Intracameral Recombinant Tissue Plasminogen Activator (rtPA) as the Primary Treatment for Secondary Pupillary Block

Abstract

Alteplase is a recombinant form of human tissue plasminogen activator (tPA) that converts plasminogen to plasmin essential for fibrinolysis. It is commonly used to treat embolic or thrombotic disorders such as ischemic stroke. Despite its rarity use in ophthalmology, we are reporting the effectiveness of recombinant tissue plasminogen activator (rtPA) in treating an eye with secondary pupillary block as a consequence of severe endophthalmitis. A patient presented with acute endophthalmitis after a complicated cataract extraction. Examination showed severe anterior chamber reaction leading to seclusion pupillae, iris bombe and presence of iridocorneal touch 360-degree. Following intracameral alteplase 2.5 microgram in 0.1 ml given, iris bombe was observed to resolve completely onehour later. Anterior chamber was also significantly deeper and slightly larger pupil compared to before rtPA injection. Due to clearer view of anterior segment, pars planar vitrectomy and extraction of intraocular lens could be performed with significant visual improvement after surgery. Our findings suggest that usage of rtPA, which is alteplase, was effective in treating secondary pupillary block due to intense anterior segment inflammation in endophthalmitis cases. Thus it is useful in replacing the conventional use of laser peripheral iridotomy in treating pupillary block, as the latter potentially aggravates the pre-existing inflammatory condition.

Full text

Med & Health Jun 2022; 17(1): 302-307
CASE REPORT
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https://doi.org/10.17576/MH.2022.1701.24
Address for correspondence and reprint request s: Safinaz Mohd Khialdin. Depart ment of Ophthalmology,
Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak,
56000 Cheras, Kuala Lumpur, Malaysia. Tel: +603-9145 5555 Email: drsafinaz_1978@yahoo.com.my
Intracameral Recombinant Tissue Plasminogen
Activator (rtPA) as the Primary Treatment for
Secondary Pupillary Block
SITI NOOR ATIKAH AR1, SAFINAZ MK1, MUSHAWIAHTI M1,
MUHAMMAD SYAMIL MS1,2, AYESHA MZ1
1Department of Ophthalmology, Faculty of Medicine, Universiti Kebangsaan Malaysia
Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur,
Malaysia
2Ophthalmology Unit, Department of Surgery, Medical and Health Sciences Faculty,
Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
ABSTRAK
Alteplase adalah sejenis pengaktif plasminogen tisu (tPA) yang telah melalui
proses bioteknologi rekombinan. Ia berfungsi dengan memangkin pertukaran
plasminogen kepada plasmin untuk proses fibrinolisis dan biasanya digunakan
untuk mengubati penyakit saluran darah tersumbat seperti strok. Walaupun ia
jarang digunakan dalam bidang oftalmologi, kami ingin melaporkan keberkesanan
pengaktif plasminogen tisu rekombinan (rtPA) untuk merawat keadaan mata yang
mempunyai saliran anak mata tersumbat (pupillary block) disebabkan penyakit
endoftalmitis. Kami membentangkan kes endoftamitis akut yang terjadi berikutan
komplikasi pembedahan katarak. Pesakit mempunyai radang pada segmen anterior
mata (anterior chamber) menyebabkan seklusio pupil (seclusion pupillae), gelemair
terkumpul di belakang iris menolak iris ke depan (iris bombe), dan menyebabkan
sentuhan iris-kornea (iridocorneal touch) 360 darjah. Satu jam selepas suntikan 2.5
mikrogram alteplase dalam 0.1 ml ke dalam gelemair mata, iris bombe dilihat telah
hilang sepenuhnya, segmen anterior mata dilihat lebih dalam dan anak mata (pupil)
kelihatan sedikit besar berbanding sebelumnya. Segmen anterior mata yang lebih
jelas membolehkan pembedahan membuang gelemaca ‘pars plana vitrectomy’
dan pengeluaran kanta intraokular boleh dilakukan lantas memberikan penglihatan
yang baik selepas pembedahan. Penemuan kami mencadangkan suntikan rtPA,
iaitu alteplase pada segmen anterior mata adalah efektif untuk rawatan ‘pupillary
block’ sekunder yang disebabkan oleh radang yang serius seperti kes endoftalmitis.
Oleh itu, penggunaan rtPA adalah berguna untuk menggantikan kebiasaan
penggunaan laser pada sisi iris (laser peripheral iridotomy) untuk merawat ‘pupillary

