A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration

Chin-Yee, David; Eck, Thomas; Fowler, Susan A.; Hardi, Angela; Apte, Rajendra S.

doi:10.1136/bjophthalmol-2015-306987

Cited by 111 publications

(93 citation statements)

References 11 publications

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“…[15][16][17]19 Furthermore, recent investigations have documented that for a better response repeated injections are needed, at least initially, irrespective of the response to therapy. 13,[20][21][22] However, very little is known about the dosing and the possible local side effects in the retina of repeated IVI. 23 Indeed, bevacizumab and ranibizumab are humanized monoclonal antibodies and thus may trigger even in humans an inflammatory reaction, as has been shown for higher doses of these substances, 24 and the trap aflibercept may even be more inflammatory.…”

Section: Discussionmentioning

confidence: 99%

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

Pierdomenico

García‐Ayuso

Jiménez-López

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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Citation: Di Pierdomenico J, García-Ayuso D, Jiménez-López M, AgudoBarriuso M, Vidal-Sanz M, VillegasPérez MP. Different ipsi-and contralateral glial responses to anti-VEGF and triamcinolone intravitreal injections in rats. Invest Ophthalmol Vis Sci. 2016;57:3533-3544. DOI:10.1167/iovs.16-19618 PURPOSE. To investigate the glial response of the rat retina to single or repeated intravitreal injections (IVI).METHODS. Albino Sprague-Dawley rats received one or three (one every 7 days) IVI of anti-rat VEGF (5 lL; 0.015 lg/lL), triamcinolone (2.5 or 5 lL; 40 lg/lL; Trigón Depot), bevacizumab (5 lL; 25 lg/lL; Avastin), or their vehicles (PBS and balanced salt solution) and were processed 7 days after the last injection. Retinas were dissected as whole mounts and incubated with antibodies against: Iba1 (Ionized Calcium-Binding Adapter Molecule 1) to label retinal microglia, GFAP (Glial Fibrillary Acidic Protein) to label macroglial cells, and vimentin to label Müller cells. The retinas were examined with fluorescence and confocal microscopy, and the numbers of microglial cells in the inner retinal layers were quantified using a semiautomatic method.RESULTS. All the injected substances caused an important micro-and macroglial response locally at the injection site and all throughout the injected retina that was exacerbated by repeated injections. The microglial response was also observed but was milder in the contralateral noninjected eyes. The IVI of the humanized antibody bevacizumab caused a very strong microglial reaction in the ipsilateral retina. Two types of macroglial response were observed: astrocyte hypertrophy and Müller end-foot hypertrophy. While astrocyte hypertrophy was widespread throughout the injected retina, Müller end-foot hypertrophy was localized and more extensive with triamcinolone use or after repeated injections. CONCLUSIONS.Intravitreal injections cause micro-and macroglial responses that vary depending on the injected agent but increase with repeated injections. This inflammatory glial response may influence the effects of the injected substances on the retina.

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Section: Discussionmentioning

confidence: 99%

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

Pierdomenico

García‐Ayuso

Jiménez-López

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Several pro re nata regimens have been evaluated as alternatives to fixed dosing regimens [5][6][7] . However, pro re nata treatment has been found to be generally inferior over the long term, a result not surprising given that treatments are only administered once retinal exudation has recurred [8] .…”

mentioning

confidence: 99%

One-Year Outcomes of a Treat-and-Extend Regimen of Aflibercept for Exudative Age-Related Macular Degeneration

Yamamoto

Okada²,

Nakayama³

et al. 2017

Ophthalmologica

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Purpose: The aim of this study was to investigate the 1-year outcomes of treat-and-extend aflibercept for exudative age-related macular degeneration (AMD) in Japan. Procedures: Clinical records of 67 patients (67 eyes) were reviewed. Monthly aflibercept was administered until resolution of exudation and maximal reduction of pigment epithelial detachment. Injection intervals were extended by 2-week units up to 12 weeks if no exudation was observed and shortened for recurrence. Results: Mean best-corrected visual acuity (logarithm of the minimum angle of resolution) improved from 0.29 to 0.14 at 12 months (p < 0.0001). Mean central retinal thickness decreased from 430 μm to 236 μm at 12 months (p < 0.0001). Fifty-nine eyes (88.0%) achieved a dry macula with a mean of 8.3 injections by study end. The injection interval was extended to 10 weeks in 44.8% and to 12 weeks in 17.9% of eyes. Conclusions: At 1 year, good outcomes were obtained using treat-and-extend aflibercept for exudative AMD in Japan.

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“…27 Their systematic review demonstrated a gain of 9.17 (S.D. 3.8) ETDRS letters as a weighted mean at one year, with 8.34 (S.D.…”

Section: Discussionmentioning

confidence: 99%

A systematic review to assess the ‘treat-and-extend’ dosing regimen for neovascular age-related macular degeneration using ranibizumab

Rufai

Almuhtaseb

Paul

et al. 2017

Eye

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Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Monthly or as-needed (PRN) dosing strategies of intravitreal ranibizumab have been established as efficacious treatment options for neovascular AMD. More recently, the "Treatand-Extend" dosing regimen (TREX) is being adopted in clinical practice as it represents a patientcentric and economical option, reducing treatment burden by extending injection intervals when possible. However, the efficacy of TREX using ranibizumab monotherapy remains to be defined. Therefore, we performed a systematic review to assess the current evidence for TREX using ranibizumab by searching MEDLINE, Embase and PubMed. Of 1,733 articles identified, nine TREX studies were included in our analysis (n=748 eyes). Average patient age was 79.25 (range: 77.34 -82.00; S.D. 7.27). Baseline BCVA ranged from 48.5 -68.9 ETDRS letters. BCVA improvement was 8.92 letters at one year (range: 6.5 -11.5; S.D. 7.54), as a weighted mean accounting for numbers of study eyes. The weighted mean number of injections at one year was 8.60 (range: 7.3 -12.0; S.D. 1.73). Previously, the landmark ANCHOR and MARINA trials reported gains of 11.3 and 7.2 letters, respectively, using monthly ranibizumab. Chin-Yee et al reported a gain of 3.5 ETDRS letters with 5.3 (S.D. 0.66) PRN ranibizumab injections as weighted means at one year in their recent systematic review. Our analysis suggests that TREX delivers visual outcomes superior to PRN and approaches similar efficacy to monthly injections. Further RCTs are needed to fully evaluate the efficacy and economy of TREX in the long-term.

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A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration

Cited by 111 publications

References 11 publications

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats

One-Year Outcomes of a Treat-and-Extend Regimen of Aflibercept for Exudative Age-Related Macular Degeneration

A systematic review to assess the ‘treat-and-extend’ dosing regimen for neovascular age-related macular degeneration using ranibizumab

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