ABSTRACT
PURPOSE: This study aimed to analyze variations in intraoperative corneal thickness during corneal cross-linking in patients with keratoconus and to investigate its possible correlation with presurgical maximal keratometry (Kmax) and pachymetry. METHODS: This was a prospective case series. We used a method similar to the Dresden protocol, with the application of hydroxypropyl methylcellulose 0.1% hypo-osmolar riboflavin in corneas between 330 and 400 µm after epithelium removal. Corneal thickness was measured using portable calipers before and immediately after epithelium removal, and 30 and 60 min after the procedure. RESULTS: The 30 patients in this study were followed up for one year. A statistically significant difference was observed in pachymetry values during the intraoperative period (p<0.0001) and an increase of 3.05 µm (95%C1: 0.56-5.54) for each diopter was seen after epithelium removal (p0.019). We found an average Kmax difference of -2.12 D between men and women (p0.013). One year after treatment, there was a statistically significant reduction in pachymetry (p<0.0001) and Kmax (p0.0170) values. CONCLUSIONS: A significant increase in pachymetry measurements was seen during the procedure, and most patients showed a regression in Kmax and pachymetry values one year after surgery.
Subject(s)
Cornea , Corneal Pachymetry , Cross-Linking Reagents , Hypromellose Derivatives , Keratoconus , Photosensitizing Agents , Riboflavin , Humans , Riboflavin/therapeutic use , Female , Keratoconus/drug therapy , Male , Corneal Pachymetry/methods , Prospective Studies , Adult , Cross-Linking Reagents/therapeutic use , Young Adult , Cornea/diagnostic imaging , Cornea/pathology , Cornea/surgery , Cornea/drug effects , Hypromellose Derivatives/therapeutic use , Photosensitizing Agents/therapeutic use , Adolescent , Treatment Outcome , Time Factors , Intraoperative Period , Reference Values , Corneal Topography/methods , Reproducibility of ResultsABSTRACT
BACKGROUND: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, and even lifelong disability. This study was to explore the effect of riboflavin (RF) on neurological rehabilitation and functional recovery after TBI. METHODS: The rat models of TBI were constructed by treating rats with controlled cortical impact (CCI). By treating TBI rats with RF, we investigated whether the administration of RF would affect the sensorimotor function and cognitive ability recovery through adhesive removal test, modified neurological severity score (mNSS), corner test, wire-grip test and the Morris water maze. The effects of RF on lesion volume and water content were investigated using hematoxylin and eosin (H&E) staining and wet-dry method. The Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to demonstrate the effect of RF on neural apoptosis. Inflammation-related cytokines of interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RF on neuroinflammation. The impact of RF on oxidative stress was assessed by measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and the platelet endothelial cell adhesion molecule-1 (CD31) staining for observing vessel density, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for measuring vascular endothelial growth factor (VEGF) mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis. RESULTS: The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability (p < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress (p < 0.05). Finally, RF increased vessel density (p < 0.01) and VEGF levels (p < 0.01) in brain tissues after TBI, promoting angiogenesis. CONCLUSION: RF benefits neurological rehabilitation after TBI by promoting neurological function recovery, ameliorating the pathogenesis after TBI, and facilitating brain vascular remodeling. These findings provide a novel mechanism for RF treating pediatric TBI.
Subject(s)
Brain Injuries, Traumatic , Riboflavin , Animals , Rats , Brain Injuries, Traumatic/rehabilitation , Brain Injuries, Traumatic/pathology , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/physiopathology , Riboflavin/pharmacology , Riboflavin/therapeutic use , Male , Humans , Rats, Sprague-Dawley , Child , Disease Models, Animal , Apoptosis/drug effects , Oxidative Stress/drug effects , Cytokines/metabolism , Recovery of Function/drug effectsABSTRACT
Purpose: Photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) stabilizes the corneal stroma and eliminates microorganisms. Numerous PACK-CXL protocols, using different energy sources and chromophores, have been applied in preclinical studies, including live animal studies, with various experimental designs and endpoints. So far, a systematic mapping of the applied protocols and consistency across studies seems lacking but is essential to guide future research. Methods: The scoping review protocol was in line with the JBI Manual for Evidence Synthesis. Electronic databases were searched (Embase, MEDLINE, Scopus, Web of Science) to identify eligible records, followed by a two-step selection process (title and abstract screening, full text screening) for record inclusion. We extracted information on (1) different PACK-CXL protocol characteristics; (2) infectious pathogens tested; (3) study designs and experimental settings; and (4) endpoints used to determine antimicrobial and tissue stabilizing effects. The information was charted in frequency maps. Results: The searches yielded 3654 unique records, 233 of which met the inclusion criteria. With 103 heterogeneous endpoints, the researchers investigated a wide range of PACK-CXL protocols. The tested microorganisms reflected pathogens commonly associated with infectious keratitis. Bacterial solutions and infectious keratitis rabbit models were the most widely used models to study the antimicrobial effects of PACK-CXL. Conclusions: If preclinical PACK-CXL studies are to guide future translational research, further cross-disciplinary efforts are needed to establish, promote, and facilitate acceptance of common endpoints relevant to PACK-CXL. Translational Relevance: Systematic mapping of PACK-CXL protocols in preclinical studies guides future translational research.
