Hyperopia and Presbyopia - part 3 ppt

53Schachar’s Theory of Accommodation operated in a darkened room, does not offer the usual accommodative stimulus but relies purely on defocus. The instrument, which requires the subject to use a bite plate for stability 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) have speculated that the possible restoration of near vision via scleral expansion could function via 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 States are now undergoing wavefront analysis to provide an objective measurement and assess mechanisms 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 as that of accommodation and presbyopia. The processes of accommodation and disaccom- modation are complex, to say the least, and involve changes in muscular, lenticular, and extralenticular components. At some time, almost every one of these components has been proposed as a factor in the development of presbyopia. We have tried in this chapter to present a balanced view of Schachar’s versus Helm- holtz’s theory of accommodation, along with experimental evidence and arguments that have been espoused by proponents of both sides. In a number of key respects, the proposed mechanisms are antithetical. The universal nature of presbyopia and the intense interest in its reversal justifies further research in this area to elucidate its pathophysiology. ACKNOWLEDGMENT Supported by the Midwest Corneal Research Foundation, Inc. REFERENCES 1. Koretz JF. Accommodation and Presbyopia. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology: Basic Sciences. Philadelphia: Saunders, 1994:270–282. 2. Schachar RA. Is Helmholtz’s theory of accommodation correct? Ann Ophthalmol 1999; 31(1): 10–17. 3. Schachar RA, Cudmore DP, Black TD. Experimental support for Schachar’s hypothesis of accommodation. Ann Ophthalmol 1993; 25:404–409. 4. Schachar RA, Cudmore DP, Black TD. A revolutionary variable focus lens. Ann Ophthalmol 1996; 28:11–18. 5. Schachar RA, Cudmore DP, Black TD, Wyant JC, Shung VW, Huang T, Mckinney RT, Rolland JP. Paradoxical optical power increase of a deformable lens by equatorial stretching. Ann Ophthalmol 1998; 30(1):10–18. 6. Schachar RA, Tello C, Cudmore DP, Liebmann JM, Black TD, Ritch R. In vivo increase of the 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 demonstrating Schachar’s hypothesis of accommodation. Ann Ophthalmol 1994; 26:4–9. 8. Schachar RA, Huang T, Huang X. Mathematical proof of Schachar’s hypothesis of accommo- dation. Ann Ophthalmol 1993; 25:59. 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 lens with age. Vis Res 1998; 38:209–229. 12. Glasser A, Croft MA, Kaufman PL. Aging of the human crystalline lens and presbyopia. Int Ophthalmol Clin 2001; 41(2):1–15. 13. Glasser A, Campbell MCW. Biometric, optical and physical changes in the isolated human crystalline 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 ac- commodation studies: a new technique using infrared retro-illumination video photography and pixel unit measurements. Trans Am Ophthalmol Soc 1997; 95:261–270. 17. Wilson RS, Merlin LM. Infrared video photographic analysis of human accommodation. Invest Ophthalmol 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-related changes 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 surgical technique 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. 5 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 recent publications in this field, I have not been able to cite many important earlier works. I extend 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 a means of shedding cells, the lens is an excellent organ in which to study aging. There are changes in lens size, shape, and mass throughout life that occur at different rates. The sagittal diameter of the lens is approximately constant at 9.0 mm., but the anteroposterior distance 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 the lens 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, they survive throughout life. The germinative epithelial cells are actively dividing cells, and the equatorial epithelial cells undergo terminal differentiation. As lens fibers form, they lose their nuclei and other intracellular organelles; in the deeper cortex, fiber cells are essentially organelle-free. The slightly tortuous course of the long fiber cells as they arch over the equator and meet near the opposite pole to form sutures has been illustrated in elegant studies by Kuszak et al. (2–4). The complexity of these sutures increases with age and may account for the increased light scattering in the zones of disjunction seen biomicroscopically. 