<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="review-article"><front><journal-meta><journal-id journal-id-type="nlm-ta">J Med Internet Res</journal-id><journal-id journal-id-type="publisher-id">jmir</journal-id><journal-id journal-id-type="index">1</journal-id><journal-title>Journal of Medical Internet Research</journal-title><abbrev-journal-title>J Med Internet Res</abbrev-journal-title><issn pub-type="epub">1438-8871</issn><publisher><publisher-name>JMIR Publications</publisher-name><publisher-loc>Toronto, Canada</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">v28i1e84753</article-id><article-id pub-id-type="doi">10.2196/84753</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Extended Reality Interventions for Osteoarthritis of the Knee and Recovery After Total Knee Arthroplasty: Systematic Review and Meta-Analyses</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Kalinowski</surname><given-names>Caleb</given-names></name><degrees>MS</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Goldsmith</surname><given-names>Elizabeth</given-names></name><degrees>PhD, MD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Anthony</surname><given-names>Maylen</given-names></name><degrees>MPH</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Landsteiner</surname><given-names>Adrienne</given-names></name><degrees>MPH, PhD</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Ullman</surname><given-names>Kristen</given-names></name><degrees>MPH</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Zerzan</surname><given-names>Nicholas</given-names></name><degrees>MPH</degrees><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Rich</surname><given-names>Tonya</given-names></name><degrees>OTR, PhD</degrees><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Calvert</surname><given-names>Collin</given-names></name><degrees>MPH, PhD</degrees><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Wilt</surname><given-names>Timothy J</given-names></name><degrees>PhD, MD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Duan-Porter</surname><given-names>Wei</given-names></name><degrees>PhD, MD</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Ewart</surname><given-names>David</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff8">8</xref></contrib></contrib-group><aff id="aff1"><institution>Veterans Affairs Evidence Synthesis Program, Center for Care Delivery Outcomes Research, Minneapolis Veterans Affairs Health Care System</institution><addr-line>One Veterans Drive</addr-line><addr-line>Minneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff2"><institution>Department of Medicine, University of Minnesota Medical School</institution><addr-line>Minnneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff3"><institution>Department of Orthopedic Surgery, University of Minnesota Medical School</institution><addr-line>Minnneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff4"><institution>Rehabilitation and Engineering Center for Optimizing Veteran Engagement and Reintegration, Minneapolis Veterans Affairs Health Care System</institution><addr-line>Minneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff5"><institution>Department of Family Medicine and Community Health, University of Minnesota Medical School</institution><addr-line>Minnneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff6"><institution>Center for Care Delivery Outcomes Research, Minneapolis Veterans Affairs Health Care System</institution><addr-line>Minneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff7"><institution>University of Minnesota School of Public Health</institution><addr-line>Minnneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><aff id="aff8"><institution>Minneapolis Veterans Affairs Health Care System</institution><addr-line>Minneapolis</addr-line><addr-line>MN</addr-line><country>United States</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Brini</surname><given-names>Stefano</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Costa</surname><given-names>Jose Ferrer</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Baker</surname><given-names>Nancy</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Caleb Kalinowski, MS, Veterans Affairs Evidence Synthesis Program, Center for Care Delivery Outcomes Research, Minneapolis Veterans Affairs Health Care System, One Veterans Drive, Minneapolis, MN, 55417, United States, 1 612-467-1919; <email>caleb.kalinowski@va.gov</email></corresp></author-notes><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>8</day><month>9</month><year>2026</year></pub-date><volume>28</volume><elocation-id>e84753</elocation-id><history><date date-type="received"><day>25</day><month>09</month><year>2025</year></date><date date-type="rev-recd"><day>29</day><month>06</month><year>2026</year></date><date date-type="accepted"><day>01</day><month>07</month><year>2026</year></date></history><copyright-statement>&#x00A9; Caleb Kalinowski, Elizabeth Goldsmith, Maylen Anthony, Adrienne Landsteiner, Kristen Ullman, Nicholas Zerzan, Tonya Rich, Collin Calvert, Timothy J Wilt, Wei Duan-Porter, David Ewart. Originally published in the Journal of Medical Internet Research (<ext-link ext-link-type="uri" xlink:href="https://www.jmir.org">https://www.jmir.org</ext-link>), 8.9.2026. </copyright-statement><copyright-year>2026</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://www.jmir.org/">https://www.jmir.org/</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://www.jmir.org/2026/1/e84753"/><abstract><sec><title>Background</title><p>Nonpharmacologic interventions are important for treating knee pain due to osteoarthritis or after total knee arthroplasty (TKA), and extended reality (XR) technology may enhance treatments for these indications.</p></sec><sec><title>Objective</title><p>This systematic review aimed to evaluate XR interventions for pain due to knee osteoarthritis (KOA) or for recovery after TKA.</p></sec><sec sec-type="methods"><title>Methods</title><p>Databases were searched through May 2023 and updated in December 2025. Eligible trials evaluated XR interventions to treat KOA pain or after TKA. We classified interventions by depth of immersion and clinical mechanism. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria to determine the certainty of evidence for prioritized outcomes. Meta-analyses were performed when &#x2265;3 studies evaluated similar comparisons, outcomes, and time points.</p></sec><sec sec-type="results"><title>Results</title><p>Eligible trials addressed KOA (k=12) or recovery after TKA (k=9). Sample sizes ranged from 36 to 306 participants, and most studies had a follow-up of &#x2264;3 months. Nineteen studies assessed pain-related functioning and pain intensity, and 5 assessed adverse events (AEs). For KOA, 10 studies examined interactive digital rehabilitation (IDR), and 2 examined virtual reality (VR)&#x2013;digitally augmented exercise (DAE). IDR for KOA may result in better pain-related functioning (low certainty of evidence [COE]; pooled standardized mean difference [SMD] &#x2212;0.59, 95% CI &#x2212;1.11 to &#x2212;0.06; prediction interval [PI] &#x2212;1.72 to 0.55; k=5) and lower pain intensity at 6&#x2010;8 weeks (low COE; pooled SMD &#x2212;0.46, 95% CI &#x2212;0.92 to 0.00; PI &#x2212;1.39 to 0.47; k=4). VR-DAE for KOA (k=2) produced inconsistent results (very low COE). For post-TKA studies, 5 examined IDR, 2 examined VR-DAE, 1 examined VR-distraction, and 1 examined VR-psychoeducation. Post-TKA IDR may result in better pain-related functioning (low [k=4] and moderate COE [k=1]) but little to no difference in pain intensity (low-moderate COE; pooled SMD at 3&#x2010;4 months &#x2212;0.12, 95% CI &#x2212;0.75 to 0.52; PI &#x2013;1.63 to 1.27; k=3). VR-psychoeducation probably results in lower pain at 4 weeks (moderate COE; k=1), and VR-distraction may result in 6 months (low COE; k=1), whereas VR-DAE produced mixed findings (k=2; very low COE). IDR was not associated with AEs, and VR may not be associated with AEs for KOA (high and low COE), though AE reporting was uncommon (k=5) and evidence was very uncertain for post-TKA.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>IDR may augment treatment for KOA and post-TKA recovery, and VR may benefit post-TKA rehabilitation. This review is the first to stratify by level of immersion, clinical mechanism, and follow-up duration and to systematically evaluate AEs. IDR may be ready for integration into KOA care, while use after TKA needs more evidence. Randomized controlled trials with implementation outcomes could determine how XR interventions can be used for KOA, whereas trials evaluating efficacy and AEs are needed before their use for post-TKA.</p></sec><sec><title>Trial Registration</title><p>PROSPERO CRD42023439903; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023439903</p></sec></abstract><kwd-group><kwd>knee pain</kwd><kwd>knee osteoarthritis</kwd><kwd>total joint arthroplasty</kwd><kwd>total knee arthroplasty</kwd><kwd>extended reality</kwd><kwd>virtual reality</kwd><kwd>rehabilitation</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><sec id="s1-1"><title>Background</title><p>Osteoarthritis of the knee is a painful chronic condition that is highly prevalent and disabling [<xref ref-type="bibr" rid="ref1">1</xref>-<xref ref-type="bibr" rid="ref3">3</xref>]. In 2008, the prevalence was estimated to be 13.9% among adults aged 25 years and older and 33.6% in those aged 65 years and older, corresponding to approximately 27 million Americans with knee osteoarthritis (KOA) [<xref ref-type="bibr" rid="ref4">4</xref>]. KOA prevalence is rising [<xref ref-type="bibr" rid="ref5">5</xref>], as are rates of total knee replacement [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>]. The direct and indirect economic costs of treating KOA are substantial and include surgical costs associated with TKA, disability among people with painful and limiting disease, and loss of work-related productivity. Direct and indirect lifetime costs for persons diagnosed with KOA were estimated in 2013 to be US $140,300 [<xref ref-type="bibr" rid="ref8">8</xref>].</p><p>Nonpharmacologic therapies (eg, exercise) are first-line treatments for KOA due to their benefits and low risks, particularly compared with opioids and invasive procedures [<xref ref-type="bibr" rid="ref9">9</xref>-<xref ref-type="bibr" rid="ref12">12</xref>]. Pharmacologic therapies are also frequently used for KOA but carry well-described adverse effects [<xref ref-type="bibr" rid="ref13">13</xref>]. When these therapies yield insufficient improvement in symptoms, patients may undergo invasive procedures, such as injections using corticosteroids or viscosupplementation, or surgical procedures, such as total knee arthroplasty (TKA), all of which are associated with risks of AEs. Nondrug treatments (eg, exercise) often require long-term adherence, making patient engagement a key factor in their effectiveness and durability. Similar nondrug treatments are also used in post-TKA rehabilitation as an integral part of postprocedure recovery.</p><p>Extended reality (XR) technology can deliver pain interventions using various clinical mechanisms, including pain self-management education, psychological skills, passive distraction, and digitally augmented exercise (DAE) [<xref ref-type="bibr" rid="ref14">14</xref>,<xref ref-type="bibr" rid="ref15">15</xref>]. The popularity of XR technologies, decreasing costs, increased availability, and innovations in XR hardware and software have contributed to increased interest in this relatively new application. XR can be categorized according to the level of immersion experienced by the user in the digital environment [<xref ref-type="bibr" rid="ref15">15</xref>]. Virtual reality (VR) presents the highest (full) level of immersion within an interactive digital environment and describes a state in which the user is fully enclosed within an artificial virtual space in which the visual sense is sealed off from the physical environment [<xref ref-type="bibr" rid="ref15">15</xref>]. For example, users may undergo guided relaxation training taking place in digitally created settings, such as a peaceful forest or relaxing seaside environment, that are visually separated from the real-world physical environment. Full immersion is typically achieved with the use of a headset. Nonimmersive technologies have been used to facilitate DAE and have historically been evaluated in the context of XR but do not incorporate the user&#x2019;s physical world into the visual experience and are referred to as interactive digital rehabilitation (IDR) for the purposes of this report. These screen-based technologies are best showcased in gaming systems like Microsoft Kinect and Nintendo Wii (Nintendo Co, Ltd) [<xref ref-type="bibr" rid="ref16">16</xref>]. XR interventions have demonstrated utility for reducing acute pain through distraction (eg, during dental procedures) [<xref ref-type="bibr" rid="ref17">17</xref>], but whether these interventions improve outcomes when integrated into treatment plans for chronic musculoskeletal pain conditions remains unclear. Prior systematic reviews of XR for KOA [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref19">19</xref>] and post-TKA rehabilitation [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref21">21</xref>] have often pooled heterogeneous XR technologies without stratifying results by level of immersion. Results at varying follow-up durations have also been pooled, and there has been a lack of systematic evaluation of adverse events (AEs). An updated synthesis is warranted given the rapid expansion of the XR evidence base in recent years and the increasing availability of XR devices in clinical and home settings.</p></sec><sec id="s1-2"><title>Key Questions</title><p>In this review, the objective was to synthesize available evidence on the benefits and harms of XR interventions for the treatment of chronic KOA pain and symptomatic recovery after TKA, with results stratified by level of immersion (VR vs IDR), clinical mechanism, and follow-up duration and with certainty of evidence summarized using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.</p><p>We present findings on KOA and post-TKA that were part of a larger systematic review undertaken to evaluate the evidence on XR therapies for treating chronic and acute pain conditions [<xref ref-type="bibr" rid="ref22">22</xref>]. Thus, the results included here focus on the following key question: What are the benefits and harms of XR interventions for the treatment of chronic knee pain due to osteoarthritis or for recovery after TKA?</p></sec></sec><sec id="s2" sec-type="methods"><title>Methods</title><sec id="s2-1"><title>Registration</title><p>A preregistered protocol for the larger review can be found on PROSPERO (International Prospective Register of Systematic Reviews; registration number <ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=439903">CRD42023439903</ext-link>). This review is reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 statement [<xref ref-type="bibr" rid="ref23">23</xref>], with search reporting following the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Literature Search Extension) [<xref ref-type="bibr" rid="ref24">24</xref>]. The PRISMA 2020 and PRISMA-S checklists are provided as <xref ref-type="supplementary-material" rid="app14">Checklist 1</xref>. There were no deviations from the registered protocol with respect to the eligible populations, interventions, comparators, outcomes, or analytic approach reported in this manuscript.