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Ophthalmology David J. Maggs, BVSc (hons), DACVO University of California, Davis Ophthalmic Examination and Diagnostic Testing
THE COMPLETE OPHTHALMIC EXAMINATION The problem-oriented approach that is now widespread in other fields of veterinary medicine is readily applied to ophthalmology. This approach progresses in a very predictable manner from recognition of a problem (client complaint, clinical lesion, altered clinical value, etc), through mechanisms that might cause such a finding, to a clinical diagnosis (Fig. 1). Application of the standard "DAMNIT" list allows selection of appropriate diagnostic tests and determines the most likely etiological diagnosis. This approach hinges upon a thorough ophthalmic examination with the ultimate goal being identification of all abnormalities. Although historical data may provide essential clues to the diagnosis, ready visualization of almost all parts of the eye means nothing can replace a complete examination. Indeed, never were the famous words "more is missed through not seeing than not knowing" more apt. Fortunately, a thorough and revealing ophthalmic examination is readily performed with just 5 guidelines, 5 skills, and minimal equipment. There are five essential requirements for a thorough ophthalmic examination:
The ophthalmic examination should be carried out in a repeatable and sequential manner to ensure that nothing is overlooked. Examining the unaffected eye prior to the affected eye in animals with unilateral disease ensures that it is not forgotten and provides information on the individual patient's normal ocular appearance. A prepared exam sheet reminds the practitioner to perform all necessary tests in the correct sequence. Mastering five procedures will provide all of the essential information from the anterior segment:
The anterior segment includes all structures in front of and including the lens. These are best-examined using focal illumination and subsequently magnification. To maximize the benefits of focal illumination, the light source should be directed from an angle that differs from the observer's viewing angle. Varying the viewing and lighting angles relative to each other permits the examiner to utilize parallax, reflections, perspective, and shadows to gain valuable information regarding lesion depth. This technique is particularly useful for examining the anterior chamber since changes within the anterior chamber can be more easily differentiated from corneal, iridal, or lenticular changes when viewed transversely. In cats and horses, the corneal curvature and anterior chamber depth are so great that limited visualization of the iridocorneal angle is also possible. The importance of a sequential anterior segment examination cannot be overstated. Following retroillumination and assessment of menace response and pupillary and palpebral reflexes, an obvious method is to begin at the front and progress to the back of the eye. This ensures that the lids (including skin, margin, and cilia), conjunctiva (nasolacrimal puncta, third eyelid, bulbar, and palpebral conjunctival surfaces), sclera, cornea (including tear film and particularly the limbus), anterior chamber, iris, and lens are examined completely. Anterior segment examination should be initiated prior to dilation so that the iris face is easily examined, however complete examination of the lens requires full dilation. Finally, the otoscope head, Optivisor or an alternate form of magnification should be used to reassess all suspected lesions identified by retroillumination and transillumination. Lesions in the clear ocular media can be very finely assessed using a combination of retroillumination and magnification. This is best achieved using the otoscope head by altering the viewing angle until the lesion is either "back lit" by the tapetal reflection or viewed against the dull non-tapetal area of the fundus while illuminated from in front. In both cases, the otoscope head is moved in or out from the eye until the lesion is in crisp focus and under full magnification against the chosen background. You will soon become familiar with and enjoy enhanced diagnostic viewing by experimenting with both techniques on all lesions. Aqueous flare is a pathognomonic sign of uveitis and is due to breakdown of the blood-ocular barrier with subsequent leakage of proteins into the anterior chamber. Aqueous flare is best detected using a very focal, intense light source in a totally darkened room. The passage taken by the beam of light is viewed from an angle. In the normal eye, a focal reflection is seen where the light strikes the cornea. The beam is then invisible as it traverses the almost protein- and cell-free aqueous humor in the anterior chamber. The light beam is visible again as a focal reflection on the anterior lens capsule and then as a diffuse beam through the body of the normal lens due to presence of lens proteins. If uveitis has allowed leakage of serum proteins into the anterior chamber then these will cause a scattering of the light as it passes through the aqueous. Aqueous flare is therefore detected when a beam of light joining the focal reflections on the corneal surface and the anterior lens capsule is visible traversing the anterior chamber. A slit lamp provides ideal conditions for detecting flare, however the beam produced by the smallest circular aperture on the direct ophthalmoscope held as closely as possible to the cornea in a completely darkened room and viewed transversely will also provide excellent results. The slit beam on the direct ophthalmoscope is not as intense and does not provide as many "edges" of light where flare can be appreciated most easily. Assessment of flare may be easier after complete pupil dilation due to the apparent dark space created by the pupil. Combined assessment of IOP and aqueous flare should be performed whenever glaucoma or uveitis is suspected because of the frequency with which these conditions co-exist. Assessment of intraocular pressure (tonometry) is essential for differentiation of the two major, vision-threatening conditions in which red-eye is the hallmark feature - uveitis and glaucoma. The availability of easily used and reasonably priced aplanation tonometers such as the Tonopen® (Ph: 1-888-TONOPEN [888-866-6736]; http://www.danscottandassociates.com/) make measurement of intraocular pressure (IOP) easier in all species, particularly cats. Unlike the Schiotz tonometer, the Tonopen measures IOP directly and does not require any conversion. It can also be held horizontally and therefore allows measurements to be performed with the patient's head held in a normal, relaxed position. Finally, it has a small probe that permits easy measurement of IOP in even the smallest feline and pediatric canine eyes. The instrument comes with an excellent instructional video and manual, however the following tips may assist you to get the most from your Tonopen. A drop of topical anesthetic is applied to the cornea. A disposable cover is placed over the Tonopen tip and the pen is turned on with firm, somewhat protracted pressure on the large black button about one third way down the shaft. The equipment should be periodically calibrated according to the manufacturer's directions. Correct patient restraint is essential. The patient should be lightly restrained so as to not artificially raise IOP. In particular, direct pressure on the jugular veins and on the globe itself via the eyelids should be avoided. I prefer to have an assistant (and not the owner!) restrain the patient's head using the angle of the mandible. I then hold the Tonopen in my dominant hand, and gently part the patient's eyelids using my non-dominant hand but such that pressure is applied to the underlying orbital rim; not globe. I then rest the hand holding the Tonopen onto the hand holding the eyelids or onto the patient's head itself and gently touch the central cornea with the Tonopen tip. Minor movements away from the cornea and very gentle "blotting" of the cornea with the tip will enhance the reliability and reproducibility of the readings while reducing the number of readings necessary. Particular attention should be paid to the "approach angle" of the Tonopen tip to the cornea. The tip's flat surface should