Predicting glaucoma onset: AIG identifies prognostic value for FD-OCT

TAKE HOME:

Analyses of data from the Advanced Imaging for Glaucoma Study showed many Fourier-domain optical coherence tomography parameters were significant risk factors for glaucoma onset in eyes that were glaucoma suspect or had pre-perimetric glaucoma.

By Cheryl Guttman Krader; Reviewed by David Huang, MD, PhD

Portland, OR-Fourier-domain optical coherence tomography (FD-OCT; also known as spectral-domain OCT) may be useful in the initial risk assessment and treatment decisions for patients at risk of developing visual field damage from glaucoma, said David Huang, MD, PhD.

This assessment was based on findings from the Advanced Imaging for Glaucoma (AIG) Study that enrolled 513 eyes with a normal or borderline visual field that were glaucoma suspect or had pre-perimetric glaucoma. Study participants were assessed every 6 months, and during a median follow-up of about 4.3 years, 55 eyes converted to perimetric glaucoma or definitive visual field damage.

Cox regression analysis was used to investigate the prognostic significance of various FD-OCT parameters and other baseline variables representing demographic characteristics, visual field parameters, and ocular characteristics. The univariate analysis identified 16 variables with prognostic significance, including five of the six FD-OCT variables tested.

Ganglion cell complex focal loss volume (GCC-FLV), a measure of focal defect in the macula, emerged as the strongest predictor of all the variables tested, with an area under the receiver operating curve (AROC) of 0.753, according to Dr. Huang.

Kaplan-Meier analyses showed that eyes with a borderline or abnormal GCC-FLV at enrollment had a 4-fold greater risk of developing visual damage within 6 years than those with a normal GCC-FVL, 41% versus 10%, respectively.

“Conventional wisdom says that an abnormal FD-OCT in a patient with a normal or borderline visual field could just be red disease,” said Dr. Huang, Peterson Professor of Ophthalmology, professor of biomedical engineering Casey Eye Institute, Oregon Health and Science University (OHSU), Portland. “However, these data suggest it is more likely to be real disease that will take several years before it manifests as visual field loss, and that appears to be especially true if there is a borderline or abnormal GCC-FLV.”

Investigators also found that compared with GCC-FVL alone, the accuracy of predicting conversion to glaucoma could be increased significantly by combining that term with age, visual field pattern standard deviation, and nerve fiber layer inferior thickness in a composite value they termed the Glaucoma Composite Conversion Index (GCCI).

The GCCI had an AROC of 0.783. With patients divided into quartiles according to their baseline GCCI, those in the highest quartile (GCCI >0.84) had about a 30% rate of conversion to glaucoma, which was almost 9-fold higher than the 3.6% conversion rate for eyes in the lowest GCCI quartile, which had values ranging from 0.33 to 0.62.

Dr. Huang is the principal investigator of the NIH-supported AIG grant, which included a prospective longitudinal observational study performed at three clinical centers (www.AIGStudy.net). Follow-up in the AIGS was completed in 2013. Of the 513 eyes that it included, 359 had pre-perimetric glaucoma with an optic nerve head or nerve fiber layer defect visible on ophthalmoscopy and the remaining 154 were categorized as glaucoma suspects based on presence of ocular hypertension or glaucoma in the fellow eye in the absence of an optic nerve head or nerve fiber layer defect.

All centers used the same platforms for FD-OCT imaging (RTVue, Optovue) and visual field testing (HFA II SITA 24-2, Carl Zeiss Meditec). The FD-OCT scans mapped disc topography, nerve fiber layer (NFL) thickness, and GCC thickness. The criterion for confirming conversion to glaucoma required three consecutive abnormal visual fields.

Gender, race, axial length, IOP, and central corneal thickness were not significant predictors of glaucoma conversion.

“Because the AIG Study is not a randomized trial, the clinician could use IOP and central corneal thickness to make treatment decisions,” he said. “Therefore, it is not surprising that these known risk factors were not predictive of glaucoma conversion, and no conclusion should be drawn from this study regarding the link between IOP, central corneal thickness and glaucoma progression based on the AIG Study.”

The AIG Study was mainly intended to test the usefulness of OCT in glaucoma evaluation. OCT results were masked to the treating clinicians during the study period, so the predictive value of OCT could be established without bias, Dr. Huang noted.

David Huang MD, PhD

E: davidhuang@fastmail.fm

This article was adapted from Dr. Huang’s presentation at the 2014 meeting of the American Academy of Ophthalmology. Dr. Huang has a significant financial interest in Carl Zeiss Meditec. Oregon Health and Science University (OHSU) and Dr. Huang have a significant financial interest in Optovue, a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU.