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## **Meet the editor**

Farhan Husain Zaidi is a Consultant Ophthalmic Surgeon at Maidstone and Tunbridge Wells NHS Trust and Honorary Fellow at Moorfields Eye Hospital in London. After graduating from University College London Medical School with Honours in 1994 he was awarded the Fellowship of the Royal College of Surgeons of England in 1997 after training in clinical surgery in general, after which he started specialising in ophthalmology obtaining the Membership of the Royal College of Surgeons of Edinburgh in ophthalmology and the Membership of the Royal College of Ophthalmologists. He was made a Fellow of the Royal College of Surgeons of Edinburgh in 2005. He was awarded a PhD in ophthalmology, surgery and vision science from Imperial College London in 2008, which included research on the light-scattering effects of cataracts in the context of searching for melanopsin-containing ganglion cell photoreceptors in humans. His higher surgical training was also based in London, the final three years of which were spent at Moorfields Eye Hospital where he worked as a registrar and in advanced sub-specialty training positions, during which time he was awarded the Fellowship of the Royal College of Ophthalmologists in 2010 before completing his higher training in 2011. In addition to practicing high volume cataract surgery and training other surgeons Farhan Zaidi has published articles in peer-reviewed journals on cataract surgery, including the relationship between surgical training, supervision and surgical outcomes. He is a reviewer for a number of peer-reviewed journals including for clinical studies in the field of cataract surgery.

Contents

**Preface IX**

**Section 1 Pre-Operative Care 1**

Chapter 2 **Prevention and Management of**

James A. Davison

Hiroshi Kobayashi

Chapter 4 **Pre-Operative Evaluation 43**  Mammie Motiang

Alparslan Apan

Chapter 6 **The History of Cataract Surgery 75**  F.J. Ascaso and V. Huerva

Farhan Husain Zaidi

Chapter 7 **Major Advances in Cataract Surgery 91**

Chapter 1 **Pathophysiology and Pre-Operative Evaluation of Patients**

Christopher Watts and Thomas A. Oetting

**Intraoperative Floppy Iris Syndrome 15**

Chapter 3 **Anticoagulant and Antiplatelet Use in Cataract Surgery and Combined with Posterior Vitrectomy 31**

Chapter 5 **Anaesthetic Management in Cataract Surgery 53**

**Section 2 Operative Surgery and the History of Cataract Surgery 73**

Chapter 8 **In-Vitro Thermal Study of Different Tips in Various Operating Modes of the Sina Phacoemulsification System 105**  Radin Tahvildari, Hanieh Fattahi and Ahmad Amjadi

**at Risk for Intraoperative Floppy Iris Syndrome (IFIS) 3**  Matthew A. Cantrell, Heather R. Bream-Rouwenhorst,

### Contents

#### **Preface XIII**

X Contents

Contents VII

Chapter 21 **Toxic Anterior Segment Syndrome (TASS) and**

Chapter 22 **Macular Edema and Cataract Surgery 323** Miltiadis K Tsilimbaris, Chrysanthi Tsika,

**Section 4 Cataract Surgery in Special Situations 337**

Chapter 23 **Cataract Surgery and Dry Eye 339** Ramin Daneshvar

Chapter 24 **Pseudoexfoliation and Cataract 353**

Chapter 25 **Cataract Surgery in Retina Patients 371**

A.C. Schefler and T.G. Murray

Chapter 28 **The Management of Age Related Cataract in Sub-Saharan Africa 419**

Chapter 26 **Cataract Surgery in Patients with a History of Retinoblastoma and Melanoma 391**

**with a Severe Learning Disorder 407**

Kemal Örnek

Chapter 27 **Cataract Surgery in People**

Nel T. Tijmes

Lawan Abdu

Rosario Díez, Lourdes Jordano and César Hita

**Prophylaxis Against Postoperative Endophthalmitis 301**

Vasilios Diakonis, Aleksandra Karavitaki and Ioannis Pallikaris

George K. Andrikopoulos and Sotirios P. Gartaganis

Chapter 22 **Macular Edema and Cataract Surgery 323**  Miltiadis K Tsilimbaris, Chrysanthi Tsika, Vasilios Diakonis, Aleksandra Karavitaki and Ioannis Pallikaris

#### **Section 4 Cataract Surgery in Special Situations 337**

Chapter 23 **Cataract Surgery and Dry Eye 339**  Ramin Daneshvar

VI Contents

Chapter 9 **Hydrodynamic Analysis and Irrigation Device Design**

Takao Tanaka, Maiko Hirose, Shigemitu Ishii,

**Iris Syndrome (IFIS) in Cataract Surgery 143**

**Vitreous Loss During Cataract Surgery 173**

Anders Behndig, Björn Lundberg and Gunnie Bäckström

Anselmo G. De Oliveira, José A. Cardillo, Fernando Paganelli, Acácio A. S. Lima-Filho and Arnóbio A. Da Silva-Júnior

**Techniques in Cataract Surgery 121**

Chapter 10 **Dual OVD (Ophthalmic Viscosurgical Devices)**

Satoshi Fujita and Keisuke Kimura

Chapter 12 **Intracameral Mydriatics in Cataract Surgery 149**

Taiji Sakamoto and Toshio Hisatomi

**Drugs for Cataract Surgery 183**

Chapter 15 **Combined Cataract and Glaucoma Surgery 197**

Rehab Ismail and Ahmed Sallam

Emin Kurt and Hüseyin Mayalı

Elvis Ojaimi and David T. Wong

Chapter 20 **Endophthalmitis Following Cataract Surgery:**

Chapter 18 **Post-Operative Infections Associated with Cataract Surgery 259**

Chapter 16 **Complications Associated with Cataract Surgery 221**

Chapter 19 **Endophthalmitis, Prevention and Treatment 265**

Avinash Pathengay, Stephen G. Schwartz, Harry W. Flynn Jr. and Darlene Miller

Chapter 17 **Early Post-Operative Complications in Cataract Surgery 245**

Baseer U. Ahmad, Igor Estrovich and Thomas Steinemann

**Clinical Features, Treatment and Prophylaxis 285**

**Sealing Technique 137**

Chapter 11 **Management of Intraocular Floppy**

Chapter 14 **Trans-Scleral Controlled-Release of**

Allan Storr-Paulsen

Chapter 13 **Chromovitrectomy in**

Atilla Bayer

**Section 3 Complications 219**

Yury Spirochkin

**for the Coaxial and Bimanual Phacoemulsification**

Preface

overall field of cataract surgery.

patients undergoing cataract surgery.

It has been a privilege to have been tasked with editing a book with an international authorship including many distinguished contributors on the topic of cataract surgery. Not only is cataract surgery the most commonly performed operation in the world but

Inevitably one must decide which topics to focus discussion on in such a work to make it readable, original, and lasting. The generality of the field of cataract surgery is considered, often through gaining a deeper insight by considering the development of advances in the field. More specific discussions have focussed on areas that have remained and likely will remain topical owing to their practical importance. I have sought to include work which is original but which underpins core aspects to the

This book is divided into four sections. The first, Pre-operative Care, is considered from a variety of perspectives – the pathophysiology of floppy iris syndrome, an area that has been topical for the best part of a decade, as well as how to reduce risk to patients from this condition. Also included are studies clearly and concisely considering the effects of antiplatelet and anticoagulant drugs in cataract and vitreoretinal surgery, followed by a broader overview of pre-operative assessment in

In the second section, Operative Surgery and the History of Cataract Surgery, a variety of topics are introduced by study of the main milestones in the development of cataract surgery, both directly but also by studying the effects of parallel advances in vision science especially optics. The chapter on Major Advances in Cataract Surgery, which I wrote myself, I included despite my duality of interest as Editor as the publishing house and my predecessor as Editor, who started the project accepted the Chapter for publication, and it remained relevant to the final book. After these overviews of cataract surgery surgical instrumentation and fluidics are discussed from a physical scientific and mathematical perspective. Studies on the use of ophthalmic viscosurgical devices to reduce intraocular pressure rises in small incision cataract surgery are presented, a topic that leads to discussions of the management of intraocular floppy iris syndrome. These are followed by descriptions of studies of a variety of pharmacological adjuncts administered during cataract surgery. Technical

cataract remains the leading cause of blindness worldwide.

### Preface

It has been a privilege to have been tasked with editing a book with an international authorship including many distinguished contributors on the topic of cataract surgery. Not only is cataract surgery the most commonly performed operation in the world but cataract remains the leading cause of blindness worldwide.

Inevitably one must decide which topics to focus discussion on in such a work to make it readable, original, and lasting. The generality of the field of cataract surgery is considered, often through gaining a deeper insight by considering the development of advances in the field. More specific discussions have focussed on areas that have remained and likely will remain topical owing to their practical importance. I have sought to include work which is original but which underpins core aspects to the overall field of cataract surgery.

This book is divided into four sections. The first, Pre-operative Care, is considered from a variety of perspectives – the pathophysiology of floppy iris syndrome, an area that has been topical for the best part of a decade, as well as how to reduce risk to patients from this condition. Also included are studies clearly and concisely considering the effects of antiplatelet and anticoagulant drugs in cataract and vitreoretinal surgery, followed by a broader overview of pre-operative assessment in patients undergoing cataract surgery.

In the second section, Operative Surgery and the History of Cataract Surgery, a variety of topics are introduced by study of the main milestones in the development of cataract surgery, both directly but also by studying the effects of parallel advances in vision science especially optics. The chapter on Major Advances in Cataract Surgery, which I wrote myself, I included despite my duality of interest as Editor as the publishing house and my predecessor as Editor, who started the project accepted the Chapter for publication, and it remained relevant to the final book. After these overviews of cataract surgery surgical instrumentation and fluidics are discussed from a physical scientific and mathematical perspective. Studies on the use of ophthalmic viscosurgical devices to reduce intraocular pressure rises in small incision cataract surgery are presented, a topic that leads to discussions of the management of intraocular floppy iris syndrome. These are followed by descriptions of studies of a variety of pharmacological adjuncts administered during cataract surgery. Technical

#### X Preface

considerations are discussed in cataract surgery when combined with trabeculectomy, non-penetrating glaucoma surgery, and less common glaucoma procedures.

In the third section of the book, Complications, in addition to a broad overview of problems from cataract surgery, the topic of endophthalmitis and its differential diagnoses includingtoxic anterior segment syndrome are considered in depth by a number of authors from different perspectives. The problem of postoperative macular oedema is also considered from basic scientific, pharmacological and clinical perspectives.

In the final section, Cataract Surgery in Special Situations, both specific conditions and extreme environments are considered. The common problem of dry eye, both before and after cataract surgery, is discussed with exceptional clarity including rarely described insights into the underlying anatomy and disturbed pathophysiology of the condition in the context of cataract surgery. The implications to the management of cataract posed by pseudoexfoliation, as well as both common and rare retinal diseases, and the very rare but important situation of patients with a history of intraocular tumours are considered in this context also. In the last two chapters the challenges posed by patients with severe learning disorders in the Netherlands are discussed, contrasting with the problems posed by even routine cataract surgery in sub-Saharan Africa.

A multi-author works poses editorial challenges, especially when the contributions involve a combination of topics ranging from the history of medicine through to highly technical descriptions of experiments from both the physical and biological sciences, including submissions from many different continents. After the importance of the topic itself my next consideration has been the clarity of presentation. Some otherwise interesting submissions could not be accepted for this reason only. With the staff from the publishing house I permitted the contributors to express themselves in the language of the international medical and scientific community in the field which uses both British English and American English. References have been accommodated in House Style or, owing to the sheer variety of articles, a format very closely resembling it balancing uniformity and readability with technical clarity. The choice of chapters should also ensure the book, or at least large sections of it, remain significantly useful and informative into the future in what is an ever-developing field which is continually advancing on many fronts.

**Farhan Husain Zaidi**

Consultant Ophthalmic Surgeon, Maidstone and Tunbridge Wells NHS Trust, Kent, Honorary Fellow, Moorfields Eye Hospital, London, UK

X Preface

perspectives.

Africa.

considerations are discussed in cataract surgery when combined with trabeculectomy,

In the third section of the book, Complications, in addition to a broad overview of problems from cataract surgery, the topic of endophthalmitis and its differential diagnoses includingtoxic anterior segment syndrome are considered in depth by a number of authors from different perspectives. The problem of postoperative macular oedema is also considered from basic scientific, pharmacological and clinical

In the final section, Cataract Surgery in Special Situations, both specific conditions and extreme environments are considered. The common problem of dry eye, both before and after cataract surgery, is discussed with exceptional clarity including rarely described insights into the underlying anatomy and disturbed pathophysiology of the condition in the context of cataract surgery. The implications to the management of cataract posed by pseudoexfoliation, as well as both common and rare retinal diseases, and the very rare but important situation of patients with a history of intraocular tumours are considered in this context also. In the last two chapters the challenges posed by patients with severe learning disorders in the Netherlands are discussed, contrasting with the problems posed by even routine cataract surgery in sub-Saharan

A multi-author works poses editorial challenges, especially when the contributions involve a combination of topics ranging from the history of medicine through to highly technical descriptions of experiments from both the physical and biological sciences, including submissions from many different continents. After the importance of the topic itself my next consideration has been the clarity of presentation. Some otherwise interesting submissions could not be accepted for this reason only. With the staff from the publishing house I permitted the contributors to express themselves in the language of the international medical and scientific community in the field which uses both British English and American English. References have been accommodated in House Style or, owing to the sheer variety of articles, a format very closely resembling it balancing uniformity and readability with technical clarity. The choice of chapters should also ensure the book, or at least large sections of it, remain significantly useful and informative into the future in what is an ever-developing field

Consultant Ophthalmic Surgeon, Maidstone and Tunbridge Wells NHS Trust, Kent,

Honorary Fellow, Moorfields Eye Hospital, London,

**Farhan Husain Zaidi**

UK

which is continually advancing on many fronts.

non-penetrating glaucoma surgery, and less common glaucoma procedures.

