Deep Learning Models Used in the Diagnostic Workup of Keratoconus: A Systematic Review and Exploratory Meta-Analysis.

PURPOSE: The prevalence of keratoconus in the general population is reported to be up to 1 of 84. Over the past 2 decades, diagnosis and management evolved rapidly, but keratoconus screening in clinical practice is still challenging and asks for improving the accuracy of keratoconus detection. Deep learning (DL) offers considerable promise for improving the accuracy and speed of medical imaging interpretation. We establish an inventory of studies conducted with DL algorithms that have attempted to diagnose keratoconus. METHODS: This systematic review was conducted according to the recommendations of the PRISMA statement. We searched (Pre-)MEDLINE, Embase, Science Citation Index, Conference Proceedings Citation Index, arXiv document server, and Google Scholar from inception to February 18, 2022. We included studies that evaluated the performance of DL algorithms in the diagnosis of keratoconus. The main outcome was diagnostic performance measured as sensitivity and specificity, and the methodological quality of the included studies was assessed using QUADAS-2. RESULTS: Searches retrieved 4100 nonduplicate records, and we included 19 studies in the qualitative synthesis and 10 studies in the exploratory meta-analysis. The overall study quality was limited because of poor reporting of patient selection and the use of inadequate reference standards. We found a pooled sensitivity of 97.5% (95% confidence interval, 93.6%-99.0%) and a pooled specificity of 97.2% (95% confidence interval, 85.7%-99.5%) for topography images as input. CONCLUSIONS: Our systematic review found that the overall diagnostic performance of DL models to detect keratoconus was good, but the methodological quality of included studies was modest.

Differences in minimal disease knowledge of keratoconus patients: results from an international survey.

BACKGROUND/AIMS: The objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition. METHODS: We recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of 'minimal keratoconus knowledge' (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient. RESULTS: Our findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score. CONCLUSIONS: Our study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

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

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

Accuracy of a New Noninvasive Automatic Ocular Surface Analyzer for the Diagnosis of Dry Eye Disease-Two-Gate Design Using Healthy Controls.

PURPOSE: The purpose of this study was to assess the diagnostic performance of measurements from a new noninvasive, automated ocular surface analyzer (IDRA) in the diagnosis of dry eye disease (DED). METHODS: We prospectively identified patients with and without DED using best practice methods. Subsequently, all participants underwent IDRA analysis, consisting of 5 components: noninvasive tear film break-up time, tear meniscus height, lipid layer interferometry, eye blink quality, and infrared meibography. The manufacturer provides cutoff values for a pathologic result for each of these components. Using a stepwise augmentation multivariate logistic regression model, we identified the components with the strongest association for the presence of DED. For the 3 components with the strongest association (interferometry, tear meniscus, and infrared meibography), we calculated the probability of DED. RESULTS: We enrolled 40 patients (80 eyes) with DED (mean age 60.5 years; women 78.3%) and 35 healthy subjects (70 eyes, mean age 31.1 years; women 21.7%). The IDRA had an area under the curve of 0.868 (95% confidence interval: 0.809-0.927) to detect DED. A normal (≥80) interferometry combined with a normal (>0.22) tear meniscus and a normal (≤40) infrared meibography was associated with an estimated probability of 18% for the presence of DED, whereas the estimated probability of DED was as high as 96% when all 3 findings were pathologic. CONCLUSIONS: The results of IDRA showed a positive concordance with routine clinical diagnostic tests. The new analyzer is an easy-to-access diagnostic tool to rule out the presence of DED in the extramural setting and to guide a timely DED treatment.

VEGF-A in Serum and Plasma Rich in Growth Factors (PRGF) Eye Drops.

BACKGROUND: Vascular endothelial growth factor (VEGF)-A, the most abundant subtype of the VEGF family in the eye, plays an important role in corneal homeostasis due to its ability to mediate corneal nerve repair. Repeated intravitreal anti-VEGF injections were shown to significantly reduce corneal nerve density, which might negatively affect corneal homeostasis and lead to a neuropathic dry eye disease. Currently, there are two effective modalities to treat dry eye while supplying VEGF to the ocular surface: serum eye drops (SED) and eye drops manufactured from plasma rich in growth factors (PRGF). The purpose of this study was to measure the VEGF-A concentration in SED and PRGF eye drops. MATERIAL AND METHODS: Ten healthy volunteers donated blood on two separate occasions, 2 - 8 days apart. Thus, a total of 20 blood samples were processed to obtain both SED and PRGF. Concentrations of VEGF-A were quantified by a Simple Plex platform run in triplicate. RESULTS: The VEGF-A concentration in SED and PRGF was very similar between the two blood samples drawn from one individual donor but showed substantial interindividual variability. However, in all 20 samples, VEGF concentrations were substantially higher in SED samples (mean 238.7 ± 146.6 pg/mL) compared to PRGF samples (mean 67.4 ± 46.3 pg/mL). Based upon the analysis of variance (ANOVA) model for the measured concentrations with fixed effects for specimen (SED vs. PRGF) and subject, the mean difference between the SED and PRGF concentration was 168.1 pg/mL (95% confidence interval: [142.4, 193.9], p < 0.001). CONCLUSION: Our study showed that the VEGF concentration was higher in SED than in PRGF. This is an important finding, particularly for potential treatment of dry eye disease in patients with neuropathic eye disease, especially in patients that received repeated anti-VEGF intravitreal injections, or in patients with Sjögren's disease, where the level of VEGF in tears might be pathologically decreased. Hypothetically, VEGF might be needed to restore ocular surface homeostasis. Although growing evidence has shown that VEGF-A plays an important role in corneal homeostasis, only a randomized prospective clinical trial will show whether supplying VEGF-A to the ocular surface might successfully restore the corneal homeostasis and overcome the problem of corneal neuropathy in these patients. For such a trial, based on our results, an undiluted SED should be preferred over a PRGF due to the higher content of VEGF-A.

Effect of Protective Measures on the Risk of SARS-CoV-2 Infection among Eye Clinic Staff Members.

BACKGROUND: Switzerland was strongly affected by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a nationwide lockdown in March 2020. Ophthalmologists were at most risk of contracting a SARS-CoV-2 infection due to their close working distance from patients. The aim of the study is to evaluate the overall effectiveness of protective measures on the risk of SARS-CoV-2 infection among employees in a large public eye hospital. MATERIAL AND METHODS: After lifting the lockdown in April 2020, standard precaution measures were taken, such as no handshaking and the use of operating face masks and a protective plastic shield on slit lamps and diagnostic devices. Only patients with no signs of SARS-CoV-2 disease were seen during the study period. Specific anti-SARS-CoV-2 IgG antibody titers were measured in eye clinic employees at the end of April 2020 (1st test phase) and in January 2021 (2nd test phase). The prevalence of SARS-CoV-2 IgG antibody titers among employees with daily patient contact was compared to staff members with no patient contact. RESULTS: The SARS-CoV-2 prevalence in employees with daily patient contact, with 0% in the 1st phase and 7.4% in the 2nd phase, was not significantly higher than the prevalence in the control group with no patient contact (0.9% in the 1st phase, p = 0.4; and 8.6% in the 2nd phase, p = 0.8). Furthermore, physicians were not at a significantly higher risk of SARS-CoV-2 infection compared to technicians, nurses, or office staff. CONCLUSIONS: This study shows that the abovementioned precaution measurements are effective in preventing transmission of SARS-CoV-2 infection in eye hospitals and enable us to resume practicing ophthalmology in a safe manner.

Ten-Year Outcome of Topography-Guided Transepithelial Surface Ablation for Refractive Myopia Treatment.

