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Objectives Children with antibody positive type 1 diabetes mellitus (type 1 diabetes) are at an increased risk of developing celiac disease (CD) which suggests a common autoimmune basis with both high-risk human lymphocyte antigen (HLA) and non-HLA factors playing a role in the pathophysiology. We aim to describe the prevalence, immune profile, and clinical characteristics of children with CD who have type 1 diabetes mellitus in Qatar. Methods All children (aged 0–18 years) attending a regional diabetes clinic with antibody positive type 1 diabetes were screened for CD. Measurement of tissue transglutaminase IgA and IgG as well as anti-endomysial antibody, was done, clinical details about the birth history, family history of diabetes and CD, age of onset, and ethnicity were collected. Results Out of the 1,325 children with antibody positive type 1 diabetes, 54 were identified to have CD on screening and then confirmed on small bowel biopsy. The prevalence of CD in the type 1 diabetes childhood population in Qatar is 4.07%. CD and type 1 diabetes were more prevalent in the Qatari children (n=32) as compared to non-Qatari (n=22) and occurred mostly in the age group 6–10 years. The most common type 1 diabetes antibodies in children with CD were glutamic acid decarboxylase and insulin autoantibody. Twelve subjects were asymptomatic for CD symptoms and picked up only on screening. Conclusions The prevalence of CD in children with type 1 diabetes in Qatar is comparable to reports from around the world. Many children were asymptomatic and thus routine screening is recommended.

The evolution of vitrectomy has led to improved suturless techniques and minimally invasive surgery. Nevertheless, the procedure requires great bimanual dexterity and poses risk for lens touch, especially in the hands of less experienced junior surgeons. We hereby present a twist technique which allows for one-handed (right or left) peripheral vitrectomy without the need for one or several hand-switches with the vitreous cutter and avoids lens touch. The technique can be used as a learning approach for junior vitreoretinal surgeons.

Purpose: To evaluate arteriovenous malformations (AVM) with swept-source (SS) optical coherence tomography (OCT) angiography (OCTA) in iris racemose hemangioma and compare it with traditional intravenous iris fluorescein angiography (IVFA). Methods: A cross-sectional observational clinical study was conducted on patients with iris racemose hemangioma with the ZEISS PLEX Elite 9000 SS OCT & OCTA. Results: Three eyes of three patients were imaged. Iris racemose hemangiomas demonstrated a tortuous, well-defined, and continuous course of the AVM. The ZEISS PLEX Elite 9000 SS OCT & OCTA allowed for a detailed visualization of the ARM and was superior to IVFA in depicting small caliber, fine vessels. Conclusions: SS-OCTA may provide a dye-free, no-injection, cost-effective method comparable to spectral domain OCTA and IVFA for diagnosing and monitoring iris racemose hemangiomas for growth and vascularity.

OBJECTIVEWe aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting.RESEARCH DESIGN AND METHODSThis randomized controlled trial included 34 participants (age 12–18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics.RESULTSDuring the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ.CONCLUSIONSAdolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.

Objectives: To present and validate the novel grading system for objective classification of corectopia.Subjects and Methods: We evaluated 28 eyes of 28 patients with or without corectopia and validated the grading and classification system for corectopia according to three major criteria: (i) direction, (ii) extent, and (iii) alteration of mydriasis. Intraclass correlation coefficient (ICC) and inter-rater agreement between 7 inexperienced and 1 experienced ophthalmologist against a golden standard (GS) were calculated.Results: The ICC for the 7 inexperienced ophthalmologists regarding the grading of direction and centration of the pupil was 0.83 (95% confidence interval (CI), 0.74 to 0.90; p

Background: The objective of this study was to evaluate glycemic outcomes using a structured initiation protocol for Hybrid Closed Loop (HCL) MiniMed 670G and Advanced Hybrid Closed Loop (AHCL) Minimed 780G system in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections. Methods: The data from two separate (HCL and AHCL system) investigations were analyzed in individuals (aged 7-18 years) with T1D on MDI therapy, both followed a structured initiation protocol. Time in Ranges, HbA1c and system characteristics were analyzed between two systems at 3 and 6 months of Automated Insulin Delivery (AID) . Results: 30 children (age 10.24 ± 2.6 years, HbA1c 8.2±1.4% (66±15.3 mmol/mol)) with HCL system and 34 children (12.5 ± 3.7 years, 8.6±1.7% (70±18.6 mmol/mol)) with AHCL system completed the planned 12 weeks of AID. TIR (70-180mg/dl) of 73.4±8.9% with HCL and 78.2±4.3% with AHCL (p=0.01) was achieved at 6 months of AID. No episodes of severe hypoglycemia or DKA were reported using both systems. Conclusion: Individuals using AHCL MiniMed 780G system had more stringent system settings, spent more time in AID with less exits, which possibly lead to further improvements of glycemic control compared to HCL MiniMed 670G system using the same structured protocol. Disclosure G.Petrovski: None. J.Campbell: Advisory Panel; Medtronic. F.Alkhalaf: None. K.Hussain: None.

