Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Update on corneal crosslinking for keratoconus and corneal ectasia.

PURPOSE OF REVIEW: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations. RECENT FINDINGS: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients. SUMMARY: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.

Long-Term Outcomes After Corneal Cross-linking for Progressive Keratoconus and Corneal Ectasia: A 10-Year Follow-Up of the Pivotal Study.

OBJECTIVES: To report on the topographic and visual outcomes 10 years after corneal cross-linking in patients with progressive keratoconus and corneal ectasia after refractive surgery. METHODS: Cross-sectional cohort study of an original, prospective, randomized, clinical trial. Patients treated in a single center cornea and refractive surgery practice as part of the U.S. pivotal trials, which led to the Food and Drug Administration approval of corneal cross-linking, were recruited for a 10-year follow-up examination. LogMar lines (LL) of uncorrected visual acuity (UCVA) and best spectacle--corrected visual acuity (BSCVA), maximum keratometry, and thinnest pachymetry were evaluated. In addition, the Belin ABCD progression display was used to determine progression (95% confidence interval) of the anterior curvature, posterior curvature, and corneal thickness of each individual eye included. RESULTS: Nineteen eyes of 13 patients treated with standard cross-linking returned for a 10-year follow-up examination. Mean maximum keratometry changed from 58.2±12.0 diopters (D) to 58.3±10.1 D, thinnest pachymetry changed from 440.6±51.6 µm to 442.3±54.4 µm, UCVA changed from 0.79±0.42 LL to 0.86±0.46 LL, and BSCVA changed from 0.38±0.26 LL to 0.33±0.34 LL, 10 years after cross-linking. Individually, 68.5% of the entire cohort, 81.8% of keratoconus eyes, and 50% of eyes with corneal ectasia remained topographically stable 10 years after standard cross-linking. CONCLUSIONS: In the entire cohort, visual acuity and topography remained stable 10 years after cross-linking. Over the long-term, eyes with keratoconus seem to be more stable than those with corneal ectasia.

Transepithelial versus Epithelium-off Corneal Collagen Cross-linking for Corneal Ectasia: A Systematic Review and Meta-analysis.

TOPIC: To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. CLINICAL RELEVANCE: Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy. METHODS: We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (Kmax) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in Kmax at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology. DISCUSSION: The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.

The effects of losartan versus beta-blockers on cardiovascular protection in marfan syndrome: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Variable effects of beta-blockers (BB) and/or angiotensin receptor blockers (ARB) were reported to retard aortic root growth in Marfan syndrome (MFS). This study aimed to compare the effects of BB therapy and ARB-related therapies on cardiovascular protection in MFS. METHODS: Studies of randomized control trials comparing the efficacy of only-BB and ARB-related (only-ARB or ARB-plus-BB) therapies for MFS published before July 31, 2018 in PubMed, Embase, and the Cochrane Library were selected. The outcomes included changes in aortic growth and cardiovascular events. RESULTS: Eight trials involving 1381 patients were included. Patients received only-BB and ARB-related therapies did not differ significantly in changes in aortic growth (aortic root diameter: standardized mean difference [SMD] = 0.04, 95% confidence interval [CI]: -0.11-0.19, p = 0.63) or cardiovascular events (aortic dissection: Peto odds ratio [OR] = 1.67, 95% CI: 0.42-6.72, p = 0.47; aortic surgery: risk ratio = 0.97, 95% CI: 0.66-1.41, p = 0.86; death: Peto OR = 2.78, 95% CI: 0.39-19.82, p = 0.31). Subgroup analysis revealed that ARB-plus-BB therapy exhibited nonsignificantly better outcomes than only-BB therapy (aortic root diameter: SMD = 0.11, 95% CI: -0.22-0.45, p = 0.52; ascending aorta diameter: SMD = 0.10, 95% CI: -0.07-0.27, p = 0.26; aortic surgery: Peto OR = 1.10, 95% CI: 0.75-1.61, p = 0.62). CONCLUSION: For cardiovascular protection in MFS, only-ARB therapy is not inferior to only-BB therapy. Moreover, the outcomes of ARB-plus-BB therapy seemed to be favourable to those of only-BB therapy.

