Factors Associated With Receipt of Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to identify factors associated with receipt of standard fluence epithelium-off crosslinking (CXL) for keratoconus (KCN). METHODS: This retrospective, cross-sectional study reviewed electronic health records of treatment-naive patients with KCN seen at the Wilmer Eye Institute between January 2017 and September 2020. Tomographic data were derived from Pentacam (Oculus, Wetzlar, Germany) devices. Multivariable population-average model using generalized estimating equations adjusting for age, sex, race, national area deprivation index, vision correction method, and disease severity was used to identify factors associated with receipt of CXL. RESULTS: From 583 patients with KCN, 97 (16.6%) underwent CXL for KCN. Patients who received CXL in at least 1 eye were significantly younger (mean 24.0 ± 7.8 years) than patients who had never undergone CXL (33.4 ± 9.3 years) ( P < 0.001). In multivariable analysis, Black patients had 63% lower odds of receiving CXL for KCN (OR: 0.37, 95% CI, 0.18-0.79) versus White patients, and older age was protective against receipt of CXL (OR: 0.89 per 1-year increase, 95% CI, 0.86-0.93). Comparison of characteristics by race demonstrated that Black patients presented with significantly worse vision, higher keratometric indices (K1, K2, and Kmax), and thinner corneal pachymetry at baseline versus White or Asian patients. CONCLUSIONS: In this clinical cohort of patients with KCN from a tertiary referral center, Black patients were less likely to receive CXL presumably because of more advanced disease at presentation. Earlier active population screening may be indicated to identify and treat these patients before they become ineligible for treatment and develop irreversible vision loss. Such strategies may improve health equity in KCN management.

Real-world socioeconomic determinants of corneal crosslinking in a national cohort.

PURPOSE: To characterize recent socioeconomic trends in patients with keratoconus/corneal ectasias undergoing corneal crosslinking (CXL). SETTING: A deidentified administrative medical claims database comprised commercial and Medicare Advantage health claims from across the United States. DESIGN: Population-based retrospective cohort study. METHODS: This study identified 552 patients with keratoconus/corneal ectasia who underwent CXL and 2723 matched controls who did not undergo CXL based on Current Procedural Terminology coding from a U.S. national insurance claims database from 2016 to 2020. For each patient, characteristics, including sex, race, age, household net worth, education level, insurance plan type, and geographic region, were extracted. Multivariate logistic regression was conducted to determine the odds of undergoing crosslinking. RESULTS: Age 30 years or older (odds ratio [OR], 0.34, P < .001) was associated with decreased likelihood of undergoing CXL. Sex, race, education, and patient income were not associated with odds of undergoing CXL. Patients with health maintenance organization insurance had lower odds of undergoing CXL (OR, 0.64, P = .047). Geographically, patients on the east coast (OR, 0.37, P < .001) and Lower Midwest (OR, 0.31, P < .001) had statistically lower odds of undergoing crosslinking. CONCLUSIONS: This is the first study to identify socioeconomic determinants of CXL, and it highlights that geographic location and insurance type may limit accessibility to patients.

Observation and assessment of the immediate use of a silicon hydrogel contact lens after transepithelial corneal cross linking: a prospective study.

