Hyperopia and Presbyopia - part 3 pps

58 ChylackThey concluded that presbyopia was actually due to the loss in ability to disaccommodatedue to increases in lens thickness, the inward movement of the ciliary ring, or both.The

53 Schachar’s Theory of Accommodation

operated in a darkened room, does not offer the usual accommodative stimulus but reliespurely on defocus The instrument, which requires the subject to use a bite plate forstability and alignment, generally takes practice to obtain reliable data, and it was unclear

if this level of training and reproducibility was achieved Glasser and colleagues (12) havespeculated that the possible restoration of near vision via scleral expansion could functionvia nonaccommodative mechanisms, such as inducing multifocality of the crystalline lens

A number of patients in the phase I clinical trial of scleral expansion in the United Statesare now undergoing wavefront analysis to provide an objective measurement and assessmechanisms that may underlie improvement in near vision after this procedure

B CONCLUSION

There are few subjects in ophthalmology capable of generating as much lively debate asthat of accommodation and presbyopia The processes of accommodation and disaccom-modation are complex, to say the least, and involve changes in muscular, lenticular, andextralenticular components At some time, almost every one of these components has beenproposed as a factor in the development of presbyopia

We have tried in this chapter to present a balanced view of Schachar’s versus holtz’s theory of accommodation, along with experimental evidence and arguments thathave been espoused by proponents of both sides In a number of key respects, the proposedmechanisms are antithetical The universal nature of presbyopia and the intense interest

Helm-in its reversal justifies further research Helm-in this area to elucidate its pathophysiology

6 Schachar RA, Tello C, Cudmore DP, Liebmann JM, Black TD, Ritch R In vivo increase ofthe human lens equatorial diameter during accommodation Am J Physiol (United States) 1996;271(3 pt 2): R670–R676

7 Schachar RA, Cudmore DP, Torti R, Black TD, Huang T A physical model demonstratingSchachar’s hypothesis of accommodation Ann Ophthalmol 1994; 26:4–9

8 Schachar RA, Huang T, Huang X Mathematical proof of Schachar’s hypothesis of dation Ann Ophthalmol 1993; 25:59

accommo-9 Schachar RA, Bax AJ Mechanism of accommodation Int Ophthalmol Clin 2001; 41(2):17–32

54 Pepose and Chung

10 Mathews S Scleral expansion surgery does not restore accommodation in human presbyopia.Ophthalmology 1999; 106:873–877

11 Glasser A, Campbell MCW Presbyopia and the optical changes in the human crystalline lenswith age Vis Res 1998; 38:209–229

12 Glasser A, Croft MA, Kaufman PL Aging of the human crystalline lens and presbyopia IntOphthalmol Clin 2001; 41(2):1–15

13 Glasser A, Campbell MCW Biometric, optical and physical changes in the isolated humancrystalline lens with age in relation to presbyopia Vis Res 1999; 39:1991

14 Glasser A, Kaufman PL The mechanism of accommodation in primates Opthalmology 1999;106(5):863–872

15 Schachar RA Presbyopia: Cause and Treatment In: Schachar RA, Roy FH eds Presbyopia:Cause and Treatment The Hague, The Netherlands: Kugler, 2001:1–20

16 Wilson RS Does the lens diameter increase or decrease during accommodation? Human commodation studies: a new technique using infrared retro-illumination video photographyand pixel unit measurements Trans Am Ophthalmol Soc 1997; 95:261–270

ac-17 Wilson RS, Merlin LM Infrared video photographic analysis of human accommodation InvestOphthalmol Vis Sci 1997; 38(suppl):S986

18 Wilson RS, Merlin LM Infrared video photographic analysis of the lens-zonular-ciliary space

in human accommodation Invest Ophthalmol Vis Sci 1998; 39(suppl):S312

19 Strenk SA, Semmlow JL, Strenk LM, Munoz P, Gronlund-Jacob J, DeMarco JK Age-relatedchanges in human ciliary muscle and lens: a magnetic resonance imaging study Invest Ophthal-mol Vis Sci 1999; 40(6):1162–1169

20 Yang GS, Yee RW, Cross WD, Chuang AZ, Ruis RS Scleral expansion: a new surgicaltechnique to correct presbyopia Invest Ophthalmol Vis Sci 1997; 38(suppl):S497

21 Smith P Disease of the crystalline lens and capsule: on the growth of the crystalline lens.Trans Ophthalmol Soc UK 1883; 3:79

22 Schachar RA Cause and treatment of presbyopia with a method for increasing the amplitude

of accommodation Ann Ophthalmol 1992; 24:445–452

Aging and the Crystalline Lens

Review of Recent Literature (1998–2001)

LEO T CHYLACK, JR.

Harvard Medical School and Brigham and Women’s Hospital,

Boston, Massachusetts, U.S.A.

