Leo T. Chylack Jr, MD
Contents
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Surgical Anatomy of the Lens |
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Optical Basis of Transparency of the Normal Lens and Light Scattering in Cataract |
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Biochemistry |
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Physiology |
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Mechanisms of Cataract Formation |
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Metabolism |
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Cataract Classification |
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Lens Opacities Classification System |
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Epidemiology, Risk Factors, and Medical Treatment of Cataract |
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CHAPTER HIGHLIGHTS |
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In the United States today, surgical extraction of the age-related cataract is the most frequently reimbursed operation in patients older than 65 years of age.[1] More than 1.4 million extractions per year are performed to restore visual function to older Americans. The technology supporting this procedure has evolved rapidly over the past 25 years as ophthalmic surgeons shifted from intracapsular to extracapsular techniques and as intraocular lenses (IOLs) replaced contact and spectacle lenses. The technology continues to evolve as new techniques and materials reduce costs and surgical complexity, and improve the optical quality of IOLs and the functional end results. In developing countries, modern techniques are being adapted by surgeons serving huge numbers of patients with cataract-related blindness. Age-related cataract (Figure 2-1) is the leading cause of visual impairment in the world today; more than 50 million individuals have cataract-related visual impairment.[2]
The timely dissemination of up-to-date surgical knowledge is one way in which skilled surgeons can address the worldwide problem of cataract-related visual impairment and blindness. This chapter focuses on the evaluation and surgical care of individual patients and thus may be more useful to the young surgeon beginning his or her training in cataract surgery or the older surgeon contemplating a change in surgical technique than to the public health official charged with organizing the treatment of cataract in millions of indigent patients. However, the most modern surgical techniques are being applied successfully even in the most primitive settings to alleviate visual loss, and we hope that this text facilitates the transfer of surgical knowledge to those areas of the world where it is badly needed.
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Figure 2-1 A, Minimal age-related nuclear cataract in an intracapsularly extracted lens. B, Moderately advanced mixed corticonuclear age-related intracapsularly extracted cataract. C, Hypermature age-related cataract. |
Surgical anatomy of the lens
The crystalline lens grows throughout life; changing its shape from a slightly rounded ovoid in childhood to a more flattened ovoid in old age. After the filling of the lens vesicle with lens fiber cells and the beginning of cortical fiber formation, the lens always contains a capsule, an anterior and equatorial layer of epithelium, a peripheral cortical region, and an inner nuclear core. In children and young adults with visually disabling cataracts, the capsule is strong, the vitreous is firm, and the ease with which the cortex and nucleus are removed is equal. In contrast, for older adults with age-related cataracts the surgeon must deal with an increasingly fragile capsule, a syneretic vitreous body, and a nucleus that may behave more like a piece of stone than a piece of living tissue. Knowledge of the surgical anatomy of the lens and of the changes that each region undergoes with age helps the surgeon to plan and execute a successful procedure regardless of the age of the patient.
Capsule
The capsule originates as the basement membrane of the epithelial cells of the embryonic lens vesicle, which it encapsulates in its entirety. As the posterior vesicle cells elongate anteriorly and fill the vesicle, the capsule assumes an anterior and posterior aspect. The anterior capsule remains a basement membrane for the epithelial cells, but the posterior capsule is now a thin membrane that is merely adherent to the fiber cells growing along its inner surface. A twofold increase in anterior capsule thickness occurs with age;[3] the capsule is always thinnest posteriorly.[4]
For more than a century accommodative changes in the lens have been attributed to the intrinsic elasticity of the capsule. It has been assumed that relaxation of lens zonules allowed capsular elasticity to deform (round up) the lens and increase accommodative power. However, more modern techniques have shown that the capsule distributes other forces on the lens (i.e., from the ciliary body) but does not act primarily to deform the shape of the lens. Mathematical modeling[5] of accommodation of the human lens has progressed and now is able to characterize some of the age-associated changes in this process.[6]
The surgeon performing neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy knows that the intrinsic elasticity or scrollability of the capsule is responsible for the expansion of the opening made by the laser pulse, and the scrolling usually occurs along the external surface of the capsular bag, suggesting that greater stress acts on the outer rather than the inner filaments of the capsule. The elastic characteristics of the capsule change with secondary cataract formation as a layer of epithelial and fibrous cells are laid down on the inner surface of the capsular scaffold. Less tendency to scroll externally exists; often, cut flaps remain protruding stiffly into the optical zone. The formation of a capsular opacity may simply represent the continuation of the sliding movement of epithelial cells along the capsule that occurs normally in the lens. On the inner surface of the anterior capsule of the intact lens, the anterior epithelial cells move from the midperiphery to the equatorial region, where they differentiate into fiber cells. Lacking a cortical region to join, the cells may continue to move posteriorly along the intact capsule and form balloon cells, and fibrous or glassy plaques.
