Retinal Membranes Research Articles

Proteomic Analysis of Retinal Mitochondria-Associated ER Membranes Identified Novel Proteins of Retinal Degeneration in Long-Term Diabetes.

The mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) is the physical contact site between the ER and the mitochondria and plays a vital role in the regulation of calcium signaling, bioenergetics, and inflammation. Disturbances in these processes and dysregulation of the ER and mitochondrial homeostasis contribute to the pathogenesis of diabetic retinopathy (DR). However, few studies have examined the impact of diabetes on the retinal MAM and its implication in DR pathogenesis. In the present study, we investigated the proteomic changes in retinal MAM from Long Evans rats with streptozotocin-induced long-term Type 1 diabetes. Furthermore, we performed in-depth bioinformatic analysis to identify key MAM proteins and pathways that are potentially implicated in retinal inflammation, angiogenesis, and neurodegeneration. A total of 2664 unique proteins were quantified using IonStar proteomics-pipeline in rat retinal MAM, among which 179 proteins showed significant changes in diabetes. Functional annotation revealed that the 179 proteins are involved in important biological processes such as cell survival, inflammatory response, and cellular maintenance, as well as multiple disease-relevant signaling pathways, e.g., integrin signaling, leukocyte extravasation, PPAR, PTEN, and RhoGDI signaling. Our study provides comprehensive information on MAM protein changes in diabetic retinas, which is helpful for understanding the mechanisms of metabolic dysfunction and retinal cell injury in DR.

Structural basis of retinal membrane guanylate cyclase regulation by GCAP1 and RD3.

Retinal membrane guanylate cyclases (RetGC1 and RetGC2) are expressed in photoreceptor rod and cone cells, where they promote the onset of visual recovery during phototransduction. The catalytic activity of RetGCs is regulated by their binding to regulatory proteins, guanylate cyclase activating proteins (GCAP1-5) and the retinal degeneration 3 protein (RD3). RetGC1 is activated by its binding to Ca2+-free/Mg2+-bound GCAP1 at low cytosolic Ca2+ levels in light-activated photoreceptors. By contrast, RetGC1 is inactivated by its binding to Ca2+-bound GCAP1 and/or RD3 at elevated Ca2+ levels in dark-adapted photoreceptors. The Ca2+ sensitive cyclase activation helps to replenish the cytosolic cGMP levels in photoreceptors during visual recovery. Mutations in RetGC1, GCAP1 or RD3 that disable the Ca2+-dependent regulation of cyclase activity are genetically linked to rod/cone dystrophies and other inherited forms of blindness. Here I review the structural interaction of RetGC1 with GCAP1 and RD3. I propose a two-state concerted model in which the dimeric RetGC1 allosterically switches between active and inactive conformational states with distinct quaternary structures that are oppositely stabilized by the binding of GCAP1 and RD3. The binding of Ca2+-free/Mg2+-bound GCAP1 is proposed to activate the cyclase by stabilizing RetGC1 in an active conformation (R-state), whereas Ca2+-bound GCAP1 and/or RD3 inhibit the cyclase by locking RetGC1 in an inactive conformation (T-state). Exposed hydrophobic residues in GCAP1 (residues H19, Y22, M26, F73, V77, W94) are essential for cyclase activation and could be targeted by rational drug design for the possible treatment of rod/cone dystrophies.

An Integrative Multi-Omics Analysis Reveals MicroRNA-143 as a Potential Therapeutic to Attenuate Retinal Angiogenesis.

Retinal neovascularization is a severe complication of proliferative diabetic retinopathy (PDR). MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. In this study, we show that miR-143-3p is significantly downregulated in the retina of a rat model of oxygen-induced retinopathy (OIR) by miRNA-sequencing. Intravitreal injection of synthetic miR-143 mimics significantly ameliorate retinal neovascularization in OIR rats. miR-143 is identified to be highly expressed in the neural retina particularly in the ganglion cell layer and retinal vasculature. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodeling. The multiomics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating hypoxia-inducible factor-1 signaling. We predict hub genes regulated by miR-143 that may be involved in mediating endothelial cell function by cytoHubba. We also demonstrate that the retinal neovascular membranes in patients with PDR principally consist of endothelial cells by CIBERSORTx. We then identify 2 hub genes, thrombospondin 1 and plasminogen activator inhibitor, direct targets of miR-143, that significantly altered in the PDR patients. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization.

