Cover StoryFrom OSN APAO

OCT an additional tool for assessing glaucoma patients

Use of ophthalmic imaging for detecting glaucoma is rising as use of visual field testing is declining. But it is too soon to fully make the switch in technology, experts say, because optical coherence tomography should be viewed as another tool in the kit instead of a replacement when it comes to assessing glaucomatous progression.

“OCT is now used routinely as part of glaucoma assessment because it offers several advantages compared to other modalities of glaucoma assessment, namely examination of the optic nerve and visual field testing.” Albert P. Lin, MD, assistant professor of ophthalmology at Baylor College of Medicine, U.S.A., said. “Both optic nerve examination and OCT are more sensitive than visual field testing in the diagnosis of glaucoma. While optic nerve examination with experienced clinicians may be more sensitive in the diagnosis of glaucoma, OCT does produce a quantifiable measurement of nerve fiber layer thickness to allow better assessment of progression in early stages of the disease.”

“For glaucoma detection, OCT is definitely ready for prime time,” OSN U.S. Edition Glaucoma Board Member Joel S. Schuman, MD, FACS, one of the originators of the technology, said. “It is something that we can use to identify the presence or absence of disease. It is probably the most useful information of any single parameter as to whether or not glaucoma is present.”

Albert P. Lin, MD, believes OCT is useful in assessing glaucoma progression because of its ability to accurately measure retinal nerve fiber layer thickness.
Albert P. Lin, MD, believes OCT is useful in assessing glaucoma progression because of its ability to accurately measure retinal nerve fiber layer thickness.

Image: Lin A

But, he said, it is not yet proven to detect progression because it lacks normative databases and longitudinal studies that would confirm correspondence between what is seen on OCT and what is detected by visual fields, the current gold standard of care.

“OCT is extremely helpful in detecting the presence or absence of glaucoma,” Schuman said. “It can be very helpful in detecting progression of glaucoma. But for progression, at this time we need other supporting evidence for progression to say that real change has occurred.”

The conventional approach for measuring retinal nerve fiber layer (RNFL) thickness is based on measurements derived from a circle scan with a diameter of approximately 3.46 mm, according to Christopher K.S. Leung, MD, MB ChB, professor of the Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, and OSN APAO Edition Board Member.

Christopher K.S. Leung, MD, MB ChB
Christopher K.S. Leung

“With a higher scan speed offered by the spectral-domain OCT, it is now feasible to measure pixel by pixel RNFL thicknesses in a map around the optic nerve head. RNFL defects typical of glaucomatous damage can be visualized and quantified in the RNFL thickness map.” Leung said. “While detecting diffuse loss of the RNFL can be difficult with red-free RNFL photography, the RNFL thickness map generated from the spectral-domain OCT permits clear visualization of both localized and diffuse RNFL defects in glaucoma.”

Teresa C. Chen, MD, who is an associate professor of ophthalmology at Harvard Medical School and practices at the Massachusetts Eye and Ear Infirmary Glaucoma Service, U.S.A., said that the relative lack of longitudinal 3-D imaging data adds to the difficulty in deciding how to interpret spectral-domain OCT findings. As a part of the Spectral Domain Optical Coherence Tomography in Glaucoma Study, her clinic is gathering data on more than 1,000 patients and seeking 5 years of follow-up on patients to address that point.

“In the next few years, we’ll have better data that can tell us how to use these newer 3-D imaging tests for the care of glaucoma patients,” Chen said. “There will be better guidelines in the future as we get better data from studies in glaucoma patients. [OCT is] a good supplemental tool that adds to the clinical exam and other test results.”

Growing use of OCT

Despite Schuman’s caveat, it seems that eye care clinicians are increasingly adopting imaging assessments over visual field exams.

“It’s widely deployed to have an imaging technology. It may be OCT. It may be the confocal scanning laser ophthalmoscope, like the Heidelberg Retina Tomograph, or scanning laser polarimetry,” Schuman said. “But OCT is very broadly used and is continuing to be deployed at a rapid rate globally.”

From 2001 to 2009, ophthalmic imaging increased dramatically as visual field testing declined considerably, Stein and colleagues noted in Ophthalmology. But the authors expressed concerns that imaging in lieu of visual field testing may hurt patients because imaging has not yet proven to be better than visual fields at detecting open-angle glaucoma or disease progression for all patients.

To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma and glaucoma suspects, the researchers conducted a retrospective, longitudinal cohort analysis of nearly 170,00 individuals with open-angle glaucoma and nearly 400,000 individuals with suspected glaucoma enrolled in a U.S. managed care network between 2001 and 2009.

