In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy

BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.MethodsA total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.ResultsThe in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.ConclusionThis study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.

Outcome and Complications of Phacoemulsification Combined with Pars Plana Vitrectomy

Aim: To determine the outcomes of phacoemulsification also examine the complications associated to phacoemulsification combined with pars plana vitrectomy. Study design: Observational study Place and duration of study: Department of Ophthalmology, Khawaja Muhammad Safdar Medical College, Allama Iqbal Memorial Teaching Hospital, Sialkot, from 15th July 2020 to 14thJanuary 2021. Methodology: Twenty patients of both genders whom had undergoing phacovitrectomy were included. Patient’s ages were ranging from 20 to 80 years. Patient’s detailed medical histories were examined after taking informed consent. Patient’s retinal diagnosis, intraocular pressure, visual acuity, intra and post-operative complications were recorded. All the patients had received clear corneal phacoemulsification and 23-guage pars plana vitrectomy. Results: There were 15(75%) male patients while 5(25%) female patients with mean age was 54.52±12.45 years. Five patients (25%) had vitreos hemorrhage, 7(35%) patients had rhegmatogenous retinal detachment, 3(15%) patients had intraocular foreign body, 2(10%) had epiretinal membrane, 2(10%) had macular hole and 1(5%) had tractional retinal detachment. Miosis and rupture of posterior capsule were the most common intraoperative complications found in 85% and 10%. Fibrin was found in 3 (15%) cases, posterior synechia was found in 2 (10%) cases. Conclusion: The phacoemulsification with pars plana vitrectomy is safe and effective treatment modalities in patients with cataract coexist with vitreoretinal disease. Keywords: Phacoemulsification, Pars plana vitrectomy, Cataract, Complications, Outcomes

Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

Foldable capsular vitreous body implantation for treatment of traumatic retinal detachment: two case reports

Retinal detachment caused by severe ocular trauma is a type of refractory vitreoretinal disease. Current treatment methods include vitrectomy combined with silicone oil tamponade. However, long-term use of silicone oil tamponade has various complications, including a risk of silicone oil dependence that eventually leads to eyeball atrophy and enucleation. Foldable capsular vitreous bodies (FCVBs) offer a good solution for these problems. However, FCVBs have not been used in large-scale clinical applications and few cases have been reported in the published literature. The main use of FCVBs, based on current evidence, is in the treatment of the relatively few (but important) patients whose eyes have no visual potential; the aim of treatment in these patients is globe preservation, rather than restoration of vision. Here, we describe two patients who underwent FCVB implantation. The findings in these patients indicated that FCVBs can effectively support the vitreous cavity and detached retina. FCVB implantation may thus offer a safe and effective method for treatment of severe retinal detachment, avoiding the inconvenience caused by silicone oil dependence and enucleation. To confirm its long-term usefulness in clinical applications, many additional case reports are needed.

Pars Plana Vitrectomy following Traumatic Ocular Injury and Initial Globe Repair: A Retrospective Analysis of Clinical Outcomes

ABSTRACT Introduction Penetrating and perforating ocular trauma are often devastating and may lead to complete visual loss in the traumatized eye and subsequent compromise of the fellow eye. A significant proportion of traumatic injuries are complex, often requiring vitreoretinal intervention to preserve vision. A retrospective analysis at a level 1 trauma center was performed to evaluate the time course, incidence, and outcomes following pars plana vitrectomy (PPV) after traumatic ocular injury and initial globe repair. Materials and Methods Eyes that underwent open globe repair following ocular trauma at Brooke Army Medical Center, between January 1, 2014 and December 30, 2016 were analyzed. Specific factors evaluated include mechanism of injury, defect size and complexity, ocular trauma score, zone of injury, associated orbital trauma, and time from injury to surgical intervention. A subset analysis was conducted specifically on eyes requiring subsequent PPV for vision preservation because of vitreoretinal disease. Surgical outcomes, time to secondary intervention, and complication rates were then assessed. Results In total, 70 eyes requiring open globe repair were examined, with 43 having undergone PPV. Average and median time to vitrectomy were 18.8 and 8 days, respectively. Eyes that underwent PPV were more likely to have an afferent papillary defect, vitreous hemorrhage, intraocular foreign body, and retinal detachment at the time of initial injury (although the latter two factors were not statistically significant), and were more likely to receive penetrating keratoplasty. Proliferative vitreoretinopathy occurred in 37.2% of eyes that underwent PPV, versus 3.7% of those that did not (P = 0.0013). Timing of PPV (i.e., before or after 14 days) had no statistically significant effect on the rate of PVR (Table I). Eyes that underwent PPV showed an improvement of visual acuity from average 2.5 logMAR following initial injury to 1.5 logMAR 6 months after PPV, equivalent to 18.7 Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained, versus 37.7 ETDRS letters gained in eyes without PPV. Among PPV eyes, early repair (&lt;14 days) was associated with greater improvement in visual acuity. Conclusion Overall, patients requiring PPV following open globe repair generally had more severe injuries and worse 6-month postoperative visual acuity. Patients who underwent more expedited vitrectomy showed greater improvement in visual acuity as measured by ETDRS letters gained.

Comparison of 27-Gauge and 25-Gauge Microincision Vitrectomy Surgery for the Treatment of Vitreoretinal Disease: A Systematic Review and Meta-Analysis

Background. We performed a systematic review and meta-analysis to evaluate the safety and effectiveness of 27-gauge (27-G) microincision vitrectomy surgery (MIVS) compared with 25-guage (25-G) MIVS for the treatment of vitreoretinal disease. Methods. A systematic electronic search was conducted in March 2020 in PubMed, Embase, and the Cochrane library. Eligible criteria for including studies were controlled trials comparing 27-G vitrectomy with 25-G vitrectomy in patients with vitreoretinal disease. The main outcomes included operation time; best corrected visual acuity (BCVA) in logMAR; postoperative intraocular pressure (IOP); primary anatomical success rate for rhegmatogenous retinal detachment (RRD) cases and postoperative central macular thickness (CMT) for idiopathic epiretinal membrane (ERM) cases; intraoperative/postoperative complications. Odds ratio (OR) and mean difference (MD) were synthesized under fixed or random effects models. Results. Eleven studies enrolling 940 eyes were identified. Among those 11 studies, six studies were on the treatment of RRD and five studies were on the treatment of ERM, so subgroup analyses were conducted. The total pooled results indicated that 27-G surgery system had obvious advantages in improving BCVA at six months after the vitrectomy (P = 0.004) and reducing intraoperative/postoperative complications (P = 0.03). However, the mean operation time was significantly longer by three minutes for 27-G compared with 25-G vitrectomy (P = 0.002). In subgroup analyses, for the treatment of ERM cases, 27-G group was associated with less complications and longer operation time. However, for the treatment of RRD cases, 27-G groups and 25-G groups were comparable in operation time, postoperative BCVA, postoperative IOP, and primary anatomical success rate. Conclusions. This meta-analysis confirmed that 27-G MIVS was an effective and safe surgical system compared with 25-G MIVS for the treatment of RRD and ERM cases, even though 27-G system needs a longer surgical time.