Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy: Results of the EUROCONDOR Clinical Trial

• DOI: 10.2337/db18-0682
• Publication Date: 2018-11-02T19:05:43Z
• Authors: Rafael Simó; Cristina Hernández; Massimo Porta; Francesco Bandello; Jakob Grauslund; Simon P. Harding; Stephen J. Aldington; Catherine Egan; Ulrik Frydkjaer-O...; José García-Arumí; Jonathan Gibson; Gabriele E. Lang; Rosangela Lattanzio; Pascale Massin; Edoardo Midena; Berta Ponsati; Luísa Ribeiro; Peter Scanlon; Conceição Lobo; Miguel Ângelo Costa; José Cunha-Vaz; ; R. Simó; C. Hernández; M. García-Ramírez; E. van Reck; E. Gil; M. Morillas; J. Cunha-Vaz; L. Ribeiro; C. Lobo; M.A. Costa; S. Nunes; J. Figueira; I. Pereira-Marques; C. Neves; C. Schwartz; M. Porta; M. Trento; O. Durando; S. Merlo; F. Bandello; R. Lattanzio; I. Zucchiatti; J. Grauslund; U. Frydkjaer-Olsen; S.P. Harding; P. Scanlon; S.J. Aldington; V. Jones; L. Johnson; S. Carter; J. Spurway; C. Egan; S. Esposti; L. Leitch-Devlin; V. Rocco; A. Rees; J. García-Arumí; M.A. Zapata; A. Boixadera; C. Macià; L. Distefano; T. Torrent; F. Casals; N. de Dios; J. Gibson; G.E. Lang; W. Jens-Ulrich; E. Christian; K. Adnan; P. Massin; A. Erginay; E. Midena; S. Vujosevic; E. Pilotto; E. Longhin; E. Convento; B. Ponsati; J. Fernández-Carn...; S. Arrastia-Casado; S. Orgué; D.T. Ramírez-Lamelas; A. Almazán-Moga; A. Salvà; L. Riera
• Keywords: 0301 basic medicine; Diabetic Retinopathy; Administration, Topical; Administration, Topical; Aged; Brimonidine Tartrate; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Humans; Middle Aged; Neuroprotective Agents; Somatostatin; Middle Aged; 3. Good health; 03 medical and health sciences; Neuroprotective Agents; Diabetes Mellitus, Type 2; Brimonidine Tartrate; Humans; Somatostatin; Aged

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit.