Eye Research Research Articles

Future Vision 2020 and Beyond-5 Critical Trends in Eye Research.

Ophthalmology has been at the forefront of many innovations in basic science and clinical research. The randomized prospective multicenter clinical trial, comparative clinical trials, the bench to beside development of diagnostic and therapeutic devices, the powerful combination of biostatistics and epidemiology, gene therapy, cell-based therapy, stem cell therapy, regenerative medicine, artificial intelligence, and the development of personalized molecular medicine continue to propel us forward. This article summarizes several critical trends in eye research.Innovative translational research continues to bring new solutions to blinding retinal diseases. The discovery of the genetic code presaged a day when the development of molecular tools and understanding of the basis of disease would lead not only to disease management but potentially lifelong cure. After decades of investigation, gene therapy is now a reality for a single autosomal recessive bi-allelic disease, Lebers Congenital Amaurosis. Its success has paved the way for a myriad of conditions once thought to be untreatable. In parallel, the progress to utilize pluripotential stem cells, immunomodulation, computational biology, and continued investigation into the fundamental mechanisms of cell and molecular biology is breathtaking in its rapidity. The next decade is likely to be the most exciting in the history of medicine. It will be essential that research progresses in a meticulously thoughtful, ethical, and collaborative process that safeguards the trust of our work and that of the society we serve.Presented as the International Award Lecture, Asia-Pacific Vitreoretinal Society meeting, November 2019, Shanghai China.

Effects of diabetes duration and HgA1C level on corneal endothelial morphology.

The aim of this study is to investigate the effects of the HbA1c level and the duration of diabetes mellitus on the corneal endothelium morphology and to compare between healthy individuals and diabetes mellitus patients with non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Ninety patients who applied to the Health Sciences University Ulucanlar Eye Training and Research Hospital between January 2016 and January 2017 were included in this prospective randomized study. In the study, 45 diabetes mellitus patients and 45 healthy individuals were evaluated. The diabetes patients were compared in terms of HbA1c level, diabetes mellitus duration, corneal endothelial cell density, coefficient of variation, standard deviation, and hexagonality with healthy control group. A statistically significant difference was found in the endothelial cell densitometer, coefficient of variation, and standard deviation measurements between the diabetes mellitus patients and the control (healthy) group. But, there was no statistically significant difference between 6A (hexagonality) and central corneal thickness measurements. There was a negative correlation between HbA1c levels and diabetes mellitus times and endothelial cell densitometer values in the patients with diabetes mellitus diagnosis and standard deviation values in the positive direction. There was a statistically significant difference between diabetes mellitus patients with the diagnosis of non-proliferative diabetic retinopathy and proliferative diabetic retinopathy in the endothelial cell densitometer and standard deviation values. But there was not any statistically significant difference between coefficient of variation, 6A, and central corneal thickness values. The endothelial cell densitometer in diabetes mellitus patients with retinopathy is lower than that in healthy individuals. There is a negative correlation between retinopathy severity and corneal endothelial cell density. Diabetes affects negatively not only vascular tissues but also avascular cornea.

Statement of Retraction: Inhibitory Effects of Arresten on bFGF-Induced Proliferation, Migration, and Matrix Metalloproteinase-2 Activation in Mouse Retinal Endothelial Cells

"Statement of Retraction: Inhibitory Effects of Arresten on bFGF-Induced Proliferation, Migration, and Matrix Metalloproteinase-2 Activation in Mouse Retinal Endothelial Cells." Current Eye Research, 45(6), p. 759This article refers to:RETRACTED ARTICLE: Inhibitory Effects of Arresten on bFGF-Induced Proliferation, Migration, and Matrix Metalloproteinase-2 Activation in Mouse Retinal Endothelial Cells

Phototherapeutic Keratectomy in Macular and Granular Dystrophy: Two-year Results

ABSTRACT Purpose To evaluate two-year outcomes of phototherapeutic keratectomy in granular and macular dystrophy and to investigate the effects of dystrophy type on results. Methods Sixty-three patients who underwent phototherapeutic keratectomy (PTK) for granular and macular dystrophy in the cornea funit of the University of Health Sciences Beyoglu Eye Research and Training Hospital were evaluated retrospectively. Patients under 18 years of age, patients with a follow-up period of less than 24 months, and patients who had previously undergone corneal surgery or excimer laser treatment were excluded from the study. Treatment values (ablation depth, optical zone, mitomycin-C (MMC) application time) and complications during and after treatment were recorded. Patients who had a decrease of two or more lines in their BCVA and those with recurrent or increased corneal opacities were considered to have severe recurrences. Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were recorded preoperatively and postoperatively at the 12th and 24th months. The values obtained before and after the PTK were compared with statistical methods. Results A total of 41 eyes (27 with granular dystrophy and 14 with macular dystrophy) were included in this study. There were no statistically significant differences between patients with granular dystrophy and macular dystrophy in terms of preoperative UCVA and BCVA, MMC application time, and follow-up period (p > .05). The mean age of patients with macular dystrophy was statistically smaller than that of patients with granular dystrophy (p = .04). The amount of ablation applied to macular dystrophy was statistically higher than for granular dystrophy (p = .03). The mean UCVA and BCVA showed statistically significant improvements at the 24th postoperative month (p < .5). There was no statistically significant difference between the UCVA and BCVA values of the patients with granular and macular dystrophy at the 12th and 24th months after the procedure. No recurrence was observed in any patient after 24 months. However, when the follow-up continued, severe recurrence was encountered in 2 patients with macular dystrophy at 26th and 40th months. Re-treatment procedures were needed in these two patients who had severe recurrence. Conclusions Phototherapeutic keratectomy is an effective and safe option for treatment in both granular and macular corneal dystrophy. Recurrence is a more common problem in patients with macular dystrophy, and recurrent therapies or keratoplasty methods are needed more frequently.

Accelerated corneal crosslinking in children with keratoconus: 5-year results and comparison of 2 protocols

To evaluate long-term clinical results of 2 different accelerated corneal crosslinking (CXL) protocols in pediatric patients with keratoconus. Beyoğlu Eye Training and Research Hospital, Istanbul, Turkey. Retrospective case-control study. Patients who were younger than 18 years were included in the study. Group 1 received 4 minutes of illumination at 30 mW/cm, and Group 2 received 5 minutes of illumination at 18 mW/cm. Uncorrected and corrected distance visual acuities, manifest refraction, corneal topographic parameters, and corneal higher-order aberrations (HOAs) were evaluated at baseline and during 1-, 3-, and 5-year follow-up visits. A total of 143 eyes from 86 patients were included in the study. There were 30 eyes in Group 1 and 113 eyes in Group 2. The mean follow-up time was 4.15 ± 0.99 years. Mean keratometry (K) and/or maximum K progressed ≥1.00 diopter (D) in 7 eyes (23.3%) in Group 1 and 19 eyes (16.8%) in Group 2 (P = .411). Mean K and/or maximum K decreased ≥2.00 D in 2 eyes (6.7%) in Group 1 and 24 eyes (21.2%) in Group 2 (P = .06). In Group 1, there were no statistically significant differences in topographic parameters during follow-up. In Group 2, there was a statistically significant reduction in total HOA and coma during the 5-year visit when compared with the preoperative visit (P = .005 and P = .045, respectively). Accelerated CXL is beneficial in terms of halting the progression of keratoconus in pediatric patients throughout 5 years of follow-up examinations. An increased irradiance with a reduced application time reduces the topographic effects of CXL.

Correspondence.

*Smt Kanuri Santhamma Center for Vitreo Retinal Diseases †Center for Ocular Regeneration (CORE), L. V. Prasad Eye Institute, Hyderabad, India Support provided by the Hyderabad Eye Research Foundation, Hyderabad, India. The funders had no role in the preparation, review, or approval of the manuscript. None of the authors has any financial/conflicting interests to disclose.

