Ocular Manifestations of Systemic Disease

Neonatal Septicemia

Neonatal septicemia in calves, foals, lambs, and kids may occur in the first few weeks after birth and may arise from umbilical infection or oral intake of bacteria.

■ Bovine Herpesvirus Type 1 (Infectious

Bovine Rhinotracheitis)

Etiology

Bovine herpesvirus type 1 (BHV-1) may involve the respiratory or reproductive tracts, nervous system, or conjunctiva or may cause widespread systemic disease (see also Chapter 31). Conjunctivitis is the most common ocular manifestation of the disease, and it may occur as an isolated clinical entity or with involvement of other body systems.^123-126

■ Clinical Signs and Differential Diagnoses Although conjunctivitis is frequently bilateral, it can be unilateral. Ocular discharge, initially serous and later becoming mucopurulent, is usually seen without blepharospasm. Chemosis may be severe, especially by 1 week after infection. Both the palpebral and the bulbar conjunctiva are injected, and petechial hemorrhages may occur.

Corneal changes of BHV-1 are differentiated from those of IBK (caused by Moraxella bovis) by their peripheral rather than central distribution and lack of corneal ulceration in BHV-1, unless BHV-1 and IBK occur concurrently in the same eye (see the Infectious Bovine Keratoconjunctivitis [IBK] section later). Corneal vascularization and opacification similar to that which occurs in malignant catarrhal fever accompanied by marked signs of anterior uveitis and other signs of generalized vasculitis has been reported occasionally.¹²⁷

Although ocular disease with BHV-1 may occur as an isolated entity, concurrent upper respiratory tract signs, including rhinitis and dyspnea, are common. Affected animals may be pyrexic, and a fall in milk yield may occur. Abortion in pregnant animals may occur following ocular manifestations of the disease.

Diagnostic Procedures BHV-1 can be recovered from infected eyes during the first 7 to 9 days of the disease but infrequently thereafter. Swabs may be taken for viral isolation in cell culture, which is probably the most reliable means of making a definitive diagnosis. Fluorescent antibody techniques may be used on conjunctival scrapings, and serology may be helpful if blood samples can be collected during the acute and convalescent stages of the disease. PCR is also being used. Histopathology to detect intranuclear inclusions is not likely to allow reliable diagnosis of the disease.^126,127

■ Pathophysiology Specific strains of the virus usually cause only one form of the disease (e.g., ocular form) in a herd. Ocular infection results in lymphoid hyperplasia, visible as white plaques.

■ Treatment and Prognosis Recovery from the con­junctival form of the disease is spontaneous within 10 to 20 days. In certain situations, palliative treatment may be helpful. This is achieved by cleaning the ocular discharge from the lids and applying a topical broad-spectrum antibiotic to prevent secondary bacterial infection. Treatment of the conjunctival form of the disease with topical antiviral agents has not been studied and would rarely be practical or cost-effective.

■ Prevention and Control Vaccination of susceptible animals is the most effective means to prevent and control the disease. BHV-1 vaccination programs are discussed in Chapter 48.

Bovine Herpesvirus Type 1 (Infectious Bovine Rhinotracheitis) in Goats

Goats are susceptible to BHV-1, which in some cases may result in ocular disease, particularly keratoconjunctivitis. In one goat with ocular signs, conjunctivitis and keratitis with keratoconus were seen 5 days after the onset of severe respira­tory illness. BHV-1 virus was isolated from ocular and nasal discharge.¹²⁸

Peste Des Petits Ruminants in Goats and Sheep

Peste des petits ruminants (PPR) is caused by a paramyxovirus of the Morbillivirus genus. This highly contagious disease affects both domestic and wild small ruminants and is characterized clinically by fever, diarrhea, depression, polypnea, conjunctivitis, lacrimation, rhinitis, erosive stomatitis, edema of eyelids, photophobia, cutaneous eruption with erythematous areas (especially noticeable in wool-free parts of the body and axilla), and lesions evolving into papules.^129,130 Ocular discharge is initially serous but becomes mucopurulent as secondary bacterial infections, which are common, develop.

