hyphema

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Available online at www.sciencedirect.com
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journal homepage: www.elsevier.com/locate/survophthal
Major review
Controversies in the pathophysiology
and management of hyphema
Svati Bansal, MBBS, MSa, Dinesh Visva Gunasekeran, MBBSb,
Bryan Ang, MMedb, Jiaying Lee, MBBSb, Rekha Khandelwal, MBBS, FRCSc,
Paul Sullivan, MBBS, FRCOphthd,
Rupesh Agrawal, MMed, FRCS (Glasg), FAMS, DNB, DOb,d,e,*
a
Department of Neuroophthamlology, Singapore National Eye Centre, Singapore, Singapore
Department of Ophthalmology, National Healthcare Group Eye Insitute, Tan Tock Seng Hospital, Singapore,
Singapore
c
Department of Ophthalmology, NKP Salve Institute of Medical Sciences, Nagpur, India
d
Medical Retina Department, Moorfields Eye Hospital, NHS Foundation Trust, London, UK
e
School of Material Science and Engineering, Nanyang Technological University, Singapore, Singapore
b
article info
abstract
Article history:
Traumatic hyphemas present dilemmas to physicians. There are numerous controversies
Received 9 May 2015
pertaining to the optimal approach to traumatic hyphema and no standardized guidelines
Received in revised form 12
for its management. We address some of these controversies and present a pragmatic
November 2015
approach. We discuss various medical agents and surgical techniques available for treat-
Accepted 23 November 2015
ment, along with the indications for their use. We address the complications associated
Available online 26 November 2015
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
Keywords:
clinical syndromes such as recurrent hyphema after placement of anterior chamber
hyphema
intraocular lenses.
traumatic glaucoma
ª 2016 Elsevier Inc. All rights reserved.
surgical drainage
angle recession
1.
Introduction
For hyphema, the accumulation of blood in the anterior
chamber, the most common cause is ocular trauma (blunt or
penetrating)33,62; 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, thrombocytopenia, and Von Willebrand disease.2,6,9,53,60,63,64,74,94 Hyphema can be a herald sign
of major intraocular trauma and can itself cause complications such as secondary hemorrhage and glaucoma.103 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
* Corresponding author: Rupesh Agrawal, MMed, FRCS (Glasg), FAMS, DNB, DO, National Healthcare Group Eye Institute, Tan Tock
Seng Hospital, Singapore 308433.
E-mail address: rupesh_agrawal@ttsh.com.sg (R. Agrawal).
0039-6257/$ e see front matter ª 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.survophthal.2015.11.005
298
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options include bed rest, head elevation, an eye shield, and the
use of pharmacologic agents (topical or systemic steroids,
antifibrinolytics, cycloplegics, miotics, aspirin, traditional Chinese medicine, 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 anemia.
We aim to address the controversies in the pathophysiology, evaluation, and management of hyphema. Because
trauma is the commonest cause, we focus our discussion on
closed-globe traumatic hyphema; however, we also analyze
special situations such as uveitis, pediatric hyphema, cataract
surgery, refractive surgery, and hyphema in patients with
sickle-cell anemia.
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 age.50 Direct orbital injury resulting in traumatic hyphema usually consists of a high-energy blow to the
orbit (61%e66%), impact from a projectile (30.2%e36%), or
injury secondary to an explosion (2.4%e3%).50,97 Athletic injuries have become a major cause of traumatic hyphema,
whereas 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 cases.49
The commonest source of blood in hyphema is a tear in
the anterior face of the ciliary body.107 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 plexus.95,107
Blunt injury is also associated with anteroposterior
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 ciliary body vessels with subsequent hemorrhage.22,95 Another possible source of initial hemorrhage is a
rapid increase in intraocular 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 angle.22
Lacerating injury may be associated with direct damage to
blood vessels and hypotony, both of which can precipitate
hyphema.107 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 iris.22
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).63,94 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 or medication should arouse the suspicion of nonaccidental injury.59 A significant but rare cause of spontaneous hyphema in children is juvenile xanthogranuloma.