Andrii Ruban,1 Beáta Éva Petrovski,2 Goran Petrovski,2– 4 Lyubomyr M Lytvynchuk5,6 1Center of Clinical Ophthalmology, Kyiv, Ukraine; 2Department of Ophthalmology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 3Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway; 4Department of Ophthalmology, University of Split School of Medicine and University Hospital Centre, Split, Croatia; 5Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Giessen, Germany; 6Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, AustriaCorrespondence: Lyubomyr M Lytvynchuk, Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Campus Giessen, Friedrichstrasse 18, Giessen, 35392, Germany, Tel +49 64198543820, Fax +49 64198543809, Email Lyubomyr.Lytvynchuk@augen.med.uni-giessen.deBackground: Despite the abundance of novel surgical approaches proposed for full thickness macular hole (FTMH) treatment, the choice of the optimal technique remains debatable Vitrectomy with «classic» internal limiting membrane peeling and gas tamponade remains the standard of FTMH surgery in many cases, but there are still very limited recent publications on the outcomes of such surgery.Purpose: To investigate the anatomical and functional result and to analyze the significance of outcome-related risk factors of the classic 25-gauge pars plana vitrectomy (PPV) with ILM peeling and gas tamponade (GT) for treatment of FTMH of different etiology.Patients and methods: Thirty-eight eyes of thirty-seven patients with FTMH who underwent 25-gauge PPV, ILM peeling and GT were recruited for this retrospective, consecutive, interventional study. Four eyes with persistent holes underwent a re-operation. Outcome-related factors were discussed.Results: The primary closure rate was 89.5% (34/38). All eyes that underwent the repeated surgery (4 cases) obtained final closure. A hole size of > 500 μm has a statistically significant effect on the primary macular hole closure (F = 0.048; &phis; = 0.38; p ˂ 0.05). In the general group (N = 38), the duration of symptoms directly correlated with age (ρ = 0.34; p = 0.04), size of the hole (ρ = 0.66; p ˂ 0.001) and BCVA before surgery (ρ = 0.59; p ˂ 0.001), after 1 month (ρ = 0.36; p = 0.03), and after 3 months (ρ = 0.35; p = 0.03). Preoperative BCVA was better in initially closed cases (Group 1) (U= 26.0; p = 0.05). In the Group 2 with primary unclosed holes, 75% of the eyes (3/4) had an axial length (AL) > 26 mm, while in Group 1 such eyes were 12.5 times less (2/34) 5.9% (F = 0.004; &phis; = 0.63; р ˂ 0.01). The ELM recovery rate at 3 months was 92% (35/38 eyes) and the restoration of EZ at 3 months was 47% (18/38 eyes). Best-corrected visual acuity of all individuals improved significantly from 0.72 ± 0.35 (logMAR) (Me = 0.7; IQR: 0.5– 0.8) to 0.25± 0.14 (logMAR) (Me= 0.2; IQR: 0.2 – 0.3) at 1 month and 0.17 ± 0.13 (logMAR) (Me= 0.2; IQR: 0.1 – 0.2) at 3 months after surgery (P = 0.0001).Conclusion: 25G PPV with ILM and GT for FTMH of different etiology provide satisfactory morphologic and functional outcomes. Elongated AL, large diameter of MH and long duration of symptoms are the risk factors for initial closure. Proper second surgery can obtain satisfactory outcomes for persistent holes.Keywords: full-thickness macular hole, pars plana vitrectomy, internal limiting membrane peeling, gas tamponade, restoration of ELM/EZ, macular hole closure

This study investigated the association between certain genetic variations and the risk of developing proliferative vitreoretinopathy (PVR) after surgery. The study was conducted on 192 patients with primary rhegmatogenous retinal detachment (RRD) who underwent 3-port pars plana vitrectomy (PPV). The distribution of single nucleotide polymorphisms (SNPs) located in genes involved in inflammation and oxidative stress associated with PVR pathways were analyzed among patients with and without postoperative PVR grade C1 or higher. A total of 7 defined SNPs of 5 genes were selected for genotyping: rs4880 (SOD2); rs1001179 (CAT); rs1050450 (GPX1); rs1143623, rs16944, rs1071676 (IL1B); rs2910164 (MIR146A) using competitive allele-specific polymerase chain reaction. The association of SNPs with PVR risk was evaluated using logistic regression. Furthermore, the possible association of SNPs with postoperative clinical parameters was evaluated using non-parametric tests. The difference between two genotype frequencies between patients with or without PVR grade C1 or higher was found to be statistically significant: SOD2 rs4880 and IL1B rs1071676. Carriers of at least one polymorphic IL1B rs1071676 GG allele appeared to have better postoperative best-corrected visual acuity only in patients without PVR (p = 0.070). Our study suggests that certain genetic variations may play a role in the development of PVR after surgery. These findings may have important implications for identifying patients at higher risk for PVR and developing new treatments.