Claims data showed the odds of patients with open-angle glaucoma undergoing visual field testing decreased by 36% from 2001 to 2005, by 12% from 2005 to 2009, and by 44% for the entire time span of 2001 to 2009. At the same time, the odds of having other ophthalmic imaging increased by 100% from 2001 to 2005, by 24% from 2005 to 2009, and by 147% for the entire time span of 2001 to 2009.

Among patients cared for exclusively by optometrists, visual field testing decreased from 66% in 2001 to 44% in 2009, compared with patients seen exclusively by ophthalmologists, for whom visual field testing decreased from 65% in 2001 to 51% in 2009. Other ophthalmic imaging increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists.

A tipping point occurred in 2008, the researchers noted, when patients with open-angle glaucoma receiving care exclusively by optometrists were more likely to undergo imaging than visual field testing.

“OCT is not only useful to evaluate structural changes of the RNFL and optic nerve head in glaucoma, it also plays an important role to detect angle closure and measure anterior segment parameters such as the anterior chamber angle width and anterior chamber depth,” Leung said.

Uncertainty of changes

David Huang, MD, PhD, was one of the original inventors of OCT as a graduate student at Massachusetts Institute of Technology, U.S.A. He built an early prototype and, with Schuman, did the first retinal imaging in the laboratory.

David Huang, MD, PhD
David Huang

“OCT tends to be more sensitive in early glaucoma and visual fields more so in later stages of glaucoma,” Huang said. “But both are valuable. If you just have a few time points over a couple years, often you can catch change on one and on the other you don’t. But the longer the patient progresses, the more the two converge.”

Schuman noted that there is less certainty about OCT as a tool for definitively assessing glaucoma progression. Abnormalities seen with OCT “occur out of step with changes occurring on the visual field. So we’ll often see a change in the OCT prior to the occurrence of a visual field defect or a visual field change. But sometimes it’s the other way around,” he said.

Lin said that visual field testing is a better tool to assess glaucoma progression in moderate to advanced disease.

“OCT is effective at assessing early glaucoma progression, but this efficacy diminishes with moderate to advanced disease. Nerve fiber layer thickness decreases significantly in early disease and can be effectively followed with OCT. In moderate to advanced disease, the remaining nerve fiber layer thickness may not change significantly even with significant glaucoma progression,” Lin said.

Schuman’s hypothesis and current research interests consider changes in the nerve fiber layer that occur sometime before the change in the visual field — perhaps a year or two, perhaps longer.

“When you see those changes occurring asynchronously, what we’re really seeing is a prior effect of glaucoma damage that already is in these sectors affected, and changes showing up on the OCT will be future change on the visual field,” he hypothesized. “That is controversial. And it’s controversial because we don’t know for sure that one necessarily reflects the other.”

Larger studies over longer periods of time will determine whether this is true, Schuman said.

Pearls and pitfalls

With any testing modality, sensitivity and specificity need to be taken into consideration.

Albert P. Lin, MD
Albert P. Lin

“It is important to realize even with an advanced diagnostic instrument, clinicians need to rely on their clinical acumen to interpret and apply the testing results appropriately,” Lin said.

In addition, it is imperative for physicians to understand that OCT should not be used as a screening tool in healthy patients who do not have risk factors or clinical findings indicating glaucoma.

“In the case of OCT, there is significant overlap between nerve fiber layer thickness in normal eyes and glaucoma eyes,” Lin said. “Based on normative database, a cutoff is established by the manufacturers and research studies. Clinical experience shows the sensitivity and specificity of OCT to be about 80% and 90%, respectively. With the aforementioned statistics, in every 200 patients, there will be one false negative and 20 false positives, based on disease prevalence of 2%.”

Lin noted another pitfall in which clinicians only look at the pie chart on the OCT printout to assess whether the nerve fiber layer is normal or abnormal.

“It is important for clinicians to examine the entire printout, including the signal strength, the centration of the measurement ring around the optic nerve, and the quality of the topography scan and contour. If these parameters are not optimal, the resulting pie chart will not be useful and should not be applied clinically,” Lin said.

When Schuman is deciding whether a patient has glaucoma, he considers the region of the defect. A pattern superiorly or inferior temporally suggests glaucoma, he said. If the ganglion cell complex is abnormal in a way that matches the nerve fiber layer, then that is an internal correspondence suggesting that the abnormality is real even if there is no visual field defect. This is called pre-perimetric glaucoma.

