Technical variability of cornea parameters derived from anterior segment OCT fitted with Fringe Zernike polynomials.

BACKGROUND: This study uses bootstrapping to evaluate the technical variability (in terms of model parameter variation) of Zernike corneal surface fit parameters based on Casia2 biometric data. METHODS: Using a dataset containing N = 6953 Casia2 biometric measurements from a cataractous population, a Fringe Zernike polynomial surface of radial degree 10 (36 components) was fitted to the height data. The fit error (height - reconstruction) was bootstrapped 100 times after normalisation. After reversal of normalisation, the bootstrapped fit errors were added to the reconstructed height, and characteristic surface parameters (flat/steep axis, radii, and asphericities in both axes) extracted. The median parameters refer to a robust surface representation for later estimates of elevation, whereas the SD of the 100 bootstraps refers to the variability of the surface fit. RESULTS: Bootstrapping gave median radius and asphericity values of 7.74/7.68 mm and -0.20/-0.24 for the corneal front surface in the flat/steep meridian and 6.52/6.37 mm and -0.22/-0.31 for the corneal back surface. The respective SD values for the 100 bootstraps were 0.0032/0.0028 mm and 0.0093/0.0082 for the front and 0.0126/0.0115 mm and 0.0366/0.0312 for the back surface. The uncertainties for the back surface are systematically larger as compared to the uncertainties of the front surface. CONCLUSION: As measured with the Casia2 tomographer, the fit parameters for the corneal back surface exhibit a larger degree of variability compared with those for the front surface. Further studies are needed to show whether these uncertainties are representative for the situation where actual repeat measurements are possible.

Prediction of IOL decentration, tilt and axial position using anterior segment OCT data.

BACKGROUND: Intraocular lenses (IOLs) require proper positioning in the eye to provide good imaging performance. This is especially important for premium IOLs. The purpose of this study was to develop prediction models for estimating IOL decentration, tilt and the axial IOL equator position (IOLEQ) based on preoperative biometric and tomographic measures. METHODS: Based on a dataset (N = 250) containing preoperative IOLMaster 700 and pre-/postoperative Casia2 measurements from a cataractous population, we implemented shallow feedforward neural networks and multilinear regression models to predict the IOL decentration, tilt and IOLEQ from the preoperative biometric and tomography measures. After identifying the relevant predictors using a stepwise linear regression approach and training of the models (150 training and 50 validation data points), the performance was evaluated using an N = 50 subset of test data. RESULTS: In general, all models performed well. Prediction of IOL decentration shows the lowest performance, whereas prediction of IOL tilt and especially IOLEQ showed superior performance. According to the 95% confidence intervals, decentration/tilt/IOLEQ could be predicted within 0.3 mm/1.5°/0.3 mm. The neural network performed slightly better compared to the regression, but without significance for decentration and tilt. CONCLUSION: Neural network or linear regression-based prediction models for IOL decentration, tilt and axial lens position could be used for modern IOL power calculation schemes dealing with 'real' IOL positions and for indications for premium lenses, for which misplacement is known to induce photic effects and image distortion.

Monte-Carlo simulation for calculating phakic supplementary lenses based on a thick and thin lens model using anterior segment OCT data.

BACKGROUND: Phakic lenses (PIOLs, the most common and only disclosed type being the implantable collamer lens, ICL) are used in patients with large or excessive ametropia in cases where laser refractive surgery is contraindicated. The purpose of this study was to present a strategy based on anterior segment OCT data for calculating the refraction correction (REF) and the change in lateral magnification (ΔM) with ICL implantation. METHODS: Based on a dataset (N = 3659) containing Casia 2 measurements, we developed a vergence-based calculation scheme to derive the REF and gain or loss in ΔM on implantation of a PIOL having power PIOLP. The calculation concept is based on either a thick or thin lens model for the cornea and the PIOL. In a Monte-Carlo simulation considering, all PIOL steps listed in the US patent 5,913,898, nonlinear regression models for REF and ΔM were defined for each PIOL datapoint. RESULTS: The calculation shows that simplifying the PIOL to a thin lens could cause some inaccuracies in REF (up to ½ dpt) and ΔM for PIOLs with high positive power. The full range of listed ICL powers (- 17 to 17 dpt) could correct REF in a range from - 17 to 12 dpt with a change in ΔM from 17 to - 25%. The linear regression considering anterior segment biometric data and the PIOLP was not capable of properly characterizing REF and ΔM, whereas the nonlinear model with a quadratic term for the PIOLP showed a good performance for both REF and ΔM prediction. CONCLUSION: Where PIOL design data are available, the calculation concept should consider the PIOL as thick lens model. For daily use, a nonlinear regression model can properly predict REF and ΔM for the entire range of PIOL steps if a vergence calculation is unavailable.

