-Standard 8/2006. Reliable in each eye with no glaucomatous depressions in either eye (not shown).

Figure 3a.

Figure 3b.

8. 24-2 SITA-Standard 8/2007. Reliable test results were again obtained from each eye. In the right eye, a cluster of test locations with depressed threshold sensitivity values are present in the nasal field of the right eye, accompanied by a significantly elevated Pattern Standard Deviation indicating irregularity of the visual field surface. Also, the Glaucoma Hemifield Test result was outside normal limits, indicating presence of significant sensitivity asymmetry between superior and inferior hemifields (Figures 3a and b).

Figure 4a.

Figure 4b.

The most recent optic disc photos, taken in August 2007 are shown in Figures 4a and b. Applying the rules of optic disc evaluation (evaluation of optic disc size, neuroretinal rim size and shape, retinal nerve fiber layer, presence of parapapillary atrophy, presence of retinal or optic disc hemorrhages (1)), these nerve heads appear to have some neuroretinal rim erosion inferotemporally, although this may be associated physiologically with their larger than average diameter. They show no RNFL defects but the fundus is lightly pigmented which reduces the visibility of the RNFL. Also there is no evidence of disc change over time. There is minimal parapapillary atrophy which may be consistent with myopia and the patient understands that mild myopic disc change may be a confounding factor for the diagnosis of glaucoma because it hinders identification of glaucomatous peripapillary atrophy. At her most recent visit on August 7, 2007, she was apprised that the early changes in her right visual field may be consistent with glaucomatous damage. It was also discussed that presence of glaucoma was not corroborated by definite optic nerve head or retinal nerve fibre layer signs of glaucomatous optic neuropathy, and that there was absence of change in the structural appearance of the disc over time. The recommendation was therefore to repeat the suspicious visual field test in one month to determine whether the apparent visual field defect was repeatable. Although the argument could be made to initiate treatment, discussion with the patient and her informed choice to continue close monitoring without treatment until definite disease was confirmed influenced the clinical management plan.

Observations and Lessons

1. This patient is compliant with visits and with one exception a good visual field test taker.

2. Her pachymetry readings suggest that her IOP readings may be overestimations and therefore at lower risk of glaucoma development than if she had exhibited thin central corneas. This offers some comfort for continued observation versus treatment recommendation. Nonetheless her history provides no repeatable evidence of raised IOP.

3. The optic nerve heads are suspicious in appearance but the retinal nerve fibre layer appears intact in both eyes and there has been no change in disc appearance compared with baseline photos from 2000.

4. The plan is to re-evaluate this patient in the near future in view of the suspicious most recent visual field test to determine whether the finding was spurious, or represents conversion to manifest glaucoma. Her next visit has been scheduled for approximately 1 month to confirm or rule out the sensitivity depressions inferiorly in the nasal visual field of the right eye. At the next visit, imaging studies will be conducted to assess optic disc topography and retinal nerve fiber layer thickness. These investigations have not been performed in the past.

5. Considerable time was spent in discussing the options of treatment versus observation at this time. If the visual field defect is found to be repeatable at the forthcoming test, treatment will be recommended. If not, the patient will be advised that close observation continues to be required, and that additional structural and function tests relevant to detection of early glaucoma will continue to be performed at future examinations.

Leo Semes, OD, FAAO

1. Fingeret M, Medeiros FA, Susanna R Jr, Weinreb RN. Five rules to evaluate the optic disc and retinal nerve fiber layer for glaucoma. Optometry. 2005;76(11):661-8.

THE OPTOMETRIC GLAUCOMA SOCIETY RESIDENCY PROGRAM

Figure 1. A group photo of the speakers and attendees at the OGS Residency Program.

Figure 2. Several of the faculty from the OGS Residency Program. From the top right, moving clockwise are Martin Wax, Mae Gordon, John Flanagan and Murray Fingeret.

The Optometric Glaucoma Society held a two-day program, dedicated to glaucoma designed for optometric residents on September 15-16, 2007. Each optometry school was represented, with residents coming from programs affiliated with schools and colleges of optometry, VA hospitals, referral centers and the Indian Health Service. Funding was provided by Alcon, with Ben Gaddie and Murray Fingeret serving as chairs and speakers included Abe Clark, PhD, John Flanagan, MCOptom, PhD, Mae Gordon, PhD and Martin Wax, MD. The topics ranged from the basics of evaluating the optic nerve and visual field to clinical trials and their applicability in practice to new medical therapies.

