Impact of Cross-Linking Procedure on Perioperative Quality of Life in Keratoconus Patients.

BACKGROUND: To evaluate the effect of crosslinking (CXL) with riboflavin for keratoconus (KC) therapy on quality of life (QoL): comparison of keratoconus patients with and without treatment. METHODS: Prospective monocentric study. We recruited patients with progressive KC and with stable disease. Patients with progressive disease received cross-linking treatment; patients with stable disease were monitored. We compared QoL in both groups over 6 months and detected the influence of cross-linking treatment on QoL. QoL was assessed by NEI-VFQ-25, EQ-5D 5L, and EQ-Visual analog scale (VAS). In the evaluation of the Nei VFQ, the subgroups LFVFS and LFSES were calculated. RESULTS: We enrolled 31 eyes of 31 patients in the intervention group and 37 eyes of 37 patients in the control group. Medians with standard deviations (SD) were calculated. All QoL-tests showed equal scores at baseline in both groups. At V2, one day after the treatment, EQ-VAS (56.4), LFVFS (57.4), and EQ5D5L (0.59) were significantly reduced. At V3 (one week after treatment), all results returned to baseline level. LFSES was not affected by the treatment. It remained stable (V2 85.4, V3 84.3). Comparing the baseline scores with the follow-up scores at month 6, we found a significant increase in QoL in all tests in the intervention group. Otherwise, the quality of life in the control group did not change over time. CONCLUSIONS: Cross-linking led only to a short-term reduction in QoL. Although the treatment is painful for a few days, no effect on general quality of life LVSES has been demonstrated. QoL already returned to baseline after one week and the patients were not limited anymore.

Much higher prevalence of keratoconus than announced results of the Gutenberg Health Study (GHS).

Keratoconus appears to be a rare corneal disease with a prevalence previously estimated at 1:2000. The aim of our study was to investigate the prevalence of keratoconus in a large German cohort and to evaluate possible associated factors. METHOD: In the population-based, prospective, monocentric cohort study, Gutenberg Health Study, 12,423 subjects aged 40-80 years were examined at the 5-year follow-up. Subjects underwent a detailed medical history and a general and ophthalmologic examination including Scheimpflug imaging. Keratoconus diagnosis was performed in two steps: all subjects with conspicuous TKC analysis of corneal tomography were included in further grading. Prevalence and 95% confidence intervals were calculated. Logistic regression analysis was carried out to investigate association with age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression. RESULTS: Of 10,419 subjects, 75 eyes of 51 subjects were classified as having keratoconus. The prevalence for keratoconus in the German cohort was 0.49% (1:204; 95% CI: 0.36-0.64%) and was approximately equally distributed across the age decades. No gender predisposition could be demonstrated. Logistic regression showed no association between keratoconus and age, sex, BMI, thyroid hormone, smoking, diabetes, arterial hypertension, atopy, allergy, steroid use, sleep apnea, asthma, and depression in our sample. CONCLUSION: The prevalence of keratoconus disease in a mainly Caucasian population is approximately tenfold higher than previously reported in the literature using latest technologies (Scheimpflug imaging). Contrary to previous assumptions, we did not find associations with sex, existing atopy, thyroid dysfunction, diabetes, smoking, and depression.

Association of birth weight with corneal aberrations in adulthood – Results from a population-based study

Purpose: Low birth weight (BW) is associated with increased corneal aberrations in childhood and alterations of corneal geometry in adulthood. Increased corneal aberrations may be a factor contributing to decreased visual function in former low BW newborns in later life. Hence, the aim of this study was to analyze the long-term effect of low BW on corneal aberrations in adulthood.MethodsIn the German population-based Gutenberg Health Study (GHS) participants (age: 40–80 years) were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). The relationship between self-reported BW and the different types of corneal aberrations was analyzed using linear regression analysis as uni- and multivariable analysis with adjustment for potential confounders. The main outcome measures were corneal aberrations defined as astigmatism (Z2−2; Z22), coma (Z3−1; Z31), trefoil (Z3−3; Z33), spherical aberration (Z40) and root-mean square of higher order aberrations (HOA; 3rd up to 8th order; aperture size: 6 mm).ResultsOverall, 5,628 participants were included in this analysis (3,004 women, aged 56.0 +/- 10.3 years). In a multivariable analysis lower BW was associated with decreased horizontal trefoil (B = 0.004 [0.001; 0.006] µm/500 g; p=.008); higher spherical aberrations (B=-0.006 [-0.008;-0.003] µm/500 g; p<.001), higher RMS (B=-0.028 [-0.042;-0.014] µm/500 g; p<.001), increased HOA (B=-0.007 [-0.010;-0.003] µm/500 g; p<.001) and increased LOA (B=-0.027 [-0.041;-0.013] µm/500 g; p<.001). No association was observed between birth weight and the other types of corneal aberrations in multivariable model.ConclusionOur results indicate an association between BW and spherical aberration in adults aged 40 to 80 years. This indicates that low BW may have an association with an altered corneal shape development which may affect optical image quality and, hence, visual function. (AU)