This chapter on aging and the crystalline lens is based on a review of the literature between

1998 and 2001 Due to the limits on the length of this chapter and the numerous recentpublications in this field, I have not been able to cite many important earlier works Iextend my apologies to the authors of these works

Bron et al (1) published an excellent general summary of the aging lens in 2000.The avascular lens grows throughout life Being enclosed by a capsule and lacking ameans of shedding cells, the lens is an excellent organ in which to study aging There arechanges in lens size, shape, and mass throughout life that occur at different rates Thesagittal diameter of the lens is approximately constant at 9.0 mm., but the anteroposteriordistance varies from 2.5 to 3.5 mm These dimensions may increase in the mature/hyperma-ture cataract In spite of decreases with age in the radius of the anterior surface of thelens and changes in the points of zonular insertion, the clear lens retains its ability to focus

an image clearly on the retina Although the central epithelial cells divide rarely, theysurvive throughout life The germinative epithelial cells are actively dividing cells, andthe equatorial epithelial cells undergo terminal differentiation As lens fibers form, theylose their nuclei and other intracellular organelles; in the deeper cortex, fiber cells areessentially organelle-free The slightly tortuous course of the long fiber cells as they archover the equator and meet near the opposite pole to form sutures has been illustrated inelegant studies by Kuszak et al (2–4) The complexity of these sutures increases withage and may account for the increased light scattering in the zones of disjunction seenbiomicroscopically Lens protein synthesis in the epithelium and superficial cortex contin-ues throughout life, but these proteins undergo several posttranslational changes, among

55

56 Chylack

which are chemical and photochemical oxidation, glycation, and racemization Antioxidantdefense mechanisms may ameliorate some of these posttranslational changes Also, withincreasing age monomeric proteins associate in covalently bound aggregates to form high-molecular-weight aggregates whose hydrodynamic radii approach in size the wavelengths

of visible light As size increases, light scattering also increases to the point of lens cation and frank cataract Changes with age in protein conformation and phospholipidcomposition of fiber membranes increase nuclear rigidity and contribute to presbyopia.This chapter considers many of these changes in more detail

opacifi-In the past 15 years, epidemiological research on age-related cataracts (ARCs) hasrevealed risk factors that pertain to behavior (e.g., diet, smoking, lifestyle, drug use) andsuggested that ARC may be a preventable disease (5,6) This is most encouraging, foreach year increasing percentages of public and private health care budgets are used toprovide surgical care for ARC

A AGING AND CHANGES IN LENS SIZE AND SHAPE

Several authors (7–12) have documented the growth of the lens throughout life Koretz

et al analyzed (24) Scheimpflug photographs of the unaccommodated lens in 100 subjectsfrom 18 to 70 years of age to determine the regions that changed with time With Scheimp-flug optics the lens image is in focus from the anterior to posterior pole The geometricdistortion of Scheimpflug images can be corrected (14), so that accuratemeasures of thelens can be obtained Koretz et al measured the lens with Hough transforms and otherimage analysis methods The radii of the anterior and posterior surfaces of the whole lensdecrease, but the volume increases with increasing age In contrast, neither the shape northe volume of the nucleus changes with age The central clear zone and center of mass

of the nucleus move anteriorly with age The correlation between lens shape and location(relative to the cornea) is very high, confirming earlier results Also, the anterior movement

of the lens with age increases the likelihood of phakic IOL–lenticular touch and tions

complica-Another study (15) explored the relationship of accommodative convergence perunit of accommodative response (AC/A ratio), refractive error, and age to determine ifthe AC/A ratio was a risk factor for myopia A high AC/A ratio was associated with—and

a risk factor for—rapid onset of myopia A higher AC/A ratio, associated with a flattercrystalline lens, increased the effort to accommodate, or “pseudocycloplegia.” Accommo-dative deficits in myopia may be the functional consequence of myopic enlargement ofthe eye This enlargement was documented in a study (16) of changes in biometric measure-ments and refractive errors over a 3-year period in eyes of university students After 3years, the mean change in refractive error (in OD) wasⳮ0.52 Ⳮ/ⳮ 0.45D (p ⬍ 0.05).

The mean lens thickness increased by 0.07 Ⳮ/ⳮ 0.10 mm (p ⬍ 0.05), and the mean

elongation of the vitreous chamber was 0.27Ⳮ/ⳮ 0.30 mm (p ⬍ 0.05) Regardless of

the original refractive error, the change in refractive error over the 3-year period wastoward myopia There were no statistically significant changes in the curvature of thecornea or depth of the anterior chamber The authors concluded that the myopic shift wasdue to an elongation of the vitreous chamber

In a study of 1-year-old chickens (17), form deprivation vision such as is obtainedthrough translucent glass or eyelids that have been sutured closed, even in fully grownbirds, was associated with a myopic shift that was similar but not as large as that inneonatal chicks The decreases in retinal dopamine seen in neonatal chicks were also seen

57 Aging and the Crystalline Lens

to a lesser degree in 1-year-old chickens These studies suggest that form deprivation isone of the mechanisms controlling eye growth and causing myopia

B AGING AND CHANGES IN REFRACTIVE ERROR

The modulation transfer function (MTF) has been used (18) to estimate the overall opticalperformance of the eye with increasing age In qualitative terms, the MTF is used to assessoptical quality of lens combinations by measuring the degree to which a point source oflight is dispersed to a spot, in this case on the retina The average MTF was determined

as a function of age and pupillary size Not surprisingly, the MTF declined in an mately linear fashion with age, but it did not vary with gender The decline in MTF mayaccount for the decline in contrast sensitivity function (CSF) with age

presby-a compenspresby-atory hypertrophy presby-as presby-accommodpresby-ative presby-amplitude decrepresby-ases with presby-age The force

of contraction is about 50% greater at the onset of presbyopia than in youth However,because of increased lenticular resistance, its effect on the amplitude of accommodation

is small Fisher claimed that the lens becomes more difficult to deform not because oflenticular sclerosis, since the lens substance does not lose water, but because the capsuleloses its elastic force with age and the lens fibers, particularly in the nucleus, becomemore compacted with age In fact, the nuclear fiber mass becomes more rigid with age,

as was shown in subsequent studies

Since Fisher’s work, considerable progress has been made in our understanding ofthe mechanisms of presbyopia In 1991 (22), Pau and Kranz used a fine conical probeand a dynamometer to measure the resistance to penetration of various layers of the lens.The resistance to penetration increased with age, due primarily to a hardening of thenucleus The cortex did not show this hardening In an interesting study of the dynamicaspects of accommodation (23), Heron et al showed that accommodation gain decreasedand the phase lag increased with age Reaction time, response time, and accommodativevelocity did not change with age for a target oscillating sinusoidally in a predictablemanner at modest amplitude The main aging effect was a longer than predicted phaselag In spite of decreasing amplitude of accommodation, other aspects of accommodativefunction were quite robust in the middle-aged eye

