Implementing and evaluating a fully functional AI-enabled model for chronic eye disease screening in a real clinical environment.

BACKGROUND: Artificial intelligence (AI) has the potential to increase the affordability and accessibility of eye disease screening, especially with the recent approval of AI-based diabetic retinopathy (DR) screening programs in several countries. METHODS: This study investigated the performance, feasibility, and user experience of a seamless hardware and software solution for screening chronic eye diseases in a real-world clinical environment in Germany. The solution integrated AI grading for DR, age-related macular degeneration (AMD), and glaucoma, along with specialist auditing and patient referral decision. The study comprised several components: (1) evaluating the entire system solution from recruitment to eye image capture and AI grading for DR, AMD, and glaucoma; (2) comparing specialist's grading results with AI grading results; (3) gathering user feedback on the solution. RESULTS: A total of 231 patients were recruited, and their consent forms were obtained. The sensitivity, specificity, and area under the curve for DR grading were 100.00%, 80.10%, and 90.00%, respectively. For AMD grading, the values were 90.91%, 78.79%, and 85.00%, and for glaucoma grading, the values were 93.26%, 76.76%, and 85.00%. The analysis of all false positive cases across the three diseases and their comparison with the final referral decisions revealed that only 17 patients were falsely referred among the 231 patients. The efficacy analysis of the system demonstrated the effectiveness of the AI grading process in the study's testing environment. Clinical staff involved in using the system provided positive feedback on the disease screening process, particularly praising the seamless workflow from patient registration to image transmission and obtaining the final result. Results from a questionnaire completed by 12 participants indicated that most found the system easy, quick, and highly satisfactory. The study also revealed room for improvement in the AMD model, suggesting the need to enhance its training data. Furthermore, the performance of the glaucoma model grading could be improved by incorporating additional measures such as intraocular pressure. CONCLUSIONS: The implementation of the AI-based approach for screening three chronic eye diseases proved effective in real-world settings, earning positive feedback on the usability of the integrated platform from both the screening staff and auditors. The auditing function has proven valuable for obtaining efficient second opinions from experts, pointing to its potential for enhancing remote screening capabilities. TRIAL REGISTRATION: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2021-10574-BO-ff.

Whole-Exome Sequencing Identifies Novel Compound Heterozygous ZNF469 Mutations in Two Siblings with Mild Brittle Cornea Syndrome.

Connective tissue diseases, including osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS), exhibit a high degree of clinical and genetic heterogeneity. We report two sisters with blue sclerae, joint hypermobility and hearing loss. Whole-exome sequencing identified two compound heterozygous ZNF469 loss-of-function mutations due to a frameshift. Since these findings indicate the presence of brittle cornea syndrome (BCS), we performed ocular optical coherence tomography (OCT) and pachymetry, which revealed a moderate decrease in corneal thickness. While only one traumatic fracture was observed in each of the patients, a detailed skeletal assessment indicated no specific patterns of bone mass and microstructure reduction as well as normal bone turnover markers. Taken together, our findings point to a mild form of brittle cornea syndrome with a phenotype compatible with the extraskeletal features of OI but also with EDS.

In vivo Histology of the Cornea - from the "Rostock Cornea Module" to the "Rostock Electronic Slit Lamp" - a Clinical "Proof of Concept" Study. / In-vivo-Histologie der Hornhaut ­ vom "Rostocker Cornea Modul" zur "Rostocker Elektronischen Spaltlampe" ­ eine klinische "Proof-of-Concept"-Studie.

