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Colin Clement,1– 4 Frank Howes,5 Alexandros Ioannidis,6 Michael Shiu,7 David Manning,8 Jed A Lusthaus,3,4,9 Simon E Skalicky,10 Todd W Goodwin11 1Eye Associates, Sydney, NSW, Australia; 2Fairfield Eye Surgery, Fairfield, NSW, Australia; 3Glaucoma Unit, Sydney Eye Hospital, Sydney, NSW, Australia; 4Discipline of Ophthalmology, The University of Sydney, Sydney, NSW, Australia; 5Eye & Laser Centre, Gold Coast, QLD, Australia; 6Vision Eye Institute, Melbourne, VIC, Australia; 7Laser Sight Centre, Melbourne, VIC, Australia; 8Hunter Cataract & Eye Centre, Charlestown, NSW, Australia; 9Eyehaus, Sydney, NSW, Australia; 10Department of Surgery Ophthalmology, University of Melbourne, Melbourne, VIC, Australia; 11NQ Eye Specialists, Currajong, QLD, AustraliaCorrespondence: Colin Clement, Eye Associates, Level 4, 187 Macquarie Street, Sydney, NSW, 2000, Australia, Tel +612 9247 9972, Email colinandkylie@me.comPurpose: To evaluate 3-year safety and efficacy of two second-generation trabecular micro-bypass stents. (iStent inject®) with phacoemulsification.Materials and Methods: This multicenter retrospective study of iStent inject implantation with phacoemulsification included data from eight surgeons across Australia. Eyes with cataract and mild to advanced glaucoma [predominantly primary open-angle (POAG), primary angle closure (PAC), or normal-tension (NTG) glaucoma] or ocular hypertension (OHT) were included. Study assessments included intraocular pressure (IOP); number of ocular hypotensive medications; proportions of eyes with 0, 1, 2, or ≥ 3 IOP-lowering medications; IOP ≤ 15 mmHg or ≤ 18 mmHg; visual fields (VF); retinal nerve fiber layer thickness (RNFL); central corneal thickness (CCT); intraoperative complications; adverse events; and secondary surgeries.Results: A total of 273 eyes underwent surgery and had 36-month follow-up. At 36 months versus preoperative, mean IOP decreased by 15.5% (16.4± 4.6 mmHg to 13.9± 3.5 mmHg; p< 0.001), and 70.3% of eyes achieved IOP of ≤ 15 mmHg (versus 49.1% preoperatively; p< 0.001). The mean medication burden decreased by 68.5% (from 1.51± 1.17 to 0.48± 0.89 medications; p< 0.001); 71.4% of eyes were medication-free (versus 21.6% preoperatively; p< 0.001), while 6.2% of eyes were on ≥ 3 medications (versus 22.3% preoperatively; p< 0.001); 96.3% of eyes maintained or reduced medications vs preoperative. Significant IOP and medication reductions occurred across glaucoma subtypes (POAG, PAC, NTG, OHT): 13– 22% for IOP (p< 0.05 for all) and 42– 94% for medication (p< 0.05 for all). Favorable safety included few adverse events; stable VF, RNFL, and CCT; and filtering surgery in only 8 eyes (2.9%) over 3 years.Conclusion: In this multicenter cohort from 8 surgeons across Australia, significant IOP and medication reductions were sustained through 3 years after iStent inject implantation with phacoemulsification. Results were favorable across different glaucoma subtypes (including POAG, PAC, NTG, OHT), severities, and surgeons, thereby underscoring the real-world relevance and efficacy of iStent inject implantation for glaucoma treatment.Keywords: microinvasive glaucoma surgery, MIGS, glaucoma, iStent inject, intraocular pressure, second generation, multicenter

Howard JM Warren,1 Gabriela Ioachim,1 Jocelyn M Powers,1 Patrick W Stroman1– 3 1Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada; 2Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada; 3Department of Physics, Queen’s University, Kingston, Ontario, CanadaCorrespondence: Patrick W StromanQueen’s University, Centre for Neuroscience Studies, 2nd Floor, Botterell Hall, 18 Stuart Street, Kingston, K7L 3N6, Ontario, CanadaTel +1-613-533-3245Email stromanp@queensu.caPurpose: The purpose of this study was to investigate the utility of data-driven analyses of functional magnetic resonance imaging (fMRI) data, by means of structural equation modeling, for the investigation of pain processing in fibromyalgia (FM).Patients and Methods: Datasets from two separate pain fMRI studies involving healthy controls (HC) and participants with FM were re-analyzed using both a conventional model-driven approach and a data-driven approach, and the results from these analyses were compared. The first dataset contained 15 women with FM and 15 women as healthy controls. The second dataset contained 15 women with FM and 11 women as healthy controls.Results: Consistent with previous studies, the model-driven analyses did not identify differences in pain processing between the HC and FM study groups in both datasets. On the other hand, the data-driven analyses identified significant group differences in both datasets.Conclusion: Data-driven analyses can enhance our understanding of pain processing in healthy controls and in clinical populations by identifying activity associated with pain processing specific to the clinical groups that conventional model-driven analyses may miss.Keywords: human, brain, pain, neuroimaging, fibromyalgia, chronic pain

Eleftheriadis N, Papaloukas C, Eleftheriadis D, Hatzitolios A, Ioannidou-Marathiotou I, Pistevou-Gompaki K. Int J Gen Med. 2009;2:63–66. The Editor and Publisher of the International Journal of General Medicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images from Figure 1A, 1B, 1C, and 1D with the same images from Figure 3A, 3B, 3D, and 3E, respectively, from the article Ioannidou-Marathiotou et al, 2010 ‘Long term chemoradiotherapy-related dental and skeletal complications in a young female with nasopharyngeal carcinoma’ (https://doi.org/10.2147/IJGM.S10825). Both articles share common authors but describe different case reports. The authors did not respond to our queries and no explanation for the alleged image duplication was provided. The Editor requested to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Ioannidou-Marathiotou I, Pistevou-Gompaki K, Eleftheriadis N, Papaloukas C. Int J Gen Med. 2010;3:187–196. The Editor and Publisher of the International Journal of General Medicine wish to retract the published article. Concerns were raised regarding the alleged duplication of images from Figure 3A, B, D, and E with the same images from Figure 1A–D, respectively, from the article Eleftheriadis et al, 2009 ‘Long-term radiotherapy related complications in children with head and neck cancer: Another era for pediatric oncologic pathology’ (https://doi.org/10.2147/IJGM.S4878). Both articles share common authors but describe different case reports. The authors did not respond to our queries and no explanation for the alleged image duplication was provided. The Editor requested to retract the article and the authors were notified of this. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Adam Ioannou,1 Irene Tsappa,2 Sofia Metaxa,3 Constantinos G Missouris2,3 1Cardiology Department, Royal Free NHS Foundation Trust, London, UK; 2Cardiology Department, Medical School, University of Cyprus, Nicosia, Cyprus; 3Cardiology Department, Frimley Health NHS Foundation Trust, London, UK Abstract: Atrial fibrillation is the most common arrhythmia worldwide, and carries a significantly increased risk of thromboembolic stroke. Initially, vitamin K antagonists were used as stroke prophylaxis; but more recently, a group of drugs known as novel oral anticoagulants have been developed. Apixaban belongs to this group of drugs, and is a factor Xa inhibitor that has emerged as a popular pharmacological agent worldwide. In this review, we will provide an overview of the pivotal trials in the development of apixaban, while also critically evaluating the new emerging real-world data, and discussing the effectiveness, safety, economic viability and future prospects of apixaban and how it impacts on patient outcomes in those with non-valvular atrial fibrillation. Keywords: apixaban, atrial fibrillation, warfarin, stroke, bleeding

Christina Fotiadou, Efstratios Vakirlis, Dimitrios Ioannides First Department of Dermatology-Venereology, Aristotle University Medical School, Thessaloniki, Greece Abstract: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory skin disease that affects the hair follicles of the aprocrine gland-bearing anatomical areas of the body. It is characterized by deep painful nodules and abscesses that rupture and contribute to the formation of sinus tracks and scarring. The management of HS is based on the assessment of disease severity and a combination of medical and surgical treatment according to the European Guidelines. Adalimumab, a recombinant, fully humanized, anti-tumor necrosis factor alpha (anti-TNF-α) monoclonal antibody, is the only officially approved treatment for the management of moderate-to-severe HS. Case reports, concerning 42 patients who received adalimumab for severe HS (with the standard dose regimen for psoriasis), reported a cumulative response rate of 58% (≥50% in 23 patients) with a relapse rate of 71% (10 out of 14 patients). The most recent and most well-powered phase III, randomized placebo-controlled trials for the evaluation of the efficacy and safety of adalimumab in treatment of moderate-to-severe HS (PIONEER studies I and II) showed that the Hidradenitis Suppurativa Clinical Response (HiSCR) rate at week 12 was significantly higher for patients randomized to adalimumab compared to placebo. Adverse events were comparable to placebo. In conclusion, adalimumab, to date, holds the most robust data regarding treatment efficacy in HS. Larger, registry-based studies are needed to further establish the efficacy and safety profile of this anti-TNF-α agent in HS. Keywords: hidradenitis suppurativa, adalimumab, treatment

