The red eye: diagnostics and treatment (Proceedings)

The "red eye" may present for many different reasons. Periocular trauma, conjunctival hyperemia, corneal vascularization, intraocular hemorrhage, and detached subalbinotic retinas may all lead to the complaint of a "red eye". Examination of the eye should lead to localization of the abnormality and standard ophthalmic testing should be performed, including schirmer tear tests, fluorescein staining, and intraocular pressures. If cytology and/or culture and sensitivity need to be submitted this should be done prior to instillation of topical fluorescein.

Most red eyes are associated with uveitis and intraocular hemorrhage. This involves deterioration of the blood:ocular barrier resulting in leaky blood vessels and extravasation of red blood cells, white blood cells, and proteins. The cause of the uveitis may be systemic or ocular only. Chronic ocular conditions such as glaucoma, cataract formation, retinal detachment, neoplasia, or post-surgical uveitis may lead to the development of pre-iridal fibrovascular membranes (PIFM's); PIFM formation is associated with chronic intraocular hypoxia and may predispose to hemorrhage. Trauma leading to uveitis may be blunt and compressive in nature or involve entry into the eye by puncture or laceration. Additionally, there are many inherited and congenital ocular syndromes that may lead to hemorrhage, such as persistent hyperplastic primary vitreous in Doberman Pinschers and Collie Eye Anomaly in Collies and Australian Shepherds. Determining the etiology will allow the best and most specific treatment. In addition to the above standard diagnostic testing blood pressures, complete physical examination, submission of bloodwork and urinalysis, ocular ultrasound, electroretinogram, MRI or CT, centesis, retrobulbar aspirates, and biopsies may be part of the diagnostic plan. When I evaluate a case, consultation with other specialists may ensue if the diagnosis is considered to be an ocular manifestation of systemic disease.

When chronic uveitis and hemorrhage secondary to an ocular condition are present therapy may involve both medical and surgical treatment. If chronic glaucoma is the issue, performing an enucleation or intrascleral prosthesis placement will relieve the pain for the patient as well the hemorrhage. Similarly, retinal detachments may respond to treatment for uveitis but surgery may be an option as well. If the retinal detachment is rhegmatogenous and recent, retinal reattachment surgery may also be performed to address the hemorrhage. Hemorrhage secondary to cataract formation may require aggressive treatment with anti-inflammatories, cataract surgery as soon as possible if the eye is visual, or enucleation or intrascleral prosthesis placement if the eye is nonvisual and painful. Neoplasia associated with hemorrhage usually leads to the recommendation for enucleation. An exception to this would be lymphoma; some of these cases respond to aggressive treatment with anti-inflammatories and immunosuppressive chemotherapeutics. Post-surgical inflammation and bleeding usually necessitates an increased schedule of anti-inflammatories, possible irrigation of the anterior chamber, injection of triamcinolone or betamethasone subconjunctivally or intravitreally. Tissue plasminogen activator (TPA) may also be injected intracamerally to address uveitis once active bleeding is controlled.