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. Antioxidant defense mechanisms may ameliorate some of these posttranslational changes. Also, with increasing 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 opacifi- cation and frank cataract. Changes with age in protein conformation and phospholipid composition of fiber membranes increase nuclear rigidity and contribute to presbyopia. This chapter considers many of these changes in more detail. In the past 15 years, epidemiological research on age-related cataracts (ARCs) has revealed risk factors that pertain to behavior (e.g., diet, smoking, lifestyle, drug use) and suggested that ARC may be a preventable disease (5,6). This is most encouraging, for each year increasing percentages of public and private health care budgets are used to provide 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 subjects from 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 geometric distortion of Scheimpflug images can be corrected (14), so that accuratemeasures of the lens can be obtained. Koretz et al. measured the lens with Hough transforms and other image analysis methods. The radii of the anterior and posterior surfaces of the whole lens decrease, but the volume increases with increasing age. In contrast, neither the shape nor the 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 complica- tions. Another study (15) explored the relationship of accommodative convergence per unit of accommodative response (AC/A ratio), refractive error, and age to determine if the 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 flatter crystalline lens, increased the effort to accommodate, or “pseudocycloplegia.” Accommo- dative deficits in myopia may be the functional consequence of myopic enlargement of the 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 3 years, the mean change in refractive error (in OD) was מ0.52 ם/מ 0.45D (p Ͻ 0.05). The mean lens thickness increased by 0.07 ם/מ 0.10 mm (p Ͻ 0.05), and the mean elongation of the vitreous chamber was 0.27 ם/מ 0.30 mm (p Ͻ 0.05). Regardless of the original refractive error, the change in refractive error over the 3-year period was toward myopia. There were no statistically significant changes in the curvature of the cornea or depth of the anterior chamber. The authors concluded that the myopic shift was due to an elongation of the vitreous chamber. In a study of 1-year-old chickens (17), form deprivation vision such as is obtained through translucent glass or eyelids that have been sutured closed, even in fully grown birds, was associated with a myopic shift that was similar but not as large as that in neonatal chicks. The decreases in retinal dopamine seen in neonatal chicks were also seen 57Aging and the Crystalline Lens to a lesser degree in 1-year-old chickens. These studies suggest that form deprivation is one 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 optical performance of the eye with increasing age. In qualitative terms, the MTF is used to assess optical quality of lens combinations by measuring the degree to which a point source of light 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 approxi- mately linear fashion with age, but it did not vary with gender. The decline in MTF may account for the decline in contrast sensitivity function (CSF) with age. C. PRESBYOPIA In an important paper appearing in 1988 (19), Fisher recounted the classic argument that presbyopia was related to the force of contraction of the ciliary muscle and the resistance to deformation of the crystalline lens. He recounted the view of Donders (20), that presby- opia was caused by a decrease in the force of contraction of the ciliary muscle with age, and the opposing view of Helmholtz (21), that the lens became more difficult to deform with age due to lenticular sclerosis. Fisher found that, in fact, the ciliary muscle undergoes a compensatory hypertrophy as accommodative amplitude decreases with 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 of lenticular sclerosis, since the lens substance does not lose water, but because the capsule loses its elastic force with age and the lens fibers, particularly in the nucleus, become more 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 of the mechanisms of presbyopia. In 1991 (22), Pau and Kranz used a fine conical probe and 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 the nucleus. The cortex did not show this hardening. In an interesting study of the dynamic aspects of accommodation (23), Heron et al. showed that accommodation gain decreased and the