Preoperative hemoglobin A1c is associated with postoperative bleeding after vitrectomy for vitreous hemorrhage in patients with diabetic retinopathy.

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.

Simultaneous intravitreal aflibercept and gas injections for submacular hemorrhage secondary to polypoidal choroidal vasculopathy.

PURPOSE: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months. RESULTS: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R2 = 0.171, P = 0.056) and a greater displacement of SMH (R2 = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001). CONCLUSIONS: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement.

Vascular tortuosity analysis in eyes with epiretinal membrane imaged by optical coherence tomography angiography.

BACKGROUND: This study aimed to evaluate macular vessel tortuosity using optical coherence tomography angiography (OCTA) and its association with visual outcomes in eyes undergoing surgery for epiretinal membrane (ERM). METHODS: The study included 22 consecutive patients who underwent vitrectomy for ERM between May 2019 and July 2020 and OCTA at Osaka University Hospital. All patients underwent ophthalmologic examinations, including swept-source OCTA. Standard vitrectomy was performed, and the patients were followed up for 6 months postoperatively. Distortion of retinal vessels was calculated using two parameters: the actual vessel length in the vessel section (VL) and the direct vessel branching point distance (BD) in the three quadrants (nasal, temporal, and superior-inferior) of the macula. We analyzed the correlation between these parameters and visual outcomes. RESULTS: Significantly longer VL was found at 1, 3, and 6 months postoperatively (p = 0.006, 0.008, and 0.022, respectively) in the temporal quadrant compared to baseline temporal VL. Significantly shorter VL was found in nasal quadrants at 1 and 3 months (p = 0.046 and p = 0.018) in the comparison of nasal baseline VL. VL/BDs were correlated with the same postoperative best-corrected visual acuity (BCVA) at 1, 3, and 6 months (p = 0.035, 0.035, and 0.042, respectively) in the superior-inferior quadrant. A significant association of changes in VL and BCVA was found at 3 and 6 months postoperatively in the nasal quadrant (p = 0.018 and 0.0455, respectively). CONCLUSIONS: Changes in vascular distortion after ERM surgery can be measured using OCTA. The change in vessels around the macula became more linear; this was associated with visual outcomes after surgery.

Association of disorganization of retinal inner layers with optical coherence tomography angiography features in branch retinal vein occlusion.

PURPOSE: To examine the associations between the disorganization of the retinal inner layers (DRIL) and optical coherence tomography angiography characteristics and visual acuity (VA) outcomes in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: In this single-center cross-sectional cohort study, the data of 43 patients with macular edema secondary to BRVO that received pro re nata anti-vascular endothelial growth factor therapy were analyzed. B-scan and en face angiographic images were obtained by swept-source-based wide-field optical coherence tomography angiography performed at a single visit 1 month after the anti-vascular endothelial growth factor therapy session and evaluated. Correlations between the vascular indices in macula-centered 3 × 3 and 12 × 12 mm2 areas and B-scan parameters, such as DRIL length and VA, were examined. RESULTS: The mean DRIL length (Rs = 0.588, p < 0.001) and the proportion of scans with DRIL out of five scans (Rs = 0.507, p = 0.001) were significantly correlated with the final best-corrected VA in patients with BRVO. DRIL length was associated with vascular density (VD) and vascular length in the macula (Rs = - 0.425, p = 0.006 and Rs = - 0.382, p = 0.013, respectively), but not with VD and vascular length in the larger areas (12 × 12 mm2). Multilinear regression analysis revealed that the extent of macular edema (p = 0.0016) and VD in the 3 × 3 mm2 area (p = 0.004) was significantly associated with the DRIL development. CONCLUSION: DRIL severity was correlated with VA and associated with the peri-macular perfusion status in eyes with BRVO. Macular edema and macular perfusion affected DRIL severity. These findings would help understand the pathogenesis of DRIL in eyes with BRVO.

Long-term outcomes of intravitreal activated protein C injection for ischemic central retinal vein occlusion: an extension trial.

