Fluocinolone acetonide intravitreal implant for the treatment of diabetic macular edema

Figures & data

Table 1 Comparison of changes in BCVA among laser and anti-VEGF studies

	Photocoagulation	Ranibizumab		Bevacizumab		Aflibercept
	DRCR.net^Citation22 n = 272 2 years	READ2^Citation38 n = 37 2 years	RESTORE^Citation16 n = 115 1 year	BOLT^Citation40 n = 37 2 years	PACORES^Citation41 n = 141 2 years	DA VINCI^Citation42 n = 45 1 year
Visual acuity
≥3 line improvement	20%	24.0%	23.0%	32.0%	–	42.2%
≥2 line improvement	34%	–	37.0%	49.0%	53%	62.0%
≥2 line loss	19%	–	4%	–	4%	–
≥3 line loss	13%	–	<1%	0.0%	–	0%
Mean letter improvement	2	7.7	6.1	8.6	11.8	12.0

Abbreviations: BCVA, best-corrected visual acuity; VEGF, vascular endothelial growth factor.

Table 2 Endpoints and results among fluocinolone device studies for the treatment of diabetic macular edema

Author	Eyes	Endpoints	Results
FAc implant
Bausch and Lomb^Citation55	80 eyes (1:1 to 0.5 mg FAc or SOC)	Retinal thickening after 6 mo	FAc significantly better (P = 0.03)
		Improvement in severity of DR after 6 mo	FAc significantly better (P = 0.01)
		Improvement or stable VA after 6 mo	80% in treatment group vs 50% in SOC (P < 0.01)
Pearson et al^Citation57	197 eyes (2:1 to 0.59 mg FAc or SOC)	Visual acuity gain of ≥three lines	28% in FAc vs 15% in SOC at 3 yrs (P < 0.05)
		Visual acuity loss of ≥three lines	19% in FAc vs 16% in SOC at 3 yrs (NS)
		Resolution of edema at center of macula	58% in FAc vs 30% SOC at 3 yrs (P < 0.001)
		Improvement in diabetic retinopathy scores	13% in FAc vs 4% SOC at 3 yrs (P < 0.001)
Pearson et al^Citation56	196 eyes (2:1 0.59 mg FAc or SOC)	Visual acuity gain of ≥15 letters	FAc significantly better until 1 yr
		Improvement in macular edema	FAc significantly better until 2 yrs
		ETDRS diabetic retinopathy severity scale	FAc improved faster, declined slower
		Leakage by FA	FAc significantly better until 2 yrs
		Maximum cystoid score	FAc significantly better until 1 yr
FAc insert
Campochiaro et al^Citation58	37 eyes (2:1 0.2 μg/day, 0.59 μg/day)	Change in BCVA at month 12	1.3 letters (low dose), 5.7 letters (high dose)
Campochiaro et al^Citation60	956 eyes (2:2:1 0.2 μg/day, 0.5 μg/day, or sham)	≥15-letter increase in VA	FAc group better through 3 years
		Mean improvement VA from baseline	FAc groups better through 3 years
		Decreased retinal thickness	FAc groups better through 2 years

Abbreviations: BCVA, best-corrected visual acuity; DR, diabetic retinopathy; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, fluorescein angiography; FAc, fluocinolone acetonide; SOC, standard of care; VA, visual acuity; NS, not significant.

Figure 1 Percentage of eyes achieving ≥15 letter gain in BCVA during follow-up between intravitreal fluocinolone acetonide devices.

Abbreviations: BCVA, best-corrected visual acuity; FAc, fluocinolone acetonide.

Table 3 Visual acuity, macular thickness, and adverse events among different steroid treatment options for diabetic macular edema

	Triamcinolone (2-year follow-up)		Dexamethasone (6-month follow-up)†		FAc implant (3-year follow-up)‡	FAc insert (3-year follow-up)
	DRCR.net^Citation22		Haller et^Citation28,Citation29		Pearson et al^Citation56	Campochiaro et al^Citation60
	1 mg (n = 256)	4 mg (n = 254)	350 μg (n = 103)	700 μg (n = 105)	0.59 mg (n = 127)	0.2 μg (n = 375)	0.5 μg (n = 393)
Visual acuity
≥15 letter improvement	15%	16%	15%	18%	31%	33%	32%
≥15 letter loss	21%	21%	NR	NR	17%*	NR	NR
Macular thickness
Baseline mean foveal thickness (μm)	405	396	446	428	419	451	461
Follow-up mean foveal thickness (μm)	319	319	403	296	309*	280	300
Mean change in foveal thickness (μm)	86	77	43	132	110*	171	161
Ocular adverse events
Cataract surgery, phakic eyes	23%	51%	NR	NR	91%	80%	87%
Increased IOP ≥ 10 mmHg from baseline	16%	33%	15%	15%	NR	NR	NR
IOP ≥ 30 mmHg	9%	21%	NR	NR	61%	NR	NR
Initiation of IOP-lowering meds	12%	30%	NR	NR	NR	38%	47%
Glaucoma surgery	0%	1%	0%	0%	33%	6%	11%
Hypotony (IOP ≤ 7 mmHg)	NR	NR	NR	NR	22%	NR	NR
Endophthalmitis	0%	0%	0%	0%	NR	NR	NR

Notes:

† Macular thickness measured at 3 months;

‡ adverse events reported after 4 years of follow-up;

* estimated from published figures.