An important part of the program was the lectures on performing clinical research, and how one may get started. The OGS-Alcon Resident Glaucoma Research Award was announced, with each of the 19 attendees encouraged to perform a clinical research project during the next 9 months. The winning project’s author will receive an honorarium as well as travel support to present their work at the next OGS Resident Program as well as at the 2008 OGS annual meeting.

MELTON AND THOMAS - THEIR VIEWS

Perspective on Target IOP

The concept of "target IOP" has been a part of the glaucoma lexicon for many years, yet it remains a somewhat nebulous, enigmatic, clinical entity. It is loosely defined as an inexact prognostication of the highest IOP environment in which the optic nerve can endure over the life of the patient. It should, therefore, be evident that determining the target IOP is 1) a "best guess" scenario, and 2) represents the epitome of "art." It should be stressed from the outset that the target IOP is a range, not a number. For example, the target IOP for a specific person might be said to be 12 to 15mmHg, not 13mmHg. The idea of a range acknowledges the inexactness of this principle. Yes, there are studies that speak to keeping the IOP below 18mmHg, and studies that demonstrate that 12.3mmHg is virtually bullet-proof against glaucomatous progression, but these data cannot be generalized to the patient at hand.

The idea of a percentage lowering of IOP has been proposed, i.e. reducing IOP by 30%, but this too is an oversimplification of complex pathophysiological processes. So, what if “target range” is cerebrally set at X +/- 2mmHg; when will we know if that range is indeed protectively accurate? The answer is probably four to eight years down the road. Untreated glaucoma is slowly progressive, at least in the vast majority of patients, and treated glaucoma (hopefully) progresses even more slowly, if at all. Certainly, the target IOP range can be modified along the way, but it may take many years to know the clinical accurateness of the predicted IOP safe harbor.

Whether to annotate the target IOP in the patient’s chart is widely debated. There are pros and cons to both approaches. Probably for medicolegal considerations, we feel it is best to omit such from the medical record. It could potentially be used against a doctor if the patient ultimately suffered vision loss, and the target IOP was not achieved (or maintained). Furthermore, the doctor could be at more medicolegal risk if the target IOP was reached and maintained, but the patient lost vision anyway. On the other hand, some practice patterns describe the need to set a target IOP and record it in the chart. We discuss with our patients a general idea of where we would like to see their pressures (i.e., "low teens," or, "mid teens"), but we do not bind ourselves with specifics.

Managing the glaucomas is challenging at best, and to overburden ourselves with micromanaging ill-defined prognostications, such as "target IOP," may not be productive. Thoroughly educating our patients regarding their disease, and engaging them in their care and management should take center stage. We see the ill-defined parameter of "target pressure" as relatively insignificant vis-à-vis the gestalt of comprehensive patient management.

Closing commentary comes from Joseph Caprioli, in the August, 2007 Archives of Ophthalmology: "Estimation of target pressure is based on a patient’s risk factors for progression, the level of IOP that caused damage, the severity of disease, and longevity. There is, of course, no way to determine in advance which IOP will be safe. There is no evidence that setting a variable target has clinical value for most patients with chronic glaucoma." We agree.

Randall K. Thomas, OD, and Ron Melton, OD

Association of International Glaucoma Societies (AIGS) 4th Global Consensus Meeting on Intraocular Pressure

Just prior to ARVO this year, the Association of International Glaucoma Societies (AIGS) held their 4th Consensus meeting which was devoted to Intraocular Pressure (IOP). Areas addressed included Basic Science, Determinants of IOP, Measurement of IOP, IOP Variation, Epidemiology of IOP, IOP as a Risk Factor for Glaucoma Development and Progression, Clinical Trials and IOP, and Target IOP in Clinical Practice. Information and the consensus points can be found at www.Glaucom.com.