be exactly parallel to the corneal surface. This is best achieved by viewing the interface between the cornea and the tip from the side. The approach angle of the Tonopen itself should be exactly perpendicular to the corneal surface. However, note that due to corneal curvature, this means the approach angle must be changed dramatically if any area other than the central cornea is used. Each time the cornea is appropriately "blotted" with the probe, an electronic tone will advise the operator that a reading has been obtained. When a suitable number of readings has been obtained, a tone of a different pitch will sound and no further readings can be obtained without restarting the Tonopen using the large black button again. The number of readings required to achieve an average varies depending on how disparate the readings are from each other and from the normal physiologic range. A small digital screen at the end distant from the tip displays the IOP in mmHg and provides an estimate of the "reliability" (coefficient of variance) of the result. This appears as a small bar above one of 4 percentage readings. This bar should be above the 5% mark or tonometry should be repeated on that eye. Across large populations, normal canine and feline IOP is reported as approximately 10-25 mmHg. However, significant variation is noted between individuals, technique, and time of day. Comparison of IOP between right and left eyes is therefore critical to interpretation of results. A good rule of thumb is that IOP should not vary between eyes of the same patient by more than 20%. The obvious application for the Tonopen is the diagnosis of glaucoma where IOP is generally elevated. However tonometry is also used to diagnose uveitis; in which IOP is lowered due to loss of function of the inflamed ciliary body. Perhaps the most important role for tonometry is the monitoring of progress of these diseases and the adjustment of medications based on these data. Uveitis
CLINICALLY RELEVANT PATHOPHYSIOLOGY Uveitis is defined as inflammation of the middle (uveal) coat of the eye. Since this tunic contains the major resident population of immunologically active cells, it has the potential to react in a very specific manner to antigenic stimuli, especially infectious organisms, and so to be an extremely important component of afferent and efferent arms of the ocular immune response. It also has the potential (particularly in cats and horses) to respond somewhat like a lymph node in a less specific manner to unidentified antigens. Less specific, and uncontrolled immunological responses can cause significant disruption of intraocular anatomical and physiological conditions and be detrimental to ocular function. This presents a major dilemma in diagnosis and treatment of intraocular inflammation. Optimal management of uveitis would include prompt, unambiguous identification and removal of the causative antigen, with minimal non-specific "damping" of immunological response. However all too often, exhaustive diagnostic searches fail to reveal the causative antigen and inflammation is so fulminate that non-specific anti-inflammatory agents become the mainstay of therapy for uveitis. The majority of small animal uveitis is infectious, immune-mediated, or neoplastic in origin. Application of the standard "DAMNIT" list will, however identify some less common causes of uveitis. Commonly implicated infectious agents vary with species. In feline uveitis, fungi (predominantly Histoplasma or Cyptococcus), FIV, FeLV, FIP, and Toxoplasma are commonly incriminated etiologic agents. Recently, the intraocular detection of Bartonella henselae and FHV-1 in some cats with uveitis has raised suspicion regarding the potential for these two agents to cause uveitis. In the dog, fungal and rickettsial organisms represent the major infectious diagnoses. In both dogs and cats, the most common primary intraocular neoplasm is melanoma. This usually causes surprisingly mild uveitis. By sharp contrast, the most common secondary ocular neoplasm - lymphoma - tends to be associated with marked breakdown of blood-ocular barrier and hypopyon formation. Other common causes of uveitis are trauma (blunt or perforating; with or without lens protein leakage), uveitis secondary to corneal ulceration (so-called "reflex uveitis"), and lens dislocation. Unfortunately, in the majority of cats with uveitis, a cause is not identified despite thorough diagnostic workup and these cases are labeled "idiopathic" or sometimes "immune-mediated". Major diagnostic, therapeutic, and prognostic considerations are therefore:
CLINICAL SIGNS AND DIAGNOSTIC TESTING FOR UVEITIS
The following discussion is intended to summarize some general concepts of diagnosis and treatment of uveitis while highlighting newer treatments, and common pitfalls of more standard therapies. The hallmark feature of uveitis is breakdown of the blood-ocular barrier. When this occurs in the anterior uvea, inflammatory transudate/exudate appears in the anterior chamber as aqueous flare, fibrin clots, hyphema, and/or hypopyon. When the same processes occur in the choroid, exudation occurs subretinally and appears as subretinal edema, hemorrhage, exudate, and ultimately retinal detachment. Other signs of acute uveitis include blepharospasm, conjunctival and episcleral hyperemia, low IOP due to hyposecretion, miosis (or, more subtly, resistance to pharmacological dilation), and a swollen or hyperemic ("muddy appearing") iris. Ocular discharge can be extremely variable. More chronically, patients with uveitis may be presented with rubeosis iridis (neovascularization over the face of the iris), dyscoria secondary to synechiae, cataract formation, keratic precipitates (KP's), or phthisis bulbi (a shrunken and fibrotic globe). Vision can be affected with acute or chronic, anterior or posterior uveitis and result from synechiation, cataract, vitreal and aqueous exudates, and/or retinal detachment. The standard diagnostic approach to patients with uveitis should begin with a thorough history and general physical examination due to the frequency with which uveitis is associated with systemic disease. Particular attention should be paid to signs of respiratory or neurological disease, fever, draining skin tracts, lameness, or diarrhea. A thorough ophthalmic exam should include an assessment of aqueous flare, retroillumination, tonometry, fluorescein staining, and PLR's. Complete examination of the anterior segment and fundus following full dilation (assuming normal IOP and no signs of lens dislocation) is essential. In cases where systemic disease or neoplasia is suspected, diagnostic testing may include CBC, serum biochemistry, urinalysis, serology for commonly implicated infectious organisms, chest or abdominal imaging, or lymph node aspirates. Ocular ultrasound is an excellent modality when opacity of the ocular media prohibits direct examination. Ocular paracentesis with subsequent cytologic and serologic analyses may be useful in cases in which less invasive means have not yielded a diagnosis. Aqueocentesis, vitreocentesis or sub-retinal aspiration is chosen based upon the major focus of inflammation. Of these, aqueocentesis is the easiest to learn and perform. It must be performed with the patient under general anesthesia and following application of topical anesthetic. An eyelid speculum assists with exposure, and the conjunctival fornix should be rinsed with dilute (1:50) Betadine solution® (not scrub). The conjunctiva and episclera are grasped just posterior to the limbus with a pair of fine-toothed forceps and a 25- or 27-gauge needle on a tuberculin syringe is introduced into the anterior chamber through or just behind the limbus. A subconjunctival tunneling approach will minimize aqueous leakage as the needle is withdrawn. Care is taken to not damage the iris, lens, or large blood vessels at the 3 and 9 o'clock positions. The needle should be carefully directed towards any obvious area of inflammatory debris or hypopyon. Slow aspiration of 0.2-0.3 ml of aqueous is possible in dogs or cats. If aspiration is too rapid then sudden hypotony may induce hemorrhage from the iris face. Prophylactic application of a topical antibiotic solution is recommended following ocular centesis. The fluid collected is placed in a sterile redtop tube and submitted for cytologic analysis. Cytospin techniques will aid diagnosis since cell numbers are usually low. Serologic analysis of the fluid is also possible and comparison of the aqueous and serum antibody levels with calculation of the Goldmann Witmer coefficient (C value) will permit estimation of intraocular antibody production. CLINICAL MANAGEMENT OF UVEITIS Treatment of uveitis in small animal patients must be tailored to the individual case based on species affected, suspected cause, severity, extent and region of uveal tract involved (anterior vs. posterior or both), and presence of other intraocular disease. There are some general therapeutic considerations for dogs and cats with uveitis:
Glaucoma CLINICALLY RELEVANT PATHOPHYSIOLOGY
At its most basic level, glaucoma pathophysiology is relatively easily summarized. Since hypersecretion from the ciliary processes is not recognized, "all" veterinary glaucomas are related to restricted outflow of aqueous humor. Following formation by the ciliary processes, normal aqueous circulation occurs through the pupil (between the lens and iris) and out through the ICA (conventional outflow). Non-conventional or "uveoscleral" outflow occurs through small "pores" in the uveal tract and directly into the vascular circulation and forms a less major route of outflow in dogs and cats. Obstruction of the ICA therefore, is the underlying cause of the majority of canine and feline glaucomas. ICA obstruction may be anatomical or functional. Anatomic obstructions may be inherited such as goniodysgenesis (pectinate ligament dysplasia) or acquired such as peripheral anterior synechiae (secondary to uveitis). Such changes are visible clinically (using gonioscopy) or histologically and cause a syndrome referred to as closed angle glaucoma. In primary open angle glaucoma (POAG), the obstruction is suspected to be a biochemical accumulation or alteration of ICA glycosaminoglycans (GAG's). POAG is seen commonly in humans, but is recognized relatively infrequently in veterinary patients. The most commonly affected breeds include the Beagle, Samoyed, and Norwegian elkhound. By sharp contrast, the majority of feline glaucoma occurs secondary to uveitis. Uveitis may cause obstruction of the ICA by one of two major mechanisms (and many less common mechanisms). In the acute phase, any or all of the processes of acute inflammation such as edema, cellular infiltration, or hemorrhage may obstruct the ICA either directly, or via swelling and displacement of the iris. More chronically, neovascularization or fibrosis of the ICA and/or peripheral anterior synechiation contribute to reduced aqueous outflow. Slow but steady increase in knowledge regarding glaucoma pathogenesis has led to increasingly complex definitions of this disease or group of diseases. In the latest edition of Gelatt's textbook, canine glaucoma is defined as follows: "Glaucoma is the final common pathway of a group of diseases with decreased retinal ganglion cell (RGC) sensitivity and function, RGC death, optic nerve axon loss and concurrent optic nerve head cup enlargement, incremental reduction in visual fields, and blindness." It is fascinating to note that there is no mention of increased intraocular pressure or of closure or malformation of the iridocorneal angle (ICA) in this definition. This shift of attention from front to back of the eye arises from knowledge that injury of sensitive retinal structures occurs very early in the glaucomatous process. This knowledge has two important clinical applications:
CLINICAL SIGNS AND DIAGNOSTIC TESTING FOR GLAUCOMA The hallmark feature of glaucoma is elevated IOP (normal IOP range = 10-20mmHg). Comparison of IOP between left and right eye in an individual patient is essential because of large variation with technique, time of day, and between individuals. A good rule of thumb is that IOP should not vary between eyes of the same patient by more than 20%. Associated inflammatory signs can be variable depending on stage of disease, rapidity of IOP elevation, species, and presence of other intraocular disease. Signs of glaucoma in cats tend to be much more subtle than those displayed by dogs. Given the difficulty predicting IOP from clinical signs and its critical role in glaucomatous retinal degeneration, measurement of IOP is critical in the assessment of most, if not all ocular disease, especially in cats. Early ocular hypertension may cause mild blepharospasm, epiphora, conjunctival hyperemia, and subtle episcleral congestion. Mydriasis may be mild and missed unless retroillumination from a distance is performed. Failure to measure IOP at this stage of disease frequently leads to misdiagnosis (typically "conjunctivitis"), inappropriate treatment, and sometimes a missed opportunity to preserve vision for a reasonable period. Rapid onset of markedly elevated IOP ("acute congestive glaucoma") will cause more marked blepharospasm, epiphora, deep episcleral vascular engorgement, and mydriasis. This is seen more commonly in dogs. Decreased or absent vision is common at this point. Corneal edema is a frequent feature of this syndrome in dogs, especially when IOP approaches 40mmHg, but is a variable feature in cats and "always" less significant than in the canine patient. Buphthalmia or stretching and enlargement of the globe with secondary signs of Haab's striae (lines of focal corneal edema and scarring secondary to breaks in Descemet's membrane) and sometimes with associated exposure keratitis or lens dislocation is seen after sustained elevation of IOP. In most patients this is a terminal stage of the disease process and vision is lost or will soon be lost. The "take home" message is that inflammatory changes and evidence of pain at all stages of disease can be surprisingly mild and often overlooked, especially in cats, suggesting that IOP should be measured even in patients with minimal signs of inflammation. Gonioscopy provides valuable information about ICA anatomy and therefore whether the glaucoma is likely to be primary. It should be a routine part of the assessment of every patient with glaucoma. Because of the cat's large cornea, the ICA can be visualized relatively easily by viewing across the anterior chamber using a focal light source and magnification (again, the otoscope head is ideal). The ventral and nasal quadrants are easiest viewed by angling the light source and otoscope head in steeply from the dorsolateral sector. A more thorough examination in cats and any examination in dogs require that a small plastic goniolens be applied to the cornea to allow complete visualization of the ICA. While this technique is relatively easily learned, familiarity with angle anatomy and interpretation of abnormal findings require practice and it is performed infrequently outside specialist practice. Fundic examination provides important clues as to stage, duration, history, and prognosis for patients with glaucoma. In dogs, the optic nerve head (ONH) may appear swollen or hyperemic (papilledema) during acute congestive glaucoma, but later appears smaller and darker (atrophic) with deep, noticeable "cupping" centrally after prolonged IOP increases. Tapetal hyper-reflectivity and generalized retinal vascular attenuation parallel optic nerve changes. The tapetal hyperreflectivity is often most notable in the region immediately surrounding the ONH and occasionally in a fan-like distribution emanating from the ONH. CLINICAL MANAGEMENT OF GLAUCOMA
Answers to three critical questions will aid in the successful management of glaucoma:
Is the glaucoma primary or secondary? Treatment of any primary cause (in addition to control of elevated IOP) is critical to management of secondary glaucoma. Glaucoma may be secondary to uveitis, intraocular tumors, hyphema, lens dislocation, or intumescent cataract formation. Therefore, the answer to this question necessitates assessment of signalment, and thorough ocular examination including gonioscopy, flare, and IOP. If a thorough assessment of intraocular anatomy is not possible, then ocular ultrasound may be considered, especially in older dogs or non-predisposed breeds where concerns are heightened regarding presence of an intraocular tumor. Primary glaucoma tends to be seen in young to middle-aged dogs of recognized breeds.
