Publications by authors named "Efstathios T Detorakis"

90 Publications

Association between HPV detection in swab samples and tissue specimens and ophthalmic pterygium recurrence.

Graefes Arch Clin Exp Ophthalmol 2021 Jun 22. Epub 2021 Jun 22.

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Purpose: To investigate the presence of HPV on the ocular surface after surgical excision of HPV infected pterygia and the possible correlation of HPV with pterygium postoperative recurrence.

Materials And Methods: Both exfoliative pterygium swab samples and respective tissue specimens were received and analyzed with real-time PCR for the detection of HPV-infected pterygia. In addition, swab samples from patients that had HPV-infected pterygia with no recurrence after 1 year of follow-up, as well as swab samples from patients with healthy conjunctiva, were analyzed.

Results: Forty eyes with pterygium of 40 patients and 40 eyes with normal conjunctiva were included in the study. HPV virus was detected in the tissue specimens of 11 patients (27.5%) and in the swabs of 9 patients (22.5%). The HPV subtypes detected were 33, 39, 45, 56, 59, 66, and 68. The swab test had sensitivity of 81.82% and 100% specificity. In 15 (43%) patients, a bare sclera technique was used for pterygium removal and eleven of these patients showed recurrence of the disease. Surgical excision with use of autologous conjunctival graft was performed in twenty patients and five of them had recurrence. Patients with recurrent disease were 12.41 times more likely to have an HPV-infected pterygium (p = 0.031). Furthermore, from the 11 HPV positive patients, six had no recurrence, 1 year after surgery. In five of them, a swab sample was taken from the site of the surgical excision 1 year after surgery and real-time PCR was negative for HPV presence.

Conclusion: Persistence of HPV infection seems to be correlated with postoperative pterygium recurrence. Further investigation with the use of the minimally invasive proposed swab technique may contribute in the understanding of pterygium pathogenesis and in the development of a more efficient treatment planning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00417-021-05267-0DOI Listing
June 2021

Causes, occupational risk and socio-economic determinants of eye injuries: a literature review.

Med Pharm Rep 2021 Apr 29;94(2):131-144. Epub 2021 Apr 29.

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Purpose: This review provides literature views on ocular trauma, with emphasis on common causes of injury, occupational risk, socio-economic factors, management peculiarities and some implications on overall care approach, from prevention to treatment.

Methods: A literature search was performed using key words in PubMed to extract the most relevant articles on ocular injuries, from an occupational point of view. Seventeen relevant articles were included out of seventy-two. Eight relevant articles were found from the references of the articles included and were also added. The total number of articles for this systematic search analysis was twenty-five. Collected information was tabulated in the Appendix.

Results: Most of the included publications were original articles. Many studies were retrospective and cross-sectional with a satisfactory rate of participant recruitment when reported. Most of eye injuries occurred in the workplace. Common eye injuries were due to foreign bodies and corneal abrasions. High-risk occupations included welders, farmers, metalworkers and grinding, construction and manufacturing workers. Most of the injuries could be preventable by using suitable protective eye devices (PED) but appropriate protection is a more complex process than it appears.

Conclusions: Findings of this review showed that it is compulsory to inform people about the risk and consequences of eye injuries. Eye care services should be designed keeping in mind geo-epidemiologic trauma etiology patterns and local health system capacity. Issues of adherence to prevention measures remain object of knowledge dissemination, educational planning and cultural appraisal. Modernizing equipment and respecting workplace regulations are tasks that deserve continuous attention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15386/mpr-1761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118212PMC
April 2021

Association of obstructive sleep apnea/hypopnea syndrome with glaucomatous optic neuropathy and ocular blood flow.

Exp Ther Med 2021 Jun 20;21(6):657. Epub 2021 Apr 20.

Department of Ophthalmology, University Hospital of Alexandroupolis, Alexandroupolis 68100, Greece.

The present study aimed to investigate the prevalence of glaucomatous optic neuropathy in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). In total, 83 subjects (45 cases of severe OSAHS and 38 controls) underwent polysomnographic assessment and were evaluated for the severity of the disease using the Apnea-Hypopnea index. A detailed ophthalmologic exam was then performed, including measurement of the intraocular pressure (IOP) with a Goldmann applanation tonometer and Pascal dynamic contour tonometer (DCT), recording of the ocular pulse amplitude measured by the Pascal DCT, standard automated perimetry and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness evaluation using optical coherence tomography. Ocular blood flow was assessed using color Doppler imaging (CDI) and ophthalmic artery indices were evaluated, including peak systolic blood velocity, end diastolic blood velocity and resistivity index (RI). There was a significant difference in the mean IOP between controls (11.03±3.85 mmHg) and cases of severe OSAHS (18.06±3.39 mmHg) when the IOP was measured by DCT (P<0.0001), but not with the Goldmann applanation tonometer (IOP, 13.97±2.85 mmHg for controls and 14.89±3.21 mmHg for cases of severe OSAHS; P=0.0877). Significant negative correlations were observed between RNFL thickness and RI (P=0.0011) in cases of severe OSAHS, as well as between GCC thickness and RI (P<0.008) in all subjects. Furthermore, a negative correlation between RI and RNFL thickness in severe cases of OSAHS suggested a hemodynamically induced vulnerability of RNFL in OSAHS. The correlation between RI and GCC thickness in all subjects suggested that impaired perfusion, more prominent in OSAHS, leads to structural changes. Therefore, cases of severe OSAHS should be monitored for changes in RNFL and GCC thickness, as well as CDI findings. Furthermore, patients with increased ophthalmic artery RIs should be monitored for changes in the GCC, regardless of the etiology of the RI increase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097189PMC
June 2021

Changes in peri-ocular anatomy and physiology in pseudoexfoliation syndrome (Review).

Exp Ther Med 2021 Jun 19;21(6):650. Epub 2021 Apr 19.

Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Greece.

Pseudoexfoliation syndrome (PEX) is characterized by the deposition of proteinaceous material in the anterior ocular segment (resulting in ophthalmic pathologies such as glaucoma and increased risk of complications in cataract surgery), but also by several systemic manifestations. The involvement of peri-ocular tissues in PEX, including the eyelid skin, lacrimal gland, conjunctiva, orbital fat and vessels, as well as the optic nerve, has been reported by several previous studies. The peri-ocular effects of PEX include the development of eyelid laxity, conjunctival chalasis, tear film abnormalities, pronounced orbital fat atrophy in response to the administration of prostaglandin analogues in pseudoexfoliative glaucoma, deficient orbital vascular supply and biomechanical changes in both the eyeball and the optic nerve. These effects may have important clinical implications, including increased difficulty in cataract surgery, ocular surface disease and eyelid margin malpositions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2021.10082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097227PMC
June 2021

MRI and dual-energy CT fusion anatomic imaging in Ru-106 ophthalmic brachytherapy.

Brachytherapy 2021 Mar 27. Epub 2021 Mar 27.

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Purpose: Brachytherapy with Ru-106 is widely used for the treatment of intraocular tumors, and its efficacy depends on the accuracy of radioactive plaque placement. Ru-106 plaques are MRI incompatible and create severe metal artifacts on conventional CT scans. Dual-energy CT scans (DECT) may be used to suppress such artifacts. This study examines the possibility of creating fusion images from MRI scans (preoperatively) and DECT scans (with the plaque in place) as a tool for confirming the anatomic accuracy of plaque placement.

Methods And Materials: Six patients with intraocular lesions (5 with choroidal melanoma and 1 with a retinal vasoproliferative lesion) were included. Fusion images of preoperative MRI scans and DECT scans with the plaque in place were created with the Demo version of the ImFusion suite (ImFusion GmbH, Munchen Germany). Clearance margins between the tumor and plaque edge in axial, transverse, and coronal planes as well as the elevation of the posterior plaque edge from the sclera were recorded and associated with the location of the lesion.

Results: Plaque-tumor clearance margins for transverse, sagittal, and coronal planes were higher for anteriorly located lesions (5.13 mm ± 0.11 [5.0-5.2], 5.10 mm ± 0.26 [4.9-5.4], and 5.33 mm ± 0.45 [4.9-5.8] respectively) than for posteriorly located lesions (4.16 mm ± 1.44 [2.5-5.1], 4.13 mm ± 1.42 [2.5-5.1], and 4.2 mm ± 1.21 [2.8-5.0], respectively). The elevation of the posterior plaque edge from the sclera was 0.33 mm ± 0.28 [0-0.5] and 0.63 mm ± 0.60 [0.7-1.2] for posterior and anterior lesions, respectively.

Conclusions: Fusion images between DECT and MRI scans may be used as a tool to confirm the accuracy of Ru-106 plaque placement in relation with the intraocular tumors in ophthalmic brachytherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brachy.2021.01.003DOI Listing
March 2021

Ultrasound elastography in ocular and periocular tissues: A review.

Curr Med Imaging 2020 Dec 14. Epub 2020 Dec 14.

Department of Ophthalmology, University Hospital of Heraklion, Crete. Greece.

Ultrasound elastography has become available in the everyday practice, allowing direct measurement of tissue elasticity with important and expanding clinical applications. Several studies that have evaluated pathological and nonpathological tissues have demonstrated that ultrasound elastography can actually improve diagnostic accuracy of underlying disease process by detecting differences in their elasticity. Ocular and periocular tissues can also be characterized for their elastic properties. In this context, comprehensive review of literature on ultrasound elastography as well as its current applications in Ophthalmology is presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1573405616666201214123117DOI Listing
December 2020

eyeWatch™ System Combined with Non-plated Intraorbital Tube Insertion for the Management of Refractory Glaucoma: A Case Series.

J Curr Glaucoma Pract 2020 May-Aug;14(2):64-67

Laboratory of Hemodynamics and Cardiovascular Technology, Lausanne, Switzerland.

Introduction: The eyeWatch™ is a novel device in glaucoma surgery aiming at the control of aqueous flow through the use of an external magnetic control unit. We propose the modification of this approach through the use of an injectable perforated tube rather than a plated valve.

Materials And Methods: Procedures were performed at the Department of Ophthalmology of the University of Crete. Three blind painful eyes of three patients were included. All patients were operated under topical anesthesia. A purpose designed blunt-ended injector was used to insert intraorbitally a perforated 4 cm-long silicone tube. The tube was then connected to an eyeWatch™ device which was placed in a standard fashion along the superior-temporal quadrant of the eyeball. The procedure was uneventful in cases I and II, whereas in case III the tube had to be trimmed by 1.5 cm because of cicatricial changes in the orbit. The eyeWatch™ was left closed (position VI) at the conclusion of surgeries. Patients were examined on the 1-day, 1-week, 2-week, 1-month, 3-month, and 6-month intervals and in one case on the 12-month interval.

