Volume 13-2, 2011
Glaucoma Opinion: Exfoliation Syndrome
Exfolative glaucoma is not a 'form' or 'type' of glaucoma, but rather an ocular manifestation of a systemic disease. Other ocular manifestations include dry eye, cataract, lens (and intraocular lens) subluxation, angle closure, retinal vein occlusion and zonular dialysis, capsular rupture and vitreous loss at the time of cataract surgery. Marked rises in IOP after dilation mandate examination of the anterior chamber for pigment and measurement of IOP after pupillary dilation. Exfoliation material (XFM) has been found in heart, lung, liver, kidney, gall bladder and meninges of patients with ocular XFS.
Growing evidence implicates oxidative stress and inflammation in XFS pathogenesis.
Elimination XFS could not only prevent glaucoma, but also many more serious disorders related to elastic tissue within the body.
Day and Night Differences in Aqueous Humor Dynamics in Patient with Ocular Hypertension (OHT)
Neither timolol nor dorzolamide have significant IOP lowering effect at night, likely due to the inability to further suppress an already decreased aqueous humor flow.
M & T:
While it appears that this is common knowledge regarding timolol, it may not be so with dorzolamide; thus, the value of consistent reading of the literature.
Which IOP Parameters Predict Glaucoma Progression?
A recent editorial in the August, 2011 issue of Archives of Ophthalmology entitled 'Intraocular Pressure Variability and Glaucoma Risk: Complex and Controversial' points out some of the difficulty in assessing the importance of long-term IOP variability as an independent risk factor for glaucoma progression.
There is currently no good evidence suggesting that such long-term IOP variability associated risk is an appropriate surrogate for risk related to short-term IOP fluctuation over 24 hours.
There is no doubt that the much anticipated development of a continuous 24-hour IOP monitoring device will shed much light on which IOP parameters are most relevant to glaucomatous disease progression.
Progression After the First OD Hemorrhage
The medical literature indicates a close relationship between the discovery of a disc hemorrhage and future optic nerve functional or structural progression. Both primary vascular disease and mechanical processes (tissue collapse) have been hypothesized to be responsible for the development of hemorrhage.
Suh et al. demonstrate that in individuals with an observed unilateral disc hemorrhage, the eye with the disc hemorrhage develops localized structural damage as detected by optical coherence tomography much more frequently than the fellow eye. This damage is extremely focal (as is the disc hemorrhage) with the damage being better detected when analyzing smaller (clock hour) segments of the peripapillary OCT image than larger (quadrant) regions. Almost all (90%) of the progression occurred without one clock hour of the optic disc hemorrhage. Careful examination of the optic disc for the presence of disc hemorrhage is critical for the diagnosis, management, and progression of glaucoma.
Expert versus Non-Experts in Assessing Changes in OD Photographs
Breusegem et al. compared the performance of 37 general ophthalmologists for detection of glaucomatous optic disc progression to a reference standard consisting of the agreement of a panel of three experienced glaucoma specialists.
The agreement among general ophthalmologists was poor overall and increased only slightly after a 30-minute training session. The percentage agreement between the non-experts and the glaucoma specialists improved from 68.5% before training to 71.4% after the training session.
Overall, the investigators confirmed that experience and expertise matters. In addition, although a short training 30-minute session somewhat improved the performance of the general ophthalmologists, the improvement was of questionable clinical significance.
A review of optic disc photographs for progression by general ophthalmologists is suboptimal at best. Additional training would likely be helpful and to be of benefit, the training needs to span over a longer period of time with possibly continuous feedback from experienced clinicians.
Agreement of Visual Field Interpretation
In general, approximately six visual fields obtained over a period of two to three years is necessary to achieve good performance (sensitivity, specificity, positive predictive and negative predictive value, etc.). Test-retest variability and other factors make it difficult to distinguish pathology related visual field changes from other confounding influences on repeated visual field examinations.
Several investigators have also demonstrated that the most commonly used procedures only agree with each other about 50-65% of the time and the reasons for the lack of agreement among these approaches remains an open question at the present time.
Glaucoma in Asian Americans
Prevalence and incidence rates of primary open-angle, normal-tension, and angle-closure glaucoma were significantly higher among the Asian Americans than among non-Hispanic whites. Normal-tension and angle-closure glaucoma rates were highest in Asian Americans as compared to non-Hispanic whites, Hispanics, and African Americans. Normal-tension glaucoma was particularly high in Japanese Americans, and angle-closure glaucoma was most prominent in those of Chinese and Vietnamese ancestry. Results are in accordance with prior studies in the individual racial groups and are clinically relevant given the rapid rise of Asian American populations in the U.S.
CSF Pressure in Ocular Hypertension
Recent comprehensive chart reviews of CSF pressures in neurological patients receiving lumbar punctures at Mayo Clinic revealed a correlation between primary open-angle glaucoma and low CSF pressure. Results from the current study confirm the possibility that higher CSF pressure provides a protective role against glaucoma, as opposed to lower CSF pressures being associated with glaucoma in the first study. The overall evidence from both studies supports the concept that a high pressure difference across the lamina cribosa, termed the translaminar pressure difference (IOP minus CSF pressure), represents a major risk factor for glaucoma more accurately than the traditional thinking of an elevated IOP. The current study and related reports have energized interests on this challenging topic in glaucoma research. A leap forward may be to develop a reliable non-invasive method for measuring CSF pressure in different body positions. The task is daunting, but potential reward is also high.
IOP Fluctuations In Wind Instrument Players
Schmidtmann et al. investigated the effect of IOP and blood pressure (BP) in professional musicians during playing brass (n=27) or woodwind (n=15) instruments. The temporary and potential dramatic elevations and fluctuations of IOP place wind instrument players at increased risk of developing open-angle glaucoma. Some of these individuals may manifest glaucoma progression with presumed 'controlled' IOP measured in the office visit. Dr. Schmidtmann says that since 1994, he has queried all of his glaucoma patients if they play brass or woodwind instruments and he enters a positive response in the patient chart.
