Retro-mode imaging of fibrovascular membrane in proliferative diabetic retinopathy after intravitreal bevacizumab injection

The F10 is a new commercially available scanning laser confocal ophthalmoscope (SLO) that can perform multiple functions. We determined the usefulness of noninvasive evaluation of proliferative diabetic retinopathy (PDR) pathologies before and after intravitreal injection of bevacizumab (IVB) using the new indirect viewing system of the retro-mode function of the F10 SLO, and compared the images histologically with surgically excised fibrovascular membrane from two cases. In PDR, neovascular vessels in fibrovascular membrane were clearly seen with the retro-mode, even after IVB and without blood flow. The F10 SLO may be useful in evaluating neovascular vessels in fibrovascular membrane in PDR and for determining the precise retinal changes in diabetic retinopathy

Characterization of protein kinase C isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization

Retinal neovascularization is a major cause of blindness and requires the activities of several signaling pathways and multiple cytokines. Activation of protein kinase C (PKC) enhances the angiogenic process and is involved in the signaling of vascular endothelial growth factor (VEGF). We have demonstrated a dramatic increase in the angiogenic response to oxygen-induced retinal ischemia in transgenic mice overexpressing PKCβ2 isoform and a significant decrease in retinal neovascularization in PKCβ isoform null mice. The mitogenic action of VEGF, a potent hypoxia-induced angiogenic factor, was increased by 2-fold in retinal endothelial cells by the overexpression of PKCβ1 or β2 isoforms and inhibited significantly by the overexpression of a dominant-negative PKCβ2 isoform but not by the expression of PKC α, δ, and ζ isoforms. Association of PKCβ2 isoform with retinoblastoma protein was discovered in retinal endothelial cells, and PKCβ2 isoform increased retinoblastoma phosphorylation under basal and VEGF-stimulated conditions. The potential functional consequences of PKCβ-induced retinoblastoma phosphorylation could include enhanced E2 promoter binding factor transcriptional activity and increased VEGF-induced endothelial cell proliferation

Transcorneal three-port vitrectomy without conjunctival incision.

Background: Although widely accepted, pars plana vitrectomy is difficult to perform when patients have a large filtering bleb. We describe technical details of 25-gauge transcorneal vitrectomy and the clinical outcomes. Methods: We performed 25-gauge transcorneal vitrectomy on seven eyes of seven patients (female: male, 4:3; age, 39 to 77 years; mean, 66.1 years) between January 2005 and February 2007. Phacoemulsification via a corneal incision was followed by continuous curvilinear capsulorrhexis (CCC) of the posterior capsule. We used a notched contact lens to perform 25-gauge transcorneal vitrectomy. Results: Four patients with idiopathic ERM and three with secondary ERM were treated by 25-gauge vitrectomy. Postoperative visual acuity was good in most of them and the cell density of the corneal endothelium was maintained. Conclusion: These advantages of this procedure are that the conjunctiva and ocular surface can be completely maintained and vitreous incarceration can be avoided. Thus, 25-gauge vitrectomy might be particularly suitable for treating glaucoma with a filtering bleb. (158 words/200 words

Foveal Thickness Fluctuation in Anti-VEGF Treatment for Branch Retinal Vein Occlusion: A Long-term Study

PURPOSE: Branch retinal vein occlusion (BRVO) causes macular edema (ME), which can be controlled with anti-VEGF treatments. However, these treatments are not curative, necessitating additional anti-VEGF treatments at recurrence. Long-term results, optimal anti-VEGF treatment regimens, and the comprehensive effects of ME recurrence are largely unknown. Thus, we aimed to examine the effects of foveal thickness (FT) fluctuation (FTF) on the visual and morphologic outcomes of anti-VEGF treatments for BRVO-ME administered via a pro re nata regimen. DESIGN: A retrospective, observational case series. SUBJECTS: This study analyzed 309 treatment-naïve patients (309 eyes) with BRVO-ME between 2012 and 2021 at a multicenter retinal practice. METHODS: The FT was assessed using OCT at each study visit. MAIN OUTCOME MEASURES: We evaluated the logarithm of the minimal angle of resolution (logMAR) best corrected visual acuity (BCVA) and the defect length of the foveal ellipsoid zone (EZ) band using OCT. RESULTS: At baseline, the mean logMAR BCVA was 0.30 ± 0.30 and the mean FT was 503 ± 162 μm. The number of anti-VEGF injections for BRVO-ME was 5.8 ± 4.6 during the mean follow-up period (50.6 ± 22.2 months). At the final examination, the mean logMAR BCVA and FT values were significantly improved compared with those at the baseline. Multiple regression analyses showed that age, baseline logMAR BCVA, and FTF were significantly associated with the final logMAR BCVA (β = 0.20, 0.35, and 0.30, respectively). Foveal thickness fluctuation (divided into groups 0-3 in ascending order of FTF) was significantly associated with logMAR BCVA and the defect length of the foveal EZ band at the final examination. The defect lengths of the foveal EZ band were longitudinally shortened in groups 0 and 1 and were slightly prolonged in groups 2 and 3. The logMAR BCVA showed improvements in groups 0 and 1 and worsened slightly in groups 2 and 3. CONCLUSIONS: Foveal thickness fluctuation was significantly associated with visual acuity and foveal photoreceptor status. Thus, the morphologic and functional prognoses of eyes with BRVO may improve with the identification of the characteristics of eyes with greater FTF and consequently controlling the FTF more strictly

Factors associated with extremely poor visual outcomes in patients with central retinal vein occlusion

