The Relationship between Furin and Chronic Inflammation in the Progression of Cervical Intraepithelial Neoplasia to Cancer: A Cross-Sectional Study.

OBJECTIVE: The current study aimed to delineate the relationship between furin and chronic inflammation while cervical intraepithelial neoplasia progresses to cancer. STUDY DESIGN: This cross-sectional study included 81 women who required colposcopic examinations. The study groups were formed based on pathological results: Group I included women with cervical intraepithelial neoplasia (CIN) I (n = 30); Group II included women with CIN II-III (n = 28); and Group III included women with cervical cancer (CC) (n = 23). Furin, ki-67, and p16 levels were evaluated based on immunostaining intensity. The inflammatory indices were calculated in parallel with the literature from routine blood samples retrieved within one week before the procedure. RESULTS: Furin expression gradually increased from CIN I to CIN II-III and from CIN II-III to CC, respectively (p < 0.001, p = 0.005). NLR, MLR, PLR, and SII were significantly higher in the CC group (p < 0.001). ROC curve analysis unveiled that NLR, MLR, PLR, and SII predicted the presence of CC with a cutoff value of 2.39 for NLR (sensitivity: 91.3%, specificity: 63.8%, AUROC: 0.79, p < 0.001); a cutoff value of 0.27 for MLR (sensitivity: 78.3%, specificity: 72.4%, AUROC: 0.77, p = 0.009); a cutoff value of 123 for PLR (sensitivity: 100%, specificity: 41.4%, AUROC: 0.70, p = 0.04); and a cutoff value of 747 for SII (sensitivity: 69.6%, specificity: 90.7%, AUROC: 0.71, p = 0.014). CONCLUSION: Furin expression increased gradually in parallel with the severity of cervical intraepithelial neoplasia. The inflammatory indices were higher in the presence of CC and denoted a good discrimination ability for predicting cervical cancer.

Classification of high-grade endometrium carcinomas using molecular and immunohistochemical methods.

OBJECTIVES: As a result of the integration of molecular changes into the histological classification of cancers, which increases diagnostic repeatability, the differences between the groups become more prominent and targeted therapies gain significance. The most comprehensive molecular study regarding endometrial carcinomas (EC) is The Cancer Genome Atlas (TCGA) project. According to TCGA, endometrial carcinomas are classified into four molecular prognostic subgroups: copy-number-low/p53-wild-type (p53wt), DNA polymerase epsilon (POLE)-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). In this study, we aim to apply the molecular classification to our high-grade endometrial cancer patients, and particularly, to identify our overtreated patients. MATERIAL AND METHODS: Ninety-seven patients diagnosed with high-grade EC in Selcuk University, Faculty of Medicine between 2009-2018 were retrospectively evaluated and classified into four subgroups. Primary outcomes of overall and progression-free survival were evaluated for clinical, pathological, and molecular features. Further, all molecular groups were divided into endometroid and non-endometrioid groups, and disease-free survival (DFS) and overall survival (OS) were investigated across groups. RESULTS: According to molecular classification, 23 patients (23.7%) were assigned to the MSI group, 21 (21.6%) to the POLEmt group, 40 (41.2%) to the p53mt group, and 13 (13.4%) to the p53wt group. Patients' DFS (p = 0.001) and OS rates (p = 0.001) were significantly different according to their molecular classification. The results of our analyses determined that, in the molecular classification of high-grade ECs, the p53mt group had the poorest prognosis and the POLEmt group had the best prognosis. Tumor size, myometrial invasion, lymphovascular space invasion (LVSI), lymph node metastasis, cervical invasion, ovarian invasion and stage showed statistically significant differences based on molecular classification (p < 0.05). CONCLUSIONS: The use of molecular classification in the clinical practice will allow more accurate prognostic prediction and more appropriate treatment planning, particularly as high-grade ECs constitute a heterogenous group with poor prognosis.

