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.

Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL)-A Scoping Review Based on Preclinical Studies.

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.

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.

Adjunctive bevacizumab therapy in an equine corneal stromal invasive squamous cell carcinoma with a 53-months follow-up.

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.

Long-term outcomes of corneal crosslinking.

PURPOSE OF REVIEW: This manuscript summarizes contemporary research from 2018 to 2023 evaluating long-term (≥2 years) outcomes of corneal crosslinking (CXL) for progressive keratoconus (KCN). RECENT FINDINGS: The standard Dresden protocol (SDP) has been utilized clinically since the early 2000 s 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 13 years 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.

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

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.

An injectable thermoresponsive-hydrogel for lamellar keratoplasty: In-situ releases celastrol and hampers corneal scars.

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.

Comparative evaluation of biomechanical changes and aberration profile following accelerated collagen cross-linking using hypo-osmolar and iso-osmolar riboflavin: A prospective study.

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.

Topical Losartan for Treating Corneal Haze After Ultraviolet-A/Riboflavin Collagen Cross-Linking.

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.

Management of Keratoconus in Down Syndrome and Other Intellectual Disability.

PURPOSE: The purpose of this study was to assess an intellectual disability (ID) cohort with keratoconus (KC) regarding ophthalmic (visual acuity and corneal tomography) and systemic characteristics and to describe an appropriate clinical algorithm for investigation and management of KC in this setting. METHODS: This was the retrospective cohort study of patients with ID (Down syndrome, autism, and other) in the cornea department of a tertiary referral ophthalmic hospital in Dublin, Ireland. Retrospective chart review was conducted on people with ID undergoing examination under anesthesia or crosslinking under general anesthetic. Key outcome data included corneal examination findings, corneal tomography, visual acuity, and examination findings (eg, type of ID, general anesthetic, and cardiac status). RESULTS: Mean age of the 24 patients was 31.9 years (66.7% male). ID type was Down syndrome (66.7%), autism (25%), and other (8.3%). KC was diagnosed in 98% of eyes, with 45.8% having untreatable advanced disease (57.1% of these bilateral), 39.6% amenable to corneal collagen crosslinking (35.7% of these bilateral), and 6.3% having corneal transplantation. Congenital heart defects were present in 37.5% of the Down syndrome group. There were no serious ocular or systemic adverse events. CONCLUSIONS: KC is strikingly prevalent in the ID population. Ireland has the highest rate of Down syndrome in Europe (26.3:10,000 live births). This group is rarely suitable for corneal transplantation, and corneal collagen crosslinking is an effective intervention to prevent progression to advanced KC in this already socially restricted group. We propose an algorithm for investigation/treatment and also recommend uniform pediatric KC screening/treatment in ID populations.

Comparison of the Effects of Temperature and Dehydration Mode on Glycerin-Based Approaches to SMILE-Derived Lenticule Preservation.

PURPOSE: The aim of this study was to explore the optimal method of small-incision lenticule extraction (SMILE)-derived lenticules, subjected to long-term preservation using glycerol, under a range of temperatures, and using an array of dehydration agents. METHODS: In total, 108 myopic lenticules were collected from patients undergoing the SMILE procedure. Fresh lenticules served as a control group for this study, whereas all other lenticules were separated into 8 groups, which were preserved at 4 different temperatures (room temperature [RT], 4, -20, and -80°C) with or without silica gel in anhydrous glycerol. Evaluated parameters included thickness, transmittance, hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemistry analyses. RESULTS: After a 3-month preservation period, lenticular thickness in these different groups was significantly increased, particularly for samples stored at RT. The mean percentage transmittance of lenticules stored at -80°C with or without silica gel was closest to that of fresh lenticules. Hematoxylin and eosin staining revealed sparsely arranged collagen fibers that were more scattered in preserved lenticules relative to fresh lenticules, particularly in RT samples. Transmission electron microscopy revealed that the fibril bundles densities in lenticules stored at RT were significantly less than those stored at other temperatures. Immunohistochemistry analyses revealed reductions in or loss of CD45 and human leukocyte antigens in all preserved lenticules relative to control samples. CONCLUSIONS: Of the tested approaches, the preservation of SMILE-derived lenticules over a 3-month period was optimal at -80°C with or without silica gel in anhydrous glycerol.

Corneal biomechanical properties following corneal cross-linking: Does age have an effect?