</p></sec><sec id="s2-2"><title>Eligibility Criteria</title><p>Eligible studies evaluated XR interventions for adults with symptomatic KOA or those who had undergone TKA. Prioritized outcomes were pain-related functioning or interference, pain intensity or severity, and AEs. Other eligible outcomes included pain global change, pain catastrophizing, and kinesiophobia, quality of life, opioid dose or use, physical performance, and adherence. AEs were defined broadly as any untoward medical event occurring during or following the intervention and, for XR interventions, specifically included cybersickness (nausea, dizziness, eye strain, or disorientation related to visual-vestibular mismatch), motion sickness, musculoskeletal injury, and falls. All results compatible with each outcome as they pertained specifically to KOA or post-TKA recovery at any timepoint were sought.</p></sec><sec id="s2-3"><title>Database Searches and Article Selection</title><p>MEDLINE, Embase, Scopus, CINAHL, and PsycINFO were searched from inception to May 2023 using subject headings and keywords for VR, exergaming, and pain, along with additional terms for conditions in which pain is a predominant symptom (eg, arthritis). Duplicate records were removed prior to abstract screening using deduplication tools in EndNote (Clarivate) [<xref ref-type="bibr" rid="ref25">25</xref>] and DistillerSR (Evidence Partners) [<xref ref-type="bibr" rid="ref26">26</xref>]. Titles and abstracts were screened in DistillerSR by 2 separate reviewers (2 separate reviewers for each reference: combination of CK, DDP, DE, CC, MA, AL, KU, NZ) with agreement from both required to exclude. Included abstracts were moved to full-text review, with eligibility again requiring consensus of 2 separate reviewers. Disagreements were resolved with input from additional team members. Excluded references are shown in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>. Database searches were not adapted from any previous review. Relevant systematic reviews identified during the database searches were hand-searched for additional articles. No search peer-review process was undertaken, and no additional sources were purposively searched or consulted. Searches were updated in December 2025 using the original search terms, with the exception of the population of interest, which was narrowed to focus solely on KOA and TKA. <xref ref-type="supplementary-material" rid="app2">Multimedia Appendices 2</xref> and <xref ref-type="supplementary-material" rid="app3">3</xref> provide detailed study eligibility criteria and complete search strategies. The study screening process and literature flow are depicted using the PRISMA 2020 flow diagram [<xref ref-type="bibr" rid="ref23">23</xref>].</p></sec><sec id="s2-4"><title>Data Abstraction</title><p>Data were abstracted by 1 reviewer and verified by a second reviewer. Abstracted data included participant characteristics and inclusion/exclusion criteria; intervention characteristics (technology and devices used, content and goals of intervention); study design and settings; and findings for primary and secondary outcomes (eg, baseline and follow-up means and SDs, change in scores and SDs of changes, and <italic>P</italic> values calculated by studies). Data were abstracted into forms constructed in DistillerSR.</p></sec><sec id="s2-5"><title>Risk of Bias Assessment</title><p>Risk of bias (RoB) assessments were conducted independently by 2 researchers using the Cochrane Risk of Bias 2.0 tool [<xref ref-type="bibr" rid="ref27">27</xref>], which was also adapted to DistillerSR. Discrepancies were resolved by consensus, with input from other parties for resolution as needed. RoB assessments for each included study [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref49">49</xref>] are shown in <xref ref-type="fig" rid="figure1">Figure 1</xref>.</p><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>Patient-reported outcome measures reported by included studies [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref49">49</xref>].</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e84753_fig01.png"/></fig></sec><sec id="s2-6"><title>Synthesis and Effect Measures</title><p>We synthesized findings from eligible studies qualitatively and, where &#x2265;3 sufficiently similar studies provided appropriate outcome data at comparable time points, performed random-effects meta-analyses using the Hartung-Knapp-Sidik-Jonkman method [<xref ref-type="bibr" rid="ref50">50</xref>-<xref ref-type="bibr" rid="ref52">52</xref>] using <italic>meta, metafor,</italic> and <italic>pimeta</italic> packages and R (version 4.3.1; R Foundation for Statistical Computing) to generate forest plots [<xref ref-type="bibr" rid="ref53">53</xref>]. We examined intervention, comparator, and participant characteristics to determine whether studies were similar, including first grouping studies by clinical indication (ie, osteoarthritis, knee pain, or post-TKA), intervention classification as VR or IDR (according to the framework proposed by Rauschnabel et al [<xref ref-type="bibr" rid="ref15">15</xref>] and Spiegal et al [<xref ref-type="bibr" rid="ref16">16</xref>]) and clinical mechanism (distraction or DAE). Distraction refers to the effect of directing attentional resources of the user away from unpleasant symptoms or stimuli, involving techniques such as music, imagery, or relaxation [<xref ref-type="bibr" rid="ref54">54</xref>,<xref ref-type="bibr" rid="ref55">55</xref>]. DAE entails an interactive process through which the user is given instruction or a demonstration of a target exercise before performing the exercise themselves [<xref ref-type="bibr" rid="ref46">46</xref>]. Author-reported XR equipment and devices are shown in <xref ref-type="supplementary-material" rid="app4">Multimedia Appendix 4</xref>.</p><p>For efficacy outcomes (measures described in <xref ref-type="table" rid="table1">Table 1</xref>), we assessed between-group differences in mean changes of continuous outcomes (ie, difference in change scores [Diff &#x0394;]), preferentially as standardized effect sizes (Diff &#x0394;/SD of change) [<xref ref-type="bibr" rid="ref56">56</xref>]. To calculate Diff &#x0394;, we subtracted the mean change in the comparator group from the mean change in the XR intervention group (&#x0394;<sub>XR</sub>&#x2013;&#x0394;<sub>C</sub>). Thus, for outcome measures in which lower scores are better (eg, pain intensity or severity), a negative value for Diff &#x0394; indicates greater improvement in the XR intervention group. <xref ref-type="table" rid="table1">Table 1</xref> provides a description of the standardized measures reported by studies and the interpretation of scores (eg, higher score is better or worse).</p><table-wrap id="t1" position="float"><label>Table 1.</label><caption><p>Patient-reported outcome measures reported by included studies.</p></caption><table id="table1" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Outcome category<break/>Measure name</td><td align="left" valign="bottom">Scoring range (number<break/>of items and domains)</td></tr></thead><tbody><tr><td align="left" valign="top">Pain-related functioning</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>WOMAC<sup><xref ref-type="table-fn" rid="table1fn1">a</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;96 (lower is better)</p></list-item><list-item><p>24 items (3 domains: physical function; pain; and stiffness)</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>KOOS<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;100 (higher is better)</p></list-item><list-item><p>42 items (5 domains: pain, ADL<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup>, sports and recreation, QoL<sup><xref ref-type="table-fn" rid="table1fn4">d</xref></sup>, and symptoms)</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>OKS<sup><xref ref-type="table-fn" rid="table1fn5">e</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;48 (higher is better)</p></list-item><list-item><p>12 items</p></list-item></list></td></tr><tr><td align="left" valign="top">Pain severity or intensity</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>VAS<sup><xref ref-type="table-fn" rid="table1fn6">f</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;10 (lower is better)</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>NRS<sup><xref ref-type="table-fn" rid="table1fn7">g</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;10 (lower is better)</p></list-item></list></td></tr><tr><td align="left" valign="top">Health-related quality of life</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>WHOQOL-BREF<sup><xref ref-type="table-fn" rid="table1fn8">h</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;100 (higher is better)</p></list-item><list-item><p>26 items (4 domains: physical health; psychological health; social relationships; and environment)</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>CDC<sup><xref ref-type="table-fn" rid="table1fn9">i</xref></sup> Health-Related Quality of Life</td><td align="left" valign="top"><list list-type="bullet"><list-item><p>Multiple indices</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>EQ-5D</td><td align="left" valign="top"><list list-type="bullet"><list-item><p>0&#x2010;1 (higher is better)</p></list-item></list></td></tr><tr><td align="left" valign="top">Kinesiophobia</td><td align="left" valign="top"/></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>TSK<sup><xref ref-type="table-fn" rid="table1fn10">j</xref></sup></td><td align="left" valign="top"><list list-type="bullet"><list-item><p>17&#x2010;68 (lower is better)</p></list-item><list-item><p>17 items (4 domains: fear of injury, dysfunctional self, perceived danger for heart problems, and avoidance of exercise)</p></list-item></list></td></tr></tbody></table><table-wrap-foot><fn id="table1fn1"><p><sup>a</sup>WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.</p></fn><fn id="table1fn2"><p><sup>b</sup>KOOS: Knee Injury and Osteoarthritis Outcome Score.</p></fn><fn id="table1fn3"><p><sup>c</sup>ADL: activities of daily living.</p></fn><fn id="table1fn4"><p><sup>d</sup>QoL: quality of life.</p></fn><fn id="table1fn5"><p><sup>e</sup>OKS: Oxford Knee Score.</p></fn><fn id="table1fn6"><p><sup>f</sup>VAS: Visual Analog Scale.</p></fn><fn id="table1fn7"><p><sup>g</sup>NRS: Numeric Rating Scale.</p></fn><fn id="table1fn8"><p><sup>h</sup>WHOQOL-BREF: World Health Organization Quality of Life Brief Version.</p></fn><fn id="table1fn9"><p><sup>i</sup>CDC: Centers for Disease Control and Prevention.</p></fn><fn id="table1fn10"><p><sup>j</sup>TSK: Tampa Scale for Kinesiophobia.</p></fn></table-wrap-foot></table-wrap><p>In determining whether there were between-group differences in efficacy outcomes, we preferentially examined standardized Diff &#x0394; and applied recommended thresholds (eg, &#x003C;0.2 indicates no between-group difference) [<xref ref-type="bibr" rid="ref56">56</xref>]. If standardized Diff &#x0394; was not reported and could not be calculated (eg, due to lack of SD or confidence intervals), we considered study analyses and interpretations of findings, as well as actual Diff &#x0394; values, to determine whether there were between-group differences. No sensitivity analyses were conducted.</p></sec><sec id="s2-7"><title>Reporting Bias Assessment</title><p>Reporting bias was not formally assessed quantitatively (eg, funnel plot asymmetry tests) because no individual meta-analytic comparison included &#x2265;10 studies, below which such tests are considered unreliable [<xref ref-type="bibr" rid="ref57">57</xref>]. We instead considered the potential for missing studies qualitatively, including inspection of trial registries and reference lists of prior systematic reviews identified during the searches.</p></sec><sec id="s2-8"><title>Certainty of Evidence Assessments</title><p>We assessed certainty of evidence (COE) for 3 prioritized outcomes, including pain-related functioning or interference, pain intensity or severity, and AEs. We rated the COE for these outcomes separately for VR and IDR interventions by clinical mechanism (DAE, distraction, or psychoeducation) and by condition (ie, KOA pain and post-TKA pain and rehabilitation). We used GRADE methodology [<xref ref-type="bibr" rid="ref58">58</xref>] to rate overall COE as high, moderate, low, or very low (<xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>). For each prioritized outcome, we used the GRADEpro Guideline Development Tool (GDT) [<xref ref-type="bibr" rid="ref59">59</xref>] to systematically evaluate 5 domains: study limitations, imprecision, inconsistency, indirectness, and other considerations. For presentation of anticipated absolute effects, data from exemplar studies used to illustrate the range and direction of findings at time points were selected on the basis of (1) lower RoB ratings and (2) the largest sample size. Certainty of evidence tables are found in <xref ref-type="supplementary-material" rid="app6">Multimedia Appendices 6</xref> and <xref ref-type="supplementary-material" rid="app7">7</xref>.</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><sec id="s3-1"><title>Overview of Included Studies</title><p>We identified 21 studies [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref49">49</xref>] (reported in 22 publications) that evaluated the use of XR interventions for patients with KOA (k=12) or post-TKA (k=9; <xref ref-type="fig" rid="figure2">Figure 2</xref>), as summarized in <xref ref-type="table" rid="table2">Table 2</xref>. The studies were mostly small to moderate in size (k=18 with a total number of participants n&#x2264;100), with a few that were larger (k=2 with n=101&#x2010;200 and k=1 with n&#x003E;200). Follow-up duration ranged from 2 weeks to 6 months with most studies (k=16) having &#x2264;3 months of follow-up. The primary clinical mechanism was consistent throughout the studies, with 19 studies [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>-<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref41">41</xref>-<xref ref-type="bibr" rid="ref49">49</xref>] using DAE and 1 study [<xref ref-type="bibr" rid="ref33">33</xref>] using distraction and 1 [<xref ref-type="bibr" rid="ref40">40</xref>] using psychoeducation. No studies reported on pain, global change, or opioid use. All but one study [<xref ref-type="bibr" rid="ref47">47</xref>] was conducted outside of the United States (k=20), and most included middle-aged (k=10 aged 30&#x2010;64 years) and older adults (k=7 aged &#x2265;65 years). One study included only young adults with posttraumatic osteoarthritis [<xref ref-type="bibr" rid="ref42">42</xref>], and mean age was not reported in k=3 studies [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref46">46</xref>]. Studies were rated as having a high RoB (k=10) [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref43">43</xref>-<xref ref-type="bibr" rid="ref46">46</xref>], some concerns for RoB (k=11) [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>-<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref40">40</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref47">47</xref>-<xref ref-type="bibr" rid="ref49">49</xref>], or a low RoB (k=1) [<xref ref-type="bibr" rid="ref29">29</xref>]. Detailed RoB assessments are shown in Figure 1. Detailed trial characteristics are found in <xref ref-type="supplementary-material" rid="app8">Multimedia Appendices 8</xref> and <xref ref-type="supplementary-material" rid="app9">9</xref>.