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Editors Selection IGR 17-4

Clinical Forms of Glaucoma: Relative Afferent Pupillary Defect in NTG

Comment by Ki Ho Park on:

74629 Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated Intraocular Pressure, Lawlor M; Quartilho A; Bunce C et al., Investigative Ophthalmology and Visual Science, 2017; 58: 5237-5241

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This is very pioneering and interesting paper. The authors investigated whether there is relative sparing of pupil function in glaucoma patients with normal pressures compared with those with high pressures. The relative afferent pupillary defect (RAPD) was quantified with the RAPDx device in 68 patients with primary open-angle glaucoma (POAG), of which 38 had normal IOPs on all-day phasing before treatment (never >21 mm Hg), with confirmed progression of glaucomatous optic neuropathy (NTG), and 30 had glaucomatous optic neuropathy associated with elevated intraocular pressures (>25 mm Hg; HP-POAG).

The difference in slope between NTG and HP-POAG was evaluated on plots of RAPD magnitude against difference in HVF MD and of RAPD magnitude against difference in RNFL thickness. The authors found that, with regard to the difference in MD, the slope for patients with NTG was flatter than that for those with HP-POAG, which means that patients with NTG have a lesser RAPD for a given level of inter-eye difference of HVF MD, as compared with patients with high IOPs. From the results, the authors hypothesized that damage to intrinsically photosensitive retinal ganglion cells (ipRGCs) differs between NTG and HP-POAG and that their data supports the theory that mitochondrial optic neuropathies have a role in NTG, as ipRGC is known to be spared in the mitochondrial optic neuropathies.

There is limitation to this study. There was no matching of disease severity between the two groups, or in any case, there was no discussion of matching in the manuscript. Actually, the MD of the left and right eyes in NTG were -8 and -7.5 dB, respectively, while those in HP-POAG were -4.7 and 5.6 dB, respectively. Further, the RNFL thickness difference between both eyes was smaller in NTG (0.6 um) than in HP-POAG (3.8 um), even though the statistical significance was not provided. So, there is a possibility that the lesser RAPD in the NTG group was at least partially affected by the inter-group disease-severity and structural-damage differences between both eyes.

There is a possibility that the lesser RAPD in the NTG group was at least partially affected by the inter-group disease-severity and structural-damage differences between both eyes

However, this paper raised the important issue that mitochondrial neuropathy might have a role in NTG, and it provided quantitative evidence in the form of plots comparing pupillary response and functional and structural optic nerve damage. Further study on mitochondrial gene sequencing and the relationship with pupil function in those or similar subgroups of patients would be in order.

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