Screening for multifocal intraocular lens implantation in cataract patients in a public hospital.

PURPOSE: To identify the rate and characteristics of cataract surgery candidates suitable for multifocal intraocular lens implantation among patients undergoing preoperative evaluation in a public hospital. MATERIALS AND METHODS: Screening was performed based on the patient's medical records, comprehensive ophthalmic examination, optical biometry (Zeiss, IOL Master 700) and optical coherence tomography (OCT) (Heidelberg, OCT Spectralis) in accordance with the relevant indications and contraindications mentioned in the pertinent literature. Patients were included in the present study if they were eligible for bilateral cataract surgery. The exclusion criteria were the presence of central nervous system or motility issues, prior refractive surgery, the presence of astigmatism greater than 1 dioptre and/or the presence of important ocular comorbidities in either eye. RESULTS: The study evaluated 1200 consecutive patients. Four hundred thirty-two patients (36%) were not eligible for bilateral surgery and were excluded from the study. Of the 768 patients included in the present study, 346 (45.1%) were considered suitable candidates. Four hundred twenty-two patients (54.9%) were excluded for one or both eyes. Among them, 121 (28.7%) were excluded because of retinal disease, 120 (28.4%) because of regular astigmatism (> 1.0 D of corneal astigmatism), 32 (7.5%) because of pseudoexfoliation or zonular instability, and 30 (7.1%) because of glaucoma or ocular hypertension; in addition, 90 (21.3%) patients were excluded for multiple reasons. Suitable candidates were significantly younger (70 and 75 years, respectively) (p < 0.001). After being informed about the potential risks and benefits of MOIL implantation, 212 of 346 (83.8%) eligible patients provided consent. CONCLUSION: Close to half of cataract patients in a public hospital were eligible for MOIL implantation, and the majority of patients would proceed to surgery. The most prevalent contraindication was macular disease.

Radial peripapillary capillary density as a predictive factor for glaucoma in eyes with ocular hypertension. An observational, comparative, single-centred study.

Background: Ocular hypertension (OH) is a condition characterized by elevated intraocular pressure (IOP) exceeding the normal range, without any evident damage to the optic nerve or visual field defects characteristic of glaucoma. It constitutes a significant precursor to the development of glaucoma, a leading cause of irreversible vision loss worldwide. Emerging evidence has shown that microcirculation alterations in eyes with OH could serve as predicting factors to identify eyes at high risk for progression to glaucoma. In view of the above, the purpose of our study is to investigate microcirculation alterations of the radial peripapillary capillary plexus using optical coherence tomography angiography (OCT-A) in patients with ocular hypertension (OH). Methods: A total of 192 eyes were included in this observational, comparative, single-centre study and were divided in two groups: OH eyes and healthy controls. OCT-A was performed to analyze microcirculation characteristics at the peripapillary area. Radial peripapillary capillary density was measured at the total area of the optic disc and at each separate region (superior, inferior, inside). The parameters of age, medical treatment for ocular hypertension, sex and retinal fiber layer thickness were evaluated. Results: Total radial peripapillary capillary density was significantly lower in patients with OH than in healthy controls Concerning the microcirculation characteristics at each separate region of the peripapillary area, the results were as follows: inferior radial peripapillary capillary density was significantly decreased in individuals with OH than in controls, while measurements in the superior peripapillary area and internal optic disc were similar in both groups. Conclusions: Our study indicates decreased radial peripapillary capillary density in eyes with OH. Microcirculation alterations in the inferior peripapillary area could potentially comprise biomarkers for OH progression to glaucoma.

Correlation Between Central Corneal Thickness and Radial Peripapillary Capillary Density, in Patients With Ocular Hypertension.

