As we draw to the end of another year
it is a time to take a few minutes to reflect. Iíve just returned from the annual meeting of the
Optometric Glaucoma Society in Orlando and 2009 will be remembered for yet another exceptional meeting. Our
speakers shared their experience and at times life-learnt philosophies. Those in attendance enjoyed
lively discussion on normal tension cases and the origins and significance of disc hemorrhage with
Dr. Louis Pasquale. In the President's Lecture we learnt about race and glaucoma in a session led by
Dr. Chris Girkin who gave an excellent update of the African Descent and Glaucoma Evaluation Study
(ADAGES). Dr. Girkin also shared his insights on the plethora of non-bleb (or sometimes not so non-bleb!)
alternatives to trabeculectomy. Our 2009 Honoree, and now the latest member of our society Dr. George Speath,
led us down the road of lifelong learning with talks on gonioscopy and evaluation of the optic nerve. The
inaugural Research Excellence Award was presented by Dr. Peng Khaw from Moorfields Eye Hospital
in London. His talk entitled "Repair to Regeneration-Translating Laboratory Discovery to Clinical Advance" was
simply astonishing. Many people talk about translational research, Dr. Khaw "lives the life". He shared his
journey of discovery that led to anti-metabolites being used routinely with trabeculectomy, and also described
successful gene therapy and the therapeutic use of stem cells. For those of you not able to attend these talks,
along with the other excellent member presentations, a synopsis will be available soon in the annual meeting
supplement kindly distributed by Review of Optometry.
Opening my post today I found the Fall report for the National Alliance for Eye and Vision Research (NAEVR). Those who are OGS members have also received this, and have been receiving monthly emails from their Executive Director, James Jorkasky. So what exactly does the organisation behind this acronym do, why is this information distributed, and do you need to know more about them? Well, AEVR, the Alliance for Eye and Vision Research is an education foundation whose goal is to educate Congress and the public about the value of eye and vision research. NAEVR, the National Alliance for Eye and Vision Research, was formed as an affiliate of AEVR with the aim of achieving best eye and vision care through advocacy and public education for eye and vision research sponsored by the National Institutes of Health (NIH), the National Eye Institute (NEI) and other federal research entities.
The Optometric Glaucoma Society is a member of the coalition of 55 professional, consumer and industry organizations involved in eye and vision research that officially support NAEVR activities. There is no doubt that delivering information to key policy makers on the importance of sustaining vision research funding is crucial. Without ongoing research activity, the potential for improved visual health care outcomes is limited. Research groups can provide new pieces of information that could translate to improvements in clinical practice if allowed to. Continued advocacy for sustained research funding becomes all the more important when constraints in public spending lead to greater competition for the dwindling contents of a limited funding pot.
Various aspects of current glaucoma patient care are based on information funded by NEI grants. As such, I urge you to take a look at the NAEVR and AEVR website, www.eyeresearch.org and to consider putting your name to a very worthy cause.
Paul GD Spry, PhD, BSc, MCOptom DipGlauc
The Lamina Cribrosa
The lamina cribrosa (LC) spans the neural canal opening and supports the retinal ganglion cell axons as they exit the eye to become the optic nerve. The LC is comprised of interconnected connective tissue "beams" each containing a capillary and wrapped by astrocytic (glial) processes. Blood flowing through the LC capillaries is supplied primarily by the short posterior ciliary arteries (SPCA) via the circle of Zinn-Haler with some anastomotic flow from recurrent branches of the central retinal artery anteriorly and posteriorly. Viewed axially, the LC has a "cribriform" or sieve-like appearance, which is particularly striking when the neural and other soft tissues are removed by enzymatic or alkali digestion techniques (1-5). Similarly striking images of the LC structure are produced by the 3-D histomorphometric reconstruction techniques developed by Downs and colleagues (6-8). Understanding the complex anatomy of the LC is important because it is believed to be the primary site of injury in glaucoma (4,6-8). Detailed images of the LC may someday even be obtained clinically in living human patients through advances in imaging technology such as second harmonic microscopy (9) and adaptive optics combined with confocal scanning laser ophthalmoscopy (CSLO) (10) or ultrahigh-resolution optical coherence tomography (11). Indeed, the cribriform appearance of the LC is manifest even upon direct ophthalmoscopy of the optic disc, where the contrast between the reflectivity of lamina connective tissue and axon bundles creates an appearance of LC "pores" within the optic cup, which can become especially prominent and abnormally elongated in eyes with advanced glaucomatous damage (12-14).
