An in vitro investigation into the impact of corneal rinsing on riboflavin/UVA corneal cross-linking.

BACKGROUND: Corneal cross-linking (CXL) using riboflavin and ultraviolet-A light (UVA) is a treatment used to prevent progression of keratoconus. This ex vivo study assesses the impact on CXL effectiveness, as measured by tissue enzymatic resistance and confocal microscopy, of including a pre-UVA corneal surface rinse with balanced salt solution (BSS) as part of the epithelium-off treatment protocol. METHODS: Sixty-eight porcine eyes, after epithelial debridement, were assigned to six groups in three experimental runs. Group 1 remained untreated. Groups 2-6 received a 16-min application of 0.1% riboflavin/Hydroxypropyl methylcellulose (HPMC) drops, after which Group 3 was exposed to 9 mW/cm2 UVA for 10 min, and Groups 4-6 underwent corneal surface rinsing with 0.25 mL, 1 mL or 10 mL BSS followed by 9 mW/cm2 UVA exposure for 10 min. Central corneal thickness (CCT) was recorded at each stage. Central 8.0 mm corneal buttons from all eyes were subjected to 0.3% collagenase digestion at 37 °C and the time required for complete digestion determined. A further 15 eyes underwent fluorescence confocal microscopy to assess the impact of rinsing on stromal riboflavin concentration. RESULTS: Application of riboflavin/HPMC solution led to an increase in CCT of 73 ± 14 µm (P < 0.01) after 16 min. All CXL-treated corneas displayed a 2-4 fold greater resistance to collagenase digestion than non-irradiated corneas. There was no difference in resistance between corneas that received no BSS rinse and those that received a 0.25 mL or 1 mL pre-UVA rinse, but each showed a greater level of resistance than those that received a 10 mL pre-UVA rinse (P < 0.05). Confocal microscopy demonstrated reduced stromal riboflavin fluorescence after rinsing. CONCLUSIONS: All protocols, with and without rinsing, were effective at enhancing the resistance to collagenase digestion, although resistance was significantly decreased, and stromal riboflavin fluorescence reduced with a 10 mL rinse. This suggests that a 10 mL surface rinse can reduce the efficacy of CXL through the dilution of the stromal riboflavin concentration.

Localized uplift, widespread subsidence, and implications for sea level rise in the New York City metropolitan area.

Regional relative sea level rise is exacerbating flooding hazards in the coastal zone. In addition to changes in the ocean, vertical land motion (VLM) is a driver of spatial variation in sea level change that can either diminish or enhance flood risk. Here, we apply state-of-the-art interferometric synthetic aperture radar and global navigation satellite system time series analysis to estimate velocities and corresponding uncertainties at 30-m resolution in the New York City metropolitan area, revealing VLM with unprecedented detail. We find broad subsidence of 1.6 mm/year, consistent with glacial isostatic adjustment to the melting of the former ice sheets, and previously undocumented hot spots of both subsidence and uplift that can be physically explained in some locations. Our results inform ongoing efforts to adapt to sea level rise and reveal points of VLM that motivate both future scientific investigations into surface geology and assessments of engineering projects.

National survey of corneal cross-linking (CXL) practice patterns in the United Kingdom during 2019.

OBJECTIVE: To provide an insight into trends in corneal cross-linking (CXL) practice in the UK, including criteria for progression of corneal ectasia, identification of patients for CXL, the CXL procedure itself and post-operative management. METHODS: All ophthalmologist members of the UK Cross-linking (UK-CXL) Consortium were invited to complete an online survey about CXL practice for the year 2019. The data collected was anonymised by site and analysed with descriptive statistics. RESULTS: Responses were received from 16 individual CXL centres (16/38; 42% response rate) and the data represented ~2,000 CXL procedures performed in the UK in 2019. The commonest indication for CXL was progressive keratoconus. Between centres, there were variations in diagnostic evaluation, patient selection for CXL, the CXL procedure and the pre- and post-operative monitoring of patients. CONCLUSION: Consistent with the wide number of CXL treatment techniques described in the published literature world-wide, variations in the monitoring of corneal ectasia, indications for CXL, CXL practice and post-CXL follow-up were found to exist between UK-based CXL centres.

Landslide Sensitivity and Response to Precipitation Changes in Wet and Dry Climates.