RETRACTED ARTICLE: Detecting disorders in retinal images using machine learning techniques

The importance of the research is to detect disorders in retinal images using machine learning techniques. Eyes play an important role in our day to day life and are the most valuable gift we have in retinal eye research, the retinal vessel parameters and accurate AVR measurement is consider as the important issues in image processing techniques. Diseases like glaucoma, exudates, and diabetic retinopathy can be observed in earlier stages by using retinal images. Diabetic retinopathy also known as diabetic eye disease which affects up to 80% of all patients who have diabetes eventually leads to blindness. To diagnosis the various disorder in earlier stage by using the retinal image based on the methodology of image processing and machine learning techniques. The retinal image is used to detect the diabetes in early stages by evaluating all the retinal blood vessels together. The proposed novel algorithm known as multi-resolution curvelet Transform and normalized graph cut segmentation to detect the optic disc and blood vessels in the fundus images efficiently. In earlier stage of this research, the pre-processing of fundus image operation for image filtration and color contrast enhancement, and next is image segmentation for blood vessels achieved by image processing techniques such as thresholding, texture, and morphological operation and finally machine learning classification algorithm are executed using convolutional neural network. This construction results in a multi resolution, local, and directional image expansion using contour segments. Results indicate that neural network is better than the other techniques for vessels classification.

RETRACTED ARTICLE: Methamphetamine causes acute toxicity in the retina of Balb/c mice

Article title: Methamphetamine causes acute toxicity in the retina of Balb/c miceAuthors: Yanlai Zhang, Qi Li, Siyuan Guan & Hao LiJournal: Cutaneous and Ocular ToxicologyVolume/Issue: Published online 07 February 2020DOI: 10.1080/15569527.2020.1722153Publisher: Taylor & Francis Group, LLCWe, the Editors and Publishers of Cutaneous and Ocular Toxicology have retracted the following article: Yanlai Zhang, Qi Li, Siyuan Guan & Hao Li (2020) Methamphetamine causes acute toxicity in the retina of Balb/c mice, Cutaneous and Ocular Toxicology, 39:2, 83–88, DOI: 10.1080/15569527.2020.1722153The article is being retracted due to image manipulation and plagiarism.An investigation was conducted and two panels from Figure 2 A were found to be published in two other articles, also as Figure 2 A. What the Figure is said to represent varies by article, and thus the conclusions of the present article cannot be considered valid. Additionally, the authors were not able to provide any of the original images presented in this article for verification.The two other articles containing panels from Figure 2 include:Yang et al. (2015) Long-Term Systemic Treatment With Methamphetamine Causes Retinal Damage in CD1 Mice. International Journal of Toxicology, DOI: 10.1177/1091581818809356Zhang et al. (2019) Systemic administration with tetrahydrocannabinol causes retinal damage in BALB/c mice. Human & Experimental Toxicology, DOI: 10.1177/0960327119886037In addition, there is significant textual overlap with another article (Lee, 2020) that was submitted prior to that of Zhang et al. Lee et al. submitted their article to Experimental Eye Research on 03 October 2019, whereas Zhang et al submitted their article to Cutaneous and Ocular Toxicology on 13 November 2019. The full citation for (Lee, 2020) is as follows:Minsup Lee, Wendy Leskova, Randa S. Eshaq, and Norman R. Harris (2020) Acute changes in the retina and central retinal artery with methamphetamine, Experimental Eye Research; 193; DOI: 10.1016/j.exer.2020.107964Zhang et al. were unable to explain the image manipulation or the textual overlap and agree to a retraction.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”.

Effect of Optical Coherence Tomography Patterns on One-year Outcomes of Aflibercept Therapy for Diabetic Macular Edema.

To evaluate the outcomes of aflibercept based on different morphologic patterns on optical coherence tomography (OCT) for diabetic macular edema (DME). Observational study. Beyoglu Eye Training and Research Hospital, Turkey from February 2016 to March 2018. Records of 115 eyes of 115 patients who were treated with aflibercept for DME were reviewed. Eyes were classified based on OCT features as diffuse retinal thickening (DRT, n=37), cystoid macular edema (CME, n=40), and serous retinal detachment (SRD, n=38). Best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) at baseline and after three doses of aflibercept at months 3, 6, 12 were recorded. Primary outcome measures were the changes in BCVA and CST at follow-up visits compared with baseline. At month 3, mean BCVA was improved in all groups. Although the increase in BCVA at month 3 was significant in DRT and CME groups, it was not significant in SRD group (p=0.03, p<0.01, and p=0.22, respectively). At month 12, BCVA significantly improved compared to baseline values in DRT, CME, and SRD groups (p=0.01, p=0.01 and p<0.01, respectively). There was no significant difference between groups in terms of BCVA at baseline and months 3, 6, 12 (p=0.13, p=0.67, p=0.54, and p=0.28, respectively). Mean CST significantly decreased compared to baseline values at the end of month 12 (all p<0.01). Aflibercept therapy provided an improvement in visual acuity and decreased CST in different morphological DME types for one year. The number of injections that could achieve this efficacy was least in DRT group, and more injections were required in SRD group.