Leaving trusted paths: Estimating corneal keratometric index in cataract surgery eyes with zero-power implants.

PURPOSE: This study aimed to estimate the corneal keratometric index in the eyes of cataract surgery patients who received zero-power intraocular lenses (IOLs). METHODOLOGY: This retrospective study analyzed postoperative equivalent spherical refraction and axial length, mean anterior curvature radius and aqueous humor refractive index to calculate the theoretical corneal keratometric index value (nk). Data was collected from 2 centers located in France and Germany. RESULTS: Thirty-six eyes were analyzed. The results revealed a mean corneal keratometric index of 1.329 ± 0.005 for traditional axial length (AL) and 1.331 ± 0.005 for Cooke modified axial length (CMAL). Results ranged from minimum values of 1.318/1.320 to maximum values of 1.340/1.340. CONCLUSION: The corneal keratometric index is a crucial parameter for ophthalmic procedures and calculations, particularly for IOL power calculation. Notably, the estimated corneal keratometric index value of 1.329/1.331 in this study is lower than the commonly used 1.3375 index. These findings align with recent research demonstrating that the theoretical corneal keratometric index should be approximately 1.329 using traditional AL and 1.331 using CMAL, based on the ratio between the mean anterior and posterior corneal curvature radii (1.22).

Evaluating keratometry and corneal astigmatism data from biometers and anterior segment tomographers and mapping to reconstructed corneal astigmatism.

BACKGROUND: To compare results from different corneal astigmatism measurement instruments; to reconstruct corneal astigmatism from the postimplantation spectacle refraction and toric intraocular lens (IOL) power; and to derive models for mapping measured corneal astigmatism to reconstructed corneal astigmatism. METHODS: Retrospective single centre study involving 150 eyes treated with a toric IOL (Alcon SN6AT, DFT or TFNT). Measurements included IOLMaster 700 keratometry (IOLMK) and total keratometry (IOLMTK), Pentacam keratometry (PK) and total corneal refractive power in 3 and 4 mm zones (PTCRP3 and PTCRP4), and Aladdin keratometry (AK). Regression-based models mapping the measured C0 and C45 components (Alpin's method) to reconstructed corneal astigmatism were derived. RESULTS: Mean C0 components were 0.50/0.59/0.51 dioptres (D) for IOLMK/PK/AK; 0.2/0.26/0.31 D for IOLMTK/PTCRP3/PTCRP4; and 0.26 D for reconstructed corneal astigmatism. All corresponding C45 components ranged around 0. The prediction models had main diagonal elements lower than 1 with some crosstalk between C0 and C45 (nonzero off-diagonal elements). Root-mean-squared residuals were 0.44/0.45/0.48/0.51/0.50/0.47 D for IOLMK/IOLMTK/PK/PTCRP3/PTCRP4/AK. CONCLUSIONS: Results from the different modalities are not consistent. On average IOLMTK/PTCRP3/PTCRP4 match reconstructed corneal astigmatism, whereas IOLMK/PK/AK show systematic C0 offsets of around 0.25 D. IOLMTK/PTCRP3/PTCRP4. Prediction models can reduce but not fully eliminate residual astigmatism after toric IOL implantation.

[Comparison of the Effect of Autologous Serum on Therapy Resistant Corneal Erosions and Ulcers on the Corneal Graft vs. the Patient's Own Cornea]. / Die Wirkung von autologen Serumaugentropfen bei therapieresistenten Erosiones und Ulcera der Kornea bei eigenem im Vergleich zu transplantiertem Gewebe.

PURPOSE: The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patient's own cornea after treatment with 100%, undiluted autologous serum eye drops. METHODS: In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed. RESULTS: 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patient's own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up. CONCLUSION: The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects - with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions.

In situ donor keratometry in deceased patients as a novel screening technique for eye banking.