Vitreous substitutes are indispensable tools in vitreoretinal surgery. The two crucial functions of these substitutes are their ability to displace intravitreal fluid from the retinal surface and to allow the retina to adhere to the retinal pigment epithelium. Today, vitreoretinal surgeons can choose among a plethora of vitreous tamponades, and the tamponade of choice might be difficult to determine in the ever-expanding range of possibilities for a favorable outcome. The currently available vitreous substitutes have disadvantages that need to be addressed to improve the surgical outcome achievable today. Herein, the fundamental physical and chemical proprieties of all vitreous substitutes are reported, and their use and clinical applications are described alongside some surgical techniques of intra-operative manipulation. The major upcoming developments in vitreous substitutes are extensively discussed, keeping a translational perspective throughout. Conclusions on future perspectives are derived through an in-depth analysis of what is lacking today in terms of desired outcomes and biomaterials technology.

Background The objective of this study was to evaluate the glycemic outcomes in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections (MDI) using a structured initiation protocol for the Advanced Hybrid Closed Loop (AHCL) Minimed 780G insulin pump system. Methods In this prospective open label single-arm, single-center, clinical investigation, we recruited children and adolescents (aged 7–17 years) with T1D on MDI therapy and HbA1c below 12.5%. All participants followed a 10-day structured initiation protocol which included 4 steps: step 1: AHCL system assessment; step 2: AHCL system training; step 3: Sensor augmented pump therapy (SAP) for 3 days; step 4: AHCL system use for 12 weeks, successfully completing the training from MDI to AHCL in 10 days. The primary outcome of the study was the change in the time spent in the target in range (TIR) of 70–180 mg/dl and HbA1c from baseline (MDI + CGM, 1 week) to study phase (AHCL, 12 weeks). The paired student t-test was used for statistical analysis and a value Results Thirty-four participants were recruited and all completed the 12 weeks study. TIR increased from 42.1 ± 18.7% at baseline to 78.8 ± 6.1% in the study phase (p p = 0.001). No episodes of severe hypoglycemia or DKA were reported. Conclusion Children and adolescents with T1D on MDI therapy who initiated the AHCL system following a 10-days structured protocol achieved the internationally recommended goals of glycemic control with TIR > 70% and a HbA1c of

Purpose The aim of this study was to estimate the 1-year costs associated with treating diabetic macular oedema (DME) patients using current intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics compared with the dexamethasone implant. Methods We conducted a descriptive cost-evaluation analysis using data from Oslo University Hospital and literature to compare three different intravitreal drugs for DME: bevacizumab, aflibercept and dexamethasone. Stratification of patients into ‘Naive’ or ‘Switch’ group was based on treatment history. We estimated the costs from healthcare and ‘extended’ healthcare perspectives. Sensitivity analysis evaluated the impact of various parameters. Results The average injections per patient per year for the Naive group (bevacizumab), Switch group (aflibercept) and dexamethasone were 9.5, 9.1 and 3.0 respectively. From a healthcare perspective, the 1-year costs for the Naive group were 15% lower (bevacizumab, €3619), and for the Switch group, 23% higher (aflibercept, €5226) compared with dexamethasone (€4252). The ‘extended’ healthcare perspective showed the cost per patient per year for bevacizumab remained nominally lower in the Naive group, while dexamethasone remained lower for the Switch group (€5116 for dexamethasone, compared to €4987 for bevacizumab and €6537 for aflibercept). Conclusions From a primary healthcare perspective, the dexamethasone as a first-line DME treatment may increase economic costs in settings where bevacizumab is used off-label. Treating resistant DMEwith dexamethasone may reduce the costs and treatment burden compared with switching to aflibercept.

PurposeTo investigate the effect of polyquaternium-1 (PQ)-preserved and benzalkonium chloride (BAK)-preserved travoprost eye drops on viability of primary human conjunctival goblet cell (GC) cultures and on secretion of mucin and cytokines. Furthermore, to evaluate the physicochemical properties of the branded travoprost eye drop Travatan® and available generics.MethodsThe effect of travoprost eye drops was evaluated on GC cultures. Cell viability was assessed through lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin secretion was evaluated by immunohistochemical staining. Secretion of interleukin (IL)-6 and IL-8 was measured using BD Cytometric Bead Arrays. pH, viscosity, droplet mass, osmolality and surface tension were measured for all included eye drops.ResultsIn the LDH assay, BAK travoprost caused significant GC loss after 2 hrs of incubation compared to the control. PQ travoprost caused no GC loss at any time point. Both PQ- and BAK travoprost caused secretion of mucin to the cytoplasma. No difference in IL-6 and IL-8 secretion was identified compared to controls. The pH values for the generics were lower (pH 6.0) than the pH value for Travatan (pH 6.7; p ConclusionBAK travoprost caused GC loss, indicating that PQ preservation may be preferable in treatment of glaucoma. Furthermore, physicochemical properties of branded and generic travoprost eye drops can not be assumed to be identical.

