Search Results (20)

Background/Objectives: Keratoconus (KC) is a corneal ectatic disease, characterized by the progressive thinning of the cornea, myopia, and astigmatism, which lead to a decrease in visual acuity. Corneal collagen crosslinking (CXL) is an efficient method of stopping the progression of the disease. The objective of this study is to investigate the endothelial and biomechanical properties of the cornea in keratoconus patients, before and after undergoing corneal collagen crosslinking. Methods: A total of 66 eyes were diagnosed with progressive keratoconus and were recommended epi-off corneal crosslinking. Before the procedure, they were investigated with corneal topography (for minimum, maximum, average keratometry, and corneal astigmatism), specular microscopy (for the following endothelial cell parameters: number, density, surface, variability, and hexagonality), and an ocular response analyzer (for the following biomechanical parameters: corneal hysteresis and resistance factor). All measurements were repeated 1 month and 6 months after the intervention. Results: Several parameters differ according to the Amsler–Krumeich stage of keratoconus: in more advanced stages, patients present higher endothelial cell variability, a lower number of endothelial cells in the paracentral region of the cornea, lower CCT and CRF, and higher keratometry and astigmatism. Endothelial cell variability and number correlate with average keratometry, and there are also strong correlations between topography and CH and CRF. After CXL, the paracentral number of endothelial cells decreased; cell variability and average cell surface increased. Conclusions: More advanced keratoconus cases present with altered corneal biomechanics and topographical parameters, the endothelial layer also being affected proportional to the stage of the disease and also slightly affected after corneal collagen crosslinking. Full article

Background/Objectives: To evaluate the timing and extent to which late keratometric changes can occur between year 7 and 12 after corneal collagen crosslinking (CXL) in patients with keratoconus. Methods: A subgroup of a retrospective cohort study of all consecutive patients who underwent CXL at our cornea center between 2007 and 2011 was analyzed. The inclusion criteria consisted of CXL according to the Dresden protocol and a full set of keratometry parameters collected by Scheimpflug tomography preoperatively and at year 7, 9 and 12 after CXL. Results: A total of 46 eyes of 35 patients were included. The most relevant keratometric parameters (Kmax, TCT, K1, K2 and anterior astigmatism) decreased statistically significantly at year 7 after CXL, while there was no relevant difference for posterior astigmatism and the flat axes of anterior and posterior astigmatism. All keratometric parameters (except for K2) remained stable between year 7 and 12 without statistically significant change, according to mixed effect model regression analysis. BCVA improved statistically significant between the baseline and year 7 and remained stable until year 12. Suspected disease progression was noted in two patients (4.3%) between year 7, 9 and 12 post-CXL. Conclusions: Keratometric and functional results improve significantly 7 years after CXL in comparison to preoperative values and show very effective stabilization without clinically relevant changes up to year 12. However, while the risk of disease progression decreases remarkably after 7 years, in rare cases, suspected progression can occur even up to year 12. Therefore, regular control visits with keratometry measurements are advisable at least every 2 to 3 years in the late postoperative course. Full article

Corneal collagen cross-linking (CXL) is a therapeutic intervention that utilizes riboflavin photochemical activation with ultraviolet-A (UV-A) light to induce covalent cross-links within the stromal corneal fibers, effectively increasing corneal biomechanical stability and halting the progressive ectasia. The method was introduced in the late 1990s in Germany at the University of Dresden. The cross-linking method using the Avedro system (Waltham, MA, USA) was approved by the US Food and Drug Administration (FDA) on 18 April 2016, based on three prospective, multicenter, randomized clinical trials for keratoconus and other corneal ectasias. Recent innovations in CXL include a range of new treatment protocols and methods, which have been introduced to further enhance the clinical effectiveness, efficiency, and safety of CXL. These modifications encompass approaches like transepithelial or epithelium-on CXL (TE-CXL or epi-on CXL), accelerated CXL (ACXL), pulsed CXL (PL-CXL), transepithelial iontophoresis-assisted crosslinking (I-CXL), diluted alcohol and iontophoresis-assisted corneal cross-linking (DAI-CXL), slit-lamp CXL, and CXL plus (combined) methods. This review synthesizes findings on currently used modifications of the cross-linking method, the effectiveness, and directions of development of this currently dominant surgical method of treating corneal ectasia. This review concentrates on the long-term follow-up data, based on publications ranging from 1998 up to 2023. Full article

