Therapeutic Penetrating Keratoplasty for Infectious Corneal Ulcers: Outcomes and Timing

Therapeutic Penetrating Keratoplasty for Infectious Corneal Ulcers: Outcomes and Timing | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Therapeutic Penetrating Keratoplasty for Infectious Corneal Ulcers: Outcomes and Timing Brady Hogan, Troy Teeples, Jennifer L. Patnaik, Scott Hauswirth, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7303657/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Therapeutic penetrating keratoplasty (PKP) is often required in severe infectious keratitis unresponsive to medical therapy. This study evaluates visual and surgical outcomes of therapeutic PKP and explores whether surgical timing influences recurrence, transplant failure, or visual outcomes. Methods A retrospective review of 56 patients who underwent PKP for infectious keratitis at a US tertiary academic center between 2014 and 2020. Clinical data including time from ulcer onset to surgery, ulcer size, causative organism, and postoperative outcomes (recurrent infection, graft failure, final VA) were analyzed. Results Of 46 patients with > 30 days of follow-up, 37.0% had persistent infection, 34.8% experienced transplant failure, and 32.6% required repeat PKP. Longer time to PKP was significantly associated with infection recurrence (median 60.0 vs 17.5 days, p = 0.02). Timing of surgery did not influence transplant failure or final VA. Conclusion Therapeutic PKP is associated with high complication rates in infectious keratitis. Earlier surgical intervention may reduce the risk of recurrent infection, though it does not appear to affect final vision or graft failure. Early surgical consideration may be warranted when infections fail to respond to medical therapy. microbial keratitis therapeutic keratoplasty corneal ulcer infectious keratitis graft failure surgical timing Full Text Infectious corneal ulcers present a challenge for ophthalmologists, particularly when medical therapy fails. For refractory infections, therapeutic penetrating keratoplasty (PKP) can be considered to eliminate infection and restore globe integrity. While therapeutic PKP has proven effective for bacterial, fungal, and acanthamoeba keratitis, post-operative complications such as graft rejection, secondary glaucoma, and persistent infection remain a concern. 1-3 The timing of intervention remains debated, due to the challenge of predicting which infections will fail medical therapy or have poorer grafting outcomes. 4-5 This study evaluates outcomes of therapeutic PKP for infectious corneal ulcers, focusing on whether the timing of surgery affects postoperative results. This retrospective analysis included 56 patients who underwent therapeutic PKP for infectious corneal ulcers between 2014 and 2020 at the University of Colorado Department of Ophthalmology. The study was conducted in accordance with the Declaration of Helsinki and approved by the Colorado Multiple Institutional Review Board (COMIRB #20-2564). Informed consent was waived by the IRB due to the retrospective nature of the study and minimal risk to participants. Preoperative variables such as ulcer size, infectious organism, visual acuity (VA), corneal perforation, and hypopyon were recorded. Therapeutic PKP was performed following the standard procedures, including excision of all necrotic or infected corneal tissue when able. Postoperatively, topical antibiotic or antifungal drops were tapered according to clinical response, and steroid drops were tapered at the clinician’s discretion. Postoperative outcomes of interest were final visual acuity (VA) 20/200 or better, transplant failure, recurrent infection, and repeat PKP. Categorical outcomes were compared using Chi-square or Fisher’s exact test, and median time to PKP was compared for binary outcomes using the Wilcoxon rank sum test. The study cohort consisted of 56 patients with a mean age of 58.3 years. Bacterial infections were the most common (55.4%), followed by fungal (10.7%), viral (7.4%), and acanthamoeba (7.4%), (Table 1). The average time from ulcer onset to PKP was 47.0 days (range 3.0 to 210 days). Preoperatively, 29.1% of patients had VA better than hand motion (range 20/25 to no light perception), and 47.3% had corneal perforation. Most patients (89.3%) had at least one form of medical insurance (Medicaid/Medicare/commercial/other) and 10.7% were uninsured. Table 1 – Demographic and clinical information at presentation for patients (N=56) n (%) Age (years), mean (SD) 58.3 (18.0) Male 29 (51.8%) Race Caucasian Hispanic African American Asian 50 (89.3%) 3 (5.4%) 2 (3.6%) 1 (1.8%) Insurance Insured Uninsured 50 (89.3%) 6 (10.7%) Time from ulcer onset to PKP (days) Mean (SD) Median (range) (n=48) 47.0 (48.5) 30.0 (3-210) Culture* Bacterial Fungal Viral Acanthamoeba Culture negative 31 (55.4%) 6 (10.7%) 4 (7.1%) 4 (7.1%) 14 (25.0%) Ulcer size >6mm 2 (n=41) 10 (24.4%) Perforation (n=55) 26 (47.3%) Hypopyon (n=52) 16 (30.8%) Donor graft size >=9mm diameter (n=52) 19 (36.5%) Presenting visual acuity better than HM (n=55) 16 (29.1%) Note: Unknowns not included in the denominators. *3 patients had