Weighing IOP fluctuation in glaucoma progression

Available evidence indicates that long-term IOP fluctuation is an important factor in glaucoma progression, said Joseph Caprioli, MD. Based on this information he encouraged ophthalmologists to consider IOP “modulation” rather than “reduction.”

Chicago-Available evidence indicates that long-term IOP fluctuation is an important factor in glaucoma progression, said Joseph Caprioli, MD.

Based on this information he encouraged ophthalmologists to consider IOP “modulation” rather than “reduction.”

“This relates to the quality of IOP control,” said Dr. Caprioli, professor of ophthalmology, University of California, Los Angeles. “The target for patients with progressing primary open-angle glaucoma at high risk should be a low mean IOP and fewer excursions of pressures into a range that may be damaging.”

Addressing the question of whether IOP fluctuation is important for glaucoma patient outcomes, Dr. Caprioli divided his review into evidence regarding the effects of instantaneous, diurnal-nocturnal (nyctohemeral), short-term, and long-term fluctuations.

He noted there is no evidence that instantaneous fluctuations in IOP-i.e., those that are caused by such factors as saccades, blinks, or eye rubbing-have any effect on glaucoma progression.

“These can be quite high excursions of IOP, although they are very brief, on the order of seconds or fractions of seconds,” Dr. Caprioli said. “It is interesting to speculate, however, that these high peaks can produce strain from IOP stress in susceptible eyes.”

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Diurnal-nocturnal fluctuations, also referred to as nyctohemeral fluctuations, describe variations that occur between day and night as a result of central or humoral factors.

Dr. Caprioli said there is also no solid evidence that nyctohemeral IOP fluctuations affect glaucoma progression, although one recent study that employed a contact lens sensor for IOP monitoring and measured visual field change in treated glaucoma patients concluded “the number of long peaks and the mean peak ratio when patients were awake were the best predictors of faster progression.”

Defining short-term fluctuation in IOP as changes occurring over a period of days to weeks, Dr. Caprioli said there is also no evidence that it affects glaucoma progression.

Speculation

One recent report, however, has led to speculation that it may have importance. The study he referred to also employed a contact lens sensor for continuous IOP recording and pointed to a correlation between IOP fluctuations measured over a day and longer-term IOP fluctuations.

Long-term fluctuation in IOP refers to changes over months to years and generally reflects variations noted from intervisit in-office IOP measurements. Findings from a post hoc analysis of data from the Advanced Glaucoma Intervention Study associated long-term IOP fluctuation with glaucoma progression in eyes with low mean IOPs and found long-term IOP fluctuation was a stronger predictor than mean IOP for visual field progression.

In the Collaborative Initial Glaucoma Treatment Study, peak IOP, standard deviation of IOP, and range of IOP were all more important than mean IOP for predicting visual field worsening.

A recent publication analyzing data from the Japanese Archive of Multicentral Databases in Glaucoma also reported a relationship between IOP fluctuation and faster progression, although the association did not hold true when mean IOP was <15 mm Hg.

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Dr. Caprioli pointed out that there are numerous other studies supporting the notion that long term IOP fluctuation influences glaucoma progression.

There are also studies that found IOP fluctuation had no effect, and they include the Ocular Hypertension Treatment Study, the Early Manifest Glaucoma Trial, the European Glaucoma Prevention Study, and the Ocular Hypertension in the Diagnostic Innovations in Glaucoma Study.

“What these studies have in common is that the patients had higher IOPs, earlier glaucoma damage, and received modest or no treatment,” he said. “There was a strong correlation of standard deviation with mean IOP, and it is hard to separate out those two effects because they are highly correlated.

“I believe these varied findings are not contradictory, but rather are complementary,” he said.

Mechanistic understanding

There have been various explanations put forth as to why IOP fluctuation can contribute to faster glaucoma progression, including lack of a steady state or breakdown of homeostatic mechanisms.

“Or, it may simply be the result of periodic excursions into IOP levels that are damaging and not often measured well,” Dr. Caprioli said.

He also discussed speculations about why nocturnal elevation of IOP may not be important for predicting glaucoma progression.

“The increase in IOP that occurs during the night is largely due to lying in a supine position,” Dr. Caprioli said. “But there is also increased perfusion pressure in the supine position that may counteract effects of IOP on susceptible tissues as well as increased CSF pressure that may counteract stresses caused by IOP on the nerve head.

“Perhaps most importantly, homeostatic mechanisms are likely to exist to compensate for regular biorhythms,” he said.