Late onset post-LASIK keratectasia with reversal and stabilization after use of latanoprost and corneal collagen cross-linking

We report a case of late onset keratectasia after laser in situ keratomileusis (LASIK) and its quick reversal and stabilization after use of latanoprost and riboflavin/ultraviolet-A corneal collagen cross-linking (CXL). A 39-year-old man with normal intraocular pressure developed a rapid deterioration of vision in his left eye 6 years after LASIK-retreatment for high myopic astigmatism. Keratectasia was diagnosed by corneal topography and ultrasound pachymetry. After two months of treatment with latanoprost and a minor intraocular pressure reduction, uncorrected distance visual acuity improved from 20/100 to 20/20 and corneal topography showed reversal of keratectasia. CXL was performed after the reversal to achieve long-term stabilization. At 1, 3, 6, 13 and 39 months followup exams after the CXL, stable vision, refraction, and topography were registered. This case shows that keratectasia may rapidly occur several years after LASIK and that a quick reversal and stabilization may be achieved by use of latanoprost followed by CXL.

Relevance. Keratoconus is a common asymmetric and usually bilateral ectatic corneal disease characterized by progressive corneal protrusion, resulting in reduced visual acuity and deterioration of optical properties. Purpose of the study. To evaluate the effectiveness of surgical treatment of keratoconus with various combined methods. Material and methods. The article presents a comparative analysis of data from patients with II and III stages of keratoconus (52 patients, 66 eyes) after implantation of intrastromal corneal ring segments with femtosecond accompaniment, followed by corneal crosslinking and corneal crosslinking, followed by implantation of intrastromal corneal ring segments with femtosecond accompaniment. Results and conclusion. The refractive result for the spherical and cylindrical components gave the best result in group 2, in which stage 1 was implantation of ICRS, and stage 2 was corneal collagen crosslinking, compared with group 1, in which stage 1 was corneal collagen crosslinking, and stage 2 was implanted ICRS. Progression stopped in 65 cases. Keywords: keratoconus, intrastromal corneal segments, femtosecond laser, corneal crosslinking.

Paediatric cornea crosslinking current strategies: A review

Transepithelial Versus Epithelium-off Corneal Cross-Linking for the Treatment of Progressive Keratoconus: A Randomized Controlled Trial

Objective:To review the literature on current applications of corneal Collagen Cross-Linking (CXL).Methods:A review of publications on corneal cross-linking was conducted. This included systemic reviews, randomized controlled clinical trials, cohort studies, case-controlled studies and case series. A summary of the publications is tabulated.Results:The original indication of riboflavin – Ultraviolet-A (UVA) induced corneal collagen cross-linking is to arrest the progression of keratoconus. Studies show that it is effective in arresting the progression of keratoconus and post-LASIK ectasia with the standard Dresden protocol (epithelium-off). There are also improvements in visual, keratometric and topographic measurements over time. Severe complications of cross-linking are rare. The epithelium-on techniques have less efficacy than the Dresden protocol. Accelerated protocols have variable results, with some studies reporting comparable outcomes to the Dresden protocol while other studies reporting less efficacious outcomes. Cross-linking combined with refractive procedures provide better visual outcome but long term studies are warranted. Cross-linking for the treatment of infective keratitis is a promising new treatment modality. Initial studies show that it is more effective for superficial rather than deep infections and for bacterial rather than fungal infections.Conclusions:Corneal cross-linking is a procedure with an expanding list of indications from the treatment of corneal ectasias to infective keratitis. While the standard Dresden protocol is established as the gold standard treatment for progressive keratoconus, the more recent protocols may require further refinements, investigative and long-term studies.

Corneal collagen cross-linking (CCL) with riboflavin and ultraviolet A irradiation has recently been introduced for treatment of corneal ectasia. Yet a CCL-induced increase in corneal rigidity may interfere with intraocular pressure (IOP) measurements. In an investigation of the effect of CCL on the accuracy of IOP measurements, IOP readings before and after CCL were compared. Ten human eye bank corneas were de-epithelialized and mounted on an artificial anterior chamber. The hydrostatically controlled reference pressure in the chamber was adjusted from 10 to 40 mm Hg in 5-mm Hg steps. IOP was measured by Goldmann applanation tonometry (GAT; Haag Streit, Könitz, Switzerland), dynamic contour tonometry (DCT; Pascal tonometer; Ziemer Ophthalmics, Port, Switzerland), and the TonoPen XL (TP; Tono-Pen XL, Medtronic, Jacksonville, FL) before and after CCL, which was performed with a 0.1% riboflavin solution and 30 minutes of UVA irradiation. Before CCL, GAT, and DCT readings showed an excellent concordance with the manometric reference pressure, whereas TP overestimated the true IOP. After CCL, the reliability of IOP readings decreased with all three tonometers. This decrease resulted in a slight overestimation of mean IOP, but there were also some potentially dangerous underestimations in some individual corneas. The mean (+/-SD) difference between IOP readings after and before CCL was +1.8 (3.5) mm Hg for DCT, +2.9 (6.1) mm Hg for GAT, and +3.1 (8.3) mm Hg for TP (P <or= 0.002 for DCT versus GAT or TP). In this in vitro model on human corneas, CCL resulted in an overestimation of true IOP by all the tested tonometers. Although the magnitude of this effect was small, care should be taken when measuring IOP with GAT after CCL, as it results in less accurate, much more variable IOP readings.