Results: No major complications were observed. The intraocular pressure (IOP) remained under 15 mm Hg without anti-glaucomatous medications in all postoperative intervals in cases I and 2 with readjustment of eyeWatch™ at position IV. In case III, despite the change of the eyeWatch™ to the open position, the IOP remained high (40 mm Hg).

Discussion: The combination of the eyeWatch™ with an insertable perforated tube instead of a standard non-valved plate may prove a valid minimally invasive option. Modifications of the technique, such as an increased number and diameter of tube perforations, increased inserted tube length, perhaps aided by a sharp-ended injector, and selection of the insertion quadrant, may increase the effectiveness of the method.

Clinical Significance: eyeWatch™ combined with a single tube instead of a plated valve is a feasible, quick, and minimally invasive technique that can be used in glaucoma surgery.

How To Cite This Article: Detorakis ET, Villamarin A, Roy S, eyeWatch™ System Combined with Non-plated Intraorbital Tube Insertion for the Management of Refractory Glaucoma: A Case Series. J Curr Glaucoma Pract 2020;14(2):64-67.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5005/jp-journals-10078-1276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695936PMC
December 2020

Orbital volume measurements from magnetic resonance images using the techniques of manual planimetry and stereology.

Natl J Maxillofac Surg 2020 Jan-Jun;11(1):20-27. Epub 2020 Jun 18.

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Crete, Greece.

Introduction: Current volume measurement techniques, for the orbit, are time-consuming and involve complex assessments, which prevents their routine clinical use. In this study, we evaluate the applicability and efficacy of stereology and planimetry in orbital volume measurements using magnetic resonance imaging (MRI).

Materials And Methods: Prospective imaging study using MRI. Sheep craniums and human subjects were evaluated. Water-filling measurements were performed in animal skulls, as the standard validation technique. Planimetry and stereology techniques were used in each dataset. Intraobserver and interobserver reliability testing were applied.

Results: In stereology customization, 1/6 systematic sampling scheme was determined as optimal with acceptable coefficient of error (3.09%) and low measurement time (1.2 min). In sheep craniums, the mean volume measured by water displacement, planimetry, and stereology was 17.81 ± 0.59 cm, 18.53 ± 0.24 cm, and 19.19 ± 0.17 cm, respectively. Planimetric and stereological methods were highly correlated ( = 0.94; ≈ 0.001). The mean difference of the orbital volume using planimetry and stereology was 0.316 ± 0.168 cm. In human subjects, using stereology, the mean orbital volume was found to be 19.62 ± 0.2 cm with a CE of 3.91 ± 0.15%.

Conclusions: The optimized stereological method was found superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/6 was successfully applied in human subjects and showed strong correlation with manual planimetry. However, optimized stereological method tended to overestimate the orbital volume by about 1 cc, a considerable limitation to be taken in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/njms.NJMS_9_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518488PMC
June 2020

Primary open angle glaucoma genetics: The common variants and their clinical associations (Review).

Mol Med Rep 2020 Aug 9;22(2):1103-1110. Epub 2020 Jun 9.

Department of Ophthalmology, University Hospital of Heraklion, 71110 Heraklion, Greece.

Glaucoma is a group of progressive optic neuropathies that have in common characteristic optic nerve head changes, loss of retinal ganglion cells and visual field defects. Among the large family of glaucomas, primary open‑angle glaucoma (POAG) is the most common type, a complex and heterogeneous disorder with environmental and genetic factors contributing to its pathogenesis. Approximately 5% of POAG is currently attributed to single‑gene or Mendelian forms of glaucoma. Genetic linkage analysis and genome‑wide association studies have identified various genomic loci, paving the path to understanding the pathogenesis of this enigmatic, blinding disease. In this review we summarize the most common variants reported thus far and their possible clinical correlations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2020.11215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339808PMC
August 2020

Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

Phys Med 2020 May 8;73:1-7. Epub 2020 Apr 8.

University of Crete, Medical School, Department of Medical Physics, 71003 Heraklion, Crete, Greece.

Purpose: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement.

Methods: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods.

Results: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation.

Conclusions: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmp.2020.03.020DOI Listing
May 2020

PET/CT and PET/MRI in ophthalmic oncology (Review).

Int J Oncol 2020 Feb 3;56(2):417-429. Epub 2020 Jan 3.

Department of Radiology, Medical School, University of Crete, 71003 Heraklion, Greece.

Orbital and ocular anatomy is quite complex, consisting of several tissues, which can give rise to both benign and malignant tumors, while several primary neoplasms can metastasize to the orbital and ocular space. Early detection, accurate staging and re‑staging, efficient monitoring of treatment response, non‑invasive differentiation between benign and malignant lesions, and accurate planning of external radiation treatment, are of utmost importance for the optimal and individualized management of ophthalmic oncology patients. Addressing these challenges requires the employment of several diagnostic imaging techniques, such as high‑definition digital fundus photography, ultrasound imaging, optical coherence tomography, optical coherence tomography (OCT)‑angiography, computed tomography (CT) and magnetic resonance imaging (MRI). In recent years, technological advances have enabled the development of hybrid positron emission tomography (PET)/CT and PET/MRI systems, setting new standards in cancer diagnosis and treatment. The capability of simultaneously targeting several cancer‑related biochemical procedures using positron emitting‑radiopharmaceuticals, while morphologically characterizing lesions by CT or MRI, together with the intrinsic quantitative capabilities of PET‑imaging, provide incremental diagnostic information, enabling accurate, highly efficient and personalized treatment strategies. Aim of the current review is to discuss the current applications of hybrid PET/CT and PET/MRI imaging in the management of patients presenting with the most commonly encountered orbital and ocular tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2020.4955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959466PMC
February 2020

Preliminary results of a semi-automated platform for pixel-based quantification of choroidal naevus progression.

