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Bilateral uveitis and hyphema in a Catalina macaw (Ara ararauna X Ara macao) with multicentric lymphoma.

Abstract: A 20-year-old, female Catalina macaw (Ara ararauna x Ara macao) was presented with bilateral uveitis and hyphema. The hyphema initially improved with 0.12% prednisolone acetate ophthalmic drops (1 drop OU q4h for 7 days), but the hyphema recurred after the drops were tapered. The bird subsequently developed inappetance, weight loss, regurgitation, and lethargy and was euthanatized 24 days after initial presentation. Necropsy revealed marked splenomegaly and hepatomegaly, with significant mucosal ulcerations of the proventriculus and petechiation associated with both kidneys. Histopathologic examination revealed multicentric lymphoma, with neoplastic cells observed in ocular, splenic, hepatic, renal, proventricular, intestinal, pancreatic, and choanal tissue. Neoplastic lymphocytes effaced the iris, ciliary body, and the choroid of the eyes, and neoplastic lymphocytes were attached to the corneal endothelium and infiltrated the sclera, episclera, and conjunctivae. Immunohistochemical results indicated that the neoplastic lymphocytes were [CD3.sup.+] and [CD79a.sup.-], which is consistent with T-cell lymphoma.

Key words: multicentric T-cell lymphoma, uveitis, corticosteroid, avian, Catalina macaw, Ara ararauna X Ara macao

Clinical Report

A 20-year-old, female Catalina macaw (Ara ararauna x Ara macao) was evaluated by the referring veterinarian for abnormalities in the right eye and diagnosed with hyphema of the right eye. The bird had been purchased 19 years previously and lived, at that time, with 6 other psittacine birds, all of which were healthy. All birds were fed a pelleted diet, vegetables, and a variety of table food, including cooked meat. The most recent addition to the household occurred approximately 2 years before the onset of the disease in this case. Results of a complete blood cell count, biochemical profile, and serum protein electrophoresis in the macaw were unremarkable, except for a mild increase in creatine kinase activity. Treatment with tobramycin 0.3% ophthalmic solution (1 drop OD q12h for 1 week) was initiated, but the hyphema in the right eye worsened, and blepharospasm developed in the left eye. The macaw's vision became impaired to the point that the bird was suspected to be blind, although its appetite and energy level remained adequate. The bird was referred to the University of Wisconsin-Madison Veterinary Medical Teaching Hospital (UW-VMTH) for further evaluation 3 days later.

On presentation to the UW-VMTH, the bird could not navigate in the examination room, consistent with poor to absent vision. To facilitate a complete physical and ophthalmic examination, the bird was sedated with midazolam hydrochloride (2 mg/kg intranasal [IN]) and butorphanol (2 mg/kg IN). The macaw was lean, weighing 1.1 kg, with a body condition of 2 of 5. Palpebral reflex was present with no indication of abnormal globe shape, retrobulbar mass, or corneal ulceration in either eye on ophthalmic examination. Direct pupillary light reflex and dazzle reflex were present within the left eye but were questionable in the right eye. Slit-lamp biomicroscopy demonstrated severe bilateral anterior uveitis characterized by moderately severe ([3.sup.+] on a scale of 0 to [4.sup.+]) aqueous flare, rubeosis iridis in both eyes, and extensive hyphema in the right eye (Fig 1A and B). The left fundus could not be visualized because of anterior segment disease. A partial view of the right fundus was possible, and the pectin and visible retina appeared within reference intervals.

[FIGURE 1 OMITTED]

In view of the presence of bilateral anterior uveitis with hyphema, a systemic disorder was suspected. Differential diagnoses included intraocular neoplasia, particularly lymphoma; infectious diseases; immune-mediated disease, such as secondary lens-induced uveitis from cataract resorption; or trauma. (1-3) The owner consented to serologic testing for West Nile virus and Chlamydia psittaci, but further recommendations for diagnostic testing were declined because of financial constraints.

Pending the results of serologic testing, the bird was prescribed 0.12% prednisolone acetate ophthalmic drops (1 drop OU q4h for 7 days). A lower concentration corticosteroid ophthalmic drop (versus the more commonly prescribed 1% solution) was used to reduce any potential systemic effects associated with absorption of the corticosteroid. Tobramycin eyedrops were discontinued. With concern for systemic immunosuppression from the corticosteroid ophthalmic drops and the general stress of handling, which could lead to secondary tungal or bacterial infections, suspensions of terbinafine (20 mg/kg PO q24h; compounded 50 mg/mL oral suspension from 250-mg tablets of terbinafine) and doxycycline (30 mg/kg PO q24h; compounded 50 mg/mL oral suspension from 100-mg capsules of doxycycline) were administered. The bird was discharged to the owner the day of presentation with instructions to continue all prescribed medications.