**Section 1**

**Pre-Operative Care**

**Section 1**

**Pre-Operative Care**

**1**

 *USA*

**Syndrome (IFIS)**

*Practice and Science, Iowa City, Iowa*

**Pathophysiology and Pre-Operative Evaluation**

**of Patients at Risk for Intraoperative Floppy Iris**

Intraoperative Floppy Iris Syndrome (IFIS) has received a significant amount of attention and subsequent research since it was first reported in 2005 (Bell et al., 2009; Blouin et al., 2007; Chang & Campbell, 2005; Chang et al., 2007; Oshika et al., 2007; Srinivasan et al., 2007; Takmaz & Can, 2007). Current and former uses of alpha-1 adrenergic receptor (α1AR) antagonists—most notably tamsulosin—appear to be at the highest risk for this surgical complication (Chang & Campbell, 2005). IFIS is characterized by loss of muscle tone in the iris, thereby preventing mydriasis and involves a triad of pupil constriction, fluttering and billowing of the iris stroma, and propensity for iris prolapse during cataract surgery (Chang & Campbell, 2005). While α1AR antagonists are often used for various urological conditions, they also block α1AR receptors in the iris dilator muscle and may worsen muscle tone and lead to the iris billowing sometimes seen in cataract surgery. Without adequate pupil dilation, IFIS reduces visualization of the surgical field, including the cataract itself. This impairs removal and can lead to other complications including rupture of the posterior capsule, which further increases the risk of other vision-threatening complications of

Since there is a significant association between α1AR antagonist use and IFIS, a brief review of the indications of α1AR antagonists is necessary to identify the at-risk population. The principal indication is treatment of benign prostatic hyperplasia (BPH). This urological disorder shares risk factors with cataract development, with advanced age being the most significant (Congdon et al., 2004). If left untreated, BPH increases risk for significant complications including acute urinary retention, recurrent urinary tract infections, and urinary incontinence (Crawford et al., 2006). In patients with mild BPH as indicated by an American Urological Association (AUA) scores of 8 or less, pharmacotherapy may not be indicated as lower urinary tract symptoms (LUTS) often improve spontaneously. Identifying

**1. Introduction**

cataract surgery (Schwinn & Afshari, 2006).

**2. Use of alpha-1 adrenergic receptor (AR) antagonists**

Matthew A. Cantrell1, Heather R. Bream-Rouwenhorst1,

*1University of Iowa College of Pharmacy, Department of Pharmacy*

*2University of Iowa Carver College of Medicine, Iowa City, Iowa*

Christopher Watts2 and Thomas A. Oetting2

### **Pathophysiology and Pre-Operative Evaluation of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS)**

Matthew A. Cantrell1, Heather R. Bream-Rouwenhorst1, Christopher Watts2 and Thomas A. Oetting2 *1University of Iowa College of Pharmacy, Department of Pharmacy Practice and Science, Iowa City, Iowa 2University of Iowa Carver College of Medicine, Iowa City, Iowa USA*

#### **1. Introduction**

Intraoperative Floppy Iris Syndrome (IFIS) has received a significant amount of attention and subsequent research since it was first reported in 2005 (Bell et al., 2009; Blouin et al., 2007; Chang & Campbell, 2005; Chang et al., 2007; Oshika et al., 2007; Srinivasan et al., 2007; Takmaz & Can, 2007). Current and former uses of alpha-1 adrenergic receptor (α1AR) antagonists—most notably tamsulosin—appear to be at the highest risk for this surgical complication (Chang & Campbell, 2005). IFIS is characterized by loss of muscle tone in the iris, thereby preventing mydriasis and involves a triad of pupil constriction, fluttering and billowing of the iris stroma, and propensity for iris prolapse during cataract surgery (Chang & Campbell, 2005). While α1AR antagonists are often used for various urological conditions, they also block α1AR receptors in the iris dilator muscle and may worsen muscle tone and lead to the iris billowing sometimes seen in cataract surgery. Without adequate pupil dilation, IFIS reduces visualization of the surgical field, including the cataract itself. This impairs removal and can lead to other complications including rupture of the posterior capsule, which further increases the risk of other vision-threatening complications of cataract surgery (Schwinn & Afshari, 2006).

#### **2. Use of alpha-1 adrenergic receptor (AR) antagonists**

Since there is a significant association between α1AR antagonist use and IFIS, a brief review of the indications of α1AR antagonists is necessary to identify the at-risk population. The principal indication is treatment of benign prostatic hyperplasia (BPH). This urological disorder shares risk factors with cataract development, with advanced age being the most significant (Congdon et al., 2004). If left untreated, BPH increases risk for significant complications including acute urinary retention, recurrent urinary tract infections, and urinary incontinence (Crawford et al., 2006). In patients with mild BPH as indicated by an American Urological Association (AUA) scores of 8 or less, pharmacotherapy may not be indicated as lower urinary tract symptoms (LUTS) often improve spontaneously. Identifying

Pathophysiology and Pre-Operative Evaluation

2010)

complications.

of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS) 5

al., 1992). Specifically, use of α1AR antagonists for BPH relieves straining and hesitancy,

Commonly used second-generation α1AR antagonists include doxazosin and terazosin, although patient tolerability to these agents is variable, with the most vexing clinical problems being orthostatic hypotension and dizziness (McNaughton-Collins & Barry, 2005). Frail geriatric patients often suffer from gait problems, and the addition of a medication that could increase the potential of a fall is undesirable. The increased α1AAR selectivity of the third-generation "uroselective" agents tamsulosin and silodosin is postulated to provide additional relief of LUTS in patients with BPH without increasing the rate of serious adverse cardiovascular effects due to systemic αAR antagonism. (Cantrell et al., 2008; Cantrell et al.,

α1AR antagonists not only therapeutically inhibit prostatic α1AR but may also selectively antagonize these receptors in the iris dilator muscle. In the iris, α1AAR mediate iris dilator smooth muscle contraction whereas iris arteriolar contraction is mediated via α1BAR. Blockade of this muscle's α1AR is hypothesized to lead to poor muscle tone and the subsequent iris billowing sometimes seen in cataract surgery (Schwinn & Afshari, 2006). Figure 1 illustrates the clinical dilemma of IFIS and the subsequent potential for surgical

Adapted or Reprinted with permission from 'Editorials: Floppy Iris Syndrome: Why BPH

Fig. 1. Iris damage following cataract surgery in a patient taking tamsulosin

2009 American Academy of Family Physicians. All Rights Reserved

Treatment Can Complicate Cataract Surgery,' June 15, 2009, American Family Physician. Copyright ©

Although Chang and Campbell first associated IFIS with tamsulosin in 2005, other available α1AR antagonists were subsequently linked to IFIS as well (Dhingra et al., 2007; Herd, 2007; Package insert Rapaflo, 2008; Settas & Fitt, 2006; Venkatesh et al., 2007).

improves bladder emptying, and increases the force of the urinary stream.

suitable candidates for this strategy, often called "watchful waiting," is critical to reduce unnecessary exposure to α1AR therapy and is recommended by the AUA to invariably reduce risk for IFIS (American Urological Association [AUA], 2010). Pharmacotherapy for BPH is indicated in patients with moderate to severe disease and includes the 5-alpha reductase inhibitors (5ARI) and α1AR receptor antagonists. The 5ARI finasteride and dutasteride inhibit conversion of testosterone to dihydrotesterone, thereby shrinking the prostate; the α1AR antagonists reduce bladder outlet obstruction by relaxing prostatic smooth muscle tissue surrounding the urethra. The currently available agents include terazosin, doxazosin, alfuzosin, tamsulosin, and silodosin. They have comparable effects in symptom reduction (Djavan et al., 2004; Marks et al., 2009). While terazosin and doxazosin were originally developed for treatment of hypertension, their use for this indication has waned largely due to publication of the ALLHAT trial which demonstrated a higher incidence of hospitalization for congestive heart failure (CHF) in the doxazosin arm relative to chorthalidone (ALLHAT, 2000). Subsequent "uroselective" agents that target the α1A AR have been developed including tamsulosin, and most recently silodosin. (Package insert Flomax 2007; Package insert Rapaflo 2008). Alfuzosin's improved tolerability is largely attributable to its extended-release formulation, which prevents peaks in serum concentrations (Roehrborn et al., 2000)

Aside from the robust data demonstrating benefit in men with BPH, these agents have an emerging role in other areas of urology including facilitating the passage of urinary caliculi, as an adjunctive treatment for chronic prostatitis, following ureteral stent placement, and also improving symptoms of overactive bladder in select patients (Anothaisintawee et al., 2011; Kaplan et al., 2006; Navanimitkul & Lojanapiwat, 2010; Singh et al., 2007). Use of α1AR is limited outside the urological arena; however, some patients are undoubtedly still taking them for treatment refractory hypertension. Finally, data suggests that prazosin—an agent no longer endorsed by the AUA for treatment of BPH due to its unfavorable adverse effect and pharmacokinetic profile—has been shown to be effective in reducing nightmares secondary to post-traumatic stress disorder (PTSD) (Dierks et al., 2007; Raskind et al., 2003). It is imperative that ophthalmologists recognize the various indications for α1AR therapy to identify those at risk for IFIS. While men are at higher risk based on their respective use of α1AR for treatment of BPH, physicians should recognize that that some women may be taking these agents for other indications as well.

#### **3. Pathophysiology of IFIS**

The α1ARs are G-protein coupled receptors and subdivided into α1AAR, α1BAR, and α1DAR subtypes. Stimulation of α1AR elicits contraction of cardiac and most innervated vascular smooth muscle throughout the body (Biaggioni & Robertson, 2009). Like the iris dilator muscle, the prostate contains a significant volume of smooth muscle rich in ARs. BPH and its associated LUTS involve the prostate, urethra, bladder, and spinal cord. The α1A and α1DAR predominate in these organs, but α1BAR are also present. As the prostate grows in BPH, there is upregulation of α1AR expression, with studies demonstrating that expression of α1AARs increases up to 9-fold and α1DARs by 3-fold. This upregulation, especially of α1AAR, is thought to be responsible for the disproportionate increase in smooth muscle contraction and worsening of LUTS in patients with BPH (Thiyagarajan, 2002). Therefore, α1AR antagonists are useful in ameliorating symptoms associated with BPH by decreasing prostatic urethral resistance although this blockade may influence iris behavior (Shapiro et

suitable candidates for this strategy, often called "watchful waiting," is critical to reduce unnecessary exposure to α1AR therapy and is recommended by the AUA to invariably reduce risk for IFIS (American Urological Association [AUA], 2010). Pharmacotherapy for BPH is indicated in patients with moderate to severe disease and includes the 5-alpha reductase inhibitors (5ARI) and α1AR receptor antagonists. The 5ARI finasteride and dutasteride inhibit conversion of testosterone to dihydrotesterone, thereby shrinking the prostate; the α1AR antagonists reduce bladder outlet obstruction by relaxing prostatic smooth muscle tissue surrounding the urethra. The currently available agents include terazosin, doxazosin, alfuzosin, tamsulosin, and silodosin. They have comparable effects in symptom reduction (Djavan et al., 2004; Marks et al., 2009). While terazosin and doxazosin were originally developed for treatment of hypertension, their use for this indication has waned largely due to publication of the ALLHAT trial which demonstrated a higher incidence of hospitalization for congestive heart failure (CHF) in the doxazosin arm relative to chorthalidone (ALLHAT, 2000). Subsequent "uroselective" agents that target the α1A AR have been developed including tamsulosin, and most recently silodosin. (Package insert Flomax 2007; Package insert Rapaflo 2008). Alfuzosin's improved tolerability is largely attributable to its extended-release formulation, which prevents peaks in serum

Aside from the robust data demonstrating benefit in men with BPH, these agents have an emerging role in other areas of urology including facilitating the passage of urinary caliculi, as an adjunctive treatment for chronic prostatitis, following ureteral stent placement, and also improving symptoms of overactive bladder in select patients (Anothaisintawee et al., 2011; Kaplan et al., 2006; Navanimitkul & Lojanapiwat, 2010; Singh et al., 2007). Use of α1AR is limited outside the urological arena; however, some patients are undoubtedly still taking them for treatment refractory hypertension. Finally, data suggests that prazosin—an agent no longer endorsed by the AUA for treatment of BPH due to its unfavorable adverse effect and pharmacokinetic profile—has been shown to be effective in reducing nightmares secondary to post-traumatic stress disorder (PTSD) (Dierks et al., 2007; Raskind et al., 2003). It is imperative that ophthalmologists recognize the various indications for α1AR therapy to identify those at risk for IFIS. While men are at higher risk based on their respective use of α1AR for treatment of BPH, physicians should recognize that that some women may be

The α1ARs are G-protein coupled receptors and subdivided into α1AAR, α1BAR, and α1DAR subtypes. Stimulation of α1AR elicits contraction of cardiac and most innervated vascular smooth muscle throughout the body (Biaggioni & Robertson, 2009). Like the iris dilator muscle, the prostate contains a significant volume of smooth muscle rich in ARs. BPH and its associated LUTS involve the prostate, urethra, bladder, and spinal cord. The α1A and α1DAR predominate in these organs, but α1BAR are also present. As the prostate grows in BPH, there is upregulation of α1AR expression, with studies demonstrating that expression of α1AARs increases up to 9-fold and α1DARs by 3-fold. This upregulation, especially of α1AAR, is thought to be responsible for the disproportionate increase in smooth muscle contraction and worsening of LUTS in patients with BPH (Thiyagarajan, 2002). Therefore, α1AR antagonists are useful in ameliorating symptoms associated with BPH by decreasing prostatic urethral resistance although this blockade may influence iris behavior (Shapiro et

concentrations (Roehrborn et al., 2000)

taking these agents for other indications as well.