The expenditure of funds to cover the costs of treating posterior capsule opacification (PCO) is exceeded only by the cost of cataract surgery,[7] so there has been considerable interest in understanding the mechanism by which PCO occurs and in devising treatments for it. Many articles have emphasized the reduction in incidence of PCO if foldable acrylic IOLs are used.[8,][9] It may be possible to reduce (or eliminate) PCO by developing improved IOL design, but a great deal of effort has been invested in studying the cell biology of this process using a variety of experimental systems (cultured human capsular bags obtained postmortem, cell culture systems, in vivo animal model systems, and in situ human observation).[10] Human lens epithelial cells can survive and multiply in serum-free cell culture, so there are intrinsic mechanisms sustaining these cells. If serum is added, however, the replication rate increases dramatically. This has led to the search for paracrine factors (proteins from other cells), and a number of candidates have been found (transferrin, basic fibroblast growth factor, epithelial growth factor, and transforming growth factor beta [TGF-β]) that either accelerate proliferation or stimulate transdifferentiation of epithelial cells into fiber cells. Also, autocrine factors (transferrin) and other cytokines have been found.[11,][12] Simply performing a capsulorrhexis will stimulate epithelial cell proliferation[13] compared with the rate in the intact lens.
In a recent study of the effects of TGF-β2 on lens epithelial cells in capsular bag cultures, Wormstone et al[14] showed that a human monoclonal antibody CAT-152 (lerdelimumab) completely neutralized the effect of the TGF-β2-induced effects on the lens epithelial cells leading to PCO. Other approaches to preventing or minimizing PCO involve the addition of cytotoxins to the haptics and/or the IOLs, but in these cases, toxicity to other intraocular cells (particularly the corneal endothelium) is a major concern. These are all well reviewed in Wormstone's article.
A point about the anterior capsule that has surgical relevance is that it is thickest in the midperiphery. More peripherally the capsule thins considerably. This may be part of the reason why a capsulorrhexis placed too far peripherally extends into the equatorial region. The capsule tears easily as a circular disc if the tear is kept within the thicker zone.
Epithelium
With age, the height of the epithelial cells decreases and the width increases. Some studies have shown that a decrease in the number of epithelial cells occurs with cataract formation; other studies have been unable to find decreased numbers of cells. No anatomic features of the epithelium exist that influence surgical technique, but all ophthalmic surgeons recognize that the epithelium is exquisitely sensitive to trauma; its key metabolic role makes it the “Achilles' heel” of the lens.
In addition to the accelerated proliferation of lens epithelial cells in response to paracrine, autocrine, and mechanical factors, these same cells may undergo apoptosis (programmed cell death) in response to oxidative stress and TGF-β2. Oxidative stress in a well-known risk factor for age-related cataract, and TGB-β2 is a growth factor associated with the cellular changes underlying PCO. It may be possible, however, to use this growth factor to increase apoptotic death of cells remaining on the posterior capsule after cataract surgery.
An excellent review of aspects of the lens epithelium that make it generally interesting to biologic scientists (no tumors were found in lens epithelium, and it is an excellent model for the effects of age on epithelial cell function) has been published.[15]
Another publication reveals the dramatic changes that occur in the lens epithelium with age,[16] showing that many “black holes” are apparent representing large areas of severely attenuated epithelial cells. In some areas there is no coverage of the overlying lens capsule. Other features (furrows, and cloudlike stuctures) are found in the aged epithelium, but none of these is associated with the type or severity of age-related cataract. It was hoped that noncontact specular microscopy could be used to identify patients at risk for cataract formation, but the changes noted are more a manifestation of aging than opacification.
Cortex
The three-dimensional structure of the fiber cells in the developing lens has been published by Shestopalov and Bassnett.[17] Using expression of green fluorescent protein in cells transfected by two different methods, they were able to show that the formation of the anterior and posterior sutures is asynchronous and that the disorganization of deep nuclear fiber cells seen in the aged lens is actually characteristic of the primary lens fibers in the embryonic lens and not a consequence of aging.
Several anatomic terms are used today to describe the different regions of the adult lens cortex:
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Peripheral cortex is just beneath the anterior epithelium or the posterior capsule. |
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Supranuclear cortex is adjacent to the adult nucleus. |
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Epinucleus is equivalent to the supranuclear region. |
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Sutures are the lines formed by abutting ends of lens fibers. |
Kuszak et al[18] have demonstrated in several studies the complex anatomy of human lens sutures (Figure 2-2). The dendritic suture structure of the adult cortical cataract often outlines the opaque cortical spoke.
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Figure 2-2 A, Scale computer-assisted drawings of the Y suture seen in normal human lenses at birth and in the fetal nucleus of senescent lenses. Left, Anterior Y suture. Right, Posterior inverted Y suture. Compare and contrast the irregular ends of secondary fiber cells overlapping to form suture branches with the regular and orderly juxtaposition of fiber cells along their length. The anterior and posterior suture patterns are directly offset as a result of opposite fiber cell end curvature. B, Scale computer-assisted drawings of the star suture seen in the cortex of normal, young adult human lenses and in the adult nucleus of normal, noncataractous, senescent lenses. Left, anterior; right, posterior. |
Additional layers of cortical fibers are added throughout life, but the posterior cortex is always thinner than the anterior cortex. What was the subcapsular region in the young child is the supranuclear or epinuclear region in the adult.