BACKGROUND: To evaluate 10-year long-term refractive visual stability and participants' satisfaction in the refractive treatment of myopic eyes undergoing topography-guided transepithelial surface ablation using a 1KHz excimer laser. PATIENTS AND METHODS: This single-center prospective survey assessed participants' satisfaction 10 years after the treatment using a non-validated questionnaire with regards to visual outcome, dry eye, and visual disturbance symptoms. Pre- and postoperative visual and refractive data were evaluated. RESULTS: Of 106 participants (54% females) with a mean patient age of 36 (± 8.6) years, 166 eyes were included. Mean preoperative spherical equivalent (SE) was - 4.23 (± 2.48) diopters (D). Uncorrected distant visual acuity (UCVA) after 10 years was ≥ 1.0 (Snellen) in 92% of the eyes. Manifest SE was within ± 1.0 D of the desired refraction in 86% of the eyes after 10 years. Mean quality of life (QOL) improvement was high (9.15 out of 10 points). Dry eye symptoms were reported by 35 out of 104 (34%) patients. Visual symptoms like halos or starbursts were reported by 24 out of 101 (24%) and 12 out of 100 (12%) patients, respectively. CONCLUSIONS: Topography-guided transepithelial surface ablation for myopia provided stable long-term results in terms of UCVA and SE. Participant satisfaction was high, with only low rates of dry eye or visual symptoms.

Efficacy of Diclofenac in Pain Reduction after Topography-Guided Transepithelial Surface Ablation.

PURPOSE: To report the efficacy of postoperative diclofenac eye drops for pain reduction in patients undergoing topography-guided transepithelial surface ablation. METHODS: Retrospective consecutive case series of patients undergoing topography-guided transepithelial surface ablation for refractive myopia treatment using a 1 KHz excimer laser. Patients were divided into three groups. Group 1 did not receive any diclofenac drops, group 2 received one diclofenac drop postoperatively (day 1), and group 3 received one drop of diclofenac postoperatively (day 1) and on the day after treatment (day 2). Postoperative pain was self-assessed by patients per eye daily for the first 4 consecutive days (days 1 to 4) after the treatment using the visual analogue scale (VAS). We compared VAS with respect to the use of additional oral or topical treatment as well as VAS with regards to the total amount of ablated tissue (< 50 µm, 50 - 100 µm, ≥ 100 µm) among the groups. RESULTS: We enrolled 163 eyes of 163 patients (55.0% female), with a mean age of 31.3 years (SD ± 6.6; range 21 - 68). We excluded 16 patients who applied other additional analgesics. Group 1 comprised 35 eyes (21%), group 2 had 21 eyes (13%), and group 3 consisted of 107 eyes (66%). Median pain score (VAS) was 5 (range 0, 10) in group 1, which was higher than in groups 2 (median 1, range 0 to 7) and 3 (median 1.5, range 0 to 7) on the day of surgery (p < 0.0001). Percentage of patients using an additional oral NSAID on days 1 and 2 was significantly higher in group 1 (69/83%) when compared to groups 2 (24/43%) or 3 (31/49%) (p < 0.001 day 1, p = 0.001 day 2). No correlation was found between pain sensation and maximum ablation depth (Spearman correlation p > 0.05). CONCLUSION: The instillation of one drop of diclofenac after topography-guided transepithelial surface ablation reduced subjective pain sensation according to VAS and decreased the need for additional topical anesthetic drops or oral NSAID.

Agreement of intraocular lens power calculation between 2 SS-OCT-based biometers.

PURPOSE: To assess agreement of measurements by 2 swept-source optical coherence tomography biometers and to evaluate the prediction error (PE) in intraocular lens power calculation with 7 formulas. SETTING: Tertiary public eye hospital. DESIGN: Consecutive observational. METHODS: Axial length (AL), keratometry (K), anterior chamber depth (ACD), lens thickness (LT), and corneal diameter (CD) were measured with the IOLMaster 700 (Biometer A) and Anterion (Biometer B). Agreement was quantified by the limits of agreement and concordance correlation coefficient (CCC). The PE, the median absolute error, and the mean absolute error of the Barrett Universal II, EVO 2.0, Haigis, Hoffer Q, Holladay 1, Kane, and SRK/T formulas were investigated after constant optimization. RESULTS: In 78 eyes from 78 patients, excellent agreement was obtained for AL (CCC >0.99), very good agreement for K, ACD, and LT (CCC >0.95), and strong agreement for CD (CCC >0.72). An additive offset of 0.07 mm was measured for ACD and LT whose mean values were higher with Biometer B (P < .001). No statistically significant difference was found between the PEs and their absolute values when comparing the results of each formula between the 2 biometers. CONCLUSIONS: Agreement of biometric measurements by the 2 biometers was high, although Biometer B provided higher mean values of ACD and LT by 0.07 mm. In cataract patients with normal eye length, measurements by the 2 biometers did not lead to different refractive outcomes with the 7 formulas investigated.

