High-Fluence Epithelium-off Accelerated Pulsed Corneal Cross-linking (15 mW/cm2; 7.2 J/cm2) for Pediatric Keratoconus: A 3-Year Retrospective Analysis.

PURPOSE: To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus. METHODS: This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm2, 15 mW/cm2, 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively. RESULTS: A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 µm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure. CONCLUSIONS: In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values. [J Refract Surg. 2024;40(3):e148-e155.].

Balanced activation of Nrf-2/ARE mediates the protective effect of sulforaphane on keratoconus in the cell mechanical microenvironment.

Keratoconus (KC) is a progressive degenerative disease that usually occurs bilaterally and is characterized by corneal thinning and apical protrusion of the cornea. Oxidative stress is an indicator of the accumulation of reactive oxygen species (ROS), and KC keratocytes exhibit increased ROS production compared with that of normal keratocytes. Therefore, oxidative stress in KC keratocytes may play a major role in the development and progression of KC. Here, we investigated the protective effect of sulforaphane (SF) antioxidants using a hydrogel-simulated model of the cell mechanical microenvironment of KC. The stiffness of the KC matrix microenvironment in vitro was 16.70 kPa and the stiffness of the normal matrix microenvironment was 34.88 kPa. Human keratocytes (HKs) were cultured for 24 h before observation or drug treatment with H2O2 in the presence or absence of SF. The levels of oxidative stress, nuclear factor E2-related factor 2 (Nrf-2) and antioxidant response element (ARE) were detected. The high-stress state of HKs in the mechanical microenvironment of KC cells compensates for the activation of the Nrf-2/ARE signaling pathway. H2O2 leads to increased oxidative stress and decreased levels of antioxidant proteins in KC. In summary, SF can reduce endogenous and exogenous oxidative stress and increase the antioxidant capacity of cells.

Outcomes of accelerated corneal cross-linking for pediatric and adult keratoconus: a comparative study.

PURPOSE: To compare the visual, refractive, and topographic outcomes of a high irradiance accelerated corneal crosslinking (ACXL) protocol after a 12-month follow-up between pediatric and adult patients with progressive keratoconus (KC). METHODS: Retrospective, comparative, cohort study. Patients with KC were divided into two groups: pediatric (≤ 18 years) and adult (> 18 years). All of them were managed with epi-OFF ACXL (30 mW/cm2, 8 min, pulsed 1:1 on and off = 7.2 J/cm2). Visual, refractive, and topographic values were measured preoperatively and at 1, 3, 6, and 12 months postoperative. KC progression, defined as a Kmax increase of ≥ 1D during follow-up, was recorded. RESULTS: Eighty-nine eyes (53 patients) were included for analysis; 45 (50.6%) eyes were from pediatric patients and 44 (49.4%) from adults. At one-year follow-up, pediatric patients experienced significantly higher rates of progression (22.2% vs. 4.5%, p = .014). Contrariwise, female gender (Beta = - 3.62, p = .018), a baseline uncorrected visual acuity of Snellen ≥ 20/60 (Beta = - 5.96, p = .007), and being ≥ 15 years at ACXL treatment (Beta = - 0.31, p = .021) were associated with non-progressive disease. A significant improvement in best-corrected visual acuity, Kmin, Km, and Kmax was recorded in both groups. Overall, 86.5% of eyes from both groups showed Kmax stabilization or improvement. CONCLUSIONS: Despite the similarity in visual, refractive, and topographic outcomes in both groups, younger age was associated with KC progression after ACXL at one year of follow-up.

The effect of transepithelial corneal collagen cross-linking treatment on optical quality of the cornea in keratoconus: 12-month clinical results.

