- Email: [email protected]
Cataracts: When to Refer
TOPICAL REVIEW
Cataracts: When to Refer Noelle La Croix, DVM, Diplomate ACVO Unique stages of cataract development have been characterized in both human and animal lenses. These lens opacities impair visual acuity and are associated with inflammation. Total lens removal is typically followed by implantation of an artificial intraocular lens to restore vision. The success of this procedure is mainly dependent on the developmental stage of the cataract to be removed. This article reviews cataract development and provides the clinician with cataract referral criteria. © 2008 Elsevier Inc. All rights reserved. Keywords: cataract, canine, lens, phacoemulsification, uveitis
I
n the last 20 years veterinary cataract surgery has progressed from extracapsular cataract extraction to small incisional phacoemulsification. The earliest cataract surgeries were considered “salvage” procedures due to their high association with multiple complications.1 However, today’s success rates approach 90% in the postoperative period.2 Long-term success rates have been found to generally decrease with the developmental age of the cataract. Surgery is far more successful on immature cataracts then those in mature or hypermature stages.2,3 The animal lens is an inhomogeneous structure that supplements the light bending power of the cornea. Of the 60 diopters (D) of total refractive power of the canine eye, the lens provides 40 D.4 Loss of the canine lens results in extensive retinal image de-focusing to aphakic vision, estimated to 20/800 or poorer.5 This is the equivalent to a human unable to focus on the large “E” of the Snellen eye chart from 20 feet away. The lens has a higher refractive index than the aqueous fluid surrounding it. This causes incoming light to converge onto the retina. The spherical shape of the lens shortens its focal length, allowing the eye itself to remain anatomically small.6 The refractive index of the lens itself changes with depth, decreasing spherical aberration. Spherical aberrations in lenses can bend light to diverse focal points resulting in blurred imaging.7 The canine lens consists of approximately 22,000 layers of fibrous epithelia surrounded by a flexible membrane. Typical canine lenses are 0.5 g, 10 mm in diameter, and 7 mm thick.8 Overall lens transparency depends on its hydration, the lamellar arrangement of its fibers, and the solubility of its pro-
The Veterinary Medical Center of Long Island, West Islip, New York. Address reprint requests to Noelle La Croix, DVM, Diplomate ACVO, Veterinary Ophthalmologist, The Veterinary Medical Center of Long Island, 75 Sunrise Highway, West Islip, New York 11795. E-mail: [email protected]. © 2008 Elsevier Inc. All rights reserved. 1527-3369/06/0604-0171\.00/0 doi:10.1053/j.ctsap.2007.12.006
46
teins. Soluble transparent proteins (crystallins) are primarily responsible for the refractive power of the lens.9 The flexible epithelial basement membrane surrounding the lens is known as the lens capsule. This capsule is semipermeable, allowing small molecules in and out of the lens.10 Developmentally the lens grows like an onion. The embryonic nucleus forms first and subsequent layers grow outward throughout life. The active primordial cells generating these layers are located directly under the anterior lens capsule. Newly emergent cells move toward the lens equator, and then elongate, forming lens fibers which adjoin with their neighbors. As these fibers compress toward the center of the lens, their joints are loosened and their soluble proteins degenerate to an insoluble state.9 The center (or nucleus) of the aging lens will naturally become denser and less flexible. This hardening of the lens is known as nuclear sclerosis.11,12 The lens must be transparent to properly focus light. There are no blood vessels in the adult animal lens, and all metabolites are transported via the surrounding aqueous humor.13 Lens fibers derive the bulk of their energy from anaerobic glycolysis.14 Energy is used to pump both sodium out of and potassium into the lens, resulting in a relatively dehydrated state. The lens also actively pumps inositol (vitamin B8) and amino acids into the lens for protein synthesis.15
Cataracts A cataract is any opacification of the lens. Crystallins within lens fibers, or the lens fibers themselves, are disorganized within a cataract. Ultimately, crystallin disorder decreases transparency or light transmittance.9 Cortical cataracts are histologically associated with disordered, swollen, and ruptured lens fibers. These ruptured fibers are not normally repaired.16 In contrast, senile nuclear cataracts are characterized by disordered crystallins within dense but ordered fibers.9 Cataracts have many etiologies including genetic,17 metabolic, environmental, and senility factors.16 A major cause of cataracts in the canine is diabetes mellitus. The lens’ dependence on anaerobic glycolysis has its pitfalls. Cataracts form in 80% of canines within 18 months
47
Volume 23, Number 1, February 2008
Figure 1. Dense nuclear sclerosis with anterior cortical opacities in the left eye of a 15-year old Poodle. (Color version of figure is available online.)
of a diagnosis of diabetes.18 In the diabetic lens glucose saturates the hexokinase enzyme of anaerobic glycolysis. Aldose reductase forms the sugar alcohol sorbitol from the excess glucose. Sorbitol dehydrogenase can then also generate fructose within the lens. These products do not diffuse across the lens capsule, causing an osmotic imbalance and subsequent influx of water from the aqueous humor. This influx ruptures lens fibers and promotes cataract formation.19 An environmental factor in cataract development is oxidative damage, caused by O2 free radicals, peroxide, and ultraviolet radiation.20 In fact, the most recent cataract-dissolving medications were designed to introduce free radical acceptors into the aqueous humor, with the goal of reversing oxidative damage. However, the effectiveness of these drops has not been established.21 Once lens fibers have been ruptured forming cataracts, they probably cannot be reformed. These cataracts (ruptured lens fibers) can only be removed by phacoemulsification.16 The advanced stages of nuclear sclerosis can be associated with cataracts in the aging canine. Nuclear sclerosis itself does not typically substantially affect vision13 except in extreme cases.22 Both cortical and capsular opacifications have been described. In the extremely aged canine, nuclear sclerosis can lead directly to the formation of nuclear cataracts16 (Fig. 1).
