Collagen Cross-linking Treatment Research Articles

Implantation of phakic intraocular lenses in patients with stabilized keratoconus

To date, extensive experience has been accumulated in the correction of high myopia and myopic astigmatism through the implantation of additional negative lenses (phakic intraocular lenses). However, the use of this method in patients with anatomically altered corneas due to keratoconus remains unresolved.Purpose: to assess the effectiveness and safety of correcting high myopia combined with myopic astigmatism by implanting phakic intraocular lenses in patients with stabilized keratoconus at stages 1–2.Materials and methods. The study encompassed results from 27 surgeries involving the implantation of phakic intraocular lenses in patients with high myopia and myopic astigmatism (12.63 ± 4.25 D). These patients had thin corneas and were diagnosed with stage 1–2 keratoconus after undergoing corneal collagen crosslinking treatment – this constituted the main group. The control group comprised 35 surgeries performed on patients with subclinical non-progressive keratoconus (Forme Fruste). All participants underwent evaluations for visual acuity dynamics and refractive stability of spherical and cylindrical components before surgery, immediately post-surgery, and then at 1, 6, and 12 months after implantation. Additional assessments included intraocular pressure measurements, gonioscopy, ultrasonic echobiometry, ultrasonic ophthalmoscopy, biomicroscopy, ophthalmoscopy, endothelial microscopy, vision character and stereopsis determination, ultrasound biomicroscopy, anterior segment optical coherence tomography, electrophysiological studies, and statistical analysis. An IPCL (a type of phakic intraocular lenses made from hydrophilic acrylic) was implanted, capable of correcting myopia up to 30 D and astigmatism up to 10 D.Results. All patients achieved high uncorrected visual acuity 0.86 ± 0.11. Astigmatism correction was successful in 96% of cases. The average postoperative vault – the distance from the back surface of the phakic intraocular lenses to the anterior lens capsule – was 527.5 ± 40.27 μm (range 460–600 μm), and the intraocular pressure was 11.7 ± 2.08 mm Hg. There was a minor decrease in corneal endothelial cell count from 2599 ± 157.3 to 2375 ± 125.3 cells/mm² in the first group and from 2614 ± 104.8 to 2375 ± 43.3 cells/mm² in the second group respectively (p > 0.05), which falls within the acceptable loss range of 4–7% from preoperative values for both groups. Throughout the observation period, there were no cases of cataract development, pigmentary glaucoma, pupillary block, or other vision-threatening complications.Conclusions. Implantation of phakic intraocular lenses in patients with early-stage stabilized keratoconus and subclinical non-progressive keratoconus provides an effective and practically safe means of correcting high myopia and astigmatism.

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

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

Exogenous Collagen Crosslinking is Highly Detrimental to Articular Cartilage Lubrication.

Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear. Here, we examined how the collagen crosslinking agents genipin (GP) and glutaraldehyde (GTA) impact cartilage lubrication using the convergent stationary contact area (cSCA) configuration. Unlike classical configurations, the cSCA sustains biofidelic kinetic friction coefficients (μk) via superposition of interstitial and hydrodynamic pressurization (i.e., tribological rehydration). As expected, glutaraldehyde- and genipin-mediated CXL increased cartilage's tensile and compressive moduli. Although net tribological rehydration was retained after CXL, GP or GTA treatment drastically elevated μk. Both healthy and "OA-like" cartilage (generated via enzymatic digestion) sustained remarkably low μk in saline- (≤0.02) and synovial fluid-lubricated contacts (≤0.006). After CXL, μk increased up to 30-fold, reaching values associated with marked chondrocyte death in vitro. These results demonstrate that mechanical properties (i.e., stiffness) are necessary, but not sufficient, metrics of cartilage function. Furthermore, the marked impairment in lubrication suggests that CXL-mediated stiffening is ill-suited to cartilage preservation or joint resurfacing.

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

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. 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). 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 12months, 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. Transepithelial CXL was effective in stabilizing the keratometric indices and improving the most corneal aberrations in keratoconic eyes 1year 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.