Association of birth weight with corneal aberrations in adulthood - Results from a population-based study.

PURPOSE: Low birth weight (BW) is associated with increased corneal aberrations in childhood and alterations of corneal geometry in adulthood. Increased corneal aberrations may be a factor contributing to decreased visual function in former low BW newborns in later life. Hence, the aim of this study was to analyze the long-term effect of low BW on corneal aberrations in adulthood. METHODS: In the German population-based Gutenberg Health Study (GHS) participants (age: 40-80 years) were examined with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). The relationship between self-reported BW and the different types of corneal aberrations was analyzed using linear regression analysis as uni- and multivariable analysis with adjustment for potential confounders. The main outcome measures were corneal aberrations defined as astigmatism (Z2-2; Z22), coma (Z3-1; Z31), trefoil (Z3-3; Z33), spherical aberration (Z40) and root-mean square of higher order aberrations (HOA; 3rd up to 8th order; aperture size: 6 mm). RESULTS: Overall, 5,628 participants were included in this analysis (3,004 women, aged 56.0 +/- 10.3 years). In a multivariable analysis lower BW was associated with decreased horizontal trefoil (B = 0.004 [0.001; 0.006] µm/500 g; p=.008); higher spherical aberrations (B=-0.006 [-0.008;-0.003] µm/500 g; p<.001), higher RMS (B=-0.028 [-0.042;-0.014] µm/500 g; p<.001), increased HOA (B=-0.007 [-0.010;-0.003] µm/500 g; p<.001) and increased LOA (B=-0.027 [-0.041;-0.013] µm/500 g; p<.001). No association was observed between birth weight and the other types of corneal aberrations in multivariable model. CONCLUSION: Our results indicate an association between BW and spherical aberration in adults aged 40 to 80 years. This indicates that low BW may have an association with an altered corneal shape development which may affect optical image quality and, hence, visual function.

Peripheral corneal thickness and associated factors - results from the population-based German Gutenberg Health Study.

PURPOSE: Changes in peripheral corneal thickness are described in various corneal diseases such as corneal ectasia. However, few data exist describing the increase in corneal thickness from central to peripheral and reporting the normal distribution of corneal thickness in rings around the corneal centre. The aim of this study was to report these cornea characteristics and investigate associated factors in a population-based setting. METHODS: The Gutenberg Health Study is a prospective, population-based study examining participants in a 5-year follow-up (age range 40-80 years) using Scheimpflug imaging. Corneal thickness was assessed in each participant at the apex, as well as in the corneal centre (thinnest corneal thickness) and in rings with 2, 4, 6, 8 and 10 mm diameter around the corneal centre, and the increase in corneal thickness towards the periphery. The relationship between corneal thickness at these locations and possible associated factors was determined using linear regression models. For this purpose, general and ocular parameters were included. RESULTS: A total of 9729 participants were included in the present analysis (4874 women, age 59.2 ± 10.8 years). Multivariable analysis showed a correlation between the increase in corneal thickness in the circles from 0 to 10 mm (diameter) and the following parameters: age (B = -0.24 µm per year, p < 0.001); body height (B = -0.04 µm, p = 0.005); smoking (B = -0.72 µm, p < 0.001); spherical equivalent (B = -0.70 µm per dioptre, p < 0.001); white-to-white distance (B = -0.75 µm/mm, p < 0.001); mean corneal radius (B = -3.61 µm/mm, p < 0.001); intraocular pressure (B = -0.12 µm/mmHg, p < 0.001); glaucoma (B = -1.94 µm, p < 0.001); and pseudophakia (B = 0.89 µm, p < 0.001). CONCLUSION: The results of the present study suggest that several general and ocular parameters are associated with peripheral corneal thickness. In the context of diagnosing glaucoma, a smaller increase in corneal thickness towards the periphery might be a new additional marker.

Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood-Results from the Population-Based German Gutenberg Health Study.

Purpose: Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40-80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and corneal thickness at different locations were assessed. Linear regression models were carried out including uni- and multivariable analyses with adjustment for age, sex, mean corneal radius, and white-to-white distance. Main outcome measures were corneal thickness at the apex, at the pupil center, and at the corneal periphery. Results: Overall, 5657 participants were successfully measured (3019 females, aged 56.0 ± 10.3 years). In multivariable analyses a lower BW was associated with a thinner corneal thickness at the apex (B = 1.71 µm/500 g, p < 0.001) and at the pupil (B = 1.69 µm/500 g, p < 0.001). These effects diminished towards the corneal periphery resulting in no differences in the perilimbal regions. Conclusion: The present study provides evidence that lower birth weight goes along with corneal thickness alterations even into adult ages of 40 to 80 years. Thinner measurements of the cornea were particularly found in the corneal center and diminished in the periphery. This indicates that there may be fetal origins affecting corneal thickness development particularly in the corneal center.

Effects of Superficial Keratectomy in Peripheral Hypertrophic Subepithelial Corneal Opacification on Front and Back Corneal Astigmatism.

PURPOSE: To evaluate changes of anterior and posterior corneal astigmatism after superficial keratectomy in peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: Patients with PHSCO, who had received superficial keratectomy with mitomycin C 0.02%, were included in this retrospective study. Scheimpflug imaging of the cornea (Pentacam®, Oculus, Wetzlar, Germany), best-corrected visual acuity (BCVA) and objective refraction were determined preoperatively and 3 months after superficial keratectomy. RESULTS: Fifteen eyes of 15 patients (age: 55 ± 16 years; range: 36-82 years) were included. The mean preoperative BCVA was logMAR 0.4 ± 0.2 and improved to logMAR 0.21 ± 0.3 (p < .01) postoperatively. The median preoperative astigmatism of the anterior corneal surface was 4.67 ± 2.4 D (range: 0.9-13.2 D) and decreased to 1.4 ± 0.4 D (range: 0.8-2.3 D) 3 months after surgery. The median astigmatism of the posterior corneal surface was 0.6 ± 0.5 D (range: 0.1-2.2 D) before surgery and decreased to 0.3 ± 0.2 D (range: 0-0.7 D) 3 months after surgery. CONCLUSION: Superficial keratectomy reduces anterior corneal astigmatism more than posterior corneal astigmatism in patients with PHSCO. Furthermore, a myopic shift and corneal steepening in the peripheral and mid-peripheral cornea was observed after removal of the subepithelial corneal opacification spots.

Corneal topometric, aberrometric and biomechanical parameters in mucopolysaccharidosis patients.

AIMS: To report corneal topometric and aberrometric values in mucopolysaccharidosis (MPS) and to investigate their correlation with biomechanical corneal parameters. METHODS: One randomly chosen eye of 20 MPS patients with no to moderate corneal clouding and one eye of 23 healthy controls with comparable age were prospectively included into this study. Corneal surface regularity was assessed by index of surface variance (ISV), -vertical asymmetry (IVA), -height asymmetry (IHA), -height decentration (IHD); keratoconus index (KI), central keratoconus index (CKI) and Zernike indices of anterior and posterior corneal surface using Scheimpflug imaging (Pentacam). Corneal resistance factor (CRF) and corneal hysteresis (CH) were assessed by Ocular Response Analyzer. Statistical analyses were performed using Mann-Whitney-Test and Spearman Correlation Coefficients. RESULTS: IVA, ISV, IHD, IHA, but not KI and CKI were significantly higher in MPS patients compared to age matched healthy controls. Spherical aberration and asphericity coefficients either at the anterior or at the posterior corneal surface differed significantly between both groups. The grade of the MPS-associated corneal opacity correlated significantly with ISV (rho = 0.52), IVA (rho = 0.54), IHA (rho = 0.57) and IHD (rho = 0.48). Density of the MPS-affected corneas correlated significantly with ISV (rho = 0.52), IVA (rho = 0.72), IHA (rho = 0.57), IHD (rho = 0.69), 3rd order horizontal trefoil aberration at the posterior (rho = 0.62) and anterior surface (rho = 0.48) as well as with CH (rho = 0.55) and CRF (rho = 0.57). Spherical aberration at the back surface correlated with CRF and CH in MPS and in healthy controls. CONCLUSIONS: This is the first study analyzing shape of the corneal surface in MPS patients. Topometric indices of corneal asymmetry are significantly increased and correlate with MPS-related corneal opacity and density. Spherical aberration and asphericity coefficient at the front and at the back corneal surface differ significantly between MPS and healthy controls.