To examine the physicochemical properties of five preservative-free (PF) 0.005% latanoprost ophthalmic products; MonoprostThe pH value, osmolality, and surface tension were examined. Cell survival was analyzed using lactate dehydrogenase and tetrazolium dye colorimetric assays. Mucin production was analyzed with immunohistochemical staining.MonoprostSignificant differences in pH value, osmolality, and surface tension were observed. However, this did not affect the viability of the goblet cells or the release of mucin. Clinical studies are required to evaluate the long-term effects of use on efficacy and safety.

Purpose To clarify how early in the development of diabetic retinopathy (DR) can oxygen (O2 ) saturation changes be detected. Methods Retinal oximetry was performed in a cross-sectional study, involving 14- to 30-year-old individuals: 185 with type 1 diabetes (T1D) and 94 controls. The subjects were divided into four groups according to the grade of DR. One-way ANOVA and post hoc tests were used to test for differences in the mean O2 saturations between the groups. Results Fifty-eight (31 %) of the T1D patients had nonproliferative DR. There was no significant difference in O2 saturations between controls and T1D patients with no DR. Arteriolar and venular O2 saturations in T1D patients were significantly higher in moderate/severe DR than in no DR (p = 0.009 and p > 0.001), while venular O2 saturation was significantly higher in mild DR than in no DR (p = 0.013). Conclusion Increase in venular O2 saturation could not be detected before mild retinopathy had developed, and the retinal O2 saturation increase was measurable on the venular side first. Our results suggest that the increase in O2 saturation is likely a consequence of DR.

Background: Non-invasive diagnostic technologies in ophthalmology have substantially transformed contemporary clinical practice. Intraoperative optical coherence tomography (iOCT) systems have recently been used for various surgical interventions, including the treatment of full-thickness macular holes (FTMHs). Materials and Methods: We conducted a systematic review on the use of iOCT and its possible benefits in the management of FTMHs, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, were assessed for all included articles. Results: 1131 articles were initially extracted, out of which 694 articles were obtained after duplicates were removed and their abstracts screened. A total of 65 articles was included for full-text review. Finally, 17 articles remained that fulfilled the inclusion criteria. Conclusions: Even though there is just a small number of studies with solid results, the use of iOCT in FTMH surgery may be a helpful tool for both novice and experienced surgeons planning and managing difficult cases. Additionally, it could be used for teaching reasons and for exploring novel surgical techniques.

Degenerative disorders of the retina (including age-related macular degeneration), which originate primarily at or within the retinal pigmented epithelial (RPE) layer, lead to a progressive disorganization of the retinal anatomy and the deterioration of visual function. The substitution of damaged RPE cells (RPEs) with in vitro cultured RPE cells using a subretinal cell carrier has shown potential for re-establishing the anatomical structure of the outer retinal layers and is, therefore, being further studied. Here, we present the principles of a surgical technique that allows for the effective subretinal transplantation of a cell carrier with cultivated RPEs into minipigs. The surgeries were performed under general anesthesia and included a standard lens-sparing three-port pars plana vitrectomy (PPV), subretinal application of a balanced salt solution (BSS), a 2.7 mm retinotomy, implantation of a nanofibrous cell carrier into the subretinal space through an additional 3.0 mm sclerotomy, fluid-air exchange (FAX), silicone oil tamponade, and closure of all the sclerotomies. This surgical approach was used in 29 surgeries (18 animals) over the past 8 years with a success rate of 93.1%. Anatomic verification of the surgical placement was carried out using in vivo fundus imaging (fundus photography and optical coherence tomography). The recommended surgical steps for the subretinal implantation of RPEs on a carrier in minipig eyes can be used in future preclinical studies using large-eye animal models.

PurposeThis study aimed to describe the effectiveness and evaluate the anatomical and functional results of surgery for macular pucker (MP) peel using a 25-gauge pars plana vitrectomy (PPV) cutter without forceps.MethodsThis study assessed a prospective consecutive case series of 14 eyes of 14 patients who underwent 25-gauge PPV for MP. The surgical procedure was performed using the new peeling technique. The edge of the membrane was engaged at the opening of the cutter by gradually increasing the vacuum. The peeling process was finished by holding a stable vacuum or regrasping the membrane in the same manner.ResultsThe study included six women and eight men patients with a mean age of 72.3 (range 59–84) years. MP peel was achieved in all cases without the need for microforceps. Patients were followed for at least 6 months. Visual acuity and retinal thickness were obtained 6 months after the surgery. Best corrected visual acuity improved from a mean pre-operative 0.6 on a logMAR scale to post-operative 0.23 (P < 0.001). Mean pre-operative Central Retinal Thickness was significantly reduced from 489.7 to 377.6 μm post-operatively (P < 0.001). There were no intra- or post-operative complications.ConclusionMP peel with a 25-gauge vitrectomy probe could be an alternative simple and safe technique. The technique does not require extra instrumentation. It results in anatomic and functional improvement in all cases.

