Palmitoylethanolamide (PEA) 4 your eyes: update


Palmitoylethanolamide protects the retina in glaucoma

Following on from earlier studies demonstrating that systemic
administration of palmitoylethanolamide (PEA), a fatty acid ethanolamide,
reduces intraocular pressure (IOP) in patients with glaucoma and ocular hypertension,1–3 Dr Caterina Gagliano has conducted a further study into the effects of systemic PEA on glaucoma. The results of the study —
Clinical trial for the evaluation of neuroprotective effects of
palmitoylethanolamide: Visual Field and Pattern-ERG — were communicated through an oral presentation at the EVER congress, held in Nice, France.

While previous studies have focused solely on the IOP-lowering effect of PEA, this study increased the dose of PEA administered and measured change in visual field, to assess the impact of PEA on the trabecular meshwork (TM) and its potential neuroprotective activity in glaucoma patients.

Discussing the rationale for the trial and its potential applications in glaucoma, Dr Gagliano explained, “Activation of the glial cells and the consequent neuroinflammatory response is increasingly recognized as aprominent neuropathological feature of glaucoma damage and should therefore be addressed.”

*About the trial*

The prospective, randomised, crossover, double-blind clinical trial
evaluated the effects of PEA on IOP, visual field (VF) and pattern-ERG (PERG) in primary open angle glaucoma (POAG) and ocular hypertension (OH) patients.

Prior to enrolment in the study, the 36 patients included were all
receiving topical treatment with timolol 0.5% and had undergone a minimum
of five VF tests using the Humphrey Visual Field Analyzer (Threshold 30-2)
over a 2-year period. Upon enrolment, study subjects were randomly assigned
to either Group A (PEA 300 mg orally twice daily) or Group B (placebo), and
were examined at baseline and after 6, 12, 18 and 24 months of treatment.
The assessment parameters were change of progression rate of VF using mean
deviation (MD) and pattern standard deviation (PSD). Comparison of means
was performed with the paired t-test.

“To monitor progressive change of retinal ganglion cell function, we used
the pattern electroretinograms twice annually over at least 2 years,” noted
Dr Gagliano. “The evaluation of the pattern ERG used the amplitude of P50
and N95, and each of the parameters were respected.”

*Results in traditional parameters*

PEA-treated patients experienced a statistically significant reduction in
IOP compared with the IOP lowering achieved by subjects receiving placebo
(16.94 ± 3.96 vs 13.8 ± 3.24 mmHg; P < 0.001). There was also a
statistically significant difference in the MD between the two groups
(Group A: –2.9 dB ± 2.93; Group B, –8.55 dB ± 6.51; P = 0.001). The change
in PSD reached statistical significance after 24 months of treatment (Group
A, 2.64 dB ± 1.47; Group B, 6.59 dB ± 6.51; P = 0.002). PERG amplitude
increased significantly (P < 0.01) in Group B patients compared with in
Group A patients: at 6, 12, 18 and 24 months, a significant decrease of P50
and N95 amplitude in PEA-treated patients was observed.

“Significant IOP reduction was observed in Group A,” summarized Dr
Gagliano. “At 24 months, the mean IOP decreased 16% from baseline.
Additionally, Circadian rhythm variance reduced from baseline by 10%, and a
statistically significant difference in the MD was found between the two
groups after 12, 18 and 24 months.”

Moreover, throughout the 2-year treatment period, PEA medication remained
safe and well tolerated, with no drug-related adverse events.

“These findings show substantial clinical benefits of PEA treatment in POAG
patients: reduction of IOP as well as significant improvement in VF and
PERG,” Dr Gagliano noted. “Based on this evidence we also assessed the
relevance of this neuroprotective effect of PEA to treatment in glaucoma


Dr Gagliano reported that the reason her team had chosen to research the
neuroprotective effect of PEA had been to examine the hypothesis that the
effect of PEA — which has been demonstrated to reduce the activation of
microglial cells, reducing chronic inflammation — could also work in the
same way to preserve or repair cells in glaucoma.

“We believe that targeting the signalling pathways in glial cells
responsible for neuroinflammation represents a promising new therapeutic
approach in glaucoma,” she asserted, adding, moreover, that PEA may also be
able to protect against neurotoxicity, and should continue to function even
once an insult has been initiated. “Treatment with PEA has an impact on the
degree of apoptosis, with up-regulation of pro-apoptotic BAX and
down-regulation of anti-apoptotic BCL-2 among the changes,” Dr Gagliano
noted, to explain this hypothesis.

“All these actions — the IOP-lowering effect as well as neuroprotection —
are mediated by receptor mechanism peroxisome proliferator activated
receptor alfa (PPR-alfa) and G-protein coupled receptor 55 (GPR55).”

*The future of glaucoma management?*

Dr Gagliano concluded her presentation by asserting that, if other clinical
trials and laboratory evidence support the results of this study, the
treatment paradigm in glaucoma has the potential to shift beyond the
current efforts to reduce IOP and will in addition begin to focus on our
ability to preserve visual function for glaucoma patients.

“Although there’s still much work to be done in this area, we shouldn’t
forget what a long way we’ve already come,” she asserted.


1. C. Gagliano *et al.*, *Invest. Ophthalmol. Vis. Sci.*,

2. A. Kumar *et al.*, *Invest. Ophthalmol. Vis. Sci.*, 2012;*53*(8):4416–4425.

3. E. Strobbe *et al.*, *Invest. Ophthalmol. Vis. Sci.*, Published on-line
before print 10 January 2013, doi: 10.1167/iovs.12-10899

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