Pseudoexfoliation and the Cataract Surgeon

From the Summer Conference presented by the Utah Ophthalmology Society

Bradford J. Shingleton, MD, Associate Professor of Ophthalmology, Harvard Medical School, President, American Society of Cataract and Refractive Surgery, Boston, MA

Educational Objectives

The goal of this program is to improve the management of cataract surgery for patients with pseudoexfoliation (PXF). After hearing and assimilating this program, the participant will be better able to:

1.   Summarize the benefits and shortcomings of medical, laser, and surgical therapies for PXF.

2.   Compare and contrast the outcomes of cataract surgery in patients with PXF with and without glaucoma.

3.   Recognize the preoperative signs of zonule weakness.

4.   Describe the importance of risk factors for PXF in predicting outcomes after phacoemulsification.

5.   Optimize pupil management, capsulorrhexis, hydrodissection and phacoemulsification, use of capsule support systems, and choice of IOLs when performing surgery on patients with PXF.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the plan­ning committee to disclose relevant financial relationships within the past 12 months that might create any personal con­flicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Shingle­ton has received research grant support from Alcon and Allergan and has served as a consultant for Bausch & Lomb, iScience Interventional, and iTherapeutics. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Shingleton was recorded at Summer Conference, held August 7, 2009, in Deer Valley, UT, and presented by the Utah Ophthalmology Society. The Audio-Digest Foundation thanks Dr. Shingleton and the Utah Ophthalmology Society for their cooperation in the production of this program.

Etiology and Pathogenesis of Pseudoexfoliation

Histopathology: central fibrillar component with amorphous debris; zonules  —  separated at insertion at ciliary body (CB); infiltrated by pseudoexfoliation (PXF) material with fragmentation; lifted off attachment to anterior capsule; intraocular pressure (IOP)  —  trabecular meshwork (TM) obstructed by PXF material; fragmentation in Schlemm’s canal; thin monolayer of endothelial cell proliferation over TM

Etiology: systemic disorder with elevated levels of plasma homocysteine; lysyl oxidase-like 1 (LOXL1) gene associ­ated with manifestations (slit lamp and glaucoma); multifactorial; bilateral with high asymmetry; patients with glaucoma and PXF in one eye have »33% lifetime chance of developing PXF in fellow eye, or 15% to 50% chance over 5 to 10 yr

Prevalence: ubiquitous, with variable levels of penetration; 0.4% to 39% prevalence in patients who have had cata­ract surgery; may account for 75% to 80% of open angle glaucoma (OAG) among Scandinavians

Pseudoexfoliation Glaucoma (PXG)

Background: most common cause of secondary OAG (20% worldwide); glaucoma presents earlier, with higher IOP; even patients with PXF and marginal elevation of IOP have severe damage, more loss of visual field (VF) at presen­tation, and rapid progression; greater diurnal fluctuation of IOP; greater rate of angle closure (acute and chronic)

Medical therapy: similar to primary OAG (POAG); study showed latanoprost (Xalatan) reduced transforming growth factors and matrix metalloproteinases, which are believed to have causal relationship to glaucoma; pilocarpine  —  may reduce release of pigment and PXF material; associated with cataracts, makes pupil smaller, and causes forward rotation of lens if zonules weak; important to follow patients closely because of rapid rate of progression

Laser therapy: most studies used argon laser trabeculoplasty (ALT), but selective LT (SLT) and micropulse-diode LT (MLT) give similar results; rule out angle closure first with gonioscopy; high rate of elevation in IOP after laser therapy in eyes with PXF (especially those with compromised optic nerve); initial response better in eyes with PXF than with POAG (study found 35% reduction in IOP at 1 yr), but response deteriorates more steeply over time than in patients with POAG; study found 80%, 50%, and 10% to 20% rates of success with ALT at 1, 5, and 10 yr, re­spectively

Surgical therapy: procedures similar to those for POAG; eyes with PXF have increased breakdown of blood-aque­ous barrier or aqueous flare (could compromise results of filtration surgery); trabeculectomies, combined proce­dures, tubes, and endocyclophotocoagulation all appropriate; response possibly not as good as for other disorders

