Diagnostic Ophthalmology Ophtalmologie diagnostique Lynne S. Sandmeyer, Bianca S. Bauer, Bruce H. Grahn
A
History and clinical signs
3-year-old spayed female golden retriever dog was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of a cloudy, painful left eye. The dog was presented to her referring veterinarian one week previously and therapy was initiated with topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis, Mississauga, Ontario), q6h, in addition to fucidic acid 1% (Fucithalmic Vet; Aventix Animal Health, Flamborough, Ontario), q12h. The menace response was absent in the left eye. Direct and consensual pupillary light reflexes were absent in the left eye as was the left to right consensual pupillary light reflex. Palpebral and occulocephalic reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 5 and 11 mm/min in the right and left eyes, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet; Tiolat, Helsinki, Finland) and were 9 and 52 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) was negative bilaterally. On direct examination the left eye had medial strabismus associated with a large, mass-like thickening at the dorsolateral aspect of the globe. Marked conjunctival hyperemia, episcleral congestion, corneal edema, and peripheral corneal vascularization were also present. Following application of 0.5% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario) biomicroscopic examination (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) revealed an opacity posterior to the lens in the left eye. Indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examination was not possible in the left eye due to corneal opacity and medial strabismus. The right eye had a single focal area of tapetal hyporeflectivity. An ocular ultrasound was completed which confirmed a complete retinal detachment with hyperechoic subretinal opacities in the left eye in addition to a hyperechoic mass in the region of the dorsolateral ciliary body. A photograph of the left eye at presentation is provided for your assessment (Figure 1a).
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 / NOVEMBER 2016
a
b Figure 1. Photograph of the left eye of a 3-year-old golden retriever dog. a — at presentation. b — 1 week later.
What are your clinical diagnosis, differential diagnoses, therapeutic plan, and prognosis? Discussion The clinical diagnoses were an intraocular mass with presumed extraocular extension, panophthalmitis, retinal detachment, and secondary glaucoma of the left eye, in addition to bilateral keratoconjunctivitis sicca. The focal retinal lesion in the right eye was considered of unknown significance at that time. The differential diagnoses for a mass lesion of the eye include neoplasia or inflammation, particularly a granulomatous inflammatory process. Retinal detachment of this type may occur with subretinal accumulation of fluid and/or cellular material which may be inflammatory or neoplastic in origin. Secondary glaucoma is a common sequela to severe intraocular inflammation as well as intraocular neoplasia. Keratoconjunctivitis sicca 1195
O P H TA LM O LO G I E D I AG N O S T I Q U E
is most often caused by immune-mediated lacrimal adenitis and was likely a separate condition. Definitive diagnosis of a mass-like lesion requires light microscopic examination of tissue. A biopsy of the thickened episcleral tissue was completed following topical anesthetic application to the area and this was submitted for light microscopic examination. The eye was blind with severe disease, so enucleation was scheduled. Diclofenac and fucidic acid therapy were continued in the left eye until surgery could be completed. Topical cyclosporine A 0.2% (Optimmune; Schering-Plough, Kirkland, Quebec) was initiated q12h in both eyes for treatment of keratoconjunctivitis sicca. A complete blood (cell) count (CBC) and a serum biochemistry profile were obtained in preparation for surgery. The CBC revealed no significant abnormalities, and serum chemistry revealed mild hypoalbuminemia and mild elevations in creatinine, amylase, and alkaline phosphatase of unknown significance. The dog returned 5 days later due to rapid enlargement of the mass and worsening of ocular discomfort (Figure 1b). The ocular examination at this time revealed more marked medial strabismus, enlargement of the mass, and thinning of the dorsolateral sclera in the left eye. Indirect ophthalmoscopy of the right eye now revealed multifocal, variably sized, areas of tapetal hyporeflectivity. The ocular diagnoses for the left eye were unchanged, and the right eye were chorioretinitis and multifocal flat retinal detachments. Bilateral ocular disease significantly increased suspicion of a systemic condition. Enucleation of the left globe was completed and the globe was submitted for light microscopic examination. The results of the biopsy taken at first presentation became available the day following enucleation and were consistent with marked chronic pyogranulomatous conjunctivitis with intralesional Blastomyces dermatiditis organisms. Light microscopic examination of the enucleated globe revealed pyogranulomatous infiltration of the choroid, limbus, and sclera containing yeast organisms morphologically consistent with Blastomyces dermatiditis organisms. Retinal detachment was confirmed with retinal