Retinal and Choroidal Vascularity Evaluation in Pediatric Radiologically Isolated Syndrome and Multiple Sclerosis.

BACKGROUND: To assess vessel density (VD) and flow of retinal plexuses and peripapillary region related with the pediatric radiologically isolated syndrome (RIS) and multiple sclerosis (MS). METHODS: We analyzed 24 eyes of 12 participants with the diagnosis of RIS, 24 eyes of 12 participants with the diagnosis of MS, and 26 eyes of 13 age- and sex-matched healthy controls in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus, foveal avascular zone, and the flow of choriocapillaris were investigated using optical coherence tomography angiography. RESULTS: Parafoveal VD and all subregion parameters in SCP were significantly decreased in the MS group compared with the controls, whereas only nasal and inferior VD were significantly decreased in the pediatric RIS group compared with the controls. Ganglion cell layer (GCL) thickness of all subregions of the inner ring was significantly decreased in the pediatric MS group compared with the control group. No significant difference was observed between the pediatric RIS group and the control group regarding thickness. CONCLUSIONS: We showed lower parafoveal VD in all subregions of SCP in pediatric MS, whereas only parafoveal nasal and inferior VD were decreased in pediatric RIS. GCL thickness of inner ring was significantly decreased in the pediatric MS, whereas GCL thickness did not change in pediatric RIS. Therefore, a decrease of parafoveal nasal and inferior VD without a decrease in thickness implies an early impairment of microvasculature in the RIS before impairment of thickness and that microvascular alterations begin from highly vascular superficial parafovea.

How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling.

Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.

Is tear proteome profile a predictor of developing uveitis in ANA-positive patients with oligoarticular juvenile idiopathic arthritis?

PURPOSE: Although less than one-third of anti-nuclear antibody (ANA) positive patients with oJIA develop uveitis, ANA positivity is still the most well-known marker for assessing the risk of uveitis in oligoarticular JIA (oJIA). Therefore, novel biomarkers are needed to better assess the risk of developing uveitis. For this purpose, we performed a comparative tear proteome analysis of uveitis patients to reveal the identity of differentially regulated proteins. DESIGN: Tear samples were collected using the Schirmer strips in 7 oJIA and 7 oJIA patients with uveitis (oJIA-U). All oJIA-U patients had developed bilateral anterior uveitis and were inactive and topical treatment-free. METHODS: The nHPLC LC-MS/MS system was used for protein identification and label-free proteome comparisons. The PANTHER and STRING analyses were carried out using UniProt accession numbers of the identified proteins. RESULTS: Patient characteristics, e.g., age, gender, disease duration, and treatments were similar. For protein identification, three different databases were searched. Twenty-two, 147, and 258 database searches, respectively. Of these, 15 were common to all three proteome databases. Of these 15 proteins, 10 proteins were upregulated, and 2 were downregulated, based on the twofold regulation criteria. The upregulated proteins were, namely, cystatin-S, secretoglobin family 1D member, opiorphin prepropeptide, mammaglobin-B, lysozyme C, mesothelin, immunoglobulin kappa constant, extracellular glycoprotein lacritin, beta-2-microglobulin, and immunoglobulin J chain. The downregulated proteins were dermcidin and prolactin-inducible protein. Among the differentially regulated proteins, cystatin-S was the most regulated protein with an 18-fold upregulation ratio in tear samples from uveitis patients. CONCLUSION: Here, the identities and regulation ratios of several proteins were revealed when tear samples from uveitis patients were compared to patients without uveitis. These proteins are putative biomarkers for assessing uveitis risk and require further attention.

Idiopathic Orbital Inflammatory Disease Attack Associated with Large Serous Detachment Without Anterior and Posterior Segment Inflammation.

Idiopathic orbital inflammatory disease is a benign, non-infectious, and non-neoplastic space-occupying orbital and peri-orbital inflammation with no identifiable local or systemic causes. Patients usually present with eyelid and periorbital erythema and edema, proptosis, and decreased eye movements. In this report, a case of large serous retinal detachment accompanying a unilateral idiopathic orbital inflammatory disease attack is discussed. It demonstrates that very extensive and highly serous retinal detachment may accompany idiopathic orbital inflammatory disease attacks. Dramatic improvement in clinical findings and imaging can be observed with high-dose steroid treatment in a short time.

