Corneal Cross-linking Research Articles

Randomized clinical trial comparing customized corneal crosslinking: epi-on in high oxygen and epi-off in room air for keratoconus.

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). Umeå University Hospital, Umeå, Sweden. Prospective, randomized, single-masked, intraindividually comparing study. 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. 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). 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.

Pediatric keratoconus in a tertiary eye hospital in Eastern province, Saudi Arabia: Patient characteristics and management outcomes.

This study investigates pediatric keratoconus in a tertiary eye hospital in Eastern Province, Saudi Arabia, aiming to understand the presenting features and treatment outcomes in this high-prevalence region. The research addresses pediatric keratoconus clinical profile and management strategies. A retrospective cohort study was conducted from 2022 to 2023, reviewing medical records of pediatric keratoconus patients. Demographic data, clinical characteristics, risk factors, presenting symptoms, and treatment outcomes were recorded. Severity staging was performed based on Amsler-Krumeich's classification. The study included 218 eyes from 109 pediatric keratoconus patients, with 65% of male and 35% of female patients. Decreased vision was the most common symptom (92%), and risk factors included a family history of keratoconus (9%) and vernal keratoconjunctivitis (6%). Stage 1 was the most frequent in both age groups (<14 years and ≥ 14 years). Treatment strategies included corneal collagen cross-linking (CXL), hard contact lenses, corneal rings, deep anterior lamellar keratoplasty (DLK), and penetrating keratoplasty. Significant improvements were observed in visual acuity, refractive errors, and tomographic parameters following these interventions. This study provides valuable insights into pediatric keratoconus in Saudi Arabia, emphasizing the importance of early diagnosis and interventions for better outcomes. Larger, multicenter prospective studies are essential for a comprehensive understanding of pediatric keratoconus and its optimal management. The findings contribute to the knowledge base and guide future research to improve patient quality of life.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5’-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Dynamics of Corneal Swelling With Hypoosmolar Riboflavin After Induction During Corneal Collagen Crosslinking in Patients With Progressive Keratoconus.

To evaluate the rate of corneal swelling induced by hypoosmolar riboflavin in patients with progressive keratoconus (KCN) with corneal thickness <400 µm after the induction phase using riboflavin with 20% dextran during epithelium-off corneal crosslinking (CXL). Prospective, nonrandomized, single-center consecutive case series. Preoperative assessments included tomography, specular microscopy, and hysteresis. After epithelial debridement, riboflavin with 20% dextran (Photrexa Viscous; Glaukos, Burlington, MA) was applied at 2-min intervals during a 30-min induction phase. Eyes that dehydrated to a minimum corneal thickness (MCT) of <400 µm after induction (postinduction pachymetry) were recruited. Hypoosmolar riboflavin 0.146% (Photrexa; Glaukos) was used every 10 s to induce stromal swelling, with pachymetry performed every 30 s until the MCT was ≥400 µm (postswelling pachymetry). Corneal swelling rate was compared with variables using regression analysis. In 31 eyes of 31 patients, mean postinduction pachymetry was 338.4 ± 28.7 μm. Hypoosmolar riboflavin induced a postswelling pachymetry of 413.4 ± 15.0 μm over a mean of 5.2 ± 3.2 min, and the average stromal swelling rate was 10.3 ± 8.7 μm/30 s. All eyes reached a postswelling pachymetry MCT ≥400 µm and no cases were aborted. Eyes with highly severe KCN (Kmax >70 and Belin/Ambrosio enhanced ectasia display final D score >17) experienced quicker swelling (14.4 ± 12.8 μm/30 s and 14.9 ± 12.4 μm/30 s, respectively; P < 0.05 for both). A thicker postinduction pachymetry was moderately associated with a faster rate of swelling (rs = 0.389; P = 0.030). Hypoosmolar riboflavin 0.146% can be safely employed in thinner corneas, allowing for swelling to ≥400 µm for epithelium-off CXL. Associations between swelling rate, KCN severity, and postinduction pachymetry were determined, allowing for a more accurate prediction of procedure time during CXL.

Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia: A Report by the American Academy of Ophthalmology

To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia. A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies. This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare. Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile. Proprietary or commercial disclosure may be found after the references.

A Standardized Protocol of Simultaneous Transepithelial Phototherapeutic Keratectomy (PTK) Followed by Corneal Collagen Crosslinking for Keratoconus.

To report outcomes in patients with progressive keratoconus who underwent a standardized protocol of transepithelial phototherapeutic keratectomy (t-PTK) laser followed by accelerated corneal collagen crosslinking (CXL). All patients with progressive keratoconus undergoing our protocol at a London clinic between 2019 and 2023 were included. The protocol involved t-PTK at 58-μm central ablation depth at a 9-mm treatment zone on the Schwind Amaris 1050RS platform. Preoperative K readings of 43.0D (both K1 and K2) were inputted for all cases. Patients then underwent CXL with a pulsed-light accelerated protocol (30 mW/cm2 for 8 minutes of UVA exposure time with 1 second on/1 second off). Seventy-nine eyes from 55 patients were included with an average follow-up of 12 months (range 6-24 months). Both mean uncorrected distance visual acuity (UDVA) and best spectacle-corrected visual acuity improved significantly from 0.42 preoperatively to 0.29 postoperatively (P < 0.01) and 0.11 to 0.06 postoperatively (P < 0.01), respectively. The refractive cylinder reduced significantly from -3.07D to -2.63D (P < 0.05). The mean Km improved from 46.15D to 45.44D (P < 0.01) and mean Kmax from 54.03D to 52.52D (P < 0.01). 77% of eyes (n = 61) exhibited Kmax improvement postoperatively, and 56% showed an improvement in UDVA (n = 44). 16% (n = 13) had worsening of vision, but of these, only 1 patient had visual loss of more than 2 lines. No eyes had corneal haze reported at the final follow-up, and none required additional treatment. This standardized simultaneous t-PTK and CXL protocol is safe and effective for the treatment of progressive keratoconus, providing visual, refractive, and topographic improvements.

The impact of interrupted corneal collagen crosslinking (CXL) treatment.

To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea. A retrospective review was conducted of all patients with keratoconus diagnosis who underwent CXL at the Department of Ophthalmology, Örebro University Hospital (USÖ) during the years 2010-2017. In total 377 eyes of 280 patients were screened for inclusion. In 17 eyes (15 patients), the treatment was interrupted due to insufficient swelling of the cornea. Patient journals were reviewed and keratometry examinations were analysed for long-term progression. Eleven eyes (nine patients) were included in the study. Five eyes showed no signs of progression after the interrupted CXL treatment. In one eye progression continued, however, first after a period of a number of years, indicating a delayed course of clinical progression. This study indicates that debridement of the corneal epithelium and riboflavin administration without intense UVA radiation may slow or arrest the progression of keratoconus, likely due to photosensitisation from ambient light.

Biomechanical changes following corneal crosslinking in keratoconus patients.

