Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

BACKGROUND: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. METHODS: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). RESULTS: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). CONCLUSIONS: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

Corneal confocal microscopy alterations in Sjögren's syndrome dry eye.

PURPOSE: To evaluate light backscattering (LB) in corneal layers in patients with primary Sjögren's syndrome dry eye (SSDE) utilizing in vivo corneal confocal microscopy (IVCM) and to determine the eventual association with the lacrimal functional test values. METHODS: A complete ophthalmic evaluation, Schirmer test with and without stimulation, break-up time (BUT) and IVCM were performed on 55 patients affected by SSDE and in an age- and sex-matched cohort of healthy participants (HP). Light backscattering, measures as light reflectivity unit (LRU), detected by IVCM at Bowman's membrane (BM) at 50 µm, at 100 µm and at 200 µm deeper than BM was compared in the two groups. The correlations between LB values and lacrimal function results were evaluated. RESULTS: In patients affected by SSDE, LB was significantly higher (p < 0.001) in each corneal layer examined (+14 ± 6.33 LRU at BM), compared with HP. A good reverse correlation between the light reflectivity measures at BM with Schirmer test with (r = -0.91) and without (r = -0.90) stimulation and BUT (r = -0.88) was found. Correlations were lower in the deeper corneal layers. CONCLUSION: Even if our results should be confirmed in further studies with a larger population, these findings show that IVCM is a device able to detect alterations in corneal layers in SSDE patients related to the lacrimal function. Light backscattering (LB) could be very useful for clinical diagnosis and management of SSDE.

In vivo human corneal deformation analysis with a Scheimpflug camera, a critical review.

Corneal morphological analysis has greatly improved in recent years, providing physicians with new and reliable parameters to study. Moreover, today corneal functional too is a routine analysis, thanks to biomechanical evaluation allowed by an ocular response analyzer (Reichert Ophthalmic Instrument, Depew, NY, USA). Corvis ST (OCULUS Optikgeräte GmbH, Wetzlar, Germany), that relies on the ultrahigh speed Scheimpflug camera, is a new device providing corneal deformation parameters measured ny scanning the cornea response to an air puff; it is an instrument able to measure intraocular pressure too. This device could open up a whole new prospective in screening, detecting and managing corneal diseases, intraocular pressure measurement and in evaluating surgical procedures involving the cornea. This paper provides a comprehensive explanation of Corvis ST measurement principles and parameters and a literature review of scientific studies.

Intraocular pressure evaluation in healthy eyes and diseased ones using contact and non contact devices.

PURPOSE: To analyze and compare intraocular pressure (IOP) values measured in healthy subjects (HS), keratoconus (KC) patients and patients that underwent myopic photorefractive keratectomy (REF), using Goldmann applanation tonometry (GAT), dynamic contour tonometry (DCT), ocular response analyzer (ORA) and Corvis ST (CST). METHODS: The study included 76 eyes of 76HS, 15 eyes of 15 KC patients and 18 eyes of 18 subjects that underwent REF. Each participant underwent a complete ophthalmic evaluation, IOP measurement with GAT, DCT, ORA and CST. RESULTS: HS showed a mean GAT value of 15.62±2.33 mm Hg, a mean DCT value of 17.44±2.51 mm Hg, a mean ORA value of 15.99±3.58 mm Hg and a mean CST value of 17.24±3.44 mm Hg. KC showed a mean GAT value of 15.07±1.83 mm Hg, a mean DCT value of 17.01±1.96 mm Hg, a mean ORA value of 13.58±2.99 mm Hg and a mean CST value of 14.37±1.89 mm Hg. REF showed a mean GAT value of 14.06±1.51 mm Hg, a mean DCT value of 15.12±2.34 mm Hg, a mean ORA value of 16.85±2.4 mm Hg and a mean CST value of 15.57±1.77 mm Hg. CONCLUSION: Our data suggest that ORA and GAT could be used interchangeably in HS; GAT, ORA and CST could be used interchangeably in KC patients and that GAT provides lower IOP values compared to the other devices in eyes previously submitted to myopic PRK.

Long-term results of corneal collagen crosslinking for progressive keratoconus.

PURPOSE: To evaluate long-term keratoconus stability after corneal crosslinking (CXL) with riboflavin. METHODS: In this prospective study, 57 eyes of 55 patients with progressive keratoconus, consecutively treated with ultraviolet A (UVA) - riboflavin CXL, were examined with the corneal topographer Pentacam, the biometer IOLMaster and the analyzer of corneal biomechanics Ocular Response Analyzer before and during a 24 months follow-up after CXL. RESULTS: Twenty-four months after CXL, there was a significant improvement in best corrected visual acuity (BCVA) (P<0.01), a significant decrease in corneal thinnest point (CTP), keratometry readings at the keratoconus apex (K max), and corneal volume (CV) (P<0.01), and a significant increase in axial eye length (AL) (P=0.01). No significant changes in anterior chamber volume (ACV) and depth (ACD), (P=0.8), corneal hysteresis (CH) (P=0.16) and corneal resistance factor (CRF) (P=0.06) were found. However, in the subgroup of patients with decreased K max readings 24 months after treatment, both CH and CRF showed a significant reduction (P<0.01). CONCLUSION: In the first month after the procedure, CXL induces a reduction in corneal volume. During the 24 months follow-up the cornea tends to recover its original volume with a persistence of the CXL efficacy.