Effect of Previous Crosslinking on Intraoperative and Postoperative Outcomes and Complication Rates of Big-Bubble Deep Anterior Lamellar Keratoplasty for Keratoconus: A Comparative Study.

PURPOSE: To compare surgical outcomes and intraoperative and postoperative complications of big-bubble deep anterior lamellar keratoplasty (DALK) in patients with and without a history of previous corneal collagen crosslinking (CXL) for keratoconus. METHODS: Patients with keratoconus who underwent DALK surgery with big-bubble technique between January 2013 and January 2018 were retrospectively reviewed. Operative findings, intraoperative and postoperative complications, and visual and refractive outcomes were recorded. Patients were divided into 2 groups: with previous CXL (CXL-DALK group: 27 eyes) and without previous CXL (DALK group: 50 eyes). All parameters were compared between groups. RESULTS: Big bubble was successfully achieved in 24 eyes (88.9%) in the CXL-DALK group and in 45 eyes (90.0%) in the DALK group (P = 0.87). Type 1 bubble was obtained in 22 eyes (91.7%) in the CXL-DALK group and in 42 eyes (93.3%) in the DALK group (P = 0.79). Intraoperative microperforation occurred in 3 eyes (11.1%) in the CXL-DALK group and in 5 eyes (10.0%) in the DALK group (P = 1). Visual and refractive outcomes were similar between groups. The mean endothelial cell loss rates were 5.7% ± 2.3 at 1 year and 10.2 ± 3.1 at 2 years in the CXL-DALK group and 6.4% ± 4.7 at 1 year and 10.9% ± 5.4 at 2 years in the DALK group. Postoperatively, persistent epithelial defect was the most common complication in both groups, and postoperative complication rates were similar between groups. CONCLUSIONS: Our results have shown that previous CXL treatment does not influence the success of bubble formation and does not increase intraoperative or postoperative complication rates of DALK surgery for keratoconus. The improvement in visual acuity and refractive errors and endothelial cell loss rates were similar between CXL treated and untreated eyes after 2 years of follow-up.

Mechanical Properties of Bioengineered Corneal Stroma.

For the majority of patients with severe corneal injury or disease, corneal transplantation is the only suitable treatment option. Unfortunately, the demand for donor corneas greatly exceeds the availability. To overcome shortage issues, a myriad of bioengineered constructs have been developed as mimetics of the corneal stroma over the last few decades. Despite the sheer number of bioengineered stromas developed , these implants fail clinical trials exhibiting poor tissue integration and adverse effects in vivo. Such shortcomings can partially be ascribed to poor biomechanical performance. In this review, existing approaches for bioengineering corneal stromal constructs and their mechanical properties are described. The information collected in this review can be used to critically analyze the biomechanical properties of future stromal constructs, which are often overlooked, but can determine the failure or success of corresponding implants.

Analysis of retinal nerve fiber layer thickness in anisometropic amblyopia via optic coherence tomography.

