Incidence of Leber hereditary optic neuropathy in 2019 in Japan: a second nationwide questionnaire survey.

BACKGROUND: Leber hereditary optic neuropathy (LHON) is an acute or subacute optic neuropathy that mainly affects young males. The first nationwide epidemiological survey of LHON was conducted in 2014 in Japan, and LHON was officially designated as a rare intractable disease by the Japanese government in 2015. We conducted a second survey of the annual incidence of LHON in 2019, and estimated the total number of patients with LHON in Japan. RESULTS: A questionnaire was sent to 997 facilities accredited by the Japanese Ophthalmological Society and/or affiliated with the councilors of the Japanese Neuro-Ophthalmology Society. Responses were received from 791 facilities, with a response rate of 79%. Fifty-five newly diagnosed cases (49 males and 6 females) of LHON were reported from 35 institutions in 2019, with a median age of 28.5 for males and 49.5 years for females. The total number of newly diagnosed cases was calculated as 69 (62 were males and 7 were females, 95% confidence interval 55-83), and the total number of patients was estimated to be 2491 (95% confidence interval: 1996-2986), suggesting a prevalence of LHON in Japan of 1:50,000. CONCLUSION: The incidence of LHON in 2019 was lower than the estimate in 2014, whereas its prevalence may be similar to that reported in other countries. The accurate estimation of the incidence and prevalence of patients with LHON requires prospective registration.

Nationwide epidemiological approach to identify associations between keratoconus and immune-mediated diseases.

BACKGROUND: The aetiology of keratoconus (KC) remains poorly understood. KC has typically been described as a non-inflammatory disorder of the cornea. Nonetheless, there is increasing presumptive evidence for the role of the immune system in the pathogenesis of KC. AIM: To evaluate the association between KC and immune-mediated diseases on a population level. We hypothesise that KC is immune-mediated rather than a predominantly degenerative disease. METHODS: Data were obtained from the largest health insurance provider in the Netherlands. Dutch residents are obligatorily insured. The data contained all medical claims and sociodemographic characteristics from all KC patients plus all those data from a 1:6 age-matched and sex-matched control group. The primary outcome was the association between KC and immune-mediated diseases, as assessed by conditional logistic regression. RESULTS: Based on our analysis of 2051 KC cases and 12 306 matched controls, we identified novel associations between KC and Hashimoto's thyroiditis (OR=2.89; 95% CI: 1.41 to 5.94) and inflammatory skin conditions (OR=2.20; 95% CI: 1.37 to 3.53). We confirmed known associations between KC and atopic conditions, including allergic rash (OR=3.00; 95% CI: 1.03 to 8.79), asthma and bronchial hyperresponsiveness (OR=2.51; 95% CI: 1.63 to 3.84), and allergic rhinitis (OR=2.20; 95% CI: 1.39 to 3.49). CONCLUSION: Keratoconus appears positively associated with multiple immune-mediated diseases, which provides a population-based argument that systemic inflammatory responses may influence its onset. The identification of these particular diseases might shed light on potential comparable pathways through which this proinflammatory state is achieved, paving the way for pharmacological treatment strategies.

Correction: The evaluation of a web-based tool for measuring the uncorrected visual acuity and refractive error in keratoconus eyes: A method comparison study.

[This corrects the article DOI: 10.1371/journal.pone.0256087.].

The evaluation of a web-based tool for measuring the uncorrected visual acuity and refractive error in keratoconus eyes: A method comparison study.