PURPOSE: To investigate the potential role of keratometry on whole globes in situ of deceased patients by assessing its repeatability and comparing it with sterile donor tomography after excision and preservation in organ culture. METHODS: A sequence of 5 measurements was taken from 40 eyes in situ of deceased patients < 24 h after death using the portable Retinomax K-plus 3 (Bon, Tokyo, Japan). Keratometry of whole globes in situ, from which sclerocorneal discs were taken for organ culture, was compared to those obtained after measuring these sclerocorneal disks through their cell culture flask in medium I after 5 ± 4 days using the anterior segment optical coherence tomograph Casia 2 (Tomey Corp., Nagoya, Japan), and to 964 different donor corneas in medium II. RESULTS: Cronbach's alpha of the in situ keratometry was 0.891 and 0.942 for the steepest and flattest corneal power (P). The steepest (44.5D) and flattest (41.1D) P as well as the astigmatism (3.4D) of in situ corneas remained unchanged after preserving sclerocorneal discs in medium I (respectively 44.7D [p = 0.09]; 41.4D [p = 0.17]; 3.3D [p = 0.09]). The comparison of the in situ values with the 964 measured different donor corneas in medium II showed significantly (p < 0.001) higher P at the steep (45.4D) and flat (43.9D) meridian and smaller astigmatism (1.4D) for sterile donor tomography. CONCLUSIONS: Measuring deceased patients' eyes in situ with the portable Retinomax K-plus 3 represents a feasible and reliably repeatable screening method in the eye bank. In comparison to donor tomography in medium I, it measures a similar power and astigmatism.

Comparison of 2 modern swept-source optical biometers-IOLMaster 700 and Anterion.

PURPOSE: To compare biometric measures from 2 modern swept-source OCT biometers (IOLMaster700 (Z, Carl-Zeiss-Meditec) and Anterion (H, Heidelberg Engineering)) and evaluate the effect of measurement differences on the resulting lens power (IOLP). METHODS: Biometric measurements were made on a large study population with both instruments. We compared axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT) and corneal front and back surface curvature measurements. Corneal curvature was converted to power vectors and total power derived using the Gullstrand formula. A paraxial lens power calculation formula and a prediction for the IOL axial position according to the Castrop formula were used to estimate differences in IOLP targeting for emmetropia. RESULTS: There were no systematic differences between measurements of AL (- 0.0146 ± 0.0286 mm) and LT (0.0383 ± 0.0595 mm), whereas CCT yielded lower (7.8 ± 6.6 µm) and ACD higher (0.1200 ± 0.0531 mm) values with H. With H, CCT was lower for thicker corneas. The mean corneal front surface radius did not differ (- 0.4 ± 41.6 µm), but the corneal back surface yielded a steeper radius (- 397.0 ± 74.6 µm) with H, giving lower mean total power (- 0.3469 ± 0.2689 dpt). The astigmatic vector components in 0°/90° and 45°/135° were the same between both instruments for the front/back surface or total power. CONCLUSION: The biometric measures used in standard formulae (AL, corneal front surface curvature/power) are consistent between instruments. However, modern formulae involving ACD, CCT or corneal back surface curvature may yield differences in IOLP, and therefore, formula constant optimisation customised to the biometer type is required.

EDOF intraocular lens design: shift in image plane vs object vergence.

BACKGROUND: To compare 2 different design scenarios of EDOF-IOLs inserted in the Liou-Brennan schematic model eye using raytracing simulation as a function of pupil size. METHODS: Two EDOF IOL designs were created and optimized for the Liou-Brennan schematic model eye using Zemax ray tracing software. Each lens was optimized to achieve a maximum Strehl ratio for intermediate and far vision. In the first scenario, the object was located at infinity (O1), and the image plane was positioned at far focus (I1) and intermediate focus (I2) to emulate far and intermediate distance vision, respectively. In the second scenario, the image plane was fixed at I1 according to the first scenario. The object plane was set to infinity (O1) for far-distance vision and then shifted closer to the eye (O2) to reproduce the corresponding intermediate vision. The performance of both IOLs was simulated for the following 3 test conditions as a function of pupil size: a) O1 to I1, b) O1 to I2, and c) O2 to I1. To evaluate the imaging performance, we used the Strehl ratio, the root-mean-square (rms) of the spot radius, and the spherical aberration of the wavefront for various pupil sizes. RESULTS: Evaluating the imaging performance of the IOLs shows that the imaging performance of the IOLs is essentially identical for object/image at O1/I1. Designed IOLs perform dissimilarly to each other in near-vision scenarios, and the simulations confirm that there is a slight difference in their optical performance. CONCLUSION: Our simulation study recommends considering the difference between object shift and image plane shift in design and test conditions to achieve more accurate pseudoaccommodation after cataract surgery.