</p><fig position="float" id="figure2"><label>Figure 2.</label><caption><p>Study selection flow diagram. ISRCTN: International Standard Randomized Controlled Trial Number; TKA: total knee arthroplasty.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e84753_fig02.png"/></fig><table-wrap id="t2" position="float"><label>Table 2.</label><caption><p>Characteristics of studies on knee osteoarthritis (KOA) and rehabilitation posttotal knee arthroplasty (TKA).</p></caption><table id="table2" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" colspan="2">Characteristic and subcategory</td><td align="left" valign="bottom">KOA<sup><xref ref-type="table-fn" rid="table2fn1">a</xref></sup> VR<sup><xref ref-type="table-fn" rid="table2fn2">b</xref></sup> (k=2)</td><td align="left" valign="bottom">KOA IDR<sup><xref ref-type="table-fn" rid="table2fn3">c</xref></sup> (k=10)</td><td align="left" valign="bottom">Post-TKA<sup><xref ref-type="table-fn" rid="table2fn4">d</xref></sup> VR (k=4)</td><td align="left" valign="bottom">Post-TKA IDR (k=5)</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="2">Mechanism of XR<sup><xref ref-type="table-fn" rid="table2fn5">e</xref></sup> intervention</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Distraction</td><td align="left" valign="top">&#x2014;<sup><xref ref-type="table-fn" rid="table2fn6">f</xref></sup></td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Psychoeducation</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Digitally augmented exercise (DAE<sup><xref ref-type="table-fn" rid="table2fn7">g</xref></sup>)</td><td align="left" valign="top">2 (100)</td><td align="left" valign="top">10 (100)</td><td align="left" valign="top">2 (50)</td><td align="left" valign="top">5 (100)</td></tr><tr><td align="left" valign="top" colspan="2">Outcomes reported</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Pain-related functioning or interference</td><td align="left" valign="top">2 (100)</td><td align="left" valign="top">9 (90)</td><td align="left" valign="top">4 (100)</td><td align="left" valign="top">4 (80)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Pain intensity or severity</td><td align="left" valign="top">2 (100)</td><td align="left" valign="top">8 (80)</td><td align="left" valign="top">4 (100)</td><td align="left" valign="top">4 (80)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Adverse events</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">3 (30)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (20)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Quality of life</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">2 (20)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">3 (60)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Kinesiophobia/pain catastrophizing</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (10)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Physical performance</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">8 (80)</td><td align="left" valign="top">3 (75)</td><td align="left" valign="top">5 (100)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Adherence</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">1 (10)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2">Sample size</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x003C;50</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">3 (30)</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>50&#x2010;75</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">6 (60)</td><td align="left" valign="top">3 (75)</td><td align="left" valign="top">2 (40)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>76&#x2010;100</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">1 (10)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>101&#x2010;200</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">2 (40)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x003E;200</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (20)</td></tr><tr><td align="left" valign="top" colspan="2">Region</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Europe</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">4 (40)</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">3 (60)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>North America</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (20)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Middle East</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">2 (20)</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Asia</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">2 (20)</td><td align="left" valign="top">2 (50)</td><td align="left" valign="top">1 (20)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>South America</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">2 (20)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2">Follow-up duration (days)</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x003C;30 days</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">5 (50)</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>30&#x2010;90 days</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">5 (50)</td><td align="left" valign="top">2 (50)</td><td align="left" valign="top">3 (60)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x003E;90 days</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">2 (40)</td></tr><tr><td align="left" valign="top" colspan="2">Mean/median age (years)</td><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x003C;30</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (10)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">&#x2014;</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>30&#x2010;64</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">8 (80)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (20)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>&#x2265;65</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (10)</td><td align="left" valign="top">3 (75)</td><td align="left" valign="top">4 (80)</td></tr><tr><td align="left" valign="top" colspan="2"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Not Reported</td><td align="left" valign="top">1 (50)</td><td align="left" valign="top">&#x2014;</td><td align="left" valign="top">1 (25)</td><td align="left" valign="top">&#x2014;</td></tr></tbody></table><table-wrap-foot><fn id="table2fn1"><p><sup>a</sup>KOA: knee osteoarthritis.</p></fn><fn id="table2fn2"><p><sup>b</sup>VR: virtual reality.</p></fn><fn id="table2fn3"><p><sup>c</sup>IDR: interactive digital rehabilitation.</p></fn><fn id="table2fn4"><p><sup>d</sup>TKA: total knee arthroplasty.</p></fn><fn id="table2fn5"><p><sup>e</sup>XR: extended reality.</p></fn><fn id="table2fn6"><p><sup>f</sup>Not applicable.</p></fn><fn id="table2fn7"><p><sup>g</sup>DAE: digitally augmented exercise.</p></fn></table-wrap-foot></table-wrap><p>Below, we provide results first for KOA studies and then for rehabilitation post-TKA. Findings for each condition are grouped according to intervention type (VR or IDR) and clinical mechanism. Detailed results are found in <xref ref-type="supplementary-material" rid="app10">Multimedia Appendices 10</xref> and <xref ref-type="supplementary-material" rid="app11">11</xref>.</p></sec><sec id="s3-2"><title>KOA</title><p>Twelve trials evaluated XR interventions for chronic knee pain due to osteoarthritis. Studies involved VR (k=2) [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref45">45</xref>] or IDR (k=10) [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] interventions compared with conventional therapy. Trial characteristics and main findings are summarized in <xref ref-type="table" rid="table3">Table 3</xref>.</p><table-wrap id="t3" position="float"><label>Table 3.</label><caption><p>Summary of findings for knee osteoarthritis interventions. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring scales vary across included studies (eg, 0-96 Likert, 0-240, or 0-2400 visual analog/numerical); raw difference-in-change (Diff &#x0394;) values for WOMAC are therefore not directly comparable across studies using different scale versions. Standardized mean differences used in the meta-analyses are unaffected by scale version.</p></caption><table id="table3" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Author, Year; Country; RoB<sup><xref ref-type="table-fn" rid="table3fn1">a</xref></sup></td><td align="left" valign="bottom">Key participant characteristics</td><td align="left" valign="bottom">Study arms, N randomized (N analyzed)</td><td align="left" valign="bottom">Setting and duration</td><td align="left" valign="bottom" colspan="4">Outcomes</td></tr><tr><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom"/><td align="left" valign="bottom">Pain-related functioning</td><td align="left" valign="bottom">Pain intensity or severity</td><td align="left" valign="bottom">Adverse events</td><td align="left" valign="bottom">Other eligible outcomes<sup><xref ref-type="table-fn" rid="table3fn2">b</xref></sup></td></tr></thead><tbody><tr><td align="left" valign="top" colspan="8">VR intervention trials</td></tr><tr><td align="left" valign="top">&#x2003;Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>]; China; some concerns<break/>&#x2003;</td><td align="left" valign="top">Knee osteoarthritis (ACR<sup><xref ref-type="table-fn" rid="table3fn3">c</xref></sup> criteria), moderate-to-severe knee pain for &#x2265;3 months; mean age NR<sup><xref ref-type="table-fn" rid="table3fn4">d</xref></sup>; 33%-43% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Smartphone VR app capturing outdoor garden scenes via headset, plus standard care; N=15 (15)</p></list-item><list-item><p>Standard care; N=15 (15)</p></list-item></list></td><td align="left" valign="top">Home; 12 weeks</td><td align="left" valign="top">WOMAC<sup><xref ref-type="table-fn" rid="table3fn5">e</xref></sup> (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 902.9 (454.8)</p></list-item><list-item><p>Comparator: 752.0 (549.3)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>6-wk: 82.6; <italic>P</italic>=.66</p></list-item><list-item><p>12-wk: &#x2013;61.3; <italic>P</italic>=.69</p></list-item></list></td><td align="left" valign="top">NRS<sup><xref ref-type="table-fn" rid="table3fn7">g</xref></sup><list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 5.9 (1.9)</p></list-item><list-item><p>Comparator: 4.8 (1.5)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>6-wk: &#x2013;0.04; <italic>P</italic>=.95</p></list-item><list-item><p>12-wk: &#x2013;0.42; <italic>P</italic>=.64<sup><xref ref-type="table-fn" rid="table3fn7">g</xref></sup></p></list-item></list></td><td align="left" valign="top">Cybersickness: 5 events in VR<sup><xref ref-type="table-fn" rid="table3fn8">h</xref></sup> group</td><td align="left" valign="top">Quality of Life<list list-type="bullet"><list-item><p>EQ-VAS<sup><xref ref-type="table-fn" rid="table3fn9">i</xref></sup></p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;&#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>]; Turkey; high<break/>&#x2003;</td><td align="left" valign="top">Knee osteoarthritis, Kellgren-Lawrence grade 2-3 (ACR criteria); mean age 53-54 years; 49%-68% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Oculus headset games focusing on lateral movements and trunk flexion to interact with virtual targets, and therapeutic ultrasound and TENS<sup><xref ref-type="table-fn" rid="table3fn10">j</xref></sup> treatment; N=41 (35)</p></list-item><list-item><p>Conventional treatment, ultrasound, and TENS; N=41 (38)</p></list-item></list></td><td align="left" valign="top">Clinic; 3 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 31.7 (6.8)</p></list-item><list-item><p>Comparator: 33.0 (7.9)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup><sup>,</sup><sup><xref ref-type="table-fn" rid="table3fn11">k</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: &#x2013;8.7</p></list-item><list-item><p>7-wk: &#x2013;5.1</p></list-item></list></td><td align="left" valign="top">VAS<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 5.6 (0.9)</p></list-item><list-item><p>Comparator: 5.8 (0.7)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: &#x2013;0.7</p></list-item><list-item><p>7-wk: &#x2013;1.1</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>6-minute walk</p></list-item><list-item><p>Berg Balance Scale</p></list-item></list></td></tr><tr><td align="left" valign="top" colspan="8">IDR<sup><xref ref-type="table-fn" rid="table3fn12">l</xref></sup> intervention trials</td></tr><tr><td align="left" valign="top">&#x2003;Buyukyilmaz et al [<xref ref-type="bibr" rid="ref28">28</xref>]; Turkey; high</td><td align="left" valign="top">Knee osteoarthritis (ACR criteria), Kellgren-Lawrence grade 2&#x2010;3, osteoarthritis-induced pain &#x2265;6 months; mean ages 59&#x2010;60, 100% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Becure Balance System (Wii-based exergame with balance board), plus conventional PT<sup><xref ref-type="table-fn" rid="table3fn13">m</xref></sup>; N=28</p></list-item><list-item><p>Conventional PT; N=28</p></list-item></list></td><td align="left" valign="top">Clinic; 8 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 47.1 (12.1)</p></list-item><list-item><p>Comparator: 53.0 (11.2)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup></p></list-item></list><list list-type="bullet"><list-item><p>4-wk: NR</p></list-item><list-item><p>8-wk: NR</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>ROM<sup><xref ref-type="table-fn" rid="table3fn14">n</xref></sup> knee flexion</p></list-item><list-item><p>Knee flexion/extension strength (kg-force)</p></list-item><list-item><p>Joint position sense (15&#x00B0;, 45&#x00B0;, and 75&#x00B0;)</p></list-item><list-item><p>TUG</p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;Carvajal-Parodi et al [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref34">34</xref>]; Chile; low</td><td align="left" valign="top">Mild-to-moderate KOA and/or HOA (ACR criteria), Kellgren-Lawrence grade 2&#x2010;3; mean age 69; 83% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Nintendo Switch exergame on 43-in television; N=30</p></list-item><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Comparator; N=30</p></list-item></list></td><td align="left" valign="top">Clinic; 4 weeks</td><td align="left" valign="top">NR</td><td align="left" valign="top">VAS<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 46.7 (19.7)</p></list-item><list-item><p>Comparator: 46.3 (24.1)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-wk: NR</p></list-item></list></td><td align="left" valign="top">&#x201C;No adverse events were reported&#x201D;</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>TUG</p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;Dal Erdogan et al [<xref ref-type="bibr" rid="ref30">30</xref>]; Turkey; high</td><td align="left" valign="top">Knee osteoarthritis, Kellgren-Lawrence stage 2&#x2010;3, mean ages 60&#x2010;61, 78% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>BTS Nirvana virtual reality rehabilitation device analyzing patient