BACKGROUND: Transepithelial corneal crosslinking (CXL) is a novel surgical approach for the treatment of keratoconus, which is a bilateral asymmetrical ophthalmological disease accompanied by progressive corneal ectasia. Silicon hydrogel (SiH) contact lenses have been extensively used in clinical ophthalmologic medicine, as a postoperative ophthalmological intervention. However, the ideal lens application duration after transepithelial CXL remains uncertain. Here, we aimed to investigate the effects and comfort of immediate corneal contact lens use after transepithelial CXL for keratoconus. METHODS: In this prospective study, 60 patients with keratoconus who underwent transepithelial CXL treatment were enrolled from September 2021 to January 2023 with a male:female ratio of 39:21, and an average age of 25.42 ± 5.47 years. The patients were divided randomly into two groups: group A contained 30 patients wearing silicone hydrogel contact lenses for 7 days postoperatively, and group B contained 30 patients wearing the same contact lenses for 3 days. Ten subjective ophthalmologic symptoms were surveyed by the patients, including pain, photophobia, foreign body sensation, tearing, burning, blurred vision, dry eyes, difficulty opening the eyes, astringency, and stinging. Ophthalmologic signs, including corneal edema and conjunctival congestion, were recorded by a single clinician on postoperative days 1, 3, and 7. RESULTS: Each surgical procedure was readily performed without complications, and both groups postoperative day 7 (P = 0.04), where group B scored (0.01 ± 0.41) lesser than group A (0.12 ± 0.29), whilst corneal edema in both groups recorded significantly different on postoperative days 5 and 7 (group A demonstrated the result of 0.17 ± 0.14 and 0.08 ± 0.11 for the respective days, whereas group B indicated 0.10 ± 0.13 and 0.03 ± 0.07 at the corresponding times). CONCLUSIONS: Immediate use of silicone hydrogel corneal lenses after transepithelial CXL effectively alleviates postoperative ocular distress, particularly with a three-day use period as the ideal duration.

A Clinical Decision Tree to Support Keratoconus Patients Considering Corneal Cross-Linking Combined with Refractive Treatment.

BACKGROUND: To develop a fast and frugal decision tree to identify keratoconus patients most likely to benefit visually from the combination of corneal cross-linking (CXL) with topography-guided photorefractive keratectomy ("CXL plus"). PATIENTS AND METHODS: The outcome of interest was an improvement in uncorrected distance visual acuity (UDVA) by at least two lines at the 12-month follow-up. Preoperative and 12-month follow-up data from patients who received CXL plus (n = 96) and CXL only (n = 96) were used in a recursive partitioning approach to construct a frugal tree with three variables (corneal thickness [>/< 430 um], patient interest in CXL plus [yes/no], and tomographic cylinder [ 3 D]). In addition, we estimated the probability of the outcome from a multivariate logistic regression model for each combination of variables used in the decision tree. RESULTS: In the complete sample, 101/192 (52.6%) patients improved by at least two lines at the 12-month follow-up. Patients affirmative in all three answers had a 75.6% (34/45) probability of gaining at least two lines of improvement in UDVA by CXL plus. The statistical model estimated a 66.0% probability for a successful outcome. CONCLUSION: A fast and frugal tree consisting of three variables can be used to select a patient group with a high likelihood to benefit from CXL plus. The tree is useful in the preoperative counseling of keratoconus patients contemplating the CXL plus option, an intervention that is not fully covered by many health insurances.

Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration.

PURPOSE: To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues. SETTING: Studio Italiano di Oftalmologia, Rome, Italy. DESIGN: Laboratory study. METHODS: 20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm 2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (k c ). RESULTS: Significant corneal tissue stiffening ( P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in k c ( R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening. CONCLUSIONS: Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.

The ABCD grading system in assessment of corneal cross-linking effect in keratoconus with different cone locations.

PURPOSE: The aim of this study was to analyse the postoperative corneal cross-linking results of corneal parameters and the ABCD grading system, depending on the cone location. METHODS: Thirty eyes of 25 patients with keratoconus (KC), who received the corneal cross-linking (CXL) treatment, were included in this study. The exclusion criteria were: patients under 18 years of age, corneal pachymetry less than 400 µm, corneal scarring, history of ocular trauma, history of ocular surgery, and corneal pathology other than KC. Patients were examined at the baseline visit, and followed-up at three, six, and twelve months after the CXL. All patients underwent visual acuity and Scheimpflug tomography at all visits. Progression parameters, keratometries, and ABCD grading were compared between the visits. Patients were classified into two groups: central and paracentral cones group (within the central 5 mm corneal zone) and peripheral cones group (outside the central 5 mm corneal zone), based on X-Y coordinates of maximal keratometry (Kmax). RESULTS: Parameter A remained relatively stable throughout the follow-up period in both groups. Parameter B and parameter C showed a significant increase in both groups postoperatively. Parameter D showed stability at the 6-month post-CXL visit in the peripheral KC group, while the central and paracentral KC group showed improvement at the 12-month post-CXL visit. CONCLUSION: There was no significant difference in the postoperative response between different cone locations in the ABCD grading system, when classifying according to the Kmax, except an earlier recovery of the parameter D in peripherally located cones.