**3. Pathophysiology of IFIS**

al., 1992). Specifically, use of α1AR antagonists for BPH relieves straining and hesitancy, improves bladder emptying, and increases the force of the urinary stream.

Commonly used second-generation α1AR antagonists include doxazosin and terazosin, although patient tolerability to these agents is variable, with the most vexing clinical problems being orthostatic hypotension and dizziness (McNaughton-Collins & Barry, 2005). Frail geriatric patients often suffer from gait problems, and the addition of a medication that could increase the potential of a fall is undesirable. The increased α1AAR selectivity of the third-generation "uroselective" agents tamsulosin and silodosin is postulated to provide additional relief of LUTS in patients with BPH without increasing the rate of serious adverse cardiovascular effects due to systemic αAR antagonism. (Cantrell et al., 2008; Cantrell et al., 2010)

α1AR antagonists not only therapeutically inhibit prostatic α1AR but may also selectively antagonize these receptors in the iris dilator muscle. In the iris, α1AAR mediate iris dilator smooth muscle contraction whereas iris arteriolar contraction is mediated via α1BAR. Blockade of this muscle's α1AR is hypothesized to lead to poor muscle tone and the subsequent iris billowing sometimes seen in cataract surgery (Schwinn & Afshari, 2006). Figure 1 illustrates the clinical dilemma of IFIS and the subsequent potential for surgical complications.

Adapted or Reprinted with permission from 'Editorials: Floppy Iris Syndrome: Why BPH

Treatment Can Complicate Cataract Surgery,' June 15, 2009, American Family Physician. Copyright © 2009 American Academy of Family Physicians. All Rights Reserved

Fig. 1. Iris damage following cataract surgery in a patient taking tamsulosin

Although Chang and Campbell first associated IFIS with tamsulosin in 2005, other available α1AR antagonists were subsequently linked to IFIS as well (Dhingra et al., 2007; Herd, 2007; Package insert Rapaflo, 2008; Settas & Fitt, 2006; Venkatesh et al., 2007).

Pathophysiology and Pre-Operative Evaluation

Table 1. Medications associated with IFIS

required bilateral cataract surgery.

those without IFIS.

population with a historically high prevalence of BPH.

diagnosed with IFIS, highlighting its clinical significance.

of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS) 7

reported that all twenty-seven patients had "poor or moderately poor dilation." A complete list of studies assessing incidence of IFIS as well as studies assessing rates of surgical complications in patients prescribed α1AR antagonists are described in Table 2

In a prospective analysis of 900 consecutive cataract surgeries among 741 patients, IFIS was observed in sixteen patients (2.2%), fourteen of whom had documented concomitant use of tamsulosin (Chang & Campbell, 2005). In the two remaining patients, one had discontinued tamsulosin three years prior to surgery, and one had no history of tamsulosin exposure. Furthermore, IFIS was reported in both eyes of the five patients taking tamsulosin that

Despite the authors' initial identification of a potentially serious complication of cataract surgery, reported limitations of the study include lack of covariate data and the modest reported use of α1AR antagonists at 1.9% (Chang & Campbell, 2005; Schwinn & Afshari, 2006). As stated above, patients with BPH may not always require pharmacologic treatment, specifically in patients with mild American Urological Association (AUA) symptom scores (AUA, 2010). This may partially explain the relatively low percentage of tamsulosin use in a

In a recent study assessing incidence, IFIS was reported to be 1.6% among 774 patients (Takmaz & Can, 2007). IFIS was documented in 14 of 18 patients (77.8%) taking tamsulosin, and consistent with the original report by Chang and Campbell, tamsulosin use overall was observed in 2.2% of patients. Duration of tamsulosin use—although increased among patients diagnosed with IFIS—was not statistically significant relative to

A recent study directly compared the incidence of IFIS attributable to tamsulosin with an active comparator group. (Blouin et al., 2007). In this retrospective study of 64 men totaling 92 eyes, there was an increased risk of IFIS in patients exposed to tamsulosin (86.4%) when compared to alfuzosin (15.4%). The adjusted odds ratio for IFIS in patients taking tamsulosin when compared to alfuzosin was 32.15 (95% confidence interval, 2.74-377.41). Furthermore, a five-fold increase in surgical complication rates was observed in patients

Potentially, the high α1AAR-specific antagonism of tamsulosin made the association easier to identify. In rabbits, tamsulosin was more effective than the non-specific α1AR antagonist alfuzosin at blocking adrenergic-mediated iris dilator contraction (Palea et al., 2008). Interestingly, functional studies assessing the affinity of different ARs as measured by pKi (negative logarithm of the equilibrium dissociation constant) reflect higher affinity of silodosin for α1AAR compared to older agents; when compared to other currently available α1AR antagonists, silodosin is 1400 times more specific in terms of α1AAR versus α1BAR binding than doxazosin and terazosin and 40 times greater compared to tamsulosin (Thiyagarajan, 2002). It remains to be seen if silodosin has a greater likelihood to cause IFIS than the other available agents.

In a rabbit study, Palea et al. suggested an additional unrecognized receptor may be involved in contraction of the iris dilator muscle as α1AR blockade with tamsulosin and alfuzosin was less prominent in the iris than the prostate (Palea et al., 2008). While α1AAR are commonly reported as the predominant subtype in the iris dilator muscle in animal studies (Suzuki et al., 2002; Yu & Koss, 2003), Flach pointed out that assuming α1AAR predominate in the human iris dilator muscle based off rabbit studies may be misleading (Flach, 2009). Nevertheless, human immunohistochemical analysis has shown α1AARs to localize to iris arteriolar muscularis and the iris dilator muscle (Panagis et al., 2010).

#### **4. Risk factors for IFIS**

The most comprehensive assessment of risk factors for IFIS was recently published. This meta-analysis included seventeen studies totaling 17,588 eyes (Chatziralli & Sergentanis, 2010). It assessed current use of α1AR antagonist therapy as well as the effect of co-variates hypertension and diabetes. Current tamsulosin use was associated with the highest risk among the groups studied. Current use of alfuzosin and terazosin was associated with lower risk relative to tamsulosin but remained statistically significant. The pooled analysis of doxazosin did not reach statistical significance; however, the authors cautioned that more studies are needed to gain statistical power. Of the covariates tested, only current hypertension increased risk for IFIS. Despite mixed results in various studies, diabetes did not emerge as a significant risk factor for IFIS. The authors concluded that, consistent with previous reports, it appears that tamsulosin use is associated with the highest risk of IFIS relative to other agents.

There is limited information regarding doxazosin, prazosin and the most recently approved agent silodosin. However, as the latter's pharmacology most resembles tamsulosin and because of its high affinity for the α1AAR, it should be presumed that there is an inherent risk with silodosin until data suggests otherwise. A complete list of medications medications associated with IFIS is described in Table 1.

#### **5. Literature review**

IFIS was originally reported in a retrospective study of 511 patients who underwent cataract surgery (Chang & Campbell, 2005). Twenty-seven patients (5.3%) totaling 40 eyes had preoperative exposure to α1AR antagonists. Ten of sixteen (62.5%) patients who received tamsulosin prior to surgery developed IFIS. In the remaining eleven patients on other α1AR antagonists, there were no documented cases of IFIS. However, the authors

Potentially, the high α1AAR-specific antagonism of tamsulosin made the association easier to identify. In rabbits, tamsulosin was more effective than the non-specific α1AR antagonist alfuzosin at blocking adrenergic-mediated iris dilator contraction (Palea et al., 2008). Interestingly, functional studies assessing the affinity of different ARs as measured by pKi (negative logarithm of the equilibrium dissociation constant) reflect higher affinity of silodosin for α1AAR compared to older agents; when compared to other currently available α1AR antagonists, silodosin is 1400 times more specific in terms of α1AAR versus α1BAR binding than doxazosin and terazosin and 40 times greater compared to tamsulosin (Thiyagarajan, 2002). It remains to be seen if silodosin has a greater likelihood to cause

In a rabbit study, Palea et al. suggested an additional unrecognized receptor may be involved in contraction of the iris dilator muscle as α1AR blockade with tamsulosin and alfuzosin was less prominent in the iris than the prostate (Palea et al., 2008). While α1AAR are commonly reported as the predominant subtype in the iris dilator muscle in animal studies (Suzuki et al., 2002; Yu & Koss, 2003), Flach pointed out that assuming α1AAR predominate in the human iris dilator muscle based off rabbit studies may be misleading (Flach, 2009). Nevertheless, human immunohistochemical analysis has shown α1AARs to localize to iris arteriolar muscularis and the iris dilator muscle (Panagis et al., 2010).

The most comprehensive assessment of risk factors for IFIS was recently published. This meta-analysis included seventeen studies totaling 17,588 eyes (Chatziralli & Sergentanis, 2010). It assessed current use of α1AR antagonist therapy as well as the effect of co-variates hypertension and diabetes. Current tamsulosin use was associated with the highest risk among the groups studied. Current use of alfuzosin and terazosin was associated with lower risk relative to tamsulosin but remained statistically significant. The pooled analysis of doxazosin did not reach statistical significance; however, the authors cautioned that more studies are needed to gain statistical power. Of the covariates tested, only current hypertension increased risk for IFIS. Despite mixed results in various studies, diabetes did not emerge as a significant risk factor for IFIS. The authors concluded that, consistent with previous reports, it appears that tamsulosin use is associated with the highest risk of IFIS

There is limited information regarding doxazosin, prazosin and the most recently approved agent silodosin. However, as the latter's pharmacology most resembles tamsulosin and because of its high affinity for the α1AAR, it should be presumed that there is an inherent risk with silodosin until data suggests otherwise. A complete list of medications medications

IFIS was originally reported in a retrospective study of 511 patients who underwent cataract surgery (Chang & Campbell, 2005). Twenty-seven patients (5.3%) totaling 40 eyes had preoperative exposure to α1AR antagonists. Ten of sixteen (62.5%) patients who received tamsulosin prior to surgery developed IFIS. In the remaining eleven patients on other α1AR antagonists, there were no documented cases of IFIS. However, the authors

IFIS than the other available agents.

**4. Risk factors for IFIS**

relative to other agents.

**5. Literature review**

associated with IFIS is described in Table 1.

reported that all twenty-seven patients had "poor or moderately poor dilation." A complete list of studies assessing incidence of IFIS as well as studies assessing rates of surgical complications in patients prescribed α1AR antagonists are described in Table 2

Table 1. Medications associated with IFIS

In a prospective analysis of 900 consecutive cataract surgeries among 741 patients, IFIS was observed in sixteen patients (2.2%), fourteen of whom had documented concomitant use of tamsulosin (Chang & Campbell, 2005). In the two remaining patients, one had discontinued tamsulosin three years prior to surgery, and one had no history of tamsulosin exposure. Furthermore, IFIS was reported in both eyes of the five patients taking tamsulosin that required bilateral cataract surgery.

Despite the authors' initial identification of a potentially serious complication of cataract surgery, reported limitations of the study include lack of covariate data and the modest reported use of α1AR antagonists at 1.9% (Chang & Campbell, 2005; Schwinn & Afshari, 2006). As stated above, patients with BPH may not always require pharmacologic treatment, specifically in patients with mild American Urological Association (AUA) symptom scores (AUA, 2010). This may partially explain the relatively low percentage of tamsulosin use in a population with a historically high prevalence of BPH.

In a recent study assessing incidence, IFIS was reported to be 1.6% among 774 patients (Takmaz & Can, 2007). IFIS was documented in 14 of 18 patients (77.8%) taking tamsulosin, and consistent with the original report by Chang and Campbell, tamsulosin use overall was observed in 2.2% of patients. Duration of tamsulosin use—although increased among patients diagnosed with IFIS—was not statistically significant relative to those without IFIS.

A recent study directly compared the incidence of IFIS attributable to tamsulosin with an active comparator group. (Blouin et al., 2007). In this retrospective study of 64 men totaling 92 eyes, there was an increased risk of IFIS in patients exposed to tamsulosin (86.4%) when compared to alfuzosin (15.4%). The adjusted odds ratio for IFIS in patients taking tamsulosin when compared to alfuzosin was 32.15 (95% confidence interval, 2.74-377.41). Furthermore, a five-fold increase in surgical complication rates was observed in patients diagnosed with IFIS, highlighting its clinical significance.

Pathophysiology and Pre-Operative Evaluation

**Reference Design Objective Population**

Assess incidence of IFIS associated with tamsulosin

Assess incidence of IFIS associated with tamsulosin

Determine incidence of IFIS in patients taking tamsulosin, effect of prophylactic measures

Report incidence, etiology and management of IFIS

a Includes patients that experienced an IFI-like syndrome

Table 2. Incidence and prevalence of IFIS in selected studies

1267 patients; 1462 eyes

579 patients; 594 eyes

438 patients; 439 eyes

within 14 days of cataract surgery increased the risk for complications.

