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

PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The 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 classify eyes correctly and predict a Kmax flattening at 1 year after CXL. Other outcome measures included change in Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. RESULTS: Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of 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 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Trends and Sociodemographic Patterns in Keratoconus Management 2015-2020: An American Academy of Ophthalmology IRIS® Registry Analysis.

PURPOSE: Investigate trends in keratoconus (KCN) treatment patterns and diagnosis age from 2015 to 2020 and evaluate sociodemographic associations with the treatment approach. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with a new KCN diagnosis from 2015 to 2020 were identified in the Academy IRIS® Registry (Intelligent Research in Sight). METHODS: Associations between sociodemographic factors and treatment were evaluated using multivariable logistic regression. MAIN OUTCOME MEASURES: Outcomes included percentages and rates of each treatment (collagen crosslinking [CXL], keratoplasty, or no procedure) from 2015 to 2020, age at diagnosis during this period, and sociodemographic factors associated with treatment type. RESULTS: A total of 66 199 patients with a new diagnosis of KCN were identified. The percentage of patients undergoing CXL increased from 0.05% in 2015 to 29.5% in 2020 (P = 0.008). The average age (standard deviation) of KCN patients decreased from 44.1 (±16.9) years in 2015 to 39.2 (±16.9) years in 2020 (P < 0.001). In multivariable analyses comparing CXL versus no procedure and keratoplasty versus no procedure, patients undergoing CXL tended to be younger with the odds of having CXL decreasing with increasing age, for example, comparing CXL and no procedure patients, using ages 0-20 years as reference, the odds ratio (OR) (95% confidence interval [CI]) decreased from 0.62 (0.57-0.67; P < 0.0001) for patients aged 21-40 years to 0.03 (0.02-0.04; P < 0.0001) for patients aged > 60 years. Men were more likely than women to have CXL (OR, 1.31; 95% CI, 1.23-1.40; P < 0.0001) and keratoplasty (OR, 1.30; 95% CI, 1.19-1.42; P < 0.0001). Black patients were less likely than White patients to have CXL (OR, 0.70; 95% CI, 0.63-0.77; P < 0.0001) and more likely to have keratoplasty (OR, 2.24; 95% CI, 2.01-2.50; P < 0.0001). Likewise, Hispanic patients had higher odds of CXL (OR, 1.12; 95% CI, 1.00-1.24; P < 0.05) and keratoplasty (OR, 1.29; 95% CI, 1.12-1.50; P < 0.001) compared with non-Hispanic patients. Collagen crosslinking and keratoplasty also varied by region and insurance status. CONCLUSIONS: A significant increase in use of CXL was noted from 2015 to 2020. Sociodemographic differences in treatment among KCN patients may reflect differences in access, use, or care patterns, and future studies should aim to identify strategies to improve access for all patients. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Revisiting rabbit models for keratoconus: A long-term study on collagenase-induced disease progression.

Keratoconus (KC) is a degenerative disorder resulting from the degradation of the stromal collagen fibril network in the cornea, leading to its thinning and conical deformation. Various studies have established animal models of KC by using the collagenase type II enzyme to gain a better understanding of the pathogenesis, however, long-term monitoring or follow-up of the models have not been reported so far. This study evaluates the long-term stability of collagenase type II-induced KC in a rabbit model. Six New Zealand rabbits were divided into 4 study groups with 3 eyes per group. The groups were control (group 1), 0.5% proparacaine + 5 min collagenase treatment on day 0 and day 30 (group 2), 0.5% proparacaine + 10 min collagenase treatment on day 0 (group 3) and, mechanical debridement + 2 min collagenase treatment on day 0 (group 4). Inflammation was observed in group 4 till week 10. Significant decrease in the central corneal thickness was observed in group 3 by week 4 (p < 0.001) however, the thickness was regained in the subsequent follow-ups in all the groups. Keratography results showed no changes in Km values but an increased astigmatic power in all groups. Scanning electron microscopy images revealed thinner collagen fibrils arranged in a mesh-like pattern above the uniform layer of the collagen lamellae in the central part of the treated corneas. Similarly, histological staining revealed loosely packed stromal fibrils in the anterior portion of the cornea which corroborates with the immunofluorescent staining results. This study revealed the remodeling of the corneal structure by eight weeks of collagenase treatment. Consequently, the possibility of creating a rabbit keratoconus model induced by collagenase may warrant further consideration.

Whole-exome sequencing screening for candidate genes and variants associated with primary sporadic keratoconus in Chinese patients.

