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preserveAspectRatio="none"><path fill="none" stroke="#000" stroke-width="36" stroke-linecap="round" style="fill:#FFF" d="m320,350a153,153 0 1,0-2,2l170,170m-91-117 110,110-26,26-110-110"></path></svg></a><a id="jr-fip-done" class="wsprkl btn" title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style"><div class="fm-sec bkr_bottom_sep"><div class="bkr_thumb"><a href="https://www.nice.org.uk" title="National Institute for Health and Care Excellence (NICE)" class="img_link icnblk_img" ref="pagearea=logo&targetsite=external&targetcat=link&targettype=publisher"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-niceng242er8-lrg.png" alt="Cover of Evidence reviews for clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema" /></a></div><div class="bkr_bib"><h1 id="_NBK607259_"><span itemprop="name">Evidence reviews for clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema</span></h1><div class="subtitle">Diabetic retinopathy</div><p><b>Evidence review H</b></p><p><i>NICE Guideline, No. 242</i></p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2024 Aug</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-6436-9</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div></div><div class="bkr_clear"></div></div><div id="niceng242er8.s1"><h2 id="_niceng242er8_s1_">1. Clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema</h2><div id="niceng242er8.s1.1"><h3>1.1. Review question</h3><p>What are the clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema?</p><div id="niceng242er8.s1.1.1"><h4>1.1.1. Introduction</h4><p>The decision to switch or stop treatment for individuals diagnosed with proliferative diabetic retinopathy or diabetic macular oedema should be based on various clinical features and factors. The knowledge of which clinical features or factors are the best indicators that treatment should be switched or stopped is therefore important as it ensures that people can get the most effective treatment at the most appropriate time. This can help to stop, or reduce, progression of diabetic retinopathy and macular oedema and improve patient outcomes. The aim of this review is therefore to assess the evidence on which are the most effective criteria for switching or stopping treatment for a person who has diabetic retinopathy or diabetic macular oedema.</p><p>This evidence review informed recommendations in the NICE guideline on the management and treatment of diabetic retinopathy, which is a new NICE guideline in this area.</p></div><div id="niceng242er8.s1.1.2"><h4>1.1.2. Summary of the protocol</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8tab1"><a href="/books/NBK607259/table/niceng242er8.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img" rid-ob="figobniceng242er8tab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.tab1"><a href="/books/NBK607259/table/niceng242er8.tab1/?report=objectonly" target="object" rid-ob="figobniceng242er8tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">Clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema. </p></div></div></div><div id="niceng242er8.s1.1.3"><h4>1.1.3. Methods and process</h4><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng242er8.appa">Appendix A</a> and the <a href="/books/NBK607259/bin/NG242-Methods.pdf">methods</a> document.</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng242er8.s1.1.4"><h4>1.1.4. Effectiveness evidence</h4><div id="niceng242er8.s1.1.4.1"><h5>1.1.4.1. Included studies</h5><p>2324 records were identified in the search for title and abstract screening. Following the title and abstract screening, 8 records were selected for full-text screening. Of these, only 2 studies were found to meet the inclusion criteria and were therefore included in the review. The re-run searches identified 164 additional studies, but none met the inclusion criteria for the review.</p><p>Of the two included studies, one was a randomised controlled trial (RCT), and the other was a comparative observational study. Both included people with diabetic macular oedema and considered criteria for switching, rather than stopping, treatment. The 2 studies considered the following criteria for switching treatment:
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<ul><li class="half_rhythm"><div>RCT: Persistent centre-involving diabetic macular oedema - recent treatment of the eye which resulted in no improvement in eye condition and/or suboptimal vision (Intervention: Bevacizumab with switch to aflibercept at week 12 vs aflibercept monotherapy)</div></li><li class="half_rhythm"><div>Observational study: Suboptimal response to the anti-VEGF loading phase (Intervention: Switch to steroids vs Anti-VEGF only).</div></li></ul></p></div><div id="niceng242er8.s1.1.4.2"><h5>1.1.4.2. Excluded studies</h5><p>See <a href="#niceng242er8.appj">Appendix J</a> for excluded studies and reasons for exclusion.</p></div></div><div id="niceng242er8.s1.1.5"><h4>1.1.5. Summary of studies included in the effectiveness evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8tab2"><a href="/books/NBK607259/table/niceng242er8.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img" rid-ob="figobniceng242er8tab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.tab2"><a href="/books/NBK607259/table/niceng242er8.tab2/?report=objectonly" target="object" rid-ob="figobniceng242er8tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Table of included studies. </p></div></div><p>See <a href="#niceng242er8.appd">Appendix D</a> for full evidence tables.</p></div><div id="niceng242er8.s1.1.6"><h4>1.1.6. Summary of the effectiveness evidence</h4><p>A mean difference less than 0 favours the intervention (anti-VEGF treatment) and a mean difference greater than 0 favours the control arm (placebo). If the confidence interval crosses the line of no effect (0) this would be interpreted as unable to differentiate between switching criteria.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8tab3"><a href="/books/NBK607259/table/niceng242er8.