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test.

PURPOSE: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). METHODS: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. RESULTS: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). CONCLUSION: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes.

Multifocal Femto-PresbyLASIK in Pseudophakic Eyes.

BACKGROUND: Presbyopia treatment in pseudophakic patients with a monofocal IOL is challenging. This study investigates the refractive results of femto-PresbyLASIK and analyzes presbyopia treatment in pseudophakic eyes. METHODS: 14 patients with 28 pseudophakic eyes were treated with femto-PresbyLASIK. The dominant eye was targeted at a distance and the non-dominant eye at -0.5 D. The presbyopic algorithm creates a steepness in the cornea center by using an excimer laser that leads to corneal multifocality. RESULTS: 6 months after surgery a refraction of -0.11 ± 0.13 D (p = 0.001), an uncorrected distance visual acuity of 0.05 ± 1.0 logMAR (p < 0.001) and an uncorrected near visual acuity of 0.15 ± 0.89 logMAR (p = 0.001) were achieved in the dominant eye. For the non-dominant eye, the refraction was -0.28 ± 0.22 D (p = 0.002), the uncorrected distance of visual acuity was 0.1 ± 1.49 logMAR, and the uncorrected near visual acuity was 0.11 ± 0.80 logMAR (p < 0.001). Spherical aberrations (Z400) were reduced by 0.21-0.3 µm in 32% of eyes, and by 0.31-0.4 µm in 26% of eyes. CONCLUSION: By steepening the central cornea while maintaining spherical aberrations within acceptable limits, PresbyLASIK created a corneal multifocality that safely improved near vision in both eyes. Thus, femto-PresbyLASIK can be used to treat presbyopia in pseudophakic eyes without performing intraocular surgery.

Mismatch of corneal specialists' expectations and keratoconus knowledge in general ophthalmologists - a prospective observational study in Switzerland.

BACKGROUND: To assess whether Swiss general ophthalmologists have the minimal keratoconus knowledge that corneal specialists would expect them to have. METHODS: Corneal specialists defined "minimal keratoconus knowledge" (MKK) with respect to definition, risk factors, symptoms and possible treatment options of keratoconus. A telephone interview survey was conducted among one hundred ophthalmologists (mean age 51.9 years (SD 9.5), 60 % male) from the German-speaking part of Switzerland. For each participant, years of work experience, number of keratoconus patients seen per year and access to a topography device were obtained. We calculated the proportion of MKK and examined in multivariate analyses whether ophthalmologists with access to topography and with greater work experience performed better than other groups. RESULTS: No single ophthalmologist had MKK. The mean MKK was 52.0 %, and the range was 28.6-81.0 %. Per 10 years of working in private practice, the MKK decreased by 8.1 % points (95 % CI: -14.2, -2.00; p = 0.01). Only 24 % of participants correctly recalled the definition of keratoconus, 9 % all risk factors, 5 % all symptoms and 20 % all treatment modalities. The MKK values were not associated with the number of keratoconus patients seen per year and the availability of topography to diagnose keratoconus. CONCLUSIONS: There is a substantial mismatch between corneal specialist' expectations and general ophthalmologists' knowledge about keratoconus. The low recall of symptoms and risk factors may explain why ophthalmologists diagnose relatively few cases of keratoconus, resulting in inefficient care delivery and delayed intervention.