1163 eyes Not

Prospective observation al study

Prospective, nonrandomi zed observation al study

Retrospectiv e cohort study

Prospective, nonrandomi zed observation al study

Fitt, 2006; Venkatesh et al., 2007).

Amin et al. (2008)

Keklikci et al. (2009)

Chen et al. (2010)

Horvath & Vultur (2011)

of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS) 9

**Overall Prevalence or Incidence of IFIS (%)**

Not available

15/579 eyes (2.6)

available

37/439 eyes (8.4)a

Following the original report suggesting a stronger link between tamsulosin and IFIS relative to other α1AR antagonists, subsequent case reports of IFIS have been published in men taking alfuzosin, doxazosin, and terazosin (Dhingra et al., 2007; Herd, 2007; Settas &

Aside from IFIS, α1AR antagonist therapy prior to cataract surgery has been shown to predispose patients to complications following cataract surgery (Bell et al., 2009). A nested case control study examined health care records of 96,128 Canadian men aged 66 years or older who had undergone cataract surgery over a 5 year period. Post-operative complications that were examined included retinal detachment, lost lens or lens fragment, or endophalmitis. Overall, 3.7% had a history of exposure to tamsulosin, and 7.7% had recently taken other alpha blockers. Cases—that is men with a history of complications were matched to control patients. The authors identified complications in 280 patients (0.3%). These cases were randomly matched to control patients based on age, surgeon, and year of procedure. Complications were more common among current users of tamsulosin. This risk was not significantly increased with exposure to other α1AR antagonists or to previous exposure to tamsulosin or other α1AR antagonists. However, tamsulosin use

**Exposure to Systemic α1AR Antagonist (%)**

Not available

Not available

Not available

15/439

eyes (3.4) Not available

**Prevalence or Incidence of IFIS in Tamsulosin-Treated Patients (%)**

13/23 eyes (56.5)

12/23 patients (52.2)

24/81 eyes (29.6)

**Comments**

Incidence of IFIS in patients treated w/α1AR = 86.7%

**Overall Prevalence or Incidence of IFIS (%)**

10/511 patients (2.0)

16/741 patients (2.2)

No IFIS: 10% of eyes; mild: 17% of eyes; moderate – severe: 73% of eyes

61/461 eyes (13.2)

13/1298 patients (1.0)

16/858 eyes (1.9)

29/2643 eyes (1.1) **Exposure to Systemic α1AR Antagonist (%)**

27/511 patients (5.3)

Not available

135/135 patients (100)

64/332 patients (19.3)

65/1298 patients (5.0)

24/858 eyes (2.8)

134/2643 eyes (5.1) **Prevalence or Incidence of IFIS in Tamsulosin-Treated Patients (%)**

10/16 patients (62.5)

15/16 patients (93.8)

150/167 eyes (89.8)

19/22 patients (86.4)

10/13 patients (76.9)

14/18 eyes (77.8)

25/58 eyes (43.1)

**Comments**

IFIS in 2/13 (15.4%) patients exposed to alfuzosin

IFIS in 2 patients exposed to terazosin and 1 patient exposed to doxazosin

IFIS in 1 of 4 eyes exposed to terazosin and 1 of 2 eyes exposed to alfuzosin

No IFIS in bunazosin (topical a1AR antagonist which is not a1AAR-specific)

group

**Reference Design Objective Population**

Assess incidence and possible causative factors of IFIS

Evaluate surgical outcomes and rate of complication s when ophthalmolo gist knew patient was taking tamsulosin

Compare IFIS risk in men taking tamsulosin vs. alfuzosin

Determine occurrence of IFIS in those exposed to systemic α1AR antagonists

Evaluate complication rates, effect of

intracameral adrenaline, and incidence of IFIS in patients taking tamsulosin

Compare incidence of IFIS with topical vs. systemic α1AR antagonists

511 patients; 706 eyes

741 patients; 900 eyes

135 patients; 167 eyes

332 patients; 461 eyes

1298 patients; 1612 eyes

774 patients; 858 eyes

1968 patients; 2643 eyes

Clinical study 1: retrospectiv e chart review

Clinical study 2: prospective case series

Prospective, multicenter, nonrandomiz ed observational series

Retrospectiv e chart review

Retrospectiv e chart review

Prospective, nonrandomi zed observation al study

Prospective, intervention al case series

Chang & Campbell, 2005

Chang et al., 2007

Blouin et al., 2007

Srinivasan et al., 2007

Takmaz & Can, 2007

Oshika et al., 2007

a Includes patients that experienced an IFI-like syndrome

Table 2. Incidence and prevalence of IFIS in selected studies

Following the original report suggesting a stronger link between tamsulosin and IFIS relative to other α1AR antagonists, subsequent case reports of IFIS have been published in men taking alfuzosin, doxazosin, and terazosin (Dhingra et al., 2007; Herd, 2007; Settas & Fitt, 2006; Venkatesh et al., 2007).

Aside from IFIS, α1AR antagonist therapy prior to cataract surgery has been shown to predispose patients to complications following cataract surgery (Bell et al., 2009). A nested case control study examined health care records of 96,128 Canadian men aged 66 years or older who had undergone cataract surgery over a 5 year period. Post-operative complications that were examined included retinal detachment, lost lens or lens fragment, or endophalmitis. Overall, 3.7% had a history of exposure to tamsulosin, and 7.7% had recently taken other alpha blockers. Cases—that is men with a history of complications were matched to control patients. The authors identified complications in 280 patients (0.3%). These cases were randomly matched to control patients based on age, surgeon, and year of procedure. Complications were more common among current users of tamsulosin. This risk was not significantly increased with exposure to other α1AR antagonists or to previous exposure to tamsulosin or other α1AR antagonists. However, tamsulosin use within 14 days of cataract surgery increased the risk for complications.

Pathophysiology and Pre-Operative Evaluation

2007).

**7. Conclusion**

the best outcome.

**8. References**

of Patients at Risk for Intraoperative Floppy Iris Syndrome (IFIS) 11

for difficulty emptying their bladder will help elicit a more accurate history. If a patient does have a history of α1AR antagonists it is also important to counsel them on the associated

The most reliable preoperative predictive feature of IFIS in a patient with a history of α1AR antagonists is poor pupillary dilation (Oetting, 2009). This can and should be noted during the office pre-operative cataract surgery evaluation, and not just on the day of surgery. When the pupil does not dilate well, the surgeon should be wary of IFIS during surgery. Although poor dilation can also be a harbinger of other intra ocular conditions such as pseudoexfoliation and trauma, recognition will help the surgeon prepare for and adapt intra operative management strategies for all possible complications (Altan-Yaycioglu. et al.,

Recognizing patients at risk for IFIS is paramount to management. Without adequate preparation and management IFIS and subsequent postoperative complications are possible. A detailed pre-operative evaluation including recognizing those at risk for IFIS will ensure

Altan-Yaycioglu, R. Yaycioglu, & O. Gul, U. et al. (2007). The effects of two systemic alpha-1

Amin, K.; Fong, K. & Horgan, SE. (2008). Incidence of intra-operative floppy iris syndrome

Anothaisintawee, T.; Attia, J. & Nickel, JC. et al. (2011). Management of chronic

Bell, CM.; Hatch, WV. & Fischer, HD. et al. (2009). Association between tamsulosin and

Biaggioni, I., & Robertson, D. (2009). Adrenoceptor Agonists & Sympathomimetic Drug, In:

 http://www.accesspharmacy.com.proxy.lib.uiowa.edu/content.aspx?aid=4520412 Blouin, MC.; Blouin, J. & Perreault, S. et al. (2007). Intraoperative floppy-iris syndrome

Calotti, F. & Steen, D. (2007). Labetalol causing intraoperative floppy-iris syndrome. *J*

Cantrell, MA.; Bream-Rouwenhorst, HR. & Hemerson, P. et al. (2010). Silodosin for benign

prostatic hyperplasia. *Ann Pharmacother*, Vol.44, No.2, (February 2010), pp. 302-310.

Cantrell, MA.; Bream-Rouwenhorst, HR. & Steffensmeier, A. et al. (2008). Intraoperative floppy iris syndrome associated with α1-adrenergic receptor antagonists. *Ann Pharmacother,*

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associated with alpha1 adrenoreceptors: comparison of tamsulosin and alfuzosin. *J*

increased risk of IFIS and subsequent risk of complications postoperatively.

Currently, risk of IFIS has only been associated with systemic use of α1AR antagonists. In a study comparing the incidence of IFIS between topical and systemic administration, no cases were observed in patients taking bunazosin, a topical, non-selective, α1AR antagonist which is not currently available in the United States (Oshika et al., 2007). In the tamsulosin comparator group, the incidence of IFIS was 1.1%. Notably, results may have differed had the topical agent used also been specific for the α1AAR subtype.

In response to multiple reports of an increased risk of IFIS, the package labeling of tamsulosin and other α1AR antagonists has been updated to reflect this potential risk. The labeling further acknowledges that benefits of stopping an α1AR antagonist prior to cataract surgery remains unknown (Package insert Flomax, 2007).

The 5ARI finasteride and the extract of saw palmetto (*Serona repens*) a type of palm plant utilized largely as alternative medicine for treatment of BPH have been linked to IFIS (Issa & Dagres, 2007; Yeu & Grostern, 2007). The patients in the aforementioned cases were specifically stated to not have received α1AR antagonists prior to cataract surgery; however, the possibility exists that the patients may have received an unrecognized α1AR antagonist either currently or in the past. No mechanism for how these agents may cause IFIS has been postulated, and the effect of how 5ARIs interact with the iris has not been studied. While confounders common to patients taking either 5ARIs or α1AR antagonists such as increased age or male gender cannot be ruled out, certainly the strongest evidence of a link between medication and IFIS is with α1AR antagonists and not 5ARIs.

Aside from α1AR antagonists, IFIS has been associated with other medications as well. Lending credence to the theory that α1AR antagonism is heavily responsible for IFIS, the antipsychotics chlorpromazine and risperidone, both mild α1AR antagonists, have been linked to IFIS in patients not previously haven received conventional α1-AR antagonists (Ford et al., 2011; Unal et al., 2007). Labetalol, a dual α1- and β-AR antagonist, has also been associated with IFIS (Calotti & Steen, 2007).

One case of acetylcholinesterase-inhibitor-associated IFIS with donepezil has been reported. The authors hypothesized that through enhancement of cholinergic activity on the pupil sphincter, the pharmacological effect of the preoperative dilating drops was overcome (Papadopoulos & Bachariou, 2007). The patient reportedly had never received an α1AR antagonist. However, a complete medication list was not documented in the case, and receipt of other α1AR antagonists cannot be ruled out.

#### **6. Pre-operative evaluation**

The relationship of α1AR antagonists to IFIS has changed the preoperative process for cataract surgeons. The pre-operative evaluation is particularly difficult as there is currently no reliable way to predict which patients will demonstrate IFIS. Furthermore as IFIS can present unilaterally the absence in one eye does not preclude the other eye from demonstrating features of IFIS in a subsequent surgery (Issa et al., 2008). During the pre operative visit, there are a number of questions and observations which may highlight for the surgeon any patients at potential risk for IFIS.

Most importantly is to ask all patients about current or former use of α1AR antagonists. Simply reviewing the current medication list is not sufficient. Many patients are unable to recall specific medication names or classes they are currently taking, much less a medication they took previously and since discontinued. Because of this, often times asking a patient or an accompanying family member if they have ever been treated for an enlarged prostate or for difficulty emptying their bladder will help elicit a more accurate history. If a patient does have a history of α1AR antagonists it is also important to counsel them on the associated increased risk of IFIS and subsequent risk of complications postoperatively.

The most reliable preoperative predictive feature of IFIS in a patient with a history of α1AR antagonists is poor pupillary dilation (Oetting, 2009). This can and should be noted during the office pre-operative cataract surgery evaluation, and not just on the day of surgery. When the pupil does not dilate well, the surgeon should be wary of IFIS during surgery. Although poor dilation can also be a harbinger of other intra ocular conditions such as pseudoexfoliation and trauma, recognition will help the surgeon prepare for and adapt intra operative management strategies for all possible complications (Altan-Yaycioglu. et al., 2007).