movements; N=18</p></list-item><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Comparator; N=18</p></list-item></list></td><td align="left" valign="top">Clinic; 3 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 65.0 (6.9)</p></list-item><list-item><p>Comparator: 61.9 (7.9)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: NR</p></list-item></list><break/>WOMAC (pain)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 10.3 (1.8)</p></list-item><list-item><p>Comparator: 10.3 (1.8)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: NR</p></list-item></list></td><td align="left" valign="top">VAS (movement)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 6.1 (1.0)</p></list-item><list-item><p>Comparator: 6.4 (1.2)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: NR</p></list-item></list><list list-type="simple"><list-item><p>VAS (rest)</p></list-item></list><list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 6.1 (1.2)</p></list-item><list-item><p>Comparator:6.1 (1.2)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: NR</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">NR</td></tr><tr><td align="left" valign="top">&#x2003;Elshazly et al [<xref ref-type="bibr" rid="ref32">32</xref>]; Saudi Arabia;<break/>&#x2003;some concerns<break/>&#x2003;</td><td align="left" valign="top">&#x2265;3 mo osteoarthritis, can walk &#x2265;30 ft without assistance, and not in any sports or PT; mean ages 58&#x2010;60, women NR</td><td align="left" valign="top">3 Arms:<list list-type="bullet"><list-item><p>Game involving standing and taking steps on virtual platform (device NR), N=20 (20)</p></list-item><list-item><p>Sensorimotor training (SMT), N=20 (20)</p></list-item><list-item><p>Walking program, N=20 (20)</p></list-item></list></td><td align="left" valign="top">Clinic; 8 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>IDR: 71.7 (3.4)</p></list-item><list-item><p>SMT&#x2014;71.7 (2.8)</p></list-item><list-item><p>Walking: 71.9 (3.1)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (IDR-SMT)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;13.5</p></list-item><list-item><p>8-week: &#x2013;19.5</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (IDR-Walking)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;14.1</p></list-item><list-item><p>8-week: &#x2013;29.9</p></list-item></list></td><td align="left" valign="top">VAS<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>IDR: 6.8 (0.9)</p></list-item><list-item><p>SMT: 6.6 (1.2)</p></list-item><list-item><p>Walking: 6.68 (0.84)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (IDR&#x2013;SMT)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;1.9</p></list-item><list-item><p>8-week: &#x2013;1.8</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (IDR-Walking)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;1.8</p></list-item><list-item><p>8-week: &#x2013;2.0</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Quality of life<list list-type="bullet"><list-item><p>CDC<sup><xref ref-type="table-fn" rid="table3fn15">o</xref></sup> Health Related</p></list-item><list-item><p>Quality of life</p></list-item><list-item><p>Physical performance position sense</p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;Jarungvittayakon et al [<xref ref-type="bibr" rid="ref36">36</xref>]; Thailand; some concerns</td><td align="left" valign="top">Knee osteoarthritis (ACR criteria), Kellgren-Lawrence grade 2&#x2010;3; mean ages 59.9&#x2010;62.1; 79%&#x2010;82% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Wearable sensor exergame (mobile app with knee sensors for airplane game requiring knee flexion/extension), plus standard conservative treatment; N=28</p></list-item><list-item><p>Standard conservative treatment (quadriceps strengthening, medications, self-care advice); N=28</p></list-item></list></td><td align="left" valign="top">Home; 6 weeks</td><td align="left" valign="top">KOOS<sup><xref ref-type="table-fn" rid="table3fn16">p</xref></sup><list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 63.0 (16.9)</p></list-item><list-item><p>Comparator: 65.4 (17.2)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>6-wk: 7.5</p></list-item></list></td><td align="left" valign="top">VAS (in motion)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 5.5 (2.0)</p></list-item><list-item><p>Comparator: 6.5 (2.4)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>6-wk: &#x2212;1.3, <italic>P</italic>=.0002</p></list-item></list><break/>VAS (at rest)<list list-type="bullet"><list-item><p>Baseline medians:</p></list-item></list><list list-type="bullet"><list-item><p>VR: 2 (IQR NR)</p></list-item><list-item><p>Comparator: 2 (IQR NR)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>6-wk: &#x2013;1.0; <italic>P</italic>=.025</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>ROM Flexion</p></list-item><list-item><p>ROM Extension</p></list-item><list-item><p>Arc of motion</p></list-item><list-item><p>TUG</p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;Lin et al [<xref ref-type="bibr" rid="ref38">38</xref>]; Taiwan; some concerns</td><td align="left" valign="top">Knee osteoarthritis (ACR criteria), Kellgren and Lawrence grade &#x2265;2, able to walk &#x003E;15 m, and not needing NSAIDs<sup><xref ref-type="table-fn" rid="table3fn17">q</xref></sup>; mean ages 56&#x2010;58, 43&#x2010;60% female</td><td align="left" valign="top">2 Arms<list list-type="bullet"><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Games involving interaction with virtual targets through lower limb and trunk movements (via sensor pad for feet), in addition to temperature therapy and TENS; N=40 (40)</p></list-item><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Temperature therapy, TENS, and conventional exercise program (stretching, stabilization exercises, etc); N=40 (40)</p></list-item></list></td><td align="left" valign="top">Clinic; 4 weeks</td><td align="left" valign="top">WOMAC (physical function)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 505.1 (328.4)</p></list-item><list-item><p>Comparator: 581.0 (383.8)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>2-week: 39.1</p></list-item><list-item><p>4-week: 60.3</p></list-item><list-item><p>8-week: 90.0</p></list-item><list-item><p>16-week: 82.8</p></list-item></list></td><td align="left" valign="top">WOMAC (pain)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 161.2 (114.7)</p></list-item><list-item><p>Comparator: 170.2 (121.3)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>2-week: 0.7</p></list-item><list-item><p>4-week: 3.9</p></list-item><list-item><p>8-week: &#x2013;19.9</p></list-item><list-item><p>16-week: 4.9</p></list-item></list></td><td align="left" valign="top">&#x201C;No adverse effects observed in either group&#x201D;</td><td align="left" valign="top">Quality of life<list list-type="bullet"><list-item><p>WHOQOL<sup><xref ref-type="table-fn" rid="table3fn18">r</xref></sup>-BREF</p></list-item></list><break/>Physical performance<list list-type="bullet"><list-item><p>Biodex stability system</p></list-item><list-item><p>10 meter walk time</p></list-item><list-item><p>Stair ascent, descent time</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Mete and Sari [<xref ref-type="bibr" rid="ref41">41</xref>]; Turkey; high</td><td align="left" valign="top">Knee osteoarthritis, Kellgren and Lawrence grade 2&#x2010;3; median ages 57&#x2010;60, 77&#x2010;88% women</td><td align="left" valign="top">2 Arms<list list-type="bullet"><list-item><p>Games involving control of on-screen avatars through knee flexion and extension, via special device (MarVAJED) with sensors for joint positions and provided auditory and visual feedback, in addition to comparator treatment; N=32 (30)</p></list-item><list-item><p>Conventional treatment with ultrasound, TENS, temperature therapy, and muscle strengthening exercises; N=32 (30)</p></list-item></list></td><td align="left" valign="top">Clinic; 6 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline medians (IQR):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 19.7 (18.2-21)</p></list-item><list-item><p>Comparator: 15.1 (9.3-18)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;: not calculable<sup><xref ref-type="table-fn" rid="table3fn19">s</xref></sup></p></list-item></list></td><td align="left" valign="top">WOMAC (pain)<break/>Baseline medians (IQR):<list list-type="bullet"><list-item><p>Intervention: 6 (5.37-7.12)</p></list-item><list-item><p>Comparator: 4.5 (4.3-6)</p></list-item></list><break/>Diff &#x0394; not calculable<sup><xref ref-type="table-fn" rid="table3fn19">s</xref></sup><break/>VAS (at rest)<list list-type="bullet"><list-item><p>Baseline medians (IQR):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 32.2 (20.8-40.0)</p></list-item><list-item><p>Comparator: 36.3 (30.0-40.0)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; not calculable<sup><xref ref-type="table-fn" rid="table3fn19">s</xref></sup></p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">&#x2003;Kinesiophobia<list list-type="bullet"><list-item><p>&#x2003;TSK<sup><xref ref-type="table-fn" rid="table3fn20">t</xref></sup></p></list-item></list><break/>&#x2003;Physical performance<list list-type="bullet"><list-item><p>&#x2003;Pedalo Balance Score</p></list-item><list-item><p>&#x2003;Knee flexion and extension ROM</p></list-item><list-item><p>&#x2003;Knee proprioception at 30&#x00B0;, 60&#x00B0;</p></list-item><list-item><p>&#x2003;Peak torque of knee flexion and extension at 120&#x00B0; and 240&#x00B0;</p></list-item></list></td></tr><tr><td align="left" valign="top">Nambi et al [<xref ref-type="bibr" rid="ref42">42</xref>]; Saudi Arabia;<break/>some concerns</td><td align="left" valign="top">Male soccer players with posttraumatic osteoarthritis &#x2265;3 months following ACL<sup><xref ref-type="table-fn" rid="table3fn21">u</xref></sup> injury (verified by orthopedic surgeon) and pain rating 4&#x2010;8; mean ages 22&#x2010;23, sex/gender not reported</td><td align="left" valign="top">3 Arms:<list list-type="bullet"><list-item><p>Games using ProKin system that required knee movements to interact with visual targets; N=20 (18-20)</p></list-item><list-item><p>Sensorimotor training (SMT); N=20 (18-20)</p></list-item><list-item><p>Control: N=20 (19-20)</p></list-item></list></td><td align="left" valign="top">Clinic; 4 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 72.3 (4.2)</p></list-item><list-item><p>SMT: 72.5 (4.5)</p></list-item><list-item><p>Control: 71.2 (3.8)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (VR&#x2013;SMT)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;22.1</p></list-item><list-item><p>8-week: &#x2013;9.8</p></list-item><list-item><p>3-month: &#x2013;14.0</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (VR&#x2013;control)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;29.3</p></list-item><list-item><p>8-week: &#x2013;31.0</p></list-item><list-item><p>3-month: &#x2013;25.1</p></list-item></list></td><td align="left" valign="top">VAS<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>Intervention: 7.2 (0.5)</p></list-item><list-item><p>SMT: 7.4 (0.4)</p></list-item><list-item><p>Control: 7.3 (0.4)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (VR&#x2013;SMT)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;2.3</p></list-item><list-item><p>8-week: &#x2013;0.8</p></list-item><list-item><p>3-month: &#x2013;0.8</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394; (VR&#x2013;control)<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>4-week: &#x2013;3.1</p></list-item><list-item><p>8-week: &#x2013;1.6</p></list-item><list-item><p>3-month: &#x2013;3.2</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">NR</td></tr><tr><td align="left" valign="top">&#x2003;Oliveira et al [<xref ref-type="bibr" rid="ref44">44</xref>]; Brazil; high<break/>&#x2003;</td><td align="left" valign="top">Knee osteoarthritis, Kellgren-Lawrence grades 2&#x2010;4, independent ambulation; mean ages 62&#x2010;63, 70%&#x2010;85% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Xbox 360 with Microsoft Kinect 360 sensor training; N=20</p></list-item><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Kinesiotherapy plus postural exercises; N=20</p></list-item></list></td><td align="left" valign="top">NR; 8 weeks</td><td align="left" valign="top">WOMAC (total)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 36.2 (13.4)</p></list-item><list-item><p>Comparator: 38.4 (14.4)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>8 wk: -0.6</p></list-item></list></td><td align="left" valign="top">VAS<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 7.5 (1.2)</p></list-item><list-item><p>Comparator: 8.0 (1.5)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>8-wk: 0.2</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>Anticipatory postural adjustments (latency, amplitude, and time to max)</p></list-item></list></td></tr><tr><td align="left" valign="top">&#x2003;Sonmez et al [<xref ref-type="bibr" rid="ref49">49</xref>]; Turkey; some concerns</td><td align="left" valign="top">Knee osteoarthritis, Kellgren-Lawrence grade 1&#x2010;3, able to walk &#x003E;15 m; mean age 60.1 (both groups), 75% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Microsoft Kinect Xbox 360 exergame; N=20</p></list-item><list-item><p><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Physiotherapy plus hot pack, TENS; N=20</p></list-item></list></td><td align="left" valign="top">Clinic; 3 weeks</td><td align="left" valign="top">WOMAC (function)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 19.5 (5.9)</p></list-item><list-item><p>Comparator: 20.4 (4.2)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3 wk: &#x2212;4.7</p></list-item></list></td><td align="left" valign="top">WOMAC (pain)<list list-type="bullet"><list-item><p>Baseline mean (SD):</p></list-item></list><list list-type="bullet"><list-item><p>VR: 6.3 (3.5)</p></list-item><list-item><p>Comparator: 7.5 (4.4)</p></list-item></list><list list-type="bullet"><list-item><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table3fn6">f</xref></sup>:</p></list-item></list><list list-type="bullet"><list-item><p>3-wk: &#x2212;0.8</p></list-item></list></td><td align="left" valign="top">&#x201C;No adverse events were observed in either group&#x201D;</td><td align="left" valign="top">Physical performance<list list-type="bullet"><list-item><p>TUG<sup><xref ref-type="table-fn" rid="table3fn22">v</xref></sup></p></list-item><list-item><p>Proprioception (right and left)</p></list-item></list></td></tr></tbody></table><table-wrap-foot><fn id="table3fn1"><p><sup>a</sup>RoB: risk of bias.</p></fn><fn id="table3fn2"><p><sup>b</sup>Results for other eligible outcomes are found in <xref ref-type="supplementary-material" rid="app10">Multimedia Appendix 10</xref>.</p></fn><fn id="table3fn3"><p><sup>c</sup>ACR: American College of Rheumatology.</p></fn><fn id="table3fn4"><p><sup>d</sup>NR: not reported.</p></fn><fn id="table3fn5"><p><sup>e</sup>WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.</p></fn><fn id="table3fn6"><p><sup>f</sup>Diff &#x0394; calculated by review team, unable to standardize as no SD for change reported.</p></fn><fn id="table3fn7"><p><sup>g</sup>NRS: numeric rating scale.</p></fn><fn id="table3fn8"><p><sup>h</sup>VR: virtual reality.</p></fn><fn id="table3fn9"><p><sup>i</sup>VAS: Visual Analog Scale.