OBJECTIVE: To detect retinal nerve fiber layer thickness differences of ambylopic and fellow eyes and ambylopic and control eyes. METHODS: The study comprised a total of 152 eyes recruited from Erzurum Region Training and Research Hospital, Turkey, between January 2018 and May 2018. Anisometropic amblyopia was the only cause of disability (visual acuity ≤ 6/12 and a difference in best-corrected visual acuity (BCVA) between the two eyes of 0.20 logMAR (2 lines on an acuity chart) in amblyopic eyes (n, 74) whereas normal eyes had a best-corrected visual acuity of 6/6 and no morbidities (n, 78). Anisometropic patients were divided into three groups as hyperopic, myopic, and cylindiric. All amblyopic eyes were compared with fellow eye and control group. Retinal nerve fiber layer thickness was analyzed using optic coherence tomography (OCT) (RTVue 100-2, Optovue, Inc. Fremont, CA). RESULTS: The mean age of the patients was 28.64 ± 8.23 years in amblyopia group and 32.23 ± 8.14 years in control group (p, 0.008). Mean best-corrected visual acuity (BCVA) was 0.36 ± 0.23 in amblyopic eyes, 0.96 ± 0.15 in fellow eyes, and 1.00 ± 0 in control group. Mean refractive error was 2.76 ± 7.84 in amblyopic eyes, 0.42 ± 1.34 in fellow eyes, and 0.12 ± 0.27 in control group. Temporal retinal nerve fiber layer thickness (RNFL-T) was 77.27 ± 10.38 µ, 79.31 ± 9.53 µ, and 81.46 ± 9.86 µ respectively in ambylopic group, fellow eyes, and control eyes (p, 0.036). Superior RNFL-T was 136.23 ± 18.52 µ, 131.91 ± 13.80 µ, and 135.56 ± 14.94 µ respectively in ambylopic group, fellow eyes, and control eyes (p, 0.204). Nasal RNFL-T was 87.99 ± 13.05 µ, 82.16 ± 12.33 µ, and 85.50 ± 10.62 µ respectively in ambylopic group, fellow eyes, and control eyes (p, 0.014). Inferior RNFL-T was 144.85 ± 18.39 µ, 140.55 ± 16.92 µ, and 143.47 ± 17.75 µ respectively in ambylopic group, fellow eyes, and control eyes (p, 0.322). There was statistically significant difference in temporal and nasal quadrants and no statistical difference in superior and inferior quadrants. DISCUSSION: The presence of amblyopia seems not to be related with RNFL-T so we could ignore anisometropic amblyopia in patients with disease that could be detected and followed via RNFL thickness. Further and larger scaled studies are needed for certain results.

Subclinical inflammation markers in hyperemesis gravidarum and ketonuria: A case-control study.

INTRODUCTION: Subclinical inflammation markers play a significant role in hyperemesis gravidarum (HEG). Simple hematological markers such as mean platelet volume (MPV), platelet distribution width (PDW), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), plateletcrit (PCT), and platelet-to-lymphocyte ratio (PLR) have been shown to reflect inflammatory burden and disease activity in several disorders. Ketonuria is a parameter used in the diagnosis of severe HEG, but its correlation with disease severity remains controversial. The relationship of subclinical inflammation markers with degree of ketonuria has not been examined previously. In this study, we aimed to determine the diagnostic value of these subclinical inflammation markers and the relationship between these markers and grade of ketonuria in patients with HEG. MATERIALS AND METHODS: A total of 94 pregnant women with a diagnosis of HEG and 100 gestational age-matched healthy pregnant women were enrolled in this retrospective study. MPV, PDW, NLR, PLR, PCT, and ketonuria were calculated and analyzed from complete blood cell counts and total urine analyses. RESULTS: Lymphocyte count was significantly higher in the control group (P < 0,001); NLR and PLR values were significantly higher in the HEG group (P < 0,001). Among inflammation markers, RDW increased significantly (P = 0,008) with an increase in ketonuria in patients with HEG. A statistically significant correlation was found between white blood cell (WBC) and NLR, PLR, PCT. A moderate uphill relationship was observed between NLR and WBC and a weak uphill linear relationship was observed between WBC and PLR and between WBC and PCT. CONCLUSIONS: PLR and NLR can be considered effective markers to aid in the diagnosis of HEG. No marker was found to correlate with ketonuria grade except RDW, although the relationship of the severity of ketonuria with severity of disease is controversial. RDW increases as the degree of ketonuria increases.

The Effect of Low-Dose Aspirin on Dry Eye Parameters and Ocular Surface Disease Index Questionnaire.