Table 1. Breeds commonly affected by primary glaucoma
(Table 1). Onset is unilateral, however the second eye usually becomes involved within 1-2 years. Secondary uveitis is typically mild and affects the glaucomatous eye only. Gonioscopy, which must frequently be performed on the opposite eye due to severity of corneal edema in the affected eye, will usually reveal a narrow to closed ICA. As already stated, glaucoma in cats may be primary but is far more likely to be secondary to chronic uveitis. At what stage is the glaucoma? From the point of view of treatment, there are three stages of glaucoma:
SPECIFIC TREATMENTS FOR GLAUCOMA
The large range of glaucoma medications can be daunting (Table 2). The following is a brief outline of some general principles of therapy with some newer medications highlighted. Bear in mind however, that there have been few controlled studies to prove the worth of individual treatments, let alone their comparative value in domestic species, especially cats. In fact, it has been suggested that some prophylactic treatments might even worsen early pathology in ocular hypertension. In some cases the exact mechanism by which medications exert their pressure lowering effect is unclear. Despite this, a couple of scientifically-based comments are possible:
Table 2. Commonly available glaucoma medications
Mannitol is a hyperosmotic drug that reduces IOP via vitreal dehydration. It is given as a slow IV bolus (1-2g/kg over 20-30 minutes) and oral water and IV fluids are withheld for at least 1-2 hours. This drug may be contraindicated if the patient has pre-existing renal or cardiac disease. Oral administration of glycerine was once popular but commonly is associated with GI disturbance, is not a potent hypotensive agent, and must not be used in diabetic patients. Carbonic anhydrase inhibitors (CAI's) reduce aqueous humor production. Methazolamide (Neptazane®, 2-5mg/kg PO BID - TID) and dichlorphenamide (Daranide®, 2-5mg/kg PO BID - TID) appear to be the best-tolerated CAI's. Daranide® can be difficult to obtain as a commercial preparation, however compounding pharmacies can formulate dichlorphenamide in tablet form. Systemic CAI's can occasionally cause GI upset, hypokalemia, or acidosis with secondary tachypnea, especially in cats. These side effects are rapidly reversible with reduction in dose or frequency. Introduction of topical CAI's such as dorzolamide (Trusopt®) or brinzolamide (Azopt®) has provided a means of reducing IOP without the same degree of systemic side effects. These require TID application in humans and dogs but, to the best of my knowledge, the dosing frequency and efficacy in cats have not been studied. The major role of the topical CAI's appears to be maintenance of lowered IOP, rather than management of acute congestive crises. Latanoprost (Xalatan®) represents a new class of drugs (synthetic prostaglandins) for treatment of glaucoma. It promotes non-conventional (or uveoscleral) outflow and also produces marked miosis after one or two applications. Its role in management of feline or canine glaucoma has not been investigated, however it failed to show an IOP-lowering effect in a recent clinical trial in normal cats. It did however reduce IOP in normal dogs. It should be used with great caution (if at all) in cases of glaucoma with significant uveitis since prostaglandins will exacerbate uveitis. CHOICE OF TREATMENT DEPENDING ON STAGE OF DISEASE
Glaucoma is coming. Prophylactic treatment for canine glaucoma has until recently been based entirely on anecdotal reports and personal preferences. There had been no controlled studies to prove the worth of individual treatments, let alone their comparative value. In fact, it had been suggested that some prophylactic treatments might even worsen early pathology in ocular hypertension. A recent large, multicenter prospective trial compared 2 treatment regimens - A) demecarium bromide (Humorsol®) and a topical corticosteroid SID and B) betaxolol (Betoptic S®) BID with an untreated control group. Results suggest that either prophylactic treatment significantly increased time to onset of glaucoma in the second eye. Although there were no significant differences between the two treatments, therapy with demecarium bromide and a corticosteroid may be preferred because of once daily application, fewer side effects, and because it encourages owners to monitor pupil size as a significant and early marker of failing prophylaxis. I now almost routinely recommend initiation of demecarium bromide and corticosteroid therapy SID in the unaffected eye at the time primary glaucoma is diagnosed in the opposite eye in dogs. Owners can be trained to elicit a PLR as they apply medication daily. Observation of a large or unresponsive pupil in the treated eye or any signs of inflammation such as corneal edema or vascular injection is considered a need for urgent veterinary attention. Humorsol® was recently discontinued as a commercial preparation, however compounding pharmacies can dispense demecarium bromide as either a 0.125% or 0.25% solution. Glaucoma is here. Acute congestive glaucoma should be treated as an emergency since vision loss appears to be dependent on magnitude and duration of IOP increase. Multi-drug therapy is recommended since a synergistic response may be afforded by combining differing drug actions and routes of application (Table 2). I typically combine 3 drugs, given via three routes, and utilizing three mechanisms:
Glaucoma has been and gone. Medical management of glaucoma is expensive, requires frequent recheck examinations for tonometry and manipulation of therapy, and is not without side effects. This is usually justified in a visual eye. However, once vision is lost, preservation of a pain free globe with minimal expense, owner effort, and patient side effects become the major goals. This is best achieved surgically. In general, three definitive surgical procedures are used routinely in management of blind, glaucomatous eyes:
Coexisting Glaucoma & Uveitis
The close anatomic and physiologic interdependence of intraocular structures is essential for the most complex of senses - vision. However, this intimate relationship also dictates that even apparently minor alterations in the milieu, anatomy, physiology, or biochemistry of one tissue will have significant ramifications for all other tissues within the eye. Clinically, this means that diagnosis of a single intraocular disease suggests others may coexist and requires that their existence be proven or excluded by thorough examination. Glaucoma, uveitis, lens dislocation (luxation or subluxation), and cataracts are commonly seen in various combinations and require particular attention (Fig. 2). In fact, the likelihood that one disease will be caused by or lead to another of the major intraocular diseases is so high that, having diagnosed on of these diseases, the clinician's goal should be to prove that the other three conditions do NOT exist. **** Although any one of the 4 major intraocular diseases may be primary, consideration of the likelihood of primary infectious vs. inherited disease in cats and dogs will assist with the clinical assessment of intraocular disease in the two species: Because we tend to line-breed cats much less commonly than dogs, the one intraocular disease than cannot be inherited (uveitis) tends to be the most common primary diagnosis in cats. (Cataracts, glaucoma and lens luxation then occur relatively commonly secondary to chronic, smoldering uveitis.) By contrast in dogs, the commonly inherited diseases (cataracts, glaucoma, and in some cases lens luxation) are more likely to be primary with uveitis secondary to them. Naturally exceptions to this rule will always occur just to fool us! **** Of these 4 disease, perhaps the most common combination is glaucoma and uveitis; particularly in cats. In most cases, uveitis is the primary insult while glaucoma occurs secondary to it. Glaucoma may be secondary to the acute (cellular) or chronic (fibrosing) inflammatory changes uveitis inflicts on the ICA. Alternatively, primary acute glaucoma often is associated with some degree of secondary uveitis, particularly in dogs and especially the Bassett hound. Regardless of which disease is primary, detection and differentiation of the two diseases can be difficult because they share many clinical signs such as blepharospasm, corneal edema, deep episcleral congestion, and ultimately decreased vision (Table 3). They can also produce sharply contrasting clinical signs; for example uveitis causes miosis while glaucoma causes mydriasis, and glaucoma is associated with increased IOP, while uveitis causes hyposecretion of aqueous and lowered IOP. Ironically, these opposing signs can increase diagnostic confusion when uveitis and glaucoma are both present since it is possible for one disease to "normalize" the aberrant clinical signs caused by the other. A final dilemma is added when one considers that treatments for one disease may be contraindicated for treatment of the other. Determination of the relative contribution of glaucoma and uveitis where they coexist in an individual patient is therefore critical.