An interesting difference exists in the relationships among the capsule, the anterior epithelial cells, and the posterior lens fibers. The posterior fibers peel off easily from the capsule during stripping and aspiration, possibly because a potential space (the embryonic lens vesicle) exists between the posterior fibers and the posterior capsule. The anterior epithelial cells remain adherent to the anterior and equatorial capsule during stripping, perhaps because the capsule is part of the cell itself (its basement membrane) and not just a structure adjacent to it.
One may see the term followability in descriptions of the technique of aspirating lens cortex. It refers to the ease with which the cortex follows the aspiration tip as it strips the cortical fibers off the posterior capsule. Also, it means easily “aspiratable.” Soft cortex is “followable;” stiff nuclear material is not.
Nucleus
Several anatomic terms refer to different concentric layers of the nucleus (Figure 2-3):
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Epinucleus is the outermost nucleus or innermost cortex. |
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Adult nucleus is the next innermost layer. |
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Fetal nucleus corresponds to the cotyledonous areas of light scattering in the clear adult lens. |
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Embryonal nucleus is the innermost core of nucleus. |
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Figure 2-3 Color slit-lamp photograph of a clear lens showing the different cortical and nuclear layers. |
Surgically, the nucleus is characterized by a densely sclerotic posterior third, a slightly less sclerotic central core, and a softer peripheral shell. Occasionally in older patients, even the outermost nuclear shell is very rigid.
Nuclear sclerosis is an ambiguous misnomer often used inconsistently by clinical ophthalmologists to describe the yellowing and opacification of the nucleus with age. Modern systems of cataract classification identify the features of color change (brunescence) and opacification (opalescence) separately.
The term sclerosis is reserved for describing a tactile property of the nucleus – the increasing rigidity of the nucleus with age. This occurs as more cholesterol is incorporated into the phospholipids of the lens membranes. The cholesterol-to-phospholipid ratio is a measure of capsular elasticity; it increases steadily with age and even more sharply after age 60 years.[19] Increasing nuclear sclerosis is responsible, in part, for the loss of the lens's focusing power on near subjects – a clinical age-related condition called presbyopia. Advanced sclerosis is also a major obstacle to phacosonication of the nucleus. If it is too sclerotic, the nucleus must be removed intact (as in a planned extracapsular extraction).
Opacification (or opalescence) of the nucleus is caused by the formation of light-scattering foci either in the nuclear fiber cytoplasm or on the nuclear plasma membranes. Light is scattered by huge protein aggregates that are formed as sulfhydryl (-SH) groups are oxidized to form protein-protein disulfide (-SS-) bonds and by larger molecular aggregates that have higher refractive indices than the monomeric proteins.[20]
The nucleus also changes color with age. The fetal lens is just a faintly perceptible yellow color; in the aged lens the nucleus may be golden yellow, orange, reddish brown, or black. This change in color is called brunescence (Figure 2-4). The change is distinct from the age-related increase in the light scattering (opalescence) of the nucleus. It is due to the accumulation of oxidized tryptophan (N-formylkynurenine), nonenzymatically glycated protein, and other chromophores. Moderate amounts of brunescence may be beneficial because chromophores absorb blue light and reduce glare. However, advanced brunescence causes a reduction in high-contrast acuity and contrast sensitivity independent of the opalescence of the nucleus.[21,][22]
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Figure 2-4 A, Minimal nuclear brunescence in an intracapsularly extracted lens photographed against a white background. B, Advanced nuclear brunescence in an intracapsularly extracted lens photographed against a white background. |
Good clinical correlation exists between the intensity of the brunescence and the hardness of the posterior nucleus. The intensity of the light scattering (opalescence) is also well correlated to the hardness of the nucleus.
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Optical basis of transparency of the normal lens and light scattering in cataract
The transparency of the normal lens is derived from its regular fiber arrangement and the minimal spatial variation in the index of refraction relative to the wavelength of incident light.[23,][24]
In the cataractous lens, more abrupt changes occur in the index of refraction because of (1) the accumulation of fluid with a low index of refraction between fiber cells in cortical and subcapsular cataracts, (2) the formation of very high-molecular-weight cytoplasmic protein aggregates in nuclear cataracts, and (3) the binding of high-molecular-weight aggregates to cellular membranes in all forms of cataracts.[25–27]
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Biochemistry
The structural proteins of the lens are divided into three main groups (alpha, beta, and gamma crystallins) in order of decreasing molecular weight. Most of the enzymes are the size of beta-crystallins. They compose the pathways of aerobic metabolism in the organelle-rich epithelium and most superficial cortical fiber cells and anaerobic metabolism in the organelle-free fiber cell cytoplasm. The main metabolic substrate of lens is glucose derived from the aqueous humor, and the energy derived from glucose is used in protein-lipid synthesis, active transport of ions and amino acids, and maintenance of normal lens hydration. Kador[28] has provided an excellent summary of lens biochemistry and metabolism.