</p></fn><fn id="table3fn10"><p><sup>j</sup>TENS: transcutaneous electrical nerve stimulation.</p></fn><fn id="table3fn11"><p><sup>k</sup>Diff &#x0394;: difference in change scores.</p></fn><fn id="table3fn12"><p><sup>l</sup>IDR: interactive digital rehabilitation.</p></fn><fn id="table3fn13"><p><sup>m</sup>PT: physical therapy.</p></fn><fn id="table3fn14"><p><sup>n</sup>ROM: range of motion.</p></fn><fn id="table3fn15"><p><sup>o</sup>CDC: Centers for Disease Control and Prevention.</p></fn><fn id="table3fn16"><p><sup>p</sup>KOOS: Knee Injury and Osteoarthritis Outcome Score.</p></fn><fn id="table3fn17"><p><sup>q</sup>NSAIDs: nonsteroidal anti-inflammatory drugs.</p></fn><fn id="table3fn18"><p><sup>r</sup>WHOQOL-BREF: World Health Organization Quality of Life Brief Version.</p></fn><fn id="table3fn19"><p><sup>s</sup>Diff &#x0394; not reported and cannot be calculated using provided result.</p></fn><fn id="table3fn20"><p><sup>t</sup>TSK: Tampa Scale for Kinesiophobia.</p></fn><fn id="table3fn21"><p><sup>u</sup>ACL: anterior cruciate ligament.</p></fn><fn id="table3fn22"><p><sup>v</sup>TUG: Timed Up and Go test.</p></fn></table-wrap-foot></table-wrap><sec id="s3-2-1"><title>VR-DAE</title><p>VR-DAE may result in better pain-related functioning and greater decreases in pain intensity when compared with conventional therapy, though evidence is inconsistent across studies (<xref ref-type="supplementary-material" rid="app6">Multimedia Appendix 6</xref>). Two studies [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref45">45</xref>] evaluated VR-DAE versus conventional therapy for KOA pain, both using head-mounted displays to deliver interactive exercise in virtual environments. &#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] (Turkey, some concerns RoB; N=82) compared 3 weeks of Oculus VR gaming (Fish Game and Monkey Game targeting balance and proprioception via lateral trunk flexion and stepping, 15 minutes/session, 5 days/week) plus conventional therapy to conventional therapy alone (therapeutic ultrasound and transcutaneous electrical nerve stimulation [TENS]). Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>] (China, some concerns RoB; N=60) evaluated a 12-week home-based smartphone VR application (VRiKnee; VR Shinecon headset) delivering guided quadriceps strengthening exercises with visual feedback (virtual flowers blooming with successful movement) compared with the same exercises without VR.</p><p>&#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] reported that the VR group showed greater improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total at 3 weeks (Diff &#x0394; &#x2212;8.7 [low COE]) and 7 weeks (Diff &#x0394; &#x2212;5.0), in contrast with Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>], who presented WOMAC total scores showing no difference between groups at either 6 weeks (Diff &#x0394; 82.6 [very low COE]) or 12 weeks (Diff &#x0394; &#x2212;61.3 [low COE]), with confidence intervals crossing zero at both time points. With respect to pain intensity, Visual Analog Scale (VAS) scores in the study by &#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] favored the VR group at 3 weeks (Diff &#x0394; &#x2212;0.7 [low COE]) and 7 weeks (Diff &#x0394; &#x2212;1.1). Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>] reported pain scores using NRS and found no difference at 6 weeks (Diff &#x0394; &#x2212;0.04 [very low COE]) or 12 weeks (Diff &#x0394; &#x2212;0.42 [moderate COE]). Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>] reported 5 events of cybersickness in the VR group; no other AEs were assessed. &#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] did not report on AEs. For nonprioritized outcomes, &#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] assessed physical performance and found inconsistent results: no difference between groups in the 6-minute walk test (Diff &#x0394; &#x2212;0.9 m at both 3 and 7 weeks) but greater improvement in the VR group on the Berg Balance Scale at both time points (Diff &#x0394;s of 1.9 and 2.9, respectively). Additionally, Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>] assessed quality of life (EQ-VAS), finding no between-group differences (<xref ref-type="table" rid="table3">Table 3</xref>).</p></sec><sec id="s3-2-2"><title>IDR-DAE</title><p>IDR may provide a medium-term benefit on pain-related functioning (very low to low COE) and pain intensity (low COE) compared with conventional therapy, but results in little to no difference in reported AEs (low to high COE), and the evidence for early and late time points was very uncertain (<xref ref-type="supplementary-material" rid="app6">Multimedia Appendix 6</xref>). Ten studies presented in 11 publications [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] evaluated IDR for pain due to KOA. IDR programs lasted 3&#x2010;10 weeks and compared IDR interventions using Microsoft Kinect (k=3) [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>], Nintendo Switch (k=1) [<xref ref-type="bibr" rid="ref29">29</xref>], Wii Balance Board (k=1) [<xref ref-type="bibr" rid="ref28">28</xref>], or proprietary sensor-based systems (k=5) [<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>] versus conventional exercise therapies (<xref ref-type="table" rid="table3">Table 3</xref>). Studies were small (total n=40&#x2010;80) and enrolled primarily middle-aged to older adults with primary KOA, with the exception of one that enrolled young male athletes with posttraumatic osteoarthritis [<xref ref-type="bibr" rid="ref42">42</xref>]. Nine studies [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] were clinic-based and one was home-based [<xref ref-type="bibr" rid="ref36">36</xref>]. Studies were rated high (k=4) [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>], some concerns (k=5) [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref49">49</xref>], or low (k=1) [<xref ref-type="bibr" rid="ref29">29</xref>] RoB.</p><p>Nine studies [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] assessed pain-related functioning using WOMAC total (k=7), WOMAC domain scores (k=1), or Knee Injury and Osteoarthritis Outcome Score (KOOS; k=1). Pooled results (<xref ref-type="fig" rid="figure3">Figure 3</xref>) showed a nonsignificant trend favoring IDR (SMD &#x2212;0.59, 95% CI &#x2212;1.62 to 0.43; PI &#x2212;2.87 to 1.65) at 3&#x2010;4 weeks (very low COE) and a small improvement in pain-related functioning (SMD &#x2212;0.59, 95% CI &#x2212;1.11 to &#x2212;0.06; PI &#x2212;1.72 to 0.55) at 6&#x2010;8 weeks (low COE). Three IDR studies were not included in the meta-analyses for pain-related functioning due to incompatible outcome measures or reporting. Lin et al (Taiwan, some concerns RoB; N=80) [<xref ref-type="bibr" rid="ref38">38</xref>] reported WOMAC domain scores (not total), showing inconsistent results over 16 weeks. Mete and Sari (Turkey, high RoB; N=64) [<xref ref-type="bibr" rid="ref41">41</xref>] reported only medians (IQR), precluding Diff &#x0394; calculation. Sonmez et al (Turkey, some concerns RoB; N=40) [<xref ref-type="bibr" rid="ref49">49</xref>], which compared against sham VR control, reported WOMAC-pain (Diff &#x0394; &#x2212;0.8) and function (Diff &#x0394; &#x2212;4.7) subscale scores at 3 weeks but not a WOMAC total score.</p><fig position="float" id="figure3"><label>Figure 3.</label><caption><p>Forest plots of random-effects meta-analyses of interactive digital rehabilitation (IDR) versus conventional exercise for knee osteoarthritis. IDR: interactive digital rehabilitation; SMD: standardized mean difference [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>].</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e84753_fig03.png"/></fig><p>Nine studies [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] assessed pain intensity using VAS (k=7) or the WOMAC-pain subscale (k=1). In pooled analysis at 3&#x2010;4 weeks (k=4), IDR showed a moderate-to-large reduction in pain intensity (very low COE), favoring IDR (SMD &#x2212;0.72, 95% CI &#x2212;1.77 to 0.34; PI &#x2212;3.01 to 1.58). At 6&#x2010;8 weeks (k=4; low COE) it showed a small reduction in pain intensity favoring IDR (SMD &#x2212;0.46, 95% CI &#x2212;0.92 to 0.00; PI &#x2212;1.39 to 0.47). Jarungvittayakon et al [<xref ref-type="bibr" rid="ref36">36</xref>] reported greater VAS reduction in the IDR group during motion (Diff &#x0394; &#x2212;1.3, <italic>P</italic>=.0002) and at rest (Diff &#x0394; &#x2212;1.0, <italic>P</italic>=.025). Guede-Rojas et al [<xref ref-type="bibr" rid="ref34">34</xref>] reported VAS Diff &#x0394; &#x2212;9.9 at 6 weeks, sustained at 14 weeks (Diff &#x0394; &#x2212;6.9).</p><p>Three studies [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] reported on AEs, with each reporting that none were observed (low to high COE) [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref49">49</xref>]. The remaining 7 studies [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>] did not address AEs, representing a significant evidence gap given the physical demands of exergaming in an older population. For other outcomes, Mete and Sari [<xref ref-type="bibr" rid="ref41">41</xref>] assessed kinesiophobia using the Tampa Scale of Kinesiophobia but only provided medians (IQRs). Two studies examined quality of life: Elshazly et al [<xref ref-type="bibr" rid="ref32">32</xref>] using the CDC Health-Related Quality of Life scale and Lin et al [<xref ref-type="bibr" rid="ref38">38</xref>] using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). There were generally small improvements in all groups with no clear between-group differences (eg, Diff &#x0394; range 0.6 to 1.9 in the WHOQOL-BREF physical domain at 16 weeks [<xref ref-type="bibr" rid="ref38">38</xref>]). Eight studies [<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>] evaluated physical performance using various measures including the 10-meter walk test, balance and position sense, range of motion (ROM), the Timed Up and Go test (TUG), strength dynamometry, and anticipatory postural adjustments. All groups generally improved, but results were inconsistent regarding which intervention group showed greater improvement. One study, Carvajal-Parodi et al [<xref ref-type="bibr" rid="ref29">29</xref>] (Chile, low RoB; N=60), reported on an adherence-related outcome with percentages of study participants who had attended &#x2265;20 therapy sessions. Little difference was shown, with 76.6% and 73.3% in IDR and comparator arms reaching this point.</p></sec></sec><sec id="s3-3"><title>Rehabilitation After TKA</title><p>Nine trials evaluated XR for rehabilitation after TKA. Four trials examined VR interventions, incorporating modalities of DAE [<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref43">43</xref>], passive distraction [<xref ref-type="bibr" rid="ref33">33</xref>], and psychoeducation [<xref ref-type="bibr" rid="ref40">40</xref>]. Five trials examined IDR [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref48">48</xref>], all of which evaluated the effectiveness of DAE. Trial characteristics and main findings are summarized in <xref ref-type="table" rid="table4">Table 4</xref>. Certainty of evidence tables are found in (<xref ref-type="supplementary-material" rid="app7">Multimedia Appendix 7</xref>). Below, we first describe findings for VR intervention trials, organized by clinical mechanism, and then present findings for IDR studies.</p><table-wrap id="t4" position="float"><label>Table 4.</label><caption><p>Summary of findings for posttotal knee arthroplasty (TKA) interventions. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring scales differ across included studies (eg, 0-96 Likert, 0-240, or 0-2400 visual analog/numerical); raw difference-in-change (Diff &#x0394;) values for WOMAC are therefore not directly comparable across studies using different scale versions. Standardized mean differences used in the meta-analyses are unaffected by scale version.</p></caption><table id="table4" frame="hsides" rules="groups"><thead><tr><td align="left" valign="top">Author, year; country; RoB<sup><xref ref-type="table-fn" rid="table4fn1">a</xref></sup></td><td align="left" valign="top">Key participant duration characteristics</td><td align="left" valign="top">Study arms: N randomized (N analyzed)</td><td align="left" valign="top">Setting and duration</td><td align="left" valign="top" colspan="4">Outcomes</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top"/><td align="left" valign="top">Pain-related functioning</td><td align="left" valign="top">Pain intensity or severity</td><td align="left" valign="top">Adverse events</td><td align="left" valign="top">Other eligible outcomes<sup><xref ref-type="table-fn" rid="table4fn2">b</xref></sup></td></tr></thead><tbody><tr><td align="left" valign="top" colspan="8">VR<sup><xref ref-type="table-fn" rid="table4fn3">c</xref></sup> intervention trials</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Fuchs et al [<xref ref-type="bibr" rid="ref33">33</xref>]; Israel; high</td><td align="left" valign="top">Patients with osteoarthritis undergoing unilateral TKA<sup><xref ref-type="table-fn" rid="table4fn4">d</xref></sup>; mean age 70 years, 52%&#x2010;63% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Nature or music film watched on Oculus while undergoing continuous passive motion therapy, N=30 (30)</p></list-item><list-item><p>Continuous passive motion therapy, N=25 (25)</p></list-item></list></td><td align="left" valign="top">Hospital; 2 days</td><td align="left" valign="top">Modified KOOS<sup><xref ref-type="table-fn" rid="table4fn5">e</xref></sup>:<break/>Baseline mean (SD):<list list-type="bullet"><list-item><p>Intervention: 36.4 (15.1)</p></list-item><list-item><p>Comparator: 34.5 (17.0) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn6">f</xref></sup> (6 mo)<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>: 1.1</p></list-item></list></td><td align="left" valign="top">VAS<sup><xref ref-type="table-fn" rid="table4fn8">h</xref></sup> Baseline median (IQR):<list list-type="bullet"><list-item><p>Intervention: 6 (5-8)</p></list-item><list-item><p>Comparator: 6 (6-8)</p><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn9">i</xref></sup> NR<sup><xref ref-type="table-fn" rid="table4fn10">j</xref></sup></p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">NR</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Jin et al [<xref ref-type="bibr" rid="ref37">37</xref>]; China; high</td><td align="left" valign="top">Patients with osteoarthritis undergoing TKA; mean age 66 years, 55%&#x2010;61% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Game using Oculus headset rowing a boat using knee flexion, N=33 (33)</p></list-item><list-item><p>Passive flexion of knee using arms, N=33 (33)</p></list-item></list></td><td align="left" valign="top">Hospital; NR</td><td align="left" valign="top">WOMAC<sup><xref ref-type="table-fn" rid="table4fn11">k</xref></sup> baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 45.0 (5.1)</p></list-item><list-item><p>Comparator: 44.2 (5.7) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>1-month: &#x2013;3.9</p></list-item><list-item><p>3-month: &#x2013;4.7</p></list-item><list-item><p>6-month: &#x2013;5.6</p></list-item></list></td><td align="left" valign="top">VAS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 7.4 (1.1)</p></list-item><list-item><p>Comparator: 7.4 (1.3) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>3-day: &#x2013;0.3</p></list-item><list-item><p>5-day: &#x2013;0.5</p></list-item><list-item><p>7-day: &#x2013;0.5</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance (3, 7, and 14 d)<list list-type="bullet"><list-item><p>ROM<sup><xref ref-type="table-fn" rid="table4fn12">l</xref></sup></p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Mazurek et al [<xref ref-type="bibr" rid="ref40">40</xref>]; Poland; some concerns</td><td align="left" valign="top">Age &#x2265;60 years, recent hip or knee joint arthroplasty; mean ages 69.5&#x2010;69.7; 62% women</td><td align="left" valign="top"><list list-type="bullet"><list-item><p>2 Arms:</p></list-item><list-item><p>VRTierOne device (HTC Vive headset) with VR rehabilitation sessions; N=34</p></list-item><list-item><p>Comparator; N=34</p></list-item></list></td><td align="left" valign="top">NR; 4 weeks</td><td align="left" valign="top">Barthel Index Baseline mean (SD):<list list-type="bullet"><list-item><p>VR: 54.6 (16.5)</p></list-item><list-item><p>Comparator: 56.2 (17.4)</p><p>Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>4-week: &#x2013;21.2; <italic>P</italic>&#x003C;.001</p></list-item></list></td><td align="left" valign="top">VAS baseline mean (SD):<list list-type="bullet"><list-item><p>VR: 5.3 (2.0)</p></list-item><list-item><p>Comparator: 4.4 (2.1) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>4-week: &#x2013;2.6; <italic>P</italic>&#x003C;.001</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance &#x00B7; Tinetti balance &#x00B7; Rivermead Motor Assessment (Gross Function, Leg/Trunk)</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Nishitha et al [<xref ref-type="bibr" rid="ref43">43</xref>]; India; high</td><td align="left" valign="top">Unilateral TKA, aged 45&#x2010;65 years; mean ages NR, sex NR</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>3D head-mounted VR with limb sensors for interactive games; N=18</p></list-item><list-item><p>Comparator; N=18</p></list-item></list></td><td align="left" valign="top">Clinic; 12 weeks</td><td align="left" valign="top">WOMAC (total) baseline mean (SD):<list list-type="bullet"><list-item><p>VR: 71.2 (0.8)</p></list-item><list-item><p>Comparator: 71.0 (0.8) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>9-week: &#x2013;11.1</p></list-item><list-item><p>12-week: &#x2013;14.3</p></list-item></list></td><td align="left" valign="top">NRS<sup><xref ref-type="table-fn" rid="table4fn13">m</xref></sup> baseline mean (SD):<list list-type="bullet"><list-item><p>VR: 8.56 (0.5)</p></list-item><list-item><p>Comparator: 8.44 (0.5) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>4-week: &#x2013;0.5</p></list-item><list-item><p>12-week: &#x2013;0.9</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance &#x00B7; ROM Flexion</td></tr><tr><td align="left" valign="top" colspan="8">IDR<sup><xref ref-type="table-fn" rid="table4fn14">n</xref></sup> intervention trials</td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Eichler et al [<xref ref-type="bibr" rid="ref31">31</xref>]; Germany; high</td><td align="left" valign="top">Patients with osteoarthritis after TKA or THA<sup><xref ref-type="table-fn" rid="table4fn15">o</xref></sup>; mean ages 53&#x2010;57 years; 49%&#x2010;54% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Exercises using Microsoft Kinect sensor, as demonstrated by an avatar, N=56 (48)</p></list-item><list-item><p>Usual care, N=55 (39)</p></list-item></list></td><td align="left" valign="top">Home (after 3 wk inpatient rehab); 3 months</td><td align="left" valign="top">WOMAC (total) Baseline mean (SD)<list list-type="bullet"><list-item><p>Intervention: 26.4 (18.5)</p></list-item><list-item><p>Comparator: 24.8 (16.4)</p><p>Standardized diff &#x0394; (3 mo)<sup>m</sup>: &#x2013;0.3</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">NR</td><td align="left" valign="top">Quality of life (3 mo)<list list-type="bullet"><list-item><p>SF-36<sup><xref ref-type="table-fn" rid="table4fn16">p</xref></sup></p></list-item></list> Physical performance (3 mo) <list list-type="bullet"><list-item><p>TUG<sup><xref ref-type="table-fn" rid="table4fn17">q</xref></sup></p></list-item><list-item><p>6-minute walk test</p></list-item><list-item><p>Stair ascend test</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Janhunen et al [<xref ref-type="bibr" rid="ref35">35</xref>]; Finland; some concerns</td><td align="left" valign="top">After first primary TKA; mean ages 66&#x2010;67; 63&#x2010;64% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Games using Microsoft Kinect, involved similar movements as home PT<sup><xref ref-type="table-fn" rid="table4fn18">r</xref></sup>, N=25 (21)</p></list-item><list-item><p>Standard PT, N=27 (25)</p></list-item></list></td><td align="left" valign="top">Home; 16 weeks</td><td align="left" valign="top">OKS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 26.7 (6.7)</p></list-item><list-item><p>Comparator: 26.9 (6.5) Standardized diff &#x0394; (4 mo)<sup><xref ref-type="table-fn" rid="table4fn19">s</xref></sup>: 0.32; <italic>P</italic>=.27<sup><xref ref-type="table-fn" rid="table4fn20">t</xref></sup></p></list-item></list></td><td align="left" valign="top">VAS Baseline mean (SD):<list list-type="bullet"><list-item><p>Intervention: 57.1 (18.3)</p></list-item><list-item><p>Comparator: 54.2 (21.6) Standardized diff &#x0394; (4 mo)<sup><xref ref-type="table-fn" rid="table4fn19">s</xref></sup>: &#x2013;0.39, <italic>P</italic>=.18<sup><xref ref-type="table-fn" rid="table4fn20">t</xref></sup></p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance (2 and 4 mo)<list list-type="bullet"><list-item><p>TUG</p></list-item><list-item><p>Short physical performance battery</p></list-item><list-item><p>Muscle force flexion, extension</p></list-item><list-item><p>ROM flexion, extension</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Piqueras et al [<xref ref-type="bibr" rid="ref46">46</xref>]; Spain; high</td><td align="left" valign="top">After primary TKA, with active ROM flexion 80&#x00B0; and extension &#x2013;10&#x00B0;, without signs of stiffness, and able to walk; mean age 73 years, 72% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Screen and leg movement sensors to instruct and monitor knee exercises, N=90 (68)</p></list-item><list-item><p>Conventional PT<sup><xref ref-type="table-fn" rid="table4fn18">r</xref></sup>, N=91 (65)</p></list-item></list></td><td align="left" valign="top">Clinic (XR<sup><xref ref-type="table-fn" rid="table4fn21">u</xref></sup>), home (control); 2 weeks</td><td align="left" valign="top">NR</td><td align="left" valign="top">VAS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 3.8 (2.01)</p></list-item><list-item><p>Comparator: 4.3 (1.93)</p><p>Standardized diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn19">s</xref></sup>:</p></list-item><list-item><p>2-week: &#x2013;0.05; <italic>P</italic>=.80<sup><xref ref-type="table-fn" rid="table4fn20">t</xref></sup></p></list-item><list-item><p>3-month: 0.22; <italic>P</italic>=.28<sup><xref ref-type="table-fn" rid="table4fn20">t</xref></sup></p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Physical performance (2-wk and 3-mo)<list list-type="bullet"><list-item><p>TUG</p></list-item><list-item><p>Quadriceps/ hamstring strength</p></list-item><list-item><p>ROM flexion, extension</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Prvu Bettger et al [<xref ref-type="bibr" rid="ref47">47</xref>]; United States; some concerns</td><td align="left" valign="top">TKA for nontraumatic conditions and expected to discharge home; mean age 65 years, 60%&#x2010;65% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Virtual telehealth system (VERA<sup><xref ref-type="table-fn" rid="table4fn22">v</xref></sup>) to demonstrate exercises (with avatar) and monitor performance, N=153 (140)</p></list-item><list-item><p>Conventional PT care, N=153 (140)</p></list-item></list></td><td align="left" valign="top">Home; 12 weeks</td><td align="left" valign="top">KOOS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 37.0 (12.0)</p></list-item><list-item><p>Comparator: 36.0 (13.0) Diff &#x0394;<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>:</p></list-item><list-item><p>6-week: &#x2013;1.8</p></list-item><list-item><p>12-week: &#x2013;0.4</p></list-item></list></td><td align="left" valign="top">NRS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 5.2 (2.1)</p></list-item><list-item><p>Comparator: 5.7 (2.0) Diff &#x0394;</p></list-item><list-item><p>12-week<sup><xref ref-type="table-fn" rid="table4fn7">g</xref></sup>: 0.2</p></list-item></list></td><td align="left" valign="top">Number of falls (12 wk):<list list-type="bullet"><list-item><p>Intervention: 19.4%</p></list-item><list-item><p>Comparator: 14.6%</p></list-item><list-item><p>Between-group difference (90% CI) 4.8% (&#x2013;2.6 to 12.3)</p></list-item></list></td><td align="left" valign="top">Physical performance (6-wk)<list list-type="bullet"><list-item><p>ROM extension, flexion</p></list-item></list></td></tr><tr><td align="left" valign="top"><named-content content-type="indent">&#x00A0;&#x00A0;&#x00A0;&#x00A0;</named-content>Shim et al [<xref ref-type="bibr" rid="ref48">48</xref>]; Korea; some concerns</td><td align="left" valign="top">Post-TKA and discharged home; mean age 68&#x2010;72 years; 75%&#x2010;82% women</td><td align="left" valign="top">2 Arms:<list list-type="bullet"><list-item><p>Exercises using Microsoft Kinect, N=28 (27)</p></list-item><list-item><p>Conventional rehabilitation, N=28 (27)</p></list-item></list></td><td align="left" valign="top">Home; 12 weeks</td><td align="left" valign="top">WOMAC (total) Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 83.1 (13.0)</p></list-item><list-item><p>Comparator: 81.1 (14.4)</p></list-item><list-item><p>Diff &#x0394; not</p></list-item><list-item><p>3-week: 1.9</p></list-item><list-item><p>12-week: &#x2013;0.8</p></list-item><list-item><p>24-week: &#x2013;2.8</p></list-item></list></td><td align="left" valign="top">NRS Baseline (SD):<list list-type="bullet"><list-item><p>Intervention: 5.7 (2.1)</p></list-item><list-item><p>Comparator: 5.5 (2.2) Diff &#x0394;</p></list-item><list-item><p>3-week: 0.2</p></list-item><list-item><p>12-week: &#x2013;0.7</p></list-item><list-item><p>24-week: 0</p></list-item></list></td><td align="left" valign="top">NR</td><td align="left" valign="top">Quality of life (3-mo)<list list-type="bullet"><list-item><p>EQ-5D</p></list-item></list> Physical performance (3, 12,<break/>and24 wk) <list list-type="bullet"><list-item><p>4 meter gait speed</p></list-item><list-item><p>Berg balance scale</p></list-item><list-item><p>Quadriceps strength</p></list-item><list-item><p>Hamstring strength</p></list-item><list-item><p>ROM</p></list-item></list></td></tr></tbody></table><table-wrap-foot><fn id="table4fn1"><p><sup>a</sup>RoB: risk of bias.</p></fn><fn id="table4fn2"><p><sup>b</sup>Results for other eligible outcomes are found in <xref ref-type="supplementary-material" rid="app11">Multimedia Appendix 11</xref>.</p></fn><fn id="table4fn3"><p><sup>c</sup>VR: virtual reality.</p></fn><fn id="table4fn4"><p><sup>d</sup>TKA: total knee arthroplasty.</p></fn><fn id="table4fn5"><p><sup>e</sup>KOOS: Knee Injury and Osteoarthritis Outcome Score.</p></fn><fn id="table4fn6"><p><sup>f</sup>Diff &#x0394;: difference in change scores.</p></fn><fn id="table4fn7"><p><sup>g</sup>Diff &#x0394; calculated by review team, unable to standardize as no SD for change reported.</p></fn><fn id="table4fn8"><p><sup>h</sup>VAS: Visual Analog Scale.</p></fn><fn id="table4fn9"><p><sup>i</sup>Diff &#x0394; not reported and cannot be calculated using provided results.</p></fn><fn id="table4fn10"><p><sup>j</sup>NR: not reported.</p></fn><fn id="table4fn11"><p><sup>k</sup>WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.</p></fn><fn id="table4fn12"><p><sup>l</sup>ROM: range of motion.</p></fn><fn id="table4fn13"><p><sup>m</sup>NRS: Numeric Rating Scale.</p></fn><fn id="table4fn14"><p><sup>n</sup>IDR: interactive digital rehabilitation.</p></fn><fn id="table4fn15"><p><sup>o</sup>THA: total hip arthroplasty.</p></fn><fn id="table4fn16"><p><sup>p</sup>SF-36: 36-Item Short Form Health Survey.</p></fn><fn id="table4fn17"><p><sup>q</sup>TUG: Timed Up and Go test.</p></fn><fn id="table4fn18"><p><sup>r</sup>PT: physical therapy.</p></fn><fn id="table4fn19"><p><sup>s</sup>standardized Diff &#x0394; calculated by review team.</p></fn><fn id="table4fn20"><p><sup>t</sup>Study reported <italic>P</italic> values for analyses comparing change scores between groups (from baseline to indicated time points).</p></fn><fn id="table4fn21"><p><sup>u</sup>XR: extended reality.</p></fn><fn id="table4fn22"><p><sup>v</sup>VERA: Virtual Exercise Rehabilitation Assistant.</p></fn></table-wrap-foot></table-wrap><sec id="s3-3-1"><title>VR Trials</title><sec id="s3-3-1-1"><title>VR-DAE (k=2)</title><p>Jin et al [<xref ref-type="bibr" rid="ref37">37</xref>] (China, high RoB; N=66) evaluated immersive VR rowing beginning on postoperative day 2, with patients performing knee flexion exercises via immersive VR (30 min; 3 times/day) compared with passive knee flexion exercises. Nishitha et al [<xref ref-type="bibr" rid="ref43">43</xref>] (India, high RoB; N=36) used 3D head-mounted VR with limb sensors for interactive games over 12 weeks. VR-DAE may result in improvements in pain-related functioning and pain intensity (low COE). At 1, 3, and 6 months, Jin et al [<xref ref-type="bibr" rid="ref37">37</xref>] reported greater improvements in WOMAC total scores (6 mo Diff &#x0394; &#x2212;5.6), as did Nishitha et al [<xref ref-type="bibr" rid="ref43">43</xref>] who reported similar improvements at 9 (Diff &#x0394; &#x2212;11.1) and 12 weeks (Diff &#x0394; &#x2212;14.3). For pain intensity, Jin et al [<xref ref-type="bibr" rid="ref37">37</xref>] reported VAS scores on postoperative days 1&#x2010;7 showing slightly greater reductions in the VR group (Diff &#x0394; &#x2212;0.5 at day 7). Nishitha et al [<xref ref-type="bibr" rid="ref43">43</xref>] showed a similar magnitude of effect at longer-term follow-up (12 wk Diff &#x0394; &#x2212;0.9). Neither VR-DAE study reported AEs. Knee ROM at 14 days showed small improvement favoring VR (Diff &#x0394; 6.7). Both authors reported improvements for VR arms relative to comparators in ROM physical performance measures, eg Diff &#x0394; 6.7 (favoring VR) at 2 weeks follow-up [<xref ref-type="bibr" rid="ref37">37</xref>].</p></sec><sec id="s3-3-1-2"><title>VR-Distraction (k=1)</title><p>Fuchs et al [<xref ref-type="bibr" rid="ref33">33</xref>] (Israel, high RoB; N=55) evaluated passive VR distraction in which patients watched nature or music films via Oculus headset during continuous passive motion (CPM) therapy on postoperative days 1&#x2010;2. The comparator received CPM only. Modified KOOS scores improved in both groups at 6 months with minimal between-group difference (Diff &#x0394; 1.1 [low COE]). Because standardized effect size could not be calculated, VAS pain intensity was reported only as medians (IQRs), which favored a greater decrease in scores with VR (very low COE). AEs were not reported. The passive nature of this intervention (distraction without exercise guidance) is mechanistically distinct from VR-DAE.