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.

Rose Bengal Photodynamic Therapy (RB-PDT) Modulates the Inflammatory Response in LPS-Stimulated Human Corneal Fibroblasts By Influencing NF-κB and p38 MAPK Signaling Pathways.

PURPOSE: To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. METHODS: Human corneal fibroblast cultures underwent 0-2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0.17 J/cm2 fluence). Interleukin-6, interleukin-8, intercellular adhesion molecule-1, interferon regulatory factor-3, interferon α2, and interferon ß1 gene expressions were determined by quantitative PCR. Interleukin-6, interleukin-8, and C-C motif chemokine ligand-4 concentrations in the cell culture supernatant were measured by enzyme-linked immunosorbent assays and intercellular adhesion molecule-1 protein level in human corneal fibroblasts by western blot. In addition, the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways were investigated by quantitative PCR and phosphorylation of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase by western blot. RESULTS: Rose bengal photodynamic therapy in 2.0 µg/mL lipopolysaccharide-stimulated human corneal fibroblasts triggered interleukin-6 and interleukin-8 mRNA (p < .0001) and interleukin-6 protein increase (p < .0001), and downregulated intercellular adhesion molecule-1 expression (p < .001). C-C motif chemokine ligand-4, interferon regulatory factor-3, interferon α2, and interferon ß1 expressions remained unchanged (p ≥ .2). Rose bengal photodynamic therapy increased IκB kinase subunit beta, nuclear factor kappa B p65, extracellular signal-regulated kinases-2, c-Jun amino terminal kinase, and p38 transcription (p ≤ .01), and triggered nuclear factor kappa B p65 and p38 mitogen-activated protein kinase phosphorylation (p ≤ .04) in lipopolysaccharide treated human corneal fibroblasts. CONCLUSION: Rose bengal photodynamic therapy of lipopolysaccharide-stimulated human corneal fibroblasts can modify the inflammatory response by inducing interleukin-6 and interleukin-8 expression, and decreasing intercellular adhesion molecule-1 production. C-C motif chemokine ligand-4, interferon regulatory factor-3, and interferon α and ß expressions are not affected by rose bengal photodynamic therapy in these cells. The underlying mechanisms may be associated with nuclear factor kappa B and p38 mitogen-activated protein kinase pathway activation.

Vector analysis of corneal astigmatism in cataractous eyes based on IOLMaster 700 biometry.

PURPOSE: The purpose of this study was to investigate the effect of the corneal back surface by comparing the keratometric astigmatism (K, derived from the corneal front surface) of a modern optical biometer against astigmatism of Total Keratometry (TK, derived from both corneal surfaces) in a large population with cataractous eyes. The results were then used to define linear prediction models to map K to TK. METHODS: From a large dataset containing bilateral biometric measurements (IOLMaster 700) in 9736 patients prior to cataract surgery, the total corneal astigmatism was decomposed into vectors for K, corneal back surface (BS), and TK. A multivariate prediction model (MV), simplified model with separation of vector components (SM) and a constant model (CM) were defined to map K to TK vector components. RESULTS: The K centroid (X/Y) showed some astigmatism with-the-rule (0.1981/-0.0211 dioptre (dpt)) whereas the TK centroid was located around zero (-0.0071/-0.0381 dpt against-the-rule) and the BS centroid showed systematic astigmatism against-the-rule (-0.2367/-0.0145 dpt). The respective TK-K centroid was located at -0.2052/-0.0302 dpt. The MV model showed the same performance (i.e. mean absolute residuum) as the SM did (0.1098 and 0.1099 dpt respectively) while the CM performed only slightly worse (0.1121 dpt mean absolute residuum). CONCLUSION: In cases where tomographic data are unavailable statistical models could be used to consider the overall contribution of the back surface to the total corneal astigmatism. Since the performance of the CM is sufficiently close to that of MV and SM we recommend using the CM which can be directly considered e.g. as surgically induced astigmatism.