Slow-moving landslides are hydrologically driven. Yet, landslide sensitivity to precipitation, and in particular, precipitation extremes, is difficult to constrain because landslides occur under diverse hydroclimatological conditions. Here we use standardized open-access satellite radar interferometry data to quantify the sensitivity of 38 landslides to both a record drought and extreme rainfall that occurred in California between 2015 and 2020. These landslides are hosted in similar rock types, but span more than ∼2 m/yr in mean annual rainfall. Despite the large differences in hydroclimate, we found these landslides exhibited surprisingly similar behaviors and hydrologic sensitivity, which was characterized by faster (slower) than average velocities during wetter (drier) than average years, once the impact of the drought diminished. Our findings may be representative of future landslide behaviors in California where precipitation extremes are predicted to become more frequent with climate change.

Returning to cataract surgery after a hiatus: a UK survey report.

OBJECTIVES: Cataract surgeons may periodically take time away from operating which can lead to skills fade. There is a paucity of research investigating the experiences of returning cataract surgeons and how different individual circumstances impact on their return. Our aim was to investigate the subjective experiences of UK ophthalmologists simultaneously returning to surgery following the nationwide elective surgical hiatus due to the Covid-19 pandemic. METHODS: An online survey was nationally distributed between 01/09/2020 and 29/10/2020 to registered UK ophthalmologists. Participants indicating a surgical hiatus of 8 weeks or more were included. RESULTS: 232 of 264 responses were analysed. Covid-19 was the most frequent reason for a surgical hiatus (median 15 weeks). Perceived operating difficulties were found in 29.1%. Transient anxiety (51.7%), reduced confidence, and perceived increased surgical time were commonplace. Trainees and females were more likely to encounter negative experiences (p < 0.001) and barriers to resource accessibility. Eyesi® and online videos were the most available and accessed pre-return resources. Childcare was five times more likely to present as a barrier to resource access for females than males. CONCLUSIONS: Technical skills fade such as capsulorhexis difficulties were commonly perceived by trainee surgeons in addition to transient anxiety, reported in more than half of all surgeons following a hiatus as short as 8 weeks. Eyesi® simulation offers the potential to negate technical de-skilling. Few had formal return plans or awareness of RCOphth guidance. We believe there is scope for more specialised and targeted support for future returning cataract surgeons thereby optimising patient care.

Understanding of Contemporary Regional Sea-Level Change and the Implications for the Future.

Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time. Despite the advances, gaps in the understanding of contemporary sea-level change remain and inhibit the ability to predict how the relevant processes may lead to future change. These gaps arise in part due to the complexity of the linkages between the drivers of sea-level change. Here we review the individual processes which lead to sea-level change and then describe how they combine and vary regionally. The intent of the paper is to provide an overview of the current state of understanding of the processes that cause regional sea-level change and to identify and discuss limitations and uncertainty in our understanding of these processes. Areas where the lack of understanding or gaps in knowledge inhibit the ability to provide the needed information for comprehensive planning efforts are of particular focus. Finally, a goal of this paper is to highlight the role of the expanded sea-level observation network-particularly as related to satellite observations-in the improved scientific understanding of the contributors to regional sea-level change.

Effects of intraocular lens glistenings on visual function: a prospective study and presentation of a new glistenings grading methodology.

OBJECTIVE: To investigate the effect of intraocular lens (IOL) glistenings on visual performance and evaluate a new glistenings grading methodology. METHODS AND ANALYSIS: Thirty-four patients (34 eyes) were recruited. Corrected distance visual acuity (CDVA), mesopic gap acuity (MGA), functional contrast sensitivity (FCS) and forward light scatter were measured (Advanced Vision and Optometric Tests, City Occupational, London, UK). The IOL centre was imaged and glistenings density graded by three observers using the Miyata scale and a new system. Inter-rater reliability, association between the two grading scales, and correlations between glistenings grades and visual performance parameters were evaluated. RESULTS: The intraclass correlation coefficient between graders for the new grading system was 0.769 (95% Confidence Interval [CI] 0.636 to 0.868). There was a significant association between the Miyata scale and the new grading system for all graders (rs=0.533-0.895, p≤0.001). There was no association between CDVA or MGA and glistenings grade (rs=- 0.098, p=0.583 and rs=0.171, p=0.359, respectively). There was no association between FCS at mesopic light levels and glistenings grade (rs=-0.032, p=0.864), or the straylight parameter and glistenings grade (rs=0.021, p=0.916). No association was found between the integrated straylight parameter and glistenings grade (rs=0.078, p=0.701). CONCLUSION: The new glistenings grading scale was highly reproducible. In this cohort, glistenings in the same hydrophobic acrylic IOL after cataract surgery were not associated with changes in visual function, as assessed by a series of tests not previously used in glistenings research.