Uveitis is ideally diagnosed via slit-lamp biomicroscopy.27 Inflammatory cells and protein will be present within the anterior chamber. Studies using fluorophotometry,28 laser flaremetry,29 and IOP30 have determined that all stages of cataract development are associated with evidence of phacolytic uveitis. This inflammation can be controlled with longterm topical steroids (1% prednisolone acetate or 0.1% dexamethasone).31 Measuring IOP is also critical in evaluating phacolytic uveitis’ progression.30 Another form of inflammation associated with cataract development is phacoclastic uveitis.26 Phacoclastic uveitis arises secondarily to traumatic rupture of the lens capsule. Many canine capsular ruptures are the result of corneal and lens scratches (“cat scratches”).32 The swelling associated with diabetic (intumescent) cataracts can also rupture the capsule.33 Phacoclastic uveitis is histologically characterized by numerous lymphocytes and prominent fibroplasia.34 This inflammation is unresponsive to medical management and will result in glaucoma, pain, and loss of vision. 26,32
Stages and Referral Cataracts can be classified by etiology, age of onset, location, appearance, and stage of progression. The stage of progression is the most widely used and useful classification.16 The most common progression stages are incipient, immature, mature, and hypermature. Incipient cataracts are the earliest to appreciate clinically and usually take up no more then 10 to 15% of lens volume8 (Fig. 2). Patients with incipient cataracts are ideal for referral to an ophthalmologist. Incipient cataract progression is dependent on both position and appearance, as evaluated by slit-lamp biomicroscopy. Incipient cataracts also allow for a clear view of the fundus for diagnosis of retinal and vitreal disease without ultrasonography. Referral is particularly useful to breed-
Inflammation Cataracts are associated with inflammation known as phacolytic uveitis.23 A small amount of crystallins normally pass out of the lens and are thought to induce T-cell tolerance.24 However, cataractous lenses exude large amounts of crystallins, overwhelming tolerance and inducing an immune response. This response is appreciated as conjunctival hyperemia, scleral injection, aqueous flare, corneal edema, decreased intraocular pressure (IOP), fibrin deposition, hypopyon, iridal swelling, keratic precipitation, miosis, and posterior synechiae.25 Uncontrolled inflammation causes and can lead to secondary glaucoma.26
Figure 2. A posterior subcapsular cortical cataract in the left eye of a 1.5-year-old Golden Retriever. This incipient cataract has a genetic basis and is associated with phacolytic uveitis causing hyperpigmentation of the iris. Developmental progression is expected. (Color version of figure is available online.)
48
Figure 3. An anterior capsular plaque in the left eye of a 6-year old bulldog. This incipient cataract does not have a genetic basis and should not developmentally progress. (Color version of figure is available online.)
Topics in Companion Animal Medicine
Figure 5. A mature intumescent cataract in the right eye of a 12-year-old diabetic American Eskimo dog. Intraocular pressure was 65 mm Hg, and therefore, the eye was not a candidate for cataract surgery. (Color version of figure is available online.)
ers in determining if an incipient cataract has a genetic basis.35 Nongenetic incipient cataracts are often appreciated as plaques or scars on the lens capsule (Fig. 3). Incipient cataracts can also be secondary to other ocular and systemic diseases.16,18,36-43 Control of primary disease can sometimes halt cataract progression and preserve vision. Not all incipient cataracts progress. Generally, congenital incipient cataracts within the lens nucleus will not progress.44 In most cases, nonprogressive incipient canine cataracts do not require surgical removal as they do not limit functional vision.8 Incipient cataracts near the active proliferative lens equator10 will often progress. In these cases, anti-inflammatory medications can help prevent phacolytic uveitis. The eye has only a limited ability to stop inflammation once it has started using a prostaglandin deactivating enzyme, PG 15dehydrogenase.45 Cataract surgery is most successful on eyes without a clinical history of phacolytic uveitis.46 The immature cataract is at the ideal stage for cataract surgery.8 Immature cataracts are characterized by low den-
sity areas, with clear lens fibers, that allow for tapetal reflection through the lens. Immature cataracts are often swollen with fluid, forming large separation clefts within the lens13 (Fig. 4). These clefts can be used as areas for lens fracture during cataract surgery.47 However, extreme swelling can result in intumescence. Intumescent lenses are associated with glaucoma, and the loss of vision via pupillary blockage and ciliary cleft closure33 (Fig. 5). Severe uveitis is also associated with intumescent lenses which leak large amounts of proteins into the aqueous humor.22 Mature cataracts typically involve the entire lens, completely obscuring tapetal reflection (Fig. 6). These advanced cataracts can be associated with uveitis, capsular plaques, and lens instability.48 Increased intraoperative and postoperative complications and decreased visual outcome are associated with mature cataract surgery.3 The lens fibers of mature cataracts continue to break down and release lens proteins. Over time, phacolytic uveitis progresses, and the
Figure 4. An immature cataract in the right eye of a 6-yearold diabetic Pug. There is prominent brown pigmentation of the medial cornea, and no associated clinical inflammation.
Figure 6. A mature cataract in the left eye of a 12-year-old diabetic American Eskimo dog. (Color version of figure is available online.)
49
Volume 23, Number 1, February 2008
Figure 7. A hypermature cataract in the left eye of a 4-yearold Boston terrier. There are multiple hyperreflective pinpoint opacities present in the lens (a hallmark of hypermaturity). The multifocal lines in the upper half of the cornea represent flash artifacts. (Color version of figure is available online.)
lens capsule wrinkles from epithelial cell proliferation and shrinkage of the lens volume.16 A hypermature cataract has a wrinkled lens capsule with a swollen milky cortex (Fig. 7). This is the result of autolysis of the lens fibers of a mature cataract.49 During cataract surgery, distorted capsules predispose them to tearing and may prevent the implantation of artificial lenses.8 In addition, some mature and hypermature cataracts are not candidates for surgery because advanced phacolytic uveitis has already caused glaucoma, retinal detachment, and/or retinal degeneration.46,50
disposing conditions (diabetes, liver or kidney disease, elevated blood pressure, etc) must be managed before cataract surgery. Infections (skin, oral, and bladder) should be resolved before cataract surgery to decrease the risk of postoperative endophthalmitis.53 Ocular and systemic issues can often be managed in tandem. Ocular issues, like phacolytic uveitis, should be stabilized before cataract surgery to achieve the best possible visual outcomes. After an initial examination, a veterinary ophthalmologist will perform two procedures to determine if an eye is a candidate for cataract surgery. The first is an electroretinogram, which displays the electrical signal produced by a retina in response to light stimuli.54 The electroretinogram helps determine if a retina is functional.55 The second procedure is ocular ultrasonography that determines the position and attachment state of a retina.50 The most successful cataract surgeries are performed on lenses within the earliest stages of cataract development. The rates of cataract postsurgical complications increase with cataract maturation.8 Ocular conditions associated with mature and hypermature cataracts often eliminate surgical options altogether.46 Postoperative care following cataract surgery is also demanding.13 Owner and patient compliance with the large and precise regimen of medications should be considered before surgery. Cataract surgery is considered an elective procedure as most animals will adapt to visual losses. However, conditions associated with cataracts (uveitis, lens luxation, glaucoma, etc) that affect an animal’s quality of life should always be addressed.47
References Veterinary Cataracts Humans typically present in earlier stages of cataracts than dogs. Human eyes contain an extremely dense area of cones (the macula and fovea) for sharp central vision.51 Any small opacity in the lens overlying this area is associated with a dramatic change in functional vision, quickly vocalized to an attending physician.52 In contrast, dogs contain a less dense area known as the “visual streak” and have an appreciably lower visual acuity than humans. If the typical human eye scores 20/20 on the Snellen eye chart, the typical canine eye would score 20/75.5 Anything below the third line of the Snellen chart would be a blur to a dog. Therefore, typical domesticated dogs do not depend on fine visual acuity to survive and will not usually show visual dysfunction with early stage cataracts. Some working or active dogs may show visual deficits with early-stage cataracts. In the veterinary world cataracts typically present in later stages, when first appreciated by owners.13 Ideally, incipient cataracts are managed medically for phacolytic uveitis. Immature and mature cataracts can often be removed with phacoemulsification. Other ocular issues must be addressed including the control of phacolytic uveitis, IOP, and tear production. As with all anesthetic surgical procedures, pre-
1. Rooks RL, Brightman AH, Musselman EE, et al: Extracapsular cataract extraction: an analysis of 240 operations in dogs. J Am Vet Med Assoc 187:1013-1015, 1985 2. Sigle KJ, Nasisse MP: Long-term complications after phacoemulsification for cataract removal in dogs: 172 cases (19952002). J Am Vet Med Assoc 228:74-79, 2006 3. Biros DJ, Gelatt KN, Brooks DE, et al: Development of glaucoma after cataract surgery in dogs: 220 cases (1987-1998). J Am Vet Med Assoc 216:1780-1786, 2000 4. Davidson MG, Murphy CJ, Nasisse MP, et al: Refractive state of aphakic and pseudophakic eyes of dogs. Am J Vet Res 54: 174-177, 1993 5. Miller PE, Murphy CJ: Vision in dogs. J Am Vet Med Assoc 207:1623-1634, 1995 6. Land MF, Nilsson DE: Aquatic eyes: the evolution of the lens, in Land MF, Nilsson DE (eds): Animal Eyes. New York, NY, Oxford University Press, 2002, pp 56-71 7. Jagger WS: The optics of the spherical fish lens. Vision Res 32:1271-1284, 1992 8. Adkins EA, Hendrix DV: Cataract evaluation and treatment in dogs. Comp Cont Educ Pract Vet 25:812-825, 2003 9. Beebe DC: The lens, in Kaufman PL, Alm A (eds): Adler’s Physiology of the Eye (ed 10). St Louis, MO, Mosby, Inc., 2003, pp 117-158 10. Samuelson DA: Ophthalmic anatomy, in Gelatt KN (ed): Vet-
50
11. 12.
13. 14.
15.
16.
17.
18.
19.
20. 21.
22. 23.
24.
25. 26. 27.
28.
29.
30.
31. 32.
33.
Topics in Companion Animal Medicine erinary Ophthalmology, vol 1 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 37-148 Giresi JC: Cataracts: how to uncover the imposter lenticular sclerosis. DVM News Mag 36:10S-13S, 2005 Tobias G, Tobias TA, Abood SK: Estimating age in dogs and cats using ocular lens examination. Comp Cont Educ Pract Vet 22:1085-1091, 2000 Dziezyc J, Brooks DE: Canine cataracts. Comp Cont Educ Pract Vet 5:81-90, 1983 Winkler BS, Riley MV: Relative contributions of epithelial cells and fibers to rabbit lens ATP content and glycolysis. Invest Ophthalmol Vis Sci 32:2593-2598, 1991 Gum GG, Gelatt KN, Esson DW: Physiology of the eye, in Gelatt KN (ed): Veterinary Ophthalmology, vol 1 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 149-182 Davidson MG, Nelms SR: Diseases of the canine lens and cataract formation, in Gelatt KN (ed): Veterinary Ophthalmology, vol 2 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 859-887 Gelatt KN, Mackay EO: Prevalence of primary breed-related cataracts in the dog in North America. Vet Ophthalmol 8:101111, 2005 Beam S, Correa MT, Davidson MG: A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases. Vet Ophthalmol 2:169-172, 1999 Basher AW, Roberts SM: Ocular manifestations of diabetes mellitus: diabetic cataracts in dogs. Vet Clin North Am Small Anim Pract 25:661-676, 1995 Williams DL: Oxidation, antioxidants and cataract formation: a literature review. Vet Ophthalmol 9:292-298, 2006 Williams DL, Munday P: The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Vet Ophthalmol 9:311-316, 2006 Ramsey DT: Cataracts: which and when to refer. Proc North Am Vet Conf 16:21-29, 2002 van der Woerdt A, Nasisse MP, Davidson MG: Lens-induced uveitis in dogs: 151 cases (1985-1990). J Am Vet Med Assoc 201:921-926, 1992 Denis HM, Brooks DE, Alleman AR, et al: Detection of antilens crystallin antibody in dogs with and without cataracts. Vet Ophthalmol 6:321-327, 2003 Gilger BC: Clinical syndromes in canine and feline uveitis. Proc Waltham/OSU Symp Small Anim Ophthalmol 25:84-89, 2001 van der Woerdt A: Lens-induced uveitis. Vet Ophthalmol 3:227-234, 2000 Berliner ML: Technique of biomicroscopy, in Berliner ML (ed): Biomicroscopy of the Eye, vol 1. New York, NY, Paul B. Hoeber, 1943, pp 64-123 Dziezyc J, Millichamp NJ, Smith WB: Fluorescein concentrations in the aqueous of dogs with cataracts. Vet Comp Ophthalmol 7:267-270, 1997 Krohne SG, Krohne DT, Lindley DM, et al: Use of laser flaremetry to measure aqueous humor protein concentration in dogs. J Am Vet Med Assoc 206:1167-1172, 1995 Leasure J, Gelatt KN, MacKay EO: The relationship of cataract maturity to intraocular pressure in dogs. Vet Ophthalmol 4:273-276, 2001 Wilkie DA: Control of ocular inflammation. Vet Clin North Am Small Anim Pract 20:693-713, 1990 Davidson MG, Nasisse MP, Jamieson VE, et al: Traumatic anterior lens capsule disruption. J Am Anim Hosp Assoc 27: 410-414, 1991 Wilkie DA, Gemensky-Metzler AJ, Colitz CM, et al: Canine
34. 35. 36.
37. 38. 39. 40. 41.
42.
43.
44. 45.
46.
47.
48.
49. 50.
51.
52.
53.
54.
55.
cataracts, diabetes mellitus and spontaneous lens capsule rupture: a retrospective study of 18 dogs. Vet Ophthalmol 9:328-334, 2006 Wilcock BP, Peiffer RL Jr: The pathology of lens-induced uveitis in dogs. Vet Pathol 24:549-553, 1987 Gelatt KN, Das ND: Animal models for inherited cataracts: a review. Curr Eye Res 3:765-778, 1984 da Costa PD, Merideth RE, Sigler RL: Cataracts in dogs after long-term ketoconazole therapy. Vet Comp Ophthalmol 6:176-180, 1996 Sapienza JS, Simo FJ, Prades-Sapienza A: Golden Retriever uveitis: 75 cases (1994-1999). Vet Ophthalmol 3:241-246, 2000 Gionfriddo JR: A challenging case: an unusual cause of blindness in a Siberian husky. Vet Med 102:172-178, 2007 Grahn B, Wolfer J: Diagnostic ophthalmology. Retinal degeneration and cataracts. 36:722-723, 1995 Kornegay JN, Green CE, Martin C, et al: Idiopathic hypocalcemia in four dogs. J Am Anim Hosp Assoc 16:723-734, 1980 Bassett JR: Hypocalcemia and hyperphosphatemia due to primary hypoparathyroidism in a six-month-old kitten. J Am Anim Hosp Assoc 34:503-507, 1998 Blocker T, van der Woerdt A: What is your diagnosis? Cataract, retinal detachment, and a large mass protruding into the vitreous cavity. 217:23-24, 2000 Ching SV, Gillette SM, Powers BE, et al: Radiation-induced ocular injury in the dog: a histological study. Int J Radiat Oncol Biol Phys 19:321-328, 1990 Grahn BH, Storey E, Cullen CL: Diagnostic ophthalmology. Bilateral incipient nuclear cataracts. 44:603-604, 2003 Wilkie DA: The background of ocular prostaglandins and their role in ophthalmic physiology and pathology. Proc Am Coll Vet Ophthalmol 20:3-12, 1989 Paulsen ME, Lavach JD, Severin GA, et al: The effect of lensinduced uveitis on the success of extracapsular cataract extraction: a retrospective study of 65 lens removals in the dog. J Am Anim Hosp Assoc 22:49-56, 1986 Wilkie DA, Colitz CM: Surgery of the canine lens, in Gelatt KN (ed): Veterinary Ophthalmology, vol 2 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 888-931 Bernays ME, Peiffer RL: Morphologic alterations in the anterior lens capsule of canine eyes with cataracts. Am J Vet Res 61:1517-1519, 2000 Fischer CA: Geriatric ophthalmology. Vet Clin North Am Small Anim Pract 19:103-123, 1989 van der Woerdt A, Wilkie DA, Myer CW: Ultrasonographic abnormalities in the eyes of dogs with cataracts: 147 cases (1986-1992). J Am Vet Med Assoc 203:838-841, 1993 Miller D: Physiologic optics and refraction, in Kaufman PL, Albert A (eds): Adler’s Physiology of the Eye (ed 10). St. Louis, MO, Mosby, Inc., 2003, pp 161-194 Jaffee NE, Jaffee MS, Jaffee GF: The decision to operate, in Jaffee NE, Jaffee MS, Jaffee GF (eds): Cataract Surgery and Its Complications (ed 6). St. Louis, MO, Mosby-Year Book, Inc., 1997, pp 2-17 Taylor MM, Kern TJ, Riis RC, et al: Intraocular bacterial contamination during cataract surgery in dogs. J Am Vet Med Assoc 206:1716-1720, 1995 Komaromy AM, Smith PJ, Brooks DE: Electroretinography in dogs and cats. Part I. Retinal morphology and physiology. 20: 343-350, 1998 Rubin LF: Clinical electroretinography in dogs. J Am Vet Med Assoc 151:1456-1469, 1967
Cataracts: When to Refer Noelle La Croix, DVM, Diplomate ACVO Unique stages of cataract development have been characterized in both human and animal lenses. These lens opacities impair visual acuity and are associated with inflammation. Total lens removal is typically followed by implantation of an artificial intraocular lens to restore vision. The success of this procedure is mainly dependent on the developmental stage of the cataract to be removed. This article reviews cataract development and provides the clinician with cataract referral criteria. © 2008 Elsevier Inc. All rights reserved. Keywords: cataract, canine, lens, phacoemulsification, uveitis
I
n the last 20 years veterinary cataract surgery has progressed from extracapsular cataract extraction to small incisional phacoemulsification. The earliest cataract surgeries were considered “salvage” procedures due to their high association with multiple complications.1 However, today’s success rates approach 90% in the postoperative period.2 Long-term success rates have been found to generally decrease with the developmental age of the cataract. Surgery is far more successful on immature cataracts then those in mature or hypermature stages.2,3 The animal lens is an inhomogeneous structure that supplements the light bending power of the cornea. Of the 60 diopters (D) of total refractive power of the canine eye, the lens provides 40 D.4 Loss of the canine lens results in extensive retinal image de-focusing to aphakic vision, estimated to 20/800 or poorer.5 This is the equivalent to a human unable to focus on the large “E” of the Snellen eye chart from 20 feet away. The lens has a higher refractive index than the aqueous fluid surrounding it. This causes incoming light to converge onto the retina. The spherical shape of the lens shortens its focal length, allowing the eye itself to remain anatomically small.6 The refractive index of the lens itself changes with depth, decreasing spherical aberration. Spherical aberrations in lenses can bend light to diverse focal points resulting in blurred imaging.7 The canine lens consists of approximately 22,000 layers of fibrous epithelia surrounded by a flexible membrane. Typical canine lenses are 0.5 g, 10 mm in diameter, and 7 mm thick.8 Overall lens transparency depends on its hydration, the lamellar arrangement of its fibers, and the solubility of its pro-
The Veterinary Medical Center of Long Island, West Islip, New York. Address reprint requests to Noelle La Croix, DVM, Diplomate ACVO, Veterinary Ophthalmologist, The Veterinary Medical Center of Long Island, 75 Sunrise Highway, West Islip, New York 11795. E-mail: [email protected]. © 2008 Elsevier Inc. All rights reserved. 1527-3369/06/0604-0171\.00/0 doi:10.1053/j.ctsap.2007.12.006
46
teins. Soluble transparent proteins (crystallins) are primarily responsible for the refractive power of the lens.9 The flexible epithelial basement membrane surrounding the lens is known as the lens capsule. This capsule is semipermeable, allowing small molecules in and out of the lens.10 Developmentally the lens grows like an onion. The embryonic nucleus forms first and subsequent layers grow outward throughout life. The active primordial cells generating these layers are located directly under the anterior lens capsule. Newly emergent cells move toward the lens equator, and then elongate, forming lens fibers which adjoin with their neighbors. As these fibers compress toward the center of the lens, their joints are loosened and their soluble proteins degenerate to an insoluble state.9 The center (or nucleus) of the aging lens will naturally become denser and less flexible. This hardening of the lens is known as nuclear sclerosis.11,12 The lens must be transparent to properly focus light. There are no blood vessels in the adult animal lens, and all metabolites are transported via the surrounding aqueous humor.13 Lens fibers derive the bulk of their energy from anaerobic glycolysis.14 Energy is used to pump both sodium out of and potassium into the lens, resulting in a relatively dehydrated state. The lens also actively pumps inositol (vitamin B8) and amino acids into the lens for protein synthesis.15
Cataracts A cataract is any opacification of the lens. Crystallins within lens fibers, or the lens fibers themselves, are disorganized within a cataract. Ultimately, crystallin disorder decreases transparency or light transmittance.9 Cortical cataracts are histologically associated with disordered, swollen, and ruptured lens fibers. These ruptured fibers are not normally repaired.16 In contrast, senile nuclear cataracts are characterized by disordered crystallins within dense but ordered fibers.9 Cataracts have many etiologies including genetic,17 metabolic, environmental, and senility factors.16 A major cause of cataracts in the canine is diabetes mellitus. The lens’ dependence on anaerobic glycolysis has its pitfalls. Cataracts form in 80% of canines within 18 months
47
Volume 23, Number 1, February 2008
Figure 1. Dense nuclear sclerosis with anterior cortical opacities in the left eye of a 15-year old Poodle. (Color version of figure is available online.)
of a diagnosis of diabetes.18 In the diabetic lens glucose saturates the hexokinase enzyme of anaerobic glycolysis. Aldose reductase forms the sugar alcohol sorbitol from the excess glucose. Sorbitol dehydrogenase can then also generate fructose within the lens. These products do not diffuse across the lens capsule, causing an osmotic imbalance and subsequent influx of water from the aqueous humor. This influx ruptures lens fibers and promotes cataract formation.19 An environmental factor in cataract development is oxidative damage, caused by O2 free radicals, peroxide, and ultraviolet radiation.20 In fact, the most recent cataract-dissolving medications were designed to introduce free radical acceptors into the aqueous humor, with the goal of reversing oxidative damage. However, the effectiveness of these drops has not been established.21 Once lens fibers have been ruptured forming cataracts, they probably cannot be reformed. These cataracts (ruptured lens fibers) can only be removed by phacoemulsification.16 The advanced stages of nuclear sclerosis can be associated with cataracts in the aging canine. Nuclear sclerosis itself does not typically substantially affect vision13 except in extreme cases.22 Both cortical and capsular opacifications have been described. In the extremely aged canine, nuclear sclerosis can lead directly to the formation of nuclear cataracts16 (Fig. 1).
Uveitis is ideally diagnosed via slit-lamp biomicroscopy.27 Inflammatory cells and protein will be present within the anterior chamber. Studies using fluorophotometry,28 laser flaremetry,29 and IOP30 have determined that all stages of cataract development are associated with evidence of phacolytic uveitis. This inflammation can be controlled with longterm topical steroids (1% prednisolone acetate or 0.1% dexamethasone).31 Measuring IOP is also critical in evaluating phacolytic uveitis’ progression.30 Another form of inflammation associated with cataract development is phacoclastic uveitis.26 Phacoclastic uveitis arises secondarily to traumatic rupture of the lens capsule. Many canine capsular ruptures are the result of corneal and lens scratches (“cat scratches”).32 The swelling associated with diabetic (intumescent) cataracts can also rupture the capsule.33 Phacoclastic uveitis is histologically characterized by numerous lymphocytes and prominent fibroplasia.34 This inflammation is unresponsive to medical management and will result in glaucoma, pain, and loss of vision. 26,32
Stages and Referral Cataracts can be classified by etiology, age of onset, location, appearance, and stage of progression. The stage of progression is the most widely used and useful classification.16 The most common progression stages are incipient, immature, mature, and hypermature. Incipient cataracts are the earliest to appreciate clinically and usually take up no more then 10 to 15% of lens volume8 (Fig. 2). Patients with incipient cataracts are ideal for referral to an ophthalmologist. Incipient cataract progression is dependent on both position and appearance, as evaluated by slit-lamp biomicroscopy. Incipient cataracts also allow for a clear view of the fundus for diagnosis of retinal and vitreal disease without ultrasonography. Referral is particularly useful to breed-
Inflammation Cataracts are associated with inflammation known as phacolytic uveitis.23 A small amount of crystallins normally pass out of the lens and are thought to induce T-cell tolerance.24 However, cataractous lenses exude large amounts of crystallins, overwhelming tolerance and inducing an immune response. This response is appreciated as conjunctival hyperemia, scleral injection, aqueous flare, corneal edema, decreased intraocular pressure (IOP), fibrin deposition, hypopyon, iridal swelling, keratic precipitation, miosis, and posterior synechiae.25 Uncontrolled inflammation causes and can lead to secondary glaucoma.26
Figure 2. A posterior subcapsular cortical cataract in the left eye of a 1.5-year-old Golden Retriever. This incipient cataract has a genetic basis and is associated with phacolytic uveitis causing hyperpigmentation of the iris. Developmental progression is expected. (Color version of figure is available online.)
48
Figure 3. An anterior capsular plaque in the left eye of a 6-year old bulldog. This incipient cataract does not have a genetic basis and should not developmentally progress. (Color version of figure is available online.)
Topics in Companion Animal Medicine
Figure 5. A mature intumescent cataract in the right eye of a 12-year-old diabetic American Eskimo dog. Intraocular pressure was 65 mm Hg, and therefore, the eye was not a candidate for cataract surgery. (Color version of figure is available online.)
ers in determining if an incipient cataract has a genetic basis.35 Nongenetic incipient cataracts are often appreciated as plaques or scars on the lens capsule (Fig. 3). Incipient cataracts can also be secondary to other ocular and systemic diseases.16,18,36-43 Control of primary disease can sometimes halt cataract progression and preserve vision. Not all incipient cataracts progress. Generally, congenital incipient cataracts within the lens nucleus will not progress.44 In most cases, nonprogressive incipient canine cataracts do not require surgical removal as they do not limit functional vision.8 Incipient cataracts near the active proliferative lens equator10 will often progress. In these cases, anti-inflammatory medications can help prevent phacolytic uveitis. The eye has only a limited ability to stop inflammation once it has started using a prostaglandin deactivating enzyme, PG 15dehydrogenase.45 Cataract surgery is most successful on eyes without a clinical history of phacolytic uveitis.46 The immature cataract is at the ideal stage for cataract surgery.8 Immature cataracts are characterized by low den-
sity areas, with clear lens fibers, that allow for tapetal reflection through the lens. Immature cataracts are often swollen with fluid, forming large separation clefts within the lens13 (Fig. 4). These clefts can be used as areas for lens fracture during cataract surgery.47 However, extreme swelling can result in intumescence. Intumescent lenses are associated with glaucoma, and the loss of vision via pupillary blockage and ciliary cleft closure33 (Fig. 5). Severe uveitis is also associated with intumescent lenses which leak large amounts of proteins into the aqueous humor.22 Mature cataracts typically involve the entire lens, completely obscuring tapetal reflection (Fig. 6). These advanced cataracts can be associated with uveitis, capsular plaques, and lens instability.48 Increased intraoperative and postoperative complications and decreased visual outcome are associated with mature cataract surgery.3 The lens fibers of mature cataracts continue to break down and release lens proteins. Over time, phacolytic uveitis progresses, and the
Figure 4. An immature cataract in the right eye of a 6-yearold diabetic Pug. There is prominent brown pigmentation of the medial cornea, and no associated clinical inflammation.
Figure 6. A mature cataract in the left eye of a 12-year-old diabetic American Eskimo dog. (Color version of figure is available online.)
49
Volume 23, Number 1, February 2008
Figure 7. A hypermature cataract in the left eye of a 4-yearold Boston terrier. There are multiple hyperreflective pinpoint opacities present in the lens (a hallmark of hypermaturity). The multifocal lines in the upper half of the cornea represent flash artifacts. (Color version of figure is available online.)
lens capsule wrinkles from epithelial cell proliferation and shrinkage of the lens volume.16 A hypermature cataract has a wrinkled lens capsule with a swollen milky cortex (Fig. 7). This is the result of autolysis of the lens fibers of a mature cataract.49 During cataract surgery, distorted capsules predispose them to tearing and may prevent the implantation of artificial lenses.8 In addition, some mature and hypermature cataracts are not candidates for surgery because advanced phacolytic uveitis has already caused glaucoma, retinal detachment, and/or retinal degeneration.46,50
disposing conditions (diabetes, liver or kidney disease, elevated blood pressure, etc) must be managed before cataract surgery. Infections (skin, oral, and bladder) should be resolved before cataract surgery to decrease the risk of postoperative endophthalmitis.53 Ocular and systemic issues can often be managed in tandem. Ocular issues, like phacolytic uveitis, should be stabilized before cataract surgery to achieve the best possible visual outcomes. After an initial examination, a veterinary ophthalmologist will perform two procedures to determine if an eye is a candidate for cataract surgery. The first is an electroretinogram, which displays the electrical signal produced by a retina in response to light stimuli.54 The electroretinogram helps determine if a retina is functional.55 The second procedure is ocular ultrasonography that determines the position and attachment state of a retina.50 The most successful cataract surgeries are performed on lenses within the earliest stages of cataract development. The rates of cataract postsurgical complications increase with cataract maturation.8 Ocular conditions associated with mature and hypermature cataracts often eliminate surgical options altogether.46 Postoperative care following cataract surgery is also demanding.13 Owner and patient compliance with the large and precise regimen of medications should be considered before surgery. Cataract surgery is considered an elective procedure as most animals will adapt to visual losses. However, conditions associated with cataracts (uveitis, lens luxation, glaucoma, etc) that affect an animal’s quality of life should always be addressed.47
References Veterinary Cataracts Humans typically present in earlier stages of cataracts than dogs. Human eyes contain an extremely dense area of cones (the macula and fovea) for sharp central vision.51 Any small opacity in the lens overlying this area is associated with a dramatic change in functional vision, quickly vocalized to an attending physician.52 In contrast, dogs contain a less dense area known as the “visual streak” and have an appreciably lower visual acuity than humans. If the typical human eye scores 20/20 on the Snellen eye chart, the typical canine eye would score 20/75.5 Anything below the third line of the Snellen chart would be a blur to a dog. Therefore, typical domesticated dogs do not depend on fine visual acuity to survive and will not usually show visual dysfunction with early stage cataracts. Some working or active dogs may show visual deficits with early-stage cataracts. In the veterinary world cataracts typically present in later stages, when first appreciated by owners.13 Ideally, incipient cataracts are managed medically for phacolytic uveitis. Immature and mature cataracts can often be removed with phacoemulsification. Other ocular issues must be addressed including the control of phacolytic uveitis, IOP, and tear production. As with all anesthetic surgical procedures, pre-
1. Rooks RL, Brightman AH, Musselman EE, et al: Extracapsular cataract extraction: an analysis of 240 operations in dogs. J Am Vet Med Assoc 187:1013-1015, 1985 2. Sigle KJ, Nasisse MP: Long-term complications after phacoemulsification for cataract removal in dogs: 172 cases (19952002). J Am Vet Med Assoc 228:74-79, 2006 3. Biros DJ, Gelatt KN, Brooks DE, et al: Development of glaucoma after cataract surgery in dogs: 220 cases (1987-1998). J Am Vet Med Assoc 216:1780-1786, 2000 4. Davidson MG, Murphy CJ, Nasisse MP, et al: Refractive state of aphakic and pseudophakic eyes of dogs. Am J Vet Res 54: 174-177, 1993 5. Miller PE, Murphy CJ: Vision in dogs. J Am Vet Med Assoc 207:1623-1634, 1995 6. Land MF, Nilsson DE: Aquatic eyes: the evolution of the lens, in Land MF, Nilsson DE (eds): Animal Eyes. New York, NY, Oxford University Press, 2002, pp 56-71 7. Jagger WS: The optics of the spherical fish lens. Vision Res 32:1271-1284, 1992 8. Adkins EA, Hendrix DV: Cataract evaluation and treatment in dogs. Comp Cont Educ Pract Vet 25:812-825, 2003 9. Beebe DC: The lens, in Kaufman PL, Alm A (eds): Adler’s Physiology of the Eye (ed 10). St Louis, MO, Mosby, Inc., 2003, pp 117-158 10. Samuelson DA: Ophthalmic anatomy, in Gelatt KN (ed): Vet-
50
11. 12.
13. 14.
15.
16.
17.
18.
19.
20. 21.
22. 23.
24.
25. 26. 27.
28.
29.
30.
31. 32.
33.
Topics in Companion Animal Medicine erinary Ophthalmology, vol 1 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 37-148 Giresi JC: Cataracts: how to uncover the imposter lenticular sclerosis. DVM News Mag 36:10S-13S, 2005 Tobias G, Tobias TA, Abood SK: Estimating age in dogs and cats using ocular lens examination. Comp Cont Educ Pract Vet 22:1085-1091, 2000 Dziezyc J, Brooks DE: Canine cataracts. Comp Cont Educ Pract Vet 5:81-90, 1983 Winkler BS, Riley MV: Relative contributions of epithelial cells and fibers to rabbit lens ATP content and glycolysis. Invest Ophthalmol Vis Sci 32:2593-2598, 1991 Gum GG, Gelatt KN, Esson DW: Physiology of the eye, in Gelatt KN (ed): Veterinary Ophthalmology, vol 1 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 149-182 Davidson MG, Nelms SR: Diseases of the canine lens and cataract formation, in Gelatt KN (ed): Veterinary Ophthalmology, vol 2 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 859-887 Gelatt KN, Mackay EO: Prevalence of primary breed-related cataracts in the dog in North America. Vet Ophthalmol 8:101111, 2005 Beam S, Correa MT, Davidson MG: A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases. Vet Ophthalmol 2:169-172, 1999 Basher AW, Roberts SM: Ocular manifestations of diabetes mellitus: diabetic cataracts in dogs. Vet Clin North Am Small Anim Pract 25:661-676, 1995 Williams DL: Oxidation, antioxidants and cataract formation: a literature review. Vet Ophthalmol 9:292-298, 2006 Williams DL, Munday P: The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Vet Ophthalmol 9:311-316, 2006 Ramsey DT: Cataracts: which and when to refer. Proc North Am Vet Conf 16:21-29, 2002 van der Woerdt A, Nasisse MP, Davidson MG: Lens-induced uveitis in dogs: 151 cases (1985-1990). J Am Vet Med Assoc 201:921-926, 1992 Denis HM, Brooks DE, Alleman AR, et al: Detection of antilens crystallin antibody in dogs with and without cataracts. Vet Ophthalmol 6:321-327, 2003 Gilger BC: Clinical syndromes in canine and feline uveitis. Proc Waltham/OSU Symp Small Anim Ophthalmol 25:84-89, 2001 van der Woerdt A: Lens-induced uveitis. Vet Ophthalmol 3:227-234, 2000 Berliner ML: Technique of biomicroscopy, in Berliner ML (ed): Biomicroscopy of the Eye, vol 1. New York, NY, Paul B. Hoeber, 1943, pp 64-123 Dziezyc J, Millichamp NJ, Smith WB: Fluorescein concentrations in the aqueous of dogs with cataracts. Vet Comp Ophthalmol 7:267-270, 1997 Krohne SG, Krohne DT, Lindley DM, et al: Use of laser flaremetry to measure aqueous humor protein concentration in dogs. J Am Vet Med Assoc 206:1167-1172, 1995 Leasure J, Gelatt KN, MacKay EO: The relationship of cataract maturity to intraocular pressure in dogs. Vet Ophthalmol 4:273-276, 2001 Wilkie DA: Control of ocular inflammation. Vet Clin North Am Small Anim Pract 20:693-713, 1990 Davidson MG, Nasisse MP, Jamieson VE, et al: Traumatic anterior lens capsule disruption. J Am Anim Hosp Assoc 27: 410-414, 1991 Wilkie DA, Gemensky-Metzler AJ, Colitz CM, et al: Canine
34. 35. 36.
37. 38. 39. 40. 41.
42.
43.
44. 45.
46.
47.
48.
49. 50.
51.
52.
53.
54.
55.
cataracts, diabetes mellitus and spontaneous lens capsule rupture: a retrospective study of 18 dogs. Vet Ophthalmol 9:328-334, 2006 Wilcock BP, Peiffer RL Jr: The pathology of lens-induced uveitis in dogs. Vet Pathol 24:549-553, 1987 Gelatt KN, Das ND: Animal models for inherited cataracts: a review. Curr Eye Res 3:765-778, 1984 da Costa PD, Merideth RE, Sigler RL: Cataracts in dogs after long-term ketoconazole therapy. Vet Comp Ophthalmol 6:176-180, 1996 Sapienza JS, Simo FJ, Prades-Sapienza A: Golden Retriever uveitis: 75 cases (1994-1999). Vet Ophthalmol 3:241-246, 2000 Gionfriddo JR: A challenging case: an unusual cause of blindness in a Siberian husky. Vet Med 102:172-178, 2007 Grahn B, Wolfer J: Diagnostic ophthalmology. Retinal degeneration and cataracts. 36:722-723, 1995 Kornegay JN, Green CE, Martin C, et al: Idiopathic hypocalcemia in four dogs. J Am Anim Hosp Assoc 16:723-734, 1980 Bassett JR: Hypocalcemia and hyperphosphatemia due to primary hypoparathyroidism in a six-month-old kitten. J Am Anim Hosp Assoc 34:503-507, 1998 Blocker T, van der Woerdt A: What is your diagnosis? Cataract, retinal detachment, and a large mass protruding into the vitreous cavity. 217:23-24, 2000 Ching SV, Gillette SM, Powers BE, et al: Radiation-induced ocular injury in the dog: a histological study. Int J Radiat Oncol Biol Phys 19:321-328, 1990 Grahn BH, Storey E, Cullen CL: Diagnostic ophthalmology. Bilateral incipient nuclear cataracts. 44:603-604, 2003 Wilkie DA: The background of ocular prostaglandins and their role in ophthalmic physiology and pathology. Proc Am Coll Vet Ophthalmol 20:3-12, 1989 Paulsen ME, Lavach JD, Severin GA, et al: The effect of lensinduced uveitis on the success of extracapsular cataract extraction: a retrospective study of 65 lens removals in the dog. J Am Anim Hosp Assoc 22:49-56, 1986 Wilkie DA, Colitz CM: Surgery of the canine lens, in Gelatt KN (ed): Veterinary Ophthalmology, vol 2 (ed 4). Ames, IA, Blackwell Publishing, 2007, pp 888-931 Bernays ME, Peiffer RL: Morphologic alterations in the anterior lens capsule of canine eyes with cataracts. Am J Vet Res 61:1517-1519, 2000 Fischer CA: Geriatric ophthalmology. Vet Clin North Am Small Anim Pract 19:103-123, 1989 van der Woerdt A, Wilkie DA, Myer CW: Ultrasonographic abnormalities in the eyes of dogs with cataracts: 147 cases (1986-1992). J Am Vet Med Assoc 203:838-841, 1993 Miller D: Physiologic optics and refraction, in Kaufman PL, Albert A (eds): Adler’s Physiology of the Eye (ed 10). St. Louis, MO, Mosby, Inc., 2003, pp 161-194 Jaffee NE, Jaffee MS, Jaffee GF: The decision to operate, in Jaffee NE, Jaffee MS, Jaffee GF (eds): Cataract Surgery and Its Complications (ed 6). St. Louis, MO, Mosby-Year Book, Inc., 1997, pp 2-17 Taylor MM, Kern TJ, Riis RC, et al: Intraocular bacterial contamination during cataract surgery in dogs. J Am Vet Med Assoc 206:1716-1720, 1995 Komaromy AM, Smith PJ, Brooks DE: Electroretinography in dogs and cats. Part I. Retinal morphology and physiology. 20: 343-350, 1998 Rubin LF: Clinical electroretinography in dogs. J Am Vet Med Assoc 151:1456-1469, 1967