Sterile Corneal Infiltrates After Combined Riboflavin-UVA Corneal Collagen Cross-Linking for Keratoconus

Sterile Corneal Infiltrates After Combined Riboflavin-UVA Corneal Collagen Cross-Linking for Keratoconus | 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 Research Article Sterile Corneal Infiltrates After Combined Riboflavin-UVA Corneal Collagen Cross-Linking for Keratoconus Aysel Pelit, Zeynep Kunt This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8316067/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 To investigate sterile corneal infiltrate seen in 14 patients after accelerated corneal collagen cross-linking (CXL) for keratoconus. Setting: Baskent University, Faculty of Medicine, Adana Clinic and Research Center, Ophthalmology Department. Methods The records for all 300 eyes of 190 cases who underwent corneal collagen cross-linking were reviewed retrospectively. Our approach for CXL was the epithelial-off surgical technique, which involved corneal de-epithelization with the administration of riboflavin for 30 minutes and exposure to 9 mW/cm 2 ultraviolet-A for 10 minutes. Results Corneal stromal infiltrate was observed in 14 of our patients after uneventful CXL treatment. Eight of the 14 patients had allergic conjunctivitis. The infiltrates were located in the anterior superficial stroma in the 9 mm peripheral region in 13 patients and centrally located in one patient. No microorganism growth seen in the samples. Corneal infiltrates were treated with topical steroids, antibiotics, and artificial tears in all patients. Complete recovery was achieved in all cases after several weeks of treatment. Conclusion Patients with allergic conjunctivitis are at increased risk of developing sterile corneal infiltrates. Corneal infiltrates can improve and resolve with appropriate treatment. Visual outcomes are good despite this complication. Corneal infiltrate Corneal collagen cross-linking keratoconus INTRODUCTION Keratoconus is a bilateral non-inflammatory progressive ectatic ocular surface disorder characterized by corneal thinning [ 1 ]. It is usually seen bilaterally but can be seen symmetrically or asymmetrically [ 1 ]. Keratoconus is a condition affecting 1 in 2000 of the population. Environmental factors such as microtrauma, oxidative damage, genetic factors, and eye scratching are thought to play roles in the etiology [ 1 ]. Symptoms of keratoconus disease, which can be seen in both genders, usually include blurred vision, increased light sensitivity, decreased visual quality, and headache. With advances in technology, keratoconus disease is diagnosed more frequently and earlier [ 1 , 2 ]. Corneal collagen cross-linking (CXL) is a treatment modality used to halt the progression of keratoconus [ 2 – 5 ]. Standard CXL is a safe and approved procedure that was shown to stabilize the progressive keratoconus. However, certain complications such as corneal haze, infectious keratitis, decreased vision, and sterile corneal infiltrates can occur with this treatment method [ 2 – 5 ]. MATERIALS AND METHODS A total of 300 (110 bilateral, 80 unilateral) eyes from 190 patients who were followed up in XXX University Faculty of Medicine, Ophthalmology Department for keratoconus and treated with corneal collagen cross-linking were retrospectively evaluated. Ethical approval for this retrospective study was obtained from XXX University medical and health Units research Board and Ethics Committee ( Project no:KA25/358, 8/10/2025) In all patients, keratoconus progression was detected before corneal collagen cross-linking treatment, which was based on topographic parameters. Patients with moderate and advanced keratoconus were included in our study. A placido disk corneal topographer (Orbscan IIZ; Bausch and Lomb, USA) showed a pattern consistent with Amsler-Krumeich stage II-III keratoconus for all eyes with maximum keratometry (Kmax ≤ 59 D, corneal thickness > 400 µm). Informed consent was obtained from the patients, and an information form was obtained for the study. Ophthalmologic examinations and surgeries were done by one of the authors (AP). CXL treatment was planned for all eyes under topical anesthesia. During the procedure, corneal epithelium was removed by using a 15 number blade in the intended 8–9 mm zone. After de-epithelization, residual corneal thickness was measured with an ultrasonic pachymetry (PalmScan AP-2000-Ultima, USA). Corneal thickness was measured above 400 µm and iso-osmolar 0.1% riboflavin solution was instilled at regular intervals of two minutes for 30 minutes (0.1% riboflavin without dextran, Meran Medicine, Istanbul, Turkey). After riboflavin administration, 9 mw/cm 2 ultraviolet-A (UV-A) light was used for 10 minutes. CBM-X Linker (CSO, Florence, Italy) was used as the UVA radiation source. The total application was 5.4 J/cm 2 . At the end of the procedure, a bandage contact lens (Purevision, Bausch and Lomb, USA) was inserted for ocular comfort. After the operation, topical antibiotics were used q.i.d. for one week (0.5% drops of moxifloxacin