Cataract Surgery Series

Background: reviewed »1100 cases of uncomplicated phacoemulsification (phaco) plus implantation of posterior chamber intraocular lens (PC IOL); follow-up of £18 yr (mean of »3 yr); »800 patients had PXF without glaucoma and 240 had PXF with glaucoma (PXG); 137 patients with unilateral PXF had surgery on both eyes

Results: 1 to 2 mm Hg decrease in mean IOP in all eyes through 7 yr; glaucoma medication requirement(GMR) de­creased over 5 yr; all eyes had significant increase in visual acuity (VA) over 7 yr; patients with PXF (no glaucoma) had consistently lower IOP (1 to 2 mm Hg) through 7 to 10 yr; patients with PXG had reduced IOP only in first year; GMR decreased by »50%, but returned to pretreatment levels by 5 to 7 yr (small number of patients became worse)

Pressure spikes: critical in patients with significant disc damage; »7% of eyes had IOP spike of >30 mm Hg at 24 hr after surgery; all had received topical miotic, b-blocker, a-agonist, and systemic carbonic anhydrase inhibitor; 4% of patients with PXF had spike in IOP (similar to that in OAG or normal populations); »20% of patients with PXG had spike; critical time for spike in IOP occurs at 2 to 8 hr; check IOP in patients who have compromised optic nerve on day of surgery

Failures: 2.7% rate of failure (ie, need for medical or laser therapy) in eyes with PXF over »5 yr; 3.7% rate (ie, need for subsequent laser or glaucoma surgery) in eyes with PXG

Preoperative IOP: modifies response; patients with PXF and higher IOP had greater postoperative reduction of IOP; age, sex, and axial length not factors; minimal reduction produced with initial IOP of 20 mm Hg, 3 to 5 mm Hg drop with initial IOP of 21 to 25 mm Hg, £10 mm Hg with initial IOP >25 mm Hg; similar effect seen in OAG; very low initial IOP (eg, 12 mm Hg) may increase slightly; patients with PXG and IOP >25 mm Hg had mean re­duction of »10 mm Hg (40% drop) at 3 yr; important for all patients, especially those with coexisting cataracts and glaucoma, PXG, and POAG

Effects of previous laser or filtration treatment: study found patients with PXG and no previous manipulation of TM had significant reduction of IOP at all times £7 yr; 51 eyes with PXG and previous laser or filtration had slight increase in IOP

Fellow eyes: reduction of IOP and GMR greater in eye with PXF

Phacoemulsification and IOL Implantation (Phaco/IOL)

Protective value: Olmstead County Study found nearly 50% rate of GMR; study of patients with PXF who received phaco found low rates of failure over 5 yr; suggests possible protective value of cataract surgery against develop­ment and progression of glaucoma in patients with PXG (possibly due to mechanical effect of aspiration or opening angle)

Phaco/IOL alone: patients with glaucoma have improved VA and decreased IOP; when rendering patients pseudo­phakic and performing temporal approach, important to have virgin conjunctiva above; filtration surgery in pseudo­phakic eyes very successful when conjunctiva mobile; tube shunts and other procedures also options; speaker frequently performs phaco/IOL alone in patients with PXF, cataract, and glaucoma without significant disc damage and loss of VF; phaco/IOL most common glaucoma procedure worldwide and has significant impact on IOP (long-term adequacy of IOP reduction unclear)

Challenges for the Cataract Surgeon

Background: patients with PXF develop cataracts more rapidly, and cataracts more nuclear and subcapsular; etiology unknown, but may involve ocular ischemia or antioxidant defense mechanism; intraoperative risks include zonule dialysis; postoperative risks include early rise in IOP, late glaucoma, increased inflammation, more deposits and synechiae, higher rate of cystoid macular edema (CME), capsular contraction, anterior chamber (AC) phimosis, and IOL subluxation after mean of 8.5 yr

Intraoperative Risks

Small pupil: possibly caused by infiltration by extracellular material and degeneration of sphincter muscle; with small capsulorrhexis, forces magnified on peripheral zonules

Zonules: infiltrated at origin where they lie over lens and at insertion; degradation and fragmentation occur

Preoperative signs of zonule weakness: phacodonesis, iridodonesis, subluxation of lens, possibly AC depth asym­metry; complicated surgery in fellow eye; increased nuclear density and age; no correlation with amount of PXF material; subluxation of lens often occurs inferiorly; AC depth asymmetry often shallower (evaluate axial depth over iris and at iris plane to lens)