Corneal collagen cross-linking (CXL) is a method for modifying the natural history of keratoconus and other corneal ectatic diseases. The authors evaluated the use of collagenase for generating an experimental model of ectasia to evaluate the topographic effects of CXL interventions. Nine human corneoscleral specimens unsuitable for transplantation were used. After epithelial debridement, mounting, and pressurization on an artificial anterior chamber, a solution of 10 mg/mL collagenase type II with 15% dextran was applied to five corneas for three hours. Three of these corneas subsequently underwent riboflavin/UV-A CXL. Scheimpflug-based tomography was performed before collagenase exposure, after collagenase exposure, and after CXL to evaluate changes in maximum axial curvature of the anterior surface (K(max)) at three IOP levels. Results were compared to four control eyes exposed to dextran alone. A statistically significant increase in K(max) was seen across all IOP levels in the collagenase group compared to the control group (+6.6 ± 1.1 diopters [D] and +0.3 ± 0.8 D, respectively, at physiological IOP). After CXL, K(max) decreased (-7.6 ± 2.0 D at physiological IOP). Anterior corneal aberrations increased after collagenase exposure and decreased after CXL. Light microscopy showed loss of normal stromal collagen architecture and localized edema after collagenase exposure. A method for generating topographic features of corneal ectasia in human tissue is demonstrated. No significant sensitivity of K(max) to IOP was observed. CXL caused regression of steepening and induced aberrations in this model, consistent with clinical trends. The model may be useful for testing modifications to standard CXL techniques.

To assess ultrastructural stromal modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus. This was a second-phase prospective nonrandomized open study in 10 patients with progressive keratoconus treated by riboflavin-UVA-induced cross-linking of corneal collagen and assessed by means of Heidelberg Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal microscopy. The eye in the worst clinical condition was treated for each patient. Treatment under topical anesthesia included corneal deepithelization (9-mm diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500 solution at 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment. Rarefaction of keratocytes in the anterior and intermediate stroma, associated with stromal edema, was observed immediately after treatment. The observation at 3 months after the operation detected keratocyte repopulation in the central treated area, whereas the edema had disappeared. Cell density increased progressively over the postoperative period. At approximately 6 months, keratocyte repopulation was complete, accompanied by increased density of stromal fibers. No endothelial damage was observed at any time. Reduction in anterior and intermediate stromal keratocytes followed by gradual repopulation has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy after riboflavin-UVA-induced corneal collagen cross-linking.

Keratoconus in children has been diagnosed relatively recently, which is explained by the difficulties of examination (low compliance, concomitant diseases). The peculiarity of keratoconus in children is that it can develop unnoticed, often remaining unrecognized until adolescence, which creates additional difficulties in early diagnosis and treatment. The corneal collagen crosslinking (CXL) method, as a minimally invasive method, is a priority in the treatment of pediatric patients. Despite the confirmed effectiveness in short-term studies, long-term results remain a key aspect for assessing the sustainability of the therapeutic effect. This article presents a clinical case of a patient with keratoconus, observed for 5 years after crosslinking. Objective: To assess the condition of the cornea and ocular surface in a pediatric patient diagnosed with: OU High myopia, myopic astigmatism. OD Keratoconus stages 2-3 operated (corneal crosslinking was performed in 2020), OS Keratoconus stages 1-2. Results: Patient N., 17 years old, was observed with a diagnosis of keratoconus stages 2-3 in the right eye. Crosslinking was performed 5 years ago, currently showing stable remission. A standard and specialized ophthalmological examination was performed. Conclusion: Corneal cross-linking is an effective technique that allows for the stabilization of progressive keratoconus in children (5-year follow-up). The effectiveness of the method has been confirmed using modern high-tech methods, such as corneotopography and the Ocular Response Analyzer (ORA).