multiple categories Among the 46 patients with at least 30 days of follow-up, 37.0% had persistent infection, 34.8% experienced transplant failure, and 32.6% required repeat PKP (Table 2). Average follow up duration for the 46 patients with more than 30 days of follow-up was 2.7 years (SD 1.7 years, range 30 days to 6 years). Patients who had recurrent infection had significantly longer time from ulcer onset to PKP than patients who did not have infection (median 60.0 days vs. 17.5 days; Wilcoxon rank sum test p-value =0.02). However, timing of surgery was not associated with transplant failure or final VA of 20/200 or better. Likewise, the size of the corneal ulcer, infectious etiology, corneal perforation, and visual acuity on initial presentation all had no association with final visual acuity outcomes, transplant failure, or recurrent infection (all p-values > 0.05). Table 2 - Postoperative Outcomes Following Therapeutic RPK in Patients with >30 Days of Follow-Up (n=46) n (%) Persistent infection 17 (37.0%) Transplant failure/rejection 16 (34.8%) Glaucoma 16 (34.8%) Required 2nd PKP 15 (32.6%) Post-op vision 20/200 or better 16 (35.6%) Microbial keratitis can be vision-threatening when unresponsive to medical therapy. In this study, we describe outcomes of therapeutic PKP for active corneal infection. One-third of patients had transplant failure, one-third had persistent infection, and only one-third achieved VA of 20/200 or better. Earlier surgery was associated with lower rates of recurrent infection; those without recurrence underwent PKP about 1.5 months earlier than those with recurrence. Delayed intervention may allow infection to spread to the limbus or sclera, increasing risk of recurrence. Our study did not find infectious etiology, ulcer size, perforation, or presenting VA to be associated with final visual outcomes or transplant failure. Most patients had poor final VA, consistent with prior reports: compared to prior research, our cohort had worse visual outcomes, though variability in follow-up and limited VA data likely influenced results. 5 While elective PKPs performed after inflammation has subsided have better outcomes, eyes with active infection, perforation, or impending perforation may necessitate earlier intervention. Prior studies have identified risk factors for needing therapeutic PKP, including delayed referral, corticosteroid use, poor initial VA, and large ulcers. 1,4 These underscore the importance of early recognition and management. This study is limited by its retrospective design, relatively small sample size, and lack of a comparison group treated without PKP. Further research is needed to identify which patients may benefit most from early surgical intervention versus continued medical therapy. Infectious corneal ulcers requiring therapeutic PKP have a high risk of persistent infection and graft failure. While the timing of surgery did not impact final VA or transplant failure, earlier intervention was associated with reduced risk of recurrent infection. Ophthalmologists should consider early PKP for infections poorly responsive to medical treatment to prevent progression and minimize complications. Further studies are needed to refine the criteria for early surgical intervention to optimize outcomes for patients with infectious corneal ulcers. Declarations Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding sources: Research for this study was supported by a Research to Prevent Blindness grant to the Department of Ophthalmology, University of Colorado. Availability of data and materials: Available from the corresponding author upon reasonable request. Competing interests: The authors declare no competing interests. Funding: Supported by an unrestricted Research to Prevent Blindness grant to the Department of Ophthalmology, University of Colorado. Author Contributions Brady Hogan contributed to data interpretation, drafting the manuscript, and revisions. Troy Teeples contributed to data interpretation and critical revision of the manuscript. Jennifer L. Patnaik contributed to study design, data analysis, and revision for intellectual content. Scott Hauswirth provided input on clinical interpretation and revised the manuscript critically for intellectual content. Karen L. Christopher conceived and supervised the study, assisted with interpretation, and provided final approval of the version to be published. All authors meet ICMJE authorship criteria, have reviewed the final manuscript, and agree to be accountable for all aspects of the work. References Sony P, Sharma N, Vajpayee RB, et al. Therapeutic keratoplasty for infectious keratitis: a review of the literature. CLAO J. 2002;28(3):111-118. Dogan C, Arslan OS. Outcomes of therapeutic and tectonic penetrating keratoplasty in eyes with perforated infectious corneal ulcer. Turk J Ophthalmol. 2019;49(2):55-60. Yalniz-Akkaya Z, Burcu A, Dogan E, et al. Therapeutic penetrating keratoplasty for infectious and non-infectious corneal ulcers. Int Ophthalmol. 2015;35(2):193-200. Sharma N, Jain M, Sehra SV, et al. Outcomes of therapeutic penetrating keratoplasty from a tertiary eye care centre in northern India. Cornea. 