#### **7. Conclusion**

10 Cataract Surgery

Currently, risk of IFIS has only been associated with systemic use of α1AR antagonists. In a study comparing the incidence of IFIS between topical and systemic administration, no cases were observed in patients taking bunazosin, a topical, non-selective, α1AR antagonist which is not currently available in the United States (Oshika et al., 2007). In the tamsulosin comparator group, the incidence of IFIS was 1.1%. Notably, results may have differed had

In response to multiple reports of an increased risk of IFIS, the package labeling of tamsulosin and other α1AR antagonists has been updated to reflect this potential risk. The labeling further acknowledges that benefits of stopping an α1AR antagonist prior to cataract

The 5ARI finasteride and the extract of saw palmetto (*Serona repens*) a type of palm plant utilized largely as alternative medicine for treatment of BPH have been linked to IFIS (Issa & Dagres, 2007; Yeu & Grostern, 2007). The patients in the aforementioned cases were specifically stated to not have received α1AR antagonists prior to cataract surgery; however, the possibility exists that the patients may have received an unrecognized α1AR antagonist either currently or in the past. No mechanism for how these agents may cause IFIS has been postulated, and the effect of how 5ARIs interact with the iris has not been studied. While confounders common to patients taking either 5ARIs or α1AR antagonists such as increased age or male gender cannot be ruled out, certainly the strongest evidence of a link between

Aside from α1AR antagonists, IFIS has been associated with other medications as well. Lending credence to the theory that α1AR antagonism is heavily responsible for IFIS, the antipsychotics chlorpromazine and risperidone, both mild α1AR antagonists, have been linked to IFIS in patients not previously haven received conventional α1-AR antagonists (Ford et al., 2011; Unal et al., 2007). Labetalol, a dual α1- and β-AR antagonist, has also been

One case of acetylcholinesterase-inhibitor-associated IFIS with donepezil has been reported. The authors hypothesized that through enhancement of cholinergic activity on the pupil sphincter, the pharmacological effect of the preoperative dilating drops was overcome (Papadopoulos & Bachariou, 2007). The patient reportedly had never received an α1AR antagonist. However, a complete medication list was not documented in the case, and

The relationship of α1AR antagonists to IFIS has changed the preoperative process for cataract surgeons. The pre-operative evaluation is particularly difficult as there is currently no reliable way to predict which patients will demonstrate IFIS. Furthermore as IFIS can present unilaterally the absence in one eye does not preclude the other eye from demonstrating features of IFIS in a subsequent surgery (Issa et al., 2008). During the pre operative visit, there are a number of questions and observations which may highlight for

Most importantly is to ask all patients about current or former use of α1AR antagonists. Simply reviewing the current medication list is not sufficient. Many patients are unable to recall specific medication names or classes they are currently taking, much less a medication they took previously and since discontinued. Because of this, often times asking a patient or an accompanying family member if they have ever been treated for an enlarged prostate or

the topical agent used also been specific for the α1AAR subtype.

surgery remains unknown (Package insert Flomax, 2007).

medication and IFIS is with α1AR antagonists and not 5ARIs.

associated with IFIS (Calotti & Steen, 2007).

**6. Pre-operative evaluation**

receipt of other α1AR antagonists cannot be ruled out.

the surgeon any patients at potential risk for IFIS.

Recognizing patients at risk for IFIS is paramount to management. Without adequate preparation and management IFIS and subsequent postoperative complications are possible. A detailed pre-operative evaluation including recognizing those at risk for IFIS will ensure the best outcome.

#### **8. References**

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*Urol*, Vol.175, No.4, (April 2006), pp. 1422-1426;discussion 1426-1427. Dhingra, N.; Rajkumar, KN. & Kumar, V. (2007). Intraoperative floppy iris syndrome with

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**1. Introduction**

turbulence.

**2. Planning**

**2**

*USA*

James A. Davison *Wolfe Eye Clinic, Iowa,*

**Prevention and Management of**

**Intraoperative Floppy Iris Syndrome**

Other than using it to attach the IOL optic in McCannel suture procedures, the iris, in any amount, only causes problems for the cataract surgeon. In its extreme, there are no iris related complications in aniridia patients, other than not having an iris. Even in normal cases, there are always some disturbances of iris tissue as evidenced by postoperative

One of the keys then to successful cataract surgery is to reduce the effect that the iris has on the intra and postoperative course of events. So during cataract surgery, the iris needs to be minimized and isolated. We dilate the pupil as much as we can which gives us better visualization and less iris to influence either directly by touching or indirectly through hydraulic means. The key is to make the iris as inconsequential as it can be by reducing its area pharmacologically or physically. If the iris area presentation is large to start with, there will be more of it to be caught in the flow of BSS and it may become floppy in the fluidic turbulence. If it is dilated and contracted, there will be less presentation of tissue to BSS flow and less muscle reaction to the buffeting of

The axiom "the pupil never gets larger during surgery" needs to be a critical part of the surgery planning process. Whatever the pupil diameter is at the start of a case, it will only stay the same or get smaller as the case goes on. We have a good estimate of surgical pupil size when we see patients in the office so we can plan ahead. Sometimes the pupil gets larger before surgery vs. the clinic because of the stronger drops used in surgery rather than in the examination lane. My general rule is that I want at least a 4.5 - 5.0 mm. pupil at the outset of surgery so that I can get an additional 0.5 mm. dilation with viscoelastic anterior chamber pressurization and I can create the tremendously important capsulorhexis in a diameter of approximately 5.0 - 5.5 mm. in ideal circumstances but at least 4.5 mm. at a minimum. But clinical circumstances may appear to require an even larger pupil because of lens and/or zonule character. So a 4.5 mm. pupil in a normal eye with an average character cataract of LOCS III NO 3.7 NC 3.7, (Chylack 1993) will likely be maintained because surgery should be routine, brief, and uneventful. But that same pupil size may not be

inflammation, pigment dispersion, and sometimes iris transillumination.

prostatic hyperplasia: a randomized, placebo-controlled trial. *Urology*, Vol.58, No. 6, (December 2001), pp. 953-959.

### **Prevention and Management of Intraoperative Floppy Iris Syndrome**

James A. Davison *Wolfe Eye Clinic, Iowa, USA*

#### **1. Introduction**

14 Cataract Surgery

Schwinn, DA. & Afshari, NA. (2006). alpha(1)-Adrenergic receptor antagonists and the iris:

Settas, G. & Fitt, AW. (2006). Intraoperative floppy iris syndrome in a patient taking

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Singh, A.; Alter, HJ. & Littlepage, A. (2007). A systematic review of medical therapy to

Srinivasan, S.; Radomski, S. & Chung, J. et al. (2007). Intraoperative floppy-iris syndrome

Takmaz, T. & Can, I. (2007). Clinical features, complications, and incidence of intraoperative

Thiyagarajan, M. (2002). α-Adrenoceptor antagonists in the treatment of benign prostate

Unal, M.; Yucel, I. & Tenlik, A. (2007). Intraoperative floppy-iris syndrome associated with chronic use of chlorpromazine. *Eye,* Vol.21, No.9, (September 2007), pp. 1241-1242. Venkatesh R.; Veena, K. & Gupta, S. et al. (2007). Intraoperative floppy iris syndrome

Yeu, E. & Grostern, R. (2007). Saw palmetto and intraoperative floppy-iris syndrome*. J*

Yu, Y. & Koss, MC. (2003). Studies of alpha adrenoceptor antagonists on sympathetic mydriasis in rabbits. *J Ocul Pharmacol Ther,* Vol.19, No.3, (June 2003), pp. 255–263.

hyperplasia. *Pharmacology,* Vol.65, No.3, (July 2002), pp. 119-128.

*Cataract Refract Surg,* Vol.33,No.5, (May 2007), pp. 927-928.

analysis. *J Urol*, Vol.147, No.4, (April 1992), pp. 1167-1170.

6, (December 2001), pp. 953-959.

pp. 1431-1432.

2007), pp. 552-563.

2007), pp. 395-396.

(February 2002), pp. 600–608.

(November-December 2007), pp. 909-913.

(September-October 2006), pp. 501-512.

prostatic hyperplasia: a randomized, placebo-controlled trial. *Urology*, Vol.58, No.

new mechanistic insights into floppy iris syndrome. *Surv Ophthalmol*, Vol.51, No.5,

alfuzosin for benign prostatic hypertrophy. *Eye*, Vol.20, No.12, (December 2006),

prostate using double immuno-enzymatic staining and color assisted image

facilitate passage of ureteral calculi. Ann Emerg Med, Vol. 50, No. 5, (November

during cataract surgery in men using alpha-blockers for benign prostatic hypertrophy. *J Cataract Refract Surg,* Vol.33, No.10, (October 2007), pp. 1826-1827. Suzuki, F.; Taniguchi, T. & Nakamura, S. et al. (2002). Distribution of alpha-1 adrenoceptor

subtypes in RNA and protein in rabbit eyes. *Br J Pharmacol,* Vol.135, No.3,

floppy iris syndrome in patients taking tamsulosin. *Eur J Ophthalmol*, Vol. 17, No.6,

associated with terazosin. *Indian J Ophthalmol,* Vol.55 No.5, (September-October

Other than using it to attach the IOL optic in McCannel suture procedures, the iris, in any amount, only causes problems for the cataract surgeon. In its extreme, there are no iris related complications in aniridia patients, other than not having an iris. Even in normal cases, there are always some disturbances of iris tissue as evidenced by postoperative inflammation, pigment dispersion, and sometimes iris transillumination.

One of the keys then to successful cataract surgery is to reduce the effect that the iris has on the intra and postoperative course of events. So during cataract surgery, the iris needs to be minimized and isolated. We dilate the pupil as much as we can which gives us better visualization and less iris to influence either directly by touching or indirectly through hydraulic means. The key is to make the iris as inconsequential as it can be by reducing its area pharmacologically or physically. If the iris area presentation is large to start with, there will be more of it to be caught in the flow of BSS and it may become floppy in the fluidic turbulence. If it is dilated and contracted, there will be less presentation of tissue to BSS flow and less muscle reaction to the buffeting of turbulence.

#### **2. Planning**

The axiom "the pupil never gets larger during surgery" needs to be a critical part of the surgery planning process. Whatever the pupil diameter is at the start of a case, it will only stay the same or get smaller as the case goes on. We have a good estimate of surgical pupil size when we see patients in the office so we can plan ahead. Sometimes the pupil gets larger before surgery vs. the clinic because of the stronger drops used in surgery rather than in the examination lane. My general rule is that I want at least a 4.5 - 5.0 mm. pupil at the outset of surgery so that I can get an additional 0.5 mm. dilation with viscoelastic anterior chamber pressurization and I can create the tremendously important capsulorhexis in a diameter of approximately 5.0 - 5.5 mm. in ideal circumstances but at least 4.5 mm. at a minimum. But clinical circumstances may appear to require an even larger pupil because of lens and/or zonule character. So a 4.5 mm. pupil in a normal eye with an average character cataract of LOCS III NO 3.7 NC 3.7, (Chylack 1993) will likely be maintained because surgery should be routine, brief, and uneventful. But that same pupil size may not be

Prevention and Management of Intraoperative Floppy Iris Syndrome 17

Fig. 1. The expander is draped over its insertion rod and has engaged the distal pupillary iris

maintainable during a longer more difficult case such as if the cataract is very soft, very hard, or if it is accompanied by an inherently loose zonule as in pseudoexfoliation, or if the iris is unusually flaccid. A pupil of 6.0 mm. is desirable at the outset of these types of difficult cases.

If the pupil is smaller than 4.5 mm. and I can't create a capsulorhexis of that diameter, I employ a mechanical device to physically enlarge it prior to performing capsulorhexis. That rule has yielded an overall rate of mechanical pupil enlargement for me of 10 % but an iris related complication rate (significant iris aspiration or prolapse or an associated posterior capsule rupture) of zero (unpublished data, JAD 2008-2011). This utilization may seem high, but the risks of problems and the significance of the problems created by a small pupil are more important to the outcome of these cases than the time and expense it takes to temporarily physically enlarge the pupil and accomplish them in normal fashion

#### **3. Pharmacologic pupil dilation**

A topical non-steroidal preparation is used 3 days prior to surgery in the hopes of reducing inflammation and maybe assisting in dilating the pupil. There are numerous ways to accomplish the instillation but, Cyclogyl 1% and NeoSynephrine 2.5% are longtime key ingredients for dilating the eye starting about 45 minutes prior to surgery. Lidocaine 1% preservative free is injected into the anterior chamber just after the normal clear corneal primary and paracentesis incisions are created. This substance also assists with initiating and maintaining pupil dilation. Epinephrine 1:10,000 (1 ml.) is used in 500 cc in the continuous irrigation of BSS

Epi-Shugarcaine (Shugar 2006), a mixture of preservative free lidocaine and epinephrine has been shown by Joel Shugar, MD to be an effective supplementary agent in maintaining pupil dilation just before phacoemulsification and again before cortex aspiration as well. Intraoperative unpreserved epinephrine preceded by topical atropine has also been demonstrated to achieve and maintain larger pupil sizes and help reduce the incidence of IFIS (Masket 2007).

#### **4. Mechanical pupil dilation**

Viscoelastic anterior chamber pressurization prior to performing capsulorhexis will generally yield 0.5 mm. diameter additional pupil dilation. I use a DuoVisc (Alcon Surgical) strategy injecting enough Viscoat (Alcon Surgical) to fill approximately 40 % of the anterior chamber and following with ProVisc (Alcon Surgical) underneath to the point that some is just refluxing out the incision as it's being injected. If I can achieve a 4.5 mm pupil, I'll generally proceed with capsulorhexis but if I can't I will mechanically dilate the pupil with one of two devices.