Background Keratoconus is mainly a noninflammatory, bilateral corneal disease, which changes stability and refractive intensity. Aim Studying the visual acuity, refraction, and keratometric data of keratoconic patients who underwent either standard or accelerated cross-linking at 6-month duration. Patients and methods A randomized, comparative study with 60 eyes of 30 keratoconus patients. The study participants were categorized into two groups: A and B. Patients in group A underwent epi off conventional corneal crosslinking according to The Dresden’s protocol (3 mW/cm2 for 30 min), while patients in group B underwent epi off accelerated corneal crosslinking (30 mW/cm2 for only 3 min). Preoperative and postoperative outcomes were evaluated and then compared. Results The conventional corneal crosslinking group showed more improvement than the accelerated corneal crosslinking group in postoperative uncorrected distant visual acuity and corrected distant visual acuity at 6 months of follow-up. The two groups were similar in terms of spherical equivalent and manifest refraction. No significant change in K1 and K2 in the both groups from preoperative at 6 months. The same results were found for 6 months of f/up of corneal topography as well as central corneal thickness (CCT) and thinnest location of cornea thickness. Conclusions The study has increased the proof on the power of conventional corneal crosslinking in comparison with accelerated corneal crosslinking at 6 months of follow up.

Unilateral progressive keratoconus associated with ipsilateral craniofacial fibrous dysplasia treated with corneal cross-linking

Background It is determined that riboflavin/ultraviolet A (UVA)-induced corneal collagen crosslinking is able to increase resistance of cornea against enzymatic digestion and has antimicrobial efficacy for various kinds of bacteria in vitro.However,its in vivo study is less now.Objective This study aimed to evaluate the efficacy of iontophoresis-mediated corneal collagen crosslinking combined with or without drugs for Staphylococcus aureus keratitis.Methods Bacterial keratitis models were induced by the interstromaly injection of Staphylococcus aureus suspension with concentration 2× 109/ml in the right eyes of 40 rabbits,and then the rabbits were randomly classified into the model group,gatifloxacin eye drops group,riboflavin/UVA corneal crosslinking group and drugs+ crosslinking group.The smearing of corneal surface was performed for the identification of bacteria 24 hours after injection.Iontophoresis-mediated riboflavin/UVA crosslinking was applied on the eyes of the riboflavin/UVA corneal crosslinking group and drugs+crosslinking group,and gatifloxacin eye drops was topically used 7 times per day on the eyes of the gatifloxacin eye drops group and drugs+crosslinking group.The corneal inflammation was examined and graded under the slit lamp biomicroscope before and after treatment.Ocular anterior segment optical coherence tomography(AS-OCT),corneal histopathology and ultrastructure were examined 14 days after treatment.The living environment of the experimental animals was maintained at 21 ℃ with a 12-hour light and dark cycle.Animals used in this study were treated in accordance with the Weifang Medical College Animal Experimentation Ethic Committee (AEEC) guidelines.The study protocol was approved by the AEEC.Results Corneal inflammation and ulcer were observed,but no significant difference was found in the inflammatory grade among the 4 groups 24 hours after injection (x2=0.293,P＞0.05).In the 14th day after injection,the corneal ulcer area was smaller and corneal edema was milder in the drugs+crosslinking group compared with the model group,gatifloxacin eye drops group and riboflavin/ UVA corneal crosslinking group,showing a significant difference in the inflammatory grade among them (x2 =38.710,P＜0.001).The cornea thickness values of ulcer zone were (428.1 ± 146.2) μm on the 14th postinjected day in the drugs+crosslinking group,which was evidently higher than those in the model group,gatifloxacin eye drops group and riboflavin/UVA corneal crosslinking group,with a significant difference among the 4 groups (F =8.310,P＜0.001).A lower degree of destruction of cornea collagen and less inflammatory cells were seen in the cornea tissue of the drugs+ crosslinking group by haematoxylin and eosin staining in comparison with other 3 groups,and normal keratocytes were much more in the drugs + crosslinking group than those in other treated groups.Conclusions Iontophoresismediated corneal collagen crosslinking can alleviate Staphylococcus aureus keratitis.The combination of crosslinking with drugs has a better effectiveness than the administration of gatifloxacin eye drops only or riboflavin/UVA corneal crosslinking only. Key words: Iontophoresis; Collagen crosslinking; Ultraviolet ray; Cross-linking reagent; Riboflavin; Staphylococcus aureus ; Keratitis