Performance of a simplified strategy for formula constant optimisation in intraocular lens power calculation.

PURPOSE: To investigate the performance of a simple prediction scheme for the formula constants optimised for a mean refractive prediction error. METHODS: Analysis based on a dataset of 888 eyes before and after cataract surgery with IOL implantation (Hoya Vivinex). IOLMaster 700 biometric data, power of the implanted lens and postoperative spherical equivalent refraction were used to calculate the optimised constants (.)opt for SRKT, HofferQ, Holladay and Haigis formula with an iterative nonlinear optimisation. For detuning start values by ±1.5 from (.)opt, the predicted formula constants (.)pred were calculated and compared with (.)opt. Formula performance metrics mean (MPE), median (MEDPE), mean absolute (MAPE), median absolute (MEDAPE), root mean squared (RMSPE) and standard deviation (SDPE) of the formula prediction error were analysed for (.)opt and (.)pred. RESULTS: (.)pred - (.)opt showed a 2nd order parabolic behaviour with maximal deviations up to 0.09 at the tails of detuning and a minimal deviation up to -0.01 for all formulae. The performance curves of different metrics of PE as functions of detuning variations show that the formula constants for zeroing MPE and MEDPE yield almost identical formula constants, optimisation for MAPE, MEDAPE and RMSPE yielded formula constants very close to (.)opt, and optimisation for SDPE could result in formula constants up to 0.5 off (.)opt which is unacceptable for clinical use. CONCLUSION: This simple prediction scheme for formula constant optimisation for zero mean refraction error performs excellently in our monocentric dataset, even for larger deviations of the start value from (.)opt. Further studies with multicentric data and larger sample sizes are required to investigate the performance in a clinical setting further.

Examination of Subbasal Nerve Plexus and Central Corneal Stromal Microstructure in Subjects With Congenital Aniridia, Using in Vivo Confocal Laser Scanning Microscopy.

PURPOSE: During life up to 70% of aniridia subjects develop aniridia-associated keratopathy (AAK). AAK is characterized by limbal stem cell insufficiency, impaired corneal epithelial cell differentiation and abnormal cell adhesion, which leads to centripetal spreading vascularization, conjunctivalization, and thickening of the cornea. Our aim was to examine the subbasal nerve plexus and central corneal stromal microstructure in subjects with congenital aniridia, using in vivo confocal laser scanning microscopy CLSM. METHODS: 31 eyes of 18 patients (55.6% males, mean age: 25.22 ± 16.35 years) with congenital aniridia and 46 eyes of 29 healthy subjects (41.4% males, mean age 30 ± 14.82 years) were examined using the Rostock Cornea Module of Heidelberg Retina Tomograph-III. At the subbasal nerve plexus, corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), and corneal nerve fiber width (CNFW) were analyzed using ACCMetrics software. Keratocyte density in the anterior, middle and posterior stroma was assessed manually. RESULTS: The CNFD (2.02 ± 4.08 vs 13.99 ± 6.34/mm2), CNFL (5.78 ± 2.68 vs 10.56 ± 2.82 mm/mm2) and CTBD (15.08 ± 15.62 vs 27.44 ± 15.05/mm2) were significantly lower in congenital aniridia subjects than in controls (p < 0.001 for all). CNFW was significantly higher in aniridia subjects than in controls (0.03 ± 0.004 vs 0.02 ± 0.003 mm/mm2) (p = 0.003). Keratocyte density was significantly lower in all stromal layers of aniridia subjects than in controls (p < 0.001 for all). Stromal alterations included confluent keratocytes, keratocytes with long extensions and hyperreflective dots between keratocytes in aniridia. CONCLUSIONS: Decrease in CNFD, CNFL, and CTBD, as well as increase in CNFW well refer to the congenital aniridia-associated neuropathy. The decreased keratocyte density and the stromal alterations may be related to an increased cell death in congenital aniridia, nevertheless, stromal changes in different stages of AAK have to be further analyzed in detail.

