Progression Despite IOP Reduction?

Look for hidden contributing factors when managing patients with normal-tension glaucoma. Roibeárd O’hÉineacháin reports from the ninth World Glaucoma E-Congress

When normal-tension glaucoma (NTG) patients progress despite low IOP, it is important to consider potential lifestyle factors, out-of-office IOP spikes, genetic predisposition, and potential non-glaucomatous causes for optic nerve degeneration, advised Professor Louis R Pasquale MD.

“In most instances, we don’t identify the real reason patients are progressing. There are no proven ways to halt progression in NTG, either by IOP lowering or non-IOP lowering approaches,” Prof Pasquale told the congress.

He noted progressive NTG is a public health problem with an estimated unilateral blindness rate of 10% and an estimated bilateral blindness rate of about 1.4% at 20 years. He also put out a call for an international consortium devoted to solving the problem of progressive NTG.

“We need a ‘wisdom of crowds’ approach to halt NTG progression, which is really one of the scourges of the twentyfirst century,” he added.

FINDING THE CAUSE FOR PROGRESSION Prof Pasquale noted that sometimes what may appear to be progressive NTG may not be glaucoma at all. He cited the case of a 74-year-old white male referred for NTG evaluation. The patient had increased cupping in his left eye, and visual field testing revealed a unilateral superior temporal hemianopsia.

“Whenever you see this, this is a pituitary tumour until proven otherwise. In this case, neuroimaging studies confirmed that diagnosis and prompt neurosurgical intervention resulted in resolution of this defect,” he said.

Other red flags for non-glaucomatous optic neuropathy include a rate of visual field loss greater than one decibel per year (compared to a more typical progression rate for NTG of 0.2 dB to -0.5 dB per year); non-congenital dyschromatopsia; and visual field defects that respect the vertical meridian, which can indicate lesions in the optic chiasm or the post-chiasmal visual pathway.

When assessing a case of progressing NTG, it is also important to take the patient’s lifestyle and occupation into consideration, Prof Pasquale said. He described the case of a 48-year-old yoga instructor referred for a third opinion regarding her apparently “normal tension” glaucoma. When asked about her occupation, she responded that she did a lot of headstand posturing in the yoga classes she ran. Subsequent IOP measurements taken while she performed a headstand showed a pressure of 50 mmHg.

Another aspect of a progressing NTG patient’s history to consider is their sleep habits. Patients with a tendency towards daytime somnolence may benefit from a sleep workup.

One should also inquire whether they are receiving medication for systemic hypertension, as taking evening doses closer to dinner time than to bedtime may reduce early morning peaks in IOP. PREDISPOSITION TO HIGHER OUT-OF-OFFICE IOP NTG progression despite IOP in the low teens during in-office readings may indicate a greater genetic predisposition to higher early morning IOP, Prof Pasquale said. He cited a study involving 176 patients with suspected or established primary open-angle glaucoma. It showed iCare HOME tonometer readings in the early morning hours were 4.3 mmHg higher among those with the highest polygenetic risk score for elevated IOP than among those with the lowest scores.

“IOP tends to be highest in the early morning when nitric oxide signalling tends to be lowest. These outside-of-the-office intraocular pressure readings could be very important in explaining why these patients progress,” he said.

Prof Pasquale also recommended investigating the possibility of Mendelian variants in patients with a family history of glaucoma in young adulthood. Variants associated with NTG include optineurin (OPTN), TANK binding kinase 1 (TBK1) and myocilin (MYOC) which are present in around 3% of NTG cases. In the case of TBK1 duplication NTG, single-digit target IOPs are necessary because although its progression rate is slow, the disease starts at a young age.

Patients who have undergone corneal refractive surgery might also require single-digit IOP targets because of low corneal hysteresis. Low corneal hysteresis is associated with greater IOP fluctuations and more rapid visual field progression, he noted.

HOW TO TREAT Prof Pasquale emphasised there is an abundance of evidence in the literature showing single-digit target IOPs slow progression in eyes with open-angle glaucoma. Research has consistently shown trabeculectomy reduces visual field progression in patients with pre-operative IOP in the mid-teens.

“Trabeculectomy must survive because trabeculectomy represents a relatively safe and effective way to achieve singledigit intraocular pressures,” he said.

Recent studies suggest that mindfulness meditation can reduce IOP still further in eyes that have already undergone trabeculectomy. In one study, patients who performed daily 45-minute mindfulness meditation sessions had significantly lower IOP and less IOP fluctuation compared to the control patients. The meditation group also had significant changes in trabecular meshwork gene expression, including upregulation of neuroprotective genes, downregulation of pro-inflammatory genes, and upregulation of nitric oxide synthase 1 (NOS1) and NOS3.

Louis R Pasquale MD, FARVO is the Shelley and Steven Einhorn Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, USA.