Keratoconus is a burden to health systems and patients worldwide. Corneal collagen crosslinking (CXL) treatment has been shown abroad to be cost-effective for treating progressive keratoconus. However, no cost-effectiveness studies have been performed in Brazil. The aim of this study was to assess the cost-effectiveness of corneal collagen crosslinking (CXL) compared with the conventional treatment for progressive keratoconus from the Brazilian Unified Health System (SUS) payer’s perspective. A lifetime microsimulation model was utilized to compare the lifetime costs and quality-adjusted life years for patients undergoing corneal collagen CXL or conventional treatment. Two groups of 5000 18-year-old patients were simulated, with one group receiving corneal CXL at the outset and the control group remaining untreated. The TreeAge Pro Healthcare 2024 software was used for modeling and analysis. Corneal collagen CXL demonstrated superior cost-effectiveness compared to the conventional treatment, with an incremental cost-effectiveness ratio of 58.26 USD/quality-adjusted life years (QALY) gained (95% CI: 58.17–58.36) and a positive incremental net monetary benefit of USD 11,613.82 (95% CI: 11,605.66–11,621.99). CXL significantly reduced the number of required corneal transplants, with a mean of 968.8 (95% CI: 959–978.58) fewer transplants per 10,000 eyes treated. The variable with the most significant impact on the incremental net monetary benefit was the duration of the CXL effect. This study concluded that corneal CXL is a highly cost-effective intervention for progressive keratoconus within the Brazilian SUS. These findings advocate for broader accessibility to this vision-saving treatment within the SUS. Full article

Purpose: To analyze the influence of dextran solution and corneal collagen crosslinking (CXL) on corneal biomechanical parameters in vitro, evaluated by Corneal Visualization Scheimpflug Technology (Corvis ST). Materials and Methods: Forty porcine eyes were included in this study. Twenty porcine eyes were instilled with dextran solution for 30 min (10 eyes in 2% dextran solution and 10 eyes in 20% dextran solution). CXL treatment was performed in 10 porcine eyes; the other 10 porcine eyes were regarded as the control group. Each eye was fixed on an experimental inflation platform to carry out Corvis measurements at different IOPs. Corneal biomechanical parameters were calculated based on Corvis measurement. Statistical analysis was used to analyze the influence of dextran solution and CXL on corneal biomechanical parameters based on Corvis parameters. Results: The corneal energy-absorbed area (A_absorbed) decreased after being instilled with dextran solution under IOP of 15 mmHg (p < 0.001); the elastic modulus (E) of the cornea instilled with 20% dextran solution was significantly higher than that instilled with 2% dextran solution (p < 0.001), since it decreased after being instilled with 20% dextran solution (p = 0.030); the stiffness parameter at the first applanation (SP-A1) increased after CXL (p < 0.001). Conclusions: Both dextran solution and CXL can change corneal biomechanical properties; the concentration of dextran solution can influence the corneal biomechanical properties, which may, in turn, affect the effectiveness of CXL. SP-A1 may be used as an effective parameter for the evaluation of CXL. Full article

Corneal crosslinking (CXL) is a medical procedure used to treat keratoconus. CXL works by strengthening the collagen fibers of the cornea through the application of riboflavin (vitamin B2) and ultraviolet (UV) light, which helps to stabilize the cornea and prevent further deterioration. There is a recognized risk that CXL can trigger the reactivation of dormant herpes simplex virus (HSV), leading to herpetic keratitis even in patients with no history of herpetic disease. We examined the medical history of 52 patients who underwent CXL procedures due to previously diagnosed keratoconus. We reviewed the patient’s medical histories to assess whether there was a herpes labialis infection and/or herpetic keratitis. Altogether, 52 eyes (from 52 patients) were analyzed. Of those, four (7.69%) patients were diagnosed with epithelial herpetic keratitis on the 5–8th day after surgery. All four patients had a history of herpes labialis and no prior HSV keratitis infection. Two patients developed herpetic keratitis despite prophylactic therapy with acyclovir 5 days before surgery. A positive history of HSV lip infection before CXL was present in 18/52 (34.62%). During a one-year follow-up period, no patient experienced a recurrence. Close follow-up is crucial for diagnosing herpetic keratitis after corneal crosslinking. The use of prophylactic antiviral therapy in patients who are asymptomatic and have a history of recurrent herpes labialis does not guarantee the prevention of infection. Full article