hydrochloride 4x1) and topical artificial tear treatment was used q.i.d for 1 month (single dose of 0.4 ml sterile containing povidone and polyvinyl alcohol drops 4x1). The patients were discharged from the hospital after the operation. All patients were followed up at day 1, day 4, week 1, month 1, month 3, and month 6. Statistical Analysis: Microsoft excel was used to perform the requisite statistical analyses. RESULTS The mean age of the 14 patients (6 men and 8 women) who developed sterile keratitis was 21.64 years (SD: 5.03). The maximum corneal curvatures for the cases that developed infiltrate were on average 51.2 (SD: 3.84 D). The thinnest corneal pachymetry on Orbscan for the 14 cases was on average 414.14 µm (SD: 12.95 µm). Four cases had steeper cornea (≥ 55) on topography. Allergic conjunctivitis was detected in eight patients. Fourteen patients developed anterior stromal corneal infiltrates within the first postoperative week. Corneal infiltrates were found to be peripheral in 13 and centrally located in one patient. All bandage contact lenses were removed and sent for microbiologic evaluation. Also corneal scrapes were taken from the corneal infiltrates of 14 patients for microscopy (gram stain and 10% KOH fresh mount), along with cultures for bacteria and fungi (blood agar, Sabouraud dextrose agar, non-nutrient agar with Escherichia coli overlay). Complete systemic and rheumatologic investigations were negative for 14 patients. Infiltrates were in the corneal periphery in 13 patients, while infiltrate was in the corneal center in 1 patient. This patient had maximum keratometry of 59 D. Corneal infiltrates were located in the anterior superficial stroma in all patients and were in the 9.0 mm zone of the cornea. No pathogenic agents were detected in corneal infiltrates according to microbiological tests and cultures. These lesions were evaluated as sterile corneal infiltrates. Demographic characteristics of the patients are shown in Table 1 . Table 1 Preoperative characteristics of patients with sterile infiltrates after CXL Patients 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Age (Years) 20 15 18 24 29 17 16 25 30 29 21 22 18 19 Sex female male female male female male female male male female female female male female Preoperative corneal thickness Topography central 441 435 430 495 482 430 419 433 487 479 500 450 456 470 Thinnest location on topography 400 402 410 435 430 406 400 412 408 404 440 421 414 416 Preoperative max K (D) 49.1 48.8 50 49.1 48.5 56.2 59 55 49.4 48.4 47.9 57.3 48.7 49.5 Refractive spherical equivalent (D) -5.5 -6.75 -3.75 -1 -2.5 -3 -7.25 -12 -2.25 -6.5 -3.75 -5.2 -3.75 -4.75 Refractive astigmatism -3.25 -2.75 -3.5 -3.25 -3.5 -5 -7.75 -4.5 -4.25 -4.25 -2.75 -5.5 -3.25 -4.25 Allergic conjunctivitis 1 1 1 0 0 1 1 1 0 0 0 0 1 1 Postoperative course and management of affected patients All patients were treated as cases of possible infective keratitis. The treatment was revised to topical antibiotic q.i.d. for one week (moxifloxacin hydrochloride 0.5% drop 4x1, Alcon lab, USA), topical steroid q.i.d on a tapering schedule for one month (loteprednol 5 mg/ml drop 4x1, Bausch Lomb, USA), and topical artificial tear treatment q.i.d for one month (single dose of 0.4 ml sterile polyvinyl alcohol and povidone drop 8x1). After four weeks of treatment, all 14 patients showed improvement and resolution of the corneal infiltrate. All topical medications, except artificial tear substitutes, were tapered and stopped. There was complete resolution of infiltrates with total epithelial healing at two month check-up after crosslinking. DISCUSSION The role and importance of CXL increases in the approach to keratoconus [ 3 ]. In the progression of keratoconus, CXL treatment is successful in stopping progression and delaying corneal transplantation [ 3 – 5 ]. Contraindications to CXL treatment include less than 400 microns of corneal thickness, previous herpetic keratitis, presence of active ocular infection, severe corneal scar or opacification, history of poor corneal epithelial healing, presence of autoimmune diseases and severe ocular surface diseases [ 3 , 4 ]. As with any treatment approach, some complications can be observed with CXL treatment. These complications include postoperative infectious keratitis, haze, persistent scars, and sterile infiltrates [ 3 ]. Although CXL treatment is not a very invasive procedure, inappropriate technique, secondary complications to low patient hygiene, and concomitant ocular surface diseases may play increasing roles in the occurrence of complications [ 4 ]. Although sterile corneal infiltrates are rare complications, various hypotheses have been proposed for the etiology [ 4 , 6 ]. Sterile corneal infiltrates can be seen as a result of CXL treatment, as well as with prolonged contact lens use, corneal surgery, systemic autoimmune diseases, and immune system-related reactions [ 6 ]. Various mechanisms such as increased cell-mediated immune response to staphylococcal antigens, phototoxic effect on stroma, alteration of natural protein structure, contact lens-induced tear pooling, and poor hygiene are thought to be involved in the etiology [ 4 , 6 – 11 ]. Although UVA is known to be bactericidal, infectious and sterile corneal infiltrates can also be seen after CXL treatment [ 3 , 6 , 7 ]. Corneal infiltrates after CXL are generally multiple and superficial, and are seen at the border of peripheral cornea or treatment zone [ 4 , 6 , 7 ]. In our study, sterile corneal infiltrates were found to be peripheral in 13 of 14 patients but centrally located in one patient. Sterile corneal infiltrates were seen in 4.6% of eyes in our study. Koller et al. reported sterile infiltrates in 7.6% of eyes and Lam et al. reported central corneal infiltrates in 2.7% of eyes in their study [ 4 , 8 ]. In the literature, there is no study that highlights risk factors for the development of sterile keratitis after uncomplicated CXL treatment. In a prospective study by Koller et al., no predictive factor for the development of sterile corneal infiltrate was identified [ 8 ]. Lam et al. reported that low corneal thickness and steeper corneal curvature were increased risk factors for the development of sterile corneal infiltrates [ 4 ]. Similarly, Kodavoor et al. 12 recommend that very high suspicion should be maintained, especially when treating patients with thinner corneas and steeper corneal curvatures. In our study, steeper corneal curvature was noted in 28.57% but the presence of associated allergic conjunctivitis was noted 57.14% in this case series. One of the hypotheses is that phototoxic effect on corneal stroma, changes in natural protein structure, and antigenicity may play roles in the etiology. UVA-riboflavin complex can induce stromal antigenicity and contribute to increase immunological response [ 11 ]. The other hypothesis by Angunawela et al. states that staphylococcal antigens that are deposited at high concentrations in areas of static tear pooling may trigger an immune response and cause sterile corneal infiltrates [ 13 ]. In our opinion, in addition of these mechanisms to allergic eye problems may trigger these reactions. Cerman et al. suggested that postoperative use of NSAIDs increased the risk of developing sterile corneal infiltrates by about four times. In this study, we did not use NSAIDs in the postoperative period [ 9 ]. In the literature, the prognosis for sterile corneal infiltrates was found to be good [ 4 , 6 – 14 ]. Similarly, improvement and resolution of sterile corneal infiltrates were observed in our patients after treatment and good visual outcomes were obtained despite this complication. In conclusion, sterile corneal infiltrates can be detected following uncomplicated CXL treatment [ 2 , 3 ]. Patients with allergic conjunctivitis appear to be at higher risk for sterile infiltrates. We believe that further studies involving large populations are needed to determine predictive factors and to investigate treatment approaches for sterile corneal infiltrates. Declarations Conflicts of interest: The authors of the study declare no conflicts of interest. Funding: This study was supported by the Research Fund of the Baskent University Acknowledgments: Not applicable. Ethics approval: Local ethics committee approval was obtained. The institution at which the study was conducted: Başkent University School of Medicine Department of Ophthalmology, Adana Hospital References Rabinowitz YS. Keratoconus. Survey of Ophthalmology 1998; 42: 297–319. Alhayek A, Lu PR. Corneal collagen cross-linking in keratoconus and other eye disease. Int J Ophthalmol 2015; 8: 407–418. Burcu A. Keratokonus tedavisinde güncel girişimsel yöntemler. Turk J Ophthalmol 2013; 43: 263–9. Lam FC, Geourgoudis P, Nanavaty MA, et al. Sterile keratitis after combined riboflavin-UVA corneal collagen cross-linking for keratoconus. Eye 2014; 28: 1297–1303. Franzco GS. Collagen cross-linking: a new treatment paradigm in corneal disease – a review. Clinical and Experimental Ophthalmology 2010; 38: 141–153. Rodriguez-Ausin P, Gutierrez-Ortega R, Arance-Gil A, et al. Keratopathy after cross-linking for keratoconus. Cornea 2011; 30: 1051–1053. Javadi MA, Feizi S. Sterile keratitis following collagen crosslinking. J Ophthalmic Vis Res 2014; 9: 510–513. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg 2009; 35: 1358–1362. Cerman E, Ozcan DO, Toker E. Sterile corneal infiltrates after corneal collagen cross-linking: evaluation of risk factors. Acta Ophthalmol 2017; 95(2): 199–204. Arora R, Jain P, Gupta D, Goyal JL. Sterile keratitis after corneal collagen crosslinking in a child. Contact Lens and Anterior Eye 2012; 35: 233–235. Ghanem RC, Netto MV, Ghanem VC, et al. Peripheral sterile corneal ring infiltrate after riboflavin-UVA collagen cross-linking in keratoconus. Cornea 2012; 31: 702–705. Kodavoor SK, Tiwari NN, Ramamurthy D. Profile of infectious and sterile keratitis after accelerated corneal collagen cross-linking for keratoconus. Oman J Ophthalmol 2020; 13(1): 18–23. Mereaux D, Knoeri J, Jouve L, et al. Sterile keratitis following standart corneal collagen crosslinking: A case series and literature review. Journal Français D’Ophthalmologie 2019; 42: 603–611. Angunawela RI, Arnalich-Montiel F, Allan BDS. Peripheral sterile corneal infiltrates and melting after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2009;35:606–607. 