bansal2016 (1)

Accepted Manuscript
Controversies in the pathophysiology and management of hyphema
Dr Svati Bansal, Dr Dinesh Visva Gunasekeran, Dr Bryan Ang, Dr Jiaying Lee, Dr
Rekha Khandelwal, Mr Paul Sullivan, Dr Rupesh Agrawal
PII:
S0039-6257(15)00217-9
DOI:
10.1016/j.survophthal.2015.11.005
Reference:
SOP 6602
To appear in:
Survey of Ophthalmology
Received Date: 9 May 2015
Revised Date:
12 November 2015
Accepted Date: 23 November 2015
Please cite this article as: Bansal S, Gunasekeran DV, Ang B, Lee J, Khandelwal R, Sullivan P, Agrawal
R, Controversies in the pathophysiology and management of hyphema, Survey of Ophthalmology
(2015), doi: 10.1016/j.survophthal.2015.11.005.
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Controversies in the pathophysiology and management of hyphema.
Authors:
Dr Svati Bansal1
Dr Dinesh Visva Gunasekeran2
Dr Bryan Ang2
Dr Jiaying Lee2
Dr Rekha Khandelwal3
Mr Paul Sullivan4
Dr Rupesh Agrawal2,4,5
1. Singapore National Eye Centre, Singapore
2. National Healthcare Group Eye Insitute, Tan Tock Seng Hospital, Singapore
3. NKP Salve Institute of Medical Sciences, Nagpur, India
4. Moorfields Eye Hospital, NHS Foundation Trust, London, UK
5. School of Material Science and Engineering, Nanyang Technological University,
Singapore
Corresponding author:
Adj Asst Prof Rupesh Agrawal
Consultant
National Healthcare Group Eye Institute
Tan Tock Seng Hospital
Singapore 308433
Email: [email protected]
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Outline:
1. Introduction
2. Pathophysiology of hyphema
3. Clinical features and examination
4. Complications
a. Increased intraocular pressure
b. Rebleeding (secondary hemorrhage)
c. Corneal blood staining
d. Optic atrophy
5. Management
a. Medical management
b. Surgical management
c. Hospitalisation & Follow ups
d. Screening for sickle cell disease or trait in patients of African
descent
6. Special situations
a. Sickle cell hemoglobinopathy
b. Hyphema in pediatric age group
c. Cataract and refractive surgery
d. Uveitis
7. Outcome measures
8. Conclusion
9. References
10. Table
11. Figures
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Abstract:
Traumatic hyphemas present dilemmas to physicians. There are numerous
controversies pertaining to the optimal approach to traumatic hyphema and no
standardised guidelines for its management We address some of these
controversies and present a pragmatic approach. We discuss the various medical
agents and surgical techniques available for treatment, along with the indications for
their use. We address the complications associated with hyphema and how to
diagnose and manage them and consider the management of hyphema in special
situations such as in children and sickle cell anemia and in rare clinical syndromes
such as recurrent hyphema after placement of anterior chamber intraocular lenses.
Key words:
Hyphema
Traumatic glaucoma
Surgical drainage
Angle recession
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1. Introduction:
Hyphema, the accumulation of blood in the anterior chamber, most common cause
is ocular trauma (blunt or penetrating)33,63 ;however, it can also be seen after
intraocular surgery or spontaneously in conditions such as rubeosis iridis, juvenile
xanthogranuloma, retinoblastoma, metastatic tumors, iris melanoma, myotonic
dystrophy, keratouveitis, leukemia, hemophilia, thrombocyotopenia, and Von
Willebrand disease
2,6,9,53,61,64,65,75,95.
Hyphema can be a herald sign of major
intraocular trauma and can itself cause complications such as secondary
hemorrhage and glaucoma104. Even small hyphemas may be associated with
significant damage to intraocular tissue.
Despite being a common condition, the management protocols for hyphema are still
unclear. Conservative management options include bed rest, head elevation, an eye
shield, and use of pharmacological agents (topical or systemic steroids,
antifibrinolytics, cycloplegics, miotics, aspirin, TCM and conjugated estrogen) 34.
Aside from the use of antifibrinolytics to prevent secondary hemorrhage, however,
there is no evidence of benefit from the use of these conservative measures 34.
Furthermore, there is a lack of consensus regarding a treatment and follow-up
strategy targeted at preventing delayed visual loss from complications of hyphema,
as well as the management of certain special situations such as concurrent sickle
cell anaemia.
We aim to address the controversies in the pathophysiology, evaluation, and
management of hyphema. Since trauma is the commonest cause, we focus our
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discussion on closed-globe traumatic hyphema; however, we also analyse special
situations such as uveitis, pediatric hyphema, cataract surgery, refractive surgery,
and hyphema in patients with sickle cell anaemia.
2. Pathophysiology of hyphema
The mean annual incidence rate of traumatic hyphema is estimated as 17/100,000
population in individuals less than 18 years of age1 and 20.7/100,000 population in
individuals less than 20 years of age50. Direct orbital injury resulting in traumatic
hyphema usually consists of a high-energy blow to the orbit (61% to 66%), impact
from a projectile (30.2% to 36%), or injury secondary to an explosion (2.4% to
3%)50,98. Athletic injuries have become a major cause of traumatic hyphema, while
accidents at work have become relatively less frequent. Kearns reported that athletic
injuries accounted for 39.2 % of 314 cases of traumatic hyphema, whereas accidents
at work were responsible for 9.9% of the cases49.
The commonest source of blood in hyphema is a tear in the anterior face of the
ciliary body108. A direct blow to the eye can rupture the blood vessels at the root of
the iris. The most frequently ruptured vessels are the major arterial circle of the iris
and its branches, the recurrent choroidal arteries, and the veins crossing the
suprachoroidal space between the ciliary body and episcleral venous plexus96,108 .
Blunt injury is also associated with antero-posterior compression of the globe and
simultaneous equatorial globe expansion. Equatorial expansion induces stress on
anterior chamber angle structures, which may lead to rupture of iris stromal and/or
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ciliary body vessels with subsequent hemorrhage22,96. Another possible source of
initial hemorrhage is a rapid increase in intra-ocular pressure (IOP) immediately after
the contusive trauma. This eventually leads to rupture of the fragile vasculature of
the iris from the pupillary sphincter and/or angle22.
Lacerating injury may be associated with direct damage to blood vessels and
hypotony, both of which can precipitate hyphema108. There is no consensus
regarding the predominant source of bleeding (angle vessels or iris sphincter
vessels) and their respective risks of rebleeding; however, current opinion is that
fragile angle vessels have the higher risk of bleeding as a result of their proximity to
the major arterial circle of the iris22.
Delayed hyphema after intraocular surgery may be the result of granulation tissue at
the wound margin or caused by damaged uveal vessels (e.g., from surgical trauma
or from intraocular lens-induced uveal trauma)64,95. This mechanism should be
considered in patients with a history of ocular surgery who present with spontaneous
hyphema.
In the pediatric age group (less than 18 years of age), hyphemas in the absence
of predisposing ocular or systemic disease/medication should arouse the
suspicion of non-accidental injury (NAI)60. A significant but rare cause of
spontaneous hyphema in children is juvenile xanthogranuloma (JXG). JXG is a
predominantly dermatological disorder most commonly presenting in children less
than 2 years old characterized by a raised, orange skin lesions occurring either
singly or in crops that will regress spontaneously. The most common ocular
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finding is diffuse or discrete iris nodules that are often quite vascular and may
bleed spontaneously. Occasionally, the lesions may present in other areas such
as ciliary body, anterior choroid, cornea, lids, and orbit47. Complications include
uveitis and glaucoma with resulting visual loss and phthisis. Biopsy of skin lesions
helps to confirm the diagnosis. The lesions classically contain an infiltrate of lipidladen histiocytes, lymphocytes, eosinophils and Touton giant cells.