Effect of cytokine-induced alterations in extracellular matrix composition on diabetic retinopathy-relevant endothelial cell behaviors

Retinal vascular basement membrane (BM) thickening is an early structural abnormality of diabetic retinopathy (DR). Recent studies suggest that BM thickening contributes to the DR pathological cascade; however, much remains to be elucidated about the exact mechanisms by which BM thickening develops and subsequently drives other pathogenic events in DR. Therefore, we undertook a systematic analysis to understand how human retinal microvascular endothelial cells (hRMEC) and human retinal pericytes (hRP) change their expression of key extracellular matrix (ECM) constituents when treated with diabetes-relevant stimuli designed to model the three major insults of the diabetic environment: hyperglycemia, dyslipidemia, and inflammation. TNFα and IL-1β caused the most potent and consistent changes in ECM expression in both hRMEC and hRP. We also demonstrate that conditioned media from IL-1β-treated human Müller cells caused dose-dependent, significant increases in collagen IV and agrin expression in hRMEC. After narrowing our focus to inflammation-induced changes, we sought to understand how ECM deposited by hRMEC and hRP under inflammatory conditions affects the behavior of naïve hRMEC. Our data demonstrated that diabetes-relevant alterations in ECM composition alone cause both increased adhesion molecule expression by and increased peripheral blood mononuclear cell (PBMC) adhesion to naïve hRMEC. Taken together, these data demonstrate novel roles for inflammation and pericytes in driving BM pathology and suggest that inflammation-induced ECM alterations may advance other pathogenic behaviors in DR, including leukostasis.

A Case Report Total Intravenous Anesthesia Combined with Peribulbar Block in Vitrectomy Operation with Heart Disorder

Introduction: Vitrectomy is eye surgery to evaluate the retina by removing the vitreous gel which is principally carried out in three stages, namely retinal detachment repair, membrane peeling, and crystalline lens. In this operation, the anesthetic technique that needs to be emphasized is not increasing intraocular pressure and avoiding the oculocardiac reflex. This operation can be performed with a peribulbar or retrobulbar block, however, total intravenous anesthesia may also be considered in patients with other comorbidities.Case Presentation: Male, 55 years old, 96 kgs, with the chief complaint of blurred vision in the last 3 weeks ago. There were no other complaints but the patient has a history of hypertension, diabetes mellitus type II, congestive heart failure with a history of mitral valve replacement (MVR), and permanent pacemaker (PPM) usage from 2015. The patient had a history of warfarin and novamox usage 7 days ago. From the exam, the patient was diagnosed with ablatio retina + post-MVR and scheduled to have a vitrectomy. The patient was positioned supine with 300 heads up. The patient was given 3 liters of oxygen via nasal cannula, premedicated with fentanyl 50 mcg, then induced with propofol 100 mg bolus intravenously until sleep nonapnea before continuing with continuous propofol via syringe pump. The patient was maintained by propofol 0.5 mg/kg BW/hour. Next, the patient was given a peribulbar block with 2mL Lidocaine 2% and 2mL Bupivacaine 0.5%. During operation, there was no significant hemodynamic fluctuation until finished. Conclusion: The patient thus will undergo vitrectomy can be performed with peripheral nerve blocks such as retrobulbar anesthesia or peribulbar anesthesia. However, after knowing about the patient’s medical history, in this case, with a history of cardiac events and also undergone open-heart surgery, total intravenous anesthesia combined with a peribulbar block was considered the most suitable technique.

