Table 7

Triamcinolone studies

Study	Participants and baseline values	Intervention	Outcome (change from baseline at study end)
DRCR Network 2008 (Ip et al/Beck et al/Bressler et al)22 61 63 64 USA Multicenter Design: 3-arm RCT Follow-up: 2 years, additional 3 year follow-up	N: 840 eyes of 693 patients Inclusion criteria: >18 years, type 1 or 2 DM, study eye: (1) BCVA (E-ETDRS) between 24 and 73 (20/320 and 20/40), (2) retinal thickening due to DMO involving the center of the macula main cause for visual loss, (3) CMT ≥250 µm, (4) no expectation of scatter photocoagulation within 4 months Exclusion criteria: any prior treatment with IV corticosteroids, peribulbar steroid injection within prior 6 months, photocoagulation for DMO within prior 15 weeks, panretinal scatter photocoagulation within prior 4 months, pars plana vitrectomy, history of open-angle glaucoma or steroid-induced IOP elevation requiring IOP-lowering treatment, and IOP ≥25 mm Hg Age: 63 SD9 years Sex: 49% female Diabetes type: 95% type 2 DM, 5% type 1 DM HbA1c: 7.9 SD1.8% Baseline VA: ETDRS letter score 59 SD11 (∼20/63) Baseline CMT: 24 SD130 µm Comorbidities: 21% pseudophakic, 2% ocular hypertension, 7% mild NPDR, 13% moderate NPDR, 40% moderately severe NPDR, 11% severe NPDR, 23.5% mild to moderate, 3% high risk PDR	Group 1 (IVT1, n=256 eyes): 1 mg IV triamcinolone (3.5 treatments) Group 2 (IVT4, n=254 eyes): 4 mg IV triamcinolone (3.1 treatments) Group 3 (L, n=330 eyes): focal/grid photocoagulation (2.9 treatments) Regimen for all groups: retreatment protocol: where indicated, retreatment was performed within 4 weeks after the follow-up visit and no sooner than 3.5 months from the time of last treatment; eyes were generally retreated unless: (1) little or no oedema involving the center of the macula present and CMT ≤225 µm, (2) VA letter score ≥79 (20/25 or better), (3) substantial improvement in macular oedema since last treatment (eg, ≥50% decrease in CMT), (4) clinically significant adverse effect from prior treatment, (5) additional treatment deemed futile (<5 letter improvement in VA letter score or lack of CMT reduction) and (6) for laser group, complete focal/grid photocoagulation already given, with no areas identified for which additional treatment was indicated Laser Modified ETDRS protocol as used in prior DRCR.net protocols	At 2 years BCVA (E-ETDRS):
				BCVA (letters)		p Value
			IVT1	−2 SD18		0.02 vs L NS vs IVT4
			IVT4	−3 SD22		0.002 vs L
			L	+1 SD17
				BCVA gain categories
			IVT1	+10 or more: 25% +9 to −9: 50% −10 – more: 26%		0.03 vs L, NS vs IVT4
			IVT4	+10 or more: 28% +9 to −9: 44% −10 or more: 28%		0.01 vs L
			L	+10 or more: 31% +9 to −9: 50% −10 or more: 19%
			Subgroups: ▸ Similar results when considering only pseudophakic eyes or eyes with minimal cataract no substantially different results based on baseline VA, baseline CMT, history of focal/grid photocoagulation for DMO ▸ 3 year results consistent with 2 year results for BCVA and CMT
			CMT (OCT):
				CMT (µm)		p Value
			IVT1	−86 SD167		<0.001 vs L, NS vs IVT4
			IVT4	−77 SD160		<0.001 vs L
			L	−139 SD148
			Progression of retinopathy:
				2 years	3 years	p Value
			IVT1	29%	35%
			IVT4	21%	30%	<0.05 vs L
			L	31%	37%