Subject(s)
Cross-Linking Reagents , Keratitis , Photosensitizing Agents , Riboflavin , Animals , Keratitis/drug therapy , Keratitis/microbiology , Cross-Linking Reagents/therapeutic use , Cross-Linking Reagents/pharmacology , Cross-Linking Reagents/chemistry , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Riboflavin/therapeutic use , Riboflavin/pharmacology , Humans , Photochemotherapy/methods , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Ultraviolet Rays , Collagen/metabolism , Corneal Cross-LinkingABSTRACT
The stiffening effect of corneal crosslinking (CXL) treatment, a therapeutic approach for managing the progression of keratoconus, has been primarily investigated using uniaxial tensile experiments. However, this testing technique has several drawbacks and is unable to measure the mechanical response of cornea under a multiaxial loading state. In this work, we used biaxial mechanical testing method to characterize biomechanical properties of porcine cornea before and after CXL treatment. We also investigated the influence of preconditioning on measured properties and used TEM images to determine microstructural characteristics of the extracellular matrix. The conventional method of CXL treatment was used for crosslinking the porcine cornea. The biaxial experiments were done by an ElectroForce TestBench system at a stretch ratio of 1:1 and a displacement rate of 2 mm/min with and without preconditioning. The experimental measurements showed no significant difference in the mechanical properties of porcine cornea along the nasal temporal (NT) and superior inferior (SI) direction. Furthermore, the CXL therapy significantly enhanced the mechanical properties along both directions without creating anisotropic response. The samples tested with preconditioning showed significantly stiffer response than those tested without preconditioning. The TEM images showed that the CXL therapy did not increase the diameter of collagen fibers but significantly decreased their interfibrillar spacing, consistent with the mechanical property improvement of CXL treated samples.
Subject(s)
Cornea , Cross-Linking Reagents , Photosensitizing Agents , Riboflavin , Animals , Cross-Linking Reagents/pharmacology , Swine , Cornea/drug effects , Riboflavin/pharmacology , Riboflavin/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Biomechanical Phenomena , Collagen/metabolism , Elasticity , Ultraviolet Rays , Keratoconus/drug therapy , Keratoconus/physiopathology , Keratoconus/metabolism , Tensile Strength , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Microscopy, Electron, TransmissionABSTRACT
Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation. GAII has been considered an autosomal recessive condition caused by pathogenic variants in the gene encoding electron-transfer flavoprotein ubiquinone-oxidoreductase (ETFDH) or in the genes encoding electron-transfer flavoprotein subunits A and B (ETFA and ETFB respectively). Variants in genes involved in riboflavin metabolism have also been reported. However, in some patients, molecular analysis has failed to reveal diagnostic molecular results. In this study, we report the outcome of molecular analysis in 28 Australian patients across the lifespan, 10 paediatric and 18 adult, who had a diagnosis of glutaric aciduria type II based on both clinical and biochemical parameters. Whole genome sequencing was performed on 26 of the patients and two neonatal onset patients had targeted sequencing of candidate genes. The two patients who had targeted sequencing had biallelic pathogenic variants (in ETFA and ETFDH). None of the 26 patients whose whole genome was sequenced had biallelic variants in any of the primary candidate genes. Interestingly, nine of these patients (34.6%) had a monoallelic pathogenic or likely pathogenic variant in a single primary candidate gene and one patient (3.9%) had a monoallelic pathogenic or likely pathogenic variant in two separate genes within the same pathway. The frequencies of the damaging variants within ETFDH and FAD transporter gene SLC25A32 were significantly higher than expected when compared to the corresponding allele frequencies in the general population. The remaining 16 patients (61.5%) had no pathogenic or likely pathogenic variants in the candidate genes. Ten (56%) of the 18 adult patients were taking the selective serotonin reuptake inhibitor antidepressant sertraline, which has been shown to produce a GAII phenotype, and another two adults (11%) were taking a serotonin-norepinephrine reuptake inhibitor antidepressant, venlafaxine or duloxetine, which have a mechanism of action overlapping that of sertraline. Riboflavin deficiency can also mimic both the clinical and biochemical phenotype of GAII. Several patients on these antidepressants showed an initial response to riboflavin but then that response waned. These results suggest that the GAII phenotype can result from a complex interaction between monoallelic variants and the cellular environment. Whole genome or targeted gene panel analysis may not provide a clear molecular diagnosis.
