INTERNATIONAL GLAUCOMA REVIEW
Volume 14-1 2012
Notes from the European Glaucoma Society
Preservative-free medical treatments are advocated especially in patients with a long life expectancy, when two or more drugs are required, and in stages of damage close to surgical intervention.
Primary angle-closure treatment with Laser Peripheral Iridoplasty (LPI) in Asia shows that in 20-30% of subjects, significant appositional closure still remains after the procedure, and only 10% of those with glaucomatous optic neuropathy are effectively controlled.
A more realistic approach to the patient's self-experience of visual field defects is related to perception of blur or missing areas rather than classical descriptions of dark and opaque scotomas.
Dynamic response of sclera may be key in glaucoma pathogenesis. Link of central corneal thickness to glaucoma may act through effect of collagen 8 variants on scleral responses to IOP. In the future, potential therapies may aim at scleral state and responsiveness.
Prevention and Screening
A nationwide screening program would reduce the incidence of glaucoma from 50% to 27% and the prevalence of blindness from glaucoma from 4.6% to 4.4%. A major problem in designing a care delivery model for any chronic occult disease is a low adherence to recommended eye examinations. A rigorously designed health education program does not significantly alter adherence with eye examinations.
M & T: Honest, eye-to-eye, ongoing discussions with patients is what we do, and we think this is about the best one can hope for.
Risk Factors: Body Mass Index and Cerebrospinal Pressure
Body mass index has a linear relationship with cerebrospinal fluid pressure.
Berhdal et al. performed a retrospective study to assess the relation between body mass index (BMI) and cerebrospinal fluid opening pressure (CSFP) on lumbar puncture (LP). The recent findings of an inverse relation between BMI and primary open-angle glaucoma (POAG), particularly among women, motivated this study. They are to be congratulated for exploring a novel potential link between BMI and POAG that might involve CSFP, as the optic nerve is a 50mm white matter tract bathed in cerebrospinal fluid. The authors found a positive linear correlation between BMI and CSFP.
Circadian IOP Patterns and Visual Field Damage in Normal Tension Glaucoma (NTG)
In this well-designed prospective study, Lee and colleagues employed the best possible conditions in collecting 24-hour data of IOP under habitual body positions from newly diagnosed and untreated glaucoma patients whose office sitting IOP readings were in the normal range. The 24-hour variations of IOP in approximately one third of the study patients were rather small and regarded to have no 24-hour IOP peak. For the remaining study patients, the 24-hour IOP peaks appeared more during the nocturnal period, about three times, than during the diurnal period. The authors also showed that the nocturnal IOP elevations were related to the change of habitual body position for sleep. If one considers only the sitting IOP for 24 hours, the nocturnal IOP elevation cannot be demonstrated. Individual IOP elevations during the nocturnal period can be substantial in some patients and make their office IOP readings misleading for glaucoma diagnosis and treatments. There is little doubt that real life IOP peaks in most glaucoma patients, including so-called normal-tension glaucoma patients [and that this peak] would occur outside regular office hours.
Trends in Ancillary Diagnosis Tests
While testing with objective imaging devices increased dramatically in the past decade, visual field testing declined meaningfully whereas fundus photography remained fairly steady. Despite small differences between patients assisted by ophthalmologists versus optometrists, the type of eyecare provider followed the same trend. Nonetheless, optometrists were more likely to change from fundus photography and visual field testing to objective imaging technologies than ophthalmologists during the same period.
The most surprising observation, however, was that more than 25% of patients with newly diagnosed suspected or established glaucoma have not undergone visual field testing within two years of diagnosis. Although new imaging technologies have had remarkable improvements in resolution and patients often prefer objective to behavioral testing, visual fields still have a key role in glaucoma diagnosis and monitoring. Moreover, automated achromatic perimetry correlates significantly with vision-related quality of life and has been employed to determine progression endpoints in the main clinical trials in glaucoma, which heightens that much of the current knowledge on risk factors and effectiveness of therapy in glaucoma is based on data obtained from functional tests. Another important point is that the technology behind visual field testing has remained relatively stable over the past decades and given its wide availability, has provided longer and more consistent information regarding the disease process than imaging technologies which are rapidly evolving and often provide results that are not interchangeable with older techniques. All patients with glaucoma or suspected glaucoma should be diagnosed and followed using both structural and functional tests, and these new objective technologies have considerable advantage over fundus photography.
M & T: Agreed; let's all do a better job.
Diagnostic Accuracy of the ISNT (inferior>superior>nasal>temporal) Rule
In many normal eyes, the rim is wider inferior than superiorly, and the difference in the physiological rim width between the superior disc region and the nasal disc region is marginal. The most important part of the ISNT rule is that the smallest part of the rim should be in the temporal disc region (i.e., the 'T' in the ISNT rule).
M & T: ISNT isn't perfect, but it helps us be more attentive to optic nerve head anatomy.
Optical Coherence Tomography: The Role of the Lamina Cribosa in Glaucomatous Optic Neuropathy
The lamina cribosa represents an important site for axonal injury in glaucoma. Glaucomatous excavation of the optic nerve head is related to posterior bowing and collapse of the lamina cribosa which is believed to impede axoplasmic flow and contribute to loss of neuronal functional and subsequent axonal death. Recent advancements in OCT technology using enhanced depth imaging (EDI) has enabled direct in-vivo visualization of the lamina and demonstrated various anatomic changes including laminar thinning, posterior migration into the sclera, loss of laminar beams, and focal disinsertion from the scleral rim. These findings not only provide critical insight regarding glaucoma pathogenesis, but also represent and opportunity for new therapeutic targets.
