Intravitreal Fluocinolone Acetonide Implant (ILUVIEN^®) for the Treatment of Retinal Conditions. A Review of Clinical Studies

Figures & data

Table 1 Summary of Most Important Studies of ILUVIEN and DMO

Study	Design	Number of Subjects	Number of Eyes	Follow Up	Key Results
Diabetic macular oedema
ICE UK Study^Citation22	A retrospective, observational cohort study involving 13 ophthalmology centers.	208	233: 207 pseudophakic and 26 phakic	12 months	1. Median (interquartile range, IQR) VA was 0.66 (0.48–1.00) LogMAR units (equivalent to 52.0 ETDRS letters) at implant, improving to 0.60 (0.38–0.90) LogMAR units (55.0 letters) at 12 months post-implant (p < 0.001). 2. In total, 44%, 30%, and 18% of people achieved an improvement in ETDRS score of ≥5, ≥10, and ≥15 letters, respectively, over the same period. Adverse effects: 1. A small but significant (p <.001) increase in median IOP was observed (median = 15.0, IQR = 13.0–18.0 mmHg at implant to 18.0, 15.0–21.0 mmHg at 12 months). 2. In the 12 months following implant, additional IOP-lowering therapy was prescribed in 15% of subjects previously not requiring such therapy.
El-Ghrably et al^Citation23	Prospective, observational, multicentre study.	57	57: 44 pseudophakic and 13 phakic. (Phakic eyes received the FAc implant following phacoemulsification).	12 months	1. Mean change from baseline CMT (452 μm) was −102 μm at month 3, −117 μm at month 6, and −126 μm at month 12. 2. The mean increase in BCVA from baseline (52.7 ETDRS letters) was 5.8 letters after 3 months, 6.7 letters at month 6, and 5.1 letters at month 12 Adverse effects: 1. 7/22 eyes lost VA, 3 lost ≥10 EDTRS letters and 2 lost ≥15 letters. Reasons for loss of VA were not provided but could have included lack of response to therapy, progression of disease state, or poor diabetic control. 2. 6 patients were on IOP-lowering medications from month 3 onwards, but none required glaucoma surgery.
FAME Studies^Citation14,Citation15	Two parallel, prospective, randomised, sham injection-controlled, double-masked, multicentre clinical trials.	Sham, n = 185	Sham, n = 185	36 months	1. Visual gain of >15 ETDRS letters by 24 months in 0.5ug group. 2. BCVA letter score gain at 24 months: Sham: 1.7; 0.2 μg: 4.4; 0.5 μg: 5.43. Adverse effects: 1. Glaucoma surgery required: Sham: 0.5%; 0.2 µg: 3.7%; 0.5 μg: 7.6%.
		0.2 µg/day, n = 375	0.2 µg/day, n = 375
		0.5 µg/day, n = 393	0.5 µg/day, n = 393
IRISS^Citation60	Prospective, observational, multicentre study.	563	593	36 months	1. 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. 2. 69% of eyes did not require additional DMO treatments. 3. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation.
Medisoft Audit Group^Citation25	Retrospective review of 14 clinical centres in the UK using electronic pseudo-anonymised medical record system.	305 patients	345	24 months	1. At 24 months, mean best-recorded visual acuity increased from 51.9 to 57.2 letters and 20.8% achieved ≥15-letter improvement. 2. Mean CSFT reduced from 451.2 to 355.5 μm. Adverse effects: 1. Overall, 13.9% of patients required IOP-lowering drops (included initiation, addition and switching of current drops), 7.2% had IOP elevation >30 mm Hg and 0.3% required glaucoma surgery.
Panos et al^Citation33	Single-centre retrospective analysis.	24 (Approx 75% of patients were black or South Asian ethnicity).	24	36 months	1. Improvement in mean best corrected visual acuity was seen at year 1 and year 3 improving from 0.62 LogMAR at baseline to 0.55 LogMAR at year 1 and 0.47 LogMAR at year 3 (all p > 0.05). 2. Mean central retinal thickness also showed a progressive reduction from 471 μm at baseline to 397 μm at year 1 and 339 μm at year 3 (all p < 0.05). Adverse effects: 1. Four eyes required intraocular pressure-lowering drops post-implant. 2. Supplementary treatment for persistent or recurrent diabetic macular oedema was necessary in 13 eyes over the total study period of 3 years. 3. Blacks, Asians and minority ethnic patients had a worse response compared with white patients.
Paladin Study^Citation34	Phase 4, nonrandomised, open-label observational, prospective study.	159	202	36months	1. mean central subfield thickness change of −60.69 mm (P < 0.0001) 2. mean BCVA change of +3.61 letters (P <0.0222) 3. treatment burden reduction of 70.5% 4. 25.53% of eyes remained rescue free Adverse effects: 1. IOP > 30mmHg occurred in 10.89% of eyes. 2. surgical rate of 1.49% attributable to steroid use