PURPOSE: To evaluate the effect of transepithelial corneal collagen crosslinking (CXL) treatment on the optical performance of the cornea at 12-month follow-up after CXL in patients with progressive keratoconus. METHODS: One hundred and ten eyes of 67 patients were included. The following corneal optical aberrations over the 4-mm-diameter pupil were recorded via Sirius dual-scanning corneal tomography: total, anterior and posterior amount of corneal higher order aberrations [HOAs], vertical coma, horizontal coma, vertical trefoil, oblique trefoil, and spherical aberration, and Strehl ratio of point spread function (PSF). RESULTS: There were significant improvements in mean root mean square error values for corneal total HOA, total coma, anterior HOA, anterior coma, and vertical coma following CXL (P > 0.05, for all). No significant changes were found in the posterior aberometric parameters. PSF value did not change after CXL (P > 0.05). The corneal topographic measurements not revealed a change in the mean simulated keratometry-1, simulated keratometry-2, and maximum keratometry compared with the baseline measurements (P > 0.05, for all). At 12 months, there was a significant improvement in the uncorrected (UCVA) and best corrected (BCVA) visual acuity (P < 0.001, both). Most corneal aberrations correlated significantly with postoperative BCVA, but changes in HOAs were not statistically associated with improvements in visual acuity. CONCLUSIONS: Transepithelial CXL was effective in stabilizing the keratometric indices and improving the most corneal aberrations in keratoconic eyes 1 year after the procedure. While the healing effect on aberrations after CXL was in total and anterior parameters, no significant changes were observed in the posterior surface. In addition, it was observed that transepithelial CXL treatment did not cause a significant change in PSF distribution data.

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.

Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study.

OBJECTIVES: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus. METHODS: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted. CONCLUSIONS: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.

In Vivo Evaluation of Corneal Biomechanics Following Cross-Linking Surgeries Using Optical Coherence Elastography in a Rabbit Model of Keratoconus.

Purpose: Validation of the feasibility of novel acoustic radiation force optical coherence elastography (ARF-OCE) for the evaluation of biomechanical enhancement of the in vivo model of keratoconus by clinical cross-linking (CXL) surgery. Methods: Twelve in vivo rabbit corneas were randomly divided into two groups. Both groups were treated with collagenase type II, and a keratoconus model was obtained. Then, the two groups were treated with CXL procedures with different irradiation energy of 15 J and 30 J (CXL-15 J and CXL-30 J, respectively). An ARF-OCE probe with an ultrasmall ultrasound transducer was used to detect the biomechanical properties of cornea. An antisymmetric Lamb wave model was combined with the frequency dispersion relationship to achieve depth-resolved elastography. Results: Compared with the phase velocity of the Lamb wave in healthy corneas (approximately 3.96 ± 0.27 m/s), the phase velocity of the Lamb wave was lower in the keratoconus region (P < 0.05), with an average value of 3.12 ± 0.12 m/s. Moreover, the corneal stiffness increased after CXL treatment (P < 0.05), and the average phase velocity of the Lamb wave was 4.3 ± 0.19 m/s and 4.54 ± 0.13 m/s after CXL-15 J and CXL-30 J treatment. Conclusions: The Young's moduli of the keratoconus regions were significantly lower than the healthy corneas. Moreover, the Young's modulus of the keratoconus regions was significantly higher after CXL-30 J treatment than after CXL-15 J treatment. We demonstrated that the ARF-OCE technique has great potential in screening keratoconus and guiding clinical CXL treatment. Translational Relevance: This work accelerates the clinical translation of OCE systems using ultrasmall ultrasound transducers and is used to guide CXL procedures.

Accelerated Corneal Cross-linking in Pediatric Patients with Progressive Keratoconus: 12-Month Follow-up Results.

PURPOSE: To evaluate effectiveness and safety of accelerated corneal cross-linking (CXL) in the treatment of keratoconus in pediatric patients. SETTING: Tertiary care hospital. DESIGN: Retrospective observational study. METHODS: In this study, case series of patients 18 years old or younger with progressive keratoconus who underwent accelerated CXL were observed. All consecutive patients underwent accelerated CXL with setting of 9 mW/cm2 for 10-minute Ultraviolet-A radiation, corresponding to a total dose of 5.4 J/cm2. Preoperative and 12-month postoperative data including uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), keratometry (K) measurements, mean spherical, and cylindrical refraction were evaluated. RESULTS: The group consisted of 28 eyes from 14 patients (10 males and 4 females). Mean age of the patients was 16.9 years (11-18 years). UDVA did not change significantly from 0.71 ± 0.54 to 0.65 ± 0.43 logMAR (P = 0.41). BDVA improved significantly from 0.30 ± 0.35 to 0.21 ± 0.34 (P = 0.006). The steep K-value decreased from 48.4 ± 4.3 to 48.0 ± 4.6 diopters, but there was no significant change in steep K-value (P = 0.35). There was no significant change in flat and mean K-value (P > 0.05). Mean spherical and cylindrical refraction were not significantly altered (P > 0.05). One patient with vernal keratoconjunctivitis showed sterile peripheral corneal infiltrates. Patient was treated with topical corticosteroids, antibiotics, and artificial tears. CONCLUSION: The findings revealed that accelerated CXL is an effective and safe procedure that halts the progression of keratoconus in pediatric patients.