necrosis and an inflammatory infiltrate was present in the subretinal space and vitreous. Inflammation was not present in the deep orbital tissues submitted with the globe. Blastomycosis is a systemic fungal 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 (1). Although direct inoculation can occur, the mode of infection is most often by inhalation. In the soil the organism is found in the hyphal form and produces conidia. Infection results when conidia are inhaled, deposited in the lungs, and incubated at body temperature. The infective conidia assume the yeast phase and the organism may then be disseminated by hematogenous or lymphatic routes to skin, lymph nodes, subcutaneous tissues, bone, eyes, testicles, and the central nervous system (CNS) (2). Although it is possible for infection to be localized, it is common for more than one organ system to be affected and clinical signs of blastomycosis depend on the tissues involved (2,3). Ocular lesions occur in up to 48% of infected dogs (4–6). The most common ocular manifestations are those of uveitis. 1196
Organisms reach the eye hematogenously and become established in the choroid eliciting a pyogranulomatous response. Extension of inflammation into the retina through exudation and granuloma formation often leads to retinal detachment (4,7). The intense posterior inflammation triggers an inflammatory response in the anterior ocular tissues resulting in anterior uveitis. Inflammation of both the posterior (choroid) and anterior uvea (iris and ciliary body) is termed endophthalmitis, while inflammation extending into other ocular tissues such as sclera is termed panophthalmitis. Secondary glaucoma is a common sequela to severe anterior uveitis and may be due to peripheral anterior synechia, or inflammatory cell infiltration of the iridocorneal angle (7,8). Pulmonary involvement is evident in approximately 88% of cases (2). A miliary to nodular interstitial pattern is most commonly observed on thoracic radiographs and may be diffuse or non-diffuse in distribution (3,5). Tracheobronchial lymphadenomegaly occurs in some dogs (2). Treatment of ocular blastomycosis must be directed at reducing the intraocular inflammation in addition to systemic antifungal therapy. Topical non-steroidal anti-inflammatory medications and corticosteroids are utilized to address anterior uveitis. The presence of chorioretinitis and retinal detachment necessitate systemic medications as topically applied corticosteroids will not penetrate the posterior segment of the eye (9). Many authors recommend anti-inflammatory doses of systemic prednisone [1 to 2 mg/kg body weight (BW) per day] for ocular blastomycosis (7,9,10). This may be associated with improved visual outcomes and does not appear to endanger the animal’s life if accompanied by appropriate antifungal therapy (7,10). The antifungal therapy of choice is itraconazole at a dose of 5 mg/kg BW, PO, q24h for at least 4 to 6 months (11). Currently it is recommended that therapy be continued for at least 1 month following radiographic evidence that pulmonary infiltrates have resolved (5,12). An addition 2 to 4 weeks of antifungal therapy is suggested if systemic corticosteroids have been used (12). Prognosis for survival of blastomycosis is good unless there is CNS involvement or severe lung disease. Prognosis for eyes and vision depends on location and severity of disease in the eye. Eyes with disease limited to the posterior segment (other than optic nerve involvement) had a 76% chance of recovery in one study (13). Another study showed that prognosis for vision is good if , 50% and guarded if . 50% of the fundus is involved (10). Anterior segment disease is associated with a poor prognosis (13). Glaucoma secondary to anterior segment disease is the most common reason for enucleation. (6,10,13,14). The recurrence rate for blastomycosis is approximately 20% and usually occurs within 1 year of completion of treatment (2). Following diagnosis in this case, the referring veterinarian initiated therapy with itraconazole. Thoracic radiographs were completed which showed a mild interstitial pattern and an enlarged thoracic lymph node indicative of mild pulmonary involvement. In the first 3 days following initiation of therapy, the dog experienced a reduced appetite and enlargement of the submandibular lymph nodes, but reportedly showed improvement over the next week. A follow-up ophthalmic examination of the right eye was recommended but was unfortunately declined. CVJ / VOL 57 / NOVEMBER 2016
References
CVJ / VOL 57 / NOVEMBER 2016
1197
D I AG N O S T I C O P H T H A LM O LO GY
1. 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. 2. Legendre AM. Blastomycosis. In: Greene CE. ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, Missouri: Saunders Elsevier, 2012: 606–614. 3. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658–664. 4. Buyukmihci N. Ocular lesions of blastomycosis in the dog. J Am Vet Med Assoc 1982;55:45–54. 5. 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. 6. 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. 7. Albert RA, Whitley RD, Crawley RR. Ocular balstomycosis in the dog. Comp Contin Educ Pract Vet 1981;3:303–311. 8. Buyukmihci NC, Moore PF. Microscopic lesions of spontaneous ocular blastomycosis in dogs. J Comp Path 1987;97:321–328.