Juvenile xanthogranuloma 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 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 orbit.47 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 lipid-laden histiocytes, lymphocytes, eosinophils,
and Touton giant cells.
Histologic examination of hyphemas reveals an erythrocyte aggregate enveloped by a pseudocapsule of fibrin-plated
coagulum.47 Clot absorption takes place by breakdown of
fibrin by fibrinolytic agents and escape of red blood cells
through the trabecular meshwork and Schlemm canal.47
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 (Fig. 1). Proptosis may be
secondary to a retrobulbar hematoma, and restriction in
ocular motility may suggest an orbital blowout fracture or a
contusive 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 (Fig. 2A) or closed-globe injuries. In patients
with open-globe injury, primary wound closure is the priority
(Fig. 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 sicklecell trait because of the higher risk of secondary glaucoma
and permanent visual loss.34 We shall focus on hyphema after
closed-globe trauma.
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Table 1 e Grading of hyphema
Grade
Volume of Diagrammatic representation
blood in AC
and clinical picture
Microhyphema Circulating
RBC’s only
Fig. 1 e Total hyphema associated with occult scleral
dehiscence.
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 1dLayered blood occupying less than one-third of
the anterior chamber.
I
<1/3rd of AC
II
1/3e1/2 of AC
III
>1/2 of AC
(continued on next page)
Fig. 2 e A: Hyphema associated with open-globe injury and
iris prolapse and B: hyphema post primary corneal
laceration repair.
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Table 1 e (continued )
Grade
Volume of Diagrammatic representation
blood in AC
and clinical picture
IV
Total
AC, anterior chamber.
Grade 2dBlood filling one-third to one-half of the anterior
chamber.
Grade 3dLayered blood filling one-half to less than total of
the anterior chamber.
Grade 4dTotal clotted blood, often referred to as “eightball” or “black” hyphema.
“Eight ball” or “black hyphema” occurs when the entire
anterior chamber is filled with blood, which takes on a darker
red color 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)93; 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 may be a worthwhile consideration to
revise the traditionally named “eight ball” hyphema to a “redball” or “three-ball hyphema” (Fig. 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, IOP, 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 (Fig. 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, posttraumatic detachments caused by retinal
dialysis progress slowly, and indentation may be safely deferred for several months. If scleral depression is not performed, a superfield 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 computed tomography 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
4.1.
Increased intraocular pressure
Almost 30% of patients with posttraumatic hyphema have an
increased IOP.22
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 hyphema.17 Secondary glaucoma is seen in 10%
of eyes with 50% hyphema, 25% if there is >50% hyphema,
and 50% if the hyphema is total.78 Patients with 8-ball
hyphema carry a 100% risk of secondary glaucoma; however,
8-ball hyphema is rarely encountered.
Fig. 3 e Different shades of red: E, B, and C: old traditional terminology is based on black (eigth) ball of snooker, however as
seen in panels B and C, D: there is presence of more bright red color and dull red color in panel D which closely resembles A:
Red (third or 11th) of snooker.
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from 45% to 67%.23,42,77 Rebleeding can be recognized clinically
by the following characteristics.
(1) An increase in the size of the hyphema.
(2) Presence of a layer of fresh blood over the older, darker clot
in the anterior chamber.
(3) Dispersed erythrocytes over the clot after the blood has
settled.
Fig. 4 e Presence of iridodialysis with hyphema.
Late secondary glaucoma may develop weeks to years after
hyphema. The incidence of late-onset glaucoma in eyes with a
history of traumatic hyphema ranges from 0%e20%.10,101,102
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
7 to 8 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 .12,69,101,102 Angle
recession in excess of 270 would further increase the risk of
glaucoma. Blanton described 2 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 and
colleagues demonstrated a statistically significant association between angle recession greater than 180 and the
development of glaucoma.46 It has already been recognized
in earlier literature that this group of patients should undergo lifelong annual examination to detect late-onset
glaucoma66; however, there is no consensus regarding the
frequency of follow-up required for patients with angle
recession of less than 180 .