phase lag increased with age. Reaction time, response time, and accommodative velocity did not change with age for a target oscillating sinusoidally in a predictable manner at modest amplitude. The main aging effect was a longer than predicted phase lag. In spite of decreasing amplitude of accommodation, other aspects of accommodative function 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 only slightly with increasing age. A decrease in the diameter of the unaccommodated ciliary muscle ring was highly correlated with advancing age. Unaccommodated lens thickness increased with age, but the thickness of the lens under accommodative effort was only slightly 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 the unaccommodated 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 disaccommodate due 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 lens fiber 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 length similar to those occurring in lenses stretched into an unaccommodated state. These phe- nomena were attributed to nonsystematic changes in lens curvatures. These data support the 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 there are 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 near task caused a small increase in the static accommodative response. In both emmetropes and late-onset myopes, near tasks also increased the interval for relaxing accommodation. These data suggest the existence of two subsystems that adapt differently to prolonged accommodative 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 ampli- tude of accommodation, the response dynamics (reaction and response times) over the adult age range (16 to 48 years) remained remarkably constant even though the amplitude 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 (H 2 O 2 ) and photo-oxida- tion (secondary to UV irradiation) have been implicated. In addition to a cumulative increase with age in the oxidative damage to lens proteins and lipids, there is also a gradual reduction in the potency of the lens antioxidant defenses. In a recent study (28), the thiol and 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 retinal tear surgery were compared. There was a statistically significant (p Ͻ 0.01), age- associated inverse relationship between the contents of P-SH and protein carbonyls. The changes were greater in cataractous than clear lenses and greater in diabetic and myopic cataracts than in age-related cataracts. The decrease in P-SH occurred earlier in diabetic and myopic cataracts than in ARCs. An increase in protein carbonyls Ͼ2 nmol/mg protein and a decrease in P-SH of Ͻ10 to 12 nmol/mg protein were always associated with lens opacification. 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 major antioxidant defenses in the lens. The GSH-redox cycle is very active in lens epithelium and cortex. 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 59Aging and the Crystalline Lens with age. The low ratio of GSH/P-SH and the relatively inactive GSH-redox cycle in the nucleus 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). With increased 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-redox cycle, there is damage to Na ם ,K ם -ATPase (an enzyme involved with many of the active transport mechanisms in LECs), to cytoskeletal proteins, and to membrane proteins in- volved in regulating membrane permeability. An excellent review of these topics has recently been published (38). As oxidative stress increases and the size of the GSH pool decreases, some proteins thiols (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 the formation 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 favored PSSG over PSSC and gamma-crystallin-S-S-G over alpha-crystallin-S-S-G. TTase was also remarkably resistant to oxidation. The TTase dethiolase activity reactivates enzymes deactivated by S-thiolation. It is this ability to regulate and repair SH-dependent enzymes that 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), was found to have an EDTA-like (chelator) structure that might bind copper. Ascorbylation led 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 of ARC (40), it was shown that chronic administration of vitamin E, but not of sodium ascorbate, restored the age-associated decrease in GSH content in rat lenses to levels comparable to those in younger rats. The age-associated decrease in lenticular glutathione peroxidase, 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-associated changes 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 much greater 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, in