{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:30:53Z","timestamp":1786336253891,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically evaluate the comparative efficacy and safety of common pharmacological strategies for managing post-photorefractive keratectomy (PRK) eye pain through a network meta-analysis, providing evidence-based guidance for clinical medication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Randomized controlled trials (RCTs) were systematically retrieved from Cochrane Library, Web of Science, PubMed, and EMbase (from inception to November 15, 2025). Using R Studio, we conducted a network meta-analysis to assess differences in Visual Analogue Scale (VAS) scores and adverse events across pharmacological interventions. SUCRA (Surface Under the Cumulative Ranking) values were calculated to determine the relative ranking of interventions, while accounting for heterogeneities in administration timing and dosage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 28 studies were included, involving 2,797 patients. In route-stratified analyses, Ofloxacin (SUCRA\u202f=\u202f0.84) and Proparacaine (0.76) were the top-ranked topical agents for analgesia, while Codeine combined with Acetaminophen (0.71) ranked highest among systemic agents. The exploratory combined network yielded identical top-three rankings, though these cross-route comparisons are susceptible to transitivity violations. Notably, effect sizes for most interventions relative to placebo spanned the line of no effect. Regarding safety, Diclofenac (SUCRA\u202f=\u202f0.81), Ketorolac (0.70), and Nepafenac (0.53) demonstrated the optimal profiles. The highest numbers of adverse events occurred with Pregabalin (39 cases), Fentanyl (20 cases), and Codeine combined with Acetaminophen (13 cases); however, safety conclusions remain limited as only seven studies reported highly heterogeneous adverse event data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ofloxacin demonstrates superior relative efficacy for pain control following PRK, while Diclofenac offers the most favorable safety profile. Clinicians should synthesize these comparative findings with individual patient profiles to optimize drug selection, ensuring a balanced approach between effective pain relief and minimized adverse risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251238092<\/jats:ext-link>\n                      , CRD420251238092.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1904962","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:21:40Z","timestamp":1786335700000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of common pharmacological strategies for post-photorefractive keratectomy pain management: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Xin","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital (Clinical College) of Xiangnan University, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital (Clinical College) of Xiangnan University, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital (Clinical College) of Xiangnan University, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital (Clinical College) of Xiangnan University, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Hospital (Clinical College) of Xiangnan University, Xiangnan University","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e001624","DOI":"10.1136\/bmjophth-2023-001624","article-title":"Prospective cohort study investigating frequency and risk factors for acute pain 1 day after refractive surgery","volume":"9","author":"Betz","year":"2024","journal-title":"BMJ Open Ophthalmol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/j.ophtha.2023.02.016","article-title":"Ocular pain after refractive surgery: interim analysis of frequency and risk factors","volume":"130","author":"Betz","year":"2023","journal-title":"Ophthalmology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/j.jcrs.2019.01.032","article-title":"Pain management after photorefractive keratectomy","volume":"45","author":"Shetty","year":"2019","journal-title":"J Cataract Refract Surg"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1097\/j.jcrs.0000000000001525","article-title":"Topical nonsteroidal anti-inflammatory drugs for management of pain after PRK: systematic review and network meta-analysis","volume":"50","author":"Ben Ephraim Noyman","year":"2024","journal-title":"J Cataract Refract Surg"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1097\/ICO.0000000000001328","article-title":"Codeine plus acetaminophen for pain after photorefractive keratectomy: a randomized, double-blind, placebo-controlled add-on trial","volume":"36","author":"Pereira","year":"2017","journal-title":"Cornea"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10792-024-03300-9","article-title":"Efficacy of gabapentin and pregabalin for treatment of post refractive surgery pain: a systematic review and meta-analysis","volume":"44","author":"Chen","year":"2024","journal-title":"Int Ophthalmol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e32875","DOI":"10.1097\/MD.0000000000032875","article-title":"Efficacy and safety of pregabalin in eye pain: a systematic review","volume":"102","author":"Shen","year":"2023","journal-title":"Medicine"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"534","DOI":"10.3928\/1081597X-20190722-01","article-title":"Treatment of ocular neuralgia after refractive surgery with bilateral orbital steroid and anesthetic injections","volume":"35","author":"Yalamanchili","year":"2019","journal-title":"J