4.2.
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 color 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 bleeding.58 One-fourth of the patients with grade I
hyphemas experience rebleeding into the anterior chamber of
the eye, as compared with two-thirds of patients with grade III
or IV hyphema.54
There has been shown to be an association of rebleeding
with race.44,78 The rates of rebleed are higher in darker skinned persons, especially blacks, when compared with whites.
One hypothesis is that melanin interferes with the clearance
of erythrocytes from the anterior chamber, causing these
differences in rebleeding rates.47
Patients with hemophilia, Von Willebrand disease, and
sickle-cell trait also have higher risk of secondary
hemorrhage.44,67
4.3.
Corneal blood staining
Corneal blood staining (Fig. 5) after hyphema has been reported in 2%e11% of cases.11,78,81 The incidence increases in
the presence of larger hyphemas, secondary hemorrhage,
prolonged clot retraction, sustained increase in IOP, and
presence of previous endothelial dysfunction.22,40,79 Read and
Goldberg found that an IOP of 25 mm Hg or greater for more
than 6 days significantly increases the risk of developing
corneal blood staining.80 They subsequently proposed surgical
intervention in cases where the hyphema does not decrease
Rebleeding (secondary hemorrhage)
Rebleeding or secondary hemorrhage occurs in 0.4% to 35% of
patients, usually 2e7 days after trauma.32,72,84 This is attributed to lysis and retraction of clot and fibrin within traumatized vessels as part of the subacute healing process.40
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
Fig. 5 e Corneal blood staining.
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by 50% after day 6.79 Corneal blood staining starts as central
straw yellow discoloration of the deep stroma that spreads
peripherally. Blood staining causes endothelial decompensation by mechanical disruption of the endothelium and also by
photosensitization of the endothelium by hemoglobinderived porphyrins in the presence of light.39,40 The blood
staining clears centripetally and may take anywhere from
several months to 2 years to clear.15,19 In children, corneal
blood staining may be further complicated by amblyopia.15
4.4.
Optic atrophy
In the setting of posttraumatic hyphema, optic atrophy may
develop secondary to traumatic nerve contusion or secondary
glaucoma. The risk of developing optic atrophy related to
elevated IOP is greater if the pressure is allowed to remain at
50 mm Hg or more for 5 days or 35 mm Hg or more for 7 days in
otherwise healthy individuals.80 Patients with sickle-cell disease or trait develop optic atrophy at lower IOPs.89
5.
Management of hyphema
The management of traumatic hyphema is directed toward
accelerating the absorption of the blood and the prevention
of complications detailed previously. There is no conclusive
evidence that hospital admission, sedation, or complete bed
rest with eye patching improves outcomes.22,34,80,109 The
indications and advantages of various management options
are discussed in the following paragraphs.
Bed rest: Some clinicians advocate strict bed rest in
hyphema to decrease the chances of secondary hemorrhage;
however, studies do not support this, and most have shown
no advantage of bed rest over quiet ambulation.10,80 Hospitalization and strict bed rest is mainly advised for patients
with severe hyphema, sickle-cell trait/disease, noncompliant
patients, children, and patients with bleeding predisposition.91,109 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 and colleagues hypothesized that patients with longstanding hyphema and prolonged light
exposure might be at risk of developing endothelial dysfunction and corneal blood staining.39,40 Although there is no evidence in the literature to support these claims,34 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.
Anticoagulant and antiplatelet medications: Anticoagulant
(e.g. warfarin sodium, heparin) and antiplatelet (e.g. aspirin,
dipyridamole, clopidogrel) medications have not been shown
to increase the risk of spontaneous hemorrhage during
intraocular surgery.7,27,48 Hence, they do not have to be
stopped before this type of surgery. After the occurrence of a
hyphema, however, these medications are at risk factors for
its persistence or rebleeding. The risk of bleeding
complications of anticoagulant medications has been reported to be significantly greater than that of antiplatelet
medications.86 Common indications for anticoagulation
therapy include atrial fibrillation, prosthetic heart valves, and
deep vein thrombosis. Antiplatelet therapy is commonly
indicated for the prevention of acute cardiac and cerebrovascular events in at-risk patients.86 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 range for the patient’s medical condition, coexisting 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.
