Retinal Disease, Degeneration And Diagnosis Nicholas J. Millichamp, BVetMed, PhD, DVOphthal, MRCVS, Diplomate, ACVO. Dept of Small Animal Medicine and Surgery College of Veterinary Medicine, Texas A & M University College Station, TX. & Central Texas Veterinary Ophthalmology Austin, TX. Diseases of the posterior segment or vitreous, retina, choroids, sclera and optic nerve (the fundus as seen through the pupil of the eye) are often poorly understood.� Since many (especially the degenerations) have hitherto defied therapy, they assume a lesser significance than diseases of the anterior segment which are often more amenable to therapy in general practice.� Nevertheless recognition of the cardinal signs of posterior segment disease can easily be mastered (using indirect ophthalmoscopy) and may give insights into conditions affecting vision or associated with other systemic maladies. In considering the fundus we need to think of a number of superimposed layers of tissue (vitreous through sclera).� Unlike almost any other tissue of the body (excepting the superficial skin layers), ophthalmoscopy allows examination of the layered tissues in detail.� In general we need to keep in mind the concept of �more or less�.� In inflammatory or neoplastic diseases the layered structures become thickened (�more�) with infiltrates into one layer affecting the view of underlying structures.� In degeneration we may see changes in appearance of a particular layer based on loss of tissue in an overlying tissue layer (�less�). �We are fortunate that our domestic species possess a tapetal layer since this makes the recognition of these pathologic processes much simpler than in atapetal species. Inflammation:� Chorioretinitis, optic neuritis, retinal detachment. Lesions of the fundus consistent with inflammation and secondary neoplasia (primary neoplasia of posterior segment is rare) appear in the tapetal fundus as dark or gray (often fuzzy or out of focus) areas of opacification, which obstruct the view of the tapetum.� Infiltrates (inflammatory cells, edema, neoplastic cells) may be in the vitreous, retina or between retina and retinal pigment epithelium, or located in the choroid (and hence tapetum itself).� Small focal thickening of the retina may appear similar to thickening of the retina due to folding as seen in retina dysplasia. Retinal blood vessels may be elevated or obscured by infiltrates.� Perivascular cuffing with light cellular infiltrates is well seen in the non-tapetal fundus.� Hemorrhages may occur (especially vasculopathies like FIP, coagulathies like rickettsial disease or associated with retinal ischemia in systemic hypertension).� Sufficient subretinal exudates or transudates will cause retinal elevation and detachment (occasionally see gray veil of retina and vessels against posterior lens as leukocoria). Signs of retinal inflammation/neoplasia/hypertension/ detachment. •   Asymmetrical, irregular lesions •   Grey/dark often fuzzy opacities over the tapetum •   Tapetal color change •   Non-tapetal white/gray opacities (edema) •   Non-tapetal pigmentary changes •   Perivascular cuffing in non-tapetum •   Hemorrhage (pre-, intra- and subretinal) •   Retinal elevation/detachment (leukocoria) •   Edema/hemorrhage of the optic nerve Changes of inflammatory nature must be distinguished from various inherited diseases, which may present with similar signs.� Retinal dysplasia in several canine breeds (usually but not always present from birth) results in retinal folding, which may resemble multifocal areas of retinal edema.� In severe cases retinal non-attachment or detachment may occur.� Collie eye anomaly presents with congenital pigmentary changes in the fundus lateral to the optic disc.� Additionally in more severely affected dogs colobomas of the optic nerve and retinal folding may result in retinal detachments and intraocular hemorrhage. The causes of chorioretinitis largely parallel those, which were discussed in consideration of anterior uveitis.� Infectious, immune mediated causes and neoplasms (usually metastatic) are commonly involved.� As with anterior uveitis the presence of bilateral lesions sharply increases the suspicion of underlying systemic disease.� Workup involves a thorough� physical and ocular examination, minimum database, serology and/or PCR for infectious diseases, chest/abdominal radiographs and ultrasound, neurological examination, blood pressure measurement and aspirates or biopsies from other affected tissues.� Ultrasonography of the posterior segment is useful where opacities of the anterior segment media or lens obscure a view of the fundus.