Joel S. Schuman, MD, FACS
Joel S. Schuman

“The clinician needs to be the most careful in diagnosing those patients,” Schuman said. “If they have other abnormalities that make you think that the patient might have glaucoma — that they have a history, that they have significant risk factors or high intraocular pressure — that’s going to sway you toward making the diagnosis in the presence of an OCT abnormality without a visual field abnormality.”

Clinicians need to make sure that the quality of the scan and analysis is adequate before accepting the OCT results.

“A poor-quality scan can give you bad or incorrect information,” Schuman said. “You’re dealing with a garbage-in, garbage-out problem.”

Huang noted that at the very low end of signal strength, the nerve fiber layer begins to look thinner. Depending upon the system, images with a loss of signal of 35 to 45 out of 100 are not as reliable.

“It’s common sense that you have to look at the images for the quality of the image processing that outlines the inner and outer borders of the nerve fiber layer,” Huang said. “You still want to look at the image to make sure the image is not cropped. Sometimes the top of the nerve fiber layer might be cut off because the position of the OCT system was a little cut off when the image was taken.”

The correspondence that clinicians think confirms a diagnosis might not be enough. If a clinician sees corresponding changes between the visual field exam and the OCT, then it is likely that the change is real, Schuman said.

“But it may be that the person who has corresponding change occurring on both OCT and visual field will actually go on to have stronger visual field loss in the corresponding area because the OCT may actually be predicting visual field damage as opposed to corresponding damage that is occurring today,” Schuman said.

Huang noted that high IOP can affect nerve fiber layer measurements.

“It’s an elastic response,” he said. “If you have a balloon and you blow it up harder, the balloon is going to be a little bit bigger and the wall is going to be thinner by a small amount. When the pressure is higher, the layers look slightly thinner because the balloon is slightly larger.”

If longitudinally the pressure is within a couple of mm Hg, it is not a significant effect. But, Huang added, “If someone’s nerve fiber layer looks thinner than a year ago but their pressure is 4 mm Hg higher, you may want to take that into account.”

Next-generation devices

Current OCT systems run between 17 KHz and 40 KHz, faster than previous generations but not as fast as the next generation of machines, which could run between 70 KHz and 100 KHz, Huang said. The faster speeds offer the potential of new measurements.

“We are now able to look at the nerve fiber layer as a map over a wider area,” Huang said. “As the analysis of that improves, there will be an improvement in diagnostic accuracy and the ability to track small changes over the long run.”

Faster processors and 3-D scans over a wider area will improve the ability to detect focal changes, Huang said. Measuring changes over a small area is more difficult, but newer technology will offer better sampling and better position tracking.

This year, Huang will finish the Advancing Imaging for Glaucoma Study, which is sponsored by the National Institutes of Health. He hopes to publish results for mapping the ganglion cell complex, which may help catch more cases of glaucoma earlier.

In addition, Huang has been taking advantage of faster scanning speeds to look at optic nerve head blood flow using OCT angiography and to look at total retinal blood flow with Doppler OCT. He has found that these perfusion measurements correlate better with visual field function than nerve fiber layer thickness and other structural measurements. Thus, the new functional OCT technology has the potential to further improve glaucoma diagnosis and tracking. – by Ryan DuBosar and Christi Fox

References:

Boling W, et al. J Glaucoma. 2012;doi:10.1097/IJG.0b013e318239c32b.

Chauhan BC, et al. Ophthalmology. 2009;doi:10.1016/j.ophtha.2009.04.031.

Kotowski J, et al. Ophthalmic Surg Lasers and Imaging. 2011;doi:10.3928/15428877-20110627-01.

Mwanza J, et al. Invest Ophthalmol Vis Sci. 2010;doi:10.1167/iovs.10-5222.

Pierro L, et al. Invest Ophthalmol Vis Sci. 2012;doi:10.1167/iovs.11-8644.

Stein JD, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2011.09.045.

Stein J, et al. Changes in the diagnostic evaluation of patients with open-angle glaucoma from 2001-2009. Presented at American Glaucoma Society annual meeting; March 2011.

Wu H, et al. J Glaucoma. 2011;doi:10.1097/IJG.0b013e3181f3eb64.

For more information:

Teresa C. Chen, MD, can be reached at +1-617-573-3674; fax: +1-617-573-3707; email: teresa_chen@meei.harvard.edu.

David Huang, MD, PhD, can be reached at Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239, U.S.A.; email: davidhuang@alum.mit.edu.

Christopher K. S. Leung, MD, MB ChB, can be reached at the Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong; 147 Argyle St., Kowloon, Hong Kong; email: cksleung.cuhk@gmail.com.