Scrapie in Sheep and Goats

The scrapie agent causes a degenerative CNS disease in sheep and less often in goats. Barnett and Palmer¹³¹ described two sheep with scrapie that also had multifocal hyperreflective areas in the tapetum, histologically seen as small areas of retina raised by an accumulation of eosinophilic material between photoreceptors and retinal pigment epithelium. The eosinophilic material was characterized as a complex lipid. It was not shown that scrapie had caused the lesions.¹³¹ Subsequently, using a monoclonal antibody, a goat with natural scrapie was found to have the scrapie prion protein in the retina, without any microscopic retinal lesions.¹³² A sheep experimentally infected with scrapie was also found to have prion proteins in the retina,¹³³ as was a sheep experimentally infected with the prion responsible for bovine spongiform encephalopathy (BSE).¹³⁴ Prion proteins can also be found in the nictitating mem- brane,^134,135 which may permit the antemortem diagnosis of scrapie. (See Chapter 35 for more information on scrapie.)

Bluetongue in Sheep and Cattle

Bluetongue is a disease of ruminants caused by an arbovirus that is transmitted by Culicoides gnats. Clinical signs include fever and vasculitis that lead to oral lesions, lameness, swollen face, pulmonary edema, and death (see Chapter 32). In pregnant ewes vaccinated with modified live virus (MLV) on day 40 of gestation, fetuses developed cerebral anomalies.¹³⁶ These anomalies have also been described in clinical cases in which ewes had been vaccinated with MLV at about 5 or 6 weeks of gestation. In addition, when the fetus was vaccinated with MLV vaccine between days 50 and 75 of gestation, lesions of retinitis and choroiditis that appeared centered around retinal vessels were noted.

Conjunctivitis and mucopurulent ocular discharge may be seen in cattle chronically infected with bluetongue virus. Although topical antibiotics could be applied to reduce second­ary bacterial infection and reduce the ocular discharge, this would rarely be necessary.¹³⁸ Systemically ill or congenitally infected animals may have anterior uveitis and corneal edema as a result of this infection.¹³⁹

Bovine Viral Diarrhea

The causative agent, bovine viral diarrhea virus (BVDV), is in the genus Pestivirus, a member of family Flaviviridae that, in congenitally affected animals, causes retinal inflammation and necrosis. Cattle infected between days 75 and 150 of gestation may produce calves with cerebellar hypoplasia or ocular lesions. Calves with ocular signs may be blind, and nystagmus may be present. Pupillary light reflexes may or may not be absent. Other abnormalities may include microphthalmia, cataract, leukocoria (as a result of either cataract or dense white inflammatory infiltrate in the anterior vitreous), retinal hemorrhages, chorioretinitis, retinal dysplasia or folds, retinal detachment, or optic neuritis or atrophy.^140-143 The optic disk may appear atrophic, and areas of tapetal color change and hyperreflectivity may be seen, with retinal vascular attenuation. In some cases, inflammatory debris may persist in the vitreous after birth, precluding adequate fundic examination. Congenital cataracts also occur in this disease, and although the patho­physiology is unknown, they probably develop secondary to the intraocular inflammation and necrosis. Cataracts mainly involve the lens cortex.

Transplacental infection may occur when the dam is infected during pregnancy. The severity of the disease is related to fetal age at the time of intrauterine infection. Severe fetal disease and often fetal death occur in cattle infected between 50 and 100 days of gestation.

Serum samples collected from affected calves before ingestion of colostrum can be submitted for serologic assessment using the serum-virus neutralization test, or virus isolation can be attempted from buffy coat cells of a whole-blood sample collected into EDTA (see Chapter 32).

