The bleeding eye (Proceedings)

Most causes for the breakdown of blood ocular barriers are a result of either 1) acute-onset of traumatic causes -either obvious sharp trauma often involving laceration of the globe, or blunt-compressive trauma or choking) or 2) is the result of a chronic ocular condition that has led to the formation of "pre-iridal fibrovascular membranes (PIFM)" as a response to chronic intraocular hypoxia. PIFM formation is usually the result of glaucoma, retinal detachment, neoplasia, or after intraocular surgery, and is associated with uveitis) or 3) is related to uveitis and blood ocular barrier disruption which is either caused by systemic illness or remains idiopathic, or 4) by other inherited or congenital ocular abnormalities, but these are rare. Examples might include hemorrhage in the posterior segment of the eye as the result of a retinal detachment (Collie Eye Anomaly), or persistent vasculature (persistent hyperplastic primary vitreous in Doberman Pinschers or Staffordshire Terriers).

Sharp and blunt traumatic ocular hemorrhage

The goals of therapy when approaching a bleeding eye always include identifying the cause of bleeding if possible (in this case we know it was trauma); preventing bleeding from recurring; controlling the resultant uveitis and limiting the sequelae of uveitis (glaucoma, cataracts, senechiae, etc). In general, surgically lavaging hyphema or pulling clots out from the anterior chamber often results in recurrence of bleeding as the anterior chamber must be decompressed and the iris is traumatized during this procedure. Lacerations to the cornea or globe should be sutured primarily (referral situation). Lacerations to the lens capsule also occur, especially when the sharp trauma includes a history of a cat scratch. If a lens capsular tear can be seen or is suspected, this requires immediate referral as other more aggressive surgical interventions including phacoemulsification of the lens may be necessary to avoid blinding phacoclastic uveitis. If medical therapy alone is indicated, strict rest and removing the potential source of trauma is the first important step. Administration of topical steroids such as 1% prednisolone acetate, or dexamethasone is recommended when bleeding is subconjunctival or intraocular and infected corneal wounds are not present. Topical hydrocortisone will not penetrate well into the anterior chamber so should not be used for the treatment of uveitis and bleeding, but can be used to limit inflammation associated with mild conjunctival hemorrhage. Initial therapy may be 3-8x/day depending on the severity of hemorrhage and inflammation. Subconjunctival injections of triamcinolone may be useful, especially in patients that cannot be medicated frequently at home. Injectable, subconjunctival steroids should be avoided when there is concurrent ulcerative/infectious keratitis, as they can have devastating effects on the eye; however oral anti-inflammatory doses of glucocorticoids can be used in these situations. Generally oral and topical NSAIDS should not be used because of their effects on platelets and clotting, which may lead to re-bleeding. Intracameral or intravitreal injections of 25ug of tissue plasminogen activator (TPA) in small animals may be of some use in breaking up clots or treatment of hemorrhage/uveitis induced secondary glaucoma. Bleeding in the posterior segment of the eye (often from blunt trauma may lead to the development of intravitreal traction bands, whereby fibrin condenses in the vitreous placing traction on the retina, ultimately leading to a detachment. TPA injections should only be attempted when the cause of hyphema is known, and has not occurred within the last 72 hours, as re-bleeding may occur. If glaucoma is beginning or anticipated, topical and/or systemic carbonic anhydrase inhibitors and timolol are indicated. Topical prostaglandin analogues such as xalatan, or drugs that worsen/cause uveitis such as pilocarpine should not be used in these cases as worsening uveitis and bleeding is expected. Intraocular pressure should be monitored regularly, especially if dilating drops are part of the treatment protocol.

PIFMs

Pre-iridal fibrovascular membranes (what they didn't teach us in veterinary school): Fibrovascular membranes form on the surface of the iris, retina and optic disc as a result of VEGF that is released in response to chronic intraocular ischemia (Gelatt). The most common causes for this are retinal detachments, glaucoma, and chronic uveitis (for a variety of causes) as well as intraocular tumors. The sources of VEGF are many. Domestic animals form PIFMs on the iris more than in the posterior segment in contrast to humans. Clinical manifestations of PIFM formation are difficult to detect in most animals, especially since the disease process may be insidious and the other eye often remains visual, so owners do not present these dogs until the second eye has had an issue.

If the cause of bleeding is unclear (no known history of trauma and no obvious wounds/bruising) my general diagnostic profile includes a CBC, manual platelet count (especially in cats given their platelet clumping issues), blood chemistry and blood pressure assessment. Clotting profiles are submitted if toxicities are possible.

However, when there is recurrent bleeding in the eye without a known history of trauma, with a normal physical exam, blood pressure, and hematologic findings, this should alert you to the possibility of recurrent uveitis (for a variety of causes) or intraocular neoplasia and therefore more specific blood testing for infectious diseases and recommended. An ocular ultrasound may also be helpful in establishing a diagnosis since often the posterior segment is not visible through the hemorrhage.

Systemic diseases suspected of causing ocular hemorrhage

The systemic diseases that result in intraocular hemorrhage are very similar to those causes of uveitis in both dogs and cats. These include viral diseases (rarely in dogs, more common in cats with FeLV, FIV and FIP), mycotic (rare in DC area unless pets travel), bacterial (E. canis, Anaplasma platys, Borrelia burgdorferi), protozoal (toxoplasmosis in cats especially), parasitic (Dirofilaria immitus), neoplastic (lymphoma, hemangiosarcoma, adenocarcinoma, metastatic ocular disease), and other primary systemic causes (hypertension, hyperviscosity syndrome, post-ionizing radiation) – Slatter 4th Ed.