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img" rid-ob="figobniceng242er8tab3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.tab3"><a href="/books/NBK607259/table/niceng242er8.tab3/?report=objectonly" target="object" rid-ob="figobniceng242er8tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Persistent centre-involving diabetic macular oedema - recent treatment of the eye which resulted in no improvement in eye condition and/or suboptimal vision (Bevacizumab first with switch to aflibercept at week 12 vs aflibercept monotherapy) (n= number <a href="/books/NBK607259/table/niceng242er8.tab3/?report=objectonly" target="object" rid-ob="figobniceng242er8tab3">(more...)</a></p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8tab4"><a href="/books/NBK607259/table/niceng242er8.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img" rid-ob="figobniceng242er8tab4"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.tab4"><a href="/books/NBK607259/table/niceng242er8.tab4/?report=objectonly" target="object" rid-ob="figobniceng242er8tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Suboptimal response to the anti-VEGF loading phase (Anti-VEGF only vs switch to steroids) (n= number of eyes). </p></div></div><p>See <a href="#niceng242er8.appf">Appendix F</a> for full GRADE and tables and <a href="#niceng242er8.appe">Appendix E</a> for forest plots.</p></div><div id="niceng242er8.s1.1.7"><h4>1.1.7. Economic evidence</h4><div id="niceng242er8.s1.1.7.1"><h5>1.1.7.1. Included studies</h5><p>A single search was performed to identify published economic evaluations of relevance to any of the questions in this guideline update (see <a href="#niceng242er8.appb">Appendix B</a>). This search retrieved 672 studies. Based on title and abstract screening, 671 of the studies could confidently be excluded for this review question. One study was excluded following the full-text review. No relevant health economic studies were included.</p></div><div id="niceng242er8.s1.1.7.2"><h5>1.1.7.2. Excluded studies</h5><p>See <a href="#niceng242er8.appj">Appendix J</a> for excluded studies and reasons for exclusion.</p><p>See the health economic study selection flow chart presented in <a href="#niceng242er8.appg">Appendix G</a>.</p></div></div><div id="niceng242er8.s1.1.8"><h4>1.1.8. Summary of included economic evidence</h4><p>No relevant health economic studies were identified to be included.</p></div><div id="niceng242er8.s1.1.9"><h4>1.1.9. Economic model</h4><p>Original health economic modelling was not conducted for this review question.</p></div><div id="niceng242er8.s1.1.10"><h4>1.1.10. The committee’s discussion and interpretation of the evidence</h4><div id="niceng242er8.s1.1.10.1"><h5>1.1.10.1. The outcomes that matter most</h5><p>The committee considered deterioration of visual acuity as a primary outcome for assessing the need to switch or stop treatment. Visual acuity is a crucial factor in evaluating the effectiveness of interventions for diabetic retinopathy and making treatment decisions.</p><p>Progression of retinopathy is also important, as this can lead to serious consequences, such as loss of vision. Quality of life is an important aspect to consider as it assesses the impact of the disease and its treatments on a person’s overall well-being and daily functioning. Similarly, driving vision, which includes factors such as peripheral vision and visual field, is crucial for safe and independent mobility. However, there was no evidence available for either quality of life or driving vision.</p></div><div id="niceng242er8.s1.1.10.2"><h5>1.1.10.2. The quality of the evidence</h5><p>The review included two studies, one of which was a moderate quality RCT, and the other was a low-quality retrospective observational study. Both studies considered switching criteria for people who have diabetic macular oedema. There was no evidence for people who have proliferative diabetic retinopathy. Evidence considered the criteria for switching treatments, but there was no evidence for when to stop treatment.</p><p>The quality of the RCT was downgraded due to concerns related to the lack of information about blinding and missing data. The observational study included a small number of participants and was downgraded because it was non-randomised, and there were concerns about how the interventions were classified. The committee also considered the limitations in the study design, where in the second year of the study, some participants who switched treatments were divided into two groups: those who switched to a dexamethasone implant and those who switched to a fluocinolone acetonide implant. Additionally, within the group that switched to the dexamethasone implant, some participants later switched to the fluocinolone acetonide implant, while others received additional anti-VEGF injections. The variation in treatments within this arm of the study made it challenging to assess the specific effects of switching to dexamethasone implants. The committee were concerned that the different interventions and subsequent switches introduced confounding factors that could impact the interpretation of the results.</p><p>The committee decided that the presence of various treatment options and switching patterns introduced complexity to the evidence and limited their ability to draw clear conclusions regarding the effects of specific switching criteria. The trial also had a small sample size and a relatively short follow-up period.