Chrysoula Pipili,1 Eirini Grapsa,1 Elli-Sophia Tripodaki,1 Sophia Ioannidou,2 Christos Manetos,1 Maria Parisi,1 Serafim Nanas1 1First Critical Care Department, 2Laboratory of Biochemistry, Evangelismos General Hospital, National and Kapodistrian University of Athens, Athens, Greece Background: Monitoring of the microcirculation may add additional information in terms of improving the adequacy of hemodialysis (HD) for patients. Withdrawal of liquid and complement activation during a HD session reduces the external pressure on the microcirculation and leads to an increased dilatation of the peripheral capillaries. The purposes of this study were to assess the effect of a single HD or hemodiafiltration session on the thenar microcirculation in patients with end-stage renal disease (ESRD) with or without diabetes, investigate the possible relationship between changes in the microcirculation and adequacy of dialysis (including Kt/V and parameters indicating secondary hyperparathyroidism), and compare microcirculation measurements obtained from patients with ESRD and those from healthy controls. Methods: This pilot prospective observational study including eleven patients with ESRD on maintenance HD (nine men of mean age 73±10.5 years, ten [91%] with hypertension), nine patients with ESRD on maintenance hemodiafiltration (six men of mean age 65.5±13.2 years, five [55.5%] with diabetes and four [44.5%] with hypertension), and eight healthy volunteers. Two paired microcirculation assessments were recorded for each HD patient before and after a dialysis session. Near infrared spectroscopy and the vascular occlusion test were used to assess the microcirculation, and blood work samples were collected before and after dialysis when the pump slowed down. Results: Patients with ESRD showed an increase in thenar cell metabolism at rest after a 4-hour HD session, and changes in cell metabolism correlated with the Kt/V of the session. Pre-dialysis tissue oxygen saturation over the 4-hour HD session correlated with pre-dialysis serum calcium and parathyroid hormones. Vascular reactivity was lower in ESRD patients receiving HD or hemodiafiltration than in healthy controls. Conclusion: Improvement in skeletal muscle microcirculation noted after a HD session was related to adequacy of dialysis. Evaluation of the microcirculation may provide additional information for management of patients on HD and identify novel targets for treatment. These preliminary findings need to be tested using a larger data set. Keywords: hemodiafiltration, near infrared spectroscopy, end stage renal disease, single-pool Kt/V

Georgia Barka,1 Georgios Tretiakov,1 Theodosios Theodosiou,2 Ioulia Ioannidou-Marathiotou31School of Dentistry, 2Biostatistics, Department of Informatics, School of Natural Sciences, 3Department of Orthodontics, School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, GreeceObjective: The purpose of the present study was to investigate the frequency of presence of third molar teeth and their distribution in each jaw and each side, according to sex, in a group of orthodontic patients with permanent dentition from northern Greece.Methods: The sample included panoramic radiographs from 220 patients with permanent dentition (mean age 13.62 ± 1.81). The Χ2 test was used to assess the relationships between the variables, and the Fisher's exact test was used in cases where the expected frequencies in each cell were

Ioannis Kallikazaros, Costas Tsioufis, Panagiotis Zambaras, Ioannis Skiadas, Marina Toutouza, Dimitrios Tousoulis, Christodoulos Stefanadis, Pavlos ToutouzasCardiology Department and University Cardiology Clinic, Hippokration Hospital of Athens, GreeceBackground: The cardioprotective role of hormonal replacement therapy remains in doubt, but interest is increasing in the vascular effects of estrogens especially in coronary circulation.Methods: Coronary blood flow (CBF) was measured in 24 postmenopausal women (age 55 ± 3 years), whose coronary arteries appeared angiographically normal, during incremental atrial pacing (AP) before and 20 minutes after intracoronary administration of either 75 ng/mL 17-β estradiol (treated group, n = 18) or 0.9% saline (controls, n = 6).Results: Before estrogen, no differences in the coronary vasomotor responses at AP between the two groups (p = NS) could be detected. After estrogen, in the treated group, at the peak of the second AP, the coronary artery diameter decreased by 0.17 mm (p < 0.005) while the CBF increased by 61 mL/min (p < 0.05). These changes differed significantly from thoseobserved at the peak of first AP (p < 0.001 for both cases). In contrast, in the control group no such changes were observed. The endothelin-1 (ET-1) levels in the coronary sinus were significantly reduced after estrogen infusion, which was negatively correlated with the degree of coronary artery constriction (r = −0.40, p = 0.03) and positively correlated with the increase in CBF (r = 0.54, p = 0.01).Conclusions: In postmenopausal women without coronary artery disease, the intracoronary estrogen infusion mediates a greater increase in CBF and is positively correlated with the reduction of the coronary sinus ET-1 levels at the peak of AP.Keywords: estrogens, coronary blood flow, endothelin-1, coronary interventions

Kari E Roberts, Ioana R PrestonPulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.Keywords: bosentan, endothelin receptor antagonists, pulmonary arterial hypertension

Genovefa D Kolovou1, Katherine Anagnostopoulou1, Nektarios D Pilatis1, Klelia D Salpea1, Ioannis S Hoursalas1, Ilias Petropoulos1, Helen I Bilianou2, Dennis V Cokkinos11Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece; 2Cardiology Department, Tzanio State Hospital, Piraeus, GreeceObjective: The aim of the present investigation was to evaluate the influence of serum triglycerides (TG) on other plasma lipids in patients to be treated for dyslipidemia.Methodology: Lipid profiles of a cohort of 801 patients (487 males and 314 females) aged 57 ± 9 years (mean ± SD) were evaluated. Patients were stratified according to their plasma lipid levels. They were divided into various groups on the basis of serum TG (≥ 150 or < 150 mg/dL) and high-density lipoprotein cholesterol (HDL-C) (≥ 40 or < 40 mg/dL).Results: Patients with TG ≥ 150 mg/dL had a higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dL, (p < 0.001). Patients with HDL-C < 40 mg/dL had a lower serum total cholesterol and higher TG compared with those with HDL-C ≥ 40 mg/dL (p = 0.011 and p < 0.0001, respectively). In all patients as well as in the subgroups, an inverse correlation between TG and HDL-C was found (r = –0.377, p < 0.001).Conclusions: Although, the metabolic pathway for TG and HDL-C is closely linked, an inverse correlation between TG and HDL-C levels seems to exist in the entire sampled population. This correlation also appears to persist in fasting patients with low levels of TG.Keywords: triglycerides, high-density lipoprotein cholesterol, dyslipidemia

Athanassios K Giarmoukakis,* Styliani V Blazaki,* Georgios C Bontzos, Argyro D Plaka, Konstantinos N Seliniotakis, Larissa D Ioannidi, Miltiadis K Tsilimbaris Department of Ophthalmology, University Hospital of Heraklion, Heraklion, Greece*These authors contributed equally to this workCorrespondence: Miltiadis K TsilimbarisUniversity Hospital of Heraklion, Heraklion 71003, Crete, GreeceTel +302810392351Fax +302810392730Email tsilimb@med.uoc.grPurpose: To assess the effect of twice-daily nepafenac ophthalmic suspension 0.3% on postoperative cystoid-macular-edema (CME).Patients and Methods: In this prospective, clinic-based, non-randomized case-series, 21 patients (21 eyes) were enrolled with either acute or chronic postoperative CME after cataract extraction. Patients were treated with twice-daily nepafenac 0.3% drops, and followed for at least a 4-month period. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT)-derived central retinal thickness (CRT) were measured.Results: From 21 patients, eight presented with acute postoperative CME and 13 with chronic CME. Mean follow-up was 4.82± 1.24 months. No adverse events were reported during the study. Baseline BCVA was 0.49± 0.36 logMAR and improved to 0.36± 0.42 logMAR at the last follow-up visit (P< 0.005). CRT decreased from 450.40± 90.74 μm at baseline to 354.60± 81.49 μm (P< 0.05), following treatment.Conclusion: Our outcomes strongly suggest that administrating nepafenac 0.3% drops on a twice-daily regimen could be a promising alternative for the management of postoperative CME. Additional studies are necessary to further validate our results.Keywords: nepafenac, postoperative macular edema, cataract operation, topical use, treatment