� Aspirates from the posterior segment should be a last resort. A specific retinopathy commonly seen in older cats is hypertensive retinopathy, which may occur secondary to hyperthyroidism, chronic renal failure, and adrenal neoplasia or occur as primary disease.� Cats typically present with a sudden onset of blindness accompanied by dilated non-responsive pupils.� The retinas are often totally detached and hemorrhage is common. Therapy of inflammatory type posterior segment disease should aim to treat the underlying cause wherever possible (e.g. in rickettsial, fungal or protozoal disease� in dogs and cats.� In some noninfectious conditions (particularly systemic hypertension in cats) medical therapy may be indicated to treat underlying systemic disease (hyperthyroidism, chronic renal failure) as well as specifically reduce the ocular changes (reducing systemic blood pressure with calcium channel blockers, beta-blockers and� ACE inhibitors).� When all� diagnostic tests have failed to reveal the presence of infectious agents or other underlying diseases systemic corticosteroids at an immunosuppressive dose and other anti-inflammatory drugs (including cytotoxic agents such as azathioprine) are indicated to treat idiopathic chorioretinitis (assumed to be specific immune mediated retinal inflammatory diseases (uveodermatologic syndrome and immune mediated thrombocytopenia in dogs).� Neoplasia affecting the posterior segment (lymphoma is perhaps the most common) is rarely amenable to effective long-term therapy. Retinal detachments may occur in dogs and less commonly in cats which are unassociated with obvious inflammatory disease.� In dogs various inherited congenital diseases (vitreoretinal dysplasia and collie eye anomaly) may predispose the retina to� detachment.� Some breeds (for instance the Bichon Frise) appear to be prone to retinal dialysis (disinsertion of the retina at the ora ciliaris retinae) and detachment.� Cataract progression � particularly to the hypermature stage and/or cataract surgery are well known� predisposing factors in the development of� retinal tears and rhegmatogenous detachments (where the vitreous passes through a retinal tear and contributes to pushing the retina from the back of the eye.� In some of these cases the extent of detachment can be limited (if caught early enough) by spot-welding (or creating a retinopexy) the retina to the underlying retinal pigment epithelium with an argon or diode laser.� In more severe detachments it may be possible to perform scleral buckling or vitreoretinal surgery to repair the detachment.� However often the detachments are severe enough once detected behaviorally by the owner that the prognosis for therapy is poor. Retinal degenerations In retinal degeneration the lesions vary in appearance depending on location in the tapetal or non-tapetal fundus.� Degenerative lesions in the tapetal fundus result in thinning of the retina over the underlying tapetum.� There is consequently a greater amount of light reflected back to the observer (less absorbed in the thinned retina) •   Hyper-reflectivity over the tapetal fundus. •   This may be localized and asymmetric �often with development of increased pigmentation in areas of� inactive chorioretinitis.� Hyperreflectivity is generally bilaterally symmetrical and� more diffuse in cases of inherited retinal degeneration (progressive retinal atrophy) or toxic retinal atrophy. •   Depigmentation and pigment clumping in the non-tapetal fundus (may be localized (post-inflammation) or diffuse� (inherited. toxic) •   Narrowing of retinal blood vessels •   Atrophy of the optic nerve may accompany later stages of severe and often inherited retinal degenerations. Various retinal degenerations occur in dogs and cats.� Focal and diffuse degeneration may occur secondary to chorioretinitis and glaucoma respectively.� The most important degenerations resulting in the loss of vision in the absence of other ocular signs fall into one of three categories: •   Inherited � progressive retinal atrophy in dogs and cats •   Idiopathic � sudden acquired retinal degeneration in dogs •   Toxic/nutritional � enrofloxacin toxicity and taurine deficiency in cats. Progressive retinal atrophy Progressive retinal atrophy is a term used to encompass a large groups of inherited degenerative diseases in many canine and some feline pure and crossbreeds.� Most of these conditions are inherited as autosomal recessive conditions (excepting X-linked PRA in the Siberian Husky and Samoyed and dominant PRA in the Mastiff).� In Abyssinian cats both recessive and dominant forms of PRA occur.� The biochemical abnormalities are understood in few of these diseases.