Corneal Intrastromal Hemorrhage – Canine

Synonyms:
Intracorneal hemorrhage
Intracorneal stromal hemorrhage

Disease Description:
Definition
Intrastromal corneal hemorrhage is an uncommon condition of older dogs. Hemorrhages consist of variably-sized, focal, well-demarcated areas of blood within corneal stroma.¹ Corneal vascularization is invariably associated with the hemorrhages. However, corneal vascularization is a relatively common finding in dogs, while intracorneal hemorrhage is uncommon. A similar phenomenon has not been reported in cats.

Disease Description in This Species:
Etiology
A definitive underlying cause has not been identified; however, corneal vascularization appears to be a prerequisite for development. Causes of corneal vascularization are numerous, with the most common being keratoconjunctivitis sicca (KCS), prior corneal surgery, corneal ulceration, and superficial keratitis.^3,4 In one study, intracorneal hemorrhage was associated with other ocular conditions in 91% of the cases, suggesting the may be a secondary ocular condition.² Logically, ocular conditions that promote corneal vascularization (e.g. KCS, corneal ulceration, chronic keratitis are likely to contribute to intracorneal hemorrhages but these conditions are common and intrastromal hemorrhages are not.^3,4) In addition, given the older age of affected dogs, other unidentified factors (e.g. increased vessel fragility) are probably present.

In one study, 59% of affected dogs with intracorneal hemorrhage had underlying systemic diseases, with diabetes mellitus, hyperadrenocorticism, hypothyroidism, and systemic hypertension being the most common.² In humans, intracorneal hemorrhage has been associated with a variety of ocular and systemic conditions.^5-8 They may also develop spontaneously, which has made identification of a specific cause difficult.^5-8

Diagnosis
Physical Examination Findings/History: Corneal hemorrhages cause no specifice clinical signs and are often incidental findings. Abnormal findings on physical examination reflect underlying or associated ocular or systemic disorders. Thorough physical examination is indicated in all dogs with intracorneal hemorrhage.

Ophthalmic Examination Findings: Diagnosis is typically made by observing free blood within the corneal stroma. Slit lamp biomicroscopy may be needed to confirm the diagnosis. An intrastromal corneal hemorrhage is a focal, well-demarcated area of light to dark red blood within the stroma. It usually occurs at the leading edge of a superficial corneal vessel. The blood often fans out away from the termination of the vessel, creating a reddish arc around a lighter center (Figures 1A, 2, 3A). Intracorneal hemorrhages are typically unilateral but can be bilateral. Neither eye appears to be predisposed. The most common area affected is the mid-central, nasal quadrant of the cornea, although the hemorrhage may occur anywhere in the cornea.^1,2 Usually a single hemorrhage is present but occasionally 2 may occur in the same cornea.

Complete ocular examination that includes Schirmer tear test, tear film evaluation, fluorescein staining, and tonometry is indicated to look for concurrent problems, such as KCS, keratitis, corneal ulcers, and cataracts.²

Other Tests: Other tests to consider include a complete blood count, biochemistry profile, urinalysis, and measurement of systemic blood pressure. Depending upon the results of these tests and presence of other clinical abnormalities, endocrine tests may be warranted.

Corneal Imaging: Although not currently used for intracorneal hemorrhages, advanced corneal imaging techniques (e.g. optic coherence tomography, biomicroscopic ultrasonography, confocal microscopy) may be helpful in the future to better characterize the nature and location of the hemorrhage, as well as to identify other underlying corneal pathology.^9-11 Confocal microscopy has become more readily available for use in clinical patients and may improve understanding of the pathology of these hemorrhages in the future.^13,14

Signalment
Intrastromal hemorrhages occur in a wide variety of breeds, as well as mixed breed dogs. One study found no breed predispositions.¹ In another study, the bichon frise was overrepresented.² Most affected dogs are older, with average age 11.4-11.5 years.^1,2 No sex predilection has been documented.

Clinical Signs
Most dogs have no clinical signs associated with the hemorrhage or may only exhibit a red eye. The characteristic lesion may be noted by the owner or discovered upon routine physical examination. Some clinical signs may be associated with the underlying cause of the corneal vascularization, such as conjunctival redness, blepharospasm, rubbing the eye, discharge, etc.² The hemorrhage itself does not appear to cause discomfort. Other physical abnormalities may be present that are related to concurrent systemic diseases.

Etiology:
Corneal irritation
Diabetes mellitus
Hyperadrenocorticism
Hypertension, systemic
Hypothyroidism
Idiopathic, unknown
Immune-mediated hemolytic anemia
Immune-mediated thrombocytopenia
Keratoconjunctivitis sicca, eyes dry
Sepsis

Breed / Species Predilection:
Bichon frise

Sex Predilection:
None

Age Predilection:
Old

Diagnostic Procedures:
None

Images:
URL: https://beta.vin.com/doc/?id=8298938

Figure 1A. Large intracorneal hemorrhage affecting approximately 40% of the corneal surface
OS of 9-yr-old, CM Labrador mix. Hemorrhage is present at the leading edge of corneal vascularization. No systemic problems were identified but a qualitative tear deficiency was diagnosed.

Figure 1B. The same eye after 4 weeks of topical cyclosporine and dexamethasone
The hemorrhage is significantly improved, with partial resolution and regression of vascularization. Yellow-brown discoloration of the stroma persists in some areas.

Figure 2. Corneal intrastromal hemorrhage
Click here to see board discussion

Figure 3A. Intrastromal corneal hemorrhage at the leading edge of corneal vessels
OS of an 11-yr-old Yorkshire terrier. Blepharospasm and a qualitative tear deficiency were present.