Can J Ophthalmol 2019 10 17;54(5):601-605. Epub 2019 Jun 17.

Eye Clinic of the University General Hospital of Heraklion, Crete, Greece.

Objective: To evaluate a novel method for choroidal naevus progression monitoring using semiautomated software for pixel-based quantification.

Methods: Retrospective analysis of patients with choroidal melanotic lesions. In total, 87 eyes fulfilled our inclusion criteria. The progression of the choroidal lesions was evaluated by 2 masked and independent investigators. Total naevus area was measured on fundoscopic images using ImageJ semiautomated segmentation at baseline examination and 5 years later. The efficacy of our method was also tested on a separate patient group applying test-retest analysis.

Results: Pixel-based analysis for objective quantification, displayed high repeatability, and reliability. We identified 4 cases of naevus size progression using the described semiautomated technique, while only 2 cases of progression were reported by simple observation. The novel method performance displayed 50% increased sensitivity over simple observation and 100% specificity.

Conclusions: The presented method of displayed higher sensitivity and specificity compared to conventional observation and photograph qualification. Our results imply that the proposed methodology may be applicable as an accurate, easily employed diagnostic tool for the early detection of size progression in melanotic choroidal lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjo.2018.12.010DOI Listing
October 2019

Human papillomavirus infection and ocular surface disease (Review).

Int J Oncol 2019 May 19;54(5):1503-1510. Epub 2019 Mar 19.

Department of Ophthalmology, University Hospital of Heraklion, 71110 Heraklion, Greece.

Human papillomavirus (HPV) infection has been implicated as a primary cause of lesions in the anogenital region, skin, oropharynx and respiratory tract. Additionally, the role of HPV in the pathogenesis of ocular surface disease has also been extensively studied. Conjunctival papilloma development has been strongly associated with the HPV infection of certain subtypes. On the other hand, the role of HPV in conjunctival pterygium, conjunctival intraepithelial neoplasia (CIN) and ocular surface squamous neoplasia (OSSN) remains controversial. Genetic predisposition and environmental factor is important in HPV hosts as regards the pathogenesis of ocular surface disease. Several studies have indicate a synergic role of HPV with ultraviolet radiation in pterygium establishment. A higher recurrence risk rate and more aggressive disease of ophthalmic pterygium is observed in cases of HPV infection. The purpose of this review was to provide a systematic review of the literature and to assist in a better understanding of the role of HPV in ocular surface disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ijo.2019.4755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438422PMC
May 2019

Estimation of Morphological Characteristics in Asymmetrical Myopic Posterior Staphyloma using Optical Coherence Tomography.

Middle East Afr J Ophthalmol 2018 Jul-Dec;25(3-4):131-136

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Crete, Greece.

Purpose: Posterior staphyloma is an ocular complication associated with high myopia and reflects degenerative changes on the sclera. Its morphology is associated with chorioretinal atrophy and myopic maculopathy. The purpose of this study was to validate the efficacy of optical coherence tomography (OCT) in providing a simple estimation of the staphyloma pattern.

Materials And Methods: Observational case-series study of high myopic patients with posterior staphylomas. Patients were examined using the star scan pattern OCT in different radial planes. Three-dimensional (3D) magnetic resonance tomography was also performed to visualize the anatomical characteristics of the posterior pole. 3D-segmentation and curvature analysis were also performed.

Results: Eight patients were totally enrolled in this pilot study. Our study pool consisted of 2 wide macular staphylomas, 2 narrow macular staphylomas, and 4 barrel-shaped staphylomas. Our preliminary results revealed that patients displayed mirror-image distortion in the steeper staphyloma axis. In the barrel-shaped subtype, no image distortion was displayed in any plane.

Conclusion: We estimated the axis of the smaller base curvature by noting the distortion pattern in the different radial axis. The recognition of pathologic axial myopia is important since there is a risk of permanent vision loss from vision to threatening sequelae.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/meajo.MEAJO_45_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348944PMC
April 2019

Normal-tension glaucoma: Pathogenesis and genetics.

Exp Ther Med 2019 Jan 26;17(1):563-574. Epub 2018 Nov 26.

Department of Ophthalmology, University Hospital of Heraklion, 71110 Heraklion, Greece.

Normal-tension glaucoma (NTG) is a multifactorial optic neuropathy which, similar to open-angle glaucomas, is characterized by progressive retinal ganglion cell death and glaucomatous visual field loss. The major distinction of NTG from open-angle glaucomas is that the intraocular pressure (IOP) does not exceed the normal range. Missing the major risk factor and target of therapy, the elevated IOP, NTG poses a clinical challenge. Several insightful reviews have been published on the pathophysiology of NTG describing the possible underlying mechanisms. The current literature available also suggests that a significant percentage of patients with NTG (as high as 21%) have a family history of glaucoma, indicating a genetic predisposition to the disease. These facts strengthen the indication that NTG remains an enigmatic process. The aim of this review was to summarize the vascular, mechanical and genetic components considered to be responsible for NTG development and to discuss the mechanisms through which they are involved in the pathogenesis of NTG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2018.7011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307418PMC
January 2019

Surface-Coil MRI for Small Peripheral Choroidal Melanoma: Imaging in a Rabbit Eye Model.

