During the Middle Ages, Arabian physicians called the diffuse white appearance (Fig. 1) of total cataracts nuzul-el-ma, which means “a flowing down of water” or “blue water.” The Carthaginian monk Constantius Africanus, of the Monte Cassino Monastery, translated the ancient Arabic manuscripts into medieval Latin and applied the word cataracta, meaning “to rush down, as a waterfall.”² In modern times, the development of devices that allow the lens to be examined at high magnification (e.g., the slit-lamp biomicroscope) has helped reveal many early changes that can occur in the human lens. Patients’ increasing visual demands, as well as advances in the field of cataract surgery, have resulted in earlier removal of cataracts, and this has made the waterfall-like appearance of advanced cataracts a rarity.

The lens maintains its clarity because of its architectural structure and composition. The lens fibers are laid down in specific arrays and are composed mainly of crystallin proteins. When biochemical or physicochemical changes develop that disrupt the architecture or result in the formation of molecules larger than 1,000 nm (10,000 Å), the affected area loses its transparency and opacity results.³

However, the resulting opacity must be located at or near the visual axis for it to affect vision and become clinically important. Very often peripheral cataracts develop without affecting the visual acuity of the patient, and are therefore considered clinically benign. These opacities may exist for many years, even decades, without necessitating any treatment other than optical correction.

Age-related cataracts appear in late adulthood and may cause a painless progressive loss of vision over the course of several years. Cataract is the leading cause of low vision in the United States⁴ and of blindness in the world.⁵ To date, studies on possible medical treatments for cataracts have not proved them to be safe and effective in humans.⁶

When the patient’s visual function becomes compromised by the cataract, the only effective treatment available today is surgical extraction and replacement of the cataractous lens with an intraocular lens. Various studies have suggested that cataract surgery is one of the most cost-effective surgical interventions.^7,8 The techniques used for the surgical extraction of cataracts are constantly being refined and improved. In the last decade, the frequency of cataract extraction has increased to more than one million per year in the United States alone, and it has become the most commonly performed surgical procedure for Medicare beneficiaries.⁹ An estimated 20.5 million Americans 40 years and older (17.2%) have cataract, and approximately 6.1 million Americans (5.1%) have undergone cataract surgery.¹

In recent attempts to develop a more uniform classification, clinical researchers have used the anatomic locations of lens opacities as a means of classifying cataracts based on photographic standards. The current consensus divides age-related cataracts into three major pure anatomic types (cortical, nuclear, and posterior subcapsular) and mixed types (combinations of these three). Classification schemes such as the Lens Opacities Classification System (LOCS) II¹⁰ and III,¹¹ the Oxford Cataract Classification System,¹² and the systems used in the Beaver Dam Eye Study,¹³ at Johns Hopkins,¹⁴ and in the Age Related Eye Diseases Study¹⁵ use photographic standards to further subdivide each major type into grades. These grades are based either on density and color (in the case of nuclear cataract) or the anatomic area affected by opacity (in the cases of cortical cataract and posterior subcapsular cataract (PSC)). One can directly grade the patient’s lens as seen with the slit-lamp (clinical grading), or evaluate photographs of the lens being studied (photographic grading). In addition, an automated grading system that uses densitometry was recently developed.^16,17

Nuclear cataracts are the most common subtype in most European-derived populations.¹⁸ Studies have documented a gradual increase in optical density of the nucleus with increasing age in normal adults with 20/20 vision (Fig. 2).¹⁹

Nuclear cataracts tend to progress slowly. The refractive index of the lens changes as the nucleus progressively hardens, which usually results in increasing myopia.^20,21 In some patients this is accompanied by optical distortion, especially of distant images, while near vision remains unaffected. A nuclear cataract is best seen with the narrow-beam direct illumination employed by the slit-lamp, which reveals the color and generalized haze or opalescence of the nucleus. In the early stages, the two halves (cotyledons) of the embryonic nucleus remain visible (Fig. 3). Later the entire nucleus appears as a homogeneous mass in contrast to the cortex (Fig. 4). Retroillumination may show the “oil droplet” effect (Fig. 5). Sometimes one may notice crystals in the lens nucleus (known as a Christmas tree cataract; Fig. 6A and B).

Nuclear cataracts are associated with physiochemical changes in the lens structural proteins (α-, β-, and γ-crystallins). These proteins undergo oxidation, nonenzymatic glycosylation, proteolysis, deamidation, phosphorylation, and carbamylation, which lead to the aggregation and formation of high-molecular-weight proteins. It was recently proposed²² that α-crystallin may play a role as a molecular chaperon in preventing the aggregation of protein. These high-molecular-weight (>1,000 nm) protein aggregates interfere with light transmission and cause light scattering in nuclear cataracts. Chemical modification of the nuclear lens protein also leads to yellowing, followed by browning and, in advanced stages, blackening.²³ Whether these color changes are related to the cataract or are independent of it is still being debated and investigated. Recent studies have also suggested that phase separation inhibitors (PSIs) may play a role in maintaining a clear nucleus, and that the loss of these PSIs may lead to nuclear cataract formation.²⁴