Table 2 Summary of Most Important Studies of ILUVIEN and NIPU

Study	Design	Number of Patients	Number of Eyes	Follow Up	Key Results
Non-infectious uveitis
Jaffe and Pavesio on behalf of the Study Investigators^Citation41	Phase 3, prospective, double-masked, multicenter study. 33 clinical centres.	129	129	36 months	1. Recurrence rate 65.5% Fac vs 97.6% Sham 2. Median period (days) without recurrence 657.0 Fac vs 70.5 Sham. 3. Mean recurrence episodes 1.7 Fac vs 5.3 Sham 4. Adjunctive therapy 57.5% Fac vs 97.6% Sham Adverse effects: 1.IOP (mmHg) mean ± standard deviation 14.5 ± 5.1 Fac vs 14.8 ± 5.3 Sham. 2. IOP-lowering surgery 5.7% Fac vs 11.9% Sham 3. Cataract surgery 73.8% Fac vs 23.8% Sham
Jaffe et al^Citation38	Ranomised controlled trial	11	11	24 months	1) Mean study eye visual acuity improved from +0.56 to +0.25 and +0.17 logMAR at 12 and 24 months after implantation, respectively (P = 0.041 and P = 0.016). 2) The average number of inflammation recurrences in the 12 months before implantation was 1.54 episodes per eye. None of the study eyes experienced a recurrence during the follow-up period. 3) Five of 11 eyes received an average of 1.6 posterior sub-Tenon triamcinolone acetonide (PSTA) injections in the 12 months preceding implantation. None required a PSTA injection after FAc implantation.
Weber et al^Citation40	Retrospective observational clinical study	8	11	42 months	1. The mean maximum decrease of central retinal thickness throughout the follow-up period was 168 ± 202 μm (± standard deviation). 2. Nine out of 11 eyes showed an improvement in corrected distance visual acuity (between + 1 and + 8 lines). 3. Intraocular pressure increases did not require additional treatment and no major ophthalmic complications occurred. Adverse effects: 1. Both phakic eyes required cataract surgery.
Parvesio and Heinz,^Citation39	Prospective, randomised, double-masked, multicentre comparison.	87	87	36 months	1. Over 36 months, more FAc treated than fellow eyes remained recurrence-free (28.8% vs 5.1%, P = 0.001; mean 1.9 vs 4.7 recurrences, respectively, P < 0.0001). 2. FAc-treated eyes gained +9.6 letters BCVA, versus a loss of −4.4 in fellow eyes (P < 0.0001). 3. Intra/periocular adjunctive injections were lower in FAc-treated than fellow eyes (20.3% vs 66.1%, P < 0.0001). 4. Topical corticosteroid use was also lower in FAc-treated than fellow eyes (27.1% vs 52.5%, P = 0.0041). Adverse effects: 1. Cataract surgery occurred in 72.0% of FAi-treated and 37.0% of fellow eyes.
Pockar et al^Citation43	A retrospective observational clinical study.	-	11	12 months	1. Mean central retinal thickness (CRT) at baseline was 435 μm ± 176, improving to 296 μm ± 67 at 12 months. 2. The mean best corrected visual acuity (BCVA) was stable at 12 months. 3. There were no observed recurrences of uveitis. Adverse effects: 1. Two eyes received adjunctive treatment for worsening CRT.
Battista et al^Citation44	Retrospective observational study	7	10	12 months	1. The area under the curve for BCVA significantly improved from month 6 (p = 0.03). 2. The CMT improved from month 1 and was persistently lower than baseline until month 12 (p < 0.001). 3. No adverse events were recorded over 1 year.
Hikal et al^Citation42	Retrospective chart review.	26	34 (30 pseudophakic and 4 phakic)	18 months	1. Macular oedema was completely resolved in 24 (70.6%) cases treated with FAc. 2. In 20 eyes (58.5%), visual acuity (VA) improved (from +1 to +5 lines) and remained stable in 9 eyes (26.5%). Adverse effects: 1. Five of the treated eyes had a relapse after 23.2 ± 14 months. Three FAc reinjections were performed and a drying of the macula was observed. 2. Three of these eyes had a cataract prior to therapy and the other developed a cataract 2.5 years after the FAc implant was administered
Buhl et al^Citation45	Retrospective cohort study	57	76	12 months	1. BCVA remained stable 2. CRT reduction (362.7 vs 309.1 μm; p = 0.04) 3. Reduced intraocular inflammation (0.82 vs 0.3; p = 0.007) Adverse effects: 1. IOP increase (13.68 vs 15.6; p = 0.0507) 2. cataract development (20% of phakic eyes)

Table 3 Summary of Most Important Studies of ILUVIEN and RVO & Irvine – Gass Syndrome

Study	Design	Number of Subjects	Number of Eyes	Follow Up	Key Results
Retinal vein occlusion
Coelho et al^Citation49	Case report	1	2 (1 was treated with FAc and 1 was used as a control)	12 months	1. BCVA improved from 20/100 to 20/25. 2. Central foveal thickness decreased from 578 μm to 393 μm. 3. IOP maintained normal, controlled by medication.
Ribeiro et al^Citation50	Prospective international review	2 (1 patient had branch retinal vein occlusion and 1 patient had ischaemic central retinal vein occlusion).	2	12 months	1. The patient with BRVO improved BCVA from counting fingers to 38 letters and central retinal thickness also improved from 616µm to 198µm. 2. The patient with the ischemic CRVO had BCVA improve from 29 to 38 letters. She also had a CRT improve from 664 µm to 271µm
Miguel-Escuder et al^Citation52	Case series	4	4	Variable	1. Complete resolution of the CMO (related to Irvine – Gass syndrome) in 3 of the 4 cases 2. One case required an additional Ozurdex implant 3. Two cases developed ocular hypertension and required drops.
Chronopoulos et al^Citation53	Retrospective study	16	16	24 months	1. At month 12, BCVA improved in 11 eyes, stabilised in 4 eyes, and decreased in 1 eye. 2. At month 24, BCVA remained improved in 5 eyes, remained stable in 5 eyes, and decreased in 1 eye 3. At 12 months, CRT improved in 13 eyes and remained unchanged in 2 eyes 4. At 24 months, CRT improved further in 8 eyes, and remained stable in 3 eyes Adverse events 1. IOP > 21mmHg in only 4 eyes, all treated successfully with drops.

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