The pathogenesis of keratoconus (KC) is complex, and genetic factors play an important role. The purpose of this study was to screen and analyse candidate genes and variants in Chinese patients with primary sporadic KC. Whole-exome sequencing (WES) was performed to identify candidate genes and variants in 105 unrelated Chinese patients with primary sporadic KC. Through a series of screening processes, 54 candidate variants in 26 KC candidate genes were identified in 53 KC patients (53/105, 50.5%). These 54 candidate variants included 10 previously identified variants in 9 KC candidate genes and 44 novel variants in 20 KC candidate genes. The previously identified variants occurred in 25.7% (27/105) of patients. Of these, 4 variants (COL6A5, c.5014T > G; CAST, c.1814G > A; ZNF469, c.946G > A; and MPDZ, c.3836A > G) were identified for the first time in Chinese KC patients. The novel variants occurred in 33.3% (35/105) of patients. Of the 26 screened KC candidate genes, 11 KC candidate genes (CAT, COL12A1, FLG, HKDC1, HSPG2, PLOD1, ITGA2, TFAP2B, USH2A, WNT10A, and COL6A5) were found to be potentially pathogenic in Chinese KC patients for the first time. Gene Ontology (GO) biological process (BP) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the 26 KC candidate genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The results showed that the KC candidate genes were significantly enriched in biological processes such as collagen fibril organization and extracellular matrix (ECM) organization and in ECM-receptor interaction and protein digestion and absorption pathways. The results further expand the spectrum of KC candidate variants and provide a basis for further KC gene studies.

Circular RNA expression profile identifies potential circulating biomarkers for keratoconus.

Early diagnosis is important for improving the outcomes of keratoconus (KC). Stable expression and a closed-loop structure of circular RNAs (circRNAs) make them ideal for the diagnosis and treatment of diseases. However, the expression pattern and potential function of circRNAs in KC is not studied yet. Hence, this study explored the circRNA expression profile of KC corneas through transcriptome sequencing and circRNA expression profile analysis. The diagnostic potential of blood circRNAs for KC was explored by analysing the circRNAs' expression levels of fifty paired blood samples from patients with KC and normal controls. The results showed that 107 significantly upregulated and 145 significantly downregulated circRNAs (|fold change| ≥ 2.0, p-value <0.05) were identified in KC tissues. Eight top differently expressed circRNAs were further validated in more cornea samples. Among them, five circRNAs expressed in peripheral blood, and four circRNAs (circ_0006156, circ_0006117, circ_0000284 and circ_0001801) showed significant downregulation in KC patients' peripheral blood too. The blood circ_0000284 expression levels of early, moderate, and advanced KC patients both were significantly lower than the controls. The blood circ_0006117 expression levels present a positive correlation with corrected distance visual acuity values, and a negative correlation with back elevation values of KC eyes. Notably, the expression levels of these circRNAs distinguished KC patients from their healthy counterparts, with the area under the curve (AUC) of circ_0000284, circ_0001801, and circ_0006117 being 0.7306, 0.6871 and 0.6701, respectively. Further, the AUC value for five circRNAs under the logistic regression model was 0.8203, indicating that they can function as effective biomarkers for the KC diagnostics. In conclusion, the expression of circRNAs showed a relationship with KC, with four significantly differentially expressed circRNAs demonstrating potential as biomarkers for the disease.

The Chinese keratoconus (CKC) cohort study.

The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.

Accuracy of intraocular lens power formulas in eyes with keratoconus: Multi-center study in Japan.

PURPOSE: To assess the accuracy of intraocular lens (IOL) power formulas, namely, SRK/T, Haigis, Barrett Universal II, Barrett True-K for keratoconus, Kane formula, and Kane formula for keratoconus, for cataract with keratoconus in Japanese eyes. SETTING: Five surgical sites in Japan. DESIGN: A retrospective case series. METHODS: Eyes with keratoconus undergoing cataract surgery were included. Postoperative refraction was compared with the prediction by the formulas. Visual acuity, manifest spherical equivalent, prediction error (PE), and mean absolute errors (MAEs) were determined 1 month postoperatively. The PE within 0.50 diopter (D), 1.00 D, and 2.00 D were compared between IOL formulas. Subgroup analysis based on the steepest keratometry (stage 1, ≤ 48 D; stage 2, > 48 D and ≤ 53 D; and stage 3, > 53 D) was performed. The relationship between PE and preoperative biometric data were assessed. RESULTS: Fifty eyes were included. The MAE of the Barrett True-K for keratoconus, Kane keratoconus, and Kane formulas were significantly lower than that of Haigis. A statistically significant difference in the prediction accuracy within ± 0.50 D was found between Kane keratoconus and Haigis. The prediction accuracy of the Barrett True-K for keratoconus, SRK/T, and Kane within ± 1.00 D was statistically significant compared with that of Haigis. In stage 3, the Barrett True-K for keratoconus had a significantly lower MAE than SRK/T and Haigis. CONCLUSION: Keratoconus-specific formulas were more accurate than existing formulas in Japanese eyes. The Barrett True-K formula for keratoconus had higher prediction accuracy in severe keratoconus.