Importance of Risk Factors

Background: study of 1,059 cases of phaco (excluded combined procedures, patients with previous vitreous surgery, scleral buckling surgery, and other complicating factors); preoperative confirmation of lens subluxation or phaco­donesis, or intraoperative documentation confirmed by direct visualization (»6% of eyes found to have weak zon­ules)

Vitrectomy: 1,021 patients did not require vitrectomy, of whom 22 (»2.2%) had weak zonules confirmed intraopera­tively (remainder had preoperative signs of weak zonules); all 22 managed with or without capsular retractors (CR), capsule tension segments (CTS), or capsule tension rings (CTR); 38 eyes (3.6%) required vitrectomy, and all had weak zonules confirmed intraoperatively; 20 of 937 patients (»2%) with no apparent preoperative risk factors required vitrectomy (much higher rate than in patients without PXF); 122 patients who had risk factors (ie, AC depth asymmetry, phacodonesis, subluxation, iridodonesis, or complicated surgery in fellow eye) had 11% rate of vitrectomy; only 2.2% of patients with AC depth asymmetry detected by slit lamp (not due to anisometropia) re­quired vitrectomy (similar to rate without preoperative signs); 39% of eyes with phacodonesis, marked iridodone­sis, or lens subluxation required vitrectomy; rate higher in patients with complicated surgery in fellow eye; speaker experienced 50% rate of vitrectomy in patients with phacodonesis or surgery in fellow eye complicated by weak zonules

Surgical Approach for PXF

Location of incision: speaker prefers posterior limbal incision; shifts more posteriorly if problems anticipated; often performs scleral tunnel and corneal flap in eyes with weak zonules; posterior incision reduces incidence of postop­erative issues (eg, astigmatism) when implanting larger IOL; avoid placing incision and paracentesis near preexist­ing blebs

Ophthalmic viscosurgical devices (OVDs): types include dispersive and cohesive; cohesive OVDs help dilate small pupil, expand capsular bag, and facilitate viscodissection of cortex

Pupil management: dilate preoperatively with topical nonsteroidal anti-inflammatory drugs (NSAIDS); use drops and pledgets for intraoperative pharmacology; important to release synechiae; avoid stretching and sphincterotomy because of concerns about intraoperative floppy iris syndrome (IFIS); use retractors and expanders (eg, Malyugin ring)

Capsulorrhexis: 5.5 mm gives appropriate coverage of implant; if too small, predisposes to AC phimosis (speaker cuts with laser), which increases stress on zonules; if too large, use of capsule support devices compromised; intact capsulorrhexis important

Central curvilinear capsulorrhexis (CCC): ballooning of AC or shift of capsular bag or lens represent high risk factors; speaker uses second instrument (eg, CR, CTS) to stabilize

Hydrodissection: should achieve free rotation of nucleus to minimize transmission of aspiration forces to capsular periphery and fornix

Phacoemulsification: all newer systems perform well; speaker uses chop technique frequently for patients with PXF, and prefers 2-instrument system; work in central zone whenever possible and avoid periphery; use lower-flow sys­tem to avoid excessive deepening and anteroposteriorly directed forces that strip zonules; staining capsule effective; rotate nucleus with engagement, aspirate, and chop in center; signs of zonular instability  —  tilt with eccentric shift; difficult rotation of nucleus; vitreous prolapse; iris epinucleus  —  high-risk zone; if edge of capsule visible because epinucleus adhering, immediately change to CR or CTS

Cortex removal: tend to strip centripetally during irrigation and aspiration; when zonules weak, tangential stripping with low- flow system and capsule support helpful; trouble signs include exaggerated posterior capsule striae, lax­ity, and collapse of capsule equator

Capsule support systems: CR  —  speaker prefers broader and longer types; nonmodified CTR improves IOL centra­tion and reduces intraoperative complications; speaker waits to insert until significant instability noted; indications include all signs of zonular weakness; does not prevent late displacement of IOL or AC phimosis; insert retractor, then shift slowly to far side to minimize displacement of capsular bag; monitor striae and inject slowly; if signifi­cant capsular weakness observed, use modified CTR; single eyelet works for eyes with PXF; suture with 9-0 poly­propylene; CTS  —  now approved for implantation; provide broad area of zonular support; not necessary to fixate with suture (possible to use removable iris hooks); breadth of Ahmed segment effective for grossly displaced lenses; use double-sutured support elements (eg, Cionni ring), expand capsule, pull up 2 sutures (keep segment in for full support); take out CTS gently; acrylic IOL has minimal effect on zonules during unfolding