</p><p>Given the limited data available, the committee could not determine which clinical features best indicate the need to switch or stop treatments. Each study used different treatments and had different criteria for switching treatments, with one study assessing specific clinical features and the other focusing on lack of response to treatment. Furthermore, the results of each study were only applicable to the specific switching criteria defined by that particular study. It was noted that neither study included an exhaustive list of features to assess treatment response and so it was not possible to determine which criteria would be the most effective. As a result, the committee decided they could not make recommendations about the best criteria or clinical features to indicate that treatments should be switched or stopped for people who have diabetic macular oedema. Instead, they made a research recommendation designed to provide further information on these criteria in future (see <a href="#niceng242er8.appk">Appendix K</a>).</p></div><div id="niceng242er8.s1.1.10.3"><h5>1.1.10.3. Benefits and harms</h5><p>The evidence for switching from bevacizumab to aflibercept at 12 weeks based on a lack of improvement in vision, suboptimal vision, or recent treatment of the eye did not demonstrate any evidence of benefit compared to aflibercept monotherapy. Given the limited evidence and the limitations of the study mentioned in the quality of the evidence section, the committee did not think they could recommend this specific switching criteria. They emphasised the importance of considering the longer-term effects of switching treatments and the need for more robust evidence in this area.</p><p>The committee were concerned that switching treatments in diabetic macular oedema requires careful consideration, taking into account factors such as treatment response, individual patient characteristics, and potential long-term effects. The committee acknowledged the need for additional research to provide a more comprehensive understanding of the effects of switching treatments and to establish appropriate criteria for guiding treatment decisions in the long term (see <a href="#niceng242er8.appk">Appendix K</a>).</p><p>The evidence for switching treatment based on a suboptimal response to an anti-VEGF loading phase showed minimal differences between people who remained on anti-VEGFs and those who met the switching criteria and changed to a dexamethasone implant. Both treatment approaches led to some improvements in visual acuity over the 2-year follow-up period. However, the evidence could not differentiate between changes in visual acuity between those who were given the switch in treatment at 2 years and those who remained on anti-VEGF monotherapy. When people switched treatment at 3 months, more people had a visual acuity gain of over 10 letters at 2 years, but no other outcomes could differentiate between those who did, or did not, follow the switching criteria. The low-quality evidence, limited definition of the switching criteria and concerns about the methods used when switching meant that the committee did not think they could recommend this as a way of deciding when to switch treatments.</p><p>The committee highlighted the importance of assessing response to treatment after the loading phase. They highlighted an additional concern about the treatment regimen used in the studies, which involved participants receiving a monthly loading dose of anti-VEGF therapy for 3 months before being assessed for treatment response. The committee expressed concerns that a 3-month loading phase may not be sufficient to accurately assess responsiveness to treatment, as it does not account for delayed responders. It is well-known that some individuals with diabetes may require longer loading phases to achieve a therapeutic response. Considering this, the committee made a recommendation to highlight the need to assess response to treatments after 12 months and then consider switching treatments if that response is suboptimal.</p><p>The committee thought that ideally there should be a list of clinical, anatomical, and biochemical features that can be used to define responsiveness to anti-VEGF therapy to help determine whether to continue, switch or stop treatment. It was discussed how the criteria for switching treatments currently varies among centres. However, there was insufficient evidence to develop this kind of recommendation and so the committee decided to make a research recommendation (see <a href="#niceng242er8.appk">Appendix K</a>). This should improve knowledge on the most important switching and stopping criteria and help make more specific recommendations in future guideline updates.</p></div><div id="niceng242er8.s1.1.10.4"><h5>1.1.10.4. Cost effectiveness and resource use</h5><p>No relevant economic evaluations were identified which addressed the cost effectiveness of the clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema. The committee discussed the importance of having a long enough loading phase of treatment to allow for a response to occur and noted that no response at all is unusual. The committee noted that continuing treatment in people who do not have a response to treatment could have resource implications such as cost of unnecessary treatment and avoidable treatment-related adverse events, so assessing response after the loading phase could minimise these costs and negative outcomes. It is expected that these assessments would happen during existing monitoring visits so would not require additional resources.</p><p>Overall, the committee were not concerned about any resource impact as a result of the recommendations as the assessments and loading phase are part of current practice.</p></div></div><div id="niceng242er8.s1.1.11"><h4>1.1.11. Recommendations supported by this evidence review</h4><p>This evidence review supports recommendations 1.6.7 to 1.6.9 and the research recommendation on effectiveness of clinical features or factors that suggest treatment should be switched or stopped.</p></div><div id="niceng242er8.s1.1.rl.r1"><h4>1.1.12. References – included studies</h4><ul class="simple-list"><div id="niceng242er8.s1.1.rl.r1.1"><h5>1.1.12.1. Effectiveness</h5><ul class="simple-list"><li class="half_rhythm"><p><div class="bk_ref" id="niceng242er8.s1.1.ref1">Busch, Catharina, Fraser-Bell, Samantha, Iglicki, Matias