Prospective Randomized Trial of Corneal Cross-linking Riboflavin Dosing Frequencies for Treatment of Keratoconus and Corneal Ectasia.

PURPOSE: To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN: Prospective, randomized, single-center equivalence trial. PARTICIPANTS: Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS: One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES: The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS: The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS: The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.

Corneal crosslinking (CXL) with 18-mW/cm2 irradiance and 5.4-J/cm2 radiant exposure-early postoperative safety.

PURPOSE: To investigate safety of accelerated corneal crosslinking during the first postoperative month. METHODS: In this retrospective study, 76 eyes of 60 patients with verified progressive keratectasia were enrolled in this study and followed for 1 month after accelerated CXL (18 mW/cm2 for 5 min, radiant exposure 5.4 J/cm2) (A-CXL(5*18)). Preoperatively, objective refraction, slit lamp inspection, and corneal tomography were performed. Early postoperative slit lamp examinations were performed on days 1 and 4. At 1 month, objective refraction, slit lamp inspection, and corneal tomography were performed. RESULTS: Gender distribution was m:f = 55:21, OD:OS was 40:36, and the average age was 26.5 ± 8.6 years at surgery. Only 71 of the 76 eyes completed the 1-month follow-up, indicating a dropout rate of 6.6%. In 7.0% (n = 5), sterile infiltrates were observed; 5.6% of eyes (n = 4) showed delayed epithelial healing (> 4 days) in 2.8% (n = 2); an infection occurred and in 1 eye (1.4%), a stromal scar was detected; no other complications, neither a loss of two or more Snellen lines at 1 month postoperatively, were observed. As a risk factor for sterile infiltrates, thin preoperative pachymetry could be identified (p = 0.027). CONCLUSIONS: This study revealed no difference in early postoperative safety between CXL using 18 mW/cm2 and standard corneal CXL. Thinner preoperative pachymetry could be identified predicting a higher rate of postoperative sterile infiltrates.

U.S. Multicenter Clinical Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after Refractive Surgery.

PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of corneal ectasia after laser refractive surgery. DESIGN: Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS: One hundred seventy-nine subjects with corneal ectasia after previous refractive surgery. METHODS: The treatment group underwent standard CXL, and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES: The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry (K), comparing treatment with control groups. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS: In the crosslinking treatment group, the maximum K value decreased by 0.7 diopters (D) from baseline to 1 year, whereas there was continued progression in the control group (1.3 D difference between treatment and control, P < 0.0001). In the treatment group, the maximum K value decreased by 2.0 D or more in 14 eyes (18%) and increased by 2.0 D or more in 3 eyes (4%). The CDVA improved by an average of 5.0 logarithm of the minimum angle of resolution (logMAR) letters. Twenty-three eyes (32%) gained and 3 eyes (4%) lost 10 or more logMAR letters. The UDVA improved 4.5 logMAR letters. Corneal haze was the most frequently reported crosslinking-related adverse finding. CONCLUSIONS: Corneal collagen crosslinking was effective in improving the maximum K value, CDVA, and UDVA in eyes with corneal ectasia 1 year after treatment, with an excellent safety profile. CXL is the first approved procedure to diminish progression of this ectatic corneal process.

Increasing Risk of Osteoporotic Fracture Is Associated With Vascular Dysfunction and Abnormal Vascular Structure in Both Men and Women.

