a case showing sustained structural and functional responses 2 years after a single treatment with iluvien ( 0.2 g / day fluocinolone acetonide , fac ) despite suboptimal responses to ranibizumab .
a 68-year - old female patient with diabetic macular oedema ( dme ) from type 2 diabetes mellitus was first diagnosed in october 2010 and had a baseline visual acuity ( va ) of 46 early treatment diabetic retinopathy study ( etdrs ) letters in the left eye .
the patient was treated with 11 intravitreal injections of ranibizumab ( 5 in combination with a small - interfering rna agent ) , and by march 2014 , va and cft were largely unchanged ( 55 etdrs letters and 774 microns ) .
the patient was treated with iluvien as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab .
an implant releasing fac at a dosage of 0.2 g / day was administered in march 2014 , and the optical coherence tomography indicated that the macula was dry after 7 days ( cft was below 300 microns ) .
va improved by 5 letters within 7 days and by 15 letters within 14 days , and this was maintained after 24 months . throughout the duration of this study , the intraocular pressure was 22 mm hg , and no glaucoma medication was administered .
in real - life uk practice , this dme patient showed a suboptimal response to multiple intravitreal injections of ranibizumab . when subsequently treated with a single injection of iluvien
, there were large and rapid improvements in va and cft that were maintained for the following 2 years .
worldwide diabetic macular edema ( dme ) is reported to have a prevalence of 6.8% and results in vision loss .
dme management can be difficult , with only around 15% of the patients achieving significant vision recovery with laser , the current standard of care .
a number of pharmacotherapies are now licensed for the treatment of dme in europe , including anti - vascular endothelial growth factor agents and corticosteroid therapies , which are used to target vascular endothelial growth pathways and inflammatory pathways , respectively . in diabetes ,
leukocytes release free radicals and enzymes that cause direct damage to endothelial cells , increasing blood retinal barrier leakage .
they also release cytokines , including vascular endothelial growth factor , tumor necrosis factor- , and interleukin-6 , which act through various signaling pathways to increase vascular permeability .
the release of cytokines with a corticosteroid  such as dexamethasone , triamcinolone or fluocinolone  has been shown to reduce dme and rehabilitate vision in several pivotal clinical studies .
iluvien contains the corticosteroid fluocinolone acetonide ( fac ) and uses microdosingtm technology to release fac at a daily rate of 0.2 g for up to 3 years .
this differs significantly from both the dexamethasone delivery system and that of triamcinolone , which are reported to have a duration of action of only up to 3 and 4 months , respectively .
the effectiveness of iluvien was demonstrated in the fame trials ( nct00344968 ) in which patients with dme who had previously shown an insufficient response to laser were treated with either a 0.2 g / day ( iluvien ) or 0.5 g / day fac implant and were compared against a sham - control treated population .
both fame trials independently met their primary endpoint and showed that significantly more patients with chronic dme treated with the 0.2 g / day fac implant experienced a 15-letter improvement in visual acuity ( va ) at month 24 than sham - control patients ( pooled data ; 34.4 vs. 13.4% ; p < 0.001 ) and that this benefit was sustained to month 36 .
functional improvements were accompanied by rapid and sustained improvements in central foveal thickness ( cft ) . in europe ,
iluvien is indicated for the treatment of vision impairment associated with chronic diabetic macular oedema considered insufficiently responsive to available therapies . since then
miss clare bailey presented the real world outcomes from a uk audit of patients treated with iluvien at the annual meeting of the royal college of ophthalmologists in birmingham , uk , between june 24 and 26 , 2016 .
this unpublished interim analysis showed that the majority of treated eyes ( 69.4% of 290 eyes ) maintained or improved va .
to date , however , relatively limited data with a longer - term follow - up of the functional and structural responses following treatment with iluvien have been reported .
the case described herein provides data for both va and cft over a 24-month follow - up period .
a 68-year - old caucasian female with type 2 diabetes mellitus had diffuse dme diagnosed in her left eye in october 2010 .
the treatment history is summarised in table 1 and was previously reported when only 6 months of follow - up were available . at diagnosis , va was 46 early treatment diabetic retinopathy study ( etdrs ) letters , converted from snellen va using the equation 85 + 50 x log ( snellen fraction ) , cft was 712 microns , and intraocular pressure ( iop ) was 22 mm hg .