5.1.
Medical management
5.1.1.
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 rebleeding.10,34,35,68,80 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 or ciliary body by immobilizing these
tissues, increasing uveoscleral flow, and preventing the formation of posterior synechia.35 Current recommendations
are to use atropine sulphate drops 3 times a day for 2 weeks;
however, optimal dosage has yet to be established through
formal clinical studies,34 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.
5.1.2.
Antifibrinolytic agents
Antifibrinolytic agents such as transhexamic acid and aminocaproic acid (ACA) have been proven to lower significantly
the rate of rebleeding after traumatic hyphema83,84; 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 resorption.34
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%e33% to 0%e4%.21,65,108
Crouch and Crouch recommended using either systemic ACA
(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.19 Topical ACA is safer because it does
not cause side effects of systemic ACA such as nausea, vomiting, and hypotension.8,19 The use of ACA is contraindicated in
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pregnancy (as it is a teratogen), with renal or hepatic
dysfunction, and in patients with high thromboembolic risk.8,19
Transhexamic 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.
5.1.3.
Corticosteroids
Topical corticosteroids are useful in preventing rebleeds. They
may stabilize the blood-ocular barrier, thereby reducing the
influx of plasminogen into the anterior chamber.8,83,84 In
addition, the antiinflammatory activity of steroids reduces
posterior synechiae formation.34 In a retrospective review of
462 patients treated over 10 years, Ng and colleagues found a
statistically significant decrease in the frequency of secondary
hemorrhage among patients treated with topical steroids.68 A
5% rebleeding rate was seen for the group of patients treated
with topical steroids (with or without cycloplegics) versus a
12% rebleeding rate for the group not treated with 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 longterm basis because of the risk of steroid-induced glaucoma.
The role of oral steroids, however, still remains controversial.73,83,84 Romano and colleagues 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.83 This protocol, first implemented in 1967, uses 40 mg/day of oral prednisone in divided
doses for adults and corresponding doses by weight for
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 and colleagues showed that patients treated with systemic steroids had an incidence of
secondary hemorrhage equal to that of patients treated with
systemic ACA.30 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 rebleed 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 ACA is contraindicated and
cannot be prescribed.
5.1.4.
Antiglaucoma medication
Elevated IOP (greater than 24 mm Hg) can be controlled with
topical beta-blockers and carbonic anhydrase inhibitors.8
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 mm Hg) may require
additional systemic medication. 1e1.5 g/Kg of mannitol may be
administered intravenously over 45 minutes twice a day.19
Systemic osmotics should be used cautiously in renal dysfunction because they can lead to hemoconcentration.
5.1.5.
Aspirin and nonsteroidal antiinflammatory drugs
The use of aspirin and other nonsteroidal antiinflammatory
drugs significantly increases the risk of secondary hemorrhage owing to their antiplatelet effect.18 The decision to stop
these medications has to be made in conjunction with the
patient’s general physician.
5.2.
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 hyphema.10,79,97 As a rule, patients with
true 8-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 IOP, corneal blood staining, and highgrade 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 Goldberg as follows26,80:
(1) IOP greater than 60 mm Hg for 2 days (to prevent optic
atrophy).
(2) 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 mm Hg with a total hyphema for 5 days
(to prevent corneal blood staining).
