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Editors Selection IGR 21-4
Clinical Forms of Glaucoma: Circadian IOP fluctuation and NTG progression
Comment by Luciano Quaranta on:
70416 The Effect of Diurnal Fluctuation in Intraocular Pressure on the Evaluation of Risk Factors of Progression in Normal Tension Glaucoma, Kim SH; Lee EJ; Han JC et al., PLoS ONE, 2016; 11: e0164876
Intraocular pressure (IOP) is not a fixed value, but fluctuates during the day (short-term fluctuation) and day by day (long-term fluctuation), similarly to other biological parameters.1-3 Although mean IOP has long been known to correlate with glaucoma progression,4,5 actually no conclusive evidence can be drawn about IOP fluctuation. In this study, Kim et al. found that long-term IOP fluctuation, corrected for diurnal IOP variation (time-adjusted long-term fluctuation, TALT), is a significant risk factor for progression in NTG patients. TALT, calculated as standard deviation (SD) of IOP measurements, was correlated to NTG progression with an impressive 5.260 hazard ratio (p = 0.029). Moreover, patients with a TALT < 1.5 were significantly less likely to have progression during the follow-up, in comparison with patients that had a TALT > 1.5.
Despite these results, the authors did not report in the text the mean and median follow-up time of the survival analysis. From survival graphs, a total follow-up time of about 250 months (~21 years) can be inferred, but it is unlikely that a big proportion of patients were followed-up so long. When reporting results of a survival analysis, survival tables should be included in the text.
Indeed, if a high percentage of patients are censored during the follow-up, survival rates may be biased. In this case, also a single failure in the final part of the curve may have an exaggerated effect on survival rates, and a shorter follow-up should be conveniently settled.
As a result of this study, correcting long-term fluctuation for diurnal IOP variation decreases the magnitude of long-term fluctuation, giving a more useful and precise datum. This is extremely interesting and suggests the existence of a repeatable diurnal IOP pattern. Indeed, there are few studies in literature that investigated the repeatability of IOP patterns in healthy and glaucomatous eyes over time, and the results are conflicting. Obviously, the information obtained from diurnal IOP testing would be of greater value if IOP behavior remained stable among patients over time (i.e., if measurement on one day provided information about IOP behavior on subsequent days). Contrary to these results, Realini et al. repeated a diurnal IOP curve in healthy and treated glaucoma patients one week apart and found only a fair to good agreement for IOP values at any time-point, and essentially no agreement for IOP change over time periods between time-points.6,7 As a consequence of these results, Realini et al. concluded that eyes of healthy and glaucoma subjects do not follow a conserved IOP pattern from day to day.
Both unadjusted and time-adjusted mean IOP over time did not emerge as a risk factor for glaucoma progression from this study. The role of IOP in NTG has been not completely cleared, however, results from the Collaborative Normal Tension glaucoma Study (CNTGS) showed that a 30% reduction of IOP from baseline may slow the progression of the disease.8 The rate of glaucoma progression in the study by Kim et al. (~41%) was quite similar to the rate of progression of the untreated group of the CNTGS (35%). This could be due to the small percentage of IOP reduction from baseline obtained with betaxolol or to other factors independent of IOP. Interestingly, while mean IOP was not a significant risk factor for progression, TALT was. The meaning of these results remains unclear. However, as IOP has a role in the determination of ocular perfusion pressure, and vascular factors are also considered important in the pathogenesis of NTG, IOP fluctuations might to a certain extent impair optic disc perfusion, independently from IOP values. It would be interesting to evaluate if these results may be reproduced in primary open angle glaucoma patients, where the role of mean IOP in the onset and progression of the disease has been well established.
References
- Quaranta L, Katsanos A, Russo A, Riva I. 24-hour intraocular pressure and ocular perfusion pressure in glaucoma. Surv Ophthalmol 2013;58(1):26-41.
- Drance SM. The significance of the diurnal phasic variation of intraocular pressure in normal and glaucomatous eyes. Trans Can Opthalmolog Soc 1960;23:131-140.
- Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open-angle glaucoma. Am J Ophthalmol 1975;79(4):557-566.
- Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120(10):1268-1279.
- The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators. Am J Ophthalmol 2000;130(4):429-440.
- Realini T, Weinreb RN, Wisniewski SR. Diurnal intraocular pressure patterns are not repeatable in the short term in healthy individuals. Ophthalmology 2010;117(9):1700-1704.
- Realini T, Weinreb RN, Wisniewski S. Short-term repeatability of diurnal intraocular pressure patterns in glaucomatous individuals. Ophthalmology 2011;118(1):47-51.
- Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 1998;126(4):487-497.
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