Risk-Adjusted CUSUM Analysis of the Learning Curve of Femtosecond Laser Assisted Cataract Surgery.

Objectives: To determine the length of the learning curve of femtosecond laser-assisted cataract surgery (FLACS) by a risk-adjusted cumulative sum method. Materials and Methods: This was a retrospective review of the first 288 FLACS performed by three surgeons over a 12-month period. The learning curves were analyzed separately for each surgeon and as pooled data via risk-adjusted cumulative sum methods. Change-point analysis was performed to estimate the length of the learning curve. Results: Rates of complications were as follows: anterior capsular tear (ACT) (3.4%), posterior capsular rupture (PCR) (0.7%), vitreous loss (0.3%), iris trauma (0.7%), Descemet's membrane tear (0.3%). There was a strong confidence level (96%) that there was a stable performance in terms of PCR after case 16 for the pooled data. Surgeon 1 did not have any cases of PCR, surgeons 2 and 3 exhibited change points at case 5 and 16, respectively (confidence levels = 99%, 98%). There was a strong confidence level (99.8%) that there was stable performance in terms of ACT after case 14 for the pooled data, however the individual surgeons demonstrated individual change points at case 1 (surgeon 1, confidence 99%), case 14 (surgeon 2, confidence 99%), and case 49 (surgeon 3, confidence 96%). Conclusions: The results suggest that there is an increased risk of ACT and PCR in FLACS within a surgeon's first 14 and 16 operations, respectively. Measures should be adopted to minimize harm to patients during this phase. However, overall rates of complications were safe.

Refractive surprise after routine cataract surgery with multifocal IOLs attributable to corneal epithelial basement membrane dystrophy.

We describe two patients in whom postsurgical refractive error occurred after routine refractive lens exchange cataract surgery with multifocal intraocular lens insertion most likely attributable to the presence of underlying corneal epithelial basement membrane dystrophy (EBMD). In Case 1, there was an unexpected hyperopic postoperative spherical equivalent refractive error of +1.50 diopters and in Case 2, a cylindrical refractive error of 2.75 diopter cylinder. We examine the possible causes of error and discuss potential management strategies to prevent and address these unpredictable postoperative outcomes. The importance of comprehensive and careful ocular surface assessment before cataract or refractive surgery as part of the presurgical workup is reemphasized. EBMD can be subtle and if overlooked, can affect the validity of biometric keratometric measurements preoperatively, resulting in an inaccurate biometry measurement, incorrect IOL selection, and reduced visual performance and patient satisfaction.

A randomized controlled trial comparing femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery.

PURPOSE: To compare the clinical results of conventional phacoemulsification surgery (CPS) with femtosecond laser-assisted cataract surgery. SETTING: Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom. DESIGN: Single-center prospective randomized interventional case-controlled trial. METHODS: Patients undergoing cataract surgery were randomized to receive either CPS or femtosecond laser-assisted cataract surgery. The surgery was performed with a femtosecond laser (Lensx), and all operations were performed with a gravity-fluidics torsional phacoemulsification machine (Infiniti). The visual acuity, refraction, central corneal thickness (CCT), central foveal thickness (CFT), endothelial cell loss, and rates of intraoperative and postoperative events were recorded. Quality of life outcomes were measured with the EuroQOL 5 dimensions questionnaire (EQ-5D) and patient-reported quality of vision was assessed with a cataract surgery patient-reported outcome measures questionnaire (Cat-PROM5). RESULTS: The study comprised 400 eyes of 400 patients who had CPS (n = 200) or femtosecond laser-assisted cataract surgery (n = 200). Seven patients (3.5%) in the femtosecond laser-assisted group were not able to complete the treatment and received CPS. The mean uncorrected distance visual acuity (logarithm of the minimum angle of resolution [logMAR]) 0.15 ± 0.21 (SD) and 0.15 ± 0.19 logMAR after CPS and femtosecond laser-assisted surgery, respectively (P = 1.0); the pinhole-corrected visual acuity was 0.04 ± 0.12 and 0.04 ± 0.12, respectively (P = 1.0); the increase in CCT was 13 ± 19 µm and 15 ± 25 µm, respectively (P = .5); and the endothelial cell loss was 9.7 ± 13.7 % and 10.2% ± 13.7, respectively (P = .76). The manifest refraction spherical equivalent error was -0.14 ± 0.60 diopters (D) after CPS and -0.12 ± 0.60 D after femtosecond laser-assisted surgery (P = .74); the mean change in CFT was 9 ± 35 µm and 6 ± 35 µm, respectively (P = .55); and the rate of posterior capsule rupture was 3% and 0%, respectively (P = .03). CONCLUSIONS: This study confirms the nonsignificant differences between 2 treatment modalities, notwithstanding a significant reduction in posterior capsule ruptures in the femtosecond laser-assisted surgery group.