Table 3 e Indications for surgical intervention for
hyphema
Serial
number
Table 2 e High-risk factors for rebleed in a patient with
hyphema
Serial number
Predisposing high-risk factor
1
2
3
4
5
6
7
Sickle-cell trait or anemia
Secondary hemorrhage
Penetrating ocular trauma
Suspected child abuse
Grade III or IV hyphema
Noncompliant patients
Intractable glaucoma
303
1
2
3
4
5
Clinical indications for surgical intervention
Microscopic corneal blood staining
In sickle-cell trait or sickle-cell disease, hyphemas of
any size and IOP >24 mm Hg for more than 24 hours
Hyphema >1/2 of the anterior chamber for >8 days
(to prevent peripheral anterior synechiae)
Total hyphema with IOP of >50 mm Hg for 4 days
(to prevent optic atrophy)
Total hyphema or >3/4 of anterior chamber volume
present for 6 days with IOP of >25 mm Hg (to prevent
corneal blood staining)
IOP, intraocular pressure.
304
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(4) Microscopic corneal blood staining.
(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.
5.2.1.
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 may be used to aspirate the blood slowly. This
will only remove liquefied portions of the clot, but is often
sufficient to normalize 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 anatomic structures and
causing rebleed. 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 is 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. In addition, the settings of the vitrector
should be on irrigate-cut-aspirate rather than irrigateaspirate-cut as the latter setting may result in rebleeding
due to traction on the clot and blood vessels. An 8-ball
hyphema can be removed with the conventional limbal clot
delivery method.
5.2.2.
Trabeculectomy and iridectomy
Trabeculectomy and iridectomy are useful adjuncts 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 therapy.41,106 Glaucoma shunts as a primary procedure have shown promising
results in such cases as well; however, this surgery may be
complicated by postoperative hypotony, choroidal effusion,
and secondary hemorrhage41 and is best reserved for patients
with intractable glaucoma.
In summary, the various surgical methods are associated
with significant risks, including damage to corneal endothelium, lens injury, prolapse of intraocular contents, and
rebleeding.87 Hence, surgical management should be reserved
for carefully selected patients at high risk of developing sight
threatening complications.
5.3.
Hospitalization and follow-up
There are no standardized 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 rebleeding.3,90,109 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
days 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 IOP.91 Based on the presence or
absence of raised IOP, optic nerve damage, or angle recession,
attending physicians can gradually lengthen follow-up
intervals.
5.4.
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
nonesickle-cell patients.55,67,89,105 Hence, screening is warranted in patients of African descent.89 Even low-grade
hyphema can lead to significant impairment of aqueous
outflow, intractable increase in IOP, and optic neuropathy in
sickle-cell disease, posing a serious threat to vision.89
6.
Special situations
6.1.
Sickle-cell hemoglobinopathies
As outlined in the previous sections, 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 hemorrhage.43 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
IOP.37,38 Making matters worse, patients with sickle-cell disease are susceptible to vascular occlusion at relatively low
IOPs or relatively brief durations of high pressures.75
Medical treatment of glaucoma poses a serious challenge
in these patients as most commonly used systemic agents are
contraindicated.36 Use of hyperosmotic or diuretic agents (e.g.,
glycerine, isosorbide, and mannitol) should be avoided, as
they may cause hemoconcentration and increased blood viscosity in the ocular microvasculature.31,36
Systemic carbonic anhydrase inhibitors cause systemic
acidosis in addition to the hemoconcentration, which increases erythrocyte sickling.31 ACA, a carbonic anhydrase inhibitor, increases the concentration of ascorbic acid in
aqueous humor and exacerbates the sickling process. This is
postulated to be because it acts as a reducing agent.4
A literature search did not reveal any definitive evidence
for the risk of systemic acidosis and hemoconcentration from
topical carbonic anhydrase inhibitors; however, their local
s u r v e y o f o p h t h a l m o l o g y 6 1 ( 2 0 1 6 ) 2 9 7 e3 0 8
efficacy may be less than that of their systemic counterparts.24
Methazolamide is the only systemic drug that can be used
safely for increased IOP in hyphema with background sicklecell disease.20
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 to prevent optic nerve damage.26
6.2.
Management of hyphema in children
The management of hyphema in infants and children requires
special considerations. First, the possibility of nonaccidental
injury or abuse must be considered. Furthermore, nontraumatic 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 etiology.22 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 injury15,22,28,52,68;
however, few ophthalmologists would advocate hospitalization 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 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 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 ACA, in managing children
with traumatic hyphema. This was done with the rationale to
control inflammation and reduce the risk of secondary hemorrhage85; 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
remain similar to adult patients.15,22,25
6.3.