Validation of the Ocular Surface Disease Index Questionnaire for Chilean patients

Ocular Surface Disease Index (OSDI) is the most commonly used questionnaire worldwide to detect dry eye disease. Although it is massively used in clinical practice in Chile, its use has not been validated yet in the country. To develop a cultural adaptation and to validate the OSDI questionnaire for the Chilean population. For cultural adaptation, a translation, retro-translation and an expert panel review was carried out. The resulting questionnaire was applied to a pilot group of twelve participants and their comments were considered for the final questionnaire version. The final questionnaire was applied to a non-random sample of 200 patients aged 53 ± 17 years (75% women). Internal consistency and construct validity were evaluated by Cronbach's alpha and exploratory factor analysis respectively. According to the OSDI score, 81% of respondents had dry eye (55% severe). Reliability was 0.91 and factor analysis resulted in three factors explaining 75.4% of the total variance. The OSDI questionnaire version obtained in this study demonstrated excellent internal consistency values and adequate construct validity making it applicable to clinical practice and dry eye research.

MicroRNAs in Vascular Eye Diseases.

Since the discovery of the first microRNA (miRNA) decades ago, studies of miRNA biology have expanded in many biomedical research fields, including eye research. The critical roles of miRNAs in normal development and diseases have made miRNAs useful biomarkers or molecular targets for potential therapeutics. In the eye, ocular neovascularization (NV) is a leading cause of blindness in multiple vascular eye diseases. Current anti-angiogenic therapies, such as anti-vascular endothelial growth factor (VEGF) treatment, have their limitations, indicating the need for investigating new targets. Recent studies established the roles of various miRNAs in the regulation of pathological ocular NV, suggesting miRNAs as both biomarkers and therapeutic targets in vascular eye diseases. This review summarizes the biogenesis of miRNAs, and their functions in the normal development and diseases of the eye, with a focus on clinical and experimental retinopathies in both human and animal models. Discovery of novel targets involving miRNAs in vascular eye diseases will provide insights for developing new treatments to counter ocular NV.

Natural course of congenital corneoscleral cyst: 10-year follow-up.

A congenital corneoscleral cyst is a rare ocular condition that has been reported after either traumatic implantation of epithelium or abnormal embryological development. Authors report long term follow-up of the corneoscleral cyst with no evidence of progression over 10-years. A 12-year-old girl presented with a whitish lesion in her left eye noticed by her parents since birth. Her best-corrected visual acuity (BCVA) was 20/20 in both eyes with simple myopic refractive error of −3.00 DS in the right eye and −2.25 DS in the left eye. On examination, there was a thin-walled multiloculated scleral cyst of size 3 × 2 mm involving limbus at 9 o'clock with intrastromal corneal cyst 1.5 mm away from the limbus. There was clear fluid in cysts and overlying conjunctiva was mobile. The intracorneal cyst was 0.5 × 1 mm [Fig. 1a] with clear surrounding stroma. The rest of the ocular examination was normal. After 10-years the patient has BCVA 20/20 with refractive error of −4.00 DS in both eyes and there was no evidence of progression [Fig. 1b]. Anterior segment optical coherence tomography done on the last follow-up reconfirm the presence of a cyst in cornea and sclera with fine communication channels seen between the two cysts [Fig. 2].Figure 1: (a) Diffuse slit-lamp photograph showing scleral cyst at 9 o'clock (red arrow) and corneal cyst (yellow arrow) at presentation. (b) Diffuse slit-lamp photograph of the left eye showing scleral cyst at 9 o'clock (red arrow) with slit section passing through corneal cyst located in the deep stroma (yellow arrow) at follow-up after 10-yearsFigure 2: AS-OCT showing the location of cyst in the anterior sclera (white arrow) and intracorneal cyst in the posterior stroma (yellow arrow) with fine communication posteriorlyDiscussion Corneal cysts have been reported as purely corneal or with associated scleral involvement. Congenital corneoscleral cysts are rare and it has been postulated that entrapped epithelial cells in limbus during scleral development lead to the formation of a cyst.[1] The indications for surgical treatment are progressive increase in the size of cyst leading to poor vision, the involvement of visual axis or astigmatism.[2] However, incomplete excision of the cyst and simple aspiration is associated with a high risk of recurrence.[3] Spontaneous resolution of cyst has also been reported.[4] Keeping in view the smaller size and peripheral location of corneal cyst authors did not intervene surgically and preferred monitoring for progression. In this case, a 10-year follow-up suggests that not all cases progress and surgical intervention can be delayed in a small peripheral intracorneal cyst which is not affecting the visual axis. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Hyderabad Eye Research Foundation, Hyderabad. Conflicts of interest There are no conflicts of interest.