Colin Clement, 1– 4 Frank Howes, 5 Alexandros S Ioannidis, 6 Michael Shiu, 7 David Manning, 8 Jed Lusthaus, 3, 4, 9 Ridia Lim, 3, 10 Simon E Skalicky, 11 Todd Goodwin 12 1Eye Associates, Sydney, NSW, Australia; 2Fairfield Eye Surgery, Fairfield, NSW, Australia; 3Glaucoma Unit, Sydney Eye Hospital, Sydney, NSW, Australia; 4Discipline of Ophthalmology, The University of Sydney, Sydney, NSW, Australia; 5Eye & Laser Centre, Gold Coast, QLD, Australia; 6Vision Eye Institute, Melbourne, VIC, Australia; 7Laser Sight Centre, Melbourne, VIC, Australia; 8Hunter Cataract & Eye Centre, Charlestown, NSW, Australia; 9Eyehaus, Sydney, NSW, Australia; 10Hunter St. Eye Specialists, Parramatta, NSW, Australia; 11Department of Surgery Ophthalmology, University of Melbourne, Melbourne, VIC, Australia; 12NQ Eye Specialists, Currajong, QLD, AustraliaCorrespondence: Colin ClementEye Associates, Level 4, 187 Macquarie Street, Sydney, NSW 2000, AustraliaTel +612 9247 9972Email colinandkylie@me.comPurpose: This multicenter study evaluated 2-year effectiveness and safety following implantation of two second-generation trabecular micro-bypass stents (iStent inject®) with phacoemulsification.Materials and Methods: This was a retrospective study of iStent inject implantation with phacoemulsification by nine surgeons across Australia. Eyes had mild to advanced glaucoma (predominantly primary open-angle/POAG, appositional angle-closure/ACG, or normal-tension/NTG) or ocular hypertension (OHT), and cataract. Evaluations included intraocular pressure (IOP); medications; proportions of eyes with 0 or ≥ 2 medications, reduced/stable medications versus preoperative, and IOP ≤ 15 mmHg; visual acuity; cup-to-disc ratio (CDR); visual fields (VF); adverse events; and secondary surgery.Results: A total of 340 eyes underwent surgery and had 24-month follow-up data. At 24 months, mean IOP decreased by 16% from 16.4± 4.7 mmHg preoperatively to 13.7± 3.1 mmHg (p< 0.001), and 77% of eyes achieved IOP of ≤ 15 mmHg versus 49% preoperatively (p< 0.001). Mean number of medications decreased by 67% to 0.49± 0.95 versus 1.49± 1.20 preoperatively (p< 0.001), with 74% of eyes medication-free versus 25% preoperatively (p< 0.001), and 14% of eyes on ≥ 2 medications versus 46% preoperatively (p< 0.001). Medication burden was reduced or stable in 98% of eyes versus preoperative. Stratified analyses showed significant IOP and medication reductions across glaucoma subtypes (POAG, ACG, NTG, OHT): 13– 22% for IOP (p< 0.01 for all) and 62– 100% for medication (p< 0.001 for all). Favorable safety included few adverse events; stable CDR, VF, and visual acuity; and filtering surgery in only 8 eyes (2.4%) over 2 years.Conclusion: This 340-eye multicenter dataset provides robust evidence of the safety and efficacy of iStent inject implantation with phacoemulsification, with significant and sustained IOP and medication reductions through 2 years. Results were similarly favorable across glaucoma subtypes (including POAG, ACG, NTG, OHT) and were attained across various glaucoma severities, clinical sites, and surgeons, highlighting the real-world versatility and utility of this treatment modality.Keywords: microinvasive glaucoma surgery, MIGS, glaucoma, iStent inject, intraocular pressure, second-generation, multicenter

Alexandros S Ioannidis, 1, 2 Marc Töteberg-Harms, 3 Timothy Hamann, 3 Christopher Hodge 1, 4, 5 1Vision Eye Institute Blackburn South, Melbourne, VIC, Australia; 2Royal Melbourne Hospital, Melbourne, VIC, Australia; 3Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland; 4Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 5Graduate School of Health, University of Technology Sydney, Sydney, NSW, AustraliaCorrespondence: Alexandros S IoannidisVision Eye Institute Blackburn South, 156 Canterbury Road, Blackburn South, VIC 3130, AustraliaTel +61 3 9877 6288Fax +61 3 9894 2691Email alexioannidis.ai@gmail.comPurpose: Simultaneous cataract and glaucoma surgery has traditionally been challenging for the anterior segment surgeon. The introduction of minimally invasive glaucoma surgery (MIGS) in conjunction with cataract surgery appears safe and effective in lowering intraocular pressure. Although a significant visual impact leading from the combined procedure is unexpected, we aim to describe the refractive outcomes in a cohort of patients undergoing simultaneous cataract removal and iStent inject and discuss the potential implications of combined surgery in patients with co-existent glaucoma.Patients and Methods: This is a retrospective consecutive case series inclusive of patients undergoing combined femtosecond laser-assisted cataract surgery and the insertion of two trabecular micro-bypass stents (iStent inject). Visual acuity, refraction and astigmatic vector analysis were collated and analysed from the preoperative and 4 weeks postoperative visits.Results: One hundred and six eyes of 89 patients from 2 surgeons were included in the original cohort. The mean absolute difference from target refraction was 0.36 ± 0.25D. 73.9% of eyes were within ± 0.5D of the refractive target and 98.9% of eyes were within ± 1.00D. 73.8% of eyes had 0.5D or less residual refractive astigmatism following the procedure.Conclusion: We present a novel cohort of glaucoma patients undergoing combined trabecular micro-bypass stents (iStent inject) and cataract surgery achieving excellent refractive outcomes. The results of this study indicate that this second-generation device is refractively neutral.Keywords: glaucoma, cataract surgery, trabecular micro-bypass stents, astigmatism, intraocular lenses

Colin I Clement,1–4 Frank Howes,5 Alexandros S Ioannidis,6 Michael Shiu,7 David Manning8 1Eye Associates, Sydney, NSW, Australia; 2Fairfield Eye Surgery, Fairfield, NSW, Australia; 3Glaucoma Unit, Sydney Eye Hospital, Sydney, NSW, Australia; 4Discipline of Ophthalmology, The University of Sydney, Sydney, NSW, Australia; 5Eye & Laser Centre Gold Coast, Southport, QLD, Australia; 6Vision Eye Institute, Melbourne, VIC, Australia; 7Laser Sight Laser Cataract & Lens Specialists, Sydney, NSW, Australia; 8Hunter Cataract & Eye Centre, Sydney, NSW, Australia Purpose: To assess the utility and safety of implanting two second-generation trabecular micro-bypass stents following cataract surgery in eyes with mild to advanced glaucoma or ocular hypertension (OHT). Patients and methods: Retrospective study of iStent®inject trabecular micro-bypass implantation with cataract surgery by five surgeons at five sites in Australia. Eyes had mild to advanced glaucoma (predominantly primary open-angle, appositional angle-closure, or pseudoexfoliative glaucoma) or OHT and cataract requiring surgery. Effectiveness measures included intraocular pressure (IOP); medication burden; and proportions of eyes with no medications, ≥2 medications, stable or decreased medications vs preoperative, and IOP ≤18 mmHg. Safety measures included visual acuity, cup-to-disc ratio (CDR), visual field (VF), complications, adverse events, and secondary surgical interventions. Patients have been followed for 12 months, and follow-up is ongoing. Results: Of the 290 total eyes that underwent surgery, 165 eyes had 12-month outcomes at the time of data collection and are included in this report. In these eyes, mean Month 12 IOP reduced by 23.2% from 18.27±5.41 mmHg preoperatively to 14.04±2.98 mmHg (P

Christina Fotiadou, Elizabeth Lazaridou, Eleni Sotiriou, Demetrios Ioannides First Department of Dermatology and Venereology, Aristotle University Medical School, Thessaloniki, Greece Abstract: The recent advances in the understanding of psoriasis pathogenesis have clarified the pivotal role of interleukin (IL)-23. It is a heterodimeric cytokine consisting of two subunits, the unique p19 and the p40, which are shared with IL-12. The basic role of IL-23 in psoriasis is the activation and maintenance of the T-helper 17 pathway. New research findings indicate that IL-23 is more important than IL-12 in the pathogenesis of psoriasis. Based on that background, the selective targeting of the IL-23p19 subunit emerged as an attractive therapeutic option and led to the development of a new category of biologic agents. Three monoclonal antibodies that selectively inhibit the IL-23p19 subunit, guselkumab, tildrakizumab, and risankizumab, are in the pipeline for the treatment of moderate-to-severe psoriasis. In this article, we review the most recent efficacy and safety data regarding these IL-23p19 inhibitors. Keywords: psoriasis, IL-23, treatment, Th17 axis, anti-IL-23p19 monoclonal antibodies