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Physiology
Active transport mechanisms are found predominantly in the epithelium, and they are involved in the movement of ions, amino acids, and other metabolites. The movement of water in the lens is governed by the movement of ions or osmotically active substances, and a disruption of the normal movement of water in the lens can lead to acute cataract formation. In patients with insulin-dependent, acidotic diabetes who are brought back to euglycemia too rapidly, a mature or hypermature cataract occasionally forms within a few hours. The cataract is caused by the rapid movement of water into the lens to neutralize the hyperosmolarity in the fiber cytoplasm resulting from the abundant sorbitol (an impermeable sugar alcohol) found there. Sorbitol is the sugar alcohol of glucose; as it accumulates in the cytoplasm, it renders the cytoplasm hypertonic relative to the extracellular space, and water moves rapidly into the fiber cell. The abrupt lowering of the index of refraction of the cytoplasm as water enters the cell results in light scattering. Trauma may disrupt epithelial active transport and water flux and result in rapid loss of lens clarity.
Although it has been known for decades that ascorbic acid is actively transported into the lens, only recently have the transport proteins been identified.[29] The specific ascorbic acid transporter SVCT2 was found in an epithelial cell line, and its gene expression was upregulated by oxidants and other cytokines. This paper suggests that such a transport system and the important antioxidant ascorbic acid may respond to the level of ambient oxidative stress.
Rae[30] provides an excellent review of lens physiology.
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Mechanisms of cataract formation
The following sections discuss the known mechanisms of cataract formation.
Osmotic stress
Osmotic stress in the diabetic cataract has been discussed previously. A similar mechanism is believed to apply in the human galactosemic cataract. In both the galactosemic and diabetic cataract, sugars are converted to their respective sugar alcohol by the enzyme aldose reductase in what is called the sorbitol pathway. The sorbitol pathway is composed of the enzymes aldose reductase and polyol dehydrogenase (iditol dehydrogenase). Like sorbitol, galactitol (dulcitol) cannot pass through plasma membranes, and once formed, it remains in the cytoplasm. Water enters the cell to neutralize the hyperosmolarity of the cytoplasm, and the epithelial and fiber cells swell. Also, low-index refraction fluid accumulates between fiber cells in sugar cataracts. Both intracellular and intercellular changes combine to create light-scattering foci and lens opacification.
The role of the sorbitol pathway in human, diabetic, age-related cataract is uncertain; there is not a lot of aldose reductase activity in the human lens epithelium and even less in the fiber cell cytoplasm of the cortex and nucleus.
When performing intraocular surgery, it is important to maintain the proper tonicity (ion concentration) and osmolarity of fluids infused into the eye. Before the introduction of salt solutions with the proper tonicity, osmolarity, and nutrient content, osmotically induced secondary cataracts were a frequent intraoperative or postoperative complication in vitrectomy surgery. In fact, the clear lens was often removed prophylactically during vitrectomy, because postoperative osmotic secondary cataract formation was seen so often.
Protein aggregation
None of the individual crystallin proteins in the clear lens is large enough to scatter light. In the aging lens and in the nuclear cataract, however, the different crystallins combine to form huge aggregates that are large enough to scatter light. The aggregation of millions of light-scattering foci in the lens constitutes a cataract. These aggregates may exist free in the cytoplasm (in nuclear cataracts) or may be bound to cell membranes (in cortical and posterior subcapsular cataracts).
Oxidative stress
Oxidative stress denotes the adverse effects of oxygen and its various redox forms on the constituents of the lens. Oxygen can exist as hydrogen peroxide, singlet oxygen, hydroxyl radical, and superoxide. There are enzyme systems in the lens that produce and destroy these redox species. The relative balance between systems that produce and systems that destroy these oxidants determines whether or not the lens suffers oxidative damage. If the defense mechanisms are deficient, hydrogen peroxide can accumulate and (1) deactivate sulfhydryl-dependent enzyme systems, (2) aggregate proteins by forming protein–protein disulfide bridges, (3) change lens color by forming chromophores, or (4) disrupt membrane structure.
An excellent brief review of glutathione (GSH), an important antioxidant in the lens, has been published.[31] GSH participates in a redox cycle in the lens and is able to detoxify hydrogen peroxide, hydroxyl radical, and dehydroascorbic acid. Loss of GSH is associated with membrane damage and protein aggregation – factors underlying early opacification.
Posttranslational protein changes
In addition to oxidative damage, other changes in lens proteins occur after the protein is formed; these constitute posttranslational changes and include nonenzymatic glycosylation, racemization, and aggregation.