</p></sec><sec id="s3-3-1-3"><title>VR-Psychoeducation (k=1)</title><p>Mazurek et al [<xref ref-type="bibr" rid="ref40">40</xref>] (Poland, some concerns RoB; N=68) evaluated VRTierOne (HTC Vive headset) delivering VR rehabilitation sessions with a psychoeducation focus over 4 weeks in patients aged &#x2265;60 years following hip or knee arthroplasty. Knee-specific data were not disaggregated from the mixed hip/knee population. Pain-related functioning, measured by the Barthel Index, showed large improvement favoring VR (Diff &#x0394; 21.2; <italic>P</italic>&#x003C;.001) and pain intensity measured by VAS showed marked reduction favoring VR (Diff &#x0394; &#x2212;2.6; <italic>P</italic>&#x003C;.001; moderate COE). AEs were not reported. Physical performance outcomes (eg, Tinetti balance and Rivermead Motor Assessment) each favored VR at 4 weeks. The large effect sizes and moderate COE for pain reduction are notable, though the mixed population and unclear intervention content limit generalizability. This was the only post-TKA VR study to achieve moderate certainty of evidence for any outcome.</p></sec></sec></sec><sec id="s3-4"><title>IDR</title><p>Compared with standard rehabilitation, IDR-DAE may result in better pain-related functioning at 3&#x2010;4 months (low COE) and probably results in better functioning at 6 months (moderate COE and 1 randomized controlled trial [RCT]). IDR may result in little to no difference in pain intensity at 2&#x2010;3 weeks (low COE), 3&#x2010;4 months (low COE), or 6 months (moderate COE), and the evidence for AEs remains very uncertain (<xref ref-type="supplementary-material" rid="app7">Multimedia Appendix 7</xref>). Five trials evaluated IDR interventions for patients post-TKA [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref48">48</xref>]. Three used Microsoft Kinect-based systems [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] and 2 used other sensor technologies that monitored participant movements and provided digital feedback [<xref ref-type="bibr" rid="ref46">46</xref>,<xref ref-type="bibr" rid="ref47">47</xref>] (<xref ref-type="table" rid="table4">Table 4</xref>). Studies ranged from small to large (n=52&#x2010;306) and follow-up ranged from 2 weeks to 6 months. Four [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] were home-based, and one [<xref ref-type="bibr" rid="ref46">46</xref>] was clinic-based. Four studies [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] reported on pain-related functioning, and 4 [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref48">48</xref>] reported on pain intensity; only one reported on AEs. One study [<xref ref-type="bibr" rid="ref31">31</xref>] included patients who had undergone total arthroplasty of the knee or hip.</p><p>Four studies [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] evaluated pain-related functioning using WOMAC [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref48">48</xref>], Oxford Knee Score (OKS) [<xref ref-type="bibr" rid="ref35">35</xref>], or KOOS [<xref ref-type="bibr" rid="ref47">47</xref>]. At 3&#x2010;4 months, findings broadly favored IDR (low COE). Eichler et al [<xref ref-type="bibr" rid="ref31">31</xref>] (Germany, high RoB; N=111) and Shim et al [<xref ref-type="bibr" rid="ref48">48</xref>] (South Korea, some concerns RoB; N=56) both found WOMAC improvement in both groups at 3 months, with small reductions favoring IDR (eg, standardized Diff &#x0394; &#x2212;0.29 [<xref ref-type="bibr" rid="ref48">48</xref>]). Likewise, Janhunen et al [<xref ref-type="bibr" rid="ref35">35</xref>] (Finland, some concerns RoB; N=52) reported greater OKS improvement in the IDR group at 4 months (standardized Diff &#x0394; 0.3). Prvu Bettger et al [<xref ref-type="bibr" rid="ref47">47</xref>] (United States, some concerns RoB; N=306)&#x2014;the largest study in the review and the only US-based trial&#x2014;found greater KOOS improvement in the traditional PT group at 6 weeks (Diff &#x0394; &#x2212;1.8) but a difference favoring IDR at 12 weeks (Diff &#x0394; 1.4). Notably, Prvu Bettger et al [<xref ref-type="bibr" rid="ref47">47</xref>] was industry-funded (ReflexionHealth), and the primary outcome was total health care costs rather than pain or function. At 24 weeks, Shim et al [<xref ref-type="bibr" rid="ref48">48</xref>] (moderate COE) reported continued WOMAC improvement favoring IDR (Diff &#x0394; &#x2212;2.8)&#x2014;the longest follow-up and the highest certainty rating for any IDR outcome in the post-TKA analysis. Piqueras et al [<xref ref-type="bibr" rid="ref46">46</xref>] (Spain, high RoB; N=181) also assessed participants using WOMAC scores. The authors, however, did not provide follow-up scores, although they stated there were &#x201C;no significant differences&#x201D; between groups. This study primarily compared delivery modality (remote vs face-to-face) rather than IDR content.</p><p>Four trials assessed pain intensity using VAS or NRS. The evidence is very uncertain on the effect of IDR in pain intensity at 2&#x2010;3 weeks (very low COE; k=2) and at 3&#x2010;4 months (low COE; k=4). At 6 months (1 RCT), IDR probably resulted in little to no difference (moderate COE; k=1). Pooled analysis at 3&#x2010;4 months (k=3) showed no differences between groups (low COE) in reduction of pain intensity (SMD &#x2212;0.12; 95% CI &#x2212;0.75 to 0.52; PI &#x2212;1.63 to 1.27; <xref ref-type="fig" rid="figure4">Figure 4</xref>; <xref ref-type="supplementary-material" rid="app7">Multimedia Appendix 7</xref>) [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>]. While not included in the pooled analysis due to intervention characteristics, Piqueras et al [<xref ref-type="bibr" rid="ref46">46</xref>] showed greater VAS reduction in the control arm at 3 months (standardized Diff &#x0394; 0.22; <italic>P</italic>=.28).</p><fig position="float" id="figure4"><label>Figure 4.</label><caption><p>Forest plot of random-effects meta-analysis of interactive digital rehabilitation (IDR) versus usual care: Pain intensity at 12 weeks (k=3). IDR: interactive digital rehabilitation; SMD: standardized mean difference [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref48">48</xref>] (<xref ref-type="supplementary-material" rid="app12">Multimedia Appendix 12</xref>).</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="jmir_v28i1e84753_fig04.png"/></fig><p>Only Prvu Bettger et al [<xref ref-type="bibr" rid="ref47">47</xref>] reported on AEs, assessing falls during 12 weeks postdischarge; 19% (n=27) of the IDR group versus 15% (n=20) of the control group experienced one or more falls. Causality was not assessed; falls may reflect age and disease status rather than the intervention (very low COE). No other AE types were assessed in any of the 5 [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref48">48</xref>] IDR post-TKA studies. With respect to other outcomes, 2 studies assessed quality of life. Shim et al [<xref ref-type="bibr" rid="ref48">48</xref>] reported EQ-5D scores at 3, 12, and 24 weeks with modest improvements in both groups and no clear between-group difference. Eichler et al [<xref ref-type="bibr" rid="ref31">31</xref>] reported 36-item Short Form health survey (SF-36) physical component scores (PCS) improving comparably in both groups at 3 months (standardized Diff &#x0394; &#x2212;0.04), with no change in mental component scores (standardized Diff &#x0394; &#x2212;0.24). All 5 studies [<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref46">46</xref>-<xref ref-type="bibr" rid="ref48">48</xref>] evaluated physical performance using TUG, 6-minute walk, Short Performance Physical Battery (SPPB), ROM, gait speed, and/or strength measures. Results were heterogeneous; Janhunen et al [<xref ref-type="bibr" rid="ref35">35</xref>] showed greater TUG improvement in the IDR group at 4 months (standardized Diff &#x0394; &#x2212;0.71; <italic>P</italic>=.04), whereas Piqueras et al [<xref ref-type="bibr" rid="ref46">46</xref>] reported greater TUG improvement in the control group at 3 months (standardized Diff &#x0394; 0.51, <italic>P</italic>=.02). Other physical performance measures showed either no differences or small inconsistent improvements between groups.</p></sec></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><sec id="s4-1"><title>Principal Findings</title><p>This systematic review evaluated the benefits and harms of XR interventions for chronic KOA pain and for symptomatic recovery after TKA, with findings stratified by level of immersion, clinical mechanism, and follow-up duration. We identified 21 eligible RCTs evaluating XR interventions for KOA pain or post-TKA rehabilitation. Despite a substantially expanded evidence base compared with previous reviews, the overall body of evidence remains limited by small study sizes, heterogeneity in intervention design and comparators, and lack of AE reporting in post-TKA. Most studies were rated as having high (k=9) or some concerns (k=11) for RoB, with only one study rated low. Findings should therefore be interpreted in light of the predominantly high or some concerns of RoB among the included studies, the low to very low GRADE certainty of evidence for most pooled outcomes, as well as the heterogeneity across interventions and follow-up durations. Pooled point estimates with 95% CIs reflect the average effect across the included studies, while prediction intervals describe the plausible range of true effects in similar future settings [<xref ref-type="bibr" rid="ref60">60</xref>].</p><p>For adults with KOA, IDR interventions showed better pain-related functioning (k=5; low COE) and lower pain intensity (k=4; low COE) at 6&#x2010;8 weeks, compared with conventional therapy. The observed standardized effect sizes fall in the small-to-moderate range [<xref ref-type="bibr" rid="ref56">56</xref>]. A consistent finding in both KOA and TKA studies was that both groups improved substantially over time, as assessed with established outcome measures (WOMAC, KOOS, and VAS), and met minimal clinically important differences (MCIDs) for these various measures (<xref ref-type="supplementary-material" rid="app13">Multimedia Appendix 13</xref> [<xref ref-type="bibr" rid="ref61">61</xref>-<xref ref-type="bibr" rid="ref65">65</xref>]). However, observed differences in change scores between groups (Diff &#x0394;) typically were small and much less than MCID, though there should be caution in using MCID to interpret between-group differences [<xref ref-type="bibr" rid="ref66">66</xref>]. Among the 10 IDR studies [<xref ref-type="bibr" rid="ref28">28</xref>-<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>,<xref ref-type="bibr" rid="ref44">44</xref>,<xref ref-type="bibr" rid="ref49">49</xref>], the single low-RoB trial [<xref ref-type="bibr" rid="ref29">29</xref>] did not report on WOMAC, and thus the pooled estimate of effects on pain-related functioning depended on data for studies with high or some concerns for RoB. VR-DAE for KOA (k=2) produced inconsistent results: short-term clinic-based benefits reported by &#x00D6;zl&#x00FC; et al [<xref ref-type="bibr" rid="ref45">45</xref>] and null findings in a longer home-based trial reported by Lo et al [<xref ref-type="bibr" rid="ref39">39</xref>] raise questions about the sustainability and generalizability of VR effects for KOA. Heterogeneity in intervention content (gaming vs guided strengthening), setting (clinic vs home), and duration (3 vs 12 weeks) limited comparability and synthesis.</p><p>Post-TKA evidence similarly indicates that IDR may result in better pain-related functioning at 3&#x2010;4 months (low COE), and this benefit probably persists at 6 months (moderate COE; 1 RCT)&#x2014;a trajectory suggesting durable functional gains from IDR-guided rehabilitation. For pain intensity, the pooled meta-analysis at 3&#x2010;4 months showed little to no difference between groups (k=3). At 6 months, pain intensity probably showed little to no difference (moderate COE; 1 RCT).</p><p>Our results broadly align with other recent reviews undertaken to evaluate effects of XR technologies for KOA. Wei et al [<xref ref-type="bibr" rid="ref18">18</xref>] evaluated immersive and nonimmersive VR technologies for patients with KOA and found improvements in pain and WOMAC total scores (moderate and low COE). Byra et al [<xref ref-type="bibr" rid="ref19">19</xref>] evaluated rehabilitation using VR and exergames in patients with KOA and found &#x201C;no conclusive evidence&#x201D; that XR interventions were more beneficial than standard rehabilitation. Both reviews included studies evaluating a range of XR technologies encompassing both VR and nonfully immersive modalities, although only Wei et al [<xref ref-type="bibr" rid="ref18">18</xref>] stratified outcomes by degree of immersion. Wei et al [<xref ref-type="bibr" rid="ref18">18</xref>] also presented subgroup analyses for pain and WOMAC scores by duration of therapy; however, in contrast with our review, neither of the previous reviews stratified results by duration of follow-up, which is of particular importance when assessing effects of an intervention for a chronic pain condition [<xref ref-type="bibr" rid="ref67">67</xref>]. Neither review evaluated AEs. Two recent reviews evaluated XR for post-TKA but neither stratified results by level of immersion. Su et al [<xref ref-type="bibr" rid="ref20">20</xref>] and Peng et al [<xref ref-type="bibr" rid="ref21">21</xref>] reported similar results for XR versus conventional rehabilitation on measures of pain and functioning (WOMAC). Pain scores improved in intervention arms at early time points, &#x2264;2 weeks and &#x2264;1 month, respectively, but neither review reported positive results at later time points. WOMAC scores showed improvement at 1 month in both reviews but disagreed at later time points (&#x003E;1&#x2010;6 months) and showed considerable heterogeneity. Though a relatively small number of studies were included in Su et al [<xref ref-type="bibr" rid="ref20">20</xref>] (k=14) and Peng et al [<xref ref-type="bibr" rid="ref21">21</xref>] (k=8), only the latter commented on the quality of evidence (Physiotherapy Evidence Database [PEDro] scale for differences in pain (low-quality) and function (high-quality) scores. Neither review evaluated AEs. By stratifying findings by level of immersion (VR vs IDR), clinical mechanism, and follow-up duration, and by appraising certainty of evidence using GRADE and systematically evaluating AEs alongside efficacy, the present review extends and complements these prior syntheses and helps clarify which XR modalities and indications are best supported by the current evidence.</p><p>The lack of high-quality (ie, low RoB) studies evaluating XR interventions for KOA and post-TKA recovery is an important gap to address in order to improve care of these populations. XR interventions are being widely tested and deployed in a variety of other acute and chronic pain conditions, but insurance coverage for potentially beneficial interventions will be contingent on sufficient evidence to demonstrate benefit (and possibly cost-effectiveness) [<xref ref-type="bibr" rid="ref68">68</xref>-<xref ref-type="bibr" rid="ref71">71</xref>]. Given the rapid development, deployment of, and diminishing costs of XR hardware and software, there is also a critical need for rigorous evaluation of associated AEs relative to their benefits so we can safely deploy these devices in clinical settings.