Outcomes of Corneal Topographical Kmax readings 3 months after Corneal Cross Linkage in Keratoconus patients.

Background and objectiveCollagen protein, which is abundant in the cornea and has a triple helix form, may be found in almost every tissue matrix in the body. Natural cross connections between monomers provide the robustness of the helical protein structure. Wollensak and his colleagues developed the Dresden Protocol, a keratoconus treatment based on Corneal Cross-Linkage. We aimed to analyse and present the findings in individuals with progressive keratoconus using topographic and refractive results after corneal collagen crosslinking treatment (CXL) (KC) after 3 months.MethodsThe study comprises a total of 100 patients who were diagnosed with progressive KC and who underwent CXL between 2021 and 2022 at KRL Hospital Islamabad, Pakistan. All eyes in this study had a preoperative topography within 1 month before CXL treatment and the follow-ups were conducted at 3 months interval.ResultsIn our investigation, 100 patients were added. The average age was 24.74 years. 77% of the patients were between the ages of 12 and 25 years, while 23% were between the ages of 26 and 50 years. In our survey, males made up 84% of the population, while females made up only 16%. The right eye was afflicted in 60% of cases, whereas the left eye was impacted in 40% of the population. Grade 2 Keratoconus affected 42% of patients, whereas Grade 1 Keratoconus affected 18%. Our findings were skewed toward men and the 12–25 age group, however in our recent study, we discovered considerable KC stability 3 months after CXL.ConclusionKeratometric readings and visual acuity were stabilised or improved with CXL treatment. Keratoconus stability can be reached 3 months following the treatment, according to our findings.

Çocuk ve erişkin Keratokonus hastalarında hızlandırılmış çapraz bağlama tedavisi sonrası Scheimpflug Kornea Dansitometri analizi

Amaç: On sekiz yaş altı ve 18 yaş üstünde keratokonus nedeniyle çapraz bağlama tedavisi (ÇB) uygulanan hastalardaki korneal dansitometri değişimlerini karşılaştırmalı olarak değerlendirmektir. Yöntem: Keratokonus tanısıyla ÇB uygulanan 55 hastanın 74 gözü çalışmaya alındı. 18 yaş ve altındaki hastalar grup 1’e dahil edilirken, 18 yaş üstündeki hastalar grup 2’ye dahil edildi. Hastaların ÇB öncesinde ve sonrasında Pentacam Scheimpflug görüntüleme sistemi ile kornea kalınlığı ve korneal dansitometri değerleri ölçülerek kaydedildi. Çapraz bağlama sonrası tüm hastaların kornea kalınlıkları ultrasonik pakimetri ile de ölçüldü ve Scheimpflug sistem ölçümleri ile karşılaştırma yapıldı. Bulgular: Grup 1’de ÇB öncesindeki korneal dansitometri değeri 19.84±2.67 GSU iken, işlem sonrası 21.54±3.32 GSU idi ve aradaki fark istatistiksel olarak anlamlıydı (p=0.048). Benzer şekilde Grup 2’deki dansitometri değeri ÇB öncesinde 18.74±1.56 GSU iken, işlem sonrasında 24.53±10.46 GSU idi ve aradaki fark anlamlıydı (p&amp;lt;0.0001). Grup 1’de Scheimpflug görüntüleme sistemi ile ÇB öncesi ölçülen kornea kalınlığı 473.04±24.23 µ iken, grup 2’de 467.89±29.09 µ idi. Her iki grupta ÇB sonrası kornea kalınlıkları sırasıyla 461.88±27.64 µ ve 446.42±32.76 µ idi ve aradaki fark iki grupta da istatistiksel olarak anlamlıydı (sırasıyla p=0.003, p&amp;lt;0.0001). Sonuç: Keratokonus hastalarında, ÇB sonrasında, çocuk ve erişkinlerde korneal bulanıklık oluşmaktadır. Erişkinlerde çocuklara göre daha fazla bulanıklık olmaktadır. Bulanıklığın takibinde korneal dansitometri objektif veriler sunar. Bulanıklık olan kornealarda kalınlık takibi için ultrasonik pakimetri, Scheimpflug kameraya göre daha doğru ölçümler sunabilir.

