A Novel Surgical Approach for Big Sheet Allogenic Retinal Pigment Epithelium-Bruch Membrane Complex Transplantation Into the Subretinal Space.

PURPOSE: Allogenic transplantation of retinal pigmented epithelium monolayer sheet has experienced bottlenecks due to imperfect surgical techniques. In this study, we developed a novel approach for allogenic transplantation of big sheets of retinal pigment epithelium (RPE)-Bruch membrane complex. METHODS: RPE-Bruch membrane complex sheets of 5 × 6 mm2 to 10 × 10 mm2 were taken from donated eyes. Through a novel approach, the sheets of RPE-Bruch membrane complex were transplanted into the subretinal space of eight eyes (8 patients) with late-stage retinitis pigmentosa. The patients were followed up for 5 ± 2 months. RESULTS: All RPE-Bruch membrane complexes were successfully inserted into the subretinal space during the surgery. Follow-up examinations also showed that the grafts attached well to the transplantation site. No rejection or retinal detachment was found. CONCLUSION: Through our technique, big sheets of allogenic RPE-Bruch membrane complexes could be implanted into the subretinal space smoothly. This novel approach may be useful for big sheet of allogenic RPE-derived or stem cells-derived RPE transplantation in the treatment of RP and other retinal dystrophic diseases.

The continuous treatment of anterior segment open globe injury: an eye injury vitrectomy study.

Background: The prognostic significance of debridement has long been demonstrated for trauma in tissues other than ocular. Unfortunately, the impact of wound healing in the anterior segment (AS) was not paid as much attention as in the posterior segment (PS). This study aims to evaluate whether a better prognosis can be obtained from continuous surgical treatment (CST) before fibrosis or scar formation in an open AS injury. Methods: In this prospective comparative cohort study, 19 eyes of 19 patients with an experience of AS open globe injury (OGI) were selected from the database of the eye injury vitrectomy study (EIVS) from January 1, 2020 to July 31, 2021. Of 19 patients, 9 who received CST were assigned to group 1, and 10 patients without CST after the initial wound repair were included in group 2. Comparison between the two groups was conducted in the final best corrected visual acuity (BCVA). Significant AS complications after injury were evaluated with χ2 test. The corneal leucoma area ratio, astigmatism, and the score of AS abnormalities were analyzed using the Student's t-test. Results: The differences of baseline clinical factors between the two groups were not statistically significant. The final BCVA was better in group 1 than in group 2 (P=0.011). The complications directly caused by AS injury, namely adhesive corneal leucoma, uneven anterior chamber, block of light passing through the pupil, and fibrosis or scarring, were more frequent in group 2 than in group 1 (P=0.011, 0.022, 0.037, and 0.040, respectively). Secondary glaucoma (3 cases) and severe AS structure destruction (2 cases) occurred only in group 2 (P=0.037 and 0.474, respectively). The area ratio of leucoma (0.79±0.44, 0.82±0.50, respectively) and corneal astigmatism (3.69±1.90, 4.50±4.80, respectively) revealed no statistical significance between the two groups. On the other hand, the score of AS abnormalities, mean values being 93.33±11.18 for group 1 and 67.00±29.46 for group 2, was statistically different (P=0.022). Conclusions: Initiating CST before fibrosis or scar formation might improve the prognosis of open AS injury, which was preferable to natural wound healing after wound repair.

Multimodal imaging of a micro-anatomical structure in the vitreous base.

BACKGROUND: To describe an ultrastructure in the vitreous base (VB) and its micro-anatomical characteristics by multimodal imaging. METHODS: Light and transmission electron microscopy of the VB were performed on specimens from post-trauma eyes and one healthy donor eye. Intra-operative fundus images associated with VB abnormalities were captured from 4 cases, including 2 retinal detachment (RD) with PVR eyes and 2 post-trauma eyes. Images during micro-anatomical observation of the three specimens were analyzed along with the fundus images obtained during vitrectomy. RESULTS: Densely packed collagen fibers were observed by light microscopy between the pigment epithelium layer and uveal tissue within the ora serrata region in specimen 1 and the post-mortem healthy eye, respectively. A similar structure was also observed by transmission electron microscopy interior to the pigment epithelium layer and exposed to the vitreous cavity in specimen 2. The collagen fibers, which were termed ciliary body-choroid-retina (CB-C-R) connector, connects to the vitreous fibers interiorly, ciliary epithelium anteriorly, peripheral retina posteriorly, and uveal tissue exteriorly. The three different RD boundaries related to the posterior edge of the VB, ora serrata, and ciliary epithelium are demonstrated with the micro-anatomical characteristics of the CB-C-R connector. CONCLUSION: The CB-C-R connector exists deep in the VB.

