Diagnostic Ophthalmology Ophtalmologie diagnostique Lynne S. Sandmeyer, Bianca S. Bauer, Bruce H. Grahn
A
History and clinical signs
5-year-old male German shepherd dog was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of blindness of approximately 14 days duration. The dog was current on vaccinations and had travelled extensively throughout Saskatchewan, Alberta, and Manitoba. The referring veterinarian initiated therapy with oral prednisone, 25 mg, q12h for 5 days, followed by 25 mg, q24h in addition to topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis, Mississauga, Ontario), q6h. Initial lethargy and decreased appetite had improved following this therapy. The menace responses, and direct and consensual pupillary light reflexes were absent bilaterally. Palpebral and occulocephalic reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 25 mm/min and 18 mm/min in the right and left eyes, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet, Tiolat, Helsinki, Finland) and were 4 mmHg and 2 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) was negative bilaterally. On direct examination peripheral corneal edema and mild corneal vascularization were noted and bullous retinal detachments were visualized through the pupils, posterior to the lens, bilaterally. Biomicroscopic examination (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) revealed mild aqueous flare bilaterally. Indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examination was completed and exudative retinal detachments with intra- and sub-retinal infiltrates were confirmed bilaterally. A photograph of the right eye at presentation is provided for your assessment (Figure 1).
What are your clinical diagnosis, differential diagnoses, therapeutic plan, and prognosis? Discussion The clinical diagnoses were bilateral endophthalmitis with chorioretinitis and exudative retinal detachment. Endophthalmitis is the terminology used to describe concurrent inflammation of the anterior (iris, ciliary body) and posterior uvea (choroid). Inflammation of the retina is common in conjunction with
Figure 1. Photograph of the right eye of a 5-year-old German shepherd dog. The photograph is focused on the region of the anterior vitreous.
choroidal involvement (chorioretinitis) due to the proximity of the tissues. Retinal detachments are a common manifestation of chorioretinitis and occur with accumulation of exudate between the photoreceptors and retinal pigment epithelium. Differential diagnoses for uveitis include infectious diseases (viral, bacterial, rickettsial, parasitic, algal, and mycotic infections), neoplasia, hyperviscosity syndrome, trauma, and immune-mediated inflammation (1). Bilateral manifestations of uveitis are suggestive of a systemic illness and warrant systemic evaluation. A minimum database in cases of bilateral uveitis includes a physical examination, complete blood (cell) count (CBC), serum biochemistry, urinalysis, and thoracic radiographs. Additional serological testing and diagnostics may be indicated based on clinical and laboratory findings, and the index of suspicion for systemic diseases. Vitreous aspiration for cytology and culture may be useful; however, these should be performed by a trained specialist due to the invasive nature of this procedure, and are often reserved for severe cases when an etiologic diagnosis cannot be achieved by other means. Treatment of anterior uveitis requires topical antiinflammatory and cycloplegic therapy. Topical 0.1% dexamethasone or 1% prednisolone acetate should be used 4 to 6 times
Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. CVJ / VOL 57 / SEPTEMBER 2016
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O P H TA LM O LO G I E D I AG N O S T I Q U E
daily for moderate to severe uveitis. Topical 1% atropine should be administered up to 4 times daily to maintain a dilated pupil in order to prevent posterior synechia, as well as to reduce painful ciliary body muscle spasm. Non-steroidal anti-inflammatory drugs are not as potent as topical corticosteroids; however, they may safely be utilized concurrently for added effect. The presence of chorioretinitis and retinal detachment necessitates systemic medications as topically applied drugs will not penetrate the posterior segment of the eye (2). Systemic corticosteroids are more potent at controlling intraocular inflammation than non-steroidal anti-inflammatory drugs and are particularly beneficial in immune-mediated disease (3). Systemic corticosteroids are also recommended by some authors in the treatment of infectious disease when done in conjunction with specific antimicrobial therapy (4,5). A CBC, serum biochemistry, and urinalysis in this case showed no significant abnormalities. Thoracic radiographs showed a small nodular lesion in the left cranial lung lobe. Serological tests for heartworm, Lyme disease, Ehrlichia canis, and Anaplasma spp., were negative. Symptomatic therapy was initiated while awaiting test results of a urine Blastomyces dermatitidis antigen test and Brucella canis and Toxoplasma gondii serology. To control anterior segment inflammation the dog was treated with topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis), q6h, in addition to prednisolone acetate 1% (Sandoz