Assessment of two-year clinical outcomes after keratoconus treatment using two different crosslinking protocols.

OBJECTIVE: This study aims to compare the long-term outcomes of standard corneal collagen crosslinking with accelerated corneal collagen crosslinking (CXL) for progressive keratoconus. PATIENTS AND METHODS: This prospective, comparative study included 79 eyes with progressive keratoconus, which were randomly assigned: 42 eyes received a standard CXL procedure, and 37 eyes were treated with the accelerated CXL protocol. We evaluated the following parameters, before the procedure and 1 month, 6 months, 12 months and 24 months postoperatively: best corrected visual acuity (BCVA), manifest refraction spherical equivalent (MRSE), cylindrical values, corneal dioptric powers on the steepest meridian (Kmax), central corneal thickness (CCT); demarcation line depth (DLD) preoperatively and 1 month after the CXL procedure. RESULTS: The BCVA, MRSE, cylindrical values, Kmax, CCT improved significantly, after both the accelerated and the standard CXL procedure. Throughout the 24-months follow-up, BCVA improvement was achieved sooner in the accelerated group (after 1 month, vs. after 3 months). However, there were no statistically significant differences between the two groups in these aspects. The DLD-to-CCT was significantly greater in the standard group (66% vs. 62%, p = 0.02). CONCLUSIONS: Standard and accelerated CXL are effective in stabilizing keratoconus progression in the long term. In clinical practice, the accelerated protocol has the added benefit of a faster visual recovery, in addition to the known reduced treatment time and increased comfort.

Assessment of the postoperative effect of corneal cross-linking on keratoconus using the ABCD grading system.

PURPOSE: To monitor the changes in the ABCD grading system during a one-year follow-up after a corneal cross-linking (CXL) procedure. METHODS: This prospective study included 30 eyes of 25 patients with keratoconus, who received the CXL treatment. The patients with a history of ocular trauma or surgery and other corneal pathology were excluded from the study. The patients were examined at the baseline visit and followed up at 3, 6, and 12 months after the CXL. All the patients underwent a standard CXL procedure with visual acuity and Scheimpflug tomography testing at each visit. The corneal parameters and ABCD grading were monitored throughout the follow-up period. RESULTS: There were no significant changes of parameter A and anterior radius curvature (ARC) in the ABCD grading system. Parameters B and D showed progression postoperatively, with an improvement of parameter D on the final visit. Parameter C showed a statistically significant increase at all three post-CXL visits, but a constant gradual decrease in the value over time. CONCLUSION: The ABCD grading system can be very useful in monitoring the progression of keratoconus (KC), but it can also help in monitoring the efficacy of corneal cross-linking. The anterior surface parameters in the ABCD grading system did not show progression in the post-CXL period, and parameters C and D showed improvement and stability a year after the procedure.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model.

AIMS: To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS: A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS: Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS: Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS: Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

Clinical Features and Burden Scores in Japanese Pediatric Migraines With Brainstem Aura, Hemiplegic Migraine, and Retinal Migraine.

BACKGROUND: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines. METHODS: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS). RESULTS: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores. CONCLUSION: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

Diagnosis and phenotypic assessment of trimethylaminuria, and its treatment with riboflavin: 1H NMR spectroscopy and genetic testing.