9. Holmberg BJ, Maggs DJ. The use of corticosteroids to treat ocular inflammation. Vet Clin North Am Small Anim Pract 2004;34:693–705. 10. 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. 11. Broemel C, Sykes J. Epidemiology, diagnosis, and treatment of blastomycosis in dogs and cats. Clin Tech in Small Anim Pract 2005; 20:233–239. 12. Legendre Am, Toal RL. Diagnosis and treatment of fungal diseases of the respiratory system. In: Kirk’s Current Veterinary Therapy XIII. Small Animal Practice. In: Bonagura JD, ed. Philadelphia, Pennsylvania: WB Saunders, 2000:815–819. 13. Brooks DE, Legendre AM, Gum GG, et al. The treatment of canine ocular blastomycosis with systemically administered itraconazole. Prog Vet Comp Ophthalmol 1991;1:263–268. 14. Hendrix DVH, Rohrbach BS, Bochsler PN, et al. Comparison of histologic lesions of endophthalmitis induced by Blastomyces dermatitidis in untreated and treated dogs: 36 cases (1986–2001). J Am Vet Med Assoc 2004;224:1317–1322.
A
History and clinical signs
3-year-old spayed female golden retriever dog was examined at the ophthalmology service at the Western College of Veterinary Medicine for evaluation of a cloudy, painful left eye. The dog was presented to her referring veterinarian one week previously and therapy was initiated with topical diclofenac sodium 0.1% (Voltaren ophtha; Novartis, Mississauga, Ontario), q6h, in addition to fucidic acid 1% (Fucithalmic Vet; Aventix Animal Health, Flamborough, Ontario), q12h. The menace response was absent in the left eye. Direct and consensual pupillary light reflexes were absent in the left eye as was the left to right consensual pupillary light reflex. Palpebral and occulocephalic reflexes were present bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 5 and 11 mm/min in the right and left eyes, respectively. The intraocular pressures were estimated with a rebound tonometer (Tonvet; Tiolat, Helsinki, Finland) and were 9 and 52 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) was negative bilaterally. On direct examination the left eye had medial strabismus associated with a large, mass-like thickening at the dorsolateral aspect of the globe. Marked conjunctival hyperemia, episcleral congestion, corneal edema, and peripheral corneal vascularization were also present. Following application of 0.5% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario) biomicroscopic examination (Osram 64222; Carl Zeiss Canada, Don Mills, Ontario) revealed an opacity posterior to the lens in the left eye. Indirect ophthalmoscopic (Heine Omega 200; Heine Instruments Canada, Kitchener, Ontario) examination was not possible in the left eye due to corneal opacity and medial strabismus. The right eye had a single focal area of tapetal hyporeflectivity. An ocular ultrasound was completed which confirmed a complete retinal detachment with hyperechoic subretinal opacities in the left eye in addition to a hyperechoic mass in the region of the dorsolateral ciliary body. A photograph of the left eye at presentation is provided for your assessment (Figure 1a).
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 / NOVEMBER 2016
a
b Figure 1. Photograph of the left eye of a 3-year-old golden retriever dog. a — at presentation. b — 1 week later.