The relationship between computed tomography findings and ocular trauma and pediatric ocular trauma scores in pediatric globe injuries: Does imaging have prognostic and diagnostic value?

BACKGROUND: The aim of this study is to assess the relationship between computed tomography (CT) findings in open globe injuries (OGIs) in pediatric patients and the pediatric ocular trauma score (POTS) and OTS in pediatric ocular trauma. METHODS: In 34 pediatric patients with OGI, CT findings were categorized into nine main categories: Scleral irregularity, lens dislocation, abnormal vitreous density, choroid-retinal layer thickening, preseptal thickness increase, intraocular foreign body and air, vitreous hemorrhage, retinal detachment, and perforation. The relationship between different types and numbers of CT findings and the POTS and OTS was evaluated. RESULTS: The mean age of trauma was 6.6±3.1. Of the patients, 9 (26.5%) were female and 25 (73.5%) were male. The most com-mon CT findings are scleral irregularity and increased preseptal thickness (47.1%). In univariate analysis, a P<0.05 was found between 16 patients with 1 or less CT findings (median POTS value 80 [71.25-90.0]) and 11 patients with 2 or 3 CT findings (median POTS value 60 [15-70]). A P<0.05 was found between 16 patients with 1 or less CT findings (median POTS value 80 [71.25-90.0]) and 7 patients with 4 or more CT findings (median POTS value 45 [25-80]). A P > 0.05 was found between 11 patients with 2 or 3 CT findings (median POTS value 60 [15-70]) and 7 patients with 4 or more CT findings (median POTS value 45 [25-80]). No significant difference was found between the number of CT findings and OTS stages. While POTS was significant (P<0.05) in patients with ab-normal vitreous density (median 45 [30-69.6]), OTS value was not significant (P>0.05). There was no significant difference between POTS and OTS in other CT findings. CONCLUSION: The number of CT findings may assist in predicting POTS and, consequently, estimating visual prognosis in pediatric patients with OGI. In emergency situations where, sufficient clinical data are unavailable, the objective findings from CT may help in assessing the severity of ocular trauma and potentially predicting long-term visual outcomes.

Expression of key SARS-CoV-2 entry molecules in surgically obtained human retinal biopsies.

PURPOSE: To investigate the presence of ACE2, TMPRSS2 and Furin, i.e., a key player in the ocular infection with SARS-COV-2, in surgically obtained human retinal tissue samples from SARS-CoV-2-negative patients, using gene expression analysis. METHODS: The mechanisms and entry paths of ocular infections have been ill-defined so far. To better understand the possible entry routes, we used surgically explanted retinal tissue from nine patients that were not infected with SARS-CoV-2 and analyzed the message expression of the three key molecules that confer viral entry into cells using polymerase chain reaction. RESULTS: The median age of the patients (n = 9) included in the study was 52 years (IQR 48, 55). Eight patients underwent surgery for rhegmatogenous retinal detachment and one patient for tractional retinal detachment. Gene expression for the proteins studied was detected in all nine patients. The results of analysis by Livak's method (2001) demonstrated a median TMPRSS2 gene expression value of 20.9 (IQR 11.7, 33.7), a median ACE2 gene expression value of 2.09 (IQR 1.14, 2.79) and a median Furin gene expression value of 8.33 (IQR 5.90, 11.8). CONCLUSION: In conclusion, TMPRSS2, Furin and ACE2 are expressed in the retina and may contribute to the retinal involvement in COVID-19 patients. Expression may vary among individuals, which may explain why some patients may be more prone to retinal involvement during SARS-CoV-2 infection COVID-19 patients than others. Variability in the expression of TMPRSS2, Furin and ACE2 proteins themselves may also explain the presence or development of retinal symptoms of varying severity.

Management of Retinal Detachment With a Coexistent Macular Hole: Submacular Placement of Retinal Autograft Through a Macular Hole.