Hyphema associated with cataract and refractive
surgery
Cataract surgery may also be associated with various degrees
of hyphema from either surgical trauma or erosion by the
haptic of the intraocular lens into the iris.63,94 With manual
small incision cataract surgery, there may be hypotony from
poor approximation of the wound on the first postoperative
day associated with a complete hyphema. With anterior
chamber implantable lenses, there is an increase in incidence
305
of hyphema. Some peculiar syndromes described with cataract surgery and associated hyphema are as follows:
6.3.1.
Swan syndrome
Characterized by recurrent intraocular bleeds even months
to years after cataract surgery involving a scleral incision.98
Swan syndrome usually presents with blurred vision with
associated mild-to-moderate degree of pain. On examination, there is hyphema 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.
6.4.
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
iridocyclitis29 and is also seen in other uveitic cases
following anterior chamber decompression. Although not
pathognomonic, Amsler sign often occurs in Fuchs heterochromic iridocyclitis 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 include the incidence of complications such as corneal blood staining, ocular
hypertension requiring surgical intervention, optic atrophy,
and rebleeding.
Poor visual outcome after resolution of hyphema is often
attributed to associated injuries from blunt trauma and is less
commonly directly from hyphema.14,49,68,70,76,96,104 Visual
outcomes after total hyphema are generally poorer than
subtotal hyphema.11,78,80
Varying incidence of glaucoma has been reported in patients with and without rebleeding, with a significantly higher
risk in patients with rebleeding.16,23,42,45,51,59,61,88,100 Read and
Goldberg found optic atrophy without glaucomatous damage
in 6% of eyes in a series of 135 cases.80 Corneal blood staining
occurs in 2%e11% of cases of traumatic hyphemas.11,17,80,87
Reported incidence of secondary hemorrhage varies from 2%
to 37%5,13,20,21,30,50,54e56,57,67,71,76,80,82,87,92,99
306
8.
s u r v e y o f o p h t h a l m o l o g y 6 1 ( 2 0 1 6 ) 2 9 7 e3 0 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 days 2 and 7,
with admission reserved for patients with high-grade
hyphema or high risk of rebleeding.
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. Antifibrinolytic agents such as ACA
remain 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 prescription of antiemetic. Physicians must also
remember to exclude contraindications such as history of
intravascular clotting disorders or pregnancy.
Surgical intervention is reserved for patients who 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
refraining 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 that
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.
8.1.
Methods of literature search
Articles were selected for review using a search in PubMed,
Scopus and MEDLINE database using the key words: Hyphema:
Table 4 e Pearls in management of hyphema
A
B
C
D
E
F
G
H
All patients of hyphema should be evaluated in detail
for systemic injuries and retained IOFB
Absolute bed rest and hospitalization is not mandatory
Topical steroids and cycloplegics are used frequently for
initial control of inflammation and rebleed
Beta blockers and prostaglandin analogues should be used
to control IOP
Avoid carbonic anhydrase inhibitors, alpha agonists and
hyperosmotics in sickle-cell disease/trait
Most aggressive treatment is needed to prevent optic
nerve damage
Recurrent hemorrhage can occur 2e7 days after trauma
Regular ophthalmic evaluation is required in patients with
angle recession >180
IOFB, intraocular foreign body; IOP, intraocular pressure.
“hyphaema”[All Fields] OR “hyphema”[MeSH Terms] OR
“hyphema”[All Fields]; Traumatic 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]).
9.
Disclosure
No financial disclosure or conflict of interest.
Acknowledgments
All authors certify that they have no affiliations with or
involvement in any organization or entity with any financial
or nonfinancial interest in the subject matter or materials
discussed in this article. Rupesh Agrawal is supported by
Clinician Scientist Career Scheme grant awarded by National
Healthcare Group (grant number: CSCS/15004), Singapore.
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