BACKGROUND: Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is challenging because this disorder is situated at the boundary between biochemistry and psychiatry. Here, we used nuclear magnetic resonance spectroscopy to assess TMAU in 13 patients. We also sequenced the FMO3 gene in 11 of these patients. Treatment with vitamin B2 was prescribed. RESULTS: Two patients (aged 3 and 9 years at the initial consultation) had a particularly unpleasant body odor, as assessed by their parents and the attending physicians. The presence of high urine TMA levels confirmed the presence of a metabolic disorder. The two (unrelated) children carried compound heterozygous variants in the FMO3 gene. In both cases, vitamin B2 administration decreased TMA excretion and reduced body odor. The 11 adults complained of an unpleasant body odor, but the physicians did not confirm this. In all adult patients, the urine TMA level was within the normal range reported for control (non-affected) subjects, although two of the patients displayed an abnormally high proportion of oxidized TMA. Seven of the 9 tested adult patients had a hypomorphic variant of the FMO3 gene; the variant was found in the homozygous state, in the heterozygous state or combined with another hypomorphic variant. All 11 adults presented a particular psychological or psychiatric phenotype, with a subjective perception of unpleasant odor. CONCLUSIONS: The results present the clinical and biochemical data of patients complaining of unpleasant body odor. Contrary to adult patients, the two children exhibited all criteria of recessively inherited trimethylaminuria, suspected by parents in infancy. B2 vitamin treatment dramatically improved the unpleasant body odor and the ratio of TMA/Cr vs TMAO/Cr in the urine in the children. Other patients presented a particular psychological or psychiatric phenotype.

Assessment of the Association Between In Vivo Corneal Biomechanical Changes After Corneal Cross-linking and Depth of Demarcation Line.

PURPOSE: To test for an association between stiffening following corneal cross-linking (CXL) and demarcation line depth. METHODS: Sixty-six eyes of 66 patients treated with CXL for progressive keratoconus were included. Dynamic corneal response parameters (DCRs) were measured with the Corvis ST (Oculus Optikgeräte GmbH; Wetzlar, Germany) on the day of CXL and after 1 month. Demarcation line was measured 4 weeks after CXL. A multivariate general linear model was used to test for an association between the change in DCRs and the ratio between demarcation line depth and the postoperative pachymetry. RESULTS: The authors found no significant associations between the change in inverse concave integrated radius (1/R) and the demarcation line ratio (P = .46), age (P = .33), sex (P = .11), preoperative maximum keratometry (P = .10), and laterality (P = .82). Similarly, there was no significant correlation between the change in 1/R and the demarcation line ratio (R2 = .002 and P = .75). However, there was a significant association between the preoperative values of 1/R and the respective change in 1/R (P < .0001). The change in 1/R was inversely proportional to the patient's preoperative 1/R; stiffer corneas (lower values of 1/R) were less affected than less stiff corneas (R2 = .23, P < .0001). CONCLUSIONS: CXL is associated with changes in DCRs, suggesting a change in corneal biomechanics following CXL. These changes do not appear to be associated with the demarcation line depth. [J Refract Surg. 2019;35(3):202-206.].

Noninvasive Assessment of Corneal Crosslinking With Phase-Decorrelation Optical Coherence Tomography.

Purpose: There is strong evidence that abnormalities in corneal biomechanical play a causal role in corneal ectasias, such as keratoconus. Additionally, corneal crosslinking (CXL) treatment, which halts progression of keratoconus, directly appeals to corneal biomechanics. However, existing methods of corneal biomechanical assessment have various drawbacks: dependence on IOP, long acquisition times, or limited resolution. Here, we present a method that may avoid these limitations by using optical coherence tomography (OCT) to detect the endogenous random motion within the cornea, which can be associated with stromal crosslinking. Methods: Phase-decorrelation OCT (PhD-OCT), based in the theory of dynamic light scattering, is a method to spatially resolve endogenous random motion by calculating the decorrelation rate, Γ, of the temporally evolving complex-valued OCT signal. PhD-OCT images of ex vivo porcine globes were recorded during CXL and control protocols. In addition, human patients were imaged with PhD-OCT using a clinical OCT system. Results: In both the porcine cornea and the human cornea, crosslinking results in a reduction of Γ (P < 0.0001), indicating more crosslinks. This effect was repeatable in ex vivo porcine corneas (change in average Γ = -41.55 ± 9.64%, n = 5) and not seen after sham treatments (change in average Γ = 2.83 ± 12.56%, n = 5). No dependence of PhD-OCT on IOP was found, and correctable effects were caused by variations in signal-to-noise ratio, hydration, and motion. Conclusions: PhD-OCT may be a useful and readily translatable tool for investigating biomechanical properties of the cornea and for enhancing the diagnosis and treatment of patients.