What are your clinical diagnosis, differential diagnoses, therapeutic plan, and prognosis? Discussion The clinical diagnoses were an intraocular mass with presumed extraocular extension, panophthalmitis, retinal detachment, and secondary glaucoma of the left eye, in addition to bilateral keratoconjunctivitis sicca. The focal retinal lesion in the right eye was considered of unknown significance at that time. The differential diagnoses for a mass lesion of the eye include neoplasia or inflammation, particularly a granulomatous inflammatory process. Retinal detachment of this type may occur with subretinal accumulation of fluid and/or cellular material which may be inflammatory or neoplastic in origin. Secondary glaucoma is a common sequela to severe intraocular inflammation as well as intraocular neoplasia. Keratoconjunctivitis sicca 1195
O P H TA LM O LO G I E D I AG N O S T I Q U E
is most often caused by immune-mediated lacrimal adenitis and was likely a separate condition. Definitive diagnosis of a mass-like lesion requires light microscopic examination of tissue. A biopsy of the thickened episcleral tissue was completed following topical anesthetic application to the area and this was submitted for light microscopic examination. The eye was blind with severe disease, so enucleation was scheduled. Diclofenac and fucidic acid therapy were continued in the left eye until surgery could be completed. Topical cyclosporine A 0.2% (Optimmune; Schering-Plough, Kirkland, Quebec) was initiated q12h in both eyes for treatment of keratoconjunctivitis sicca. A complete blood (cell) count (CBC) and a serum biochemistry profile were obtained in preparation for surgery. The CBC revealed no significant abnormalities, and serum chemistry revealed mild hypoalbuminemia and mild elevations in creatinine, amylase, and alkaline phosphatase of unknown significance. The dog returned 5 days later due to rapid enlargement of the mass and worsening of ocular discomfort (Figure 1b). The ocular examination at this time revealed more marked medial strabismus, enlargement of the mass, and thinning of the dorsolateral sclera in the left eye. Indirect ophthalmoscopy of the right eye now revealed multifocal, variably sized, areas of tapetal hyporeflectivity. The ocular diagnoses for the left eye were unchanged, and the right eye were chorioretinitis and multifocal flat retinal detachments. Bilateral ocular disease significantly increased suspicion of a systemic condition. Enucleation of the left globe was completed and the globe was submitted for light microscopic examination. The results of the biopsy taken at first presentation became available the day following enucleation and were consistent with marked chronic pyogranulomatous conjunctivitis with intralesional Blastomyces dermatiditis organisms. Light microscopic examination of the enucleated globe revealed pyogranulomatous infiltration of the choroid, limbus, and sclera containing yeast organisms morphologically consistent with Blastomyces dermatiditis organisms. Retinal detachment was confirmed with retinal necrosis and an inflammatory infiltrate was present in the subretinal space and vitreous. Inflammation was not present in the deep orbital tissues submitted with the globe. Blastomycosis is a systemic fungal 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 (1). Although direct inoculation can occur, the mode of infection is most often by inhalation. In the soil the organism is found in the hyphal form and produces conidia. Infection results when conidia are inhaled, deposited in the lungs, and incubated at body temperature. The infective conidia assume the yeast phase and the organism may then be disseminated by hematogenous or lymphatic routes to skin, lymph nodes, subcutaneous tissues, bone, eyes, testicles, and the central nervous system (CNS) (2). Although it is possible for infection to be localized, it is common for more than one organ system to be affected and clinical signs of blastomycosis depend on the tissues involved (2,3). Ocular lesions occur in up to 48% of infected dogs (4–6). The most common ocular manifestations are those of uveitis. 1196
Organisms reach the eye hematogenously and become established in the choroid eliciting a pyogranulomatous response. Extension of inflammation into the retina through exudation and granuloma formation often leads to retinal detachment (4,7). The intense posterior inflammation triggers an inflammatory response in the anterior ocular tissues resulting in anterior uveitis. Inflammation of both the posterior (choroid) and anterior uvea (iris and ciliary body) is termed endophthalmitis, while inflammation extending into other ocular tissues such as sclera is termed panophthalmitis. Secondary glaucoma is a common sequela to severe anterior uveitis and may be due to peripheral anterior synechia, or inflammatory cell infiltration of the iridocorneal angle (7,8). Pulmonary involvement is evident in approximately 88% of cases (2). A miliary to nodular interstitial pattern is most commonly observed on thoracic radiographs and may be diffuse or non-diffuse in distribution (3,5). Tracheobronchial lymphadenomegaly occurs in some dogs (2). Treatment of ocular blastomycosis must be directed at reducing the intraocular inflammation in addition to systemic antifungal therapy. Topical non-steroidal anti-inflammatory medications and corticosteroids are utilized to address anterior uveitis. The presence of chorioretinitis and retinal detachment necessitate systemic medications as topically applied corticosteroids will not penetrate the posterior segment of the eye (9). Many authors recommend anti-inflammatory doses of systemic prednisone [1 to 2 mg/kg body weight (BW) per day] for ocular blastomycosis (7,9,10). This may be associated with improved visual outcomes and does not appear to endanger the animal’s life if accompanied by appropriate antifungal therapy (7,10). The antifungal therapy of choice is itraconazole at a dose of 5 mg/kg BW, PO, q24h for at least 4 to 6 months (11). Currently it is recommended that therapy be continued for at least 1 month following radiographic evidence that pulmonary infiltrates have resolved (5,12). An addition 2 to 4 weeks of antifungal therapy is suggested if systemic corticosteroids have been used (12). Prognosis for survival of blastomycosis is good unless there is CNS involvement or severe lung disease. Prognosis for eyes and vision depends on location and severity of disease in the eye. Eyes with disease limited to the posterior segment (other than optic nerve involvement) had a 76% chance of recovery in one study (13). Another study showed that prognosis for vision is good if , 50% and guarded if . 50% of the fundus is involved (10). Anterior segment disease is associated with a poor prognosis (13). Glaucoma secondary to anterior segment disease is the most common reason for enucleation. (6,10,13,14). The recurrence rate for blastomycosis is approximately 20% and usually occurs within 1 year of completion of treatment (2). Following diagnosis in this case, the referring veterinarian initiated therapy with itraconazole. Thoracic radiographs were completed which showed a mild interstitial pattern and an enlarged thoracic lymph node indicative of mild pulmonary involvement. In the first 3 days following initiation of therapy, the dog experienced a reduced appetite and enlargement of the submandibular lymph nodes, but reportedly showed improvement over the next week. A follow-up ophthalmic examination of the right eye was recommended but was unfortunately declined. CVJ / VOL 57 / NOVEMBER 2016
References
CVJ / VOL 57 / NOVEMBER 2016
1197
D I AG N O S T I C O P H T H A LM O LO GY
1. 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. 2. Legendre AM. Blastomycosis. In: Greene CE. ed. Infectious Diseases of the Dog and Cat. 4th ed. St. Louis, Missouri: Saunders Elsevier, 2012: 606–614. 3. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658–664. 4. Buyukmihci N. Ocular lesions of blastomycosis in the dog. J Am Vet Med Assoc 1982;55:45–54. 5. 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. 6. 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. 7. Albert RA, Whitley RD, Crawley RR. Ocular balstomycosis in the dog. Comp Contin Educ Pract Vet 1981;3:303–311. 8. Buyukmihci NC, Moore PF. Microscopic lesions of spontaneous ocular blastomycosis in dogs. J Comp Path 1987;97:321–328.
9. Holmberg BJ, Maggs DJ. The use of corticosteroids to treat ocular inflammation. Vet Clin North Am Small Anim Pract 2004;34:693–705. 10. 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. 11. Broemel C, Sykes J. Epidemiology, diagnosis, and treatment of blastomycosis in dogs and cats. Clin Tech in Small Anim Pract 2005; 20:233–239. 12. Legendre Am, Toal RL. Diagnosis and treatment of fungal diseases of the respiratory system. In: Kirk’s Current Veterinary Therapy XIII. Small Animal Practice. In: Bonagura JD, ed. Philadelphia, Pennsylvania: WB Saunders, 2000:815–819. 13. Brooks DE, Legendre AM, Gum GG, et al. The treatment of canine ocular blastomycosis with systemically administered itraconazole. Prog Vet Comp Ophthalmol 1991;1:263–268. 14. Hendrix DVH, Rohrbach BS, Bochsler PN, et al. Comparison of histologic lesions of endophthalmitis induced by Blastomyces dermatitidis in untreated and treated dogs: 36 cases (1986–2001). J Am Vet Med Assoc 2004;224:1317–1322.