In a very elegant study of accommodation in vivo using magnetic resonance imaging(MRI) in humans, Strenk et al (24) showed that the muscle’s contraction decreased onlyslightly with increasing age A decrease in the diameter of the unaccommodated ciliarymuscle ring was highly correlated with advancing age Unaccommodated lens thicknessincreased with age, but the thickness of the lens under accommodative effort was onlyslightly age-dependent Their data shed light on what has been a lens paradox—namely,the decrease in the ciliary muscle’s diameter and an increase in lens thickness in theunaccommodated eye These changes showed the greatest correlation with increasing age

58 Chylack

They concluded that presbyopia was actually due to the loss in ability to disaccommodatedue to increases in lens thickness, the inward movement of the ciliary ring, or both.The issue of whether the changes in the human lens are due to changes in the lensfiber mass or changes in the lens capsule were addressed directly in a recent study (25)

of the biometric, optical, and physical properties of capsulated and decapsulated lenses.Lens focal lengths, thicknesses, surface curvatures, and spherical aberrations were mea-sured for paired eye-bank lenses Decapsulating the lens caused changes in focal lengthsimilar to those occurring in lenses stretched into an unaccommodated state These phe-nomena were attributed to nonsystematic changes in lens curvatures These data supportthe concepts that lens hardening is an important factor in presbyopia and that aging changes

in the lens are not limited to the loss of accommodation and cataract In addition thereare substantial changes in the optical and physical properties of the lens with aging

It is known that myopes have shallower accommodative stimulus/response functions(26), due possibly to reduced sensitivity to defocus Jiang and White showed that a neartask caused a small increase in the static accommodative response In both emmetropesand late-onset myopes, near tasks also increased the interval for relaxing accommodation.These data suggest the existence of two subsystems that adapt differently to prolongedaccommodative effort

Heron et al studied dynamic accommodation responses to small, abrupt changes in

an accommodation stimulus (27) They concluded that for small stimuli within the tude of accommodation, the response dynamics (reaction and response times) over theadult age range (16 to 48 years) remained remarkably constant even though the amplitude

ampli-of accommodation decreased progressively with age

D AGING, OXIDATIVE STRESS, LENS OPACIFICATION AND

CATARACT

Considerable evidence has accumulated implicating oxidative stress as a major risk factor

in age-related cataract (ARC) formation Both chemical oxidation (H2O2) and tion (secondary to UV irradiation) have been implicated In addition to a cumulativeincrease with age in the oxidative damage to lens proteins and lipids, there is also a gradualreduction in the potency of the lens antioxidant defenses In a recent study (28), the thioland carbonyl contents of 62 cataractous (age-related idiopathic, diabetic, and myopic)lenses and age- and sex-matched clear lenses from patients undergoing vitrectomy or giant

photo-oxida-retinal tear surgery were compared There was a statistically significant (p⬍ 0.01), associated inverse relationship between the contents of P-SH and protein carbonyls Thechanges were greater in cataractous than clear lenses and greater in diabetic and myopiccataracts than in age-related cataracts The decrease in P-SH occurred earlier in diabeticand myopic cataracts than in ARCs An increase in protein carbonyls⬎2 nmol/mg proteinand a decrease in P-SH of⬍10 to 12 nmol/mg protein were always associated with lensopacification

age-The tripeptide glutathione (GSH) is present at high concentrations (4 to 6 mM) (29)

in the young lens and in the cortex of older lenses It has been identified as one of the majorantioxidant defenses in the lens The GSH-redox cycle is very active in lens epithelium andcortex Via this cycle, the lens detoxifies hydrogen peroxide, other active oxygen species,and dehydroascorbic acid There appear to be separate mechanisms in LECs for the detoxi-fication of hydrogen peroxide and hydroxyl radical Recently, Truscott (30) and Moffat

et al (31) demonstrated a barrier to free diffusion of GSH within the lens that increases

59 Aging and the Crystalline Lens

with age The low ratio of GSH/P-SH and the relatively inactive GSH-redox cycle in thenucleus make the nucleus more susceptible to oxidative stress than the cortex That, indeed,this is the case has been demonstrated in animal models with hyperbaric oxygen (32),UVA irradiation (33,34), and the glutathione peroxidase knockout mouse (35–37) Withincreased oxidative stress in nuclei of lenses in these animal models, there is an increase

in protein disulfides and light scattering Also with reduced activity of the GSH-redoxcycle, there is damage to NaⳭ, KⳭ-ATPase (an enzyme involved with many of the activetransport mechanisms in LECs), to cytoskeletal proteins, and to membrane proteins in-volved in regulating membrane permeability An excellent review of these topics hasrecently been published (38)