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RTPA for Secondary Pupillary Block
Med & Health Jun 2022;17(1): 302-307
block’, kerana rawatan laser boleh memburukkan keadaan inflamasi pada segmen
anterior mata.
Kata kunci: endoftalmitis, pengaktif plasminogen tisu, segmen anterior
ABSTRACT
Alteplase is a recombinant form of human tissue plasminogen activator (tPA) that
converts plasminogen to plasmin essential for fibrinolysis. It is commonly used to
treat embolic or thrombotic disorders such as ischemic stroke. Despite its rarity
use in ophthalmology, we are reporting the effectiveness of recombinant tissue
plasminogen activator (rtPA) in treating an eye with secondary pupillary block
as a consequence of severe endophthalmitis. A patient presented with acute
endophthalmitis after a complicated cataract extraction. Examination showed
severe anterior chamber reaction leading to seclusion pupillae, iris bombe and
presence of iridocorneal touch 360-degree. Following intracameral alteplase 2.5
microgram in 0.1 ml given, iris bombe was observed to resolve completely one-
hour later. Anterior chamber was also significantly deeper and slightly larger pupil
compared to before rtPA injection. Due to clearer view of anterior segment, pars
planar vitrectomy and extraction of intraocular lens could be performed with
significant visual improvement after surgery. Our findings suggest that usage of
rtPA, which is alteplase, was effective in treating secondary pupillary block due to
intense anterior segment inflammation in endophthalmitis cases. Thus it is useful
in replacing the conventional use of laser peripheral iridotomy in treating pupillary
block, as the latter potentially aggravates the pre-existing inflammatory condition.
Keywords: anterior chamber, endophthalmitis, tissue plasminogen activator
Early treatment following correct
diagnosis is essential to optimise the
visual outcome.
The systemic use of tissue
plasminogen activator (tPA) has been
approved since 1988 for thrombolysis
in coronary artery disease. Since then,
this drug has been extended to other
indications, including the eye. Its
safety and effectiveness for treatment
of fibrin-related complications of
ocular inflammation including
endophthalmitis was reported in
INTRODUCTION
Endophthalmitis is defined as severe
eye inflammation involving anterior and
posterior segments due to an infectious
agent. It is a sight-threatening condition
that can occur as a complication of
ocular surgery or trauma, or following
systemic infection. Common signs
of endophthalmitis include reduced
visual acuity, conjunctival injection,
presence of cells and flare in anterior
chamber and vitritis (Durand 2013).

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Med & Health Jun 2022;17(1): 302-307 Siti Noor Atikah A.R. et al.
multiple studies (Damji et al. 2001; Wu
& Wang 2009; Riaz et al. 2006). Severe
anterior segment inflammation does
not only cause poor visualisation of
the posterior segment, synechiae that
is formed can also leads to secondary
pupillary block. Traditionally, laser
iridotomy is the treatment of choice
for pupillary block. This procedure
however, may potentially aggravate the
pre-existing inflammatory condition.
Moreover, in severe fibrin reaction,
anterior chamber details could not
be distinguished thus hindering laser
iridotomy procedure. We report the
use of recombinant tissue plasminogen
activator (rtPA) as a first line treatment
for secondary pupillary block in a
case of severe endophthalmitis. As
a fibrinolytic agent, it accelerates the
clearance of fibrin in endophthalmitis,
thus preventing devastating
complications of endophthalmitis such
as loss of vision.
CASE REPORT
A 69-year-old man with background
of diabetes mellitus underwent a
complicated phacoemulsification
surgery which was converted to extra
capsular cataract extraction (ECCE)
followed by implantation of intraocular
lens (IOL) on his right eye in a private
ophthalmology centre. Patient
received topical Dexamethasone
0.1% and topical Moxifloxacin 0.5%
post-operatively. At 2 weeks post-
operatively, he developed acute
endophthalmitis and was given
intravitreal Vancomycin, Ceftazidime
and Dexamethasone once. However,
he defaulted subsequent follow-up
and presented to us 2 weeks later
with a complaint of right eye redness
and pain. Examination revealed visual
acuity of hand movement with severe
inflammation in the anterior chamber
with no fundus view. IOL was noted
to be subluxated inferiorly. B-scan
showed loculations in the vitreous
but no retinal detachment. Intraocular
Figure 1: Prior to intracameral rtPA shows fibrin
over the pupil and intraocular lens causing
seclusion pupillae, iris bombe is not clearly
seen in this photo but anterior chamber was
very shallow with complete iridocorneal touch
360 degree
Figure 2: Following intracameral rtPA, fibrin
reduced, anterior chamber deeper, iris bombe
less and pupil slightly enlarged.

