J. Fernando Arevalo, MD, FACS Reinaldo A. Garcia, MD Juan G. Sanchez, MD Caracas, Venezuela

Age-related cataract is the most common cause of reversible blindness worldwide, whereas the most common cause of irreversible legal blindness in this group of pa­tients is age-related macular degeneration. Both cataract and AMD may contribute to visual disability in patients age 60 years or older. Re­cently, some studies have demonstrated that cataract sur­gery may improve vision in AMD patients in the short term.^1,2 Other studies, however, suggest that cataract surgery may be a "risk factor" for ex­u­da­tive or neovascular AMD in the long term.^2,3

This article will discuss the evidence for and against an association between cat­aract surgery  and the development of advanced AMD. (See Figure 1).

Epidemiological Studies

Figure 1. Phacoemulsification combined with foldable intraocular lens implantation.

Various studies have suggested an association between cataract and the development of AMD. In the Bea­ver Dam Eye Study, nuclear sclerosis at base­line was associated with an increased incidence of early (soft drusen) but not late (cho­roidal neovascularization or geographic atrophy) AMD.⁴ The hypo­thesis proposed to explain this association states that both AMD and cat­a­ract may sh­are one or more common risk factors in­cluding age, diet, light ex­posure and/or genetic factors. The association of AMD and nuclear sclerosis was also observed in the Ches­a­peake Bay Watermen Study,⁵ however the Fra­mingham Eye Study⁶ and the Blue Moun­­tains Eye Study⁷ did not find this association. While the reasons for such varying re­sults are not clear, confounding factors or ascertainment biases related to life-long exposure histories could account for the differences.⁸

Pathophysiology and Clinical Studies

The major protective barrier to near-ultraviolet radiation (300 to 400 nm) is provided by the crystalline lens. It has been theorized that this "yellow filter" further protects the retina against blue light in the visible spectrum.⁹ Therefore, cataract may be protective against the development of AMD, and cataract re­moval may result in an increased risk of AMD. Other possible mechanisms proposed for this association include:

1) Post-surgical inflammation and the invasion of lymphocytes known to release angiogenic cytokines.¹⁰

2) Macular exposure and toxicity related to the operating mi­croscope and light.¹¹

3) Improved visualization and detection of AMD after cataract surgery.

4) An as-yet unidentified  com­mon risk factor or stim­­ulus shared by both AMD and cataract.¹²

A retrospective/prospective study evaluated progression of AMD after unilateral extracapsular cat­a­ract extraction and intraocular lens implantation (ECCE + IOL) in bi­lat­eral, symmetric, early AMD pa­tients.¹³ Wet AMD developed in 19 percent of eyes that un­derwent surgery compared to 4 per­­cent of fellow unoperated eyes. Risk factors associated with wet AMD de­velopment were soft drusen, and male gender (See Figure 2). A 1998 prospective study reported on pa­tients with bilateral early AMD who had undergone unilateral cat­aract surgery with a history of stable AMD and previous cataract surgery in the fellow eye: 27 percent of second op­erated eyes showed progression to wet AMD (See Figure 3). In addition, pseudophakic eyes with stable AMD for at least one year underwent YAG-laser posterior capsulotomy and developed wet AMD in 13 percent of eyes within 12 months compared to none of the fellow eyes. Soft drusen, systemic hypertension, and YAG-laser posterior capsulotomy were believed to be important risk factors (See Figure 4).¹⁴

Nevertheless, other au­thors have found significant improvement in both visual function, and quality of life in patients with AMD who underwent cat­a­ract surgery.² One retrospective study designed to determine if there was func­tional and subjective benefit of cat­aract extraction in pa­tients with AMD included 99 cases.¹ The re­searchers found that 81 percent of cases had an improvement in best-cor­­rected visual acuity, and 67 percent felt that the operation had been worth­­while. Another group reported a prospectively designed study of 187 pa­tients with and without AMD who un­der­went cataract sur­gery; significant improvements both in terms of quality of life and visual function were achieved.¹⁵ The group observed no in­creased incidence of wet AMD. In addition, a 2002 report presented the Age-Related Eye Dis­ease Study (AREDS) data and concluded that cataract surgery did not increase the risk of developing neovascular AMD. (Ferris FL, Chew EY. Recent new findings in age related macular degeneration (AMD) in the Age-Related Eye Disease Study (AREDS), part 2. The 35th Annual Retina Society Meeting. San Fran­cisco, CA 2002.)

Figure 2A. Color fundus photograph showing high-risk soft drusen and pigmentary retinal pigment epithelium changes in the right eye. B. Disciform scarring in the left eye. Such patients may be at highest risk for the progression of AMD following cataract surgery.

A recent ­­­pre­­sen­­­­ta­­­­tion at the EUR­E­T­­INA Con­gress 2005 involved a randomized, multicenter pro­spec­tive study of 320 patients with dry AMD and con­clud­ed that cat­aract surgery does not seem to influence the progression of the disease in its early course. (Bin­der S, Brunner S, Krebs Ilse, Stol­ba U, Falk­ner C. AMD and cataract sur­gery: The ECAM Study. In­ter­me­di­ate re­port. 5th EURETINA Con­gress 2005. Bar­ce­lona, Spain 2005.)