As oxidative stress increases and the size of the GSH pool decreases, some proteinsthiols (P-SH) are converted to protein-thiol mixed disulfides (29), either protein-S-S-glutathione (PSSG) or protein-S-S-cysteine (PSSC) The formation of PSSG precedes theformation of PSSP (29) and increases insolubilization of lens proteins Lou et al (29)discovered that the early oxidative damage could be reversed if the oxidant was removed

in time This reversal is mediated by the enzyme thiol transferase (TTase), recently found

in the lens Lou et al showed that recombinant TTase, although requiring GSH for activity,was much more efficient in dethiolating lens proteins than GSH alone TTase favoredPSSG over PSSC and gamma-crystallin-S-S-G over alpha-crystallin-S-S-G TTase wasalso remarkably resistant to oxidation The TTase dethiolase activity reactivates enzymesdeactivated by S-thiolation It is this ability to regulate and repair SH-dependent enzymesthat suggests that TTase plays an important role in ARC formation

In a study (39) of ascorbate oxidation and advanced glycation in the lens, the major

advanced glycation end product (AGE), N(epsilon)-carboxymethyl-L-lysine (CML), wasfound to have an EDTA-like (chelator) structure that might bind copper Ascorbylationled to increased CML formation, copper binding, and free radical formation in the lens.These results suggested that there is a vicious cycle in the lens between AGE formation,lipoxidation, metal binding, and oxidative damage It is possible that chelators may play

a role in the therapy of ARC

In another interesting study of the possible value of antioxidants in the treatment ofARC (40), it was shown that chronic administration of vitamin E, but not of sodiumascorbate, restored the age-associated decrease in GSH content in rat lenses to levelscomparable to those in younger rats The age-associated decrease in lenticular glutathioneperoxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase was not re-versed by chronic administration of either vitamin E or sodium ascorbate (40)

In addition to the age-associated change in lens proteins, there are age-associatedchanges in lens lipids The percentage of sphingolipid nearly doubles with age, and there

is also an increase in hydrocarbon chain saturation with age These increases were muchgreater in the deeper layers of the lens (41) These data support the idea that the degree

of lipid hydrocarbon order is determined by the amount of lipid saturation, and this, inturn, is regulated by the content of saturated sphingolipid Hyperbaric oxygen treatmentincreases the lipid disorder in the nucleus and the levels of lipid hydroxyl, hydroperoxyl,and aldehydes The transparency of the nucleus is also reduced as these lipid oxidationproducts accumulate in the lens

The Roche European-American Cataract Trial (REACT) (42,43), the first tive, randomized, placebo-controlled clinical trial of oral vitamins E and C, and beta-carotene suggested that antioxidant treatment might slow the progression of ARC A smallbut statistically significant deceleration of ARC was found after 3 years of treatment in

prospec-60 Chylack

a cohort of American and British patients In this study, the beneficial effect was seen inthe entire cohort and in the subgroup of American patients but not in the subgroup ofBritish patients The basis for the different responses of American and British patients tothe antioxidant treatment was not clear but may have been due to the fact that the Britishpatients had slightly more advanced cataracts at entry

E AGING AND THE ZONULE

There has been very little research on the effects of aging on the zonule Recently, however,

a light and electron microscopic study of the human ciliary zonule has been published(44) The organization of the zonule as it inserts into the ciliary body was studied Fibrillin

is the major constituent of the zonule and also of microfibrils Mutations in the fibrillingene are thought to underlie the zonular abnormalities of Marfan’s syndrome With aging,the zonular fiber becomes more fragile, increasing the risk of ocular pathology

3 Kuszak JR, Sivak JG, Weerheim JA Lens optical quality is a direct function of lens suturalarchitecture Invest Ophthalmol Vis Sci 1991; 32:2119–2129

4 Kuszak JR, Bertram BA, Macsai MS, Rae JL Sutures of the crystalline lens: a review ScanElectron Microsc 1984; 3:1369–1378

5 Rowe NG, Mitchell PG, Cumming RG, Wans JJ Diabetes, fasting blood glucose, and related cataract: the Blue Mountains Eye Study Ophthalm Epidemiol 2000; 7:103–114

age-6 Klein BE, Klein R, Lee KE Diabetes, cardiovascular disease, selected cardiovascular diseaserisk factors, and the 5-year incidence of age-related cataract and progression of lens opacities:the Beaver Dam Eye Study Am J Ophthalmol 1998; 126:782–790

7 Kwok LS, Coroneo MT Temporal and spatial growth patterns in the normal and cataractoushuman lens Exp Eye Res 2000; 71:317–322

8 Bron AJ, Vrensen GF, Koretz J, Maraini G, Harding JJ The ageing lens Ophthalmologica2000; 214:86–104

9 Treton J and Courtois Y Evidence for a relationship between longevity of mammalian speciesand a lens growth parameter Gerontology 1989; 35:88–94

10 Brown N The change in lens curvature with age Exp Eye Res 1974; 19:175–183

11 Nordmann J, Fink H, Hockwin O Growth curve of the human lens Graefes Arch Klin ExpOphthalmol 1974; 191:165–175

12 Spencer RP Change in weight of the humanlens with age Ann Ophthalmol 1976; 8:440–441

13 Koretz JF, Cook CA, Kaufman PL Aging of the human lens: changes in lens shape at diopter accommodation J Opt Soc Am A Opt Image Sci Vis 18:2665–2672

zero-14 Richards DW, Russell SR, Anderson DR A method for improved biometry of the anteriorchamber with a Scheimpflug technique Invest Ophthalmol Vis Sci 1988; 29:1826–1835

15 Mutti DO, Jones LA, Moeschberger ML, Zadnik K AC/A ratio, age, and refractive error inchildren Invest Ophthalmol Vis Sci 2000; 41:2469–2478