the patient had phacoemulsification plus intraocular lens insertion in the left eye in february 2012 .
intravitreal triamcinolone acetonide was also administered to treat the persistent dme postoperatively . at the first postoperative visit ,
va was 70 etdrs letters , cft was 278 microns , and iop was 20 mm hg . over the next 5 months , va ( 50 etdrs letters ) and cft ( 805 microns ) progressively worsened , and the patient was admitted into the matisse trial in september 2012 to test the effects of ranibizumab plus a small - interfering rna agent .
between october 2012 and march 2014 , the patient received 5 injections of ranibizumab plus the small - interfering rna agent and then subsequently listed for 2 further courses of 3 intravitreal injections of ranibizumab . by the end of this stage of treatment , by 1 month after the final injection of ranibizumab , the dme had recurred , va was 55 etdrs letters , cft was 774 microns , and iop was 17 mm hg .
the patient 's dme was now chronic ( over 18 months of duration ) , relapsing , and her crt had fluctuated wildly through the different treatment phases , which is believed to have a deleterious effect on the function of the retina and , more specifically , on the visual function due to the presence of submacular fluid .
it was at this stage that the patient was treated with iluvien according to nice ta301 ( please see http://www.nice.org.uk/guidance/ta301/chapter/1-guidance ) .
figure 1 shows the response of va and cft after a single iluvien implant without any further treatment to this eye over the next 2 years . within 7 days
, va had increased to 61 etdrs letters and cft had decreased to 267 microns . within 2 weeks , va had improved further to 70 etdrs letters , which is the legal requirement to hold a driving license in the uk .
these early improvements were then largely maintained throughout the next 24 months without further intervention , as shown in figure 1 .
figure 2 shows optical coherence tomography scans before and after iluvien implantation , illustrating the structural improvement that occurred alongside the functional improvement in vision .
over the course of the 2-year period , iop remained below 21 mm hg , and no iop - lowering medication was required .
this is the first case that the authors are aware of , which shows that a single injection of the 0.2 g / day fac implant leads to rapid improvements ( within 7 days ) in va and cft that are maintained over 2 years of follow - up .
this was despite 11 previous injections of ranibizumab , which failed to control the dme prior to treatment with iluvien .
the functional and structural responses presented herein are consistent with those reported in the fame trials , with rapid and marked responses observed early and being sustained in the long term
. this patient will continue to be monitored to see if the responses reported in controlled clinical trials are replicated with a single injection in real - life uk practice over a 36-month period .
this article does not contain any new studies with human or animal subjects performed by any of the authors .
f. quhill has attended advisory boards and speaker engagements and has been remunerated for these by alimera sciences .
 importancea case showing sustained structural and functional responses 2 years after a single treatment with iluvien ( 0.2 g / day fluocinolone acetonide , fac ) despite suboptimal responses to ranibizumab.observationsa 68-year - old female patient with diabetic macular oedema ( dme ) from type 2 diabetes mellitus was first diagnosed in october 2010 and had a baseline visual acuity ( va ) of 46 early treatment diabetic retinopathy study ( etdrs ) letters in the left eye . 
 central foveal thickness ( cft ) was 712 microns . 
 the patient was treated with 11 intravitreal injections of ranibizumab ( 5 in combination with a small - interfering rna agent ) , and by march 2014 , va and cft were largely unchanged ( 55 etdrs letters and 774 microns ) . 
 the patient was treated with iluvien as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab . 
 an implant releasing fac at a dosage of 0.2 g / day was administered in march 2014 , and the optical coherence tomography indicated that the macula was dry after 7 days ( cft was below 300 microns ) . 
 this was sustained at 6 , 12 , and 24 months after the treatment . 
 va improved by 5 letters within 7 days and by 15 letters within 14 days , and this was maintained after 24 months . throughout the duration of this study , the intraocular pressure was 22 mm hg , and no glaucoma medication was administered.conclusions and relevancein real - life uk practice , this dme patient showed a suboptimal response to multiple intravitreal injections of ranibizumab . when subsequently treated with a single injection of iluvien , there were large and rapid improvements in va and cft that were maintained for the following 2 years . 
Importance
Observations
Conclusions and Relevance
Background
Case Presentation
Conclusion
Statement of Ethics
Disclosure Statement