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pressure (IOP) was 4 mmHg on the
right eye.
Repeated intravitreal Ceftazidime
(Duopharma, Malaysia) 2.25mg/0.1ml,
Vancomycin (Mylan Lab, India)
1mg/0.1ml and Dexamethasone
(Duopharma, Malaysia) 0.4mg/ 0.1ml
were given. He was also started on
oral Moxifloxacin (Bayer, Germany)
400 mg daily, in combination with 2
hourly dose of topical Moxifloxacin
0.5% (Alcon, Singapore), 6 hourly
Dexamethasone 0.1% (Alcon, Belgium)
and daily Atropine 1% (Alcon, Belgium).
The cornea was very hazy with the
presence of Descemet striations. He
was prepared for pars plana vitrectomy.
On the following day, worsening of
the anterior chamber reaction was
noted causing seclusio pupillae with
shallow anterior chamber. Iris bombe
and iridocorneal touch were present
360-degrees (Figure 1), while the IOP
was still 12 mmHg. Following topical
anesthesia, 25 micrograms of rtPA,
Alteplase (Boringer, Germany) in 0.1 ml
of saline was injected intracamerally
through the inferonasal limbus using a
30-gauge needle. One hour following
injection, the fibrin reduced, anterior
chamber was deeper, iris bombe
resolved completely and pupil was
slightly larger (Figure 2). The patient
was subsequently arranged for IOL
explantation and vitrectomy. Surgery
was uneventful, and the patient was
left aphakic. Upon discharge, his vision
improved to 6/36 assisted with +10D
lens. Vitreous culture did not grow any
organism.
DISCUSSION
Acute endophthalmitis is an ocular
emergency which requires prompt
diagnosis and treatment. The most
important component of therapy
is intravitreal antibiotic injection.
However, even with correct timing
of starting antibiotic therapy, intense
inflammation may lead to severe fibrin
reaction in anterior and posterior
segment which may result in posterior
synechiae, seclusio pupillae, peripheral
anterior synechiae, iris bombe, and
secondary angle-closure glaucoma
(Durand 2013).
Alteplase is a recombinant form of
tPA, which is a proteolytic enzyme
in serine protease family found on
endothelial cells. It is essential for
fibrinolysis and acts as thrombolytic
agent. Tissue plasminogen activator
converts plasminogen to plasmin once
it bounds to fibrin, which subsequently
promotes fibrin degradation (Damji
et al. 2001). Tissue plasminogen
activator dissolves clots rapidly, within
minutes to hours and it also has a
short biological half-life. The use of
alteplase for acute cases of ischemic
stroke, myocardial infarction, massive
pulmonary embolism, and occlusion
of central venous access devices
(CVADs) is permitted by Food and Drug
Administration (FDA). Although it is not
routinely used in ophthalmology, the
high efficacy of intracameral rtPA has
been reported for treatment of anterior
chamber fibrin formation following
cataract extraction, trabeculectomy,
combined cataract and glaucoma
surgery, penetrating keratoplasty, as
well as vitrectomy (Damji et al. 2001;
Georgiadis et al. 2003; Wedrich et
al. 1997). Moreover, the effectiveness

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of rtPA to treat severe fibrin reaction
was also demonstrated in case of
endophthalmitis (Wu & Wang 2009),
and recalcitrant anterior uveitis (Patrick
et al. 2018). Thus intracameral rtPA is
probably underused in our fraternity.
In the present case, the clinical
indication for rtPA was secondary
pupillary block with iris bombe in a
severely inflamed eye. A randomised
prospective study by Heiligenhaus
et al. (1998) revealed significant
reduction of synechiae and successful
synechiolysis after intracameral tPA
injection in patients with intraocular
fibrin formed following cataract
surgery (Heiligenhaus et al. 1998).
Intracameral rtPA was also noticed to
be effective in decreasing the incidence
of pupillary dysfunction due to the
posterior synechiae formation and
fibrin deposition at pupillary region,
as shown in the study (Heiligenhaus
et al. 1998). In another reports, fibrin
membrane dependent pupillary block
was shown successfully treated with
intracameral tPA injection (Akcetin et
al. 2015; Yoshino et al. 2012). These
reports suggest the use of rtPA as
the primary treatment for both fibrin
reactions after cataract surgery and
secondary pupillary block.
Meanwhile, Wu & Wang (2009)
reported enlargement of pupillary
size 24 hours after rtPA injection in
endophthalmitis patients. In addition
to previous studies, this study also
demonstrated the effectiveness of
using intracameral injection of rtPA
in endophthalmitis, which eventually
facilitates vitreous and fundus
examination, including vitrectomy if
needed. This will be a very valuable
advantage for these type of patients
as vitrectomy can be challenging not
only if the cornea is hazy due to the
severe anterior chamber reaction,
low IOP and even worse if the pupil
is small. Manipulation of pupil during
surgery will eventually induce intense
inflammation post operatively.
In terms of timing of rtPA injection
following fibrin formation, various
literatures reported successful
fibrinolysis within hours of injection
(Riaz et al. 2006; Damji et al. 2001;
Erol et al. 2003). In a study by Dotan
et al. (2014), they demonstrated the
therapeutic effect of rtPA in refractory
toxic anterior segment syndrome
(TASS) patients. In their case, it is
of different mechanism whereby
the TASS is caused by breakdown
of blood-aqueous barrier thus the
initial hypothesis is that injection
administration later (after 16 days of
cataract surgery) would show better
outcome than earlier intervention
(within 10-15 days of cataract surgery)
(Dotan et al. 2014). However, the study
has proven that regardless the timing
of injection following cataract surgery,
fibrinolysis rate as well as visual acuity
improvement have no statistically
significant different. Successful
fibrinolysis was shown in all subjects
in the report. In our case, successful
fibrinolysis was observed as early as
one hour post rtPA injection. In case of
fibrin membrane pupillary block, the
rtPA injection should be given as soon
as fibrin formation is noted because
further delay could raise IOP and
further optic nerve damage.

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CONCLUSION
Intracameral rtPA, which is alteplase,
is useful in replacing the conventional
use of laser peripheral iridotomy in
treating fibrin membrane pupillary
block.
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Received: 16 Jun 2021
Accepted: 31 Aug 2021