BACKGROUND: Osteoporosis and cardiovascular disease are major public health problems. A number of clinical studies have shown a link between osteoporosis and cardiovascular disease, but there is no information on the associations of risk of osteoporotic fracture with vascular function and vascular structure.Methods and Results:The risk of major osteoporotic fracture was calculated using the World Health Organization fracture risk assessment tool (FRAX); vascular function was assessed using flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), and vascular structure was assessed on brachial artery intima-media thickness (IMT) in 414 subjects (241 men and 173 women) who underwent health examinations. On univariate regression, FRAX was negatively correlated with FMD (total, r=-0.16, P<0.001; men, r=-0.19, P=0.003; women, r=-0.25, P<0.001) and NID (total, r=-0.22, P<0.001; men, r=-0.19, P=0.003; women, r=-0.30, P<0.001) and was positively correlated with brachial artery IMT (total, r=0.12, P=0.02; men, r=0.22, P<0.001; women, r=0.33, P<0.001). On multivariate analysis FRAX remained an independent predictor of FMD, NID, and brachial artery IMT in both men and women. CONCLUSIONS: Increase in the risk of osteoporotic fracture evaluated on FRAX is associated with vascular dysfunction and abnormal vascular structure in both men and women. Osteoporosis should be monitored in order to reduce the risk of cardiovascular events.

Marfan Sartan: a randomized, double-blind, placebo-controlled trial.

AIMS: To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS: A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving ß-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION: Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. ß-Blocker therapy alone should therefore remain the standard first line therapy in these patients.

Aortic Root Dilatation in Mucopolysaccharidosis I-VII.

The prevalence of aortic root dilatation (ARD) in mucopolysaccharidosis (MPS) is not well documented. We investigated aortic root measurements in 34 MPS patients at the Children's Hospital of Orange County (CHOC). The diagnosis, treatment status, age, gender, height, weight and aortic root parameters (aortic valve annulus (AVA), sinuses of Valsalva (SoV), and sinotubular junction (STJ)) were extracted by retrospective chart review and echocardiographic measurements. Descriptive statistics, ANOVA, and paired post-hoc t-tests were used to summarize the aortic dimensions. Exact binomial 95% confidence intervals (CIs) were constructed for ARD, defined as a z-score greater than 2 at the SoV. The patient age ranged from 3.4-25.9 years (mean 13.3 ± 6.1), the height from 0.87-1.62 meters (mean 1.24 ± 0.21), and the weight from 14.1-84.5 kg (mean 34.4 ± 18.0). The prevalence of dilation at the AVA was 41% (14/34; 95% CI: 25%-59%); at the SoV was 35% (12/34; 95% CI: 20%-54%); and at the STJ was 30% (9/30; 95% CI: 15%-49%). The highest prevalence of ARD was in MPS IVa (87.5%). There was no significant difference between mean z-scores of MPS patients who received treatment with hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT) vs. untreated MPS patients at the AVA (z = 1.9 ± 2.5 vs. z = 1.5 ± 2.4; p = 0.62), SoV (z = 1.2 ± 1.6 vs. z = 1.3 ± 2.2; p = 0.79), or STJ (z = 1.0 ± 1.8 vs. z = 1.2 ± 1.6; p = 0.83). The prevalence of ARD was 35% in our cohort of MPS I-VII patients. Thus, we recommend screening for ARD on a routine basis in this patient population.

Accelerated Corneal Collagen Cross-linking for Postoperative LASIK Ectasia: Two-Year Outcomes.