Bovine Leukosis

Lymphosarcoma in adult cattle is usually caused by bovine leukemia virus (BLV), although noninfectious sporadic cases are reported in young animals. Lymphosarcoma is the most common orbital neoplasm in cattle and may result in unilateral or bilateral progressive exophthalmos.^146,147 If undiagnosed, exposure keratitis and chemosis develop. Intraocular involve­ment can occur, although this is less common than orbital neoplasia. Generalized lymphadenopathy or other signs of generalized lymphosarcoma usually accompany the orbital form. Specific serologic tests for BLV will confirm the diagnosis. Enucleation or exenteration is rarely indicated because of the poor systemic prognosis for affected animals. Differential considerations for progressive exophthalmos include orbital cellulitis, in some instances due to actinomycosis or actinobacil­losis, frontal or maxillary sinusitis, or nasal or orbital neoplasia (especially squamous cell carcinoma).

Tuberculosis in Cattle

Tuberculosis caused by Mycobacterium bovis may cause granu­lomatous lesions in the eye of affected cattle. The uveal tract (iris, ciliary body, or choroid) is initially affected, with later expansion of granulomas into other ocular structures. Uveitis, keratitis, and chorioretinitis with retinal detachment are seen clinically.¹⁴⁸

Malignant Catarrhal Fever

Malignant catarrhal fever (MCF) is a sporadic disease charac­terized by fever, lymphadenopathy, and generalized vasculitis resulting in inflammation of the mucosal membranes of the mouth, nose, and eye; the skin; and the GI and nervous systems, with variable but usually high mortality. The African form is caused by alcelaphine herpesvirus type 1. The North American form is caused by a similar virus, ovine herpesvirus type 2.^149,150

Various forms of the disease are described on the basis of clinical signs (see Chapter 32). Ocular involvement is seen in the acute “head and eye” form, which is the most common presentation of the disease. Ocular signs include photophobia, epiphora, episcleral injection and scleritis, severe conjunctivitis, perilimbalcorneal edema and vascularization, anterior uveitis, and exophthalmia. Less significantly, and difficult to diagnose clinically, retinal vasculitis may develop. Corneal edema and anterior uveitis were the most commonly reported ocular signs in a recent report of cows with MCF.¹⁵¹ The degree of corneal edema at initial examination did not correlate with survival; however, the resolution of corneal edema and uveitis was associated with survival. Corneal edema and uveitis progressed despite supportive care in animals that did not survive. Bullous keratopathy may develop as a result of edema in the anterior cornea, with subsequent rupture of bullae to form painful corneal erosions.¹⁵² The absence of central corneal ulceration distinguishes the disease from IBK, and the severity of the ocular lesions is worse than would be expected with BHV-1, BVDV mucosal disease, or bluetongue. Differentiating this disease from rinderpest could be clinically difficult in areas where both are endemic in cattle.

Serology and PCR are being used to confirm the clinical diagnosis.^153,154 The microscopic ocular lesions are those of a nonsuppurative uveitis and vasculitis. The lesions involve the conjunctiva, cornea, anterior uvea, and retinal blood vessels; the choroid is rarely involved. Serofibrinous and cellular infiltrates develop in the uvea and retina as a result of vasculitis and thrombosis. Perivascular cuffing and optic neuritis may be detected histologically.^155-157

Prognosis for the eyes and the animal's recovery is poor.^152,158 Most importantly, in endemic areas cattle should be kept away from sheep, which may act as a reservoir for the disease, and affected animals should be isolated.¹⁵⁹

Thromboembolic Meningoencephalitis

Thromboembolic meningoencephalitis (TEME) is a fatal septicemia caused by infection with Histopbilus somni (see Chapter 35). Calves and young adult cattle can be affected, but the disease most often occurs in feedlot cattle younger than 1 year of age. The organism is capable of damaging vascular endothelial cells and activating blood clotting. Therefore most of the ocular histologic signs are related to thrombosis of retinal vessels.