PURPOSE: In this article, a submacular autologous neurosensory retinal transplantation technique is presented in patients with large macular hole (MH) accompanying retinal detachment. METHODS: In the surgical procedure, 23-G pars plana vitrectomy and peripheral vitrectomy were performed. An autologous neurosensory retinal patch, which should be larger than the diameter of the MH, was released from a suitable quadrant. The retinal patch was grasped using a 23 gauge microforceps and then passed through the MH and placed under the macula. Liquid perfluorocarbon (PFCL) was injected, and the retina was reattached. A subfoveal autologous neurosensory retinal patch was repositioned in the center of the MH with gentle manipulation under fluid perfluorocarbon, if necessary. Laser retinopexy was applied to peripheral tears under PFCL Subsequently, a 5,000-cSt silicone oil-PFCL exchange was also performed. RESULTS: Four eyes of four patients were operated on using the technique described earlier. Silicone oil was removed from two patients, and the macular holes were closed in all patients at the last follow-up. CONCLUSION: This technique has been beneficial in refractory MHs and can improve the visual potential in eyes with MHs.

Based on the Real-Life Data of Türkiye; Comparison of Anatomical and Functional Outcomes of Phakic and Pseudophakic Patients in Wet Type Age-Related Macular Degeneration.

Objectives: The aim of the study was comparison of wet-type age-related macular degeneration in phakic and pseudophakic patients in terms of anatomical and functional success based on the real-life data of Türkiye. Methods: The multicenter retrospective real-life study data of the. retinal study group were used in this study. Among 867 eyes of 867 patients were included in the study. Patients were divided into two groups according to the status of the lens; phakic group and pseudophakic group. The follow-up period of the two groups, the number of injections at the 1st, 2nd, and 3rd years, and changes in the central macular thickness (CMT, µ) and visual acuity (VA, logMAR) of the patients at the beginning, 6th, 12th, 24th, and 36th months were examined. Results: In our study, the number of injections in the 1st, 2nd, and 3rd years, respectively, was 4.2±2.0, 1.8±1.9, and 1.0±1.7 in the phakic group, and 3.9±2.0, 1.7±1.9, and 0.8±1.4 in the pseudophakic group. When the two groups were compared in terms of the number of injections, there was a statistically significant difference in the 1st year, but there was no significant difference in the 2nd and 3rd years (p=0.001, p=0.350, and p=0.288, respectively). There was no statistically significant difference between the groups in terms of CMT in the baseline, 6th, 12th, 24th, and 36th months (p=0.991, p=0.327, p=0.652, p=0.599, and p=0.873, respectively). Although there was no difference in VA between groups at the beginning (p=0.052), the phakic group showed statistically better VA in controls at 3rd, 6th, 12th, 24th, and 36th months (p=0.001, p=0.001, p=0.000, p=0.000, and p=0.003, respectively). Conclusion: Differences in the number of injections and visual results between phakic and pseudophakic patients in wet type AMD may necessitate the creation of different treatment and follow-up protocols.

Results of anti-VEGF treatment for neovascular AMD in eyes with different baseline visual acuity in Turkish population-based on real life data-Bosphorus retina study group.

BACKGROUND: To investigate the anatomical and visual outcomes of the patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF), according to the baseline best-corrected visual acuity (BCVA) based on the multicenter real-life data. METHODS: Five-hundred-ninety patients who had taken the Pro Re Nata (PRN) treatment regimen with three loading doses and at least one year of follow-up were included. The patients were divided into three groups according to the baseline BCVA: Group 1 (BCVA ≥ 1.3 Logmar), Group 2 (1.3 Logmar > BCVA ≥ 0.3 Logmar), and Group 3 (BCVA ≤ 0.2 Logmar). BCVA, central macular thickness (CMT), and the number of injections and visits were evaluated. RESULTS: There were 175, 322, and 93 patients in Group 1, Group 2, and Group 3, respectively. The number of visits and injections in the 1st year was not different between the groups (p = 0.58 and p = 0.08) and was 7.09 and 4.41 (Group 1), 6.59 and 5.58 (Group 2), 6.77 and 4.08 (Group 3). There was a significant difference in CMT between the baseline and 12th month in Group 1 and Group 2 (p < 0.001, p < 0.001, respectively) but not in Group 3 (p = 0.84). BCVA was significantly better in the 12th month in Group 1 (p < 0.001), slightly worse in Group 2 (p = 0.79), and significantly worse in Group 3 (p < 0.001). CONCLUSION: This study provides evidence that an inadequate number of injections cannot protect vision. Moreover, it can cause vision loss, especially in the eyes with good vision.