INTRODUCTION: Confocal in vivo microscopy is an established method in ophthalmology research. As it requires contact coupling and calibration of the instruments is suboptimal, this method has been only rarely used in clinical routine work. As a result of close collaboration between physicists, information scientists and ophthalmologists, confocal laser scanning microscopy (CLSM) of the eye has been developed in recent years and a prototype can now be used in patients. The present study evaluates possible clinical uses of this method. MATERIAL AND METHODS: The essential innovations in CLSM are (1) a newly designed coupling element with superficial adaptation to corneal curvature and (2) the use of a dual computerised piezo drive for rapid and precise focusing. In post-processing and after elastic imaging registration of the individual images parallel to the surface, it is also possible to produce sagittal sections resembling a split lamp and with resolution in the micrometer range. The concept was tested on enucleated pig bulbi and tested on normal volunteers and selected patients with diseases of the cornea. RESULTS: Simultaneous imaging in planes parallel to the surface and in sagittal planes provided additional information that can help us to understand the processes of wound healing in all substructures of the cornea and the role of immune competent cells. Possible clinical uses were demonstrated in a volunteer with healthy eyes and several groups of patients (keratoconus after CXL, recurrent keratitis, status after PRK). These show that this new approach can be used in morphological studies at cellular level in any desired and appropriate test plane. CONCLUSIONS: It could be shown that this new concept of CLSM can be used clinically. It can provide valuable and novel information to both preclinical researchers and to ophthalmologists interested in corneal disease, e.g. density of Langerhans cells and epithelial stratification in ocular surface diseases.

Semi-quantitative assessments of dextran toxicity on corneal endothelium: conceptual design of a predictive algorithm.

Dextran is added to corneal culture medium for at least 8 h prior to transplantation to ensure that the cornea is osmotically dehydrated. It is presumed that dextran has a certain toxic effect on corneal endothelium but the degree and the kinetics of this effect have not been quantified so far. We consider that such data regarding the toxicity of dextran on the corneal endothelium could have an impact on scheduling and logistics of corneal preparation in eye banking. In retrospective statistic analyses, we compared the progress of corneal endothelium (endothelium cell loss per day) of 1334 organ-cultured corneal explants in media with and without dextran. Also, the influence of donor-age, sex and cause of death on the observed dextran-mediated effect on endothelial cell counts was studied. Corneas cultured in dextran-free medium showed a mean endothelium cell count decrease of 0.7% per day. Dextran supplementation led to a mean endothelium cell loss of 2.01% per day; this reflects an increase by the factor of 2.9. The toxic impact of dextran was found to be time dependent; while the prevailing part of the effect was observed within the first 24 h after dextran-addition. Donor age, sex and cause of death did not seem to have an influence on the dextran-mediated toxicity. Based on these findings, we could design an algorithm which approximately describes the kinetics of dextran-toxicity. We reproduced the previously reported toxic effect of dextran on the corneal endothelium in vitro. Additionally, this is the first work that provides an algorithmic instrument for the semi-quantitative calculation of the putative endothelium cell count decrease in dextran containing medium for a given incubation time and could thus influence the time management and planning of corneal transplantations.

Pseudolentogenic astigmatic effect of multifocal intraocular lenses: non-corneal ocular residual astigmatism (N-CORA) as a new parameter in astigmatic change analysis.

PURPOSE: This study was initiated to introduce the term non-corneal ocular residual astigmatism (N-CORA) as a new parameter in astigmatic change analysis after implantation of two different types of non-toric, multifocal intraocular lenses (MIOL). METHODS: Seventy-two eyes from 72 consecutive patients after MIOL surgery were studied in terms of a retrospective, cross-sectional data analysis. Two types of spherical MIOL were used. Surgical technique in all patients was a 2.4-mm incision phacoemulsification, performed by one surgeon. To investigate the magnitude and axis of astigmatic changes, the true corneal astigmatism and Alpins vector method were applied. RESULTS: There were no statistically significant between-group differences related to the preoperative refraction or ocular residual astigmatism (ORA). After surgery, the mean refractive surgically induced astigmatism (RSIA) and the topographic SIA (TSIA) did not differ significantly between the lenses. The magnitude and orientation of ORA and N-CORA changed after surgery. CONCLUSIONS: There are no statistically significant differences in postoperative ORA in magnitude or axis when implanting different types of MIOL. The similarity of N-CORA between both MIOL types shows that both diffractive and refractive asymmetric MIOLs with plate haptics have the same pseudolentogenic astigmatic effect which could be presented in terms of the newly introduced parameter N-CORA.