The anatomy of the lamina cribosa is complex and the mechanism by which neuronal damage may occur at the level of the lamina is multifunctional. Deformation of the lamina may produce direct compression of axonal borders within the laminar pores, changes in axoplasmic flow with neurotriptin deficiency, and alterations in axonal perfusion by compression of blood vessels. In addition, the lamina represents the interface between the intraocular pressure (IOP) and intracranial pressure (ICP). Dynamic changes in IOP, ICP, and systemic blood pressure may alter the configuration of the lamina and optic nerve head anatomy and need to be carefully considered when interpreting EDI scans.
Novel therapeutic targets may one day be directed at the lamina to provide increased structural support to axons passing through the lamina pores.
In-vivo Evaluation of Focal Lamina Cribosa Defects in Glaucoma
Focal lamina cribosa (LC) defects were found in 34 of 38 eyes with glaucoma (89%), while such change was not detected in any of the healthy eyes. The location of the focal LC defects correlated well with the location of structural and functional glaucomatous damage. They mostly occurred in the inferior or inferotemporal far periphery of the LC and presented clinically as neuroretinal rim thinning and notching. These findings suggest that mechanisms of LC deformation in glaucoma include focal loss of laminar beams in addition to the general changes in its thickness or position. These findings underscore the importance of LC evaluation in glaucoma in addition to the conventional structural assessment of the optic nerve head.
Glaucoma Progression: Combination of Risk Factors and SAP Data
Visual fields are the most common method used to monitor individuals with glaucoma for progression. Fields are performed over time with the clinician deciding if change has occurred, and if so, what the rate of change is. Analyzing progressing fields for the rate of change (trend analysis) is relatively new, with a regression analysis program commonly used. Measurement variability or noise must be considered as the clinician decides whether the results are real and glaucoma has gotten worse. This is an important decision as it is usually associated with an advancement in therapy, and one the clinician struggles with as he/she decides whether the results are credible. Often additional fields are performed for confirmation, delaying the decision making. Doctors will also incorporate other information as they decide whether to believe the results such as which eye has the higher intraocular pressure (IOP), how high the IOP is, which optic nerve has greater damage, has the optic nerve(s) changed recently, etc.
When a limited number of fields are available, one can still address whether progression has occurred by relying on other clinical measurements.
M & T: Always analyze ALL clinically relevant parameters when making clinical decisions.
Combination of Structural and Functional Measurements to Improve Estimates of Rates of Glaucomatous Progression
Almost ten years ago, the first consensus meeting of the World Glaucoma Association on Glaucoma Diagnosis recommended that patients with or suspected glaucoma should be monitored with a combination of structural and functional tests. The detection of optic disc and visual field changes simultaneously increases the likelihood that true glaucomatous progression has occurred, as opposed to measurement variability. However, these simultaneous structural and functional changes are not always seen and cases of disagreement pose as a major challenge for clinicians when tailoring glaucoma therapy.
Topical Medical Management of Pediatric Glaucoma
Prostaglandin analogues were the most commonly prescribed medication as monotherapy (39%) followed by nonselective beta blockers (21%). When beta blockers were used as monotherapy, they were most commonly prescribed in the lowest concentrations possible (0.1 and 0.25%). As for effectiveness, the median percentage IOP reduction as monotherapy was the same for the prostaglandins and beta blockers (17.2%) with similar responder rates for these groups consistent with the phase 3 latanoprost vs. timolol 12-week, randomized, double-masked, multicenter study. Almost 20% with monotherapy had systemic side effects; the prostaglandin group with the least and brimonidine tartrate 0.2% with the most. Brimonidine tartrate should not be used in children less than six years of age.
Adherence to Therapy: The Role of Intensive Patient Counseling
Gray and colleagues randomized 127 newly diagnosed ocular hypertensive or open-angle glaucoma patients who were prescribed topical drop therapy to receive usual care or to have a face-to-face assessment focusing on issues that might affect adherence. The initial meeting lasted a bit more than an hour and about five additional face-to-face or phone meetings were held, but these were shorter. Some patients also received additional contact during the year. A previous publication for these authors had documented that most eye doctors provide limited information to their patients about glaucoma and that patients have a relatively poor understanding of their condition.
The intervention was notably effective. In an intention-to-treat analysis, 70% of the intervention arm subjects were fully adherent compared to 43% in the usual care arm. Of note, the intervention arm included ten subjects (out of 64) who did not receive the intervention, nine of whom had poor adherence. As documented previously in the other research on adherence, eye pressure was similar in the two arms, which likely indicates better drop taking at the time of the visits.
Providing intensive counseling can improve patient adherence to therapy and should stimulate interest in identifying how best to integrate this kind of care into routine practice.
M & T: Would we not all agree that optometrists spend considerable more fact-to-face time (and talk more with our patients) than our surgical counterparts? This is yet another sound reason why O.D.s should be the primary caretakers of patients with glaucoma. Optometry, from a purely humanitarian perspective, needs to rise to the occasion!