2014;33(2):114-118. Raj A, Bahadur H, Dhasmana R. Outcome of therapeutic penetrating keratoplasty in advanced infectious keratitis. J Curr Ophthalmol. 2018;30(4):315-320. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7303657","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":496839392,"identity":"c6253863-4e48-45a6-92d2-7c2f7289159a","order_by":0,"name":"Brady Hogan","email":"","orcid":"","institution":"University of Colorado School of Medicine, Anschutz Medical Campus","correspondingAuthor":false,"prefix":"","firstName":"Brady","middleName":"","lastName":"Hogan","suffix":""},{"id":496839393,"identity":"4dcb0f3c-4f92-46e7-a772-b7173414d009","order_by":1,"name":"Troy Teeples","email":"","orcid":"","institution":"University of Colorado School of Medicine, Anschutz Medical Campus","correspondingAuthor":false,"prefix":"","firstName":"Troy","middleName":"","lastName":"Teeples","suffix":""},{"id":496839394,"identity":"f9dacb87-7d2b-44de-bf2a-ddf77787e203","order_by":2,"name":"Jennifer L. 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For refractory infections, therapeutic penetrating keratoplasty (PKP) can be considered to eliminate infection and restore globe integrity. While therapeutic PKP has proven effective for bacterial, fungal, and acanthamoeba keratitis, post-operative complications such as graft rejection, secondary glaucoma, and persistent infection remain a concern.\u003csup\u003e1-3\u003c/sup\u003e The timing of intervention remains debated, due to the challenge of predicting which infections will fail medical therapy or have poorer grafting outcomes.\u003csup\u003e4-5\u003c/sup\u003e This study evaluates outcomes of therapeutic PKP for infectious corneal ulcers, focusing on whether the timing of surgery affects postoperative results.\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis included 56 patients who underwent therapeutic PKP for infectious corneal ulcers between 2014 and 2020 at the University of Colorado Department of Ophthalmology. The study was conducted in accordance with the Declaration of Helsinki and approved by the Colorado Multiple Institutional Review Board (COMIRB #20-2564). Informed consent was waived by the IRB due to the retrospective nature of the study and minimal risk to participants. Preoperative variables such as ulcer size, infectious organism, visual acuity (VA), corneal perforation, and hypopyon were recorded. Therapeutic PKP was performed following the standard procedures, including excision of all necrotic or infected corneal tissue when able. Postoperatively, topical antibiotic or antifungal drops were tapered according to clinical response, and steroid drops were tapered at the clinician\u0026rsquo;s discretion. Postoperative outcomes of interest were final visual acuity (VA) 20/200 or better, transplant failure, recurrent infection, and repeat PKP. Categorical outcomes were compared using Chi-square or Fisher\u0026rsquo;s exact test, and median time to PKP was compared for binary outcomes using the Wilcoxon rank sum test.\u003c/p\u003e\n\u003cp\u003eThe study cohort consisted of 56 patients with a mean age of 58.3 years. Bacterial infections were the most common (55.4%), followed by fungal (10.7%), viral (7.4%), and acanthamoeba (7.4%), (Table 1). The average time from ulcer onset to PKP was 47.0 days (range 3.0 to 210 days). Preoperatively, 29.1% of patients had VA better than hand motion (range 20/25 to no light perception), and 47.3% had corneal perforation. Most patients (89.3%) had at least one form of medical insurance (Medicaid/Medicare/commercial/other) and 10.7% were uninsured.\u003c/p\u003e\n\u003cp\u003eTable 1 \u0026ndash; Demographic and clinical information at presentation for patients (N=56)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years), mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e58.3 (18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e29 (51.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Caucasian\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Hispanic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;African American\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Asian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (89.3%)\u003c/p\u003e\n \u003cp\u003e3 (5.4%)\u003c/p\u003e\n \u003cp\u003e2 (3.6%)\u003c/p\u003e\n \u003cp\u003e1 (1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInsurance\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Insured\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Uninsured\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (89.3%)\u003c/p\u003e\n \u003cp\u003e6 (10.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime from ulcer onset to PKP (days)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Mean (SD)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=48)\u003c/p\u003e\n \u003cp\u003e47.0 (48.5)\u003c/p\u003e\n \u003cp\u003e30.0 (3-210)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCulture*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Bacterial\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Fungal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Viral\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Acanthamoeba\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Culture negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31 (55.4%)\u003c/p\u003e\n \u003cp\u003e6 (10.7%)\u003c/p\u003e\n \u003cp\u003e4 (7.1%)\u003c/p\u003e\n \u003cp\u003e4 (7.1%)\u003c/p\u003e\n \u003cp\u003e14 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUlcer size \u0026gt;6mm\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=41)\u003c/p\u003e\n \u003cp\u003e10 (24.