Blunt and penetrating trauma may require surgical repair. If corneal trauma is present as well as hemorrhage, but no obvious periocular or blunt trauma, a radiograph of the head should be performed as gunshot wounds may create corneal rupture and hemorrhage without any other abnormalities. Lavage of the intraocular hemorrhage may be helpful in some situations to prevent adhesions and sequelae such as glaucoma. However, there is a significant risk that bleeding may recur once the clots are disrupted. The canine eye unfortunately responds to any insult with significantly more inflammation than the human eye and trauma that may not be blinding to a person may result in blindness and painful sequelae for a dog. Cats have more stable blood:ocular barriers and are more tolerant of chronic uveitis and acute inflammation. If the cornea or sclera has been lacerated the laceration should be cultured and surgically repaired. Usually 9-0 vicryl is recommended for repair and creates the least scarring; the repair is done under the operating microscope. Adjunctive conjunctival grafting may be required if the cornea or sclera has a large deficit. If the lens capsule has been disrupted adjunctive cataract surgery may be required at the same time or the cornea repaired and the lens surgery planned for the future; there may be advantages to trying control the uveitis prior to lens surgery. Generally, if the lens capsule rupture is greater than 2 mm there is a risk for the development of severe phacoclastic uveitis. I have treated lacerations with both medical and/or surgical therapy; I had a case which seemed stable with medical treatment, but in which very severe phacoclastic uveitis developed 4 months after the injury requiring immediate cataract surgery. Many cases of lens capsule rupture develop a focal cataract and posterior synechiation but seem fairly stable on long term anti-inflammatory therapy; this is a necessity though and good client education is very important for ensuring the patient stays on anti-inflammatories. Medical treatment post-surgically or as primary treatment for lens trauma should be both topical and systemic. Topical 1% prednisolone acetate q 2-6 hrs and oral prednisone at 0.5 mg/lb divided b.i.d. are my general dosages. Adjunctive subconjunctival and intracameral injections of steroids may also be administered; I typically use 5 mg triamcinolone subconjunctivally. Topical and oral antibiotics are also recommended if infection could be a complication. Additionally, glaucoma medications, usually avoiding prostaglandin analogues, as they may increase uveitis, are also dispensed if uveitic glaucoma or glaucoma secondary to the formation of intraocular adhesions and traction bands is a possibility. If corneal health is compromised topical anti-inflammatory meds may not be used as frequently or eliminated. Lastly, pain medication is dispensed; oral buprenorphine is my drug of choice for cats and either Tramadol or codeine for dogs.

Many cases of intraocular hemorrhage are ocular manifestations of systemic disease. Hypertension is a frequent reason for referral and once the diagnosis is established treatment of the uveitis with prednisolone acetate as described above; low dose oral steroids are also dispensed. I usually use 0.25 mg/lb s.i.d. or divided b.i.d. Calcium channel blockers, such as amlodipine and ACE inhibitors are drugs of choice. Blood pressure, general blood work and urinalysis, especially urine protein, should be monitored. If a cardiac etiology is suspected, assessment by a cardiologist is recommended. Oral and topical NSAIDS are generally not utilized since they may exacerbate renal disease and lead to vascular fragility that may increase hemorrhage. Intraocular pressure should also be monitored as secondary glaucoma is a risk. Ophthalmic exam usually reveals serous retinal detachments with dot or flame hemorrhages and tortuous retinal vasculature. Hemorrhages may take significantly longer to resolve, even when retinal reattachment occurs quickly. Overall, prognosis for vision is good if the retinas have recently detached. Cats are seen more frequently than dogs, however treatment and prognosis is the same for both. Even when vision returns once the retinas reattach, significant retinal degeneration will be present on examination. Lack of PLR on initial exam is consistent with a poorer prognosis.

Other systemic causes of hemorrhage include infectious and metabolic causes of uveitis. Thrombocytopenia may lead to ocular changes. Infectious disease, neoplasia, drug-induced reactions, and immune-mediated disease are all common etiologies. Infectious diseases include arthropod-borne organisms: Babesia, Borrelia, Cytauxzoon, Dirofilaria, Ehrlichia spp., Leishmania, Rickettsia, etc.; viruses, including canine distemper virus, herpesvirus, parvovirus, adenovirus; fungal and bacterial organisms, including Candida, Histoplasma, Leptospira spp., etc. Neoplastic etiologies include lymphoma, leukemia, and multiple myeloma. Medications that impair platelet production or lead to platelet destruction include chloramphenicol, azathioprine, cyclophosphamide, doxorubicin, etc. Thrombocytopenia may present as both periocular and intraocular hemorrhage and petechiation. Therapy is directed at the underlying cause. Topical prenisolone acetate is used to address uveitis; topical tropicamide or atropine may also be utilized depending on the degree of uveitis.