Ocular residual astigmatism (ORA) in pre-cataract eyes prior to and after refractive lens exchange.

The purpose of this study was to analyze ocular residual astigmatism (ORA) before and after implantation of two different optical types of non-toric multifocal intraocular lenses (MIOL) in pre-cataract patients. This retrospective cohort study analyzed 72 eyes from 72 consecutive patients after MIOL surgery . To investigate magnitude and axis of astigmatic changes, the concepts of true corneal astigmatism and Alpins vector method were applied. There were no statistically significant between-group differences prior to surgery. The mean refractive surgically induced astigmatism (RSIA) (P = 0.063) and the topographic SIA (TSIA) (P = 0.828) did not differ significantly between the lenses, and the summated vector mean for ORA was reduced in terms of magnitude by approximately 0.30 Diopter. ORA in pseudophakic eyes mainly results from the posterior corneal surface and less from IOL tilting, postoperative posterior capsule shrinkage, or secondary cataract.

Role of preoperative cycloplegic refraction in LASIK treatment of hyperopia.

BACKGROUND: Previous studies have suggested that, to improve refractive predictability in hyperopic LASIK treatments, preoperative cycloplegic or manifest refraction, or a combination of both, could be used in the laser nomogram. We set out to investigate (1) the prevalence of a high difference between manifest and cycloplegic spherical equivalent in hyperopic eyes preoperatively, and (2) the related predictability of postoperative keratometry. METHODS: Retrospective cross-sectional data analysis of consecutive treated 186 eyes from 186 consecutive hyperopic patients (mean age 42 [±12] years) were analyzed. Excimer ablation for all eyes was performed using a mechanical microkeratome (SBK, Moria, France) and an Allegretto excimer laser platform. Two groups were defined according to the difference between manifest and cycloplegic spherical equivalent which was defined as ≥1.00 diopter (D); the data was analyzed according to refractive outcome in terms of refractive predictability, efficacy, and safety. RESULTS: In 24 eyes (13 %), a preoperative difference of ≥1.00D between manifest spherical equivalent and cycloplegic spherical equivalent (= MCD) occurred. With increasing preoperative MCD, the postoperative achieved spherical equivalent showed hyperopic regression after 3 months. There was no statistically significant effect of age (accommodation) or optical zone size on the achieved spherical equivalent. CONCLUSIONS: A difference of ≥1.00D occurs in about 13 % of hyperopia cases. We suggest that hyperopic correction should be based on the manifest spherical equivalent in eyes with preoperative MCD <1.00D. If the preoperative MCD is ≥1.00D, treatment may produce manifest undercorrection, and therefore we advise that the patient should be warrned about lower predictability, and suggest basing conclusions on the arithmetic mean calculated from the preoperative manifest and cycloplegic spheres.

Postoperative refractive error after phacovitrectomy for epiretinal membrane with and without macular oedema.

PURPOSE: This study was initiated to investigate whether the presence of macular oedema influenced intraocular lens (IOL) power calculation in eyes with epiretinal membrane. METHODS: The files of patients undergoing combined phacoemulsification were retrospectively reviewed. Two groups were defined according to presence of macular oedema. The main outcome measure was the IOL power prediction error (PE). Secondary outcome measures were the correlation between preoperative macular thickness, absolute change of macular thickness and dioptric shift. The mean postoperative PE achieved with the Haigis formula was compared with the PE that would have been obtained had the SRKII and HofferQ formulas been used. RESULTS: We investigated 47 eyes of 47 consecutive patients. Regardless of the IOL formula used, the PE was on average higher in eyes without macula oedema (group 1). The myopic dioptric shift was dependent on preoperative macular thickness and absolute change of macular thickness. This association was more markedly pronounced in group 1. CONCLUSIONS: Increased retinal thickness is the main cause for underestimation of the cornea-photoreceptor layer distance, and therefore could contribute to inaccuracy in IOL power calculations. The current results show that a myopic shift tends to be less pronounced in cases where a macula oedema is present. Eyes with pure traction have less predictable refractive results in terms of higher PE and dioptric shift.