PURPOSE: To evaluate the effects of acetylsalicylic acid (aspirin) on tear film parameters and dry eye disease. METHODS: Fifty-seven patients using low-dose aspirin regularly for antiaggregant purposes as well as 49 controls, who required antiaggregant treatment but who had not yet started, were included in the study. Tear osmolarity, tear break-up time (TBUT), Schirmer and Oxford grading of ocular surface staining were performed on all patients and dry eye symptomatology was assessed using the ocular surface disease index questionnaire (OSDI). RESULTS: The mean osmolarity was 302.11 ± 16.22 mOsm/L in the aspirin group and 313.88 ± 19.57 mOsm/L in the control group (P < 0.01). The mean Schirmer's score was 24.16 ± 10.52 mm and 21.94 ± 10.11 mm (P = 0.232), TBUT was 13.61 ± 3.31 s and 10.39 ± 4.46 s (P < 0.01), OSDI score was 5.15 ± 5.98 and 16.94 ± 14.17 (P < 0.01), and Oxford score was 0.12 ± 0.33 and 0.12 ± 0.44 in aspirin and control groups, respectively (P = 0.99). Dry eye diagnosis was lower in the aspirin group, but statistical significance was present only in TBUT and osmolarity-based dry eye diagnosis (P ≤ 0.01). In terms of symptom-based dry eye diagnosis with the threshold of OSDI ≥23, none of the aspirin group had dry eye diagnosis, whereas 32.6% of the control group had the diagnosis (P < 0.01). CONCLUSIONS: The use of low-dose aspirin might be great option for treatment of ocular surface inflammatory disease through increasing TBUT and decreasing tear osmolarity with a resultant symptomatic satisfaction.

Alterations of Choroidal Thickness With Diabetic Neuropathy.

PURPOSE: To evaluate the effect of diabetic polyneuropathy on choroidal thickness in type 2 diabetes patients. METHODS: Forty-one diabetic polyneuropathy (DPN) patients with no or mild retinopathy, 50 non-DPN diabetic patients with no or mild retinopathy, and 42 healthy controls without any retinal complaint were included in the study. All participants underwent detailed ophthalmic examinations. Choroidal thickness (CT) measurements were performed by the same independent technician in the morning between 9 and 11 AM to avoid diurnal variations. Perpendicular CT was measured from the outer edge of the hyperreflective retinal pigment epithelium to the inner sclera at seven locations: the fovea; and 500, 1000, and 1500 µm temporally and nasally to the fovea. RESULTS: The groups were age and sex matched (P > 0.05). The mean subfoveal CT values were significantly different in groups with a thickening trend from control to non-DPN and DPN (P < 0.01). The mean values for subfoveal CT in control, non-DPN, and DPN groups were 241.12 ± 52.71, 279.82 ± 51.42, and 304.71 ± 54.92 µm, respectively. The same thickening trend was also evident in all other six measurement points with statistical significance (P < 0.01). CONCLUSIONS: Diabetic patients had increased CT compared to healthy controls. The presence of neuropathy in diabetes patients caused additional choroidal thickening, compared to nonneuropathic patients.

Mineralocorticoid receptor gene - 2G/C polymorphism in central serous chorioretinopathy and relation of polymorphism with plasma cortisol levels / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the mineralocorticoid receptor ( MR) gene - 2G/ C single nucleotide polymorphism in central serous chorioretinopathy ( CSCR ), polymorphism and plasma cortisol level relationship. METHODS: Sixty CSCR patients and 50 controls were included in the study. Inclusion criteria for patients were acute manifestation of CSCR characterized by serous retinal detachment, RPE detachment or dysfunction without evidence of any other possible cause of fluid exudation, such as choroidal neovascularization, inflammation or infiltration. Peripheric blood sample was collected from the participants between 8 and 10 a. m. to avoid the diurnal changes of cortisol levels. MR (NR3C2) gene polymorphism ( rs2070951 ) and plasma cortisol levels sere studied. RESULTS: The genotype frequencies in CSCR group were G/ C (46. 6% ), G/ G (26. 7%) and C/ C (26. 7%). There was no statistically significant difference in terms of genotype distribution among groups ( P = 0. 96 ). The plasma cortisol levels were also studied and the results were 401. 2±162. 1 nmol/ L in the CSCR group and 296. 8±130. 1 nmol/ L in the control group and the difference was statistically significant ( P CONCLUSION: The MR (NR3C2) gene polymorphism is not associated with CSCR and the plasma cortisol levels.

