TREATMENT OF POST-TRAUMATIC TRABECULAR MASHWORK THROMBOSIS
AND SECONDARY GLAUCOMA WITH INTRACAMERAL TISSUE PLASMINOGEN
ACTIVATOR IN PREVIOUSLY UNRECOGNIZED SICKLE CELL ANEMIA
Assistant professor Ksenija Karaman MD PhD, Srdjana Culic1 MD, Ivana Erceg2 MD Vida
Culic1 MD, Alen Sinicic MD, Ilza Salamunic3 spec. med. biochemistry
Department of Ophthalmology, Clinical Hospital Split and Split School of Medicine, Split,
Croatia
1
Clinical Hospital Split, Pediatrics Clinic, Split, Croatia
2
Clinical Hospital Split, Laboratory for Clinical and Forensic Genetics, Split, Croatia
3
Clinical Hospital Split, Clinical Laboratory, Split, Croatia
Corresponding author:
Assoc. prof. Ksenija Karaman, MD, PhD
Palmotićeva 10, 21 000 Split, Croatia
Phone:
+385 21 556408
Fax number:
+385 21 556407
E-mail: ksenija.karaman@st.hinet.hr
ABSTRACT
Background. Here we present a benefit of intracameral tissue plasminogen activator (t-PA)
aplication in a child with previously unrecognized sickle cell anemia, post-traumatic hyphema,
sickling of red cells, thrombosis in trabecular mashwork and consecutive acute glaucoma.
Patient and Methods. Thirteen year-old African boy was admitted to hospital, with symptoms
of acute glaucoma and partial hyphema after right eye trauma. Visual acuity of affected eye was
0.5 and intraocular pressure (IOP) 46 mm Hg. Despite a common therapy three days later clinical
condition of patient's right eye was getting worst expressing total hyphema. Visual acuity was
only hand motion (HM) and IOP 53 mmHg. Aqueous humor with hyphema was aspirated and 20
µg of t-PA was injected into anterior chamber contemporary. Cytological examination of
aqueous humor revealed 10% sickled erythrocytes, hemoglobin electrophoresis discovered
hemoglobin S and diagnosis of sickle cell disease (SCD) was confirmed. Unsolved trabecular
mashwork thrombosis was indication for second intracameral aplication of 20 μg t-PA. Results.
Intraocular aplication of t-PA has revealed excellent results in post-traumatic hyphema with
trabecular mashwork thrombosis in patient with sickle cell anemia. Complete resolution of blood
cloth in the anterior chamber and trabecular mashwork was achieved. Two-years follow up
revealed permanent normalisation of IOP and visual acuity. Conclusion. Successful outcome
with anterior chamber paracentesis and intracameral injection of t-PA is our encouraging novel
approach, which we highly recommend in treatment of post-traumatic hyphema in SCD.
Key words: post-traumatic hyphema; trabecular mashwork thrombosis; acute glaucoma; sickle
cell anemia; tissue plasminogen activator
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INTRODUCTION
Sickle cell disease is inherited hematological disorder characterized with sickle cell hemoglobin
(Hb S) which differs from the normal only by one amino acid substitution in the β-chain of
hemoglobin (HbβS), resulting with less flexible sickle red blood cells (SS RBCs) (1). Sickle cell
anemia is a recessive disease characterized with sickling of the red cells under reduced oxygen
tension. The major cause of morbidity and mortality in SCD is vascular occlusion. Episodic
occurence of vasoocclusive events precipitate acute painful episodes leading to organ failure and
death. The severity of SCD increases with higher leukocyte count because of their adherence to
vascular endothelium facilitating vaso-occlusion. The treatment modalities that reduce leukocyte
adhesion molecules expression might confer clinical benefit (2). The ophthalmic manifestations
of SDC are present in various segments of the eye which include the conjuctiva, iris, retina and
optic nerve. After traumatic hyphema patients with SCD tend to have more severe ophthalmic
complications, such as glaucoma and vaso-occlusive retinopathy leading to retinal detachments
and vitreous hemorrhages (3). Sickling phenomenon and consecutive thrombosis may cause
opturation of trabecular mashwork and increased IOP.
Most reports of traumatic hyphema indicate prevalence of 70% or greater in pediatric population,
and the average duration of the uncomplicated hyphema is 5 to 6 days (4). Usually, traumatic
hyphema is succesfuly treated topicaly with midriatics and antibiotics. There is no consensus
regarding use of systemic antifibrinolytic agents, indications for hospitalization, or timing for
surgical intervention in management of traumatic hyphema (5). Clinical benefit of so far used
therapy is questionable. Up to date intracameral injection of t-PA seems to be safe and effective
method for the treatment of unresolved total hyphema and several studies indicates the promising
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features of this drug. However, to our knowledge, intracameral application of t-PA in treatment
of post-traumatic hyphema in patients with SCD was not recorded yet.