I employ the Graether Pupil Expander (EagleVision) which was invented by John Graether, MD in 1991 (Graether 1996) and use it part of the time i.e. in normal eyes with small pupils. Its advantages are the average time it takes to accomplish the insertion, about 30 - 60 seconds, removal in about 10 seconds, and the fact that no additional incisions are needed.

maintainable during a longer more difficult case such as if the cataract is very soft, very hard, or if it is accompanied by an inherently loose zonule as in pseudoexfoliation, or if the iris is unusually flaccid. A pupil of 6.0 mm. is desirable at the outset of these types of

If the pupil is smaller than 4.5 mm. and I can't create a capsulorhexis of that diameter, I employ a mechanical device to physically enlarge it prior to performing capsulorhexis. That rule has yielded an overall rate of mechanical pupil enlargement for me of 10 % but an iris related complication rate (significant iris aspiration or prolapse or an associated posterior capsule rupture) of zero (unpublished data, JAD 2008-2011). This utilization may seem high, but the risks of problems and the significance of the problems created by a small pupil are more important to the outcome of these cases than the time and expense it takes to temporarily physically enlarge the pupil and accomplish them in normal

A topical non-steroidal preparation is used 3 days prior to surgery in the hopes of reducing inflammation and maybe assisting in dilating the pupil. There are numerous ways to accomplish the instillation but, Cyclogyl 1% and NeoSynephrine 2.5% are longtime key ingredients for dilating the eye starting about 45 minutes prior to surgery. Lidocaine 1% preservative free is injected into the anterior chamber just after the normal clear corneal primary and paracentesis incisions are created. This substance also assists with initiating and maintaining pupil dilation. Epinephrine 1:10,000 (1 ml.) is used in 500 cc in the

Epi-Shugarcaine (Shugar 2006), a mixture of preservative free lidocaine and epinephrine has been shown by Joel Shugar, MD to be an effective supplementary agent in maintaining pupil dilation just before phacoemulsification and again before cortex aspiration as well. Intraoperative unpreserved epinephrine preceded by topical atropine has also been demonstrated to achieve and maintain larger pupil sizes and help reduce the incidence of

Viscoelastic anterior chamber pressurization prior to performing capsulorhexis will generally yield 0.5 mm. diameter additional pupil dilation. I use a DuoVisc (Alcon Surgical) strategy injecting enough Viscoat (Alcon Surgical) to fill approximately 40 % of the anterior chamber and following with ProVisc (Alcon Surgical) underneath to the point that some is just refluxing out the incision as it's being injected. If I can achieve a 4.5 mm pupil, I'll generally proceed with capsulorhexis but if I can't I will mechanically dilate the pupil with

I employ the Graether Pupil Expander (EagleVision) which was invented by John Graether, MD in 1991 (Graether 1996) and use it part of the time i.e. in normal eyes with small pupils. Its advantages are the average time it takes to accomplish the insertion, about 30 - 60 seconds, removal in about 10 seconds, and the fact that no additional

difficult cases.

fashion

**3. Pharmacologic pupil dilation**

continuous irrigation of BSS

**4. Mechanical pupil dilation**

IFIS (Masket 2007).

one of two devices.

incisions are needed.

Fig. 1. The expander is draped over its insertion rod and has engaged the distal pupillary iris

Prevention and Management of Intraoperative Floppy Iris Syndrome 19

Fig. 3. The Lester hook and side port manipulator have just completed a kind of cross handed stretching maneuver and are about to be withdrawn. The expander is fully engaged and the pupil size will be maintained throughout the entire case. The Lester hook will engage the small proximal strap and easily withdraw the expander at the conclusion of the

Interestingly, it is easier to insert in smaller pupils rather than medium sized ones because the pupillary iris tissue more tightly grabs the attachment points if the pupil is smaller rather than if it is larger where it tends to fall off. But, I worry that, at least in my hands, the downward pressure required to place the device may have a tendency to create some zonular fiber disruption in some cases. This has never been clinically significant to me but I still tend not to use it in patients with pseudoexfoliation or trauma cases which have an

In those patients with pseudoexfoliation and a potentially weak zonule, medium size pupils or eyes with very compact anterior segment anatomy, I generally employ Grieshaber iris retractors (Alcon Surgical). Their disadvantage is that they require 4 additional incisions and take about 2 minutes to place and maybe 30 seconds to remove. I orient them in a square pattern by creating incisions with a 22,5 degree blade. I create all four of the incisions first, and then create the paracentesis incision for my left hand and 2.4 mm keratome primary incision before introducing intracameral lidocaine or

case

viscoelastic.

already loose zonule propensity.

Fig. 2. As the insertion rod is withdrawn, the expander is engaged distally and on the left side but has missed engaging the pupil on the right side.

Fig. 2. As the insertion rod is withdrawn, the expander is engaged distally and on the left

side but has missed engaging the pupil on the right side.

Fig. 3. The Lester hook and side port manipulator have just completed a kind of cross handed stretching maneuver and are about to be withdrawn. The expander is fully engaged and the pupil size will be maintained throughout the entire case. The Lester hook will engage the small proximal strap and easily withdraw the expander at the conclusion of the case

Interestingly, it is easier to insert in smaller pupils rather than medium sized ones because the pupillary iris tissue more tightly grabs the attachment points if the pupil is smaller rather than if it is larger where it tends to fall off. But, I worry that, at least in my hands, the downward pressure required to place the device may have a tendency to create some zonular fiber disruption in some cases. This has never been clinically significant to me but I still tend not to use it in patients with pseudoexfoliation or trauma cases which have an already loose zonule propensity.

In those patients with pseudoexfoliation and a potentially weak zonule, medium size pupils or eyes with very compact anterior segment anatomy, I generally employ Grieshaber iris retractors (Alcon Surgical). Their disadvantage is that they require 4 additional incisions and take about 2 minutes to place and maybe 30 seconds to remove. I orient them in a square pattern by creating incisions with a 22,5 degree blade. I create all four of the incisions first, and then create the paracentesis incision for my left hand and 2.4 mm keratome primary incision before introducing intracameral lidocaine or viscoelastic.

Prevention and Management of Intraoperative Floppy Iris Syndrome 21

Fig. 5. The retractor on the lower left is being pushed into the anterior chamber with a tying forceps for a length of about 1.0 mm. The iris will hug the retractor in its new position within a second just as it already has the retractor on the lower right. Just that much less retraction under the phacoemulsification tip allows the iris to fall away from it and not

During the sculpting phase of contemporary in situ fracture phacoemulsification there is a balanced and continuous inflow and outflow of BSS. This equilibrium exists because of the advantages of modern cataract surgery equipment and technique. Only a small volume controlled leakage of BSS is observed to leak around the infusion sleeve. A similar amount of leakage occurs during the quadrant removal phase of the surgery as well. Unnecessary surgeon generated motions are eliminated as are extremes and consequent substantial

Most machines can create this scenario to varying degrees. I use the Alcon Infiniti (Alcon Surgical) micro-coaxial system. In this system, all of the components are matched to each other in order to minimize imprecision and maximize efficiency, reproducibility, and safety. The 2.4 mm. keratome is capable of creating a perfect 2.4 mm. width with a 1.8 mm. length shelf incision before the introduction of viscoelastic. This can be accomplished while the 22.5

**5. Physically dampening hydraulic shock and minimizing turbulence**

suffer damage from its vibration.

changes in vacuum and occlusion levels.

degree angle paracentesis blade stabilizes the globe.

Fig. 4. The capsulorhexis has just been completed using Trypan blue dye. The retractors have been placed in each quadrant and fairly fully retracted to expose the anterior capsule for CCC creation and hydrodissection.

Prior to introducing the phacoemulsification tip, I loosen the proximal retractors so that the iris falls posterior and will not be rubbed by the phaco tip and sleeve during emulsification of the lens.

Fig. 4. The capsulorhexis has just been completed using Trypan blue dye. The retractors have been placed in each quadrant and fairly fully retracted to expose the anterior capsule

Prior to introducing the phacoemulsification tip, I loosen the proximal retractors so that the iris falls posterior and will not be rubbed by the phaco tip and sleeve during emulsification

for CCC creation and hydrodissection.

of the lens.

Fig. 5. The retractor on the lower left is being pushed into the anterior chamber with a tying forceps for a length of about 1.0 mm. The iris will hug the retractor in its new position within a second just as it already has the retractor on the lower right. Just that much less retraction under the phacoemulsification tip allows the iris to fall away from it and not suffer damage from its vibration.

#### **5. Physically dampening hydraulic shock and minimizing turbulence**

During the sculpting phase of contemporary in situ fracture phacoemulsification there is a balanced and continuous inflow and outflow of BSS. This equilibrium exists because of the advantages of modern cataract surgery equipment and technique. Only a small volume controlled leakage of BSS is observed to leak around the infusion sleeve. A similar amount of leakage occurs during the quadrant removal phase of the surgery as well. Unnecessary surgeon generated motions are eliminated as are extremes and consequent substantial changes in vacuum and occlusion levels.

Most machines can create this scenario to varying degrees. I use the Alcon Infiniti (Alcon Surgical) micro-coaxial system. In this system, all of the components are matched to each other in order to minimize imprecision and maximize efficiency, reproducibility, and safety. The 2.4 mm. keratome is capable of creating a perfect 2.4 mm. width with a 1.8 mm. length shelf incision before the introduction of viscoelastic. This can be accomplished while the 22.5 degree angle paracentesis blade stabilizes the globe.

Prevention and Management of Intraoperative Floppy Iris Syndrome 23

Fig. 7. The 0.9 mm. outside diameter 12 degree shaft bend tip is surrounded by the Ultra infusion sleeve through a 2.4 mm. clear corneal incision in the micro-coaxial system.

relatively two-dimensional plate.

For sculpting, I use relatively low settings featuring a bottle height of 78 cms, surgeon control of continuous longitudinal phacoemulsification maximum 90%, vacuum of 50 mmHg., and AFR of 14 cc./min. I use enough power as necessary to efficiently sculpt to a level without displacing the lens that will create circumstances that yield four equal nuclear fragments after cracking. If the lens is hard, I'll use the tip on its side in sculpt mode to reduce the size of the quadrants by buzzing off their internal corners thus rendering them a

Fig. 6. The 22.5 degree angle paracentesis blade stabilizes the globe by pulled slightly upward and toward the surgeon while the 2.4 mm keratome is used to create the primary incision.)

The Ultra infusion sleeve is specifically designed to use within that incision surrounding the 0.9 mm. outside diameter shaft phacoemulsification tip (12 degree shaft bend mini-flare, 45 degree aperture angle, ABS featured).

Fig. 6. The 22.5 degree angle paracentesis blade stabilizes the globe by pulled slightly upward and toward the surgeon while the 2.4 mm keratome is used to create the primary

The Ultra infusion sleeve is specifically designed to use within that incision surrounding the 0.9 mm. outside diameter shaft phacoemulsification tip (12 degree shaft bend mini-flare, 45

incision.)

degree aperture angle, ABS featured).

Fig. 7. The 0.9 mm. outside diameter 12 degree shaft bend tip is surrounded by the Ultra infusion sleeve through a 2.4 mm. clear corneal incision in the micro-coaxial system.

For sculpting, I use relatively low settings featuring a bottle height of 78 cms, surgeon control of continuous longitudinal phacoemulsification maximum 90%, vacuum of 50 mmHg., and AFR of 14 cc./min. I use enough power as necessary to efficiently sculpt to a level without displacing the lens that will create circumstances that yield four equal nuclear fragments after cracking. If the lens is hard, I'll use the tip on its side in sculpt mode to reduce the size of the quadrants by buzzing off their internal corners thus rendering them a relatively two-dimensional plate.

Prevention and Management of Intraoperative Floppy Iris Syndrome 25

Fig. 9. The lower left quadrant has been de-bulked and the upper right one is about to be

shaved in similar fashion.

Fig. 8. Moderate width grooves have been sculpted through the nucleus creating 4 quadrants to be removed.

Fig. 8. Moderate width grooves have been sculpted through the nucleus creating 4

quadrants to be removed.

Fig. 9. The lower left quadrant has been de-bulked and the upper right one is about to be shaved in similar fashion.

Prevention and Management of Intraoperative Floppy Iris Syndrome 27

Fig. 11. The second quadrant is about to be engaged by the tip aperture which has been

turned on its side for safer and easier access.

Fig. 10. All four quadrants have been debulked of the most firm central nuclear material leaving the more soft shell to be centralized and aspirated during quadrant removal.

In normal cases with normal size pupils, the quadrant removal settings are increased to a still fairly modest bottle height of 85 cms., vacuum of 400 mm. Hg and AFR 35 cc. /min. maintaining a rise time of -1 but changing to a torsional motion with vacuum triggered interjected longitudinal ultrasonic tip motion (I.P., Alcon Surgical) (Vacuum Trigger = 90% of 400 mm. Hg, On Time = 7 msec, Longitudinal/Torsional ratio = 1.0). Continuous longitudinal ultrasound may be needed in extremely hard lenses in which I also use a rise time of -1 on the Infiniti to slow the rate of vacuum accumulation. In cases with borderline pupils, I reduce the aspiration flow rate to 25 cc/min in either IP or longitudinal to reduce flow, turbulence, iris fluttering, and miosis. This is extremely effective in maintaining pupil size.

Fig. 10. All four quadrants have been debulked of the most firm central nuclear material leaving the more soft shell to be centralized and aspirated during quadrant removal.

size.

In normal cases with normal size pupils, the quadrant removal settings are increased to a still fairly modest bottle height of 85 cms., vacuum of 400 mm. Hg and AFR 35 cc. /min. maintaining a rise time of -1 but changing to a torsional motion with vacuum triggered interjected longitudinal ultrasonic tip motion (I.P., Alcon Surgical) (Vacuum Trigger = 90% of 400 mm. Hg, On Time = 7 msec, Longitudinal/Torsional ratio = 1.0). Continuous longitudinal ultrasound may be needed in extremely hard lenses in which I also use a rise time of -1 on the Infiniti to slow the rate of vacuum accumulation. In cases with borderline pupils, I reduce the aspiration flow rate to 25 cc/min in either IP or longitudinal to reduce flow, turbulence, iris fluttering, and miosis. This is extremely effective in maintaining pupil

Fig. 11. The second quadrant is about to be engaged by the tip aperture which has been turned on its side for safer and easier access.