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-8316067","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557832186,"identity":"e629c7c6-edae-4e7f-818d-d2491cbdd158","order_by":0,"name":"Aysel Pelit","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYLCCBwYMcgwMPKRoSTAwMCZVC4NBYgPRWvhn5B58kFDwJ33D8bMHH3xgsJPTbSCgReJGXrIB0GG5G87kJRvOYEg2NjtAyJobOWYSYC0HcsykeRgOJG4jpEX+Ro75D6CWdIPzb4jUYgC0BRRiCSAGcVoMz7xLBjrM2HDmjTfGhjMMiPCL3PHcgx8+/JGT5zufY/jgQ4WdHGHvC+RAaAWwSgNCykGA/wyElm8gRvUoGAWjYBSMSAAAzRRDSwo+BzQAAAAASUVORK5CYII=","orcid":"","institution":"Başkent University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Aysel","middleName":"","lastName":"Pelit","suffix":""},{"id":557832187,"identity":"cae11b47-5afc-4d6e-9397-09ebd1903e7e","order_by":1,"name":"Zeynep Kunt","email":"","orcid":"","institution":"Başkent University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zeynep","middleName":"","lastName":"Kunt","suffix":""}],"badges":[],"createdAt":"2025-12-09 09:53:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8316067/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8316067/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97954139,"identity":"7a474dd1-a1bf-4765-9c94-02ff9bc1bd0f","added_by":"auto","created_at":"2025-12-11 07:44:23","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":42846,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/78c69d78694e8e65572d4cc4.docx"},{"id":98422513,"identity":"9a8d1f2f-7aa8-4321-93f1-e498e3f440b8","added_by":"auto","created_at":"2025-12-17 16:31:10","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3899,"visible":true,"origin":"","legend":"","description":"","filename":"ecfa4a999c584b24abc0f4f54091c3a3.json","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/e171d28262d7095c8dc3c070.json"},{"id":97954135,"identity":"fb12847c-ac4f-4c32-9482-f5761726f7e2","added_by":"auto","created_at":"2025-12-11 07:44:22","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":50187,"visible":true,"origin":"","legend":"","description":"","filename":"ecfa4a999c584b24abc0f4f54091c3a31enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/44d03c98c7161896863981e7.xml"},{"id":97954136,"identity":"7ca450aa-ae97-4ade-a225-6984f4d610e9","added_by":"auto","created_at":"2025-12-11 07:44:22","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":46376,"visible":true,"origin":"","legend":"","description":"","filename":"ecfa4a999c584b24abc0f4f54091c3a31structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/91ac2989f4530d4c4f4efdac.xml"},{"id":98423523,"identity":"e0ad5c83-efd0-4fd8-ad2f-9f4b12bd2a51","added_by":"auto","created_at":"2025-12-17 16:32:20","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":54261,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/8ac6cf9b0e1b1c3fdd06d4a5.html"},{"id":100857666,"identity":"f3e32630-0325-4b32-9d10-ccfe1f7a8e16","added_by":"auto","created_at":"2026-01-22 07:18:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":392232,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8316067/v1/d2e1f329-5cb6-4c07-afff-f229af21cfe8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sterile Corneal Infiltrates After Combined Riboflavin-UVA Corneal Collagen Cross-Linking for Keratoconus","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eKeratoconus is a bilateral non-inflammatory progressive ectatic ocular surface disorder characterized by corneal thinning [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is usually seen bilaterally but can be seen symmetrically or asymmetrically [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Keratoconus is a condition affecting 1 in 2000 of the population. Environmental factors such as microtrauma, oxidative damage, genetic factors, and eye scratching are thought to play roles in the etiology [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Symptoms of keratoconus disease, which can be seen in both genders, usually include blurred vision, increased light sensitivity, decreased visual quality, and headache. With advances in technology, keratoconus disease is diagnosed more frequently and earlier [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCorneal collagen cross-linking (CXL) is a treatment modality used to halt the progression of keratoconus [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Standard CXL is a safe and approved procedure that was shown to stabilize the progressive keratoconus. However, certain complications such as corneal haze, infectious keratitis, decreased vision, and sterile corneal infiltrates can occur with this treatment method [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eA total of 300 (110 bilateral, 80 unilateral) eyes from 190 patients who were followed up in XXX University Faculty of Medicine, Ophthalmology Department for keratoconus and treated with corneal collagen cross-linking were retrospectively evaluated. Ethical approval for this retrospective study was obtained from XXX University medical and health Units research Board and Ethics Committee ( Project no:KA25/358, 8/10/2025) In all patients, keratoconus progression was detected before corneal collagen cross-linking treatment, which was based on topographic parameters.