Integrative study of gene expression datasets in retinal samples of Diabetic Retinopathy

Diabetic Retinopathy is prevalent among patients with uncontrolled hyperglycemia resulting in vision loss. Despite numerous challenges to create a link among these conditions, the characterization of pathological neovascularization causing retinal damage due to the prognosis of early non-proliferative diabetic retinopathy to late proliferative diabetic retinopathy needs deep understanding. In this study, meta-analysis-based integration of gene expression datasets for the fibrovascular membrane of PDR and neural retina of NPDR were compared, to investigate the differentially expressed genes involved in retinal angiogenesis. Human samples with gene expression profiling of the same experiment type and platform with sufficient information for analysis were included in the study. The studies from cell lines and non-human studies, human samples that include serum, cornea, lens, and/or other ocular tissues or fluids, and studies that lack basic information for analysis were excluded. The microarray datasets available in the Gene Expression Omnibus database of the early and late stages in DR were screened to find common gene expression profiles. Using the INMEX bioinformatics tool, significantly upregulated and downregulated genes in the neural retina of Non-Proliferative Diabetic Retinopathy and fibrovascular membrane of Proliferative Diabetic Retinopathy were compared and studied by the combine effect size method. Using the STRING database PPI network, 50 upregulated and 50 downregulated genes were used to find the key candidate genes involved in retinal disease/degeneration in eye/retinal tissues. In the extensive gene expression meta-analysis performed using INMEX bioinformatics tool, overall, 7935 differentially expressed genes were identified and the respective heatmap was created by using the visualization tools of INVEX. STRING database PPI network identified Retinol Binding Protein 3, Neural Retina Leucine Zipper, S-Antigen Visual Arrestin, Peripherin 2, and Aryl Hydrocarbon Receptor Interacting Protein Like-1 to be the most highly ranked hub genes. The newly discovered potential genes related to retinal angiogenesis causing FVM formation in DR may provide insight into the cellular pathogenesis of NPDR to PDR.

Influence of very-long-chain polyunsaturated fatty acids on membrane structure and dynamics

The unique attributes of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), their long carbon chains (n > 24) and high degree of unsaturation, impart unique chemical and physical properties to this class of fatty acids. The changes imparted by VLC-PUFA 32:6 n-3 on lipid packing and the compression moduli of model membranes were evaluated from π-A isotherms of VLC-PUFA in 1,2-distearoyl-sn-3-glycero-phosphocholine (DSPC) lipid monolayers. To compare the attractive or repulsive forces between VLC-PUFA and DSPC lipid monolayers, the measured mean molecular areas (MMAs) were compared with the calculated MMAs of an ideal mixture of VLC-PUFA and DSPC. The presence of 0.1, 1, and 10 mol % VLC-PUFA shifted the π-A isotherm to higher MMAs of the lipids comprising the membrane and the observed positive deviations from ideal behavior of the mixed VLC-PUFA:DSPC monolayers correspond to repulsive forces between VLC-PUFAs and DSPC. The MMA of the VLC-PUFA component was estimated using the measured MMAs of DSPC of 47.1 ± 0.7 Å2/molecule, to be 15,000, 1100, and 91 Å2/molecule at 0.1, 1, and 10 mol % VLC-PUFA:DSPC mixtures, respectively. The large MMAs of VLC-PUFA suggest that the docosahexaenoic acid tail reinserts into the membrane and adopts a nonlinear structure in the membrane, which is most pronounced at 0.1 mol % VLC-PUFA. The presence of 0.1 mol % VLC-PUFA:DSPC also significantly increased the compression modulus of the membrane by 28 mN/m compared with a pure DSPC membrane. The influence of VLC-PUFA on lipid “flip-flop” was investigated by sum-frequency vibrational spectroscopy. The incorporation of 0.1 mol % VLC-PUFA increased the DSPC flip-flop rate fourfold. The fact that VLC-PUFA promotes lipid translocation is noteworthy as retinal membranes require a high influx of retinoids which may be facilitated by lipid flip-flop.