Comparison of Accelerated and Standard Corneal Collagen Cross-Linking Treatments in Experimental Fungal Keratitis for Aspergillus fumigatus.

Introduction To compare accelerated and standard corneal collagen cross-linking (CXL) treatments in experimental Aspergillus keratitis models. Methods Twenty-six New Zealand rabbits were divided into two groups: a 1% voriconazole combined with standard CXL group, and a 1% voriconazole combined with accelerated CXL group. The ulcer area, corneal opacity, and corneal neovascularization score were measured via slit-lamp imaging, and the corneal and corneal epithelial thickness and ulcer depth were measured via anterior segment optical coherence tomography (AS-OCT). The duration of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling (day 0) and at 1, 4, 7, 14, 21, and 28 days after the intervention. Results The area and depth of the ulcer decreased in both groups after CXL (all P < 0.05). Interestingly, the ulcer area in the accelerated CXL group still tended to increase on the first day after CXL although the difference was not statistically significant (P=0.6649). On the 21st and 28th days after CXL, the ulcer area and depth of the standard CXL group were larger and deeper than those of the accelerated CXL group (all P < 0.05). The ulcer healing time in the accelerated CXL group was 18.67 ± 6.21 days, while that in the standard CXL group was 23.55 ± 4.72 days, and the difference was statistically significant (P=0.0475). Conclusions Both accelerated and standard CXL can significantly inhibit the progression of Aspergillus keratitis corneal ulcers and promote ulcer healing. The accelerated CXL was superior to the standard CXL, which could control infection faster and promote ulcer healing. However, it is important to note that there may be a risk of early deterioration of the ulcer with accelerated CXL.

Comparison of Corneal Collagen Cross-Linking and Voriconazole Treatments in Experimental Fungal Keratitis for Aspergillus fumigatus.

AimsTo compare the antifungal efficacy of corneal cross-linking (CXL) and voriconazole in experimental Aspergillus keratitis models.MethodsThirty-nine New Zealand rabbits were divided into three groups: a control group, a voriconazole group (M group), and a voriconazole combined with CXL group (CXL-M group). The ulcer area was measured via slit lamp imaging, the corneal and corneal epithelial thickness, and ulcer depth was measured via anterior segment optical coherence tomography (AS-OCT). The existence time of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling and at 1, 4, 7, 14, 21, and 28 days after intervention.ResultsIn the CXL-M group, ulcer area and depth decreased continuously from Day 4 to Day 28 after CXL (all P < 0.05). In the CXL-M group, ulcer area and depth were smaller than those in the other two groups from Day 4 to Day 21 after CXL (all P < 0.05, except ulcer area in the CXL-M vs. M group on Day 21). The duration of hyphae in the CXL-M group was significantly shorter than in the other two groups (P = 0.025). On Day 28, in CXL-M group, corneal thickness was thicker than baseline (P < 0.05). Meanwhile, in CXL-M group, corneal and corneal epithelial thickness were significantly thinner than in the other two groups (P < 0.001). The CXL-M group had no complications, such as corneal perforation, at the end of the study.ConclusionsVoriconazole combined with CXL is effective in treating Aspergillus-infected keratitis. Combined therapy could effectively inhibit Aspergillus, accelerate corneal repair, and shorten the course of the disease.

Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits.