Best fit formula approach in delayed sequential bilateral cataract surgery.

BACKGROUND: We evaluated whether the best-fit intraocular lens (IOL) power formula for the first operated eye (BF1) was also the most accurate formula for the second eye. METHODS: This was a retrospective study of 152 patients who underwent uncomplicated delayed bilateral cataract surgery with a minimum delay of 3 weeks using only one 1-piece IOL (HOYA, Vivinex) at the Medical University of Vienna, Austria. Seven different formulae (Barrett Universal II, Castrop, Haigis, Hoffer Q, Holladay 1, Kane, and SRK/T) were investigated to test the formula selection approach with regard to the calculated mean and median absolute prediction errors (MAE/MedAE). RESULTS: The mean intraindividual difference in axial length was 0.2 mm (±0.3 mm). BF1 coincided with the best-fit formula for the second eye (BF2) in 56% of patients (p < 0.05). Using BF1 for the second eye led to a lower MedAE (0.22 dioptre, D) than using a formula at random (0.33 D) and was less accurate than using the best-fit formula for each eye separately (0.1 D). The MedAEs of all formulae were generally low, ranging from 0.28 to 0.35 D. CONCLUSION: Using BF1 for the second eye led to a lower MedAE than the random selection of a formula. Therefore, BF1 can be used for the second eye if the surgeon is unsure of the choice of formula.

Phototherapeutic Keratectomy for Salzmann's Nodular Degeneration. What Effect Does the Choice of Excimer Laser Have on Treatment Success? / Phototherapeutische Keratektomie bei Salzmannʼscher nodulärer Degeneration. Welche Auswirkung hat die Wahl des Excimerlasers auf den Erfolg der Behandlung?

PURPOSE: The aim of this study was to assess the difference in treatment success after phototherapeutic keratectomy (PTK) for Salzmann's nodular degeneration (SND) using two excimer lasers with different specifications. PATIENTS AND METHODS: 272 PTK procedures, which had been performed on 246 eyes with SND from 181 patients, were retrospectively examined in the period from 2007 to 2017. Until 2014 the excimer laser MEL70 (Carl Zeiss Meditec Vertriebsgesellschaft mbH, Oberkochen, Germany) was used for PTK following manual pannectomy, and after 2014 the excimer laser Amaris 750S (Schwind eye-tech-solutions GmbH, Kleinostheim, Germany) was used. Treatment success was assessed on basis of visual acuity, refraction, and astigmatism, as well as pachymetry and endothelial cell count, recorded at the following time points: T1 = preoperative, T2 = 6-week follow-up, T3 = 6-month follow-up. The Wilcoxon-Mann-Whitney U test and the chi-square test with a significance level of 5% were used to compare the data. RESULTS: A significantly higher improvement of 0.17 ± 0.33 logMAR could be shown for visual acuity in the Schwind group (p < 0.013) after 6 months. In the Zeiss group, visual acuity improved by only 0.11 ± 0.36 (logMAR p < 0.057). Regarding refraction, a significant reduction of the spherical equivalent (SEQ) (p < 0.001) by 3.35 ± 2.76 diopters (D) after 6 months could only be shown for the Schwind group. SEQ did not change significantly in the Zeiss group (p < 0.676). The topographic astigmatism was significantly improved after 6 months in both study groups, by 1.73 ± 1.99 D in the Schwind group (p < 0.001) and by 1.99 ± 2.21 D in the Zeiss group (p < 0.0001). Haze had to be treated in 12.7% of the cases in the Schwind group and in 16.2% of the cases in the Zeiss group. No endothelial cell damage was found in either group. CONCLUSIONS: In both study groups, the patients with SND clearly benefited from PTK. However, a significantly higher advantage for visual acuity and refraction was shown for the Schwind group compared with the Zeiss group. In contrast to the usual hyperopic effect of PTK in other diagnoses, PTK in SND showed a "myopic shift", which can be explained by the often midperipheral SND nodes and the associated asymmetric tear film pooling prior to surgery.

The Biomechanical E-Staging: In Vivo Biomechanics in Keratoconus. / Das biomechanische E-Staging: In-vivo-Biomechanik beim Keratokonus.