Novel pathogenic TGFBR1 variant identified in an adult with acquired retinal arterial macroaneurysm in loeys-dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder of the connective tissue that has phenotypic overlap with Marfan syndrome，but the aortic root dissections can be more aggressive and ocular findings in LDS may be very different than Marfan syndrome. METHODS: Review of one case of LDS with novel retinal findings. RESULTS: A 30-year-old female with LDS was found to have retinal arterial macroaneurism (RAM) in the left eye. Local laser photocoatulation and intravitreal anti-VEGF was applied but exudative retinal detachment developed soon after that. Transscleral diode photocoagulation was then performed and subretinal fluid was resolved. CONCLUSION: RAM is a unique finding of LDS related to a novel mutation of TGFBR1.

Analysis of Clinical Characteristics of Patients with Recurrent Cytomegalovirus Retinitis after Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To analyze and summarize the clinical and imaging characteristics of patients with cytomegalovirus retinitis (CMVR) relapse after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective case series study recruited patients with CMVR after HSCT. The study compared the patients with stable lesions and CMV-negative aqueous humor after treatment with those with relapse lesions and a CMV DNA load in aqueous humor which had increased again after treatment. The observation indexes were basic clinical information, best-corrected visual acuity, wide-angle fundus photography, optical coherence tomography (OCT), blood CD4+ T lymphocyte count, and aqueous humor CMV load of the patients. We summarized the data and statistically analyzed the differences between the relapse and non-relapse groups, as well as the correlations of the observed indicators. RESULTS: The study recruited 52 patients with CMVR (82 eyes) after HSCT, of whom 11 patients (15 eyes) had recurrence after treatment (21.2%). The recurrence interval was 6.4 ± 4.9 months. The final best-corrected visual acuity of recurrent patients was 0.3 ± 0.3. The number of CD4+ T lymphocytes in recurrence patients at the time of onset was 126.7 ± 80.2/mm3. The median CMV DNA load detected in aqueous humor at the time of recurrence was 8.63 × 103 copies/mL. There was a significant difference in the CD4+ T lymphocyte count between the recurrence and the non-recurrence groups at onset. The onset of visual acuity in recurrence patients was significantly correlated with final visual acuity and recurrence lesion area. The fundus of recurred CMVR showed increased marginal activity of the original stable lesion. Concurrently, yellow-white new lesions appeared around the stable, atrophic, and necrotic lesions. OCT showed new diffuse hyperreflexic lesions in the retinal neuroepithelial layer near the old lesions. Inflammatory punctate hyperreflexes were observed in the vitreous, with vitreous liquefaction and contraction. CONCLUSION: This study suggests that the clinical features, fundus manifestations, and imaging features of CMVR recurrence after HSCT are different from those at the initial onset. Patients should be closely followed up after their condition is stable to be alert for CMVR recurrence.

Towards the Objective Speech Assessment of Smoking Status based on Voice Features: A Review of the Literature.

BACKGROUND AND OBJECTIVE: In smoking cessation clinical research and practice, objective validation of self-reported smoking status is crucial for ensuring the reliability of the primary outcome, that is, smoking abstinence. Speech signals convey important information about a speaker, such as age, gender, body size, emotional state, and health state. We investigated (1) if smoking could measurably alter voice features, (2) if smoking cessation could lead to changes in voice, and therefore (3) if the voice-based smoking status assessment has the potential to be used as an objective smoking cessation validation method. METHODS: A systematic review of the scientific literature was conducted to compile studies on smoking status assessment based on voice features. We searched nine scientific databases for original studies involving the effects of smoking on voice features, the effects of smoking cessation on voice features. RESULTS: A total of 34 studies were identified for review. We found that fundamental frequency, jitter, shimmer, harmonics to noise ratio, and other voice features are affected by smoking and could be used to assess smoking status. CONCLUSION: Speech assessment of smoking status based on voice features has potential as a smoking status validation method, as it is simple, reliable, and less time-consuming. Furthermore, this study provides recommendations for future research on the objective speech assessment of smoking status based on voice features.