Clinical Characteristics and Treatment of Ophthalmic Sequelae of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at a Tertiary Eyecare Centre in Hungary.

INTRODUCTION: This study analysed the causative factors and clinical characteristics of acute and chronic ocular sequelae of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) treated at a large third-referral centre in a developed country (Hungary) over a 15-year period. METHODS: This was a retrospective review of patients with acute and/or chronic SJS/TEN who were managed between 2006 and 2020 at the Department of Ophthalmology of Semmelweis University in Budapest, Hungary. For each subject, clinical data, including patient demographics, clinical history, causative agents of SJS/TEN, and conservative and surgical treatment details, were reviewed. RESULTS: Ninety-six eyes of 48 patients were included (28 female; 58.3%); the age at disease onset was 32.1 ± 22.4 years. The most common causative factors were medicines (n = 36; 75.0%). Among these drugs, 29.2% were nonsteroidal anti-inflammatory drugs (NSAIDs) (n = 14), 20.8% were antibiotics (n = 10) and 14.6% were antiepileptic drugs (n = 7). In patients with chronic SJS/TEN, the most commonly found ocular sequelae were conjunctival hyperaemia in 45 (56.3%) eyes, symblepharon in 38 (47.5%) eyes, trichiasis/distichiasis in 37 (46.3%) eyes, corneal neovascularization in 31 (38.8%) eyes and corneal scarring in 29 (36.3%) eyes. In patients with chronic SJS/TEN, the most frequently used topical conservative treatment included antibiotics in 53 (66.3%) eyes, preservative-free artificial tears in 50 (62.5%) eyes and topical corticosteroids in 42 (52.5%) eyes of 40 patients. The most frequently performed ocular surgeries for managing chronic ocular sequelae in patients with SJS/TEN were epilation for trichiasis (n = 27; 33.8%), cataract surgery (n = 14; 17.5%), entropion surgery (n = 12; 15.0%), penetrating keratoplasty (PK) (n = 11; 13.8%) and amniotic membrane transplantation (n = 4; 5.0%). CONCLUSION: Our results suggest that NSAIDs, antibiotics and antiepileptic drugs are the most common causative factors for SJS/TEN in Hungary. Like in other countries, in Hungary, the ocular management of patients with acute and chronic SJS/TEN is heterogeneous, and most cases do not follow modern therapeutic guidelines.

Surrogate optimisation strategies for intraocular lens formula constant optimisation.

PURPOSE: To investigate surrogate optimisation (SO) as a modern, purely data-driven, nonlinear adaptive iterative strategy for lens formula constant optimisation in intraocular lens power calculation. METHODS: A SO algorithm was implemented for optimising the root mean squared formula prediction error (rmsPE, defined as predicted refraction minus achieved refraction) for the SRKT, Hoffer Q, Holladay, Haigis and Castrop formulae in a dataset of N = 888 cataractous eyes with implantation of the Hoya Vivinex hydrophobic acrylic aspheric lens. A Gaussian Process estimator was used as the model, and the SO was initialised with equidistant datapoints within box constraints, and the number of iterations restricted to either 200 (SRKT, Hoffer Q, Holladay) or 700 (Haigis, Castrop). The performance of the algorithm was compared to the classical gradient-based Levenberg-Marquardt algorithm. RESULTS: The SO algorithm showed stable convergence after fewer than 50/150 iterations (SRKT, HofferQ, Holladay, Haigis, Castrop). The rmsPE was reduced systematically to 0.4407/0.4288/0.4265/0.3711/0.3449 dioptres. The final constants were A = 119.2709, pACD = 5.7359, SF = 1.9688, -a0 = 0.5914/a1 = 0.3570/a2 = 0.1970, C = 0.3171/H = 0.2053/R = 0.0947 for the SRKT, Hoffer Q, Holladay, Haigis and Castrop formula and matched the respective constants optimised in previous studies. CONCLUSION: The SO proves to be a powerful adaptive nonlinear iteration algorithm for formula constant optimisation, even in formulae with one or more constants. It acts independently of a gradient and is in general able to search within a (box) constrained parameter space for the best solution, even where there are multiple local minima of the target function.