Ocul Oncol Pathol 2018 Nov 13;4(6):364-369. Epub 2018 Jun 13.

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Greece.

Introduction: Imaging of small peripheral choroidal melanomas remains challenging in clinical and experimental settings, requiring wide-field ophthalmoscopy modalities. In this study, we applied surface-coil MRI to assess imaging feasibility for small peripherally located choroidal melanoma in a rabbit eye model.

Methods: A female albino rabbit with a body weight of 2.8 kg was immunosuppressed with intramuscular cyclosporine 15 mg/kg daily for 3 days prior to inoculation of 14 million 92.1 line melanoma cells into the peripheral suprachoroidal space of the right eye. The experimental animal continued to receive the same dosage of cyclosporine daily for 26 days postinoculation until the day of sacrifice. On that interval, it underwent surface-coil MRI scanning using various protocols and models subsequently sacrificed to allow histological evaluation. A comparative examination of various MRI sequences for optimal lesion imaging was performed, based on semiquantitative criteria.

Results: Imaging quality and superimposed artifacts varied across different sequences and the optimal tumor delineation from adjacent tissues was achieved in T1-weighted sequences.

Conclusions: MRI of small peripheral choroidal melanomas is feasible in a rabbit model using surface coils, particularly in T1-weighted sequences. Findings may be used as a basis for further development of this technique for experimental and clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000486789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288665PMC
November 2018

Diurnal and 24-h Intraocular Pressures in Glaucoma: Monitoring Strategies and Impact on Prognosis and Treatment.

Adv Ther 2018 11 20;35(11):1775-1804. Epub 2018 Oct 20.

Department of Vision Sciences, Glasgow Caledonian University, Glasgow, UK.

The present review casts a critical eye on intraocular pressure (IOP) monitoring and its value in current and future glaucoma care. Crucially, IOP is not fixed, but varies considerably during the 24-h cycle and between one visit and another. Consequently, a single IOP measurement during so-called office hours is insufficient to characterize the real IOP pathology of a patient with glaucoma. To date IOP remains the principal and only modifiable risk factor for the development and progression of glaucoma. Only by evaluating IOP characteristics (mean, peak and fluctuation of IOP) at diagnosis and after IOP-lowering interventions can we appreciate the true efficacy of therapy. Unfortunately, a major limiting factor in glaucoma management is lack of robust IOP data collection. Treatment decisions, advancement of therapy and even surgery are often reached on the basis of limited IOP evidence. Clearly, there is much room to enhance our decision-making and to develop new algorithms for everyday practice. The precise way in which daytime IOP readings can be used as predictors of night-time or 24-h IOP characteristics remains to be determined. In practice it is important to identify those at-risk glaucoma patients for whom a complete 24-h curve is necessary and to distinguish them from those for whom a daytime curve consisting of three IOP measurements (at 10:00, 14:00 and 18:00) would suffice. By employing a staged approach in determining the amount of IOP evidence needed and the rigour required for our monitoring approach for the individual patient, our decisions will be based on more comprehensive data, while at the same time this will optimize use of resources. The patient's clinical picture should be the main factor that determines which method of IOP monitoring is most appropriate. A diurnal or ideally a 24-h IOP curve will positively impact the management of glaucoma patients who show functional/anatomical progression, despite an apparently acceptable IOP in the clinic. The potential impact of nocturnal IOP elevation remains poorly investigated. The ideal solution in the future is the development of non-invasive methods for obtaining continuous, Goldmann equivalent IOP data on all patients prior to key treatment decisions. Moreover, an important area of future research is to establish the precise relationship between 24-h IOP characteristics and glaucoma progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-018-0812-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223998PMC
November 2018

Ex vivo orbital volumetry using stereology and CT imaging: A comparison with manual planimetry.

Eur Radiol 2019 Mar 22;29(3):1365-1374. Epub 2018 Aug 22.

Department of Ophthalmology, University Hospital of Heraklion, 71110, Stavrakia, Heraklion, Crete, Greece.

Objectives: To evaluate the applicability of stereology and planimetry in orbital volume measurements using computed tomography (CT) and to compare the results between the two measurements.

Methods: Experimental study using sheep craniums for CT imaging. Water filling measurements were performed, as the validation technique. Quantification techniques were also evaluated in five human subjects. To examine the proportion of agreement among measurements, we tested intra- and inter-observer agreement.

Results: For stereology customization, a 1/8 systematic sampling scheme was considered as optimal; this resulted in a low coefficient of error (2.59 %) and low measurement time (1.9 mins). In sheep craniums, mean volume measured by water displacement, planimetry and stereology was 17.81 ± 0.59 cm, 17.87 ± 0.68 cm and 17.54 ± 0.49 cm, respectively. Total volumes, obtained by stereology, were highly correlated with the water-filling method (r=0.893; p = 0.001) and a paired t-test showed significant difference between methods (t=3.047; p = 0.014). Planimetry results displayed a high correlation with the water-filling method (r=0.957; p ≈ 0.001) but no statistically significant difference was found (p = 0.154). Mean difference using planimetry and stereology was 0.332 ± 0.322 cm. In human subjects, using stereology, the estimated volume ranged between 18.57 cm and 19.27 cm, and the mean orbital volume was 19.05 ± 0.50 cm with CE=3.75 ± 0.16 %. Mean measure time was 2.1 ± 0.1 mins.