Belin's ABCD keratoconus classification system allows keratoconus staging based on the criteria of anterior (A) and posterior (B) corneal curvature, thinnest corneal thickness (C), and best spectacle-corrected visual acuity (D). These parameters also provide a progression assessment, but do not take corneal biomechanics into account. The analysis of corneal biomechanics by the Corvis ST (Oculus, Wetzlar, Germany) allows for separation of healthy and keratoconus corneas, based on the Corvis Biomechanical Index (CBI) and the Tomographic Biomechanical Index (TBI). As Corvis ST measurements are highly reliable and are independent of keratoconus severity, a biomechanical parameter was developed for keratoconus corneas based on the linear term of the CBI. This provides biomechanical keratoconus staging. The Corvis Biomechanical Factor (CBiF) is the basis for the introduction of the biomechanical E-staging, which augments the ABCD classification to the ABCDE classification, thus including the cornerstone of corneal biomechanics. This article highlights strengths and limitations of the ABCDE classification. "Unilateral keratoconus" supposedly turns out to be mostly a snapshot of a highly asymmetric keratectasia. Regular astigmatism is sometimes an important differential diagnosis to keratectasia and may be difficult to differentiate from it. Furthermore, the use of the biomechanical E-staging in daily practice for progression assessment of keratoconus and after its treatment by corneal cross-linking or implantation of intracorneal ring segments will be demonstrated and discussed.

Assessment of Rose Bengal Photodynamic Therapy on Viability and Proliferation of Human Keratolimbal Epithelial and Stromal Cells In Vitro.

PURPOSE: To investigate the effect of Rose Bengal photodynamic therapy (RB-PDT) on viability and proliferation of human limbal epithelial stem cells (T-LSCs), human corneal epithelial cells (HCE-T), human limbal fibroblasts (LFCs), and human normal and keratoconus fibroblasts (HCFs and KC-HCFs) in vitro. METHODS: T-LSCs and HCE-T cell lines were used in this research. LFCs were isolated from healthy donor corneal limbi (n = 5), HCFs from healthy human donor corneas (n = 5), and KC-HCFs from penetrating keratoplasties of keratoconus patients (n = 5). After cell culture, RB-PDT was performed using 0.001% RB concentration and 565 nm wavelength illumination with 0.14 to 0.7 J/cm2 fluence. The XTT and the BrdU assays were used to assess cell viability and proliferation 24 h after RB-PDT. RESULTS: RB or illumination alone did not change cell viability or proliferation in any of the cell types (p ≥ 0.1). However, following RB-PDT, viability decreased significantly from 0.17 J/cm2 fluence in HCFs (p < 0.001) and KC-HCFs (p < 0.0001), and from 0.35 J/cm2 fluence in T-LSCs (p < 0.001), HCE-T (p < 0.05), and LFCs ((p < 0.0001). Cell proliferation decreased significantly from 0.14 J/cm2 fluence in T-LSCs (p < 0.0001), HCE-T (p < 0.05), and KC-HCFs (p < 0.001) and from 0.17 J/cm2 fluence in HCFs (p < 0.05). Regarding LFCs proliferation, no values could be determined by the BrdU assay. CONCLUSIONS: Though RB-PDT seems to be a safe and effective treatment method in vivo, its dose-dependent phototoxicity on corneal epithelial and stromal cells has to be respected. The data and experimental parameters applied in this study may provide a reliable reference for future investigations.

A Comparison of Optical Biometers Used in Children for Myopia Control.

PURPOSE: To assess the reproducibility (i.e., inter-device reliability) of the biometers Topcon MYAH, Oculus Myopia Master, and Haag-Streit Lenstar LS900 with the Carl Zeiss IOLMaster 700 and the intra-subject repeatability in myopic children in order to reliably detect axial growth for myopia management. METHODS: Twenty-two myopic children (11.1 ± 2.4 yr) with a spherical equivalent of - 3.53 ± 2.35 D were examined with each of the biometers to assess axial length (AL) and corneal parameters (steepK, flatK, meanK, vectors J0, J45), and16 of these children agreed to a second round of measurements. Reproducibility of the first measurements between the IOLMaster and every other biometer was assessed employing a Bland-Altman approach and paired Student's t-test. Repeatability was assessed as intra-subject standard deviation and was used to estimate the minimum time interval required between two AL measurements to reliably detect axial growth of an eye of at least 0.1 mm/year. RESULTS: Repeatability for AL measurements was as follows: IOLMaster: 0.05 mm, Myopia Master: 0.06 mm, Myah: 0.06 mm, Lenstar: 0.04 mm; the respective minimal time interval for axial growth assessment in myopia management was estimated as 5.6, 6.6, 6.7, and 5.0 months, respectively. Best reproducibility of the AL measurement was found between IOLMaster and Lenstar [95% Limits of Agreement (LoA) for reproducibility - 0.06 to 0.02]. As regards to the measured means, Lenstar gave measures of AL that were longer than with the IOLMaster by 0.02 mm (p < 0.001). Myopia Master measures of meanK were significantly lower (by 0.21 D with p < 0.001) than the values from the IOLMaster. As for J0, all biometers deviated significantly from IOLMaster measurements (p < 0.05). CONCLUSION: Generally good agreement was observed between all the biometers. When assessing myopia progression in children, a time frame of at least 6 months between the AL measurements is advisable in order to reliably determine any deviation from a normal growth pattern.

