Large Field of View Corneal Epithelium and Bowman's Layer Thickness Maps in Keratoconic and Healthy Eyes.

PURPOSE: To assess differences between epithelium thickness (ET) and Bowman's layer thickness (BLT) maps in keratoconic eyes and healthy eyes. DESIGN: Cross-sectional study. METHODS: Setting: institutional. STUDY POPULATION: 47 patients (1 eye) with keratoconus (KC) and 20 healthy subjects (1 eye). OBSERVATION PROCEDURE: epithelium and Bowman's layer measurements were performed by using custom-designed polarization-sensitive optical coherence tomography (PS-OCT) with a conical scanning optics design. En face corneal ET and BLT maps with a diameter of 11 mm were computed. Main outcome measurements were mean ET and BLT of 25 sectors; the thinnest (minET, minBLT) and thickest sectors (maxET, maxBLT) were assessed. Ratios between thinnest/thickest sectors (R1) and between mean ET and BLT of the inferior temporal quadrant/superior nasal quadrant (R2) were calculated (R1ET, R1BLT; R2ET, R2BLT). Receiver operator characteristic (ROC) curve analysis was used to assess the diagnostic power of statistically different parameters. RESULTS: In healthy eyes, smooth ET maps were observed. KC eyes showed a "doughnut pattern." The BLT maps of healthy eyes had a smooth appearance, but highly irregular "moth"-like damage pattern could be observed in keratoconic eyes. Highest area under the curve values were found for the thinnest sector of the BLT map, the R1ET, and the thinnest sector of the ET map. CONCLUSIONS: PS-OCT imaging enables the visualization of significant differences of the corneal epithelium and the Bowman's layer in en face maps covering almost the entire cornea. ET and BLT profiles could clearly show their diagnostic importance for the distinguishing of keratoconic eyes and healthy eyes.

Visual outcome and surgical results in children with Marfan syndrome.

IMPORTANCE: To determine visual and surgical results in children with Marfan syndrome. BACKGROUND: Marfan syndrome involves ocular complications which can lead to visual disturbance and amblyopia. Data about the visual and surgical results in children with Marfan syndrome is vital for the clinical management of these patients. DESIGN: Retrospective data analysis. PARTICIPANTS: Eighty-two eyes of 41 patients with a genetically proved diagnosis of Marfan syndrome. METHODS: Medical records of patients with Marfan syndrome were reviewed between 2007 and 2017. Ocular complications, visual acuity (VA) of patients with/without lensectomy and surgical method were evaluated. MAIN OUTCOME MEASURES: VA outcomes of patients with Marfan syndrome with/without surgical repair of ectopia lentis. RESULTS: In 27 (66%) of the 41 patients a bilateral subluxation of the lens was visible and 14 (52%) patients received lensectomy. The mean age at initial presentation was 12.3 ± 9 years and mean follow-up was 3 years (range 1-7). VA varied from 1.2 to -0.1 logMAR at first examination. At initial presentation, mean VA was 0.1 ± 0.7 logMAR in patients with a normal lens status (n = 14) and 0.3 ± 0.5 logMAR in patients with subluxation of the lens (n = 27) (P < .01). VA improved from 0.2 ± 0.5 logMAR to 0.1 ± 0.5 logMAR (P = .06) in children with subluxation of the lens who did not need a lensectomy (n = 12) and from 0.5 ± 0.5 logMAR to 0.2 ± 0.5 logMAR (P = .02) in patients who were referred to lensectomy with/without secondary lens implantation. CONCLUSIONS AND RELEVANCE: In Marfan syndrome subluxation of the lens was found in the majority of children. Improvement of VA resulted in children with subluxation of the lens and following lensectomy.

Corneal crosslinking for pellucid marginal degeneration.