Purpose To investigate any possible relationship between the central corneal thickness and the radial peripapillary capillary density detected by optical coherence tomography (OCT) angiography in eyes with ocular hypertension. Materials and methods In this observational study, 135 eyes were examined. OCT angiography of the optic disc (4.5 mm) and ultrasound corneal pachymetry were performed in all cases. Age, medical treatment for ocular hypertension, sex, and retinal nerve fiber layer thickness were evaluated. The main indices of blood flow were also examined. Spearman correlation coefficients were used to explore the association between two continuous variables. Results A directly proportional significance regarding the correlation between central corneal thickness and radial peripapillary network was indicated in eyes with ocular hypertension (p = .036). Conclusions Central corneal thickness and radial peripapillary capillary density constitute two essential screening parameters for patients with ocular hypertension.

Arthroscopic Removal of Tenosynovial Giant-Cell Tumors of the Cruciate Ligaments. Presentation of Two Cases.

BACKGROUND: Tenosynovial giant-cell tumor (GCT) arising from cruciate ligaments consists a rather rare entity. Predominantly areas where this tumor appears are the palmar sides of fingers and toes. The involvement of larger joints such as the knee or the ankle is rather rare, but, in the case of synovial joints, the knee joint is particularly affected. Furthermore, rare seems to be the intra-articular localization of the tenosynovial GCT of the tendon sheath. Hereby, we present an arthroscopic approach of treatment with two cases. CASE REPORTS: The first case was a 32-year-old male with a GCT arising from the anterior cruciate ligament (ACL). The second case was a 26-year-old male with a GCT arising from the posterior cruciate ligament (PCL). In the first case, a round-shaped mass with a reddish-brown color was located just anterior to the ACL and impeded the full extension of the knee joint, while, in the second case, a well-circumscribed oval-shaped mass was found with a peduncle attached to the synovium of the PCL. After arthroscopic excision, both patients became asymptomatic, with complete lack of pain and full ROM. CONCLUSIONS: There is a lack of clinical features for the GCT of the knee, and thus, a thorough clinical examination is prudent. Usually, the diagnosis is set after an investigation based on suspicion. This entity can present with symptoms of instability and patients may present signs of mechanical derangement. With the knee joint, meniscal symptoms and locking are often present. The best non-invasive technique to diagnose this tumor has been reported to be the magnetic resonance imaging. Arthroscopic excision has been reported as a safe and effective procedure for treatment.

Generation of Non-Small Cell Lung Cancer Patient-Derived Xenografts to Study Intratumor Heterogeneity.

Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients' peripheral blood and found that the presence of CTCs expressing epithelial-to-mesenchymal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were under-represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice.

Clinical Activity of an hTERT-Specific Cancer Vaccine (Vx-001) in "Immune Desert" NSCLC.

BACKGROUND: Tumors can be separated into immunogenic/hot and non-immunogenic/cold on the basis of the presence of tumor-infiltrating lymphocytes (TILs), the expression of PD-L1 and the tumor mutation burden (TMB). In immunogenic tumors, TILs become unable to control tumor growth because their activity is suppressed by different inhibitory pathways, including PD-1/PD-L1. We hypothesized that tumor vaccines may not be active in the immunosuppressive microenvironment of immunogenic/hot tumors while they could be efficient in the immune naïve microenvironment of non-immunogenic/cold tumors. METHODS: The randomized phase II Vx-001-201 study investigated the effect of the Vx-001 vaccine as maintenance treatment in metastatic non-small cell lung cancer (NSCLC) patients. Biopsies from 131 (68 placebo and 63 Vx-001) patients were retrospectively analyzed for PD-L1 expression and TIL infiltration. TILs were measured as tumor-associated immune cells (TAICs), CD3-TILs, CD8-TILs and granzyme B-producing TILs (GZMB-TILs). Patients were distinguished into PD-L1(+) and PD-L1(-) and into TIL high and TIL low. FINDINGS: There was no correlation between PD-L1 expression and Vx-001 clinical activity. In contrast, Vx-001 showed a significant improvement of overall survival (OS) vs. placebo in TAIC low (21 vs. 8.1 months, p = 0.003, HR = 0.404, 95% CI 0.219-0.745), CD3-TIL low (21.6 vs. 6.6 months, p < 0.001, HR = 0.279, 95% CI 0.131-0.595), CD8-TIL low (21 vs. 6.6 months, p < 0.001; HR = 0.240, 95% CI 0.11-0.522) and GZMB-TIL low (20.7 vs. 11.1 months, p = 0.011, HR = 0.490, 95% CI 0.278-0.863). Vx-001 did not offer any clinical benefit in patients with TAIC high, CD3-TIL high, CD8-TIL high or GZMB-TIL high tumors. CD3-TIL, CD8-TIL and GZMB-TIL were independent predictive factors of Vx-001 efficacy. CONCLUSIONS: These results support the hypothesis that Vx-001 may be efficient in patients with non-immunogenic/cold but not with immunogenic/hot tumors.