Repeatability and agreement of two ocular biometers with single and dual Scheimpflug cameras in keratoconus eyes.

BACKGROUND: To evaluate the repeatability and agreement of two different ocular biometers and Scheimpflug devices in keratoconus eyes. METHODS: This prospective, comparative trial took place at the University hospital, Goethe University, Frankfurt am Main, Germany. We included eyes with keratoconus, one eye per patient, randomly selected. Measurements were taken with Galilei G6 (Ziemer, Switzerland) and Pentacam AXL (Oculus, Germany), three consecutive measurements each. Repeatability and agreement were evaluated for simulated keratometry (simK), astigmatism (simA), maximum keratometry (KMax) and its axis, total keratometry (TCP), axial length (AL), anterior chamber depth (ACD), and thinnest pachymetry (TCT). RESULTS: Both devices showed an excellent repeatability with intra class correlation (ICC) of > 0.97 for all parameters. The 95% limits of repeatability (LoR95%) and agreement (LoA95%) were narrow for all parameters. The Galilei G6 had a narrower LoAR95% for TCT (2.1 µm vs. 4.6 µm), but a wider LoR95% for KMax (0.52D vs. 1.18D). No relevant difference was found for the other parameters. Agreement between the devices was good to moderate, especially for simK and TCP. CONCLUSIONS: Both devices show excellent repeatability with narrow LoR95% and high ICC for all parameters. The only relevant difference was found for KMax and TCT in favor of Pentacam AXL and Galilei G6, respectively. Agreement was good to moderate, and most parameters should not be considered interchangeable.

Quantitative evaluation of morphological and functional changes in meibomian glands and lipid layer thickness in patients with and without keratoconus.

PURPOSE: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC). METHODS: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups. RESULTS: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05). CONCLUSIONS: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus.

Evaluation of a new portable corneal topography system for self-measurement using smartphones: a pilot study.

PURPOSE: Herein, we propose the use of the "KeraVio Ring", which is a portable, selfie-based, smartphone-attached corneal topography system that is based on the Placido ring videokeratoscope. The goal of this study was to evaluate and compare corneal parameters between KeraVio Ring and conventional corneal tomography images. METHODS: We designed the KeraVio Ring as a device comprising 3D-printed LED rings for generating Placido rings that can be attached to a smartphone. Two LED rings are attached to a cone-shaped device, and both corneas are illuminated. Selfies were taken using the KeraVio Ring attached to the smartphone without assistance from any of the examiners. Captured Placido rings on the cornea were analysed by intelligent software to calculate corneal parameters. Patients with normal, keratoconus, or LASIK-treated eyes were included. Anterior segment optical coherence tomography (AS-OCT) was also performed for each subject. RESULTS: We found highly significant correlations between the steepest and flattest keratometry, corneal astigmatism, and vector components obtained with the KeraVio Ring and AS-OCT. In subjects with normal, keratoconus, and LASIK-treated eyes, the mean difference in corneal astigmatism between the two devices was -0.8 ± 1.4 diopters (D) (95% limits of agreement (LoA), -3.6 to 2.0), -1.8 ± 3.7 D (95% LoA, -9.1 to 5.5), and -1.5 ± 1.3 D (95% LoA, -4.0 to 1.1), respectively. CONCLUSIONS: The experimental results showed that the corneal parameters obtained by the KeraVio Ring were correlated with those obtained with AS-OCT. The KeraVio Ring has the potential to address an unmet need by providing a tool for portable selfie-based corneal topography.

Biomechanical changes following corneal crosslinking in keratoconus patients.

PURPOSE: To evaluate the biomechanical and tomographic outcomes of keratoconus patients up to four years after corneal crosslinking (CXL). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

PURPOSE: To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Expression of matrix metalloproteinases and their inhibitors in corneal stromal fibroblasts and keratocytes from healthy and keratoconus corneas.

PURPOSE: To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas. METHODS: Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant. RESULTS: KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively. CONCLUSION: This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC.

