February 22, 2018

BPH Medications and Intraoperative Floppy Iris Syndrome

Benign prostatic hyperplasia or BPH is a common disorder in older men, and typically presents with symptoms of urinary hesitancy, weak stream, nocturia, incontinence and recurrent urinary tract infections.1   Treatment options for this condition include alpha blockers, 5-alpha reductase inhibitors, alternative therapies such as saw palmetto extract, and surgical intervention such as transurethral resection of the prostate (TURP).  Alpha-receptor antagonists, a popular class of medication, promote smooth muscle relaxation by inhibiting smooth muscle contraction in the prostatic urethra.1   This class of medication works well for moderate to severe BPH symptoms, and is divided into two categories: selective and non-selective agents.  Non-selective agents also inhibit alpha-adrenergic receptors  in the smooth muscle of the vasculature, and therefore reduce blood pressure, but have the undesirable side-effect of orthostatic hypotension.  Non-selective agents include doxazosin (Cardura), terazosin (Hytrin), and prazosin (Minipress).  In an effort to improve the side effect profile of this class of medication, selective alpha-antagonists were designed, which do not affect blood pressure.  Selective agents include tamsulosin (Flomax) and alfuzosin (Uroxatral).  Tamsulosin is an alpha-1A-adrenergic receptor antagonist.  In 2005, Chang and Campbell described an unusual syndrome during cataract surgery characterized by a flaccid iris leading to billowing of the iris, a tendency for the iris to prolapse through surgical incisions, and progressive pupillary constriction limiting visualization during surgery.  They termed this syndrome Intraoperative Floppy Iris Syndrome or IFIS.2   This syndrome can occur with any of the alpha-antagonists, but is particularly common with tamsulosin, and is speculated to be due to a high concentration of alpha-1A receptors in the iris dilator smooth muscle which, when inhibited, leads to deficient muscle tone.3  A meta-analysis performed in 2011 showed that the odds ratio for IFIS was 40-fold higher with tamsulosin than that of alfuzosin, which is the agent next most commonly associated with the syndrome2, and a retrospective study reported that 86% of patients using Tamsulosin had IFIS compared to 15% of patients using alfuzosin5.  This syndrome is of particular concern to ophthalmologists,  because it increases the risk of complications during cataract surgery, including iris trauma, dropped lens fragments, and posterior capsular rupture.  Two issues make this situation even more complicated: at present, there is no reliable way to predict those patients who will develop IFIS prior to surgery, and the syndrome can occur despite stopping the medication.  In fact, there is no evidence that stopping the medication prior to surgery is of any benefit, and cases of IFIS have been reported as long as a year after stopping therapy.This raises the question of how to best address the issue.  At present, there are two recommendations put forth by ASCRS and the American Academy of Ophthalmology:4

      1.  Speak with the patient’s ophthalmologist before starting alpha-1 antagonists in patients with known cataracts, particularly if considering tamsulosin (Flomax)

      2.  Remind patients taking alpha-1 antagonists to report this medication to their ophthalmologist before having any eye surgery

Additionally, it may be reasonable to consider the class of 5-alpha reductase inhibitors such as Avodart (finasteride) and Proscar (dutasteride) first, or choose a nonselective alpha-antagonist before moving to a selective agent such as tamsulosin, given its very high incidence of associated IFIS.  While techniques and tools are available to help cataract surgeons reduce the risk of complications in patients with IFIS, the best option is to try and avoid the situation through planning and coordinated care.


1.   Diagnosis and management of benign prostatic hyperplasia.  Edwards JL.  Am Fam Physician. 2008 May 15;77(10):1403-10. Review.

2.  Risk factors for intraoperative floppy iris syndrome: a meta-analysis.  Chatziralli IP, Sergentanis TN.  Ophthalmology. 2011 Apr;118(4):730-5. Epub 2010 Dec 18.

3.   ASCRS White Paper: clinical review of intraoperative floppy-iris syndrome.  Chang DF, Braga-Mele R, Mamalis N, Masket S, Miller KM, Nichamin LD, Packard RB, Packer M; ASCRS Cataract Clinical Committee.  J Cataract Refract Surg. 2008 Dec;34(12):2153-62. Review.

4.   Floppy iris syndrome: why BPH treatment can complicate cataract surgery.  Chang DF.  Am Fam Physician. 2009 Jun 15;79(12):1051, 1055-6.