Acta OphthalmologicaEarly View LETTER TO THE EDITOR Corneal crosslinking ameliorates the extent of corneal oedema in subsequent acute keratoconus in an ex vivo model Antonia Howaldt, Corresponding Author Antonia Howaldt [email protected] orcid.org/0000-0001-7596-8073 Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Correspondence Antonia Howaldt, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne D-50937, Germany. Email: [email protected]Search for more papers by this authorWei Zhang, Wei Zhang Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorShuya Deng, Shuya Deng Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorMartina Becker, Martina Becker Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorYanhong Hou, Yanhong Hou orcid.org/0000-0003-2248-8441 Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorThomas Clahsen, Thomas Clahsen Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, GermanySearch for more papers by this authorFelix Bock, Felix Bock Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, GermanySearch for more papers by this authorClaus Cursiefen, Claus Cursiefen Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany CECAD, Cluster of Excellence, University of Cologne, Cologne, GermanySearch for more papers by this author Antonia Howaldt, Corresponding Author Antonia Howaldt [email protected] orcid.org/0000-0001-7596-8073 Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Correspondence Antonia Howaldt, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne D-50937, Germany. Email: [email protected]Search for more papers by this authorWei Zhang, Wei Zhang Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorShuya Deng, Shuya Deng Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorMartina Becker, Martina Becker Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorYanhong Hou, Yanhong Hou orcid.org/0000-0003-2248-8441 Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, GermanySearch for more papers by this authorThomas Clahsen, Thomas Clahsen Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, GermanySearch for more papers by this authorFelix Bock, Felix Bock Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, GermanySearch for more papers by this authorClaus Cursiefen, Claus Cursiefen Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany CECAD, Cluster of Excellence, University of Cologne, Cologne, GermanySearch for more papers by this author First published: 31 May 2023 https://doi.org/10.1111/aos.15712 Antonia Howaldt and Wei Zhang contributed equally. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES Ghanem, R.C., Santhiago, M.R., Berti, T.B., Thomaz, S. & Netto, M.V. (2010) Collagen crosslinking with riboflavin and ultraviolet-a in eyes with pseudophakic bullous keratopathy. Journal of Cataract and Refractive Surgery, 36, 273– 276. Raiskup, F., Theuring, A., Pillunat, L.E. & Spoerl, E. (2015) Corneal collagen crosslinking with riboflavin and ultraviolet-a light in progressive keratoconus: ten-year results. Journal of Cataract and Refractive Surgery, 41, 41– 46. Søndergaard, A.P., Ivarsen, A. & Hjortdal, J. (2013) Reduction of stromal swelling pressure after UVA-riboflavin cross-linking. Investigative Ophthalmology and Visual Science, 54, 1625– 1634. Spoerl, E., Hoyer, A., Pillunat, L.E. & Raiskup, F. (2011) Corneal cross-linking and safety issues. The open ophthalmology journal, 5, 14– 16. Stock, R.A., Thumé, T. & Bonamigo, E.L. (2017) Acute corneal hydrops during pregnancy with spontaneous resolution after corneal cross-linking for keratoconus: a case report. Journal of Medical Case Reports, 11, 1– 3. Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Objective To evaluate the efficacy and safety of phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) combined with corneal collagen cross-linking (CXL) in preventing the progression of post-laser-assisted in situ keratomileusis (LASIK) keratectasia. Methods In this prospective, self-controlled study, 16 eyes of 14 patients with post-LASIK keratectasia underwent PTK and PRK combined with CXL procedures. None of the 14 patients had keratoconus before LASIK. The main outcomes were measured and recorded at baseline and at months 1, 3, and 6 after LASIK. The measured parameters included logarithm of the minimum angle of resolution (LogMAR) of the uncorrected visual acuity (UCVA), LogMAR of the best-corrected visual acuity (BCVA), central corneal thickness (CCT), maximum front keratometry (Kmax), and endothelial cell density (ECD). Data were analyzed using Wilcoxon rank sum test. Results PTK and PRK combined with CXL appeared to halt the progression of post-LASIK keratectasia without apparent complications. LogMAR UCVA improvements were statistically significant (P<0.01) at 1, 3, and 6 months postoperatively (M=0.10, 0.10, and 0.00, respectively). There was also a significant reduction in Kmax (P<0.05) at postoperative months 1, 3 and 6. At 6 months after surgery, M of CCT was decreased (P<0.01). There were no significant changes in LogMAR BCVA or ECD during 6 months of follow-up. Conclusion PTK+PRK+CXL is effective and safe in treating post-LASIK keratectasia. Without apparent complications, it can improve UCVA and reduce Kmax after surgery. Key words: Corneal collagen cross-linking; Keratectasia; Phototherapeutic keratectomy; Photorefractive keratectomy; Refractive reconstruction

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