Diagnosis of forme fruste keratoconus with scheimpflug photography in Ghanaian patients.

AIM: This study aimed to differentiate moderate to high myopic astigmatism from forme fruste keratoconus using Pentacam parameters and develop a predictive model for early keratoconus detection. METHODS: We retrospectively analysed 196 eyes from 105 patients and compared Pentacam variables between myopic astigmatism (156 eyes) and forme fruste keratoconus (40 eyes) groups. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values, and a logistic regression model was used to refine the diagnostic accuracy. RESULTS: Statistically significant differences were observed in most Pentacam variables between the groups (p < 0.05). Parameters such as the Index of Surface Variance (ISV), Keratoconus Index (KI), Belin/Ambrosio Deviation Display (BAD_D) and Back Elevation of the Thinnest Corneal Locale (B.Ele.Th) demonstrated promising discriminatory abilities, with BAD_D exhibiting the highest Area under the Curve. The logistic regression model achieved high sensitivity (92.5%), specificity (96.8%), accuracy (95.9%), and positive predictive value (88.1%). CONCLUSION: The simultaneous evaluation of BAD_D, ISV, B.Ele.Th, and KI aids in identifying forme fruste keratoconus cases. Optimal cut-off points demonstrate acceptable sensitivity and specificity, emphasizing their clinical utility pending further refinement and validation across diverse demographics.

Management of corneal melting after collagen cross-linking for keratoconus: a case report and a review of the literature.

PURPOSE: We describe the management of a case of severe corneal melting after corneal cross-linking (CXL) treated with a staged approach using a conjunctival flap followed by deep anterior lamellar keratoplasty (DALK). METHODS: A 12-year-old male developed severe corneal melting with pending perforation after an accelerated epithelium-off CXL protocol. We initially treated the patient with a conjunctival flap to prevent perforation. Three months later, we performed DALK to restore vision. RESULTS: Conjunctival flap surgery allowed us to avoid corneal perforation and penetrating keratoplasty (PK) à chaud. Once the inflammation had resolved, we recessed the conjunctiva and performed DALK for optical purposes. Twelve months later, the graft was clear and the corrected visual acuity was 20/25 (Snellen). No complications occurred after surgery. CONCLUSIONS: Although CXL is considered a safe procedure, in rare cases it can lead to serious complications, such as corneal haze, infectious and non-infectious keratitis, stromal melting and perforation. Corneal melting and perforation are usually managed by emergency PK. Herein we suggest a staged approach involving an emergency conjunctival flap followed by DALK at a later time that allowed us to avoid PK à chaud.

A new technique to implant intracorneal ring-segments from the perilimbal region: one-year prospective pilot study report.

BACKGROUND: Recently a new surgical technique for intracorneal ring-segments (ICRS) assisted by femtosecond laser (FSL) called ByLimB was developed, involving the creation of the incision from a paralimbic region. This study aims to evaluate the safety and efficacy of the ByLimb technique following one year of follow-up. METHODS: A prospective, single-center study was conducted at the Zaldivar Institute in Buenos Aires, Argentina. Keratoconus patients with indication for ICRS-FSL assisted procedure, operated with the ByLimb technique were included. By using the ByLimb technique, the ICRS are placed without affecting the tunnel's roof, and the end of the ICRS is always away from the incision area. Visual acuity, topographic astigmatism, and the occurrence of complications were evaluated. Safety index was the main outcome and efficacy indes was a complimentary outcome. RESULTS: A total of 17 eyes completed the 12-month follow-up period. The safety index was 1.10 (mean postoperative corrected distance visual acuity (CDVA) in decimal: 0.76/preoperative CDVA: 0.69), while the efficacy index was 0.89 (mean postoperative uncorrected distance visual acuity UDVA in decimal: 0.62/preoperative CDVA: 0.69). Mean preoperative astigmatism was 5.3 ± 2.3, decreasing twelve months after surgery at 2.1 ± 1.2 (p < 0.001). No eye loss lines of vision and no intraoperative complications were observed. During the first month after surgery, an improper positioning of the ICRS based on topographic assessment was detected in five cases. A second procedure was performed, which consisted of opening the incision and introducing a Sinsky hook, through which the ICRS was mobilized and placed in its correct position. No incisional alterations, signs of infection, anterior segment anomalies, or fundus alterations were observed. CONCLUSION: FSL-assisted ICRS implantation through the perilimbal region has demonstrated an adequate safety index one year post-surgery. Additionally, this technique has facilitated accurate realignment of ICRS during secondary surgical interventions within one-month post-surgery. While the current findings are promising, continued follow-up of these cases is warranted.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

Femtosecond thin-flap laser assisted in situ keratomileusis for correction of post-penetrating keratoplasty ametropia: long-term outcome.