Culturing Limbal Epithelial Cells of Long-term Stored Corneal Donors (Organ Culture) In Vitro - A Stepwise Linear Regression Algorithm.

PURPOSE: To assess various potential factors on human limbal epithelial cell (LEC) outgrowth in vitro using corneal donor tissue following long-term storage (organ culture) and a stepwise linear regression algorithm. METHODS: Of 215 donors, 304 corneoscleral rings were used for our experiments. For digestion of the limbal tissue and isolation of the limbal epithelial cells, the tissue pieces were incubated with 4.0 mg/mL collagenase A at 37 °C with 95% relative humidity and a 5% CO2 atmosphere overnight. Thereafter, limbal epithelial cells were separated from limbal keratocytes using a 20-µm CellTricks filter. The separated human LECs were cultured in keratinocyte serum-free medium medium, 1% penicillin/streptomycin (P/S), 0.02% epidermal growth factor (EGF), and 0.3% bovine pituitary extract (BPE). The potential effect of donor age (covariate), postmortem time (covariate), medium time (covariate), size of the used corneoscleral ring (360°, 270°180°, 120°, 90°, less than 90°) (covariate), endothelial cell density (ECD) (covariate), gender (factor), number of culture medium changes during organ culture (factor), and origin of the donor (donating institution and storing institution, factor) on the limbal epithelial cell outgrowth was analyzed with a stepwise linear regression algorithm. RESULTS: The rate of successful human LEC outgrowth was 37.5%. From the stepwise linear regression algorithm, we found out that the relevant influencing parameters on the LEC growth were intercept (p < 0.001), donor age (p = 0.002), number of culture medium changes during organ culture (p < 0.001), total medium time (p = 0.181), and size of the used corneoscleral ring (p = 0.007), as well as medium time × size of the corneoscleral ring (p = 0.007). CONCLUSIONS: The success of LEC outgrowth increases with lower donor age, lower number of organ culture medium changes during storage, shorter medium time in organ culture, and smaller corneoscleral ring size. Our stepwise linear regression algorithm may help us in optimizing LEC cultures in vitro.

Decreased FABP5 and DSG1 protein expression following PAX6 knockdown of differentiated human limbal epithelial cells.

PAX6 haploinsufficiency related aniridia is characterized by disorder of limbal epithelial cells (LECs) and aniridia related keratopathy. In the limbal epithelial cells of aniridia patients, deregulated retinoic acid (RA) signaling components were identified. We aimed to visualize differentiation marker and RA signaling component expression in LECs, combining a differentiation triggering growth condition with a small interfering RNA (siRNA) based aniridia cell model (PAX6 knock down). Primary LECs were isolated from corneoscleral rims of healthy donors and cultured in serum free low Ca2+ medium (KSFM) and in KSFM supplemented with 0.9 mmol/L Ca2+. In addition, LECs were treated with siRNA against PAX6. DSG1, PAX6, KRT12, KRT 3, ADH7, RDH10, ALDH1A1, ALDH3A1, STRA6, CYP1B1, RBP1, CRABP2, FABP5, PPARG, VEGFA and ELOVL7 expression was determined using qPCR and western blot. DSG1, FABP5, ADH7, ALDH1A1, RBP1, CRABP2 and PAX6 mRNA and FABP5 protein expression increased (p ≤ 0.03), PPARG, CYP1B1 mRNA expression decreased (p ≤ 0.0003) and DSG1 protein expression was only visible after Ca2+ supplementation. After PAX6 knock down and Ca2+ supplementation, ADH7 and ALDH1A1 mRNA and DSG1 and FABP5 protein expression decreased (p ≤ 0.04), compared to Ca2+ supplementation alone. Using our cell model, with Ca2+ supplementation and PAX6 knockdown with siRNA treatment against PAX6, we provide evidence that haploinsufficiency of the master regulatory gene PAX6 contributes to differentiation defect in the corneal epithelium through alterations of RA signalling. Upon PAX6 knockdown, DSG1 differentiation marker and FABP5 RA signaling component mRNA expression decreases. A similar effect becomes apparent at protein level though differentiation triggering Ca2+ supplementation in the siRNA-based aniridia cell model. Expression data from this cell model and from our siRNA aniridia cell model strongly indicate that FABP5 expression is PAX6 dependent. These new findings may lead to a better understanding of differentiation processes in LECs and are able to explain the insufficient cell function in AAK.

