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postoperative uveitis associated with inflammatory membrane formation occurs in less than 3% of cases after uneventful cataract surgery and intraocular lens ( iol ) implantation .
complications from resultant membrane formation include iol displacement , pupillary block glaucoma , posterior capsule opacification , and side - effects from prolonged topical steroid treatment .
intracameral injection of recombinant tissue plasminogen activator ( rtpa ) , a highly potent fibrinolytic protein used for systemic thrombolysis , has been shown to successfully lyse fibrin membranes [ 25 ] .
reported uncommon complications of intracameral rtpa include corneal oedema , band keratopathy , anterior chamber turbidity , and hyphaema , while iol opacification would not appear to have been previously reported [ 68 ] .
we report 7 cases of iol opacification subsequent to rtpa treatment for postoperative inflammatory membranes following uneventful phacoemulsification and hydrophilic acrylic one - piece iol implantation ( rayner c - flex 570c and superflex 620h ) . to the best of our knowledge ,
this is the first report of hydrophilic acrylic iol opacification following the use of intracameral rtpa .
three patients had type 2 diabetes and treated proliferative retinopathy , and one patient presented with phacomorphic glaucoma requiring urgent cataract surgery .
two patients had medically controlled systemic hypertension but none had abnormal albumin or serum calcium levels .
all patients underwent uneventful cataract phacoemulsification and posterior chamber iol implantation under local anaesthesia between august 2002 and september 2009 .
two percent hydroxypropylmethylcellulose ( coatel ) and balanced salt solution ( bss ) were used in all cases .
the rayner c - flex 570c iol was implanted in 4 patients and the rayner superflex 620h was implanted in 3 patients .
no remaining viscoelastic material or soft lens matter was observed at the end of all procedures .
inflammatory membrane formation was noted within 1 week in three patients and between 2 and 4 weeks in the remaining 4 patients .
intracameral rtpa ( actilyse ) was prepared under sterile conditions using 50  mg vials of rtpa diluted with 50  ml of sterile water to create a 1  mg / ml solution .
1050  l of this solution was injected into the anterior chamber using an insulin syringe with a 30-gauge needle
. slit lamp examination and intraocular pressure measurement were performed 2 and 24 hours after rtpa treatment .
the frequency of dexamethasone 0.1% was increased to be hourly by day , together with chloramphenicol 6 hourly and cyclopentolate 1% 8 hourly .
further reviews were scheduled at weeks 1 and 3 and at 6 months after treatment .
opacified iols were viscodissected with sodium hyaluronate ( healon ) , with care taken to avoid manipulation of the opacified portion .
one patient required bisection of the iol and anterior vitrectomy due to severe adhesion between the iol and lens capsule .
explanted iols were placed in a sterile container with neutral buffered formalin 10% before they were sent for laboratory analysis .
two explanted iols were sent to the laboratories for ophthalmic devices research , sullivan 's island , south carolina , usa , for light microscopy and histochemical analysis .
another iol was sent for light microscopy , scanning electron microscopy , and x - ray spectrometry at the international vision correction research centre , department of ophthalmology , university of heidelberg , germany .
detailed techniques for preparation and staining of explanted iols for calcium have been described elsewhere .
briefly , iols were photographed under a light microscope and were subsequently treated with special stains for calcium ( von kossa 0.5% and alizarin red 1% ) . the iols were reexamined and photographs were again taken .
full - thickness sections were made through the opacified portion and the iols were restained for cross - sectional examination .
scanning electron microscopy ( sem ) and energy - dispersive x - ray spectrometry ( eds ) for elemental analysis were also separately performed .

 table 1 summarises the preoperative comorbidities , procedures performed , and subsequent treatment for the 7 patients .
inflammatory membranes developed between 1 and 4 weeks postoperatively , and resolution of inflammatory membrane occurred within 24 hours after intracameral rtpa in all cases .
iol exchange was carried out in 3 patients with a mean final bcva of 0.20 logmar .
three other patients declined iol exchange and 1 patient was deemed unsuitable for further surgery due to poor visual potential secondary to neovascular glaucoma .
macroscopic and microscopic findings on all explanted iols were highly comparable . on macroscopic examination , fine granular whitish opacities were observed in the central part of all explanted iol optics ( figure 1 ) .
light microscopy revealed diffuse fine granular deposits on as well as below the anterior surface of the nonencapsulated optic .
these deposits stained positively with von kossa and alizarin red and were linearly distributed parallel to the anterior iol surface , diminishing towards the periphery and posteriorly .
cross - sectional sem of opacified iol showed crystalline deposits distributed close to the surface of the iol ( figure 2 ) .
analysis with eds confirmed the presence of calcium and phosphate ( figure 2(d ) ) within the compound .
iol opacification is an infrequent complication after uneventful cataract surgery , resulting in symptoms of visual loss or glare , necessitating iol exchange in some cases . to our knowledge
, this is the first report of iol opacification due to calcification following the use of rtpa for postoperative fibrinous membranes after cataract surgery .
a number of cases of iol opacification have previously been reported ; almost all were involving hydrophilic acrylic iols from various manufacturers [ 915 ] .