During follow-up conversations, the owner reported that both eyes appeared improved by day 7 after presentation to the UW-VMTH. In addition, the owner reported that the bird appeared to have vision in the left eye and the right eye hyphema had resolved. The prednisolone ophthalmic drops were reduced to q6-8h, but clinical signs of hyphema in the left eye and reduced vision in both eyes recurred 2^1 days later.

At the recheck examination, 13 days after initial presentation to the UW-VMTH, the bird was quiet, alert, and responsive and had lost 4.5% of its body weight. The ophthalmic examination was unchanged from the previous examination with severe bilateral uveitis apparent on slit-lamp biomicroscopy; however, the left eye at that time had extensive hyphema that largely obscured the anterior chamber (Fig 1C). Iridal nodules were observed in the left eye, although the degree of hyphema precluded a detailed examination of the anterior segment. The right eye had a 3+ aqueous flare (Fig ID), as well as marked iridal nodules. Results of the serologic tests showed the West Nile virus titer was negative, and the titer for C psittaci, by direct-complement fixation, was positive at 1:32. However, chlamydial infection was considered unlikely to be the underlying cause of the ocular and clinical signs, and the positive titer was believed to be associated with previous exposure, not an active infection. No respiratory signs were present at any time in this bird or any other bird in the household.

Based on the clinical findings (bilateral involvement and recurrent hyphema) and progression of the clinical signs, a systemic cause, such as neoplasia, was suspected. Further diagnostic evaluation, including diagnostic imaging and fineneedle aspiration of the left anterior chamber, was recommended. Because of financial constraints, the owner elected to continue medical therapy as previously prescribed (0.12% prednisolone acetate q4h) with an addition of meloxicam (0.5 mg/kg PO q12h) for increased anti-inflammatory effect.

During the ensuing days, the bird continued to be depressed, have a poor appetite, and lose weight. The macaw then began to regurgitate any food offered. Because of worsening clinical signs, poor quality of life, and poor prognosis, the owners elected euthanasia 11 days after the recheck examination (25 days after the initial examination at UW-VMTH). A necropsy was completed immediately after euthanasia.

[FIGURE 2 OMITTED]

Results of necropsy confirmed bilateral uveitis and revealed marked splenomegaly, marked hepatomegaly with necrosis, multifocal mucosal ulcerations of the proventriculus with intraluminal digested blood, and bilateral nephropathy with subcapsular petechiations. Histopathologic examination showed large sheets of neoplastic lymphocytes expanding and infiltrating the parenchyma of multiple organs, including eyes (Fig 2), spleen, liver, kidneys (Fig 3), proventriculus (Fig 4), intestines, pancreas, and choana. Within the eyes, neoplastic lymphocytes had expanded and effaced the iris leaflets, ciliary body, and the choroid (Fig 2) infiltrating the sclera and episclera near the optic nerve, with additional multifocal regions of conjunctival involvement. Neoplastic masses were confirmed reaching into the anterior chamber (Fig 2), likely forming the previously documented iridal nodules. Free-floating neoplastic lymphocytes were documented against the endothelium, with accumulation of fibrin in the anterior chamber of the right eye. Within the gastrointestinal tract, there was marked, mural thickening and effacement of all layers by the neoplastic lymphocytes within the proventriculus (Fig 4), duodenum, small intestines, and colon. However, only the proventriculus had multifocal ulceration of the mucosal epithelium and intraluminal hemorrhage. Results of immunohistochemical staining for CD3 and CD79a showed the neoplastic cells were CD3 (Fig 3B) and CD79a-, findings that are consistent with a T-cell lymphoma.

[FIGURE 3 OMITTED]

[FIGURE 4 OMITTED]

Paraffin-embedded tissue (10-[micro]m paraffin scrolls) from this Catalina macaw were tested by polymerase chain reaction (PCR) for avian viruses that cause lymphoma with previously described methodology (Avian Disease and Oncology Laboratory, Agricultural Research Service, US Department of Agriculture, East Lansing, MI, USA). (4) The paraffin-embedded tissue was tested for the following viruses with primers previously described: Marek's disease virus glycoprotein B (primers MD-gB TM.5/TM.3), (5) Marek's disease virus pp38 (primers MDCv-F/R), (4) avian leukosis virus subtype J (primers Compton-H5/H7), (6) avian leukosis virus subtypes A E (primers ComptonH5/AD1), (6) reticuloendotheliosis virus (primers SNVLTR-F/R), (7) and the cellular host gene glyceraldehyde-3-phosphate dehydrogenase (primers GDH-TM2.5/TM2.3). (8) All results were negative.