Conclusions: Stereological measurements were superior to manual planimetry in terms of user effort and time spent. Stereology sampling of 1/8 was successfully applied in human subjects and yielded a strong correlation with manual planimetry.

Key Points: • Stereology can be applied to measure the orbital volume using computed tomography. • Stereological measurements display high correlation with gold standard planimetry and combine low coefficient of error (2.59%) with low measurement time (1.9 min). • Stereology is superior in terms of user effort and time spent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-018-5691-9DOI Listing
March 2019

Long-term Follow-up of Patients receiving Intraocular Pressure-lowering Medications as Cataract Surgery Candidates: A Case-control Study.

J Curr Glaucoma Pract 2017 Sep-Dec;11(3):107-112. Epub 2017 Oct 27.

Associate Professor, Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Aim: In this study, we reviewed demographics and biometric characteristics among patients receiving chronic β-blockers and prostaglandins (PGs) for primary open-angle glaucoma. We compared the age at the time of cataract surgery in different patient groups and in a control group which was not under any medication.

Materials And Methods: Retrospective chart review of glau-comatous patients who underwent cataract extraction at the Department of Ophthalmology of the University Hospital of Heraklion, Crete, Greece, between January 1998 and December 2016 was done. Age at cataract surgery, axial length (AL), and preoperative and postoperative best-corrected visual acuities (BCVAs) were recorded. A cohort of patients without glaucoma who were operated for cataract extraction was also evaluated.

Results: In all, 320 patients were reviewed. There were significant results in mean age difference between the beta-antagonist and the PG group [3.05 years, 95% confidence interval (CI) 1.54-4.57] and between the beta-antagonist group with the patients receiving a combined therapy (3.02 years, 95% CI 1.14-4.91). No significant difference was found between the PG and the combination group. All the three treated groups had a significant lower mean age than the control group at the time of cataract surgery.

Conclusion: Based on our study, we concluded that there might be a possible association between chronic treatment with beta-antagonist agents and earlier cataract surgical time in the treated eye.

Clinical Significance: Intraocular pressure control is often usually achieved using ophthalmic agents. Their topical and systemic effects should be monitored precisely. Earlier cataract formation might be an important side effect which the physician has to keep in mind before choosing the suitable medication. Bontzos G, Agiorgiotakis M, Detorakis ET. Long-term Follow-up of Patients receiving Intraocular Pressure-lowering Medications as Cataract Surgery Candidates: A Case-control Study. J Curr Glaucoma Pract 2017;11(3):107-112.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5005/jp-journals-10028-1234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684242PMC
October 2017

Animal Models of Uveal Melanoma for Localized Interventions.

Crit Rev Oncog 2017 ;22(3-4):187-194

Department of Ophthalmology, University Hospital of Heraklion, Crete, Greece.

Uveal melanoma is the most common primary intraocular malignancy in adults, carrying a significant risk for death from metastatic disease. Treatment efforts aim toward local tumor control and early detection and management of metastases. Animal models are a valuable tool in the study of the molecular, genetic, and cellular events associated with the development of uveal melanoma and the evaluation of the therapeutic potential for various treatment methods. So far, several spontaneous, transgenetic, or induced animal models have been used, each presenting distinct advantages and disadvantages. This review article systematically presents an analysis of these animal models aimed at localized interventions; We aim to assist researchers with the selection of the optimal animal model based on their particular research targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1615/CritRevOncog.2018024510DOI Listing
April 2019

EX-PRESS® Implant Position and Function: Comparative Evaluation with Ultrasound Biomicroscopy and Optical Coherence Tomography.

Middle East Afr J Ophthalmol 2016 Jan-Mar;23(1):110-4

Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Greece; Department of Refractive Surgery, Institute of Vision and Optics, Crete, Greece.

Purpose: This study evaluated the feasibility of anterior segment optical coherence tomography (OCT) and ultrasound biomicroscopy (UBM) for the imaging of EX-PRESS(®) implant.

Materials And Methods: This nonrandomized comparative case series was performed at the Department of Ophthalmology of the University Hospital of Heraklion, Crete, Greece. The Ellex Eye Cubed (40 MHz) UBM and the Zeiss Visante OCT systems were used. The filtering bleb morphology (BL), aqueous outflow (AS), and tube position (TB) were evaluated by two independent observers using a quality scale of 1 (worst) to 4 (best). Data were also collected on corneal and iris clearance from the tip of the tube (CC and IC, respectively). Data from both the devices were statistically analyzed. P < 0.05 was considered as statistically significant.

Results: Ten eyes of 10 patients (6 males) with EX-PRESS(®) implant were examined. TB, AS, and BL scores using UBM were 2.40 ± 0.39, 3.45 ± 0.72, and 2.45 ± 0.64, respectively. TB, AS, and BL scores for OCT were 3.35 ± 0.41, 1.55 ± 0.43, and 2.55 ± 0.55, respectively. AS was significantly higher with UBM whereas the opposite was true for TB. Differences in BL between OCT and UBM were not statistically significant (P > 0.05).

Conclusion: Imaging of the EX-PRESS(®) implant is feasible with both UBM and OCT. Both modalities allow visualization of the position of the implant tube in relation to the iris or cornea and delineate the internal structure of the filtering bleb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0974-9233.171774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759887PMC
August 2016

Pterygium concomitant with other ocular surface lesions: Clinical implications and pathogenetic links.

Exp Ther Med 2016 Jan 13;11(1):69-72. Epub 2015 Nov 13.