16 Kinge B, Midelfart A, Jacobsen G, Rystad J Biometric changes in the eyes of Norwegianuniversity students—a three-year longitudinal study Acta Ophthalmol Scand 1999; 77:648–652

61 Aging and the Crystalline Lens

17 Papastergiou GI, Schmid GF, Laties AM, Pendrak K, Lin T, Stone RA Induction of axial eyeelongation and myopic refractive shift in one-year-old chickens Vis Res 1998; 38:1883–1888

18 Guirao A, Gonzalez C, Redondo M, Geraghty E, Norrby S, Artal P Average optical mance of the human eye as a function of age in a normal population Invest Ophthalmol VisSci 1999; 40:203–213

perfor-19 Fisher RF The mechanics of accommodation in relation to presbyopia Eye 1988; 2:646–649

20 Donders FC On the anomalies of accomodation and refraction of the eye: with a preliminaryessay on physiological dioptrics London: The New Sydenham Society, 1864

21 von Helmholtz H Treatise on Physiological Optics, translated from the 3d German ed Vol

1 JPC Southall, ed Handbuch der physiologischen Optik (English) Rochester, NY: TheOptical Soc America, 1924

22 Pau H, Kranz J The increasing sclerosis of the human lens with age and its relevance toaccommodation and presbyopia Graefes Arch Clin Exp Ophthalmol 1991; 229:294–296

23 Heron G, Charman WN, Gray LS Accommodation responses and ageing Invest OphthalmolVis Sci 1999; 40:2872–2883

24 Strenk SA, Semmlow JL, Strenk LM, Munoz P, Gronlund-Jacob J, DeMarco JK Age-relatedchanges in human ciliary muscle and lens: a magnetic resonance imaging study Invest Ophthal-mol Vis Sci 1999; 40:1162–1169

25 Glasser A, Campbell MC Biometric, optical and physical changes in the isolated humancrystalline lens with age in relation to presbyopia Vision Res 1999; 39:1991–2015

26 Jiang BC, White JM Effect of accommodative adaptation on static and dynamic tion in emmetropia and late-onset myopia Optom Vis Sci 1999; 76:295–302

accommoda-27 Heron G, Charman WN, Schor C Dynamics of the accommodation response to abrupt changes

in target vergence as a function of age Vis Res 2001; 41:507–519

28 Boscia F, Grattagliano I, Vendemiale G, Micelli-Ferrari T, Altomare E Protein oxidation andlens opacity in humans Invest Ophthalmol Vis Sci 2000; 41:2461–2465

29 Lou MF Thiol regulation in the lens J Ocul Pharmacol Ther 2000; 16:137–148

30 Truscott RJ Age-related nuclear cataract: a lens transport problem Ophthalmic Res 2000; 32:185–194

31 Moffat BA, Landman KA, Truscott RJ, Sweeney MH, Pope JM Age-related changes in thekinetics of water transport in normal human lenses Exp Eye Res 1999; 69:663–669

32 Borchman D, Giblin FJ, Leverenz VR, Reddy VN, Lin LR, Yappert MC, Tang D, L Li Impact

of aging and hyperbaric oxygen in vivo on guinea pig lens lipid and nuclear light scatter.Invest Ophthalmol Vis Sci 2000; 41:3061–3073

33 Balasubramanian D Ultraviolet radiation and cataract J Ocul Pharmacol Ther 2000; 16:285–297

34 Weinreb O, vanRijk FA, Steely HT, Dovrat A, Bloemendal H Analysis of UVA-relatedalterations upon aging of eye lens proteins by mini two-dimentional polyacrylamide gel elect-rphoresis Ophthalm Res 2000; 32:195–204

35 Spector A, Kuszak JR, Ma W, Wang RR, Ho YS, Yang Y The effect of photochemical stressupon thelenses of normal and glutathione peroxidase–1 knockout mice Exp Eye Res 1998;67:457–471

36 Spector A, Ma W, Wang RR, Yang Y, Ho YS The contribution of GSH peroxidase-1, catalase,and GSH to the degradation of H2O2 by the mouse lens Exp Eye Res 1997; 64:477–485

37 Reddy VN, Lin LR, Ho YS, Magnenat JL, Ibaraki N, Giblin FJ, Dang L Peroxide-induceddamage in lenses of transgenic mice with deficient and elevated levels of glutathione peroxi-dase Ophthalmologica 1997; 211:192–200

38 Giblin FJ Glutathione: a vital lens antioxidant J Ocul Pharmacol Ther 2000; 16:121–135

39 Saxena P, Saxena AK, Cui XL, Obrenovich M, Gudipaty K, Monnier VM Transition catalyzed oxidation of ascorbate in human cataract extracts: possible role of advanced glycationend products Invest Ophthalmol Vis Sci 2000; 41:1473–1481

metal-62 Chylack

40 Campisi A, Di Giacomo C, Russo A, Sorrenti V, Vanella G, Acquaviva R, Li Volti G, Vanella

A Antioxidant systems in rat lens as a function of age: effect of chronic administration ofvitamin E and ascorbate Aging (Milano) 1999; 11:39–43

41 Borchman D, Giblin FJ, Leverenz VR, Reddy VN, Lin LR, Yappert MC, Tang D, Li L Impact

of aging and hyperbaric oxygen in vivo on guinea pig lens lipids and nuclear light scatter.Invest Ophthalmol Vis Sci 2000; 41:3061–3073