reported 2 cases of surface calcification of hydrophilic acrylic rayner c - flex 570c implants related to inflammatory membrane formation after combined vitrectomy and cataract surgery .
similar to their report , we found localised calcification on the anterior and subsurface within the capsulorhexis area on both the c - flex and the superflex iols .
such calcification is independent of the manufacturing and packaging process and is thus classified as secondary calcification relating to environmental causes .
iol calcification has been associated with systemic disease , intraocular surgery , inflammation , or drug administration [ 5 , 9 , 1618 ] .
breakdown of blood - aqueous barrier ( bab ) and disruptions to aqueous calcium homeostasis are thought to lead to dystrophic calcium - phosphate precipitation on the iol , although the precise mechanism remains unclear .
reported a case series of 15 patients with hydrophilic acrylic iol opacification following descemet stripping automated endothelial keratoplasty ( dsaek ) , in which they identified air injection for dsaek graft rebubbling as a significant risk factor .
analysis of the opacified iols demonstrated findings identical to those observed in our study , using similar methodology . in our series , all cases had postoperative inflammatory membranes that were successfully treated with rtpa . in our unit ,
we are not aware of any other pseudophakic patients who had received intracameral rtpa injections .
thus it would be suggested that intracameral rtpa injection is an absolute risk factor for iol opacification . in response to our findings , we stopped further usage of intracameral rtpa in cases of postoperative inflammatory membrane formation , and we have not observed any cases of iol opacification since .
these cases were also reported to the medicines & healthcare products regulatory agency in the united kingdom .
we hypothesise that rtpa contributes to iol opacification through its action on aqueous calcium - phosphate homeostasis and possible disruption of the blood - aqueous barrier ( bab ) .
intracameral rtpa lyses fibrinous inflammatory membranes and in doing so releases sequestered calcium from the fibrinous matrix .
it also introduces phosphate ions contained in its buffer solution , which may potentiate abnormal calcium precipitation . a case report of band keratopathy formation after
recent laboratory model has also shown that calcification occurred when the iol was exposed to a supersaturated solution of calcium and phosphate ions , and the reaction is initiated within the iol towards the anterior iol surface due to ionic diffusion .
this coincides with our observation and may explain the preferential calcification on the anterior subsurface / surface of the hydrophilic iol .
similar to air injection in dsaek graft rebubbling , rtpa injection may also lead to further disruption of the bab .
this may be due to the induction of nonplasminogen intracellular signalling pathways [ 22 , 23 ] or the mechanical effect of the injection itself .
although intraocular inflammation could be solely responsible for iol opacification , it fails to explain the strong association between iol opacification and the use of rtpa .
the dosages of rtpa used in our patients were within the range reported by previous authors ( 325  g ) in all except 2 cases [ 24 , 24 ] .
it is plausible that the higher doses in the 2 cases may have exacerbated the extent of iol opacification , although this has not been formally quantified .
cases of iol opacification occurred during a period when our unit exclusively used rayner iols .
c - flex and superflex differ in the size of the optic ( 5.75  mm and 6.25  mm in diameter , resp . ) and the range of diopter power ( + 8.0 to + 34.0d and 10.0 to + 22.0d , resp . ) , but they are both hydrophilic acrylic one - piece monofocal iols . however , there was no evidence of any manufacturing defects on the explanted iols in our histopathological analysis .
this study highlights that intracameral injection of rtpa for the treatment of postoperative inflammatory membranes could lead to iol opacification requiring iol exchange .
the limitations of this study were its retrospective nature and the small number of cases involved .
the intraocular effects of rtpa may be more extensive than previously thought , and further laboratory investigations on this are needed .
caution should be exercised in using rtpa to treat inflammatory membranes following intraocular surgery , especially in the presence of hydrophilic iols .
purpose . to report 7 cases of intraocular lens ( iol ) opacification following treatment of postoperative anterior chamber fibrin with recombinant tissue plasminogen activator ( rtpa ) after cataract surgery 
 . methods . 
 retrospective case series of 7 eyes in 7 patients who developed iol opacification after receiving rtpa for anterior chamber inflammatory membrane formation resulting from phacoemulsification cataract surgery . 
 three explanted iols were investigated with light microscopy , histochemical analysis , scanning electron microscopy , and x - ray spectrometry . 
 results . 
 all patients underwent uncomplicated cataract surgery and posterior chamber hydrophilic iol implantation . 
 anterior chamber inflammatory membranes developed between 1 and 4 weeks of surgery and were treated with intracameral rtpa . 
 iol opacification was noted between 4 weeks and 6 years after rtpa treatment with reduced visual acuity , and iol exchange was carried out in 3 patients . 
 light microscopy evaluation revealed diffuse fine granular deposits on the anterior surface / subsurface of iol optic that stained positive for calcium salts . 
 scanning electron microscopy ( sem ) and energy - dispersive x - ray spectrometry ( eds ) confirmed the presence of calcium and phosphate on the iol . 
 conclusions . 
 intracameral rtpa , though rapidly effective in the treatment of anterior chamber inflammatory membranes following cataract surgery , may be associated with iol opacification .