PURPOSE: To explore the effect of age on corneal biomechanical properties following corneal cross-linking (CXL). METHODS: A total of 12 pairs of human eye-banked corneas (24 corneas, from 14 females and 10 males) were used in the study. The mean donor age was 48.5 years (ranging from 26 to 71 years). Corneas were divided into three age groups: A (26-41 years), B (42-57 years) and C (58-71 years), with four pairs in each group. For each pair, the right corneas were cross-linked using accelerated CXL with UVA (10 mW/cm2) and riboflavin, while the left corneas served as controls and were not exposed to either UVA irradiation or riboflavin. The corneal elastic modulus of the anterior, mid and posterior corneal stroma was measured using nanoindentation. RESULTS: The difference in the corneal elastic modulus following CXL was significant in the anterior (p = 0.00002) and mid stroma (p = 0.001); however, the difference was not significant in the posterior stroma (p = 0.27) when compared to control corneas. The corneal elastic modulus of the anterior stroma increased by 178.44% in Group A, 119.7% in Group B and 50.73% in Group C compared to control corneas. For the mid stroma, the elastic modulus increased by 47.35% in Group A, 25% in Group B and 24.56% in Group C. No differences were observed in the posterior stroma between age groups. CONCLUSIONS: Corneal elasticity showed a greater response to CXL in the younger group compared to older groups. CXL treatment showed effectiveness in enhancing stromal strength, and the effect was concentrated in the anterior and mid stroma with minimal impact on the posterior stroma in all age groups.

Transepithelial Diluted Alcohol and Iontophoresis-Assisted Corneal Crosslinking for Progressive Keratoconus in Adults: 4-Year Clinical Results.

PURPOSE: The aim of this study was to compare the 4-year clinical outcomes of transepithelial diluted alcohol and iontophoresis-assisted corneal crosslinking (DAI-CXL) and standard corneal crosslinking (S-CXL) in adults with progressive keratoconus. METHODS: This retrospective study included 36 eyes of 36 keratoconic patients who underwent DAI-CXL (n = 18) or S-CXL (n = 18). Best spectacle-corrected visual acuity (BSCVA) and corneal topography parameters were analyzed at baseline and at 1, 2, 3, and 4 years of follow-up. Corneal demarcation line depth (DLD) at 1 month was measured, and the relation of DLD with corneal thickness (DL%) was assessed. RESULTS: BSCVA improved significantly only in S-CXL (P = 0.01). A significant decrease in maximum keratometry and mean keratometry occurred at 4 years in both groups (all P < 0.05), and these changes were similar in both groups (all P > 0.05). There was a significant reduction in the thinnest corneal thickness in S-CXL (P = 0.01); however, the mean thinnest corneal thickness in DAI-CXL remained stable (P = 0.094). Higher-order aberrations and coma aberration decreased significantly in both groups at 4 years (all P < 0.05), with a higher decrease in S-CXL (all P < 0.05). Spherical aberration showed a significant reduction only in S-CXL (P = 0.005). In contrast to the similar mean DLD in both groups, DL% in DAI-CXL was significantly greater than that in S-CXL (P = 0.032). There were no correlations between the improvement in BSCVA, maximum keratometry, mean keratometry, higher-order aberrations, and the mean DLD and DL% (all P > 0.05). CONCLUSIONS: DAI-CXL was as effective as S-CXL in arresting the progression of keratoconus and showed similar clinical results to S-CXL at the 4-year follow-up.

Outcomes After Corneal Crosslinking for Keratoconus in Children and Young Adults.

PURPOSE: The aim of this study was to assess the effect of corneal crosslinking on vision and keratometry in children and young adults with progressive keratoconus. METHODS: A retrospective medical records review of patients aged 22 years or younger with keratoconus who underwent corneal crosslinking between January 2013 and November 2019 at Byers Eye Institute at Stanford University was conducted. Outcome measures included logarithm of the Minimum Angle of Resolution corrected distance visual acuity (CDVA); keratometry, including maximum keratometry (Kmax); pachymetry; and total wavefront aberration. Measurements were taken at baseline and at 12 and 24 months postoperatively. RESULTS: Fifty-seven eyes of 49 patients aged 12 to 22 years were assessed. The mean preoperative CDVA was logarithm of the Minimum Angle of Resolution 0.38 ± 0.32 (20/48), with a mean postoperative CDVA of 0.29 ± 0.31 (20/39) and 0.31 ± 0.31 (20/41) at 12 and 24 months postoperatively, respectively. Compared with preoperative mean Kmax, there was an improvement of -0.8 diopters (D) to a mean postoperative Kmax of 59.1 ± 9.1 D at 12 months and -1.3 D to 59.7 ± 8.8 D at 24 months. Subanalysis excluding the second eye of patients who underwent bilateral crosslinking showed similar results. Linear mixed modeling showed significant improvement in Kmax at both 12 and 24 months postoperatively. Minimum central corneal thickness initially decreased but stabilized at 24 months after crosslinking. Total wavefront aberration remained stable. CONCLUSIONS: Corneal crosslinking stabilizes, and in some cases improves, visual and corneal parameters in pediatric and young adult patients with keratoconus. The procedure is safe and well-tolerated and may prevent keratoconus progression in young patients.

The ABCD Keratoconus Grading System-A Useful Tool to Estimate Keratoconus Progression in the Pediatric Population.