Phase separation
One reversible mechanism of aggregation is phase separation.[32] As the temperature drops, certain protein molecules form large groups; although the individual protein molecules are not covalently bound together, the size of the group is large enough to scatter light. This mechanism applies to the cold cataract often seen in cooled calf lenses. Its relevance to human cataract is yet unknown. Whether or not phase-separated proteins are more likely to form covalently bound aggregates remains to be determined.
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Metabolism
Aberrant lens metabolism is suspected as a causative mechanism in many cataracts, but there is little evidence supporting this suspicion in humans. When specific abnormalities have been sought in cataractous lens epithelium, surprisingly normal metabolic activity has often been found. In the older human lens, there is little metabolic activity in the cortex and nucleus, even in the clear lens. Except for the declining ability of the lens to metabolically resist oxidative damage, there is little evidence that cataract formation is a metabolic event.
Of particular interest is the ability of the lens to accumulate dietary antioxidants. A recent study of one of the dietary carotenoids, lycopene, showed that this substance reduced the osmotic effects associated with galactose exposure and the extent of oxidative damage.[33] This report suggests that this dietary carotenoid can get into the lens where it does help to offset osmotic and oxidative stress.
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Cataract classification
Rationale
Until recently, there has been little need to accurately classify cataract type or severity. Traditionally, clinicians have used anatomic (cortical, nuclear, etc.) or etiologic (radiation, steroid, etc.) terms to describe the type of cataract. Descriptors of cataract severity have been based on coarse, subjective scales and have included terms such as immature, advanced immature, and mature. As basic scientists developed means of identifying and quantitating mechanisms of human cataract formation, it became necessary to more accurately and consistently describe or classify cataracts.[34–37] Also, as pharmaceutical companies encountered drugs with cataractogenic toxicity and as epidemiologists began to study the risk factors of human cataract formation, better systems of cataract classification were needed. Several have been developed, and they include the Lens Opacities Classification System, versions I to III (LOCS I to III);[38–40] the Oxford Cataract Classification System;[41,][42] the Wilmer System;[43,][44] and the Wisconsin System.[45] The World Health Organization (WHO), in collaboration with many of the originators of the other cataract classification systems, sponsored the development and testing of a “simplified” cataract grading scheme which was published in 2002.[46] The simplification refers to the ability to use this system in the field and the reduced number of standards needed to grade the severity of cataract. The WHO anticipates using this system to estimate the type and severity of cataracts in patients who are blind from cataract. Such data will help host countries to plan their programs to care for these patients and for patients likely to soon become cataract blind. The reduced number or standard images in the WHO's system may reduce the applicability of this system to studies aimed at detecting the smallest amount of cataractous change in the shortest possible period (e.g., assessing the cataractogenic potential of new system drug candidates or measuring the impact of nonsurgical treatments of age-related cataract in the shortest possible time).
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Lens opacities classification system
A purposely degraded image of the set of LOCS III standards is reproduced in Figure 2-5. This figure is to be used only to understand the general format of the LOCS III standards. The images in Figure 2-5 should not be used for grading cataracts in patients because theimage quality has been purposely degraded.[40] Non-degraded LOCS III standard images are available from the author. In the LOCS III system, the grader, working at the slit-lamp microscope with a set of standards on a nearby light box, estimates separately the extent of cortical and subcapsular cataract, the intensity of light scattering in the nucleus, and the color of the nucleus. Grades are in decimal form; for example, a cortical cataract, the severity of which is judged to be intermediate between cortical standards 2 and 3, would be graded 2.5. Similar grades could be generated for different degrees of nuclear opalescence and nuclear color. The LOCS II and III systems have been validated[47] and used widely in pharmaceutical trials, natural history studies, and other epidemiologic studies.
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Figure 2-5 Lens Opacities Classification System, version III (LOCS III). Note: This figure illustrates only the format of the LOCS III standards: these standard images should not be used for grading cataracts in patients as the image quality of all standards has been purposely degraded. LOCS III consists of six standards to grade nuclear opalescence (NO) and nuclear color (NC), five to grade cortical cataract (C), and five to grade posterior subcapsular cataract (P). Non-degraded standard images are available from the author. |
There has been some interest in using the LOCS II and III systems in clinical practice. It has been considered helpful in following the severity of a cataract and communicating information about cataract type and severity to patients. It has also been used to grade the intensity of nuclear opalescence and color in planning phacoemulsification surgery.[48] The greater the LOCS III grade for nuclear opalescence and nuclear color, the more likely it is that the nucleus will be sclerotic. Little apparent correlation exists between the ease of aspirating an opaque cortex or subcapsular lens fibers and the LOCS III grade. Clear cortex can be aspirated as easily as opaque cortex.
Objective documentation of cataract
Even finer grading of cataract severity is possible with standardized lens photography and techniques of image analysis. Such techniques include measurement of nuclear density,[49,][50] the area of cortical or subcapsular opacity,[51,][52] or the color of the nucleus[53,][54] using Scheimpflug slit images, retroillumination images, or color slit images, respectively. These techniques allow measurement of the rates of change in cataract severity in different populations.