IOL choices: lens placed in bag or sulcus (speaker favors bag); in eyes that lack capsular integrity, use scleral sutur­ing (not chamber lens), iris suturing, or iris enclavation, and implant AC IOL (appropriate for most patients); all new-generation IOL materials appropriate, but silicone possibly associated with greater AC phimosis; all-acrylic lenses unfold slowly; avoid plate haptic design; speaker favors neutrally aspheric technology, but not lenses with correction for spherical aberration (because if shifting occurs, these cause greater aberrations); speaker does not use accommodating or multifocal lenses in patients with PXF; placement of AC IOL much quicker than scleral sutured PC IOL; if no gross disruption of angle present, current generation AC IOL satisfactory

Anterior vs pars plana vitrectomy: speaker performs hybrid of both; cannot have vitreous to paracentesis or to ker­atome incision; avoid traction; for pars plana vitrectomy, speaker makes scleral tunnels and flaps and inserts ring; posterior segment surgeon performs vitrectomy, and speaker sutures in PC lens

Results: compared eyes that underwent phaco and vitrectomy to those without vitrectomy; both groups had good vi­sual improvement and reduction of IOP and GMR; vitrectomy group required more intensive postoperative care; comparison of AC lenses vs PC lenses (whether in sulcus, sutured, or sutured to iris) showed equal improvement of vision, IOP, and GMR; slightly higher complication rate seen with AC lens; equal results for anterior vitrectomy vs posterior pars plana vitrectomy

Suggested Reading

Altan-Yaycioglu R et al: Clinical factors associated with floppy iris signs: a prospective study from two centers. Ophthal­mic Surg Lasers Imaging 40:232, 2009; Altan-Yaycioglu R et al: Intraocular pressure after phacoemulsification in eyes with pseudoexfoliation. J Cataract Refract Surg 35:953, 2009; Balestrazzi A et al: Spontaneous in-the-bag intraocular lens luxation into the vitreous cavity: last-stage complication of pseudoexfoliative syndrome after phacoemulsification. Ophthal­mologica 223:339, 2009; Challa P: Genetics of pseudoexfoliation syndrome. Curr Opin Ophthalmol 20:88, 2009; David D et al: Late in-the-bag spontaneous intraocular lens dislocation: evaluation of 86 consecutive cases. Ophthalmology 116:664, 2009; Desai MA, Lee RK: The medical and surgical management of pseudoexfoliation glaucoma. Int Ophthalmol Clin 48:95, 2008; Dubois VD et al: Unilateral capsular phimosis with an acrylic IOL and two capsular tension rings in pseudo­exfoliation. Clin Experiment Ophthalmol 37:631, 2009; Kim DB: Cross chop: Modified rotationless horizontal chop tech­niques for weak zonules. J Cataract Refract Surg 35:1335, 2009; Menapace R: Posterior capsulorhexis combined with optic buttonholing: an alternative to standard in-the-bag implantation of sharp-edged intraocular lenses? A critical analysis of 1000 consecutive cases. Graefes Arch Clin Exp Ophthalmol 246:787, 2008; Shingleton BJ et al: Pseudoexfoliation and the cataract surgeon: preoperative , intraoperative, and postoperative issues related to intraocular pressure, cataract, and in­traocular lenses. J Cataract Refract Surg 34:1101, 2009; Tarkkanen A: Is exfoliation syndrome a sign of systemic vascular disease? Acta Ophthalmol 86:832, 2008; Tektas OY, Lutjen-Drecoll E: Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp Eye Res 88:769, 2009; Topouzis F, Anastasopoulos E: Incidence of pseudoexfoliation syndrome. Am J Ophthalmol 148:181, 2009; Venkatesh R et al: Severe anterior capsular phimosis following acrylic intra­ocular lens implantation in a patient with pseudoexfoliation. Ophthalmic Surg Lasers Imaging 39:228, 2008.