Discussion

This case report describes an unusual presentation of lymphoma in a psittacine bird, in which the primary clinical sign was bilateral uveitis. In this bird, as in mammals with ocular lymphoma, the anterior uveitis was characterized by aqueous flare, rubeosis iridis, and hyphema. Usually, diagnosis of uveitis is made through recognition of typical ocular clinical signs and tonometry, whenever possible. (1) Effective treatment of anterior uveitis most often includes topical or systemic treatment or both of nonsteroidal or steroidal anti-inflammatory medications to control the ocular inflammation, as well as addressing the underlying cause of the inflammation. (9) In this macaw, topical steroids, initially topical 0.12% prednisolone acetate, appeared to reduce inflammation within the eyes because the hyphema in the right eye resolved, and the vision appeared to improve. However, when the topical corticosteroids were tapered, the uveitis worsened and did not improve, despite increasing the corticosteroid dosing frequency back to 6 times a day and adding oral meloxicam. Topical corticosteroid medications in avian patients must be used with caution because systemic absorption of corticosteroids can contribute to immunosuppression. (2,3) Topical atropine, as used in mammals, was not an option because of the striated muscle within the bird iris. (1) The combination of an oral nonsteroidal anti-inflammatory agent and a topical steroid was selected in this patient to provide greater inflammatory control as well as pain relief, but caution should be taken with this combination, and feces should be monitored for melena, which may suggest gastrointestinal ulceration. Unfortunately, financial constraints prevented further diagnostic testing, and as such, definitive antemortem diagnosis of lymphoma was not achieved in this case.

Uveitis in avian species is associated with trauma, infections (viral, bacterial, fungal, or protozoal), immune-mediated inflammation, cataracts, and neoplasia. (1,3,10) Some infectious disease agents that can cause severe inflammation within the bird eye are West Nile virus, avian encephalomyelitis virus, Marek's disease virus (gallid herpesvirus 2), Pasteurella multocida, septicemia from salmonellosis or Mycoplasma gallisepticum, toxoplasmosis, and mycotic endophthalmitis from disseminated aspergillosis or candidiasis. (1) In this case, West Nile virus was ruled out, and the macaw was treated for potential bacterial and fungal infections. West Nile virus has been shown to cause chorioretinitis in birds. (3,10) In retrospect, testing for Toxoplasma gondii may have been prudent because cooked meat was fed in the diet and T gondii is a reported cause of chorioretinitis in birds, even though thoroughly cooking meat should prevent transmission. (1,2,10) Another common cause of hyphema and aqueous flare is blunt or sharp trauma, which is a common cause of uveitis and hyphema in wild birds. (1-3) However, trauma was not considered a likely cause in this case because of the husbandry, history, and recurrent bilateral nature of the clinical signs. In mammals, hyphema has also been associated with a variety of coagulopathies, thrombocytopenia, bone marrow disease, hyperviscosity syndrome, and systemic hypertension, although these entities are not currently reported causes of hyphema in birds.

To our knowledge, uveitis secondary to lymphoma has not been reported in a psittacine species. In mammals, such as dogs and cats, lymphoma is a common differential diagnosis for uveitis, especially when hyphema is a prominent feature. (9) However, diagnosis of lymphoma can be challenging. In some cases, specifically when an extensive systemic workup is not possible, a lack of response to medical treatment is used to support a clinical suspicion of neoplasia. Ocular aspiration and cytologic evaluation can also represent viable diagnostic tools in the diagnosis of lymphoma, especially when clinical changes have contributed to blindness. (9)

The most common form of lymphoid neoplasia in psittacine and passerine birds is lymphoma. (11) In a previously reported psittacine lymphoma case, (11) a high white blood cell count with an absolute lymphocytosis, monoclonal gammopathy, (12) and hypercalcemia was reported. (13) In this Catalina macaw, no changes in the white blood cell count, calcium level, or serum protein electrophoresis were evident. However, as the disease progressed, the owner elected not to repeat assessments of the white blood cell count, biochemical profile, and protein electrophoresis.

The most commonly affected tissues associated with lymphoma in birds are the liver, (12-14) spleen, (12-15) and kidneys, (13) although lymphoma has been documented in several tissues. (11,15,16) In this macaw, lymphoma was found throughout the body, including the liver, spleen, kidneys, eyes, gastrointestinal tract, pancreas, and choana. Lymphoma develops in the primary or secondary lymphoid tissues and spreads to other tissues of the body. The organ system from which this macaw's lymphoma originated is unknown because the neoplastic process was diffuse at time of necropsy. The ulcerations within the proventriculus could be secondary to the lymphoma within the walls of the proventriculus but could also have been an adverse effect of systemic absorption of the prednisolone and the oral meloxicam.