Tear Osmolarity, Break-up Time and Schirmer's Scores in Parkinson's Disease.

OBJECTIVES: Dry eye is an important problem in Parkinson's disease (PD) with a potential to affect life quality. Tear osmolarity, accepted as the gold standard in dry eye diagnosis, has not been studied in this subset of patients so far. Therefore, in this study we aimed to evaluate tear osmolarity, Schirmer's test scores and tear film break-up time (TBUT) in PD patients. MA­TE­RI­ALS AND MET­HODS: PD patients with a minimum follow-up of 1 year and healthy controls who admitted for refractive abnormalities were enrolled to the study. Subjects using any systemic medication with a possibility to affect tear tests were not included in the study. The presence of any ocular surface disorder, previous ocular surgery, previous dry eye diagnosis, any topical ophthalmic medication or contact lens use were other exclusion criteria. Age, gender, disease duration, and Hoehn and Yahr (H&Y) score for disease severity were noted, and blink rate (BR), Schirmer's test score, TBUT and tear osmolarity of the right eye were measured in both groups. RE­SULTS: Thirty-seven PD patients and 37 controls were enrolled to the study. The groups were age and gender matched. The mean disease duration and H&Y score were 5.70±2.64 years and 1.70±0.93, respectively. H&Y staging and disease duration were not correlated to BR, Schirmer's scores, TBUT, or tear osmolarity (p>0.05). The mean BR was 8.54±4.99 blinks/minute in PD patients and 11.97±6.36 blinks/minute in the control group. Mean Schirmer's scores, TBUT and osmolarity values were 9.08±4.46 mm, 11.38±4.05 seconds and 306.43±12.63 mOsm/L in the PD group and 17.16±9.57 mm, 12.81±3.66 seconds and 303.81±16.13 mOsm/L in the control group. The differences were significant only in BR and Schirmer's scores. CONCLUSION: BR and Schirmer's scores decreased significantly in PD patients. Although not significant, the demonstrated tear osmolarity increment might be important to document the dry eye and inflammatory process of the ocular surface in PD patients.

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

BACKGROUND: To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats. METHODS: Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA. RESULTS: The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

Ganglion cell-inner plexiform layer thickness in patients with Parkinson disease and association with disease severity and duration.

BACKGROUND: To evaluate the average, minimum, and 6-sectoral macular ganglion cell-inner plexiform layer (GC-IPL) thickness measured by spectral domain optical coherence tomography (SD-OCT) in patients with Parkinson disease (PD), as well as average and 4-sectoral retinal nerve fiber layer (RNFL) thickness and to determine whether thickness parameters are correlated to disease severity and duration. METHODS: Patients with PD (n = 54) and age-matched healthy controls (n = 54) were prospectively examined with SD-OCT. Randomly selected eyes of all subjects were included. The average, minimum, and 6-sectoral (superior, superotemporal, superonasal, inferonasal, inferior, and inferotemporal) GC-IPL thickness values were analyzed. Average and 4-sectoral (inferior, superior, temporal, and nasal) peripapillary RNFL thicknesses were also evaluated. Each parameter was compared between patients with PD and age-matched healthy controls. PD severity was quantified with the Hoehn and Yahr (HY) scale. A correlation analysis was performed to evaluate the association between SD-OCT measurements and the duration and severity of PD. RESULTS: The mean age of patients with PD and age-matched healthy controls was 66.62 ± 8.71 years and 66.68 ± 7.85 years, respectively. Disease duration ranged from 1 to 15 years with a mean of 5.12 years. The mean PD severity, according to the HY scale, was 2.26 (range, 1-5). SD-OCT measurements revealed significant differences in inferior and temporal peripapillary RNFL values between groups (P = 0.018 and P = 0.031, respectively). All GC-IPL thickness parameters were statistically lower in the patients with PD when compared with the healthy controls (P < 0.001). PD duration was not correlated to any of the RNFL thicknesses, but PD severity was correlated inversely only with inferior peripapillary RNFL thickness (P = 0.006). Average, inferior (P = 0.011), inferotemporal (P = 0.007), and superotemporal (P = 0.007) GC-IPL thicknesses were correlated inversely with both PD severity and duration. CONCLUSIONS: Retinal dopaminergic neurodegeneration in patients with PD can be detected with macular GC-IPL thickness measurements. Macular GC-IPL thickness was correlated with PD severity and duration. It may be used to follow disease progression and efficacy of the neuroprotective treatment in patients with PD.