More specifically, systemic causes of retinal hemorrhages in the dog and cat include:

Infectious diseases (E. canis, RMSF, Lyme, Blastomycosis, coccidiomycosis), parasitic (ophthalmyiasis interna), cardiac/vascular/hematologic disorders (systemic hypertension (cats more often than dogs), hyperviscosity syndrome (FIP or multiple myeloma), polycythemia, thrombocytopenia of many different causes (see next paragraph), platelet function disorder, anemia (must be severe, and only clinically appreciated in cats), or von Willebrand's disease; metabolic disease (Diabetes mellitus in dogs); toxic causes (anticoagulant toxicity); Neoplastic disease (lymphoma, multiple myeloma; other systemic causes (post-ionizing radiation, or GME) – Slatter, 4th Ed.

The rule outs for thrombocytopenia in dogs and cats is not the intention of this lecture, and Dr. Hyman is covering the ocular manifestations of systemic diseases of dogs and cats in much greater detail, so we will spend little time on this. However for reference, the most common causes for thrombocytopenia in dogs are infectious diseases such as monocytic ehrlichiosis, infectious cyclic thrombocytopenia, Babesia, and RMSF), neoplasias such as myo and lymphoproliferative disorders, and many different types of carcinomas or sarcomas. Immune-mediated thrombocytopenia, drug toxicities and chemotherapy, and platelet consumption from vasculitis, neoplasia, and DIC are also possible.

Ocular manifestations of hematologic disorders may include both extraocular and intraocular hemorrhage. Extraocular hemorrhages may be mild and subtle, or may be severe as the type often seen such as when there is traumatic proptosis of the globe, with continual bleeding and apparent absence of clotting. Intraocular bleeding can manifest as hyphema with blood filling a small portion of (the inferior) or the entirety of the anterior chamber; hemorrhage into the iris (iridal petechias) which may take on a multifocal or radial pattern; vitreal hemorrhages (which are often subtle and seen in the inferior vitreous, but can be severe), as well as pre-retinal, intra-retinal, and sub-retinal (choroidal) hemorrhages which take on more classic appearances depending on what layers of the retina they are affecting (see slide presentation). When large amounts of hemorrhage occurs in the vitreous and retina (enough so that you cannot clearly see these structures), retinal detachments should be anticipated or may have occurred, and can usually be confirmed with the use of an ultrasound. An ultrasound evaluation may also reveal posterior segment causes for bleeding such as a tumor, and help to establish a prognosis and proper treatment (surgery). Your physical examination and baseline laboratory findings will enable you to select further more specific tests to determine if an underlying systemic causes is present in these cases.

Remember that the treatment of intraocular hemorrhage associated with systemic disease is usually associated with uveitis and may be chronic. Some exceptions include the small hemorrhages reported with metabolic conditions such as diabetes mellitus in dogs. In general, it is thought that bleeding diasthesis does not typically occur until platelet numbers drop below 50,000 and is more common in acute then in chronic conditions – the same appears to apply to the eye.

Most treatments for intraocular hemorrhage associated with uveitis include the use of both aggressive topical and systemic glucorticoids (at an anti-inflammatory dose), and topical mydriatics (atropine or tropicamide). Drugs like atropine helps prevent posterior synechiae and controls painful iridocyclospasm, but may increase the risk for the development of secondary glaucoma. Prophylactic antiglaucoma therapy should also be considered if intraocular pressure is approaching the high end of normal pressure as pressure should be generally be low if there is severe intraocular inflammation.

More on systemic hypertension in dogs and cats

Hypertensive ocular hemorrhage does occur in dogs, although the blinding sequelae are more often seen in cats, given the greater incidence of kidney disease and associated bullous retinal detachments. Ocular lesions seen with systemic hypertension include tortuous retinal blood vessels, pre-retinal, intraretinal, and subretinal hemorrhages and bullous retinal detachments. Secondary retinal degeneration from ischemia and inflammation often occurs. Aged cats often present for severe mydriasis and blindness as a result of bullous detachments related to hypertension. Topical steroidal medications may be initiated to try and prevent secondary glaucoma if bleeding occurs, and/or significant anterior segment inflammation is present – I prefer topical prednisolone acetate 1% and low dose oral steroids – since NSAIDs are more likely to cause further renal compromise or bleeding. The prognosis for regaining some vision is fair if the retinas re-attach within the first few weeks and severe choroidal hemorrhages have not occurred. It may take months for pre-retinal and retinal hemorrhages to resolve completely once the hypertension is controlled with medications. Calcium channel blockers such as amlodipine and ACE inhibitors are typically the drugs of choice and referring veterinarians and ophthalmologists must work together to monitor these patients.

Inherited or congenital ocular anomalies

Those associated with intraocular hemorrhage can include persistent hyperplastic primary vitreous (where there may be hemorrhage into the lens itself), persistent hyaloid artery (although frank hemorrhage associated with this condition is rare, unless cataract surgery is attempted), merle ocular dysgenesis and Collie Eye Anomaly – where retinal detachment or hemorrhage can occur. Usually the key is that there is an obvious structural abnormality with the eye itself in a suspected breed. Referral to an ophthalmologist for treatment is recommended in these complex cases.

More specific examples of case management of ocular hemorrhage were presented in the lecture

References

Veterinary Ophthalmology: Gelatt's 4th Ed.

Fundamentals of Veterinary Ophthalmology – Slatter 4th Ed (Maggs).