Diabetic macular edema: it is more than just VEGF

Singer, Michael; Kermany, Daniel; Waters, Jana; Jansen, Michael; Tyler, Lyndon

doi:10.12688/f1000research.8265.1

Cited by 37 publications

(27 citation statements)

References 12 publications

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“…Although the recently reported results from the DRCR.net Protocol T study showed substantially better visual outcomes, the DRCR.net protocols are difficult to follow in a real-life setting for clinicians in most parts of the world [21][22][23] . The pathogenesis of DME is complicated and, in addition to VEGF, also involves inflammatory cytokines and even vitreoretinal interface abnormalities [24][25][26] . Current mainstays of DME management are control of systemic factors, focal/grid laser for non-center-involving DME, anti-VEGF agents for center-involving DME, steroids, and vitrectomy [25][26][27] .…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of DME is complicated and, in addition to VEGF, also involves inflammatory cytokines and even vitreoretinal interface abnormalities [24][25][26] . Current mainstays of DME management are control of systemic factors, focal/grid laser for non-center-involving DME, anti-VEGF agents for center-involving DME, steroids, and vitrectomy [25][26][27] . The ability to identify early on those patients who are likely to respond poorly to long-term anti-VEGF therapy would allow more timely consideration of alternative treatment regimens that might prove more effective in optimizing visual outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Early Response to Ranibizumab Is Associated with 12-Month Outcome in Diabetic Macular Edema after Prior Macular Laser Therapy

Sheu

Lee²

2017

Ophthalmologica

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Purpose: To evaluate the efficacy of ranibizumab in persistent or recurrent diabetic macular edema (DME) after previous laser therapy. Methods: This prospective, interventional study consisted of a 3-month period of scheduled ranibizumab treatment followed by a 9-month period of pro re nata treatment. Results: A total of 21 eyes (18 patients) were included. Both best corrected visual acuity and central retinal thickness had statistically significantly improved from baseline at month 12 (p < 0.001). The mean number of injections within these 12 months was 7.8 ± 2.6 (range 3-11). The visual change at month 12 did not vary by more than 5 letters from the response observed at week 12. Conclusions: Our study showed a beneficial effect from ranibizumab in DME patients previously treated with macular laser therapy. The response at week 12 was sustained up to 1 year. A suboptimal early visual response may predict a long-term suboptimal response and help identify patients who would benefit from an alternative regimen.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Early Response to Ranibizumab Is Associated with 12-Month Outcome in Diabetic Macular Edema after Prior Macular Laser Therapy

Sheu

Lee²

2017

Ophthalmologica

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“…DME management can be difficult, with only around 15% of the patients achieving significant vision recovery with laser, the current standard of care [2]. A number of pharmacotherapies are now licensed for the treatment of DME in Europe, including anti-vascular endothelial growth factor agents and corticosteroid therapies [3], which are used to target vascular endothelial growth pathways and inflammatory pathways, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Inhibiting the release of cytokines with a corticosteroid – such as dexamethasone, triamcinolone or fluocinolone – has been shown to reduce DME and rehabilitate vision in several pivotal clinical studies [3]. ILUVIEN contains the corticosteroid fluocinolone acetonide (FAc) and uses microdosingTM technology to release FAc at a daily rate of 0.2 μg for up to 3 years [5].…”

Section: Introductionmentioning

confidence: 99%

Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation

Quhill

2016

Case Rep Ophthalmol

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Importance: A case showing sustained structural and functional responses 2 years after a single treatment with ILUVIEN (0.2 µg/day fluocinolone acetonide, FAc) despite suboptimal responses to ranibizumab. Observations: A 68-year-old female patient with diabetic macular oedema (DME) from type 2 diabetes mellitus was first diagnosed in October 2010 and had a baseline visual acuity (VA) of 46 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Central foveal thickness (CFT) was 712 microns. The patient was treated with 11 intravitreal injections of ranibizumab (5 in combination with a small-interfering RNA agent), and by March 2014, VA and CFT were largely unchanged (55 ETDRS letters and 774 microns). The patient was treated with ILUVIEN as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab. An implant releasing FAc at a dosage of 0.2 µg/day was administered in March 2014, and the optical coherence tomography indicated that the macula was dry after 7 days (CFT was below 300 microns). This was sustained at 6, 12, and 24 months after the treatment. VA improved by 5 letters within 7 days and by 15 letters within 14 days, and this was maintained after 24 months. Throughout the duration of this study, the intraocular pressure was ≤22 mm Hg, and no glaucoma medication was administered. Conclusions and Relevance: In real-life UK practice, this DME patient showed a suboptimal response to multiple intravitreal injections of ranibizumab. When subsequently treated with a single injection of ILUVIEN, there were large and rapid improvements in VA and CFT that were maintained for the following 2 years.

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“…5,11,12 Although effective, this is limited to treating the pathology, but not the underlying biochemical changes, and results in permanent retinal scarring. 13 Intravitreal administration of corticosteroids is beneficial for some patients with DME. 14 The mechanisms of action of these agents include nonspecific anti-inflammatory properties 14 ; VEGF is the primary mediator of the breakdown in blood-retinal barrier characteristic of DME.…”

mentioning

confidence: 99%

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

Gale

Berger²,

Gilbert

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Gale JD, Berger B, Gilbert S, et al. A CCR2/5 inhibitor, PF-04634817, is inferior to monthly ranibizumab in the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59:2659-2669. https://doi.org/10.1167/iovs.17-22731 PURPOSE. Ligands for the proinflammatory C-C chemokine receptor types 2 and 5 (CCR2 and CCR5) are elevated in the eyes of patients with diabetic macular edema (DME). We evaluated the efficacy and safety of PF-04634817, an oral CCR2/5 dual antagonist, versus intravitreal ranibizumab, in adult subjects with DME. METHODS.In this phase II, randomized, placebo-controlled, double-masked study, eligible subjects ( ‡18 years of age) had type 1 or 2 diabetes and DME with best-corrected visual acuity (BCVA) of 20/32 or worse (letter score 78), and up to 20/320 or better ( ‡24 letter score), in the study eye. Subjects were assigned randomly 1:1 to once-daily (QD) oral PF-04634817 200 mg plus masked sham therapy as placebo or monthly intravitreal ranibizumab 0.3/0.5 mg plus QD oral placebo. The primary objective was to evaluate the efficacy of PF-04634817 compared with ranibizumab in change from baseline in BCVA after 12 weeks in a noninferiority design. Noninferiority was based on BCVA 80% confidence interval (CI): there had to be a less than three letter loss in the PF-04634817 arm compared with the ranibizumab arm. RESULTS.A total of 199 subjects were randomized. Least squares mean difference in change in BCVA from baseline to week 12 in the study eye for the PF-04634817 arm was À2.41 letters (80% CI: À3.91, À0.91; P ¼ 0.04) compared with ranibizumab. PF-04634817 was well tolerated.CONCLUSIONS. Treatment with oral CCR2/5 receptor dual antagonist PF-04634817 was associated with a modest improvement in BCVA, but did not meet the predefined noninferiority criteria compared with intravitreal ranibizumab.

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Diabetic macular edema: it is more than just VEGF

Cited by 37 publications

References 12 publications

Early Response to Ranibizumab Is Associated with 12-Month Outcome in Diabetic Macular Edema after Prior Macular Laser Therapy

Early Response to Ranibizumab Is Associated with 12-Month Outcome in Diabetic Macular Edema after Prior Macular Laser Therapy

Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

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