Gillies et al Sutter et al 32 136–138 Australia Design: 2-arm placebo-controlled RCT Follow-up: 2 years, additional 3-year follow-up	N: 69 eyes of 43 patients Inclusion criteria: patients with persistent (≥3 months after adequate laser treatment) DMO involving the central fovea, BCVA in the affected eye ≤6/9 Exclusion criteria: uncontrolled glaucoma, loss of vision due to other causes, systemic treatment with >5 mg prednisolone (or equivalent) daily, intercurrent severe systemic disease, any condition affecting follow-up or documentation Age: 62.4–69.6 SD9.2–12.5 years Sex: 52% female Diabetes type: not reported HbA1c: 7.63–8.28 SD1.12–1.41 Baseline VA: ETDRS letter score 60.5–61.3 SD11.9–13.2 Baseline CMT: 439–444 SD101–125 µm Comorbidities: 25% pseudophakic	Group 1 (IVT, n=34 eyes): 4 mg (0.1 ml) IV triamcinolone acetonide (mean 2.6 injections over 2 years) Group 2 (C, n=35 eyes): placebo injection (subconjunctival saline injection) (mean 1.8 injections over 2 years) Regimen for all groups: retreatment considered at each visit as long as treatments were at least 6 months apart (retreatment if VA decreased ≥5 letters from previous peak value and persistent CMT >250 µm), if no improvement after 4 weeks, further laser treatment was applied (n=1 laser treatment in intervention group, n=16 in placebo group, p=0.0001) Laser ETDRS protocol	At 2 years BCVA (ETDRS):
				BCVA (letters)		p Value
			IVT	+3.1		0.01 vs C
			C	−2.9
				CVA gain categories
			IVT	+10 or more: 21% +9 to −9: 70% −10 or more: 9%		0.013 vs C
			C	+10 or more: 12% +9 to −9: 62% −10 or more: 25%
			CMT (OCT):
				CMT (µm)		p Value
			IVT	−125		0.009 vs C, difference between groups 59 µm (95% CI 15 to 104)
			C	−75
Gillies et al33 Australia Design: 2-arm RCT Follow-up: 24 months	N: 84 eyes of 54 patients Inclusion criteria: DMO involving the central fovea, CMT ≥250 µm, BCVA 17–70 letters (∼20/40–20/400), laser treatment could be safely delayed for 6 weeks without significant adverse effects Exclusion criteria: uncontrolled glaucoma, controlled glaucoma but with a glaucomatous visual field defect, loss of vision resulting from other causes, systemic treatment with >5 mg prednisolone (or equivalent) daily, retinal laser treatment within 4 months, intraocular surgery within 6 months, concurrent severe systemic disease, any condition affecting follow-up or documentation Age: 65.4–66.9 SD8.9–9.5 years Sex: 38.1–47.6% female Diabetes type: not reported HbA1c: 7.81–8.02 SD1.44–1.63% Baseline VA: letter score 55.2–55.5 SD11.3–12.5 Baseline CMT: 482.1–477.4 SD122.7–155.5 µm Comorbidities: not reported	Group 1 (IVTL, n=42 eyes): 4 mg (0.1 ml) IV triamcinolone acetonide followed by laser treatment (at least 1 retreatment in 2nd year in 69%) Group 2 (L, n=42 eyes): sham injection followed by laser treatment (at least 1 retreatment in 2nd year in 45%) Regimen for all groups: retreatment with injection followed by laser at discretion of chief investigator, with at least 6 weeks between treatments; no retreatment if: (1) investigator considered the macula nearly flat and CMT <300 µm; (2) VA was ≥79 letters (20/25) or VA had improved by ≥5 letters compared with the best VA after treatment or baseline acuity; (3) laser treatment was considered by the investigator as inappropriate or had no potential for improvement	At 24 months BCVA (ETDRS):
				BCVA (letters)		p Value
			ITL	+0.76		NS vs L
			L	−1.49
				BCVA gain categories
			IVTL	+10 or more: 36% +9 to −9: 31% −10 or more: 33%		0.049 vs L
			L	+10 or more: 17% +9 to −9: 59% −10 or more: 24%
			Subgroups: ▸ BCVA outcome not significantly affected by cataract surgery CMT (OCT):
				CMT (µm)	p Value
			IVTL	−137.1		NS vs L
			L	−109.6
Kim et al45 Korea Design: 2-arm RCT Follow-up: 3 years	N: 86 eyes of 75 patients Inclusion criteria: diffuse DMO 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 (IVT, n=38 eyes): 4 mg IV triamcinolone (1.88 additional treatments, completion 68.1%) Group 2 (IVTL, n=48 eyes): macular laser photocoagulation 4 weeks after 4 mg IV triamcinolone (0.92 additional treatments, completion 77.1%) Regimen for all groups: additional treatment possible, criteria not mentioned Laser protocol not reported	At 3 years BCVA: not reported Outcomes related to DMO:
				No DMO recurrence		p Value
			IVT	3.9%
			IVTL	24.3%		0.028 vs IVT
				Time DMO not present
			IVT	10.33 months
			IVTL	19.88 months		0.027 vs IVT
Lam et al34 Hong Kong Design: 3-arm RCT Follow-up: 6 months (2 years planned)	N: 111 eyes of 111 patients Inclusion criteria: >18 years, type 1 or 2 DM, clinically significant DMO (ETDRS), CMT ≥250 µm Exclusion criteria: macular oedema due to causes other than diabetic maculopathy, signs of vitreomacular traction, proliferative diabetic retinopathy, aphakia, history of glaucoma or ocular hypertension, macular ischemia, any laser procedure within 3 months, ocular surgery within 6 months, significant media opacities Age: 64.7–67.2 SD8.2–10.3 years Sex: 42–59% female Diabetes type: not reported HbA1c: not reported Baseline VA: ETDRS logMAR 0.64–0.72 SD0.34–0.36 Baseline CMT: 385–424 SD91–108 µm Comorbidities: 66–84% phakic eyes	Group 1 (IVT, n=38 eyes): 4 mg IV triamcinolone (no retreatments) Group 2 (IVTL, n=36 eyes): 4 mg IV triamcinolone followed by grid laser photocoagulation (ETDRS) (laser treatment once the macular oedema had reduced to <250 µm at the foveal center or at 1 to 2 months after injection, whichever was earlier) Group 3 (L, n=37 eyes): grid laser photocoagulation (n=3 retreatments) (no retreatments) Regimen for all groups: in case of recurrence or persistence of macular oedema, retreatment offered according to study group, at intervals no less than 4 months Laser ETDRS protocol	At 6 months BCVA (ETDRS):
				BCVA improvement		p Value
			IVT	−0.7 SD 10.7 log MAR Plus ≥15 letters: 5%		NS between groups
			IVTL	−1.1 SD 10.8 log MAR Plus ≥15 letters: 3%
			L	−1.6 SD 11.5 log MAR Plus ≥15 letters: 5%
			CMT (OCT):
				CMT (µm)		p Value
			IVT	342 SD124 (−54)		NS between groups, <0.01 vs baseline
			IVTL	307 SD181 (−116)		<0.01 vs baseline
			L	350 SD169 (−35)
Ockrim et al/Sivaprasad et al42 62 UK Design: 2-arm RCT Follow-up: 1 year	N: 88 eyes of 88 patients Inclusion criteria: clinically significant DMO persisting ≥4 months, ≥1 previous laser treatment, BCVA 6/12–3/60, VA in fellow eye ≥3/60, duration visual loss <24 months Exclusion criteria: significant macular ischemia, baseline IO >23 mm Hg, glaucoma, coexistent renal disease, loss of VA due to other causes, previous vitrectomy, intraocular surgery within 3 months of study entry, previous inclusion in other DR trials, inability to return to follow-up, inability to give informed consent Age: 62.3–64.8 SD7.5–10.1 years Sex: 28.9–34.9% female Diabetes type: 97.8–100% type 2 DM HbA1c: 7–7.8 IQR6.5–8.7% Baseline VA: ETDRS letter score 53.0–54.6 SD13.3–14.2 Baseline CMT: 410.4–413.4 SD127.8–134.1 µm Comorbidities: 17.8–19.5% PDR, 13.3–18.6% pseudophakia, 15–17.8% posterior vitreous detachment	Group 1 (IVT, n=43 eyes): 4 mg IV triamcinolone (mean number of IVT injections 1.8 (range 1–3)) Group 2 (L, n=45 eyes): ETDRS laser photocoagulation (mean number of grid laser sessions 2.1 (range 1–3)) Regimen for all groups: patients retreated at 4 and 8 months if they had persistent macular oedema Laser ETDRS protocol	At 12 months BCVA (ETDRS):
				BCVA (letters)		p Value
			IVT	−0.2		NS vs L
			L	+1.7
				Plus ≥15 letters
			IVT	4.8%		NS vs L
			L	12.2%
			CMT (optical coherence tomography):
				CMT (µm)		p Value
			IVT	−91.3		NS vs L
			L	−63.7

BCVA, best corrected visual acuity; C, control; CMT, central macular thickness; CPL, control plus laser; 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; RDL, ranibizumab plus deferred laser; RPL, ranibizumab plus laser; SOC, standard of care; SP, systolic pressure; SRFA, fluocinolone; TPL, triamcinoloine plus laser; VA, visual acuity; VEGF, vascular endothelia growth factor.