Comparison of Standard Versus Accelerated Corneal Collagen Cross-Linking for Keratoconus: A Meta-Analysis.

Purpose: To systematically compare epithelial-off standard (SCXL) to accelerated corneal collagen cross-linking (ACXL) for the treatment of keratoconus. Methods: PubMed, Embase, the Cochrane Library, and the US trial registry were searched for trials comparing SCXL and ACXL for keratoconus up to October 2017. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Primary outcomes were changes in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness (CCT), and endothelial cell density (ECD). Results: Eleven trials were included. For primary outcomes, SCXL showed a greater reduction in Kmax (SMD 0.32; 95% CI 0.16, 0.48) than ACXL. For secondary outcomes, the decrease in CCT (SMD 0.32; 95% CI 0.03, 0.61) and ECD (SMD 0.26; 95% CI 0.06, 0.46) was less with ACXL than with SCXL. For the other outcomes, there were no statistically significant differences. Conclusions: SCXL has a greater effect in terms of reduction in Kmax than ACXL, while ACXL induces less reduction in CCT and ECD than SCXL. Further well-designed randomized controlled trials comparing ACXL and SCXL are indicated.

Refractive outcomes after limbal relaxing incisions or femtosecond laser arcuate keratotomy to manage corneal astigmatism at the time of cataract surgery.

PURPOSE: To compare the results of manual limbal relaxing incisions (LRIs) performed during conventional phacoemulsification surgery with those of nonpenetrating femtosecond laser arcuate keratotomies performed during femtosecond laser-assisted cataract surgery to manage corneal astigmatism. SETTING: Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom. DESIGN: Randomized case-controlled trial. METHODS: This was a secondary outcome of a randomized controlled trial comparing 400 patients treated with conventional phacoemulsification surgery or femtosecond laser-assisted cataract surgery. All patients with corneal astigmatism greater than 0.9 diopter (D) were offered LRIs or femtosecond laser arcuate keratotomy based on the original randomization. Visual acuity, postoperative refraction, and corneal topography were recorded 4 weeks postoperatively. Vector analysis was performed using the Alpins method. RESULTS: Fifty-one eyes of 51 patients received LRIs, and 53 eyes of 53 patients received femtosecond arcuate keratotomies. The mean target induced astigmatism was 1.50 D and 1.38 D, respectively, with 1.02 D and 1.23 D surgically induced astigmatism (P = .21), resulting in the femtosecond arcuate keratotomy group having a smaller difference vector (1.17 D versus 0.89 D; P = .02) and a greater correction index (0.48 versus 0.73; P = .02). Forty-four percent of patients in the femtosecond arcuate keratotomy group and 20% in the LRI group attained a postoperative cylinder of less than 0.50 D (P = .01). CONCLUSIONS: The femtosecond arcuate keratotomy group achieved a higher correction index and a smaller difference vector. The femtosecond arcuate keratotomy patients showed less postoperative cylinder than LRI patients.

Constant strain accumulation rate between major earthquakes on the North Anatolian Fault.

Earthquakes are caused by the release of tectonic strain accumulated between events. Recent advances in satellite geodesy mean we can now measure this interseismic strain accumulation with a high degree of accuracy. But it remains unclear how to interpret short-term geodetic observations, measured over decades, when estimating the seismic hazard of faults accumulating strain over centuries. Here, we show that strain accumulation rates calculated from geodetic measurements around a major transform fault are constant for its entire 250-year interseismic period, except in the ~10 years following an earthquake. The shear strain rate history requires a weak fault zone embedded within a strong lower crust with viscosity greater than ~1020 Pa s. The results support the notion that short-term geodetic observations can directly contribute to long-term seismic hazard assessment and suggest that lower-crustal viscosities derived from postseismic studies are not representative of the lower crust at all spatial and temporal scales.