Report of a germline double heterozygote in MSH2 and PALB2.

BACKGROUND: Carriers with pathogenic variants in MSH2 have increased risk to develop colorectal, endometrium, ovarian, and other types of cancer. The PALB2 is associated with breast, ovarian, pancreatic, and prostate cancer. We describe the case of a 42-year-old female diagnosed with endometrial cancer at the age of 42 years with a strong family history of colorectal cancer, which was referred to our private diagnostic laboratory for genetic testing. METHODS: In this study, we performed next-generation sequencing (NGS) using an amplicon based 26 genes panel. The presence of multi-exonic copy number variations (CNVs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A gross deletion of the genomic region encompassing exons 11-16 of the MSH2 and the loss-of-function variant c.757_758delCT, p.(Leu253Ilefs*3) in the PALB2 were identified in the proband. CONCLUSIONS: Multigene analysis using NGS technology allows the identification of pathogenic variants in genes that would normally not be tested based on the patient diagnosis. In our case these results explained not only the personal and/or family history of cancer but also allowed the surveillance for prevention of other cancer types. Moreover, the detection of large genomic rearrangements should be routinely included in hereditary cancer testing.

Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRPα Expression.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. METHODS: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: (a) tumor center (TC), (b) invasive front (IF), (c) normal parenchyma adjacent to the tumor, and (d) tumor positive and negative draining lymph nodes (LNs). RESULTS: We observed: (a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs; (b) a dominant type 2 immune response in the TME, which is more pronounced in the TC; (c) an emerging role of CD47-SIRPα axis; and (d) a similar immune cell topography independently of the neoadjuvant chemotherapy. CONCLUSION: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities.

The first report of a 5-year period cancer registry in Greece (2009-2013): a pathology-based cancer registry.

Cancer registries are essential in health care, since they allow more accurate planning of necessary health services and evaluation of programs for cancer prevention and control. The Hellenic Society of Pathology (HSP) having recognized the lack of such information in Greece has undertaken the task of a 5-year pathology-based cancer registry in Greece (2009-2013). In this study, > 95% of all pathology laboratories in the national health system hospitals and 100% of pathology laboratories in private hospitals, as well as > 80% of private pathology laboratories have contributed their data. The most common cancer types overall were as follows: breast cancer (18.26%), colorectal cancer (15.49%), prostate cancer (13.49%), and lung cancer (10.24% of all registered cancers). In men, the most common neoplasms were as follows: prostate cancer, colorectal cancer, lung cancer, and gastric cancer. In women, the most common neoplasms were as follows: breast cancer, colorectal cancer, thyroid cancer, and lung cancer. The data on cancer burden in Greece, presented herein, fill the void of cancer information in Greece that affects health care not only nationally but Europe-wise.

Causes and management of small pupil in patients with cataract.