The aim of this study was to compare the efficacy of Photo-Activated Chromophore for Keratitis - Corneal Collagen Cross-linking (PACK-CXL) of three different total UVA fluence levels and topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits. This is an interventional experimental study including both eyes of 16 rabbits (32 eyes). Fungal keratitis was induced by intrastromal injection of Fusarium Solani into the cornea. The rabbits were then divided into four groups (8 eyes for each) from which group A received Voriconazole eye drops and considered as control group. Group B, C, D received single PACK-CXL session with total fluence levels of 7.2, 10.0 and 15.0 J/cm2 for each respectively. Daily clinical examination was recorded and all corneas were removed for microbiology and histopathology on day ten. The mean clinical signs score eyes treated with high fluence PACK-CXL showed evident clinical improvement from fourth to tenth day of treatment. This improvement was equivalent to that of Voriconazole treatment. The results showed better improvement with increasing the UVA total fluence levels but this difference was not statistically significant (P < 0.05). Similarly, the median CFU/ml declined on increasing UVA fluence but with no statistically significant values. Histopathological examination revealed better improvement of inflammatory signs on higher fluence levels compared to lower ones. High intensity PACK-CXL (30 mW/cm2) was as effective as Voriconazole in the treatment of fungal keratitis in rabbits. Increasing the fluence of UVA was associated with slightly better clinical outcomes with no added risks. More clinical studies are needed to confirm these results.

The histopathological findings in excised upper eyelids of patients with dermatochalasis following collagen cross-linking treatment.

To evaluate the histopathological effects of collagen cross-linking (CCL) on excised skin samples of patients undergoing upper eyelid blepharoplasty due to dermatochalasis. This study examined 74 excised eyelid skin samples from 37 dermatochalasis patients. Following an upper eyelid blepharoplasty, CCL with hypotonic riboflavin (0.1%) was applied. Both treated (right eyelid, CCL group) and untreated eyelid specimen (left eyelid, non-CCL group) sections were stained with hematoxylin-eosin and Masson's trichrome. The sections were evaluated for the following parameters: the collagen status (parallel, oblique, and perpendicular), the distance between collagen fibers, the diameter of collagen fibers, and the length of collagen fibers. There were no statistically significant differences in the collagen status, the distance between collagen fibers, the diameter of collagen fibers, and the length of collagen fibers between the CCL and non-CCL groups (p > 0.05 for all). Although the lack of statistically significant differences, the structure of the treated eyelid collagen fibers was more parallel in 48% of the participants than in the untreated ones. For male patients, a statistically significant shorter distance between collagen fibers was observed in the CCL group (8.05 ± 2.04µm) compared to the non-CCL group (9.97 ± 2.33µm) (p = 0.042). In this study, more parallel collagen structures and tightly packed collagen fibers were detected in eyelid samples following CCL treatment. The authors note that the results of this study may be promising for further research, so the effect of CCL therapy on the eyelid may be an interesting subject for the treatment of non-severe or surgically inadequately corrected dermatochalasis.

Analysis of Tear Function Outcomes following Collagen Cross-Linking Treatment in Ectatic Corneas

Purpose To analyze tear function outcomes following collagen cross-linking (CXL) treatment in ectatic corneas. Methods Fifty-seven eyes of 34 patients were included, and patients with keratoconus who underwent epithelium-on (epi-on) or epithelium-off (epi-off) CXL were evaluated. The following tests were performed preoperatively and at 1, 3, 6, and 12 months postoperatively: best-corrected visual acuity (BCVA), maximum keratometry value (Kmax), ocular surface disease index (OSDI) questionnaire, slit-lamp examination, tear meniscus height, first noninvasive Keratograph breakup time (1st NIKBUT), average NIKBUT, and bulbar redness. Results BCVA improved in both epi-on and epi-off groups at most follow-up points, but was not significantly different between groups. At 12-month follow-up, Kmax in the epi-on and epi-off groups improved after CXL, but there was no significant difference between the groups. The OSDI in both groups decreased after operation compared with before surgery, and there was no significant difference between the two groups. Comparing the two groups, only the change in the tear meniscus height at 6 months postoperatively was statistically significant, and the pre- and postoperative values of the two groups were within the normal range (>0.20 mm). The change was small and had no clinical significance. There was no change in the 1st NIKBUT and average NIKBUT between the epi-on and epi-off groups. A change in bulbar redness was significantly better in the epi-off group than in the epi-on group at 3 months postoperatively. Comparing the effects at 1 year postoperatively, both groups had positive results in OSDI, NIKBUT, tear meniscus height, and bulbar redness. Conclusion Both epi-on and epi-off CXL can control the progression of keratoconus, although epi-off CXL is more effective. Both methods have a positive effect on dry eye, which can improve the condition of the tear film and reduce dry eye symptoms in patients with keratoconus.