PURPOSE: To evaluate the outcome of a web-based digital assessment of visual acuity and refractive error, compared to a conventional supervised assessment, in keratoconus patients with complex refractive errors. MATERIAL AND METHODS: Keratoconus patients, aged 18 to 40, with a refractive error between -6 and +4 diopters were considered eligible. An uncorrected visual acuity and an assessment of refractive error was taken web-based (index test) and by manifest refraction (reference test) by an optometrist. Corrected visual acuity was assessed with the prescription derived from both the web-based tool and the manifest refraction. Non-inferiority was defined as the 95% limits-of-agreement (95%LoA) of the differences in spherical equivalent between the index and reference test not exceeding +/- 0.5 diopters. Agreement was assessed by a Bland-Altman analyses. RESULTS: A total of 100 eyes of 50 patients were examined. The overall mean difference of the uncorrected visual acuity measured -0.01 LogMAR (95%LoA:-0.63-0.60). The variability of the differences decreased in the better uncorrected visual acuity subgroup (95%LoA:-0.25-0.55). The overall mean difference in spherical equivalent between the index and reference test exceeded the non-inferiority margin: -0.58D (95%LoA:-4.49-3.33, P = 0.008). The mean differences for myopic and hyperopic subjects were 0.09 diopters (P = 0.675) and -2.06 diopters (P<0.001), respectively. The corrected visual acuities attained with the web-based derived prescription underachieved significantly (0.22±0.32 logMAR vs. -0.01±0.13 LogMAR, P <0.001). CONCLUSIONS: Regarding visual acuity, the web-based tool shows promising results for remotely assessing visual acuity in keratoconus patients, particularly for subjects within a better visual acuity range. This could provide physicians with a quantifiable outcome to enhance teleconsultations, especially relevant when access to health care is limited. Regarding the assessment of the refractive error, the web-based tool was found to be inferior to the manifest refraction in keratoconus patients. This study underlines the importance of validating digital tools and could serve to increase overall safety of the web-based assessments by better identification of outlier cases.

Intraoperative Optical Coherence Tomography-Assisted Descemet Membrane Endothelial Keratoplasty: Toward More Efficient, Safer Surgery.

PURPOSE: To evaluate the clinical value of intraoperative optical coherence tomography (iOCT) and prolonged overpressure in Descemet membrane endothelial keratoplasty for surgical safety, efficiency, and outcome. METHODS: All Descemet membrane endothelial keratoplasties performed by the same surgeon from November 2016 through April 2018 at the University Medical Center Utrecht were included, including 6 months of follow-up. The primary outcome was the prevalence of adverse events, and the secondary outcomes included critical decision-making and surgery time. Surgeries that included prolonged (ca. 12 minutes) overpressurization of the globe were classified as group 1, and those without prolonged overpressurization of the globe were classified as group 2. In all cases, iOCT was used to determine the graft orientation, apposition, and assessment of interface fluid. RESULTS: A total of 38 cases were included for analysis. In groups 1 and 2, 7 (43.6%) and 4 (18.1%) adverse events, respectively, were recorded (P = 0.29). Specifically, in groups 1 and 2, 4 and 3 cases, respectively, required rebubbling because of graft dislocation (P = 0.15). In 43% of surgeries, iOCT proved to be of value for surgical decision-making. Surgery time differed significantly between groups 1 and 2 (P < 0.001) and was the result of a shortened pressurization time in group 2. CONCLUSIONS: iOCT provides a direct assessment of the graft orientation and apposition, allowing the surgeon to refrain from prolonged pressurization of the globe after graft insertion. Optimizing the surgical protocol using iOCT can lead to a significant reduction in surgery time without compromising surgical safety or outcome.

Prospective 3-arm study on pain and epithelial healing after corneal crosslinking.

PURPOSE: To investigate the effect of 3 regimes on pain and wound healing after corneal crosslinking (CXL). SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN: Prospective cohort study. METHODS: Consecutive progressive keratoconus patients who underwent 9 mW/cm epithelium-off CXL were included. Patients received a bandage contact lens (n = 20), occlusive patch (n = 20), or antibiotic ointment (n = 20) after treatment. Pain scores and quality of life, measured by the McGill Pain Questionnaire and Visual Analogue Scale (VAS), were analyzed. Epithelial healing after 2 days, correlations between pain and psychological factors that influence pain perception (depression anxiety stress score and pain catastrophizing score), and oral pain medication were evaluated. RESULTS: Sixty eyes of 52 patients were analyzed. On average, patients experienced considerable pain after CXL (median VAS score 6.2, range 0 to 10). The postoperative regimen did not significantly affect pain scores, although the antibiotic ointment group reported a higher VAS score (median VAS score 7.2 vs 6.7 and 6.0; P = .57). Occlusive patching showed a trend to quicker resolution of epithelial defects (85% completely healed vs 65% with lenses and 70% with antibiotic ointment; P = .43). Correlations with pain-modulating psychological factors were weak (R < 0.3) and not significant. The use of pain medication corresponded poorly to the prescribed use. CONCLUSION: This study demonstrated clinical equivalence of 3 regimes in combating postoperative pain after routine CXL. Wound healing appeared quicker in the occlusive patch group and therefore might be the best standard of care after CXL. The clinical tradition of using bandage contact lenses should be reevaluated.