Here, we examined prognostic factors for extremely poor visual outcomes in patients with central retinal vein occlusion (CRVO) in actual practices. We included 150 consecutive eyes with treatment-naïve acute CRVO from four different facilities and observed them for over 24 months. Macular edema (ME) was treated with one or three monthly anti-vascular endothelial growth factor injections (1 or 3 + pro re nata). According to the final Snellen visual acuity (VA), we divided the patients into very poor VA (< 20/200) and control (≥ 20/200) groups and examined risk factors for poor final visual outcomes. The baseline Snellen VA was hand motion to 20/13. The mean number of anti-VEGF injections for ME was 5.3 ± 3.7 during the follow-up period. In total, 49 (32.7%) patients exhibited a very poor final VA; this group comprised significantly older patients with a significantly poorer baseline VA (P < 0.01 for both) than the control group. Comorbid internal carotid artery disease and diabetic retinopathy were significantly associated with a poor final VA. In actual clinical practice, visual outcomes may be extremely poor despite ME treatment in certain patients with CRVO, with advanced age, poor baseline VA, and comorbid internal carotid artery disease and diabetic retinopathy being significant risk factors

Succinate Increases in the Vitreous Fluid of Patients With Active Proliferative Diabetic Retinopathy

Purpose: To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. Design: Comparative case series. Methods: A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. Results: Mean vitreous succinate levels were 1.27 μM in ERM and 2.20 μM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 μM; quiescent PDR: 1.02 μM; active PDR with intravitreal bevacizumab injection: 1.20 μM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. Conclusions: Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate

RETINAL BLOOD FLOW LEVELS MEASURED BY LASER SPECKLE FLOWGRAPHY IN PATIENTS WHO RECEIVED INTRAVITREAL BEVACIZUMAB INJECTION FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION

Purpose: To report retinal blood flow levels measured by Laser speckle flowgraphy in three patients after they received an intravitreal bevacizumab injection (IVB) for macular edema secondary to central retinal vein occlusion (CRVO). Methods: Three patients (3 eyes) being treated with IVB (1.25 mg/0.05 mL) for secondary macular edema of CRVO were examined. Laser speckle flowgraphy analyses of the blood flow were based on the examinations of mean blur rate (MBR) at the major vessels of the optic disk. Central retinal thickness (CRT) was measured by optical coherence tomography using Macular Cube 512 128 scanning protocol. Results: After the first IVB, Case 1 exhibited an increase in MBR and decrease in CRT. After 4months, an additional injectionwas required because of a subsequentMBR decrease and CRT increase, which led to an increase inMBR and decrease in CRT similar to that observed after the first treatment. Subsequently, blood flow has continued to improve without additional IVB. Macular edema recurrence in Case 2 led to 3 further IVBs over a 6-month period. Although increases inMBRanddecreases inCRTwerenoted,MBRvalues tendedtodeclineafter eachIVB. In Case 3, macular edema recurrence led to 5 additional IVBs being carried out within a 1-year period. Continuous MBR increases and CRT decreases were observed in the patient after each IVB. By measuringMBR using laser speckle flowgraphy,wemay predict the prognosis of CRVO. Conclusion: Mean blur rate increases after IVB were confirmed by laser speckle flowgraphy in three patients. Even though CRVO pathology backgrounds can vary, laser speckle flowgraphy may be useful in both determining the CRVO prognosis and in evaluating treatment efficacy

The suboptimal structures find the optimal RNAs: homology search for bacterial non-coding RNAs using suboptimal RNA structures

Non-coding RNAs (ncRNAs) are regulatory molecules encoded in the intergenic or intragenic regions of the genome. In prokaryotes, biocomputational identification of homologs of known ncRNAs in other species often fails due to weakly evolutionarily conserved sequences, structures, synteny and genome localization, except in the case of evolutionarily closely related species. To eliminate results from weak conservation, we focused on RNA structure, which is the most conserved ncRNA property. Analysis of the structure of one of the few well-studied bacterial ncRNAs, 6S RNA, demonstrated that unlike optimal and consensus structures, suboptimal structures are capable of capturing RNA homology even in divergent bacterial species. A computational procedure for the identification of homologous ncRNAs using suboptimal structures was created. The suggested procedure was applied to strongly divergent bacterial species and was capable of identifying homologous ncRNAs

Decorrelation Signal of Diabetic Hyperreflective Foci on Optical Coherence Tomography Angiography

Diabetic hyperreflective foci in the outer retinal layers are a clinically relevant finding on optical coherence tomography (OCT) images, although their characteristics remain to be elucidated. Here we investigated the decorrelation signal around hyperreflective foci on OCT angiography (OCTA) images in diabetic retinopathy (DR). We retrospectively reviewed sufficient quality OCTA images from 102 eyes of 66 patients that were obtained using split-spectrum amplitude-decorrelation angiography algorithm. Most confluent hyperreflective foci were randomly deposited or appeared in a radiating array on the en-face structural OCT images in the inner nuclear layer (INL) or Henle’s fiber layer (HFL), respectively. Within the INL, hyperreflective foci were not accompanied by decorrelation signals and attached to capillaries on OCTA images. Decorrelation signals were sometimes delineated in hyperreflective foci in the HFL and other times appeared to be pseudopod-like or wrapping around hyperreflective foci, referred to as reflectance-decorrelated foci. The decorrelation signal intensity of hyperreflective foci in the HFL was associated with logMAR VA (R = 0.553, P < 0.001) and central subfield thickness (R = 0.408, P < 0.001) but not with DR severity. These data suggest that reflectance-decorrelated foci on OCTA images are clinically relevant as well as shed lights on the properties in diabetic hyperreflective foci