An Investigation of the Effects of Riboflavin Concentration on the Efficacy of Corneal Cross-Linking Using an Enzymatic Resistance Model in Porcine Corneas.

Purpose: To investigate riboflavin concentration on enzymatic resistance following corneal cross-linking (CXL). Methods: Ninety-six porcine eyes were divided into five groups in two treatment runs. Group 1 remained untreated. Group 2 received riboflavin 0.05%, group 3 riboflavin 0.1%, group 4 riboflavin 0.2%, and group 5 riboflavin 0.3%. Treated eyes underwent CXL with ultraviolet A at 9 mW/cm2 for 10 minutes. Eight-millimeter discs from each cornea were submerged in pepsin digest solution. In the first run, disc diameters were measured daily. After 10 days, dry weights were recorded from five samples in each group. In the second run, dry weights were recorded in five samples in each group at 10 and 20 days. Results: CXL-treated corneas took longer to digest than untreated (P < 0.001). Although eyes treated with higher riboflavin concentrations generally took longer to digest, there were no significant differences between groups (P = 0.3). Dry weights at 10 days demonstrated, with each increase in concentration, an increase in weight of residual undigested tissue (P < 0.001). In the second run, with each increase in riboflavin concentration there was an increase in weight of residual tissue (P < 0.001) at 10 days. At 20 days, the dry weight was lower with 0.05% riboflavin compared to 0.3% (P < 0.001) and 0.2% and 0.1% solutions (P < 0.05), with no other difference between groups. Conclusions: There is a consistent dose-response curve with higher concentrations of riboflavin achieving greater CXL efficacy, suggesting that manipulation of riboflavin dosage as well as the UVA protocol can be used to optimize CXL.

Evaluation of a hub-and-spoke model for the delivery of femtosecond laser-assisted cataract surgery within the context of a large randomised controlled trial.

AIMS: To test a hypothesis that cataract operating room (OR) productivity can be improved with a femtosecond laser (FL) using a hub-and-spoke model and whether any increase in productivity can offset additional costs relating to the FL. METHODS: 400 eyes of 400 patients were enrolled in a randomised-controlled trial comparing FL-assisted cataract surgery (FLACS) with conventional phacoemulsification surgery (CPS). 299 of 400 operations were performed on designated high-volume theatre lists (FLACS=134, CPS=165), where a hub-and-spoke FLACS model (1×FL, 2×ORs=2:1) was compared with independent CPS theatre lists. Details of operative timings and OR utilisation were recorded. Differences in productivity between hub-and-spoke FLACS and CPS sessions were compared using an economic model including testing hypothetical 3:1 and 4:1 models. RESULTS: The duration of the operation itself was 12.04±4.89 min for FLACS compared with CPS of 14.54±6.1 min (P<0.001). Total patient time in the OR was reduced from 23.39±6.89 min with CPS to 20.34±5.82 min with FLACS (P<0.001)(reduction of 3.05 min per case). There was no difference in OR turnaround time between the models. Average number of patients treated per theatre list was 9 for FLACS and 8 for CPS. OR utilisation was 92.08% for FLACS and 95.83% for CPS (P<0.001). Using a previously established economic model, the FLACS service cost £144.60 more than CPS per case. This difference would be £131 and £125 for 3:1 and 4:1 models, respectively. CONCLUSION: The FLACS hub-and-spoke model was significantly faster than CPS, with patients spending less time in the OR. This enabled an improvement in productivity, but insufficient to meaningfully offset the additional costs relating to FLACS.

Time and motion studies of National Health Service cataract theatre lists to determine strategies to improve efficiency.