Although conjunctivitis may be seen, the main ocular findings are in the fundus. Retinal hemorrhages and exudates may be focal or diffuse. Retinal infiltrates may elevate the retina and involve the vitreous. Retinal edema, hemorrhage and necrosis, vascular thrombosis, and infiltration of the retina and vitreous with neutrophils are seen histologically. Eosinophilic cytoid bodies (swollen axons) are seen in the nerve fiber layer of the retina. Retinal detachments may result from retinal edema. Later in the disease, areas of chorioretinitis result in chorio­retinal scars. The anterior segment is less involved in this disease than in MCF, in which keratitis and anterior uveitis are usual.¹⁶⁰,¹⁶¹

Leptospirosis in Horses and Cows

Leptospirosis is caused by a filamentous bacterium known as a spirochete. Disease is seen in most domestic animals as well as humans. Various serovars of Leptospira interrogans sensu stricto, Leptospira kirschneri, and Leptospira santarosai have been shown to affect various organs (e.g., kidneys, liver, spleen, muscles, CNS, eyes) and have been associated with abortions.¹⁶² These organisms primarily cause a vasculitis and endotheliitis in these organs.¹⁶³

Because leptospiral organisms cause vasculitis, it is reasonable to assume that uveitis may be present in an acute infection, and this has been reported in horses during the acute phase of leptospirosis.¹⁶⁴ Uveitis has also been seen experimentally in a calf during acute disease.¹⁶⁵ However, the role of leptospires in uveitis seen weeks to months after the acute disease remains much more controversial. Evidence for such a role is most complete in the horse, in which leptospiral uveitis and its role in equine recurrent uveitis (ERU) or “periodic ophthalmia” have been described.^166-168 ERU is an immune-mediated disorder that is the leading cause of blindness in horses (see the Immune- Mediated Ocular Diseases section later). Although the recurrent episodes of ERU are not directly caused by reinfection with microorganisms or parasites, numerous bacterial, viral, pro­tozoal, and parasitic organisms have been implicated in the initiation of the syndrome. In one outbreak of leptospirosis on a small farm, uveitis was not seen until 18 to 24 months after the acute outbreak of leptospirosis. Treatment with systemic antibiotics did not seem to affect the uveitis. In that study, serum titers to Leptospira interrogans serovar pomona often remained high for at least 6 years.¹⁶⁶ In another study, uveitis was seen in 22 eyes of 18 ponies experimentally infected with L. interrogans serovar pomona. The earliest sign of uveitis was seen at 1 year after inoculation. Cataract formation and posterior synechiae were also seen, as were recurrences of overt uveitis.¹⁶⁷

Recently, leptospiral organisms have been identified using PCR¹⁶⁸ or by culture^168-170 in the eyes of horses with ERU. A study in California using a PCR assay for Leptospira showed that 30 of 55 eyes (21 of 30 horses) with ERU had detectable Leptospira DNA in their aqueous humor.¹⁶⁸ In other studies, treatment with systemic antibiotics did not decrease the inflammation.^170-172 In Western Europe a total of 618 vitreous and/or aqueous samples were taken from the eyes of 501 horses with either active ERU or a history of ERU. Leptospires were isolated from 199 (32.2%) of the samples. Most belonged to serogroup grippotyphosa, with the rest in serogroup australis, sejroe, pomona, or javanica)6 In contrast, 36 samples of vitreous from 21 normal horses did not grow Ieptospires.¹⁷⁰ Although leptospires are involved in ERU in many horses with this syndrome, controlling or treating this disease remains a problem. The best means of symptomatic control of ERU at this time appears to be the use of ocular bioerodible cyclosporine A implants that are surgically placed within the suprachoroidal space, with the goal of controlling immune-mediated intraocular inflammation.¹⁷³ In the same study, cyclosporine was been shown to be toxic to L. interrogans in vitro at the same concentra­tion that was achieved in uveal tissue with the suprachoroidal implant.¹⁷³ (See also the Equine Recurrent Uveitis section later.)

