IOP FLUCTUATION

The arguments for and against a correlation between IOP fluctuation and glaucoma onset and progression both have their strong adherents, and better designed studies, specifically focused on IOP fluctuation, may be necessary to settle the debate to the satisfaction of all. That was the apparent conclusion of a debate on the topic held at the 10th European Glaucoma Society Congress. Anders Heijl MD, PhD took up the argument that the evidence does not support the theory that greater fluctuations of IOP predict a greater likelihood of glaucomatous damage. “The question has to be, is IOP fluctuation an independent risk factor for glaucoma, even when we take the mean IOP into account? This must be tested with methods that take both fluctuation and IOP levels into account, that is, a multivariate analysis. IOP fluctuations should then be measured during the same time and with the same type of treatment,†said Dr Heijl, Skane University Hospital Malmo, Lund University, Sweden.

He noted that two of the most often cited studies in favour of a correlation for IOP fluctuation and the likelihood of glaucoma onset or progression fail to meet those criteria. One of the studies, by Bengt Bergea MD and associates in Sweden (Bergeå et al, Ophthalmology 1999;106: 997-1005) appeared to show that glaucomatous eyes with lower amounts of daytime IOP fluctuation have a better visual field prognosis compared to those with greater IOP daytime fluctuation. The study included 82 patients with newly detected untreated glaucoma. All had high IOPs and were participants in a randomised clinical trial comparing primary laser trabeculoplasty with medication. All underwent automated perimetry and a daytime IOP curve assessment every second month during the two-year follow-up. Dr Heijl noted that, in their analysis, the study’s authors did not include comparisons between patients’ IOP levels and fluctuations from the same time period. Furthermore, they only partially included the IOP values that patients achieved during treatment in their analysis but always included baseline IOP values.

Moreover, the correlation between IOP fluctuation and visual field loss only appeared to hold true in the patients with pseudoexfoliative glaucoma. Primary openangle glaucoma (POAG) patients with wider IOP fluctuations actually tended to have less visual field progression. The results of another study, conducted by Sanjay Asrani MD and associates (Asrani et al, J Glaucoma. 2000;9:134-142), also seemed to suggest that large diurnal fluctuations in IOP are an independent risk factor in patients with glaucoma. It included 166 patients with a baseline IOP less than 25 mmHg and a baseline fluctuation determined at by home tonometry measurements. Dr Heijl noted that there were several potentially confounding factors built into the design of that study. For example, the authors excluded 61 per cent of initially included patients, most often because of IOP greater or equal to 25 mmHg during followup, he said.

In contrast to those studies, diurnal IOP fluctuation was not an independent risk factor for glaucomatous visual field loss in high-risk ocular hypertension in a study that Dr Heijl co-authored with Dr Boel Bengtsson PhD (Bengtsson et al, Graefes Arch Clin Exp Ophthalmol 2005; 243:513 -518). The study included 90 patients recruited from 1981 to 1987 monitored every three months for 10 years or until glaucomatous field defects developed. The results of a multivariate analysis showed that while mean IOP level was highly significant, IOP range was not significant “The bottom line is that mean IOP is related to progression. IOP fluctuation is also related to progression, but only because it is higher in eyes with higher mean IOP there is no evidence that IOP fluctuations, diurnal or test-retest are independent risk factors for progression,†Dr Heijl added.

Peak IOP higher in eyes with wider range of pressure

Anastasios G Konstas MD, PhD presented the argument in favour of a possible link between IOP fluctuation and glaucomatous damage and progression, maintaining that such an association actually has yet to be disproved. We must distinguish between two different parameters: 24-hour IOP fluctuation and long-term IOP fluctuation or variation. Although it remains controversial whether long-term IOP fluctuation established with single, infrequent IOP readings impacts glaucoma progression (vs mean IOP) it should be remembered that many factors influence long-term fluctuation (treatment changes, adherence timing of IOP measurements etc), he said. “There is considerable evidence suggesting that wide fluctuation of diurnal or 24-hour IOP plays a role in glaucoma development and progression. Moreover, and unlike long-term fluctuations of IOP, there is no convincing evidence that 24-hour fluctuation does not influence glaucoma progression,†said Prof Konstas, from the 1st University Department of Ophthalmology, AHEPA Hospital, Thessaloniki, Greece.

He noted that optimisation of 24-hour IOP control has gained acceptance as the best way of reducing the risk of progressive damage to the optic nerve and visual loss. Most clinicians believe that a reduced 24-hour IOP fluctuation with therapy should be a consideration in glaucoma care and will safeguard their patients against long-term progression. Further, cumulative evidence suggests that a wide fluctuation of 24-hour ocular perfusion pressure is a key risk factor for glaucoma progression. Potentially of greater importance is the reduction of 24-hour fluctuation in advanced glaucoma. He noted that reduced 24-hour fluctuation may be the key benefit provided by successful surgery (Konstas et al Ophthalmology 2006).

He cited two studies supporting an association between diurnal IOP fluctuation and glaucoma onset. In one of the studies, wide diurnal IOP fluctuation was more common among ocular hypertension patients who developed glaucoma (Odberg et al, Acta Ophth 1987, 65: 27–29). In another study wide fluctuation of IOP appeared to be a predictor of retinal nerve fibre layer defects and glaucoma development (Gonzalez et al, Int Ophth 1996; 20: 113-115).

However, it is often difficult to separate the impact upon glaucoma progression achieved through reduction of 24-hour peak IOP from that achieved through reduction of 24-hour IOP fluctuation, he said. It is likely that peak 24-hour pressure may be of greater importance in treated patients who continue to progress despite apparently good pressure control in the clinic. The results of another study, which Prof Konstas and his associates conducted, indicated a strong linear correlation between untreated peak 24-hour IOP in exfoliative glaucoma patients and POAG patients and mean field defect at the time of diagnosis (Konstas et al, Arch Ophth 1997 ;115(2):182-185). “The evidence we need for the future is a long-term study investigating the precise prognostic impact and value of each 24-hour IOP parameter,†Prof Konstas added.