New Scheimpflug camera device in measuring corneal power changes after myopic laser refractive surgery.

PURPOSE: To assess the accuracy of a combined Scheimpflug camera-Placido disk device (Sirius, CSO, Italy) in evaluating corneal power changes after myopic photorefractive keratectomy (PRK). METHODS: Two hundred and thirty-seven eyes of 237 patients that underwent myopic PRK with a refractive error, measured as spherical equivalent, ranging from -10.75 D to -0.5D (mean -4.63 ± 2.21D), were enrolled in this study. Corneal power evaluation using Sirius were performed before, 1, 3 and 6 months after myopic PRK. Mean simulated keratometry (SimK) and mean pupil power (MPP) were measured. Correlations between changes in corneal power, measured with SimK and MPP, and variations in subjective refraction, calculated at corneal plane, were evaluated using Pearson test at every follow up; differences between preoperative and postoperative data were evaluated with the Student paired t-test. RESULTS: A good correlation has been detected between the variations in subjective refraction measured at corneal plane 1, 3 and 6 months after myopic PRK and both SimK (R(2) = 0.8463; R(2) = 0.8643; R(2) = 0.7102, respectively) and MPP (R(2) = 0.6622; R(2) = 0.5561; R(2) = 0.5522, respectively) but corneal power changes are statistically undervalued for both parameters (p < 0.001). CONCLUSIONS: Even if our data should be confirmed in further studies, SimK and MPP provided by this new device do not seem to accurately reflect the changes in corneal power after myopic PRK.

Comparison between Corvis and other tonometers in healthy eyes.

PURPOSE: To determine the agreement of intraocular pressure (IOP) values in healthy eyes among Goldmann applanation tonometer, dynamic contour tonometer, ocular response analyzer and Corvis. Additionally, to study the relationship between their differences with central corneal thickness (CCT) and corneal curvature (CK). METHODS: Seventy-six eyes of 76 healthy subjects were examined. Every subject underwent a complete ophthalmic evaluation, a Pentacam scan and three consecutive IOP measurements with each instrument (DCT, GAT, ORA and CST). IOP measurements provided by each device were compared with each other and the differences between them were correlated with morphological parameters obtained by Pentacam (CCT and CK). Statistical analysis was performed using SPSS software, version 18.0. RESULTS: The mean age of enrolled subjects was 36.8 ± 10.6 years old. The mean IOP measurements that were obtained with GAT, DCT, ORA and CST was 15.62 ± 2.33 mmHg, 17.44 ± 2.51 mmHg, 15.99 ± 3.58 mmHg and 17.24 ± 3.44 mmHg respectively. The mean CCT was 543.63 ± 36.15 µm, the mean CK was 43.35 ± 1.23 D. GAT and ORA provided IOP values not showing a statistical difference; CST and DCT IOP measurements did not show a statistical difference whereas CST provided statistically higher IOP values both than GAT and both ORA. CONCLUSIONS: According to our data, CST produces IOP values that are notably higher than GAT measures; therefore they cannot be used interchangeably. If CST should be used as the next gold standard, higher IOP values will come to be considered normal.

Evaluation of corneal deformation analyzed with a Scheimpflug based device.

PURPOSE: To evaluate the correlation between corneal biomechanical and morphological data in healthy eyes. METHODS: A complete clinical eye examination of naïve eyes was followed by tomographic (Pentacam, Oculus, Wetzlar, Germany) and biomechanical (Corvis ST, Oculus, Wetzlar, Germany) evaluation. Linear regression between central corneal thickness (CCT), corneal volume (CV) and anterior corneal curvature measured with Sim'K (SK), versus corneal deformation parameters measured with Corvis ST have been run using SPSS software version 18.0. RESULTS: Seventy-six eyes of 76 healthy subjects (44 women and 32 men) with a mean age of 36.84 ± 10.74 years and a mean refractive error of -0.55 ± 1.68 D (measured as spherical equivalent) were evaluated. Corneal deformation parameters were weakly correlated with corneal morphological parameters and with spherical equivalent. Although the correlations between deformation amplitude versus SK and between SK versus Velocity of Applanation 2, were higher than the others (R(2) = 0.28 and 0.26 respectively), none of them was statistically significant (p>0.01). CONCLUSIONS: According with these findings, Corvis ST seems to be able to provide an analysis of corneal deformation independent from corneal morphological characteristics. If these data will be confirmed in further studies, this device could be useful in the management and screening of eyes with corneal diseases.