The retinal pigment epithelium (RPE) forms an important cellular monolayer, which contributes to the normal physiology of the eye. Damage to the RPE leads to the development of degenerative diseases, such as age-related macular degeneration (AMD). Apart from acting as a physical barrier between the retina and choroidal blood vessels, the RPE is crucial in maintaining photoreceptor (PR) and visual functions. Current clinical intervention to treat early stages of AMD includes stem cell-derived RPE transplantation, which is still in its early stages of evolution. Therefore, it becomes essential to derive RPEs which are functional and exhibit features as observed in native human RPE cells. The conventional strategy is to use the knowledge obtained from developmental studies using various animal models and stem cell-based exploratory studies to understand RPE biogenies and developmental trajectory. This article emphasises such studies and aims to present a comprehensive understanding of the basic biology, including the genetics and molecular pathways of RPE development. It encompasses basic developmental biology and stem cell-based developmental studies to uncover RPE differentiation. Knowledge of the in utero developmental cues provides an inclusive methodology required for deriving RPEs using stem cells.

Synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy is a non-destructive and chemically sensitive technique for the rapid detection of changes in the different components of the cell’s biomacromolecular profile. Reactive oxygen species and oxidative stress may cause damage to the DNA, RNA, and proteins in the retinal pigment epithelium (RPE), which can further lead to age-related macular degeneration (AMD) and visual loss in the elderly. In this study, human primary RPEs (hRPEs) were used to study AMD pathogenesis by using an established in vitro cellular model of the disease. Autophagy—a mechanism of intracellular degradation, which is altered during AMD, was studied in the hRPEs by using the autophagy inducer rapamycin and treated with the autophagy inhibitor bafilomycin A1. In addition, oxidative stress was induced by the hydrogen peroxide (H2O2) treatment of hRPEs. By using SR-FTIR microspectroscopy and multivariate analyses, the changes in the phosphate groups of nucleic acids, Amide I and II of the proteins, the carbonyl groups, and the lipid status in the hRPEs showed a significantly different pattern under oxidative stress/autophagy induction and inhibition. This biomolecular fingerprint can be evaluated in future drug discovery studies affecting autophagy and oxidative stress in AMD.

Hanna Haave,1,&ast; Beáta Éva Petrovski,1,&ast; Micha&lstrok; Zaj&aogon;c,2 Xhevat Lumi,3 Wassiliki Melekidou,4 Lyubomyr Lytvynchuk,4,5 Andrii Ruban,6 Ljubo Znaor,7,8 Jerzy Nawrocki,2 Zofia Anna Nawrocka,2,&ast; Goran Petrovski1,9,&ast; 1Department of Ophthalmology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; 2Ophthalmic Clinic “Jasne Blonia”, Lodz, Poland; 3Eye Hospital, University Medical Centre, Ljubljana, Slovenia; 4Department of Ophthalmology, Justus Liebig University, University Hospital Giessen and Marburg GmbH, Giessen, Germany; 5Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria; 6Center of Clinical Ophthalmology, Kyiv, Ukraine; 7Department of Ophthalmology, University of Split School of Medicine, Split, Croatia; 8Department of Ophthalmology, University Hospital Centre, Split, Croatia; 9Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Oslo, Norway&ast;These authors contributed equally to this workCorrespondence: Goran Petrovski, Center for Eye Research, Department of Ophthalmology, Oslo University Hospital, Kirkeveien 166, Oslo, 0450, Norway, Tel +47 2301 5163, Email goran.petrovski@medisin.uio.noPurpose: To analyze the functional and anatomical parameters of lamellar macular hole (LMH) surgery with internal limiting membrane peeling and determine which surgical technique provides the best visual outcome.Methods: This is a retrospective multicenter cross-sectional study on patients who underwent pars plana vitrectomy (PPV) for LMH with or without combined phaco-vitrectomy, as well as gas-, air- or BSS-tamponade. Pre- and postoperative examination included best corrected visual acuity (BCVA) measurements for functional comparison and optical coherence tomography (OCT) scans to determine the contributing anatomical parameters.Results: A total of 66 consecutive patients were included (age: 71.79 ± 8.52 years), of which 47 (71.2%) were diagnosed as tractional type LMH, and 19 patients (28.8%) as degenerative type. An epiretinal membrane (ERM) was present in 63 of the patients (95.5%), LMH-associated epiretinal proliferation (LHEP) was present in 19 patients (28.8%), and 16 patients (24.2%) had concomitant ERM and LHEP. In the group of tractional LMH, the mean central foveal thickness (CFT) was 81.1% thicker (P < 0.05) than in the degenerative group. Thirty-one patients (47.0%) underwent a combined phaco-vitrectomy procedure, while the rest underwent 23G, 25G or 27G PPV. Seventeen of the 66 patients received gas-tamponade (25.7%)-either SF6 or C3F8, 26 received air-tamponade (39.4%), while the remaining 23 patients received balanced salt solution (BSS)-tamponade (34.9%) during vitrectomy. The total BCVA showed significant improvement postoperatively (p < 0.001) and accordingly in the following groups: tractional LMH type (p < 0.001), degenerative type (p < 0.001), simple PPV (p < 0.001), phaco-vitrectomy (p < 0.001), BSS injection (p < 0.01), gas-tamponade (p < 0.05). None of the patients included in the study developed a full thickness macular hole postoperatively.Conclusion: PPV provided a high success rate and functional improvement for treating LMH for both tractional and degenerative types, as well as combined phaco-vitrectomy treatment when cataract was present.Keywords: lamellar macular hole, surgical outcomes, tractional, degenerative, BCVA, OCT