It is therefore important to consider changes in the appearance of
LC poresalong with any other signs of structural change such as neural rim thinning, excavation, loss of
the retinal nerve fiber layer, appearance of disc hemorrhages, etc.when examining serial stereo-photographs
of glaucoma patients and suspects. These changes can represent neural loss and/or deformation of the connective
tissue architecture within the optic nerve head, itself likely to be prognostic for future glaucomatous vision loss.
Another sign of potential glaucomatous structural alterations in the LC that should serve as an alert are acquired
pits of the optic nerve (APON).
Tony Litwak, OD, FAAO and Brad Fortune, OD, PhD
Imaging Adds Value to the Diagnostic Picture
The HRT 2 image (Figure 3) shows a disc slightly larger than average with much of the disc occupied by the cup (red area). The Moorfields Regression Analysis (MRA) shows several sectors flagged in each eye at the lowest probability of falling within the normal range (red x); consistent with rim tissue that is thinner than expected in each eye taking into account the disc size. The GDx printout (Figure 4) also shows that both eyes have thinner than expected RNFL, with a NFI of 51 OD and 47 OS showing a high probability of each eye being glaucomatous. The RNFL maps show loss superiorly and inferiorly in each eye. The Optovue OCT printout (Figure 5) also shows thinning of the RNFL in each eye, flagged as yellow on the outer rim diagram (middle level of probability). The ganglion cell complex (GCC) analysis also shows thinning in the macula region, which supports the RNFL analysis. For this analysis, thinned areas are visible at the highest probability values in both eyes (red areas on the GCC section of the printout).
The Cirrus OCT (Figure 6A) printout shows mild RNFL thinning, similar to the Optovue printout. Greater thinning is seen in the OD, which is also similar to the other devices. The superior quadrant analysis OD is flagged at the lowest probability value. The TSNIT curve shows the RNFL to be just within the confidence limits of the normal range. Figures from the Cirrus (Figure 6B, C) show cross sectional scans of the optic disc. Currently, there is no optic disc statistical analysis (disc size, rim area, etc) but this should be available shortly. The final imaging printout is from the Topcon 3D OCT (Figure 7A, B). With this device, the OCT image is registered against a retinal view. The RNFL thickness may be mapped but probability limits are not available at this time but should be available shortly.
Progressive Normal Tension Glaucoma
On examination, corrected visual acuity was 20/20 in each eye with mildly myopic refractive correction. A 2.25D add was prescribed to allow reading vision of 0.37M at approximately 16". IOP by Goldmann applanation tonometry was 16 mmHg in each eye and gonioscopy revealed open angles and appearances of all structures being within normal limits. Dilated stereoscopic fundus evaluation revealed suspicious appearing optic discs with inter-eye cup-to-disc ratio (CDR) asymmetry (CDR OD>OS) corresponding to an asymmetry in disc diameter. There was also probable erosion of the inferotemporal neuroretinal rim (NRR) in each eye that was more apparent OD, and these ONH signs were considered to be suspicious of glaucomatous optic neuropathy. Disc appearances were documented using Polaroid© film and are shown in Figure 1. Visual field testing was ordered (see Figure 2). The SITA strategy was not available when this patient presented so 30-2 FASTPAC visual field tests were performed. The visual field tests were reliably performed by the patient. There is a single location that is deeply depressed in the superior nasal field of the right eye (see pattern deviation probability plot) with shallow sensitivity reductions present predominantly at the peripheral test locations in left eye. A diagnosis of suspect glaucoma was made and the patient was asked to return in six months. Repeated visual field testing in 1996 (Figure 3), revealed the deep nasal defect in the right eye to be repeatable, although fewer test locations were found to have reduced sensitivity in the left eye compared with the previous test. On the basis of the nasal defect in the right visual field being repeatable and corresponding to the area of NRR thinning, the patient was considered to have both structural and functional damage and the diagnosis was therefore modified to open angle glaucoma. Treatment was offered in the form of topical drops and the patient was prescribed latanoprost 0.005% (Xalatan®, Pfizer) and asked to return in 3 weeks. At a pressure of 16mmHg, the patient is considered to have normal tension glaucoma. A target IOP of 9-11 mmHg was established. When these visits took place the results of the CNTGS had been published and the recommendation was to lower IOP by at least 30% (1).