42 Chylack Jr LT, Wolfe JK, Friend J, Tung W, Singer DM, Brown NP, Hurst MA, Kopcke W,Schalch W Validation of methods for the assessment of cataract progression in the RocheEuropean-American Anticataract Trial (REACT) Ophthalm Epidemiol 1995; 2:59–75

43 Chylack Jr LT, Phelps-Brown N, Bron A, Hurst M, Kopcke W, Thien U, Schalch W, theREACT Group The Roche European American Cataract Trial (REACT): a randomized clinicaltrial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression

of age-related cataract Ophthalm Epidemiol 2002; 9:49–80

44 Hanssen E, Franc S, Garrone R Fibrillin-rich microfibrils: structural modifications duringageing in normal human zonule J Submicrosc Cytol Pathol 1998; 30:365–369

Hyperopia

IVO JOHN DUALAN and PENNY A ASBELL

Mount Sinai Medical Center, New York, New York, U.S.A.

A CONTACT LENS VS REFRACTIVE SURGERY

1 History of Contact Lens

Why would anyone choose contact lenses over refractive surgery? Contact lenses havebeen around for decades and are therefore true, tried, and tested Surgical procedures, onthe other hand, are still considered innovative, and no long-term follow-up data are yetavailable Contact lenses were first described and used well over a century ago but cameinto popular use after World War II, where the first hard contact lenses, made of polymeth-ylmethacrylate (PMMA), were introduced In the 1960s the advent of soft lens materialsmade of hydroxy-ethyl methacrylate (HEMA) led to the widespread use of contact lenses

in the United States In the 1970s rigid gas-permeable lenses were introduced, and in the1980s astigmatic and presbyopic connecting lenses became available Flexibility of lensuse increased with the introduction of extended-wear contact lenses in the 1980s anddisposable lenses that can be replaced weekly, monthly, and even daily The last decade hasseen advances in contact lenses for correcting presbyopia, including bifocal and multifocalcontact lenses

2 Market Information

Currently, it is estimated in the United States that over 30 million people use contactlenses Some 80% are using soft lenses and approximately 20% are using rigid gas-permea-ble lenses

Contact lenses offer individuals a readily available method of correcting refractiveerrors that can be personalized to their individual needs Excellent visual acuity is routinelyattained with contact lenses; 100% likely see 20/40 or better and well over 95% achieve20/20 or better, though visual “results” with contact lenses are rarely reported Contact

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64 Dualan and Asbell

lenses are relatively inexpensive, and though there are ongoing costs in terms of replacingthe lenses, the lens care solutions, and having follow-up care, the expenditures are modestcompared to the significant initial outlay for refractive surgery Contact lenses can easily

be exchanged as patient’s refractive error changes and so allows children and young adults

to be fitted even before the refractive error has completely stabilized In addition, olderindividuals have an option to change to presbyopic contact lenses as the need for additionalcorrection for good near vision increases Perhaps the key to the success of contact lenses

is their flexibility: the ability to change lenses to meet patients’ changing visual needsand even give them the ability to return to spectacles or other vision correction method

at any time Most refractive surgery procedures are permanent and irreversible If for anyreason a patient is unhappy or dissatisfied with the surgical results, he or she “cannot goback again.”

B REFRACTIVE SURGERY VERSUS CONTACT LENSES FOR THE

CORRECTION OF REFRACTIVE ERRORS

1 The Contact Lens Candidate

As with any patient seeking correction of a refractive error, a complete eye exam isindicated This would include obtaining a good history It is important to determine howthe patient will be using the refractive correction and whether it is to be used for a specificactivity such as skiing, swimming, computer use, etc Medical problems that might increasethe risk of wearing contact lenses could include diabetes mellitus, immunosuppression,severe allergies, and possibly occupational hazards such as exposure to volatile gases Theeye examiner needs must be particularly attentive to lid function, since spreading of a tearfilm by blinking is central for the good fit of a contact lens Evaluation for possible dryeyes is essential, since a poor tear film can interfere with the patient’s ocular health and/

or comfort with lenses

Relative contraindications to contact lens wear are not different from those beingconsidered when a patient is being evaluated a patient for refractive surgery: the inability

to understand the risks and benefits of the correction modality, immunosuppressed patients,patients with only one functional eye, history of previous ocular problems including her-petic keratitis, previous ocular surgery such as glaucoma filtering procedures, chronic use

of topical medications such as steroids, severe dry eyes, neovasclarization of the cornea,corneal dystrophies, and pregnancy The key issues regarding more of contraindicationsthat are specific to the fitting of contact lenses include patients who are unable or notwilling to participate in appropriate lens care and follow-up care, patients who are unable

to learn to insert and remove contact lenses or do not have a family member who canassist with this process, and patients who may have poor hygiene, which may put them

at increased risk for infections associated with contact lens use

C SOFT CONTACT LENSES

Soft contact lenses are made of a plastic called hydrogel that can be shaped into lensesbut maintains its flexibility and provides immediate quality vision and comfort for mostpatients

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1 Advantages of Soft Contact Lenses

Immediate comfort is clearly the advantage of these lenses Soft contact lenses are generallylarge in diameter and extend beyond the cornea and limbus and fit under the upper lidmargin Though there is slight movement with each blink because of the size of the lensand the flexibility of the material, little sensation is associated with soft contact lens use.Adaptation to soft contact lenses is rapid and patients can begin enjoying quality visionalmost from the moment the lenses are placed