Aim: The aim of this study was to evaluate corneal cross-linking (CXL) for keratoconus in pediatric patients. Materials and methods: After keratometric qualification according to the Amsler–Krumeich system, corneal collagen cross-linking was performed using ultraviolet light and photosensitizing riboflavin drops in 111 eyes of 74 children with a mean age of 15 ± 1.67 years. None of the children studied wore contact lenses before the procedure. Visual acuity, intraocular pressure, keratometry, and pachymetry parameters were analyzed before and after corneal cross-linking. Results: Visual acuity was 0.64 ± 0.31 and 0.66 ± 0.29 before CXL and at the end of the follow-up, respectively; the difference was not statistically significant. The mean intraocular pressure before CXL was 14.48 ± 3.13 mmHg, while the mean value at the end of the follow-up was 14.23 ± 3.03 mmHg; no statistically significant difference was found. Pre- and post-CXL astigmatism was 3.98 ± 2.34 Dcyl and 3.63 ± 1.86 Dcyl, respectively; the difference was not statistically significant. The mean keratometry before CXL was 47.99 ± 3.96 D; the mean post-follow-up value was 47.74 ± 3.63 D. The mean corneal thickness (pachymetry) at the apex of the keratoconus—the thinnest zone of the cornea—before CXL was 492.16 ± 38.75 µm, while the mean value at the end of the follow-up was 479.99 ± 39.71 µm; the difference was statistically significant. Conclusions: Corneal cross-linking is an effective method for preventing keratoconus progression in children. However, further and detailed ophthalmic follow-up of patients who underwent CXL before the age of 18 is highly advisable. Full article

Background: The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the molecular changes occurring after the procedure. Among many cytokines, β-NGF seems to play an important role in the healing processes of corneal damage. Therefore, its role in the regenerative process after CXL treatment may affect the course of treatment and its final results. Tear samples from 52 patients were collected in this prospective study. Additionally, the patients also had a number of tests performed, including corneal topography using optical coherence tomography. Flat (K 1), steep (K 2), cylindrical (CYL), and central corneal thickness (CCT) keratometry were assessed. The tear samples were collected, and other tests were performed before the CXL procedure and afterwards, during the 12-month follow-up period. The NGF concentration was measured using the Bio-Plex Magnetic Luminex Assay. Lower levels of NGF-β were detected in the KC patients than in the control group (p < 0.001). The day after the procedure, the NGF-β level was significantly lower (on average by 2.3 pg/mL) (p = 0.037) than before the procedure, after which, the level of the reagent increases, but only in the group with the advanced cone, one month after CXL it was significantly higher (p = 0.047). Regarding the correlation of NGF with topographic measurements, the following were found: NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 before the CXL procedure; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 one month after CXL; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with CYL nine months after CXL; and, after twelve months, NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K2 and K1. Corneal sensitivity did not statistically and significantly correlate with the level of NGF-β secretion. Our study suggests that NGF may be crucial in the development and progression of KC as well as in the repair mechanisms after CXL surgery. Further research is needed on the role of NGF and other inflammatory biomarkers for rapid diagnosis and selection of targeted therapy in patients with keratoconus. Full article