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et al. (2019) Real-world outcomes of non-responding diabetic macular edema treated with continued anti-VEGF therapy versus early switch to dexamethasone implant: 2-year results. Acta diabetologica
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56(12): 1341–1350
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[<a href="https://pubmed.ncbi.nlm.nih.gov/31541334" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31541334</span></a>]</div></p></li><li class="half_rhythm"><p><div class="bk_ref" id="niceng242er8.s1.1.ref2">Jhaveri, Chirag D, Glassman, Adam R, Ferris, Frederick L
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3rd
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et al. (2022) Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. The New England journal of medicine
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387(8): 692–703
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[<a href="/pmc/articles/PMC9714135/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9714135</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/35833805" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 35833805</span></a>]</div></p></li></ul></div><div id="niceng242er8.s1.1.rl.r1.2"><h5>1.1.12.2. Economic</h5><ul class="simple-list"><p>No economic studies were included.</p></ul></div></ul></div></div></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng242er8.appa"><h3>Appendix A. Review protocols</h3><p id="niceng242er8.appa.et1"><a href="/books/NBK607259/bin/niceng242er8-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">What are the clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema?</a><span class="small"> (PDF, 234K)</span></p></div><div id="niceng242er8.appb"><h3>Appendix B. Literature search strategies</h3><div id="niceng242er8.appb.s1"><h4>Search design and peer review</h4><p>NICE information specialists conducted the literature searches for the evidence review. The searches were run in September 2022. This search report is compliant with the requirements of PRISMA-S.</p><p>The MEDLINE strategy below was quality assured (QA) by a trained NICE information specialist. All translated search strategies were peer reviewed to ensure their accuracy. Both procedures were adapted from the 2016 PRESS Checklist.</p><p>The principal search strategy was developed in MEDLINE (Ovid interface) and adapted, as appropriate, for use in the other sources listed in the protocol, taking into account their size, search functionality and subject coverage.</p></div><div id="niceng242er8.appb.s2"><h4>Review Management</h4><p>The search results were managed in EPPI-Reviewer v5. Duplicates were removed in EPPI-R5 using a two-step process. First, automated deduplication is performed using a high-value algorithm. Second, manual deduplication is used to assess ‘low-probability’ matches. All decisions made for the review can be accessed via the deduplication history.</p></div><div id="niceng242er8.appb.s3"><h4>Limits and restrictions</h4><p>English language limits were applied in adherence to standard NICE practice and the review protocol.</p><p>Limits to exclude, comment or letter or editorial or historical articles or conference abstract or conference paper or “conference review” or letter or case report were applied in adherence to standard NICE practice and the review protocol. The limit to remove animal studies in the searches was the standard NICE practice, which has been adapted from: Dickersin, K., Scherer, R., & Lefebvre, C. (1994). Systematic Reviews: Identifying relevant studies for systematic reviews. BMJ, 309(6964), 1286
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[<a href="/pmc/articles/PMC2541778/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2541778</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/7718048" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7718048</span></a>].</p></div><div id="niceng242er8.appb.s4"><h4>Search filters</h4><p id="niceng242er8.appb.et1"><a href="/books/NBK607259/bin/niceng242er8-appb-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (188K)</span></p></div><div id="niceng242er8.appb.s5"><h4>Limits and restrictions</h4><p>English language limits were applied in adherence to standard NICE practice and the review protocol.</p><p>Limits to exclude, comment or letter or editorial or historical articles or conference abstract or conference paper or “conference review” or letter or case report were applied in adherence to standard NICE practice and the review protocol.</p><p>The limit to remove animal studies in the searches was the standard NICE practice, which has been adapted from: Dickersin, K., Scherer, R., & Lefebvre, C. (1994). Systematic Reviews: Identifying relevant studies for systematic reviews. BMJ, 309(6964), 1286
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[<a href="/pmc/articles/PMC2541778/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2541778</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/7718048" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7718048</span></a>].</p></div><div id="niceng242er8.appb.s6"><h4>Search filters</h4><p id="niceng242er8.appb.et2"><a href="/books/NBK607259/bin/niceng242er8-appb-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (152K)</span></p></div></div><div id="niceng242er8.appc"><h3>Appendix C. Effectiveness evidence study selection</h3><p id="niceng242er8.appc.et1"><a href="/books/NBK607259/bin/niceng242er8-appc-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (103K)</span></p></div><div id="niceng242er8.appd"><h3>Appendix D. Effectiveness evidence</h3><p id="niceng242er8.appd.et1"><a href="/books/NBK607259/bin/niceng242er8-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.1.1.
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Busch, 2019
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</a><span class="small"> (PDF, 177K)</span></p><p id="niceng242er8.appd.et2"><a href="/books/NBK607259/bin/niceng242er8-appd-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">D.1.2.