Histologic examination of hyphemas reveals an erythrocyte aggregate enveloped by
a pseudocapsule of fibrin-plated coagulum47 .Clot absorption takes place by
breakdown of fibrin by fibrinolytic agents and escape of red blood cells through the
trabecular meshwork and Schlemm’s canal47 . Agents that open the trabecular
meshwork thus accelerate clot absorption.
3. Clinical features and examination
The importance of a detailed history and a thorough ocular and systemic evaluation
cannot be stressed enough. The nature of the injury points to the likely type of
damage sustained and therefore the prognosis. The priority in trauma is always to
stabilize airway, breathing, and circulation, and make an assessment for threats to
life. This is followed by an ophthalmic evaluation that includes inspection for gross
ocular injury, evaluation of the adnexae, visual acuity, pupillary function, ocular
motility, and the position of the globes.
Extensive conjunctival chemosis and hemorrhage may indicate an occult scleral
rupture (Figure 1). Proptosis may be secondary to a retrobulbar hematoma, and
restriction in ocular motility may suggest an orbital blowout fracture or a contusive
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head injury. Every attempt should be made to examine the adnexal region carefully
and rule out any associated orbital or head trauma. Hyphema can be associated with
open globe (Figure 2A) or closed globe injuries. In patients with open globe injury,
primary wound closure is the priority (Figure 2B). One should not attempt surgical
washout of hyphema in open globe injuries as the blind approach could lead to
adverse consequences. Surgical washout can be considered in patients with nonresolving hyphema or sickle cell trait because of the higher risk of secondary
glaucoma and permanent visual loss34. We shall focus on hyphema following closed
globe trauma.
Patients should be examined carefully to document and grade the hyphema (Table
1). The following clinical grading system is commonly used in the assessment of
traumatic hyphemas:
Grade 1 - Layered blood occupying less than one third of the anterior chamber
Grade 2 - Blood filling one third to one half of the anterior chamber
Grade 3 - Layered blood filling one half to less than total of the anterior chamber
Grade 4 - Total clotted blood, often referred to as “eight ball” or “black” hyphema
"Eight ball" or "black hyphema" occurs when the entire anterior chamber is filled with
blood, which takes on a darker red colour due to the impaired circulation in the
aqueous. The term “eight-ball hyphema” or “black-ball hyphema” was coined by
Smith and Regan in 1957 (after the dark ‘eight ball’ in snooker) 94; however, we have
observed that these total hyphemas often still retain a bright or dull red appearance
that more closely resembles the ‘third’ or the ‘eleventh’ ball in snooker. Therefore, it
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may be a worthwhile consideration to revise the traditionally named ‘eight ball’
hyphema to a “red-ball” or “three-ball hyphema” (Figure 3). A true dark “eight-ball”
hyphema carries a much worse prognosis than a bright red hyphema.
In addition to anterior segment examination, an assessment of visual acuity,
pupillary reactions, intraocular pressure, and extraocular movements must be made.
Hyphema may be associated with other signs of anterior segment trauma such as
traumatic cataract, damage to the trabecular meshwork, corneat, zonules, and iris
(Figure 4).
Fundus examination should be performed at the earliest possible opportunity to rule
out concomitant posterior segment trauma such as giant retinal tears that may
require prompt intervention. Indirect ophthalmoscopy using scleral depression in an
eye with traumatic hyphema is controversial. Clinicians are concerned that pressing
on the globe may cause a rebleed by mechanical distraction of the formed clot. The
exact pathophysiology behind the rebleed following scleral depression is not well
established. One explanation is a coup-countercoup mechanism similar to that in
blunt ocular trauma, which results in clot retraction and causes rebleeding.
We recommend gentle scleral depression to examine the peripheral retina in closed
globe injury. This will allow the ophthalmologist to exclude peripheral retinal tears
and retinal dialysis, as these complications may require surgical intervention. An
exception would be eyes that have had severe contusion, in which case we
recommend deferring scleral depression until several weeks have passed. Unlike
giant retinal tears, post-traumatic detachments caused by retinal dialysis progress
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slowly, and indentation may be safely deferred for several months. If scleral
depression is not performed, a super field condensing lens should be used to
examine the periphery. Furthermore, B-scan should be done if the hyphema
obscures the view of the posterior segment.
Radiological investigations (X-Ray or CT scans) are required in cases of suspected
intraocular foreign body, blowout fracture of the orbit, or head injury. Ultrasound
biomicroscopy can identify suspected anterior segment injury not clearly visible on
clinical examination. Ultrasound biomicroscopy is a proven ancillary tool useful for
ruling out angle recession, iridodialysis or cyclodialysis cleft, and occult foreign body
in the anterior chamber.
4. Complications
a. Increased intraocular Pressure (IOP)
Almost 30% of patients with post-traumatic hyphema have an increased IOP22.
An acute rise in IOP occurs from obstruction of the trabecular meshwork by
erythrocytes, fibrin, debris, and platelets. The likelihood of increased IOP is
proportionate to the severity of hyphema17. Secondary glaucoma is seen in 10%
of eyes with ≤50% hyphema, 25% if there is >50% hyphema, and 50% if the
hyphema is total79. Patients with eight-ball hyphema carry a 100% risk of
secondary glaucoma; however, eight-ball hyphema is rarely encountered.
Late secondary glaucoma may develop weeks to years after hyphema. The
incidence of late-onset glaucoma in eyes with a history of traumatic hyphema
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ranges from 0–20%10,102,103. The main causes of late onset glaucoma are
peripheral anterior synechiae formation, increased outflow resistance in angle
recession, fibrosis of the trabecular meshwork, and siderosis of the trabecular
endothelium.
Gonioscopic evaluation is recommended conventionally after seven to eight days
after resolution of hyphema to rule out angle recession; however, like indentation, we
prefer to wait for several weeks before attempting gonioscopy. Up to 10% of patients
are prone to develop late-onset glaucoma if the degree of angle recession exceeds
180°12,70,102,103. Angle recession in excess of 270° would further i ncrease the risk of
glaucoma. Blanton described two periods of elevated IOP, between 2 months and 2
years after the injury and 10 to 15 years after injury. Careful gonioscopy has
revealed that between 71% and 86% of traumatized eyes have angle recession 46.
The degree of angle recession is not proportional to the amount of hyphema. Some
small hyphemas produce large, deep recessions. A recent review by Ng et al
demonstrated a statistically significant association between angle recession greater
than 180° and the development of glaucoma
46.
It has already been recognised in
earlier literature that this group of patients should undergo lifelong annual
examination to detect late-onset glaucoma67; however, there is no consensus in the
literature regarding the frequency of follow-up required for patients with angle
recession of less than 180 degrees.
b. Rebleeding (secondary hemorrhage)
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Rebleeding or secondary hemorrhage occurs in 0.4% to 35% of patients, usually 2-7
days after trauma73,85. This is attributed to lysis and retraction of clot and fibrin within
traumatized vessels as part of the subacute healing process40.
It is important to arrange early follow-up to detect this condition as it can
significantly alter the visual prognosis through serious complications such as
corneal blood staining, amblyopia, secondary glaucoma, and optic atrophy.
Estimates of the incidence of glaucoma with rebleeding are high, ranging from 45
to 67%
23,42.
Rebleeding can be recognized clinically by the following
characteristics.
(i) An increase in the size of the hyphema
(ii) Presence of a layer of fresh blood over the older, darker clot in the anterior
chamber
(iii) Dispersed erythrocytes over the clot after the blood has settled.
Total and near total hyphemas often appear dark red. Their color lightens as they
start to liquefy and resolve as part of the normal healing process. This change in
colour should be distinguished from secondary hemorrhage.
A significant reduction of vision (<20/200), an initial hyphema of more than one third
of the anterior chamber, and elevated IOP at presentation are significant risk factors
for secondary bleeding59. One-fourth of the patients with grade I hyphemas
experience rebleeding into the anterior chamber of the eye, as compared with twothirds of patients with grade III or IV hyphema54.