CircFAT1 regulates retinal pigment epithelial cell pyroptosis and autophagy via mediating m6A reader protein YTHDF2 expression in diabetic retinopathy

Diabetic retinopathy (DR) is a serious blinding complication of diabetes. At present, the therapeutic intervention effect is limited. We aimed to investigate the circRNA expression profiles in retinal proliferative fibrovascular membranes of patients with DR and explore the effect of circFAT1 on pyroptosis and autophagy of high glucose (HG)-induced retinal pigment epithelial (RPE) cells and its molecualr mechanism. In this study, circRNA sequencing was performed to determine the expression profiles of circRNAs in DR patients. The expression of circFAT1 was measured by qRT-PCR. Cell counting kit-8, transmission electron microscope, western blot, immunofluorescence and enzyme-linked immunosorbent assay were conducted to explore the roles of HG and circFAT1 in RPE cell pyroptosis and autophagy. RNA pull down was used to determine the binding protein of circFAT1. Our data showed that HG significantly reduced the viability of RPE cells, inhibited cell autophagy and contributed to cell pyroptosis. In addition, a total of 189 differentially expressed circRNAs (DEcircRNAs) were identified between DR patients and non-DR patients, including 93 upregulated and 96 downregulated DEcircRNAs in the retinal proliferative fibrovascular membranes of DR patients. Pathway analysis showed that DEcircRNAs were mainly involved in MAPK signaling pathway, TGF-beta signaling pathway and adherens junction. Moreover, circFAT1 was significantly downregulated in retinal proliferative fibrovascular membranes of DR patients and HG-induced RPE cells. CircFAT1 overexpression remarkably enhanced the expression of LC3B, while reduced the expression of GSDMD in HG-induced RPE cells. RNA pull down combined with western blot analysis indicated that circFAT1 bound to m6A reader YTHDF2. YTHDF2 overexpression significantly increased the protein expression of LC3B in HG-induced RPE cells. In summary, circFAT1 promoted autophagy and inhibited pyroptosis of RPE cells induced by HG, and could combine with YTHDF2. This study provides new ideas for DR prevention and treatment.

Effect of aging and lifestyle on healthy macular photoreceptors and retinal pigment epithelium-Bruch membrane complex thickness.

Investigate how aging and some lifestyle factors correlate with changes in macular photoreceptor and retinal pigment epithelium-Bruch membrane complex layers thickness in a sample of healthy population by using OCT segmentation technique. A cross-sectional study conducted at the ophthalmology department in the Medical City in Baghdad. All participants underwent an interview of medical history and lifestyle habits. Maculae of all participants were scanned using spectral domain optical coherence tomography, followed by manual segmentation of retinal layers. The study included 152 healthy participants (152 eyes), their mean age was 57.3 ± 6.7 years, gender distribution was 82(53.9%) males and 70(46.1%) females. There was a decrement in retinal pigment epithelium-Bruch membrane layer thickness at central subfield (500 µm radius from fovea minimum) by - 0.178 µm/year (p = 0.019), inner macula (500-1500 µm radius from fovea minimum) by - 0.263 µm/year (p = 0.002), outer macula (1500-3000 µm radius from fovea minimum) by - 0.225 µm/year (p = 0.015) with no statistically significant effect on photoreceptor thickness. Physical activity and smoking had statistically no significant effect on these layers thickness, however smokers had higher photoreceptor thickness at fovea minimum and central subfield. Body mass index increase by one kg/m2 correlated with a decrement in photoreceptor layer thickness by - 0.108 µm (p = 0.007). Aging process affected the retinal pigment epithelium-Bruch membrane complex and photoreceptor layer thickness in a healthy population, and this process can be slowed down by avoiding some lifestyles which aggravate these changes like obesity.