Quantitative analysis of preclinical ocular microvascular changes in Multisystemic Inflammatory Syndrome in Children (MIS-C) detected by optical coherence tomography angiography.

OBJECTIVES: To evaluate the macular and optic nerve head (ONH) vascular density, foveal avascular zone area, and outer retina and choriocapillaris flow in Multisystemic Inflammatory Syndrome in Children (MIS-C) using optical coherence tomography angiography (OCTA). METHODS: Thirty-four eyes of 34 patients with MIS-C and 36 age and sex-matched healthy controls were investigated in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, FAZ parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. RESULTS: All VD parameters in SCP were significantly lower in MIS-C patients. There was no significant difference between the groups in VD parameters of both DCP and ONH, as well as FAZ area and FAZ perimeter. However, foveal density (FD-300) was significantly decreased in the MIS-C group. (p = 0.024). The outer retina flow area at 1 mm, 2 mm, and 3 mm radius and CC flow area at 1 mm and 2 mm radius were significantly lower in the MIS-C group than in the control group. Although CC flow area at 3 mm radius was decreased in the MIS-C group compared to healthy controls, the difference was not statistically significant. CONCLUSIONS: We demonstrated a decreased vessel density in SCP, choriocapillaris flow area, and outer retinal flow area in MIS-C patients. Hence, we proposed that OCTA could reveal retinal and choroidal microvascular changes in MIS-C patients who were completely healthy before the diagnosis of MIS-C.

Subclinical Retinal Capillary Abnormalities in Juvenile Systemic Lupus Erythematosus without Ocular Involvement.

PURPOSE: This study aimed to evaluate subclinical retinal microvascular changes with OCTA in juvenile systemic lupus erythematosus (JSLE) patients without ocular involvement. METHODS: Ten eyes of 10 JSLE and 13 eyes of 13 age and sex-matched healthy controls (HCs) were enrolled. The superficial (SCP) and deep capillary plexus (DCP), FAZ parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. RESULTS: All vessel density (VD) parameters in DCP were significantly lower in JSLE group compared to HCs. There was no significant difference between the groups in VD parameters of both SCP and ONH, FAZ, outer retina and choriocapillaris flow area. All DCP VD parameters showed a good ability to differentiate JSLE from HCs. CONCLUSION: OCTA could detect retinal vascular impairment in the deep macular region in JSLE patients with normal ocular examination. Furthermore, all DCP VD parameters have a good ability to discriminate JSLE from HCs.

Expert recommendations for the management of diabetic macular edema with intravitreal dexamethasone implant: A Turkish Delphi study.

PURPOSE: To provide consensus on the clinical use of intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in Turkey. METHODS: A panel of 22 retina experts prepared 77 statements of recommendation, and 80 retinal specialists practicing in Turkey were chosen to vote either in support or against each one. A Delphi-based method was used through which the ophthalmologists were able to view all of the results anonymously after two rounds and modify their subsequent answers. The survey was conducted via a mini website, and statements without consensus were resent to the specialists with the latest vote results a week later. RESULTS: A total of 72 ophthalmologists answered the first and second round questions. After the first stage, consensus was achieved on 55 of the statements, leaving 22 without agreement. After the second stage, consensus was reached on 11 of the remaining statements. Strong consensus was achieved on statements regarding the etiopathogenesis of DME and the first-line indications and safety of the DEX implant procedure. The panel recommended the use of DEX implant for patients with an arterial thromboembolic event in the last three months and also agreed that pro re nata DEX implant treatment not only provides better outcomes for DME patients but also reduces the treatment burden for those who could not receive an adequate number of anti-vascular endothelial growth factor (VEGF) injections. CONCLUSION: This study provides clinical consensus and recommendations about the use of DEX implant in the clinical practice of DME management in Turkey.

Comparison of Ranibizumab Treatment Response of Superior and Inferior Temporal Branch Retinal Vein Occlusion: A Year Follow-Up.

Objectives: The aim of the study was to compare ranibizumab treatment response of macular edema secondary to superior and inferior temporal branch retinal vein occlusion. Methods: Sixty-four eyes of 64 patients treated with 0.5 mg/0.05 mL ranibizumab due to macular edema secondary to branch retinal vein occlusion were enrolled in this retrospective study. Thirty-eight eyes with superior temporal branch retinal vein occlusion were classified as Group 1 and 26 eyes with inferior temporal branch retinal vein occlusion as Group 2. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and the number of intravitreal injections were evaluated and compared between the groups. Results: The mean baseline, 3rd, 6th, 9th, and 12th month BCVA values in Group 1 were 0.77±0.47, 0.37±0.20, 0.37±0.22, 0.38±0.24, and 0.35±0.18 logarithm of the minimum angle of resolution (logMAR) and in Group 2 were 0.75±0.45, 0.37±0.18, 0.35±0.19, 0.32±0.17, and 0.28±0.20 logMAR, respectively. The mean baseline, 3rd, 6th, 9th, and 12th month CMT values in Group 1 were 522.92±136.01, 318.03±66.65, 287.53±48.27, 271.95±32.47, and 280.47±91.66 µm and in Group 2 were 524.08±145.51, 289.85±53.08, 268.96±31.57, 260.77±30.22, and 244.04±44.78 µm, respectively. BCVA and CMT improved significantly within both groups after the treatment (p<0.05) and there was no statistically significant difference between the groups (p>0.05). However, a significantly higher number of injections was needed for Group 1. Conclusion: Ranibizumab improved the visual and anatomical outcomes similarly in both superior and inferior temporal branch retinal vein occlusion with macular edema. However, more frequent injections were needed to achieve the same efficacy in superior temporal branch retinal vein occlusion.

Preclinical ocular microvascular changes in juvenile dermatomyositis: A pilot optical coherence tomography angiography study.

OBJECTIVES: To evaluate the macular and optic nerve head (ONH) vascular density, foveal avascular zone area, and outer retina and choriocapillaris flow in juvenile dermatomyositis (JDM) using optical coherence tomography angiography (OCTA). METHODS: Ten eyes of 10 patients with JDM and 15 age and sex-matched healthy controls were investigated in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus (DCP), ONH, foveal avascular zone (FAZ) parameters, the flow area of the outer retina, and choriocapillaris were evaluated using OCTA. RESULTS: Vessel density (VD) of the parafovea (p = 0.036) and parafoveal subregions (p = 0.041 for superior hemifield, p = 0.031 for inferior hemifield, p = 0.012 for superior, p = 0.019 for nasal, p = 0.026 for inferior, and p = 0.048 for temporal) in DCP were significantly lower in the JDM group compared to healthy controls. A high inverse correlation between disease duration and these parameters was found except parafoveal superior VD in DCP. There was no significant difference between the groups in VD parameters of SCP and ONH, FAZ parameters, outer retina, and choriocapillaris flow area as well as thickness parameters. (p > 0.05 for all). Furthermore, ROC analysis revealed that all parafoveal DCP parameters showed good ability to differentiate JDM from healthy controls. CONCLUSIONS: We demonstrated a decreased vessel density in the deep parafoveal region in JDM. As a result, we hypothesized that OCTA could detect retinal microvascular changes in JDM patients who did not have clinical evidence of ocular involvement.

Evaluation of macular and peripapillary vascular parameter change in healthy subjects after caffeine intake using optical coherence tomography angiography.

PURPOSE: To observe the effects of caffeine intake on vessel densities in macular and peripapillary regions and to analyze the correlations of vascular properties of these two interlinked regions in healthy volunteers using optical coherence tomography angiography (OCTA). METHODS: In this prospective randomized, double-masked, placebo-controlled study, 120 participants were grouped into two groups: sixty subjects as a study group, which received caffeine and sixty subjects as a placebo group, which received a placebo. OCTA imaging was performed at baseline and 1 h after drug intake. Changes in macular and radial peripapillary capillary (RPC) vessel densities (VD) and foveal avascular zone (FAZ) parameters and correlation of these parameters were analyzed. RESULTS: Baseline macular and RPC VD and FAZ parameters showed no significant difference between study and placebo groups (P > 0.05 for all). VD parameters in all segments of superficial and deep macular regions and peripapillary region showed a statistically significant decrease after caffeine intake (P < 0.001 for all). All macular superficial VD parameters showed a positive correlation with deep perifovea VD (P < 0.05 for all). Also, superficial perifovea VD was positively correlated with all deep macular VD parameters except deep fovea VD (P < 0.05 for all). CONCLUSION: We show that caffeine causes a decrease in macular and peripapillary vessel densities in healthy subjects, and correlations were observed between macular and peripapillary VD parameters. We believe that future studies are needed to support the effect of caffeine on peripapillary VD and the idea of using deep perifovea VD as the main parameter to estimate superficial macular parameters.