PURPOSE: Our previous 1-year pilot study evaluated the efficacy of intravitreally injected activated protein C (APC) in 10 eyes with ischemic central retinal vein occlusion (CRVO). The reperfusion of the areas of retinal nonperfusion (RNP) exceeded 50% of the baseline in five (50%) eyes 1 year after the APC injection. The current study evaluated the long-term efficacy and safety of intravitreal APC. METHODS: The 10 eyes in the pilot study were included in this study. Other treatments were administered at the physicians' discretion after the pilot study. We evaluated visual acuity (VA), central retinal thickness (CRT) and perfusion status, and adverse events and severity over the long term. RESULTS: The median follow-up was 60 months (range, 48-68 months). Compared with baseline, the post-treatment VA improved significantly (P < 0.001) from 1.39 to 1.06 logarithm of the minimum angle of resolution. The CRT improved significantly (P < 0.001) from 1090 to 195 µm at the last visit. The RNP areas decreased from an average 29.7 disc areas (DAs) at baseline to an average 16.5 DAs at the last examination (mean, 40 ± 6.5 months after the first APC treatment). No adverse events were related to intravitreal APC. CONCLUSION: No complications were associated with intravitreal APC, the clinical course improved, and improved RNP was maintained for the long term, suggesting that intravitreal APC may be an alternative treatment for CRVO.

Flow pattern and perforating vessels in three different phases of myopic choroidal neovascularization seen by swept-source optical coherence tomography angiography.

PURPOSE: To compare the choroidal neovascularization (CNV) flow patterns and the relationship between perforating vessels (PVs) and CNV in the three different stages of networks in myopic CNV (mCNV) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This retrospective study included 28 eyes with mCNV that was divided into three phases (active, scar, and atrophic) and observed by SS-OCTA. SS-OCTA findings, with special focus on the relationship between the PVs and CNV, were compared among the three phases. RESULTS: Overall, the CNV signal was detected in 31 of the 34 areas of CNV (91%); in the active, scar, and atrophic phases, respectively, CNV signals were detected in eight of eight areas of CNV (100%), 10 of 11 areas of CNV (91%), and 13 of 15 areas of CNV (86%). Two signal patterns were observed in each phase, i.e., dense and loop; in the atrophic phase, seven eyes were unclassifiable. The ratio between the dense and loop patterns did not differ significantly among the phases. In 30 of 34 areas of CNV for which clear images were obtained, the PVs and CNV were connected directly or indirectly in 19 area of CNV, and in five areas of CNV, trunk-like vessels were connected to the PVs within the CNV. The numbers of foveal or parafoveal CNVs accompanied by PVs were significantly (p=0.0048) greater than those of the extrafoveal CNV. CONCLUSIONS: OCTA provides detailed observation of mCNV and the relationship between CNV and PVs. Although the CNV signal pattern does not differ depending on the degree of atrophy, there are cases in which only the trunk-like vessels connect to the PVs within the CNV in the atrophic phase without CNV flow signal.

Impact of photoreceptor density in a 3D simulation of panretinal laser photocoagulation.

BACKGROUND: During panretinal photocoagulation (PRP), the outer retina, especially the photoreceptors, are destroyed. During such procedures, the impact of the retinal photocoagulation, which is performed in the same photocoagulated area, may change if it is applied to different locations with different photoreceptor densities. Thus, we aimed to evaluate the influence of photoreceptor density on PRP. METHODS: We constructed a three-dimensional (3D) average distribution of photoreceptors with 3D computer-aided design (CAD) software using previously derived photoreceptor density data and calculated the number of photoreceptors destroyed by scatter PRP and full-scatter PRP (size 400-µm on the retina, spacing 1.0 spot) using a geometry-based simulation. To investigate the impact of photoreceptor density on PRP, we calculated the ratio of the number of photoreceptors destroyed to the total number of photoreceptors, termed the photoreceptor destruction index. RESULTS: In this 3D simulation, the total number of photoreceptors was 96,571,900. The total number of photoreceptors destroyed by scatter PRP and full-scatter PRP were 15,608,200 and 19,120,600, respectively, and the respective photoreceptor destruction indexes were 16.2 and 19.8%, respectively. CONCLUSIONS: Scatter PRP is expected to have 4/5 of the number of photoreceptors destroyed by full-scatter PRP.

miR-30a-5p inhibition promotes interaction of Fas+ endothelial cells and FasL+ microglia to decrease pathological neovascularization and promote physiological angiogenesis.

