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Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2.
Retina. 2011 Nov; 31(10):2084-94.R

Abstract

PURPOSE

To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2 ruboxistaurin (RBX) protein kinase C β inhibitor trials.

METHODS

Patients in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity ≥45 letters (∼20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy level 47A/B-53E, and no previous panretinal photocoagulation in ≥1 eye. Patients received placebo (N = 401) or RBX 32 mg/day (N = 412). Data from the 2 studies were combined and masked evaluation of retinal photographs was performed for cause of visual decline in all patients experiencing sustained moderate visual loss (≥15-letter loss sustained for the last 6 months of study).

RESULTS

In the studies combined, sustained moderate visual loss occurred in 10.2% of placebo-treated patients versus 6.1% of RBX-treated patients (P = 0.011). A ≥15-letter gain occurred in 2.4% of placebo versus 4.7% of RBX eyes (P = 0.021) and a ≥15-letter loss occurred in 11.4% versus 7.4%, respectively (P = 0.012). Diabetic macular edema was the probable primary cause of vision loss. Among eyes without focal/grid photocoagulation at baseline, fewer RBX group eyes (26.7%) required initial focal/grid photocoagulation versus placebo (35.6%; P = 0.008). No safety concerns were identified.

CONCLUSION

Analysis of data combined from two similar studies adds further statistical significance to RBX's beneficial effects on visual loss, need for focal laser, and vision gain, most likely through effects on macular edema.

Authors+Show Affiliations

Joslin Diabetes Center, Beetham Eye Institute, Department of Ophthalmology, Harvard University Medical School, Boston, Massachusetts, USA. lpaiello@joslin.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21862954

Citation

Aiello, Lloyd Paul, et al. "Oral Protein Kinase C Β Inhibition Using Ruboxistaurin: Efficacy, Safety, and Causes of Vision Loss Among 813 Patients (1,392 Eyes) With Diabetic Retinopathy in the Protein Kinase C Β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C Β Inhibitor-Diabetic Retinopathy Study 2." Retina (Philadelphia, Pa.), vol. 31, no. 10, 2011, pp. 2084-94.
Aiello LP, Vignati L, Sheetz MJ, et al. Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2. Retina (Philadelphia, Pa). 2011;31(10):2084-94.
Aiello, L. P., Vignati, L., Sheetz, M. J., Zhi, X., Girach, A., Davis, M. D., Wolka, A. M., Shahri, N., & Milton, R. C. (2011). Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2. Retina (Philadelphia, Pa.), 31(10), 2084-94. https://doi.org/10.1097/IAE.0b013e3182111669
Aiello LP, et al. Oral Protein Kinase C Β Inhibition Using Ruboxistaurin: Efficacy, Safety, and Causes of Vision Loss Among 813 Patients (1,392 Eyes) With Diabetic Retinopathy in the Protein Kinase C Β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C Β Inhibitor-Diabetic Retinopathy Study 2. Retina (Philadelphia, Pa). 2011;31(10):2084-94. PubMed PMID: 21862954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2. AU - Aiello,Lloyd Paul, AU - Vignati,Louis, AU - Sheetz,Matthew J, AU - Zhi,Xin, AU - Girach,Aniz, AU - Davis,Matthew D, AU - Wolka,Anne M, AU - Shahri,Nazila, AU - Milton,Roy C, AU - ,, PY - 2011/8/25/entrez PY - 2011/8/25/pubmed PY - 2012/3/1/medline SP - 2084 EP - 94 JF - Retina (Philadelphia, Pa.) JO - Retina (Philadelphia, Pa.) VL - 31 IS - 10 N2 - PURPOSE: To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2 ruboxistaurin (RBX) protein kinase C β inhibitor trials. METHODS: Patients in these 3-year, randomized, placebo-controlled, double-masked, Phase 3 trials had best-corrected Early Treatment Diabetic Retinopathy Study visual acuity ≥45 letters (∼20/125 Snellen), Early Treatment Diabetic Retinopathy Study retinopathy level 47A/B-53E, and no previous panretinal photocoagulation in ≥1 eye. Patients received placebo (N = 401) or RBX 32 mg/day (N = 412). Data from the 2 studies were combined and masked evaluation of retinal photographs was performed for cause of visual decline in all patients experiencing sustained moderate visual loss (≥15-letter loss sustained for the last 6 months of study). RESULTS: In the studies combined, sustained moderate visual loss occurred in 10.2% of placebo-treated patients versus 6.1% of RBX-treated patients (P = 0.011). A ≥15-letter gain occurred in 2.4% of placebo versus 4.7% of RBX eyes (P = 0.021) and a ≥15-letter loss occurred in 11.4% versus 7.4%, respectively (P = 0.012). Diabetic macular edema was the probable primary cause of vision loss. Among eyes without focal/grid photocoagulation at baseline, fewer RBX group eyes (26.7%) required initial focal/grid photocoagulation versus placebo (35.6%; P = 0.008). No safety concerns were identified. CONCLUSION: Analysis of data combined from two similar studies adds further statistical significance to RBX's beneficial effects on visual loss, need for focal laser, and vision gain, most likely through effects on macular edema. SN - 1539-2864 UR - https://www.unboundmedicine.com/medline/citation/21862954/Oral_protein_kinase_c_β_inhibition_using_ruboxistaurin:_efficacy_safety_and_causes_of_vision_loss_among_813_patients__1392_eyes__with_diabetic_retinopathy_in_the_Protein_Kinase_C_β_Inhibitor_Diabetic_Retinopathy_Study_and_the_Protein_Kinase_C_β_Inhibitor_Diabetic_Retinopathy_Study_2_ L2 - http://dx.doi.org/10.1097/IAE.0b013e3182111669 DB - PRIME DP - Unbound Medicine ER -