Laser in situ keratomileusis for astigmatism ≤ 0.75 diopter combined with low myopia: a retrospective data analysis.

BACKGROUND: This study examined the refractive and visual outcome of wavefront-optimized laser in situ keratomileusis (LASIK) in eyes with low myopia and compound myopic astigmatism ≤ 0.75 diopter (D). METHODS: 153 eyes from 153 consecutive myopic patients (74 male, 79 female; mean age at surgery 40.4 ± 10.4 years) who had a preoperative refractive cylinder ≤ 0.75 D and a manifest sphere between -0.25 D and -2.75 D, and who had completed 4-month follow-up. Three subgroups defined by the magnitude of preoperative manifest refractive cylinder (0.25, 0.50, and 0.75 D) were formed. Manifest refraction, uncorrected and corrected visual acuity were assessed pre- and postoperatively. The astigmatic changes achieved were determined using the Alpins vector analysis. RESULTS: After 4 months (120.0 ± 27.6 days) of follow-up, a mean uncorrected distant visual acuity of 0.07 ± 0.11 logMAR and a mean manifest refraction spherical equivalent of -0.06 ± 0.56 D were found. There was no statistically significant difference in efficacy and safety between the preoperative cylinder groups. Astigmatic overcorrection for preoperative cylinder of ≤ 0.50 D was suggested by the correction index, the magnitude of error, the index of success, and the flattening index. CONCLUSIONS: Low myopic eyes with a preoperative cylinder of ≤ 0.50 D were significantly overcorrected with regard to cylinder correction when combined with low myopic LASIK. Accordingly, we are cautious in recommending full astigmatic correction for eyes with low myopia and manifest cylinder of ≤ 0.50 D.

Anterior and posterior corneal changes after crosslinking for keratoconus.

PURPOSE: To evaluate anterior and posterior changes in corneal topography and tomography after corneal crosslinking (CXL) in eyes with progressive keratoconus. METHODS: Scheimpflug analyses (Pentacam, Oculus) of 20 eyes with keratoconus performed before and after corneal CXL were included into retrospective analysis. Mean follow-up was 2 years. Changes in topographic, tomographic, and pachymetric values were statistically analyzed applying analysis of variance. Further, the distance and direction between the anterior maximum keratometry (K(max)) and the apex as well as the distance and direction between the thinnest point in corneal thickness (TPCT) and the corneal apex before and after CXL were studied. RESULTS: Two years after CXL, a statistically significant reduction of the keratometry at the flat meridian (-0.8 D, p < 0.05), the steep meridian (-0.5 D, p < 0.05), the "index of surface variance" (-5.3, p < 0.05), and the "index of highest decentration" (-0.05, p < 0.05) could be demonstrated. While the elevation of the front surface at the apex decreased (-1.5 µm, p < 0.05), the back elevation at the apex (+2 µm, p < 0.05) increased. Although not reaching statistical significance, the maximum front and back elevation demonstrated the same trend; while maximum front elevation data remained stable (-0.3 µm, p = 0.961), maximum back elevation data increased (+6.7 µm, p = 0.122). The corneal thickness at the apex (-22.0 µm, p < 0.001) and the TPCT (-20.0 µm, p < 0.001) decreased, leading to an increase of the corneal thickness progression from the corneal apex to the periphery. The position of K(max) and TPCT remained stable. CONCLUSIONS: Corneal topography proved to be useful in the follow-up for CXL because of significant changes in the keratometry. Increasing posterior elevation values, despite a stabilized anterior corneal surface, might be a sign of ongoing ectatic changes in the posterior corneal surface.

