Table 6.

Dexamethasone and fluocinolone studies

Study	Participants and baseline values	Intervention	Outcome (change from baseline at study end)
Dexamethasone
Callanan et alUSA44 Design: 2-arm RCT Follow-up: 12 months	N: 253 eyes of 253 patients Inclusion criteria: diffuse DMO, CMT ≥275 µm, BCVA ≥34 and ≤70 letters Exclusion criteria: not reported Age: not reported Sex: not reported Diabetes type: not reported HbA1c: not reported Baseline VA: not reported Baseline CMT: not reported Comorbidities: not reported	Group 1 (DIL, n=126 eyes): dexamethasone IV implant followed by laser photocoagulation after 1 month (mean 1.6 implants; 78.6% completion) Group 2 (L, n=127 eyes): laser alone (79.5% completion) Regimen for all groups: if needed, patients were retreated with the dexamethasone implant at months 6 or 9, and with laser at months 4, 7 and 10; mean 2.2 laser treatments per patient Laser protocol not reported	At 12 months BCVA:
				Plus ≥10 letters (%)	p Value
			DIL	28	NS vs L
			L	24
			▸ Patients in DIL group had significantly greater increases in BCVA from baseline than patients in the laser group (p<0.05) at months 1–9 only CMT (OCT): ▸ Patients in DIL group had significantly greater mean reductions from baseline in CMT at months 1 and 6 only (p<0.001)
Haller et al59 USA Multicenter Design: 3-arm RCT Follow-up: 6 months (180 days), primary outcome 3 months (90 days)	N: 171 eyes of 171 patients Inclusion criteria: ≥12 years, DMO persisting for ≥90 days after laser treatment or medical therapy, BCVA by ETDRS between 20/40 (67 letters) and 20/200 (35 letters) due to clinically detectable DMO; analysis includes only eyes with DMO associated with DR Exclusion criteria: history of vitrectomy in the study eye; use of systemic, periocular, or intraocular steroids within 30 days of enrolment; moderate or severe glaucoma in the study eye; poorly controlled hypertension (SP >160 mm Hg or DP >90 mm Hg); poorly controlled diabetes (HbA1c >13%) Age: 62.9–63.8 years SD10.2–12.0 Sex: 45.6–49.1% female Diabetes type: not reported HbA1c: 7.3–7.6% Baseline VA: letter score 54.4–54.7 SD9.96–11.88 Baseline CMT: 417.5–446.5 µm SD123.7–155.9 Comorbidities: 19–21% prior cataract extraction	Group 1 (DDS350, n=57 eyes): 350 µg dexamethasone IV drug delivery system, implanted into the vitreous cavity Group 2 (DDS700, n=57 eyes): 700 µg dexamethasone IV drug delivery system, implanted into the vitreous cavity Group 3 (C, n=57 eyes): no treatment Regimen for all groups: eyes demonstrating a VA loss of ≥5 letters could be treated with any other therapy (including laser photocoagulation and IV triamcinolone) (n=4 with photocoagulation or IV triamcinolone in the C group, n=2 in the DDS350 group, none in the DDS700 group)	At 90 days BCVA (ETDRS):
				Plus ≥10 letters	p Value
			DDS350	21% (graph)	NS vs C
			DDS700	33%	0.007 vs C
			C	12%
			CMT (OCT):
				CMT (µm)	p Value
			DDS350	−42.57 SD95.96	NS (p=0.07) vs C
			DDS700	−132.27 SD160.86	<0.001 vs C
			C	+30.21 SD82.12
			At 180 days BCVA (ETDRS):
				Plus ≥10 letters	p Value
			DDS350	20% (graph)	NS vs C
			DDS700	33% (graph)	NS vs C
			C	23% (graph)
Fluocinolone
FAME Study (Campochiaro et al/Campochiaro et al)29 60 Multicenter international Design: 3-arm placebo-controlled RCT Follow-up: 24 months; abstract with 36 month outcomes	N: 956 eyes of 956 patients Inclusion criteria: DMO, CMT ≥250 µm despite at least 1 prior focal/grid macular laser photocoagulation treatment, BCVA ETDRS letter score between 19 and 68 (20/50–20/400) Exclusion criteria: glaucoma, ocular hypertension, IOP >21 mm Hg, taking IOP lowering drops; laser treatment for DMO within 12 weeks of screening, any ocular surgery in the study eye within 12 weeks of screening; ocular or systemic steroid therapy; active ocular infection; pregnancy Age: 62.5 SD9.4 years Sex: 40.6% Diabetes type: 6.6% type 1 DM, 92% type 2 DM, 1.4% uncertain HbA1c: 7.8 