Using bioinformatic protein sequence similarity to investigate if SARS CoV-2 infection could cause an ocular autoimmune inflammatory reactions?

Although severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection have emerged globally, findings related to ocular involvement and reported cases are quite limited. Immune reactions against viral infections are closely related to viral and host proteins sequence similarity. Molecular Mimicry has been described for many different viruses; sequence similarities of viral and human tissue proteins may trigger autoimmune reactions after viral infections due to similarities between viral and human structures. With this study, we aimed to investigate the protein sequence similarity of SARS CoV-2 with retinal proteins and retinal pigment epithelium (RPE) surface proteins. Retinal proteins involved in autoimmune retinopathy and retinal pigment epithelium surface transport proteins were analyzed in order to infer their structural similarity to surface glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), envelope protein (E), ORF1ab polyprotein (orf1ab) proteins of SARS CoV-2. Protein similarity comparisons, 3D protein structure prediction, T cell epitopes-MHC binding prediction, B cell epitopes-MHC binding prediction and the evaluation of the antigenicity of peptides assessments were performed. The protein sequence analysis was made using the Pairwise Sequence Alignment and the LALIGN program. 3D protein structure estimates were made using Swiss Model with default settings and analyzed with TM-align web server. T-cell epitope identification was performed using the Immune Epitope Database and Analysis (IEDB) resource Tepitool. B cell epitopes based on sequence characteristics of the antigen was performed using amino acid scales and HMMs with the BepiPred 2.0 web server. The predicted peptides/epitopes in terms of antigenicity were examined using the default settings with the VaxiJen v2.0 server. Analyses showed that, there is a meaningful similarities between 6 retinal pigment epithelium surface transport proteins (MRP-4, MRP-5, RFC1, SNAT7, TAUT and MATE) and the SARS CoV-2 E protein. Immunoreactive epitopic sites of these proteins which are similar to protein E epitope can create an immune stimulation on T cytotoxic and T helper cells and 6 of these 9 epitopic sites are also vaxiJen. These result imply that autoimmune cross-reaction is likely between the studied RPE proteins and SARS CoV-2 E protein. The structure of SARS CoV-2, its proteins and immunologic reactions against these proteins remain largely unknown. Understanding the structure of SARS CoV-2 proteins and demonstration of similarity with human proteins are crucial to predict an autoimmune response associated with immunity against host proteins and its clinical manifestations as well as possible adverse effects of vaccination.

Effect of aflibercept on proliferative vitreoretinopathy: Proteomic analysis in an experimental animal model.

PURPOSE: The aim of this study was to monitor inflammatory, proliferative and progressive effects of proliferative vitreoretinopathy (PVR) and aflibercept treatment in dispase induced PVR rat model by proteomic analysis. MATERIAL AND METHODS: A total of 35 male Long Evans pigmented rats were divided into three groups, namely, PVR (dispase+saline), PVR+aflibercept (dispase+aflibercept) and control. The PVR group received 2 µl of 0.03 IU/µl dispase and 2 µl saline, the PVR+aflibercept group received 2 µl of 0.03 IU/µl and 2 µl of 40 mg/ml aflibercept at the first day of the experiment. At the end of the 6th week all retina and vitreous specimens were collected by evisceration and transferred to the proteomics laboratory for analysis. Proteomic analysis by 2D gel electrophoresis coupled with MALDI-TOF/TOF was performed. RESULTS: In the PVR and PVR+aflibercept group 16 different proteins that were identified to be differentially regulated in comparison to the control group. In the PVR+aflibercept group, ENO1, ENO2, LDH-B, PEBP-1 and GS levels were higher than the PVR group. In addition, the association of proteins such as UCHL, PEBP1, PDHB and ENO1 with PVR has been demonstrated for the first time. CONCLUSION: STRING analysis elucidated the functional protein-protein interaction among the differentially regulated proteins and highlighted that those proteins mainly played roles in carbon and nucleotide metabolisms. Functional analysis of the differentially regulated proteins indicated the presence of inflammation, gliosis and retinal damage in the PVR group. Aflibercept treatment had pronounced effect on prevention of inflammation and retinal damage while causing a slight increase in gliosis. However, aflibercept treatment was not effective enough to normalize the levels of differentially regulated proteins of the PVR group. Therefore, we predict that the treatment dose of aflibercept used in this study was below of its ideal concentration and should be increased in the future studies. The differential regulation of these structural proteins in this study should shed some light to the mechanism of glial wound formation in the retina and guide future treatment modalities.