The present study evaluated the effectiveness and safety of corneal collagen cross-linking (CXL). A total of 886 eyes with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standard epithelium-off Dresden protocol. Visual outcomes, maximum keratometry (Kmax), demarcation line measurements, and complications were recorded. Visual outcomes and keratometric data were analyzed in a subgroup comprising 610 eyes. Uncorrected distance visual acuity (UDVA) improved from 0.49 ± 0.38 LogMAR to 0.47 ± 0.39 LogMAR (p = 0.03, n = 610) three years after the procedure, while corrected distance visual acuity (CDVA) improved from 0.15 ± 0.14 LogMAR to 0.14 ± 0.15 LogMAR (p = 0.007, n = 610). A significant reduction of Kmax from 56.28 ± 6.10 to 54.98 ± 6.19 (p < 0.001, n = 610) was observed three years after CXL. In five eyes (0.82%, 5/610) keratoconus progression continued after CXL. Three eyes were retreated successfully with documented refractive and topographic stability after five years. In the 35 eyes that completed 10 years of follow-up, mean visual acuity and topographic parameters remained stable. In conclusion, CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure. Full article

Collagen crosslinking (CXL) is a widely used treatment to halt the progression of keratoconus (KC). Unfortunately, a significant number of patients with progressive KC will not qualify for CXL, including those with corneas thinner than 400 µm. The present study aimed to investigate the molecular effects of CXL using in vitro models, mirroring the normal, as well as thinner corneal stroma seen in KCs. Primary human corneal stromal cells were isolated from healthy (HCFs) and keratoconus (HKCs) donors. Cells were cultured and stimulated with stable Vitamin C resulting in 3D self-assembled extracellular matrix (ECM), cell-embedded, constructs. CXL was performed on (a) thin ECM with CXL performed at week 2 and (b) normal ECM with CXL performed at week 4. Constructs without CXL served as controls. All constructs were processed for protein analysis. The results showed modulation of Wnt signaling, following CXL treatment, as measured by the protein levels of Wnt7b and Wnt10a, correlated to the expression of α-smooth muscle actin (SMA). Further, the expression of a recently identified KC biomarker candidate, prolactin-induced protein (PIP), was positively impacted by CXL in HKCs. CXL-driven upregulation of PGC-1 and the downregulation of SRC and Cyclin D1 in HKCs were also noted. Although the cellular/molecular impacts of CXL are largely understudied, our studies provide an approximation to the complex mechanisms of KC and CXL. Further studies are warranted to determine factors influencing CXL outcomes. Full article

A large retrospective study evaluated the safety of a post-operative therapy protocol after epithelium-off corneal collagen cross-linking (CXL). In total, 1703 eyes of the 1190 patients with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standardized technique (Dresden protocol: 0.1% riboflavin solution containing dextran 20% for 30 min during the soaking phase followed by 30-min ultraviolet A irradiation (3 mW/cm²)). Postoperatively, a bandage contact lens was applied, and therapy included a topical fluoroquinolone antibiotic until the epithelium healed, followed by topical fluorometholone treatment for three weeks. Post-operative complications were recorded and analyzed. No cases of infectious keratitis occurred, whereas peripheral sterile infiltrates were observed in 1.17% of cases. Trace haze was typically present but did not have an impact on visual acuity. In fifteen cases (0.88%), visually significant anterior stromal opacity developed. Mild signs of dry eye were observed in 22 eyes (1.29%). The present study demonstrates that a post-operative treatment protocol including fluoroquinolone antibiotics and a BCL in the first phase until complete epithelial healing, followed by a three-week period of topical steroid treatment is safe and not associated with the development of microbial keratitis. Full article

Infectious keratitis is a severe infection of the eye, which requires urgent care in order to prevent permanent complications. Typical cases are usually diagnosed clinically, whereas severe cases also require additional tools, such as direct microscopy, corneal cultures, molecular techniques, or ophthalmic imaging. The initial treatment is empirical, based on the suspected etiology, and is later adjusted as needed. It ranges from topical administration of active substances to oral drugs, or to complex surgeries in advanced situations. A novel alternative is represented by Photoactivated Chromophore Corneal Collagen Cross-Linking (PACK-CXL), which is widely known as a minimally invasive therapy for corneal degenerations. The purpose of this review is to identify the main diagnostic and prognostic factors which further outline the indications and contraindications of PACK-CXL in infectious keratitis. Given the predominantly positive outcomes in the medical literature, we ponder whether this is a promising treatment modality, which should be further evaluated in a systematic, evidence-based manner in order to develop a clear treatment protocol for successful future results, especially in carefully selected cases. Full article

Background: Corneal collagen cross-linking (CXL) has become the gold standard for mild and moderate stages to stop the progression of keratoconus. We analyzed some corneal topography indices to compare iontophoresis epi-on and iontophoresis epi-off techniques throughout a two-year follow-up. Methods: A total of 64 eyes of 49 patients who underwent CXL were recruited. In 30 eyes the epi-off technique was performed, whereas the remaining 34 eyes were treated with the epi-on technique. All patients underwent a complete ophthalmologic examination that included CDVA, central and thinnest corneal thickness, Schirmer test I, TBUT test, and the Ocular Surface Disease Index. Results: In both groups, a significant improvement in visual function was recorded. No statistically significant differences between Kmax, Mean K, Flat K, Steep K values were found. Statistically significant differences (p < 0.05) between the epi-on and epi-off groups’ pachymetry before and after 24 months follow-up as well as between the epi-on and epi-off groups’ topographically thinnest point in the immediate post-surgery and 24 months after surgery were recorded. Conclusion: Our study highlighted that both techniques are valid in mid-term corneal stabilization. The advantage of the new iontophoresis epi-off cross-linking technique could be found in a faster imbibing time of the cornea, therefore reducing surgical times, with a lower risk of complications. Full article

Background: This paper’s objective is to analyze patients with keratoconus who developed sterile infiltrate after corneal collagen cross-linking (CXL), and to evaluate possible risk factors for their occurrence. Methods: 543 medical histories of patients after cross-linking (Epi-off, Epi-on) procedure performed according to the Dresden protocol were analyzed retrospectively. Results: Sterile corneal infiltrates occurred in four men (0.7%) in the age range (16–28) years, the average age being 20.3. The average time from procedure to onset of symptoms was 3.5 days (2–5 days). Inflammatory infiltration resolved in all patients, leaving scars on corneal stroma in two patients. Corneal healing time ranged from 4–12 weeks. In vivo confocal microscopy (IVCM), round inflammatory cells, and Langerhans cells in the epithelium and Bowman’s layer were observed at the site of infiltration. The Optical coherence tomography (OCT) shows hyperreflective lesions of various sizes which decreased over time. The corneal topographic parameters and Best-corrected visual acuity (BCVA) improved after the CXL procedure in all of the described cases. Conclusions: Most likely, damage to the epithelium and the phototoxic effect of the procedure is of significant importance in the formation of sterile corneal infiltrates. Appropriate classification and selection of CXL procedures in combination with protective measures in people at risk may have an overwhelming impact on the incidence of this complication. Full article

Keratoconus is the most common primary corneal ectasia characterized by progressive focal thinning. Patients experience increased irregular astigmatism, decreased visual acuity and corneal sensitivity. Corneal collagen crosslinking (CXL), a minimally invasive procedure, is effective in halting disease progression. Historically, keratoconus research was confined to ex vivo settings. In vivo confocal microscopy (IVCM) has been used to examine the corneal microstructure clinically. In this review, we discuss keratoconus cellular changes evaluated by IVCM before and after CXL. Cellular changes before CXL include decreased keratocyte and nerve densities, disorganized subbasal nerves with thickening, increased nerve tortuosity and shortened nerve fibre length. Repopulation of keratocytes occurs up to 1 year post procedure. IVCM also correlates corneal nerve status to functional corneal sensitivity. Immediately after CXL, there is reduced nerve density and keratocyte absence due to mechanical removal of the epithelium and CXL effect. Nerve regeneration begins after 1 month, with nerve fibre densities recovering to pre-operative levels between 6 months to 1 year and remains stable up to 5 years. Nerves remain tortuous and nerve densities are reduced. Corneal sensitivity is reduced immediately postoperatively but recovers with nerve regeneration. Our article provides comprehensive review on the use of IVCM imaging in keratoconus patients. Full article