Subject(s)
Electron-Transferring Flavoproteins , Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Humans , Female , Male , Child , Adult , Child, Preschool , Electron-Transferring Flavoproteins/genetics , Adolescent , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/genetics , Queensland , Riboflavin/therapeutic use , Young Adult , Infant , Iron-Sulfur Proteins/genetics , Cohort Studies , Oxidoreductases Acting on CH-NH Group Donors/genetics , Infant, Newborn , Mutation , Whole Genome SequencingABSTRACT
Objectives: To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE). Materials and Methods: In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment. Results: Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 µm, and -0.21±0.63 µm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 µm, and -0.51±0.58 µm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up. Conclusion: The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.
Subject(s)
Corneal Topography , Cross-Linking Reagents , Keratomileusis, Laser In Situ , Photosensitizing Agents , Refraction, Ocular , Visual Acuity , Humans , Retrospective Studies , Keratomileusis, Laser In Situ/methods , Keratomileusis, Laser In Situ/adverse effects , Male , Female , Adult , Dilatation, Pathologic/etiology , Refraction, Ocular/physiology , Cross-Linking Reagents/therapeutic use , Treatment Outcome , Photosensitizing Agents/therapeutic use , Young Adult , Collagen , Lasers, Excimer/therapeutic use , Follow-Up Studies , Riboflavin/therapeutic use , Photochemotherapy/methods , Corneal Diseases/surgery , Corneal Diseases/etiology , Corneal Diseases/diagnosis , Corneal Diseases/physiopathology , Cornea/pathology , Cornea/surgery , Postoperative Complications/diagnosis , Myopia/surgery , Myopia/physiopathology , Ultraviolet RaysABSTRACT
PURPOSE: To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation. METHODS: Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation. RESULTS: The median age was 29 years in the CXL group and 24.0 years in the non-CXL group (P > .05), respectively. All topographical and visual parameters before implantation were similar in both groups (P > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group (P = .030, .018, and .039, respectively). CONCLUSIONS: CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. [J Refract Surg. 2024;40(6):e392-e397.].
Subject(s)
Collagen , Corneal Stroma , Corneal Topography , Cross-Linking Reagents , Keratoconus , Photosensitizing Agents , Prostheses and Implants , Prosthesis Implantation , Refraction, Ocular , Visual Acuity , Humans , Keratoconus/physiopathology , Keratoconus/metabolism , Keratoconus/drug therapy , Keratoconus/surgery , Corneal Stroma/metabolism , Corneal Stroma/surgery , Cross-Linking Reagents/therapeutic use , Visual Acuity/physiology , Adult , Male , Female , Photosensitizing Agents/therapeutic use , Retrospective Studies , Young Adult , Refraction, Ocular/physiology , Collagen/metabolism , Corneal Pachymetry , Riboflavin/therapeutic use , Photochemotherapy/methods , Adolescent , Ultraviolet Rays , Corneal Transplantation/methods , Middle Aged , Corneal Cross-LinkingABSTRACT
PURPOSE: The purpose of this review was to summarize the different surgical approaches combining photorefractive keratectomy (PRK) and corneal crosslinking (CXL), present each protocol template in a simple format, and provide an overview of the primary outcomes and adverse events. METHODS: A literature review was conducted as outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eight different databases were searched. Papers were included if PRK was immediately followed by CXL. RESULTS: Thirty-seven papers met the inclusion criteria of a total yield of 823. The latest research into simultaneous PRK and CXL has been shown to not only stabilize the cornea and prevent keratoconus progression but also improve the visual acuity of the patient. Improvements in uncorrected distance visual acuity and (spectacle) corrected distance visual acuity were found to be significant when considering all protocols. There were also significant reductions in K1, K2, mean K, Kmax, sphere, cylinder, and spherical equivalent. Random-effects analysis confirmed these trends. Corrected distance visual acuity was found to improve by an average of 0.18 ± 1.49 logMAR (Cohen's D [CD] 0.12; P <0.02). There was also a significant reduction of 2.57 ± 0.45 D (CD 5.74; P <0.001) in Kmax. Cylinder and spherical equivalent were also reduced by 1.36 ± 0.26 D (CD 5.25; P <0.001) and 2.61 ± 0.38 D (CD 6.73; P <0.001), respectively. CONCLUSIONS: Combining the 2 procedures appears to be of net benefit, showing stabilization and improvement of ectatic disease, while also providing modest gains in visual acuity. Since customized PRK and CXL approaches appear superior, a combination of these would likely be best for patients.