Prednisolone; Sandoz Canada, Boucherville, Quebec), q6h. Oral prednisone was continued as prescribed to address the posterior segment inflammation. As we were suspicious of an infectious agent, we also initiated therapy with doxycycline (Sanis Health, Dieppe, New Brunswick), 5 mg/kg body weight (BW) twice daily for 14 days. The Blastomyces dermatitidis urine antigen test result was positive and Brucella canis and Toxoplasma gondii tests were negative when they became available 14 days later. Re-evaluation at that time showed reduction of anterior uveitis but no improvement in the retinal detachments. Oral itraconazole (Sporanox; Janssen, Toronto, Ontario) was initiated at a dose of 5 mg/kg BW, q24h and the oral prednisone dose was gradually tapered and discontinued over the following 14 days. Serum biochemistry was recommended in 2 weeks for blood analysis to monitor for hepatotoxicity that can occur with itraconazole therapy (6). Thoracic radiographs and an examination by a veterinary ophthalmologist were recommended in 30 and 60 days to monitor response to therapy. As the owners were re-locating out of province, follow-up examinations were completed at a local animal hospital. Blastomycosis is a systemic infection caused by Blastomyces dermatitidis, a dimorphic soil fungus. The organism is endemic in central and southeastern United States, and the Canadian provinces of Quebec, Ontario, Manitoba, and Saskatchewan. Geographic distribution of cases in southern Saskatchewan and Manitoba closely follows the Qu’Appelle and Assiniboine river systems (7). In the prairie provinces there has been a significant increase in number of cases from 2001 to 2010 compared to 1990 to 2000 (7). Infection usually occurs via inhalation of the fungal hyphae which assume a yeast form at body temperature and dissemi996
nate hematogenously or through the lymphatics to skin, lymph nodes, subcutaneous tissues, bone, testicles, eyes, and the central nervous system (CNS). Ocular lesions occur in up to 48% of cases and the most common manifestations are those of uveitis (8). Ocular infection initially occurs in the choroid eliciting pyogranulomatous inflammation which leads to retinal detachment, subretinal, intraretinal, and choroidal granuloma formation. Anterior segment inflammation occurs later in the course of the disease (9–11). Due to the mode of infection, pulmonary disease is usually present and miliary to nodular interstitial patterns on thoracic radiographs are reported to be most common (6,12–14). In this case ocular disease was the most prominent clinical manifestation of infection, although there was evidence of mild pulmonary disease (one nodule) on thoracic radiographs. Treatment of ocular blastomycosis is directed at reducing the intraocular inflammation and administering systemic antifungal therapy. Anti-inflammatory doses of systemic prednisone (1 to 2 mg/kg per day) for ocular blastomycosis is recommended to address posterior segment inflammation as topical medications will not penetrate to this level (2,4,9). This may be associated with improved visual outcomes and does not appear to endanger the animal’s life provided appropriate antifungal therapy is given (2,4). Antifungal therapy should be continued for at least 1 month following radiographic evidence that pulmonary infiltrates have resolved (6,14). An additional 2 to 4 weeks of antifungal therapy is suggested if systemic corticosteroids have been used (6). Prognosis for survival with blastomycosis is generally good; however, CNS involvement or severe lung disease are indicators of a poorer prognosis for life. The recurrence rate for blastomycosis is approximately 20% and reappearance of disease usually occurs within 1 year of completion of treatment (12). Prognosis for eyes and vision depends on location and severity of disease in the eye. Generally, the posterior segment is infected initially and infection progresses to the anterior segment. Anterior segment disease is associated with a poor prognosis and glaucoma secondary to anterior segment disease is the most common reason for enucleation (2,8,15). Eyes with disease limited to the posterior segment (other than optic nerve involvement) have a better prognosis, with one study reporting a 76% chance of recovery in such cases (15).
References 1. Hendrix DVH. Diseases and surgery of the canine anterior uvea. In: Gelatt KN, Gilger BC, Kern TJ, eds. Veterinary Ophthalmology. 5th ed. Ames, Iowa: John Wiley & Sons, 2013:1146–1198. 2. Holmberg BJ, Maggs DJ. The use of corticosteroids to treat ocular inflammation. Vet Clin North Am Small Anim Pract 2004;34:693–705. 3. Andrew SE, Abrams KL, Brooks DE, et al. Clinical features of steroid responsive retinal detachments in twenty-two dogs. Vet and Comp Ophthalmol 1997;7:82–87. 4. Finn MJ, Stiles J, Krohne SG. Visual outcome in a group of dogs with ocular blastomycosis treated with systemic antifungals and systemic corticosteroids. Vet Ophthalmol 2007;10:299–303. 5. Krohne SG. Canine systemic fungal infections. Vet Clin North Am Small Anim Pract 2000;30:1063–1090. 6. Legendre Am, Toal RL. Diagnosis and treatment of fungal diseases of the respiratory system. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, Pennsylvania: WB Saunders Company, 2000:815–819.
CVJ / VOL 57 / SEPTEMBER 2016
CVJ / VOL 57 / SEPTEMBER 2016
12. Legendre AM. Blastomycosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St Louis, Missouri: Saunders Elsevier, 2012:606–614. 13. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658–664. 14. Crews LJ, Feeney DA, Jessen CR, Newman AB. Radiographic findings in dogs with pulmonary blastomycosis: 125 cases (1989–2006). J Am Vet Med Assoc 2008;232:215–221. 15. Brooks DE, Legendre AM, Gum GG, Laratta LJ, Abrams KL, Morgan RV. The treatment of canine ocular blastomycosis with systemically administered itraconazole. Prog Vet Comp Ophthalmol 1991;1:263–268.
997
D I AG N O S T I C O P H T H A LM O LO GY
7. Davies JL, Epp T, Burgess HJ. Prevalence and geographic distribution of canine and feline blastomycosis in the Canadian prairies. Can Vet J 2013;54:753–760. 8. Bloom JD, Hamor RE, Gerding PA, Jr. Ocular blastomycosis in dogs: 73 cases, 108 eyes (1985–1993). J Am Vet Med Assoc 1996;209:1271–1274. 9. Albert RA, Whitley RD, Crawley RR. Ocular balstomycosis in the dog. Comp Contin Educ Pract Vet 1981;3:303–311. 10. Buyukmihci NC, Moore PF. Microscopic lesions of spontaneous ocular blastomycosis in dogs. J Comp Path 1987;97:321–328. 11. Buyukmihci N. Ocular lesions of blastomycosis in the dog. J Am Vet Med Assoc 1982;55:45–54.
A
History and clinical signs
5-year-old male German shepherd dog was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of blindness of approximately 14 days duration. The dog was current on vaccinations and had travelled extensively throughout Saskatchewan, Alberta, and Manitoba. The referring veterinarian initiated therapy with oral prednisone, 25 mg, q12h for 5 days, followed by 25 mg, q24h in addition to topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis, Mississauga, Ontario), q6h. Initial lethargy and decreased appetite had improved following this therapy. The menace responses, and direct and consensual pupillary light reflexes were absent bilaterally. Palpebral and occulocephalic reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 25 mm/min and 18 mm/min in the right and left eyes, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet, Tiolat, Helsinki, Finland) and were 4 mmHg and 2 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) was negative bilaterally. On direct examination peripheral corneal edema and mild corneal vascularization were noted and bullous retinal detachments were visualized through the pupils, posterior to the lens, bilaterally. Biomicroscopic examination (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) revealed mild aqueous flare bilaterally. Indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examination was completed and exudative retinal detachments with intra- and sub-retinal infiltrates were confirmed bilaterally. A photograph of the right eye at presentation is provided for your assessment (Figure 1).
What are your clinical diagnosis, differential diagnoses, therapeutic plan, and prognosis? Discussion The clinical diagnoses were bilateral endophthalmitis with chorioretinitis and exudative retinal detachment. Endophthalmitis is the terminology used to describe concurrent inflammation of the anterior (iris, ciliary body) and posterior uvea (choroid). Inflammation of the retina is common in conjunction with
Figure 1. Photograph of the right eye of a 5-year-old German shepherd dog. The photograph is focused on the region of the anterior vitreous.
choroidal involvement (chorioretinitis) due to the proximity of the tissues. Retinal detachments are a common manifestation of chorioretinitis and occur with accumulation of exudate between the photoreceptors and retinal pigment epithelium. Differential diagnoses for uveitis include infectious diseases (viral, bacterial, rickettsial, parasitic, algal, and mycotic infections), neoplasia, hyperviscosity syndrome, trauma, and immune-mediated inflammation (1). Bilateral manifestations of uveitis are suggestive of a systemic illness and warrant systemic evaluation. A minimum database in cases of bilateral uveitis includes a physical examination, complete blood (cell) count (CBC), serum biochemistry, urinalysis, and thoracic radiographs. Additional serological testing and diagnostics may be indicated based on clinical and laboratory findings, and the index of suspicion for systemic diseases. Vitreous aspiration for cytology and culture may be useful; however, these should be performed by a trained specialist due to the invasive nature of this procedure, and are often reserved for severe cases when an etiologic diagnosis cannot be achieved by other means. Treatment of anterior uveitis requires topical antiinflammatory and cycloplegic therapy. Topical 0.1% dexamethasone or 1% prednisolone acetate should be used 4 to 6 times
Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4. Use of this article is limited to a single copy for personal study. Anyone interested in obtaining reprints should contact the CVMA office ([email protected]) for additional copies or permission to use this material elsewhere. CVJ / VOL 57 / SEPTEMBER 2016
995
O P H TA LM O LO G I E D I AG N O S T I Q U E
daily for moderate to severe uveitis. Topical 1% atropine should be administered up to 4 times daily to maintain a dilated pupil in order to prevent posterior synechia, as well as to reduce painful ciliary body muscle spasm. Non-steroidal anti-inflammatory drugs are not as potent as topical corticosteroids; however, they may safely be utilized concurrently for added effect. The presence of chorioretinitis and retinal detachment necessitates systemic medications as topically applied drugs will not penetrate the posterior segment of the eye (2). Systemic corticosteroids are more potent at controlling intraocular inflammation than non-steroidal anti-inflammatory drugs and are particularly beneficial in immune-mediated disease (3). Systemic corticosteroids are also recommended by some authors in the treatment of infectious disease when done in conjunction with specific antimicrobial therapy (4,5). A CBC, serum biochemistry, and urinalysis in this case showed no significant abnormalities. Thoracic radiographs showed a small nodular lesion in the left cranial lung lobe. Serological tests for heartworm, Lyme disease, Ehrlichia canis, and Anaplasma spp., were negative. Symptomatic therapy was initiated while awaiting test results of a urine Blastomyces dermatitidis antigen test and Brucella canis and Toxoplasma gondii serology. To control anterior segment inflammation the dog was treated with topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis), q6h, in addition to prednisolone acetate 1% (Sandoz Prednisolone; Sandoz Canada, Boucherville, Quebec), q6h. Oral prednisone was continued as prescribed to address the posterior segment inflammation. As we were suspicious of an infectious agent, we also initiated therapy with doxycycline (Sanis Health, Dieppe, New Brunswick), 5 mg/kg body weight (BW) twice daily for 14 days. The Blastomyces dermatitidis urine antigen test result was positive and Brucella canis and Toxoplasma gondii tests were negative when they became available 14 days later. Re-evaluation at that time showed reduction of anterior uveitis but no improvement in the retinal detachments. Oral itraconazole (Sporanox; Janssen, Toronto, Ontario) was initiated at a dose of 5 mg/kg BW, q24h and the oral prednisone dose was gradually tapered and discontinued over the following 14 days. Serum biochemistry was recommended in 2 weeks for blood analysis to monitor for hepatotoxicity that can occur with itraconazole therapy (6). Thoracic radiographs and an examination by a veterinary ophthalmologist were recommended in 30 and 60 days to monitor response to therapy. As the owners were re-locating out of province, follow-up examinations were completed at a local animal hospital. Blastomycosis is a systemic infection caused by Blastomyces dermatitidis, a dimorphic soil fungus. The organism is endemic in central and southeastern United States, and the Canadian provinces of Quebec, Ontario, Manitoba, and Saskatchewan. Geographic distribution of cases in southern Saskatchewan and Manitoba closely follows the Qu’Appelle and Assiniboine river systems (7). In the prairie provinces there has been a significant increase in number of cases from 2001 to 2010 compared to 1990 to 2000 (7). Infection usually occurs via inhalation of the fungal hyphae which assume a yeast form at body temperature and dissemi996