Evangelos I Kritsotakis,1 Flora Kontopidou,2 Eirini Astrinaki,3 Maria Roumbelaki,4 Eleni Ioannidou,5 Achilles Gikas6 1School of Health and Related Research, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK; 2Healthcare Associated Infections and Antimicrobial Resistance Office, Hellenic Center for Disease Control and Prevention, Athens, 3Infection Control Committee, University Hospital of Heraklion, 4Department of Nursing, Technological Educational Institute of Crete, Heraklion, 5Department of Internal Medicine, Rethymnon General Hospital, Rethymnon, 6Department of Internal Medicine and Infectious Diseases, University Hospital of Heraklion, Heraklion, Greece Background: Assessing the overall burden of healthcare-associated infections (HAIs) is challenging, but imperative in evaluating the cost-effectiveness of infection control programs. This study aimed to estimate the point prevalence and annual incidence of HAIs in Greece and assess the excess length of stay (LOS) and mortality attributable to HAIs, overall and for main infection sites and tracer antimicrobial resistance (AMR) phenotypes and pathogens.Patients and methods: This prevalent cohort study used a nationally representative cross-section of 8,247 inpatients in 37 acute care hospitals to record active HAIs of all types at baseline and overall LOS and in-hospital mortality up to 90 days following hospital admission. HAI incidence was estimated using prevalence-to-incidence conversion methods. Excess mortality and LOS were assessed by Cox regression and multistate models correcting for confounding and time-dependent biases.Results: HAIs were encountered with daily prevalence of 9.1% (95% confidence interval [CI] 7.8%–10.6%). The estimated annual HAI incidence was 5.2% (95% CI 4.4%–5.3%), corresponding to approximately 121,000 (95% CI 103,500–123,700) affected patients each year in the country. Ninety-day mortality risk was increased by 80% in patients with HAI compared to those without HAI (adjusted hazard ratio 1.8; 95% CI 1.3–2.6). Lower respiratory tract infections, bloodstream infections, and multiple concurrent HAIs doubled the risk of death, whereas surgical site and urinary tract infections were not associated with increased mortality. AMR had significant impact on the daily risk of 90-day mortality, which was increased by 90%–110% in patients infected by carbapenem-resistant gram-negative pathogens. HAIs increased LOS for an average of 4.3 (95% CI 2.4–6.2) additional days. Mean excess LOS exceeded 20 days in infections caused by major carbapenem-resistant gram-negative pathogens.Conclusion: HAIs, alongside with increasing AMR, pose significant burden to the hospital system. Burden estimates obtained in this study will be valuable in future evaluations of infection prevention programs.Keywords: nosocomial infections, antibiotic resistance, length of stay, mortality, prevalence, incidence

Elizabeth Lazaridou,1 Chrysovalantis Korfitis,2 Christina Kemanetzi,1 Elena Sotiriou,1 Zoe Apalla,1 Efstratios Vakirlis,1 Christina Fotiadou,1 Aimilios Lallas,1 Demetrios Ioannides1 1First Department of Dermatology and Venereology, Aristotle University Medical School, Thessaloniki, Greece; 2Department of Dermatology, 401 General Army Hospital, Athens, Greece Abstract: Rosacea is a chronic skin disease characterized by facial erythema and telangiectasia. Despite the fact that many hypotheses have been proposed, its etiology remains unknown. In the present review, the possible link and clinical significance of Helicobacter pylori in the pathogenesis of rosacea are being sought. A PubMed and Google Scholar search was performed using the terms “rosacea”, “H.pylori”, “gastrointestinal disorders and H.pylori”, “microorganisms and rosacea”, “pathogenesis and treatment of rosacea”, and “risk factors of rosacea”, and selected publications were studied and referenced in text. Although a possible pathogenetic link between H. pylori and rosacea is advocated by many authors, evidence is still interpreted differently by others. We conclude that further studies are needed in order to fully elucidate the pathogenesis of rosacea. Keywords: eradication, Helicobacter pylori, pathogenesis, rosacea

Alexandros Takis,1 Dimitrios Alonistiotis,1 Nikolaos Ioannou,1 Evgenia Kontou,1 Maria Mitsopoulou,1 Dimitrios Papaconstantinou2 1Second Department of Ophthalmology, University of Athens, “Attikon” Hospital, Athens, 2First Department of Ophthalmology, University of Athens, General Hospital of Athens “G Genimatas”, Athens, Greece Purpose: To evaluate and follow-up the retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus type 2 compared to a group of healthy individuals with similar demographic characteristics.Patients and methods: This is a prospective, noninvasive, observational case series study. For the purposes of the study, 27 eyes of diabetic patients without diabetic retinopathy, 24 eyes of patients with mild retinopathy, and 25 normal age-matched subjects (control group [CG]) were examined. All participants underwent complete ophthalmological examination and imaging with GDx variable corneal compensation scanning laser polarimetry. Follow-up was 2 years for all three groups.Results: The mean inferior average was statistically significantly lower in both diabetic groups compared to CG at baseline examination and during follow-up. The nerve fiber indicator (NFI) was higher in both diabetic groups compared to CG, both at baseline examination and during follow-up. The NFI was 21.7±11.9 and 22.0±11.8 for the diabetic group without retinopathy, 20.8±9.6 and 21.9±9.8 for the group with mild retinopathy, and 15.3±5.4 and 15.9±5.5 for the normal subjects, at baseline and 24 months, respectively. There was no statistically significant reduction of the RNFL thickness in all three groups compared to baseline examination.Conclusion: This is the first long-term study documenting the RNFL thickness in diabetic patients in comparison with normal controls. Although the lower RNFL was found thinner in diabetics, the 2-year follow-up showed no significant reduction of RNFL thickness in all groups, indicating that RNFL damage may occur early in diabetic patients. Keywords: RNFL, GDx, diabetic retinopathy, glaucoma

Zoe Apalla,1 Chrysoula Papageorgiou,1 Aimilios Lallas,1 Elena Sotiriou,1 Elizabeth Lazaridou,1 Efstratios Vakirlis,1 Athanassios Kyrgidis,2 Demetrios Ioannides1 1First Department of Dermatology, Aristotle University, 2Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Aristotle University, Thessaloniki, Greece Abstract: Vismodegib is approved for the treatment of adult patients with metastatic (mBCC) or locally advanced basal cell carcinoma (laBCC) that have recurred following surgery or for those who are not good candidates for surgery (risk/benefit ratio is against patient’s benefit, either because of the general condition or because of the expected morbidity from the surgery) or radiation therapy. This article provides an evidence-based review of its current place in therapy. Analytically, the clinical implications in the management of laBCCs and mBCCs and possible new indications, including the neoadjuvant use before surgical excision, are discussed, while in the end, the challenges regarding class-related adverse events and their optimal management are highlighted. Keywords: vismodegib, sonic hedgehog inhibitors, basal cell carcinoma, treatment, review

Efstratios Vakirlis, Grigorios Theodosiou, Zoe Apalla, Michael Arabatzis, Elizabeth Lazaridou, Elena Sotiriou, Aimilios Lallas, Demetrios Ioannides First Department of Dermatology, Aristotle University Medical School, Thessaloniki, Greece Background: The incidence of skin diseases in children is influenced by hereditary, social, and environmental factors. The objective of this study was to determine the incidence of pediatric dermatoses at a University Hospital in Northern Greece. Patients and methods: We reviewed epidemiologic data of 940 patients, aged 0–18 years, who were referred to the outpatient clinic of a University Hospital between January 2013 and December 2015. Demographic data and the frequency of the various diagnoses in various age groups were studied. Results: Nine hundred and forty children and adolescents with 1020 diagnoses were included in the study (52.8% females and 47.2% males). The 10 most frequent diagnoses were: dermatitis/eczema (31.5%), viral infections (12.5%), pigmentary disorders (7.4%), melanocytic nevi (5.8%), alopecia areata (5.8%), acne (5.6%), nail disorders (3.3%), vascular malformations and hemangiomas (2.9%), psoriasis (2.6%), and bacterial infections (2.6%). Atopic dermatitis was the most prevalent dermatosis in all age groups accounting for a total of 20.9% of the study population. A remarkably high incidence of various forms of mastocytosis (2.2%) was seen in our data. Conclusion: Atopic dermatitis is the most frequent pediatric dermatosis in all age groups. Viral infections, pigmentary disorders, and nevi account for a significant proportion of the referrals. The high incidence of mastocytosis in our study may be attributed to overdiagnosis, overestimation due to the relatively small study population, or it may represent the real incidence of mastocytosis in our region. The low incidence of acne in our study may be attributed to the fact that only severe cases are referred to our hospital. Keywords: epidemiology, pediatric dermatology, atopic dermatitis, infection-viral, mastocytosis