A discussion took place regarding the different tonometers available. One question discussed was whether new forms of tonometry, such as Dynamic Contour Tonometry (DCT) or Rebound Tonometry, offer advantages over Goldmann Applanation Tonometry (GAT). From data currently available, GAT was felt to be the most precise (lowest measurement variability) instrument but this view may change if future studies demonstrate greater precision with these newer instruments. One point raised was that both the DCT and the Ocular Response Analyzer (ORA) may be less sensitive to changes in corneal biomechanics following keratorefractive surgery and have less variance. The frequency of tonometry calibration was discussed and what represents an acceptable calibration error margin. Surprisingly, most individuals in the room were unfamiliar with GAT calibration and how often it should be done. Few remembered ever having to send a tonometer back to the manufacturer and most felt that a +/- 2mm Hg margin of error was sufficient. Clearly, one advantage of a tonometer like the DCT is that it is self calibrating and alerts the operator if problems have developed.

A discussion about the variation in IOP throughout the day and night occurred. The IOP tends to be higher in the supine than sitting position, and increases during the night time hours. It was noted that “correction nomograms that adjust IOP based upon central corneal thickness (CCT) are neither valid or useful in individual patients”. Large amounts of corneal edema produce an underestimation of IOP when measured with the applanation tonometer. This issue is most important on the day that a contact lens wearer presents for a comprehensive eye exam. Edema associated with contact lens wear, if excessive, can impact IOP measurements.

A discussion ensued in regards to which IOP variable (mean, peak, or fluctuation) was most important in regards to the development and progression of glaucoma? Previous studies have discussed long-term IOP variability or fluctuation as being a risk factor for the progression of glaucoma. Recent work has questioned the importance of long-term IOP variability on glaucoma progression. Surgery appears to reduce IOP fluctuation better than medication. Two IOP provocative tests have been available: steroid and water drinking test. There is no data to support the use of the steroid test, as the increased IOP response when the eye is challenged with a topical steroid does not offer good predictive power. Surprisingly, the water drinking test in which a person drinks a fixed amount of fluid and the IOP monitored appears to be promising and may predict short-term IOP fluctuation and peak IOP.

The concept of target IOP was discussed and how it may be applied clinically. Target IOP is a guess as it "can not be determined with any certainty in a particular patient." "There is no validated algorithm for the determination of a target IOP. This does not, however negate it use in clinical practice." "The use of a target IOP in glaucoma requires periodic re-evaluation, entailing the detection of the presence or absence of glaucomatous progression, the effect of therapy upon the patient’s quality of life, and whether the patient has developed any new systemic illness that might affect the risk/benefit ratio of therapy."

From the meeting it became apparent that there is a great deal of new information in regards to IOP, and the next few years will be exciting times as clinicians are challenged with how to interpret this old test.

Murray Fingeret, OD

Click this link to view the IOP consensus meeting document.

World Glaucoma Congress

The World Glaucoma Congress is a biannual meeting developed by the World Glaucoma Association (formerly the Association of International Glaucoma Societies or AIGS). The meeting was held in Singapore this past July with representation from all of the world’s glaucoma organizations. The conference spanned four days during which glaucoma specialists, general practice ophthalmologists and optometrists, leaders from Singapore’s medical community and government, and international figures came together to discuss and debate various issues about glaucoma. Experts on each topic presented new findings from clinical and scientific studies in their fields of interest, then debated controversies, finer points and subtleties during subsequent sessions. Eight members of the Optometric Glaucoma Society participated. The program is available at the World Glaucoma Association’s website.

One unique feature of the meeting was a series of debates among experts that were interspersed throughout the meeting. Debate questions were varied;

1. Quality of life for glaucoma patients-is it important and how can it be measured?
2. How early should glaucoma be treated?
3. Are normal tension and primary open angle glaucoma two different diseases?
4. Is clinical data collected too sparsely to be able to judge meaningful progression?
5. Can the concept of blood flow be used in the management of glaucoma?
6. Can FDT and SWAP be used to monitor glaucoma suspects with normal fields?
7. Is there a role for fixed combination therapy?
8. Does myopia affect glaucoma?
9. Open-angle glaucoma- medial treatment versus laser trabeculoplasty?

These debates among experts were lively and informative. The debate concerning diagnosis of early glaucoma was fascinating. One point challenged the prevailing manner in which resources are allocated, with the concern that too much of the research and development effort is focused on instruments and software for detection of preperimetric glaucoma, resulting in reduced emphasis on the detection and management of those patients with the most aggressive, potentially blinding cases. The tools we have to recognize when people are getting worse are crude, relatively speaking, and yet this should be one crucial area to which we pay greater attention.