Accuracy of wavefront aberrometer refraction vs manifest refraction in cataract patients: impact of age, ametropia and visual function.

BACKGROUND: To evaluate accuracy of WASCA wavefront aberrometry (WA) refraction in comparison to manifest refraction (MR) in an older population awaiting cataract surgery. METHODS: Prospectively, refractive errors of 130 eyes were determined by WA and MR. Mean age was 65.9 (SD 11.81), corrected distance visual acuity (CDVA) averaged 0.20 logMar (SD 0.57), mean manifest sphere was 0.23 dioptres (D, SD 3.39) and manifest astigmatism amounted to -1.25 D (SD 1.21). For further analysis, refractive values were transformed into power vector components: spherical equivalent (SE), Jackson cross cylinder at 0° and 45° (J0 and J45). The 'limits of agreement' approach, regression analysis, correlation analysis, and ANOVA were applied and additionally compared to 28 healthy eyes (mean VA -0.1 logMAR) of a group of young subjects (mean age 33.9). RESULTS: SE measures in myopia correlated highly between WA and MR (r = 0.917, p < .001). In hyperopia this correlation was moderately high (r = 0.800, p < .001). For all subjects, correlations between WA and MR for J0 and J45 were r = 0.742 (p < .001) and r = 0.760 (p < .001) respectively. WA measurements revealed larger agreement ranges with increasing myopia and astigmatism. Controlled for possible confounding variables of age, VA, and refractive state, no statistically significant effects were found. Across nearly all conditions, WA measured significantly higher myopic and astigmatic values than MR. Most effects were replicated in the reference group. CONCLUSIONS: WA refraction can provide valuable information in previously under-researched conditions such as reduced VA (cataract-related), advanced age, and hyperopia. However, loss of optical media transparency will inherently reduce accuracy of WA. Further studies are needed to define cut-off values for automated wavefront quality grading and intra-operative application of WA in refractive surgery.

Mesopic pupil size in a refractive surgery population (13,959 eyes).

PURPOSE: To evaluate factors that may affect mesopic pupil size in refractive surgery candidates. METHODS: Medical records of 13,959 eyes of 13,959 refractive surgery candidates were reviewed, and one eye per subject was selected randomly for statistical analysis. Detailed ophthalmological examination data were obtained from medical records. Preoperative measurements included uncorrected distance visual acuity, corrected distance visual acuity, manifest and cycloplegic refraction, topography, slit lamp examination, and funduscopy. Mesopic pupil size measurements were performed with Colvard pupillometer. Relationship between mesopic pupil size and age, gender, refractive state, average keratometry, and pachymetry (thinnest point) were analyzed by means of ANOVA (+ANCOVA) and multivariate regression analyses. RESULTS: Overall mesopic pupil size was 6.45 ± 0.82 mm, and mean age was 36.07 years. Mesopic pupil size was 5.96 ± 0.8 mm in hyperopic astigmatism, 6.36 ± 0.83 mm in high astigmatism, and 6.51 ± 0.8 mm in myopic astigmatism. The difference in mesopic pupil size between all refractive subgroups was statistically significant (p < 0.001). Age revealed the strongest correlation (r = -0.405, p < 0.001) with mesopic pupil size. Spherical equivalent showed a moderate correlation (r = -0.136), whereas keratometry (r = -0.064) and pachymetry (r = -0.057) had a weak correlation with mesopic pupil size. No statistically significant difference in mesopic pupil size was noted regarding gender and ocular side. The sum of all analyzed factors (age, refractive state, keratometry, and pachymetry) can only predict the expected pupil size in <20% (R = 0.179, p < 0.001). CONCLUSIONS: Our analysis confirmed that age and refractive state are determinative factors on mesopic pupil size. Average keratometry and minimal pachymetry exhibited a statistically significant, but clinically insignificant, impact on mesopic pupil size.