\u003c/p\u003e\u003cp\u003ePatients with moderate and advanced keratoconus were included in our study. A placido disk corneal topographer (Orbscan IIZ; Bausch and Lomb, USA) showed a pattern consistent with Amsler-Krumeich stage II-III keratoconus for all eyes with maximum keratometry (Kmax\u0026thinsp;\u0026le;\u0026thinsp;59 D, corneal thickness\u0026thinsp;\u0026gt;\u0026thinsp;400 \u0026micro;m). Informed consent was obtained from the patients, and an information form was obtained for the study.\u003c/p\u003e\u003cp\u003eOphthalmologic examinations and surgeries were done by one of the authors (AP). CXL treatment was planned for all eyes under topical anesthesia. During the procedure, corneal epithelium was removed by using a 15 number blade in the intended 8\u0026ndash;9 mm zone. After de-epithelization, residual corneal thickness was measured with an ultrasonic pachymetry (PalmScan AP-2000-Ultima, USA). Corneal thickness was measured above 400 \u0026micro;m and iso-osmolar 0.1% riboflavin solution was instilled at regular intervals of two minutes for 30 minutes (0.1% riboflavin without dextran, Meran Medicine, Istanbul, Turkey). After riboflavin administration, 9 mw/cm\u003csup\u003e2\u003c/sup\u003e ultraviolet-A (UV-A) light was used for 10 minutes. CBM-X Linker (CSO, Florence, Italy) was used as the UVA radiation source. The total application was 5.4 J/cm\u003csup\u003e2\u003c/sup\u003e. At the end of the procedure, a bandage contact lens (Purevision, Bausch and Lomb, USA) was inserted for ocular comfort. After the operation, topical antibiotics were used q.i.d. for one week (0.5% drops of moxifloxacin hydrochloride 4x1) and topical artificial tear treatment was used q.i.d for 1 month (single dose of 0.4 ml sterile containing povidone and polyvinyl alcohol drops 4x1). The patients were discharged from the hospital after the operation. All patients were followed up at day 1, day 4, week 1, month 1, month 3, and month 6.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis:\u003c/h2\u003e\u003cp\u003eMicrosoft excel was used to perform the requisite statistical analyses.\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe mean age of the 14 patients (6 men and 8 women) who developed sterile keratitis was 21.64 years (SD: 5.03). The maximum corneal curvatures for the cases that developed infiltrate were on average 51.2 (SD: 3.84 D). The thinnest corneal pachymetry on Orbscan for the 14 cases was on average 414.14 \u0026micro;m (SD: 12.95 \u0026micro;m). Four cases had steeper cornea (\u0026ge;\u0026thinsp;55) on topography. Allergic conjunctivitis was detected in eight patients.\u003c/p\u003e\u003cp\u003eFourteen patients developed anterior stromal corneal infiltrates within the first postoperative week. Corneal infiltrates were found to be peripheral in 13 and centrally located in one patient. All bandage contact lenses were removed and sent for microbiologic evaluation. Also corneal scrapes were taken from the corneal infiltrates of 14 patients for microscopy (gram stain and 10% KOH fresh mount), along with cultures for bacteria and fungi (blood agar, Sabouraud dextrose agar, non-nutrient agar with Escherichia coli overlay). Complete systemic and rheumatologic investigations were negative for 14 patients. Infiltrates were in the corneal periphery in 13 patients, while infiltrate was in the corneal center in 1 patient. This patient had maximum keratometry of 59 D. Corneal infiltrates were located in the anterior superficial stroma in all patients and were in the 9.0 mm zone of the cornea. No pathogenic agents were detected in corneal infiltrates according to microbiological tests and cultures. These lesions were evaluated as sterile corneal infiltrates.\u003c/p\u003e\u003cp\u003eDemographic characteristics of the patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePreoperative characteristics of patients with sterile infiltrates after CXL\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"15\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (Years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative corneal thickness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTopography central\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e441\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e435\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e430\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e495\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e482\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e430\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e419\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e433\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e487\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e479\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e450\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e456\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e470\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThinnest location on topography\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e402\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e410\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e435\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e430\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e406\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e400\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e412\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e408\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e404\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e440\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e421\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e414\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e416\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative max K (D)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e49.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e48.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e56.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e49.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e48.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e47.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e57.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e48.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e49.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractive spherical equivalent (D)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-6.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-7.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-2.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-3.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e-5.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e-3.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e-4.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRefractive astigmatism\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-3.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-2.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-3.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-7.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-4.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-4.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-2.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e-5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e-3.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e-4.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAllergic conjunctivitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003ePostoperative course and management of affected patients\u003c/h3\u003e\n\u003cp\u003eAll patients were treated as cases of possible infective keratitis. The treatment was revised to topical antibiotic q.i.d. for one week (moxifloxacin hydrochloride 0.5% drop 4x1, Alcon lab, USA), topical steroid q.i.d on a tapering schedule for one month (loteprednol 5 mg/ml drop 4x1, Bausch Lomb, USA), and topical artificial tear treatment q.i.d for one month (single dose of 0.4 ml sterile polyvinyl alcohol and povidone drop 8x1).\u003c/p\u003e\u003cp\u003eAfter four weeks of treatment, all 14 patients showed improvement and resolution of the corneal infiltrate. All topical medications, except artificial tear substitutes, were tapered and stopped. There was complete resolution of infiltrates with total epithelial healing at two month check-up after crosslinking.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe role and importance of CXL increases in the approach to keratoconus [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In the progression of keratoconus, CXL treatment is successful in stopping progression and delaying corneal transplantation [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eContraindications to CXL treatment include less than 400 microns of corneal thickness, previous herpetic keratitis, presence of active ocular infection, severe corneal scar or opacification, history of poor corneal epithelial healing, presence of autoimmune diseases and severe ocular surface diseases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As with any treatment approach, some complications can be observed with CXL treatment. These complications include postoperative infectious keratitis, haze, persistent scars, and sterile infiltrates [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Although CXL treatment is not a very invasive procedure, inappropriate technique, secondary complications to low patient hygiene, and concomitant ocular surface diseases may play increasing roles in the occurrence of complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough sterile corneal infiltrates are rare complications, various hypotheses have been proposed for the etiology [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Sterile corneal infiltrates can be seen as a result of CXL treatment, as well as with prolonged contact lens use, corneal surgery, systemic autoimmune diseases, and immune system-related reactions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Various mechanisms such as increased cell-mediated immune response to staphylococcal antigens, phototoxic effect on stroma, alteration of natural protein structure, contact lens-induced tear pooling, and poor hygiene are thought to be involved in the etiology [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough UVA is known to be bactericidal, infectious and sterile corneal infiltrates can also be seen after CXL treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Corneal infiltrates after CXL are generally multiple and superficial, and are seen at the border of peripheral cornea or treatment zone [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In our study, sterile corneal infiltrates were found to be peripheral in 13 of 14 patients but centrally located in one patient. Sterile corneal infiltrates were seen in 4.6% of eyes in our study. Koller et al. reported sterile infiltrates in 7.6% of eyes and Lam et al. reported central corneal infiltrates in 2.7% of eyes in their study [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the literature, there is no study that highlights risk factors for the development of sterile keratitis after uncomplicated CXL treatment. In a prospective study by Koller et al., no predictive factor for the development of sterile corneal infiltrate was identified [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Lam et al. reported that low corneal thickness and steeper corneal curvature were increased risk factors for the development of sterile corneal infiltrates [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Similarly, Kodavoor et al.\u003csup\u003e12\u003c/sup\u003e recommend that very high suspicion should be maintained, especially when treating patients with thinner corneas and steeper corneal curvatures.\u003c/p\u003e\u003cp\u003eIn our study, steeper corneal curvature was noted in 28.57% but the presence of associated allergic conjunctivitis was noted 57.14% in this case series.\u003c/p\u003e\u003cp\u003eOne of the hypotheses is that phototoxic effect on corneal stroma, changes in natural protein structure, and antigenicity may play roles in the etiology. UVA-riboflavin complex can induce stromal antigenicity and contribute to increase immunological response [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The other hypothesis by Angunawela et al. states that staphylococcal antigens that are deposited at high concentrations in areas of static tear pooling may trigger an immune response and cause sterile corneal infiltrates [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In our opinion, in addition of these mechanisms to allergic eye problems may trigger these reactions.\u003c/p\u003e\u003cp\u003eCerman et al. suggested that postoperative use of NSAIDs increased the risk of developing sterile corneal infiltrates by about four times. In this study, we did not use NSAIDs in the postoperative period [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the literature, the prognosis for sterile corneal infiltrates was found to be good [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11 CR12 CR13\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similarly, improvement and resolution of sterile corneal infiltrates were observed in our patients after treatment and good visual outcomes were obtained despite this complication.\u003c/p\u003e\u003cp\u003eIn conclusion, sterile corneal infiltrates can be detected following uncomplicated CXL treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients with allergic conjunctivitis appear to be at higher risk for sterile infiltrates. We believe that further studies involving large populations are needed to determine predictive factors and to investigate treatment approaches for sterile corneal infiltrates.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflicts of interest: The authors of the study declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding: This study was supported by the Research Fund of the Baskent University\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgments: Not applicable.\u003c/p\u003e\n\u003cp\u003eEthics approval: Local ethics committee approval was obtained.\u003c/p\u003e\n\u003cp\u003eThe institution at which the study was conducted: Başkent University School of Medicine Department of Ophthalmology, Adana Hospital\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRabinowitz YS. Keratoconus. Survey of Ophthalmology 1998; 42: 297\u0026ndash;319.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlhayek A, Lu PR. Corneal collagen cross-linking in keratoconus and other eye disease. Int J Ophthalmol 2015; 8: 407\u0026ndash;418.