Visual Field Index Overlooks Neural Loss in Early Glaucoma

Miriam E. Tucker

March 05, 2014

WASHINGTON, DC — The visual field index underestimates the amount of neural loss in eyes affected by glaucoma, particularly in early disease, a new study suggests.

"In early disease, we should rely less on the visual field index," said Amir Marvasti, a graduating medical student from Boston University School of Medicine and future resident at the University of California San Diego Shiley Eye Center.

Underlying ganglion cell loss is used to calculate the index, "however, we found that in early disease, the visual field index overestimates the amount of neural tissue left in glaucoma," he told Medscape Medical News. In other words, "it underestimates the amount of neural loss," he explained.

Marvasti presented the study findings here at the American Glaucoma Society 24th Annual Meeting. First results were published in PLoS One (2013;8:e76590).

His team used 2 methods — visual function and structural abnormalities — to assess the extent of glaucoma. The visual field index indicates functional visual abnormality, and the loss of retinal ganglion cells indicates structural abnormalities in the retinal nerve fiber layer.

The multicenter study enrolled 1245 eyes from 1245 participants in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study (ADAGES). All eyes underwent standard automated perimetry and time-domain optical coherence tomography. The mean age of the study subjects was 58 years.

Of the 1245 eyes, 35% had glaucomatous visual field defects, 19% had glaucomatous optic neuropathy without visual field abnormalities, 19% had ocular hypertension, and 28% were healthy and served as the control group.

Because retinal ganglion cells can't be directly counted in vivo, Marvasti and his team estimated the number using a formula derived from previous work (Prog Retin Eye Res. 2010;29:249-271).

Using statistical methods, Marvasti and colleagues determined the relation between the age-corrected percentage of remaining retinal ganglion cells and the visual field index, which is also an age-adjusted measure.

The relation was nonlinear; the extent of index change accompanying a given loss of ganglion cells varied by disease severity.

For example, in early-stage glaucoma, a very large loss of 100,000 ganglion cells corresponded to a 0.3% change in the visual field index. In early-moderate disease, the same neural loss corresponded to a 3.0% change, in late-moderate disease to a 13.5% change, and in advanced-stage disease to a 22.1% change.

Table. Functional and Structural Measures

Condition of Eye Mean Visual Field Index, % Estimated Remaining Ganglion Cells, %
Healthy 99.1 95.1
Ocular hypertension 99.1 93.4
Glaucomatous optic neuropathy with normal visual fields 98.7 85.1
Glaucoma 87.5 66.9

 

"Large ganglion cells losses can occur with very small index changes, especially in early to moderate disease. In other words, a 1% loss of visual field index does not represent the same amount of neural loss across the disease spectrum," Marvasti explained.

Moreover, when visual field index was plotted against the age-adjusted percentage of remaining retinal ganglion cells, results suggested "that the relation is nonlinear even when age is taken into account."

 
It's a useful tool, but the index is really most useful in the more moderate stages of disease.
 

"It's a useful tool, but the index is really most useful in the more moderate stages of disease," said session moderator Louis Cantor, MD, from the Eugene and Marilyn Glick Eye Institute in Indianapolis.

"I think doctors are relying on it, probably more than the evidence supports that we should, especially in early disease. One of the hardest things to do in practice is to segregate our patients and look at them differently," he told Medscape Medical News.

"We should consider disease severity when we look at rates of change in visual field index. Estimates of ganglion cells may be a better method of measuring rates of progression in glaucoma," Marvasti explained.

Previous studies have demonstrated that a combination of structural and functional tests leads to better disease staging and prediction of progression than either used individually.

"Fortunately, advances in imaging technologies are allowing us to define the structure much better. We're not seeing similar advances in functional assessment," Dr. Cantor told Medscape Medical News.

He noted that newer optical coherence tomography technologies that directly measure the thickness of the ganglion cell layer might eventually supplant the need to estimate retinal ganglion cells. "I don't think it would show much difference from what they showed, but I think it would help refine how much more sensitive the structural measure is becoming, compared with the functional measure," he said.

This study was funded in part by the National Eye Institute and by participant retention incentive grants in the form of glaucoma medication at no cost from Alcon Laboratories, Allergan, Pfizer, Santen, the EyeSight Foundation of Alabama, and Research to Prevent Blindness. Some of Mr. Marvasti's coauthors report receiving financial or research support from Carl-Zeiss Meditec, Heidelberg Engineering, Optovue, and Kowa. Dr. Cantor reports having consulted for Allergan, Mati Therapeutics, and Aerie Pharmaceutical.

American Glaucoma Society (AGS) 24th Annual Meeting: Abstract 10. Presented February 28, 2014.

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