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There has been shown to be an association of rebleeding with race
44,79.
The rates of
rebleed are higher in darker skinned persons, especially African Americans, when
compared with Caucasians. One hypothesis is that melanin interferes with the
clearance of erythrocytes from the anterior chamber, causing these differences in
rebleeding rates47.
Patients with haemophilia, von Willebrand’s disease, and sickle cell trait also have
higher risk of secondary haemorrhage44,68.
c. Corneal blood staining
Corneal blood staining (Figure 5) after hyphema has been reported in 2-11% of
cases11,79,82. The incidence increases in the presence of larger hyphemas,
secondary hemorrhage, prolonged clot retraction, sustained increase in IOP and
presence of previous endothelial dysfunction22,40,80. Read and Goldberg81 found that
an IOP of 25mmHg or greater for more than 6 days significantly increases the risk of
developing corneal blood staining. They subsequently proposed surgical intervention
in cases where the hyphema does not decrease by 50% after day 6 80. Corneal blood
staining starts as central straw yellow discoloration of the deep stroma which
spreads peripherally. Blood staining causes endothelial decompensation by
mechanical disruption of the endothelium and also by photosensitization of the
endothelium by hemoglobin-derived porphyrins in the presence of light39,40. The
blood staining clears centripetally and may take anywhere from several months to 2
years to clear15,19. In children, corneal blood staining may be further complicated by
amblyopia15.
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d. Optic atrophy
In the setting of post -traumatic hyphema, optic atrophy may develop secondary to
traumatic nerve contusion or secondary glaucoma. The risk of developing optic
atrophy related to elevated intraocular pressure is greater if the pressure is allowed
to remain at 50 mmHg or more for 5 days or 35 mmHg or more for 7 days in
otherwise healthy individuals81. Patients with sickle cell disease/trait develop optic
atrophy at lower intraocular pressures90.
5. Management of hyphema
The management of traumatic hyphema is directed towards accelerating the
absorption of the blood and the prevention of complications detailed above. There is
no conclusive evidence that hospital admission, sedation, or complete bed rest with
eye patching improves outcomes22,34,81,110 The indications and advantages of various
management options are discussed below.
Bed rest: Some clinicians advocate strict bed rest in hyphema to decrease the
chances of secondary haemorrhage; however, studies do not support this and most
have shown no advantage of bed rest over quiet ambulation 10,81. Hospitalization and
strict bed rest is mainly advised for patients with severe hyphema, sickle cell
trait/disease,
non-compliant
patients,
children,
and
patients
with
bleeding
predisposition92,110. Head elevation allows blood to layer inferiorly. This will promote
visual rehabilitation and prevent clot formation in the pupillary axis.
Eye patching: Traditionally, eye patching with metal shield protection was
advocated until resolution of hyphema. It was believed that the patching increases
patient comfort and provides immobilization for proper healing of corneal abrasions if
any. Gottsch et al39,40 hypothesised that patients with longstanding hyphema and
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prolonged light exposure might be at risk of developing endothelial dysfunction and
corneal bloodstaining. Although there is no evidence in the literature to support these
claims34, it is still recommended that patients with hyphema wear a hard plastic
shield at all times (including sleep) for the practical purpose of preventing further
trauma to the injured eye.
Anti-coagulant and anti-platelet medications: Anti-coagulant (e.g. warfarin
sodium, heparin) and anti-platelet (e.g. aspirin, dipyridamole, clopidogrel)
medications have not been shown to increase the risk of spontaneous haemorrhage
during intraocular surgery7,27,48. Hence, they do not have to be stopped prior to this
type of surgery. After the occurrence of a hyphema, however, these medications are
at risk factors for its persistence or re-bleeding. The risk of bleeding complications of
anticoagulant medications have been reported to be significantly greater than that of
antiplatelet medications87. Common indications for anti-coagulation therapy include
atrial fibrillation, prosthetic heart valves, and deep vein thrombosis. Anti-platelet
therapy is commonly indicated for the prevention of acute cardiac and
cerebrovascular events in at-risk patients87. Therefore, the decision to stop these
medications after the occurrence of hyphema must be made on a case-by-case
basis in consultation with the patient’s primary care physician.
Evaluation of the patient’s suitability to stop or reduce these medications involves
consideration of the desired therapeutic international normalized ratio (INR) range for
the patient’s medical condition, co-existing medical conditions which may further
affect clotting ability (e.g. chronic liver disease, bone marrow suppression), and the
time taken for normal clotting and coagulation to be restored after stopping these
medications.
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a. Medical management:
Mydriatics and cycloplegics: Most studies have not found that the use of
mydriatics or cycloplegics in hyphema improves the final visual acuity or prevents the
occurrence of complications such as re-bleeding10,34,35,69,81. The use of cycloplegic
agents such as topical atropine (an antimuscarinic cycloplegic) decreases the risk of
development of posterior synechiae, provides greater comfort in patients with
concurrent iritis, and permits visualization of the posterior pole 35. They also have the
theoretical benefit of reducing the risk of secondary hemorrhage from the iris/ ciliary
body by immobilizing these tissues, increasing uveo-scleral flow, and preventing the
formation of posterior synechia35. Current recommendations are to use atropine
sulphate drops three times a day for two weeks; however, optimal dosage has yet to
be established through formal clinical studies34 and less frequent dosing should
suffice as long as adequate cycloplegia is maintained. That being said, cycloplegics
must be used cautiously in patients with narrow angles.
Antifibrinolytic agents: Antifibrinolytic agents such as trans-hexamic acid and
aminocaproic acid (ACA) have been proven to lower significantly the rate of rebleeding after traumatic hyphema84,85; however, in most studies, antifibrinolytic
agents do not offer any major advantage in preventing most of the complications
related to hyphema, and may possibly delay clot resorption34.
ACA, a lysine analogue, competitively inactivates plasmin, thereby preventing clot
lysis by stabilizing the interface between the clot and vessel wall. Studies reveal that
topical ACA is as effective as systemic ACA in reducing the incidence of rebleeding 8.
In some studies, ACA was found to decrease the incidence of rebleeding from 22–
33% to 0–4%21,66,109. Crouch and Crouch19 recommended using either systemic ACA
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(50 mg/kg for 5 days with a maximum dose of 30 g/d) or topical ACA, 1 drop every 4
hours in the affected eye for 5 days in patients with hyphema. Topical ACA is safer
because it does not cause side effects of systemic ACA such as nausea, vomiting,
and hypotension8,19. The use of ACA is contraindicated in pregnancy (as it is a
teratogen), with renal or hepatic dysfunction, hand in patients with high
thromboembolic risk8,19. Trans-hexamic acid, another lysine analogue, has also been
shown to inhibit clot fibrinolysis at the site of injured blood vessels 8. We recommend
routine prescription of antiemetics with these drugs if systemic preparations are
used.
Corticosteroids: Topical corticosteroids are useful in preventing rebleeds. They
may stabilize the blood-ocular barrier, thereby reducing the influx of plasminogen
into the anterior chamber8,84,85. In addition, the anti-inflammatory activity of steroids
reduces posterior synechiae formation34. In a retrospective review of 462 patients
treated over 10 years, Ng et al69 found a statistically significant decreae in the
frequency of secondary hemorrhage among patients treated with topical steroids. A
5% rebleeding rate was seen for the group of patients treated with topical steroids
(with or without cycloplegics) vs. a 12% rebleeding rate for the group treated without
topical steroids (with or without cycloplegics). Although a short course of topical
steroids is recommended as a first line therapy for hyphema, they should not be
used on a long term basis due to the risk of steroid-induced glaucoma.