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerforation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=55)\u003c/p\u003e\n \u003cp\u003e26 (47.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypopyon\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=52)\u003c/p\u003e\n \u003cp\u003e16 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDonor graft size \u0026gt;=9mm diameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=52)\u003c/p\u003e\n \u003cp\u003e19 (36.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePresenting visual acuity better than HM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e(n=55)\u003c/p\u003e\n \u003cp\u003e16 (29.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Unknowns not included in the denominators.\u003c/p\u003e\n\u003cp\u003e*3 patients had multiple categories\u003c/p\u003e\n\u003cp\u003eAmong the 46 patients with at least 30 days of follow-up, 37.0% had persistent infection, 34.8% experienced transplant failure, and 32.6% required repeat PKP (Table 2). Average follow up duration for the 46 patients with more than 30 days of follow-up was 2.7 years (SD 1.7 years, range 30 days to 6 years). \u0026nbsp;Patients who had recurrent infection had significantly longer time from ulcer onset to PKP than patients who did not have infection (median 60.0 days vs. 17.5 days; Wilcoxon rank sum test p-value =0.02). However, timing of surgery was not associated with transplant failure or final VA of 20/200 or better. \u0026nbsp;Likewise, the size of the corneal ulcer, infectious etiology, corneal perforation, and visual acuity on initial presentation all had no association with final visual acuity outcomes, transplant failure, or recurrent infection (all p-values \u0026gt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 - Postoperative Outcomes Following Therapeutic RPK in Patients with \u0026gt;30 Days of Follow-Up (n=46)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePersistent infection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e17 (37.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTransplant failure/rejection\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e16 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlaucoma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e16 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRequired 2nd PKP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e15 (32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 266px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePost-op vision 20/200 or better\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 168px;\"\u003e\n \u003cp\u003e\u0026nbsp;16 (35.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eMicrobial keratitis can be vision-threatening when unresponsive to medical therapy. In this study, we describe outcomes of therapeutic PKP for active corneal infection. One-third of patients had transplant failure, one-third had persistent infection, and only one-third achieved VA of 20/200 or better. Earlier surgery was associated with lower rates of recurrent infection; those without recurrence underwent PKP about 1.5 months earlier than those with recurrence. Delayed intervention may allow infection to spread to the limbus or sclera, increasing risk of recurrence.\u003c/p\u003e\n\u003cp\u003eOur study did not find infectious etiology, ulcer size, perforation, or presenting VA to be associated with final visual outcomes or transplant failure. Most patients had poor final VA, consistent with prior reports: compared to prior research, our cohort had worse visual outcomes, though variability in follow-up and limited VA data likely influenced results.\u003csup\u003e5\u0026nbsp;\u003c/sup\u003eWhile elective PKPs performed after inflammation has subsided have better outcomes, eyes with active infection, perforation, or impending perforation may necessitate earlier intervention. Prior studies have identified risk factors for needing therapeutic PKP, including delayed referral, corticosteroid use, poor initial VA, and large ulcers.\u003csup\u003e1,4\u003c/sup\u003e These underscore the importance of early recognition and management.\u003c/p\u003e\n\u003cp\u003eThis study is limited by its retrospective design, relatively small sample size, and lack of a comparison group treated without PKP. Further research is needed to identify which patients may benefit most from early surgical intervention versus continued medical therapy.