Subject(s)
Collagen , Cross-Linking Reagents , Keratoconus , Photochemotherapy , Photorefractive Keratectomy , Photosensitizing Agents , Riboflavin , Ultraviolet Rays , Visual Acuity , Photorefractive Keratectomy/methods , Humans , Cross-Linking Reagents/therapeutic use , Photosensitizing Agents/therapeutic use , Collagen/metabolism , Visual Acuity/physiology , Keratoconus/drug therapy , Keratoconus/surgery , Keratoconus/physiopathology , Keratoconus/metabolism , Riboflavin/therapeutic use , Photochemotherapy/methods , Lasers, Excimer/therapeutic use , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Corneal Stroma/surgery , Combined Modality Therapy , Refraction, Ocular/physiology , Clinical ProtocolsSubject(s)
Corneal Topography , Cross-Linking Reagents , Keratoconus , Photochemotherapy , Photosensitizing Agents , Riboflavin , Humans , Keratoconus/drug therapy , Keratoconus/diagnosis , Cross-Linking Reagents/therapeutic use , Photosensitizing Agents/therapeutic use , Riboflavin/therapeutic use , Photochemotherapy/methods , Collagen/metabolism , Corneal Stroma/metabolism , Corneal Stroma/pathology , Corneal Stroma/drug effects , Ultraviolet Rays , Corneal Dystrophies, Hereditary/diagnosis , Visual Acuity/physiology , Disease Progression , Corneal Cross-LinkingABSTRACT
PURPOSE: This study aimed to report the long-term results of combined topography-guided photorefractive keratectomy (PRK) and accelerated corneal collagen cross-linking (CXL) for keratoconus using the Zeiss refractive coordinated system. METHODS: A prospective interventional study was conducted in a tertiary eye care hospital in South India. Patients with mild-to-moderate progressive keratoconus and corneal pachymetry greater than 450 µm were included. They underwent customized topography-guided PRK followed by CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and keratometry readings and complications were evaluated at 1, 3, 6, 12, and 24 months postoperatively. RESULTS: Thirty patients (30 eyes) were included in the study. All study parameters showed a statistically significant improvement postoperatively over baseline values. At 24 months, the mean UDVA improved from 0.8 ± 0.180 logarithm of the minimum angle of resolution (logMAR) to 0.38 ± 0.118 logMAR ( P -value <0.001) and CDVA improved from 0.467 ± 0.142 logMAR to 0.227 ± 0.078 logMAR ( P -value <0.001). The mean flat, steep, and maximum keratometry values were significantly reduced by 2.133, 3, and 4.54 diopters, respectively, at the last follow-up examination ( P -value <0.001). CONCLUSION: The combined topography-guided PRK and accelerated CXL procedure seem to be a promising treatment alternative for early keratoconus. This is the first such study on the Zeiss refractive coordinated system. However, further studies with a larger study population and longer follow-up periods are required to draw final conclusions about the benefits of this procedure in keratoconus.