The role of oral steroids however still remains controversial74,84,85. Romano et al84
have suggested that use of a systemic steroid regimen in the Yasuna “No Touch”
and “No Touch PLUS” protocols, provide the best results in non-Scandinavian
populations. This protocol, first implemented in 1967, uses 40 mg/d of oral
prednisone in divided doses for adults and corresponding doses by weight for
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children (approximately 0.6 mg/kg). In a series of studies using the Yasuna protocol,
the rebleed rate for all patients combined was 0.7%. Farber et al 30 showed that
patients treated with systemic steroids had an incidence of secondary hemorrhage
equal to that of patients treated with systemic ACA. Further randomized controlled
trials are required to determine the efficacy of systemic corticosteroids compared
with systemic ACA. From our perspective, oral prednisone can be a reasonable
alternative to antifibrinolytic therapy for patients with high re-bleeding risk (Table 2).
For instance, in patients with von Willebrand disease, elevated IOP associated with
the primary or secondary bleed can lead to grave consequences, and oral
corticosteroid therapy should be considered. This is particularly relevant in patients
with sickle cell disease or other intravascular clotting disorders and in pregnant
patients, as aminocaproic acid is contraindicated and cannot be prescribed.
Anti-glaucoma medication: Elevated IOP (greater than 24 mm Hg) can be
controlled
with
topical
beta-blockers
and
carbonic
anhydrase
inhibitors8.
Acetazolamide lowers plasma pH, which promotes sickling of erythrocytes 8.
Therefore, methazolamide is preferred in patients with sickle cell trait or anemia, as it
has a lower propensity for metabolic acidosis compared to acetazolamide 20. Severe,
uncontrolled IOP (greater than 35 mmHg) may require additional systemic
medication. 1-1.5g/Kg of mannitol may be administered intravenously over 45
minutes twice a day19. Systemic osmotics should be used cautiously in renal
dysfunction because they can lead to hemoconcentration.
Aspirin and NSAIDS: The use of aspirin and other NSAIDS significantly increases
the risk of secondary haemorrhage owing to their antiplatelet effect 18. The decision to
stop these medications have to be made in discussion with the patient’s general
physician.
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b. Surgical Management:
Our experience is consistent with current evidence that surgical management is only
warranted in a small proportion of carefully selected patients, approximately 5% to
7.2% of all patients with hyphema10,80,98. As a rule, patients with true eight-ball
hyphemas require prompt surgical intervention. In other cases it is required only if
medical therapy fails (Table 3). Clinical indications for surgical evacuation are
persistently elevated intraocular pressure, corneal blood staining, and high grade
hyphema. These parameters should therefore be monitored and recorded in the
clinical evaluation and follow-up of these patients. We recommend that surgical
evacuation be considered according to the empirical criteria proposed by Read and
Goldberg26,81 as follows:
1.
2.
IOP greater than 60 mm Hg for 2 days (to prevent optic atrophy).
IOP greater than 24 mm Hg over the first 24 hours or if repeated IOP spikes
more than 30 mm Hg in sickle cell disease or trait.
3.
IOP greater than 25 mmHg with a total hyphema for 5 days (to prevent corneal
bloodstaining).
4.
Microscopic corneal bloodstaining.
5.
The hyphema fails to resolve to less than 50% of the anterior chamber volume
by 8 days (to prevent peripheral anterior synechiae formation).
There are varied surgical modalities for management of hyphema depending on the
severity and density of hyphema. These will be elaborated on in the following
section.
Anterior chamber washout and clot removal: The most common surgical
approach used is the limbal paracentesis needle drainage. Surgeons may opt to do
this as an outpatient procedure. A 27-gauge needle attached to a tuberculin syringe
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may be used to aspirate the blood slowly. This will only remove liquefied portions of
the clot, but is often sufficient to normalise the IOP and restore aqueous flow.
Anterior chamber washout using an irrigating Simcoe cannula can be done if the
hyphema has not yet organized. When managing organized hyphema, anterior
chamber washout using an automated anterior vitrectomy through limbal or clear
corneal incisions can be performed. Vitrectomy can debulk the clot without shearing
the anatomical structures and causing re-bleed. Anterior chamber stability must be
maintained (by raising the height of the bottle and through use of cohesive
viscoelastic agents) and hypotony should be avoided to minimize subsequent
bleeding. The infusion port can be used to maintain a constant irrigation and the clot
cut and aspirated with the help of a vitrectomy cutter introduced through a clear
corneal incision. Care should be taken to avoid iatrogenic trauma to the lens, iris, or
corneal endothelium. Viscodissection can be used to separate the adherent
hyphema from underlying iris. Also, the settings of the vitrector should be on irrigate
- cut – aspirate (ICA) rather than irrigate-aspirate-cut (IAC) as the latter setting may
result in rebleeding due to traction on the clot and blood vessels. An eight-ball
hyphema can be removed with the conventional limbal clot delivery method.
Trabeculectomy and iridectomy: Trabeculectomy and iridectomy are useful
adjuncts with clot removal in management of clots associated with large hyphema.
Trabeculectomy modulated with either mitomycin C or 5-flurouracil can be combined
with clot expression in patients with glaucoma not controlled by maximal medical
therapy41,107. Glaucoma shunts as a primary procedure have shown promising
results in such cases as well. However this surgery can be complicated by
postoperative hypotony, choroidal effusion and secondary haemorrhage41 and is
best reserved for patients with intractable glaucoma.
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In summary, the various surgical methods are associated with significant risks,
including damage to corneal endothelium, lens injury, prolapse of intraocular
contents, and rebleeding88. Hence surgical management should be reserved for
carefully selected patients at high risk of developing sight threatening complications.
c. Hospitalization and Follow-up: There are no standardised guidelines for the
admission of a patient with hyphema and similarly for frequency of follow-up visits.
Both hospitalization and follow up are governed by the degree of hyphema and risk
of rebleeding3,91,110. Patients with high grade hyphema or high risk of rebleed (Table
2) may be admitted for daily examination and close monitoring. Other patients will
benefit from close outpatient follow up on day 2 and 7, to allow early detection of
rebleeding (which can occur in up to one third of patients) or indications for surgical
intervention (as outlined in the previous section). Subsequently, once hyphema has
resolved and the patient is no longer on topical medication, physicians can safely opt
for quarterly follow up to monitor intraocular pressure92. Based on presence or
absence of raised intraocular pressure, optic nerve damage, or angle recession,
attending physicians can gradually lengthen follow up intervals.
d. Screening for sickle cell disease or trait in patients of African descent:
Patients with sickle cell disease or trait have a higher incidence of secondary
hemorrhage, increased IOP, and optic atrophy in the setting of traumatic hyphema
compared to non-sickle cell patients55,68,90,106. Hence, screening is warranted in
patients of African descent90. Even low grade hyphema can lead to significant
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impairment of aqueous outflow, intractable increase in intraocular pressure, and
optic neuropathy in sickle cell disease, posing a serious threat to vision90.
6. SPECIAL SITUATIONS
a. Sickle cell hemoglobinopathies: As outlined above, patients with sickle cell
disease are at significantly elevated risk of developing complications of hyphema.
These patients have been found to have enhanced fibrinolysis which explains the
predisposition to secondary hemorrhage43. Furthermore, sickled erythrocytes face
greater resistance in passing through the outflow channels of the trabecular
meshwork, as they are less pliable than normal biconcave erythrocytes. Hence they
slow the process of hyphema resolution, and lead to exaggerated increase in
IOP37,38. Making matters worse, patients with sickle cell disease are susceptible to
vascular occlusion at relatively low intraocular pressures or relatively brief durations
of high pressures76.
Medical treatment of glaucoma poses a serious challenge in these patients as most
commonly used systemic agents are contraindicated36. Use of hyperosmotic/ diuretic
agents (e.g., glycerine, isosorbide, and mannitol) should be avoided, as they may
cause
hemoconcentration
and
increased
blood
viscosity
in
the
ocular
microvasculature31,36.
Systemic carbonic anhydrase inhibitors (CAI) cause systemic acidosis in addition to
the hemoconcentration, which increases erythrocyte sickling31. ACA, a CAI,
increases the concentration of ascorbic acid in aqueous humor and exacerbates the
sickling process. This is postulated to be due to it acting as a reducing agent4.