Ischemia-induced angiogenesis contributes to various neuronal and retinal diseases, and often results in neurodegeneration and visual impairment. Current treatments involve the use of anti-VEGF agents but are not successful in all cases. In this study we determined that miR-30a-5p is another important mediator of retinal angiogenesis. Using a rodent model of ischemic retinopathy, we show that inhibiting miR-30a-5p reduces neovascularization and promotes tissue repair, through modulation of microglial and endothelial cell cross-talk. miR-30a-5p inhibition results in increased expression of the death receptor Fas and CCL2, to decrease endothelial cell survival and promote microglial migration and phagocytic function in focal regions of ischemic injury. Our data suggest that miR-30a-5p inhibition accelerates tissue repair by enhancing FasL-Fas crosstalk between microglia and endothelial cells, to promote endothelial cell apoptosis and removal of dead endothelial cells. Finally, we found that miR-30a levels were increased in the vitreous of patients with proliferative diabetic retinopathy. Our study identifies a role for miR-30a in the pathogenesis of neovascular retinal disease by modulating microglial and endothelial cell function, and suggests it may be a therapeutic target to treat ischemia-mediated conditions.

Anterior segment Scheimpflug imaging for detecting primary angle closure disease.

PURPOSE: To evaluate the capability of anterior segment Scheimpflug imaging for detecting primary angle closure disease (PACD): primary angle closure suspect, primary angle closure, and primary angle closure glaucoma, using cutoff points derived from reference databases of healthy subjects. METHODS: Eighty-seven patients with PACD and 49 age-matched control subjects were included. We evaluated the sensitivity and specificity of anterior chamber depth (ACD), anterior chamber volume (ACV), and anterior chamber angle (ACA) to differentiate patients with PACD from controls. Additionally, the study's raw data was analyzed via receiver operating characteristic curves for comparison. RESULTS: One standard deviation from the normative data's mean values was used as the cutoff point and yielded a sensitivity and specificity of 96.2% and 92.6% for ACD, 97.1% and 75.9% for ACV, and 93.3% and 72.2% for ACA, respectively. Receiver operating characteristic analysis of the raw data showed the area under the curve to be 0.984, 0.975, and 0.931 for ACD, ACV, and ACA, respectively. CONCLUSIONS: Our study demonstrated that the parameters of anterior segment Scheimpflug imaging, particularly ACD, accurately discriminate PACD. This was the first study to validate the device's normative data in a separate population. With its high reproducibility, ease of use, non-invasiveness, and speed, anterior segment Scheimpflug imaging is a potentially powerful screening tool for PACD.

Antibody-Mediated Inhibition of Tspan12 Ameliorates Vasoproliferative Retinopathy Through Suppression of ß-Catenin Signaling.

BACKGROUND: Anti-angiogenic biologicals represent an important concept for the treatment of vasoproliferative diseases. However, the need for continued treatment, the presence of nonresponders, and the risk of long-term side effects limit the success of existing therapeutic agents. Although Tspan12 has been shown to regulate retinal vascular development, nothing is known about its involvement in neovascular disease and its potential as a novel therapeutic target for the treatment of vasoproliferative diseases. METHODS: Rodent models of retinal neovascular disease, including the mouse model of oxygen-induced retinopathy and the very low density lipoprotein receptor knockout mouse model were analyzed for Tspan/ß-catenin regulation. Screening of a phage display of a human combinatorial antibody (Ab) library was used for the development of a high-affinity Ab against Tspan12. Therapeutic effects of the newly developed Ab on vascular endothelial cells were tested in vitro and in vivo in the oxygen-induced retinopathy and very low density lipoprotein receptor knockout mouse model. RESULTS: The newly developed anti-Tspan12 Ab exhibited potent inhibitory effects on endothelial cell migration and tube formation. Mechanistic studies confirmed that the Ab inhibited the interaction between Tspan12 and Frizzled-4 and effectively modulates ß-catenin levels and target genes in vascular endothelial cells. Tspan12/ß-catenin signaling was activated in response to acute and chronic stress in the oxygen-induced retinopathy and very low density lipoprotein receptor mouse model of proliferative retinopathy. Intravitreal application of the Ab showed significant therapeutic effects in both models without inducing negative side effects on retina function. Moreover, combined intravitreal injection of the Ab with a known vascular endothelial growth factor inhibitor, Aflibercept, resulted in significant enhancement of the therapeutic efficacy of each monotherapy. Combination therapy with the Tspan12 blocking antibody can be used to reduce anti-vascular endothelial growth factor doses, thus decreasing the risk of long-term off-target effects. CONCLUSIONS: Tspan12/ß-catenin signaling is critical for the progression of vasoproliferative disease. The newly developed anti-Tspan12 antibody has therapeutic effects in vasoproliferative retinopathy and can enhance the potency of existing anti- vascular endothelial growth factor agents.