turn, is regulated by the content of saturated sphingolipid. Hyperbaric oxygen treatment increases 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 oxidation products accumulate in the lens. The Roche European-American Cataract Trial (REACT) (42,43), the first prospec- 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 small but statistically significant deceleration of ARC was found after 3 years of treatment in 60 Chylack a cohort of American and British patients. In this study, the beneficial effect was seen in the entire cohort and in the subgroup of American patients but not in the subgroup of British patients. The basis for the different responses of American and British patients to the antioxidant treatment was not clear but may have been due to the fact that the British patients 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 fibrillin gene 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. REFERENCES 1. Bron AJ, Vrensen GF, Koretz J, Maraini G, Harding JJ. The ageing lens. Ophthalmologica 2000; 214:86–104. 2. Kuszak JR, Sivak JG, Herbert KL, Scheib S, Garner W, Graff G. The relationship between rabbit lens optical quality and sutural anatomy after vitrectomy. Exp Eye Res 2000; 71: 267–281. 3. Kuszak JR, Sivak JG, Weerheim JA. Lens optical quality is a direct function of lens sutural architecture. Invest Ophthalmol Vis Sci 1991; 32:2119–2129. 4. Kuszak JR, Bertram BA, Macsai MS, Rae JL. Sutures of the crystalline lens: a review. Scan Electron Microsc 1984; 3:1369–1378. 5. Rowe NG, Mitchell PG, Cumming RG, Wans JJ. Diabetes, fasting blood glucose, and age- related cataract: the Blue Mountains Eye Study. Ophthalm Epidemiol 2000; 7:103–114. 6. Klein BE, Klein R, Lee KE. Diabetes, cardiovascular disease, selected cardiovascular disease risk 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 cataractous human lens. Exp Eye Res 2000; 71:317–322. 8. Bron AJ, Vrensen GF, Koretz J, Maraini G, Harding JJ. The ageing lens. Ophthalmologica 2000; 214:86–104. 9. Treton J and Courtois Y. Evidence for a relationship between longevity of mammalian species and 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 Exp Ophthalmol 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 zero- diopter accommodation. J Opt Soc Am A Opt Image Sci Vis 18:2665–2672. 14. Richards DW, Russell SR, Anderson DR. A method for improved biometry of the anterior chamber 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 in children. Invest Ophthalmol Vis Sci 2000; 41:2469–2478. 16. Kinge B, Midelfart A, Jacobsen G, Rystad J. Biometric changes in the eyes of Norwegian university students—a three-year longitudinal study. Acta Ophthalmol Scand 1999; 77: 648–652. 61Aging and the Crystalline Lens 17. Papastergiou GI, Schmid GF, Laties AM, Pendrak K, Lin T, Stone RA. Induction of axial eye elongation 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 perfor- mance of the human eye as a function of age in a normal population. Invest Ophthalmol Vis Sci 1999; 40:203–213. 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 preliminary essay 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: The Optical Soc America, 1924. 22. Pau H, Kranz J. The increasing sclerosis of the human lens with age and its relevance to accommodation and presbyopia. Graefes Arch Clin Exp Ophthalmol 1991; 229:294–296. 23. Heron G, Charman WN, Gray LS. Accommodation responses and ageing. Invest Ophthalmol Vis Sci 1999; 40:2872–2883. 24. Strenk SA, Semmlow JL, Strenk LM, Munoz P, Gronlund-Jacob J, DeMarco JK. Age-related changes 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 human crystalline 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 accommoda- tion in emmetropia and late-onset myopia. Optom Vis Sci 1999; 76:295–302. 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 and lens 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 the kinetics 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-related alterations 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 stress upon 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-induced damage 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 metal- catalyzed oxidation of ascorbate in human cataract extracts: possible role of advanced glycation end products. Invest Ophthalmol Vis Sci 2000; 41:1473–1481. 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 of vitamin 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 Roche European-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, the REACT Group. The Roche European American Cataract Trial (REACT): a randomized clinical trial 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 during ageing in normal human zonule. J Submicrosc Cytol Pathol 1998; 30:365–369. [...]