Listeria Monocytogenes in Sheep, Cattle, and Horses

Listeriosis in ruminants is manifested mainly as either an encephalitis or a septicemia in neonates, or as a reproductive problem manifested by abortion. Ocular signs with the neural form include facial nerve paralysis and ptosis, often unilateral, on the side of the central lesion; medial strabismus, often on the ipsilateral side because of involvement of the abducens nucleus; nystagmus; and amaurosis.¹⁷⁴ Uveitis with hypopyon has been described in chronic cases.¹⁷⁵

Listeria monocytogenes has been cultured from conjunctival smears taken from sheep and cattle with keratoconjunctivitis.¹⁷⁶ In most of the sheep, Branhamella (Neisseria) ovis was also cultured. Clinical signs included conjunctival hyperemia, epiphora, photophobia, and corneal opacification. Treatment with topical chlortetracycline was curative. Walker and Morgan¹⁷⁷ describe two sheep that developed unilateral anterior uveitis. L. monocytogenes was cultured from the conjunctiva of each animal. Both animals recovered after treatment with parenteral ampicillin and topical antibiotics. L. monocytogenes has been cultured from the conjunctivae of three cows with keratitis (one with keratitis and uveitis) and from a corneal scraping of one horse with keratitis.¹⁷⁸ L. monocytogenes has been cultured from the cornea and conjunctiva of horses with chronic keratitis and keratoconjunctivitis.^179,180 Early treatment with broad-spectrum antibiotics may be effective in some cases.

Rabies

Rabies remains one of the most serious zoonotic diseases today.¹⁸¹ It can affect any mammal, and reports of rabies disease and death have been reported in all of the large animal species of concern in this chapter.^181,182 Ophthalmic signs of rabies are usually secondary to systemic illness and neurologic impairment and may include prolapse of the nictitating membrane, stra­bismus, nystagmus, and vision loss.^181-185 Prevention is the best approach to disease control, since affected animals must neces­sarily be destroyed once affected.¹⁸⁶ Fortunately, preexposure vaccination is highly effective, and postexposure (before the development of clinical signs) prophylaxis (immediate vaccina­tion against rabies, a strict isolation period of 90 days, and administration of booster vaccinations during the third and eighth weeks of the isolation period) may be effective in unvaccinated domestic animals if administered promptly.¹⁸⁶

Other Bacterial Disease in Horses

Salmonella spp. cause one of the more common and serious bacterial enteritides in foals and adult horses. It is often accompanied by septicemia in foals. Anterior uveitis and hypopyon have been seen in animals with salmonellosis, and Salmonella spp. can sometimes be cultured from these eyes.¹⁸⁷

R. equi is a gram-positive coccobacillus that causes bron- 187189

chopneumonia in young foals.¹⁸' ¹⁸⁹ Ihe systemic inflammatory response may result in a fibrinous anterior uveitis. Therapy involves systemic treatment of the pneumonia and topical and/ or systemic antiinflammatory treatment for the uveitis.

Strangles is a respiratory infection caused by Streptococcus equi subsp. equi that can have an accompanying ocular dis- charge.¹⁹⁰ Chorioretinal depigmentation was noted in the nontapetal fundus of several horses in one group clinically diagnosed with strangles. Because these lesions repigmented with time, it was suggested that they were caused by embolism to the choroid during bacteremia.¹⁹¹ One case of panophthalmitis caused by S. equi in a horse has been described.¹⁹² Ten days after a bout of strangles, this horse developed anterior uveitis that progressed to corneal stromal abscesses and panophthal­mitis. S. equi was cultured from the eye at enucleation. S. equi has also been isolated from infected corneal wounds in horses without systemic signs of strangles. These cases are treated aggressively, as with any bacterial keratitis.