Superficial keratectomy, PTK, and mitomycin C as a combined treatment option for Salzmann's nodular degeneration: a follow-up of eight eyes.

PURPOSE: To analyze the treatment outcomes (safety and efficacy) of manual superficial keratectomy, phototherapeutic keratectomy (PTK), and intraoperative application of mitomycin C (MMC) for Salzmann nodular degeneration (SND). METHODS: In this retrospective study, we analyzed the records of eight eyes of five patients with Salzmann nodular degeneration (SND) who were treated between December 2006 and May 2008 at the University Eye Clinic Hamburg, Eppendorf, Germany. This case study includes data previously published within a single case report. Patients were followed-up pre- and postoperatively by slit-lamp biomicroscopy, digital photography, and corneal topography. All of the eight eyes were followed-up for at least 12 months, whereas in four eyes, follow-up was done for more than 24 months. PTK was performed with a 193-nm Ar-F excimer laser (Allegretto 200; WaveLight AG, Erlangen, Germany) within a 7-mm optical zone. Mitomycin C 0.02% was applied after PTK for 30 s. Postoperatively, a therapeutic contact lens was administered until corneal epithelial healing, which occurred usually at the forth postoperative day. Then local steroid therapy (prednisolone 1%) eye drops fours times per day was given for the following 4 weeks. RESULTS: Mean BCVA preoperatively was 0.61 logMAR (i.e., 20/80 Snellen equivalent or 0.25 decimal). There was a significant increase of BCVA by average of four reading lines (far distance) up to ten reading lines (p < 0.001). Mean BCVA postoperatively was 0.2 logMAR (i.e., 20/32 Snellen equivalent or 0.63 decimal). Treatment of SND led to a dramatic reduction of hyperopia (myopic shift) corresponding to a marked increase of best-corrected visual acuity (BCVA). Preoperatively documented hyperopic progression was stopped and refraction remained stable during the follow-up period in all eyes. Corneal topography showed regular astigmatism. During follow-up after treatment, the corneas appeared clear on slit-lamp examination. CONCLUSIONS: Our follow-up and the small treatment numbers are not sufficient to finally prove the superiority of the combined treatment modality (superficial keratectomy, PTK, and MMC) for SND, but the results of our study are promising. Longer follow-up and a larger cohort are warranted for proving MMC to be an effective, successful, and safe method in the armamentarium for treating and preventing Salzmann degeneration.

Quality of life in stable and progressive 'early-stage' keratoconus patients.

PURPOSE: To analyse the vision-related quality of life (vr-QoL) in stable and progressive keratoconus (KC) patients with a still good visual acuity. METHODS: Combined prospective/cross-sectional study design. The Refractive Status and Vision Profile (RSVP) and the National Eye Institute Visual Functioning - 25 (NEI-25) questionnaire were used in 16 emmetropic, 32 myopic and 56 KC patients, whereby KC patients with a stable (n = 26) and patients with a progressive stage (n = 30) and some of them before and after corneal cross-linking (CXL; n = 10) were included. All patients had a DCVA in at least one eye of ≥0.7 (decimal chart). RESULTS: The analyses revealed a minor decline of the vr-QoL from emmetropes to myopes to early KC patients with a stable disease. Nonetheless, sociological subscales (i.e. 'social functioning', 'role difficulties' and 'dependency') did not display statistically significant differences comparing these groups. In progressive KC, we could demonstrate a statistically significant decline also of these sociological subscales, which did not improve after CXL. CONCLUSION: Due to a still high and almost unaffected vr-QoL in early KC patients and the distinct decline after progression without rehabilitation after CXL, a reconsideration of current strategies to perform CXL only after a progression is diagnosed should be re-evaluated.

Analysis of excimer laser treatment outcomes and corresponding angle κ in hyperopic astigmatism.