Rationale and Methodology of The PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study [PIONEER

To describe the rationale, design and methodology of a geographically-representative and population-based study investigating the epidemiology, impact, personal and economic burden of age-related eye diseases, declining visual and other sensory systems in Asians aged >60 years in Singapore.PIONEER (The PopulatION HEalth and Eye Disease PRofilE in Elderly Singaporeans Study) is currently a cross-sectional study targeting 3152 Chinese, Malay and Indian adults who are Singapore citizens or permanent residents aged 60 years and older living across Singapore. The study is intended to be longitudinal, with several waves of data planned to be collected in the future. The sampling frame consisted of 7000 names derived from age, gender and ethnicity-stratified random sampling of individuals >60 years. Selected individuals were invited via letters, home visits, and telephone calls for a clinical assessment at the Singapore Eye Research Institute. Individuals with limited mobility were examined in a custom-designed mobile eye clinic. Questionnaires were subsequently administered at participants’ homes by trained interviewers in their preferred language. A total of 3,299 participants (from East, West, North and South Singapore) were approached from December 2017 to November 2019. Of these, 953 (28.5%) were deemed ineligible. Out of 2,346 eligible participants, 904 (38.5%) refused, and 1,442 (61.5%) attended our clinical testing protocol, giving an initial response rate of 61.5%. Of these, 1,170 (81%) were cognitively able to complete the questionnaire assessment. The mean age±SD of our participants was 73.8±8.6 years; n=798 (55.3%) were female; and 828 (57.4%) were of Chinese ethnicity. The findings from this study will allow a deeper understanding of the risk factors and impact of aging in Asian populations, particularly in relation to the visual function and other functional system.

Relationship between mean macular thickness and visual acuity in diabetic patients

Objective The aim of the study was to correlate the relationship between optical coherence tomography (OCT) changes and visual acuity in patients with diabetic retinopathy (DR) compared with nondiabetic healthy persons. Patients and methods This study was done at Alforsan Eye Research Center, Assiut, Egypt. OCT was done at the center in the period from January 2018 to October 2018. This study was performed on 142 eyes of 71 adults who were divided into two groups. The first group was the diabetic group that included 102 eyes of 51 patients, whereas the second group was the nondiabetic group that included 40 eyes of 20 control. Results In this study, the mean macular thickness in normal individuals was (224.61 ± 8.8 μm). The authors found that the mean macular thickness of the diabetic patients included in this study was (327.9 ± 11.2 μm), which represents a statistically significant increase in thickness compared with the control (P Conclusion This study indicated that the CMT in OCT has a negative moderate correlation with visual acuity, which means that patients with decreased macular thickness have better visual acuity. The authors also reported a positive mild correlation between age in years and CMT, which means that increase in the age of patients was associated with an increase in CMT.

Treatment of Chalazian: a Comparative Cross-sectional Study

Introduction: Chalazion is a common eyelid margin disorder manifesting as granulomatous inflammation associated with meibomian gland lipids. There are three methods of treating chalazian: IntralesionalTriamcinolone Acetonide (0.1-0.3 ml of 40mg/ml), Incision and Curettage and Conservative Treatment (hot compression +lid hygiene + antibiotic ointment).Methods: Patients with chalazian presenting to the Outpatient Department (OPD) of the Lumbini Eye Institute and Research Center (LEIRC) from 15 March 2017 to 15 July 2017 were included in the study. They underwentany of the three procedures (Conservative Treatment or Triamcinolone Acetonide Injection or Incision and Curettage) according to their choice. We compared all three methods of treatment of chalazion on follow upvisit at 2 weeks, which was done to determine effectiveness in terms of reduction of size or complete resolution of the chalazia.Results: Out of 112 patients enrolled in study 65(58%) were females and 47(42%) were male with a male: female ratio of (0.7:1). The mean age of involvement was 25.7years (SD 10.3). At 2 weeks follow up there wascomplete resolution in incision and curettage (I and C) group 77 % (41/53) and in Triamcinolone Acetonide (TA) injection group 63 %( 20/32). Pearson’s correlations showed that I and C were superior to any other forms of intervention for any size of chalazian followed by intralesional injection of TA.Conclusion: Incision and Curettage remained the best choice for the treatment of chalazion followed by triamcinolone acetonide injection but may need multiple injections.