Key advantages of soft contact lens use are

Adaptation

Comfort

High-quality visual acuity

Ability to use on an intermittent basis

Ease of fitting

Ease of contact lens care

Correction of a wide range of refractive errors

Soft contact lenses can usually be fitted in one visit, with a brief follow-up to ensurethat they continue to provide excellent comfort and vision Few unscheduled visits arerequired, and patients typically return every 6 to 12 months for a follow-up that includesevaluation for other ocular diseases, such as glaucoma and to ensure the general ocularhealth as well continued proper use of the contact lenses

2 Disadvantages of Soft Contact Lenses

Unlike myopes, hyperopes may have difficulties with visualization of contact lenses duringhandling, since these patients do not have any near point in focus Deposits can develop

on the lenses, which can interfere with comfort and vision Patients who may be exposed

to environmental hazards such as volatile chemicals and those who have poor or inadequatetear film are presently not good candidates for the use of soft contact lenses

3 Lens Selection

There are a variety of things to be considered in picking a soft contact lens for a particularpatient Most soft lenses come in predetermined parameters from the manufacturer, thoughsome can be custom-ordered for a particular prescription, such as lenses for patients withhigh astigmatism Soft contact lenses vary in water content: low range (30 to 45% water),medium content (40 to 58% water), and high content (60 to 80% water) The amount ofwater is a factor in the oxygen permeability of the lens and also influences comfort andease of handling Contact lens parameters include the base curve of the central optic zoneand the diameter of the lens Typically, a trial lens will be placed to evaluate the fit anddetermine the refractive correction needed to account for the reduced vertex distance andresidual astigmatism Many manufacturers supply practitioners with trial lenses that canthen be dispensed on the initial visit Replacement lenses can then be sent directly to thepatient’s home or work for added convenience

Another key consideration in fitting a soft lens is the wear schedule For patientswho might need intermittent correction, as for social events or sports, one-day disposablelenses may very well be suitable Other patients do well with daily-wear disposable lensesthat are replaced weekly or biweekly Soft lenses can also be used on a flexible replacement

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schedule: weekly, monthly, or quarterly They can also be dispensed as extended-wearlenses, typically being left in place for 6 to 7 days and then removed and disposed of andreplaced by new contact lenses Past studies suggest that the use of extended-wear contactlenses significantly increases the risk of corneal infections However, new lens materialshave become available that have significantly increased oxygen permeability and dispos-ability of lenses and possibly may have reduced the risks of extended-wear usage Conven-tional lenses that are used day in and day out are still available but are less commonlyprescribed, since they offer none of the advantages of disposable lenses, including theregular use of a Fuch sterile lens offering assured quality vision and comfort with eachnew lens

D RIGID GAS PERMEABLE CONTACT LENS

The original cosmetic lenses made of a hard material (PMMA) and are still available todaybut are rarely used in new fittings in the United States Newer materials afford increasedoxygen to the cornea and greater comfort while providing better rigidity than soft contactlenses Several rigid gas-permeable (RGP) materials are available, including silicone acry-late and fluorine copolymers as well as others

1 Key Advantages of RGP

The key advantages of RGP contact lenses are that they are manufactured “to order,”allowing for adjustments for an individual’s visual needs to achieve the best fit RGPsallow for sharp, excellent visual quality and lens durability

The advantages of rigid gas permeable lenses are

Quality of vision

Durability of lens material

Ability to correct astigmatism

In-office modification possible

Resistance to formation of lens deposit

Increased suitability in patients with poor tear film

Ease of lens handling

2 Disadvantages of Gas-Permeable Contact Lenses

A period of adaptation is needed for the patient to become comfortable with the lenses.This varies from patient to patient but usually is about 2 weeks long Comfort is not

“instantaneous,” and these lenses are less likely to provide the “wow factor,” which may

be routine with soft contact lenses Fitting RGP lenses can be more challenging, butmodifications can allow for the best fit for an individual patient Possible corneal thinningwith long-term contact lens wear is another disadvantage

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depend the material chosen and patient’s visual needs, whether these involve daily wear

or extended-wear use More recently, frequent lens replacement has been introduced evenfor rigid gas permeable lenses Intermittent use is inadvisable, since an adaptation period

is needed to achieve maximum comfort with RGP lenses

E ASTIGMATISM

Soft contact lenses can be used in patients needing astigmatic corrections If the patient’srefractive error demonstrates only a small amount of astigmatism (under 1.00 D) and theastigmatism is a small amount of the spherical correction (less than one-third), a softspherical contact lens will adequately correct vision However, greater degrees of astigma-tism can easily be corrected with toric soft contact lenses RGP lenses can be used tocorrect astigmatism whether it is corneal or lenticular in origin Various methods havebeen developed to stabilize the soft lens to match the orientation of the astigmatic correc-tion These include prism ballast (weighting the lens more heavily on the bottom), trunca-tion (removing a section of the upper and/or lower part of the lens), or a combination ofthe two methods, and “slab off” (a change in the lens periphery using pressure from theeyelids to maintain the position)

The fitting of soft toric lenses usually involves using a trial set and then orderingthe appropriate lenses for an individual patient These lenses have a surface orientationmark to demonstrate whether there is lens rotation, indicating that the astigmatism mightnot be corrected One must observe the orientation mark on the soft contact lens when it

is fitted on the eye Typically, the mark is located at the 6 o’clock position, and one mustobserve whether the rotation is clockwise or counterclockwise A mnemonic that can helpthe fitter to remember how to order the appropriate lens is LARS: left add, right subtract.This means that if the lens rotates to the left, one adds to the amount of trial lens rotation

to the axis from the spectacle refraction However, if the rotation, is to the right, then onesubtracts the amount of lens rotation from the axis obtained in the spectacle refraction.Soft lenses come in a variety of astigmatic corrections, which are available in disposable

or frequent lens replacement styles, for correcting 2 to 3 D These lenses are not indicatedfor greater amounts of astigmatism and irregular astigmats RGP contact lenses, on theother hand, easily correct corneal astigmatism Typically a spherical RGP contact lensmay correct up to 3 D of astigmatism For greater amounts of astigmatism, a toric RGPlens can be made Most manufacturers provide customer service information over thetelephone or by e-mail through the Internet This procedure can help in fitting patientswho have significant astigmatism that may not be adequately corrected with standard lensmaterials