... 20/ 63 20 /32 20/125→20/50 20/125→20/50 20/ 63 20/40 20/125→20/ 63 20/105→20 /36 20/118→20/47 20/160→20/80 20/200→20/40 20/200→20/50 20 /30 →20/40 20/80→20/40 ⌬UDVA ⌬Cyl (D) 0.25Ϯ0.29 0.47Ϯ0. 53 0.16Ϯ0.49 0 .30 Ϯ0 .37 0.25Ϯ0.29 0.15 0.15 0.92Ϯ1.46 0.17Ϯ0 .38 0.15Ϯ0.58 NA NA ⌬SE (D) Ϫ0.55Ϯ0 .33 Ϫ1.64Ϯ0.61 Ϫ0.79Ϯ0.65 Ϫ0.52Ϯ0 .35 Ϫ1.41Ϯ0. 53 Ϫ2.15 Ϫ1.50 Ϫ2.08Ϯ1. 13 Ϫ1. 83 0.88 Ϫ1.22Ϯ0.88 Ϫ2.07Ϯ0.11 Ϫ1.25 0.54 0. 43 0.59... peripheral corneal flattening and central corneal steepening, with a greater change in curvature being produced with two-ring treatment.(41) Two-year follow-up of low hyperopic treatment with eight spots at a 6 mm diameter revealed stable refractive effect, similar to the 1-year data (42) Eighteen-month follow up of low hyperopia treatment with two octagonal staggered rings at 6- and 7-mm diameter also confirmed... 7.5, 7.0, and 9.0 and 6.5 and 9.0 mm No patients saw J2 or better preoperatively, and 75% saw J2 or better 6 months postoperatively In phase II, 79% of patients were within 1 D of emmetropia, and 89% of patients had uncorrected visual acuity of 20/40 or better at 1 year follow-up After initial regression, the refractive results were stable at the 6-month follow-up for patients in both phase I and phase... However, there were no sight-threatening complications Goggin and Lavery reported treatment of 11 eyes with mean preoperative spherical equivalent of ‫ 20.1 ע 60.2ם‬D and postoperatively to ‫ 55.0 ע 115.0ם‬D after 1-year follow-up (56) a total of 91% were 20/40 or better and 82% were within ‫00.1ע‬ D of the target spherical equivalent 4 LTK for LASIK-Induced Hyperopia LASIK is a safe and effective technique... laser spots at 6.5 and 9.0 mm to produce a 4-D correction (34 ) Only 25% of patients were within ‫ 00.1ע‬D of intended correction In addition, ‫ 52.1ם‬to ‫ 05.2ם‬D astigmatism was induced with 50% regression of refractive effect at 2 years postoperatively Eggink et al treated 55 hyperopic eyes with one ring of eight spots with a treatment diameter of 6, 7, or 8 mm (35 ) The 6- and 7-mm-diameter treatments... smooth and homogeneous transition zone up to 9 mm, and a second, limbal transition zone, of more than 9 mm Let us remember that the corneal periphery offers also the advantage of a greater thickness (Fig 14) 8 Laser Thermokeratoplasty and Wavefront-Guided LTK SHAHZAD I MIAN and DIMITRI T AZAR Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Schepens Eye Research Institute, and. .. fiberoptic handpiece brought into direct contact with the cornea The spot size is variable and dependent on the diameter of the fiber optic handpiece (Summit Technology, Waltham, MA, 0.7 mm; Technomed, Baesweiler, Germany, 0.55 mm) Depending on the degree of hyperopia, rings of eight spots are applied with a treatment zone of 6.5 and 9.0 mm, 7.0 and 9.0 mm, and 7.5 mm with the Summit Ho:YAG LTK and 6, 7,... to moderate hyperopia (46) Thirty-nine eyes with preoperative spherical equivalent of ‫ 79.0 ע 59.2ם‬D (1.50 to 4.75 D) were treated with two radial rings of eight spots with diameters of 5 and 6 mm (Group A), 6 and 7 mm (Group B), or 6.5 and 7.5 mm (Group C) Uncorrected distance visual acuity improved in all three groups at 1-year follow-up The mean change in spherical equivalent was 31 .1 ע 80.2מ‬... thickness (47) In this study, 57 eyes, with a mean preoperative spherical equivalent of ‫ 22.0 ע 08 .3 ‬D (1.50 to 5.00 D), were treated with Ho:YAG LTK, applying 90 Mian and Azar two or three rings of eight spots, with 6-, 7-, and 8-mm-zone diameters The mean spherical equivalent at 15 months was reduced to ‫ 61.0 ע 37 .1ם‬D In all, 57.8% of the eyes were ‫ 00.1ע‬D of intended correction, while 21% were ‫ 05.0ע‬D... 12-month follow-up, there was no difference between the mean preoperative spectacle-corrected visual acuity and the mean postopera- Laser Thermokeratoplasty 91 tive uncorrected visual acuity There was a mean increase of ‫ 02.1 ע 06.4ם‬D in central keratometric power Contact Ho:YAG LTK was also evaluated for correction of hyperopia and astigmatism after PRK Eggink et al reported limited efficacy and . over PSSC and gamma-crystallin-S-S-G over alpha-crystallin-S-S-G. TTase was also remarkably resistant to oxidation. The TTase dethiolase activity reactivates enzymes deactivated by S-thiolation (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 the formation of PSSP (29) and. 41 :30 61 30 73. 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-related alterations