Identification and characterization of a resident vascular stem/progenitor cell population in preexisting blood vessels.

Vasculogenesis, the in-situ assembly of angioblast or endothelial progenitor cells (EPCs), may persist into adult life, contributing to new blood vessel formation. However, EPCs are scattered throughout newly developed blood vessels and cannot be solely responsible for vascularization. Here, we identify an endothelial progenitor/stem-like population located at the inner surface of preexisting blood vessels using the Hoechst method in which stem cell populations are identified as side populations. This population is dormant in the steady state but possesses colony-forming ability, produces large numbers of endothelial cells (ECs) and when transplanted into ischaemic lesions, restores blood flow completely and reconstitutes de-novo long-term surviving blood vessels. Moreover, although surface markers of this population are very similar to conventional ECs, and they reside in the capillary endothelium sub-population, the gene expression profile is completely different. Our results suggest that this heterogeneity of stem-like ECs will lead to the identification of new targets for vascular regeneration therapy.

A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice.

Interactions between astrocytes and endothelial cells (ECs) are crucial for retinal vascular formation. Astrocytes induce migration and proliferation of ECs via their production of vascular endothelial growth factor (VEGF) and, conversely, ECs induce maturation of astrocytes possibly by the secretion of leukemia inhibitory factor (LIF). Together with the maturation of astrocytes, this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production in ECs are unclear. Here we show that apelin, a ligand for the endothelial receptor APJ, induces maturation of astrocytes mediated by the production of LIF from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis; however, aberrant overgrowth of endothelial networks with immature astrocyte overgrowth was induced. When ECs were stimulated with apelin, LIF expression was upregulated and intraocular injection of LIF into APJ-deficient mice suppressed EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in the maturation process of retinal angiogenesis.

Ligand-independent Tie2 dimers mediate kinase activity stimulated by high dose angiopoietin-1.

Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells (ECs). It has dual roles in promoting angiogenesis and stabilizing blood vessels, and it has been suggested that Tie2 forms dimers and/or oligomers in the absence of angiopoietin-1 (Ang1); however, the mechanism of ligand-independent dimerization of Tie2 and its biological significance have not been clarified. Using a bimolecular fluorescence complementation assay and a kinase-inactive Tie2 mutant, we show here that ligand-independent Tie2 dimerization is induced without Tie2 phosphorylation. Moreover, based on the fact that Tie1 never forms heterodimers with Tie2 in the absence of Ang1 despite having high amino acid sequence homology with Tie2, we searched for ligand-independent dimerization domains of Tie2 by reference to the difference with Tie1. We found that the YIA sequence of the intracellular domain of Tie2 corresponding to the LAS sequence in Tie1 is essential for this dimerization. When the YIA sequence was replaced by LAS in Tie2 (Tie2YIA/LAS), ligand-independent dimer was not formed in the absence of Ang1. When activation of Tie2YIA/LAS was induced by a high dose of Ang1, phosphorylation of Tie2 was limited compared with wild-type Tie2, resulting in retardation of activation of Erk downstream of Tie2. Therefore, these data suggest that ligand-independent dimerization of Tie2 is essential for a strong response upon stimulation with high dose Ang1.

Spontaneous separation of secondary epiretinal membrane after vitrectomy for retinal detachment.

Purpose: While secondary epiretinal membranes (ERMs) are well-documented postoperative complications following rhegmatogenous retinal detachment (RRD) surgery, literature addressing the mechanisms of spontaneous resolution, particularly in cases involving vitrectomy, remain limited. In this case report, we describe the spontaneous resolution of secondary ERM in an amateur boxer following traumatic RRD surgery. Observations: Pars plana vitrectomy was performed for traumatic RRD in a 20-year-old man. Secondary ERM formation was observed one month after RRD surgery, resulting in retinal distortion. The ERM began to peel spontaneously and disappeared one year after surgery. His visual function did not deteriorate in the meantime. Conclusions and Importance: Spontaneous ERM separation is possible even after vitrectomy. This is the first published observation of the formation and spontaneous disappearance of secondary ERM after vitrectomy without intervention.

Optical coherence tomography angiography imaging in peripheral commotio retinae: A case report.

Purpose: We present a case of traumatic commotio retinae (CR), in which blood flow was evaluated using optical coherence tomography angiography (OCTA). Observations: An 18-year-old Japanese man presented with traumatic retinal detachment and CR in his left eye, which had been hit by a handball. Fundus examination revealed peripheral retinal tear extending from the 1 to 3 o'clock position with retinal detachment, and CR near the area of tear. Fluorescein angiography (FA) confirmed an ischemic area near the retinal tear area at the CR. The patient underwent successful scleral buckling and cryopexy. Sequential OCTA imaging was performed and we were able to determine perfusion in the CR area, with maintained blood flow. Conclusions and importance: In blunt eye trauma, peripheral commotio retinae can be assessed non-invasively over time using OCTA. OCTA is a useful method for evaluating peripheral retinal whitened areas.

Embedding Technique versus Conventional Internal Limiting Membrane Peeling for Lamellar Macular Holes with Epiretinal Proliferation.

PURPOSE: To examine the outcomes of pars plana vitrectomy (PPV) with lamellar hole-associated epiretinal proliferation (LHEP) embedding and conventional internal limiting membrane (ILM) peeling for lamellar macular holes (LMHs) with LHEP. DESIGN: Retrospective observational study. SUBJECTS: Forty eyes of 39 consecutive patients with LMHs and LHEP who underwent 3-port PPV with a minimum follow-up of 3 months. METHODS: We compared the results of eyes that underwent PPV with LHEP embedding and ILM peeling (group E) with those of eyes that underwent PPV with ILM peeling only (group I) from September 2010 to September 2021. We confirmed whether the LHEP was embedded using postoperative OCT in all the cases. MAIN OUTCOME MEASURES: Postoperative best-corrected visual acuity (BCVA) and the development of macular holes (MHs) were assessed. RESULTS: The mean patient age was 73.3 years. The mean follow-up duration was 23.1 months. There were 23 and 17 eyes in groups E and I, respectively. Preoperative BCVA (P = 0.774) and central retinal thickness (CRT) (P = 0.800) did not differ significantly between the 2 groups. The final BCVA in group E was better than that in group I (P = 0.059). The final CRT in group E was thicker than that in group I (P < 0.001). Postoperatively, a significant improvement in BCVA was observed in group E at 3 months (P = 0.001) and at the final visit (P < 0.001). None of the eyes in group E developed postoperative MHs, whereas 5 eyes in group I developed postoperative MHs. CONCLUSIONS: Pars plana vitrectomy using the LHEP embedding technique improved visual acuity significantly and yielded better anatomic outcomes than those with PPV using conventional ILM peeling; MH formation did not occur. Embedding LHEP is more effective than conventional surgical procedures for LMHs.

Relationship between Full-Thickness Macular Hole Onset and Posterior Vitreous Detachment: A Temporal Onset Theory.

Purpose: To evaluate the relationship between full-thickness macular hole (FTMH) onset and perifoveal posterior vitreous detachment using OCT data. Design: Retrospective study. Participants: A total of 742 patients with FTMH or impending macular hole (MH) in ≥ 1 eye, as determined by ophthalmoscopy and OCT. Methods: Macular holes were staged using OCT results. Patients with the posterior vitreous membrane clearly detected in the OCT images and vitreoretinal adhesion size ≤ 1500 µm-eyes with MH stages 1-3-were included in the study. The contralateral eyes were also included in the analyses if they showed the focal type of vitreomacular adhesion (VMA) (i.e., vitreoretinal adhesion ≤ 1500 µm). The distance between the posterior vitreous membrane and the surface of the retina was defined as the posterior vitreous separation height (PVSH). Using the OCT images, PVSHs of each eye in 4 directions (nasal, temporal, superior, and inferior) at 1 mm from the center of the MH or fovea were calculated. Main Outcome Measures: The main outcome measures were PVSHs according to the MH stage and VMA, the relationship of the foveal inner tear with PVSH, and the likelihood of a foveal inner tear based on the direction. Results: The PVSH trends in each of the 4 directions were as follows: VMA < MH stage 1 = MH stage 2 < MH stage 3. Initial MH stage 2 (onset of FTMH) was defined as the presence of a gap in only 1 of the 4 directions from the center of the MH. With increased PVSH, the likelihood of a gap increased (P = 0.002), and a temporal gap was more likely to occur than a nasal gap (P = 0.002). Conclusions: At FTMH onset, a foveal inner tear likely appears on the temporal side or the side showing a high PVSH value. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraoperative optical coherence tomography observation with perfluorocarbon tamponade for subretinal membranes in proliferative vitreous retinopathy.