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Jhaveri, 2022
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</a><span class="small"> (PDF, 181K)</span></p></div><div id="niceng242er8.appe"><h3>Appendix E. Forest plots</h3><p id="niceng242er8.appe.et1"><a href="/books/NBK607259/bin/niceng242er8-appe-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">E.1.1. Switching criteria: Persistent centre-involved diabetic macular oedema, Recent treatment of eye no recent improvement in eye condition and or Suboptimal vision (Bevacizumab first with switch to Aflibercept at week 12 vs Aflibercept monotherapy)</a><span class="small"> (PDF, 146K)</span></p><p id="niceng242er8.appe.et2"><a href="/books/NBK607259/bin/niceng242er8-appe-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">E.1.2. Switching criteria: Suboptimal response to anti-VEGF loading phase (Anti-VEGF vs switch to steroids in 2nd year)</a><span class="small"> (PDF, 117K)</span></p><p id="niceng242er8.appe.et3"><a href="/books/NBK607259/bin/niceng242er8-appe-et3.pdf" class="bk_dwnld_icn bk_dwnld_pdf">E.1.3. Switching criteria: Suboptimal response to anti-VEGF loading phase (Anti-VEGF vs early switch (3 months) to DEX implant)</a><span class="small"> (PDF, 117K)</span></p></div><div id="niceng242er8.appf"><h3>Appendix F. GRADE tables</h3><p id="niceng242er8.appf.et1"><a href="/books/NBK607259/bin/niceng242er8-appf-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">F.1.1. Switching criteria: Persistent centre-involved diabetic macular oedema, Recent treatment of eye no recent improvement in eye condition and or Suboptimal vision (Bevacizumab first with switch to Aflibercept at week 12 vs Aflibercept monotherapy)</a><span class="small"> (PDF, 178K)</span></p><p id="niceng242er8.appf.et2"><a href="/books/NBK607259/bin/niceng242er8-appf-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">F.1.2. Switching criteria: Suboptimal response to anti-VEGF loading phase (Anti-VEGF vs switch to steroids in 2<sup>nd</sup> year)</a><span class="small"> (PDF, 156K)</span></p></div><div id="niceng242er8.appg"><h3>Appendix G. Economic evidence study selection</h3><p id="niceng242er8.appg.et1"><a href="/books/NBK607259/bin/niceng242er8-appg-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (103K)</span></p></div><div id="niceng242er8.apph"><h3>Appendix H. Economic evidence tables</h3><p>There are no included studies for this review question.</p></div><div id="niceng242er8.appi"><h3>Appendix I. Health economic model</h3><p>Original health economic modelling has not been conducted for this review question.</p></div><div id="niceng242er8.appj"><h3>Appendix J. Excluded studies</h3><div id="niceng242er8.appj.s1"><h4>Clinical evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8appjtab1"><a href="/books/NBK607259/table/niceng242er8.appj.tab1/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobniceng242er8appjtab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.appj.tab1"><a href="/books/NBK607259/table/niceng242er8.appj.tab1/?report=objectonly" target="object" rid-ob="figobniceng242er8appjtab1">Table</a></h4><p class="float-caption no_bottom_margin">- Not a relevant study design Non comparative study</p></div></div></div><div id="niceng242er8.appj.s2"><h4>Economic evidence</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng242er8appjtab2"><a href="/books/NBK607259/table/niceng242er8.appj.tab2/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobniceng242er8appjtab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng242er8.appj.tab2"><a href="/books/NBK607259/table/niceng242er8.appj.tab2/?report=objectonly" target="object" rid-ob="figobniceng242er8appjtab2">Table</a></h4></div></div></div></div><div id="niceng242er8.appk"><h3>Appendix K. Research recommendations – full details</h3><div id="niceng242er8.appk.s1"><h4>K.1.1. Research recommendation</h4><p>What are the clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema?</p></div><div id="niceng242er8.appk.s2"><h4>K.1.2. Why this is important</h4><p>There are several treatment strategies for people with proliferative diabetic retinopathy or diabetic macular oedema. It is still unclear how to assess non responsiveness to the various treatments, and it is important for clinicians to know when to consider switching someone to another form of treatment, or when they should stop treatment. A better understanding of which clinical, biochemical, and anatomical characteristics indicate that someone would benefit from a change in treatment will help clinicians to provide patients with the most effective treatment options and reduce the complications associated with proliferative diabetic retinopathy and diabetic macular oedema.</p></div><div id="niceng242er8.appk.s3"><h4>K.1.3. Rationale for research recommendation</h4><p id="niceng242er8.appk.et1"><a href="/books/NBK607259/bin/niceng242er8-appk-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (124K)</span></p></div><div id="niceng242er8.appk.s4"><h4>K.1.4. Modified PICO table</h4><p id="niceng242er8.appk.et2"><a href="/books/NBK607259/bin/niceng242er8-appk-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (102K)</span></p></div></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Evidence reviews underpinning recommendation 1.6.7 to 1.6.9 and research recommendation 1 in the NICE guideline</p><p>These evidence reviews were developed by NICE</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="http://wales.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div><div class="small"><span class="label">Bookshelf ID: NBK607259</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/39288243" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">39288243</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng242er8tab1"><div id="niceng242er8.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">Clinical features or factors that suggest treatment should be switched or stopped for people diagnosed with proliferative diabetic retinopathy or diabetic macular oedema</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_niceng242er8.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><td headers="hd_b_niceng242er8.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">
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<p>People diagnosed with proliferative diabetic retinopathy.</p>
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<p>People diagnosed with diabetic macular oedema</p>
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</td></tr><tr><th id="hd_b_niceng242er8.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intervention</th><td headers="hd_b_niceng242er8.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">
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<p>Switching/stopping treatments according to clinical features or criteria specified in trial protocol (for example, response to treatment)</p>
