Effectiveness of 190 µg Fluocinolone Acetonide and 700 µg Dexamethasone Intravitreal Implants in Diabetic Macular Edema Using the Area-Under-the-Curve Method: The CONSTANT Analysis

Figures & data

Table 1 Baseline Characteristics of Patients in the FAME and MEAD Trials (Full DME Group)

	FAME		MEAD
	Sham Control	FAc 0.2 µg/Day	Sham Control	DEX 700 µg
Participants, n	185	375	350	351
Age, years, mean (SD)	61.9 (9.6)	63.0 (9.3)	62.5 (9.5)	62.5 (9.2)
Male, %	58.4	57.3	62.0	60.7
Duration of diabetes, years, mean (SD)	16.4 (8.5)	17.1 (9.4)	15.9 (9.1)	16.5 (9.0)
HbA1c, %, mean (SD)	7.8 (1.7)	7.8 (1.6)	7.5 (1.1)	7.6 (1.2)
Lens status, % phakic/% pseudophakic	65.4/34.6	62.7/37.3	71.1/28.9	75.5/24.5
Mean ETDRS letter score (SD)	54.7 (11.3)	53.3 (12.7)	56.9 (8.7)	56.1 (9.9)
Mean CRT (SD), µm	451.3 (152.0)	461.1 (160.1)	460.9 (132.6)	463.0 (157.1)
Prior therapies, n (%)
Laser	185 (100.0)	375 (100.0)	243 (69.4)	231 (65.8)
Intravitreal corticosteroid	28 (15.2)^a	63 (16.8)^a	61 (17.4)	58 (16.5)
Anti-VEGF	10 (5.4)^a	26 (6.9)^a	26 (7.4)	25 (7.1)
None	0 (0.0)	0 (0.0)	89 (25.4)	104 (29.6)

Notes: The MEAD trial reported the efficacy and safety outcomes from a total of 1048 patients with DME and the FAME trials reported outcomes from a total of 956 subjects. ^aTime since last intravitreal injection was ≥1 year to injection of the FAc implant.

Abbreviations: Anti-VEGF, anti-vascular endothelial growth factor; CRT, central retinal thickness; DEX, dexamethasone; DME, diabetic macular edema; ETDRS, Early Treatment Diabetic Retinopathy Study; FAc, fluocinolone acetonide; FAME, Fluocinolone Acetonide for Macular Edema; HbA1c, glycated hemoglobin; SD, standard deviation.

Table 2 Baseline Characteristics of Patients with Persistent or Recurrent DME in the FAME and MEAD Trials

	FAME		MEAD
	Sham Control	FAc 0.2 µg/Day	Sham Control	DEX 700 µg
Participants, n	112	209	261	247
Age, years, mean (SD)	62.9 (9.4)	63.7 (8.9)	63.0 (9.1)	63.0 (8.3)
Male, %	60.7	57.4	64.4	60.7
Duration of diabetes, years, mean (SD)	17.9 (8.3)	18.3 (9.4)	16.2 (9.7)	16.4 (8.7)
HbA1c, %, mean (SD)	7.7 (1.5)	7.8 (1.6)	7.5 (1.0)	7.5 (1.1)
Lens status, % phakic/% pseudophakic	58.9/41.1	54.5/45.5	68.6/31.4	73.7/26.3
Mean ETDRS letter score (SD)	54.0 (11.2)	52.2 (13.4)	56.1 (9.1)	55.2 (9.6)
Mean CRT (SD), µm	461.8 (153.5)	456.2 (165.9)	472.0 (131.0)	478.0 (153.0)
Prior therapies, n (%)
Laser	112 (100.0)	209 (100.0)	243 (93.1)	231 (93.5)
Intravitreal corticosteroid	19 (17.0)^a	39 (18.7)^a	61 (23.4)	58 (23.5)
Anti-VEGF	6 (5.4)^a	19 (9.1)^a	26 (10.0)	25 (10.1)
None	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

Notes: The MEAD trials reported the efficacy and safety outcomes from a total of 1048 patients with DME and the FAME trials reported outcomes from a total of 956 subjects. ^aTime since last intravitreal injection was ≥1 year to injection of the FAc implant.

Abbreviations: CRT, central retinal thickness; DEX, dexamethasone; ETDRS, Early Treatment Diabetic Retinopathy Study; FAc, fluocinolone acetonide; FAME, Fluocinolone Acetonide for Macular Edema; HbA1c, glycated hemoglobin; SD, standard deviation.

Figure 1 Effect of treatment with FAc (A) and DEX (B) versus sham on BCVA over 36 months in the FAME and MEAD clinical trials.

Abbreviations: BCVA, best-corrected visual acuity; DEX, dexamethasone; ETDRS, Early Treatment Diabetic Retinopathy Study; FAc, fluocinolone acetonide; FAME, Fluocinolone Acetonide for Macular Edema.

Table 3 Mean Visual Acuity Outcomes Based on AUC Calculations in the FAME and MEAD Trials

	Full DME				Persistent or Recurrent DME
	Sham-DEX (n=350)	DEX 700 µg (n=351)	Sham-FAc (n=185)	FAc 0.2 µg/Day (n=375)	Sham-DEX (n=261)	DEX 700 µg (n=247)	Sham-FAc (n=112)	FAc 0.2 µg/Day (n=209)
Mean AUC (SD)	2.0 (7.98)	3.5 (8.43)	1.61 (10.29)	5.17 (11.88)	1.5 (7.5)	3.2 (8.7)	1.87 (9.62)	6.92 (11.95)
Mean AUC difference between treatment and sham (95% CI; p-value)		1.4 (0.2–2.6; p=0.023)		4.5 (2.4–6.5; p<0.001)		1.6 (non-reported; p=0.024)		5.3 (2.7–7.9; p<0.001)
Mean AUC difference between FAc 0.2 µg/day and DEX 700 µg (95% CI; p-value)				1.67 (0.17–3.17; p=0.029)				3.42 (1.56–5.28; p<0.001)

Abbreviations: AUC, area-under-the-curve; CI, confidence interval; DEX, dexamethasone; DME, diabetic macular edema; FAc, fluocinolone acetonide; FAME, Fluocinolone Acetonide for Macular Edema; SD, standard deviation.

Figure 2 Comparison of AUC in FAME (FAc) and MEAD (DEX) subgroups.

Abbreviations: AUC, area-under-the-curve; BCVA, best-corrected visual acuity; DEX, dexamethasone; DME, diabetic macular edema; FAc, fluocinolone acetonide; FAME, Fluocinolone Acetonide for Macular Edema.

Figure 3 Difference between percentage of actively treated and sham control patients experiencing adverse events. The MEAD trial reported the efficacy and safety outcomes from a total of 1048 patients with DME, and the FAME trial reported outcomes from a total of 956 subjects. Data from Hall J. Hall. Correspondence. Retina. 2017;37(3):e34–e37.²¹

Note: *Requiring IOP-lowering drops.

Abbreviations: AE, adverse event; DME, diabetic macular edema; FAME, Fluocinolone Acetonide for Macular Edema; IOP, intraocular pressure.

Hall J. Correspondence. Retina. 2017;37(3):e34–e37. doi:10.1097/IAE.0000000000001547

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