Another of the symposiums dealt with glaucoma presents in different locations around the world. The program on glaucoma in Asia described the contrasts between regions of Asia. For example, Normal Tension Glaucoma is especially prevalent in Japan, as compared with other Asian communities. Another point discussed was why the prevalence of angle closure glaucoma is equal to open angle glaucoma, yet the vast majority of blindness relates to the closed angle forms.

Another session dealt with a new area, glaucoma patient organizations (GPOs). The Association of International Glaucoma Patient Organizations (AIGPO) was established over the past year to create a resource for patients with glaucoma. This group, acting as an umbrella organization, is creating a template to guide and encourage formation of other patient organizations. The goals are to empower patients and to positively affect patient care. Many of us have patients who are searching for answers and become frustrated at the inability to connect with others who have similar problems. Hopefully, GPOs will become more common and important as a resource for those with glaucoma.

Over the past four years, the WGA convened a series of consensus meetings related to: structure-function, glaucoma surgery, angle closure glaucoma, and intraocular pressure. The major points from each of the meetings have been developed into presentations that were recently released. The presentations review the findings and are available at the WGA and OGS website.

The World Glaucoma Congress (WGC) is a treat for anyone with an interest in glaucoma. To interact with the world’s experts in your field, be directly exposed to their wisdom, and to witness their debates is an incredible experience. The good news is that the next WGC will take place in Boston on July 8-11, 2009 with all optometrists from around the world invited to attend.

Murray Fingeret, OD, Brad Fortune, OD PhD

If you would like us to answer a clinical question, please send it to paul.spry@ubht.nhs.uk with "OGS question" as the subject. The questions can concern anything related to glaucoma, for example, analysis of an optic nerve image, optic disc, a challenging case or side effect of a medication. We welcome your questions and we will try to address as many as possible in each issue.

Question: A clinician has a patient with optic disc drusen and what appears to be visual field loss, possibly progressive. The IOPs have never been elevated and corneal thickness is average. No pertinent medical or ocular history is seen. Is there any justification to use IOP lowering agents, or is it a question of monitoring and hoping the field loss does not impact visual function?”

Andy Gurwood, OD, answers: Optic nerve disc drusen (ONDD) are retained hyaline bodies in the anterior optic nerve. ONDD are encountered in approximately 1% of the general population and are bilateral in 70% of cases. The condition occurs primarily in Caucasians and is believed to demonstrate an autosomal dominant inheritance pattern with incomplete penetrance. Typically, patients with ONDD remain asymptomatic, however, patients who have errosive damage to the overlying axons of the retinal ganglion cells may experience acuity loss, visual field loss and even APD if the condition is both significant and asymmetric. Reports of recurrent, transient visual obscurations, vein and artery occlusion have been reported in the literature in association with disc drusen. These ecressences represent acellular laminated concretions, often partially calcified, possibly related to the accumulation of axoplasmic derivatives of degenerating retinal nerve fibers. Within the optic nerve, the hyaline bodies are confined to the anterior lamina cribosa and thus may compress and compromise the nerve fibers and vascular supply, leading to visual field defects and disc hemorrhages. Along with slowly developing optic atrophy in extreme cases, disruption of the juxtapapillary tissue can result in choroidal neovascular membrane formation leading to subretinal hemorrhage and disciform retinal scarring. (Sowka, Gurwood, Kabat, Handbook of ocular disease management) Since the mechanism of loss associated with this phenomeneon is compressive/degenerative, lowering IOP to decrease the resistance against neural circulation, while a novel approach, has never been associated in the literature with reversing or preventing the compromise associated with the primary mechanism of the process. While there is plausible reason to suspect that lowering IOP could be protective, there is no evidence to suggest that it has the capability of reversing the mechanical effects ONDD have on axons they physically erode.

I therefore conclude the therapy is unwarranted. Finally, the concept of neuroprotection remains controversial in human eyes. There is little evidence to suggest that these agents are available to make penetration into the human eye, in the correct concentration to perform their service and less evidence to suggest that in human eyes, they reverse or arrest neurodegenerative processes.

Andy Gurwood, OD

Douglas R. Anderson, MD, answers: I don't think anyone knows. There are no data to guide us. Enlarging drusen are said to be able to cause increasing field defects, unknown mechanism but perhaps mechanical damage to axons. There is another optic neuropathy of unknown etiology that causes increasing field defects, and the level of IOP seems to affect the rate at which that damage occurs, and we call it "glaucoma".