Scheimpflug imaging of the anterior segment following simultaneous cross-linking with topography-guided custom ablation treatment for keratoconus.

To report alterations in the anterior segment following accelerated corneal collagen cross-linking and topo-guided customized ablation treatment with the Nidek vision excimer laser system (Nidek Co., Ltd., Gamagori, Japan) in a single procedure. We reviewed the medical records of patients who underwent cross-linking for progressive keratoconus. We divided patients into four groups based on the treatment protocol. Eyes were evaluated regarding uncorrected distance visual acuity, corrected distance visual acuity, keratometry (maximum [Kmax], equivalent keratometry readings, Ksteep and Kflat parameters), corneal elevations (anterior and posterior), the anterior radius of curvature, the posterior radius of curvature, anterior chamber volume, anterior chamber depth, anterior chamber angle and the pachymeter of the thinnest locale of the cornea before the surgery and at 1, 3, 6, and 12 months after the procedure. We included 259 eyes of 227 patients with progressive keratoconus who underwent treatment. The mean respective baseline uncorrected distance visual acuity and corrected distance visual acuity were: 0.68 ± 0.45 and 0.34 ± 0.40 in Group 1; 0.82 ± 0.44 and 0.33 ± 0.23 in Group 2; 0.61 ± 0.36 and 0.21 ± 0.17 in Group 3; and 0.65 ± 0.38 and 0.23 ± 0.18 in Group 4; logMAR did not show significant difference among the groups (p=0.14 and p=0.06, respectively). Visual improvements were better in the combined surgery groups. Mean Kmax in Groups 1, 2, 3, and 4 were 57.24 ± 7.51, 59.26 ± 6.94, 53.73 ± 4.60, and 54.31 ± 4.25 diopter (D), respectively. Group 1 demonstrated increased Kmax for 6 months. Maximum flattening by 3.38 ± 2.35 D 1 year after surgery was observed in Group 4 (p<0.05). Decreased anterior chamber angle, anterior chamber depth, and anterior chamber volume were similar, indicating the stability of the anterior chamber. Visual and anatomical improvement is better, with improved stability of the anterior segment, in combined surgery groups compared with cross-linking alone.

Evaluation of unilateral corneal collagen cross-linking on fellow untreated eyes of patients with keratoconus.

This study aimed to examine the effects of unilateral corneal collagen cross-linking treatment on visual acuity and the topographic findings of the fellow untreated eye of patients who had bilateral progressive keratoconus. Patients with progressive keratoconus who underwent cross-linking treatment were screened retrospectively. A total of 188 untreated eyes of 188 patients whose eyes were treated unilaterally with either standard or accelerated cross-linking and refused cross-linking procedure for the fellow eye were included. Visual acuity and topographic findings of the fellow untreated eyes were obtained preoperatively and postoperatively at the 1st, 3rd, 6th, 12th, 24th, 30th, and 36th months. The change over time of variables examined was similar in the untreated eyes of patients who received standard and accelerated cross-linking methods (p>0.05). At the 12th month, 136 (95.8%) untreated eyes were stable according to progression criteria. Only 4 (8%) eyes were progressive at the 24th month. No progression was observed in any of the 16 patients with a 36-month follow up. The results showed that the fellow untreated eyes of patients with bilateral progressive keratoconus did not have significant progression rates after unilateral cross-linking treatment.

Fourier analysis of corneal Scheimpflug imaging: clinical use in keratoconus.