Outcomes after corneal crosslinking treatment in paediatric patients with keratoconus.

PURPOSE: This study aims to determine the efficacy and safety of accelerated corneal crosslinking in children with keratoconus. METHODS: The study enrolled 64 patients aged 16 years or younger, each contributing one eye for a total of 64 eyes for analysis. Participants underwent an accelerated form of corneal cross-linking with 15 min of ultraviolet A irradiation at a rate of 7 mW/cm2, resulting in a cumulative energy dose of 5.4 J/cm2. The primary outcome measures were best corrected visual acuity (BCVA) and corneal tomography at 6 and 12 months post-intervention. Parameters assessed included BCVA, spherical and cylindrical refraction, keratometry (K1 and K2), maximum keratometry (Kmax) and thinnest corneal thickness (TCT). These metrics were documented preoperatively and then again at 6 and 12 months postoperatively. In addition, any ocular or systemic conditions related to keratoconus were recorded for each participant. RESULTS: The results showed an improvement in BCVA at 12 months after surgery. K1 showed a decrease at both post-operative follow-ups while K2 remained constant throughout the observation period. Kmax showed a notable decrease at the 12 month postoperative follow-up. Although the TCT showed an initial decrease, it reached a stable state after 12 months of crosslinking. Refractive values remained stable at all subsequent examinations. Notably, no complications such as corneal opacity, non-healing epithelial defects or corneal infections occurred during the follow-up period. The most common ocular comorbidity was allergic conjunctivitis (34.4%). CONCLUSION: The findings suggest that accelerated corneal crosslinking treatment is effective in slowing or halting the progression of keratoconus. Furthermore, there were no persistent overt complications observed at 12 months after the procedure.

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.

A comparison of conventional and accelerated corneal crosslinking: corneal epithelial remodeling and in vivo confocal microscopy analysis.

PURPOSE: To evaluate the effect of conventional and accelerated corneal crosslinking (CXL) on visual acuity, corneal topography, corneal epithelial thickness, and subbasal nerve morphology in progressive keratoconus patients. METHODS: In this prospective and randomized study, twenty eyes of 20 patients were treated with conventional CXL (3 mW/cm2, 30 min, C-CXL) and 19 eyes of 19 patients were treated with accelerated CXL (9 mW/cm2, 10 min, A-CXL). The spherical equivalent, uncorrected visual acuity, best-corrected visual acuity, keratometric measurements, demarcation line measurement and epithelial thickness mapping analyses, and subbasal nerve morphology with in vivo confocal microscopy (IVCCM) were evaluated at baseline and at postoperative months 1, 3 and 6. RESULTS: At postoperative 6 months, a significant improvement was observed in all keratometric values in both treatment groups (p < 0.05). All epithelial thickness indices, except central, temporal, and inferotemporal thickness, were reduced at 1 month postoperatively in both treatment groups. The epithelial map uniformity indices (standard deviation and difference between min-max thickness) were significantly lower than the baseline values at all time points after CXL in both treatment groups (p < 0.001). Compared with the preoperative values, there was a significant decrease in all IVCCM parameters at 1 month postoperatively (p < 0.05). At 6 months postoperatively, corneal nerve fiber density and corneal nerve branch density recovered to preoperative values in the A-CXL group, whereas corneal nerve regeneration was not complete in the C-CXL group. CONCLUSION: Both conventional and accelerated CXL treatments appear to be effective in halting the progression of KC. Corneal epithelial irregularity slightly improves after CXL. The regeneration of subbasal nerves is faster after A-CXL treatment.

Oxygen-supplemented and topography-guided epithelium-on corneal crosslinking with pulsed irradiation for progressive keratoconus.