To evaluate the biomechanical and tomographic outcomes of keratoconus patients up to four years after corneal crosslinking (CXL). In this longitudinal retrospective-prospective single-center case series, the preoperative tomographic and biomechanical results from 200 keratoconus eyes of 161 patients undergoing CXL were compared to follow-up examinations at three-months, six-months, one-year, two-years, three-years, and four-years after CXL. Primary outcomes included the Corvis Biomechanical Factor (CBiF) and five biomechanical response parameters obtained from the Corvis ST. Tomographically, the Belin-Ambrósio deviation index (BAD-D) and the maximal keratometry (Kmax) measured by the Pentacam were analyzed. Additionally, Corvis E-staging, the thinnest corneal thickness (TCT), and the best-corrected visual acuity (BCVA) were obtained. Primary outcomes were compared using a paired t-test. The CBiF decreased significantly at the six-month (p < 0.001) and one-year (p < 0.001) follow-ups when compared to preoperative values. E-staging behaved accordingly to the CBiF. Within the two- to four-year follow-ups, the biomechanical outcomes showed no significant differences when compared to preoperative. Tomographically, the BAD-D increased significantly during the first year after CXL with a maximum at six-months (p < 0.001), while Kmax decreased significantly (p < 0.001) and continuously up to four years after CXL. The TCT was lower at all postoperative follow-up visits compared to preoperative, and the BCVA improved. In the first year after CXL, there was a temporary progression in both the biomechanical CBiF and E-staging, as well as in the tomographic analysis. CXL contributes to the stabilization of both the tomographic and biomechanical properties of the cornea up to four years postoperatively.

An Effective Treatment for Progressive Keratoconus with Two-Year Outcomes: Accelerated Epithelium-on Corneal Cross-Linking

Purpose: Corneal collagen cross-linking is a surgical technique for progressive keratoconus. There are several technical modifications with varying clinical outcomes. This study aimed to evaluate the long-term outcomes of the accelerated epithelium-on collagen cross-linking. Design &amp; Methods: A retrospective study was performed on progressive keratoconus patients treated via the accelerated epithelium-on collagen cross-linking who completed the 24th-month follow-up. We included 111 eyes of 77 patients. Clinical variables, including visual acuity, aberrometry, topographic measurements, and refractive outcomes, were evaluated at the postoperative 12th and 24th months. Results: There was a significant improvement in postoperative visual acuity in 50.4% of the patients (p

Combined DSAEK With Cataract Surgery in a Patient With Fuchs Endothelial Corneal Dystrophy and Keratoconus After Corneal Crosslinking

Purpose: To report a combined Descemet stripping automated endothelial keratoplasty (DSAEK) with cataract surgery in a case of Fuchs endothelial corneal dystrophy (FECD) and keratoconus after corneal crosslinking combined with photorefractive keratectomy. Methods: We report a case of a 56-year-old woman with a history of subclinical keratoconus who underwent corneal crosslinking (CXL) plus 7 years ago. At presentation, the patient complained of blurry vision, which was more prominent in the morning over the past few years, and frequent changes of spectacle prescription ever since the initial treatment with CXL plus. Post-CXL plus corneal tomographies revealed progressive corneal flattening of 6.20 diopters (D) and 6.50 D in the right (OD) and left (OS) eye, respectively, in terms of mean keratometry values over a period of 7 years, which resulted in significant hyperopia. Corrected distance visual acuity (CDVA) at presentation was 20/50 in the OD and 20/200 in the OS. Slit-lamp examination revealed guttae (diagnosis of FECD) with associated posterior corneal edema and advanced nuclear sclerotic cataracts in both eyes. Combined DSAEK with cataract surgery was performed on the left eye. Results: One year after the combined procedure, CDVA improved to 20/25, with the correction of (−0.25, −4.25 × 25). Slit-lamp examination revealed a clear cornea without evidence of corneal edema or scarring. Corneal tomography indicated discontinuation of the corneal flattening in the left eye while the fellow eye continued to flatten. Conclusions: Combined DSAEK with cataract surgery provides an effective surgical option for patients with FECD after CXL plus procedures for keratoconus, offering fast visual rehabilitation and functional visual outcomes.