Brucella abortus has been suggested as a cause for ERU,¹⁸⁷ although serum agglutination titers for B. abortus in normal horses and horses with ERU are similar.¹⁹³ This organism is certainly capable of inducing intraocular inflammation, although its role in recurrence or persistence of uveitis is unknown.

A case of anterior uveitis and bilateral chorioretinitis with retinal detachments has been described in a horse from Denmark as a result of a mycobacterial infection. Acid-fast organisms were seen in both eyes as well as in numerous other organs. Mycobacterium avium was cultured from these organs.¹⁹⁴

Other Viral Diseases in Horses

Equine adenovirus is a DNA virus that causes bronchopneu­monia (type 1) or GI signs (type 2) in foals, especially if they are immunodeficient. Mucopurulent nasal and ocular discharge accompanies the respiratory system disease. Histologically, swelling and necrosis of conjunctival cells with intranuclear inclusions are seen, with accumulation of neutrophils in the lumina and adventitia of uveal blood vessels.¹⁹⁵ Treatment of the conjunctivitis is supportive, with lubricants and anti­inflammatory medications.

Equine viral arteritis is a rare disease caused by an RNA virus classified as Arteriviridae. Most animals are subclinically infected, but ocular and nasal discharge, rash, pyrexia, rhinitis, leukopenia, edema (palpebral, periorbital, limb, or ventral), and abortions and neonatal death are seen.^196,197 Corneal opacity and photophobia have also been described.¹⁹⁸ The virus characteristically causes a panvasculitis.

Borrelia burgdorferi, the agent of Lyme disease, has been most often described as causing polyarthritis in horses, cows, and dogs. However, one case of ocular disease has been reported in a pony infected with B. burgdorferi)" Unilateral anterior and posterior uveitis was noted, and spirochetes were found in the anterior chamber. Other clinical signs included arthritis and synovitis of both carpal joints. Some discuss this agent as a potential contributor to chronic immune-mediated uveitis (ERU).

Equine herpesvirus serotype 1 (EHV-1) is a cause of rhi­nopneumonitis in horses. It has been cultured from cases of superficial punctate keratitis in the horse; the significance of these isolations is unknown.²⁰⁰ Six foals were experimentally inoculated intranasally with EHV-1.²⁰¹ All developed typical mild signs of upper respiratory infection. One foal developed vision problems 1 month after inoculation. Bilateral chorio­retinitis was diagnosed. Necropsy findings included chorioretinal degeneration and demyelination of the optic nerve and mononuclear cell infiltrate in parts of the choroid, retina, and CNS.²⁰¹ These findings are not surprising in that EHV-1 causes vasculitis and CNS disease in horses.²⁰² Retinal detachments and optic neuritis are possible as well. Treatment is not usually successful.

African Horse Sickness is caused by an orbivirus that is transmitted by Culocoides insects. It results in profound bulging

of the supraorbital fossa, the soft tissue depression above the dorsal orbital rim, which is considered a hallmark of this disease.^203,204 This swelling is due to retrobulbar edema and increased vascular pressure. Chemosis and protrusion of the conjunctiva from between the palpebral fissure is often seen as well. The systemic disease is characterized by either respira­tory and/or cardiac impairment and has a high rate of mortal- ity.^203,204 Control of an outbreak in an endemic region (Africa, Middle East) involves quarantine and usually euthanasia of affected animals, vector control, and vaccination of unaffected animals.^203,204

Equine influenza is one of the most common infectious diseases of the respiratory tract of horses. It is endemic in the equine population of the United States and throughout much of the world. This condition is highly contagious, and the virus spreads rapidly through groups of horses in aerosolized droplets dispersed by coughing. Clinical signs begin abruptly and include fever, serous nasal discharge, submandibular lymphadenopathy, and a harsh, dry, nonproductive cough.²⁰⁵ Ocular signs are secondary and are usually limited to conjunc­tivitis with serous to mucopurulent ocular discharge.²⁰⁵ The severity of clinical signs depends on the degree of existing immunity, among other factors.²⁰⁶ Younger animals are most susceptible, but immunity in an older horse can be overwhelmed in animals frequently exposed at shows.²⁰⁵ Vaccination of at-risk individuals is recommended.