CASE REPORT
A previously healthy 13-year-old boy, born in marriage of African father and Caucasian mother,
was admitted to our department 4 hours after being accidentally hit in the right eye by handball.
He complained of headache, right eye pain, photophobia and epiphora. His father died of heart
attack when he was 36-year-old.
Slit-lamp examination revealed ciliary injected conjunctiva, corneal edema with 2 mm hyphema
and marked cell and flare in the anterior chamber. Pupillary examination showed irregular and
enlarged pupil with poor reaction to light. IOP was 46 mm Hg (normal <21 mm Hg) and visual
acuity of the right eye was 0.5. Because of corneal edema the fundus of his right eye was not
visualized in detail. A diagnostic work-up, including a complete blood count, electrolytes, urine
analysis, x-ray and computed tomography of the orbit, was unremarkable.
Diagnosis of traumatic hyphema, iritis and secondary glaucoma of the right eye was made. Initial
treatment included topical and subconjunctival steroids, topical timolol, oral acetozolamide, and
systemic 10% mannitol.
Three days later there was total hyphema in the anterior chamber and IOP was 53 mm Hg,
despite the treatment (Fig. 1). Visual acuity of the affected eye was only hand motion. According
to clinical data, therapy failure, and boy’s background (African), suspicion of sickle cell anemia
has appeared.
At this point, surgery was performed: anterior chamber lavage to evacuate hyphema, partial
evacuation of blood cloth, and 20 µg of t-PA was injected into the anterior chamber.
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After surgery transcorneal oxygen therapy was applied, as well as 1000 ml of 0.9% NaCl with
5% glucose solution per day.
Surgery temporarily decreased IOP and ameliorated symptoms, but day later IOP increased again
and persisted. However, only partial hyphema remained (1mm) with cell and flare in the anterior
chamber.
Second surgery was performed four days later. Lavage of anterior chamber was done and 20 μg
of t-PA was injected again. During the second surgery aqueous humor with hyphema was
aspirated by paracentesis and cytological examination was accomplished. Fresh preparation and
staining of aqueous humor has revealed that 10% of erythrocytes from hyphema were sickle cells
(Fig. 2). In the meantime hemoglobin electrophoresis revealed hemoglobin S (Fig.3).
After second surgery IOP normalized, cornea became completely clear, corneal edema resolved,
cell and flare in the anterior chamber were negative, while the pupil remained irregular. Fundus
examination revealed normal optic nerve disc and two blot hemorrhages at the periphery of the
retina. Visual acuity was 1.0.
Folic acid, acetylsalicylic acid and vasodilators (verapamil) were included in therapy and patient
was discharged home. He continued to do well and his IOP remained normal as well as his
vision.
Fundus examination 24 days after injury showed peripheral retinal artery occlusions and
ischemical lesions at 5, 6 and 11 hours. Closely associated with sickle cell retinopathy, in the
same eye, partial iris atrophy was observed which is believed to be secondary to the vasoocclusive process in the iris (Fig. 4).
Sickle cell retinopathy remained unchanged first three months, but follow-up after four months
showed normal retina with no signs of retinal artery occlusions.
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Pattern visual evoked potential (VEP) of his right eye showed normal P 100 wave amplitude and
elongated P 100 wave latency (116.6 ms), but four months later, pattern VEP P100 wave latency
normalized. Visual field was normal all the time.
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DISCUSSION
In differential diagnosis of hyphema and increased IOP sickle cell anemia has to be considered.
Although peripheral blood examination of our patient did not show sickle red cells, 10% of red
cells from hyphema in the anterior chamber had sickle cell shape. All that points out how
important is to perform aqueous humor examination when complications of traumatic hyphema
occurs.
Successful outcome with anterior chamber paracentesis and intracameral injection of t-PA is our
encouraging novel approach, which we highly recommend in treatment of post-traumatic
hyphema in SCD. Tissue plasminogen activator is a fibrin specific fibrinolytic and potent
thrombolytic agent that has been shown to be effective in accelerating the clearance of fibrin
clots from anterior chamber. The results in five eyes with post-traumatic total hyphema (without
sickle cell) suggest that t-PA is a useful addition in managing of total hyphema (6,7).