Uveitis from ocular lymphoma is rare in avian species, except in poultry due to Marek's disease. Lymphoma secondary to viral infections in poultry has been widely studied because of its economic impacts. (11) The most common viruses associated with lymphoma in poultry are Marek's disease virus, avian leukosis virus, and reticuloendotheliosis virus. (11) The most common cause of ocular neoplasia in chickens is Marek's disease, caused by a herpesvirus, which can lead to ocular lymphomatosis, with uveitis as a common clinical sign. (10,17) However, these avian tumor viruses can also affect the ocular tissue of nonpoultry species because ocular lymphoma from reticuloendotheliosis virus has been reported in a peafowl (Pavo species). (18,19)

In general, ocular neoplasia is not common in avian species. (10,18) In one report examining 284 avian, ocular-pathology cases during a 29-year period, only 15 cases (5.2%) of 9 different ocular tumors were found. (18) Six of these cases were lymphoma, and most were birds from the order Galliformes (peacock [Pavo species], chicken, and tragopan [Tragopan species]). (18) However, one case was a sun conure (Aratinga solstitialis) with lymphocytes effacing and infiltrating the uvea. (18) Another report described periorbital lymphoma in the lower right eyelid of a scarlet macaw (Ara macao), (20) whereas a third report found periorbital lymphoma in an African grey parrot (Psittacus erithacus) causing exophthalmos. (21) Limited research has been performed to assess viral causes of lymphoma in psittacine species, and no clear association has been determined to date. (11) In the macaw we describe, no viral particles were observed histologically in tissues, and results of PCR testing of paraffin-embedded tissues for the major lymphoma-causing viruses of poultry were negative.

Chemotherapy for lymphoma in psittacine species has been attempted in several cases. (14,22) A green-winged macaw (Ara chloropterd) with chronic lymphocytic leukemia treated with prednisone, chlorambucil, and cyclophosphamide survived 81 weeks. (14) An umbrella cockatoo (Cacatua alba) with nonepitheliotropic cutaneous B-cell lymphoma went into complete remission with vincristine and chlorambucil and remained so for 8 years after discontinuing chemotherapy. (22) An Amazon parrot (Amazona species) with lymphoid leukosis, treated with prednisone, survived 32 weeks. (23) An African grey parrot with malignant lymphoreticular neoplasia treated with orthovoltage x-ray teletherapy survived 8 weeks. (21) A Moluccan cockatoo (Cacatua moluccensis) with lymphoma was treated with prednisone, cyclophosphamide, vincristine, doxorubicin, L-asparagine, and [alpha]-interferon, which caused remission of the solid tumor but only a stable disease state for the leukemic phase of the disease. (24) In this macaw, the lymphocytes were [CD3.sup.+], which indicates a T-cell origin. This appears to be a common finding in psittacine lymphoma cases. (13-15) However, more research is needed to further understand the types of avian lymphoma and their responses to chemotherapy.

This report indicates that lymphoma should be considered as a differential diagnosis for psittacine birds with anterior uveitis and hyphema. This is the first report, to our knowledge, of intraocular lymphoma in a macaw.

Acknowledgements: We thank Dr Sharman Hoppes (Texas A&M University) for providing a blood sample from a Catalina macaw that was used as a negative control for PCR testing for avian viruses.

References

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(13.) De Wit M, Schoemaker NJ, Kik MJ, Westerhof I. Hypercalcemia in two Amazon parrots with malignant lymphoma. Avian Dis. 2003; 47(1):223 228.

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(16.) Coleman CW, Oliver R. Lymphosarcoma in a juvenile blue and gold macaw (Ara ararauna) and a mature canary (Serinus canarius). J Assoc Avian Ver. 1994; 8(2):64-68.

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Jennifer C. Hausmann, DVM, Christoph Mans, DrMedVet, Dipl ACZM, Allyson Gosling, DVM, Jaimie L. Miller, DVM, Tamara Chamberlin, DVM, John R. Dunn, DVM, MS, PhD, Paul E. Miller, DVM, Dipl ACVO, and Kurt K. Sladky, MS, DVM, Dipl ACZM, Dipl ECZM

From the Departments of Surgical Sciences (Hausmann, Mans, Gosling, P. E. Miller, Sladky) and Pathobiological Sciences (J. L. Miller, Chamberlin), School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, WI 53706, USA; and the Avian Disease and Oncology Laboratory, Agricultural Research Service, US Department of Agriculture, 4279 E Mount Hope Road, East Lansing, Ml 48823, USA (Dunn).
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Title Annotation:Clinical Report
Author:Hausmann, Jennifer C.; Mans, Christoph; Gosling, Allyson; Miller, Jaimie L.; Chamberlin, Tamara; Dun
Publication:Journal of Avian Medicine and Surgery
Article Type:Clinical report
Date:Jun 1, 2016
Words:3490
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