Repeatability of biometric measures from the IOLMaster 700 in a cataractous population.

PURPOSE: The purpose of this study was to investigate the repeatability of biometric measures and also to assess the interactions between the uncertainties in these measures for use in an error propagation model, using data from a large patient cohort. METHODS: In this cross-sectional non-randomised study we evaluated a dataset containing 3379 IOLMaster 700 biometric measurements taken prior to cataract surgery. Only complete scans with at least 3 successful measurements for each eye performed on the same day were considered. The mean (Mean) and standard deviations (SD) for each sequence of measurements were derived and analysed. Correlations between the uncertainties were assessed using Spearman rank correlations. RESULTS: In the dataset with 677 eyes matching the inclusion criteria, the within subject standard deviation and repeatability for all parameters match previously published data. The SD of the axial length (AL) increased with the Mean AL, but there was no noticeable dependency of the SD of any of the other parameters on their corresponding Mean value. The SDs of the parameters are not independent of one another, and in particular we observe correlations between those for AL, anterior chamber depth, aqueous depth, lens thickness and corneal thickness. CONCLUSIONS: The SD change over Mean for AL measurement and the correlations between the uncertainties of several biometric parameters mean that a simple Gaussian error propagation model cannot be used to derive the effect of biometric uncertainties on the predicted intraocular lens power and refraction after cataract surgery.

Monte-Carlo simulation of a thick lens IOL power calculation.

BACKGROUND: The purpose of this Monte-Carlo study is to investigate the effect of using a thick lens model instead of a thin lens model for the intraocular lens (IOL) on the resulting refraction at the spectacle plane and on the ocular magnification based on a large clinical data set. METHODS: A pseudophakic model eye with a thin spectacle correction, a thick cornea (curvatures for both surfaces and central thickness) and a thick IOL (equivalent power PL derived from a thin lens IOL, Coddington factor CL (uniformly distributed from -1.0 to 1.0), either preset central thickness LT = 0.9 mm (A) or optic edge thickness ET = 0.2 mm, (B)) was set up. Calculations were performed on a clinical data set containing 21 108 biometric measurements of a cataractous population based on linear Gaussian optics to derive spectacle refraction and ocular magnification using the thin and thick lens IOL models. RESULTS: A prediction model (restricted to linear terms without interactions) was derived based on the relevant parameters identified with a stepwise linear regression approach to provide a simple method for estimating the change in spectacle refraction and ocular magnification where a thick lens IOL is used instead of a thin lens IOL. The change in spectacle refraction using a thick lens IOL with (A) or (B) instead of a thin lens IOL with identical power was within limits of around ±1.5 dpt when the thick lens IOL was placed with its haptic plane at the plane of the thin lens IOL. In contrast, the change in ocular magnification from considering the IOL as a thick lens instead of a thin lens was small and not clinically significant. CONCLUSION: This Monte-Carlo simulation shows the impact of using a thick lens model IOL with preset LT or ET on the resulting spherical equivalent refraction and ocular magnification. If IOL manufacturers would provide all relevant data on IOL design data and refractive index for all power steps, this would make it possible to perform direct calculations of refraction and ocular magnification.

Evaluation of statistical correction strategies for corneal back surface astigmatism with toric lenses: a vector analysis.