Table 3. Differentiation of coexistent glaucoma and uveitis
DETECTION OF COEXISTING GLAUCOMA AND UVEITIS
Combined assessment of pupil size (larger with glaucoma, smaller with uveitis), aqueous flare (more marked or bilateral with primary uveitis), and IOP (low with uveitis alone, high with glaucoma alone, and impossible to predict when both diseases are present) will allow determination of the relative roles of glaucoma and uveitis in the pathology seen. Here are some helpful "rules of thumb":
TREATMENT OF COEXISTING GLAUCOMA AND UVEITIS
Treatment of coexisting uveitis and glaucoma provides a dilemma for veterinarians. Firstly, medications indicated for one disease are frequently contraindicated for treatment of the other. And, secondly, successful treatment of one disease will often expose or at least exacerbate clinical signs of the other. For example, control of inflammation in uveitis, may well return the ciliary processes to their normal rate of aqueous production, thereby revealing reduced outflow through a compromised ICA, and resulting in a rapid and harmful rise in IOP. Therefore, the only method of treatment in such complex cases is careful tailoring of medications based on extremely frequent monitoring of clinical progress. These are cases that will benefit greatly from frequent rechecking of IOP. Although choice of medications for this disease complex must be more individualized than for perhaps any other in ophthalmology, some general guidelines are possible:
Clinical Assessment of the Posterior Segment
PERFORMING THE FUNDIC EXAM
Fundic examination is probably the greatest challenge in the ophthalmic exam. Fortunately, anterior segment abnormalities tend to outnumber fundic abnormalities in general practice. Funduscopy is however critical in the assessment of animals presenting with visual disturbance, pupil abnormalities, or systemic disease. Traditionally, there have been two methods for viewing the fundus; indirect and direct ophthalmoscopy. Recently, Welch Allyn (The Panoptic®) and Keeler (The Wide Angle Twin Mag®) have both introduced new ophthalmoscopes that combine some of the best features of both methods. The Direct Ophthalmoscope. This instrument hangs on the walls of most veterinary exam rooms the world over and yet is not the best method for examining the fundus. It is used by turning the lens power to "0", selecting the largest circle of light that it emits, turning the light to almost full brightness, turning the room lights off or to a dim setting, and resting the brow rest of the ophthalmoscope against the operator's brow. Ideally the operator's right eye should be used for examining the patient's right eye and vice versa, although some people have trouble using their non-dominant eye. The examiner should hold the animals eyes open while an assistant holds the head steady. Begin viewing at arm's length from the patient and move around until a bright tapetal reflection is obtained (as for retroillumination). The examiner should then slowly approach the animal, while always aiming at the tapetal reflection of the eye to be examined. Good focus in a normal patient should be reached within just a few centimeters of the eye. It is therefore sometimes useful to extend the index finger of the hand holding the ophthalmoscope so as to rest against the patient's cheek. The direct ophthalmoscope presents a highly magnified, upright image of a very small region of the patient's fundus. In compliant (human) patients this instrument can then be used to slowly and sequentially examine the whole fundus in minute detail. In our patients, this small filed of view frequently means that areas of the retina, particularly peripherally, are never examined and that one area of the retina cannot readily be compared to another region. The Indirect Ophthalmoscope. Although more technically difficult when first learned, indirect ophthalmoscopy is the preferred method for examining the veterinary fundus. The reasons for this are the larger field of view that is permitted by this technique. This permits the examiner to compare regions of the fundus one against the other such that focal areas of subtle pathology may be detected by comparison with neighboring normal areas. It also makes a complete exam of the whole fundus more likely and easier than when performed with direct ophthalmoscopy. The perceived downfalls are that the image is les magnified, however this can be countered by moving closer to the patient while performing indirect ophthalmoscopy or by a subsequent (more magnified) examination of any "suspect" areas using the direct ophthalmoscope. Another difficulty for beginning ophthalmoscopists is that indirect ophthalmoscopy produces an inverted view. This makes navigation around the fundus and correct geographic localization of lesions a little more difficult at first but can be readily overcome with practice. I prefer to use a Volk 20D or 2.2 Pan Retinal indirect lens. (Dan Scott and Associates. Ph: 1-888-866-6736; http://www.danscottandassociates.com/). The Welch Allyn Panoptic® or Keeler Wide Angle Twin Mag® Ophthalmoscopes. Welch Allyn has recently released a new ophthalmoscope that produces a view with many of the best features of those produced using direct and indirect ophthalmoscopy. The image produced is upright, moderately magnified and includes more of the fundus than is possible with the direct ophthalmoscope but less than that provided by the indirect ophthalmoscope. Perhaps best of all, it is extremely user friendly and encourages fundic exams - and that is a good thing! The scope may be purchased alone, fits directly onto the standard Welch Allyn handset already in your clinic, and is available from Dan Scott & Associates (Ph: 1-888-866-6736; http://www.danscottandassociates.com/). And so, which ophthalmoscope? For the specialist ophthalmologist, indirect ophthalmoscopy for the initial fundic examination followed, when necessary, by direct ophthalmoscopy to view areas of interest detected during indirect ophthalmoscopy remains the preferred method of performing a complete fundic examination. In general practice, the Panoptic provides a very useful compromise between these two techniques and in my opinion provides a view that is definitely superior to that provided by the standard direct ophthalmoscope. No matter which ophthalmoscope you use, the golden rules seem to be:
ANATOMY FOR THE FUNDIC EXAM
A grasp of one simple fact is of critical importance when learning to interpret fundic changes: the fundus is not a single structure. Rather, the fundus is a collective term describing all structures in the posterior portion of the globe that can be viewed with the ophthalmoscope. The fundus therefore includes the sclera, choroid, tapetum (in most dogs and cats), retinal pigment epithelium (RPE), neural retina, optic nerve head, and retinal vasculature. Normal appearance of each of these structures varies with species, breed, age, and coat/skin color of the animal. Appearance of each structure is further altered by the appearance of each overlying structure (i.e. all structures between it and the examiner's ophthalmoscope). The number of permutations of normal fundic appearance, particularly in the dog is therefore huge and remains a major hurdle to overcome in interpreting ophthalmoscopic findings. Recognition of various disease conditions adds another layer of complexity. A working understanding of clinically relevant fundic anatomy is the most important tool for overcoming this challenge. The "build a fundus" approach seems helpful. This approach begins with the posterior-most (or outermost) layer of the fundus (i.e., the sclera) and sequentially adds layers on top of each other as viewed ophthalmoscopically from the front of the eye. "BUILD A FUNDUS" The sclera in most animals is a tan-white color. Its innermost layer (the lamina fusca) is pigmented to a degree that can usually be predicted by skin color (not hair color). The sclera is usually not visible due to overlying layers of the fundus. However, occasionally (especially in cases of choroidal hypoplasia) the sclera is clearly visible. The most common scleral abnormalities that cause altered fundic appearance are 1) posterior scleritis, which can extend to cause inflammation of the more readily observed fundic structures (chorioretinitis) and even retinal detachment; 2) regional scleral absence or thinning (Scleral ectasia or staphyloma), which allows an out-pouching of the overlying choroid and retina; and 3) orbital masses can impress the sclera and globe causing an area of fundus to appear out of focus compared to surrounding areas. Unless the mass is attached to the sclera, this raised (defocused) area will move across the fundus with change in globe position. The choroid is the posterior uvea and is composed of large blood vessels with variable amounts of melanin typically arranged in a somewhat linear fashion between blood vessels. Again, degree of pigmentation is usually related to skin color. The choroid therefore lends a generalized orange-red hue to the fundus, frequently in a somewhat striped or "tigroid" pattern. Visualization of the choroid may be altered by presence or absence of a tapetum and degree of pigmentation of the RPE. Posterior uveitis (or chorioretinitis) is the most common funduscopically visible choroidal pathology. This can appear as choroidal (sub-retinal) hemorrhage, edema, or exudation, all of which are likely to cause altered tapetal appearance and/or retinal detachment. The tapetum is actually part of the choroid but is considered separately because it is variably present in the dorsal (superior) fundus of small animal patients. Its absence is considered a normal variation seen more commonly in sub-albinotic or merled breeds such as various oriental cats, collie dogs, and Aussie shepherds, etc. Its color is dependent on its thickness and therefore is expected to vary somewhat across the whole tapetum, especially at the tapetal/non-tapetal junction and surrounding the optic nerve head. Orange, green, and yellow tapeta are common. Some dark-skinned dogs such as Schnauzers, and Scottish Terriers may have a blue tapetum. Size of the tapetum varies greatly between individuals but tends to increase in size with increased body size. In general, the cat tapetum is relatively thick and therefore appears a reasonably homogeneous green/yellow. The tapetal area of the cat's fundus is usually large and tends to incorporate the optic nerve head. Primary tapetal pathology is rare, however changes in funduscopic appearance of the tapetum are observed very frequently. These result from changes in the subjacent choroid and/or overlying retina and are discussed in those sections. The retinal pigment epithelium (RPE) is perhaps poorly named since it is variably pigmented but uniformly present in the normal fundus. It is predictably non-pigmented where it overlies the tapetum and is usually a relatively homogenous liver to dark brown/black color in the ventral (inferior) non-tapetum. There is a gradation of pigment intensity at the tapetal/non-tapetal border. Degree of pigmentation is generally reduced or absent in animals with lightly pigmented coats/skin, especially merle animals. The most frequent pathologic changes involving the RPE are alterations in the degree of melanosis; i.e., depigmentation of the non-tapetal fundus seen most dramatically in uveodermatological or VKH-like syndrome in dogs, or hyperpigmentation secondary to any chronic, inflammatory process. The neurosensory retina is slightly translucent and therefore alters the intensity of light reflected from the tapetum to the observer. Thus it tends to pass unnoticed in the normal fundic exam. Observation of "tapetal hyper-reflectivity" is actually due to retinal thinning which has allowed more light to be reflected from a normal tapetum. Conversely, any thickening of the retina due to edema, cellular infiltration, hemorrhage, or pigmentation will reduce or even obstruct the tapetal reflection. Retinal vasculature varies between individuals and species. Both arterioles and venules can be seen in dogs and cats. Arterioles are thinner and straighter than venules. In the cat there are usually 3 large venules arranged in a somewhat tilted "T" pattern. The large vessels arc around and are absent in an area just temporal to the disc known as the area centralis. This is the equivalent of the human macula and is rich in cone photoreceptors and ganglion cells. In the dog, 3-4 major venules radiate out from the optic nerve head arranged in a pattern that approximates an inverted "Y". An area centralis is not seen in the canine fundus. In both species, blood vessels should extend to the retinal periphery, bifurcating frequently but without excessive tortuosity. Changes visible funduscopically are usually due to systemic diseases (vasculitis, hypertension, anemia, hyperlipidemia, hyperviscosity), or local retinal vascular changes such as attenuation as seen with retinal degenerations. The optic nerve head (ONH or optic papilla or optic disc) appearance also varies between individuals and species. In the cat it appears to be a small, dark, gray/black, non-myelinated circle within the tapetum or near the tapetal/non-tapetal border. Variable degrees of ONH myelination in dogs dictate that normal ONH appearance may range from small, flat and circular through larger, raised, and irregular triangular-shaped. ONH position in dogs relative to the tapetal/non-tapetal border is extremely variable and dependent on tapetal size. Frequently observed pathology includes inflammatory changes (hyperemia, edema, hemorrhage, or cellular infiltration), "cupping", or atrophy. CLINICAL ASSESSMENT OF THE FUNDUS
With the build a retina approach, all alterations (normal variations and disorders) in fundic appearance can then be interpreted using "fundic mathematics". I.e., all alterations represent either "addition" of cells or fluid (blood, melanocytes, exudate, transudate, metastatic neoplastic cells, etc) that obscure your view of part/s of the fundus. What parts of the fundus that are obscured and what parts overly the "additional" cells or fluid can be used to assess the depth of the lesion within the fundus. Alternatively, altered appearance can represent a "subtraction" or loss of some normal fundic constituent, thus exposing underlying constituents. Perhaps the best example is retinal thinning or atrophy in which case the tapetal "sheen" is interpreted as "hyper-reflective". With this fundamental understanding of the fundic layers, I ask myself 5 questions when assessing the fundus:
GENERAL CLINICAL SIGNS & DIAGNOSTIC TESTING
Animals with retinal or optic nerve disease are most commonly presented for visual disturbance or pupil abnormalities. Visual disturbance can vary from subtle decreases in certain components of vision such as peripheral vs. central vision, or night vs. day vision or more commonly, as total blindness. Common pupil abnormalities include mydriasis or anisocoria. Basic neuro-ophthalmic testing should include assessment of cranial nerves involved in ocular function (CN II - VII), the central visual pathways, and the visual cortex. This can be performed reasonably completely with relatively few simple tests:
If the patient fails to blink in response to a menacing gesture, the palpebral test should be performed to ensure that the facial nerve (CN VII) is functional. This involves stimulating the trigeminal nerve (CN V) by gentle tapping the lateral or medial canthus with a finger. A stronger blink response is generated with stimulation at the medial canthus than the lateral. The corneal reflex involves the same general pathway as the palpebral but determines CN V function within the cornea rather than the eyelid/s. It is performed by stretching a small wisp of cotton fiber off the head of a Q-tip and using this to lightly stimulate the cornea. Clearly, this test should be performed prior to application of topical anesthetic and subtly enough to avoid eliciting a menace response. Behavioral testing is a superior assessment of vision than the menace response in many ways. Various behavioral tests are described. Although maze testing is very successful in dogs it is rarely practical in cats. The "dangling fish" test and visual placing test are two other behavioral tests of vision that are particularly useful in cats and smaller dogs. The "dangling fish" test involves following a visual stimulus without auditory or olfactory clues. Although cotton wool balls are convenient, cats appear more stimulated by some of the toys on a string attached to a short rod that are available in pet stores. Visual placing tests are performed as in the standard neurological examination. The patient is supported in the examiner's arms and moved slowly towards a counter or tabletop. The normal response is to extend one or both front legs as the table is approached but before a foot touches the table. All visual tests should be critically performed as all animals (but particularly blind animals) have exceptionally "heightened" non-visual senses relative to our own. Complete assessment of unilateral vision problems should always be performed for each of the vision tests. Each eye should be sequentially blindfolded or at least covered with the hand, however this is not always well tolerated, especially by cats. Behavioral tests should be performed in gradually increasing ambient light levels to test for nyctalopia (night blindness) because some animals (perhaps, especially those that have diminished vision!) rapidly familiarize themselves with their environment or begin to ignore other visual stimuli. Testing in gradually diminishing light levels may fail to identify these patients. Further discussion of visual disturbances in textbooks frequently emphasizes visual and pupillary light response pathways, which can be very complex when learned by rote. Fortunately, in the majority of cases faced in the typical clinical setting, reduced or absent vision can be approached in a simple, mechanistic manner. This rapidly focuses attention on the section of the pathway most likely affected and permits a short-list of causes to be compiled. Visual disturbances result from one (or more) of the three following mechanisms:
Light does not reach the retina. Visualization of the fundic reflex using retroillumination will provide valuable information regarding clarity of the visual media. If light is transmitted and reflected clearly through the cornea, aqueous humor, lens (and pupil), and vitreous, so that the fundic reflex is uninterrupted, then this mechanism of visual loss is eliminated. Further clinical examination and testing is then directed at the retina, optic nerve, and CNS. Potential causes of decreased vision that may be detected by retroillumination include severe corneal opacification, hyphema, cataract, extensive posterior synechiae, vitreal hemorrhage, and retinal detachment. The retina is not functioning normally. Careful examination of the retina following complete pupil dilation and preferably using indirect ophthalmoscopy is essential for detection of the common fundic abnormalities that are associated with decreased vision. These include retinal and/or optic nerve degeneration, optic neuritis, retinal detachment, and chorioretinitis. These diagnoses are discussed more fully below. If the retina appears anatomically (funduscopically) normal, then an electroretinogram (ERG) is required to differentiate functional retinal disturbances from CNS (and optic nerve) disease. The ERG measures the electrical potential generated by retinal cells when stimulated with a flash of light. Its routine use is limited to specialty practice. Other tests of retinal (and CNS) function are less specific. The PLR does assess retinal function, however comparatively few functional photoreceptors are necessary for a complete PLR. By comparison, normal functional vision dictates that a complex, cumulative, and integrated response is elicited from numerous specialized photoreceptors, transmitted to the visual cortex, and there transformed into the learned perception we interpret as vision. Presence of a PLR does not therefore determine that retinal function is normal. The brain and/or optic nerve are not functioning normally. Central visual disturbances present the greatest challenge for diagnosis, especially in general practice. CNS involvement is suggested in patients with signs of central neurological disturbance or deficits in other cranial nerves, especially those that originate near, or follow paths similar to, the optic nerve (CN II). These include CN III (Oculomotor), CN IV (Trochlear), CN V (Trigeminal), CN VI (Abducens), and CN VII (Facial). Assessment of doll's eye response (III, IV, & VI), PLR (II & III), resting globe position (III, IV, & VI), and facial and corneal reflexes (V & VII) can be performed easily and rapidly in most patients. Space occupying lesions involving the optic nerve should be tested for by retropulsion of the globe within the orbit. The dazzle reflex is elicited by sudden stimulation of the eye with an extremely bright light source. The response is a rapid blink and sometimes averting head movement. This is a subcortical reflex and is perhaps more akin to a painful than a visual response. This reflex is mediated by the same pathways as those used for vision until immediately prior to the visual cortex. At this point, nerve fibers involved in the dazzle reflex enter the superior colliculi. It is therefore useful for differentiating cortical blindness (positive dazzle reflex) from blindness secondary to damage to any other part of the visual pathway which, if complete, will fail to elicit a dazzle reflex. Results of dazzle and palpebral reflexes, menace response, and vision testing with various lesions are summarized in Table 4.
Table 4. Expected neuro-ophthalmic test results with various lesions.
The swinging flashlight test is an underutilized but very valuable and easily performed clinical test that can further define the anatomic location of a lesion in the visual pathway. This test requires a darkened room so that iris excursions are maximal when stimulated by a bright, focal light. One eye is stimulated with the light source for 2-3 seconds before the light is rapidly swung to the opposite eye. The pupil of the stimulated eye should always constrict even though it will be partially constricted prior to direct stimulation. Pupil dilation in response to the light being swung into that eye is considered a positive swinging flashlight test (sometimes referred to as a "Marcus-Gunn" sign) and is abnormal. A positive swinging flashlight test is pathognomonic for a unilateral prechiasmal neurological lesion on the side in which the inappropriate pupil dilation is noted. Prechiasmal refers to any part of the optic nerve anterior to the chiasm and includes the retina. Blindness due to a lesion caudal to the optic chiasm causes a negative swinging flashlight response (normal pupil constriction). Specific Disease Processes Involving the Fundus
RETINAL DETACHMENT
Retinal detachments are likely to occur via one of three mechanisms:
Treatment of rhegmatogenous or traction detachments requires referral to a veterinary ophthalmologist who is performing surgical correction, however treatment of exudative/transudative detachments may be possible in general practice. The most common causes for exudative/transudative detachments are:
Suspicion of retinal detachment should be heightened if any of the following are noted:
HYPERTENSIVE RETINOPATHY
Ocular pathology secondary to elevated systemic blood pressure is being recognized with increasing frequency. The syndrome is seen most frequently in older cats where it may be primary or secondary to renal disease, hyperthyroidism, and other systemic diseases. Dogs are affected less commonly. Posterior segment changes include retinal edema, increased prominence or tortuosity of the retinal, retinal hemorrhage, and retinal detachment. Anterior segment changes such as iridal aneurysms or hyphema are also seen. Systolic blood pressure (BP) > 160mmHg appears to be associated with retinal pathology. Serial measurements may be necessary to detect hypertension in some animals. Concurrent assessment of renal and thyroid function is recommended. The first choice for treatment of feline hypertension is the calcium channel-blocking drug - amlodipine (Norvasc®). Therapy can be initiated at 0.625mg PO SID for an adult cat. BP and ocular findings should be reassessed in 1 week. If there is insufficient reduction in BP at this point, if ocular lesions are failing to resolve, and if signs of toxicity (anorexia, hypotension, etc) have not been observed, the dose may be increased to 1.25mg PO SID. Addition of drugs that lower BP via alternative mechanisms such as ?-blockers or ACE-inhibitors may be necessary if monotherapy with amlodipine is not successful. Concurrent management of renal disease or hyperthyroidism will greatly assist in resolution of hypertensive retinopathy and restoration of vision. Even when primary hypertension is suspected, re-assessment of BUN, creatinine, and urinalysis as blood pressure is lowered may reveal previously occult renal dysfunction. PROGRESSIVE RETINAL ATROPHY (PRA)
PRA is a collective term for a series of degenerative retinal diseases that share a number of characteristics. PRA is seen infrequently in cats, but is common in purebred dogs. The funduscopic appearance is similar in both species. PRA has now been reported in almost all canine breeds and in a number of feline breeds (including Persians, Siamese, and Abyssinians) where it is believed to be inherited as an autosomal recessive trait. The degenerative process begins after retinal maturation is complete, typically in young to middle-aged animals. The first clinical evidence in dogs is usually nyctalopia (night blindness) due to early rod photoreceptor degeneration. The PLR's may well be normal at this stage, especially when stimulated by a bright light source, however, some owners present dogs for altered ocular appearance due to wide pupil dilation. Later involvement of cones causes loss of day vision (hemeralopia). Although the pathogenesis of the photoreceptor degeneration appears similar in cats, many cats presumably "disguise" the early phases of disease from their owners. As a result, they are presented once they begin to lose vision in brighter ambient light and have relatively advanced funduscopic changes. No ocular inflammation is seen with this process in either species and treatment is not possible. The most common associated pathology is cataract formation. Observation that the cataract begins in the posterior lens cortex has led to the suggestion that diffusible toxins resulting from retinal degradation are responsible for cataractogenesis. Diagnosis is suggested by signalment and confirmed with maze testing in dim and then bright ambient light, and fundic examination. Usually by the time nyctalopia is noted by owners, there are substantial and diagnostic changes visible funduscopically. These include tapetal hyper-reflectivity and vascular attenuation (due to retinal atrophy), irregular, mottled changes in RPE pigmentation that lend a somewhat mosaic appearance to the non-tapetal fundus, and terminally pallor and reduction in size of the ONH (atrophy). Electrodiagnostic confirmation may be necessary when disease is slowly progressive or where veterinary attention is sought early in the disease process by an attentive owner. No treatment is possible, but due to gradual onset of blindness, patients usually adjust very well. Patients with cataracts should be monitored for lens-induced uveitis and treated medically if this is noted. Clearly, cataract surgery is not helpful in these patients. Two books that may assist some owners to adjust to their pet's blindness have been published recently: "Living with Blind Dogs" (ISBN 0-9672253-0-2) and "Blind dogs' Stories: Tales of Triumph, Humor, and Heroism" (ISBN 0-9672253-1-0). http://petcarebooks.com/ (503) 631-3491 Also consider referring owners to a website set up just for owners of blind dogs: http://www.blinddogs.com/ SUDDEN ACQUIRED RETINAL DEGENERATION (SARD)
Sudden acquired retinal degeneration is probably the second most common retinal degeneration in dogs. It has not been reported in cats. Affected dogs tend to be middle-aged or older. Females may be over-represented and many patients seem to be overweight. They are presented for peracute visual loss without signs of inflammation. Clinical examination usually reveals normal PLR's and no observable fundic abnormalities. Non-specific signs of retinal degeneration identical to those seen in PRA are first observed 4-8 weeks after onset of blindness. Occasionally dogs will simultaneously demonstrate signs of canine Cushing's syndrome including PU/PD, polyphagia, weight gain, and panting. Some of these patients will also have biochemistry, urinalysis, and endocrine changes that are supportive of the diagnosis. These clinical signs and biochemical changes usually resolve spontaneously in a short period and do not warrant treatment. Acute vision loss with normal PLR's is also consistent with a diagnosis of cortical blindness and for this reason, some owners will choose to verify the diagnosis. This is done most simply with an electroretinogram that will be extinguished in SARD but normal in cortical blindness. No treatment is possible. OPTIC NEURITIS AND PAPILLEDEMA
Inflammation of the optic nerve can occur alone or in association with more generalized CNS disease, increased CSF pressure, and/or chorioretinitis. Papilledema describes edema of the optic nerve without other discernible signs of inflammation. Vision is normal. On fundic examination the optic nerve appears to "bulge" into the vitreous and it is difficult to maintain the optic nerve and retina in focus simultaneously. Optic neuritis describes more marked inflammatory infiltration and/or hemorrhage involving the optic nerve. These patients are blind. Unless there is coexistent chorioretinitis, ocular inflammation may be minor. Common causes of inflammation include infectious organisms (particularly Cryptococcus), GME and other idiopathic immune-mediated diseases, and rarely neoplasia. Increased CSF pressure causes papilledema only. The standard diagnostic approach includes:
FELINE CENTRAL RETINAL DEGENERATION
Feline central retinal degeneration (FRCD) describes a slowly progressive retinal degeneration affecting first the area centralis (an area rich in cone photoreceptors and ganglion cells just temporal to the ONH). The disease is seen in cats whose diet is deficient in taurine, however many cats who present with identical clinical signs have no evidence of current or prior taurine deficiency. Five stages have been characterized: Stage 1: Increased granularity of the area centralis Stage 2: Ellipsoidal hyper-reflective lesion at the same site Stage 3: Appearance of a second hyper-reflective area opposite the first (on the nasal side of the ONH) Stage 4: Coalescence of the two zones to form a horizontal band superior to the ONH. Stage 5: Total generalized, retinal degeneration (indistinguishable from other advanced retinal degenerations). This is likely to occur about 9 months after onset of taurine deficiency. Ophthalmoscopic signs become apparent approximately 3-7 months after introduction of a taurine deficient diet. Cats displaying these signs should be assessed for taurine deficiency. Correction of dietary taurine intake will prevent further progression of the disease, however ophthalmoscopic changes are permanent. Taurine deficiency has also been associated with cardiomyopathy; therefore investigation of concurrent cardiac disease should be undertaken. ENROFLOXACIN-ASSOCIATED RETINAL DEGENERATION
Recently, a number of cats have been noted to undergo rapid, complete and usually irreversible retinal degeneration while being administered enrofloxacin for a variety of conditions. Typically, cats are presented for rapid vision loss and are noted to have widely dilated pupils. No age, breed, or sex predilection has been determined and no consistent underlying condition (for which the enrofloxacin was prescribed) has been identified. The single and cumulative doses of enrofloxacin incriminated and the duration of therapy prior to onset of blindness range widely. In a published retrospective series, one cat received < 5mg/kg once daily for 8 days prior to the onset of signs. Perhaps the most striking feature of this disease is the rapidity with which ophthalmoscopic changes occur. In some cases retinal degeneration is advanced at the time of presentation; sometimes within days of starting the drug. One of the apparently early signs of toxicity is mydriasis in some animals. Typical signs of retinal degeneration including marked hyper-reflectivity and attenuation of retinal blood vessels are noted; sometimes in association with mottling of the non-tapetal fundus. No evidence of pain or inflammation is noted and no treatment is possible (other than cessation of the drug). The extent to which vision is regained in these cases seems highly variable but is usually minimal. As usual, the cat does everything possible to confuse us about its visual recovery by adapting superbly to diminished vision! The manufacturer (Bayer) is aware of the problem and has worked promptly and responsibly with the FDA to ensure proper communication about, and investigation of this problem. They have conducted initial studies to investigate the association. These preliminary studies confirmed retinal toxicity at doses of 20 mg/kg and greater. This led to their recommendation that the feline dose be reduced to 5 mg/kg PO q24 hours. This may be best divided so as 2.5 mg/kg is provided BID. As always, it is prudent to restrict the use of enrofloxacin in cats to those cases in which culture or experience suggests it is indicated. It is essential that no cat receives a prescribed dose greater than 5mg/kg daily. Please note also that the parenteral preparation of Baytril is NOT licensed for use in cats. Finally, it is essential that suspected new cases be reported to the relevant authorities. Bayer themselves continue to thoroughly investigate all cases and to transmit this information to the federal authorities Online reporting (of all adverse drug reactions, not just those relating to Baytril in cats) is available by contacting the Center for Veterinary Medicine, Food and Drug Administration at the web address: www.fda.gov/cvm/contactcvm/contactCVM.html and following a link for "Report a Drug Reaction". You can also submit an adverse drug reaction to the Center for Veterinary Medicine by telephoning 1-888-332-8387.The report that you fill in here will also reach the FDA and the drug company involved. |