Meridional ocular magnification after cataract surgery with toric and non-toric intraocular lenses.

BACKGROUND: Overall ocular magnification (OOM) and meridional ocular magnification (MOM) with consequent image distortions have been widely ignored in modern cataract surgery. The purpose of this study was to investigate OOM and MOM in a general situation with an astigmatic refracting surface. METHODS: From a large dataset containing biometric measurements (IOLMaster 700) of both eyes of 9734 patients prior to cataract surgery, the equivalent (PIOLeq) and cylindric power (PIOLcyl) were derived for the HofferQ, Haigis, and Castrop formulae for emmetropia. Based on the pseudophakic eye model, OOM and MOM were extracted using 4 × 4 matrix algebra for the corrected eye (with PIOLeq/PIOLcyl (scenario 1) or with PIOLeq and spectacle correction of the residual refractive cylinder (scenario 2) or with PIOLeq remaining the residual uncorrected refractive cylinder (blurry image) (scenario 3)). In each case, the relative image distortion of MOM/OOM was calculated in %. RESULTS: On average, PIOLeq/PIOLcyl was 20.73 ± 4.50 dpt/1.39 ± 1.09 dpt for HofferQ, 20.75 ± 4.23 dpt/1.29 ± 1.01 dpt for Haigis, and 20.63 ± 4.31 dpt/1.26 ± 0.98 dpt for Castrop formulae. Cylindric refraction for scenario 2 was 0.91 ± 0.70 dpt, 0.89 ± 0.69 dpt, and 0.89 ± 0.69 dpt, respectively. OOM/MOM (× 1000) was 16.56 ± 1.20/0.08 ± 0.07, 16.56 ± 1.20/0.18 ± 0.14, and 16.56 ± 1.20/0.08 ± 0.07 mm/mrad with HofferQ; 16.64 ± 1.16/0.07 ± 0.06, 16.64 ± 1.16/0.18 ± 0.14, and 16.64 ± 1.16/0.07 ± 0.06 mm/mrad with Haigis; and 16.72 ± 1.18/0.07 ± 0.05, 16.72 ± 1.18/0.18 ± 0.14, and 16.72 ± 1.18/0.07 ± 0.05 mm/mrad with Castrop formulae. Mean/95% quantile relative image distortion was 0.49/1.23%, 0.41/1.05%, and 0.40/0.98% for scenarios 1 and 3 and 1.09/2.71%, 1.07/2.66%, and 1.06/2.64% for scenario 2 with HofferQ, Haigis, and Castrop formulae. CONCLUSION: Matrix representation of the pseudophakic eye allows for a simple and straightforward prediction of OOM and MOM of the pseudophakic eye after cataract surgery. OOM and MOM could be used for estimating monocular image distortions, or differences in overall or meridional magnifications between eyes.

Prediction of corneal back surface power - Deep learning algorithm versus multivariate regression.

BACKGROUND: The corneal back surface is known to add some against the rule astigmatism, with implications in cataract surgery with toric lens implantation. This study aimed to set up and validate a deep learning algorithm to predict corneal back surface power from the corneal front surface power and biometric measures. METHODS: This study was based on a large dataset of IOLMaster 700 measurements from two clinical centres. N = 19,553 measurements of 19,553 eyes with valid corneal front (CFSPM) and back surface power (CBSPM) data and other biometric measures. After a vector decomposition of CFSPM and CBSPM into equivalent power and projections of astigmatism to the 0°/90° and 45°/135° axes, a multi-output feedforward neural network was derived to predict vector components of CBSPM from CFSPM and other measurements. The predictions were compared with a multivariate linear regression model based on CFSPM components only. RESULTS: After pre-conditioning, a network with two hidden layers each having 12 neurons was derived. The dataset was split into training (70%), validation (15%) and test (15%) subsets. The prediction error (predicted corneal back surface power CBSPP - CBSPM) of the network after training and crossvalidation showed no systematic offset, narrower distributions for CBSPP - CBSPM and no trend error of CBSPP - CBSPM vs. CBSPM for any of the vector components. The multivariate linear model also showed no systematic offset, but broader distributions of the prediction error components and a systematic trend of all vector components vs. CFSPM components. CONCLUSION: The neural network approach based on CFSPM vector components and other biometric measures outperforms the multivariate linear model in predicting corneal back surface power vector components. Modern biometers can supply all parameters required for this algorithm, enabling reliable predictions for corneal back surface data where direct corneal back surface data are unavailable.