Albert P. Lin, MD, can be reached at 2002 Holcombe Blvd., 112C, Houston, TX 77030, U.S.A.; +1-713-791-1414; email: alin@bcm.edu.

Joel S. Schuman, MD, FACS, can be reached at Department of Ophthalmology, UPMC Eye Center, 203 Lothrop St., Suite 816, Pittsburgh, PA 15213, U.S.A.; +1-412-647-2205; email: schumanjs@upmc.edu.

Disclosure: Chen has no personal relevant financial disclosures. Huang receives OCT-related patent royalties from Optovue and Carl Zeiss Meditec, as well as grant support, stock options and speaker honorarium from Optovue. Leung receives research support/speaker honorarium from Carl Zeiss Meditec, Optovue, Tomey, Heidelberg Engineering and Topcon. Lin has no relevant financial disclosures. Schuman receives royalties for intellectual property licensed by MIT and MEEI to Carl Zeiss Meditec.

 

POINTCOUNTER 

What are the public health implications for OCT screening for glaucoma?

POINT

OCT needs to meet screening criteria

OCT has to meet certain criteria to have a role in widespread glaucoma screening.

Anne L. Coleman

There are well-known criteria for mass screening. The disease should be common and serious, as we know glaucoma is. The screening test should be highly accurate. The natural history needs to be understood, there needs to be acceptable resources for treatment, and the treatment should favorably influence outcomes.

One of the problems that we have had with glaucoma is that it is not very prevalent in the general population in the U.S.; it is around 2%.

Sensitivity and specificity are very important for looking at the validity of the test, and it is the positive predictive value — the probability that a label of “positive” is actually a true case — that determines whether the screening program will be cost effective.

The Agency for Healthcare Research and Quality Screening for Glaucoma: Comparative Effectiveness report issued in 2012 said that there really is no one test or group of tests that would be suitable for screening for glaucoma, including OCT.

Considerations for screening with any device include not only how good the device is, but also whether the device is transportable and durable. You do not want it falling apart when you put it in a van and take it out for mass screenings in the general population.

In addition, you want it to be usable with a standard wall outlet. You want it to be rapid. You want to have few poor quality scans. You want it to be relatively inexpensive so that community groups can afford it and use it. You want those lay people to be able to understand what the results mean and then refer those patients who fail borderline tests to appropriate clinical offices for evaluation.

 

Reference:

http://effectivehealthcare.ahrq.gov/ehc/products/182/1025/CER59_GlaucomaScreening_executivesummary.pdf.

Anne L. Coleman, MD, PhD, is the Fran and Ray Stark Professor of Ophthalmology and Epidemiology at the University of California-Los Angeles Jules Stein Eye Institute, U.S.A. Disclosure: Coleman has no relevant financial disclosures.

COUNTER

Questions arise as imaging devices are integrated

As ocular imaging devices have been integrated into clinical practices, public health considerations have emerged: Do these devices have adequate sensitivity and specificity? How valuable are these tests at identifying patients with glaucoma? Do patients from minority racial–ethnic groups have access to these technological innovations?

Joshua D. Stein

From a public health perspective, mischaracterizing patients as having glaucoma when they do not can result in unnecessary patient fear and anxiety, interventions, treatments, side effects and costs. Likewise, mischaracterizing patients as being disease-free when they do have glaucoma can result in the patient’s false sense of security, making follow-up care less likely until damage has occurred.

In the future, I hope to see the normative databases for ocular imaging devices expanded, with inclusion of larger numbers and improved diversity of patients. It is also important for device companies to fully disclose the number and characteristics of patients in their normative databases.

There needs to be improved compatibility between OCT devices and models so patients can be longitudinally monitored for glaucoma progression, even when using different equipment. It is essential that the output from devices be open source so providers can extract individual data elements and integrate them into electronic health records.

All patients should have access to technological innovations, regardless of their race or ethnicity, education level, socioeconomic status and geographic location. And providers need to be educated on the strengths and limitations of ocular imaging devices — how they can be an excellent adjunct to, but not a replacement for, some of the more traditional tests for glaucoma.

 

Joshua D. Stein, MD, MS, an Assistant Professor of Ophthalmology and Visual Sciences, specializes in glaucoma at the University of Michigan W.K. Kellogg Eye Center, U.S.A. Disclosure: Stein has no relevant financial disclosures.

Derived from FDA/American Glaucoma Society Workshop on the Validity, Reliability, and Usability of Glaucoma Imaging Devices, Oct. 5, 2012. http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm318305.htm.

Use of ophthalmic imaging for detecting glaucoma is rising as use of visual field testing is declining. But it is too soon to fully make the switch in technology, experts say, because optical coherence tomography should be viewed as another tool in the kit instead of a replacement when it comes to assessing glaucomatous progression.

“OCT is now used routinely as part of glaucoma assessment because it offers several advantages compared to other modalities of glaucoma assessment, namely examination of the optic nerve and visual field testing.” Albert P. Lin, MD, assistant professor of ophthalmology at Baylor College of Medicine, U.S.A., said. “Both optic nerve examination and OCT are more sensitive than visual field testing in the diagnosis of glaucoma. While optic nerve examination with experienced clinicians may be more sensitive in the diagnosis of glaucoma, OCT does produce a quantifiable measurement of nerve fiber layer thickness to allow better assessment of progression in early stages of the disease.”

“For glaucoma detection, OCT is definitely ready for prime time,” OSN U.S. Edition Glaucoma Board Member Joel S. Schuman, MD, FACS, one of the originators of the technology, said. “It is something that we can use to identify the presence or absence of disease. It is probably the most useful information of any single parameter as to whether or not glaucoma is present.”

Albert P. Lin, MD, believes OCT is useful in assessing glaucoma progression because of its ability to accurately measure retinal nerve fiber layer thickness.
Albert P. Lin, MD, believes OCT is useful in assessing glaucoma progression because of its ability to accurately measure retinal nerve fiber layer thickness.

Image: Lin A

But, he said, it is not yet proven to detect progression because it lacks normative databases and longitudinal studies that would confirm correspondence between what is seen on OCT and what is detected by visual fields, the current gold standard of care.

“OCT is extremely helpful in detecting the presence or absence of glaucoma,” Schuman said. “It can be very helpful in detecting progression of glaucoma. But for progression, at this time we need other supporting evidence for progression to say that real change has occurred.”

The conventional approach for measuring retinal nerve fiber layer (RNFL) thickness is based on measurements derived from a circle scan with a diameter of approximately 3.46 mm, according to Christopher K.S. Leung, MD, MB ChB, professor of the Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, and OSN APAO Edition Board Member.

Christopher K.S. Leung, MD, MB ChB
Christopher K.S. Leung

“With a higher scan speed offered by the spectral-domain OCT, it is now feasible to measure pixel by pixel RNFL thicknesses in a map around the optic nerve head. RNFL defects typical of glaucomatous damage can be visualized and quantified in the RNFL thickness map.” Leung said. “While detecting diffuse loss of the RNFL can be difficult with red-free RNFL photography, the RNFL thickness map generated from the spectral-domain OCT permits clear visualization of both localized and diffuse RNFL defects in glaucoma.”

Teresa C. Chen, MD, who is an associate professor of ophthalmology at Harvard Medical School and practices at the Massachusetts Eye and Ear Infirmary Glaucoma Service, U.S.A., said that the relative lack of longitudinal 3-D imaging data adds to the difficulty in deciding how to interpret spectral-domain OCT findings. As a part of the Spectral Domain Optical Coherence Tomography in Glaucoma Study, her clinic is gathering data on more than 1,000 patients and seeking 5 years of follow-up on patients to address that point.

“In the next few years, we’ll have better data that can tell us how to use these newer 3-D imaging tests for the care of glaucoma patients,” Chen said. “There will be better guidelines in the future as we get better data from studies in glaucoma patients. [OCT is] a good supplemental tool that adds to the clinical exam and other test results.”

PAGE BREAK

Growing use of OCT

Despite Schuman’s caveat, it seems that eye care clinicians are increasingly adopting imaging assessments over visual field exams.

“It’s widely deployed to have an imaging technology. It may be OCT. It may be the confocal scanning laser ophthalmoscope, like the Heidelberg Retina Tomograph, or scanning laser polarimetry,” Schuman said. “But OCT is very broadly used and is continuing to be deployed at a rapid rate globally.”

From 2001 to 2009, ophthalmic imaging increased dramatically as visual field testing declined considerably, Stein and colleagues noted in Ophthalmology. But the authors expressed concerns that imaging in lieu of visual field testing may hurt patients because imaging has not yet proven to be better than visual fields at detecting open-angle glaucoma or disease progression for all patients.

To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma and glaucoma suspects, the researchers conducted a retrospective, longitudinal cohort analysis of nearly 170,00 individuals with open-angle glaucoma and nearly 400,000 individuals with suspected glaucoma enrolled in a U.S. managed care network between 2001 and 2009.