Refract Surg"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1167\/tvst.12.3.7","article-title":"Topical ocular TRPV1 antagonist SAF312 (Libvatrep) for postoperative pain after photorefractive keratectomy","volume":"12","author":"Thompson","year":"2023","journal-title":"Transl Vis Sci Technol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1007\/s10792-022-02214-8","article-title":"The use of topical nalbuphine in different concentrations to control pain after photorefractive keratectomy","volume":"42","author":"Mattout","year":"2022","journal-title":"Int Ophthalmol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"323","DOI":"10.4045\/tidsskr.13.1145","article-title":"VAS--Visuell Analog Skala [VAS--Visual Analog Scale]","volume":"134","author":"Faiz","year":"2014","journal-title":"Tidsskr Nor Laegeforen"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane collaboration's tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ Clin Res Ed"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e1003082","DOI":"10.1371\/journal.pmed.1003082","article-title":"CINeMA: an approach for assessing confidence in the results of a network meta-analysis","volume":"17","author":"Nikolakopoulou","year":"2020","journal-title":"PLoS Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/s0886-3350(96)80005-8","article-title":"Efficacy and safety of topical diclofenac in reducing ocular pain after excimer photorefractive keratectomy","volume":"22","author":"Tutton","year":"1996","journal-title":"J Cataract Refract Surg"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3928\/1081-597X-19961101-11","article-title":"Diclofenac and ketorolac in the treatment of pain after photorefractive keratectomy","volume":"12","author":"Weinstock","year":"1996","journal-title":"J Refract Surg"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/s0161-6420(97)30139-0","article-title":"Dilute topical proparacaine for pain relief after photorefractive keratectomy","volume":"104","author":"Shahinian","year":"1997","journal-title":"Ophthalmology"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3928\/1542-8877-19980501-03","article-title":"A prospective randomized trial of topical soluble 0.1% indomethacin versus 0.1% diclofenac versus placebo for the control of pain following excimer laser photorefractive keratectomy","volume":"29","author":"Assouline","year":"1998","journal-title":"Ophthalmic Surg Lasers"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/s0149-2918(98)80073-8","article-title":"Comparative study of the analgesic efficacy of flurbiprofen and diclofenac in patients following excimer laser photorefractive keratectomy","volume":"20","author":"Appiotti","year":"1998","journal-title":"Clin Ther"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"661","DOI":"10.3928\/1081-597X-19991101-10","article-title":"Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group","volume":"15","author":"Rajpal","year":"1999","journal-title":"J Refract Surg"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/j.jcrs.2004.05.019","article-title":"Safety and efficacy of ketorolac tromethamine 0.4% ophthalmic solution in post-photorefractive keratectomy patients","volume":"30","author":"Solomon","year":"2004","journal-title":"J Cataract Refract Surg"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.clinthera.2006.04.004","article-title":"Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: a phase II, randomized, double-masked trial","volume":"28","author":"Colin","year":"2006","journal-title":"Clin Ther"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1007\/BF02849978","article-title":"Double-masked study of the effects of Nepcafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy","volume":"24","author":"Donnenfeld","year":"2007","journal-title":"Adv Ther"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1007\/BF02877774","article-title":"Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK)","volume":"24","author":"Durrie","year":"2007","journal-title":"Adv Ther"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3928\/1081597X-20080401-11","article-title":"Effects of topical nepafenac on corneal epithelial healing time and postoperative pain after PRK: a bilateral, prospective, randomized, masked trial","volume":"24","author":"Caldwell","year":"2008","journal-title":"J Refract Surg"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3928\/1081597X-20090201-07","article-title":"Topical bromfenac 0.09% vs. ketorolac 0.4% for the control of pain, photophobia and discomfort following PRK","volume":"25","author":"Sher","year":"2009","journal-title":"J Refract Surg"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"934","DOI":"10.3928\/1081597X-20100212-06","article-title":"Effect of topical 0.5% morphine on postoperative pain after photorefractive keratectomy","volume":"26","author":"Faktorovich","year":"2010","journal-title":"J Refract Surg"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.jcrs.2010.10.040","article-title":"Effect of preemptive topical diclofenac on postoperative pain relief after photorefractive keratectomy","volume":"37","author":"Mohammadpour","year":"2011","journal-title":"J Cataract Refract Surg"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.jcrs.2010.08.041","article-title":"Oral gabapentin for photorefractive keratectomy pain","volume":"37","author":"Kuhnle","year":"2011","journal-title":"J Cataract Refract Surg"},{"key":"ref29","first-page":"S199","article-title":"Preoperative topical