To evaluate the clinical use of Fourier analysis of videokeratography data in the diagnosis and follow-up of keratoconus (KC). We conducted a chart review of consecutive patients presented to our cornea clinic. A team of two experienced cornea specialists divided the patients into three groups: normal cornea, forme fruste KC (FFKC), and clinical KC. The exclusion criteria were a history of previous ocular surgery, any accompanying corneal pathology other than KC, high myopia (>6.00 diopters), amblyopia, pregnancy, breastfeeding, or any current autoimmune disease. The data of Fourier series harmonic analysis were evaluated for their diagnostic capacity using the receiver operating characteristic (ROC) curve. A binary logistic regression analysis was also conducted to construct a diagnostic model. A total of 259 eyes showed progression in the clinical KC group and underwent a combination of accelerated corneal collagen cross-linking and topography-guided customized treatment with an excimer laser. The study included 1262 eyes (618 normal, 530 KC, and 114 FFKC) of 1262 patients. We observed that maximum decentration (MaxDec) was almost as good as maximum keratometry (Kmax) in detecting progressive KC. The area under the curve (AUC) was 0.95 for KC [95% confidence interval (CI): 0.93-0.96] and 0.84 for FFKC (95%CI: 0.79-0.88). Higher predictive accuracy was obtained using a model combining the spherical component, MaxDec, irregularity, and regular astigmatism in the center of the cornea (AUC: 0.97; sensitivity: 89%, and specificity: 96%). Decentration, Kmax, and posterior radii of curvatures from a 3.0-mm optical zone centered on the thinnest point of the cornea provide the highest accuracy with low reproducibility of Kmax.

Topography-guided corneal surface laser ablation combined with simultaneous accelerated corneal collagen cross-linking for treatment of keratoconus

Backgroundto study the outcomes of topography-guided customized excimer laser subepithelial ablation combined with accelerated CXL for progressive keratoconus.MethodsThirty-one eyes of 30 patients with progressive keratoconus were included in this prospective study. Topography-guided excimer laser ablation without refractive correction was performed. Simultaneous accelerated collagen cross-linking with ultraviolet light of 30 mW/cm2 for 4 min was followed. Uncorrected distance visual acuity (UCVA), manifest refraction, corrected distance visual acuity (CDVA), tomograghy were examined at postoperative 1, 6, and 12 months.ResultsUDVA improved slightly after surgery (P > 0.05). BSCDVA improved significantly from 0.32 ± 0.20 logMAR to 0.15 ± 0.14 logMAR at postoperative 12 months (P < 0.05). During 12-month follow-ups, there were no significant differences in manifest refraction and corneal keratometry except for maximal keratometry value of the anterior surface (Kapex), which decreased significantly from 57.23 ± 5.09D to 53.13 ± 4.47D (P < 0.05). Even though the thinnest corneal thickness decreased from 465 ± 24 μm to 414 ± 35 μm (P < 0.05), curvature asymmetry index front (SIf), keratoconus vertex front (KVf) and Baiocchi Calossi Versaci index front (BCVf) decreased significantly till postoperative 12 months (P < 0.05). Corneal higher-order aberrations and coma also decreased significantly till 12 months after surgery (P < 0.05).ConclusionsTopography-guided surface ablation without refractive correction combined with simultaneous accelerated collagen cross-linking provided good stability in refraction and corneal curvature, and also showed significant improvement in BSCDVA, corneal regularity and corneal optical quality.