PURPOSE: To evaluate the effectiveness and safety of accelerated corneal collagen cross-linking for postoperative LASIK ectasia after 2 years. METHODS: A prospective, single-center case series was performed with patients treated for postoperative LASIK ectasia. All eyes underwent accelerated corneal collagen cross-linking (CCL-Vario Crosslinking; Peschke Meditrade GmbH, Zurich, Switzerland) at 9 mW/cm(2) for 10 minutes. The main outcome measures were changes in uncorrected distance visual acuity, corrected distance visual acuity, central corneal thickness, corneal topography, and endothelial cell density. These parameters were assessed at baseline and at the 6-month and 1- and 2-year follow-up visit. RESULTS: The study enrolled 40 eyes of 24 patients (15 male and 9 female) with a mean age of 33.8 ± 7.5 years (range: 24 to 52 years) that attained at least 2 years of follow-up. The surgical procedure was uneventful in all cases. All eyes stabilized after treatment without any further signs of progression and no statistically significant changes in the mean uncorrected distance visual acuity (P = .649), corrected distance visual acuity (P = .616), mean keratometry (P =.837), steep keratometry (P = .956), ultrasonic pachymetry (P = .135), slit-scanning pachymetry (P = .276), and endothelial cell density (P = .523). In addition, 72.5% of the patients presented stable or gains of Snellen lines over time. CONCLUSIONS: Accelerated corneal collagen cross-linking seems to be safe and effective in halting postoperative LASIK ectasia progression after 2 years of follow-up. However, a longer follow-up period with a larger cohort is needed to validate these findings.

Epithelial and stromal remodeling after corneal collagen cross-linking evaluated by spectral-domain OCT.

PURPOSE: To evaluate changes in corneal epithelial and stromal thickness after corneal collagen cross-linking (CXL) in eyes with keratoconus and postoperative corneal ectasia using spectral-domain optical coherence tomography (SD-OCT). METHODS: Anterior segment SD-OCT (RTVue-100; Optovue, Inc., Fremont, CA) was used to compare regional corneal epithelial and stromal thickness in eyes with keratoconus and ectasia before CXL and 1 and 3 months after CXL. The anterior surface of the cornea, epithelium-Bowman's layer interface, and posterior reflective surface were used as anatomical landmarks to measure epithelial and stromal thickness, respectively. Regional thickness was assessed centrally and at 21 points 0.5 mm apart across the central 6 mm of the corneal vertex in the horizontal and vertical meridians. RESULTS: Thirty-one eyes from 30 patients were evaluated, including 17 eyes (17 patients) with keratoconus and 14 eyes (13 patients) with ectasia. Preoperatively, a highly irregular epithelial thickness profile and distribution was observed in both groups. After CXL, epithelial thickness was significantly thinner 2.5 and 2 mm below and 1.5 mm above the corneal apex (49.26 ± 5.69 µm; range: 43 to 62 µm), and 2.5 and 1 mm nasal and 2 mm temporal to the corneal apex (46.66 ± 4.53 µm; range: 39 to 57 µm) compared to preoperative values (P < .05 for all measurements). Epithelial thickness standard deviations were significantly lower (by 3 to 6 µm) 3 months after CXL, compared to ranges before CXL in both the vertical and horizontal meridians for keratoconus and ectasia (P = .048). No significant differences were found between epithelial remodeling in keratoconus and corneal ectasia (P = .98). No significant or consistent stromal changes were found for either group. CONCLUSIONS: Significant epithelial remodeling occurs after CXL in eyes with keratoconus and corneal ectasia, creating a similar, more regularized thickness profile in all meridians in the early postoperative period. This pattern of remodeling may facilitate interpretation of corneal curvature and thickness changes after CXL and may be related to visual acuity after CXL.

Contact lens-assisted collagen cross-linking (CACXL): A new technique for cross-linking thin corneas.