AIM: To provide a quantitative assessment of cataract theatre lists focusing on productivity and staffing levels/tasks using time and motion studies. METHODS: National Health Service (NHS) cataract theatre lists were prospectively observed in five different institutions (four NHS hospitals and one private hospital). Individual tasks and their timings of every member of staff were recorded. Multiple linear regression analyses were performed to investigate possible associations between individual timings and tasks. RESULTS: 140 operations were studied over 18 theatre sessions. The median number of scheduled cataract operations was 7 (range: 5-14). The average duration of an operation was 10.3 min±(SD 4.11 min). The average time to complete one case including patient turnaround was 19.97 min (SD 8.77 min). The proportion of the surgeons' time occupied on total duties or operating ranged from 65.2% to 76.1% and from 42.4% to 56.7%, respectively. The correlations of the surgical time to patient time in theatre was R2=0.95. A multiple linear regression model found a significant association (F(3,111)=32.86, P<0.001) with R2=0.47 between the duration of one operation and the number of allied healthcare professionals (AHPs), the number of AHP key tasks and the time taken to perform these key tasks by the AHPs. CONCLUSIONS: Significant variability in the number of cases performed and the efficiency of patient flow were found between different institutions. Time and motion studies identified requirements for high-volume models and factors relating to performance. Supporting the surgeon with sufficient AHPs and tasks performed by AHPs could improve surgical efficiency up to approximately double productivity over conventional theatre models.

Cost-Effectiveness Analysis of Corneal Collagen Crosslinking for Progressive Keratoconus.

PURPOSE: To evaluate the cost effectiveness of corneal collagen crosslinking (CXL) for progressive keratoconus from the healthcare payer's perspective. DESIGN: A probabilistic Markov-type model using data from published clinical trials and cohort studies. PARTICIPANTS: Two identical cohorts, each comprising 1000 virtual patients with progressive bilateral keratoconus, were modeled; one cohort underwent CXL and the other cohort received no intervention. METHODS: Both cohorts were modeled and evaluated annually over a lifetime. Quality-adjusted life years (QALYs), total cost, disease progression, and the probability of corneal transplantation, graft failure, or both were calculated based on data from published trials and cohort studies. These outcomes were compared between the 2 cohorts. In our base scenario, the stabilizing effect of CXL was assumed to be 10 years; however, longer durations also were analyzed. One-way sensitivity analyses were performed to test the robustness of the outcomes. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio (ICER), defined as euros per QALY. RESULTS: Assuming a 10-year effect of CXL, the ICER was €54 384/QALY ($59 822/QALY). When we adjusted the effect of CXL to a lifelong stabilizing effect, the ICER decreased to €10 149/QALY ($11 163/QALY). Other sensitivity and scenario analyses that had a relevant impact on ICER included the discount rate, visual acuity before CXL, and healthcare costs. CONCLUSIONS: Corneal collagen crosslinking for progressive keratoconus is cost effective at a willingness-to-pay threshold of 3 times the current gross domestic product (GDP) per capita. Moreover, a longer stabilizing effect of CXL increases cost effectiveness. If CXL had a stabilizing effect on keratoconus of 15 years or longer, then the ICER would be less than the 1 × GDP per capita threshold and thus very cost effective.

Corneal collagen crosslinking for corneal ectasias: a review.

PURPOSE: To review the published literature on corneal collagen crosslinking (CXL). METHODS: Importance has been placed on seminal publications, systemic reviews, meta-analyses, and randomized controlled clinical trials. Where such evidence was not available, cohort studies, case-controlled studies, and case series with follow-up greater than 12 months were examined. RESULTS: Corneal collagen crosslinking with riboflavin and ultraviolet A (UVA) 370 nm radiation appears to be capable of arresting the progression of ectatic corneal disorders, with most studies reporting significant improvements in visual, keratometric, and topographic measurements. Its mode of action at the molecular level is undetermined. Follow-up is limited to 5-10 years but suggests sustained stability and enhancement in corneal shape with time. Nearly all published long-term data and comparative studies are with epithelium-off techniques. Epithelium-on investigations suggest some efficacy but less than with epithelium-off treatments and long-term data are unavailable. Accelerated techniques with higher UVA fluencies and shorter treatments times, delivering the same UVA energy dosage, are the subject of recent investigation, with some laboratory and clinical studies suggesting reduced efficacy compared to the standard 3 mW/cm2 for 30 minutes irradiation procedure. Combined methodologies of CXL with techniques such as photorefractive keratectomy and intrastromal rings show promise but long-term follow-up is indicated. Sight-threatening complications of CXL are rare. CONCLUSIONS: Studies of epithelium-off CXL with irradiation at 3 mW/cm2 for 30 minutes support its efficacy. Refinement in techniques may allow for safer and more rapid procedures with less patient discomfort but require further investigation.