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Epidemiology, risk factors, and medical treatment of cataract
Epidemiology and risk factors of age-related cataract
Many risk factors of age-related cataract have been identified during the past 20 years.[55–57] Factors that increase the risk of age-related cataract include female sex, smoking, heavy alcohol intake, limited education, use of corticosteroids, increased sun exposure, black race, dehydrating diarrhea, myopia, protein-deficient and specific amino acid-deficient diets, and diabetes mellitus. Factors that lower the risk of cataract include the use of multivitamin supplements and, possibly, aspirin.[58,][59]
Medical treatment of cataract
Many surgeons have expressed their conviction that surgery is the only appropriate treatment of cataract-related visual loss or blindness. In many parts of the world, however, there are too few surgeons and too many patients with visually disabling cataract. In these situations, the ability to address the age-related cataract problem with a medical, nutritional, or environmental approach would greatly reduce suffering and the need for medical and surgical care. Viewing cataract-related blindness from a worldwide perspective places the nonsurgical management of cataract in the proper context.
In many parts of the world, drugs with alleged anticataract efficacy are marketed widely and enjoy huge sales. None of these preparations has been shown to be effective through rigorous clinical investigative methods. Until recently, many countries were allowed to market drugs proved safe even though they were not proved effective. In countries in which medical practitioners are unable to offer cataract surgery to patients with cataract-related visual loss, use of preparations with purported anticataract efficacy and positive placebo effects might be understandable. However, the economic cost of using these nostrums is high, and such economic resources might be better spent on improving the surgical care delivered to such patients.
A National Eye Institute-sponsored 5-year study of the natural history of age-related cataract formation (the Longitudinal Study of Cataract) has been completed.[60,][61] This study measured the rates of cortical, nuclear, and posterior subcapsular cataract formation and rates of nuclear brunescence. It also related personal, environmental, occupational, and nutritional data to these rates and provided insights into nonsurgical methods of intervening to slow the rates of age-related cataract formation (e.g., decrease smoking, use multivitamin antioxidants, avoid high body mass index [obesity]).
Two prospective, randomized, placebo-controlled clinical trials of the effect of antioxidant vitamins on the rate of age-related cataract have been published.[62,][63] Interestingly, the Roche European American Cataract Trial (REACT) showed that a micronutrient mixture containing vitamin C, vitamin E, and beta-carotene was able to produce a small deceleration of progression of age-related cataract. The Age-Related Eye Disease Study (AREDS) trial using a similar mixture, but with lower dosages, showed no beneficial effects on cataract progression. Knowing whether or not these vitamins and beta-carotene slow age-related cataract will have to await the completion of a third randomized, placebo-controlled trial.
Unfortunately, at present, few additional medical anticataract agents have potential. In the United States, a phase separation inhibitor was tested as a means of slowing or preventing the nuclear cataract that follows vitrectomy and was found to have no beneficial effect. At present, it is particularly frustrating to have the technology to test anticataract drug efficacy but few anticataract agents to test.
Fortunately, in countries with great shortages of surgical practitioners, there are now low-cost, modern, surgical options for caring for patients with cataract-related blindness. From the cataract camps in India to the technician-staffed operating rooms in Africa, one sees ingenious ways of providing surgical care for patients with cataract where it is most needed.
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References
[1]. Stark W.J., Sommer A., Smith R.E.: Changing trends in intraocular lens implantation. Arch Ophthalmol 1989; 107:1441.
[2]. International Agency for the Prevention of Blindness: World blindness and its prevention, New York, Oxford University Press, 1980.
[3]. Tripathi R.C., Tripathi B.J.: Lens morphology, aging, and cataract. J Gerontol 1983; 38:258.
[4]. Fincham E.F.: The mechanism of accommodation. Br J Ophthalmol 1937; 8:5.
[5]. Koretz J.F., Handelman G.H.: A model for accommodation in the young human eye: the effects of elastic anisotropy on the mechanism. Vision Res 1983; 23:1679.
[6]. Burd H.J., Judge S.J., Cross J.A.: Numerical modeling of the accommodating lens. Vision Res 2002; 42:2235.
[7]. Bertelmann E., Kojetinsky C.: Posterior capsule opacification and anterior capsule opacification. Curr Clin Ophthalmol 2001; 12:35.
[8]. Apple D.J., Peng Q., Visessook N., et al: Eradication of posterior capsule opacification: documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained post-mortem. Ophthalmology 2001; 108:505.
[9]. Javdani S.M., Huygens M.M., Callebaut F.: Neodymium:YAG capsulotomy rates after phacoemulsification with hydrophobic and hydrophilic acrylic intraocular lenses. Bull Soc Belge Ophtalmol 2002; 283:13.
[10]. Wormstone M.: Posterior capsule opacification: a cell biological perspective. Exp Eye Res 2002; 74:337.
