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Should There Be More Concern Regarding the Ubiquitous Use of Nasal and Inhaled Corticosteroids

Written by Larry J Alexander OD FAAO Friday, 01 February 2013

As with most things in my life, I seem to learn things the hard way. A few years ago, I was following a 47 year-old patient with a strong family history of glaucoma. He came in every 6 months and was particularly annoying because he always asked more questions than I deemed appropriate. His intraocular pressure always ran around 16 mm Hg O.U. but on one particular day I measured 27 mm Hg. I told him that it appeared that we should start treatment with a prostaglandin and we agreed that he should recheck in one month. There was no apparent structural damage nor functional loss and the angles were open by gonioscopy. When he returned in one month his pressure was down but he said he thought “I had missed something and that he was sure he shouldn’t be on medication.”

Well, as you can imagine I was insulted because doctors know everything.  He said he had gone onto the internet and found that one of the medications he was using could create the rise in IOP and that medication was the Nasonex that he had been using for years.  I had reviewed those issues within the last 2 years and assured him that the literature reported no association.  I also reviewed his chart and there was no mention of Nasonex….he revealed that he didn’t really consider a nose spray a medication so did not report it.  To make a long story short we discontinued the Nasonex, the pressure went down and he became a glaucoma suspect again.  With all that being said, the patient was a steroid responder and certainly that is a prognostic indictor for the future development of glaucoma.  That was coupled with a strong family history.  At that point I started re-reviewing the literature and found some interesting issues.  When I had originally seen the patient, the Nasonex insert did not list a rise in IOP as a potential complication.  Now the website lists glaucoma as a potential problem but sites it as a pre-treatment issue.

Can this:

image2

Cause this?

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Important Safety Information about NASONEX http://www.nasonex.com/nasx/index.jsp Some people may have eye problems, including glaucoma and cataracts. You should have regular eye exams.

Also there are a number of blogs and websites addressing the litigious issues associated with this medication.  Likewise there are websites advertising the acquisition of these products without a prescription. 

NASAL AND INHALED STEROIDS

AVAILABLE PRODUCTS

Some of the nasal steroid medications which are used to treat nasal allergy symptoms include:

  1. Beconase
  2. Flonase
  3. Nasocort
  4. Nasonex
  5. Rhinocort
  6. Veramyst
  7. Qnasl
  8. Zetonna
  9. generic fluticasone

Some of the Inhaled steroid medications which are used for asthma control include: http://www.webmd.com/asthma/guide/asthma-control-with-anti-inflammatory-drugs

  1. Advair (a combination drug that includes a steroid and a long-acting bronchodilator drug)
  2. Aerobid
  3. Asmanex
  4. Azmacort
  5. Dulera (a combination drug that also includes a long-acting bronchodilator drug)
  6. Flovent
  7. Pulmicort
  8. Symbicort (a combination drug that includes a steroid and a long-acting bronchodilator drug)
  9. Qvar

Even on webmd.com under the side effects, there is no mention the possibility of glaucoma developing: http://www.webmd.com/allergies/guide/allergy-medications?page=2

Potential steroid side effects with long-term use include:
Growth suppression, Diabetes, Cataracts of the eyes, Bone thinning osteoporosis, Muscle weakness

Side effects of inhaled steroids may include cough, hoarseness, or fungal infections of the mouth.

ASSESSMENT OF THE STUDIES

My objective in this report is not to damn the utilization of nasal and inhaled corticosteroids, as the drug class both improves and saves lives.  My objective is, rather, to increase the awareness of the potential rise in IOP associated with these medications, especially over the long term and determine the risk factors based on scientific evidence and clinical logic.

While the scientific reports are controversial and somewhat contentious, there must be a health alert issued on the use and abuse of topical, inhaled and intranasal steroids regarding the potential impact on the genesis of glaucoma.  While considered by most doctors and patients to be relatively innocuous (my patient did not even consider it a drug) the following evidence-based reports support the caution of judicious use of topical, inhaled and intranasal steroids.

STUDIES THAT SUPPORT THE HYPOTHESIS THAT NASAL AND INHALED GLUCOCORTICOIDS MAY PRECIPITATE INCREASE INTRAOCULAR PRESSURE

A recommendation in a 1995 study was that “Corticosteroids by nasal spray or inhalation may cause ocular hypertension in susceptible patients.” The authors mandated surveillance of IOP in patients using these medications. 1 Unfortunately the characteristics of the “susceptible patients” were not elucidated.  Another landmark study reported that users of high doses of inhaled steroids prescribed regularly for 3 or more months were at increased risk for increased IOP and should have intraocular pressure monitoring. The authors go on to say that prolonged administration of high doses of inhaled glucocorticoids increases the risk of Ocular Hypertension and Primary Open Angle Glaucoma.  They reported that patients with asthma who take high doses of inhaled steroids for more than three months were 44% more likely to develop glaucoma than non-users of intranasal steroids.  A high dose was defined as 1500 mcg or more of flunisolide or 1600 mcg or more of any other inhaled steroid. 2  In a companion paper Garbe et al concluded that “Prolonged administration of high doses of inhaled corticosteroids increases the likelihood of undergoing cataract extraction in elderly patients.” 3 A 2003 paper stated that about 30% of people are considered to be potential steroid responders.  This author also stated that logic would dictate that regular eye examinations are indicated for persons taking steroids. 4 A 2009 report cited that “About 40% of the general population will develop elevated intraocular pressure (IOP) within 4–6 weeks of topical ocular administration of Glucocorticoids.” 5