Purpose Dysfunction of the retinal pigment epithelium (RPE) causes numerous forms of retinal degeneration. RPE replacement is a modern option to save vision. We aimed to test the results of transplanting cultured RPEs on biocompatible membranes. Methods We cultivated porcine primary RPE cells isolated from cadaver eyes from the slaughterhouse on two types of membranes: commercial polyester scaffolds Transwell (Corning Inc., Kenneburg, ME, USA) with 0.4 µm pore size and prepared Poly (L-lactide-co-DL-lactide) (PDLLA) nanofibrous membranes with an average pore size of 0.4 µm. Results Five types of assays were used for the analysis: immunocytochemistry (ICC), phagocytosis assay, Western blotting, real-time qPCR (RT-qPCR) and electron microscopy. RT-qPCR demonstrated that RPEs cultured on nanofibrous membranes have higher expressions of BEST1 (bestrophin 1), RLBP1 (retinaldehyde-binding protein 1), RPE65 (retinal pigment epithelium-specific 65 kDa protein), PAX6 (transcription factor PAX6), SOX9 (transcription factor SOX9), DCT (dopachrome tautomerase) and MITF (microphthalmia-associated transcription factor). ICC of the RPEs cultured on nanofibrous membranes showed more intensive staining of markers such as BEST1, MCT1 (monocarboxylate transporter 1), Na+ /K+ ATPase, RPE65 and acetylated tubulin in comparison with commercial ones. Additionally, the absence of α-SMA proved the stability of the RPE polarization state and the absence of epithelial-to-mesenchymal transition. RPE possessed high phagocytic activity. Electron microscopy of both membranes confirmed a confluent layer of RPE cells and their genuine morphological structure, which was comparable to native RPEs. Conclusions Retinal pigment epitheliums cultured on polylactide nanofibrous membranes improved the final quality of the cell product by having better maturation and long-term survival of the RPE monolayer compared to those cultured on commercial polyester scaffolds. PDLLA-cultured RPEs are a plausible source for the replacement of non-functioning RPEs during cell therapy.

Context Idiopathic type 1 diabetes is characterized by the absence of autoantibodies and the underlying mechanisms are not clear. Objective We aimed to study the epidemiology, describe the clinical characteristics, and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes. Methods This was a prospective study of type 1 diabetes patients attending Sidra Medicine from 2018 to 2020. Autoantibodies (GAD65, IAA, IA-2A, and ZnT8) were measured and genetic testing was undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes were compared with patients with autoimmune type 1 diabetes. Results Of 1157 patients with type 1 diabetes, 63 were antibody-negative. Upon genome sequencing, 4 had maturity onset diabetes of the young (MODY), 2 had Wolfram syndrome, 1 had H syndrome, and 3 had variants of uncertain significance in MODY genes; 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10 to 14 years. C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average body mass index was in the normal range and 33% of the patients had a history of diabetic ketoacidosis (DKA). Conclusion Four percent of the children had idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the 2 groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is unknown but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

Purpose To determine the contribution of retinal vessel density (VD), central retinal vessel diameter and retinal oxygen (O2) saturation independently of other known risk factors in the development of non-proliferative diabetic retinopathy (NPDR). Methods Macular optical coherence tomography angiography (OCTA), central retinal artery/vein equivalent diameter (CRAE/CRVE) measurements and retinal oximetry were performed in a cross-sectional study of 166 eyes from 166 individuals with type 1 diabetes (T1D) aged 14–30 years. Multiple logistic regression analysis was used to investigate whether O2 saturation, retinal vessel diameters and vessel density in the deep capillary plexus (VD-DCP) were associated with NPDR, when adjusting for known risk factors. The individuals were allocated to one group without and one group with NPDR. Results Multiple logistic regression analysis showed that age (OR = 1.25, 95% CI: 1.04–1.49) and AV-difference in O2 saturation (OR = 0.85, 95% CI 0.77–0.93) were significantly associated with NPDR. Conclusion Our findings suggest that age and lower AV-O2 saturation difference contribute to explaining the grade of NPDR independently of other well-known risk factors. Reduced delivery of O2 to the retinal tissue is associated with the development of NPDR in young patients with T1D and should be given appropriate weight in the risk stratification at early stages of the disease.