PURPOSE: To report a novel method of contact lens-assisted corneal cross-linking (CACXL) in eyes with thin corneas. METHODS: Patients diagnosed as having progressive keratectasia with a minimum corneal thickness less than 400 and greater than 350 µm after epithelial abrasion were included. After epithelial abrasion, the iso-osmolar riboflavin 0.1% in dextran was applied every 3 minutes for 30 minutes. An ultraviolet barrier-free soft contact lens (0.09-mm thickness, 14-mm diameter) soaked in iso-osmolar riboflavin 0.1% for 30 minutes was placed on the cornea. Once the minimum corneal thickness value was confirmed to be greater than 400 µm, the ultraviolet-A irradiance was started along with instillation of iso-osmolar riboflavin 0.1% in the pre-corneal and pre-contact lens region. Intraoperative minimum corneal thickness changes were recorded with ultrasound pachymetry and optical coherence tomography. Postoperative visual acuity, corneal topography (Orbscan; Bausch & Lomb, Rochester, NY), endothelial cell loss (EM-3000; Tomey, Nagoya, Japan), and stromal demarcation line (Visante; Carl Zeiss Meditec, Jena, Germany) were measured. RESULTS: Fourteen eyes underwent the procedure. Mean preoperative minimum corneal thickness after epithelial abrasion was 377.2 ± 14.5 µm (range: 350 to 398 µm). There was a significant difference in minimum functional corneal thickness (Friedman test, P = .000) intraoperatively, before epithelial abrasion, after epithelial abrasion, and with contact lens and riboflavin film. Mean minimum functional corneal thickness after the contact lens was 485.1 ± 15.8 µm (range: 458 to 511 µm). Mean absolute increase in the minimum corneal thickness along with the contact lens and pre-corneal riboflavin film was 107.9 ± 9.4 µm (range: 90 to 124 µm). Mean depth of stromal demarcation line was 252.9 ± 40.8 µm (range: 208 to 360 µm). There was no significant endothelial loss (P = .063) and the corneal topography was stable at the last follow-up (P = .505). CONCLUSIONS: CACXL technique was effective and safe in performing cross-linking in corneas less than 400 µm after epithelial abrasion and appeared effective based on stromal demarcation line depth.

Corneal collagen cross-linking: a review of 1-year outcomes.

PURPOSE: To review outcomes of corneal collagen cross-linking (CXL) for keratoconus (KC) or ectasia in a cornea subspecialty practice. METHODS: Results from controlled clinical trials at a single site cornea subspecialty practice, including 104 eyes (66 KC and 38 ectasia). Outcomes and the natural course of changes in postoperative parameters including maximum keratometry (KMax), uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA) over 12 months are reviewed. In addition, corneal topography indices, wavefront higher-order aberrations, and the natural history of wound healing after CXL are discussed. Characteristics associated with CXL outcomes are reviewed as well. In predicting treatment outcomes for KMax and BCVA, the preoperative patient characteristics examined were gender, age, disease group, cone location, thinnest pachymetry, UCVA, BCVA, and KMax. RESULTS: At 1 year, an average of 1.7 diopter (D) flattening in KMax was found. Mean BCVA improved slightly more than 1 line (from 0.35±0.24 to 0.23±0.21 logMAR). All postoperative parameters similarly follow a trend of worsening between baseline and 1 month, and improvement thereafter. More specifically, quantitative improvements are typically seen at 3 months and may continue between 3 and 12 months. A review of baseline patient characteristics indicated that (1) eyes with preoperative KMax of 55 D or steeper were 5.4 times more likely to gain 2 D or more of KMax flattening at 1 year after CXL, and (2) eyes with preoperative BCVA of 20/40 or worse were 5.9 times more likely to gain 2 or more Snellen lines at 1 year after CXL. Conversely, no baseline characteristic was found to correlate with treatment complications of continual topographic steepening or loss of vision. CONCLUSIONS: Corneal collagen cross-linking seems to be effective in decreasing progression of KC, with improvements in optical measures in many patients. Postoperative parameters discussed within this review followed a seemingly reproducible trend in their natural course over 12 months. Generally, the trend observed was immediate worsening between baseline and 1 month, resolution at approximately 3 months, and improvement thereafter. In predicting outcomes after CXL, no patient characteristics showed correlations with negative treatment outcomes such as loss of vision or continual topographic steepening. However, steeper KMax (≥55 D) and poorer BCVA (≤20/40) at the time of treatment correlated with better postoperative KMax and BCVA outcomes at 1 year, respectively. These outcome predictors should be considered when offering CXL to patients with KC or postoperative corneal ectasia.