Claims data showed the odds of patients with open-angle glaucoma undergoing visual field testing decreased by 36% from 2001 to 2005, by 12% from 2005 to 2009, and by 44% for the entire time span of 2001 to 2009. At the same time, the odds of having other ophthalmic imaging increased by 100% from 2001 to 2005, by 24% from 2005 to 2009, and by 147% for the entire time span of 2001 to 2009.

Among patients cared for exclusively by optometrists, visual field testing decreased from 66% in 2001 to 44% in 2009, compared with patients seen exclusively by ophthalmologists, for whom visual field testing decreased from 65% in 2001 to 51% in 2009. Other ophthalmic imaging increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists.

A tipping point occurred in 2008, the researchers noted, when patients with open-angle glaucoma receiving care exclusively by optometrists were more likely to undergo imaging than visual field testing.

“OCT is not only useful to evaluate structural changes of the RNFL and optic nerve head in glaucoma, it also plays an important role to detect angle closure and measure anterior segment parameters such as the anterior chamber angle width and anterior chamber depth,” Leung said.

Uncertainty of changes

David Huang, MD, PhD, was one of the original inventors of OCT as a graduate student at Massachusetts Institute of Technology, U.S.A. He built an early prototype and, with Schuman, did the first retinal imaging in the laboratory.

David Huang, MD, PhD
David Huang

“OCT tends to be more sensitive in early glaucoma and visual fields more so in later stages of glaucoma,” Huang said. “But both are valuable. If you just have a few time points over a couple years, often you can catch change on one and on the other you don’t. But the longer the patient progresses, the more the two converge.”

Schuman noted that there is less certainty about OCT as a tool for definitively assessing glaucoma progression. Abnormalities seen with OCT “occur out of step with changes occurring on the visual field. So we’ll often see a change in the OCT prior to the occurrence of a visual field defect or a visual field change. But sometimes it’s the other way around,” he said.

Lin said that visual field testing is a better tool to assess glaucoma progression in moderate to advanced disease.

“OCT is effective at assessing early glaucoma progression, but this efficacy diminishes with moderate to advanced disease. Nerve fiber layer thickness decreases significantly in early disease and can be effectively followed with OCT. In moderate to advanced disease, the remaining nerve fiber layer thickness may not change significantly even with significant glaucoma progression,” Lin said.

PAGE BREAK

Schuman’s hypothesis and current research interests consider changes in the nerve fiber layer that occur sometime before the change in the visual field — perhaps a year or two, perhaps longer.

“When you see those changes occurring asynchronously, what we’re really seeing is a prior effect of glaucoma damage that already is in these sectors affected, and changes showing up on the OCT will be future change on the visual field,” he hypothesized. “That is controversial. And it’s controversial because we don’t know for sure that one necessarily reflects the other.”

Larger studies over longer periods of time will determine whether this is true, Schuman said.

Pearls and pitfalls

With any testing modality, sensitivity and specificity need to be taken into consideration.

Albert P. Lin, MD
Albert P. Lin

“It is important to realize even with an advanced diagnostic instrument, clinicians need to rely on their clinical acumen to interpret and apply the testing results appropriately,” Lin said.

In addition, it is imperative for physicians to understand that OCT should not be used as a screening tool in healthy patients who do not have risk factors or clinical findings indicating glaucoma.

“In the case of OCT, there is significant overlap between nerve fiber layer thickness in normal eyes and glaucoma eyes,” Lin said. “Based on normative database, a cutoff is established by the manufacturers and research studies. Clinical experience shows the sensitivity and specificity of OCT to be about 80% and 90%, respectively. With the aforementioned statistics, in every 200 patients, there will be one false negative and 20 false positives, based on disease prevalence of 2%.”

Lin noted another pitfall in which clinicians only look at the pie chart on the OCT printout to assess whether the nerve fiber layer is normal or abnormal.

“It is important for clinicians to examine the entire printout, including the signal strength, the centration of the measurement ring around the optic nerve, and the quality of the topography scan and contour. If these parameters are not optimal, the resulting pie chart will not be useful and should not be applied clinically,” Lin said.

When Schuman is deciding whether a patient has glaucoma, he considers the region of the defect. A pattern superiorly or inferior temporally suggests glaucoma, he said. If the ganglion cell complex is abnormal in a way that matches the nerve fiber layer, then that is an internal correspondence suggesting that the abnormality is real even if there is no visual field defect. This is called pre-perimetric glaucoma.

Joel S. Schuman, MD, FACS
Joel S. Schuman

“The clinician needs to be the most careful in diagnosing those patients,” Schuman said. “If they have other abnormalities that make you think that the patient might have glaucoma — that they have a history, that they have significant risk factors or high intraocular pressure — that’s going to sway you toward making the diagnosis in the presence of an OCT abnormality without a visual field abnormality.”