Giovanni Cochetti,1 Francesco Barillaro,1 Emanuele Cottini,1 Francesco D’Amico,1 Alberto Pansadoro,1 Solajd Pohja,1 Andrea Boni,1 Roberto Cirocchi,2 Veronica Grassi,2 Rosa Mancuso,1 Elisa Silvi,1 Katifenia Ioannidou,1 Maria Giulia Egidi,1 Giulia Poli,1 Ettore Mearini1 1Department of Surgical and Biomedical Science, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Terni, Italy; 2Department of Surgical Sciences, University of Perugia, Terni, Italy Abstract: Pneumoscrotum is the term used to describe the presence of air within the scrotum and includes scrotal emphysema as well as pneumatocele. The etiology varies; in some cases, pneumoscrotum may be due to life-threatening disease like pneumothorax or Fournier gangrene. Despite this, pneumoscrotum is a rarely debated issue. We present two different cases of pneumoscrotum and a review of the literature. The first case report is about a 29 year old male patient affected by Duchenne syndrome who showed pneumoscrotum after cardiopulmonary resuscitation that was performed for asphyxic crisis and cardiovascular arrest. We carried out local puncture with an 18-gauge needle, and the pneumoscrotum was successfully solved. The second case report is about a 56 year old male with pneumoscrotum due to Fournier gangrene who underwent radical exeresis of all necrotic tissues and drainage. This is why most of the scrotal skin and all of the penis skin were removed; as a result, the testicles, epididymis, and cavernosa corpora were externalized. On postoperative day one, the patient was feverless and underwent hyperbaric chamber therapy. No postoperative complications occurred. Accurate evaluation of the pneumoscrotum is always needed. Despite the benign course of most of the clinically evident pneumoscrotum cases, this condition should never be underestimated. Keywords: cardiopulmonary resuscitation, Fournier gangrene, pneumoscrotum, spontaneous causes, traumatic causes

Magdalini Triantafylla,1 Horace F Massa,2 Doukas Dardabounis,1 Zisis Gatzioufas,2 Vassilios Kozobolis,1 Konstantinos Ioannakis,1 Irfan Perente,1,3 Georgios D Panos1,21Department of Ophthalmology, University General Hospital of Alexandroupolis, School of Medicine, University of Thrace, Alexandroupolis, Greece; 2Department of Ophthalmology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland; 3Beyoglou Eye Research and Teaching Hospital, Istanbul University, Istanbul, TurkeyAbstract: Degenerative ocular conditions, such as age-related macular degeneration, diabetic retinopathy, retinal vein occlusions, and myopic degeneration, have become a major public health problem and a leading cause of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) drugs seem to be an effective and safe treatment for these conditions. Ranibizumab, a humanized monoclonal antibody antigen-binding fragment, which inhibits all biologically active isoforms of VEGF-A, is still the gold standard treatment for the majority of these pathological entities. In this review, we present the results of the most important clinical trials concerning the efficacy and safety of ranibizumab for the treatment of degenerative ocular conditions.Keywords: age-related macular degeneration, diabetic macular edema, retinal vein occlusion, anti-VEGF, safety, efficacy, quality of life

Christina Fotiadou, Elizabeth Lazaridou, Demetrios Ioannides First Department of Dermatology–Venereology, Aristotle University Medical School, Thessaloniki, Greece Abstract: Psoriasis is a chronic inflammatory cutaneous disorder affecting 2%–4% of the world's population. The prevalence of the disease in childhood and adolescence ranges between 0.5% and 2%. The management of psoriasis in adolescence is an intriguing and complicated task. Given the paucity of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, physicians must rely on published experience from case reports both from the field of dermatology as well as from the application of these drugs for other pediatric conditions coming from the disciplines of rheumatology, gastroenterology, and oncology. Psoriatic adolescents deal with a potentially disfiguring and lifelong disease that could permanently impair their psychological development. It must be clarified to them that psoriasis does not have a permanent cure, and therefore the main goal of treatments is to establish disease control and prolonged periods between flares. The majority of adolescents suffer from mild psoriasis, and thus they are treated basically with topical treatment modalities. Phototherapy is reserved for adolescents with mild-to-moderate plaque disease and/or guttate psoriasis when routine visits to specialized centers do not create practical problems. Systemic agents and biologics are administered to patients with moderate-to-severe plaque psoriasis, pustular psoriasis, or erythrodermic psoriasis. Keywords: adolescent psoriasis, pediatric psoriasis, treatment, systemic treatment, biologic agents

Alexandros Takis,1 Dimitrios Alonistiotis,1 Dimitrios Panagiotidis,1 Nikolaos Ioannou,1 Dimitris Papaconstantinou,2 Panagiotis Theodossiadis1 1Ophthalmological University Clinic of Athens, Attikon Hospital, Athens, Greece; 2Ophthalmological University Clinic of Athens, Geniko Kratiko Hospital, Athens, Greece Background: The retinal nerve fiber layer (RNFL) thickness in patients with diabetes mellitus type 2 was compared to normal subjects of similar age and sex, having first excluded any risk factors for glaucoma. The correlation between the RNFL thickness and the severity of diabetic retinopathy was investigated at its primary stages and with other ocular and diabetic parameters. Methods: A prospective, case series study was carried out. Twenty-seven diabetic patients without diabetic retinopathy, 24 diabetic patients with mild retinopathy, and 25 normal, age-matched subjects underwent a complete ophthalmological examination and imaging with scanning laser polarimetry for the evaluation of the RNFL. Multivariate analysis was applied in order to investigate the correlation between RNFL and diabetic parameters, such as age, duration of diabetes, insulin therapy, levels of glycosylated hemoglobin; and ocular parameters, such as cup to disc ratio, levels of normal intraocular pressure, and central corneal thickness. Results: The mean inferior average of RNFL and the temporal-superior-nasal-inferior-temporal standard deviation were statistically significantly lower in both diabetic groups, and the nerve fiber index was higher (P=0.04) compared to the normal group. There was no statistically significant difference between the diabetic groups. The factor analysis showed no significant correlation between the RNFL and the previously mentioned diabetic and ocular parameters. Conclusion: The existence of diabetes should be seriously considered in evaluating the results of scanning laser polarimetry. Multivariate analysis for RNFL was used for the first time. Keywords: diabetes, glaucoma, RNFL, SLP

Ioannis M Aslanides,1 Sara Padroni,1 Samuel Arba Mosquera,2 Antonis Ioannides,1 Achyut Mukherjee11Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece; 2Schwind eye-tech-solutions GmbH, Kleinostheim, GermanyPurpose: To evaluate postoperative pain, corneal epithelial healing, development of corneal haze, refractive outcomes, and corneal aberrations in a novel one-step, modified transepithelial photorefractive keratectomy (PRK), termed All-surface laser ablation (ASLA), compared to conventional, alcohol-assisted PRK.Materials and methods: Sixty eyes of 30 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent conventional alcohol-assisted PRK in one eye (control group) and ASLA-modified transepithelial PRK in the other (30 eyes in each treatment arm). Primary endpoints were postoperative pain and haze scores at 1 day, 3 days, 1 week, and 1, 3, 6, and 12 months. Secondary endpoints included visual acuity at 1, 3, 6, and 12 months, corneal aberrations at 3, 6, and 12 months, and early and late onset haze. Refractive predictability, safety, and efficacy of the two methods were considered.Results: The average age of the cohort was 29 years (standard deviation [SD]: 9; range: 18–46), and the average spherical equivalent refractive error was -4.18 diopters (SD: 1.9). At 3 days after surgery, the average pain score was 64% lower in the ASLA group (P < 0.0005). At this point, 96% of ASLA eyes had no epithelial defect, whereas 43% in the alcohol-assisted group did not achieve complete epithelial healing, and required replacement of bandage contact lens. The haze level was consistently lower in the ASLA group at all time points from 1 to 6 months.Conclusion: This study shows that the ASLA technique may have a future role in refractive surgery, due to the fact that it offers faster epithelial healing, lower pain scores, and significantly less haze formation.Keywords: cornea, ASLA, PRK, alcohol, transepithelial, epithelium, laser

Paul Zarogoulidis1,2, Ioanna Alexandropoulou1,2, Gioulia Romanidou3, Theocharis G Konstasntinidis1,2, Eirini Terzi3, S Saridou1, Athanasios Stefanis1, Kostas Zarogoulidis1,2, TC Constantinidis1,21Regional Laboratory of Public Health, East Macedonia-Thrace, Komotini, Greece; 2Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Komotini, Greece; 3Department of Internal Medicine, General Municipal Hospital (“Sismanoglio” of Komotini), Komotini, GreeceIntroduction: There are at least 40 types of Legionella bacteria, half of which are capable of producing disease in humans. The Legionella pneumophila bacterium, the root cause of Legionnaires’ disease, causes 90% of legionellosis cases.Case presentation: We describe the case of a 60-year-old woman with a history of diabetes mellitus and arterial hypertension who was admitted to our hospital with fever and symptoms of respiratory infection, diarrhea, and acute renal failure. We used real-time polymerase chain reaction (PCR) to detect L. pneumophila DNA in peripheral blood and serum samples and urine antigen from a patient with pneumonia. Legionella DNA was detected in all two sample species when first collected.Conclusion: Since Legionella is a cause of 2% to 15% of all community-acquired pneumonias that require hospitalization, legionellosis should be taken into account in an atypical pulmonary infection and not be forgotten. Moreover, real-time PCR should be considered a useful diagnostic method.Keywords: Legionnaires’ disease, Lionella pneumophila