Repeatability of Diurnal IOP Patterns
What can we learn from this article about our clinical assumptions on IOP? Simply, diurnal IOP patterns are not repeatable in the short term in treated patients with glaucoma (of note, the authors had similar findings in healthy subjects of similar age). The current study demonstrates that diurnal IOP performed on one day inadequately reflects diurnal IOP variability in the short term. For the clinician this means assessing IOP reduction after starting a glaucoma medication by checking IOP at the same time of day before and after is not supported by scientific evidence. Given the lack of a reproducible IOP diurnal pattern, confirming IOP change by multiple measurements is more accurate and less likely to be affected by diurnal variability.
M & T:
Here is another reason (as mentioned above) to do several IOP assessments in order to really understand the IOP behavior of a patient.
Aqueous Humor Dynamics Change From Day to Night
Circadian variations are particularly interesting since nocturnal IOP is minimally changed at night when measured in the same position as during the day. This occurs despite a decrease in aqueous humor flow of approximately 50% that occurs at night, originally demonstrated by Brubaker and colleagues and consistently replicated by other researchers. If all other factors remained the same, we would expect a significant drop in IOP at night, and not the pattern that is observed. A decrease in tomographic outflow facility and uveoscleral outflow appear to compensate for the reduction in aqueous humor production at night.
M & T:
This is why, when prescribing a topical beta-blocker, we direct that it is to be used shortly upon awakening (when IOP tends to be at its highest). Beta-blockers are pretty much "therapeutic-neutral" at night when aqueous production is physiologically reduced 50%, which gives merit to the rational use of long half-life beta-blockers such as timolol and levobunolol only once daily, shortly after awakening.
Perkins applanation versus Icare rebound tonometry
The measurements of the Icare tonometer tended to be higher compared to the measurements taken by the Perkins applanation tonometer (2.6 4.0mmHg).
As in the study the real IOP was not known it is impossible to judge which instrument measures the IOP more accurately.
Icare Rebound Tonometer in Infants
The Icare rebound tonometer does not require the use of topical anesthetic to obtain measurements of IOP, and has proven reproducible and similar to the Goldmann applanation in adults and in cooperative children.
Icare tonometry was not possible in 6/49 infants; one additional infant had readings with more than 3mmHg spread; hence Icare tonometry was possible in 39/46 (85%) subjects.
This study confirms that Icare tonometry is well tolerated in most infants, and provides normative IOP values for the unanesthetized healthy infant's eye.
Diagnostic Accuracies of Three OCT Devices
Recent advances in spectral domain optical coherence tomography (SDOCT) imaging technologies have resulted in a new generation of instruments with greater resolution, shorter acquisition time, and three-dimensional imaging capabilities. However, these technical advancements may not necessarily translate into better discriminating ability for glaucoma diagnosis.
The study found that average, superior, and inferior RNFL thickness values had the largest AUC (0.85-0.88), and that the three SD-OCT technologies [evaluated] had comparable diagnostic capabilities for detection of glaucoma patients with visual field loss, despite their differences in axial resolution and acquisition time. It should be noted that the ability to discriminate glaucomatous eyes is directly proportional to the severity of the disease across the entire spectrum of this condition.
M & T:
So, purchase the least expensive of these devices and have nerve fiber thickness measurements available to help with the glaucoma assessment. We stress here that this RNFL assessment is only a component of the comprehensive glaucoma workup. Do not micromanage patient care based on any single diagnostic test; rather, look at the comprehensive, big picture!
Peripapillary Atrophy (PPA) and Spectral Domain (SD)-OCT
The presence and area of PPA (particularly beta-zone PPA) is associated not only with glaucoma onset but also with rapid visual field progression in eyes with established disease. Therefore, PPA detection and measurement is important for risk assessment in clinical practice. The present study is a first step towards developing objective methods to identify and measure PPA using imaging devices. Additionally, the authors described micro-structural characteristics of PPA that closely resemble the ones described in age-related macular degeneration (AMD). This finding supports the hypothesis that PPA could be a surrogate sign of accelerated aging of the optic nerve complex.
M & T:
While a critical analysis of beta-zone microanatomy is not a standard-of-care at this time, we would encourage the clinician to be cognizant of its presence, and take general note of it. The clinical implications of PPA are just now becoming known. Stay tuned.
Agreement RNFL in Three SD-OCT instruments
The authors conclude that measurements from these instruments should not be used interchangeably, and histological studies are needed to determine which one is more accurate. What does this mean for the practicing clinician? Direct comparisons should not be made between results obtained with different instruments, and during follow-up, a patient may benefit from repeated exams using the same SD-OCT.
Iris Thickness in PACG
These findings suggest iris thickness may play an important role in the etiology of primary angle-closure glaucoma (PACG). This supports the hypothesis that a thick iris increases pressure differential between the posterior chamber and the anterior chamber, causing the peripheral iris to bow forwards and block the trabecular meshwork.
However, cross-sectional study of known anatomic factors in angle-closure eyes cannot fully explain the etiology of PACG. To the authors' point, the risk factors for PACG are family history, female gender, increasing age, ethnicity (especially in Chinese, Mongolians, Indian and Eskimos/Intuits), shallow anterior chamber and shorter axial length.
The iris volume increases after pupil dilation in narrow-angle eyes predisposed to acute angle closure.
M & T:
Ten years ago, corneal thickness was found to hold high clinical relevance. We wonder if/when the day will come that we will be routinely assessing iris thickness.