Prevention and Management of Intraoperative Floppy Iris Syndrome 29

secondary effects on the iris are minimized as well. In extremely hard nuclei, it may be sometimes necessary to use longitudinal phacoemulsification during the occlusion mode of

Preventing a floppy iris is much easier than managing it. By definition, an iris with or without a baseline flaccid tone only becomes floppy because of the turbulence it experiences

3. If the pupil size is small and there is too much iris surface area to start with, the pupil should be mechanically dilated i.e. the iris area should be made smaller. In normal circumstances, a 4.5 mm. pupil and capsulorhexis diameter will be the minimum considered. Because of the affects of capsule contraction syndrome, it is particularly important to create at least a 5.0 mm. diameter capsulorhexis in patients with

6. A huge reduction in turbulence can be accomplished by using a low bottle height and aspiration flow rate during quadrant removal. Reducing the AFR to 25 cc/min. and maintaining a BSS bottle height of 78 cm. creates a quiet chamber, minimal turbulence,

7. If the iris does becomes floppy but the pupil size is still reasonable to continue phacoemulsification (depending on where in the process one is), additional Viscoat may tamponade turbulence effects on the iris, keep the pupil from becoming even smaller,

8. Whether the iris is floppy or not, if the pupil comes down to a level that makes the surgeon uncomfortable with the adequacy of visualization and the ability to execute surgical maneuvers, things can get difficult. That is, it's not so much about discovering if the iris will become floppy; it's more about the initial size of the pupil and attempting to maintain it by exercising smooth surgical technique through controlled hydrodynamics. If visualization becomes compromised because of pupil reduction or if iris is aspirated, iris retractors can still be placed at any stage during phacoemulsification, or even during the cortex aspiration stage if necessary. It's always better to stop and take a few moments to improve the situation and finish in an orderly

David Chang M.D. and John R. Campbell M. D. made an important discovery of an association of intraoperative complications caused by irises which appeared to be floppy during phacoemulsification in patients who were shown to be taking Tamsulosin (Flomax). (Chang 2005) Ever since then ophthalmic surgeons have been concerned about "Flomax patients" and iris related complications during cataract surgery. Even in television commercials for the product, patients are advised to reveal to their eye surgeons if they are

once surgery has begun and BSS is flowing around it. Prevention is the key:

4. Reduce nucleus bulk during sculpting with low vacuum and AFR

and virtually no iris fluttering and pupil diameter reduction.

5. Use a longer rise time to reach maximum vacuum (-1 for me on the Infiniti).

fashion rather than to continue on an unnecessarily higher risk course.

quadrant removal to create this smooth balance.

1. Use maximal pharmacologic dilation.

pseudoexfoliation (Davison 1993).

and allow the case to be finished safely.

**7. Opinions on floppy iris syndrome**

on the medication.

2. Create perfect incisions.

**6. Prevention**

Fig. 12. The second quadrant has been centralized and the tip is oriented obliquely for best visualization and separation from the posterior capsule during its aspiration.

This reduction in flow creates a very quiet and stable anterior chamber and virtually eliminates any iris fluttering and consequent pupil size reduction. I'll usually shave the corners away during sculpting in these cases too, even if the nucleus is average firmness or soft so that the volume of material that is removed during this phase of surgery will be less. An additional measure which can be helpful is the injection of some additional Viscoat into the anterior chamber, especially preceding removal of the last quadrant. This protects the cornea, posterior capsule, and creates some additional dampening of hydraulic shock to the iris. To prevent thermal effects of the moving phacoemulsification tip at the incision, it's important to re-establish outflow by applying vacuum in foot position 2 prior to engaging phacoemulsification energy in foot position 3.

Modern machines like the Infiniti have minimized post-occlusion surge but there are still some shock waves transmitted to the iris by the quick oscillations of IOP secondary to the varying degrees of occlusion and pressure changes associated with aspiration of nuclear fragments in the quadrant removal mode. These pulsations are reduced by reducing the AFR to 25 while efficient removal of firm fragments is still possible using proportionally greater ultrasonic and vacuum contributions. It is most efficient to create a dynamic and continuous balance of ultrasonic energy, vacuum, and outflow during this phase of phacoemulsification. That way the extremes in pressure and flow are minimized and their secondary effects on the iris are minimized as well. In extremely hard nuclei, it may be sometimes necessary to use longitudinal phacoemulsification during the occlusion mode of quadrant removal to create this smooth balance.

### **6. Prevention**

28 Cataract Surgery

Fig. 12. The second quadrant has been centralized and the tip is oriented obliquely for best

This reduction in flow creates a very quiet and stable anterior chamber and virtually eliminates any iris fluttering and consequent pupil size reduction. I'll usually shave the corners away during sculpting in these cases too, even if the nucleus is average firmness or soft so that the volume of material that is removed during this phase of surgery will be less. An additional measure which can be helpful is the injection of some additional Viscoat into the anterior chamber, especially preceding removal of the last quadrant. This protects the cornea, posterior capsule, and creates some additional dampening of hydraulic shock to the iris. To prevent thermal effects of the moving phacoemulsification tip at the incision, it's important to re-establish outflow by applying vacuum in foot position 2 prior to engaging

Modern machines like the Infiniti have minimized post-occlusion surge but there are still some shock waves transmitted to the iris by the quick oscillations of IOP secondary to the varying degrees of occlusion and pressure changes associated with aspiration of nuclear fragments in the quadrant removal mode. These pulsations are reduced by reducing the AFR to 25 while efficient removal of firm fragments is still possible using proportionally greater ultrasonic and vacuum contributions. It is most efficient to create a dynamic and continuous balance of ultrasonic energy, vacuum, and outflow during this phase of phacoemulsification. That way the extremes in pressure and flow are minimized and their

visualization and separation from the posterior capsule during its aspiration.

phacoemulsification energy in foot position 3.

Preventing a floppy iris is much easier than managing it. By definition, an iris with or without a baseline flaccid tone only becomes floppy because of the turbulence it experiences once surgery has begun and BSS is flowing around it. Prevention is the key:

#### **7. Opinions on floppy iris syndrome**

David Chang M.D. and John R. Campbell M. D. made an important discovery of an association of intraoperative complications caused by irises which appeared to be floppy during phacoemulsification in patients who were shown to be taking Tamsulosin (Flomax). (Chang 2005) Ever since then ophthalmic surgeons have been concerned about "Flomax patients" and iris related complications during cataract surgery. Even in television commercials for the product, patients are advised to reveal to their eye surgeons if they are on the medication.

**3**

*Japan*

**Anticoagulant and Antiplatelet Use in Cataract Surgery and Combined**

*Department of Ophthalmology, Kanmon Medical Center, Shimonoseki,*

Patients receiving long-term anticoagulant and antiplatelet medications pose a clinical challenge when therapy needs intraocular surgery, including cataract surgery and vitrectomy [1-3]. Maintaining antiplatelet and anticoagulation places them at risk for serious bleeding complications, whereas discontinuing these medications puts them at risk of thromboembolic complications [4-6]. Currently, there is little consensus on the appropriate perioperative treatment of patients on long-term acetylsalicylic acid (aspirin) and warfarin therapy [7-9]. In this study, we compared the incidence of hemorrhagic and nonhemorrhagic complications and visual course of phacoemulsification alone and combined phacoemulisification and vitrectomy between patients who maintained or discontinued

A total of 824 consecutive cases of 532 patients undergoing cataract surgery alone and of 69 consecutive cases of 69 patients undergoing combined cataract and vitreous surgery for the treatment of epiretinal membrane and macular hole who had been administered warfarin and/or aspirin for 6 months or longer between April 2005 and March 2009 were studied (Table 1). Before April 2007, all patients discontinued the drugs prior to the surgery. After

> Anticoagulant and antiplatelet medications

Table 1. Outline of patients with discontinuation and maintenance of anticoagulant and/or

No Financial support has been received by any authors and none of the authors has any proprietary

Maintenance subgroup 258 (403)

Discontinuation subgroup 33 (33) Maintenance subgroup 36 (36)

Phacoemulsification alone group Discontinuation subgroup 274 (421)

**1. Introduction**

anticoagulant and/or antiplatelet medications.

**2. Patients and methods**

Combined phacoemulsification and

interest in the subject matter presented.1

vitrectomy group

antiplatelet medications

**with Posterior Vitrectomy**

1Hiroshi Kobayashi

Number of patients (Number of cases)

The author feels that the relationships between Flomax and floppy iris complications are in fact a statistical one. Almost all of the floppy iris cases of in their series were on Flomax but only about 60% of the patients who were on Flomax developed intraoperative floppy iris syndrome IFIS (Chang 2005). Mechanical stretching of the iris to make the pupil larger seemed to make the iris even more exposed to increased floppiness.

Even if patients are not on alpha 1 adrenergic antagonist, often patients with medium size pupils seem to have irises which suddenly flutter within the turbulence of BSS flow within the anterior chamber and behind the iris during phacoemulsification. Many times in these cases, the very first fluttering seems to initiate an almost immediate pupil constriction thus beginning the cascade to smaller and smaller pupil size because of increasing iris area and consequent increased capture of fluidic turbulence and more iris fluttering, just like a sailboat's larger jib catches more wind.

#### **8. References**

### **Anticoagulant and Antiplatelet Use in Cataract Surgery and Combined with Posterior Vitrectomy**

1Hiroshi Kobayashi *Department of Ophthalmology, Kanmon Medical Center, Shimonoseki, Japan*

#### **1. Introduction**

30 Cataract Surgery

The author feels that the relationships between Flomax and floppy iris complications are in fact a statistical one. Almost all of the floppy iris cases of in their series were on Flomax but only about 60% of the patients who were on Flomax developed intraoperative floppy iris syndrome IFIS (Chang 2005). Mechanical stretching of the iris to make the pupil larger

Even if patients are not on alpha 1 adrenergic antagonist, often patients with medium size pupils seem to have irises which suddenly flutter within the turbulence of BSS flow within the anterior chamber and behind the iris during phacoemulsification. Many times in these cases, the very first fluttering seems to initiate an almost immediate pupil constriction thus beginning the cascade to smaller and smaller pupil size because of increasing iris area and consequent increased capture of fluidic turbulence and more iris fluttering, just like a

Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J

Chylack LT. The lens opacities classification system III. Arch Ophthalmol. June 1993; 111:

Masket S, Belani S. Combined preoperative topical atropine sulfate 1% and intracameral

Shugar JK. Use of epinephrine for IFIS prophylaxis. J Cataract Refract Surg. July 2006; 32:

nonpreserved epinephrine hydrochloride 1:2500 for management of intraoperative

Davison JA. Capsule Contraction Syndrome. J Cataract Refract Surg 1993; 19: 582-589. Graether JM. Graether pupil expander for managing the small pupil during surgery. J

floppy-iris syndrome. J Cataract Refract Surg 2007; 33:580-582.

seemed to make the iris even more exposed to increased floppiness.

sailboat's larger jib catches more wind.

Cataract Refract Surg. 2005; 31:664-673.

Cataract Refract Surg 1996; 22:530-535.

**8. References**

831-836.

1074-1075.

Patients receiving long-term anticoagulant and antiplatelet medications pose a clinical challenge when therapy needs intraocular surgery, including cataract surgery and vitrectomy [1-3]. Maintaining antiplatelet and anticoagulation places them at risk for serious bleeding complications, whereas discontinuing these medications puts them at risk of thromboembolic complications [4-6]. Currently, there is little consensus on the appropriate perioperative treatment of patients on long-term acetylsalicylic acid (aspirin) and warfarin therapy [7-9]. In this study, we compared the incidence of hemorrhagic and nonhemorrhagic complications and visual course of phacoemulsification alone and combined phacoemulisification and vitrectomy between patients who maintained or discontinued anticoagulant and/or antiplatelet medications.