5.   Intraoperative floppyiris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin.  Blouin MC, Blouin J, Perreault S, Lapointe A, Dragomir A.  J Cataract Refract Surg. 2007 Jul;33(7):1227-34.

Association of Topiramate with Acute Bilateral Angle-Closure Glaucoma

Topiramate is an antiepileptic medication which has been FDA approved since 1996 to manage seizure disorders, and FDA approved since 2004 as migraine prophylaxis1.  It has also been used off-label as a weight-loss agent, and to treat depression, neuropathic pain and bipolar disorder.2   Topiramate is structurally unrelated to any other epileptic agent, as it consists of a sulfamate-substituted monosaccharide (fructose), and therefore has a side effect profile unique to its structure.2   It is excreted renally, and its most common adverse effects include: dizziness, ataxia, psychomotor slowing, weight loss, and nephrolithiasis3.  In 2001, a case of uveal effusion syndrome leading to secondary angle-closure glaucoma was reported by Banta et al4.   Between July of 2001 and October of 2002, over 115 case reports of ocular side effects and topiramate therapy had been described, most of which were bilateral acute angle-closure glaucoma.  Now well recognized, the mechanism is thought to be related to forward rotation of the iris-lens diaphragm due to supraciliary effusions, which leads to transient myopia and in some cases secondary angle-closure5.  Interestingly, in almost all cases, the angle-closure glaucoma is bilateral.  The most common presenting symptom in these patients is blurred vision, although ocular pain, headache, nausea and vomiting, pupillary abnormalities, conjunctival hyperemia and corneal edema can all be seen with acute episodes.  A majority of these cases (roughly 85%) occur within the first two weeks of starting topiramate therapy, and do not seem to be dose related, although some cases appear to be precipitated by an increase in dosage regimen2.  This particular type of angle-closure is unusual, but important to recognize for several reasons.  First, it is induced by topiramate and reversible (although other sulfa containing medications can cause the same syndrome), with several cases showing recurrences of signs and symptoms with rechallenge of medication, and therefore the treatment of choice is cessation of the medication.  Secondly, it usually causes angle-closure bilaterally, which is unusual in pupillary block acute angle-closure, and has the potential to cause total vision loss if not identified/treated appropriately.  Finally, standard therapy such as laser iridotomy is ineffective in treating this type of angle-closure glaucoma, as pupillary block is not present.  Instead, the treatment of choice is cycloplegics, which dilate the pupil and move the lens-iris diaphragm posteriorly, and are absolutely contraindicated in typical pupillary-block angle-closure glaucoma.  Therefore, the therapy of choice for this condition is the COMPLETE OPPOSITE for typical pupillary block angle-closure glaucoma.  Other ocular side effects have been associated with topiramate including: onset of acute bilateral myopia (up to 8.75 diopters), bilateral suprachoroidal effusions, blepharospasm, and myokymia; nystagmus and diplopia have been seen in roughly 15% of patients on larger doses of 200 mg to 400 mg daily2.  While these side effects may also be problematic, they do not have the potential to lead to permanent visual loss.

Therefore, if you start a patient on topiramate therapy, it is important to instruct them to notify you immediately with any visual changes, particularly within the first two weeks of starting therapy, or when increasing their dosage regimen.  If a patient does complain of visual changes or other symptoms such as eye pain, headache, or nausea, they should be referred immediately for ophthalmologic evaluation, and if examination findings confirm acute onset of myopia or angle-closure glaucoma, the drug should be stopped or tapered as soon as feasible based on their indication for therapy.


1.  Peripheral iridoplasty efficacy in refractory topiramate-associated bilateral acute angle-closure glaucoma.   Zalta AH, Smith RT.  Arch Ophthalmol. 2008 Nov;126(11):1603-5.

2.  Topiramateassociated acute, bilateral, secondary angle-closure glaucoma.  Fraunfelder FW, Fraunfelder FT, Keates EU.  Ophthalmology. 2004 Jan;111(1):109-11.

3.  Case reports and small case series: topiramate-induced acute myopia and retinal striae.  Sen HA, O’Halloran HS, Lee WB.  Arch Ophthalmol. 2001 May;119(5):775-7.

4.  Presumed topiramate-induced bilateral acute angle-closure glaucoma.  Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS.  Am J Ophthalmol. 2001 Jul;132(1):112-4.

5.  Uveal effusion and secondary angle-closure glaucoma associated with topiramate use.  Sankar PS, Pasquale LR, Grosskreutz CL.  Arch Ophthalmol. 2001 Aug;119(8):1210-1.


