Preservative-free glaucoma therapies: double standards anyone?

December 13, 2018
Dr Anastasios G.P. Konstas
Dr Anastasios G.P. Konstas

Ophthalmologists often seek simplicity. We search for an easy answer, and insist for example, that in glaucoma management, medical therapy is made up of simple algorithms and that a prescription we write will translate into real life therapy.  Being optimists we often see positive health outcomes that are not even there.

So, perhaps a more critical and sober way of thinking about current glaucoma care may help us all. Today worldwide, medical therapy in glaucoma consists of a simple, and popular narrative: treatment starts with a preserved prostaglandin monotherapy (often generic latanoprost) and when this step proves insufficient, combined preserved therapy ensues.  In reality, before long, glaucoma therapy-related ocular surface disease develops and its repercussions negatively influence therapy success and outcome. 

There are good reasons to believe that this traditional approach to glaucoma medical therapy is not as good as we like to think and the success of our therapy long term leaves a lot to be desired.  The simplest reason for concern is that the rate of blindness in glaucoma is increasing rather than decreasing.1

Next, the ageing demographics and the increased exposure to the disease gradually conspire against us.  More importantly considerable scientific evidence now suggests that in clinical practice many glaucoma patients suffer severe consequences from the use of preserved medical therapy.2,3

It is increasingly hard to understand why in Europe we continue to prescribe preserved antiglaucoma therapies for most patients.  Why, knowing what we know today, do preservative-free therapies still only comprise a small segment of the overall glaucoma market (7% of the unit market).  The paradox is most ophthalmologists confess in private that they consider preservative-free drops superior.

Moreover, if they had glaucoma they definitely would be using preservative-free therapies 100% of the time!  Alarmingly, here is a situation where many ophthalmologists fail to practice what they hear in scientific meetings, or say in private that they would reserve for themselves. This approach cannot be right.  Over time it will unnecessarily damage the health of our patient’s eyes and such a double standard could also strain the delicate doctor-patient relationship. 

Apparently, the stumbling block in widely adopting preservative-free therapies is their higher cost.  This concern and a confusing set of health policies dictate rationing of preservative-free therapies and the “inevitable choice” of cheaper preserved (especially generic) medications.

However this poorly evidenced dogma needs closer scrutiny and longer term analysis.

First and foremost, our key responsibility is to heal, and not to adhere to health policies that lack scientific rationale while try to limit health costs.  Moreover, one should include in this agenda the overall, long term cost of unsuccessful glaucoma therapy due to preserved therapies. It can be convincingly argued that a significant proportion of failed glaucoma surgeries is a direct consequence of cumulative toxicity by preservatives.4

Beyond unsuccessful therapy, cost comparisons should somehow also take into account the only too real socio-economic “cost” of a higher rate of progression and visual loss, and the costs of the resultant dependency. For these reasons I find restricted finance based discussion on the cost of preserved versus preservative-free drops both short-sighted and problematic. For us ophthalmologists the key issue should be the insidious damage that preserved drops inflict to the ocular surface of our patients.  It is the limited success of long term glaucoma therapy and the inevitable penalty we will pay with more severe ocular surface disease, fibrosis and unsuccessful surgery that should concern us.

It is worrying, in this context, that even today the choice of preservative-free medications in many developing European countries is fairly limited.  It is also not encouraging that even in developed European countries, like Greece, the pressing priority seems to be rather cutting immediate costs rather than improving health care and outcomes to limit long term expenditure. The evolution of this treatment paradigm is not helped by there being insufficient evidence on the tangible long-term benefits that accrue with preservative-free therapies.  This relates to issues such as the difficulty and cost of conducting long-term controlled studies and partly to the novelty of these therapies.

This should not, however, be an excuse for inactivity.  All published short-term clinical studies involving treated glaucoma patients with ocular surface disease have confirmed a direct benefit by switching from preserved to preservative-free medications.3  It is logical to assume that longer-term studies will confirm an even greater benefit. 

So the battle to curb glaucoma therapy-related ocular surface disease and to enhance the success of medical therapy with preservative-free therapies should be fought on many fronts.  It is time to scrutinize our current approach to antiglaucoma medical therapy: the use of preservative-free medications is depressingly low and this should change.  Greater availability and employment of these agents will improve future outcomes of glaucoma therapy.

All this comes at a time when a better understanding emerges on how the success of antiglaucoma therapy crucially depends on improving adherence.  There is a profound, positive effect on adherence from the use of more tolerable, patient-friendly topical therapies.  

It should not be too surprising that we ophthalmologists, like doctors in other specialties, may not practice what we preach.  The current situation with preserved antiglaucoma therapies makes no sense. The real challenge is to optimize lifelong, glaucoma therapy as much as possible. Reducing the burden of preservative toxicity serves this purpose.  There is an avalanche of evidence showing that preservatives are detrimental to ocular surface health.  Now comes the hard part of implementing this new preservative-free therapy paradigm, to bring about a positive turning point in glaucoma management.  We need to practice what we preach.

It is, after all, our duty to best maintain the health of the eyes of our patients.

Disclosures:

Anastasios G. P. Konstas, MD, PhD, is affiliated with the 1st University Department of Ophthalmology, AHEPA Hospital, Thessaloniki, Greece. The views expressed are those of Dr. Konstas and do not reflect those of Ophthalmology Times Europe or UBM Medica.

References:

1. Bourne RR, Taylor HR, Flaxman SR et al. Number of people blind or visually impaired by glaucoma worldwide and in world regions 1990-2010: a meta-analysis. PLoS One 2016;11:e0162229.
2. Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F.  Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res 2010;29:312-34.
3. Holló G, Katsanos A, Boboridis KG, Irkec M, Konstas AGP.  Preservative-free prostaglandin analogs and prostaglandin/timolol fixed combinations in the treatment of glaucoma: efficacy, safety and potential advantages. Drugs 2018;78:39-64.
4. Boimer C, Birt CM. Preservative exposure and surgical outcomes in glaucoma patients: The PESO study. J Glaucoma 2013;22:730–5.