Proteomics and personalized medicine in eye research and ophthalmology

AbstractProteomics is a novel option to detect biomarkers and drugable targets of various eye diseases. It can be used in experimental studies to study pathological processes as well as to detect clinically meaningful biomarkers and end point. It can be performed by using different specimens ranging from non‐invasively obtained tear samples and impression cytologic specimens to biopsies and various types of cell samples. Tear samples reflects not only the state of ocular surface but also that of other ocular structures or systemic state of the human body. Biopsies of ocular tissues are targeted way to detect various biological processes involved in eye diseases and processes involved in them like Inflammation, wound healing and angiogenesis. These are vital processes involved in the defense mechanisms of the human body and pathogenesis of many eye diseases, thus having potential to be in the development on novel therapies for eye diseases. These mechanisms are also important factors in ocular surgeries e.g. corneal, vitreoretinal and glaucoma surgery and thus a way to improve their success. In the future, proteomic biomarkers have a great potential to be tools of personalized medicine in choosing the best therapeutic options for each individual patient and to improve the cost‐effectiveness of the health care.

Immunology and the elder eye

AbstractSeveral eye diseases occur more frequently in the elderly, such as age‐related macular degeneration (AMD), primary open angle glaucoma and intraocular melanoma. Inflammation has become an important player, and while in the past AMD was considered purely a vessel disease, it has become clear that macrophages and complement play an important role in the development of the leaky vessels. The function of macrophages changes when we age. As Makitie and Kivela had shown that macrophages have a prognostic value in uveal melanoma, we started to investigate the role of aging in the development of ocular tumors in a mouse model. Ly observed that depletion of macrophages had no effect in young mice, but prevented intraocular tumor growth in old mice. Maat, Bronkhorst and Brouwer showed that specific chromosomal abnormalities in a uveal melanoma are associated with prognosis, influx of macrophages and a high vessel density.While working on this, I learned about a patient with glaucoma who had the impression that her visual field had decreased when she had the flu. Around the same time, Dr Dong Feng Chen of the Schepens Eye Research Institute in Boston developed a murine glaucoma model. A Dutch PhD student, Dr Khanh Vu, set out to determine whether inflammation plays a role in glaucoma, and indeed, glaucomatous damage following high eye pressure increased through the induction of immune responses. High eye pressure led to influx of macrophages and T cells into the retina, and the induction of specific antibodies and T cell responses. The T cells are directed against heat shock proteins, which become expressed after trauma. Blocking T cell immune response limited the loss of retinal ganglion cells and axons in the mouse after glaucoma induction. The anti‐heat shock immune response did not develop when the mouse lacked a microbiome. Patients with glaucoma also showed anti‐heat shock protein antibodies and T cell responses.These data show that inflammation plays a role in several age‐related eye disease, including age‐related macular degeneration, uveal melanoma and glaucoma.Makitie T. et al. Tumor‐infiltrating macrophages (CD68+ cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci 2001; 42: 1414‐1421. Bronkhorst I.H. et al. Detection of M2 macrophages in uveal melanoma and relation with survival. Invest Ophtalmol Vis Sci 2011; 52: 643‐650. Doi: 10.1167/iovs.10‐5979. Ly L.V. et al. In aged mice, outgrowth of intraocular melanoma depends on proangiogenic.M2 type macrophages. J Immunol. 2010; 185: 3481‐3488. Chen H. et al. Commensal microflora‐induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun 2018; Aug 10;9(1): 3209. Doi: 10.1038/s41467‐018‐05681‐9

ESGCT 27th Annual Congress In collaboration with SETGyc Barcelona, Spain October 22–25, 2019 Abstracts