Corneal Anterior Power Calculation for an IOL in Post-PRK Patients.

PURPOSE: After corneal refractive surgery, there is an overestimation of the corneal power with the devices routinely used to measure it. Therefore, the objective of this study was to determine whether, in patients who underwent photorefractive keratectomy (PRK), it is possible to predict the earlier preoperative anterior corneal power from the postoperative (PO) posterior corneal power. A comparison is made using a formula published by Saiki for laser in situ keratomileusis patients and a new one calculated specifically from PRK patients. METHODS: The Saiki formula was tested in 98 eyes of 98 patients (47 women) who underwent PRK for myopia or myopic astigmatism. Moreover, anterior and posterior mean keratometry (Km) values from a Scheimpflug camera were measured to obtain a specific regression formula. RESULTS: The mean (±SD) preoperative Km was 43.50 (±1.39) diopters (D) (range, 39.25 to 47.05 D). The mean (±SD) Km value calculated with the Saiki formula using the 6 months PO posterior Km was 42.94 (±1.19) D (range, 40.34 to 45.98 D) with a statistically significant difference (p < 0.001). Six months after PRK in our patients, the posterior Km was correlated with the anterior preoperative one by the following regression formula: y = -4.9707x + 12.457 (R² = 0.7656), where x is PO posterior Km and y is preoperative anterior Km, similar to the one calculated by Saiki. CONCLUSIONS: Care should be taken in using the Saiki formula to calculate the preoperative Km in patients who underwent PRK.

Corneal Biomechanical Changes After Myopic Photorefractive Keratectomy.

PURPOSE: To study the corneal biomechanical and morphological changes after photorefractive keratectomy (PRK) and the correlation with morphological parameters. METHODS: 119 eyes of 75 subjects with a refraction ranging between -0.50 D and -14.50 D (mean = -4.7 ± 2.3 D) were included in this study. The differences in corneal hysteresis (CH) and corneal resistance factor (CRF) one, three, and six months after PRK have been correlated with effective treatment, central corneal thickness (CCT), and corneal volume (CV) variations at any follow-up utilizing the Pearson Index. Differences between preoperative and postoperative values of the analyzed parameters have been checked with Student T test. RESULTS: Both CH and CRF showed a significant (p < 0.01) decrease at one, three, and six months' follow-up. CONCLUSION: Our findings suggest that after myopic PRK there is a significant decrease of CH and CRF immediately after treatment that remains stable over the follow-up.

Evaluation of corneal deformation analyzed with Scheimpflug based device in healthy eyes and diseased ones.

This study was designed to evaluate the correlation between corneal biomechanical and morphological data in healthy eyes, eyes that underwent myopic photorefractive keratectomy (PRK), keratoconus affected eyes, and keratoconus affected eyes that underwent corneal collagen crosslinking (CCC). Complete clinical eye examination of all eyes was followed by tomographic (Pentacam, Oculus, Wetzlar, Germany) and biomechanical (Corvis ST, Oculus, Wetzlar, Germany) evaluation. Differences among Corvis ST (CST) parameters in the different groups have been performed. Linear regression between central corneal thickness (CCT), intraocular pressure (IOP), and anterior corneal curvature measured with Sim'K (KM), versus corneal deformation parameters measured with Corvis ST in the different groups, has been run using SPSS software version 18.0. We evaluated 64 healthy eyes of 64 patients with a mean refractive error of -0.65 ± 1.68 D (measured as spherical equivalent), 17 eyes of 17 patients that underwent myopic PRK for a mean refractive defect of -4.91 ± 2.05 D (measured as spherical equivalent), 16 eyes of 16 patients affected by keratconus (stage 2-3 of Amsler Classification), and 13 eyes of 13 patients affected by keratoconus that underwent CCC. Our data suggest that corneal curvature would have a greater influence on corneal deformation than CCT; in fact KM values are more strongly associated with more CST parameters both about corneal change in shape and both about the corneal ability to come back at original shape.

Intraocular lens power calculation: a challenging case.

PURPOSE: To highlight different methods in calculating intraocular lens (IOL) power in the case of undetectable keratometric (K) readings. CASE REPORT: A 54-year-old woman was referred to us for cataract surgery in her left eye. The slit lamp examination revealed the presence of corneal scars that did not allow us to take reliable K readings. To calculate them, the following regression formula was used: K= Rx-42.613/-0.0424*AL. The IOL power calculation was performed aiming at a postoperative error = -0.5 diopters. One month after surgery, the uncorrected visual acuity was 20/100 and the best spectacles corrected visual acuity was 20/25 with +1.0 -4 × 180 (-1.0 diopter spherical equivalent). CONCLUSIONS: This seems to be a reliable method to calculate the IOL power when K readings are undetectable, but to make a definitive statement, prospective studies are needed.

