Cataract surgery is one of the most commonly performed surgical procedures worldwide. During this surgery, the pupil needs to be adequately widened (dilated) to allow the surgeon to safely access and remove the clouded lens. In some patients, however, the iris - the colored part of the eye that controls pupil size, behaves unexpectedly during surgery. Instead of remaining stable, it becomes floppy, billows in response to fluid currents inside the eye, and the pupil progressively narrows despite the use of dilating eye drops. This condition is called Intraoperative Floppy Iris Syndrome (IFIS) and can make cataract surgery significantly more difficult, increasing the risk of complications such as iris damage, rupture of the lens capsule, or loss of the lens into the back of the eye.

IFIS was first described in men taking alpha-1 adrenergic receptor antagonists (alpha-blockers), most commonly used to treat an enlarged prostate. Over time, other medications have also been linked to IFIS in both sexes. However, women develop IFIS less frequently than men, largely because alpha-blockers are prescribed less often in women. Despite this lower frequency, when IFIS occurs in women, it tends to be more severe and is associated with higher rates of surgical complications. This suggests that additional, as yet unidentified, factors may predispose women to IFIS, particularly those not taking any of the medications known to cause it.

This study was designed to identify which factors increase the risk of IFIS in women undergoing routine cataract surgery. We prospectively evaluated female cataract patients at a tertiary eye center. Before surgery, all patients completed a structured questionnaire covering their medical history, current and past medications, prior surgical procedures, and eye health. Standardized pupil size measurements were obtained under different lighting conditions. During surgery, each case was evaluated for the presence and severity of IFIS by two independent senior ophthalmologists reviewing the surgical video recordings. The central hypothesis of this study is that factors beyond medication use, including prior surgical history, may independently contribute to IFIS risk in women.

Background and Rationale Intraoperative floppy iris syndrome (IFIS) represents a well-recognized surgical challenge during phacoemulsification cataract surgery, historically attributed to alpha-1 adrenergic receptor antagonist (α1-ARA) use, predominantly in men receiving treatment for benign prostatic hyperplasia. Emerging evidence suggests that IFIS in women follows a distinct epidemiological and clinical pattern: lower overall incidence but disproportionately higher severity and complication rates compared to male patients. The pharmacological and non-pharmacological determinants of IFIS in women remain incompletely characterized. This study was designed to prospectively determine the prevalence of IFIS in a female cataract population and identify its independent clinical risk factors, with emphasis on factors operating independently of α1-ARA exposure.

Data Collection Framework

Preoperative data collection is structured around three domains:

Domain 1 - Systemic history: Standardized face-to-face interview documenting comorbidities (diabetes mellitus, hypertension, thyroid dysfunction, rheumatological disease), current medications with duration of use, urinary incontinence status and its treatment, and complete surgical history (cardiovascular, abdominal, gynecologic - specifically myomectomy, hysterectomy, and bilateral salpingo-oophorectomy).

Domain 2 - Ocular parameters: Best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure by non-contact tonometry, ocular biometry (axial length, anterior chamber depth), iris morphology (color, pseudoexfoliation, iridodonesis), and pupil diameter under scotopic, mesopic, and photopic conditions via integrated pupillography software.

Domain 3 - Pharmacological mydriasis response: Rather than a fixed time-based protocol, adequacy of dilation is confirmed by functional assessment - absence of the direct pupillary light reflex upon penlight examination by a single designated investigator. Dilated pupil diameter is recorded upon confirmed dilation. This approach was selected to capture inter-individual variability in mydriatic response, particularly relevant in patients with potential iris dilator dysfunction.

Outcome Ascertainment The primary outcome - IFIS diagnosis and grading - is determined through dual independent review. The operating surgeon provides the initial intraoperative assessment; a second senior ophthalmologist, blinded to clinical data, independently reviews the surgical video recording. IFIS classification requires consensus between both reviewers; discordant cases are not classified as IFIS. This two-reviewer consensus model minimizes ascertainment bias and ensures diagnostic consistency across the study period.

IFIS severity is graded on a four-point scale (Chang and Campbell, 2005): Grade 0 (stable iris); Grade 1 (iris billowing, no prolapse or significant miosis); Grade 2 (billowing with prolapse or ≥2 mm pupil reduction); Grade 3 (billowing with both prolapse and ≥2 mm pupil reduction).

Surgical Standardization To minimize surgeon-related confounding, all procedures are performed by three designated senior surgeons using an identical phacoemulsification platform, standardized incision architecture (2.2 mm temporal clear corneal), and uniform fluidic parameters. Intracameral epinephrine (1:10,000) is administered routinely in all cases following side-port construction. Intraoperative adjuncts - capsular tension rings, iris hooks, pupil expansion devices, and corneal sutures - are recorded as secondary outcome variables reflecting surgical complexity attributable to IFIS.

Quality Assurance Data are entered prospectively into a dedicated case record form at each patient encounter. Questionnaire responses are verified against available medical records where possible. Surgical video recordings are archived for all cases to enable post-hoc independent review and audit. IFIS grading discordances between the two reviewers are documented and adjudicated by a third senior ophthalmologist.

Inclusion Criteria:

• Female sex
• Age 50 years or older
• Scheduled for elective phacoemulsification cataract surgery at the study center
• Ability to provide reliable responses to the preoperative assessment questionnaire
• Written informed consent obtained

Exclusion Criteria:

• Cataract of non-senile etiology (traumatic, uveitic, or drug-induced)
• Iris structural or functional abnormalities including coloboma, iris neovascularization, synechiae, and iridoschisis
• History of previous intraocular surgery
• Prior iris-related laser procedures including laser iridoplasty or peripheral iridotomy
• History of scleral buckle surgery
• Inability to complete the preoperative questionnaire reliably
• IFIS diagnosis made by an assessor outside the designated review panel
• Visual acuity of light perception, light projection, or hand motion only at baseline

Only female participants are eligible for this study. The study was specifically designed to investigate the prevalence and risk factors of IFIS in women, a population that has been understudied relative to male patients. Eligibility is restricted to individuals who self-identify as female.

Female patients aged 50 years and older presenting for elective phacoemulsification cataract surgery at a tertiary ophthalmology clinic. The study population represents a consecutive clinical sample drawn from the routine surgical caseload of the center, reflecting a diverse urban and semi-urban patient population referred from both primary and secondary care settings.

Individual participant data will not be shared due to the retrospective nature of the surgical history questionnaire and the sensitive personal health information collected, including gynecologic and systemic surgical history. Patient confidentiality and data protection regulations preclude public sharing of individual-level data. Aggregate de-identified summary data supporting the findings of this study will be available upon reasonable request to the corresponding author following publication.