Corneal Surface Elevation and Thickness in Relation to the Fit of Rigid Contact Lenses in Keratoconus and After Corneal Cross-Linking

Corneal Surface Elevation and Thickness in Relation to the Fit of Rigid Contact Lenses in Keratoconus and After Corneal Cross-Linking

Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial

PurposeTo validate the ability of theranostic imaging biomarkers in assessing the propensity of corneal cross-linking (CXL) in flattening the maximum keratometry (Kmax) index. DesignProspective, randomized, multicenter, masked clinical trial (NCT05457647). ParticipantsFifty patients with progressive keratoconus. InterventionParticipants were stratified to undergo epithelium-off (epi-off; 25 eyes) and epithelium-on (epi-on; 25 eyes) CXL protocols using UV-A medical device incorporating theranostic software module. The device used controlled UV-A light both for performing CXL and for estimating the corneal riboflavin concentration (riboflavin score) and assessing treatment effect (theranostic score) in real time. A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epi-off and epi-on protocols respectively. All eyes underwent 9 minutes UV-A irradiance at 10 mW/cm2. Main Outcome MeasuresThe primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to correctly classify eyes and positively predict a Kmax flattening at 1 year after CXL. Other outcome measures were the change of Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction, and central corneal thickness one year after CXL. ResultsAccuracy and precision of the combined use of theranostic imaging biomarkers in predicting eyes that had more than 0.1 diopter (D) Kmax flattening at 1 year were 91% and 95% respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR: -2.11, -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 LogMAR (IQR: -0.3, 0.0 LogMAR; P < 0.001 and IQR: -0.2, 0.0 LogMAR; P < 0.001 respectively). There were no significant changes in endothelial cell density (P = 0.33) and central corneal thickness (P = 0.07) 1 year postoperatively. ConclusionsThe study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epi-off and epi-on CXL protocols. The concentration of riboflavin and its UV-A light mediated photo-activation in the cornea are the primary factors determining CXL treatment efficacy.

Combined topography-guided photorefractive keratectomy and corneal collagen crosslinking.

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. 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. 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). 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.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions: theoretical basis.

Keratoconus is an ectatic condition characterized by gradual corneal thinning, corneal protrusion, progressive irregular astigmatism, corneal fibrosis, and visual impairment. The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages, gas-permeable rigid contact lenses, scleral lenses, implantation of intrastromal corneal ring or corneal transplants for most advanced stages. In keratoconus cases showing disease progression corneal collagen crosslinking (CXL) has been proven to be an effective, minimally invasive and safe procedure. CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation, resulting in stromal crosslinks formation. The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models, from the original Dresden protocol to the most recent developments in the technique, reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols. Finally, the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Merging Photorefractive Keratectomy and Collagen Crosslinking: An Analysis of Literature and a Guide to Prevalent Protocols.

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. 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. 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. 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.

Comparison of Corneal Biomechanical Efficacy Between Rose Bengal-Green Light and Riboflavin-UVA Crosslinking

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.

Current trends in the management of corneal neovascularization.

The aim of this study was to highlight recent developments in the medical and surgical management of corneal neovascularization (NV). Improved understanding and diagnostic criteria among clinicians have led to advancements in the characterization of corneal NV and objective assessment of treatment response through ancillary imaging devices. Developments in corneal NV treatments, such as antivascular endothelial growth factor, fine needle diathermy, and photodynamic therapy, have improved treatment success rates and visual outcomes. More recent surgical treatment advancements include corneal cross-linking, endothelial keratoplasty, and mitomycin intravascular chemoembolization. Finally, a greater appreciation of the molecular pathogenesis and angiogenic factors involved in corneal NV has identified numerous potential targeted therapies in the future. The management of corneal NV has evolved to include several standalone and combination medical and surgical options. Additionally, improvements in quantifying corneal NV and understanding its molecular basis have contributed to new management strategies with improved outcomes.