BACKGROUND: The purpose of the study was to present the causes and management of small pupil (<6 mm) in Greek patients with cataract. METHODS: About 1144 consecutive patients with cataract comprised the study group. The pupil size was measured after maximal dilation by means of Rosenbaum cards and Colvard pupillometer. Dilation regimen included phenylephrine 10%, tropicamide 1%, cyclopentolate 1%, and ketorolac trometamol 0.5% administered 3 times at 5 min intervals starting 1 h before surgery. The presence of possible risk factors for small pupil was recorded. The need of additional maneuvers and devices to dilate the pupil during cataract surgery was examined, and the complication rate in cases with small pupils was recorded. RESULTS: Small pupil was observed in 78 out of 1144 eyes (6.8%, 95% confidence interval = 5.2%-8.8%). Nine eyes had pupil size <4 mm (0.78%) preoperatively. Six cases (0.52%) developed intraoperative pupillary miosis. The major cause of small pupil was pseudoexfoliation (PEX) in 47.4% (37/78) of patients. No significant associations were observed regarding age, gender, history of diabetes mellitus, the maturity of cataract, and phacodonesis. Techniques for small pupil management included pupil stretching in 14 cases (17.9%), use of iris hooks in 6 cases (7.7%), iris sphincter cuts in 2 cases (2.6%), and placement of a Malyugin Ring in 4 cases (5.1%). Seven eyes (9%) with small pupil had capsular rupture versus 16 eyes (1.5%) with normal dilation (P < 0.001). CONCLUSIONS: Small pupil is not very common in Greek population, is mostly caused by PEX, and it is associated with increased complication rate.

Effect of Glaucoma Medication in Tear Film Osmolarity of Patients Without Symptoms of Ocular Discomfort.

PURPOSE: To evaluate tear film osmolarity in patients with no symptoms of ocular discomfort treated with intraocular pressure (IOP)-lowering medication and compare it with tear film osmolarity of controls. METHODS: This was a cross-sectional study of 61 patients with glaucoma or ocular hypertension (study group) and 32 age-matched normals (control group). Neither group of patients reported ocular discomfort. Tear film osmolarity was measured with the TearLab Osmolarity System (TearLab Corp, San Diego, CA), and results were compared between groups. Correlation of osmolarity with parameters associated with medication use (time, number of medications, and number of instillations) was assessed. RESULTS: Mean age of the patients in the medication group was 71±10.18 years and in the control group was 69±10.23 years (P=0.247). In the medication group, the tear film osmolarity was 295.56±12.54 mOsms/L and in the control group, it was 294.84±14.73 mOsms/L (P=0.807). Regarding the percentage of patients with tear film hyperosmolarity (osmolarity≥316 mOsms/L), in the group of normal patients, 3 had osmolarity more than or equal to the selected cutoff value (9.3%) and in the medication group, 7 patients (8.2%). Difference of the percentage between groups was not statistically significant (P=0.999, chi-square test). Tear film osmolarity in the medication group was not correlated to any of the parameters related to treatment. CONCLUSIONS: Patients treated with IOP-lowering medication do not exhibit tear film hyperosmolarity as long as they do not report symptoms of ocular discomfort.

Evaluation of the Icare-ONE rebound tonometer as a self-measuring intraocular pressure device in normal subjects.

