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Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy.
Ophthalmology. 2015 Feb; 122(2):367-74.O

Abstract

PURPOSE

To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR).

DESIGN

Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials.

PARTICIPANTS

Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness ≥275 μm.

METHODS

Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group.

MAIN OUTCOME MEASURES

Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR.

RESULTS

At month 36, a greater proportion of ranibizumab-treated eyes had ≥2- or ≥3-step DR improvement compared with sham/0.5 mg crossover. A ≥3-step improvement was achieved at 36 months by 3.3%, 15.0%, and 13.2% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P < 0.0001). Through 36 months, 39.1% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3% and 17.1% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy.

CONCLUSIONS

Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing anti-vascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin. Electronic address: msip@wisc.edu.Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin.Joslin Diabetes Center, Harvard Department of Ophthalmology, Boston, Massachusetts.Genentech, Inc., South San Francisco, California.

Pub Type(s)

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

Language

eng

PubMed ID

25439595

Citation

Ip, Michael S., et al. "Long-term Effects of Therapy With Ranibizumab On Diabetic Retinopathy Severity and Baseline Risk Factors for Worsening Retinopathy." Ophthalmology, vol. 122, no. 2, 2015, pp. 367-74.
Ip MS, Domalpally A, Sun JK, et al. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015;122(2):367-74.
Ip, M. S., Domalpally, A., Sun, J. K., & Ehrlich, J. S. (2015). Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology, 122(2), 367-74. https://doi.org/10.1016/j.ophtha.2014.08.048
Ip MS, et al. Long-term Effects of Therapy With Ranibizumab On Diabetic Retinopathy Severity and Baseline Risk Factors for Worsening Retinopathy. Ophthalmology. 2015;122(2):367-74. PubMed PMID: 25439595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. AU - Ip,Michael S, AU - Domalpally,Amitha, AU - Sun,Jennifer K, AU - Ehrlich,Jason S, Y1 - 2014/11/18/ PY - 2014/03/27/received PY - 2014/05/05/revised PY - 2014/08/18/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/4/15/medline SP - 367 EP - 74 JF - Ophthalmology JO - Ophthalmology VL - 122 IS - 2 N2 - PURPOSE: To assess the effects of intravitreal ranibizumab on diabetic retinopathy (DR) severity when administered for up to 3 years, evaluate the effect of delayed initiation of ranibizumab therapy on DR severity, and identify baseline patient characteristics associated with the development of proliferative DR (PDR). DESIGN: Exploratory analyses of phase III, randomized, double-masked, sham-controlled multicenter clinical trials. PARTICIPANTS: Adults with diabetic macular edema (DME) (N = 759), baseline best-corrected visual acuity 20/40 to 20/320 Snellen equivalent, and central foveal thickness ≥275 μm. METHODS: Patients were randomized to monthly 0.3 or 0.5 mg ranibizumab or sham injections. Sham participants could switch to 0.5 mg ranibizumab during the third year (sham/0.5 mg crossover). Baseline risk factors were evaluated to explore potential associations with development of PDR. Time to first development of PDR was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by group. MAIN OUTCOME MEASURES: Study eye change on the Early Treatment Diabetic Retinopathy Study severity scale and a composite clinical outcome evaluating progression to PDR based on photographic changes plus clinically important events defining PDR. RESULTS: At month 36, a greater proportion of ranibizumab-treated eyes had ≥2- or ≥3-step DR improvement compared with sham/0.5 mg crossover. A ≥3-step improvement was achieved at 36 months by 3.3%, 15.0%, and 13.2% of sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab-treated eyes, respectively (P < 0.0001). Through 36 months, 39.1% of eyes in the sham/0.5 mg group developed PDR, as measured by composite outcome, compared with 18.3% and 17.1% of eyes treated with 0.3 or 0.5 mg ranibizumab, respectively. The presence of macular capillary nonperfusion at baseline seems to be associated with progression to PDR in ranibizumab-treated eyes but did not meaningfully influence visual acuity improvement in eyes with DME after ranibizumab therapy. CONCLUSIONS: Ranibizumab, as administered to patients with DME for 12 to 36 months in these studies, can both improve DR severity and prevent worsening. Prolonged delays in initiation of ranibizumab therapy may limit this therapeutic effect. Although uncommon, the development of PDR still occurs in a small percentage of eyes undergoing anti-vascular endothelial growth factor therapy and may be related to the presence of macular nonperfusion. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/25439595/Long_term_effects_of_therapy_with_ranibizumab_on_diabetic_retinopathy_severity_and_baseline_risk_factors_for_worsening_retinopathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(14)00822-7 DB - PRIME DP - Unbound Medicine ER -