Figure 3B. The same eye after 4 weeks of topical tacrolimus and dexamethasone
The hemorrhage has resolved and marked vascular regression is noted. Mild corneal pigmentation is still present. Note incidental iris atrophy at 1 o’clock.

Treatment / Management:
SPECIFIC THERAPY
Specific therapy has not been elucidated; however, identification and treatment of underlying ocular conditions (especially surface diseases), and systemic disease is warranted.

SUPPORTIVE THERAPY
If ocular surface disease is present, appropriate treatment with topical lacrimogenic (e.g. cyclosporine, tacrolimus) and/or anti-inflammatory drugs (e.g. corticosteroid, nonsteroidal anti-inflammatory drug) is warranted. Caution must be exercised when using topical anti-inflammatories in the presence of severe KCS because of the risk for corneal ulceration. They are contraindicated in the presence of corneal ulceration.

Treatments reported for intracorneal hemorrhage include topical anti-inflammatories q 12 hrs, topical antibiotics, and lubricants.^1,2 Response to therapy has varied.^1,2 Tear stimulants (e.g. cyclosporine, tacrolimus) have been shown to have antiangiogenic and anti-inflammatory properties, and anecdotally they appear to be beneficial.¹²

MONITORING and PROGNOSIS
Most hemorrhages improve over time, as long as any underlying cause of corneal vascularization is treated appropriately.^1,2 In one study, 60% of lesions resolved, with an average time to resolution of 198 days.² Improvement of some lesions can be seen within 30 days (Figures 1B, 3B). After resolution, long-term effects can include yellow-brown staining in the area of the previous hemorrhage, fibrosis or corneal degeneration, lipid infiltration, pigmentation, and/or stromal thinning. In one study, vascularization persisted and the lesion did not improve in 30% of affected eyes.¹ However, overall prognosis is good. Intracorneal hemorrhages have not resulted in blindness.

Special Considerations:
Other Resources
Recent VIN Message Board discussions on corneal intrastromal hemorrhage
2014 VIN Rounds on corneal opacities
Ophthalmology Fun Case 110
For more images, see the Corneal Intrastromal Hemorrhages – Dog slideshow in the Image Library
For more images, see the Corneal Intrastromal Hemorrhages, Part 2 – Dog slideshow in the Image Library

Differential Diagnosis:
Chronic superficial keratitis (pannus)
Corneal endothelial pigmentation
Corneal granulation
Corneal neoplasia
Corneal ulceration or persistent erosion associated with vascularization
Corneal vascularization without hemorrhage
Hyphema
Limbal mass invading the cornea, e.g. nodular granulomatous episcleritis

References:

1. Matas M, Donaldson D, Newton RJ: Intracorneal hemorrhage in 19 dogs (22 eyes) from 2000 to 2010: a retrospective study. . Vet Ophthalmol 2012 Vol 15 (2) pp. 86-91.
2. VioletteN P, Ledbetter E C: Intracorneal stromal hemorrhage in dogs and its associations with ocular and systemic disease: 39 cases. . Vet Ophthalmol 2017 Vol 20 (1) pp. 27-33.
3. Chow DW, Westermeyer HD: Retrospective evaluation of corneal reconstruction using ACell Vet(™) alone in dogs and cats: 82 cases. Vet Ophthalmol 2016 Vol 19 (5) pp. 357-66.
4. Gilger BC, Gelatt K N: Diseases and Surgery of the Canine Cornea and Sclera. Veterinary Ophthalmology, 4th ed. Blackwell Publishing, Ames IA pp. 690-725.
5. Freiberg F J, Salgado P J, Grehn F, et al: https://www.ncbi.nlm.nih.gov/pubmed/22388776. Eur J Ophthalmol 2012 Vol 22 (5) pp. 823-5.
6. Gismondi M, Brusini P: Intracorneal hematoma after canaloplasty. Eur J Ophthalmol 2013 Vol 23 (3) pp. 442.
7. Kaiura T L , Seedor J A, Koplin R S: Subepithelial intracorneal hemorrhage in a soft contact lens user.. Eye Contact Lens 2004 Vol 30 (3) pp. 120-1.
8. Sudha V, Burgess SE: Spontaneous intracorneal haemorrhage. Br J Ophthalmol 1999 Vol 83 (6) pp. 868-8.
9. Vallone L V, Enders A M, MohammedH O, et al: In vivo confocal microscopy of brachycephalic dogs with and without superficial corneal pigment. Vet Ophthalmol 2017 Vol 20 (4) pp. 294-303.
10. Wolfel A E, Pederson S L, Cleymaet A M, et al: Canine central corneal thickness measurements via Pentacam-HR(®) , optical coherence tomography (Optovue iVue(®) ), and high-resolution ultrasound biomicroscopy. Vet Ophthalmol 2017 Vol 0 (0) pp. 0.
11. Ledbetter E C, Norman M L, Starr J K: Vet Ophthalmol. Vet Ophthalmol 2016 Vol 19 (3) pp. 220-29.
12. Bucak Y Y , Erdurmus M, Terzi E H, et al: Inhibitory effects of topical cyclosporine A 0.05% on immune-mediated corneal neovascularization in rabbits. Graefes Arch Clin Exp Ophthalmol 2013 Vol 251 (11) pp. 2555-61.
13. STrom AR, Coretes DE, Thomasy SM et al: In vivo ocular imaging of the cornea of the normal female laboratory beagle using confocal microscopy. Vet Ophthalmol 2016 Vol 19 (1) pp. 63-67.
14. Vallone LV, Enders AM, Mohammed HO, et al: In vivo confocal microscopy of brachycephalic dogs with and without superficial corneal pigment. Vet Ophthalmolol 2017 Vol 20 (4) pp. 294-30.

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