The patient failed to attend for any scheduled future monitoring visits but re-presented 13 years later, aged 70, in 2009. He had not sought any eye care in the intervening period. Fundus photos from that visit are shown in Figure 4 and a number of obvious changes in disc appearance can be seen, including further inferior temporal rim thinning, an associated RNFL defect and baring of a small circumlinear arteriole at the inferior pole of the right disc. A disc hemorrhage can also be seen in the same area. Visual fields performed on the same date are shown in Figure 5 with the previous single defective test location in the right eye having extended to become an arcuate defect that encompasses many test locations in the superior hemifield. The left visual field also shows a moderate retinal nerve fiber layer type defect. The diagnosis was re-confirmed as normal tension glaucoma. The patient was offered a treatment recommendation of the prostaglandin analog travoprost 0.004% (Travatan®, Alcon Laboratories) once daily in each eye. This switch in medication was consistent with the patientís medical pharmacy coverage.
When making a diagnosis of normal tension glaucoma, it is important to consider the potential impact of central corneal thickness (CCT). CCT may represent a risk factor for primary open-angle glaucoma (POAG) as well as being a confounding influence on Goldmann applanation readings that may reclassify the case as POAG if the cornea is sufficiently thin. Results of the OHTS, which highlighted the significance of CCT as a risk factor for conversion from ocular hypertension to glaucoma, were published in the interval during which the patient was lost to follow up (2). Pachymetry was performed when the patient returned in 2009 and was found to be OD/OS: 434/442 micrometers. This has more than one implication. First, the measured IOP is likely to be an underestimate of the true IOP. Second, if the IOP had previously been measured any higher (it was 20 mmHg at one point), then this patient's classification as NTG might have been incorrect, and in fact, the correct diagnosis may be POAG (3).
Complicating this case further is the initial appearance of the optic nerves. The left ONH, especially could be interpreted to be an inferiorly tilted disc with RPE thinning. This would be expected to result in a relative superior visual field depression. Such a defect was present initially (1995) and had deepened by the examination in 2009 demonstrating visual field progression. So, on the basis of structural and functional progression there is ample evidence to refine the diagnosis and offer treatment to lower the IOP.
The patient's IOP responded to travoprost by decreasing to 13mmHg OD and 14 mmHg OS. While this is above the
initial target IOP, this was considered sufficient in view of the slow rate of progression whilst untreated over
the preceding 13 years, as well as the patient's increased age and lack of deep paracentral loss that might otherwise
threaten fixation in either eye. He will continue to be monitored for further progression with both subjective and
objective measures, with education and encouragement regarding both compliance and attendance (4,5).
Detection of progressive visual field loss is an essential element of glaucoma patient care. There are many different methods that can help us determine whether a series of visual fields exhibits either progressive or stable defects. These range from simple 'eyeballing' of successive test results, through to use of ordinal grading schemes as employed in large multinational trials (e.g. AGIS, CIGTS, EMGTS) or to other complex statistically-based methods such as those that look for change 'events' (e.g. GCP, GPA) or those that look for trends (e.g. linear regression of global indices such as MD (e.g. STATPAC overview analysis) or for individual test points (e.g. Progressor). Each of these has advantages and disadvantages which generally manifest an important clinical relevance as a trade-off or compromise between relative sensitivity for change detection versus specificity in unchanging eyes.
In a previous issue of the EJ, we reviewed a paper by Chauhan et al. [link to Vol 3, issue2, Visual Field Review] that introduced the concept that performing a greater number of repeated visual field tests over the first two years of a patients' follow-up permits one to establish a good baseline and assist in identification of those who are exhibiting more rapid progression. In the "New Ideas in glaucoma" paper session at the last ARVO meeting, Crabb and Garway-Heath of London suggest a variation of this theory by examining the hypothesis that estimates of glaucomatous visual field progression improve if more tests are performed at both the beginning and end of a defined FU period, compared with the conventional approach of regular periodic tests. They called their approach, "Wait and See."