Other hematologic diseases with possible ocular involvement include anemia, hyperlipidemia, hyperviscosity syndrome, and polycytemia. Anemia may be associated with pale retinal vasculature and retinal hemorrhages. The pathogenesis of the hemorrhages may be from vessel wall hypoxia resulting from the anemia. In cats, FeLV infection may be associated with anemia and retinal hemorrhages. Mycoplasma haemofelis infection may also lead to anemia in cats. Hyperviscosity syndrome and polycythemia may lead to retinal detachments, hemorrhage and uveitis. Treatment is described in many internal medicine texts.

In this area of the country rickettsial diseases may be commonly associated with ocular signs. Canine cyclic thrombocytopenia is caused by Anaplasma platys, a bacterial organism that replicates in platelets. Ophthalmologically, uveitis, including hemorrhage, that is responsive to topical corticosteroids ± atropine may be noted. Oral treatment consists of doxycycline to eliminate the bacteria. Canine ehrlichiosis is a tick-borne disease produced by multiple species (Ehrlichia canis, E. chaffeensis, E. ewingii, E. equii, Anaplasma platys, A. phagocytophila, and Neorickettsia risticii). Clinically, an acute phase, a subclinical phase, and a chronic phase are noted. Different studies report a range in prevalence of ocular lesions from 10-37%. The ocular lesions are a result of decreased platelet numbers or from vasculitis. Treatment includes doxycycline to address the etiologic agent and oral and topical steroids to address the uveitis. Atropine may also be utilized if anterior uveitis is present. Rocky Mountain Spotted Fever is caused by Rickettsia rickettsia, another tick-borne organism. Ocular signs include conjunctivitis, chemosis, petechiation of the conjunctiva, iris, and retina, hyphema, anterior uveitis, retinal edema and vasculitis. Treatment for the ocular signs consists of topical anti-inflammatories ± atropine.

Bartonella spp. bacteria may cause ocular signs in cats. Cats may be infected with several different species; B. hensalae, B. clarridgeiae, B. elizabethae, B. koehlerae, and B. weissii have been isolated in cats. Uveitis, blepharitis, conjunctivitis, keratitis, and chorioretinitis may occur. Treatment with doxycycline or azithromycin is effective.

Canine distemper virus may cause conjunctivitis with serous to mucopurulent discharge. The virus may be associated with keratoconjunctivitis sicca via an inflammatory reaction of lacrimal gland tissue. Keratitis and corneal ulceration may be associated with the change in tear production. Chorioretinitis and optic neuritis leading to blindness occur as well. Treatment is mainly symptomatic and supportive in the form of topical lubricants and antibiotics. Prednisone in anti-inflammatory doses is used to treat the optic neuritis.

The feline corona virus may lead to feline infectious peritonitis (FIP) that has ocular manifestations. The most common sign is bilateral granulomatous anterior uveitis. Fibrin and keratic precipitates may be present in the anterior segment and chorioretinitis and retinal vessel cuffing in the posterior segment. Retinal hemorrhages, detachments and optic neuritis may also occur. Treatment for both the ocular manifestations as well as the primary disease is symptomatic. Ocular treatment consists of topical, subconjunctival, and systemic steroidal and non-steroidal anti-inflammatories. Atropine may also be utilized for the uveitis, as well as glaucoma medications for secondary glaucoma.

Feline immunodeficiency virus (FIV) and the feline leukemia virus (FeLV) may both cause ocular manifestations. Anterior uveitis and conjunctivitis occur most frequently with FIV. Pars planitis may also occur leading to posterior lens capsule white precipitates and anterior vitreal precipitates. Treatment for FIV is symptomatic consisting of topical anti-inflammatories. Oral prednisone and atropine may be also be utilized as needed. The anterior uveitis is easier to control than the pars planitis. FeLV may cause anisocoria and spastic pupil syndrome associated with viral effects on the ciliary ganglion and short ciliary nerves. In utero infection with FeLV may lead to retinal dysplasia and diffuse uveitis. The most dramatic effect of FeLV occurs with its association with lymphosarcoma. The uveal tract is a common site for spread of lymphocytes and this leads uveitis. Treatment of the primary disease and use of topical anti-inflammatories may help to control the uveitis. As the disease progresses glaucoma medications may need to be instituted.