#### **2. Patients and methods**

A total of 824 consecutive cases of 532 patients undergoing cataract surgery alone and of 69 consecutive cases of 69 patients undergoing combined cataract and vitreous surgery for the treatment of epiretinal membrane and macular hole who had been administered warfarin and/or aspirin for 6 months or longer between April 2005 and March 2009 were studied (Table 1). Before April 2007, all patients discontinued the drugs prior to the surgery. After

Table 1. Outline of patients with discontinuation and maintenance of anticoagulant and/or antiplatelet medications

No Financial support has been received by any authors and none of the authors has any proprietary interest in the subject matter presented.1

Anticoagulant and Antiplatelet Use in Cataract Surgery and Combined with Posterior Vitrectomy 33

and cardiovascular events such as deep vein thrombosis, myocardial ischemia, and myocardial infarction. Hemorrhagic complications were defined as subconjunctival hemorrhage and hyphema, or retinal, vitreous and choroidal/suprachoroidal hemorrhage. Hypotony was defined as an intraocular pressure of less than 4 mmHg after surgery, while the criteria of Teehasaenee and Ritch [11] were used to define shallow anterior chamber. An intraocular pressure spike was defined as an intraocular pressure on the first postoperative day that was greater than or equal to 3 mmHg higher than the level

A Student's t-test was used to evaluate the continuous variables, while a paired t-test was used was used to evaluate the difference in intraocular pressures between the follow-up intervals. All t-tests were two-tailed. Categoric variables were evaluated by using the chisquare test, the Fisher exact test, or the Spearman rank correlation, as appropriate. Results

For the pairing of groups, baseline values for age, sex, BCVA, and prothrombin timeinternational normalized ratio (PT-INR) were used for matching. When correlations between paired observations were noted, we used the F-test to examine the variances

Patient demographics are summarized in Table 2. No significant differences were found between the two subgroups for age, sex, or BCVA in the phacoemulsification alone group and the combined phacoemulsification and vitrectomy group. In patients who were administered warfarin, mean PT-INR was 1.94 ± 0.77 in the maintenance subgroup and 1.87 ± 0.62 in the discontinuation subgroup in the phacoemulsification alone group (P = 0.3) and 1.89 ± 0.57 in the maintenance subgroup and 2.23 ± 0.66 in the maintenance subgroup in the

**Phacoemulsification alone group:** As seen in Table 3, there were no systemic complications or any significant intraoperative bleeding noted for the two subgroups. There were 87 eyes (21.6 %) in the maintenance subgroup and 46 eyes (10.9%) in the discontinuation subgroup that exhibited subconjunctival hemorrhage of greater than one quadrant (P < 0.0001). On the first postoperative day, microscopic hyphema was seen in 26 eyes (6.5%) in the maintenance subgroup and in 11 eyes (2.6%) in the discontinuation subgroup (P = 0.0078), whereas no apparent hyphema was found in the two subgroups. Within 1 week of the surgical procedure, all bleeding had stopped without affecting the visual acuity. There was also no vitreous or choroidal/ suprachoroidal hemorrhage found in either of the two subgroups. There were 5 posterior capsule rupture and 2 vitreous loss in the maintenance subgroup and 7 posterior capsule rupture and 3 vitreous loss in the discontinuation subgroup, respectively (posterior capsule rupture: P = 0.6; vitreous loss: P = 0.7) (Table 3). No significant differences were noted for the incidence of non-hemorrhagic intraoperative complications between the

were defined as being statistically significant when P < 0.05.

combined phacoemulsification and vitrectomy group (P = 0.0249).

**3.1 Hemorrhagic and non-hemorrhagic complications**

observed preoperatively.

**2.2 Statistical analysis**

between the two populations.

**3. Results Baseline**

two subgroups.

April 2007, all patients maintained the treatment at the time of surgery (Table 1). The discontinuation subgroups consisted of patients who ceased taking warfarin and/or aspirin 1 week before the surgery, with their therapies then restarted 2 days postoperatively. The study protocol and consent forms were approved by the Human Subjects Committee.

#### **2.1 Surgical procedure and postoperative interventions**

#### **Cataract surgery**

Phacoemulsification and intraocular lens implantation was performed through a superior sclerocorneal incision after scleral cauterization. Sub-Tenon anesthesia with 2% lidocaine (Xylocaine, Asteras, Tokyo, Japan) was employed using Fukasaku's blunt subtenon's cannula (Handaya, Tokyo, Japan). A standard phacoemulsification technique was used. In all cases, a three-piece hydrophobic acrylic intraocular lens (AcrySof™ MA30BM; Alcon, Fort Worth, TX, USA) was implanted. Sodium hyaluronate 1% (Healon, AMO, Santana, CA, USA) was used as viscoelastics.

#### **Vitrectomy for epiretinal membrane and macular hole**

A standard three port pars plana vitrectomy was performed in all patients after sub-Tenon anesthesia, phacoemulsification and intraocular lens implantation. We achieved a complete posterior vitreous detachment during pars plana vitrectomy using a vitreous cutter. For patients with epiretinal membrane, the membranes were removed with a slightly bent microvitreoretinal blade or internal limiting membrane forceps. For patients with macular hole, the internal limiting membranes around the macular hole were removed in assistance with triamcinolone acetonide or indocyanine green. Sulfur hexafluoride (20%) was used for gas tamponade. Patients remained in the prone position for 7-10 days postoperatively.

#### **Postoperative management**

In both groups, all patients were given topical levofloxacin, dexamethasone and diclofenac three times daily during the first 2 weeks, with the drugs then tapered off over the next 3 months.

#### **Evaluation of outcomes**

Before enrollment, patients had an ocular and systemic history taken as well as slit-lamp biomicroscopy, visual acuity, a physical examination, and dilated fundoscopy. Bestcorrected visual acuity (BCVA) was measured, with the log of the minimum angle of resolution (LogMAR) then calculated and used for all statistical analyses. Intraocular pressure was measured using Goldmann applanation tonometry while a slit-lamp examination was used to clinically grade the preoperative nuclear sclerosis as per the method of Emery and Little [10]. After pupil dilation, ophthalmoscopic and slit-lamp biomicroscopic examinations were employed to assess retinal, vitreous and choroidal/suprachoroidal hemorrhages. For patients with epiretinal membrane and macular hole, we performed optical coherence tomography (OCT) scanning (OCT scanner 3000 and Cirrus, Humphrey Instruments, San Leandro, California) before and 1, 3, and 6 months after surgery. The fovea was identified as the patient's fixation point or with the fundus monitor in the OCT device. The cross-sectional images were normalized and smoothed using OCT plug-in software. Patients were also assessed intraoperatively and at every postoperative visit for the presence of general complications, which included cerebral events such as transient ischemic attack and cerebral infarction and hemorrhage, and cardiovascular events such as deep vein thrombosis, myocardial ischemia, and myocardial infarction. Hemorrhagic complications were defined as subconjunctival hemorrhage and hyphema, or retinal, vitreous and choroidal/suprachoroidal hemorrhage. Hypotony was defined as an intraocular pressure of less than 4 mmHg after surgery, while the criteria of Teehasaenee and Ritch [11] were used to define shallow anterior chamber. An intraocular pressure spike was defined as an intraocular pressure on the first postoperative day that was greater than or equal to 3 mmHg higher than the level observed preoperatively.

#### **2.2 Statistical analysis**

A Student's t-test was used to evaluate the continuous variables, while a paired t-test was used was used to evaluate the difference in intraocular pressures between the follow-up intervals. All t-tests were two-tailed. Categoric variables were evaluated by using the chisquare test, the Fisher exact test, or the Spearman rank correlation, as appropriate. Results were defined as being statistically significant when P < 0.05.

For the pairing of groups, baseline values for age, sex, BCVA, and prothrombin timeinternational normalized ratio (PT-INR) were used for matching. When correlations between paired observations were noted, we used the F-test to examine the variances between the two populations.

#### **3. Results**

#### **Baseline**

32 Cataract Surgery

April 2007, all patients maintained the treatment at the time of surgery (Table 1). The discontinuation subgroups consisted of patients who ceased taking warfarin and/or aspirin 1 week before the surgery, with their therapies then restarted 2 days postoperatively. The study protocol and consent forms were approved by the Human Subjects Committee.

Phacoemulsification and intraocular lens implantation was performed through a superior sclerocorneal incision after scleral cauterization. Sub-Tenon anesthesia with 2% lidocaine (Xylocaine, Asteras, Tokyo, Japan) was employed using Fukasaku's blunt subtenon's cannula (Handaya, Tokyo, Japan). A standard phacoemulsification technique was used. In all cases, a three-piece hydrophobic acrylic intraocular lens (AcrySof™ MA30BM; Alcon, Fort Worth, TX, USA) was implanted. Sodium hyaluronate 1% (Healon, AMO, Santana, CA,

A standard three port pars plana vitrectomy was performed in all patients after sub-Tenon anesthesia, phacoemulsification and intraocular lens implantation. We achieved a complete posterior vitreous detachment during pars plana vitrectomy using a vitreous cutter. For patients with epiretinal membrane, the membranes were removed with a slightly bent microvitreoretinal blade or internal limiting membrane forceps. For patients with macular hole, the internal limiting membranes around the macular hole were removed in assistance with triamcinolone acetonide or indocyanine green. Sulfur hexafluoride (20%) was used for gas tamponade. Patients remained in the prone position for 7-10 days postoperatively.

In both groups, all patients were given topical levofloxacin, dexamethasone and diclofenac three times daily during the first 2 weeks, with the drugs then tapered off over the next 3

Before enrollment, patients had an ocular and systemic history taken as well as slit-lamp biomicroscopy, visual acuity, a physical examination, and dilated fundoscopy. Bestcorrected visual acuity (BCVA) was measured, with the log of the minimum angle of resolution (LogMAR) then calculated and used for all statistical analyses. Intraocular pressure was measured using Goldmann applanation tonometry while a slit-lamp examination was used to clinically grade the preoperative nuclear sclerosis as per the method of Emery and Little [10]. After pupil dilation, ophthalmoscopic and slit-lamp biomicroscopic examinations were employed to assess retinal, vitreous and choroidal/suprachoroidal hemorrhages. For patients with epiretinal membrane and macular hole, we performed optical coherence tomography (OCT) scanning (OCT scanner 3000 and Cirrus, Humphrey Instruments, San Leandro, California) before and 1, 3, and 6 months after surgery. The fovea was identified as the patient's fixation point or with the fundus monitor in the OCT device. The cross-sectional images were normalized and smoothed using OCT plug-in software. Patients were also assessed intraoperatively and at every postoperative visit for the presence of general complications, which included cerebral events such as transient ischemic attack and cerebral infarction and hemorrhage,

**2.1 Surgical procedure and postoperative interventions**

**Vitrectomy for epiretinal membrane and macular hole**

**Cataract surgery**

USA) was used as viscoelastics.

**Postoperative management**

**Evaluation of outcomes**

months.

Patient demographics are summarized in Table 2. No significant differences were found between the two subgroups for age, sex, or BCVA in the phacoemulsification alone group and the combined phacoemulsification and vitrectomy group. In patients who were administered warfarin, mean PT-INR was 1.94 ± 0.77 in the maintenance subgroup and 1.87 ± 0.62 in the discontinuation subgroup in the phacoemulsification alone group (P = 0.3) and 1.89 ± 0.57 in the maintenance subgroup and 2.23 ± 0.66 in the maintenance subgroup in the combined phacoemulsification and vitrectomy group (P = 0.0249).

#### **3.1 Hemorrhagic and non-hemorrhagic complications**

**Phacoemulsification alone group:** As seen in Table 3, there were no systemic complications or any significant intraoperative bleeding noted for the two subgroups. There were 87 eyes (21.6 %) in the maintenance subgroup and 46 eyes (10.9%) in the discontinuation subgroup that exhibited subconjunctival hemorrhage of greater than one quadrant (P < 0.0001). On the first postoperative day, microscopic hyphema was seen in 26 eyes (6.5%) in the maintenance subgroup and in 11 eyes (2.6%) in the discontinuation subgroup (P = 0.0078), whereas no apparent hyphema was found in the two subgroups. Within 1 week of the surgical procedure, all bleeding had stopped without affecting the visual acuity. There was also no vitreous or choroidal/ suprachoroidal hemorrhage found in either of the two subgroups. There were 5 posterior capsule rupture and 2 vitreous loss in the maintenance subgroup and 7 posterior capsule rupture and 3 vitreous loss in the discontinuation subgroup, respectively (posterior capsule rupture: P = 0.6; vitreous loss: P = 0.7) (Table 3). No significant differences were noted for the incidence of non-hemorrhagic intraoperative complications between the two subgroups.

Anticoagulant and Antiplatelet Use in Cataract Surgery and Combined with Posterior Vitrectomy 35

respectively (vitreous hemorrhage: P = 0.3; retinal hemorrhage: P = 0.3) (Table 3). Within 1 month of the surgical procedure, bleeding was not found without affecting the visual acuity. There was no vitreous or choroidal/suprachoroidal hemorrhage found in either of the two subgroups. No significant difference was found in non-hemorrhagic complications between

Discontinuation

P

group

0 (0.0%) 0 (0.0%) -

Discontinuation

P

group

36 eyes 33 eyes

403 eyes 421 eyes

group

Cerebral events 0 (0.0%) 0 (0.0%) - Cardiovascular events 0 (0.0%) 0 (0.0%) -

Hyphema (> 1mm) 0 (0.0%) 0 (0.0%) - Microscopic hyphema 26 (6.5%) 11 (2.6%) 0.0078 Vitreous hemorrhage 0 (0.0%) 0 (0.0%) - Retinal hemorrhage 6 (1.4%) 3 (0.7%) 0.3

Early perforation 7 (1.7%) 9 (1.1%) 0.7 CCC tear 13 (4.0 %) 18 (4.3%) 0.4 Posterior capsule rupture 5 (1.2%) 7 (1.7%) 0.6 Vitreous loss 2 (0.4%) 3 (0.3%) 0.7 Nucleus drop 0 (0.0%) 0 (0.0%) -

Hypotony 0 (0.0%) 0 (0.0%) - IOP spike 16 (3.9%) 13 (3.1%) 0.5 Corneal edema 8 (2.0%) 10 (2.4%) 0.7 Shallow/flat anterior chamber 0 (0.0%) 0 (0.0%) - Distorted pupil 2 (0.0%) 3 (0.0%) 0.7 IOL dislocation 0 (0.0%) 0 (0.0%) - Vitreous herniation 0 (0.0%) 0 (0.0%) - Retinal detachment 0 (0.0%) 0 (0.0%) - Endophthalmitis 0 (0.0%) 0 (0.0%) -

group

Subconjunctival hemorrhage 87 (21.6%) 46 (10.9%) < 0.0001

the two subgroups (Table 3).

**Systemic complications**

**Hemorrhagic complications**

Choroidal/suprachoridal

**Non-hemorrhagic complications** Intraoperative complications

**Early postoperative complications**