They found that wait and see achieved;
1. Closer estimates to the true rate of progression than conventional examination strategies (the spread of estimated rate of loss reduced by 25%);
2. Detection or a higher proportion of truly progressive test locations, correctly identifying approximately 95% of progressive locations compared with approximately 60% and approximately 80% detection for conventional 2/yr and 3/yr strategies respectively;
3. Lower false positive rates of <1% compared with 2.5 and 6% for 2/yr and 3/yr respectively.
Overall, these gains meant that when compared with the conventional strategy of using 3 tests/year, their wait and see approach reduced the number of visual field tests required to identify progression, saving 1 test over a 2 year period.
At face value, these data suggest that wait and see may be a promising alternative to regular testing, providing the results can be validated empirically. However, although this strategy appears both efficient and able to discriminate well between stable and progressive field series, leaving periods of 2 or more years between field tests means that there is potential for delay in detection of those individuals with rapid progression to be missed. As such, wait and see is likely to be best suited to specific scenarios, such as clinical trials of a defined length, rather than routine clinical follow-up.
Paul GD Spry, PhD, BSc, MCOptom DipGlauc
1. D.P. Crabb, D.F. Garway-Heath. Wait and See: Varying the Interval Between Visits to Get Better Estimates of the Rate of Visual Field Progression in Glaucoma. Invest Ophthalmol Vis Sci. 2009;50:E-Abstract 1669.
Optic Disc Hemorrhages: Glaucomaís pregame or halftime show?
Where do optic disc hemorrhages fit in the glaucomatous disease process?
There has been a sense for some time among glaucoma practitioners and researchers that optic disc hemorrhages (DH) are harbingers or precursors of frank glaucomatous damage and that they probably precede loss of neuroretinal rim tissue and nerve fiber layer by a short time and precede damage in corresponding areas of the visual field by a longer time. A series of presentations (1, 2) at this yearís ARVO meeting have cast DH in a new light. Taken together, they suggest that DH appear as an integral part of the glaucomatous pathophysiological process, occurring in concert with visual field change, rather than as a precursor.
In the first presentation (1), the authors evaluated the rate and location of visual field deterioration before and after detection of DH in patients with glaucoma. Pointwise linear regression (Progressor) was used to calculate global and localized rates of visual field change both before and after DH was detected. 168 DHs were observed in 120 patients. DH occurred most often in the inferotemporal (62%), temporal (14%), and superotemporal (11%) sectors. Mean (±standard deviation) global visual field deterioration rates before and after DH were -0.80 ± 1.2 and -1.07 ± 1.4 dB/yr respectively, however these rates were not significantly different (p = 0.30). The mean rates of deterioration for visual field locations corresponding to the DH were -1.17 ± 1.5 dB/yr before and -1.90 ± 2.4 dB/yr after DH (also not significantly different; p = 0.06). Rates of visual field worsening, both before and after DH, were significantly more rapid than in eyes without DH (p < 0.05). DH appeared in a disc sector corresponding to the visual field region that displayed the fastest rate of worsening very often (80% of the time). After the occurrence of DH, the corresponding visual field regions continued to undergo the fastest rates of visual field deterioration in almost all eyes (92%).
Eyes with nasal DHs generally showed slower rates of visual field deterioration and less agreement between DH location and the location of past or future visual field change. This is not surprising given the scant attention the temporal visual field, corresponding to the nasal optic nerve head (ONH), is given in the 24-2 test pattern.