� The diagnosis of progressive retinal atrophy is based (currently) on behavioral signs (especially night blindness) and the presence of the typical lesions described above. Clinically we broadly divide PRA into early and late onset forms depending on whether the signs develop in the first year of life or later in life.� The electroretinogram (if stimulated correctly) may be useful in early diagnosis and in understanding the pathophysiology of the disease.� More recently genetic testing of whole blood samples or frozen semen has become available.� Optigen (www.optigen.com) based in Ithaca, NY has produced tests for Congenital Stationary Night Blindness in Briards and PRA (various types and genotypes) in various canine breeds (Table 1).� The tests used in most of these breeds are marker-based or linkage-based tests which will reliably identify homozygous normal dogs.� Since most are recessive diseases a proportion of the tested dogs are found to be carriers (but will not become affected with the disease themselves and a proportion are homozygous affected dogs which will develop the disease). Table 1. Tests for inherited retinal diseases in dogs available from Optigen in June 2001. Briard Cardigan Welsh Corgi Chesapeake Bay Retriever English Cocker Spaniel Irish Setter Labrador Retriever Mastiff Miniature Schnauzer Poodle Portuguese Water Dog Samoyed Siberian Husky Sloughies The tests used in some breeds (e.g. Irish Setter, Samoyed and Siberian Huskies are mutation-based testswhich more accurately identify normal, carrier and affected dogs. PRA varies considerably in its clinical appearance between and even within breeds.� More than one genetic form of PRA occurs in some breeds (for instance poodles and miniature schnauzers) which complicates the genetic testing picture at present.� Genetic diagnosis promises to facilitate eradication of inherited retinal diseases by enabling a diagnosis at a much earlier age than currently possible clinically or by electroretinography. Sudden Acquired Retinal Degeneration (SARD) SARD is a canine disease of unknown etiology.� The presenting sign is a rapid onset of blindness (often over a few days).� Usually at examination the animal is totally blind although the PLR may be present.� The fundus (and actually the entire eye) initially looks normal in most� (but not all) cases.� The differential diagnosis includes optic neuritis (for instance in GME), pituitary tumor or CNS blindness (related to neoplasia).� SARD is easily differentiated from these other conditions with an electroretinogram which is extinguished in SARD but normal in the other conditions which do not involve the retina.� We know of no way to prevent this disease at present and there is no therapy. Retinal degenerations in cats (taurine, PRA, enrofloxacin) PRA also occurs in cats � the biochemical defect in one form of PRA in Abyssinian cats is the same as in Irish Setters.� Late and early onset forms of PRA have been reported in the Abyssinian.� PRA also occur in Persians and sporadically has been reported in other breeds.� The clinical appearance is similar to dogs, although cats will often compensate behaviorally to a� much greater extent than dogs. Nutritional deficiency of taurine results in feline central retinal degeneration (FCRD) with typical band like lesions of tapetal hyperreflectivity in the central retina above the level of the optic disc.� With progression of the disease the entire fundus becomes affected and is then indistinguishable from any other causes of� diffuse retinal degeneration.� Affected cats should be monitored for dilated cardiomyopathy.� FCRD is seen less commonly in recent years since supplementation of feline diets with taurine. Enrofloxacin has recently been associated with retinal degeneration in cats at the recommended dose rate.� Affected cats present with rapid onset of blindness after systemic enrofloxacin administration.� Affected cats have typical lesions of retinal degeneration.� Discontinuation of enrofloxacin as soon as visual problems are noted may result in improvement in vision in some, but not all cases.� No doubt guidelines will be forthcoming regarding the use of enrofloxacin in cats in view of increasing numbers of anecdotal adverse reaction reports as well as published data or its potential toxicity. Further Reading      Narfstrom, K, Ekesten, B: Diseases of the canine ocular fundus.� In:� Veterinary Ophthalmology, ed, Gelatt, KN, 1999 (3rd ed).� Baltimore, Lippincott, Williams and Wilkins. 869-933      Barnett, KC and Crispin SM: Feline Ophthalmology, An Atlas and Text 1998, London, W.B.Saunders Company.      Glaze, MB, Gelatt, KN:� Feline Ophthalmology.� In:� Veterinary Ophthalmology, ed, Gelatt, KN, 1999 (3rd ed).� Baltimore, Lippincott, Williams and Wilkins. 997-1052