The Prevalence of Glaucoma in Young People.

BACKGROUND: Earlier information on the prevalence of glaucoma among children in Germany was based solely on estimates. Reported values for congenital glaucoma range from 1 in 10 000 to 1 in 68 000 depending on ethnic origin. The estimate for juvenile glaucoma is 1 in 44 000. METHODS: The Gutenberg Health Study is a populationbased, prospective, monocentric cohort study with 15 010 participants aged 35 to 74. To determine the history-based prevalence of childhood glaucoma, participants were asked about the diagnosis of glaucoma, any operations for glaucoma that were performed, regular use of drugs for glaucoma, and the age of onset of glaucoma. The affected individuals were classified in four groups based on the age of onset: congenital (<2 years), juvenile (2 to <18 years), late juvenile (18 to <40 years), and early adult (40 to <45 years). In the identified glaucoma patients, the visual acuity, intraocular pressure, corneal thickness, visual fields, and optic discs were evaluated. RESULTS: 352 persons were identified from their medical history as having glaucoma. The weighted prevalences in the four groups were 0% in the congenital group, 0.01% (95% confidence interval [0, 0.03]) in the juvenile group, 0.16 % ([0.09; 0.23]) in the late juvenile group, and 0.17% ([0.15; 0.19]) in the early adult group. For participants over age 45, the weighted prevalence of glaucoma was 1.98% [1.7; 2.2]. CONCLUSION: In our cohort, the history-based prevalence of juvenile glaucoma was 0.01% (2 patients). The prevalence was an order of magnitude higher (0.16%) between the ages of 18 and 40, and two orders of magnitude higher at later ages (1.98%). The burden of disease seems to be markedly higher than previously assumed.

Modulatory effect of different riboflavin compositions on the central corneal thickness of African keratoconus corneas during collagen crosslinking.

PURPOSE: A pilot investigation to transfer the established corneal collagen crosslinking (CXL) procedure in European eyes into clinically affected African eyes and to optimize the treatment by adapting the riboflavin composition. MATERIALS AND METHODS: CXL was performed in 15 eyes (11 patients) with advanced stages of keratoconus in the Eye Clinic of Bafoussam in the West Region of Cameroon. The following six riboflavin compositions with different portions of active swelling additives were applied: Solution 1 (0.5% methylhydroxypropylcellulose [MHPC]), solution 2 (1.0% MHPC), solution 3 (1.7% MHPC), solution 4 (5% dextran), solution 5 (10% dextran) and solution 6 (no active swelling ingredient). The central corneal thickness (CCT) was measured by ultrasound pachymetry before and after de-epithelialization and at least every 10 min during CXL. RESULTS: THE APPLICATION OF THE RIBOFLAVIN SOLUTIONS RESULTED IN THE FOLLOWING MEAN FINAL CCT VALUES: 172 ± 15% using solution 1 (60 min/n = 5); 183 ± 8% using solution 2 (60 min/n = 5); 170% using solution 3 (60 min/n = 1); 80% using solution 4 (45 min/n = 1); 99% using solution 5 (45 min/n = 1) and 150 ± 13% using solution 6 (50 min/n = 2). CONCLUSIONS: The combination of riboflavin compositions with swelling and stabilizing effects on the corneal stroma seems necessary in African eyes with advanced keratoconus. Further studies are required to confirm these primary results.

Brimonidine versus dapiprazole: Influence on pupil size at various illumination levels.