Late contralateral recurrence of retinal detachment in incontinentia pigmenti: A case report

BACKGROUNDIncontinentia pigmenti (IP) is a rare X-linked genetic disease. It mainly manifests as skin lesions and causes problems in the eyes, teeth, bones, and central nervous system. Of the various ocular manifestations, the most severe with difficult recovery is retinal detachment (RD). Here, we report an unusual case of bilateral asymmetrical RD. CASE SUMMARYWe present the case of an 11-year-old Chinese girl with IP who complained of sudden blurring of vision in the left eye. At that time, she had been blind in her right eye for 4 years. RD with traction was observed in both eyes. A massive retinal proliferative membrane, exudation, and hemorrhage were seen in the left eye. We performed vitrectomy in her left eye. Her visual acuity recovered to 20/50, and her retina had flattened within 2 d after surgery. During the 3-mo follow-up, we performed retinal laser treatment of the non-perfused retinal area in her left eye. Eventually, her visual acuity returned to 20/32, and no new retinal abnormalities developed. CONCLUSIONIn patients with IP with fundal abnormalities in one eye, it is important to focus on the rate of fundal change in the other eye. RD in its early stages can be effectively treated with timely vitrectomy and laser photocoagulation.

The Carotenoid Cleavage Dioxygenase Gene CCD7-B, at Large, Is Associated with Tillering in Common Wheat

Wheat, an important cereal crop, is responsible for the livelihoods of many people, and a component of national food security. Tillering, which determines plant architecture and spike number, is a critical agronomic trait of wheat. The carotenoid cleavage dioxygenase 7 (CCD7) has an important effect on the growth of tillers or lateral branches and lateral roots of plants. In order to study the relationship between CCD7 and tillering in wheat, CCD7-B was isolated from 10 Chinese wheat varieties with different tiller numbers. Subsequently, bioinformatics, allelic variation analysis, and field experiments were performed. Wheat CCD7-B belongs to the retinal pigment epithelial membrane receptor (RPE65) superfamily; it displays the greatest homology with monocot CCD7 proteins. Phylogenetic analysis of wheat CCD7-B proteins indicated division into dicotyledonous and monocotyledonous clades. Allelic variation analysis of CCD7-B via SrgAI enzyme digestion (a marker of cleaved amplified polymorphic sequences) suggested that 262 Chinese wheat micro-core collections and 121 Chinese wheat major cultivars from the Yellow and Huai River Valley winter wheat region can be divided into two groups: CCD7-B1 (C/T/T) and CCD7-B2 (G/C/A). CCD7-B1 showed better allelic variation than did CCD7-B2 for increasing the number of effective tillers of wheat varieties in China. This study provides reference data for the application of CCD7-B alleles to wheat breeding and supports further research regarding the mechanism of tillering in common wheat.

Cross-sectional assessment of the ellipsoid zone and the retinal pigment epithelium-Bruch membrane complex after systemic isotretinotin use

Purpose To evaluate the cross-sectional areas of the retinal pigment epithelium-Bruch membrane complex (RPE-B) and ellipsoid zon (EZ) and the thickness of the macula, retinal nerve fibre layer (RNFL), and ganglion cell-inner plexiform layer (GC-IPL) in patients using short-term systemic isotretinoin. Method A total of 43 right eyes of 43 patients treated with systemic isotretinoin for acne vulgaris were included in this prospective study. Macula, GC-IPL, RNFL thicknesses and central cross-sectional EZ and RPE-B areas were evaluated with optical coherence tomography (Zeiss, Cirrus HD OCT 5000) prior to treatment and in first, second and third months after the onset of isotretinoin treatment. For the measurement of EZ and RPE-B area, foveal EDI-OCT scans were binarized by using the public domain software ImageJ 1.51 s. Results Mean duration of isotretinoin treatment was 77 ± 15 days and mean dose was 2228 ± 574 milligrams. There was a statistically significant increment in central cross-sectional EZ and RPE-B areas in each follow-up examination, when analysed by repeated measurement analysis (p:0.002 and p:0.006, respectively). There was no correlation between total isotretinoin dose and the difference between final and basal EZ and RPE-B areas (p > 0.05, for both). When repeated measurements in follow-up examinations were compared, GC-IPL thicknesses except the superotemporal region (p:0.040) and RNFL thicknesses did not show a significant difference (p > 0.05). There was not any significant relation between total isotretinoin dose and 3rd month and basal measurement differences in macula, GC-IPL and RNFL thicknesses in any area (p > 0.05, for all). Conclusion There has been an increase in the area of RPE-B and EZ with short-term use of isotretinoin therapy. Future studies examining the relationship between functional tests and the RPE-B and EZ areas may provide more in-depth information on the effects of isotretinoin in the eye.