PURPOSE: To investigate the prevalence of preoperative, intraoperative, and postoperative angle κ in hyperopic eyes and its effect on the refractive outcomes of excimer laser vision correction. SETTING: University Hospital Hamburg and Care Vision Refractive Centers, Germany. DESIGN: Retrospective multicenter study. METHODS: Hyperopic patients after laser in situ keratomileusis and before retreatment because of hyperopic regression were included. Three treatment groups were defined based on the magnitude of preoperative angle κ defined as low (<0.25 mm), moderate (0.25 to 0.50 mm), or high (>0.50 mm). RESULTS: The study analyzed 170 hyperopic eyes of 112 patients (mean age 29.8 years ± 10.04 [SD], range 21 to 62 years). The preoperative angle κ was low, moderate, or high in 23, 49, and 98 cases, respectively. In eyes with a preoperative angle κ of 0.25 mm or more, changes in the x-axes and y-axes of angle κ and its magnitude were statistically significant (P < .05) between preoperative and intraoperative measurements. In these eyes, intraoperative angle κ (offset) was statistically significantly smaller (P < .05), and Purkinje images were statistically significantly more caudal (P < .001). Treatment predictability was independent from using preoperative or intraoperative angle κ, and there were no statistically significant differences in efficacy or safety. CONCLUSIONS: A preoperative magnitude of angle κ as high as 0.50 mm or higher was present in more than 50% of regressed hyperopic eyes. Measuring angle κ preoperatively did not reflect its real-time intraoperative magnitude. Using the preoperatively larger angle κ as an intraoperative offset might result in a too nasally centered ablation that causes topographic and optical drawbacks; therefore, centering the ablation based on the intraoperative measured offset is recommended.

Features of Marfan syndrome not listed in the Ghent nosology - the dark side of the disease.

Introduction: The revised Ghent nosology presents the classical features of Marfan syndrome. However, behind its familiar face, Marfan syndrome hides less well-known features.Areas covered: The German Marfan Organization listed unusual symptoms and clinical experts reviewed the literature on clinical features of Marfan syndrome not listed in the Ghent nosology. Thereby we identified the following features: (1) bicuspid aortic valve, mitral valve prolapse, pulmonary valve prolapse, tricuspid valve prolapse, (2) heart failure and cardiomyopathy, (3) supraventricular arrhythmia, ventricular arrhythmia, and abnormal repolarization, (4) spontaneous coronary artery dissection, anomalous coronary arteries, and atherosclerotic coronary artery disease, tortuosity-, aneurysm-, and dissection of large and medium-sized arteries, (5) restrictive lung disease, parenchymal lung disease, and airway disorders, (6) obstructive- and central sleep apnea, (7) liver and kidney cysts, biliary tract disease, diaphragmatic hernia, and adiposity, (8) premature labor, and urinary incontinence, (9) myopathy, reduced bone mineral density, and craniofacial manifestations, (10) atrophic scars, (11) caries, and craniomandibular dysfunction, (12) headache from migraine and spontaneous cerebrospinal fluid leakage, (13) cognitive dysfunction, schizophrenia, depression, fatigue, and pain, (14) and activated fibrinolysis, thrombin, platelets, acquired von Willebrand disease, and platelet dysfunction.Expert commentary: Future research, nosologies, and guidelines may consider less well-known features of Marfan syndrome.

Endothelial Cell Count in Eye Bank Corneal Grafts: Impact of Death Cause and Donor Diseases.

PURPOSE: The purpose of this study is to analyze the impact of death causes and documented donor diseases on initial endothelial cell counts (after retrieval) and the development of corneal graft endothelia during organ culture. METHODS: The retrospective statistic analyses was conducted on a data set of 10,185 human corneas prepared at the Hamburg Eye Bank. RESULTS: Although we observed that death by gunshot trauma or alcoholism seems to be associated with marginally higher endothelium cell counts (independently from donor age), we could prove that only donor age is a relevant predictive parameter for the initial cell-density of the endothelium and its development in vitro. CONCLUSION: We conclude that an extension of prospective quality parameters for donor selection additional to donor age (such as individual causes of death) is not necessary.