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<p>Limited to the following interventions being considered under other review questions in the guideline for this population:
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<ul><li class="half_rhythm"><div>Vitrectomy</div></li><li class="half_rhythm"><div>Laser photocoagulation</div></li><li class="half_rhythm"><div>Anti-VEGF agents</div></li><li class="half_rhythm"><div>Intravitreal steroids</div></li><li class="half_rhythm"><div>Combinations of the treatments listed above</div></li></ul></p>
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</td></tr><tr><th headers="hd_b_niceng242er8.tab1_1_1_2_1" id="hd_b_niceng242er8.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Comparator</th><th id="hd_b_niceng242er8.tab1_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Not switching/stopping treatments.</th></tr><tr><th id="hd_b_niceng242er8.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_niceng242er8.tab1_1_1_4_1 hd_b_niceng242er8.tab1_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>Primary:</b>
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</p>
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<p>Best corrected visual acuity
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<ul><li class="half_rhythm"><div>Best correct visual acuity will be presented per eye when this data is available in the study.</div></li><li class="half_rhythm"><div>Per patient data will only be extracted when this data is not presented in a study.</div></li></ul>
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Progression of proliferative diabetic retinopathy or macular oedema</p>
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<p>
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<b>Secondary:</b>
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</p>
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<p>Quality of life (measured using validated tool)</p>
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<p>Driving vision (dichotomous outcome, number of participants with vision sufficient to allow driving).</p>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng242er8tab2"><div id="niceng242er8.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Table of included studies</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.tab2_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_niceng242er8.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Longest Follow-up time</th><th id="hd_h_niceng242er8.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_niceng242er8.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intervention</th><th id="hd_h_niceng242er8.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparator</th><th id="hd_h_niceng242er8.tab2_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><th id="hd_h_niceng242er8.tab2_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Criteria for switching</th></tr></thead><tbody><tr><th headers="hd_h_niceng242er8.tab2_1_1_1_1 hd_h_niceng242er8.tab2_1_1_1_2 hd_h_niceng242er8.tab2_1_1_1_3 hd_h_niceng242er8.tab2_1_1_1_4 hd_h_niceng242er8.tab2_1_1_1_5 hd_h_niceng242er8.tab2_1_1_1_6" id="hd_b_niceng242er8.tab2_1_1_1_1" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">RCT</th><th headers="hd_h_niceng242er8.tab2_1_1_1_7" id="hd_b_niceng242er8.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></th></tr><tr><td headers="hd_h_niceng242er8.tab2_1_1_1_1 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_2 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng242er8.tab2_1_1_1_3 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Diabetic macular oedema</p>
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<p>Aflibercept group – Median age (IQR): 60 (55-66), Female 48%</p>
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<p>Bevacizumab-First Group – Median age (IQR): 61 (54-67, Female 48%</p>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_4 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bevacizumab-First, (1.25 mg) with switch to aflibercept (2.0 mg) from 12 weeks (n=154 eyes)</td><td headers="hd_h_niceng242er8.tab2_1_1_1_5 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Aflibercept-Monotherapy 2.0 mg (n=158 eyes)</td><td headers="hd_h_niceng242er8.tab2_1_1_1_6 hd_b_niceng242er8.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity letter score</td><td headers="hd_h_niceng242er8.tab2_1_1_1_7 hd_b_niceng242er8.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Persistent centre-involved diabetic macular oedema</p>
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<p>Recent treatment of eye</p>
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<p>No recent improvement in eye condition,</p>
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<p>Suboptimal vision<sup>1</sup></p>
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</td></tr><tr><th headers="hd_h_niceng242er8.tab2_1_1_1_1 hd_h_niceng242er8.tab2_1_1_1_2 hd_h_niceng242er8.tab2_1_1_1_3 hd_h_niceng242er8.tab2_1_1_1_4 hd_h_niceng242er8.tab2_1_1_1_5 hd_h_niceng242er8.tab2_1_1_1_6" id="hd_b_niceng242er8.tab2_1_1_3_1" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">Observational – retrospective cohort study<sup>2</sup></th><th headers="hd_h_niceng242er8.tab2_1_1_1_7" id="hd_b_niceng242er8.tab2_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></th></tr><tr><td headers="hd_h_niceng242er8.tab2_1_1_1_1 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_2 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng242er8.tab2_1_1_1_3 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Treatment Naïve diabetic macular oedema,</p>
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<p>Anti-VEGF only – mean age (SD): 60 (10.2)</p>
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<p>Anti-VEGF with switch to steroids 2<sup>nd</sup> year – mean age (SD): 62.1 (13.1)</p>
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<p>Early switch to DEX implant – mean age (SD): 64 (12.7)</p>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_4 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Anti-VEGF throughout 1st year +switch to steroids in 2nd year (n=14 eyes)</p>
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<p>Early switch to DEX implant (n=29 eyes)</p>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_5 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Only anti-VEGF during study period</p>
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<p>(65.9% Ranibizumab, 15.9% Aflibercept, 18.2% Bevacizumab) (n=44 eyes)</p>
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</td><td headers="hd_h_niceng242er8.tab2_1_1_1_6 hd_b_niceng242er8.tab2_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity, letter score / logMAR</td><td headers="hd_h_niceng242er8.tab2_1_1_1_7 hd_b_niceng242er8.tab2_1_1_3_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Not provided:</p>