[11]. Majima K.: Human lens epithelial cells proliferate in response to exogenous EGF and have EGF and EGF receptor. Ophthalmic Res 1995; 27:356.
[12]. Wormstone I.M., Tamiya S., Marcantonio J.M., et al: Hepatocyte growth factor and c-Met expression in human lens epithelial cells. Invest Ophthalmol 2000; 41:4216.
[13]. Rakic J.M., Galand A., Vrensen G.F.: Separation of fibers from the capsule enhances mitotic activity of human lens epithelium. Exp Eye Res 1997; 64:67.
[14]. Wormstone I.M., Tamiya S., Anderson I., et al: TGF-beta2-induced matrix modification and cell transdifferentiation in the human lens capsular bag. Invest Ophthalmol Vis Sci 2002; 43:2301.
[15]. Bhat S.P.: The ocular lens epithelium. Biosci Rep 2001; 21:537.
[16]. Balaram M., Kuszak J.R., Ayaki M., et al: Noncontact specular microscopy of human lens epithelium. Invest Ophthalmol Vis Sci 2000; 41:474.
[17]. Shestopalov V.I., Bassnett S.: Three-dimensional organization of primary lens fiber cells. Invest Ophthalmol Vis Sci 2000; 41:859.
[18]. Kuszak J.R., Bertram B.A., Macsai M.S., et al: Sutures of the crystalline lens: a review. Scanning Electron Microsc 1984; 3:1369.
[19]. Li L.K., So L., Spector A.: Age-dependent changes in the distribution and concentration of human lens cholesterol and phospholipids. Biochim Biophys Acta 1987; 917:112.
[20]. Siezen R.J., Owen E.A.: Physicochemical characterization of high-molecular-weight alpha-crystallin subpopulations from the calf lens nucleus. Biochim Biophys Acta 1983; 749:227.
[21]. Chylack Jr L.T., Padhye N., Khu P.M., et al: Loss of contrast sensitivity in diabetic patients with LOCS II classified cataract. Br J Ophthalmol 1993; 77:7.
[22]. Chylack Jr L.T., Jakubicz G., Rosner B., et al: Contrast sensitivity and visual acuity, as functions of cataract type and extent. J Cataract Refract Surg 1993; 19:399.
[23]. Benedek G.B.: Theory of transparency of the eye. Appl Opt 1971; 10:459.
[24]. Trokel S.: The physical basis for transparency of the crystalline lens. Invest Ophthalmol 1962; 1:493.
[25]. Tripathi R.C., Tripathi B.J.: Morphology of the normal, aging, and cataractous human lens. II. Optical zones of discontinuity and senile cataract. Lens Res 1983; 1:43.
[26]. Harding C.V., Maisel H., Chylack Jr L.T., et al: The structure of the human cataractous lens. In: Maisel H., ed. The ocular lens: structure, function and pathology, New York: Marcel Dekker; 1985.
[27]. Vrenson G., Willekens B.: Biomicroscopy and scanning electron microscopy of early opacities in the aging human lens. Invest Ophthalmol Vis Sci 1990; 31:1582.
[28]. Kador P.F.: Biochemistry of the lens: intermediary metabolism and sugar cataract formation. In: Albert D.M., Jakobiec F.A., ed. Principles and practice of ophthalmology (basic sciences), Philadelphia: WB Saunders; 1994:146.
[29]. Kannan R., Stolz A., Ji Q., et al: Vitamin C transport in human lens epithelial cells: evidence for the presence of SVCT2. Exp Eye Res 2001; 73:159.
[30]. Rae J.: Physiology of the lens. In: Albert D.M., Jakobiec F.A., ed. Principles and practice of ophthalmology (basic sciences), Philadelphia: WB Saunders; 1994:123.
[31]. Giblin F.J.: Glutathione: a vital lens antioxidant. J Ocular Pharmacol Ther 2000; 16:121.
[32]. Clark J.I., Benedek G.B.: Phase diagram for cell cytoplasm from the calf lens. Biochem Biophys Res Commun 1980; 95:482.
[33]. Mohanty I., Joshi S., Trivedi D., et al: Lycopene prevents sugar-induced morphological changes and modulates antioxidant status of human lens epithelial cells. Br J Nutr 2002; 88:347.
[34]. Marcantonio J.M., Duncan G., Davies P.D., et al: Classification of human senile cataracts by nuclear color and sodium content. Exp Eye Res 1980; 31:227.
[35]. Chylack Jr L.T., Lee M.R., Tung W.H., et al: Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) Methods I: instrumentation and technique. Invest Ophthalmol Vis Sci 1983 1983; 24:424.1983
[36]. Chylack Jr L.T., White O., Tung W.H.: Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) Methods II: staged simplification of cataract classification. Invest Ophthalmol Vis Sci 1984; 25:166.
[37]. Chylack Jr L.T., Ransil B.J., White O.: Classification of human senile cataractous change by the American Cooperative Cataract Research Group (CCRG) Methods III: the association of nuclear color (sclerosis) with extent of cataract formation, age and visual acuity. Invest Ophthalmol Vis Sci 1984; 25:174.
[38]. Chylack Jr L.T., Leske M.C., Sperduto R., et al: Lens Opacities Classification System. Arch Ophthalmol 1988; 106:330.
[39]. Chylack Jr L.T., Leske M.C., McCarthy D., et al: Lens Opacities Classification System II (LOCS II). Arch Ophthalmol 1989; 107:991.
[40]. Chylack Jr L.T., Wolfe J.K., Singer D.M., et al: The Lens Opacities Classification System, Version III (LOCS III). Arch Ophthalmol 1993; 111:831.
[41]. Sparrow J.M., Bron A.J., Brown N.A.P., et al: The Oxford clinical cataract classification and grading system. Int Ophthalmol 1986; 9:207.
[42]. Sparrow J.M., Ayliffe W., Bron A.J., et al: Inter-observer and intra-observer variability of the Oxford clinical cataract classification and grading system. Int Ophthalmol 1988; 11:151.
[43]. West S.K., Taylor H.R.: The detection and grading of cataract: an epidemiological perspective. Surv Ophthalmol 1986; 31:175.
[44]. Taylor H.R., West S.K.: The grading of lens opacities. Aust NZ J Ophthalmol 1989; 17:81.
[45]. Klein BEK, Magii YL, Neider MW et al. Wisconsin system for classification of cataracts from photographs. NTIS Accession No. PB 90-138306. Available from National Technical Information Service, 5285 Port Royal Rd., Springfield, VA 22161.
[46]. Thylefors B., Chylack Jr L.T., Konyama K., et al: A simplified cataract grading system. Ophthalmic Epidemiol 2002; 9:83.
[47]. Maraini G., Pasquini P., Tomba M.C., et al: The Italian-American Cataract Study Group: An independent evaluation of the Lens Opacities Classification System (LOCS II). Ophthalmology 1989; 96:611.
[48]. Davison J.A., Chylack Jr L.T.: Clinical application of the lens opacities classification system III in the performance of phacoemulsification. J Cataract Refract Surg 2003; 29:138-145.
[49]. Chylack Jr L.T., Mantel G., Wolfe J., et al: Monitoring cataract with LOCS II and counterpart objective measures: lovastatin and the human lens, results of a two year study. Optom Vis Sci 1993; 70:937.
[50]. Chylack L.T., McCarthy D., Khu P.: Use of Topcon SL-45 Scheimpflug slit photography to measure longitudinal growth of nuclear cataracts in vivo. Lens Res 1988; 5:83.
[51]. Wolfe J.K., Chylack Jr L.T.: Objective measurement of cortical and subcapsular opacification in retroillumination photographs. Ophthalmic Res 1990; 22:62.
[52]. Wolfe J.K., Chylack Jr L.T.: Differentiation between cortical and posterior subcapsular cataract using pattern matching in computerized image analysis. Invest Ophthalmol Vis Sci 1989; 31:353.
[53]. Herzberg S., McCarthy D., Kansupada K., et al: Positional dependence of objective measures of nuclear color in the lens: correlation with LOCS II score. Invest Ophthalmol Vis Sci 1989; 31:352.
[54]. Chylack Jr L.T., Wolfe J.K., Friend J., et al: Quantitating cataract and nuclear brunescence: the Harvard and LOCS systems. Optom Vis Sci 1993; 70:886.
[55]. Leske M.C., Chylack L.T., Suh-Wuh W., et al: The lens opacities case control study: risk factors for cataract. Arch Ophthalmol 1991; 109:244.
[56]. The Italian-American Study Group: Risk factors for age-related cortical, nuclear, and PSC cataracts. Am J Epidemiol 1991; 133:541.
[57]. Harding J.J., van Heyningen R.: Epidemiologv and risk factors for cataract. Eye 1987; 1:537.
[58]. Cotlier E., Sharma Y.R.: Aspirin and senile cataracts in rheumatoid arthritis. Lancet 1981; 1:338.
[59]. Seddon J.M., Christen W.G., Manson J.E., et al: Low-dose aspirin and risks of cataract in a randomized trial of US physicians. Arch Ophthalmol 1991; 109:252.
[60]. Leske M.C., Chylack Jr L.T., Wu S.Y., et al: Incidence and progression of nuclear opacities in the Longitudinal Study of Cataract. Ophthalmology 1996; 103:705.
[61]. Leske M.C., Chylack Jr L.T., He Q., et al: Incidence and progression of cortical and posterior subcapsular opacities: the Longitudinal Study of cataract. Ophthalmology 1997; 104:1987.
[62]. Chylack Jr L.T., Brown N.P., Bron A., et al: The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow the progression of age-related cataract. Ophthalmic Epidemiol 2002; 9:49.
[63]. AREDS Research Group: A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta-carotene for age-related cataract and vision loss: AREDS Report No. 9. Arch Ophthalmol 2001; 119:1439.