Guideline for the treatment of no light perception eyes induced by mechanical ocular trauma.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

Electroacupuncture of Weizhong (BL-40) Acupoint Inspires Muscular Satellite Cell Regeneration and Promotes Muscle Repair Capacity after Back Muscle Injury in Sprague-Dawley Rat Model.

Background: Back muscle injury is the most common illness involved in aged people. Muscular satellite cells, playing a key role in the muscle repairing process, are gradually losing their regenerative ability with aging, which attenuates the injured muscle repairing process. Electroacupuncture at Weizhong acupoint has been widely used in the treatment of young and aged patients with back muscle damage. Its efficacy has been proven by a randomized double-blind placebo clinical trial. However, the rehabilitation mechanisms are largely unknown. This study will explore the possible mechanisms associated with electroacupuncture at the Weizhong acupoint (BL 40) promoting muscle repairing ability. Method: A total of 58 male and female Sprague-Dawley rats were divided into a younger group (4-month-old) and an aged group (16-month-old), younger and aged rats were further divided as a sham, injured, injured rats treated with electroacupuncture at Weizhong point or treated with Non-Weizhong point groups. The back muscle injury model was produced in rats as a previously described method with modification. Furthermore, Weizhong acupoints underwent electroacupuncture treatment with 15 V magnitude, 2 Hz/10 Hz frequency density, 1.0 mA current intensity, and 10 min each day for 10 consecutive days using HANS's electroacupuncture apparatus. After the last treatment, the paravertebral muscles and serum of all animals were undergone histological, immunohistochemistry, and flow cytometry analysis. Serum levels of Creatine Kinase (CK) and proinflammatory cytokine, interleukin 6 (IL-6), were measured separately by using ELISA kit. Results: Electroacupuncture of Weizhong (BL 40) acupoints significantly attenuated back muscle damage in both young and aged rats, increasing PAX7 (a marker of muscle satellite cells) and MYOD (major marker of myoblasts) cells, simultaneously, reducing serum proinflammatory cytokines, IL-6, and downregulation of p38 MAPK signaling in aged muscular satellite cells. Conclusion: Our studies suggest that electroacupuncture of Weizhong (BL 40) acupoints can restore aged back muscular satellite cells and their regeneration capacity. These suggested electroacupuncture may be a potential means of promoting rehabilitation for muscular injury in aged patients.

Long-Term Ultrastructural Outcomes of Autologous Transplantation of Retinal Pigment Epithelium-Partial Thickness Choroid (RPE-PTC) Sheet in Rabbits.

BACKGROUND: To observe the ultrastructural outcomes of autologous transplantation of retinal pigment epithelium-partial-thickness choroidal (RPE-PTC) sheets in rabbits after 6 months. METHODS: Eighteen pigmented rabbits were used in this study. Among them, nine rabbits were used for autologous transplantation of RPE-PTC sheets. Tissue sections were observed under a transmission electron microscope for one, three, and six months after transplantation, respectively. RESULTS: One, three, and six months after the autologous transplantation of RPE-PTC sheets, the inner and outer segments of photoreceptor cells were arranged regularly, and the connection between the inner and outer segments was normal. The inner structure of the RPE cells and tight junctions among them remained normal. Phagocytosis of outer segment of photoreceptor cells could also be observed in RPE cells. The structure of the Bruch's membrane appeared loose, rather than being dense as normal, and it was undulated after one and three months, while it became dense after six months. The graft and the bed were healed well, the boundary was unclear, and the graft was vascularized after one, three, and six months, respectively. CONCLUSIONS: Our findings revealed that the RPE-PTC sheets could quickly rebuild blood vessels, thereby maintaining the normal physiological functions of RPE cells, as well as the survival and functional status of photoreceptor cells for a long-time.