Prevalence of corneal astigmatism before cataract surgery in Caucasian patients.

PURPOSE: To analyze and quantify the pattern of corneal astigmatism in patients awaiting cataract surgery to provide information for cataract surgeons and intraocular lens (IOL) manufacturers and to establish the demand for toric IOLs in a hospital. METHODS: This cross-sectional retrospective study evaluated keratometric (K) values measured by partial coherence interferometry (IOLMaster) in cataract surgery candidates, who were then analyzed and correlated by age and axial length (AL) ranges. RESULTS: The study evaluated the K values in 757 eyes of 380 patients with a mean age of 71.9 ± 10.2 years (range 33-96 years). The mean corneal astigmatism was 1.02 ± 0.69 D (range 0.06-4.57 D). It was 1 D or higher in 316 (41.74%) eyes. The mean AL was 23.56 ± 1.35 mm (range 20.53-31.86 mm). CONCLUSIONS: Our study shows that roughly 50% of the eyes have more than 1 D of astigmatism. The results can help hospitals plan and analyze the amount and costs of using toric IOLs in patients with corneal astigmatism.

Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization.

Transcriptional silencing by CpG island hypermethylation plays a critical role in endometrial carcinogenesis. In a collection of benign, premalignant and malignant endometrial lesions, a methylation profile of a complete gene panel, such steroid receptors (ERα, PR), DNA mismatch repair (hMLH1), tumor-suppressor genes (CDKN2A/P16 and CDH1/E-CADHERIN) and WNT pathway inhibitors (SFRP1, SFRP2, SFRP4, SFRP5) was investigated in order to demonstrate their pathogenetic role in endometrial lesions. Our results indicate that gene hypermethylation may be an early event in endometrial endometrioid tumorigenesis. Particularly, ERα, PR, hMLH1, CDKN2A/P16, SFRP1, SFRP2 and SFRP5 revealed a promoter methylation status in endometrioid carcinoma, whereas SFRP4 showed demethylation in cancer. P53 immunostaining showed weak-focal protein expression level both in hyperplasic lesions and in endometrioid cancer. Non-endometrioid cancers showed very low levels of epigenetic methylations, but strong P53 protein positivity. Fisher exact test revealed a statistically significant association between hMLH1, CDKN2A/P16 and SFRP1 genes methylation and endometrioid carcinomas and between hMLH1 gene methylation and peritumoral endometrium (p < 0.05). Our data confirm that the methylation profile of the peritumoral endometrium is different from the altered molecular background of benign endometrial polyps and hyperplasias. Therefore, our findings suggest that the methylation of hMLH1, CDKN2A/P16 and SFRP1 may clearly distinguish between benign and malignant lesions. Finally, this study assessed that the use of an epigenetic fingerprint may improve the current diagnostic tools for a better clinical management of endometrial lesions.

Slow cooling of human oocytes: ultrastructural injuries and apoptotic status.

OBJECTIVE: To identify the damages caused by slow cooling human metaphase II (MII) oocytes comparing the ultrastructure, inner mitochondrial membrane potential (DeltaPsim), and apoptotic status of fresh and cryopreserved oocytes. DESIGN: Experimental study. SETTING: University biology research unit and private IVF unit. PATIENT(S): Fresh and cryopreserved supernumerary MII oocytes donated from women undergoing IVF cycles. MAIN OUTCOME MEASURE(S): Ultrastructure was assessed by transmission electron microscopy (TEM), mitochondrial function by means of the fluorescent DeltaPsim reporter JC-1, and apoptotic status through fluorescent labeling with the pan-caspase inhibitor fluorescein isothiocyanate conjugate (FITC)-VAD FMK, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. RESULT(S): Compared to fresh oocytes, frozen/thawed (F/T) oocytes showed reduced cortical granule densities (F/T 3.35 +/- 1.94/10 microm vs. fresh 10.30 +/- 3.9/10 microm), swelling of smooth endoplasmic reticulum (F/T 0.084 +/- 0.03 microm(2) vs. fresh 0.040 +/- 0.02 microm(2)), decreased electron density of the mitochondrial matrix and damage to the mitochondrial membranes, low DeltaPsim of pericortical mitochondria, but no signs of apoptosis. CONCLUSION(S): Slow cooling is associated with cortical granule exocytosis, swelling of smooth endoplasmic reticulum vesicles, and mitochondrial damage, but does not induce early or late apoptotic events. The observed injuries might be responsible for the reduced developmental competence of cryopreserved oocytes.