</p></sec><sec id="s4-2"><title>Limitations</title><p>Defining the characteristics of interventions by level of immersion (VR vs IDR) can be challenging, as existing frameworks for XR technologies sometimes differ in where boundaries are drawn [<xref ref-type="bibr" rid="ref72">72</xref>]. Although most previous systematic reviews of XR interventions for pain did not stratify results by level of immersion, we sought to operationalize the distinction between full immersion (ie, VR) and nonimmersive digitally augmented experiences (ie, IDR) in order to provide greater clarity on benefits and harms attributable to each group. To do this, we relied on author descriptions of interventions, which were sometimes limited. To ensure that a broad range of clinically relevant XR interventions were evaluated, we included IDR interventions that many would consider minimally immersive (eg, Microsoft Kinect), which could potentially dilute the impact of more immersive XR interventions (that were not VR). Finally, we limited eligibility to English-language studies, but we did identify studies conducted in predominantly non&#x2013;English speaking countries.</p></sec><sec id="s4-3"><title>Evidence Gaps and Recommendations for Future Research</title><p>The evidence on XR interventions for pain related to KOA or TKA is hampered by small sample sizes, short duration of follow-up, and lack of robust reporting on AEs. Methodological concerns were frequently encountered in the included studies, including most frequently missing outcome data and deviations from the intended interventions. Higher-quality studies addressing these concerns are needed to reliably compare the effects of XR to non-XR therapies.</p><p>Consistent with the early state of the science in an emerging field, most of the studies included in this report, along with 3-quarters of ongoing or recently completed trials on XR interventions for chronic pain, were small (n&#x003C;100) [<xref ref-type="bibr" rid="ref73">73</xref>]. Small sample sizes limit the effects of randomization on balancing baseline measures and unmeasured confounding [<xref ref-type="bibr" rid="ref74">74</xref>]. As described above, we compared between-group change in outcome measures to avoid imbalances created by small sample size and imbalanced confounders, but between-group change is still subject to some amount of confounding. Future studies with sample sizes sufficient to effectively balance participants by measured and unmeasured confounders will facilitate rigorous assessment of the efficacy of IDR interventions for KOA and recovery post-TKA.</p><p>Included studies also were limited to short-term follow-up, with most (n=16) only reporting on outcomes at less than 6 months. This renders confidence in the effects of XR in the longer-term treatment of KOA, a chronic disease, uncertain. Further, assessment of whether XR interventions improve medium- and long-term outcomes post-TKA is important when considering the added cost, complexity, and potential for AEs entailed by XR. Longer trials are needed to adequately assess the effects of XR interventions on symptoms of KOA and recovery after TKA.</p><p>Lack of reporting of AEs is a critical gap to address in future research, particularly for VR interventions and for post-TKA populations, as AEs are an important component of the patient experience and often influence whether someone will start or continue an intervention [<xref ref-type="bibr" rid="ref75">75</xref>]. AEs should be assessed systematically and reported for each arm and involve participant interviews with open-ended questions and/or checklists [<xref ref-type="bibr" rid="ref76">76</xref>]. Accurate observation of rare but potentially serious AEs will require substantially larger studies but is an essential safety assessment, particularly for the TKA population performing intensive daily exercise programming early after surgery.</p><p>Finally, only 6 [<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref40">40</xref>,<xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref45">45</xref>] of 21 included studies evaluated the effects of more immersive (VR) technologies. This is a critical evidence gap given the pace at which VR technologies are evolving and the high likelihood that they will be applied to areas of clinical need as the barriers to developing high-quality software to support them are lessened. Further, no study compared VR and IDR interventions to explore the potential for relative effects of higher levels of intervention immersion. These comparative effectiveness studies are needed given the increased complexity and cost of VR relative to IDR interventions.</p></sec><sec id="s4-4"><title>Conclusions</title><p>In patients with KOA, IDR interventions may result in small improvements in pain-related functioning and pain intensity at 6&#x2010;8 weeks compared with conventional therapy (low COE). Evidence for VR interventions in KOA is limited to 2 trials with inconsistent results. For post-TKA rehabilitation, IDR may result in better pain-related functioning at 3&#x2010;4 months (low COE), with benefits probably persisting at 6 months (moderate COE; 1 RCT). IDR may result in little to no difference in pain intensity at 2&#x2010;3 weeks and 3&#x2010;4 months (low COE) and probably results in little to no difference at 6 months (moderate COE; 1 RCT). VR-delivered psychoeducation showed promise for post-TKA pain reduction in a single trial (moderate COE) but requires replication. AE reporting was absent in the majority of studies but suggested acceptably low rates in those that did (high and low COE for KOA and post-TKA, respectively). Larger high-quality RCTs with longer follow-up, standardized outcome reporting, and systematic safety monitoring are needed before XR interventions can be recommended as standard-of-care adjuncts for recovery after both KOA and TKA. By organizing findings around level of immersion, clinical mechanism, and follow-up duration, as well as systematically appraising AEs alongside efficacy outcomes, this review provides clinicians, patients, and policymakers with an actionable framework for translating current evidence into future practice. The most defensible near-term clinical implication is that IDR-based exercise is reasonable to consider as an adjunct to conventional KOA care in real-world settings, while broader VR adoption and routine integration of XR into post-TKA rehabilitation should await additional high-quality evidence with longer follow-up periods and systematic safety monitoring.</p></sec></sec></body><back><ack><p>Use of AI-Assisted Tools</p><p>The authors declare the use of generative AI in the research and writing process. According to the Generative AI Delegation Taxonomy (GAIDeT) 2025, the following tasks were delegated to generative AI (GenAI) tools under full human supervision: (1) writing the literature review, (2) data cleaning, (3) data curation and organization, (4) data analysis, (5) visualization, (6) text generation, (7) proofreading and editing, (8) summarizing text, and (9) reformatting. The GenAI tool used was Claude 4. Responsibility for the final manuscript lies entirely with the authors. GenAI tools are not listed as authors and do not bear responsibility for the final outcomes. Declaration submitted by DE.</p></ack><notes><sec><title>Funding</title><p>This work is funded by VA Health Systems Research, Evidence Synthesis Program (09&#x2010;009). The funding source had no role in the design, conduct, or reporting of the review or in the decision to submit the manuscript for publication. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the VA or the United States government.</p></sec><sec><title>Data Availability</title><p>The datasets supporting the findings in this study are available within the article&#x2019;s supplementary materials. Data extraction template forms and analytic code are available upon request.</p></sec></notes><fn-group><fn fn-type="con"><p>CK and DE contributed to the initial drafting of the manuscript. All authors contributed to the conception, design, and review and editing of the review. EG, MA, AL, KU, CK, NZ, WM, CC, TW, and DT contributed to data collection, interpretation, and analysis. EG, TJW, and WDP contributed to supervision and project administration. All authors reviewed and approved the manuscript.</p></fn><fn fn-type="conflict"><p>None declared.</p></fn></fn-group><glossary><title>Abbreviations</title><def-list><def-item><term id="abb1">AE</term><def><p>adverse event</p></def></def-item><def-item><term id="abb2">COE</term><def><p>certainty of evidence</p></def></def-item><def-item><term id="abb3">CPM</term><def><p>continuous passive motion</p></def></def-item><def-item><term id="abb4">DAE</term><def><p>digitally augmented exercise</p></def></def-item><def-item><term id="abb5">Diff &#x0394;</term><def><p>difference in change scores</p></def></def-item><def-item><term id="abb6">GDT</term><def><p>Guideline Development Tool</p></def></def-item><def-item><term id="abb7">GRADE</term><def><p>Grading of Recommendations, Assessment, Development, and Evaluation</p></def></def-item><def-item><term id="abb8">IDR</term><def><p>interactive digital rehabilitation</p></def></def-item><def-item><term id="abb9">KOA</term><def><p>knee osteoarthritis</p></def></def-item><def-item><term id="abb10">KOOS</term><def><p>Knee Injury and Osteoarthritis Outcome Score</p></def></def-item><def-item><term id="abb11">MCID</term><def><p>minimal clinically important difference</p></def></def-item><def-item><term id="abb12">NRS</term><def><p>Numeric Rating Scale</p></def></def-item><def-item><term id="abb13">OKS</term><def><p>Oxford Knee Score</p></def></def-item><def-item><term id="abb14">PCS</term><def><p>SF-36 physical component score</p></def></def-item><def-item><term id="abb15">PEDro</term><def><p>Physiotherapy Evidence Database</p></def></def-item><def-item><term id="abb16">PRISMA</term><def><p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p></def></def-item><def-item><term id="abb17">PRISMA-S</term><def><p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses Literature Search Extension</p></def></def-item><def-item><term id="abb18">PROSPERO</term><def><p>International Prospective Register of Systematic Reviews</p></def></def-item><def-item><term id="abb19">PT</term><def><p>physical therapy</p></def></def-item><def-item><term id="abb20">RCT</term><def><p>randomized controlled trial</p></def></def-item><def-item><term id="abb21">RoB</term><def><p>risk of bias</p></def></def-item><def-item><term id="abb22">ROM</term><def><p>range of motion</p></def></def-item><def-item><term id="abb23">SF-36</term><def><p>36-item Short Form health survey</p></def></def-item><def-item><term id="abb24">SPPB</term><def><p>Short Performance Physical Battery</p></def></def-item><def-item><term id="abb25">TENS</term><def><p>transcutaneous electrical nerve stimulation</p></def></def-item><def-item><term id="abb26">TKA</term><def><p>total knee arthroplasty</p></def></def-item><def-item><term id="abb27">TUG</term><def><p>Timed Up and Go test</p></def></def-item><def-item><term id="abb28">VAS</term><def><p>Visual Analog Scale</p></def></def-item><def-item><term id="abb29">VR</term><def><p>virtual reality</p></def></def-item><def-item><term id="abb30">WHOQOL-BREF</term><def><p>World Health Organization Quality of Life Brief Version</p></def></def-item><def-item><term id="abb31">WOMAC</term><def><p>Western Ontario and McMaster Universities Arthritis Index</p></def></def-item><def-item><term id="abb32">XR</term><def><p>extended reality</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref id="ref1"><label>1</label><nlm-citation citation-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Elliott</surname><given-names>AM</given-names> </name><name name-style="western"><surname>Smith</surname><given-names>BH</given-names> </name><name name-style="western"><surname>Penny</surname><given-names>KI</given-names> </name><name name-style="western"><surname>Cairns Smith</surname><given-names>W</given-names> </name><name name-style="western"><surname>Alastair Chambers</surname><given-names>W</given-names> 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pub-id-type="medline">29372930</pub-id></nlm-citation></ref></ref-list><app-group><supplementary-material id="app1"><label>Multimedia Appendix 1</label><p>Excluded references.</p><media xlink:href="jmir_v28i1e84753_app1.docx" xlink:title="DOCX File, 48 KB"/></supplementary-material><supplementary-material id="app2"><label>Multimedia Appendix 2</label><p>Eligibility criteria.</p><media xlink:href="jmir_v28i1e84753_app2.doc" xlink:title="DOC File, 36 KB"/></supplementary-material><supplementary-material id="app3"><label>Multimedia Appendix 3</label><p>Search strategies.</p><media xlink:href="jmir_v28i1e84753_app3.doc" xlink:title="DOC File, 134 KB"/></supplementary-material><supplementary-material id="app4"><label>Multimedia Appendix 4</label><p>Author-reported XR equipment and devices.</p><media xlink:href="jmir_v28i1e84753_app4.docx" xlink:title="DOCX File, 57 KB"/></supplementary-material><supplementary-material id="app5"><label>Multimedia Appendix 5</label><p>Grade Working Group grades of evidence.</p><media xlink:href="jmir_v28i1e84753_app5.docx" xlink:title="DOCX File, 14 KB"/></supplementary-material><supplementary-material id="app6"><label>Multimedia Appendix 6</label><p>Certainty of evidence tables for knee osteoarthritis studies.</p><media xlink:href="jmir_v28i1e84753_app6.docx" xlink:title="DOCX File, 79 KB"/></supplementary-material><supplementary-material id="app7"><label>Multimedia Appendix 7</label><p>Certainty of evidence tables for posttotal knee arthroplasty studies.</p><media xlink:href="jmir_v28i1e84753_app7.docx" xlink:title="DOCX File, 63 KB"/></supplementary-material><supplementary-material id="app8"><label>Multimedia Appendix 8</label><p>Detailed characteristics for included trials on knee osteoarthritis pain.</p><media xlink:href="jmir_v28i1e84753_app8.docx" xlink:title="DOCX File, 70 KB"/></supplementary-material><supplementary-material id="app9"><label>Multimedia Appendix 9</label><p>Detailed characteristics for included trials on total knee arthroplasty.</p><media xlink:href="jmir_v28i1e84753_app9.docx" xlink:title="DOCX File, 53 KB"/></supplementary-material><supplementary-material id="app10"><label>Multimedia Appendix 10</label><p>Detailed results for knee osteoarthritis studies.</p><media xlink:href="jmir_v28i1e84753_app10.docx" xlink:title="DOCX File, 137 KB"/></supplementary-material><supplementary-material id="app11"><label>Multimedia Appendix 11</label><p>Detailed results for included total knee arthroplasty studies.</p><media xlink:href="jmir_v28i1e84753_app11.docx" xlink:title="DOCX File, 89 KB"/></supplementary-material><supplementary-material id="app12"><label>Multimedia Appendix 12</label><p>Detailed Characteristics for TKA</p><media xlink:href="jmir_v28i1e84753_app12.docx" xlink:title="DOCX File, 53 KB"/></supplementary-material><supplementary-material id="app13"><label>Multimedia Appendix 13</label><p>Outcome measure minimal clinically important difference (MCID) reference table.</p><media xlink:href="jmir_v28i1e84753_app13.docx" xlink:title="DOCX File, 20 KB"/></supplementary-material><supplementary-material id="app14"><label>Checklist 1</label><p>PRISMA checklist.</p><media xlink:href="jmir_v28i1e84753_app14.docx" xlink:title="DOCX File, 35 KB"/></supplementary-material></app-group></back></article>