PURPOSE: To evaluate the ABCD grading system in pediatric keratoconus. METHODS: A retrospective cohort analysis of all children with keratoconus followed up at the Shamir medical center between 2010 and 2017. A recommendation by the treating physician to undergo corneal crosslinking (CXL) was used as an estimate for clinically significant disease progression. The ABCD grading was not available to the treating physician and was computed post hoc. The ABCD grading was compared between patients who required CXL with those who did not. A single eye of each patient was included. RESULTS: Fifty eyes of 50 children were analyzed. The mean age at presentation was 15.56 ± 1.36 years. In 23 eyes, progression of keratoconus was recorded and CXL was performed (CXL-group). On presentation, the stable and CXL groups did not differ significantly in their clinical parameters. In the CXL-group, a statistically significant increase was seen in the ABCD staging (P < 0.001). In the stable group, the ABCD staging did not change significantly in parallel visits (P = 0.87). An increase of 1 point in the sum of the ABCD staging showed a 5-fold risk for undergoing CXL (odds ratio = 5.28; 95% CI, 1.82-15.34). There was no significant change in the Amsler-Krumeich classification in the CXL group. CONCLUSIONS: Among a cohort of pediatric patients with keratoconus, worsening in the ABCD grading was associated with disease progression, whereas no significant change was demonstrated in the Amsler-Krumeich classification The ABCD grading system is a useful tool for initial assessment of disease progression in the pediatric population, in which early recognition is of paramount importance.

Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid.

Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-κB subunit) ablation in K14+ corneal epithelial stem cells not only disrupts corneal regeneration but also results in age-dependent epithelial deterioration, which triggers aberrant wound-healing processes including stromal remodeling, neovascularization, epithelial metaplasia, and plaque formation at the central cornea. These anomalies are largely recapitulated in normal mice that age naturally. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre; Relaf/f mice and naturally aged mice. Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. This study thus uncovers the major mechanisms governing corneal maintenance, regeneration, and aging and identifies the NF-κB-retinoic acid pathway as a therapeutic target for corneal disorders.

Diffuse Lamellar Keratitis in a Patient Undergoing Collagen Corneal Cross-Linking 18 Years After Laser In Situ Keratomileusis Surgery.

PURPOSE: To report a case of diffuse lamellar keratitis (DLK) after corneal collagen cross-linking in an eye with a remote history of laser in situ keratomileusis (LASIK) surgery. METHODS: This is a case report and literature review. RESULTS: This report describes the development of unilateral stage IV DLK in a patient who underwent bilateral corneal cross-linking for corneal ectasia 18 years after LASIK surgery. The patient was treated with high-dose topical steroids that were tapered over 1 month and multiple flap lifts. The ultimate best-corrected visual outcome was 20/60. CONCLUSIONS: DLK is a potential sight-threatening complication of refractive surgery that can occur at any time in the postoperative period, even years after the procedure. Undergoing a subsequent corneal procedure that may disrupt or promote inflammation within the surgical flap-stromal interface, such as corneal collagen cross-linking, is a recognized risk factor for the development of DLK. This case suggests that patients with any history of LASIK surgery undergoing corneal cross-linking or other lamellar corneal surgeries may benefit from closer follow-up (eg, daily) than patients with no history of LASIK.

Keratoconus Management With Customized Photorefractive Keratectomy by Artificial Intelligence Ray-Tracing Optimization Combined With Higher Fluence Corneal Crosslinking: The Ray-Tracing Athens Protocol.

PURPOSE: The aim of this study was to report novel ray-tracing customization of surface excimer laser ablation combined with higher fluence corneal crosslinking (CXL) in the stabilization and normalization of ectasia and visual rehabilitation of progressive keratoconus. METHODS: A 28-year-old man with bilateral progressive keratoconus was treated with Athens protocol: CXL combined with photorefractive surface ablation customized by a novel artificial intelligence platform calculating lower- and higher-order aberrations based on wavefront, Scheimpflug tomography, and interferometry axial length data from a single diagnostic device. Visual acuity, refractive error, keratometry, optical coherence tomography and Scheimpflug tomography, and endothelial cell density were evaluated over 12 months. RESULTS: Keratoconus stabilized in both eyes. Uncorrected distance visual acuity changed from 20/80 to 20/20 in the OD and from 20/40 to 20/25 in the OS at 12 months. Keratometry changes were as follows: from 40.7 and 42.7 at 165.1 degrees to 41.4 and 43.1 at 169.3 degrees in the OD and from 40.9 and 42.6 at 15.9 degrees to 44.1 and 44.7 at 9.8 degrees in the OS. Corneal surface normalization was as follows: index of height decentration from 0.115 to 0.099 and index of surface variance from 77 to 67 in the OD and index of height decentration from 0.066 to 0.014 and index of surface variance from 49 to 31 in the OS. CONCLUSIONS: We introduced in this study the management of progressive keratoconus with CXL combined with novel excimer laser customization using several independent up-to-now diagnostics calculated by software, evaluating bidirectional theoretical ray tracing. It bears the potential advantage of addressing more accurately normalization of the distorted human eye optics associated with corneal ectasia, compared with using anterior corneal surface data or wavefront data alone.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.