diclofenac and ketorolac in prevention of pain and discomfort following photorefractive keratectomy: a randomized double-masked placebo-controlled clinical trial","volume":"3","author":"Razmju","year":"2012","journal-title":"Int J Prev Med"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"106","DOI":"10.5301\/ejo.5000143","article-title":"Pregabalin and gabapentin for post-photorefractive keratectomy pain: a randomized controlled trial","volume":"22","author":"Pakravan","year":"2012","journal-title":"Eur J Ophthalmol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1089\/jop.2012.0161","article-title":"Efficacy of extended-release oral diclofenac in postoperative pain management after photorefractive keratectomy","volume":"29","author":"Eslampour","year":"2013","journal-title":"J Ocul Pharmacol Ther"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1111\/ceo.12343","article-title":"Effect of topical diclofenac on postoperative photorefractive keratectomy pain: a randomized, controlled trial","volume":"42","author":"Eslampoor","year":"2014","journal-title":"Clin Experiment Ophthalmol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1016\/j.jcrs.2014.05.029","article-title":"Comparison of analgesic effect of preoperative topical diclofenac and ketorolac on postoperative pain after photorefractive keratectomy","volume":"40","author":"Hong","year":"2014","journal-title":"J Cataract Refract Surg"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1089\/jop.2013.0208","article-title":"Pregabalin versus placebo in postoperative pain relief of patients' status post photorefractive keratectomy: a double-masked, randomized, prospective study","volume":"30","author":"Meek","year":"2014","journal-title":"J Ocul Pharmacol Ther"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1089\/jop.2013.0125","article-title":"Efficacy and safety of transdermal fentanyl in the control of postoperative pain after photorefractive keratectomy","volume":"30","author":"Lee","year":"2014","journal-title":"J Ocul Pharmacol Ther"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/ICL.0000000000000524","article-title":"Comparison between diclofenac and ketorolac ophthalmic drops for pain management after photorefractive keratectomy: a randomized clinical study","volume":"45","author":"Mohammadpour","year":"2019","journal-title":"Eye Contact Lens"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.2147\/OPTH.S255441","article-title":"Survey of postoperative pain in photorefractive keratectomy using topical versus oral nonsteroidal anti-inflammatory drugs","volume":"14","author":"Ripa","year":"2020","journal-title":"Clin Ophthalmol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"324","DOI":"10.35975\/apic.v25i3.1527","article-title":"Comparison of postoperative pain in photorefractive keratectomy using topical versus oral nonsteroidal anti\u2013inflammatory drugs","volume":"25","author":"Javaid","year":"2021","journal-title":"Anaesth Pain Intensive Care"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3928\/1081597X-20210701-01","article-title":"Pain control following photorefractive keratectomy: a prospective clinical trial comparing codeine versus oxycodone for the management of postoperative pain","volume":"37","author":"Palochak","year":"2021","journal-title":"J Refract Surg"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1177\/11206721221082301","article-title":"Bandage contact lens soaked in 0.1% diclofenac to relieve early postoperative pain and foreign body sensation after transepithelial photorefractive keratectomy","volume":"32","author":"Wang","year":"2022","journal-title":"Eur J Ophthalmol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1097\/AJP.0000000000000746","article-title":"Efficacy and safety of low-dose codeine-containing combination analgesics for pain: systematic review and meta-analysis","volume":"35","author":"Shaheed","year":"2019","journal-title":"Clin J Pain"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1097\/ICU.0000000000000486","article-title":"Pain management after photorefractive keratectomy","volume":"29","author":"Golan","year":"2018","journal-title":"Curr Opin Ophthalmol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1097\/ICU.0000000000000170","article-title":"Current trends in pain management after photorefractive and phototherapeutic keratectomy","volume":"26","author":"Fay","year":"2015","journal-title":"Curr Opin Ophthalmol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"3049","DOI":"10.1007\/s40123-024-01040-8","article-title":"Postoperative pain comparison between alcohol-assisted and transepithelial photorefractive keratectomy using nepafenac treatment: a novel study","volume":"13","author":"Gomel","year":"2024","journal-title":"Ophthalmol Ther"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.2147\/IMCRJ.S554111","article-title":"A case of corneal melting associated with topical diclofenac after phacovitrectomy for macular pucker in a patient with rheumatoid arthritis","volume":"18","author":"Tripodi","year":"2025","journal-title":"Int Med Case Rep J"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1904962\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:21:42Z","timestamp":1786335702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1904962\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":45,"alternative-id":["10.3389\/fmed.2026.1904962"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1904962","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1904962"}}