The authors concluded that the visual field showed its most rapid worsening in regions that corresponded to where DHs would later appear and that these visual field regions continued to worsen most rapidly after DH, although perhaps at a slightly faster rate. They also suggested that local neuroretinal rim structural collapse, with corresponding localized visual field worsening, might predispose a particular region of the ONH to DH. Visual field worsening continues because of the ongoing structural damage Ė with corresponding loss of, or damage to, RGC axons. The authors closed by stating that "...DH should be viewed not only as a risk factor for future progression but also as evidence of past localized progression" within the structure of the ONH and the corresponding regions of the visual field. Clinically, this suggests that whenever a DH is detected, it is likely that visual field change has already occurred in the corresponding region. This is not the same as saying that the visual field will be outside normal limits in the corresponding location, as sensitivity may have been in the high end of normal prior to disease development. If previous visual fields exist for a patient in whom a DH is observed it would be worth performing a change analysis if possible rather than looking at fields 'side by side' as both visual fields may still be within normal limits yet change may have occurred since the initial test was performed. One question that this study does not answer is whether the DHs detected were ever the 'first' DH in each eyesomething that in reality is impossible to know. Could it be that there is something truly foreboding about the very first DH in an eye that is developing glaucoma and that the first DH almost always occur before the visual field has changed appreciably?
In a second presentation (2) from the same group, the authors examined whether recurrent DH is associated with a faster rate of functional decline when compared with eyes in which only a single DH was detected during follow up. It is important to recognize at the outset that clinicians probably only detect a small minority of all DHs that occur in the eyes of their patients, largely because many DHs occur and resolve between patient visits. However, it is safe to assume that patients in whom numerous DHs are detected are likely to be having more of them (assuming, perhaps incorrectly, that a greater number of DHs is not a reason for more frequent follow up). Disc photographs of glaucoma patients with ≥ 5 SITA-Standard 24-2 fields were examined for the presence of DH. Eyes with one DH were compared to eyes that had >1 DH during follow up. Pointwise linear regression analysis (Progressor) was used to calculate rates of visual field change after DH. Fifty-six patients were identified with DH, 40 with one and 16 with > 1. Patients with recurrent DH had significantly less visual field damage at baseline (MD = -2.75 ± 4.0 vs. -5.6 ± 5.0 dB, p < 0.01). However, the rate of visual field deterioration was not significantly different (-0.86 ± 0.8 vs. -0.67 ± 1.0 dB/Yr, p = 0.38). Interestingly, recurrent DH occurred within 2 clock hours of the initial DH in 88% of cases, and in the hemifield with less visual field damage in 75% of eyes with multiple DHs. In conclusion the authors suggest that recurrent DH is not necessarily associated with a faster rate of visual field decline. A potential clinical message that can be drawn from this study when combined with the previous one is that detection of a DH might cause one to become more vigilant or aggressive in a patient with suspected or actual glaucoma, but the appearance of DH at subsequent visits might not be reason to escalate further.
Shaban Demirel, BScOptom, PhD
1. De Moraes CV, Prata TS, Liebmann CA, Ritch R, Tello C, Liebmann JM. Localized visual field loss predicts the location of future disc hemorrhage and subsequent visual field progression. Invest Ophthalmol Vis Sci. 2009;50:E-Abstract 6197.
2. Beck HC, De Moraes CGV, Prata TS, Folgar FA, Ahrlich K, Teng CC, Ritch R, Tello C, Liebmann JM. Recurrent disc hemorrhage does not increase the rate of visual field progression. Invest Ophthalmol Vis Sci. 2009;50:E-Abstract 5835.
All ARVO abstracts from 2009 can be searched from the 'Meetings and abstracts' section of the ARVO website at www.ARVO.org
New Glaucoma Care Guideline Launched for England and Wales
from the National Institute of Health and Clinical Excellence.
If you would like us to answer a clinical question, please send it to
email@example.com 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.
In our last issue, we asked you what you thought about risk factors for glaucoma development.
The question of central corneal thickness (CCT) being an independent risk factor for glaucoma development
remains to be conclusively determined. Poll 1 shows that the complex nature of this question is reflected by
a little more than twice as many respondents believing a cornea thinner than the expected average is
associated with the development of glaucoma (58% vs 25%). Evidence for this, particularly outside
ocular hypertensives, is not strong but ongoing study of ocular biomechanics including cornea, lamina cribrosa
and peripapillary sclera may reveal a relationship in the future.
With regard to the most important risk factors, Poll 3 shows that each of the four choices were considered by
some to be the most important for the development of primary open angle glaucoma. Family history, specifically a
sibling with glaucoma, was rated the most important risk factor by 42% of respondents, while an additional 26% selected age.