PURPOSE: To compare actual and formula-predicted postoperative refractive astigmatism using measured posterior corneal power measurements and 4 different empiric posterior corneal astigmatism correction models. SETTING: Tertiary care center. DESIGN: Single-center retrospective consecutive case series. METHODS: Using a dataset of 211 eyes before and after tIOL implantation (Hoya Vivinex), IOLMaster 700 (IOLM) or Casia2 (CASIA) keratometric and front/back surface corneal power measurements were converted to power vector components C0 (0/90 degrees) and C45 (45/135 degrees). Differences between postoperative and Castrop formula predicted refraction at the corneal plane using the labeled parameters of the tIOL and the keratometric or front/back surface corneal powers were recorded as the effect of corneal back surface astigmatism (BSA). RESULTS: Generally, the centroid of the difference shifted toward negative C0 values indicating that BSA adds some against the rule corneal astigmatism (ATR). From IOLM/CASIA keratometry, the average difference in C0 was 0.39/0.32 diopter (D). After correction with the Abulafia-Koch, Goggin, La Hood, and Castrop nomograms, it was -0.18/-0.24 D, 0.27/0.18 D, 0.13/0.08 D, and 0.17/0.10 D. Using corneal front/back surface data from IOLM/CASIA, the difference was 0.18/0.12 D. CONCLUSIONS: The Abulafia-Koch method overcorrected the ATR, while the Goggin, La Hood, and Castrop models slightly undercorrected ATR, and using measurements from the CASIA tomographer seemed to produce slightly less prediction error than IOLM.

Impact of uncertainties in biometric parameters on intraocular lens power formula predicted refraction using a Monte-Carlo simulation.

PURPOSE: The purpose of this study was to investigate the uncertainty in the formula predicted refractive outcome REFU after cataract surgery resulting from measurement uncertainties in modern optical biometers using literature data for within-subject standard deviation Sw. METHODS: This Monte-Carlo simulation study used a large dataset containing 16 667 preoperative IOLMaster 700 biometric measurements. Based on literature Sw values, REFU was derived for both the Haigis and Castrop formulae using error propagation strategies. Using the Hoya Vivinex lens (IOL) as an example, REFU was calculated both with (WLT) and without (WoLT) consideration of IOL power labelling tolerances. RESULTS: WoLT the median REFU was 0.10/0.12 dpt for the Haigis/Castrop formula, and WLT it was 0.13/0.15 dpt. WoLT REFU increased systematically for short eyes (or high power IOLs), and WLT this effect was even more pronounced because of increased labelling tolerances. WoLT the uncertainty in the measurement of the corneal front surface radius showed the largest contribution to REFU, especially in long eyes (and low power IOLs). WLT the IOL power uncertainty dominated in short eyes (or high power IOLs) and the uncertainty of the corneal front surface in long eyes (or low power IOLs). CONCLUSIONS: Compared with published data on the formula prediction error of refractive outcome after cataract surgery, the uncertainty of biometric measures seems to contribute with ⅓ to ½ to the entire standard deviation. REFU systematically increases with IOL power and decreases with axial length.

Surgical management of complicated Descemet's membrane detachment in corneas without prior endothelial keratoplasty.

PURPOSE: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention. METHODS: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD. RESULTS: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes. CONCLUSION: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly.

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.

A Cross-sectional Analysis of 556 Eyes Entering the Homburg Aniridia Centre.