Ten differentially expressed proteins in the tear film of dogs with diabetic retinopathy

AbstractPurposeA common early lesion of diabetic retinopathy in human patients and a diverse range of animal models is retinal capillary basement membrane thickening occur within 6 months of induction of diabetes. This hallmark pathology of diabetic microvascular disease is used in the evaluation of drug‐mediated modulation of diabetic retinopathy in a range of animal models. Moreover results from published clinical practice have shown that more than 22% of dogs with naturally contracted diabetes mellitus develop ophtalmoscopic signs of retinal hemorrhages or microaneurysms in a relatively short time from onset of the disease. Therefore, we hypothesize that changes in the retina in such dogs results in changes in the protein profile of tear fluid, that can be of the diagnostic or therapeutic value and can contribute to the better understanding the pathophysiology mechanisms underlying that disease. The objective of this study was to identify the protein content of tear film in dogs with naturally contracted diabetes mellitus with and/ without retinopathy, and its comparison with the content of control group. That approach results with mapping out the comprehensive proteome of tear film in diabetic dog and the may contribute to development a noninvasive method to detect potential protein candidates for diabetic retinopathy biomarkers in tear film.MethodsTear film was collected with Schirmer strips from the canine diabetic patients with/ and without retinopathy and sex‐ and age‐matched control group.The study was conducted on 24 dogs (8 dogs in each group).Two‐dimensional electrophoresis was performed followed by MALDI‐TOF mass spectrometry identification of differential proteins. Quantitative analysis of the differentiating electrophoretic spots was done with 2Delta software. Metabolic pathways associated with those proteins were identified with Panther GO software.ResultsAltogether, 5 significantly differentially expressed proteins were identified. Of those, 4 were downregulated, and 1 was upregulated in the tear film of diabetic patients with retinopathy. Pathway analysis revealed that the proteins were associated with multiple pathways involved in biological regulation, cellular and metabolic process and cellular component organization.ConclusionsTear film protein analysis provides a novel way to screen diabetic retinopathy biomarkers in dogs.

Tractional retinal detachment and juxtapapillary retinal capillary hemangioma in a 6-year-old girl: A case report

A 6-year-old girl with visual impairment in the right eye (OD) was referred for an eye evaluation. The fundus of the OD showed a fibrotic orange endophytic lesion located adjacent to the optic disc. In retinal optical coherence tomography, a local tractional retinal detachment and choroidal neovascular membrane were observed together also with the presence of subretinal fluid. Due to the vision of the OD evolved to nonlight perception in the following exam, enucleation was performed. The pathology report was correlated with hemangioblastoma. Herein, we describe a case of a young girl with a retinal hemangioblastoma with quick evolution and without prior systemic diagnosis.

Glucocorticoids Promote Extracellular Matrix Component Remodeling by Activating YAP in Human Retinal Capillary Endothelial Cells.

Remodeling of extracellular matrix (ECM) components of endothelial cells is the main cause of retinal vascular basement membrane (BM) thickening, which leads to the initiation and perpetuation of microvasculopathy of diabetic retinopathy (DR). Excessive amounts of glucocorticoids (GCs) are related to the presence and severity of DR, however transcriptional effects of GCs on the biology of human retinal capillary endothelial cells (HRCECs) and its impacts on DR are still unclear. Here, we showed that GC (hydrocortisone) treatment induced ECM component [fibronectin (FN) and type IV collagen (Col IV)] expression and morphological changes in HRCECs via the glucocorticoid receptor (GR), which depended on the nuclear translocation of YAP coactivator. Mechanistically, GCs induced stress fiber formation in HRCECs, while blocking stress fiber formation inhibited GC-induced YAP nuclear translocation. Overexpression of FN, but not Col IV, activated YAP through the promotion of stress fiber formation via ECM-integrin signaling. Thus, a feedforward loop is established to sustain YAP activity. Using mRNA sequencing of HRCECs with overexpressed YAP or GC treatment, we found a similarity in Gene Ontology (GO) terms, differentially expressed genes (DEGs) and transcription factors (TFs) between the two RNA-seq datasets. In vivo, YAP was activated in retina vascular ECs of STZ-induced diabetic mice, and TF prediction analysis of published RNA-seq data of dermal vascular ECs from T2DM patients showed that GR and TEAD (the main transcription factor for YAP) were enriched. Together, GCs activate YAP and promote ECM component (FN and Col IV) remodeling in retinal capillary endothelial cells, and the underlying regulatory mechanism may provide new insights into the vascular BM thickening of the retina in the early pathogenesis of DR.