The Lucerne Protocol for the Production of Autologous Serum Eyedrops.

BACKGROUND: There are a variety of protocols for manufacturing autologous serum (AS) eye drops. The Lucerne protocol for the production of AS eye drops uses a slightly reduced gravitational (g)-force and time for the centrifugation process (2500 × g for 10 minutes), compared to previously published optimised protocols, to obtain high levels of epitheliotropic growth factors (3000 × g for 15 minutes). The goal of this study was to compare the concentrations of growth factors, albumin and lysozyme in autologous serum eye drops manufactured with these protocols. MATERIAL AND METHODS: Blood from 5 healthy volunteers was placed in plastic tubes without an anticoagulant. Tubes from each donor were left in a vertical position for 2 hours at room temperature to facilitate coagulation, followed by centrifugation at either 2500 × g for 10 minutes or at 3000 × g for 15 minutes at room temperature. The serum levels of beta nerve growth factor (ß-NGF), transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A) were measured in triplicate with a multi-analyte Simple Plex platform. The Simple Plex cartridge allows each sample to be run in triplicate for each analyte and prevents any interaction between the antibody components for each biomarker. The serum level of albumin was measured by turbidimetric immunoassay Tina-quant and of lysozyme by single radial immunodiffusion assay. RESULTS: For all analytes, the reduced g-force and centrifugation time did not result in a significant difference in serum levels. CONCLUSIONS: The Lucerne protocol for the production of autologous serum eye drops with reduced g-force and a shorter centrifugation time does not affect the concentrations of the main epitheliotropic growth factors, albumin and lysozyme, in AS eye drops.

Do Patients With Keratoconus Have Minimal Disease Knowledge?

PURPOSE: To assess whether Swiss adult citizens diagnosed with keratoconus have the minimal knowledge that a corneal specialist would expect they should have. METHODS: Experts defined the "minimal keratoconus knowledge" (MKK) with respect to definition, risk factors, symptoms, and possible treatment options of keratoconus. A survey was performed in 167 patients with keratoconus [mean age 38.8 years (SD 13.9), 77.7% male] in 5 specialized institutions. Of each participant, salient clinical characteristics, highest educational level, paramedical background, and specific health experience with keratoconus in the social surrounding were obtained. We calculated the proportion of MKK and examined whether patients with higher education and greater disease experience would perform better than those from other groups in multivariate analyses. RESULTS: No single citizen reached 100% MKK. The mean MKK was 35.2%, and the range was 0% to 76.2%. Participants with a university degree had only a moderately higher MKK [+8.7% (95% confidence interval: 4.4-13.0); P < 0.001]. Per age decile, the MKK declined by 3.1% (95% confidence interval: 1.2-4.9), P = 0.002. Disease duration, severity of keratoconus in Kmax values, and history of surgical treatment did not significantly increase MKK. Surprisingly, MKK was also lower in patients with a paramedical background [-6.3% (-14.1 to 1.4); P = 0.107]. CONCLUSIONS: This sample of Swiss patients with keratoconus did not know more than a third of the MKK. We found a little difference within various subgroups. There is a substantial mismatch between caregivers' expectations of patients' knowledge and patients' active knowledge regarding their condition. This may lead to an inefficient care delivery and misunderstandings.

Don't be afraid of the dark - OCT angiography through a black intraocular lens.

PURPOSE: To report a case in which optical coherence tomography (OCT) and OCT angiography (OCT-A) allowed imaging of the posterior pole in a patient fitted with a black occlusive intraocular lens (IOL). OBSERVATIONS: Following retinal central artery occlusion, a 52-year-old patient suffered from disturbing residual light perception. Occlusive contact lenses blocked the light insufficiently, so that the patient had to rely on an eye patch for relief of symptoms. After no neovascularization had formed during an observation period of 12 months, a black IOL (Morcher 85F) was implanted, blocking wavelengths in the visible spectrum but allowing transmission in the near-infrared spectrum. Slit lamp photography, OCT and OCT-A were performed pre- and postoperatively. Postoperatively, slit lamp photography could no longer provide images of the posterior pole, proving the effective blockade of wavelengths in the visible light spectrum. In contrast, transmission in the near-infrared spectrum allowed for OCT and OCT-A imaging of the fundus. The complete suppression of the disturbing perception of light succeeded only temporarily. CONCLUSIONS AND IMPORTANCE: The implantation of a black IOL does not prevent the imaging of the retinal microvasculature by OCT-A. Black IOLs can therefore be considered even if continued monitoring of the vascular situation of the posterior pole is required.