Toxoplasma gondii may infect both dogs and cats leading to ocular manifestations. Although cats are the definitive host, dogs and other mammals may act as intermediate hosts. Cats are affected more frequently with ocular manifestations. In dogs ocular signs included mononuclear anterior uveitis, retinitis, choroiditis, extraocular myositis, scleritis, and optic neuritis. In cats chorioretinitis with hemorrhage is the most common ocular manifestation. Although T. gondii does not usually cause systemic disease in dogs and cats, it is a significant cause of ocular lesions in otherwise healthy dogs and cats. It should be on the differential list for uveitis regardless of systemic signs. Treatment consists of oral anti-inflammatories, ± atropine and oral clindamycin at recommended dosages.

Fungal diseases may affect both dogs and cats, however are not as common in the midatlantic area as in other parts of the country. Aspergillosis, blastomycosis, histoplasmosis, and cryptococcosis have been diagnosed. Coccidioidomycosis is usually found in the southwest. Aspergillosis results in panuveitis, chorioretinitis, exudative retinal detachments and endophthalmitis. Treatment for the uveitis is symptomatic, utilizing topical anti-inflammatories. Systemic treatment consists of long term administration of amphotericin B, itraconazole, or fluconazole. Overall prognosis is poor. Blastomycosis results from infection by Blastomyces dermatitidis. Cats are not as commonly affected. Young intact male dogs represent a higher risk group. Ocular involvement in dogs occurs in 48% of cases and 50% of the lesions are bilateral. Ocular signs have been the only lesion present in 3% of cases. The initial lesion is often pyogranulomatous choroiditis resulting in anterior uveal inflammation. Retinal and subretinal granulomas develop which progress to exudative retinal detachments. Optic neuritis, retinal and vitreal hemorrhages and orbital cellulitis may also occur. Itraconazole is currently the treatment of choice and prognosis is associated with the degree of pulmonary involvement at the onset of treatment. Topical treatment is as for other uveitides. Up to 80% of dogs may be cured. Histoplasma capsulatum causes ocular signs in 66% of infected dogs. Lesions are observed in the anterior choroid, iris, ciliary body, and sclera. The choroid is the most commonly affected ocular tissue. Posterior segment lesions are similar to other fungal diseases. Treatment is difficult with poor response to antifungal therapy in dogs that have progressed to ocular lesions. Cryptococcosis is less common in dogs than cats. In dogs the most common lesion is granulomatous to pyogranulomatous chorioretinitis. Retinal hemorrhage may be present, as well as mild anterior uveitis. In cats C. neoformans is most commonly reported. Chorioretinitis with granulomatous inflammation and retinal detachments, anterior uveitis, exophthalmos and optic neuritis may occur. Diagnosis may be made based on organisms in vitreal or subretinal fluid aspiration. Fluconazole in combination with amphotericin B is the treatment of choice in dogs. Cats respond better to itraconazole. The prognosis is guarded in dogs due to the frequency of CNS involvement. Cats may be treated successfully but treatment is generally long term.

Treatment of congenital disorders with topical and oral steroids is recommended, as previously described. Dogs with PHPV that is severe may be treated prior to hemorrhage by cataract surgery and excision of the retrolental plaque. The persistent hyaloid vessel is cauterized to prevent hemorrhage. Although frequently successful the owner should be aware that hemorrhage is a potential complication of treatment.

References

1. Veterinary Ophthalmology, 4th ed., Gelatt KN, editor, Blackwell Publishing, Ames IA 2007.

2. Ophthalmic Disease in Veterinary Medicine, Martin CL, Manson Publishing, 2005.