Subject(s)
Collagen , Corneal Topography , Cross-Linking Reagents , Keratoconus , Photochemotherapy , Photorefractive Keratectomy , Photosensitizing Agents , Refraction, Ocular , Riboflavin , Visual Acuity , Humans , Photorefractive Keratectomy/methods , Keratoconus/surgery , Keratoconus/diagnosis , Keratoconus/drug therapy , Keratoconus/physiopathology , Keratoconus/metabolism , Male , Prospective Studies , Female , Photosensitizing Agents/therapeutic use , Collagen/metabolism , Cross-Linking Reagents/therapeutic use , Visual Acuity/physiology , Adult , Young Adult , Photochemotherapy/methods , Riboflavin/therapeutic use , Refraction, Ocular/physiology , Follow-Up Studies , Lasers, Excimer/therapeutic use , Ultraviolet Rays , Surgery, Computer-Assisted/methods , Cornea/surgery , Cornea/pathology , Adolescent , Corneal Stroma/metabolism , Corneal Stroma/surgery , Treatment Outcome , Combined Modality TherapyABSTRACT
PURPOSE: To investigate corneal biomechanical changes after corneal cross-linking (CXL) treatments with rose bengal-green light (RB-CXL) and riboflavin-UVA (RF-CXL). METHODS: A total of 60 freshly enucleated lamb eyes were obtained for this experimental study. Fifteen eyes were treated with RB-CXL using 0.1% RB solution (Group 1), 15 eyes were treated with RB-CXL using 0.2% RB solution (Group 2), 15 eyes were treated with RF-CXL using 0.1% RF solution (Group 3), and 15 eyes were used as controls (Group 4). The same treatment protocol (10-minute irradiation using a total of 5.4 J/cm2 energy) was applied to all treatment groups. To evaluate corneal biomechanical changes, the stress-strain test was used for both the treated and control corneas. The elastic modulus was calculated using the tension strain curves obtained during the test. RESULTS: The average elastic modulus values were calculated to be 18.9, 23.5, 22.3, and 14.1 MPa in Groups 1, 2, 3, and 4, respectively. Statistically significant differences were found between the groups (p < 0.001 for Group 1 vs. 2; p < 0.001 for Group 1 vs. 3; p < 0.001 for Group 1 vs. 4; p = 0.002 for Group 2 vs. 3; p < 0.001 for Group 2 vs. 4; and p < 0.001 for Group 3 vs. 4). CONCLUSIONS: In this study, the efficacy of RB-CXL treatment applied using different concentrations of RB solutions at a total energy of 5.4 J/cm2 was investigated, and 0.2% RB solution was found to have at least as much and even more effective than the RF-CXL (0.1% RF) on the corneal elasticity module. These results are encouraging for the treatment of ectatic corneas particularly below 400 µm. It is considered that the findings obtained from this study will guide future experimental and clinical studies.
Subject(s)
Cornea , Elasticity , Photochemotherapy , Photosensitizing Agents , Riboflavin , Rose Bengal , Ultraviolet Rays , Animals , Biomechanical Phenomena , Collagen/metabolism , Cornea/drug effects , Cornea/physiopathology , Cross-Linking Reagents , Disease Models, Animal , Elastic Modulus , Elasticity/drug effects , Elasticity/physiology , Elasticity/radiation effects , Fluorescent Dyes , Green Light , Keratoconus/drug therapy , Keratoconus/physiopathology , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/pharmacology , Riboflavin/therapeutic use , Rose Bengal/pharmacology , SheepABSTRACT
Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases.
Subject(s)
Acanthamoeba Keratitis , Keratoconus , Microscopy, Confocal , Acanthamoeba Keratitis/diagnosis , Acanthamoeba Keratitis/drug therapy , Humans , Male , Keratoconus/drug therapy , Keratoconus/diagnosis , Adolescent , Riboflavin/therapeutic use , Collagen , Photosensitizing Agents/therapeutic use , Cross-Linking Reagents/therapeutic use , Visual Acuity , Cornea/parasitology , Cornea/pathology , Acanthamoeba/isolation & purification , Corneal Stroma/pathology , Corneal Stroma/parasitologyABSTRACT
PURPOSE OF REVIEW: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations. RECENT FINDINGS: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients. SUMMARY: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.