The Independent Effect of Various Cross-Linking Treatment Modalities on Treatment Effectiveness in Keratoconus.

PURPOSE: To investigate the 1-year outcomes of using various corneal cross-linking (CXL) techniques for treating keratoconus. METHODS: Setting: This is a prospective longitudinal cohort study performed at a tertiary academic medical center. PATIENT POPULATION: Six hundred seventy eyes of 461 patients with progressive keratoconus who underwent CXL were followed up for 1 year. INTERVENTION: Eight combinations of CXL modalities were assessed, including 2 different CXL techniques (transepithelial or epithelium-off), 7 riboflavin formulations, and 2 ultraviolet-A protocols (conventional 3 mW/cm or accelerated 9 mW/cm). Patients treated using the Dresden protocol were used as the reference group. MAIN OUTCOME MEASURES: Primary outcomes were maximum keratometry and mean keratometry 1 year after treatment. Multivariable linear regression was used which provides ß coefficients (ß). Secondary outcomes were uncorrected and corrected distance visual acuity, manifest refractive spherical equivalent, and corneal thickness 1 year after treatment. RESULTS: Four treatment modalities differed significantly from the reference group regarding both maximum keratometry and mean keratometry: the transepithelial CXL (TE-CXL) group (ß = 1.422; P = 0.001), 1 riboflavin formulation (Meran ß = 1.210; P = 0.02), and both the 9 mW/cm protocols (Vibex Rapid ß = 1.751; P < 0.001 and Collagex ß = 1.170, P < 0.001). Overall, the visual outcome, manifest refractive spherical equivalent, and corneal thickness were similar among the treatment modalities. Infections were rare (1.6% of cases); however, re-treatment was required for 33.3% of cases that underwent TE-CXL. CONCLUSIONS: TE-CXL, the use of Meran riboflavin, and applying the accelerated irradiation protocol appeared to be associated with reduced efficacy regarding controlling keratoconus progression. One-third of cases treated using TE-CXL required re-treatment.

Validation of an Independent Web-Based Tool for Measuring Visual Acuity and Refractive Error (the Manifest versus Online Refractive Evaluation Trial): Prospective Open-Label Noninferiority Clinical Trial.

BACKGROUND: Digital tools provide a unique opportunity to increase access to eye care. We developed a Web-based test that measures visual acuity and both spherical and cylindrical refractive errors. This test is Conformité Européenne marked and available on the Easee website. The purpose of this study was to compare the efficacy of this Web-based tool with traditional subjective manifest refraction in a prospective open-label noninferiority clinical trial. OBJECTIVE: The aim of this study was to evaluate the outcome of a Web-based refraction compared with a manifest refraction (golden standard). METHODS: Healthy volunteers from 18 to 40 years of age, with a refraction error between -6 and +4 diopter (D), were eligible. Each participant performed the Web-based test, and the reference test was performed by an optometrist. An absolute difference in refractive error of <0.5 D was considered noninferior. Reliability was assessed by using an intraclass correlation coefficient (ICC). Both uncorrected and corrected visual acuity were measured. RESULTS: A total of 200 eyes in 100 healthy volunteers were examined. The Web-based assessment of refractive error had excellent correlation with the reference test (ICC=0.92) and was considered noninferior to the reference test. Uncorrected visual acuity was similar with the Web-based test and the reference test (P=.21). Visual acuity was significantly improved using the prescription obtained by using the Web-based tool (P<.01). The Web-based test provided the best results in participants with mild myopia (ie, <3 D), with a mean difference of 0.02 (SD 0.49) D (P=.48) and yielding a corrected visual acuity of >1.0 in 90% (n=77) of participants. CONCLUSIONS: Our results indicate that Web-based eye testing is a valid and safe method for measuring visual acuity and refractive error in healthy eyes, particularly for mild myopia. This tool can be used for screening purposes, and it is an easily accessible alternative to the subjective manifest refraction test. TRIAL REGISTRATION: Clinicaltrials.gov NCT03313921; https://clinicaltrials.gov/ct2/show/NCT03313921.