Laboratory of Clinical Virology, University of Crete, Medical School, Heraklion 71409, Greece.

In the present study, we aimed to evaluate the co-existence of ophthalmic pterygium with other ocular surface lesions in a cohort of patients from the Cretan population. This is a retrospective evaluation of all pterygia in patients examined and treated at the Department of Ophthalmology of the University Hospital of Heraklion, Greece during an 8-year period (from June 2006 to June 2014). A total of 158 cases was examined. Ocular surface images and medical history were evaluated in order to detect concomitant ocular surface pathological conditions. Concomitant lesions included conjunctival nevi (5 cases, 3.16%), iris nevi (4 cases, 2.53%), conjunctival papillomas (8 cases, 5.06%), conjunctival intraepithelial neoplasia (CIN; 4 cases, 2.53%) and 6 cases of hypertophy of the plica semilunaris (3.79%). Of note, pterygium was overlying the iris which was occupied by the iris nevus in 2 out of the 4 cases of iris nevus. Overall, our data indicate that ophthalmic pterygium may often co-exist with other clinically significant ocular surface lesions. The association of ophthalmic pterygium with conjunctival papillomas or CIN stresses the potential involvement of human papilloma virus in the pathogenesis of ophthalmic pterygium, whereas the topographical association of pterygium with iris nevus may offer support to the transcameral light pathway pathogenetic mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2015.2865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4726895PMC
January 2016

Pupil response to tropicamide following corneal crosslinking.

Eur J Ophthalmol 2016 Aug 28;26(5):394-7. Epub 2016 Jan 28.

Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, Crete - Greece.

Purpose: To evaluate the effect of corneal crosslinking (CXL) with ultraviolet A (UVA) irradiation on pupil response to tropicamide 0.5% instillation.

Methods: This prospective interventional study enrolled 17 patients (19 eyes) with progressive keratoconus who underwent CXL with UVA irradiation. Central corneal thickness (CCT) was evaluated with the use of anterior segment optical coherence tomography (Visante OCT 3.0). Pupil diameter was measured with the use of Colvard infrared pupillometer before the instillation of tropicamide 0.5% and after the instillation of tropicamide every 5 minutes for total duration of 30 minutes. Corneal epithelial integrity was examined with the use of fluorescein dye staining. Measurements were performed 1 day preoperatively and 1 month postoperatively, with emphasis on simulating the same light conditions regarding the pupil measurements.

Results: No intraoperative or postoperative complications were observed in any of the patients. Mean CCT decreased significantly (p<0.001) 1 month postoperatively. Mean postoperative pupil size did not change significantly at any time point compared to the mean preoperative measurements.

Conclusions: The CXL procedure seems not to impair effectiveness of topical drugs, using pupil size measurements after tropicamide 0.5% instillation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/ejo.5000758DOI Listing
August 2016

Non-Invasive Ocular Rigidity Measurement: A Differential Tonometry Approach.

Acta Medica (Hradec Kralove) 2015 ;58(3):92-7

Department of Ophthalmology, University Hospital of Heraklion, Greece.

Purpose: Taking into account the fact that Goldmann applanation tonometry (GAT) geometrically deforms the corneal apex and displaces volume from the anterior segment whereas Dynamic Contour Tonometry (DCT) does not, we aimed at developing an algorithm for the calculation of ocular rigidity (OR) based on the differences in pressure and volume between deformed and non-deformed status according to the general Friedenwald principle of differential tonometry.

Methods: To avoid deviations of GAT IOP from true IOP in eyes with corneas different from the "calibration cornea" we applied the previously described Orssengo-Pye algorithm to calculate an error coefficient "C/B". To test the feasibility of the proposed model, we calculated the OR coefficient (r) in 17 cataract surgery candidates (9 males and 8 females).

Results: The calculated r according to our model (mean ± SD, range) was 0.0174 ± 0.010 (0.0123-0.022) mmHg/μL. A negative statistically significant correlation between axial length and r was detected whereas correlations between r and other biometric parameters examined were statistically not significant.

Conclusions: The proposed method may prove a valid non-invasive tool for the measurement method of OR, which could help in introducing OR in the decision-making of the routine clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14712/18059694.2015.99DOI Listing
March 2016

Effect of the Regenerative Agent Poly(Carboxymethylglucose Sulfate) on Corneal Wound Healing After Corneal Cross-Linking for Keratoconus.

Cornea 2015 Aug;34(8):928-31

*Faculty of Medicine, Department of Ophthalmology, Vardinoyiannion Eye Institute of Crete (VEIC), University of Crete, Heraklion, Greece; †Department of Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL; and ‡Bâtiment 4 bis, Department of Ophthalmology, University Hospital, Brest, France.

Purpose: To evaluate the effect of a regenerative agent (RGTA) [Cacicol20-poly(carboxymethyl glucose sulfate); OTR3, Paris, France] on corneal reepithelialization and pain after corneal cross-linking (CXL) for keratoconus.

Methods: In this prospective comparative (contralateral) clinical study, patients with bilateral progressive keratoconus underwent CXL treatment. The corneal epithelium during CXL was removed using transepithelial phototherapeutic keratectomy (Cretan protocol). One eye of each patient was randomly instilled with an RGTA (Cacicol20) once a day (study group), whereas the fellow eye was instilled with artificial tears (control group). Patients were examined daily until complete reepithelialization. Postoperative examinations included slit-lamp biomicroscopy to assess the epithelial defect size and subjective evaluation of pain.