If you consider patients with myopia above 5 diopters and evaluate the following chart reporting the findings of a 1966 study you will see that these patients are more prone to be steroid responders as well.   This chart also demonstrates the strong relationship of steroid response to family relationships.  Known POAG patients demonstrated a very strong response to steroids, as do POAG Offspring, POAG Siblings and Patients above 5 diopters of myopia. 6

This observation is further corroborated by a 1999 report that stated that persons with a family history of glaucoma, have a strong association between inhaled corticosteroid use and the presence of either glaucoma or elevated IOP. 7

Gartlehner et al evalutated th safety of inhaled corticosteroids in patients with COPD and stated that “Observational evidence, however, indicates a dose-related risk of cataract and open-angle glaucoma.” 8 

Steroid Response in Various Groupings of Patients6

table

Dr. Rick Wilson in the Wills site http://willsglaucoma.org/steroid-use-and-iop reports in a discussion that 5% of the general population of patients are steroid responders while 95% of POAG patients are steroid responders.   That is fairly consistent with the table shown above.  He further states that if steroid use is prolonged, 50% or more of the population are steroid responders.

A 2005 study reported that significant reduction in IOP occurred with nasal steroid discontinuation in patients with glaucoma. 9 This was corroborated in a 2010 report suggesting that discontinuing nasal steroids might lower intraocular pressure in glaucoma. 10 A 2012 report blatantly states “Glucocorticoids (GCs) are potent anti-inflammatory agents used successfully to treat a variety of diseases, but with several potentially serious side effects. In the eye, Glucocorticoid therapy can cause ocular hypertension and secondary open-angle glaucoma.” 11-13

STUDIES THAT DO NOT SUPPORT THE HYPOTHESIS THAT NASAL AND INHALED GLUCOCORTICOIDS MAY PRECIPITATE INCREASE INTRAOCULAR PRESSURE

In contrast to the studies that advocate caution in the use of nasal and inhaled steroids, Ozturk et al reported in 1998 that hat intranasal corticosteroids can be used safely for prolonged periods without increasing the risk of ocular hypertension or Posterior Subcapsular Catatracts. 14  In a 2000 study looking at the treatment of asthma for 12-20 weeks at dosages of glucocorticoids at 200 to 1600 microg/day there was no report of increased IOP. 15  In a prospective population-based cohort study of 3,939 participants of the Rotterdam Study aged 55 years and older during a mean follow-up of 9.8 years, the use of five classes of steroids were analyzed related to the development of glaucoma.  The conclusion was that “None of the classes of steroids were associated with the incidence of OAG in this elderly population.” 16  Another 2011 report also concluded that there were no increased odds of cataracts or glaucoma with the use of inhaled corticosteroids in a cohort of patients with COPD. 17 A 2011 study of the 2-year treatment of children with allergic rhinitis prescribed intermittent intranasal budesonide showed no ocular side effects whatsoever. 18

Another 2011 study also reported that long-term intermittent treatment for 3-6 years with inhaled corticosteroids seemed to be safe in reference to ocular issues. 19 A 2005 report attested to the fact that the use of inhaled steroids in children with asthma was probably safe as far as not inducing posterior subcapsular cataract or ocular hypertension. 20 And yet another 2009 review exhibited an equivocal summary of the relationship of intranasal steroids to intraocular pressure.  They state that the “steroid-induced response is highly variable.” 21  A 2010 study concluded that in a large group of elderly patients treated for airway disease the use of high-dose inhaled corticosteroids did not result in an increase in the risk of increased intra-ocular pressure or glaucoma that required treatment. 22 Peters states that inhaled corticosteroids have minimal side effects when taken at recommended dosages and the benefits far outweigh the risks of uncontrolled asthma. 23 This is echoed in other articles as well. 24  However, Rossi advocates room for improvement in both the understanding and use of inhaled corticosteroids. 25

The elusive final answer is still being chased by the research community.  The topic of The Effect of Nasal Steroids on Intraocular Pressure in Ocular Hypertension or Controlled Glaucoma was recently addressed in an AGS 2011 Abstract.   The study was a prospective randomized double-masked trial to evaluate the effect of 6 weeks of nasal steroids on IOP in ocular hypertension or controlled POAG.  This was a report of a Clinical Trial supported by the government.  http://clinicaltrials.gov/ct2/show/study/NCT00775489  The conclusion was that “OH and POAG subjects show no evidence of a steroid response following 6 weeks of twice daily beclomethasone nasal spray.”  26

CONCLUSIONS AND ADVICE

The entire topic regarding the potential of increased intraocular pressure secondary to the use of nasal and inhaled glucocorticoids then brings us back to the dilemma of benefits versus complications.  If a medication produces side effects that are vision threatening should the medication not be used?  Of course not, but the health care team must be cognizant of the possibilities, monitor the patient accordingly, and intervene when necessary.