Figure 3. A patient with stable, dry maculopathy for at least six months who developed neovascular AMD four months following cataract surgery. Note the late hyperfluorescence with fluorescein angiography early (A) and late (B).

Some studies, however, have suggested a role for cataract surgery in the development or progression of AMD. The findings to date from previous studies in the literature warrant clarification of the hypothesis that cat­aract surgery could increase the long-term risk for late-stage AMD. At the 1999 Am­er­ican Academy of Oph­thal­mo­logy Annual Meeting in Orlando, Fla., a prospective study of progression was reported in­volving patients with bilateral dry AMD who un­derwent unilateral cat­aract surgery by phaco­emul­sification and foldable IOL (See Figure 5). Of 22 pa­tients, 3 (14 per­cent) de­vel­oped wet AMD compared to none of the fellow eyes. A group using three large population-based studies (the Salisbury Eye evaluation with 2,520 subjects be­tween 65 and 84 years, the Pro­yecto VER with 4,774 His­panic pa­tients aged 40 and older, and the Bal­ti­more Eye Sur­vey with 4,396 subjects aged 40 and older) found modest evidence that cat­aract surgery may be as­so­ciated with a greater pre­valence of late-stage AMD.¹² Such findings have prompted investigators to suggest that cataract extraction may be best con­sid­ered in eyes in which the cat­­a­ract has caused a decrease in function, and that close follow up of such eyes is in­di­cat­ed.² Similarly, others have proposed ECCE plus IOL surgery in patients with moderate dry AMD only when their vis­ual acuity is less than 20/200 based on their re­sults showing that all pa­tients who de­mon­strat­ed ag­gravation of AMD after surgery were less than 20/200.¹⁶ (See Figure 6).

Figure 4. An aphakic patient after YAG-laser posterior capsulotomy, a possible risk factor for the development of neovascular AMD following cataract surgery.

IOLs with Blue-light Protection

Exposure to ultraviolet light has been postulated as a cause of AMD, perhaps through damage to the retinal pigment epithelium. It seems logical, therefore, to replace the aging, yellowing lens with a blue light-ab­sorbing yellow IOL in cat­a­ract surgery.¹⁸ However, there are conflicting reports in the literature regarding this issue. It has been difficult to prove the role of light exposure in AMD epidemiologically be­cause it is hard to determine an individual's cumulative light exposure retrospectively.¹⁷ In fact, cumulative ultraviolet ex­posure has been found to be only weakly as­sociated with AMD in epid­e­miological studies.⁸ Al­though the Acry­Sof Natural IOL (Alcon Labs) de­creases acute retinal phototoxic damage from intense violet light in cell culture and experimental animals, much long­er-term, lower light-level ex­pe­riments will be needed to es­tablish the relevance of these studies to the human aging retina.¹⁹ Based on different pub­lished studies,^4,5,8,19 we have graded in order of importance the epidemiological risk factors of AMD and we could categorize them as follows:

Figure 5. A patient with bilateral dry AMD who underwent unilateral cataract surgery in the right eye by phacoemulsification plus foldable IOL, who developed neovascular AMD after surgery. Note the active hemorrhage within the lesion and leakage in the fluorescein angiogram.

 • Category 1 (definitive proof): age and smoking;

 • Category 2 (controversial re­sults): race, systemic hypertension, car­di­o­vascular disease, low se­rum omega-3, high in­take of sat­urated fats and cholesterol, and hereditary factors;

 • Category 3 (no conclusive evidence): sunlight ex­posure and alcohol use.

Some have suggested that blue light is needed for optimal vision.¹⁹ In theory, the Acrysof Nat­ural IOL decreases the risk of acute UV-phototoxicity but psychophysical studies have found that filtering blue in addition to violet light can reduce scotopic sensitivity, a natural function which declines with ag­ing and is even worse in people with AMD.¹⁹ Yellow IOLs have been reported to provide 50-percent less ul­­tra­violet protection than sun­glasses, prompting some to recommend that Acrysof Natural IOL users should wear sunglasses in bright environments, and that the optimal IOL should transmit as much blue light as possible to ensure good VA.¹⁹ Moreover, light exposure may play a role in the de­vel­opment of AMD in some people, but little or no role in others.

Figure 6. A patient with a cataract and a visual acuity of less than 20/200.

The issue of whether cataract sur­gery is a risk factor for the development or progression of AMD re­mains controversial, with some studies supporting and other studies re­futing an association. While both subjective and objective visual function improvement can clearly be achieved after cataract surgery in most eyes with AMD, the possibility that AMD might develop or progress in some eyes would seem to suggest that cataract surgery in patients with AMD should be reserved for those patients who stand to gain the most by the removal of their cataract.