Comparison between Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Levels in Rhegmatogenous Retinal Detachment.

Introduction This study aimed to assess vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels within vitreous and blood serum samples of patients with rhegmatogenous retinal detachment (RRD) and their relationship to the development of proliferative vitreoretinopathy (PVR). Methods Seventeen eyes of patients with RRD were included in the RRD group and divided into three subgroups: RRD without PVR, RRD with PVR grades A and B, and RRD with PVR grade C. Five control eyes (nucleus and intraocular lens drop) were included in this study. Blood serum and vitreous samples were collected during vitrectomy. VEGF-A and PDGF-AA levels were determined by enzyme-linked immunosorbent assay. Results The mean vitreous VEGF-A level in the RRD group was 131.71 ± 58.25 pg/mL, and the mean vitreous PDGF-AA level was 174.62 ± 65.17 pg/mL. Both levels were significantly higher in the RRD group compared with the control group (p < 0.05). Vitreous VEGF-A and PDGF-AA levels were the highest in RRD with PVR grade C subgroup, with mean levels of 179.87 ± 21.02 pg/mL and 229.44 ± 14.09 pg/mL, respectively (p < 0.05). The vitreous VEGF-A/PDGF-AA ratios in the RRD subgroups were completely different. Conclusion Based on the tendency of VEGF-A and PDGF-AA levels, RRD surgery has to be performed as soon as possible prior to retinal cell death and membrane proliferative formation.

Clinical Evaluation of an Instrument-Integrated OCT-Based Distance Sensor for Robotic Vitreoretinal Surgery

PurposeTo assess the efficacy of an instrument-integrated OCT (iiOCT)-based distance sensor during robotic vitreoretinal surgery using the Preceyes Surgical System (PSS; Preceyes B.V.).DesignSingle-center interventional study.ParticipantsPatients requiring vitreoretinal surgery.MethodsFive patients were enrolled. Standard preoperative OCT images were obtained. After vitrectomy, a predefined set of actions was performed using the iiOCT-based sensor. Images then were processed to assess the signal-to-noise ratio (SNR) at various angles to the retina and at different distances between the instrument tip and the retinal surface. Preoperative and intraoperative OCT images were compared qualitatively and quantitatively.Main Outcomes MeasuresThe feasibility in performing surgical tasks using the iiOCT-based sensor during vitreoretinal surgery, the SNR when imaging the retina, differences among intraoperative and preoperative OCT images, and characteristics of intraoperative retinal movements detected with the iiOCT-based probe.ResultsSurgeons were able to perform all the tasks but one. The PSS was able to maintain a fixed distance. The SNR of the iiOCT-based sensor signal was adequate to determine the distance to the retina and to control the PSS. Analysis of iiOCT-based sensor A-scans identified 3 clearly distinguishable retinal layers, including the inner retinal boundary and the interface at the retinal pigment epithelium–Bruch’s membrane. Thickness values differed by less than 5% from that measured by preoperative OCT, indicating its accuracy. The Fourier analysis of iiOCT-based sensor recordings identified anteroposterior retinal movements attributed to heartbeat and respiration.ConclusionsThis iiOCT-based sensor was tested successfully and promises reliable use during robot-assisted surgery. An iiOCT-based sensor is a promising step toward OCT-guided robotic retinal surgery.

Foveal microstructure and visual function in patients with lamellar macular hole, epiretinal membrane foveoschisis or macular pseudohole.