PURPOSE: To evaluate the long-term clinical outcomes of femtosecond thin-flap LASIK (femto-LASIK) for correction of refractive error after penetrating keratoplasty in keratoconus-affected eyes. SETTING: a private ophthalmology clinic. DESIGN: Prospective interventional case series. METHODS: This prospective interventional case series enrolled 22 eyes of 22 patients who underwent femto-LASIK for the management of post-penetrating keratoplasty ametropia. The refractive error, uncorrected (UDVA), and corrected (CDVA) distance visual acuities and vector analysis were reported in short-term and long-term period after surgery. RESULTS: The mean age was 32.7 ± 7.5 years (range, 23 to 47 years) at the surgery time. The average time between PK and femto-LASIK was 42.5 ± 31.7 months. The average follow-up duration after femto-LASIK was 81.2 ± 18.6 months. The mean preoperative UDVA significantly improved from 0.47 ± 0.15 logMAR to 0.35 ± 0.14 logMAR at 12 months (P = 0.048) and 0.4 ± 0.17 at final follow-up exam (P = 0.007). CDVA was 0.22 ± 0.1 at baseline which improved to 0.18 ± 0.15 and 0.15 ± 0.1 logMAR at 12 and 81 months, respectively. (Ps = 0.027, 0.014). The mean cylinder before surgery was - 5.04 ± 1.4D which significantly decreased to -1.5 ± 0.8 D at 12 months postoperatively. (P < 0.001). There was a significant increase in refractive astigmatism from 12 months to 81 months postoperatively (-3.1 ± 2.0, P = 0.002). At the final visit, the efficacy index was 0.83, and the safety index was 1.16. CONCLUSIONS: Despite the short-term outcome indicated that femo-LASIK was effective for correction of post-keratoplasty ametropia during short-term period, a notable regression in its effect was observed in the long-term follow-up. Therefore, the predictability of this technique might decrease in the long-term.

Differences in anterior chamber depth in keratoconus patients with binocular very asymmetry ectasia.

BACKGROUND: To evaluate the difference in anterior chamber depth (ACD) between two eyes among keratoconus patients with binocular very asymmetric ectasia (VAE) and to explore the influencing factors. METHODS: The corneal curvature and ACD in both eyes of patients with VAE were measured by Sirius (version 3.2, CSO, Italy) at the following points: corneal vertex, maximum curvature (apex), and the 1.5 mm, 2.5 mm, and 3.5 mm superior-, inferior-, nasal-, temporal-paracentral from center. The mean pupil power (MPP) and corneal morphology parameters were also measured. Correlations between ACD and curvature and morphology parameters were analyzed by linear regression. RESULTS: 172 eyes of 86 patients (9 to 45 years) were classified into the VAE-N (n = 86) group and the VAE-E group (n = 86) based on the corneal morphology. The central (3.32 ± 0.27 mm versus 3.43 ± 0.29 mm, P < 0.001) and paracentral ACDs increased significantly in the VAE-E group, and the corneal morphology parameters were also significantly higher. The central ACD was significantly correlated with the MPP (r = 0.465), KVf/b (Keratoconus Vertex front/back) (r = 0.306, r = 0.327), and BCVf/b (Baiocchi Calossi Versaci front/back) (r = 0.356, r = 0.416). Linear regression showed good relationships between △ACD and △MPP (R2 = 0.429) and △KVf/b (R2 = 0.504, R2 = 0.536). CONCLUSIONS: The ACD was larger in the VAE-E group. The difference in ACD between the VAE-E and VAE-N groups was significantly correlated with corneal curvature and the extent of corneal elevation, indicating the influences of both the corneal magnification effect and corneal ectasia on ACD.

Mini review: human clinical studies of stem cell therapy in keratoconus.

Treatment of keratoconus is one of the most interesting research fields for researchers in the world. Regenerative medicine based on human stem cells in the treatment of keratoconus has recently received attention. Despite extensive laboratory and animal studies in regenerative medicine of cornea, there are limited clinical studies in keratoconus. These studies showed promising results of stem cell therapy. In initial studies, the transplantation of these cells into stroma was associated with increased vision and improved corneal parameters without side effects. In this article, we tried to review different aspects of keratoconus stem cell therapy, including cell extraction and culture, surgical procedure, effectiveness and safety of this method in human clinical studies.