Changes in higher order aberrations after central corneal regularization - a comparative two-year analysis of a semi-automated topography-guided photorefractive keratectomy combined with corneal cross-linking.

BACKGROUND: The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and optics. While corneal cross-linking (CXL) aims at stopping disease progression, "CXL-Plus" combines CXL with excimer laser ablation to improve visual function. Central Corneal Regularization (CCR) represents a therapeutic excimer laser modality specifically designed to smoothen the ectatic corneal shape and to reduce higher order aberrations (HOA). We set out to compare CXL-Plus, consisting of CXL combined with CCR, with CXL by itself for patients with progressive keratoconus. METHODS: Retrospective 2-year matched group analysis of patients who either underwent CXL-Plus (n = 28) or CXL as a sole procedure (n = 28) for progressive keratoconus. Main outcome parameters were HOA, visual function and tomographic results 12 and 24 months postoperatively. RESULTS: After 12 months, the total HOA root mean square wavefront error was reduced from 0.79 ± 0.30 to 0.40 ± 0.19 µm (CXL-Plus; p <  0.0001) and changed from 0.71 ± 0.28 to 0.73 ± 0.36 µm (CXL; p = 0.814). Uncorrected distance visual acuity improved from 0.70 ± 0.35 to 0.36 ± 0.29 logMAR (CXL-Plus; p = 0.0002) and from 0.65 ± 0.39 to 0.46 ± 0.37 logMAR (CXL; p = 0.067), translating to gains of three or more lines in 50% (CXL-Plus) and 36% (CXL) of patients. The steepest keratometry value (Kmax) regressed by 5.84 D (CXL-Plus; p <  0.0001) and 0.66 D (CXL; p = 0.752). For none of the investigated parameters a statistically significant change could be shown between 12 and 24 months. CONCLUSIONS: CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

Keratoconus Characteristics Used in Randomized Trials of Surgical Interventions-A Systematic Review.

PURPOSE: To investigate descriptions and inclusion criteria of keratoconus used in randomized trials assessing the efficacy of surgical and nonsurgical interventions. METHODS: Systematic review: we searched (Pre-)Medline and the Cochrane Library from inception until December 2018 and checked the reference lists of included articles and reviews. We included randomized trials assessing the efficacy of any kind of keratoconus treatment. No language restrictions were imposed. We assessed articles against the inclusion criteria, extracted relevant data including any kind of keratoconus description, and examined the methodological quality. RESULTS: Searches retrieved 459 nonduplicate records, and we included 57 randomized controlled trials investigating 9 different surgical interventions with the most used primary outcome measure being maximum keratometry. Only 15 (26.3%) described eligibility parameters regarding keratoconus staging/classification, of which 12 studies used the Amsler-Krumeich classification. Eleven studies were published before 1997 (before publication of the Consolidated Standards of Reporting Trials statement), and none of these described the use of a classification. From 1997 onward, 15 of 46 studies (32.6%) described the incorporation of a classification system (P = 0.051). The average methodological quality of included trails was modest. CONCLUSIONS: The evidence from randomized trials, even after introduction of the Consolidated Standards of Reporting Trials statement, remains ill-formed regarding a careful definition of keratoconus. This is unfortunate because imprecisions regarding the specification of included patients preclude clinicians to assess applicability, that is, the extent to which they can use inferences drawn from study participants regarding efficacy and adverse events in the care of individual patients.