\u003c/p\u003e\n\u003cp\u003eInfectious corneal ulcers requiring therapeutic PKP have a high risk of persistent infection and graft failure. While the timing of surgery did not impact final VA or transplant failure, earlier intervention was associated with reduced risk of recurrent infection. Ophthalmologists should consider early PKP for infections poorly responsive to medical treatment to prevent progression and minimize complications. Further studies are needed to refine the criteria for early surgical intervention to optimize outcomes for patients with infectious corneal ulcers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eCompeting interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003eFunding sources: Research for this study was supported by a Research to Prevent Blindness grant to the Department of Ophthalmology, University of Colorado.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: Available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding: Supported by an unrestricted Research to Prevent Blindness grant to the Department of Ophthalmology, University of Colorado.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eBrady Hogan contributed to data interpretation, drafting the manuscript, and revisions.\u003c/p\u003e\n\u003cp\u003eTroy Teeples contributed to data interpretation and critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003eJennifer L. Patnaik contributed to study design, data analysis, and revision for intellectual content.\u003c/p\u003e\n\u003cp\u003eScott Hauswirth provided input on clinical interpretation and revised the manuscript critically for intellectual content.\u003c/p\u003e\n\u003cp\u003eKaren L. Christopher conceived and supervised the study, assisted with interpretation, and provided final approval of the version to be published.\u003c/p\u003e\n\u003cp\u003eAll authors meet ICMJE authorship criteria, have reviewed the final manuscript, and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSony P, Sharma N, Vajpayee RB, et al. Therapeutic keratoplasty for infectious keratitis: a review of the literature. CLAO J. 2002;28(3):111-118.\u003c/li\u003e\n\u003cli\u003eDogan C, Arslan OS. Outcomes of therapeutic and tectonic penetrating keratoplasty in eyes with perforated infectious corneal ulcer. Turk J Ophthalmol. 2019;49(2):55-60.\u003c/li\u003e\n\u003cli\u003eYalniz-Akkaya Z, Burcu A, Dogan E, et al. Therapeutic penetrating keratoplasty for infectious and non-infectious corneal ulcers. Int Ophthalmol. 2015;35(2):193-200.\u003c/li\u003e\n\u003cli\u003eSharma N, Jain M, Sehra SV, et al. Outcomes of therapeutic penetrating keratoplasty from a tertiary eye care centre in northern India. Cornea. 2014;33(2):114-118.\u003c/li\u003e\n\u003cli\u003eRaj A, Bahadur H, Dhasmana R. Outcome of therapeutic penetrating keratoplasty in advanced infectious keratitis. J Curr Ophthalmol. 2018;30(4):315-320.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"microbial keratitis, therapeutic keratoplasty, corneal ulcer, infectious keratitis, graft failure, surgical timing","lastPublishedDoi":"10.21203/rs.3.rs-7303657/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7303657/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTherapeutic penetrating keratoplasty (PKP) is often required in severe infectious keratitis unresponsive to medical therapy. This study evaluates visual and surgical outcomes of therapeutic PKP and explores whether surgical timing influences recurrence, transplant failure, or visual outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e A retrospective review of 56 patients who underwent PKP for infectious keratitis at a US tertiary academic center between 2014 and 2020. Clinical data including time from ulcer onset to surgery, ulcer size, causative organism, and postoperative outcomes (recurrent infection, graft failure, final VA) were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf 46 patients with \u0026gt;\u0026thinsp;30 days of follow-up, 37.0% had persistent infection, 34.8% experienced transplant failure, and 32.6% required repeat PKP. Longer time to PKP was significantly associated with infection recurrence (median 60.0 vs 17.5 days, p\u0026thinsp;=\u0026thinsp;0.02). Timing of surgery did not influence transplant failure or final VA.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eTherapeutic PKP is associated with high complication rates in infectious keratitis. Earlier surgical intervention may reduce the risk of recurrent infection, though it does not appear to affect final vision or graft failure. Early surgical consideration may be warranted when infections fail to respond to medical therapy.\u003c/p\u003e","manuscriptTitle":"Therapeutic Penetrating Keratoplasty for Infectious Corneal Ulcers: Outcomes and Timing","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-12 11:56:55","doi":"10.21203/rs.3.rs-7303657/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d87b36ee-eb73-4cce-970f-08e712b93000","owner":[],"postedDate":"August 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-23T20:53:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-12 11:56:55","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7303657","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7303657","identity":"rs-7303657","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}