Subject(s)
Collagen , Cross-Linking Reagents , Keratoconus , Photochemotherapy , Photosensitizing Agents , Riboflavin , Ultraviolet Rays , Keratoconus/drug therapy , Humans , Cross-Linking Reagents/therapeutic use , Riboflavin/therapeutic use , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Dilatation, Pathologic/drug therapy , Collagen/metabolism , Corneal Stroma/metabolismABSTRACT
PURPOSE OF REVIEW: This manuscript summarizes contemporary research from 2018 to 2023 evaluating long-term (≥2âyears) outcomes of corneal crosslinking (CXL) for progressive keratoconus (KCN). RECENT FINDINGS: The standard Dresden protocol (SDP) has been utilized clinically since the early 2000âs to treat ectatic disorders, primarily progressive KCN and postrefractive ectasia. Various modifications have since been introduced including accelerated and transepithelial protocols, which are aimed at improving outcomes or reducing complications. This review summarizes data demonstrating that the SDP halts disease progression and improves various visual and topographic indices (UDVA, CDVA, Kmax, K1, K2) up to 13âyears postoperatively. Accelerated and transepithelial protocols have been found to be well tolerated alternatives to SDP with similar efficacy profiles. Studies focusing on pediatric populations identified overall higher progression rates after CXL. All protocols reviewed had excellent safety outcomes in adults and children. SUMMARY: Recent studies revealed that SDP successfully stabilizes KCN long term, and a variety of newer protocols are also effective. Pediatric patients may exhibit higher progression rates after CXL. Further research is required to enhance the efficacy and ease of these protocols.
Subject(s)
Collagen , Cross-Linking Reagents , Keratoconus , Photochemotherapy , Photosensitizing Agents , Riboflavin , Visual Acuity , Humans , Keratoconus/drug therapy , Keratoconus/physiopathology , Cross-Linking Reagents/therapeutic use , Photosensitizing Agents/therapeutic use , Riboflavin/therapeutic use , Photochemotherapy/methods , Collagen/therapeutic use , Visual Acuity/physiology , Ultraviolet Rays , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Treatment Outcome , Corneal TopographyABSTRACT
PURPOSE: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus. METHODS: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day. RESULTS: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar. CONCLUSION: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL.
Subject(s)
Cross-Linking Reagents , Eye Infections, Fungal , Keratoconus , Photosensitizing Agents , Rhizopus , Riboflavin , Humans , Male , Keratoconus/drug therapy , Keratoconus/diagnosis , Adolescent , Photosensitizing Agents/therapeutic use , Rhizopus/isolation & purification , Riboflavin/therapeutic use , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/diagnosis , Cross-Linking Reagents/therapeutic use , Photochemotherapy , Mucormycosis/drug therapy , Mucormycosis/diagnosis , Mucormycosis/microbiology , Postoperative Complications/drug therapy , Ultraviolet Rays , Corneal Ulcer/microbiology , Corneal Ulcer/drug therapy , Corneal Ulcer/diagnosis , Antifungal Agents/therapeutic use , Corneal Stroma/metabolism , Corneal Stroma/microbiology , Visual Acuity , Corneal Topography , Keratitis/microbiology , Keratitis/drug therapy , Keratitis/diagnosisABSTRACT
PURPOSE: The purpose of this study was to report our first clinical experience using topical losartan for the treatment of severe corneal haze after epithelium-off corneal cross-linking (CXL). METHODS: A 20-year-old man presented with clinically significant corneal haze in the right eye 1 month following Ultraviolet-A/Riboflavin Epithelium-off Collagen CXL. Haze progressed to a deep stromal scar, and vision was 20/150 with no improvement on refraction, 60 days after CXL. After unsuccessful treatment with topical corticosteroids, the patient elected to start off-label treatment with topical losartan 0.8 mg/mL, administered 6 times per day. RESULTS: After 3 months of initiating topical losartan, the right eye vision improved to preoperative vision of 20/40-1. Corneal haze was significantly reduced as observed on slitlamp examination and on Scheimpflug corneal tomography (Pentacam; OCULUS, Inc. Arlington, WA). CONCLUSIONS: Topical losartan, a transforming growth factor-ß inhibitor, is a potential treatment in clinically significant corneal haze following epithelium-off corneal CXL. This clinical experience highlights the potential efficacy of topical losartan as a novel therapeutic option in such cases, but further clinical studies are needed.