PURPOSE: To investigate the effects of customized topography-guided epithelium-on crosslinking (epi-on CXL) with oxygen supplementation on procedural efficacy and corrected distance visual acuity (CDVA) in patients with progressive keratoconus (KC) at 1 year. SETTING: Private eye clinic, Brisbane, Australia. DESIGN: Retrospective, single-center, nonrandomized case series. METHODS: Topography-guided epi-on CXL using the Mosaic system was performed on patients with progressive KC. Oxygen goggles; transepithelial riboflavin; and pulsed, high UV-A irradiance (1 second on, 1 second off; 30 mW/cm2) were applied to enhance oxygen kinetics and bioavailabilities of riboflavin and UV-A. Guided by baseline topography, a higher UV-A dose (15 J/cm2) was applied to the area of steepest anterior curvature with decreasing fluence (as low as 7.2 J/cm2) toward the outer 9 mm. Postoperative CDVA and maximum keratometry (Kmax) were evaluated. RESULTS: 102 eyes (80 patients) were followed for 11.5 ± 4.8 months. At the latest follow-up, mean CDVA (logMAR), mean K, and Kmax (diopters [D]) improved from 0.18 ± 0.28, 46.2 ± 3.8, and 53.0 ± 5.67 at baseline to 0.07 ± 0.18, 45.8 ± 3.7, and 51.9 ± 5.56, respectively (P < .001). 3 eyes (3%) lost more than 1 CDVA line, and another 3 eyes (3%) had increased Kmax greater than 2 D. 43 eyes were followed for at least 12 months (n = 43): mean CDVA, mean K, and Kmax improved from 0.19 ± 0.33 logMAR, 46.5 ± 3.5 D, and 53.6 ± 5.67 D to 0.07 ± 0.17 logMAR, 46.0 ± 3.5 D, and 52.33 ± 5.49 D, respectively (P ≤ .002). No complications were observed. CONCLUSIONS: Tailoring oxygen-supplemented epi-on CXL with differential UV-A energy distributions, guided by baseline topography, in patients with KC seems to be safe and effective. At 1 year, study reports sustained improved CDVA and corneal stabilization.

Comparison of refractive surgeries (SMILE, LASIK, and PRK) with and without corneal crosslinking: systematic review and meta-analysis.

Corneal crosslinking (CXL) is used for treating keratoconus and post-laser in situ keratomileusis ectasia. However, refractive surgery is not usually performed with prophylactic CXL. Therefore, we performed a meta-analysis comparing outcomes of refractive surgeries with vs without prophylactic CXL. We systematically searched databases for studies comparing refractive surgeries for myopic correction with vs without prophylactic corneal crosslinking. Review Manager 5.4.1 was used to perform statistical analysis. We included 2820 eyes from 28 studies. Compared with refractive surgery alone, surgery with prophylactic CXL resulted in decreased central corneal thickness, corrected distance visual acuity logMAR, and safety and efficacy indices. There were no significant differences in postoperative uncorrected distance visual acuity of 20/20 or better at ≥12 months and other visual outcomes among both groups. More randomized controlled trials with standard crosslinking protocols are needed to analyze the prophylactic use of crosslinking with refractive surgeries.

Analysis of Cytokine and Chemokine Level in Tear Film in Keratoconus Patients before and after Corneal Cross-Linking (CXL) Treatment.

Keratoconus (KC) is a degenerative corneal disorder whose aetiology remains unknown. The aim of our study was to analyse the expressions of cytokines and chemokines in KC patients before and after specified time intervals after corneal cross-linking (CXL) treatment to better understand the molecular mechanisms occurring before and after CXL in KC patients process of corneal regeneration.; Tear samples were gathered from 52 participants immediately after the CXL procedure and during the 12-month follow-up period. All patients underwent a detailed ophthalmological examination and tear samples were collected before and after CXL at regular intervals: 1 day before and after the surgery, at the day 7 visit, and at 1, 3, 6, 9, and 12 months after CXL. The control group consisted of 20 healthy people. 10 patients were women (50%) and 10 were men (50%). The mean age was 30 ± 3 years of age. Tear analysis was performed using the Bio-Plex 3D Suspension Array System. Corneal topography parameters measured by Scheimpflug Camera included: keratometry values (Ks, Kf), PI-Apex, PI-Thinnest, Cylinder.; All the 12 months post-op values of the KC patients' topographic measurements were significantly lower than the pre-op. As for the tear cytokine levels comparison between the patient and control groups, cytokine levels of TNF-α, IL-6, and CXCL-10, among others, were detected in lower amounts in the KC group. The pre-op level of IL-6 exhibited a significant increase the day after CXL, whereas comparing the day after the procedure to 12 months after CXL, this showed a significant decrease. Both TNF-α and IL-1 showed a significant decrease compared to the day before and after CXL. We observed significantly higher levels of IL-1ß, IL-10, IFN-γ and TNF-α in moderate and severe keratoconus than in mild keratoconus (p < 0.05). We also demonstrated a statistically significant positive correlation between both pre-op and 12 months after CXL TNF-α, IFN-γ, IL-6 and Ks and Kf values (p < 0.05, r > 0); Alterations of inflammatory mediators in tear fluid after CXL link with topographic changes and may contribute to the development and progression of KC.