Calculation of Equivalent and Toric Power in AddOn Lenses Based on a Monte Carlo Simulation.

INTRODUCTION: Additional lenses implanted in the ciliary sulcus (AddOn) are one option for permanent correction of refractive error or generate pseudoaccommodation in the pseudophakic eye. The purpose of this paper was to model the power and magnification behaviour of toric AddOn and to show the effect sizes with a Monte Carlo simulation. METHODS: Anonymized data of a cataractous population uploaded for formula constant optimization were extracted from the IOLCon platform. After filtering out data with refractive spherical equivalent (RSEQ) between -0.75 and 0.25 dpt and refractive cylinder (RCYL) lower than 0.75, for each of the N = 6,588 records, a toric AddOn was calculated which transfers the refraction error from spectacle plane to AddOn plane using a matrix-based calculation strategy based on linear Gaussian optics. The equivalent (AddOnEQ) and toric (AddOnCYL) power of the AddOn and the overall lateral magnification change and meridional magnification were derived for the situations before and after AddOn implantation, and a linear modelling was fitted for all 4 parameters. RESULTS: RSEQ is the dominant effect size in the prediction of AddOnEQ and overall change in magnification (ΔM), whereas the lens position (LP), corneal thickness (CCT), and mean corneal radius (CPa) play a minor role. In a simplified model, AddOnEQ can be estimated by 0.0179 + 1.4104 RSEQ. RCYL and corneal radius difference (CPad) are the dominant effect sizes in the prediction of AddOnCYL and the change in meridional magnification (ΔMmer), whereas LP, CCT, CPa, and RSEQ play a minor role. In a simplified model, AddOnCYL can be predicted by -0.0005 + 0.0328 CPad + 1.4087 RCYL. Myopic eyes gain in overall magnification, whereas in hyperopic eyes, we observe a loss. Meridional distortion could be in general reduced to 35% on average with a toric AddOn. CONCLUSION: Our simulation shows that with a linear model, the equivalent and toric AddOn power, as well as overall change in magnification, meridional distortion before and after AddOn implantation, and the reduction in meridional distortion, can be easily predicted from the biometric data in pseudophakic eyes with moderate refractive error.

Reliability and efficiency of corneal thickness measurements using sterile donor tomography in the eye bank.

To evaluate the reliability and efficiency of sterile pachymetric measurements of donor corneas based on tomographic data using two different methods: a "manual" and a "(semi-)automated" method. Twenty-five (25) donor corneas (50%) stored in MI and 25 (50%) in MII were imaged 5 times consecutively using an anterior segment OCT (AS-OCT). The central corneal thickness (CCT) was measured both with the manual measurement tool of the AS-OCT (= CCTm) and with a MATLAB self-programmed software allowing (semi-)automated analysis (= CCTa). We analyzed the reliability of CCTm and CCTa using Cronbach´s alpha (α) and Wilcoxon signed-Rank Test. Concerning CCTm, 68 measurements (54.4%) in MI and 46 (36.8%) in MII presented distortions in the imaged 3D-volumes and were discarded. Concerning CCTa, 5 (4%) in MI and 1 (0.8%) in MII were not analyzable. The mean (± SD) CCTm was 1129 ± 6.8 in MI and 820 ± 5.1 µm in MII. The mean CCTa was 1149 ± 2.7 and 811 ± 2.4 µm, respectively. Both methods showed a high reliability with a Cronbach´s α for CCTm of 1.0 (MI/MII) and for CCTa of 0.99 (MI) and 1.0 (MII). Nevertheless, the mean SD of the 5 measurements was significantly higher for CCTm compared to CCTa in MI (p = 0.03), but not in MII (p = 0.92). Sterile donor tomography proves to be highly reliable for assessment of CCT with both methods. However, due to frequent distortions regarding the manual method, the (semi-)automated method is more efficient and should be preferred.