Clinicopathological study of the polypoidal lesions of polypoidal choroidal vasculopathy.

PURPOSE: To investigate the pathogenic features of the polypoidal lesions from the specimens of polypoidal choroidal vasculopathy extracted from human subjects. METHODS: Seven specimens of polypoidal lesions extracted from five eyes of six patients (mean age, 60.16 ± 10.41 years) of polypoidal choroidal vasculopathy were examined. The polypoidal lesions were obtained by surgical excision. Thereafter, a histopathological analysis of the specimens was performed. RESULTS: The polypoidal lesions were oval nodules located underneath the retinal pigment epithelium. A pathological study of the lesions revealed that Bruch's membrane schisis was observed in all specimens and they were all located in the Bruch's membrane. The Bruch's membrane schisis and serosanguineous materials constituted the main structure of the lesions in five of the seven specimens, with small vessels being observed in two specimens. One specimen was composed of two polypoidal lesions of different characteristics, and one specimen had a neovessel membrane complex with several polypoidal lesions. Inflammatory cells and blood vessels were observed in the polypoidal lesion of the specimen with neovessel membrane complex. CONCLUSION: Polypoidal lesions of polypoidal choroidal vasculopathy are abnormalities of the Bruch's membrane. The lesions are characterized by the Bruch's membrane schisis, which is filled with serosanguineous materials. The lesions are progressive and may contain inflammatory cells and blood vessels.

Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy.

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.

A Novel Synthetic Precursor of Styryl Sulfone Neuroprotective Agents Inhibits Neuroinflammatory Responses and Oxidative Stress Damage through the P38 Signaling Pathway in the Cell and Animal Model of Parkinson's Disease.

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson's disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.

Mechanism and prognostic indicators for explosion-related eye trauma: eye injury vitrectomy study.

PURPOSE: To explore the clinical features, surgical interventions and prognosis of injured eyes following explosion and to develop the risk factors for poor prognosis. METHODS: A nested case-control study. To the date of 31 December 2018, 99 explosion-related eye globes were selected from the Eye Injury Vitrectomy Study database, which is a multicenter prospective cohort study and began in 1990s. All cases selected underwent vitreoretinal surgery or enucleation and were followed up for at least 6 months. Clinically meaningful preoperative variables and outcomes were used to develop logistic regression models. RESULTS: The unfavourable outcomes were defined as silicone oil-filled eyes, phthisis bulbi, enucleation and anatomically restored eyes whose final BCVA is worse than initial vision after 6 months of follow-up. The proportion of unfavourable outcomes was 92.0%, 60.9% and 66.7% in large festive fireworks, detonator and beer bottle groups respective. The anatomic and visual outcome of injured eyes with combined injury of blast wave and projectile were worse than that of ruptured eyes (Fisher's exact = 0.041). The extrusion of iris/lens (OR = 3.20, p = 0.015), PVR-C (OR = 6.08, p = 0.036) and choroid damage (OR = 5.84, p = 0.025) is independent risk factors of unfavourable prognosis for explosion-related eye trauma. CONCLUSION: The extrusion of iris/lens, PVR-C and choroid damage is the independent risk factors for unfavourable outcomes in explosion-related eye trauma. There is a unique injury mechanism in explosion-related eye trauma. SUMMARY STATEMENT: Through the nested case-control study, the extrusion of iris/lens, PVR-C, and choroid damage are the independent risk factors for unfavorable outcomes in explosion-related eye trauma. The mechanism of open globe mixture and close globe mixture in explosion-related eye trauma need more cases and participating units to explore together in the future.

Prognostic factors and long-term outcomes of eye-globe perforation: Eye injury vitrectomy study.

PURPOSE: To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. METHODS: The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. RESULTS: Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. CONCLUSION: The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.

Novel Suturing Methods for the Management of Traumatic Choroidal Avulsion in Globe Injuries.