PURPOSE: To evaluate the influence of dapiprazole versus brimonidine on pupil size at various illumination levels. SETTING: Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. METHODS: In randomized prospective study, 19 healthy volunteers received 2 ophthalmic solutions, dapiprazole and brimonidine, 1 in each eye, for intraindividual comparison. Before and after application, pupil diameter was measured using an infrared binocular pupillometer at 3 illumination levels (0.03, 0.82, and 6.4 lux). RESULTS: Only slight pupil dilation was observed under scotopic conditions after application of both agents. After 20 minutes, the median reduction in pupil width was 1.4 mm for brimonidine and 0.9 mm for dapiprazole. These effects were statistically significant for both agents (both P < .001). The maximum effect was observed after 40 minutes and remained stable through the next measurement at 180 minutes. Under mesopic lighting conditions, only a slight effect (<1 mm) was seen. CONCLUSIONS: Pupil mydriasis at scotopic illumination levels was reduced by both drugs in a similar fashion. Because of the slightly stronger effect of brimonidine, application of this agent 20 minutes before activities in dimly lit areas or at night may be recommended for photic phenomena following refractive surgery.

Epithelial tight junction proteins as potential antibody targets for pancarcinoma therapy.

Recombinant monoclonal antibodies are beginning to revolutionize cancer therapy. In combination with standard chemotherapy, high response rates have been reported with antibodies of the human IgG1 isotype for treatment of non-Hodgkin's lymphoma and breast cancer. It is becoming apparent that targets for antibody-based therapies do not necessarily need to be absent from normal tissues but can be present there either in low copy numbers or with binding epitopes shielded from the therapeutic antibody. Here, we studied whether claudin proteins that form tight junctions in normal epithelia are still expressed on carcinoma cells and whether their extracellular domains can be recognized by antibodies. We show that mRNAs of claudins 1, 3, 4, and 7 are all expressed in different human carcinoma cell lines, while claudin 8 was selectively expressed in breast and pancreas cancer lines. Chicken polyclonal antibodies were raised against peptides contained within predicted extracellular domains of claudins 1, 3, and 4. Affinity-purified IgG fractions for claudins 3 and 4 were monospecific and bound to human breast and colon carcinoma lines, but not to a line of monocytic origin. Claudin 3 antibodies also homogeneously stained human renal cell carcinoma tissue and micrometastatic tumor cells as identified by cytokeratin staining in bone marrow biopsies of breast cancer patients. Fluorescence-activated cell sorting and immunocytochemistry indicated that claudin antibodies bound to the surface of tumor cells. By analogy to other tumor-associated antigens that are differentially accessible to antibodies on tumor vs normal tissue, we propose that certain claudin proteins have potential as targets for novel antibody-based therapies of carcinomas.

Refractive lens exchange with an array multifocal intraocular lens.

PURPOSE: To prospectively evaluate safety, efficacy, predictability, stability, complications, and patient satisfaction after refractive lens exchange (clear lens extraction) followed by posterior chamber implantation of a multifocal intraocular lens (IOL). METHODS: Fifty eyes of 25 patients (mean age 51 years, range 44 to 62 years) with preoperative spherical equivalent refraction between -15.50 and +5.75 D and cylinder between 0 and 1.50 D underwent bilateral implantation of a zonal progressive multifocal IOL (Array, AMO). RESULTS: Eyes were divided into group A (n=24; myopia, average preoperative spherical equivalent refraction -7.11 +/- 3.25 D (-1.75 to -15.50 D), and group B (n=26; hyperopia, average preoperative spherical equivalent refraction +3.04 +/- 1.04 D). Follow-up was 6 months in all eyes. Postoperatively, all eyes of both groups were within +/-1.00 D of target refraction. No eye in group A and three eyes in group B sustained a loss of one line of BSCVA. Forty-seven eyes (94%) remained unchanged or gained one or more lines of their preoperative BSCVA. In all eyes, postoperative UCVA was 20/40 or better. When compared to preoperative, uncorrected near visual acuity improved (statistically significant). All patients achieved uncorrected binocular visual acuity of 20/30 and J4 or better. Patient satisfaction was extremely high; no intra- or postoperative complications were reported. CONCLUSION: Six-month results of implantation of the AMO Array multifocal IOL for refractive lens exchange demonstrated safety, efficacy, and predictability in correcting high ametropia and significant improvement of uncorrected near and distance visual acuity.