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A literature search did not reveal any definitive evidence for the risk of systemic
acidosis and hemoconcentration in topical CAI; however, it has been reported that
their
local
efficacy
may
be
less
than
that
of
their
systemic
counterparts24.Methazolamide is the only systemic drug reported to be used safely
for increased IOP in hyphema with background sickle cell disease20.
In conclusion, we recommend treating hyphema aggressively in this subgroup of
patients. The IOP should be kept low by using a combination of topical drugs such
as timolol, apraclonidine, or brimonidine. Systemic therapy with methazolamide can
be considered in recalcitrant cases. Surgical intervention should be instituted earlier
and at lower IOP thresholds than normal patients in order to prevent optic nerve
damage26.
b. Management of hyphema in children
The
management
of
hyphema
in
infants
and
children
requires
special
considerations. First, the possibility of non-accidental injury (NAI) or abuse must be
considered.
Furthermore,
non-traumatic
etiologies
of
hyphema
such
as
retinoblastoma, juvenile xanthogranuloma of the iris, and bleeding diathesis from
blood dyscrasias such as leukemia should also be explored.
Hyphema is a common admitting diagnosis in children sustaining ocular trauma 25.
Injury with toys (balls, stones, projectiles) is the predominant etiology22. The rate of
rebleeding of hyphema in children is similar to that in adults 15,22,52. In the past,
hospitalization had been recommended for the first few days after the
injury15,22,28,52,69; however, few ophthalmologists would advocate hospitalisation for
hyphema today. Instead, patients can be discharged with emphasis and advice on
strict avoidance of physical activity. Children younger than 5 years of age are more
ACCEPTED MANUSCRIPT
likely to develop long term visual impairment secondary to amblyopia from visual
deprivation by media opacity (hyphema, traumatic cataract, or corneal blood
staining)11. Minimizing the interval between the injury and the restoration of media
clarity is hence a priority in these patients. Monocular occlusion after injury to protect
against further mechanical injury should be minimized, as the expected benefit from
an occlusive dressing must be weighed against the risk of inducing amblyopia in
young children.
Some authors report the use of systemic steroids with or without topical steroids,
instead of aminocaproic acid, in managing children with traumatic hyphema. This
was done with the rationale to control inflammation and reduce the risk of secondary
haemorrhage86; however, because of the potential for systemic steroids to interfere
with growth, we do not recommend this. Final visual outcome and prognosis of
hyphema in children remains similar to adult patients15,22,25.
c. Hyphema associated with cataract and refractive surgery:
Cataract surgery may also be associated with various degrees of hyphema 64,95 from
either surgical trauma or erosion by the haptic of the intraocular lens into the iris.
With manual small incision cataract surgery, there may be hypotony from poor
approximation of wound on the first postoperative day associated with a complete
hyphema. With more and more anterior chamber implantable lenses available, there
is an increase in incidence of hyphema. Some peculiar syndromes described with
cataract surgery and associated hyphema are as follows:
Swan syndrome: Characterized by recurrent intraocular bleeds even months to
years after cataract surgery involving a scleral incision99 Swan syndrome usually
ACCEPTED MANUSCRIPT
presents with blurred vision with associated mild to moderate degree of pain. On
examination there is hyphema and/or vitreous hemorrhage and neovascularisation of
the angle that is best managed by either focal argon laser photocoagulation or direct
diathermy of the new vessels or surgical excision of the vessels or scleral wound
resuturing. With clear corneal incision cataract surgery becoming more widely used,
the incidence of this syndrome has reduced greatly; however, in developing
countries where manual small incision cataract surgery is still performed, one may
need to consider this entity in cases of recurrent hyphema seen post cataract
surgery.
d. Uveitis with hyphema: Anterior uveitis has been described to be associated with
hyphema in cases of Reiter syndrome, juvenile chronic arthritis, ankylosing
spondylitis, idiopathic anterior uveitis and Herpes simplex. In these cases, hyphema
has been found to be associated with increased inflammation. Conservative
management with topical steroids is the treatment of choice. Bleeding in the anterior
chamber (Amsler sign) following paracentesis has been described in Fuchs
heterochromic iridocyclitis (FHI)29 and is also seen in other uveitic cases following
anterior chamber decompression. Although not pathognomonic for FHI, Amsler sign
often occurs in FHI from rupturing of the fine rubeotic vessels crossing the trabecular
meshwork. These fragile vessels may also lead to hyphema secondary to pressure
from gonioscopy or applanation tonometry.
7. Outcome measures
Proposed primary outcome measures that can be evaluated in the management of
hyphema are visual acuity and stage of hyphema. Secondary outcome measures
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include the incidence of complications such as corneal blood staining, ocular
hypertension requiring surgical intervention, optic atrophy, and re-bleeding.
Poor visual outcome following resolution of hyphema is often attributed to associated
injuries from blunt trauma, and is less commonly directly from
hyphema14,49,69.71,77,97,105. Visual outcomes following total hyphema are generally
poorer than subtotal hyphema11,79,81.
Varying incidence of glaucoma has been reported in patients with and without
rebleeding, with a significantly higher risk in patients with
rebleeding16,23,42,45,51,60,62,89,101. Read and Goldberg81 found optic atrophy without
glaucomatous damage in 6% of eyes in a series of 135 cases. Corneal blood
staining occurs in 2-11% of cases of traumatic hyphemas11,17,81,88. Reported
incidence of secondary hemorrhage varies from 2% to 37%
5,13,20,21,30,50,54,55,56,58,68,72,77,81,83,88,93,100
8. Conclusions and recommendations
In summary, hyphema is a common clinical condition that carries a good visual
prognosis if managed timely and appropriately (Table 4). A careful systemic and
ophthalmic examination to rule out any associated injuries is important. It is also
imperative to rule out a history of sickle cell disease or trait, particularly in African
patients with hyphema. Most patients can be followed-up as outpatients on day 2
and 7, with admission reserved for patients with high grade hyphema or high risk of
re-bleeding.
The primary aim of treatment is to prevent the development of complications.
Supportive treatment and medical management with cycloplegics and topical
steroids are the mainstay of treatment. Anti-fibrinolytic agents such as ACA remain
ACCEPTED MANUSCRIPT
an alternative to topical steroids in certain patients, such as children or those with a
history of steroid-induced glaucoma; however, if systemic treatment is used, we
recommend co-prescription of anti-emetic. Physicians must also remember to
exclude contraindications such as history of intravascular clotting disorders, or
pregnancy.
Surgical intervention is reserved for patients whom are nonresponsive to medical
therapy or at high risk of complications that lead to visual impairment. Secondary
hemorrhage and glaucoma are the most common complications. Secondary
glaucoma can develop even years after the initial insult, hence the importance of
routine quarterly follow up visits after the primary condition has resolved.
Hyphema in children is best managed by head elevation and refrain from physical
activity, along with medical management. Shielding the eye should be considered to
prevent further mechanical trauma to the eye during the initial healing process.
Attending physicians must also be aware of special conditions and syndromes
associated with hyphema which impact management strategy. For instance, rare
entities such as sickle cell disease and blood dyscrasias should be kept in mind,
especially in patients that develop intractable hyphemas.
Methods of literature search:
Articles were selected for review using a search in pubmed, scopus and medline
database
using
"hyphema"[MeSH
the
key
Terms]
words:
OR
Hyphema:
"hyphema"[All
"hyphaema"[All
Fields];
Traumatic
Fields]
OR
hyphema:
traumatic[All Fields] AND ("hyphaema"[All Fields] OR "hyphema"[MeSH Terms] OR
"hyphema"[All Fields]); Spontaneous hyphema: spontaneous[All Fields] AND
("hyphaema"[All Fields] OR "hyphema"[MeSH Terms] OR "hyphema"[All Fields]).