Pearls and Recommendations to the Anterior Segment Surgeon • Progression of AMD occurred more often in eyes with unilateral extracapsular cataract extraction and intraocular lens. • Development of AMD in the second operated eye (ECCE + IOL) appears to be independent of stability of prior uneventful surgery. • YAG-laser posterior capsulotomy is an apparent risk factor in some patients. • Soft drusen were found to be a significant risk factor. • Phacoemulsification with foldable IOL is associated with lower postoperative development of AMD (13 percent) due to reduced intraocular inflammation. • Early visual function improvement (objective and subjective) can be achievable in operated eyes. • Preoperative evaluation of the status of AMD by a retina specialist is recommended. •Preoperative photodynamic therapy and/or anti-vascular endothelial growth factor (anti-VEGF) therapy if necessary and possible. • Explain to the patient the possibility of progression of AMD (13 to 24 percent) after cataract surgery. • Surgery should be performed when the visual benefit is greater than the risk: VA £ 20/200. • Use of operating microscopes with ultraviolet light filter. • Phacoemulsification and foldable IOL should the preferred method. • Early fundus postoperative evaluation (3 months) with fluorescein angiography and optical coherence tomography if needed. • Postoperative PDT and/or anti-angiogenics if necessary.

This article was supported in part by the Arevalo-Coutinho Foundation for Research in Ophthalmology (FACO), Caracas, Venezuela. The authors practice in the Retina and Vitreous Service, Clinica Oftalmo­lógica Centro Caracas, and the Are­valo-Coutinho Foundation for Re­search in Ophthalmology, Ca­racas. They have no proprietary or financial in­terest in any products or techniques de­scribed in this article.

Contact Dr. Arevalo at Clinica Of­tal­mologica Centro Caracas, Edif. Cen­tro Caracas PH-1, Av. Panteon. San Bernardino, Caracas 1010, Ve­ne­zuela. Phone: (58-212) 576-8687. Fax: (58-212) 576-8815. E-mail: areval1@telcel.net.ve.

1. Shuttleworth GN, Luhishi EA, Harrad RA. Do patients with age related maculopathy and cat­a­ract benefit from cataract surgery? Br J Ophthal­mol 1998;82:611-6.

2. Armbrecht AM, Findlay C, Aspinall PA, Hill AR, Dhillon B. Cataract surgery in patients with age-related macular degeneration: one-year outcomes. J Cataract Refract Surg 2003;29:686-93.

3. Wang JJ, Klein R, Smith W, Klein BE, Tomany S, Mitchell P. Cataract surgery and the 5-year incidence of late-stage age-related maculopathy: pooled findings from the Beaver Dam and Blue Mountains eye studies. Ophthalmology 2003;110:1960-7.

4. Klein R, Klein BE, Wong TY, Tomany SC, Cruickshanks KJ. The association of cataract and cataract surgery with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. Arch Ophthalmol 2002;120:1551-8.

5. West SK, Rosenthal FS, Bressler NM, Bressler SB, Munoz B, Fine SL, Taylor HR. Exposure to sun­light and other risk factors for age-related macular degeneration. Arch Ophthalmol 1989;107:875-9.

6. Sperduto RD, Hiller R, Seigel D. Lens opacities and senile maculopathy. Arch Ophthalmol 1981;99:1004-8.

7. Wang JJ, Mitchell PG, Cumming RG, Lim R. Cataract and age-related maculopathy: the Blue Mountains Eye Study. Ophthalmic Epidemiol 1999;6:317-26.

8. Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004;137:486-95.

9. Smith BT, Belani S, Ho AC. Light energy, cat­a­ract surgery, and progression of age-related macular degeneration. Curr Opin Ophthalmol 2005;16:166-9.

10. van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, Pameyer JH, de Jong PT. Increased prevalence of disciform macular degeneration after cataract extraction with implantation of an intraocular lens. Br J Ophthalmol 1994;78:441-5.

11. Libre PE. Intraoperative light toxicity: a possible explanation for the association between cataract surgery and age-related macular degeneration. Am J Ophthalmol 2003;136:961.

12. Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD. Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies. Am J Ophthalmol 2003;135:849-56.

13. Pollack A, Marcovich A, Bukelman A, Oliver M. Age-related macular degeneration after extracapsular cataract extraction with intraocular lens implantation. Ophthalmology 1996;103:1546-54.

14. Pollack A, Bukelman A, Zalish M, Leiba H, Oliver M. The course of age-related macular degeneration following bilateral cataract surgery. Ophthalmic Surg Lasers 1998;29:286-94.

15. Armbrecht AM, Findlay C, Kaushal S, Aspinall P, Hill AR, Dhillon B. Is cataract surgery justified in patients with age related macular degeneration? A visual function and quality of life assessment. Br J Ophthalmol 2000;84:1343-8.

16. Hawkins WR. AMD after ECCE with IOL im­plant. Ophthalmology 1997;104:900.

17. Nilsson SE. Are there advantages in implanting a yellow IOL to reduce the risk of AMD? Acta Ophthalmol Scand 2004;82:123-5.

18. Mainster MA. Intraocular lenses should block UV radiation and violet but not blue light. Arch Ophthalmol 2005;123:550-5.