The cortical cataract is often the most common subtype of opacity seen in African-derived populations.¹⁸ The cortical layer is approximately 2 mm thick anterior and posterior to the nucleus in adults, and its metabolically active new cortical fibers are continuously laid down by the bow region cells. The cortical layer is less compact than the nucleus and is therefore more prone to becoming overhydrated as the result of an electrolyte imbalance. This may eventually lead to disruption of the lens cortical fibers, as demonstrated in diabetes²⁵ (Fig. 7) and galactosemia.²⁶ It has therefore been proposed that this type of cataract may be partly caused by osmotic stress. Early changes may include signs such as vacuoles, water clefts, and lamellar separation (Fig. 8). These changes may come and go over time, but eventually they may lead to damage and irreversible opacification of some fibers. Recent studies have also suggested that an abnormality of the maturation process of the lens fibers may lead to subsequent poor development of the primary, secondary, and tertiary sutures, resulting in the formation of cortical cataracts.²⁷

Cortical opacities have been clinically observed to develop earliest in the inferior half of the lens, especially the lower nasal quadrant.²⁸ Epidemiologic²⁹ and laboratory studies³⁰ have suggested that cortical cataracts may be caused by ultraviolet rays from sunlight. The supraorbital margins may block the ultraviolet rays from falling over the upper part of the lens, thus making cortical cataract less frequent in the upper quadrants. Eventually these opacities also develop in the periphery in other quadrants, resulting in a circular array of spokes and peripheral cuneiform opacities (Fig. 9). Bands of central cortical fibers may become prominent and opacify centrally (Fig. 10). However, most cortical cataracts remain in the periphery for many years, even decades, before the central axis of the lens becomes involved, causing loss of vision late in the development of the cataract.

It has been observed that some individuals may have cortical opacities covering the entire anterior cortical and posterior cortical area (Fig. 11), and yet have 20/40 or better Snellen visual acuity under standard testing conditions. However, these patients may have severe disability glare such that under simulated bright lights their visual acuity may decrease to 20/80 or worse.³¹ They may also have decreased contrast sensitivity. These individuals tend to do well indoors but have difficulty driving during bright, sunny days, and at night because of oncoming headlights. Treatment in these cases must be decided on an individual basis, and surgery may be indicated when the expected benefits outweigh the surgical risks.

This type of cataract is best seen with retroillumination, which gives an enhanced picture of the cortical spokes and vacuoles by the shadows they cast as the light is reflected back by the fundus. Direct illumination helps clarify the level of the opacities (see discussion in the Posterior Subcapsular Cataract section below).

The PSC is the least prevalent subtype in most population-based studies.¹⁸ These cataracts often occur in combination with nuclear or cortical cataracts in the later stages. They are easily noticed on retroillumination because they are usually located centrally, and may interfere with funduscopy (Fig. 12). In early stages, patients usually complain of subjective symptoms such as glare disability³² and difficulty focusing on near objects. This is because when the pupil constricts during accommodation, the light entering the eye becomes concentrated centrally, where the PSC is also located. This causes light scattering and interferes with the ability of the eye to focus an image on the macula. In addition, these opacities lie at or near the nodal point of the eye, further interfering with focusing of the image on the macula.

One can examine this type of cataract with direct illumination, using the narrow and broad beams of the slit-lamp to show the characteristic granular inner surface immediately in front of the posterior capsule (Fig. 13). The problem with this technique, however, is that patients may not tolerate any prolonged direct illumination because of the glare. Retroillumination is therefore more useful for revealing the outline of the opacity, since it is usually seen as an “island” in the center of the posterior capsule, which is further highlighted by the shadow cast by the opacities.³³ However, in the early stages of this type of cataract, the dust-like particles that might be noticeable in the central posterior subcapsular area with direct illumination disappear or are difficult to see with retroillumination (Fig. 14). Eventually this “dusting” becomes dense enough to cast a shadow and thus appear on retroillumination. The smooth orange background of the fundus helps to highlight the rough, irregular pseudopodia-like edges of the central opacity. In advanced stages, the PSC may become a thick, calcified plaque (Fig. 15). During surgery, excessively vigorous scraping or vacuuming of the calcified opacity can lead to rupture of the posterior capsule. Usually, small remnants that are left behind after surgery are reabsorbed and do not interfere with vision; otherwise, they are easily treated with a neodymium : yttrium (Nd:YAG) aluminum garnet laser. Pathologic evidence suggests that most PSCs result from the migration of bow region cells into the potential space (along with accumulated cellular debris) between the posterior capsule and the cortex.^34,35,36

PSC may also result from irradiation or steroid ingestion, or it may be associated with diabetes, high myopia,^{37,38,39,40,41} retinal degeneration (e.g., retinitis pigmentosa),^42,43 and gyrate atrophy.^44,45 In some cases, the PSC eventually may be pushed to the cortex as new fibers are laid down and the offending agent is no longer present (Fig. 16A and B).

Sometimes more than one of the above-described varieties of cataract will occur together in a lens (Fig. 17). In general, a cataract will start as a pure type but eventually become mixed as the other lens regions become involved in the degenerative process.