More than 20% of Americans suffer from allergic rhinitis and intranasal steroids are an effective and ostensibly safe first line treatment.  Allergic rhinitis is present in up to 75% of patients with asthma and patients with allergic rhinitis are three times more likely to develop asthma. 27 The use of intranasal steroids is increasing in the population. If doctors practice patient care on incontrovertible evidence-based medicine only then a look at the topic of the possibility that nasal or inhaled steroid use being a threat to increased IOP would render an equivocal verdict.  Having said that, what kind of logical approach can we then take to this potential problem.  The use and abuse of nasal and inhaled steroids is ubiquitous so if there were a direct cause and effect relationship the world would be covered with steroid-induced glaucoma.  We cannot advocate the abolishment of the use of these medications for the same reason that we cannot advocate the discontinuance of aspirin used to help minimize the risk of cardiovascular and cerebrovascular disease based on a recent newsflash regarding the link of aspirin use to age-related macular degeneration.  In the report the authors state that regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular age-related macular degeneration. 28  http://www.ncbi.nlm.nih.gov/pubmed/23288416

The question then becomes, what advice can be digested from the studies cited that can be advantageous to our management of the patient.  Well, first of all “If it’s in the chair it isn’t rare.”  Remember how I got my education on the topic.  To develop what appears to be the logical approach to the possibility of IOP elevation secondary to nasal and inhaled steroids mandates a review of the following report from 2001.  One mustn’t ignore this in the evidence-based literature.  To quote the abstract directly, “Inhalation steroid therapy can cause ocular hypertension or open angle glaucoma. The authors describe the case of a young girl who presented with raised intraocular pressure and headaches due to the prolonged administration of nasal and inhalation steroids. The ophthalmologist should monitor the intraocular pressure in patients who use inhalation or nasal steroid therapy on a regular base. The physician or paediatrician should be aware of this complication in children with headaches or diminished visual acuity.” 29

The conclusion based on the studies presented is that patients may develop increased IOP from nasal and inhaled steroids.  If the drug is stopped in time or if there is intervention with anti-glaucoma treatment, there is no damage.  The issue then becomes, who are the most likely patients that could develop increased IOP from the use of nasal or inhaled glucocorticoids.  What categories of patients are at risk?  Who should we worry about?  The list below highlights those at greatest risk, but a conservative approach would be to assume risk for all who use nasal or inhaled glucocorticoids and manage them accordingly. 

  • Patients who currently are being treated for glaucoma or
  • Patients who have been identified as being at risk for glaucoma
  • Patients who are offspring of patients who were identified with glaucoma
  • Patients with siblings with glaucoma
  • Patients with myopia over 5 diopters
  • Patients who are known steroid responders
  • Patients who are required to use higher dosages for a prolonged period of time…there appeared to be a dosage/duration connection in some of the reports.  Note that a number of the studies that report no relationship are short-term studies, even the latest Clinical Trial reported as an AGS abstract.

The critical reality is that susceptible patients will feel nothing and will notice nothing until the damage has been done.  The concept is very similar to the plaquenil toxicity issue. Characteristics of plaquenil retinal toxicity can be related to dosage, duration, presence of kidney dysfunction, and the presence of liver dysfunction.  Discontinuation of plaquenil therapy to all would be ludicrous but not paying attention to the potential risks in certain patients would be tantamount to negligence.  Discontinuance of nasal and inhaled steroids would, likewise, be ludicrous.

With that in mind, health care providers must communicate this information to patients and include a place on the medical history for nasal and or inhaled steroids.  If we don’t do it, the patients will go online to find the information.  Likewise, you should send out a letter to pharmacists and health care providers stating that you are there to provide the assurance that their patients are not going to develop increased IOP on these medications.  This is an educational issue for health care providers that is quite simply good medicine. 

The lesson from my own experience is “If it’s in the chair, it isn’t rare.”

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About the Author(s)

Larry J Alexander OD FAAO

Larry J Alexander OD FAAO

Dr. Alexander (1948-2016) was a 1971 graduate of Indiana University School of Optometry. He served in the US Navy then served as a Professor at the University of Alabama Birmingham School of Optometry. Larry contributed to a number of chapters in textbooks and has published three editions of Primary Care of the Posterior Segment, as well as contributed to the professional literature. He also lectured extensively in the area of ocular and systemic disease. His areas of special interest included dysfunctional tear syndrome, glaucoma and macular degeneration.  His lessons are the basis for this site and he will be dearly missed. 

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