Clinical Evaluation and Validation of the Dutch Crosslinking for Keratoconus Score.

Importance: Defining keratoconus progression is fundamental in clinical decision making because crosslinking treatments are indicated when the disease is considered progressive. Currently, there is no consensus which parameters should be used to define progression. Objective: To assess and validate a novel clinical scoring system as an easy-to-use assessment tool for crosslinking treatment in patients with keratoconus. Design, Setting, and Participants: Prospective cohort study at 2 academic treatment centers. Patients with keratoconus referred between January 1, 2012, and June 30, 2014, with 2-year follow-up were included. Analysis began March 2017. Interventions: The Dutch Crosslinking for Keratoconus (DUCK) score is based on changes in 5 clinical parameters that are routinely assessed: age, visual acuity, refraction error, keratometry, and subjective patient experience. The DUCK score is derived by scoring 0 to 2 points per item, and cutoffs were determined by clinical experience. We compared the DUCK scores to the conventional 1.0-diopter increase in maximum keratometry criterion, within the last 12 months, in a longitudinal discovery and a validation cohort. Sensitivity analyses and intraitem correlations were performed. Main Outcomes and Measures: Overall treatment rate reduction and the duly withheld treatment rate. Results: A total of 504 eyes of 388 patients were available for analysis on disease progression in the course of 12 and 24 months. Baseline patient characteristics of the discovery cohort and the validation cohort were comparable in terms of age (mean [SD], 26.8 [8.3] years vs 26.3 [9.1]), sex (216 of 332 [65%] vs 123 of 172 [72%] men), and maximum keratometry (mean [SD], 53.5 [7.1] vs 52.7 [6.3]). Adhering to the DUCK score, rather than maximum keratometry, was associated with a reduction in overall treatment rate by 23% (95% CI, 18%-30%), without increasing the risk of disease progression (ie, the rate of progression for both groups was equal; ±0%). The DUCK score appears to better identify eyes that were duly withheld treatment by 35% (95% CI, 22%-49%). Conclusions and Relevance: These results provide validation of the DUCK score as a tool to determine whether a crosslinking treatment might be warranted. Compared with the conventional maximum keratometry criterion of more than 1.0 diopter, the DUCK score may better select patients who might benefit from crosslinking treatment. Potentially, it may prevent unnecessary treatments, reduce exposure to treatment risks, and improve the cost effectiveness of crosslinking.

Autorefraction Versus Manifest Refraction in Patients With Keratoconus.

PURPOSE: To compare visual performance using autorefraction and manifest refraction assessments in patients with keratoconus and investigate whether autorefraction measurements lead to suboptimal visual performance. METHODS: Corrected distance visual acuity (CDVA) was measured in 90 eyes of 61 patients with keratoconus with both autorefraction and manifest refraction, in a random order. Maximum keratometry (Kmax), cone location, and wavefront aberration were determined with Scheimpflug tomography. The difference between the autorefraction and manifest refraction outcomes was converted to vectors and a multivariable analysis was performed to identify potential underlying causes of this difference. RESULTS: A significantly better CDVA was achieved with manifest refraction (0.06 vs 0.29 logMAR [20/23 vs 20/38 Snellen], P < .001). After vector analysis, a mean difference of 4.83 diopters was found between autorefraction and manifest refraction. Increased Kmax was strongly and significantly associated with better visual performance of manifest refraction compared to autorefraction (B = 0.496, P = .002). CONCLUSIONS: This study showed that a superior CDVA is achieved with manifest refraction compared to autorefraction in patients with keratoconus. Furthermore, the difference between the two refraction methods increases as the cornea steepens. According to this study, autorefraction is unreliable in patients with keratoconus and should be avoided. [J Refract Surg. 2018;34(1):30-34.].