PURPOSE: Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present. In order to develop better treatment options for this rare disease, an aniridia center must be established. The purpose of this work is to summarize ophthalmic findings of aniridia subjects examined at the Department of Ophthalmology, Saarland University Medical Center in Homburg. METHODS: Our retrospective single-center study included patients who underwent a comprehensive ophthalmic examination through the head of the KiOLoN ("Kinderophthalmologie", Orthoptics, Low Vision and Neuroophthalmology) Unit of the department between June 2003 and January 2022. Data at the first examination time point have been included. RESULTS: Of 286 subjects, 556 eyes of (20.1 ± 20.1 years; 45.5% males) were included. There was nystagmus in 518 (93.7%) eyes, and strabismus in 327 (58.8%) eyes. There were 436 (78.4%) eyes with age-appropriate axial length, 104 (18.7%) eyes with microphthalmos, and 13 (2.3%) eyes with buphthalmos. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia-associated keratopathy (AAK) stages: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%), and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type was significantly positively correlated with AAK stage, lens properties, presence of glaucoma, congenital macular, and optic nerve head properties (p < 0.001 for all), while complete aniridia showed the most complications. CONCLUSIONS: At the Homburg Aniridia Center, the most common ophthalmic signs in congenital aniridia were AAK, iris malformation, cataract, and macular hypoplasia. The iris malformation type may indicate future expression of AAK, cataract, and glaucoma development and it is correlated with a congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long-term follow-up.

Limitations of constant optimization with disclosed intraocular lens power formulae.

PURPOSE: To investigate the effect of formula constants on predicted refraction and limitations of constant optimization for classical and modern intraocular lens (IOL) power calculation formulae. SETTING: Tertiary care center. DESIGN: Retrospective single-center consecutive case series. METHODS: This analysis is based on a dataset of 888 eyes before and after cataract surgery with IOL implantation (Hoya Vivinex). Spherical equivalent refraction predSEQ was predicted using IOLMaster 700 data, IOL power, and formula constants from IOLCon ( https://iolcon.org ). The formula prediction error (PE) was derived as predSEQ minus achieved spherical equivalent refraction for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulae. The gradient of predSEQ (gradSEQ) as a measure for the effect of the constants on refraction was calculated and used for constant optimization. RESULTS: Using initial formula constants, the mean PE was -0.1782 ± 0.4450, -0.1814 ± 0.4159, -0.1702 ± 0.4207, -0.1211 ± 0.3740, and -0.1912 ± 0.3449 diopters (D) for the SRKT, Hoffer Q, Holladay, Haigis, and Castrop formulas, respectively. gradSEQ for all formula constants (except gradSEQ for the Castrop R) decay with axial length because of interaction with the effective lens position (ELP). Constant optimization for a zero mean PE (SD: 0.4410, 0.4307, 0.4272, 0.3742, 0.3436 D) results in a change in the PE trend over axial length in all formulae where the constant acts directly on the ELP. CONCLUSIONS: With IOL power calculation formulae where the constant(s) act directly on the ELP, a change in constant(s) always changes the trend of the PE according to gradSEQ. Formulae where at least 1 constant does not act on the ELP have more flexibility to zero the mean or median PE without coupling with a PE trend error over axial length.

Evaluation of corneal power from an AS-OCT thick lens model and ray tracing: reliability of the keratometer index.

PURPOSE: To investigate and compare different strategies of corneal power calculations using keratometry, paraxial thick lens calculations and ray tracing. SETTING: Tertiary care center. DESIGN: Retrospective single-center consecutive case series. METHODS: Using a dataset with 9780 eyes of 9780 patients from a cataractous population the corneal front (Ra/Qa) and back (Rp/Qp) surface radius/asphericity, central corneal thickness (CCT), and entrance pupil size (PUP) were recorded using the Casia 2 tomographer. Beside keratometry with the Zeiss (PK Z ) and Javal (PK J ) keratometer index, a thick lens paraxial formula (PG) and ray tracing (PR) was implemented to extract corneal power for pupil sizes from 2 mm to 5 mm in steps of 1 mm and PUP. RESULTS: With PUP PK Z /PK J overestimates the paraxial corneal power PG in around 97%/99% of cases and PR in around 80% to 85%/99%. PR is around 1/6 or 5/6 diopters (D) lower compared with PK Z or PK J . For a 2 mm pupil PR is around 0.20/0.91 D lower compared with PK Z /PK J and for a 5 mm pupil PR is comparable with PK Z (around 0.03 D lower) but around 0.70 to 0.75 D lower than PK J . CONCLUSIONS: "True" values of corneal power are mostly required in lens power calculations before cataract surgery, and overestimation of corneal power could induce trend errors in refractive outcome with axial length and lens power if compensated with the effective lens position.