Introduction: The COVID-19 pandemic forced health authorities to issue restrictive measures on daily activities from March 12th to June 15th, 2020 (‘lockdown’) in Qatar, which may have influenced the glycemic control in patients with type 1 diabetes (T1D). The aims of the study was to evaluate glycemic control between Multiple Daily Injections (MDI) and Hybrid Closed Loop (HCL) system in children and adolescent with T1D during the lockdown. Methods: This single-center analysis included 168 patients with T1D, using MDI or HCL system MiniMed 670G (Medtronic, Northridge, USA) at least 3 months before the study. Glycemic control from face-to-face visits, three months before lockdown were analyzed and compared to face to face or remote visits during the lockdown of 3 months. Data was collected through the electronic medical record system and reports generated by Carelink Therapy Management Software. HbA1c, glucose and insulin data were analyzed before and 3 months after restrictions. Results: Patients were analyzed in two groups: 1) 92 patients (age 12.4±3.1 years, female:51) on MDI and 2) 76 patients (age 11.2±2.6 years, female:36) HCL system. HbA1c in patients on MDI increased from 8.3±1.5% (67±16.4 mmol/mol) before lockdown to 8.9±1.7% (74±18.6 mmol/mol) during the lockdown, compared to patients on HCL system, where HbA1c remained stable (7.0±0.9% (53±9.8 mmol/mol) to 7.1±1.2% (54±13.1mmol/mol) respectively). No significant difference on DKA events were found in MDI group, before and after lockdown, while no DKA was noted in HCL group during the study. No severe hypoglycemia was observed in both groups. Remote visits were 54% in patients on HCL system, compared to 38% in patients on MDI during the lockdown. Conclusion: Children and adolescents using HCL system maintained stabile glycemic control during the lockdown compared to patient on MDI, where the glycemic control deteriorated. Disclosure G. Petrovski: None. J. Campbell: None. K. Hussain: None. Alkhalaf and consultants/educators: n/a.

Purpose: To explore the ability of optical coherence tomography (OCT) to noninvasively estimate pulsatile and static intracranial pressure (ICP). Methods: An OCT examination was performed in patients who underwent continuous overnightmonitoring of the pulsatile and static ICP for diagnostic purpose. We included two patient groups, patients with idiopathic intracranial hypertension (IIH ; n = 20) and patients with no verified cerebrospinal fluid disturbances (reference ; n = 12). Several OCT parameters were acquired using spectral-domain OCT (RS-3000 Advance ; NIDEK, Singapore). The ICPmeasurementswere obtained using a parenchymal sensor (Codman ICP MicroSensor ; Johnson & Johnson, Raynham, MA, USA). The pulsatile ICP was determined as the mean ICPwave amplitude (MWA), and the static ICPwas determined as the mean ICP. Results: The peripapillary Bruch's membrane angle (pBA) and the optic nerve head height (ONHH) differed between the IIH and reference groups and correlated with both MWA and mean ICP. Both OCT parameters predicted elevated MWA. Area under the curve and cutoffs were 0.82 (95% confidence interval [CI], 0.66-0.98) and -0.65 degrees (sensitivity/specificity ; 0.75/0.92) for pBA and 0.84 (95% CI, 0.70-0.99) and 405 mu m (0.88/0.67) for ONHH. Adjusting for age and body mass index resulted in nonsignificant predictive values for mean ICP, whereas the predictive value for MWA remained significant. Conclusions: This study provides evidence that the OCT parameters pBA and ONHH noninvasively can predict elevated pulsatile ICP, represented by the MWA. Translational Relevance: OCT shows promise as a method for noninvasive estimation of ICP.

The present organization of the healthcare services is very vulnerable to the Coronavirus disease 19 (COVID- 19) outbreak. There are several unanswered questions: can the disease be transmitted asymptomatically? ; what happens after the 14- day incubation period? ; should the quarantined subjects without symptoms for 6–8 days be released? ; should release from quarantine be allowed if the repeated test(s) are positive? ; does COVID-19 affect or manifest itself in the eye or the tear fluid? These are but a few questions related to the COVID-19 pandemic. In principle, a working cycle equal to the incubation period or cycle of any infectious disease type can be implemented in such a way for any upcoming epidemic or pandemic worldwide. This would allow half of the healthcare staff remaining unexposed or passing the incubation time in isolation, while the other half keeping the frontline and the healthcare services from collapse. The provided plan will indeed remain under the scrutiny of time and societal development in the future, but as of today, this may be one of the few rational reorganization and survival methods for healthcare providers.