Subject(s)
Collagen , Corneal Opacity , Cross-Linking Reagents , Losartan , Photosensitizing Agents , Riboflavin , Ultraviolet Rays , Visual Acuity , Humans , Losartan/administration & dosage , Losartan/therapeutic use , Male , Riboflavin/therapeutic use , Collagen/metabolism , Young Adult , Corneal Opacity/drug therapy , Corneal Opacity/etiology , Photosensitizing Agents/therapeutic use , Keratoconus/drug therapy , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Photochemotherapy/methods , Ophthalmic Solutions , Administration, TopicalABSTRACT
PURPOSE: To establish new criteria for the progression of keratoconus, taking into account a Pentacam HR (high resolution) tomographers repeatability limit. METHODS: This is a retrospective observational study, including 224 eyes in 154 patients diagnosed with keratoconus and patients treated with crosslinking, with a follow-up of at least one year, in which the new progression score of the Cruces University Hospital for keratoconus progression was analyzed. This score takes into account: maximum keratometry, thinnest corneal thickness, maximum posterior elevation, vertical coma and RMS of high order aberrations, all based on the tomographer repeatability limit. The effectiveness or not of crosslinking was determined. RESULTS: The Receiver Operating Characteristics (ROC) curves obtained in our validation met the criteria by being far from the reference diagonal. Moreover, young patients are more likely to have keratoconus that progresses, and the percentage of patients that showed progression was 14.3% of the eyes studied, with the most advanced keratoconus showing the least progression. Taking into account the new progression score of the Cruces Hospital, we would have indicated crosslinking in 2 eyes only and we observed that none progressed one year after treatment. CONCLUSIONS: The the new progression score of the Cruces University Hospital is a method based on the real repeatability limit for keratoconic eyes. Moreover, it is easy to interpret and can be implemented with Pentacam software. It provides a numerical value that evaluates both the anterior and posterior surfaces of the cornea and corneal aberrations in the evolution of keratoconus.
Subject(s)
Cornea , Corneal Topography , Disease Progression , Keratoconus , ROC Curve , Humans , Keratoconus/diagnosis , Keratoconus/physiopathology , Retrospective Studies , Female , Male , Adult , Corneal Topography/methods , Young Adult , Cornea/pathology , Cornea/diagnostic imaging , Follow-Up Studies , Cross-Linking Reagents/therapeutic use , Visual Acuity/physiology , Adolescent , Photosensitizing Agents/therapeutic use , Riboflavin/therapeutic use , Collagen/metabolism , Photochemotherapy/methods , Middle AgedABSTRACT
PURPOSE: To compare the changes encountered in corneal biomechanics and aberration profile following accelerated corneal collagen cross-linking (CXL) using hypo-osmolar and iso-osmolar riboflavin in corneal thicknesses of <400 and >400 microns, respectively. METHODS: This is a prospective, interventional, comparative study involving 100 eyes of 75 patients with progressive keratoconus. Eyes were divided into two groups based on corneal thickness: group 1 included eyes with a corneal thickness of <400 microns who underwent hypo-osmolar CXL, and group 2 included eyes with a corneal thickness of >400 microns who underwent iso-osmolar CXL. Corneal biomechanical and aberration profiles were evaluated and compared between groups. RESULTS: In group 1, all higher-order aberrations (HOA) except secondary astigmatism significantly decreased from baseline; however, in group 2, only coma and trefoil decreased. The corneal resistance factor and corneal hysteresis significantly improved in both groups, which was significantly greater in group 2 than in group 1. The change in inverse radius, deformation amplitude, and tomographic biomechanical index was significantly improved in group 2 as compared to group 1. CONCLUSION: Improvement in corrected distance visual acuity and decrease in HOA were significantly better in the hypo-osmolar CXL group; however, the improvement in biomechanical strength of the cornea was significantly better in the iso-osmolar group.