Short-Term Effect of Rose Bengal Photodynamic Therapy (RB-PDT) on Collagen I, Collagen V, NF-κB, LOX, TGF-ß and IL-6 Expression of Human Corneal Fibroblasts, In Vitro.

PURPOSE: To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor ß1 (TGF-ß1) and interleukin-6 (IL-6) expression in healthy and keratoconus human corneal fibroblasts (HCFs and KC-HCFs), 24 h after Rose Bengal photodynamic therapy (RB-PDT). METHODS: HCFs were isolated from healthy human corneal donors (n = 5) and KC-HCFs from elective penetrating keratoplasties (n = 5). Both cell cultures underwent RB-PDT (0.001% RB concentration, 0.17 J/cm2 fluence) and 24 h later collagen I, collagen V, NF-κB, LOX, TGF-ß1 and IL-6 mRNA and protein expression have been determined using qPCR and Western blot, IL-6 concentration in the cell culture supernatant by ELISA. RESULTS: TGF-ß1 mRNA expression was significantly lower (p = 0.02) and IL-6 mRNA expression was significantly higher in RB-PDT treated HCFs (p = 0.01), than in HCF controls. COL1A1, COL5A1 and TGF-ß1 mRNA expression was significantly lower (p = 0.04; p = 0.02 and p = 0.003) and IL-6 mRNA expression was significantly higher (p = 0.02) in treated KC-HCFs, than in KC-HCF controls. TGF-ß1 protein expression in treated HCFs was significantly higher than in HCF controls (p = 0.04). IL-6 protein concentration in the HCF and KC-HCF culture supernatant after RB-PDT was significantly higher than in controls (p = 0.02; p = 0.01). No other analyzed mRNA and protein expression differed significantly between the RB-PDT treated and untreated groups. CONCLUSIONS: Our study demonstrates that RB-PDT reduces collagen I, collagen V and TGF-ß1 mRNA expression, while increasing IL-6 mRNA and protein expression in KC-HCFs. In HCFs, RB-PDT increases TGF-ß1 and IL-6 protein level after 24 h.

Secondary Data Analysis of Inflammation-Related mRNAs in Conjunctival Impression Cytology Samples of Aniridia Patients.

PURPOSE: Aniridia is a rare corneal disease that is often associated with aniridia-associated keratopathy (AAK). In AAK, the conjunctival tissue crosses the limbal border, forming a corneal pannus that extends into the corneal center. With increasing AAK severity, corneal pannus formation, vascularization, and ocular surface inflammation increase. The purpose of this study was to investigate inflammation-related mRNA expression in conjunctival epithelial cells in AAK and its relationship with AAK severity. METHODS: Using impression cytology, bulbar conjunctival cells were sampled from 20 subjects with congenital aniridia and 20 age-matched and sex-matched healthy control subjects. RNA was extracted, and mRNA analyses were performed using microarray, which was evaluated for inflammatory markers. RESULTS: In the analyzed aniridia subjects, 70 deregulated mRNAs encoding proinflammatory or antiinflammatory cytokines or factors associated with chronic inflammation, including increased IL-1, IL-8, and MIP3A/CCL20 mRNA. The most downregulated mRNA was TIMP3, and the most upregulated mRNA was Protein c-Fos.Of the 70 mRNAs, 14 inflammation-related genes were altered only in the mild AAK forms, whereas only 2 mRNAs were altered only in the severe AAK forms (TLR4 and PPARG). CONCLUSIONS: The expression of numerous proinflammatory and antiinflammatory cytokines is deregulated at the ocular surface of aniridia subjects with mild AAK. Thus, early antiinflammatory treatment may prevent or slow down corneal scarring and pannus formation in aniridia subjects.

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.