PURPOSE: To compare Icare ONE rebound self-tonometer (ICRBT) measurements with Goldman applanation tonometry (GAT). METHODS: A trained examiner instructed each of 60 normal subjects on use of the ICRBT. Each subject then took two measurements of his/her own pressure using the ICRBT. Finally, a different examiner, who was masked to the earlier readings, measured IOP by GAT. Bland­Altman limits of agreement (LOA), intraclass correlation coefficients (ICCs), Kappa values, and paired t-test were used to assess the agreement between the two methods. Pearson's correlation coefficient was used for correlation analysis. RESULTS: All of the subjects were able to obtain correct measurements with ICRBT after three attempts. The mean intraocular pressure with ICRBT and GAT measurements were 16.0 ± 3.3 mmHg and 13.7 ± 2.5 mmHg respectively. The mean difference between patient's ICRBT and technician's GAT measurements was 2.3 mmHg (p < 0.001). In 63% (38/60) of the cases the IOP difference (ICRBT − GAT) was within ± 3 mmHg. The weighted Kappa for the IOP measurements of the two methods was 0.49 (95% CI: 0.30­0.68, p < 0.001), indicating acceptable agreement. A significantly positive correlation was found between ICRBT IOP measurements and central corneal thickness (CCT) (r = 0.48, p < 0.001). In addition, the difference in IOP measurements (ICRBT − GAT) between the two methods was positively correlated with CCT (r = 0.31, p = 0.015), indicating that greater thickness is associated with greater differences between the two methods. CONCLUSION: The ICRBT was reliable in the hands of normal subjects, and may be used for self-monitoring of IOP. ICRBT measurements generally overestimated GAT measurements.

Comparison of dynamic contour tonometry with Goldmann applanation tonometry in glaucoma practice.

PURPOSE: To compare intraocular pressure (IOP) readings taken using dynamic contour tonometry (DCT) with IOP readings taken with Goldmann applanation tonometry (GAT) in eyes with glaucoma or ocular hypertension. METHODS: The present study included 100 eyes in 100 patients with glaucoma or ocular hypertension. After pachymetry DCT and GAT were performed. Intraocular pressures as measured with DCT and GAT were compared with one another and with central corneal thickness (CCT). RESULTS: Mean DCT IOP measurements (20.1 +/- 4.3 mmHg) were significantly (p < 0.001) higher than GAT IOP values (17.9 +/- 4.7 mmHg). The mean difference between DCT and GAT measurements was 2.1 mmHg (range -3.4 to 9.7 mmHg). The difference followed a normal distribution. Measurements made with DCT and GAT correlated significantly with one another (Spearman's rho = 0.761, p < 0.001). Neither GAT nor DCT measurements showed a significant correlation with CCT (537 +/- 39 microm, range 458-656 microm). Multivariate regression analysis has shown that the difference between DCT and GAT is influenced significantly by ocular pulse amplitude (r = -0.334, p = 0.001) and it is not influenced by CCT (r = -0.106, p = 0.292). CONCLUSIONS: In eyes with glaucoma or ocular hypertension, DCT facilitates suitable and reliable IOP measurements which are in good concordance with GAT readings. Variation in CCT cannot by itself explain the differences in measurements taken with DCT and GAT in a number of eyes.

Study of patients with ocular hypertension with scanning laser polarimetry and short-wavelength automatic perimetry.

AIMS: To compare and correlate retinal nerve fiber layer (RNFL) measurements obtained by scanning laser polarimetry (SLP) with defects detected by short-wavelength automatic perimetry (SWAP) in eyes with ocular hypertension (OHT). METHODS: SLP and SWAP were performed in 96 eyes of 48 consecutive patients with OHT. RESULTS: Twenty-five eyes (26%) had SWAP visual field defects. Twenty-seven eyes (28.1%) had abnormal RNFL evaluation defined by the GDx neural network ('number' > 29). Fourteen eyes of 10 patients (14.5%) had abnormal RNFL evaluation and SWAP visual field defects. RNFL thickness measurements were significantly reduced in eyes with abnormal SWAP. A weak but statistically significant correlation between the 'number' and pattern standard deviation (r = 0.3, p = 0.006) and the corrected pattern standard deviation (r = 0.3, p = 0.007) in SWAP was found. Areas of abnormal RNFL thickness corresponded to the localization of the SWAP visual field defects in corrected pattern deviation plots in 10 of the 14 eyes with defects in both tests. CONCLUSIONS: SWAP visual field defects frequently coexist and correspond with abnormalities of RNFL detected by SLP in eyes with OHT. In certain eyes, however, the two methods detect different glaucoma properties.