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<p><i>‘There was no predefined treatment protocol, and treatment decisions could have differed between centres</i>.</p>
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<p><i>Reasons for switching therapies were not assessed’</i>.</p>
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<p>But all participants had a suboptimal response to anti-VEGF loading phase</p>
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</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng242er8.tab2_1"><p class="no_margin">See <a href="#niceng242er8.appd">Appendix D</a>, <a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a> evidence table for how criteria were defined.</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="niceng242er8.tab2_2"><p class="no_margin">Non-randomised study. Authors adjusted for age, gender, stage of diabetic retinopathy, EZ disruption at baseline, lens status at baseline</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng242er8tab3"><div id="niceng242er8.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Persistent centre-involving diabetic macular oedema - recent treatment of the eye which resulted in no improvement in eye condition and/or suboptimal vision (Bevacizumab first with switch to aflibercept at week 12 vs aflibercept monotherapy) (n= number of eyes)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">No. studies</th><th id="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Sample size</th><th id="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Effect size (95% CI)</th><th id="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Quality</th><th id="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Interpretation of effect</th></tr></thead><tbody><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mean change in visual acuity over 2-year study period<sup>1</sup></td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD −0.80 (−2.50, 0.90)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity (letter score) at 2 years</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD 1.00 (−2.41. 4.41)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity – number of eyes 20/20 or better</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.00 (0.88,1.14)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity – number of eyes 20/40 or better</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.02 (0.88,1.18)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity – number of eyes 20/200 or worse</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.34 (0.07,1.67)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - Mean change from baseline in letter score at 2 years</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD 1.80 (−1.30, 4.90)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - Improvement by ≥ 15 letters</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.09 (0.88, 1.36)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - Improvement by ≥ 10 letters</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.00 (0.87, 1.14)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - Worsening by ≥ 10 letters</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.57 (0.20, 1.66)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - Worsening by ≥ 15 letters</td><td headers="hd_h_niceng242er8.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref2" rid="niceng242er8.s1.1.ref2">Jhaveri 2022</a>, RCT)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">260</td><td headers="hd_h_niceng242er8.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.52 (0.16, 1.67)</td><td headers="hd_h_niceng242er8.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Moderate</td><td headers="hd_h_niceng242er8.tab3_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="niceng242er8.tab3_1"><p class="no_margin">The primary outcome was the time-averaged change in the visual-acuity letter score over a period of 104 weeks. The score was derived by calculating the area under the curve (AUC) over the 104-week period for the change in visual acuity from baseline and dividing by the length of follow-up.</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng242er8tab4"><div id="niceng242er8.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Suboptimal response to the anti-VEGF loading phase (Anti-VEGF only vs switch to steroids) (n= number of eyes)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.tab4_lrgtbl__"><table><thead><tr><th id="hd_h_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_niceng242er8.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">No. studies</th><th id="hd_h_niceng242er8.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Sample size</th><th id="hd_h_niceng242er8.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Effect size (95% CI)</th><th id="hd_h_niceng242er8.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Quality</th><th id="hd_h_niceng242er8.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Interpretation of effect</th></tr></thead><tbody><tr><th headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_h_niceng242er8.tab4_1_1_1_2 hd_h_niceng242er8.tab4_1_1_1_3 hd_h_niceng242er8.tab4_1_1_1_4 hd_h_niceng242er8.tab4_1_1_1_5 hd_h_niceng242er8.tab4_1_1_1_6" id="hd_b_niceng242er8.tab4_1_1_1_1" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">Anti-VEGF only vs Switch to steroids in 2<sup>nd</sup> year (n= number of eyes)</th></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity logMAR – 24 months</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD 0.05 (−0.09, 0.19)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity – mean change in letters month 3-24</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD 4.40 (−1.38, 10.18)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity gain ≥ 5 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.32 (0.75, 2.33)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity gain ≥ 10 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 2.00 (0.96, 4.16)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">VA loss ≥ 5 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.24 (0.03, 1.69)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><th headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_h_niceng242er8.tab4_1_1_1_2 hd_h_niceng242er8.tab4_1_1_1_3 hd_h_niceng242er8.tab4_1_1_1_4 hd_h_niceng242er8.tab4_1_1_1_5 hd_h_niceng242er8.tab4_1_1_1_6" id="hd_b_niceng242er8.tab4_1_1_7_1" colspan="6" rowspan="1" style="text-align:left;vertical-align:top;">Anti-VEGF only vs early switch (3 months) to DEX implant (n=number of eyes)</th></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity – mean logMAR at 24 months</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD −0.02 (−0.13, 0.09)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity - change in letters from month 3-24</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MD 6.10 (−0.03, 12.23)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity gain ≥ 5 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 1.60 (1.05, 2.43)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Favours early switch to DEX implant</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity gain ≥ 10 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 2.34 (1.29, 4.26)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Favours early switch to DEX implant</td></tr><tr><td headers="hd_h_niceng242er8.tab4_1_1_1_1 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Visual acuity loss ≥ 5 letters at month 24 (from month 3)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_2 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 (<a class="bibr" href="#niceng242er8.s1.1.ref1" rid="niceng242er8.s1.1.ref1">Busch 2019</a>, observational)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_3 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">73</td><td headers="hd_h_niceng242er8.tab4_1_1_1_4 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">RR 0.58 (0.23, 1.46)</td><td headers="hd_h_niceng242er8.tab4_1_1_1_5 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td><td headers="hd_h_niceng242er8.tab4_1_1_1_6 hd_b_niceng242er8.tab4_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unable to differentiate</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng242er8appjtab1"><div id="niceng242er8.appj.tab1" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.appj.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.appj.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Blanc, Julie, Deschasse, Clemence, Kodjikian, Laurent
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et al. (2018) Safety and long-term efficacy of repeated dexamethasone intravitreal implants for the treatment of cystoid macular edema secondary to retinal vein occlusion with or without a switch to anti-VEGF agents: a 3-year experience. Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
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256(8): 1441–1448 [<a href="https://pubmed.ncbi.nlm.nih.gov/29855706" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29855706</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Not a relevant study design</p>
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<p>Non comparative study</p>
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</td></tr><tr><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Hogg, Hd Jeffry; Di Simplicio, Sandro; Pearce, Mark S (2021) Ranibizumab and aflibercept intravitreal injection for treatment naïve and refractory macular oedema in branch retinal vein occlusion. European journal of ophthalmology
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31(2): 548–555
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[<a href="https://pubmed.ncbi.nlm.nih.gov/32009462" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32009462</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Does not contain a population of people with diabetic retinopathy or diabetic macular oedema</td></tr><tr><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Liu, Y., Cheng, J., Gao, Y.
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et al. (2020) Efficacy of switching therapy to aflibercept for patients with persistent diabetic macular edema: A systematic review and meta-analysis. Annals of Translational Medicine
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8(6): 382
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[<a href="/pmc/articles/PMC7186737/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7186737</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32355826" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32355826</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>- Not a relevant study design</p>
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<p>Systematic review</p>
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</td></tr><tr><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Rush, R.B. and Rush, S.W. (2022) Faricimab for Treatment-Resistant Diabetic Macular Edema. Clinical Ophthalmology
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16: 2797–2801
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[<a href="/pmc/articles/PMC9420435/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC9420435</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/36042912" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 36042912</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Did not adjust for confounding</td></tr><tr><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Sarao, Valentina, Veritti, Daniele, Furino, Claudio
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et al. (2017) Dexamethasone implant with fixed or individualized regimen in the treatment of diabetic macular oedema: six-month outcomes of the UDBASA study. Acta ophthalmologica
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95(4): e255–e260
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[<a href="https://pubmed.ncbi.nlm.nih.gov/28139100" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28139100</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in protocol</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng242er8appjtab2"><div id="niceng242er8.appj.tab2" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK607259/table/niceng242er8.appj.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng242er8.appj.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng242er8.appj.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Title</th><th id="hd_h_niceng242er8.appj.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_niceng242er8.appj.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Ramsey, D.J., Poulin, S.J., Lamonica, L.C.
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et al. (2021) Early conversion to aflibercept for persistent diabetic macular edema results in better visual outcomes and lower treatment costs. Clinical Ophthalmology
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15: 31–39
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[<a href="/pmc/articles/PMC7802895/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7802895</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33447009" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33447009</span></a>]
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</td><td headers="hd_h_niceng242er8.appj.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Exclude - not relevant comparator</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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