Evaluation of Keratoconus Patients Refractive Status Before and after Corneal Collagen Cross-linking

Background: Corneal Collagen Cross Linking (CXL) incorporated with riboflavin solution activated by UV (Ultraviolet) irradiation is a modern promising treatment protocol for keratoconus. Evaluation of the clinical effect of CXL treatment on keratoconus patients was the aim of this study. Methods: This Quasi Experimental (before-and-after) study was comprised with 50 patients, having progressive keratoconus (progression was documented by Corneal Topography), reported to Cornea Clinic, CMH Dhaka, from February 2022 to January 2023. Before and after the CXL procedure; un-corrected and best-corrected visual acuity of study population was documented using Snellen visual acuity chart. Auto-refractometry readings were also noted. Results: Among the 50 study subjects; 26 (52%) were men and 24 (48%) were female, age was 24.14 ± 5.07 (mean+SD) years and age range was 18-35 years. Mean preoperative spherical power was −1.84 ± 0.82 Diopter (D) and mean cylindrical power was −3.66 ± 0.97 D. Postoperatively, mean spherical power was found −1.15 ± 0.55 D and mean cylindrical power was −2.87 ± 0.99 D. After CXL treatment; significant vision improvement found in 15 (30%) patients (p&lt;0.05). Conclusion: Despite strengthening the corneal stromal collagen bond and halting the keratoconus progression, CXL treatment stabilize the refractive status of keratoconus patient and also in some extent, it improves vision. Bangladesh Armed Forces Med J Vol 56 No (2) December 2023, pp 45-50

Biomechanical and histological changes associated with riboflavin ultraviolet-A-induced CXL with different irradiances in young human corneal stroma

Keratoconus (KC) is a degenerative condition affecting the cornea, characterized by progressive thinning and bulging, which can ultimately result in serious visual impairment. The onset and progression of KC are closely tied to the gradual weakening of the cornea's biomechanical properties. KC progression can be prevented with corneal cross-linking (CXL), but this treatment has shortcomings, and evaluating its tissue stiffening effect is important for determining its efficacy. In this field, the shortage of human corneas has made it necessary for most previous studies to rely on animal corneas, which have different microstructure and may be affected differently from human corneas. In this research, we have used the lenticules obtained through small incision lenticule extraction (SMILE) surgeries as a source of human tissue to assess CXL. And to further improve the results' reliability, we used inflation testing, personalized finite element modeling, numerical optimization and histology microstructure analysis. These methods enabled determining the biomechanical and histological effects of CXL protocols involving different irradiation intensities of 3, 9, 18, and 30 mW/cm2, all delivering the same total energy dose of 5.4 J/cm2. The results showed that the CXL effect did not vary significantly with protocols using 3–18 mW/cm2 irradiance, but there was a significant efficacy drop with 30 mW/cm2 irradiance. This study validated the updated algorithm and provided guidance for corneal lenticule reuse and the effects of different CXL protocols on the biomechanical properties of the human corneal stroma.

Keratoconus Progression Determined at the First Visit: A Deep Learning Approach With Fusion of Imaging and Numerical Clinical Data.

Multiple clinical visits are necessary to determine progression of keratoconus before offering corneal cross-linking. The purpose of this study was to develop a neural network that can potentially predict progression during the initial visit using tomography images and other clinical risk factors. The neural network's development depended on data from 570 keratoconus eyes. During the initial visit, numerical risk factors and posterior elevation maps from Scheimpflug imaging were collected. Increase of steepest keratometry of 1 diopter during follow-up was used as the progression criterion. The data were partitioned into training, validation, and test sets. The first two were used for training, and the latter for performance statistics. The impact of individual risk factors and images was assessed using ablation studies and class activation maps. The most accurate prediction of progression during the initial visit was obtained by using a combination of MobileNet and a multilayer perceptron with an accuracy of 0.83. Using numerical risk factors alone resulted in an accuracy of 0.82. The use of only images had an accuracy of 0.77. The most influential risk factors in the ablation study were age and posterior elevation. The greatest activation in the class activation maps was seen at the highest posterior elevation where there was significant deviation from the best fit sphere. The neural network has exhibited good performance in predicting potential future progression during the initial visit. The developed neural network could be of clinical significance for keratoconus patients by identifying individuals at risk of progression.