Von Helmholtz's ophthalmometer: historical review and experience with one of the last surviving original devices.

Hermann von Helmholtz (1821-1894) was one of the most important scientists of the nineteenth century in optics and ophthalmology. One of his significant contributions in the field of vision sciences was the invention of the ophthalmometer in 1850, which was the precursor of the keratometers still used in clinical practice today. However, this development tends to be little recognized, and to be overshadowed by others of the achievements of this singular scientist. This review describes the historical setting behind the von Helmholtz's ophthalmometer and its mechanism. We also describe the modifications that were later made to the design. We report on our experience measuring a living human cornea with one of the last surviving devices in the world. The ophthalmometer by von Helmholtz marked the beginning of an era in the ophthalmology of the late nineteenth century, and although its original design was not broadly used in the clinical practice, and later abandoned, it opened the way for the development of practical systems very similar to the ones that we use even today.

Higher order optical aberrations and visual acuity in a randomized controlled trial comparing transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus.

PURPOSE: The purpose of this study was to compare the effects of transepithelial crosslinking (trans-CXL) versus epithelium-off crosslinking (epi-off CXL) for progressive keratoconus with respect to the development of higher order aberrations (HOAs) and their effects on visual acuity. MATERIALS AND METHODS: A total of 61 patients were randomized and examined preoperatively and 1, 3, 6, and 12 months postoperatively in an academic referral center. Total corneal HOAs were compared between the two treatment groups using mixed linear modeling. Types of HOAs (coma, trefoil, and spherical aberration) that differed between groups were entered in a multivariable analysis to test their effect on uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). RESULTS: The epi-off CXL group had more flattening in maximal keratometry compared to the trans-CXL group (P=0.02). UDVA did not differ significantly between the groups (P=0.59); however, CDVA was significantly more improved in the trans-CXL group (P=0.02). Horizontal trefoil improved more in the epi-off group compared to the trans-CXL group (P=0.04), whereas the other HOAs were virtually unchanged in both groups. Differences in changes in HOAs between the two groups had no effect on either UCVA (P=0.76) or CDVA (P=0.96). CONCLUSION: Although HOAs are clinically relevant determinants of vision quality in keratoconus patients, the change in total HOAs post treatment did not differ between the trans-CXL and epi-off CXL groups. Only horizontal trefoil differed significantly post treatment between the trans-CXL and epi-off CXL groups. However, this difference did not independently affect either UDVA or CDVA. Trans-CXL provides no benefit over epi-off CXL regarding visual relevant HOAs.

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.

Age-specific Incidence and Prevalence of Keratoconus: A Nationwide Registration Study.

PURPOSE: To determine the age-specific incidence and prevalence of keratoconus in the modern era of diagnostics. DESIGN: Epidemiologic study. PARTICIPANTS: Total of 4.4 million patients from a mandatory health insurance database. METHODS: Data were extracted from the largest health insurance provider in the Netherlands. Patients aged 10-40 years were defined as the relevant age category for newly diagnosed keratoconus and the annual incidence of newly diagnosed keratoconus was determined. The prevalence of keratoconus was estimated based on the annual incidence, mean age at diagnosis, and average life expectancy. Main outcome measure was the annual incidence and prevalence of keratoconus. RESULTS: The annual incidence of keratoconus was 1:7500 in the relevant age category (13.3 cases per 100 000, 95% confidence interval [CI]: 11.6-15.2) and the estimated prevalence of keratoconus in the general population was 1:375 (265 cases per 100 000, 95% CI: 260-270). These values are 5-fold to 10-fold higher than previously reported values in population studies. The mean age at diagnosis was 28.3 years and 60.6% of diagnosed patients were male. CONCLUSIONS: Both the annual incidence and the prevalence of keratoconus were 5-fold to 10-fold higher than previously reported.

Predictors for treatment outcomes after corneal crosslinking for keratoconus: a validation study.