Collagen cross-linking beyond corneal ectasia: A comprehensive review.

The history of corneal cross-linking (CXL) dates back to 2003 when some German scientists investigated possible treatments to harden the corneal structure to increase its resistance in ectatic corneal diseases. Nowadays, CXL is considered the most effective therapy in ectatic corneal diseases due to its proven efficacy in hardening the cornea, thus halting the development of the disease. Since 2003, CXL applications have dramatically expanded and have been implemented in several other areas such as infectious keratitis, corneal edema, and before performing keratoplasty for various purposes. Moreover, several irradiation patterns are being studied to correct refractive errors, taking into account the corneal refractive changes that occur after the procedure. Currently, scleral cross-linking is also being investigated as a potential therapy in cases of progressive myopia and glaucoma. In this article, we provide a comprehensive overview of the available applications of cross-linking in nonectatic ocular conditions and highlight the possible future indications of this procedure.

Clinical, Anatomical, and Densitometric Changes following Dresden vs. Accelerated Corneal Cross-Linking in Progressive Keratoconus.

BACKGROUND: To compare clinical, anatomical, and densitometric changes following Dresden (DCXL) vs. accelerated (ACXL) corneal UVA cross-linking (CXL; Avedro KXL, Geuder, Heidelberg, Germany) in progressive keratoconus (KC). METHODS AND MATERIAL: In this retrospective study, we analyzed 20 patients following DCXL (3 mW/cm², 30 min, 5.4 J/cm²) and 44 patients following ACXL (9 mW/cm², 10 min, 5.4 J/cm²) between January 2016 and February 2020. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), steepest keratometry (Kmax), keratoconus index (KI), thinnest pachymetry (Pthin), and corneal densitometry (CD) were measured before and 3, 6, 12, and 24 months after CXL. RESULTS: During the follow-up period, no changes in UCVA, BSCVA, Kmax, KI, or Pthin occurred. CCT significantly decreased 3 months after DCXL (p = 0.032) and ACXL (p = 0.006). At the 12- and 24-month follow-up, CCT remained decreased in the DCXL (p = 0.035, 0.036, respectively) but not in the ACXL group. At the 12-month follow-up, the reduction in CCT was significantly greater in DCXL compared to ACXL (p = 0.012). At the 3-, 6-, 12-, and 24-month follow-ups, we found a significant increase in the anterior stroma CD following DCXL (p = 0.019, 0.026, 0.049, 0.047, respectively) but not ACXL. The CD changes were localized in the central concentric zones (0.0 to 6.0 mm). No intra- or postoperative complications occurred. CONCLUSION: ACXL and DCXL effectively halted KC progression. ACXL proved to be a safe time-saving alternative to conventional DCXL. DCXL led to a reduction in CCT and an increment in the CD of the central anterior stroma during 24 months of follow-up.

Comparison of two different 360-degree intrastromal corneal rings combined with simultaneous accelerated-corneal cross-linking.

PURPOSE: to compare five-year outcomes of two complete intracorneal implants (MyoRing versus annular-shaped intracorneal implant [AICI]) combined with accelerated corneal cross-linking (A-CXL) in progressive KCN. METHODS: In this historical cohort study, preoperative and postoperative visual, refractive, tomographic, biomechanical, and aberrometric parameters of 27 eyes of 27 patients who underwent implantation of two complete rings (13 AICI and 14 MyoRing) combined with A-CXL were recorded. RESULTS: The mean age of patients in "AICI plus A-CXL" and "MyoRing plus A-CXL" groups were 28.1 ± 4.6 and 26.3 ± 3.8 years, respectively. All pre- and postoperative visual and refractive parameters between the two groups were not significantly different (p > 0.05). Comparing pre- and postoperative tomographic measurements showed that anterior corneal surface (ACS) flat-K and corneal thickness at pachymetric apex significantly improved for MyoRing plus A-CXL group after five years (p < 0.05). On the other hand, ACS K-max and mean-K values were significantly improved for AICI plus A-CXL group after five years (p < 0.05). Both groups revealed significant improvements in ACS steep-K and corneal astigmatism (p < 0.05). Five years after surgery, the high order aberration in the AICI group (2.60 ± 0.83) was significantly better than the MyoRing group (1.70 ± 0.43) (p = 0.007). CONCLUSIONS: Both complete intrastromal rings (MyoRing or AICI) combined with A-CXL significantly Improved visual, refractive, and corneal aberrometric, biomechanical, and tomographic parameters and halt the progression of KCN with comparable long-term outcomes.