F PRESBYOPIA

1 Monovison

Currently refractive surgery also offers presbyopic correction primarily with the use ofmonovison, where one eye is corrected for distance and the other eye for near use Thisprocedure has been used successfully for many years with contact lens patients In fact,before refractive surgeries, often a trial monovison using contact lenses is indicated tohelp a patient decide if this is appropriate for the planned permanent refractive procedure

to be done Monovision offers simplicity both for the patient and the contact lens fitter

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However, some patients do not get used to the 2 D of anisometropia induced with sion fitting and note reduced stereopsis; they sometimes need an overrefraction in specta-cles for driving and other demanding visual tasks Another option in such patients is toreduce the anisometropia to approximately 1.25 D, which usually resolves symptoms, but

monovi-by doing so the patient should understand there will be an increased need for glasses forcloser vision compared to midrange vision

2 Bifocal Contact Lenses

There are basically two designs in bifocal contact lenses Alternating-vision bifocal contactlenses provide for a slight range movement of the patient’s gaze from distance to near

A slight twist of the lens provides an altered path for the light rays into the eye and how

it is refracted The lenses can be made in a segmented bifocal-style, similar to bifocalspectacles, or they can be made in a concentric bifocal style The distance vision is in thecentral part of the lens and the peripheral portion of the lens is for near vision In bothstyles, the lens must move slightly for patients to have good vision as they change theirfocus from distance to near

An alternative bifocal contact lens design provides simultaneous vision, wherebylight rays from both distant and near object pass through the lens and pupil The patient’sbrain then selects the object to regard and bring into focus This type of lens is available

in several different types, including the concentric bifocal which has an annular design,with distance vision in the center and the near vision in the peripheral part of the contactlens; an aspheric “multifocal” design, where there is an increase in plus power as onemoves from the center to the periphery of the lens as a result of the changing curvature

of the lens as oppose to a single based curve; and the diffractive bifocal type, which hassmall concentric circular facets of varying refractive ability that are alternated to providethe appropriate additional power needed for near vision near the center of the lens Lensesdiffer in their ability to be fitted, requiring careful attention to centering of the lens andthe relationship of the lens size to the patient’s pupil size Typically, a practitioner becomesexpert in one or two bifocal lens types and acquires the experience and knowledge to pickpatients appropriately and fit them quickly The availability of soft bifocal contact lenses,which may also disposable, allows for an easier fit with the use of trial lenses As withrefractive surgery, however, monovision probably continues to be the mainstay, consider-ing the presbyopic patient today

G CONCLUSION

In conclusion, we will probably always have patients who prefer to use contact lenses andspectacles for their refractive correction These modalities offer quality visual acuity aswell as stability and affordability In addition, the development of new materials for contactlenses, particularly those offering extended wear, may very likely present a competitivealternative to refractive surgery This is especially true if the material for extended weardemonstrates increased safety and comfort compared to older lens materials It remains

to be seen whether this goal of extended wear and comfort can in fact be associated normalcorneal physiology and the maintenance of a risk-free use of contact lenses With furtherresearch and an increasing number of people seeking “hassle free” vision correction, wemay yet see the emergence of “permanent” contact lenses

Surgical Treatment Options for Hyperopia and Hyperopic Astigmatism

PAOLO VINCIGUERRA and FABRIZIO I CAMESASCA

Istituto Clinico Humanitas, Milan, Italy

A TREATMENT OF HYPEROPIA

With initial experience, the refractive surgeon may more or less consciously consider thetreatment of hyperopia as a situation opposite to but similar to myopia Disappointingly,laser refractive surgery for hyperopia has often led to more unsatisfactory results andcomplications than for myopia (1–3) If we examine carefully a corneal surface afterhyperopic ablation, we may notice several important peculiarities

The main concern is the transition zone: in treating myopia we create just onetransition zone; while in the treatment of hyperopia, central corneal curvature is increasedand two transition zones are needed, featuring double change in curvature and a medianflexus point (Fig 1) This double transition zone is the most critical point of hyperopiatreatment (4) The most central of these two transition zones cannot be considered as part

of the optical zone (Fig 2) This portion of the induced curvature is used to generate arefractive effect but features a flexus with variation in curvature and is connected to theperipheral corneal curvature through the second curvature zone Therefore, in comparingmyopic and hyperopic treatments with the same ablation diameter, the hyperopic opticalzone will be smaller than the myopic one

With the hyperopic ablation, the corneal curvature is changed, but the corneal ology is maintained up to the middle periphery The ablation diameter must be planned

physi-to fit the zone of curvature inversion right where the normal peripheral cornea flattens.Using the elevation map, the surgeon must calculate the maximal corneal diameter andplace the flexus on the flat peripheral cornea, thus preserving the normal corneal physiology(Fig 3) If the flexus area is positioned centrally, far from this peripheral area of physiologi-cal corneal flattening, multifocality and high-order optical aberrations will be induced

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