13 Clinical Trials Summary
13.0 Introduction
13.1 Cornea
13.2 Cataract
13.3 Medical Retina – Age-Related Macular Degeneration (AMD)
13.4 Medical Retina - Diabetes
13.5 Medical Retina – Retinal Vein Occlusion (RVO)
13.6 Vitreoretinal Surgery
13.7 Glaucoma
13.8 Oculoplastics
13.9 Paediatrics
13.10 Neuro-Ophthalmology
13.11 Ocular Oncology
13.4 Medical Retina - Diabetes
IVB = Bevacizumab, IVR = Ranibizumab, IVA = Aflibercept, IVTA = Triamcinolone
DCCT [xxxiv]
T1DM
Strict BSL control in T1DM reduces development and progression of DR, DMO, need for laser, and nephropathy & neuropathy
Hainsworth, D.P., Bebu, I., Aiello, L.P. et al. 2019. Risk Factors for Retinopathy in Type 1 Diabetes: The DCCT/EDIC Study. Diabetes Care 42(5) 875-882.
UKPDS [xxxv]
T2DM
Strict BSL control in T2DM reduces DR progression and microvascular complications
Tight blood pressure control reduces progression of DR
Kaiser, P.K. 2006. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: 5-year results of two randomized clinical trials with an open-label extension: TAP report no. 8. Graefes Arch Clin Exp Ophthalmol 244(9) 1132-1142
FIELD [xxxvi,xxxvii]
Fenofibrate
Fenofibrate in T2DM reduces need for laser treatment for ALL DR (unrelated to concentration of plasma lipids)
Keech, A., Simes, R.J., Barter, P. et al. 2005. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 366(9500) 1849-1861.
Keech, A.C., Mitchell, P., Summanen, P.A. et al. 2007. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 370(9600) 1687-1697.
ACCORD [xxxviii,xxxix]
T2DM
Intensive BSL and lipid control reduced rate of progression of retinopathy in those with high risk of cardiovascular disease
Intensive BSL control caused more systemic hypoglycaemic episodes
2016. Persistent Effects of Intensive Glycemic Control on Retinopathy in Type 2 Diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On Study. Diabetes Care 39(7) 1089-1100.
Chew, E.Y., Ambrosius, W.T., Davis, M.D. et al. 2010. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 363(3) 233-244.
ETDRS [xl]
Early Treatment Diabetic Retinopathy Study
Macular laser for “CSMO” reduces moderate visual loss
CSMO = 1. DMO within 500 microns of the fovea, 2. Hard exudate within 500 microns of the fovea associated with DMO, 3. Disc area of DMO within disc diameter of the fovea
PRP for high risk PDR; severe NPDR defined (any of: 4 quadrants retinal haemorrhages, 2 quadrants venous beading, 1 IRMA)
PRP can worsen DMO in the short-term
1985. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 103(12) 1796-1806.
DRS [xli]
Diabetic Retinopathy Study
PRP for high risk PDR halves risk of severe VA loss, causes macular oedema
1976. Preliminary report on effects of photocoagulation therapy. The Diabetic Retinopathy Study Research Group. Am J Ophthalmol 81(4) 383-396.
DRVS [xlii]
Diabetic Retinopathy Vitrectomy Study
“Early” (1 - 6 months) vitrectomy useful for severe VH
Abraham, P., Yue, H. and Wilson, L. 2010. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. Am J Ophthalmol 150(3) 315-324.e311.
Protocol I [xliii,xliv]
Focal/grid laser vs IVR + prompt laser vs IVR + deferred laser vs IVTA + prompt laser
IVR + prompt or deferred laser better than focal/grid laser alone
IVTA + prompt laser better than focal/grid laser alone in pseudophakes but causes IOP rise
5 Year results: IVR + prompt laser no better than IVR + deferred laser
Bressler, S.B., Glassman, A.R., Almukhtar, T. et al. 2016. Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema. American Journal of Ophthalmology 164 57-68.
Elman, M.J., Ayala, A., Bressler, N.M. et al. 2015. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment: 5-Year Randomized Trial Results. Ophthalmology (Rochester, Minn) 122(2) 375-381.
Protocol T [xlv]
IVR vs IVA vs IVB
IVR = IVA = IVB for DMO when VA ≥ 6/12 (20/40)
At 1 year: IVA superior for DMO when VA ≤ 6/15 (20/50)
At 2 years: IVA no longer superior for DMO when VA ≤ 6/15 (20/50)
Diabetic Retinopathy Clinical Research, N., Wells, J.A., Glassman, A.R. et al. 2015. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. The New England Journal of Medicine 372(13) 1193-1203.
Protocol S [xlvi]
IVR monthly vs PRP for PDR
At 2 years: IVR non-inferior to PRP for PDR.
IVR had less DMO, vitrectomy rates and visual field loss
Network, W.C.f.t.D.R.C.R. 2015. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA 314(20) 2137-2146.
CLARITY [xlvii]
IVA vs. PRP for PDR without baseline DMO
At 1 year: IVA non-inferior and superior to PRP for PDR
IVA had less DMO, vitreous haemorrhage rates and visual field loss
Sivaprasad, S., Prevost, A.T., Vasconcelos, J.C. et al. 2017. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. The Lancet (British edition) 389(10085) 2193-2203.
Protocol V [xlvii]
IVA vs. Focal laser (with rescue IVA vs. Observation (with rescue IVA) for DMO with “very good” vision
At 2 years: Initial observation or focal laser at baseline (with rescue IVA if required) non-inferior to IVA only for DMO with “very good” initial vision (≥ 6/7.5, 20/25)
Baker, C.W., Glassman, A.R., Beaulieu, W.T. et al. 2019. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA 321(19) 1880-1894.
RESTORE [xlix]
IVR vs. IVR/laser vs laser
IVR or IVR/laser better than laser alone for DMO
Mitchell, P., Bandello, F., Schmidt-Erfurth, U. et al. 2011. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 118(4) 615-625
RISE/RIDE [l]
Phase III IVR
IVR effective for DMO
Nguyen, Q.D., Brown, D.M., Marcus, D.M. et al. 2012. Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE. Ophthalmology 119(4) 789-801.
VIVID/VISTA [li]
Phase III IVA
IVA effective for DMO
Heier, J.S., Korobelnik, J.F., Brown, D.M. et al. 2016. Intravitreal Aflibercept for Diabetic Macular Edema: 148-Week Results from the VISTA and VIVID Studies. Ophthalmology 123(11) 2376-2385.
BOLT [lii]
IVB vs. more laser (when laser failed)
IVB effective for DMO
Michaelides, M., Kaines, A., Hamilton, R.D. et al. 2010. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology 117(6) 1078-1086.e1072.
MEAD [liii]
Dexamethasone implant vs laser
Dexamethasone intravitreal implant effective for DMO, but causes cataract and glaucoma
Boyer, D.S., Yoon, Y.H., Belfort, R., Jr. et al. 2014. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology 121(10) 1904-1914.
A comprehensive list of up to date DRCR.net studies is available on their website: [liv]
DRCR.net. 2020. DRCR.net Publications [online]: JAEB Center for Health Reserach. Available at: https://public.jaeb.org/drcrnet/pubs [Accessed 8th June 2020].
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