ACCEPTED MANUSCRIPT
Conflict of interest statement:
All authors certify that they have no affiliations with or involvement in any
organization or entity with any financial interest (such as honoraria; educational
grants; participation in speakers’ bureaus; membership, employment, consultancies,
stock ownership, or other equity interest; and expert testimony or patent-licensing
arrangements), or non-financial interest (such as personal or professional
relationships, affiliations, knowledge or beliefs) in the subject matter or materials
discussed in this manuscript.
Disclosure: No financial disclosure or conflict of interest. RA is supported by
Clinician Scientist Career Scheme grant awarded by National Healthcare Group,
Singapore.
ACCEPTED MANUSCRIPT
References
1. Agapitos
PJ, Noel LP, Clarke WN.Traumatic hyphema in children.
Ophthalmology.1987;94:1238.
Arentsen JJ, Green WR. Melanoma of the iris: report of 72 cases treated
2.
surgically. Ophthalmic Surg.1975; 6:23–37.
3.
Baker RS, Wilson MR, Flowers CW, et al. A population-based survey of work-
related ocular injury diagnosis, cause of injury, resource utilization, and
hospitalization outcome. Ophthal Epidemiol.1999;6:159.
Becker B. The effects of the carbonic anhydrase inhibitor, acetazolamide, on
4.
the composition of the aqueous humor. Am J Ophthalmol.1955;40:129–36.
Bedrossian
5.
RH.
The
management
of
traumatic
hyphema.
Ann
Ophthalmol.1974;6:1016–8.
Behrendt H, Wenniger-Prick LM Leukemic iris infiltration as the only site of
6.
relapse in a child with acute lymphoblastic leukemia: temporary remission with highdose chemotherapy. Med Pediatr Oncol. 1985 ;13:352–6.
7.
Benzimra JD, Johnston RL, Jaycock P, Galloway PH, Lambert G, Chung AK,
Eke T, Sparrow JM, EPR User Group. The Cataract National Dataset electronic
multicentre audit of 55,567 operations: antiplatelet and anticoagulant medications.
Eye (Lond). 2009; (1):10-6.
8. Berrıos
9.
RR, Dreyer EB .Traumatic hyphema. 1995; Int Ophthalmol Clin 35:93.
Blanksma LJ, Hooijmans JM. Vascular tufts of the pupillary border causing a
spontaneous hyphaema. Ophthalmologica. 1979; 178:297–302.
10.
Britten MJA. Follow-up of 54 cases of ocular contusion with hyphema. Br J
Ophthalmol .1965; 49:120–7.
ACCEPTED MANUSCRIPT
11.
Brodrick JD. Corneal blood staining after hyphaema. Br J Ophthalmol.
1972;56:589–93.
12.
Canavan YM, Archer DB.Anterior segment consequences
of
blunt
ocular
injury. Br J Ophthalmol .1982; 66:549–55.
13.
Cassel GH, Jeffers JB, Jaeger EA.Wills Eye Hospital Traumatic Hyphema
Study. Ophthalmic Surg. 1985;16:441–3.
14.
Cho J, Jun BK, Yee YJ.Factors associated with poor visual outcome after
traumatic hyphema. Korean J Ophthalmol .1998; 12: 122–9.
15.
Cohen SB, Fletcher ME, Goldberg MF, Jednock NJ. Diagnosis
and
management of ocular complications of sickle hemoglobinopathies: Part V.
Ophthalmic Surg .1986; 17:369–74
16.
Cole JG, Byron HM. Evaluation of 100 eyes with traumatic hyphema:
intravenous urea. Arch Ophthalmol.1964; 71:35–43.
17.
Coles WH. Traumatic hyphema: an analysis of 235 cases. South Med J.1968;
61:813–6.
18.
Crawford JS, Lewandowski RL, Chan W .The effect of aspirin on rebleeding in
traumatic hyphema. Am J Ophthalmol.1975; 80: 543–5.
19.
Crouch ER Jr, Crouch ER. Management of traumatic hyphema: therapeutic
options. J Pediatr Ophthalmol Strabismus .1999; 36:238.
20.
Crouch ER Jr, Frenkel M. Aminocaproic acid in the treatment of traumatic
hyphema. Am J Ophthalmol .1976; 81:355–60.
21.
Crouch ER Jr, Williams PB, Gray MK, et al.Topical aminocaproic acid in the
treatment of traumatic hyphema. Arch Ophthalmol .1997; 115:1106–12.
ACCEPTED MANUSCRIPT
22.
Crouch ER, Williams PB .Trauma: ruptures and bleeding,
in
Tasmani W,
Jager EM (eds): Duane’s Clinical Ophthalmology. Philadelphia, PA, Lippincott, 1993,
pp 1-18.
23.
Darr JL, Passmore JW.Management of traumatic hyphema. Am J Ophthalmol.
1967; 63:134–6.
24.
Deepak Gupta. Glaucoma due to ocular injury, in Deepak Gupta (ed).
Glaucoma diagnosis and management, Philadelphia, Lippincott, 2005, pp 157.
25.
DeRespinis PA, Caputo AR, Fiore PM, Wagner RS . A survey of severe eye
injuries in children. Am J Dis Child.1989;143:711–6.
26.
Deutsch TA, Weinreb RN, Goldberg MF. Indications for surgical management
of hyphema in patients with sickle cell trait. Arch Ophthalmol.1984;102:566–9.
27.
Dunn AS, Turpie AG. Perioperative management of patients receiving oral
anticoagulants: a systematic review. Arch Intern Med. 2003;163(8):901-8.
28.
Edwards WC, Layden WE. Traumatic hyphema. A report of 184 consecutive
cases. Am J Ophthalmol.1973;75:110–6.
29.
Ellingson FT. The uveitis-glaucoma-hyphema syndrome associated with the
Mark VIII anterior chamber lens implant. J Am Intraocul Implant Soc.1978; 4(2):50-3.
30.
Farber MD, Fiscella R, Goldberg MF. Aminocaproic acid versus prednisone
for the treatment of traumatic hyphema. Ophthalmology.1991;98:279.
31.
Finch CA. Pathophysiologic aspects of sickle cell anemia. Am J Med.1972;
53:1–6.
32.
Fong LP. Secondary hemorrhage in traumatic hyphema—predictive factors
for selective prophylaxis. Ophthalmology.1994; 101: 1583.
33.
Ghafari AB, Siamian H, Aligolbandi K, Vahedi M. Hyphema caused by trauma.
Med Arch.2013; 67(5):354-6.
ACCEPTED MANUSCRIPT
34.
Gharaibeh A, Savage HI, Scherer RW, Goldberg MF, Lindsley K. Medical
interventions
for
traumatic
hyphema.
Cochrane
Database
Syst
Rev.2011;
(1)CD005431.
35.
Gilbert HD, Jensen AD. Atropine in the treatment of traumatic hyphema. Ann
Ophthalmol .1973; 5:1297–300.
36.
Goldberg MF. The diagnosis and treatment of secondary glaucoma after
hyphema in sickle cell patients. Am J Ophthalmol.1979; 87:43–9.
37.
Goldberg MF, Dizon R, Raichand M, Goldbaum M. Sickled erythrocytes,
hyphema and secondary glaucoma: III. Effects of sickle cell and normal human blood
samples in rabbit anterior chambers. Ophthalmic Surg .1979; 10:52–61.
38.
Goldberg MF, Tso MO. Sickled erythrocytes, hyphema, and secondary
glaucoma: VII. The passage of sickled erythrocytes out of the anterior chamber of
the human and monkey eye: light and electron microscopic studies. Ophthalmic
Surg. 1979; 10: 89–123.
39.
Gottsch JD, Graham CR Jr, Hairston RJ, et al. Protoporphyrin IX
photosensitization of corneal endothelium. Arch Ophthalmol .1989; 107:1497–500.
40.
Gottsch JD, Messner EP, McNair DS, et al. Corneal blood staining: an animal
model. Ophthalmology.1986;93:797.
41.
Graul TA, Ruttum MS, Lloyd MA, et al Trabeculectomy for traumatic hyphema
with increased intraocular pressure. Am J Ophthalmol.1994;117:155–9.