PURPOSE: To report the efficacy of intraoperative optical coherence tomography (iOCT) in locating proliferative membranes or strands subretinally or preretinally during pars plana vitrectomy for proliferative vitreoretinopathy (PVR) or old rhegmatogenous retinal detachment. METHODS: After removing the vitreous and apparent epiretinal membranes, vitreous fluid was exchanged for perfluorocarbon. Lesions of the retinal folds or persistently detached retinas, suspected to be subretinal membrane lesions, were examined using iOCT in three eyes with PVR. RESULTS: iOCT showed subretinal or preretinal structures in all three patients. A subretinal structure with underlying fluid was removed through an intentional hole in a patient. In another patient, a subretinal structure without underlying fluid was not removed. In the remaining patient, the preretinal membranes detected with iOCT could be peeled successfully. CONCLUSION: iOCT examination with perfluorocarbon tamponade effectively identified the correct location of proliferative membranes or strands, namely preretinal or subretinal. This imaging technique helps surgeons determine whether an intentional hole should be made to remove the subretinal structure during vitrectomy. iOCT, combined with perfluorocarbon tamponade, leads to safer and more effective surgery for PVR.

Bioactive extracellular vesicles from a subset of endothelial progenitor cells rescue retinal ischemia and neurodegeneration.

Disruption of the neurovascular unit (NVU) underlies the pathophysiology of various CNS diseases. One strategy to repair NVU dysfunction uses stem/progenitor cells to provide trophic support to the NVU's functionally coupled and interdependent vasculature and surrounding CNS parenchyma. A subset of endothelial progenitor cells, endothelial colony-forming cells (ECFCs) with high expression of the CD44 hyaluronan receptor (CD44hi), provides such neurovasculotrophic support via a paracrine mechanism. Here, we report that bioactive extracellular vesicles from CD44hi ECFCs (EVshi) are paracrine mediators, recapitulating the effects of intact cell therapy in murine models of ischemic/neurodegenerative retinopathy; vesicles from ECFCs with low expression levels of CD44 (EVslo) were ineffective. Small RNA sequencing comparing the microRNA cargo from EVshi and EVslo identified candidate microRNAs that contribute to these effects. EVshi may be used to repair NVU dysfunction through multiple mechanisms to stabilize hypoxic vasculature, promote vascular growth, and support neural cells.

The Caliber of Optociliary Shunt Vessels Is Associated with Macular Blood Flow and Visual Acuity in Central Retinal Vein Occlusion.

Purpose: To define the role of optociliary shunt vessels (OSVs) in eyes with central retinal vein occlusion (CRVO) using OCT angiography (OCTA) with macular parameters. Design: Retrospective, observational, consecutive case series. Participants: Forty-one eyes in 38 consecutive patients with CRVO were analyzed in this study. Methods: Optic disc and macula were imaged by swept-source OCTA (3 × 3 mm) as well as by high-quality fundus photography. Main Outcome Measures: We compared macular vessel density (VD) and visual acuity between eyes in which OSVs developed and those in which they did not. Furthermore, we measured the diameter of the OSVs and analyzed the correlation with macular VD and visual acuity. Results: Optociliary shunt vessels were found in 25 eyes (61%). Central retinal vein occlusion with OSVs did not show any statistical difference compared with CRVO without OSVs in either macular VD of the total retina (0.31 ± 0.07 and 0.26 ± 0.09, respectively; P = 0.0937) or final best-corrected visual acuity (BCVA) (0.30 ± 0.43 logarithm of the minimum angle of resolution [logMAR] and 0.59 ± 0.54 logMAR, respectively; P = 0.0705). The mean OSV diameter was 71 ± 30 µm in CRVO with OSV. The diameter of the OSVs was correlated positively with superficial VD (r = 0.443; P = 0.027), deep VD (r = 0.494; P = 0.012), and total VD (r = 0.491; P = 0.013). Furthermore, the OSV diameter was also negatively correlated with BCVA (logMAR) at the final visit (r = -0.531; P = 0.006). Conclusions: The results demonstrated that the diameter of the OSVs was associated with macular VD and visual acuity in patients with CRVO. The development of large OSVs on the optic disc may be a good indicator of the maintenance of blood flow in the macula.