Analysis of the outcomes of three different cross-linking protocols for treatment of paediatric keratoconus: A multicentre randomized controlled trial.

PURPOSE: To analyse long-term outcomes of standard cross-linking (SCXL), accelerated cross-linking (ACXL) and transepithelial cross-linking (TCXL) in the treatment of progressive paediatric keratoconus regarding stability, safety and efficacy. METHODS: This prospective multicentre randomized controlled trial included 97 eyes of 97 paediatric patients with stages I-III ABCD keratoconus grading system, who were randomized into three groups; SCXL group (control group, n = 32; 3 mW/cm2 × 30 min/5.4 J/cm2 ), ACXL (n = 33; 18 mW/cm2 × 5 min/5.4 J/cm2 ) and TCXL (n = 32; 18 mW/cm2 × 5 min/5.4 J/cm2 ). Subjective refraction, uncorrected and corrected visual acuity, keratometry and pachymetry measurements using corneal topography were recorded preoperatively and 1, 2 and 3 years postoperatively. RESULTS: SCXL group exhibited significant successive improvements in the mean visual, refractive and keratometric parameters throughout the entire postoperative 3 years while ACXL group exhibited significant improvements in visual and keratometric parameters in the first postoperative year that remained stable in second and third postoperative years. TCXL group exhibited significant progressive deterioration in all mean parameters compared to SCXL and ACXL (p < 0.0001). Both SCXL and ACXL revealed final 100% success rate with good stability while TCXL revealed final 22% failure rate with keratoconus progression (p < 0.0001). CONCLUSION: SCXL and ACXL were comparable in halting keratoconus progression and achieved good stability and safety; however, SCXL was more efficient than ACXL as it yielded greater significant postoperative mean visual, refractive and keratometric improvements achieving smoother corneal remodelling. Both SCXL and ACXL were much superior to TCXL. SCXL is the best CXL treatment option for paediatric keratoconus while ACXL is a good and effective alternative.

Clinical Results of Accelerated Iontophoresis-Assisted Epithelium-on Corneal Cross-linking for Progressive Keratoconus in Children.

PURPOSE: To evaluate the clinical characteristics of pediatric patients with progression of keratoconus after accelerated iontophoresis-assisted epithelium-on corneal cross-linking (I-ON CXL) and to assess the efficacy and safety of re-treatment using accelerated epithelium-off CXL (epi-OFF CXL). METHODS: Sixteen eyes of 16 patients (mean age: 14.6 ± 2.5 years) with keratoconus underwent I-ON CXL. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, maximum keratometry index (Kmax), minimum corneal thickness, elevation front and elevation back measured at the thinnest point, total higher order aberrations root main square (HOA RMS), coma RMS, and spherical aberration. An increment of Kmax greater than 1.00 diopter (D) and a decrease of greater than 20 µm in pachymetry were considered to determine the progression of keratoconus. Patients with progression of keratoconus after I-ON CXL were re-treated using an epi-OFF CXL protocol. RESULTS: Two years after I-ON CXL, 12 patients showed progression of keratoconus, whereas 4 patients were stable. There was significant worsening of Kmax (P = .04) and steepest keratometric reading (P = .01). Furthermore, a significant correlation was documented between progression of keratoconus and age (P = .02). These patients were re-treated using an epi-OFF protocol and after 2 years all patients were stable, and a statistically significant reduction of the mean Kmax (P = .007), HOA RMS (P = .05), and coma RMS (P = 05) was observed. CONCLUSIONS: I-ON CXL was ineffective in the treatment of pediatric keratoconus in younger children, whereas it had an efficacy of 2 years in older children. Re-treatment using epi-OFF CXL proved effective to halt progression of keratoconus after I-ON CXL failure. [J Pediatr Ophthalmol Strabismus. 2024;61(1):44-50.].