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBurcu A. Keratokonus tedavisinde g\u0026uuml;ncel girişimsel y\u0026ouml;ntemler. Turk J Ophthalmol 2013; 43: 263\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLam FC, Geourgoudis P, Nanavaty MA, et al. Sterile keratitis after combined riboflavin-UVA corneal collagen cross-linking for keratoconus. Eye 2014; 28: 1297\u0026ndash;1303.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFranzco GS. Collagen cross-linking: a new treatment paradigm in corneal disease \u0026ndash; a review. Clinical and Experimental Ophthalmology 2010; 38: 141\u0026ndash;153.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRodriguez-Ausin P, Gutierrez-Ortega R, Arance-Gil A, et al. Keratopathy after cross-linking for keratoconus. Cornea 2011; 30: 1051\u0026ndash;1053.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJavadi MA, Feizi S. Sterile keratitis following collagen crosslinking. J Ophthalmic Vis Res 2014; 9: 510\u0026ndash;513.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg 2009; 35: 1358\u0026ndash;1362.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCerman E, Ozcan DO, Toker E. Sterile corneal infiltrates after corneal collagen cross-linking: evaluation of risk factors. Acta Ophthalmol 2017; 95(2): 199\u0026ndash;204.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eArora R, Jain P, Gupta D, Goyal JL. Sterile keratitis after corneal collagen crosslinking in a child. Contact Lens and Anterior Eye 2012; 35: 233\u0026ndash;235.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGhanem RC, Netto MV, Ghanem VC, et al. Peripheral sterile corneal ring infiltrate after riboflavin-UVA collagen cross-linking in keratoconus. Cornea 2012; 31: 702\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKodavoor SK, Tiwari NN, Ramamurthy D. Profile of infectious and sterile keratitis after accelerated corneal collagen cross-linking for keratoconus. Oman J Ophthalmol 2020; 13(1): 18\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMereaux D, Knoeri J, Jouve L, et al. Sterile keratitis following standart corneal collagen crosslinking: A case series and literature review. Journal Fran\u0026ccedil;ais D\u0026rsquo;Ophthalmologie 2019; 42: 603\u0026ndash;611.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAngunawela RI, Arnalich-Montiel F, Allan BDS. Peripheral sterile corneal infiltrates and melting after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2009;35:606\u0026ndash;607.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Corneal infiltrate, Corneal collagen cross-linking, keratoconus","lastPublishedDoi":"10.21203/rs.3.rs-8316067/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8316067/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo investigate sterile corneal infiltrate seen in 14 patients after accelerated corneal collagen cross-linking (CXL) for keratoconus.\u003c/p\u003e\u003ch2\u003eSetting:\u003c/h2\u003e\u003cp\u003eBaskent University, Faculty of Medicine, Adana Clinic and Research Center, Ophthalmology Department.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe records for all 300 eyes of 190 cases who underwent corneal collagen cross-linking were reviewed retrospectively. Our approach for CXL was the epithelial-off surgical technique, which involved corneal de-epithelization with the administration of riboflavin for 30 minutes and exposure to 9 mW/cm\u003csup\u003e2\u003c/sup\u003e ultraviolet-A for 10 minutes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eCorneal stromal infiltrate was observed in 14 of our patients after uneventful CXL treatment. Eight of the 14 patients had allergic conjunctivitis. The infiltrates were located in the anterior superficial stroma in the 9 mm peripheral region in 13 patients and centrally located in one patient. No microorganism growth seen in the samples. Corneal infiltrates were treated with topical steroids, antibiotics, and artificial tears in all patients. Complete recovery was achieved in all cases after several weeks of treatment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003ePatients with allergic conjunctivitis are at increased risk of developing sterile corneal infiltrates. Corneal infiltrates can improve and resolve with appropriate treatment. Visual outcomes are good despite this complication.\u003c/p\u003e","manuscriptTitle":"Sterile Corneal Infiltrates After Combined Riboflavin-UVA Corneal Collagen Cross-Linking for Keratoconus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-11 07:44:18","doi":"10.21203/rs.3.rs-8316067/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":"9101966f-83cf-41cb-9afb-d958db6a384f","owner":[],"postedDate":"December 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-18T17:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-11 07:44:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8316067","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8316067","identity":"rs-8316067","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}