42.
Gregersen E. Traumatic hyphema I and II. Acta Ophthalmol (Copenh)
1962;40:192-201.
43.
Hagger D, Wolff S, Owen J, Samson
D.Changes
in
coagulation
and
fibrinolysis in patients with sickle cell disease compared with healthy black controls.
Blood Coagul Fibrinolysis.1995;6:93–9.
ACCEPTED MANUSCRIPT
44.
Hallet C, Willoughby C, Shafiq A, et al. Pitfalls in the management of a child
with mild haemophilia A and a traumatic hyphema. Haemophilia.2000;6:118.
45.
Henry
MM.
Nonperforating
eye
injuries
with
hyphema.
Am
J
Ophthalmol.1960;49:1298–300.
46.
Howard GM, Hutchinson BT, Fredrick AR Jr. Hyphema resulting from blunt
trauma—gonioscopic, tonographic, and ophthalmoscopic observation following
resolution of the hemorrhage. Trans Am Acad Ophthalmol Otolaryngol.1965;69:
294–306.
47.
Karcioglu ZA, Mullaney PB. Diagnosis and management of iris juvenile
xanthogranuloma. J Paediatr Ophthalmol Strabismus.1997;34(1):44-51.
48.
Katz J, Feldman MA, Bass EB, Lubomski LH, Tielsch JM, Petty BG, Fleisher
LA, Schein OD, Study of Medical Testing for Cataract Surgery Team. Risks and
benefits of anticoagulant and antiplatelet medication use before cataract surgery.
Ophthalmology. 2003;110(9):1784−1788.
49.
Kearns P. Traumatic Hyphema: a retrospective study of 314 cases . Br J
Ophthalmol .1991;75(3):137-41.
50.
Kennedy RH, Brubaker RF. Traumatic hyphema in a defined population. Am J
Ophthalmol.1988; 106:123.
51.
Kitazawa Y.Management of traumatic
hyphema
with
glaucoma.
Int
Ophthalmol Clin.1981; 21:167–81.
52.
Kraft SP, Christianson MD, Crawford JS, et
al
.Traumatic
hyphema
in
children. Treatment with epsilon-aminocaproic acid. Ophthalmology.1987; 94:1232–
7.
53.
Kurz GH, Zimmerman LE. Spontaneous hyphema and acute glaucoma as
initial signs of recurrent iris melanoma. Arch Ophthalmol. 1963; 69:581–2.
ACCEPTED MANUSCRIPT
54. Kushner
55.
AG. Traumatic hyphema. Surv Ophthalmol .1959; 4:2-10.
Kutner B, Fourman S, Brein K, et al. Aminocaproic acid reduces the risk of
secondary hemorrhage in patients with traumatic hyphema. Arch Ophthalmol.1987;
105:206–8.
56.
Lai JC, Fekrat S, Barron Y, Goldberg MF.Traumatic hyphema in children: risk
factors for complications. Arch Ophthalmol.2001;119:64–70.
57.
Lai WW, Bhavnani VD, Tessler HH, et al. Effect of melanin on traumatic
hyphema in rabbits. Arch Ophthalmol.1999;117:789.
58.
Laughlin RC.Anterior chamber hemorrhage in nonperforating injuries. Trans
Pac Coast Otoophthalmol Soc Annu Meet .1948;29:133–40.
59.
Lawrence T, Wilison D, Harvey J.The incidence of secondary hemorrhage
after traumatic hyphema. Ann Ophthalmol.1990;22: 276.
60.
Leone CR Jr. Traumatic hyphema in children. J Pediatr Ophthalmol.1966; 3:7–
13.
61.
Lifschitz T, Yermiahu T, Biedner B, Yassur Y.Traumatic total hyphema in a
patient with severe hemophilia. J Pediatr Ophthalmol Strabismus.1986;23:80–1.
62. Loring
63.
MJ .Traumatic hyphema. Am J Ophthalmol .1958;45:873– 80.
Luksza L, Homziuk M, Nowakowska-Klimek M, Glasner L, Iwaszkiewicz-
Bilikiewicz B. Traumatic Hyphema caused by eye injuries. Klin Oczna.2005;107 (46):250-1.
64.
Magargal LE, Goldberg RE, Uram M, et al. Recurrent microhyphema in the
pseudophakic eye. Ophthalmology.1983;90:1231–4.
65.
McDonald CJ, Raafat A, Mills MJ, Rumble JA. Medical and surgical
management of spontaneous hyphaema secondary to immune thrombocytopenia. Br
J Ophthalmol.1989;73:922–5.
ACCEPTED MANUSCRIPT
66.
McGetrick JJ, Jampol LM, Goldberg MF, et al. Aminocaproicacid decreases
secondary hemorrhage after traumatic hyphema. Arch Ophthalmol.1983;101:1031–
3.
Mooney
67.
D.
Angle
recession
and
secondary
glaucoma.
Br
J
Ophthalmol.1973;57(8):608-12.
68.
Nasrullah A, Kerr NC.Sickle cell trait as a risk factor forsecondary hemorrhage
in children with traumatic hyphema. Am J Ophthalmol.1997;123:783.
69.
Ng CS, Strong NP, Sparrow JM, Rosenthal AR.Factors
related
to
the
incidence of secondary haemorrhage in 462 patients with traumatic hyphema.
Eye.1992;6:308–12.
70.
Ng DS, Ching RH, Chan CW. Angle-recession glaucoma: long-term clinical
outcomes over a 10-year period in traumatic microhyphema. Int Ophthalmol.
2015; 35(1):107-113.
71.
Ohrstrom A. Treatment of traumatic hyphaema with corticosteroids and
mydriatics. Acta Ophthalmol (Copenh).1972; 50: 549–55.
72.
Palmer DJ, Goldberg MF, Frenkel M, et al A
comparison
of
two
dose
regimens of epsilon aminocaproic acid in the prevention and management of
secondary traumatic hyphemas. Ophthalmology.1986;93:102–8.
73.
Pilger IS. Medical treatment of traumatic hyphema. Surv Ophthalmol.1967;
20:28.
74.
Pollard ZF Two hundred more traumatic hyphema cases with no rebleeds on
the Yasuna Oral Steroids No Touch Protocol. Correspondence. Binocul Vis
Strabismus Q.2000;15:250.
75. Rad
AS ,Kheradvar. A Juvenile xanthogranuloma: concurrent involvement of
skin and eye. Cornea .2001;20(7):760-2.
ACCEPTED MANUSCRIPT
76.
Radius RL, Finkelstein D. Central retinal artery occlusion(reversible in sickle
trait) with glaucoma. Br J Ophthalmol.1976;60:428–30.
77.
the
Rahmani B, Jahadi HR. Comparison of tranexamic acid and prednisolone in
treatment
of
traumatic
hyphema.
A
randomized
clinical
trial.
Ophthalmology.1999;106:375–9.
78.
Rahmani B, Jahadi HR, Rajaeefard A. An analysis of risk for secondary
hemorrhage in traumatic hyphema. Ophthalmology.1999;106:380–5.
79.
80.
Rakusin W.Traumatic hyphema. Am J Ophthalmol.1972;74:284–92.
Read J. Traumatic hyphema: surgical vs medical management. Ann
Ophthalmol.1975;7:659–62.
81.
Read J, Goldberg MF. Comparison of medical treatment for
traumatic
hyphema. Trans Am Acad Ophthalmol Otolaryngol.1974;78:799.
82.
Romano PE. Management of traumatic hyphema. Perspect Ophthalmol.1981;
5:33–8
83.
Romano PE, Hope GM. The effect of age and ethnic background on the
natural rebleed rate in untreated traumatic hyphema in children. Metab Pediatr Syst
Ophthalmol.1990;13:26– 31.
84.