Anthoula T Tsoumani1,2, Ioannis C Asproudis1, Dimitrios Damigos21Department of Ophthalmology University Hospital of Ioannina, 2Department of Medical Psychology, Postgraduate Course of “Pain Management”, University of Ioannina, GreeceBackground and objective: To evaluate the level of pain during phacoemulsification and foldable intraocular lens implantation under instillation of tetracaine 0.5% eyedrops versus a combination of lidocaine 2% gel and instillation of tetracaine eyedrops.Methods: This prospective, randomized, controlled study included 51 patients undergoing phacoemulsification under topical anesthesia. They were randomized into two groups based on the topical anesthetic method they were to receive. Preoperatively all patients were asked to answer a questionnaire. One hour postoperatively, they were asked to grade their intraoperative and postoperative pain on a visual analog scale from 0 to 10.Results: There were no statistically significant differences between the two methods of anesthesia. Gender and the presence of relatives or friends were independent factors playing a significant role in pain sensitivity.Conclusions: The combination of lidocaine 2% gel and tetracaine eyedrops does not have a better analgesic result than a single instillation of tetracaine 0.5% eyedrops.Keywords: ophthalmic pain, cataract, phacoemulsification, tetracaine eyedrops, lidocaine gel, topical anesthesia

Ioannis Asproudis1, Felekis Taxiarchis1, Elena Tsanou2, Spiridon Gorezis2, Eikaterini Karali3, Sapfo Alfantaki3, Antigoni Siamopoulou-Mauridou3, Miltiadis Aspiotis11University Eye Clinic of Ioannina, Greece; 2Epirus Vision Center, Ioannina, Greece; 3Department of Child Health, University of Ioannina, GreeceObjective: To evaluate the characteristics and visual prognosis of juvenile idiopathic arthritis-associated uveitis (JIA).Methods: A retrospective review was performed on 56 patients who met the criteria for JIA to identify those with uveitis and related complications. Patients were referred to and were examined in the Pediatric Department of the University Hospital of Ioannina, between 1995 and 2007.Results: The prevalence of JIA-associated uveitis was high. Despite this and the related complications, the final visual outcome was satisfactory in the majority of the cases. Authors did not observe any correlation between prognosis and sex, age at the onset of uveitis or arthritis, pattern of arthritis, or positivity for antinuclear antibodies (ANA).Conclusion: We found a remarkably high prevalence of uveitis and related ocular complications in 7 (28%) of the patients, and the rate of poor visual outcome was 12%.Keywords: idiopathic arthritis, uveitis, visual complications, autoimmune disease

Dimitrios A Karagiannis1, Ioannis D Ladas2, Efstratios Parikakis1, Ilias Georgalas2, Athanasios Kotsolis2, Giorgos Amariotakis1, Vasileios Soumplis1, Panagiotis Mitropoulos11Ophthalmiatrio Eye Hospital of Athens, Athens, Greece; 2First Department of Ophthalmology, Medical School of Athens University, General Hospital of Athens, Athens, GreeceObjective: To report our experiences in changing from intravitreal bevacizumab to ranibizumab in age-related macular degeneration (AMD).Design: Retrospective case series.Participants and methods: We retrospectively reviewed the records of 34 patients (36 eyes) who were treated with monthly injections of intravitreal bevacizumab for six months and then switched to monthly injections of ranibizumab for 12 months. Best-corrected visual acuity measurements (BCVA), contact lens biomicroscopy, optical coherence tomography (OCT), and fluorescein angiography were performed at the baseline examination and then monthly. Chi-square test was used for statistical analysis.Results: Following bevacizumab treatment, retinal thickness decreased (P = 0.033) while BCVA improved (P = 0.040). Changing from bevacizumab to ranibizumab resulted in a transient decrease in BCVA (P = 0.045) and an increase in retinal thickness (P = 0.042). In addition, three eyes presented with a large subretinal hemorrhage. However, final retinal thickness was better than the initial thickness and the value following the bevacizumab course. No major ocular or systemic side effects were noted.Conclusions: Ranibizumab was clinically effective in the long term but the change of treatment from bevacizumab to a half-size molecule with less half-life in the vitreous such as ranibizumab contributed to a transient “instability” in the eye which may have triggered the large subretinal hemorrhage. There is insufficient experience reported in the literature in switching from one agent to another. A prospective study with controls is necessary to determine whether it is safe to change from one medication to another.Keywords: age-related macular degeneration, bevacizumab, ranibizumab, subretinal hemorrhage

Ceri J Phillips, Ioan HumphreysInstitute for Health Research, School of Health Science, Swansea University, Swansea, Wales, UKAbstract: Multiple sclerosis (MS) is one of the most common causes of neurological disability in young and middle-aged adults, with current prevalence rates estimated to be 30 per 100,000 populations. Women are approximately twice as susceptible as males, but males are more likely to have progressive disease. The onset of the disease normally occurs between 20 and 40 years of age, with a peak incidence during the late twenties and early thirties, resulting in many years of disability for a large proportion of patients, many of whom require wheelchairs and some nursing home or hospital care. The aim of this study is to update a previous review which considered the cost-effectiveness of disease-modifying drugs (DMDs), such as interferons and glatiramer acetate, with more up to date therapies, such as mitaxantrone hydrochloride and natalizumab in the treatment of MS. The development and availability of new agents has been accompanied byan increased optimism that treatment regimens for MS would be more effective; that the number, severity and duration of relapses would diminish; that disease progression would be delayed; and that disability accumulation would be reduced. However, doubts have been expressed about the effectiveness of these treatments, which has only served to compound the problems associated with endeavors to estimate the relative cost-effectiveness of such interventions.Keywords: multiple sclerosis, disease management, immunomodulatory drugs, cost-effectiveness, cost-effectiveness analysis, cost-utility analysis

Georgios Kitsos, Christos Gartzios, Ioannis Asproudis, Eleni BagliOphthalmology Department, University of Ioannina, Ioannina, GreeceObjective: The evaluation of central corneal thickness (CCT) in subjects with pesudoexfoliation glaucoma (PEXG), primary open-angle glaucoma (POAG), and in normotensive individuals with or without pseudoexfoliation syndrome (PXS). Study design/patients and methods: CCT was evaluated with ultrasound pachymetry in a total of 179 individuals: 32 had bilateral PEXG, 55 had bilateral POAG, 35 had PXS, and 57 were healthy individuals without PXS.Results: CCT in PEXG eyes (526.00 ± 34.30 µm) was significantly thinner compared to POAG eyes (549.36 ± 39.3 µm) (P = 0.027) and normal control eyes with (550.64 ± 39.0 µm) or without PXS (547.36 ± 33.1 µm), (P = 0.039 and 0.048 respectively). No statistically significant difference was found comparing CCT values of POAG eyes to control group eyes.Conclusion: The evaluation of CCT is necessary in all patients with glaucoma and especially in those with PEXG due to the thinner cornea and the risk of underestimation of intraocular pressure.Keywords: CCT, pesudoexfoliation syndrome, glaucoma

Eleni Bagli, Christos Gartzios, Ioannis Asproudis, Georgios KitsosUniversity Eye Clinic of Ioannina, Ioannina, GreecePurpose: The comparison of one-site versus two-site phacotrabeculectomy in patients with pseudoexfoliation glaucoma (PEXG) and primary open-angle glaucoma (POAG), with respect to intraocular pressure (IOP), antiglaucomatous medication (AM) requirements and visual acuity (VA).Methods: Forty-seven patients (eyes) with cataract and POAG and 46 sex- and age-matched patients with cataract and PEXG were randomized to one- or two-site phacotrabeculectomy and reviewed with a follow-up at three years.Results: Mean preoperative IOP was 22.04 ± 2.27 mmHg and 22.92 ± 2.35 mmHg in POAG and PEXG groups (p > 0.05) using a mean of 2.76 ± 0.74, 2.74 ± 0.69 AM, respectively (p > 0.05). After three years of follow-up, the mean IOP was 15.04 ± 1.57 mmHg in the one-site, 15.04 ± 1.99 mmHg in the two-site group with POAG, 15 ± 1.8 mmHg in the one-site, 15.32 ± 1.31 mmHg in the two-site group with PEXG, using a mean of 0.68 ± 0.69, 0.84 ± 0.75, 0.96 ± 0.67, and 0.8 ± 0.62 AM, respectively. Mean IOP and AM postoperatively were significantly less compared to preoperatively for each group (p < 0.05). No difference was observed in mean IOP and AM between the four groups at three years postoperatively (p > 0.05). VA improved similarly in four groups at the three-year follow-up (p < 0.05). Intraoperative, postoperative complications, and need for 5-fluorouracil injections were similar between the surgical groups.Conclusion: One-site and two-site phacotrabeculectomy without the use of antimetabolites intraoperatively were similarly safe and effective in IOP control over a three-year follow-up period in patients with POAG and PEXG.Keywords: phacotrabeculectomy, pseudoexfoliation, glaucoma