PURPOSE: To investigate the efficacy of corneal crosslinking (CXL) for pellucid marginal degeneration (PMD). SETTING: Medical University of Vienna. DESIGN: Retrospective study. METHODS: In eyes with a crab-claw pattern on corneal topography of a study cohort of 808 eyes, manual measurements of the cornea's thinnest point on the inferior vertical Scheimpflug image (mCTi) and on the superior vertical Scheimpflug image (mCTs) were conducted. Eyes with paralimbal thinning were supposed as having PMD and included. A ratio between mCTi and mCTs was calculated. CXL was performed by irradiation of the inferior periphery of the cornea. During the follow-up, the mCTi, the mean keratometry (K) values in a central zone of 5.0 mm and in a 2.5 mm zone of the inferior cornea and the topographical corneal astigmatism were measured. The corrected distance visual acuity (CDVA) was also evaluated. Patients were followed postoperatively for 12 months. RESULTS: Forty-eight eyes showed a crab-claw pattern in corneal topography. Twenty-two eyes matched the inclusion criteria for PMD and 16 eyes underwent CXL. The mCTi increased during the 12-month follow-up. The K value in the 2.5 mm zone of the inferior cornea decreased after 1 year, whereas the K value in the central zone of 5.0 mm remained stable. The corneal astigmatism continuously decreased, and the CDVA improved after 1 year. CONCLUSION: Manual pachymetric measurements in Scheimpflug images showed the potential for screening for PMD and the evaluation of the efficacy of CXL in eyes with PMD in the study cohort. A thickening of the mCTi and a flattening in the inferior part of the cornea was observed.

Distinguishing Keratoconic Eyes and Healthy Eyes Using Ultrahigh-Resolution Optical Coherence Tomography-Based Corneal Epithelium Thickness Mapping.

PURPOSE: To find differences in epithelial thickness (ET) maps of eyes with keratoconus (KC) and healthy eyes. DESIGN: Institutional cross-sectional study. METHODS: In this study 40 keratoconic eyes and 76 healthy eyes were scanned using a custom-built ultrahigh-resolution optical coherence tomography system. Automated segmentation ET maps with 17 subsectors were calculated (central, temporal inferior, temporal superior, nasal inferior, and nasal superior area). The thinnest point of the epithelium (minET), the thickest point of the epithelium (maxET), and the thinnest point diagonally opposing the thickest point (ETmax/op) were additional parameters. Ratios were calculated as follows: minET/diagonally opposing point (R1), maxET/diagonally opposing point (R2), inferior temporal area/superior nasal area (RTI/NS), and inferior/superior hemisphere (RI/S). Furthermore, collected parameters were analyzed regarding their diagnostic accuracy (area under the curve; AUC). RESULTS: Statistically significant differences were as follows: central ET, 46.25 ± 2.56/50.91 ± 1.66; minET, 38.50 ± 2.10/46.79 ± 1.27; ETmax/op, 47.14 ± 2.45/49.60 ± 1.57; temporal inferior area: 43.93 ± 2.95/51.04 ± 1.51 (all mean ± standard deviation, µm); R1, 0.76 ± 0.09/0.93 ± 0.04; R2, 1.08 ± 0.04/1.21 ± 0.16; RTI/NS, 0.85 ± 0.08/1.02 ± 0.04; RI/S: 0.92 ± 0.07/0.99 ± 0.02. AUC values were R1: 0.979 (confidence interval [CI]: 0.957-1.000), RTI/NS: 0.977 (CI: 0.951-1.000), and minET: 0.928 (CI: 0.880-0.977). CONCLUSIONS: Epithelial thickness maps could clearly visualize different ET patterns. Parameters with the highest potential of diagnostic discrimination between eyes with KC and healthy eyes were, in descending order, R1, RTI/NS, and minET. Consequently, epithelial thickness irregularity and asymmetry seem to be the most promising diagnostic factor in terms of discriminating between keratoconic eyes and healthy eyes.

Correlation between central stromal demarcation line depth and changes in K values after corneal cross-linking (CXL).