Results: The study enrolled 18 patients (36 eyes). The mean epithelial defect size for study and control groups was 19.6 ± 4.2 mm versus 21.5 ± 2.8 mm, respectively, at day 1 (P = 0.019) and 6.4 ± 3.4 mm versus 7.9 ± 4.3 mm, respectively, at day 2 (P = 0.014). At day 3 postoperatively, 61.1% of study eyes were fully reepithelialized, compared with 11.1% of control eyes (P = 0.002).

Conclusions: RGTA (Cacicol20) instillation seems to result in faster corneal reepithelialization after CXL in this study. However, there was no significant effect in subjective pain/discomfort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ICO.0000000000000484DOI Listing
August 2015

INTRA-SCLERAL PARATHALAMUS IMPLANT: EFFICACY AND SAFETY IN RABBIT EYES.

Acta Medica (Hradec Kralove) 2014 ;57(4):151-6

Institute of Vision & Optics, University of Crete, Greece.

Purpose: A variety of anti-glaucomatous shunt designs have been proposed so far. This study evaluates the feasibility of a novel shunt design, the intra-scleral parathalamus implant (IPI), in a rabbit eye model.

Methods: Ten healthy albino rabbits were included. Measurements of the IOP, using TonoPenXL, as well as ocular rigidity (OR) and aqueous outflow facility (AO), using a previously described methodology, were performed in both eyes of each animal. Subsequently, the IPI was implanted at the left eye of all animals whereas the right eye served as control. Measurements of IOP were repeated at weekly intervals for 2 months postoperatively whereas measurements of OR and AO were repeated at the 1st and 2nd postoperative week.

Results: The IOP decreased significantly whereas the AO increased significantly postoperatively at the operated eyes. A significant postoperative decrease in OR was also recorded at the operated eyes. Respective differences at the fellow eyes were statistically not significant. Two animals developed postoperative complications and were excluded from follow-up.

Conclusions: Results imply that the implantation of the IPI is feasible in rabbit eyes with significant favorable effects on the IOP, AO and OR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14712/18059694.2015.80DOI Listing
August 2015

Corneal topography with upper eyelid platinum chain implantation using the pretarsal fixation technique.

Med Hypothesis Discov Innov Ophthalmol 2015 ;4(1):9-13

2nd Otolaryngology Department, University of Athens, Athens, Greece.

Purpose: To determine the effect of upper eyelid platinum chain implantation, with the pretarsal fixation technique, on corneal astigmatism.

Methods: This is a prospective, cohort study. Fifteen eyes of 15 patients underwent upper eyelid platinum chain implantation, with the pretarsal fixation technique, for facial nerve palsy. Information recorded included patient demographics, etiology for facial palsy, weight of the implant, time from onset of paresis to upper eyelid platinum chain implantation, associated surgical procedures, and preoperative and postoperative corneal topography measurements.

Results: Of the 15 patients studied, 10 were male and five were female. The mean age was 55.9 ± 13.8 years (range, 33-87 years). The most common etiology for facial palsy was acoustic neuroma. The weight of the implant ranged from 0.6 to 1.6gr (median 1.2gr). The time from onset of paresis to upper eyelid platinum chain implantation varied from 1 week to 3 months (median 1 month). Four patients had an associated procedure to correct the effect of paralytic ectropion. There was no statistically significant difference in with the rule astigmatism before and after platinum chain implantation.

Conclusions: Upper eyelid platinum chain implantation, with the pretarsal fixation technique, does not appear to cause significant change in corneal astigmatism. This is contrary to data for pretarsal gold weight implantation, which does induce significant with the rule astigmatism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389292PMC
April 2015

Corneal Collagen Cross-Linking Mushroom Shape Demarcation Line Profile After Limited Bowman's Membrane Removal by Phototherapeutic Keratectomy.

Open Ophthalmol J 2015 23;9:17-9. Epub 2015 Feb 23.

Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.

Purpose: To report a corneal collagen cross-linking (CXL) mushroom shape demarcation line profile after limited Bowman's membrane removal by phototherapeutic keratectomy (PTK).

Methods: Case report.

Results: A twenty-one-year-old male with progressive keratoconus underwent mechanical epithelial debridement (at an 8.5 mm zone) followed by PTK (at a 5.0 mm zone and in a 10 μm depth) and CXL. No intra- or early postoperative complications were found. Evaluation of the corneal stromal demarcation line depth using anterior segment optical coherence tomography revealed a mushroom shape profile.

Conclusion: It seems that removal of the Bowman's layer leads to greater depth of the corneal stromal demarcation line.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1874364101509010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348732PMC
March 2015

Transient anisocoria after corneal collagen cross-linking.

Case Rep Ophthalmol Med 2014 8;2014:487860. Epub 2014 Sep 8.

Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.

Purpose. To report a case with transient anisocoria after corneal collagen cross-linking (CXL). Methods. Case report. Results. A 24-year-old male underwent corneal collagen cross-linking (CXL) in his right eye for keratoconus. At the end of the procedure, the pupil of the treated eye was irregular and dilated, while the pupil of the fellow eye was round, regular, and reactive (anisocoria). The following day, pupils were round, regular, and reactive in both eyes. Conclusion. Anisocoria may be a transient and innocuous complication after CXL. A possible cause for this complication might be the anesthetic drops used before and during the surgical procedure or/and the ultraviolet A irradiation during the treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/487860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171036PMC
October 2014