Abbreviations: FAc, fluocinolone acetonide; IOP, intraocular pressure; NR, not reported.

Table 4 Advantages and disadvantages of different therapies for diabetic macular edema

	Advantages	Disadvantages
Photocoagulation	Low risk of complications	Many patients do not respond
	Well-studied
	Inexpensive
Triamcinolone	Efficacy well-established	Many patients do not respond
	Inexpensive	High rate of cataract progression
		High rate of increased IOP
		Regular injections and follow-up
Dexamethasone	Decreased follow-up	High rate of cataract progression
		High rate of increase IOP
		Not well-studied in DME
Anti-VEGF therapy	Very strong efficacy	Regular injections and follow-up
	Most patients responsive
	Well-studied
Vitrectomy	Effective in patients with poor VA	Efficacy not well-established
		Requires procedure in operating room
FAc implant	Strong efficacy	Very high rate of cataract progression
	Decreased follow-up	High rate of increased IOP
		Increased risk for IOP-lowering surgery
		Requires procedure in the operating room
FAc insert	Strong efficacy	Very high rate of cataract progression
	Decreased follow-up	High rate of increased IOP
		Increased risk for IOP-lowering surgery

Abbreviations: DME, diabetic macular edema; FAc, fluocinolone acetonide; IOP, intraocular pressure; VA, visual acuity; VEGF, vascular endothelial growth factor.

Diabetic Retinopathy Clinical Research Network A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema Ophthalmology 2008 115 9 1447 1449 18662829

 PubMed Web of Science ®Google Scholar

Nguyen QD Shah SM Khwaja AA READ-2 Study Group Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study Ophthalmology 2010 117 11 2146 2151 20855114

 PubMed Web of Science ®Google Scholar

Mitchell P Bandello F Schmidt-Erfurth U RESTORE study group The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema Ophthalmology 2011 118 4 615 625 21459215

 PubMed Web of Science ®Google Scholar

Rajendram R Fraser-Bell S Kaines A A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3 Arch Ophthalmol 2012 130 8 972 979 22491395

 PubMed Web of Science ®Google Scholar

Arevalo JF Lasave AF Wu L Pan-American Collaborative Retina Study Group (PACORES) Intravitreal bevacizumab plus grid laser photocoagulation or intravitreal bevacizumab or grid laser photocoagulation for diffuse diabetic macular edema: results of the Pan-American Collaborative Retina Study Group at 24 Months Retina 2013 33 2 403 413 23222389

 PubMed Web of Science ®Google Scholar

Do DV Nguyen QD Boyer D DA VINCI Study Group One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema Ophthalmology 2012 119 8 1658 1665 22537617

 PubMed Web of Science ®Google Scholar

Fluocinolone acetonide ophthalmic–Bausch and Lomb: fluocinolone actinide Envision TD implant Drugs R D 2005 6 2 116 119 15777105

 PubMedGoogle Scholar

Pearson PA Levy B Comstock T Fluocinolone Acetonide Implant Study Group Fluocinolone acetonide intravitreal implant to treat diabetic macular edema: a 3–year results of a multi–center clinical trial Invest Ophthalmol Vis Sci 2006 47 E-Abstract 5442

 Google Scholar

Pearson PA Comstock TL Ip M Fluocinolone acetonide intravitreal implant for diabetic macular edema: a 3-year multicenter, randomized, controlled clinical trial Ophthalmology 2011 118 8 1580 1587 21813090

 PubMed Web of Science ®Google Scholar

Campochiaro PA Hafiz G Shah SM Famous Study Group Sustained ocular delivery of fluocinolone acetonide by an intravitreal insert Ophthalmology 2010 117 7 1393 1399 20202684

 PubMed Web of Science ®Google Scholar

Campochiaro PA Brown DM Pearson A FAME Study Group Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema Ophthalmology 2012 119 10 2125 2132 22727177

 PubMed Web of Science ®Google Scholar

Kuppermann BD Blumenkranz MS Haller JA Dexamethasone DDS Phase II Study Group Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema Arch Ophthalmol 2007 125 3 309 317 17353400

 PubMed Web of Science ®Google Scholar

Haller JA Kuppermann BD Blumenkranz MS Dexamethasone DDS Phase II Study Group Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema Arch Ophthalmol 2010 128 3 289 296 20212197

 PubMed Web of Science ®Google Scholar