Romano PE, Phillips PJ. Traumatic hyphema: a critical review of the
scientifically catastrophic history of steroid treatment thereof, and a report of 24
additional cases with no rebleeding after treatment with the Yasuna Systemic
Steroid, No Touch PLUS protocol. Binocle Vis Strabismus Q .2000;15:187.
85.
Romano PE, Robinson JA. Traumatic hyphema: A comprehensive review of
the past half century. Binocul Vis Strabismus Q. 2000;15:175.
86.
Rynne MV, Romano PE. Systemic corticosteroids in thetreatment of traumatic
hyphema. J Pediatr Ophthalmol Strabismus.1980;17:141–3.
ACCEPTED MANUSCRIPT
87.
Saxena R, Koudstaal P. Anticoagulant versus antiplatelet therapy
for
preventing stroke in patients with nonrheumatic atrial fibrillation and a history of
stroke
or
transient
ischemic
attack.
Cochrane
Database
Syst
Rev.2004;
traumatic
hyphema.
(4):CD000187.
88.
Shammas
HF,
Matta
CS.
Outcome
of
Ann
Ophthalmol.1975;7:701.
89.
Shea M. Traumatic hyphema in children. Can Med Assoc J .1957;76:466–9.
90.
Shingleton BJ, Hersh PS. Traumatic hyphema, in Shingleton BJ, Hersh PS,
Kenyon KR (eds): Eye Trauma. St Louis, MO, Mosby, 1991, pp 104-116.
91.
Shiuey Y, Lucarelli MJ. Traumatic hyphema: outcomes of outpatient
management. Ophthalmology.1998;105(5):851-5.
92.
Shiuey
Y,
Lucarelli
MJ.
Traumatic
hyphema:
outcomes
of
patient
management. Ophthalmology.1998;105:851.
93.
Skalka HW. Recurrent hemorrhage in traumatic hyphema. Ann Ophthalmol.
1978;10:1153–7.
94.
Smith B, Regan WF Jr. Blow-out fracture of the orbit; mechanism
and
correction of internal orbital fracture. Am J Ophthalmol.1957;44(6):733-9.
95.
Speakman JS. Recurrent hyphema after surgery. Can J Ophthalmol.1975;
10:299–304.
96.
Spoor TC. Anterior segment injuries:
Blunt ocular trauma—What
happens
when the eye is struck by a blunt object? in Spoor TC (ed): An Atlas of Ophthalmic
Trauma. London, Mosby, 1997,pp 35-49.
97.
Spoor TC, Hammer M, Belloso H. Traumatic hyphema. Failure of steroids to
alter its course: a double- blind prospective study. Arch Ophthalmol.1980;98:116–9.
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98.
Spoor TC, Kwitko GM, O’Grady JM, et al. Traumatic hyphema in an urban
population. Am J Ophthalmol. 1990;109:23.
99. Swan,
K.C. Hyphema due to wound vascularization after cataract extraction.
Arch Ophthalmol. 1973; 89, 87-90.
100. Thomas
MA, Parrish RK 2nd, Feuer WJ. Rebleeding after traumatic hyphema.
Arch Ophthalmol.1986;104:206–10.
101. Thygeson
P, Beard C. Observations in traumatic hyphema. Am J Ophthalmol.
1952;35:977–85.
102.
Tonjum AM. Gonioscopy in traumatic hyphema. Acta Ophthalmol (Copenh)
196;44:650–64.
103.
Tonjum AM. Intraocular pressure and facility of outflow late after ocular
contusion. Acta Ophthalmol (Copenh).1968;46:886–908.
104.
Turkcu FM, Yuksel H, Sahin A, Caca l. Demographic and etiological
characteristics of children with traumatic serious hyphema. Ulus Travma Acil Cerrahi
Derg.2013;19(4):357-62.
105.
Volpe NJ, Larrison WI, Hersh PS, et al. Secondary hemorrhage in traumatic
hyphema.1991; Am J Ophthalmol 112:507–13.
106.
Wax MB, Ridley ME, Magargal LE. Reversal of retinal and optic disc ischemia
in a patient with sickle cell trait and glaucoma secondary to traumatic hyphema.
Ophthalmology.1982;89: 845–51.
107. Weiss
JS, Parrish RK, Anderson DR. Surgical therapy of traumatic hyphema.
Ophthalmic Surg.1983;14:343–5.
108. Wilson
FM II.Traumatic hyphema: Pathogenesis and management.
Ophthalmology.1980;87:910.
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109.
Wilson TW, Jeffers JB, Nelson LB. Aminocaproic acid prophylaxis in traumatic
hyphema. Ophthalmic Surg.1990;21:807–9.
110.
Wilson TW, Nelson LB, Jeffers JB, et al. Outpatient management of traumatic
hyphemas. Ann Ophthalmol.1990;22:366.
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Table 1: Grading of Hyphema
Grade
Microhyphema
Volume of blood
Diagrammatic representation & clinical
in AC
picture
TI
PR
Circulating
RBC’s only
I
<1/3rd of AC
II
1/3-1/2 of AC
III
>1/2 of AC
IV
Total
M
D
US
N
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Table 2: High risk factors for rebleed in a patient with hyphema
Predisposing high risk factor
1
Sickle cell trait or anemia
2
Secondary hemorrhage
3
Penetrating ocular trauma
4
Suspected child abuse
5
Grade III or IV hyphema
6
Non-compliant patients
7
Intractable glaucoma
T
R
S
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Table 3: Indications for surgical intervention for hyphema
Clinical indications for surgical intervention
1
Microscopic corneal blood staining
In sickle cell trait or sickle cell disease, hyphemas of any size and IOP >
2
24 mm Hg for more than 24 hours
P
I
R
Hyphema >1/2 of the anterior chamber for > 8 days (to prevent
3
peripheral anterior synechiae)
Total hyphema with IOP of >50 mm Hg for 4 days (to prevent optic
4
atrophy)
U
Total hyphema or >3/4 of anterior chamber volume present for 6 days
5
N
A
with IOP of > 25 mm Hg (to prevent corneal blood staining)
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Table 4: Pearls in management of hyphema
All patients of hyphema should be evaluated in detail for systemic injuries
A
and retained IOFB
B
Absolute bed rest and hospitalization is not mandatory
Topical steroids and cycloplegics are used frequently for initial control of
C
inflammation and rebleed
D
R
Beta blockers and prostaglandin analogues should be used to control IOP
Avoid carbonic anhydrase inhibitors, alpha agonists and hyperosmotics in
E
Sickle cell disease/trait
U
F
Most aggressive treatment is needed to prevent optic nerve damage
G
Recurrent haemorrhage can occur 2-7 days after trauma
A
M
Regular ophthalmic evaluation is required in patients with angle recession
H
> 180 degrees
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Figure Legends:
Figure 1: Total Hyphema associated with occult scleral dehiscence
Figure 2: Hyphema associated with open globe injury and iris prolapse (2A) and
hyphema post primary corneal laceration repair (2B)
Figure 3: Different shades of red: Old traditional terminology is based on black
(8th) ball of snooker (3E), however as seen in 3B and 3C, there is presence of more
bright red colour and dull red colour in 3D which closely resembles Red (3 rd or 11th)
of snooker (3A).
Figure 4: Presence of Iridodialysis with Hyphema
Figure 5: Corneal blood staining
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Figure 1: Total Hyphema associated with occult scleral dehiscence
A
M
U
N
PI
R
C
S
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Figure 2: Hyphema associated with open globe injury and iris prolapse (2A) and
hyphema post primary corneal laceration repair (2B)
S
N
U
M
C
A
E
C
T
P
D
E
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Figure 3: Different shades of red: Old traditional terminology is based on black
(8th) ball of snooker (3E), however as seen in 3B and 3C, there is presence of more
bright red colour and dull red colour in 3D which closely resembles Red (3 rd or 11th)
of snooker (3A).
IPR
C
Figure4: Presence of Iridodialysis with Hyphema
C
A
E
C
DT
EP
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Figure 5: Corneal blood staining
A
M
U
N
PI
R
C
S