SD1.59% Baseline VA: ETDRS letter score 53.4 SD12.23 Baseline CMT: 469.0 SD164.78 µm Comorbidities: 47.1% cataract at baseline, 62.7–67.4% phakic	Group 1 (0.5, n=375 eyes): intravitreal insert releasing 0.2 µg/day fluocinolone acetonide (FA) (2, 3, or 4 treatments received by 21.3, 1.9 and 0.3%) Group 2 (SRFA0.5, n=393 eyes): intravitreal insert releasing 0.5 µg/day fluocinolone acetonide (2, 3, or 4 treatments received by 22.6, 2.5 and 0.3%) Group 3 (C, n=185 eyes): sham injection (2, 3, or 4 treatments received by 19.5, 2.7 and 1.6%) Regimen for all groups: patients could receive rescue focal/grid laser therapy any time after the first 6 weeks for persistent oedema (35.2–36.7% in FA groups, 58.9% control group, p<0.001); treatments were allowed every 3 months for persistent or recurrent oedema; patients eligible for another FA insert at 1 year if ≥5 letter reduction in BCVA or >50 µm CMT increase from best status	At 24 months BCVA (ETDRS):
				BCVA (letters)	p Value
			SRFA0.2	+4.4	0.02 vs C
			SRFA0.5	+5.4	0.017 vs C
			C	+1.7
				Plus ≥15 letters (%)	p Value
			SRFA0.2	29	0.002 SRFA vs C
			SRFA0.5	29
			C	16
			Subgroups: ▸ BCVA benefits only in pseudophakic eyes (cataract surgery before or during the study), in phakic eyes, BCVA letter score was reduced by 5 (high dose) and 9 (low dose) from baseline at 24 months CMT (optical coherence tomography):
				CMT (µm)	p Value
			SRFA0.2	−167.8	0.005 vs C
			SRFA0.5	−177.1	<0.001 vs C
			C	−111.3
			▸ effect maintained at 36 months At 36 months
				Plus ≥15 letters	p Value
			SRFA0.2/0.5	28.7%	0.018 SRFA vs C
			C	18.9%
Pearson et al43 USA Multicenter Design: 2-arm RCT Follow-up: 36 months	N: 196 patients Inclusion criteria: persistent or recurrent unilateral or bilateral DMO with retinal thickening involving fixation of ≥1 disc area in size, ETDRS visual acuity of ≥20 letters (20/400) to ≤68 letters (20/50) and ≥1 macular laser treatment in the study eye more than 12 weeks prior to enrolment Exclusion criteria: Ocular surgery within 3 months prior to enrolment, uncontrolled IOP within the past 12 months while on ≥1 antiglaucoma medication, IOP of ≥22 mm Hg at screening while on ≥1 antiglaucoma medication, peripheral retinal detachment in the area of implantation or media opacity precluding diagnosis of status in the study eye Age: 61.4–62.7 years Sex: 41.7–42% female Diabetes type: 62.3–70% on insulin HbA1c: not reported Baseline VA: not reported Baseline CMT: not reported Comorbidities: not reported	Group 1 (SRFA, n=127): 0.5 mg sustained release fluocinolone acetonide intravitreal implant Group 2 (SOC, n=69): standard of care—either repeat laser or observation Laser ETDRS protocol	At 3 years BCVA:
				Gain ≥15 letters	p Value
			SRFA	31%	NS
			SOC	20%
				Loss ≥15 letters
			SRFA	17%	NS
			SOC	14%
			CMT:
				Mean change in baseline CMT	p Value
			SRFA	−86	NS
			SOC	−110

BCVA, best corrected visual acuity; C, control; CMT, central macular thickness; CSME, clinically significant macular oedema; DDS, dexamethasone; DIL, dexamethasone followed by laser; DM, diabetes mellitus; DMO, diabetic macular oedema; DP, diastolic pressure; DR, diabetic retinopathy; HR QoL, health-related quality of life; IOP, intraocular pressure; IV, intravitreal; IVB, intravitreal bevacizumab; IVP, intravitreal pegaptanib; IVR, intravitreal ranibizumab; IVT, intravitreal triamcinolone; IVTL, intravitreal triamcinolone plus laser; IVVTE, intravitreal VEGF Trap Eye; L, laser; MLT/MPC, macular laser therapy/macular photocoagulation; NEI VFQ-25, National Eye Institute Visual Function Questionnaire-25; NPDR, non-proliferative diabetic retinopathy; NR, not reported; OCT, optical coherence tomography; PDR, proliferative diabetic retinopathy; PRP, panretinal photocoagulation; RCT, randomised controlled trial; SOC, standard of care; SP, systolic pressure; SRFA, fluocinolone; VA, visual acuity; VEGF, vascular endothelia growth factor.