Do the two mechanisms have any overlapping pathogenic features such that one is aggravated by the other? Even if drusen are present, is the person even immune from NTG? We have all seen cases of abnormally high IOP with drusen present, but we haven't often considered whether NTG might occur in a person with drusen when we find drusen and an IOP in the normal range. But should we give it some thought when the IOP is 19 or 20 mm Hg, and strictly speaking not abnormal? It is true that on rare occasion people with drusen have glaucomatous excavation of the disc, such that there is obvious cupping and perhaps some baring of the drusen to make them more visible. Usually, however, the dilemma arises when the drusen produce a heaped up disk, there are field defects, and the IOP is high, and cupping is not recognized. Most clinicians decide that it is best to lower the abnormally high IOP, not knowing whether it will help or not. Tolerated medications and laser would seem an appropriate estimated risk/benefit ratio, if the medication is not producing any risk. Filtration surgery might be done in one eye of a bilateral case if the field is progressing, and a couple of years later if the progression halts in the operated eye but not the un-operated eye, then do the second eye. But except for individual cases in which there is a demonstration of benefit, no one knows, and it seems reasonable to lower the IOP in people with drusen and field defects with tolerated medical and laser treatment, if the IOP is abnormal or maybe even in the upper normal range. I think that's what most people decide to do. Whether it is helpful we may never know. I don't think I can remember a case of progressive field loss in a patient with drusen and historically elevated IOP, almost always if not always treated to make IOP lower. Maybe the treatment works. Maybe they wouldn't have progressed anyway, being stable drusen in an ocular hypertensive. We'll never know.

Douglas R. Anderson, MD
Professor of Ophthalmology and Douglas R. Anderson Chair in Ophthalmology
Dept of Ophthalmology, Univ. of Miami Leonard M. Miller School of Medicine, Bascom Palmer Eye Institute.

Harry Quigley, MD, answers: As described by Doug, I know of no study that has lowered IOP to test for an effect in any optic neuropathy other than glaucoma (and AION, for which it was not successful in a trial to see the effect on the fellow eye--Alphagan only, I believe).

I tell patients that I am not sure if lowering their IOP would help or hurt them (flexing the lamina cribrosa the "wrong" way might be just as bad as doing nothing).

If a patient had progressive field loss documented in both eyes with disc drusen, I would offer substantial IOP lowering for one eye.

Harry Quigley, MD
A. Edward Maumenee Professor of Ophthalmology
Director, Glaucoma Service; Director, Dana Center for Preventive Ophthalmology
Wilmer Institute, Johns Hopkins University

The results of our latest poll are available. With respect to the question of verifying calibration, 52% of respondents do not verify accuracy of their tonometer, 30% check every six months. Only 1 in 5 will recheck the calibration of their tonometer at least once every three months if not more frequently. Over 3/4’s of respondents have never had to send their tonometer back to the manufacturer for recalibration. These findings appear to be in consensus with opinions expressed in the AIGS tonometry consensus meeting demonstrating that a regular calibration routine, although ideal, is not in place in many clinics.

The frequency of blood pressure measurements is variable across our responses. Fifty-four percent of those reporting check blood pressure at least once a year.

The effect of corneal thickness on intraocular pressure measurement has received much attention in recent years. The precise effect of corneal thickness is still being clarified. Fifty-five percent of respondents think of the corneal thickness and effect on IOP in general terms. Nearly 1 in 5 respondents see corneal thickness as a risk factor independent of the effect on IOP. This spread of opinion does not seem surprising and reflects that to be found in peer-reviewed literature on this subject.

John McSoley, OD

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Editor in Chief Paul Spry PhD MCOptom Associate Editors Brad Fortune, OD, PhD Shaban Demirel, BScOptom, PhD Algis Vingrys BScOptom, PhD

Editorial Board Douglas Anderson MD Paul Artes PhD MCOptom Dick Bennett OD Murray Fingeret, OD Ron Harwerth, PhD Chris Johnson, PhD Tony Litwak, OD John McSoley, OD Ron Melton, OD Bruce Onofrey, OD, RPh Leo Semes, OD Randall Thomas, OD Thom Zimmerman, MD, PhD   Art/Production Director Joe Morris

 

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