Association of Normal Tension Glaucoma and Obstructive Sleep Apnea/Hypopnea Syndrome

Several recent studies have shown an association between moderate and severe obstructive sleep apnea/hypopnea syndrome (OSAHS), and normal tension glaucoma (NTG).  The prevalence of NTG increases with age, and is roughly 0.2% in patients aged 43 to 54 years, and 1.6% in patients over 75 years of age1.  A recent study by Lin et al.showed a prevalence of 5.7% in patients with obstructive sleep apnea of all severity, and 7.1% in patients with moderate to severe OSAHS1.  Other studies have shown an even higher prevalence of NTG, as high as 27%2.  Despite the variability in prevalence between studies, it is clear that there is a strong association between OASHS and NTG.  Why is this, and why is it important?  Our current understanding of NTG identifies risk factors for developing NTG.  These include abnormal ocular blood flow, abnormal blood coagulation, systemic hypotension, ischemic vascular diseases, and autoimmune disease1.  One possible explanation is that OSAHS creates transient hypoxemia and increased vascular resistance, which impairs optic nerve head perfusion and leads to nerve tissue injury at what would otherwise be tolerable intraocular pressures1.  Patients with OSAHS by definition suffer from five to sometimes hundreds of episodes of hypoxia and hypercapnia nightly, lasting anywhere from ten seconds up to two minutes.  These repeated episodes would then lead to repetitive nerve injury and eventually axonal death, loss of viable nerve tissue, and visual field loss.  Episodic hypoxia also leads to increased risk of hypertension, pulmonary hypertension, cardiac arrhythmias, myocardial infarction, congestive heart failure, and cerebrovascular accidents, and so NTG may represent the ophthalmic manifestations of the effects of repeated systemic hypoxia1.  It is also possible that the treatment for OSAHS may exacerbate optic nerve perfusion difficulties.  A study by Kiekens et al. showed that CPAP therapy caused additional IOP increase, particularly at night, a time when blood pressure and perfusion pressure tends to be low3.  It is particularly important to remember this association because the intraocular pressure, which has traditionally been used as a major determinant in whether or not someone has glaucoma, is normal on evaluation.  In these cases, if the clinician is not paying particular attention to the structure of the optic nerve, and specifically looking for this disorder, the diagnosis can be missed.  Untreated and unrecognized, over time this can lead to irreversible vision loss and potentially blindness.  Several studies confirm that patients with OSAHS have reduced nerve fiber layer measurements, indicating nerve tissue loss, and a high incidence of visual field defects, confirming that many of these patients may have visual impairment occurring and not be aware of a problem4,5.

So, the next time you are taking care of a patient with OSAHS, you may want to ask if they have specifically been evaluated for NTG, and consider referring them for evaluation if they have not.  Like most chronic diseases, early detection and treatment is paramount in achieving good outcomes.  Conversely, ophthalmologists evaluating patients with normal tension glaucoma should consider referral and evaluation for OSAHS, as this may be an identifiable and treatable risk factor for the disease.


1.   Normal Tension Glaucoma in Patients With Obstructive Sleep Apnea/Hypopnea Syndrome.  Lin PW, Friedman M, Lin HC, Chang HW, Wilson M, Lin MC.  J Glaucoma. 2010 Sep 16. [Epub ahead of print]

2.  Prevalence of glaucoma in patients with obstructive sleep apnoea–a cross-sectional case-series.  Bendel RE, Kaplan J, Heckman M, Fredrickson PA, Lin SC.  Eye (Lond). 2008 Sep;22(9):1105-9. Epub 2007 May 4.

3.   Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea.  Kiekens S, Veva De Groot, Coeckelbergh T, Tassignon MJ, van de Heyning P, Wilfried De Backer, Verbraecken J.  Invest Ophthalmol Vis Sci. 2008 Mar;49(3):934-40.

4.   Moderate to severe obstructive sleep apnoea patients is associated with a higher incidence of visual field defect.  Tsang CS, Chong SL, Ho CK, Li MF.  Eye (Lond). 2006 Jan;20(1):38-42

5.  Retinal nerve fibre layer measurements are reduced in patients with obstructive sleep apnoea syndrome.  Kargi SH, Altin R, Koksal M, Kart L, Cinar F, Ugurbas SH, Ayoglu F.  Eye (Lond). 2005 May;19(5):575-9.

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