Corneal Collagen Cross-Linking in the Management of Keratoconus in Canada: A Cost-Effectiveness Analysis.

PURPOSE: To use patient-level microsimulation models to evaluate the comparative cost-effectiveness of early corneal cross-linking (CXL) and conventional management with penetrating keratoplasty (PKP) when indicated in managing keratoconus in Canada. DESIGN: Cost-utility analysis using individual-based, state-transition microsimulation models. PARTICIPANTS: Simulated cohorts of 100 000 individuals with keratoconus who entered each treatment arm at 25 years of age. Fellow eyes were modeled separately. Simulated individuals lived up to a maximum of 110 years. METHODS: We developed 2 state-transition microsimulation models to reflect the natural history of keratoconus progression and the impact of conventional management with PKP versus CXL. We collected data from the published literature to inform model parameters. We used realistic parameters that maximized the potential costs and complications of CXL, while minimizing those associated with PKP. In each treatment arm, we allowed simulated individuals to move through health states in monthly cycles from diagnosis until death. MAIN OUTCOME MEASURES: For each treatment strategy, we calculated the total cost and number of quality-adjusted life years (QALYs) gained. Costs were measured in Canadian dollars. Costs and QALYs were discounted at 5%, converting future costs and QALYs into present values. We used an incremental cost-effectiveness ratio (ICER = difference in lifetime costs/difference in lifetime health outcomes) to compare the cost-effectiveness of CXL versus conventional management with PKP. RESULTS: Lifetime costs and QALYs for CXL were estimated to be Can$5530 (Can$4512, discounted) and 50.12 QALYs (16.42 QALYs, discounted). Lifetime costs and QALYs for conventional management with PKP were Can$2675 (Can$1508, discounted) and 48.93 QALYs (16.09 QALYs, discounted). The discounted ICER comparing CXL to conventional management was Can$9090/QALY gained. Sensitivity analyses revealed that in general, parameter variations did not influence the cost-effectiveness of CXL. CONCLUSIONS: CXL is cost-effective compared with conventional management with PKP in the treatment of keratoconus. Our ICER of Can$9090/QALY falls well below the range of Can$20 000 to Can$100 000/QALY and below US$50 000/QALY, thresholds generally used to evaluate the cost-effectiveness of health interventions in Canada and the United States. This study provides strong economic evidence for the cost-effectiveness of early CXL in keratoconus.

Conventional and Iontophoresis Corneal Cross-Linking for Keratoconus: Efficacy and Assessment by Optical Coherence Tomography and Confocal Microscopy.