The management of traumatic hyphema has been controversial for many years. Various studies
have left unanswered questions, such as whether antifibrinolytics are as effective in children as
adults, in white patients as black, and in patients with normal hemoglobin as well as those with
sickle cell hemoglobinopathies (8). In patients with hyphema and SCD application of
antifibrinolytics are contraindicated for blocking the cloth lysis.
Although transcorneal oxygen therapy can reduce intraocular pressure in patients with glaucoma
from sickle cell hyphema (9), our experience did not confirm that.
Hyphemas in patients with sickle cell hemoglobinopathies, whether traumatically or surgically
induced, may have devastating effects on the eye. Early anterior chamber paracentesis may be
the best treatment for this type of hyphema-induced secondary glaucoma (10). Complications of
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traumatic hyphema include increased IOP, peripheral anterior synechiae, optic atrophy, corneal
bloodstaining, secondary hemorrhage, and accommodative impairment (11). In addition,
occlusions of the retinal vasculature are the initiating event in sickle cell retinopathy. In our case
acetylsalicilic acid and vasodilators improved reperfusion of the peripheral retinal vessels. Sickle
cell retinopathy in its advanced form is complicated by preretinal neovascularization, vitreous
hemorrhage, and retinal detachment (12).
The high risk of secondary thrombosis with potential ocular damage in patients with traumatic
hyphema and sickle cell anemia supports the benefit of hospitalization.
The fact that acute chest syndrome is a leading cause of death among patients with sickle cell
disease (13), it can be presumed that our patient’s father also had SCD, unfortunately
unrecognized and untreated.
In conclusion, as blinding or sight-threatening damage may occur to the retina or optic nerve,
appropriate screening and patient management of sickle cell are vital to the continued quality of
life for these patients and it is very important public health issue.
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REFERENCES
1. Turhan A, Weiss LA, Mohandas N, Coller BS, Frenette PS. Primary role for adherent
leukocytes in sickle cell vascular occlusion: A new paradigm. Proc Natl Acad Sci
2002;99(5):3047-3051.
2. Okpala I, Daniel Y, Haynes R, Odoemene D, Goldman J. Relationship between the clinical
manifestations of sickle cell disease and the expression of adhesion molecules on white blood
cells. Eur J Haematol 2002;69(3):135-144.
3. To KW, Nadel AJ. Ophthalmologic complications in hemoglobinopathies. Hematol Oncol
Clin North Am 1991;5(3):535-548.
4. Crouch ER Jr, Crouch ER. Management of traumatic hyphema: therapeutic options. J Pediatr
Ophthalmol Strabismus 1999;36(5):238-250; quiz 279-280.
5. Kelly JL, Blomquist PH. Management of traumatic hyphema in Texas. Tex Med
2002;98(4):56-61.
6. Laatikainen L, Mattila J. The use of tissue plasminogen activator in post-traumatic total
hyphaema. Graefes Arch Clin Exp Ophthalmol 1996;234(1):67-68.
7. Kim MH, Koo TH, Sah WJ, Chung SM. Treatment of total hyphema with relatively low-dose
tissue plasminogen activator. Ophthalmic Surg Lasers 1998;29(9):762-766.
8. Gottsch JD. Hyphema: diagnosis and management. Retina 1990;10 Suppl 1:S65-71.
9. Benner JD. Transcorneal oxygen therapy for glaucoma associated with sickle cell hyphema.
Am J Ophthalmol 2000;130(4):514-515.
10. Goldberg MF. Sickled erythrocytes, hyphema, and secondary glaucoma: I. The diagnosis and
treatment of sickled erythrocytes in human hyphemas. Ophthalmic Surg 1979;10(4):17-31.
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11. Walton W, Von Hagen S, Grigorian R, Zarbin M. Management of traumatic hyphema. Surv
Ophthalmol 2002;47(4):297-334.
12. Cohen SB, Fletcher ME, Goldberg MF, Jednock NJ. Diagnosis and management of ocular
complications of sickle hemoglobinopathies: Part V. Ophthalmic Surg 1986;17(6):369-374.
13. Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, at all. Causes
and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome
Study Group. N Engl J Med 2000;342(25):1855-1865.
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FIGURE LEGENDS
Figure 1
Post-traumatic total hyphema of the right eye.
Figure 2
Photomicrograph of aqueous humor (May-Grunwald, Giemsa, x100). Arrow indicates
erythrocyte from hyphema with alteration in sickle cell shape.
Figure 3
Hemoglobin electrophoresis on cellulose acetate at pH 8.6 following staining with Ponceau-S.
Arrow indicates prominent band for HbS trait.
Figure 4
Right eye after treatment, arrow indicates partial iris atrophy.
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