Corneal Lamb wave imaging for quantitative assessment of collagen cross-linking treatment based on comb-push ultrasound shear elastography

Keratoconus, a serious corneal disorder, often causes highly irregular astigmatism and different degrees of visual impairment. Riboflavin/UVA corneal collagen cross-linking(CXL) is currently approved for effective treatment of keratoconus by enhancing the mechanical strength of collagen fibers in the cornea. However, few methods are capable of quantitatively and non-destructively assessing the mechanical properties of the cornea before and after CXL treatments. This study developed a corneal viscoelasticity imaging method based on comb-push ultrasound shear elastography (CUSE) and implemented this method on a Verasonics™ Vantage 256 ultrasound open system with a high-frequency linear array ultrasound transducer. Push beams were generated by three teeth each consisting of 10 elements (working frequency = 10.41 MHz) for inducing Lamb wave propagation in the cornea, and then the system immediately switched to the plane wave imaging mode using 60 elements in the middle (working frequency = 18 MHz). This method can provide a high-resolution 2D Lamb wave velocity image overlapping with a B-mode image as well as quantitative viscoelasticity estimation according to experimentally obtained phase velocity dispersion of Lamb waves. The validation experiments were performed on ex vivo porcine corneas, and the accuracy of elasticity estimation was verified by a tensile test. The results showed that the shear elasticity increased and the viscosity decreased after CXL treatment. The shear elasticity results (reported as mean ± standard deviation) of one control group with no CXL treatment and three CXL-treated groups named as 10 min, 30 min, and 60 min groups according to UV irradiation time were 14.62 ± 3.38 kPa, 49.47 ± 3.63 kPa, 116.54 ± 23.99 kPa, and 197.89 ± 39.64 kPa, respectively, which was in agreement with the results of tensile tests. The ultrasound safety measurement indicated that this method could have acceptable safety, but further to ocular tissue and vision function. The study demonstrated the possibility of using a commercial ultrasound system to obtain high-resolution images of corneal mechanical properties as well as the ability to quantify changes induced by CXL treatment. Therefore, the proposed method could serve as a helpful tool in the studies related in corneal biomechanics.

A Prospective, Comparative, Clinical Study to Evaluate the Safety and Efficacy of Two Different 0.1% Riboflavin Solutions Used in Collagen Crosslinking Treatment for Patients with Keratoconus.

PurposeTo compare the safety and efficacy of 0.1% riboflavin in two different solutions which is used in corneal collagen crosslinking (CXL) for the treatment of keratoconus.MethodsThis was a prospective, randomized, comparison study which included 100 eyes of 61 patients with progressive keratoconus who underwent CXL with riboflavin 0.1% solution as a photosensitizer, using the standard Dresden protocol of using 3mW/cm2 UV-A irradiation for 30 minutes which corresponds to a total energy of 5.4 J/cm2. The recruited patients were divided into 2 groups ie, Flavin Group and Peschke-D group by computer generated randomization. Postoperative examinations were conducted on 1 day, 1 month, 3 months, 6 months and 12 months after the crosslinking.ResultsFor both groups, the mean manifest spherical equivalent (SE), astigmatism, best corrected distance visual acuity, keratometry values, thinnest pachymetry values, demarcation line depth and endothelial cell density preoperatively and at postoperative 12 months were comparable with no statistically significant differences. At 12 months postoperatively, 62% of eyes in the Flavin group, and 68% of eyes in the Peschke-D group had postoperative manifest SE of within ± 1.00 D. During UV-A exposure, the cornea in the Flavin group showed intraoperative thinning of 112 microns (27%) as compared with a thinning of 108.12 microns (26.5%) observed in the Peschke group (p=1.67) from the initial pachymetry readings. No eye in either group had any immediate or long-term postop vision threatening complications such as infectious keratitis, corneal melt, non-resolving corneal oedema or endothelial decompensation.ConclusionBoth riboflavin solutions were equally safe and effective in the management of progressive keratoconus, and resulted in similar changes in terms of mean manifest spherical equivalent (SE), astigmatism, best corrected distance visual acuity, keratometry values, thinnest pachymetry values, demarcation line depth and endothelial cell density at the end of 12 months postoperatively.Trial Registration NumberCtri/2019/11/021841 (Www.ctri.nic.in).