PURPOSE: To compare the efficacy, safety, and microstructural corneal changes during 2 years after conventional corneal collagen cross-linking (C-CXL) and transepithelial corneal CXL by iontophoresis (I-CXL) for keratoconus. METHODS: Eighty eyes of 80 patients with progressive keratoconus were treated by C-CXL (n = 40) or I-CXL (n = 40). Patients were investigated before surgery and 1, 3, 6, 12, and 24 months after treatment. We measured central corneal thickness and maximal simulated keratometry values (Kmax) and performed specular microscopy and in vivo confocal microscopy at each time point. The demarcation line was assessed 1 month after treatment. RESULTS: Kmax remained stable after I-CXL during the entire study period (P = 0.56), whereas the average keratometry increased by 0.2 diopter (50.9 ± 5.6-51.1 ± 5.2). Kmax significantly decreased 1 (P = 0.02) to 2 years (P < 0.01) after C-CXL, with an average decrease of 1.1 diopters (49.9 ± 4.5-48.8 ± 4.2). The failure rate of I-CXL was 20% and that of C-CXL 7.5%. The demarcation line was superficially visible in 35% of cases after I-CXL compared with 95% of cases after C-CXL. Endothelial cell density and central corneal thickness remained stable during the entire study period. The change in Kmax 2 years after C-CXL and I-CXL and the preoperative Kmax were negatively correlated (r = 0.14, P = 0.013, and r = 0.17, P = 0.007, respectively). CONCLUSIONS: I-CXL halted progression of keratoconus less efficiently than did C-CXL after 2 years of follow-up. Longer prospective studies are still needed to ensure I-CXL efficacy.

[Assessment of postoperative pain after corneal collagen cross-linking by iontophoresis vs the rapid epithelium-off technique in progressive keratoconus patients]. / Évaluation de la douleur en postopératoire de cross-linking du collagène cornéen en comparant la procédure par iontophorèse à la technique épithélium-off rapide chez des patients atteints de kératocône évolutif.

INTRODUCTION: Cross-linking (CXL) increases corneal biomechanical strength in progressive keratoconus. Since riboflavin cannot penetrate intact corneal epithelium, removal of epithelium is necessary for the classic CXL procedure (epi-off), but can cause severe postoperative pain. To avoid this problem, a method preserving the epithelium (epi-on) is used. In this study, we aimed to evaluate and compare postoperative pain after epi-off CXL and epi-on CXL. MATERIALS AND METHODS: We present a retrospective study assessing the level of pain postoperatively in 38 patients between the age of 12 and 53 years who underwent CXL procedures at the University Hospital of Clermont-Ferrand from July 2013 to May 2014. Epi-off consisted of manual corneal de-epithelialization and riboflavin instillation for 20minutes, followed by UVA exposure for 9minutes. The epi-on technique used an applicator on the eye, filled with riboflavin, and a generator delivered a continuous low-level current for 5minutes. The duration of light exposure was similar in both groups. Postoperative medications were the same for both techniques. Assessment of pain and analgesic intake were reported by the patient on paper questionnaires. Pain was evaluated from preoperatively up until the end of the month. Statistical analyses were performed in bilateral formulation to an alpha type I and error risk of 5%. RESULTS: Twenty-three epi-off patients and 15 epi-on patients. Twenty-nine men and 9 women (76.3%/23.7%). Mean age: 28 years. Reference base time was the return from the operating room. In the epi-off group, pain increased significantly until the morning of D2 and did not return to its intraoperative level until noon D2, 1.8±2.0 vs 2.5±2.5 (P=0.12). Pain remained stable until the morning of D4. From noon D4 until D30, it was significantly less than intraoperatively 1.8±2.0 vs 0.7±1.4 (P=0.01). In the epi-on group, pain was significantly higher than intraoperatively until noon of D1 2.5±2.2 vs 3.8±2.5 (P=0.01). From the evening of D1, it returned to its intraoperative level until the evening of D2 2.5±2.2 vs 2±1.7 (P=0.34). From the morning of D3 it was significantly less than intraoperatively 2.5±2.2 vs 0.8±0.9 (P=0.001). Considering all measurement times, there was no significant difference between the two groups (P=0.75), except from evening of D2 until evening of D3 in favor of iontophoresis: 1.9±2.3 vs 1.0±1.3 (P=0.038). DISCUSSION: Epi-on seems less painful in the short term (up to noon of D1 for epi-on vs morning of D2 for epi-off) and with a shorter duration than epi-off. This can be explained by the absence of corneal de-epithelialization. However, the reduction in pain is not significant at all postoperative times, and a risk of epithelial abrasion during placement and removal of the corneal applicator may exist. CONCLUSION: Iontophoresis maintains the corneal epithelium, decreases pain and improves patient comfort. A new study involving more patients and strict monitoring of medication intake would strengthen the validity of these results.