Clinicians need to make sure that the quality of the scan and analysis is adequate before accepting the OCT results.

“A poor-quality scan can give you bad or incorrect information,” Schuman said. “You’re dealing with a garbage-in, garbage-out problem.”

Huang noted that at the very low end of signal strength, the nerve fiber layer begins to look thinner. Depending upon the system, images with a loss of signal of 35 to 45 out of 100 are not as reliable.

“It’s common sense that you have to look at the images for the quality of the image processing that outlines the inner and outer borders of the nerve fiber layer,” Huang said. “You still want to look at the image to make sure the image is not cropped. Sometimes the top of the nerve fiber layer might be cut off because the position of the OCT system was a little cut off when the image was taken.”

PAGE BREAK

The correspondence that clinicians think confirms a diagnosis might not be enough. If a clinician sees corresponding changes between the visual field exam and the OCT, then it is likely that the change is real, Schuman said.

“But it may be that the person who has corresponding change occurring on both OCT and visual field will actually go on to have stronger visual field loss in the corresponding area because the OCT may actually be predicting visual field damage as opposed to corresponding damage that is occurring today,” Schuman said.

Huang noted that high IOP can affect nerve fiber layer measurements.

“It’s an elastic response,” he said. “If you have a balloon and you blow it up harder, the balloon is going to be a little bit bigger and the wall is going to be thinner by a small amount. When the pressure is higher, the layers look slightly thinner because the balloon is slightly larger.”

If longitudinally the pressure is within a couple of mm Hg, it is not a significant effect. But, Huang added, “If someone’s nerve fiber layer looks thinner than a year ago but their pressure is 4 mm Hg higher, you may want to take that into account.”

Next-generation devices

Current OCT systems run between 17 KHz and 40 KHz, faster than previous generations but not as fast as the next generation of machines, which could run between 70 KHz and 100 KHz, Huang said. The faster speeds offer the potential of new measurements.

“We are now able to look at the nerve fiber layer as a map over a wider area,” Huang said. “As the analysis of that improves, there will be an improvement in diagnostic accuracy and the ability to track small changes over the long run.”

Faster processors and 3-D scans over a wider area will improve the ability to detect focal changes, Huang said. Measuring changes over a small area is more difficult, but newer technology will offer better sampling and better position tracking.

This year, Huang will finish the Advancing Imaging for Glaucoma Study, which is sponsored by the National Institutes of Health. He hopes to publish results for mapping the ganglion cell complex, which may help catch more cases of glaucoma earlier.

In addition, Huang has been taking advantage of faster scanning speeds to look at optic nerve head blood flow using OCT angiography and to look at total retinal blood flow with Doppler OCT. He has found that these perfusion measurements correlate better with visual field function than nerve fiber layer thickness and other structural measurements. Thus, the new functional OCT technology has the potential to further improve glaucoma diagnosis and tracking. – by Ryan DuBosar and Christi Fox

References:

Boling W, et al. J Glaucoma. 2012;doi:10.1097/IJG.0b013e318239c32b.

Chauhan BC, et al. Ophthalmology. 2009;doi:10.1016/j.ophtha.2009.04.031.

Kotowski J, et al. Ophthalmic Surg Lasers and Imaging. 2011;doi:10.3928/15428877-20110627-01.

Mwanza J, et al. Invest Ophthalmol Vis Sci. 2010;doi:10.1167/iovs.10-5222.

Pierro L, et al. Invest Ophthalmol Vis Sci. 2012;doi:10.1167/iovs.11-8644.

Stein JD, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2011.09.045.

Stein J, et al. Changes in the diagnostic evaluation of patients with open-angle glaucoma from 2001-2009. Presented at American Glaucoma Society annual meeting; March 2011.

Wu H, et al. J Glaucoma. 2011;doi:10.1097/IJG.0b013e3181f3eb64.

For more information:

Teresa C. Chen, MD, can be reached at +1-617-573-3674; fax: +1-617-573-3707; email: teresa_chen@meei.harvard.edu.

David Huang, MD, PhD, can be reached at Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239, U.S.A.; email: davidhuang@alum.mit.edu.

Christopher K. S. Leung, MD, MB ChB, can be reached at the Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong; 147 Argyle St., Kowloon, Hong Kong; email: cksleung.cuhk@gmail.com.