Relation of anatomy with function following the surgical treatment of idiopathic epiretinal membrane: a multicenter retrospective study.

PURPOSE: To investigate the prognostic factors associated with functional and anatomical outcomes and to assess the longitudinal course of visual acuity and retinal morphology after vitreoretinal surgery for idiopathic epiretinal membrane (ERM). METHODS: This multicenter, retrospective study included a total of 634 eyes who underwent surgery for idiopathic ERM in 22 academic centers nationwide in Turkey. Data on best-corrected visual acuity (BCVA) and optical coherence tomography features (central foveal thickness (CFT), ERM and foveal contour morphology, ellipsoid zone (EZ) integrity) were collected and compared at baseline, 6-month, 12-month, and 24-month follow-ups. Prognostic factors for functional (having ≥ 20/25 Snellen BCVA) and anatomical (having normal/shallow foveal contour) recoveries after surgery were investigated by means of multivariate regression analyses. A cutoff value of preoperative BCVA optimizing functional recovery was calculated using receiver operating characteristic curve analysis. RESULTS: At a median follow-up of 24 months, 37.4% of the eyes achieved ≥ 20/25 BCVA and 54% regained normal or shallow foveal contour. Functional recovery was more likely in eyes with better baseline BCVA and intact EZ (R2 = 0.356, p < 0.001). The cutoff baseline BCVA value for good visual prognosis was 0.35 logarithm of the minimum angle of resolution (Snellen 20/44) (sensitivity 60%, specificity 85%, p < 0.001). Anatomical recovery was negatively associated with advanced age, higher baseline CFT, foveal herniation-type ERM morphology, and internal limiting membrane (ILM) peeling (R2 = 0.225, p < 0.001). The negative effect of ILM peeling on anatomical recovery was not significant after the first postoperative year (p = 0.05). Mean BCVA values and foveal morphology progressively improved at each visit. Cases with convex baseline foveal contour continued to change towards normal foveal depression over 24 months of follow-up, which took longer than the eyes with shallow/flat contoured cases. One-third of eyes with severe baseline EZ defects showed recovery at follow-up and achieved significantly greater visual acuity gains than the remaining eyes with persistent defects (p < 0.001). CONCLUSIONS: Functional and anatomical restoration of the eyes appears to be a slow process after ERM surgery. This process may take much longer in eyes with worse foveal morphology at baseline. Although photoreceptor disruption may be reversible in some eyes, full functional recovery is unlikely when it persists.

Correlation of Visual Recovery and Increased Ellipsoid Zone Reflectivity After Successful Macular Hole Surgery.

Objectives: To assess changes in reflectivity of the retinal pigment epithelium (RPE), ellipsoid zone (EZ), and external limiting membrane (ELM) on spectral domain-optical coherence tomography (SD-OCT) images and the effects of reflectivity changes on visual acuity improvement after vitrectomy in macular hole patients. Materials and Methods: Twenty-four eyes of 24 patients with idiopathic full-thickness macular hole closed after vitrectomy were retrospectively reviewed. The "plot profile" function of the medical imaging software was used by a single masked physician to analyze RPE, EZ, and ELM reflectivity on OCT images at postoperative 1 month and 12 months. Results: Absolute and relative EZ reflectivity showed highly significant increases at postoperative 12 months compared to 1 month (p<0.001 and p<0.001, respectively). Absolute and relative EZ reflectivity changes from postoperative month 1 to month 12 after macular hole surgery were significantly correlated with best corrected visual acuity improvement (p=0.012 and p=0.020, respectively). Conclusion: EZ reflectivity can be a predictor of functional and anatomical improvement after macular hole surgery.