To assess the efficacy of dynamic intraoperative spectral-domain optical coherence tomography (iSD-OCT) imaging for inverted internal limiting membrane (ILM) flap technique (IILMFT) in large macular hole (MH) surgery. Prospective, non-randomized, observational study was conducted on 8 eyes of 7 patients with large, chronic and recurrent MHs, which were treated by pars plana vitrectomy (PPV) with IILMFT. All patients underwent standard pre- and postoperative examination. The iSD-OCT imaging was performed using microscope integrated systems before, during, and after ILM peeling. The iSD-OCT data were post-processed using graphic software and reviewed for tissue behavior and instruments position. The real-time iSD-OCT-assisted IILMFT allowed for real-time imaging of the entire surgery with visualization of the MH, vitreoretinal instruments, and all steps of inverted ILM flap formation. In spite of shadowing created by the steel instruments, it was possible to follow and control the distance between the instrument tips and retinal layers. Dynamic imaging of the surgical maneuvers including ILM peeling and mechanical apposition of MH edges revealed the iatrogenic impact on the retina (depression and appearance of hyporeflective zones). iSD-OCT imaging could confirm the proper position of the inverted ILM flap at the very end of the surgery after fluid-air exchange. iSD-OCT imaging is an effective tool for learning and performing a well-controlled and safe inverted ILM flap technique in patients with large MH. Clinical significance of the structural iSD-OCT findings has to be further studied.

Age-related macular degeneration (AMD) is a multi-factorial disease that is the leading cause of irreversible and severe vision loss in the developed countries. It has been suggested that the pathogenesis of dry AMD involves impaired protein degradation in retinal pigment epithelial cells (RPE). RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, DNA and lipids and evoke tissue deterioration during the aging process. The ubiquitin-proteasome pathway and the lysosomal/autophagosomal pathway are the two major proteolytic systems in eukaryotic cells. NRF-2 (nuclear factor-erythroid 2-related factor-2) and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) are master transcription factors in the regulation of cellular detoxification. We investigated the role of NRF-2 and PGC-1α in the regulation of RPE cell structure and function by using global double knockout (dKO) mice. The NRF-2/PGC-1α dKO mice exhibited significant age-dependent RPE degeneration, accumulation of the oxidative stress marker, 4-HNE (4-hydroxynonenal), the endoplasmic reticulum stress markers GRP78 (glucose-regulated protein 78) and ATF4 (activating transcription factor 4), and damaged mitochondria. Moreover, levels of protein ubiquitination and autophagy markers p62/SQSTM1 (sequestosome 1), Beclin-1 and LC3B (microtubule associated protein 1 light chain 3 beta) were significantly increased together with the Iba-1 (ionized calcium binding adaptor molecule 1) mononuclear phagocyte marker and an enlargement of RPE size. These histopathological changes of RPE were accompanied by photoreceptor dysmorphology and vision loss as revealed by electroretinography. Consequently, these novel findings suggest that the NRF-2/PGC-1α dKO mouse is a valuable model for investigating the role of proteasomal and autophagy clearance in the RPE and in the development of dry AMD. Keywords: Aging, Autophagy, Degeneration, Oxidative stress, Protein aggregation, Proteasome

Background Type 1 diabetes is the most common type of diabetes mellitus (DM) in children. It can be sporadic in onset or cluster in families, which comprises parent-offspring and sib-pair subgroups. The risk of developing DM in first-degree relatives of affected individuals is 8–15 fold higher. There is limited data about familial DM from the Gulf region. This study aims to describe the clinical, biochemical and genetic characteristics of sib-pair familial type 1 diabetes in Qatar. Methods Every child with DM following up at Sidra Medicine was recruited. Data was collected regarding clinical features, family history, type 1 diabetes autoantibodies and whole genome sequencing was performed. Genetic analysis for MODY genes and HLA association analysis was conducted. Results 44 families with sib-pair familial diabetes were identified. Of these, 2 families had 4 affected siblings and 5 families had 3 affected siblings. The majority are of Qatari ethnicity and the most common autoantibody was GAD65. The most common age of onset in the proband was 5–9 years while it was 10–14 years in subsequent siblings. The occurrence of DKA & HbA1c levels were lower in the second affected sibling. No relevant MODY gene variants were found. HLA analysis found 15 variants in at least 50% of the subjects. Most common were HLA-F*01*01*01G, HLA- DPA1*01*03*01G, HLA- DRB3*02*02*01G, HLA- E*01*01*01G & DRB4*03*01N. Conclusions The prevalence of sib-pair diabetes is 3.64%. The second affected siblings were older. MODY is unlikely and Class I and II HLA genes was present in sib-pair diabetes.