Viral encephalitis caused by either Eastern equine encepha­lomyelitis (EEE) virus, Western equine encephalomyelitis (WEE) virus, or Venezuelan equine encephalomyelitis (VEE) virus is borne and transmitted by mosquito vectors and often has a seasonal presentation.²⁰⁷ Any and all signs attributable to cortical and thalamic lesions may be seen with these condi­tions. Neurologic deficits may be asymmetric, since lesions are not necessarily symmetrically distributed. Clinical signs include altered mentation, aimless wandering, head pressing, circling, inability to swallow, irregular ataxic gait, paresis and paralysis, convulsions, and death. Ophthalmic signs include vision loss, nystagmus, strabismus, mydriasis, and abnormalities of PLRs.²⁰⁷ In contrast, neurologic lesions with West Nile virus (WNV) encephalomyelitis are more prevalent in the brainstem and spinal cord than in the cortical and thalamic regions.^208-210 Thus horses with WNV may present with signs of spinal cord ataxia, hyperesthesia, and muscle fasciculations as well. Ophthalmic signs may include vision loss, facial paralysis (with secondary exposure keratitis), anterior and/or posterior 208210

uveitis, and optic neuritis.^{208 210} !here is no specific therapy for viral encephalitis. Symptomatic support might include fluid therapy, antiinflammatory agents if indicated, and anticonvul­sants if necessary. Topical lubricants for the eyes may be necessary.

Cryptococcosis, Histoplasmosis, and Aspergillosis in Horses

Cryptococcus neoformans is a pathogenic fungus that may cause systemic infection in horses and other mammals. Ocular signs are not usually reported in horses with cryptococcosis, although there are reports of frontal sinus granuloma with retrobulbar mass causing exophthalmos, periorbital swelling, blindness, and optic neuritis.^211-212 The chorioretinitis associated with C. neoformans seen in other species has not been described in the horse, cow, or small ruminant. Cryptococcus albidus has been cultured from the cornea of a horse with chronic keratitis.²¹³ Diagnosis is based on histopathologic evidence of fungal hyphae in tissue samples or on cytology, as well as a positive culture.

Histoplasma farciminosum, a fungal agent found mainly in Africa, is responsible for epizootic lymphangitis, a disease manifested with nodules and draining lesions of the subcutane­ous lymphatic system.²¹⁴ A conjunctival form of this disease results from deposition of the organism on the ocular mucous membranes by biting flies. Ocular signs include serous to mucopurulent discharge, blepharedema, and conjunctival papules. Disease progression leads to ulceration of the papules, which may result in secondary keratitis and/or obstruction and erosion of the lacrimal duct. Diagnosis is mainly by cytologic analysis and culture, although serologic assays are also available. Amphotericin B is the treatment of choice, and a vaccine is available for horses in endemic areas. Organisms consistent with Histoplasma spp. were seen on cytology of a corneal scraping taken from a horse with chronic keratitis.²¹⁵ This horse was successfully treated with topical fluconazole.

Aspergillus spp. are considered opportunistic fungi that rarely cause systemic disease in immunocompetent horses. Aspergillosis may be a cause of guttural pouch mycosis and may also occur secondary to chronic obstructive pulmonary disease.^216,217 Associated ocular signs can include Horner's syndrome, facial nerve palsy, and blindness resulting from ischemic optic neuritis secondary to extension of disease.²¹⁶ These organisms are ubiquitous in the environment, and horses are frequently exposed. Treatment with systemic antifungal agents may be attempted, but the prognosis is guarded and dependent on the underlying disease process and severity of the lesions. In contrast to the systemic form of the disease, local Aspergillus infections in the cornea are common (see the Fungal Keratitis in Horses section earlier).