To compare the foveal microstructures, such as the prevalence of epiretinal proliferation (EP) and residual ellipsoid zone (EZ), in eyes with lamellar macular hole (LMH), epiretinal retinal membrane (ERM) foveoschisis and macular pseudohole (MPH), and to investigate the association of the foveal microstructure with visual functions. In addition to the prevalence of EP, we calculated the residual EZ index within 1mm and 3 mm (rEZ1 and rEZ3) in all examined eyes. Comparisons were conducted to baseline characteristics (logMAR visual acuity [logMAR VA], metamorphopsia score [Mave], central retinal thickness [CRT], the prevalence of EP, rEZ1 and rEZ3) between MPH, ERM foveoschisis and LMH subgroups. The relationships (1) between logMAR VA and each of age, type (MPH, ERM foveoschisis and LMH), the prevalence of EP, rEZ1, rEZ3, spherical equivalent (SE) and CRT and (2) between Mave and each of variables were investigated. Fifty-one eyes of 48 patients were enroled. The mean age was 65.2 ± 11.1 years. Ten eyes were diagnosed as LMH, 22 eyes as ERM foveoschisis and 19 eyes as MPH, respectively. There was a significant difference in CRT only between LMH and ERM foveoschisis (p = 0.023). There was a tendency toward significance in rEZ1 between LMH and ERM foveoschisis (p = 0.057), but not in rEZ3. The optimal model for logMAR VA included age, rEZ1, SE and CRT. On the other hand, the optimal model for Mave included the prevalence of EP, rEZ1 and SE. Microstructural observations are useful to predict visual functions in LMH, ERM foveoshisis and MPH.

Inflammatory retinal and choroidal neovascularization in a case of post-fever immune retinitis

The development of retinal and choroidal neovascularization in posterior uveitis is attributed to the angio-inflammatory drive with/without ruptures in the retinal pigment epithelium-Bruch's membrane complex. We report a unique case of a 15-year-old Asian-Indian female who developed immune retinitis post-typhoid fever along with simultaneous retinal and choroidal neovascularization. After ruling out infectious etiologies, she was initiated on a course of systemic steroids considering that the retinitis had immune-mediated pathogenesis. Subsequently, the retinitis lesion and choroidal neovascular membrane healed with scarring while the retinal neovascular complex showed fibrotic regression.

Primary Antiphospholipid Syndrome: A Hidden Predisposing Factor for Retinal Vein Occlusion and Choroidal Neovascular Membrane Formation Among Young Population

Background &amp; Objectives: Antiphospholipid syndrome can lead to variable systemic and ophthalmic manifestations. The study aims to establish the relationship between retinal vein occlusion (RVO) or choroidal neovascular membrane (CNVM) with Antiphospholipid Syndrome (APS). Methods: A multicentric prospective cross-sectional study was carried out in three major eye centers in Bahrain that included The Eye Infirmary, Bahrain Royal Hospital, and King Hamad University Hospital. All young patients aging from 35 to 50 years, presenting with either RVO or CNVM and not known to have any underlying systemic disease were included in the study. Antiphospholipid confirmatory tests and coagulation profiles were done for all patients. Results: Total number of fourteen eyes of ten patients were enrolled in the study. Six patients had RVO, three out of them had central retinal vein occlusion (CRVO) and three had branch retinal vein occlusion (BRVO). Four patients had bilateral CNVM (total of 8 eyes). All patients recorded high activated partial thromboplastin time (aPTT) readings, six out of ten patients were labeled as primary APS, four of them had positive anti-cardiolipin antibodies and the other two patients were positive for plasma lupus anticoagulant. Conclusion: APS should be considered as an etiological factor in all cases of retinal vein occlusion and choroidal neovascular membrane affecting young otherwise healthy individuals. In this study, 60% of patients who fit the inclusion criteria were labeled as primary APS patients. Timely investigations and treatment in these cases can prevent major catastrophic thrombotic events which may involve any system or organ in the body. Keywords: Antiphospholipid syndrome, Blood coagulation tests, Eye, Lupus coagulation inhibitor, Retinal vein occlusion