Tomographic and Biomechanical Scheimpflug Imaging for Keratoconus Characterization: A Validation of Current Indices.

PURPOSE: To analyze the potential benefit of the newly developed Tomography and Biomechanical Index (TBI) for early keratoconus screening. METHODS: In this retrospective study, the discriminatory power of the corneal tomography Belin/Ambrósio Enhanced Ectasia Display (BAD-D) index and the newly developed Corvis Biomechanical Index (CBI) and TBI to differentiate between normal eyes, manifest keratoconus eyes (KCE), very asymmetric keratoconus eyes with ectasia (VAE-E), and their fellow eyes with either regular topography (VAE-NT) or regular topography and tomography (VAE-NTT) were analyzed by applying the t test (for normal distribution), Wilcoxon matched-pairs test (if not normally distributed), and receiver operating characteristic curve (ROC). The DeLong test was used to compare the area under the ROC (AUROC). Further, the cut-offs of the analyzed indices presented in a study by Ambrósio et al. from 2017 were applied in the study population to enable a cross-validation in an independent study population. RESULTS: All indices demonstrated a high discriminative power when comparing normal and advanced keratoconus, which decreased when comparing normal and VAE-NT eyes and further when analyzing normal versus VAE-NTT eyes. The difference between the AUROCs reached a statistically significant level when comparing TBI versus BAD-D analyzing normal versus all included keratoconic eyes (P = .02). The TBI presented with the highest AUROCs throughout all conducted analyses when comparing different keratoconus stages, although not reaching a statistically significant level. Applying the cut-offs presented by Ambrósio et al. to differentiate between normal and VAE-NT in the study population, the accuracy was reproducible (accuracy in our study population with an optimized TBI cut-off: 0.72, with the cut-off defined by Ambrósio et al. 0.67). CONCLUSIONS: The TBI enables karatoconus screening in topographical and tomographical regular keratoconic eyes. To further improve the screening accuray, prospective studies should be conducted. [J Refract Surg. 2018;34(12):840-847.].

Keratoconus Screening With Dynamic Biomechanical In Vivo Scheimpflug Analyses: A Proof-of-Concept Study.

PURPOSE: This proof-of-concept study was designed to analyze the ability of in vivo biomechanical corneal analyses with the corneal visualization Scheimpflug technology (CorvisST; Oculus Optikgeräte, Wetzlar, Germany) to differentiate between normal eyes and eyes with manifest keratoconus after strictly eliminating the potential confounding factors intraocular pressure (IOP) and central corneal thickness (CCT). METHODS: In this retrospective, cross-sectional study, after pairwise matching for CCT and IOP, 29 normal eyes and 29 keratoconic eyes (one eye from each patient) were selected as study population. Older CorvisST parameters and the new Corvis Biomechanical Index (CBI), including several biomechanical and one tomographic parameter, as well as an adjusted CBI (aCBI) (including only biomechanical parameters), were compared regarding their discriminative ability between both groups. RESULTS: None of the CorvisST parameters of the former software version demonstrated statistically significant differences between normal and keratoconic eyes. On the other hand, the CBI and aCBI reached accuracies of 0.91 and 0.93, respectively, to discriminate between CCT- and IOP-matched normal and keratoconic eyes (CBI: [AUC/sensitivity/specificity]: 0.961/0.90/0.93; aCBI: [AUC/sensitivity/specificity]: 0.986/0.93/0.93). CONCLUSIONS: This study demonstrated that the concept of keratoconus screening with the CorvisST is effective in differentiating keratoconic from non-keratoconic eyes. The next steps will be testing the indices in subclinical keratoconus cases and hopefully combining biomechanical analyses with already established topography and tomography indices to further improve current keratoconus screening. [J Refract Surg. 2017;33(11):773-778.].