Previous research suggested that baseline corrected distance visual acuity (CDVA) and maximum keratometry (Kmax) are the predictors for effectiveness of corneal crosslinking (CXL) for keratoconus. The aim of this study was to validate the previously determined predictors in a new treatment cohort. A prospective cohort of 112 eyes in 90 consecutive patients was used to validate the results of 102 eyes in 79 patients from our previous prospective cohort. All patients were treated using epithelium-off corneal CXL in a tertiary hospital setting. Primary outcomes were changes in CDVA (LogMAR) and Kmax between baseline and 1-year post-treatment. Predictive factors for both outcomes were determined using univariable and multivariable analyses. Lower pretreatment CDVA was found to be the sole independent factor predicting an improvement in CDVA 1 year after CXL (ß coefficient: -0.476, P < 0.01). Kmax flattening is more likely to take place in eyes with preoperative central cones (ß coefficient: 0.655, P < 0.01). These results are consistent with our initial research and indicate high reproducibility in the new cohort. The previously postulated prediction model for postoperative CDVA showed limited predictive value in the validation cohort (R 2 = 0.15). The clinical implication of these results is that patients with lower pretreatment visual acuity are more likely to benefit from CXL (with respect to visual acuity), and patients with more central cones will benefit more in terms of cone flattening. Furthermore, those results can be used to guide customization of the crosslinking treatment.

Higher-order aberrations 1 year after corneal collagen crosslinking for keratoconus and their independent effect on visual acuity.

PURPOSE: To evaluate the effect of corneal collagen crosslinking (CXL) in progressive keratoconus patients on higher-order aberrations (HOAs) and the effect of change in HOAs on visual acuity between baseline and 1 year after CXL. SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN: Prospective cohort study. METHODS: This study included consecutive keratoconus patients who were treated with epithelium-off CXL and followed for a minimum of 1 year. The following corneal HOAs were measured with Scheimpflug tomography (Pentacam HR type 70900): coma, trefoil, spherical aberration, and total corneal HOAs. A 2-tailed paired-samples t test was used to compare baseline and postoperative aberrations. Multivariable linear regression was applied to assess the independent effects of HOA subtypes on changes in uncorrected (UDVA) and corrected (CDVA) distance visual acuity. RESULTS: Overall, the degree of corneal HOAs in the patient cohort (N = 187) was relatively unchanged after CXL, with a mean change of -1.34% (P = .272). Horizontal coma contributed most to the total amount of HOAs but was virtually unchanged on average. The HOA subtype of spherical aberrations decreased significantly (-15.68%) (P < .001). There was no effect of the change in HOAs on the change in CDVA; however, there was a significant effect of the change in horizontal coma on the change in UDVA (P = .003; B -0.475). CONCLUSIONS: Corneal HOAs in general were relatively unchanged from baseline to 1 year after CXL in eyes with progressive keratoconus. A change in horizontal coma had a strong and independent effect on UDVA. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking.

PURPOSE: Keratoconus is characterized by corneal ectasia and irregular astigmatism, which can lead to diminished vision and corneal scarring. Approximately 10-20% of patients with keratoconus eventually require a corneal transplant. Corneal cross-linking (CXL) is a relatively new treatment that may help prevent the need for corneal transplantation. Here, we investigated whether the introduction of CXL has reduced the number of corneal transplants performed annually. METHODS: Data regarding the transplantation procedures performed in patients under the age of 50 years were extracted from the Dutch National Organ Transplant Registry. The number of corneal transplants performed prior to (i.e. in 2005 through 2007) and following the introduction of CXL (i.e. in 2012 through 2014) were compared. Furthermore, a trend analysis on annual keratoplasties over time was performed. RESULTS: Approximately 25% fewer corneal transplants were performed in the 3-year period following the introduction of CXL compared to the 3-year period prior to the introduction of CXL (201 versus 269 transplants, respectively; p = 0.005). Age, gender and visual acuity were similar between the patient groups in the two time periods. Trend analysis also demonstrated a significant decrease in the amount of corneal transplants (p = 0.001). CONCLUSION: Significantly fewer corneal transplants were performed for treating keratoconus following the nationwide introduction of CXL. This reduction suggests that corneal cross-linking can significantly reduce the need for corneal transplantation.