Ilias Georgalas1, Petros Petrou2, George Kalantzis2, Dimitrios Papaconstantinou2, Chrysanthi Koutsandrea2, Ioannis Ladas21Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, NHS, Athens, Greece; 2Department of Ophthalmology, University of Athens, Athens, GreecePurpose: To evaluate the efficacy and safety of Neodymium:YAG (Nd:YAG) laser capsulotomy for posterior capsule opacification (PCO) following combined phacoemulsification and vitrectomy for the treatment of cataract in association with macular hole (MH) or epiretinal membrane (ERM).Methods: Retrospective clinical study of 34 eyes of 34 patients who underwent combined cataract surgery and vitrectomy, developed PCO, and subsequently underwent Nd:YAG laser capsulotomy. Follow-up examinations included visual acuity measurement, evaluation of intraocular lens (IOL) centration, intraocular pressure (IOP) measurement, and dilated fundus examination.Results: Nd:YAG laser capsulotomy was performed in all 34 eyes. The mean age of the patients was 65.08 years (range 45–87) and the mean follow up period was 11.05 months (range 4–23). The mean time elapsed between the last intraocular operation and the development of PCO was 10.00 months for patients with previous ERM and 15.33 for those with MH (P = 0.001, t-test for equality of means). None of our patients developed recurrence of MH, retinal detachment, IOL dislocation, or permanent IOP elevation.Conclusion: In our study, the most remarkable observation is that no complication occurred after the YAG capsulotomy, possibly because the eyes were vitrectomized and vitreous seems to play an important role in the occurrence of post-Nd:YAG complications. In addition we noted that PCO seems to occur earlier in the eyes undergoing combined surgery for cataract and ERM when compared with those where combined phacoemulsification and vitrectomy are performed for cataract and MH.Keywords: Nd:YAG capsulotomy, phacoemulsification, vitrectomy

Ilias Georgalas, Alexandros A Rouvas, Dimitrios A Karagiannis, Athanasios I Kotsolis, Ioannis D LadasDepartment of Ophthalmology, Medical School of Athens University, Athens, GreeceAbstract: This is a case report of a 83-year-old man with choroidal neovascularization (CNV), due to age-related macular degeneration (AMD) in his right eye. Digital fluorescein (FA) and indocyanine green angiography (ICG) were performed, which disclosed predominantly classic subfoveal CNV and a dilated and tortuous feeding complex. The visual acuity was 20/800. Anti-vascular endothelial growth factor (anti-VEGF) treatment was suggested, however, the patient was not keen to receive an intraocular injection. Modified photodynamic therapy (PDT) with spot size enlarged, to include not only the CNV lesion but the feeding complex as well, was performed. Ten days after one session of PDT, ICG showed absence of leakage from the CNV and complete occlusion of the feeding complex. The visual acuity gradually improved to 20/100 and remained stable during the following 23 months. No evidence of CNV leakage was seen in the FA and ICG during the follow up period. Adjustment of the PDT spot size to include the detectable by ICG feeding complex might be an additional option in order to close the subfoveal CNV and might be considered as an alternative to intravitreal injection of anti-VEGF in selected cases where anti-VEGF treatment is not available.Keywords: age-related macular degeneration, choroidal neovascularization, photodynamic treatment, feeder vessel

Dimitrios Brouzas, Antonios Charakidas, Ioannis Ladas, Michael ApostolopoulosDepartment of Ophthalmology, University of Athens, Athens, GreeceIntroduction: We report on three cases of visual loss due to nonarteritic anterior ischemic optic neuropathy that developed during the course of refractory anemia, a subtype of myelodysplastic syndrome.Patients and methods: Patients underwent fundus, visual field examination, and fluorescein angiography. A thrombophilic tendency investigation including prothrombin time, partial thromboplastin time, protein C, free protein S, and antithrombin III, polymerase chain reaction and hybridisation to allele-specific oligonucleotide probes and a bone marrow biopsy were also performed.Results: Relative recovery of visual function was noted in two patients, a 58-year-old man and a 67-year-old woman, whereas the vision of the third patient, a 62-year-old man, showed only marginal improvement during the follow-up period. Two patients received vigorous blood transfusion during hospitalization, while dosage adjustment of the erythropoietin infusion was decided for the third one. Thrombophilic tendency was not identified in any patient.Discussion: Chronic anemia, as presented in myelodysplastic syndrome’s refractory anemia subtype, probably in the presence of additional factors, such as hypotension, is likely to be complicated by optic neuropathy, possibly through a mechanism of anemic hypoxia and/or microvascular insufficiency.Keywords: myelodysplastic syndrome, anemia, optic neuropathy

M Kathryn Steiner1, Ioana R Preston21Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Pulmonary Critical Care and Sleep Division, Department of Medicine, Tufts Medical Center, Boston, MA, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodymanics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH.Keywords: ambrisentan, bosentan, endothelin receptor antagonists, pulmonary arterial hypertension, sitaxsentan

Haris Carageorgiou1, Antonios C Sideris1, Ioanna Messari1, Chrissoula I Liakou1, Stylianos Tsakiris21Department of Pharmacology, 2Department of Physiology, Medical School, University of Athens, Athens, GreeceAbstract: We investigated the effects of rivastigmine (a cholinesterase inhibitor) and selegiline ((-)deprenyl, an irreversible inhibitor of monoamineoxidase-B), alone and in combination, on brain acetylcholinesterase (AChE), (Na+, K+)-, Mg2+-ATPase activities, total antioxidant status (TAS), and learning performance, after long-term drug administration in aged male rats. The possible relationship between the biochemical and behavioral parameters was evaluated.Methods: Aged rats were treated (for 36 days) with rivastigmine (0.3 mg/kg rat/day ip), selegiline (0.25 mg/kg rat/day im), rivastigmine plus selegiline in the same doses and way of administration as separately. Aged and adult control groups received NaCl 0.9% 0.5 ml ip.Results: TAS was lower in aged than in adult rats, rivastigmine alone does not affect TAS, decreases AChE activity, increases (Na+, K+)-ATPase and Mg2+-ATPase activity of aged rat brain and improves cognitive performance. Selegiline alone decreases free radical production and increases AChE activity and (Na+, K+)-ATPase activity, improving cognitive performance as well. In the combination: rivastigmine seems to cancel selegiline action on TAS and AChE activity, while it has additive effect on (Na+, K+)-ATPase activity. In the case of Mg2+-ATPase selegiline appears to attenuate rivastigmine activity. No statistically significant difference was observed in the cognitive performance.Conclusion: Reduced TAS, AChE activity and learning performance was observed in old rats. Both rivastigmine and selesiline alone improved performance, although they influenced the biochemical parameters in a different way. The combination of the two drugs did not affect learning performance.Keywords: aged rat, brain enzymes, TAS, learning, rivastigmine, selegiline

Antigone S Papavasiliou, Irene Nikaina, Ioanna Rizou, Stratos AlexandrouDepartment of Neurology, Pendeli Children’s Hospital, Athens, GreeceAbstract: Attention deficit hyperactivity disorder (ADHD) is treated with stimulants and psycho-educational remedial programs despite limited literature support for the latter. This study aimed to examine changes in a “Test of Visual Perceptual Skills” (TVPS) that has not been previously reported in children with ADHD enrolled in such a program.Methods: Sixteen children, 7–11 years old, with ADHD were involved in occupational therapy and special education geared towards attention training. Six months later methylphenidate 1 mg/kg/day was prescribed. It was not taken by eight children because of family choice. The TVPS was given twice, upon diagnosis, and 8 months post-intervention. The groups were compared by a repeated measures analysis of variance (ANOVA) with medication as a between groups factor and test-retest scores as within factor.Results: All children demonstrated increases in total scores in the second measurement. Medicated children scored higher but ANOVA showed a nonsignificant F for the two groups, medicated and unmedicated (F = 0.0031, p = 0.9563), indicating a non-differential effect of the two levels of treatment. It revealed a significant F for the pre- and post-treatment total TVPS scores (F = 30.91, p < 0.0001) indicating a significant difference between pre- and post-treatment tests. The interaction between pre-post treatment and level of treatment (medicated–unmedicated) was nonsignificant (F = 2.20, p = 0.1604).Conclusion: TVPS scores improved in all children following intervention. Medicated children did better, but differences were nonsignificant.Keywords: ADHD, stimulants, psycho-educational therapy, TVPS

Antonis Ioannides1, Nikolaos D Georgakarakos2, Ibrahim Elaroud3, Petros Andreou1 1Ophthalmology Department, Mid-Essex Hospitals NHS Trust, Chelmsford, 2Institute of Ophthalmology, University College London, London, 3Ophthalmology Department, Mid-Yorkshire Hospitals NHS Trust, Yorkshire, UK Abstract: Cotton-wool spots (CWSs) are common retinal manifestations of many diseases including diabetes mellitus, systemic hypertension, and acquired immunodeficiency syndrome. Clinically they appear as whitish, fluffy patches on the retina and eventually fade with time. In this study, spectral domain optical coherence tomography (SD-OCT) with mapping was used to demonstrate in vivo the characteristics of an isolated CWS in a 59-year-old patient as well as its appearance immediately after ophthalmoscopic resolution. Presented here is the work-up and management of this clinical problem for the ophthalmologist. The authors propose that SD-OCT could be a valuable research tool in characterizing and following the dynamic CWS changes at individual retinal layer level, with potential clinical applications as a screening or diagnostic tool in CWS-related diseases. Keywords: SD-OCT, spectral domain optical coherence tomography, retinal lesion