Albert P. Lin, MD, can be reached at 2002 Holcombe Blvd., 112C, Houston, TX 77030, U.S.A.; +1-713-791-1414; email: alin@bcm.edu.

Joel S. Schuman, MD, FACS, can be reached at Department of Ophthalmology, UPMC Eye Center, 203 Lothrop St., Suite 816, Pittsburgh, PA 15213, U.S.A.; +1-412-647-2205; email: schumanjs@upmc.edu.

PAGE BREAK

Disclosure: Chen has no personal relevant financial disclosures. Huang receives OCT-related patent royalties from Optovue and Carl Zeiss Meditec, as well as grant support, stock options and speaker honorarium from Optovue. Leung receives research support/speaker honorarium from Carl Zeiss Meditec, Optovue, Tomey, Heidelberg Engineering and Topcon. Lin has no relevant financial disclosures. Schuman receives royalties for intellectual property licensed by MIT and MEEI to Carl Zeiss Meditec.

 

POINTCOUNTER 

What are the public health implications for OCT screening for glaucoma?

POINT

OCT needs to meet screening criteria

OCT has to meet certain criteria to have a role in widespread glaucoma screening.

Anne L. Coleman

There are well-known criteria for mass screening. The disease should be common and serious, as we know glaucoma is. The screening test should be highly accurate. The natural history needs to be understood, there needs to be acceptable resources for treatment, and the treatment should favorably influence outcomes.

One of the problems that we have had with glaucoma is that it is not very prevalent in the general population in the U.S.; it is around 2%.

Sensitivity and specificity are very important for looking at the validity of the test, and it is the positive predictive value — the probability that a label of “positive” is actually a true case — that determines whether the screening program will be cost effective.

The Agency for Healthcare Research and Quality Screening for Glaucoma: Comparative Effectiveness report issued in 2012 said that there really is no one test or group of tests that would be suitable for screening for glaucoma, including OCT.

Considerations for screening with any device include not only how good the device is, but also whether the device is transportable and durable. You do not want it falling apart when you put it in a van and take it out for mass screenings in the general population.

In addition, you want it to be usable with a standard wall outlet. You want it to be rapid. You want to have few poor quality scans. You want it to be relatively inexpensive so that community groups can afford it and use it. You want those lay people to be able to understand what the results mean and then refer those patients who fail borderline tests to appropriate clinical offices for evaluation.

 

Reference:

http://effectivehealthcare.ahrq.gov/ehc/products/182/1025/CER59_GlaucomaScreening_executivesummary.pdf.

Anne L. Coleman, MD, PhD, is the Fran and Ray Stark Professor of Ophthalmology and Epidemiology at the University of California-Los Angeles Jules Stein Eye Institute, U.S.A. Disclosure: Coleman has no relevant financial disclosures.

COUNTER

Questions arise as imaging devices are integrated

As ocular imaging devices have been integrated into clinical practices, public health considerations have emerged: Do these devices have adequate sensitivity and specificity? How valuable are these tests at identifying patients with glaucoma? Do patients from minority racial–ethnic groups have access to these technological innovations?

Joshua D. Stein

From a public health perspective, mischaracterizing patients as having glaucoma when they do not can result in unnecessary patient fear and anxiety, interventions, treatments, side effects and costs. Likewise, mischaracterizing patients as being disease-free when they do have glaucoma can result in the patient’s false sense of security, making follow-up care less likely until damage has occurred.

In the future, I hope to see the normative databases for ocular imaging devices expanded, with inclusion of larger numbers and improved diversity of patients. It is also important for device companies to fully disclose the number and characteristics of patients in their normative databases.

There needs to be improved compatibility between OCT devices and models so patients can be longitudinally monitored for glaucoma progression, even when using different equipment. It is essential that the output from devices be open source so providers can extract individual data elements and integrate them into electronic health records.

PAGE BREAK

All patients should have access to technological innovations, regardless of their race or ethnicity, education level, socioeconomic status and geographic location. And providers need to be educated on the strengths and limitations of ocular imaging devices — how they can be an excellent adjunct to, but not a replacement for, some of the more traditional tests for glaucoma.

 

Joshua D. Stein, MD, MS, an Assistant Professor of Ophthalmology and Visual Sciences, specializes in glaucoma at the University of Michigan W.K. Kellogg Eye Center, U.S.A. Disclosure: Stein has no relevant financial disclosures.

Derived from FDA/American Glaucoma Society Workshop on the Validity, Reliability, and Usability of Glaucoma Imaging Devices, Oct. 5, 2012. http://www.fda.gov/MedicalDevices/NewsEvents/WorkshopsConferences/ucm318305.htm.