PURPOSE: A stromal demarcation line (DL) after corneal cross-linking (CXL) has lately been suggested as a surrogate parameter for the success of CXL. The aim of this study was to investigate the correlation between depth of the central DL 1 month and the change in K values 12 months after CXL. METHODS: Treatment-naive subjects with keratoconus were treated using an accelerated CXL protocol [A-CXL(9*10)]. Depth of the DL/relative depth of the DL (DL%) was measured using Visante OCT imaging 1 month postoperatively (OP). Kmax/K2.5 (preOP) and change in Kmax/K2.5 (preOP - 12 months postOP) were assessed using corneal tomography (Pentacam HR, Oculus GmBH). RESULTS: Forty eyes were treated following the A-CXL(9*10). The mean DL depth was 200 ± 99 µm (range 71 to 479)/mean DL% = 42.70 ± 20.00% (range 17-90). There was no statistically significant correlation between stromal depth of the DL and change in Kmax or K2.5, respectively (Spearman rho DL/∆Kmax - 0.14 and DL/∆K2.5 - 0.14). Between DL% and the changes in maximum K values or K2.5, no statistically significant correlation was found as well (Spearman rho DL%/∆Kmax - 0.10 and DL%/∆K2.5 - 0.19). Mean change in Kmax after 12 months was - 0.68 ± 2.26 diopters (D) (median - 0.35 D) and - 0.82 ± 1.6 D (median - 0.65 D) for K2.5 (p = 0.07; p = 0.02). CONCLUSIONS: No statistically significant correlation was found between the stromal central depth of the DL and any outcome parameter for CXL after 12 months. Therefore, the interpretation of the DL as a predictive parameter for the effect of the procedure may not apply.

EFFECT OF PATIENTS' CLINICAL INFORMATION ON THE DIAGNOSIS OF AND DECISION TO TREAT RETINOPATHY OF PREMATURITY.

PURPOSE: To evaluate the effect of patients' clinical information on experts' diagnoses of retinopathy of prematurity (ROP) and decisions to treat. METHODS: Seven experts assessed wide-field fundus photographs of eyes of 52 premature infants of ≤30 weeks' gestational age or ≤1,500 g birthweight (BW) for ROP diagnosis (stage, plus disease, and aggressive posterior ROP) and the necessity for treatment for 2 days. On Day 1, they were masked to all patient data. On Day 2, they were given information on gestational age and BW. RESULTS: A significant shift in the experts' ratings toward a less aggressive ROP grading stage (P = 0.006) and less frequent decision for intervention (P = 0.021) was observed after receipt of patients' clinical information. This was truer for heavier/less premature infants (gestational age ≥ 28 0/7 weeks or BW ≥ 900 g) than those with very low BWs/high prematurity (gestational age < 24 0/7 weeks or BW < 600 g) (ROP stage P = 0.009 vs. P = 0.399, treatment decision P = 0.022 vs. P = 0.648). CONCLUSION: These results suggest knowledge of patients' clinical information influences the grading of ROP disease and decision for treatment. Retinopathy of prematurity staging seemed to be set at a lower level and the decision for treatment at a higher threshold for heavier/less premature babies. Our findings may have implications for further refinements in ROP assessment.

Inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity.

PURPOSE: To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). DESIGN: Prospective intra- and inter-rater reliability analysis. METHODS: In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. RESULTS: Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0-5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). CONCLUSIONS: ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

Twin-twin transfusion syndrome as a possible risk factor for the development of retinopathy of prematurity.

PURPOSE: The objective of this study was to evaluate the correlation between twin-twin transfusion syndrome (TTTS) and the development of retinopathy of prematurity (ROP) in premature infants. METHODS: Fifty-one infants who were less than 32 postmenstrual gestational weeks at birth or with a birth weight less than 1,501grams were included in this longitudinal observational study. The infants were matched by gestational age and birth weight, and divided into three groups: multiples with TTTS, multiples without TTTS, and singletons. The primary outcome variable was the incidence of ROP in infants affected by TTTS versus infants not affected by TTTS. Secondary outcome variables were multiple pregnancy, gestational age, and birth weight. RESULTS: Infants affected by TTTS showed a significantly higher incidence of ROP than infants not affected by TTTS (p < 0.01). TTTS donors and TTTS recipients were both at greater risk of developing ROP. ROP occurred in infants with TTTS whose gestational age at birth was significantly higher than that of infants with ROP who were not affected by TTTS (p = 0.01). Multiple pregnancy itself was not a risk factor for ROP disease. CONCLUSIONS: Infants affected by TTTS during pregnancy are at high risk of developing ROP, even if they were born at an older gestational age. Special awareness in ROP screening is necessary for these infants.

Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is well accepted as an easy-to-use contraceptive with an excellent side-effect profile. It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release of the steroid. Its contraceptive use is approved for 5 years. The aim of this study was to determine the plasma concentration of LNG and its variation with time in patients with in-dwelling LNG-IUS Mirena®. STUDY DESIGN: In this study, we determined LNG plasma concentrations in 110 women with LNG-IUS at different time points of use. Time from insertion of the system in the study population ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using a validated liquid chromatography-tandem mass spectrometry assay. RESULTS: The mean±SD LNG plasma level in all women was 147±59 pg/mL. A highly significant negative correlation between LNG plasma level and LNG-IUS time of use could be demonstrated. In the first year of use, LNG plasma level was as high as 191±71 pg/mL, decreasing to 157±68 pg/mL in the second year and 134±41 pg/mL in the third year. Even after exceeding the recommended period of LNG-IUS use, systemic LNG concentrations were detectable: 133±38 pg/mL in the sixth year, 133±48 pg/mL in the seventh year and 117±45 pg/mL in the eighth year. Furthermore, a significant negative correlation between LNG plasma level and body mass index could be shown. CONCLUSION: Systemic LNG concentrations can be found in all patients with LNG-IUS IUS. However, concentrations are much lower than in other forms of LNG application. Moreover, this study demonstrates that a systemic effect of LNG-IUS can also be found after the recommended contraceptive lifespan of 5 years.

An ultra-sensitive online SPE-LC-MS/MS method for the quantification of levonorgestrel released from intrauterine devices.

A selective and sensitive liquid chromatography-tandem mass spectrometry method for the determination of very low levonorgestrel (D-(-)-norgestrel) serum levels such as those found in patients using levonorgestrel-releasing intrauterine devices (IUDs) was developed. To achieve the sub-nanomolar sensitivity needed to measure such serum levels, a diethyl ether extraction sample preparation protocol was applied prior to the online solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) assay. Analyte quantification from the selected reaction monitoring experiments relied on the use of sixfold deuterated norgestrel as internal standard. The final method was linear up to 1.50 ng/ml with a lower limit of quantification (LLOQ) of 0.05 ng/ml. It was found to be precise and accurate with imprecision <8% and bias <6% assessed at three control levels. Total analyte recovery measured in patient pools at three concentration levels was found to exceed 92%. Matrix interferences were excluded by post-column analyte infusion experiments. As a proof of concept, a set of IUD patient serum samples was screened for their levonorgestrel content. A total of 97.5% (n = 94) of the samples did show serum levels exceeding the LLOQ, proving the applicability of the assay in relevant clinical cohorts. This method must not be used for diagnostic or therapeutic purposes, since it did not undergo formal performance evaluation in the sense of the in vitro diagnostic directive (98/79/EG) of the European community.

Oxygen utilization in newborns at delivery.

AIMS: To evaluate the arteriovenous (AV) pH difference in cord blood as a possible indicator of fetal O(2)-utilization at delivery. Furthermore to examine which maternal, fetal and obstetrical factors lead to elevated O(2)-utilization. METHODS: In this retrospective study all singleton live births, delivered within a four-month period at the University Hospital in Innsbruck, Austria, were analyzed. In total 491 deliveries were evaluated. Arterial and venous cord blood samples were collected at birth and analyzed by using a Radiometer ABL 510. RESULTS: Spontaneous deliveries showed a highly significant elevation in AV-difference (pH 0.10) as compared to cesarean sections (pH 0.05). In spontaneous births, the AV-difference was high in the case of low arterial cord blood pH (P<0.01), as well as in nuchal cord (P<0.01), high parity (P<0.01), very short labor (P<0.05) and elevated birth size and weight (P<0.05). CONCLUSIONS: As a result of increased fetal stress at birth, spontaneous delivery leads to higher O(2)-utilization than cesarean section, which is detectable in an elevated AV-difference. The AV-difference in combination with absolute pH-values can be used for the objective evaluation of fetal O(2)-utilization and consecutively the fetal stress at birth.