nate hematogenously or through the lymphatics to skin, lymph nodes, subcutaneous tissues, bone, testicles, eyes, and the central nervous system (CNS). Ocular lesions occur in up to 48% of cases and the most common manifestations are those of uveitis (8). Ocular infection initially occurs in the choroid eliciting pyogranulomatous inflammation which leads to retinal detachment, subretinal, intraretinal, and choroidal granuloma formation. Anterior segment inflammation occurs later in the course of the disease (9–11). Due to the mode of infection, pulmonary disease is usually present and miliary to nodular interstitial patterns on thoracic radiographs are reported to be most common (6,12–14). In this case ocular disease was the most prominent clinical manifestation of infection, although there was evidence of mild pulmonary disease (one nodule) on thoracic radiographs. Treatment of ocular blastomycosis is directed at reducing the intraocular inflammation and administering systemic antifungal therapy. Anti-inflammatory doses of systemic prednisone (1 to 2 mg/kg per day) for ocular blastomycosis is recommended to address posterior segment inflammation as topical medications will not penetrate to this level (2,4,9). This may be associated with improved visual outcomes and does not appear to endanger the animal’s life provided appropriate antifungal therapy is given (2,4). Antifungal therapy should be continued for at least 1 month following radiographic evidence that pulmonary infiltrates have resolved (6,14). An additional 2 to 4 weeks of antifungal therapy is suggested if systemic corticosteroids have been used (6). Prognosis for survival with blastomycosis is generally good; however, CNS involvement or severe lung disease are indicators of a poorer prognosis for life. The recurrence rate for blastomycosis is approximately 20% and reappearance of disease usually occurs within 1 year of completion of treatment (12). Prognosis for eyes and vision depends on location and severity of disease in the eye. Generally, the posterior segment is infected initially and infection progresses to the anterior segment. Anterior segment disease is associated with a poor prognosis and glaucoma secondary to anterior segment disease is the most common reason for enucleation (2,8,15). Eyes with disease limited to the posterior segment (other than optic nerve involvement) have a better prognosis, with one study reporting a 76% chance of recovery in such cases (15).
References 1. Hendrix DVH. Diseases and surgery of the canine anterior uvea. In: Gelatt KN, Gilger BC, Kern TJ, eds. Veterinary Ophthalmology. 5th ed. Ames, Iowa: John Wiley & Sons, 2013:1146–1198. 2. Holmberg BJ, Maggs DJ. The use of corticosteroids to treat ocular inflammation. Vet Clin North Am Small Anim Pract 2004;34:693–705. 3. Andrew SE, Abrams KL, Brooks DE, et al. Clinical features of steroid responsive retinal detachments in twenty-two dogs. Vet and Comp Ophthalmol 1997;7:82–87. 4. Finn MJ, Stiles J, Krohne SG. Visual outcome in a group of dogs with ocular blastomycosis treated with systemic antifungals and systemic corticosteroids. Vet Ophthalmol 2007;10:299–303. 5. Krohne SG. Canine systemic fungal infections. Vet Clin North Am Small Anim Pract 2000;30:1063–1090. 6. Legendre Am, Toal RL. Diagnosis and treatment of fungal diseases of the respiratory system. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, Pennsylvania: WB Saunders Company, 2000:815–819.
CVJ / VOL 57 / SEPTEMBER 2016
CVJ / VOL 57 / SEPTEMBER 2016
12. Legendre AM. Blastomycosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 4th ed. St Louis, Missouri: Saunders Elsevier, 2012:606–614. 13. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658–664. 14. Crews LJ, Feeney DA, Jessen CR, Newman AB. Radiographic findings in dogs with pulmonary blastomycosis: 125 cases (1989–2006). J Am Vet Med Assoc 2008;232:215–221. 15. Brooks DE, Legendre AM, Gum GG, Laratta LJ, Abrams KL, Morgan RV. The treatment of canine ocular blastomycosis with systemically administered itraconazole. Prog Vet Comp Ophthalmol 1991;1:263–268.
997
D I AG N O S T I C O P H T H A LM O LO GY
7. Davies JL, Epp T, Burgess HJ. Prevalence and geographic distribution of canine and feline blastomycosis in the Canadian prairies. Can Vet J 2013;54:753–760. 8. Bloom JD, Hamor RE, Gerding PA, Jr. Ocular blastomycosis in dogs: 73 cases, 108 eyes (1985–1993). J Am Vet Med Assoc 1996;209:1271–1274. 9. Albert RA, Whitley RD, Crawley RR. Ocular balstomycosis in the dog. Comp Contin Educ Pract Vet 1981;3:303–311. 10. Buyukmihci NC, Moore PF. Microscopic lesions of spontaneous ocular blastomycosis in dogs. J Comp Path 1987;97:321–328. 11. Buyukmihci N. Ocular lesions of blastomycosis in the dog. J Am Vet Med Assoc 1982;55:45–54.