Effects of corneal cross-linking on ocular response analyzer waveform-derived variables in keratoconus and postrefractive surgery ectasia.

PURPOSE: To assess changes in Ocular Response Analyzer (ORA) waveforms after UVA/riboflavin corneal collagen cross-linking (CXL) using investigator-derived and manufacturer-supplied morphometric variables in patients with keratoconus (KC) and postrefractive surgery ectasia. DESIGN: Prospective randomized trial of a standard epithelium-off CXL protocol. PARTICIPANTS: Patients with progressive KC (24 eyes of 21 patients) or postrefractive surgery ectasia (27 eyes of 23 patients) were enrolled. METHODS: Replicate ORA measurements were obtained before and 3 months after CXL. Pretreatment and posttreatment waveform variables were analyzed for differences by paired Student t tests using measurements with the highest waveform scores. MAIN OUTCOME MEASURES: Corneal hysteresis, corneal resistance factor, 37-s generation manufacturer-supplied ORA variables, and 15 investigator-derived ORA variables. RESULTS: No variables were significantly different 3 months after CXL in the KC group, and no manufacturer-supplied variables changed significantly in the postrefractive surgery ectasia group. Four custom variables (ApplanationOnsetTime, P1P2avg, Impulse, and Pmax) increased by small but statistically significant margins after CXL in the postrefractive surgery ectasia group. CONCLUSIONS: Changes in a small subset of investigator-derived variables suggested an increase in corneal bending resistance after CXL. However, the magnitudes of these changes were low and not commensurate with the degree of clinical improvement or prior computational estimates of corneal stiffening in the same cohort over the same period. Available air-puff-derived measures of the corneal deformation response underestimate the biomechanical changes produced by CXL.

Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial.

AIM: Patients with Marfan syndrome have an increased risk of life-threatening aortic complications, mostly preceded by aortic dilatation. Treatment with losartan, an angiotensin-II receptor-1 blocker, may reduce aortic dilatation rate in Marfan patients. METHODS AND RESULTS: In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome. The primary endpoint was aortic dilatation rate at any predefined aortic level after 3 years of follow-up, as determined by magnetic resonance imaging. A total of 233 participants (47% female) underwent randomization to either losartan (n = 116) or no additional treatment (n = 117). Aortic root dilatation rate after 3.1 ± 0.4 years of follow-up was significantly lower in the losartan group than in controls (0.77 ± 1.36 vs. 1.35 ± 1.55 mm, P = 0.014). Aortic dilatation rate in the trajectory beyond the aortic root was not significantly reduced by losartan. In patients with prior aortic root replacement, aortic arch dilatation rate was significantly lower in the losartan group when compared with the control group (0.50 ± 1.26 vs. 1.01 ± 1.31 mm, P = 0.033). No significant differences in separate clinical endpoints or the composite endpoint (aortic dissection, elective aortic surgery, cardiovascular death) between the groups could be demonstrated. CONCLUSION: In adult Marfan patients, losartan treatment reduces aortic root dilatation rate. After aortic root replacement, losartan treatment reduces dilatation rate of the aortic arch.

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia.

UNLABELLED: Abstract Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases. MATERIALS AND METHODS: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30 min, and after 10 min of ultraviolet A irradiation. RESULTS: Eleven eyes of eleven patients with progressive keratoconus (n = 10) and iatrogenic corneal ectasia (n = 1) were included in this study. The mean thinnest pachymetric measurements were 391.82 ± 30.34 µm (320-434 µm) after de-epithelialization of the cornea, 435 ± 21.17 µm (402-472 µm) following 30 min instillation of isotonic riboflavin solution without dextran and 431.73 ± 20.64 µm (387-461 µm) following 10 min of ultraviolet A irradiation to the cornea. CONCLUSION: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.