Marilita Michael Moschos1, Yan Guex-Crosier2, Ioannis Margetis1, Leonidas Zografos21Department of Ophthalmology, University of Athens, Greece; 2Jules Gonin Eye Hospital, University of Lausanne, SwitzerlandPurpose: To investigate six cases of annular cyclitis.Methods: All patients with impairment of visual acuity underwent complete ophthalmologic examination, color fundus photography, laboratory tests and fluorescein angiography. Indocyanine green (ICG) angiography and B-scan ultrasonography were also performed in three cases in order to diagnose the disease.Results: All patients presented a unilateral or bilateral granulomatous uveitis, associated with inflammatory annular cyclitis. They had a shallow anterior chamber, a mildly elevated intraocular pressure (under 25 mm Hg) and an annular serous retinal detachment. A resolution was observed after specific therapy associated with systemic prednisolone therapy and antiglaucomatous drops.Conclusion: This is the first description of an observational study of six patients with inflammatory annular cyclitis.Keywords: cyclitis, uveitis, malignant glaucoma

Dimitrios Karagiannis1, Ilias Georgalas2, Ioannis Ladas2, Parikakis Eustratios1, Panagiotis Mitropoulos11Second Department of Ophthalmiatrion Eye Hospital, NHS, Athens, Greece; 2Department of Ophthalmology, “G.Genimatas” General Hospital, Athens, GreeceAbstract: A 65-year-old lady presented with decreased vision in her left eye (LE). Best corrected visual acuity (BCVA) was 1/20. Complete examination showed idiopathic juxtafoveal retinal telangiectasis associated with subretinal neovascularization and she was treated with intravitreal ranibizumab every month for three months in the LE. After four months, her BCVA increased to 3/10. Fluorescein angiography (FA) showed minimal leakage and optical coherence tomography (OCT) confirmed absence of intra- or subretinal fluid in the macula. Examinations were repeated monthly for another 12 months and showed no recurrence. Intravitreal ranibizumab showed promising results for subretinal neovascularization due to idiopathic juxtafoveal retinal telangiectasis. A prospective study with large series of patients and controls may be necessary in order to determine the effectiveness of this treatment.Keywords: idiopathic juxtafoveal retinal telangiectasis, ranibizumab, subretinal neovascularization

Ioannis D Ladas, Marilita M Moschos, Thanos D Papakostas, Athanasios I Kotsolis, Ilias Georgalas, Michail ApostolopoulosDepartment of Ophthalmology, “G. Gennimatas” Hospital of Athens, University of Athens, Athens, GreecePurpose: The purpose of this observational case report is to describe a case of skin rash after intravitreal use of bevacizumab.Methods: A 50-year-old man with choroidal neovascularization in the right eye due to age-related macular degeneration was treated with three intravitreal injections of bevacizumab.Results: Twelve days after the first injection, the patient developed a maculopapular rash on his forehead and on both temporal regions around his eyes. The rash disappeared eight days after treatment with topical corticosteroids. A skin rash with the same distribution reappeared 14 days after the second and 10 days after the third injection. Similarly, it disappeared five and seven days after the use of the same treatment. The follow-up period was 15 months after the third injection. During the follow-up period the rash did not reappear.Conclusion: This case report may initiate further investigation of similar cases to support this observation, as there are a lack of reports of skin rash after intravitreal administration of bevacizumab.Keywords: skin rash, bevacizumab, age-related macular degeneration

Ilias Georgalas, Dimitris Papaconstantinou, Ioannis Tservakis, Chrysanthi Koutsandrea, Ioannis Ladas“G.Gennimatas” Hospital of Athens, NHS, Athens, GreeceAbstract: We report a case of a patient with age-related macular degeneration, who had undergone trabeculectomy nine years earlier, and developed severe hypotony and bleb leak after treatment with intravitreal injections of ranibizumab. Although the incident is rare, in patients with longstanding filtering blebs, who need treatment with antivascular endothelial growth factors, close follow-up may be advocated, since the occurrence of bleb rupture could lead to permanent vision loss.Keywords: trabeculectomy, ranibizumab, age-related macular degeneration

Paris G Tranos1, Ilias Georgalas2, Panagiota Founti1, Ioannis Ladas21Papageorgiou University Hospital, Thessaloniki, Greece; 2Department of Ophthalmology, “G.Genimatas” Hospital, Athens, GreecePurpose: To present an unusual case of cytomegalovirus (CMV) retinitis in a patient with Wegener’s granulomatosis.Results: A 54-year-old lady with Wegener’s granulomatosis presented with decreased vision in her left eye. Wegener’s retinal vasculitis was diagnosed initially and the patient received treatment with oral steroids. Three days later the patient developed typical CMV retinitis.Conclusion: The likelihood of CMV retinitis in patients with Wegener’s granulomatosis should not be overlooked. Increased awareness in such cases is very important since CMV retinitis may present with less typical manifestations, which makes the correct diagnosis more challenging.Keywords: cytomegalovirus retinitis, Wegener’s granulomatosis, ganciclovir

Purpose: We describe an alternative automated technique that consists of simultaneous anterior capsule puncture and decompression of the capsular bag by using an insulin needle attached to the aspiration tubing of the phacoemulsification device to prevent the occurrence of the "Argentinian Flag sign" during capsulorhexis in intumescent cataract., Setting: Instituto de Olhos de Assis and Center of Specialties Hoftalmed, located in the state of São Paulo, Brazil., Design: Prospective interventional study., Methods: Eighty-eight eyes of 88 patients with white or intumescent cataracts were included in this study. Routine clear cornea incision, capsule staining with trypan blue, intracameral anesthesia, and ophthalmic viscoelastic device were used before the procedure. A 26-gauge needle was connected to the phacoemulsification aspiration tubing using a double male Luer connector for irrigation, and aspiration was inserted into the anterior chamber through a new paracentesis incision with the bevel facing down. Immediately after insertion, automated aspiration of the liquefied cortex was performed to remove anterior intralenticular material and achieve capsular decompression. Compression of the nucleus with the needle tip was performed to remove any liquefied material trapped between the posterior surface of the nucleus and the posterior capsule. All surgeries were performed using the same phacoemulsification and parameters. The rate of complete continuous capsulorhexis was observed and noted., Results: No complications were observed in any of the cases. A single-stage, continuous, and well-centered capsulorhexis was achieved in 100% of cases., Conclusion: We conclude that a simultaneous puncture and decompression of the capsular bag using an insulin needle attached to the aspiration tubing of the phacoemulsification machine effectively avoided the "Argentinian Flag sign" in intumescent cataract surgery., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Antunes et al.)

Purpose: To compare clinical outcomes in a prospective trial of cataract surgery patients bilaterally implanted with two different trifocal intraocular lenses (IOLs) with very similar optical designs but consisting of different IOL materials (hydrophobic and hydrophilic)., Patients and Methods: Fifty-one patients (102 eyes) were randomized to receive trifocal IOLs bilaterally - FineVision POD F (hydrophilic) or FineVision POD F GF (hydrophobic) (both PhysIOL, Liége, Belgium). The follow-up period was 3 months. Outcome measurements included uncorrected distance (UDVA), corrected distance (CDVA), distance-corrected intermediate (DCIVA), and distance-corrected near visual acuity (DCNVA), refraction, negative dysphotopsia, optical quality of vision, contrast sensitivity under photopic and mesopic conditions, halometry (discrimination index), and patient-reported outcomes., Results: At the final study visit, mean (SD) values for binocular UDVA, CDVA, DCIVA (80 cm), and DCNVA (40 cm) were -0.01 (0.06), -0.04 (0.04), 0.09 (0.10), and 0.10 (0.09) logMAR, respectively, for POD F, and 0.01 (0.08), -0.03 (0.03), 0.08 (0.1), and 0.13 (0.11) respectively, for POD F GF. Defocus assessments showed a continuous curve with a functional range of visual acuity (≤0.15 logMAR) from ~30 cm to infinity in both groups. The discrimination index was >0.85 for all patients, and both groups showed similar contrast sensitivity under photopic and mesopic conditions. At 3 months, no patient reported negative dysphotopsia, and high satisfaction rates were observed., Conclusion: Clinical outcomes showed no significant difference between each lens when measured at 1 month and 3 months after implantation. This equally good clinical performance of hydrophilic and hydrophobic trifocal lenses allows the surgeon to choose the IOL material based on personal preferences or patients' needs., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Poyales et al.)