Efficacy and Safety of Corneal Collagen Crosslinking in Treatment of Progressive Keratoconus with Consideration to the Long-Term Results

Efficacy and Safety of Corneal Collagen Crosslinking in Treatment of Progressive Keratoconus with Consideration to the Long-Term Results

Xanthine oxidase enzyme activity in keratoconic corneal epithelium.

To assess the activity of xanthine oxidase (XO) enzyme in keratoconic corneal epithelium and to evaluate its relationship with the keratoconus (KC) severity. This prospective and randomized study included 66 eyes of 54 KC patients who received corneal collagen cross-linking treatment and 43 eyes of 32 patients who underwent photorefractive keratectomy due to their refractive error. During surgical procedures, the corneal epithelium was mechanically scraped and gathered to analyze the XO enzyme activity spectrophotometrically. The KC group was subdivided into three groups (stages 1, 2, and 3) according to the Amsler-Krumeich classification. The results were compared between the KC and the control group and in between KC subgroups. No significant differences in age and gender were found between the KC and control groups (p = 0.064 and p = 0.296, respectively). The mean XO activity levels of the KC and control groups were 173.57 ± 87.61 and 223.70 ± 99.52mIU/mg, respectively (p < 0.001). In KC group, 33 eyes were at stage 1, 19 were at stage 2, and 14 were at stage 3. No significant difference was observed between KC subgroups regarding XO activity levels (p = 0.681). In this study, our findings revealed that ultraviolet-related pro-oxidant XO enzyme may have a role in the etiopathogenesis of KC. Further studies are needed to support our result. When we started this study in 2018, we did not have a "Clinical Trials Registration." However, we have ethics committee approval (date: 21. 02. 2018/No: 22).

Comparison of ocular discomfort after three different epithelial debridement techniques for corneal collagen cross-linking in keratoconus treatment.

Purpose:To compare the severity and duration of ocular discomfort after three different epithelial debridement techniques for corneal collagen cross-linking in the treatment of keratoconus.Methods:Fifty-five patients (65 eyes) known to have keratoconus were enrolled in this retrospective study. The eyes were divided into three groups based on the technique used for epithelial debridement for corneal collagen cross-linking procedure; excimer laser transepithelial phototherapeutic keratectomy was used in group 1 (18 eyes), alcohol-assisted epithelial removal was used in group 2 (27 eyes), and mechanical epithelial debridement was used in group 3 (20 eyes). Preoperative and postoperative (third month) best-corrected visual acuity (BCVA) using Snellen chart, objective refraction, and keratometry results were recorded. The results of the questionnaire obtained from the patient’s medical records were reviewed regarding their subjective evaluation of postoperative symptoms including foreign body sensation, tearing, photophobia, and burning at the end of the first postoperative week. Paired-samples t test was used to compare preoperative and postoperative clinical findings. One-way analysis of variance (ANOVA) was used to analyze the differences between three independent groups.Results:BCVA improved from 0.51 ± 0.27 to 0.58 ± 0.21 (p = 0.05). Objective mean spherical and cylindrical refraction decreased from −5.08 ± 2.78D to −4.46 ± 2.91D (p = 0.22) and from −3.45 ± 2.73D to −3.03 ± 1.97D (p = 0.25). Mean maximum keratometry reading (Kmax) decreased from 57.63 ± 4.73D to 56.13 ± 4.47D (p = 0.001). The mean score for foreign body sensation was the highest in group 3 (4.50 ± 0.53) and the lowest in group 1 (2.10 ± 1.85) (p = 0.01). The mean scores for tearing, photophobia, and burning sensation were comparable in three groups (p = 0.84, p = 0.13, and p = 0.61, respectively). The duration of photophobia was the shortest in group 1 (1.50 ± 2.37 days), followed by group 3 (2.00 ± 1.31 days) and group 2 (4.00 ± 1.83 days) (p = 0.04).Conclusions:The severity and duration of adverse subjective symptoms during the first postoperative week after corneal collagen cross-linking appear to be milder with epithelial debridement using excimer laser transepithelial technique compared with -assisted debridement and mechanical debridement.