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Role of IOP fluctuations debated as possible glaucoma risk factor
Studies find contradictory results regarding the significance of IOP fluctuation in glaucomatous damage.
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Studies have shown that IOP reduction slows the progression of glaucomatous optic nerve damage, but the role of IOP fluctuations in that progression remains unclear, according to clinicians.
Mean IOP has been considered one of the most important risk factors in determining glaucoma progression, but this is now being re-examined as physicians look at the influence of diurnal curves, Peter A. Netland, MD, PhD, said. Clinical research is under way to establish whether IOP fluctuations are an independent risk factor of glaucoma progression.
In a telephone interview with Ocular Surgery News, Dr. Netland said IOP fluctuations are measured in the diagnosis and treatment of glaucoma patients, but the exact role of those fluctuations has been contradicted in studies.
“IOP fluctuations are a factor that we do take into account when we’re evaluating patients,” he said.
A growing body of research
Studies such as the Collaborative Normal Tension Glaucoma Study, the Collaborative Initial Glaucoma Treatment Study and the Advanced Glaucoma Intervention Study have shown that lowering IOP assists in managing glaucoma progression.
Studies, including those by Bergea, Asrani and Oliver, have also cited IOP fluctuations as an important risk factor in managing glaucoma progression. However, other studies have found that IOP fluctuations do not play a significant role in determining glaucoma progression, according to Dr. Netland.
He cited a cohort study by Bengtsson and colleagues that found while elevated IOP was a strong factor for glaucoma progression, IOP fluctuation was not an independent risk factor.
The researchers examined results from the Early Manifest Glaucoma Trial that did not include post-progression IOP values. Excluding those results could have biased the study because larger fluctuations often occur after more intensive treatment, according to the study authors.
Dr. Netland said excluding post-progression data could bias studies that rule out IOP fluctuations as a factor because they do not consider the potential for bigger fluctuations in pressure resulting from therapy.
“Clinicians are trying to sort through this information and determine what they need to do clinically,” Dr. Netland said.
In a telephone interview with OSN, Adam C. Reynolds, MD, described the two types of IOP fluctuation — long term and short term, the latter of which is also referred to as intravisit fluctuation.
In the Advanced Glaucoma Intervention Study, Dr. Reynolds said patients who had intravisit fluctuation of less than 3 mm Hg performed better than patients who had fluctuations of more than 3 mm Hg.
He said that in patients followed over 10 years, fluctuation made a difference in progression for those with moderate to severe glaucoma.
However, in the Early Manifest Glaucoma Trial, intravisit fluctuation was found to not be an independent risk factor. Patients in that study had early glaucoma, Dr. Reynolds said, which could have affected the results.
Dr. Reynolds said some data on IOP fluctuations are being collected from studies that evaluated other endpoints, and there are a few prospective studies directly addressing the subject. He said further study and debate at meetings and in journals could assist in helping clinicians reach a consensus on the subject.
Diagnosis
According to Dr. Netland, clinicians have taken IOP fluctuations into account for some time in their diagnosis and treatment of glaucomatous patients. Extreme degrees of fluctuation, observed in intermittent angle closure and other conditions, have been clinically associated with glaucomatous optic nerve damage and even visual field loss.
What is new, he said, is the issue of whether diurnal variation range is strongly correlated with glaucomatous damage and how it can assist physicians in determining severity of the disease. Determining a safe degree of daily fluctuation for each patient and managing wide fluctuations are questions that researchers are now seeking to answer.
He said some clinicians take multiple measurements during office hours, after office hours and over extended periods of time to obtain the most accurate picture of IOP fluctuations. Those measurements help provide a more comprehensive assessment of the severity of the disease and can aid in choosing treatment, he said.
“I think many clinicians are looking more actively for these fluctuations and trying to characterize them in individual patients more accurately,” Dr. Netland said.
Dr. Reynolds said measuring diurnal curves is especially helpful in determining if patients are ocular hypertensive. Measuring those curves is also helpful to determine the best line of treatment in patients just diagnosed with glaucoma. If physicians take multiple IOP measurements before starting treatment, they can monitor the progression of the fluctuations after therapy is initiated, he said.
“Physicians are starting to look at what patients’ pressures do during the day untreated and then treating them, and then seeing if you’re really suppressing their diurnal curve and flattening it,” he said. “If they’re not, maybe the treatment needs to be changed or made more aggressive.”
Treatment
IOP fluctuations can play a role not only in diagnosis, but also in choosing the best glaucoma therapy, according to Dr. Netland. Some drugs, such as prostaglandin analogues and topical carbonic anhydrase inhibitors, are better at reducing the range of IOP fluctuation in a day, he said.
Studies have also shown that surgical treatment and laser trabeculoplasty can reduce the range of fluctuation.
According to Dr. Reynolds, the focus in glaucoma treatment has shifted to increasing outflow instead of decreasing inflow. Research appears to show that trabecular outflow regulates diurnal curves and prevents them from spiking, taking the focus in treatment away from simply lowering IOP, he said.
“It’s not just lowering the IOP. It’s [helping trabecular] outflow work better,” Dr. Reynolds said. “That’s the system that regulates pressure from minute to minute, hour to hour, and that appears to be the problem in glaucoma.”
A 24-hour monitoring device is needed to observe IOP fluctuations, according to Dr. Reynolds. Both Dr. Reynolds and Dr. Netland said such a device, which is currently not available, could assist in recording the most accurate IOP fluctuations.
Dr. Reynolds said a 24-hour monitoring device could separate abnormal, glaucomatous spikes in IOP from normal spikes that are caused by activities such as standing and lying down. He said the device would probably show that pressure in glaucoma patients fluctuates more often and remains higher than it does in those without glaucoma.
For more information:
- Peter A. Netland, MD, PhD, can be reached at Hamilton Eye Institute, 930 Madison Ave., Suite 100, Memphis, TN 38163; 901-448-6650; e-mail: mesmith@utmem.edu.
- Adam C. Reynolds, MD, can be reached at 1438 N. Ellington, Eagle, ID 83616; 208-373-1200; e-mail: adamreynolds@cableone.net.
References:
- Asrani S, Zeimer R, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9:134-142.
- Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126:498-505.
- Bengtsson B, Leske MC, Hyman L, Heijl A. Fluctuation of intraocular pressure and glaucoma progression in the Early Manifest Glaucoma Trial. Ophthalmology. 2007;114:205-209.
- Bergea B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology. 1999;106:997-1004.
- Lichter PR, Musch DC, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108:1943-1953.
- Oliver JE, Hattenhauer MG, et al. Blindness and glaucoma: A comparison of patients progressing to blindness from glaucoma with patients maintaining vision. Am J Ophthalmol. 2002;133:764-772.
- The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:429-440.
- Erin L. Boyle is an OSN Staff Writer who covers all aspects of ophthalmology.