Change in tear film characteristics in visual display terminal users.

PURPOSE: To evaluate changes in symptoms and tear film characteristics in young computer users. METHODS: Fifty-one computer users and 26 controls were evaluated at the beginning and the end of the working day. Subjects with ocular or systemic disease, history of ocular surgery, use of contact lenses or glasses with antireflective surfaces, and use of topical or systemic medications were excluded from the study. Computer use duration, Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, Schirmer test, tear break-up time (TBUT), and ocular surface vital dye staining were performed prevocationally and postvocationally. RESULTS: The mean age was 31.2 ± 6.3 years in computer users and 33.7 ± 5.8 in controls. The mean reported computer use was 6.9 ± 2.7 hours/day in computer users and 0.4 ± 0.5 hours/day in controls. The mean prevocational and postvocational values in computer users for OSDI, osmolarity, TBUT, and Schirmer test were 23.2 ± 16.6 and 27.0 ± 17.6, 306.6 ± 14.9 and 311.0 ± 12.5 mOsm/L, 13.9 ± 4.0 and 13.2 ± 3.8 seconds, 22.7 ± 11.8 and 20.6 ± 12.5 mm, respectively. The vocational change was significant for all parameters in the computer user group but not in the control group. The osmolarity-based dry eye diagnosis was 27.4% in the computer users while it was 15.4% in the control group. Oxford score was only grade 1 in 5.9% of visual display terminal users and did not change at the end of the day. CONCLUSIONS: Both symptoms and signs of dry eye increased significantly with computer use. Approximately 1 of every 3-4 computer users was found to have dry eye with higher tear osmolarity values.

The effect of intracameral anesthesia on macular thickness and ganglion cell-inner plexiform layer thickness after uneventful phacoemulsification surgery: prospective and randomized controlled trial.

BACKGROUND: To evaluate the effect of intracameral lidocaine anesthesia on macular thickness and macular ganglion cell-inner plexiform layer (GC-IPL) thickness following uneventful phacoemusification in healthy subjects. METHODS: This is a prospective, randomized and double- masked study. One hundred eyes of 74 consecutive patients were randomized to receive intracameral preservative-free lidocaine 1 % (intracameral lidocaine group) or intracameral injection of balanced salt solution (sham injection group) at the time of the phacoemulsification surgery. Preoperative and postoperative macular thickness analyses with spectral domain optical coherence tomography (SD-ODT) were performed and the results between the two groups were compared. RESULTS: Postoperatively, both the central foveal thickness (CFT) and the thickness of perifoveal macula were significantly improved in both groups (p < 0.001). There was no statistically significant difference between CFT and the inner and outer macular zone thicknesses of the two groups at any follow-up time. In both groups, GC-IPL thickness was significantly increased at the first week and first month visits (p < 0.001). There was no statistically significant difference between GC-IPL thickness measurements of the two groups at any follow-up time. CONCLUSION: The current study demonstrated that supplementary intracameral lidocaine 1 % did not cause more macular thickening than the intracameral sham injection during a follow-up period of 3 months. The present study also showed a tendency for a transient increase in high definition SD-OCT-based GC-IPL thickness measurements within a few months following cataract surgery under both intracameral lidocaine anesthesia and intracameral sham injection.