Assessment of the tomographic values in keratoconic eyes after collagen crosslinking procedure.

GOAL: This study aimed to investigate the differences in values of K1 and K2 readings, the central corneal thickness (PAH) before the collagen crosslinking procedure (CXL) and 3, 6, 12 months later. METHODS: 64 eyes were evaluated in retrospective cross sectional study. The corneal biomechanical parameters were taken with WaveLight Allegro Oculyzer produced by Alcon before the CXL, 3,6, 12 months after the procedure. The curvature of K1 reading and K2 reading were taken and the central corneal thickness were considered due to the time after CXL. RESULTS: The value of K1 reading before the treatment was 48.8 diopters (D) (46.65-50.50) and was statistically significant lower comparing to the value of K1 3 months after the collagen CXL procedure 46.30 D (43.57-49.45) (p=0.0006), K1 reading one year post collagen CXL procedure was 47.20 D (44.35-50.07) (p=0.002). The value of K2 reading before the collagen CXL procedure was 52.65 D (47.55-54.72), 3 months after the procedure was 51.4 (45.05-54.0), 6 months later 48.55 D (47.20-50.62), 12 months later 51.30 D (47.22-54.77). There is statistically significant lower value of K2 reading 6 months after the treatment comparing to the values 3 months postoperatively (p=0.014). However there is significantly lower values of K2 reading 12 months postoperatively comparing to preoperative period (p=0.006). The value of central corneal thickness preoperative was 431.0 microns (398.0-446.25), 3 months after collagen CXL procedure was 373.50 microns (363.25-430.75), 6 months later 435.0 microns (360.0-464.75), 12 months after the CXL procedure was 429.50 microns (357.75-496.25). There is statistically significant lower values of central corneal thickness 3 months after collagen CXL treatment comparing to the central corneal thickness preoperative (p<0.005). There is statistically significant lower values of pachymetry 12 months after the CXL procedure comparing to the values 6 months later (p=0.036) and those preoperativelly (p=0.032). There is no statistically significant difference in the values of central corneal thickness in the period from 3 and 6 months postoperatively. CONCLUSION: After riboflavin-UVA CXL in eyes with keratokonus there was significant decrease in central corneal thickness 3 and 6 months after the procedure and the thickness is almost the same 12 months. However, K2 (Kmax) reading is significantly changed 3 and 6 months later and is followed by changing of K1 reading.

Dynamic Scheimpflug-based assessment of keratoconus and the effects of corneal cross-linking.

PURPOSE: To evaluate the ability of the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) to distinguish between normal and keratoconic corneas and detect the possible stiffening effect of corneal cross-linking (CXL) in vivo. METHOD: A retrospective study including 86 eyes of 86 participants (27 patients with untreated keratoconus, 27 patients with CXL-treated keratoconus, and 32 normal patients). The prospective study included 9 keratoconic eyes measured 24 days before and 97 days after CXL. RESULTS: The following parameters from the Corvis ST showed a significant difference between keratoconic and normal eyes: intraocular pressure, corneal thickness, first applanation time, highest concavity (HC) radius, HC deformation amplitude, and HC deflection amplitude (analysis of variance, P < .0001). Receiver operating characteristic curve analysis showed the highest area under the curve for HC deflection amplitude (0.942, P < .0001). Prediction intervals for individual measurements within the two groups overlapped considerably. No significant difference was found between the untreated and CXL-treated keratoconus groups (analysis of variance, P > .05). Measurements performed before and after CXL in the same patients showed significant difference in HC deformation amplitude (P = .018), HC time (P = .018), and second applanation time (P = .027). CONCLUSIONS: Although the corneal deformation characteristics differed between groups of keratoconic and normal eyes, this study showed that the standard parameters of the Corvis ST cannot readily be used for diagnosis of keratoconus in the individual patient or to document the effect of CXL in vivo.