Xenotransplantation of transgenic porcine pancreatic islets offers a promising alternative source to circumvent current limitations posed by the scarcity of allogeneic donors. We have investigated the feasibility to generate tissue engineered SLA silenced islet cell clusters (ICC) to decrease xenogeneic immune responses Pancreatic islets single cell suspensions were generated by enzymatic digestion of porcine ICCs. Single cells were silenced for SLA expression by lentiviral vectors encoding for Nanoluciferase as reporter gene and for short hairpin RNAs targeting beta2-microglobulin or class II transactivator, respectively. SLA transcripts were evaluated by real-time PCR and protein levels by flow cytometry and fluorescence microscopy analyses. The effect of SLA silencing was evaluated in human T and NK cell cytotoxicity assays. SLA-silenced pancreatic beta-cells were then reassembled into ICCs in stirred bioreactors. SLA class I silencing reached a level of up to 84% and class II by up to 50% on pancreatic islet cell. Silencing SLA expression did not affect cell viability and the insulin-producing beta-cell phenotype. Xenogeneic T-cell immune responses (p < 0.05) as well as antibody-mediated cellular-dependent immune responses (p < 0.01) were significantly decreased. Silencing SLA class I expression did not increase susceptibility to NK-cell cytotoxicity. In stirred bioreactors, tissue engineered islets showing the typical 3D-structure and morphology of ICC were assembled from SLA-silenced pancreatic cell suspensions. These data shows the feasibility to generate low immunogenic porcine ICC from transgenic pigs after single cell engineering and post-transduction islet reassembling that might serve as a robust alternative to allogeneic pancreatic islet cell transplantation.

Neurokinin-1 Receptor Antagonism Ameliorates Dry Eye Disease by Inhibiting Antigen-Presenting Cell Maturation and T Helper 17 Cell Activation

Neuroinflammation plays an important role in the pathogenesis of ocular surface disease, including dry eye disease (DED), but little is known about the contribution of substance P (SP) to DED. In this study, we investigated the expression of SP at the ocular surface and evaluated its effect on maturation of antigen-presenting cells (APCs), the key cell component involved in the induction of type 17 helper T-cell (Th17) response in DED. The effect of topical blockade of SP signaling was further investigated using neurokinin-1 receptor (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results demonstrate that SP is constitutively expressed at the ocular surface, and trigeminal ganglion neurons are the major source of SP in DED. SP derived from trigeminal ganglion enhanced the expression of major histocompatibility complex class II maturation marker by bone marrow-derived dendritic cells, an effect that is abrogated by blockade of SP signaling using NK1R antagonist spantide. Finally, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of major histocompatibility complex class II, reduced Th17 cell activity, and ameliorated DED severity. These findings are of translational value, as they suggest that antagonizing NK1R-mediated SP signaling may be an effective strategy in suppressing Th17-mediated ocular surface disease.

Vertical rectus muscle union combined with lateral rectus plication for complete abducens nerve palsy.

The aim of this study was to report our postoperative results concerning the vertical rectus (VR) muscle union combined with lateral rectus (LR) plication for the treatment of large-angle esotropia (ET) in complete abducens nerve palsy. Medical records from 36 patients who had undergone the VR union procedure for ET treatment due to sixth-nerve palsy between July 2014 and July 2018 at Beyoglu Eye Research and Training Hospital were reviewed. One week before surgery, all patients underwent a 4-IU botulinum toxin A (btx) injection into the ipsilateral medial rectus (MR). All patients then underwent a VR muscle union procedure. A non-absorbable suture was inserted through the lateral muscular margin of each VR muscle at approximately 1/5 the width from the edge at 10mm distance from the VR insertion. Both sutures were then tied to each other above the LR. Plication of the LR muscle using a non-absorbable suture was performed in all cases. The study population consisted of 14 (38.9%) females and 22 (61.1%) males. The mean age was 36.31 ± 19.16years. The mean preoperative deviation angle in primary gaze into distance was 47.77 ± 18.48 prism diopter (PD). The mean deviation angle 1year after surgery was -1.0 ± 6.62 PD. Abduction improved from -4.27 ± 0.46 to -1.88 ± 0.96. The VR muscle union in combination with LR plication appears to be an effective treatment procedure for complete abducens nerve palsy patients.