Subject(s)
Collagen , Cornea , Corneal Topography , Cross-Linking Reagents , Keratoconus , Photosensitizing Agents , Riboflavin , Ultraviolet Rays , Visual Acuity , Adolescent , Adult , Female , Humans , Male , Young Adult , Biomechanical Phenomena , Collagen/metabolism , Cornea/diagnostic imaging , Cornea/physiopathology , Cornea/drug effects , Corneal Stroma/metabolism , Corneal Stroma/drug effects , Corneal Wavefront Aberration/physiopathology , Cross-Linking Reagents/therapeutic use , Follow-Up Studies , Keratoconus/drug therapy , Keratoconus/physiopathology , Keratoconus/diagnosis , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Prospective Studies , Refraction, Ocular/physiology , Riboflavin/therapeutic use , Visual Acuity/physiology , ChildABSTRACT
PURPOSE: We aimed to compare the efficacy and safety of accelerated contact lens-assisted cross-linking (CA-CXL) with Lotrafilcon B and Comfilcon A lenses in keratoconus (KC) patients with thin corneas. STUDY DESIGN: Retrospective, single-center study. MATERIALS AND METHODS: We retrospectively included 51 eyes of 39 KC patients with corneal thickness <400µm after epithelial scraping (Epi-off), who underwent accelerated CA-CXL treatment with Lotrafilcon B (n=20) and Comfilcon A (n=31). Uncorrected and corrected distance visual acuity (UDVA and CDVA), manifest refraction values, corneal topographic data and endothelial cell density were recorded at preoperative and postoperative 1st, 3rd and 6th month controls. RESULTS: CDVA in the Comfilcon A group was higher than CDVA before surgery at 6 months postoperatively (p<0.001). When the two lenses were compared, CDVA was found to be significantly higher in the Lotrafilcon B group in the preoperative, postoperative 1st month and 3rd month values, but there was no significant difference between the postoperative 6th month values (p=0.028, p=0.018, p=0.044, p=0.181, respectively). The maximum keratometry (Kmax) value at the 6th month after surgery in the Comfilcon A group was significantly lower than in the Lotrafilcon B group (p=0,009). There was no significant difference between the endothelial cell density values between the groups (p=0.623, p=0.609, p=0.794, p=0.458, respectively). There was no significant difference between the progression, regression, and stability rates of the two groups (p=0.714). CONCLUSIONS: Accelerated CA-CXL with Lotrafilcon B and Comfilcon A silicone hydrogel lenses is a safe and effective method to stop progression in patients with thin corneas.
Subject(s)
Contact Lenses, Hydrophilic , Corneal Cross-Linking , Keratoconus , Photochemotherapy , Riboflavin , Adolescent , Adult , Female , Humans , Male , Young Adult , Cell Count , Collagen/metabolism , Cornea/pathology , Corneal Stroma/metabolism , Corneal Topography , Endothelium, Corneal/pathology , Follow-Up Studies , Keratoconus/diagnosis , Keratoconus/physiopathology , Keratoconus/drug therapy , Keratoconus/therapy , Keratoconus/metabolism , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Refraction, Ocular/physiology , Retrospective Studies , Riboflavin/therapeutic use , Treatment Outcome , Ultraviolet Rays , Visual Acuity/physiologyABSTRACT
PURPOSE: To compare clinical outcomes of customized transepithelial (epi-on) corneal crosslinking (CXL) in high oxygen and customized CXL with epithelial removal (epi-off) in room air for keratoconus (KC). SETTING: Umeå University Hospital, Umeå, Sweden. DESIGN: Prospective, randomized, single-masked, intraindividually comparing study. METHODS: 32 participants with bilateral progressive KC were treated with bilateral customized topography-guided CXL, 30 mW/cm 2 ; 7.2 to 15 J/cm 2 and were randomized to epi-on in one eye (32 eyes) and epi-off in the fellow eye (32 eyes). Uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), maximal keratometry (Kmax), subjective ocular discomfort, low-contrast visual acuities (LCVAs) at 10% and 2.5% contrast, ocular and anterior corneal wavefront aberrations, manifest refractive spherical equivalent, endothelial cell count (ECC), and adverse events were assessed through 24 months. RESULTS: Both treatments showed improvements at 24 months in UDVA; -0.16 ± 0.24 ( P < .001) and -0.13 ± 0.20 logMAR ( P = .006), respectively, CDVA; -0.10 ± 0.11 ( P < .001) and -0.10 ± 0.12 ( P = .001), Kmax; -1.74 ± 1.31 ( P < .001) and -1.72 ± 1.36 D ( P < .001). LCVA 10% improved for both protocols ( P < .001), but LCVA 2.5% improved for epi-on CXL only ( P = .001). ECC was unaltered, and no adverse events occurred. The epi-on eyes had significantly less discomfort symptoms during the whole first week posttreatment ( P < .05). CONCLUSIONS: High-oxygen customized epi-on CXL is a viable alternative to room air customized epi-off CXL, with faster improvements in CDVA and LCVA and less early ocular discomfort.