PURPOSE: To explore the long-term efficacy of novel choroidal suturing methods including trans-scleral mattress suturing (TSS) and intraocular suturing (IOS) in the treatment of choroidal avulsion. DESIGN: Prospective cohort, hospital-based study. METHODS: A total of 24 patients who were diagnosed with choroidal avulsion were enrolled in this study. The demographic characteristics, baseline information of trauma, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were collected before surgery, and the anatomic abnormities of the globe were recorded before or during surgery. All patients were diagnosed with choroidal avulsion and underwent choroid suturing treatment during vitrectomy, postoperative functional variables including BCVA and IOP, anatomic variables including retinal and choroidal reattachment rate, and silicone oil migration rate, which were recorded at the regular follow-ups at least 1 year after surgery. RESULTS: All patients with open globe injury involved zone III, 70.8% of the patients presented with two quadrants of the avulsed choroid, and 29.2% with one quadrant involved; moreover, all patients had complications with retinal detachment (RD), of which 58.3% of patients had closed funnel retinal detachment. TSS was applied in nineteen patients and IOS in five patients. Postoperatively, a significant improvement on LogMAR BCVA was observed at each follow-up from 3.57 ± 0.69 before surgery to 2.82 ± 0.98 at the last follow-up (p < 0.05), and the proportion of no light perception (NLP) was also reduced from 69.6 to 37.5%. IOP was markedly elevated from 6.4 ± 4.1 mmHg preoperatively to 11.3 ± 4.3 mmHg at the last follow-up (p < 0.05). Choroidal reattachment was achieved in 91.7% of patients; two patients were observed with silicone oil migration at 3 months after surgery and underwent drainage of suprachoroidal silicone oil and sclera buckling. Meanwhile, retinal attachment was observed in 95.8% of patients, only one patient developed partial RD due to postoperative proliferative vitreoretinopathy, and secondary vitrectomy was performed; all patients were observed with complete retinal and choroidal attachment at the last follow-up. Eventually, four patients were silicone oil-free, and 20 patients were silicone oil-dependent. CONCLUSIONS: Choroidal suturing proved to be an effective method to fix the avulsed choroid, which greatly improved the BCVA and maintained the IOP, and efficiently increased the choroidal and retinal reattachment rate and preservation of the eyeball.

Traumatic choroidal injuries - classification, incidence, diagnosis and prognosis twenty-year results of Eye Injury Vitrectomy Study.

PURPOSE: To characterize the classification, incidence, diagnosis and prognosis of traumatic choroidal injuries. METHODS: Subjects were selected from the database of the Eye Injury Vitrectomy Study (EIVS) and were examined for occurrences of different categories of choroidal injuries. Standard photographs were collected. Anatomical and visual outcomes were assessed in patients with greater than 1 year of follow-up. Eyes that had no light perception (NLP) and/or phthisis bulbi were defined as having had unfavourable outcomes. The percentage of eyes with an unfavourable outcome was analysed for different types of choroidal injuries. RESULTS: Nine categories of choroidal injuries with distinctive features were identified in the EIVS database. The incidence and the percentage of eyes with an unfavourable outcome in each injury category were as follows: suprachoroidal effusion, 21.2% (7.2%); suprachoroidal haemorrhage, 12.8% (11.2%); massive suprachoroidal haemorrhage, 4.0% (64.9%); choroidal avulsion, 4.2% (92.2%); traumatic chorioretinal rupture, 1.8% (13.3%); choroidal rupture, 4.8% (6.8%); choroidal loss, 1.6% (79.3%); choroidal hole, 1.1% (5.3%); and choroidal damage at the wound site, 39.2% (17.7%). CONCLUSIONS: Ocular trauma can cause a variety of choroidal injuries that have distinctive features, some of which are associated with a high frequency of unfavourable prognoses.

Effect of intravitreal ranibizumab pretreatment on vitrectomy in young patients with proliferative diabetic retinopathy.

BACKGROUND: Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR. METHODS: This was a prospective nonrandomized comparative study. Young patients (<40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery. RESULTS: In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P<0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome. CONCLUSIONS: IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

Simultaneous expression of two pathogenic genes in four Chinese patients affected with inherited retinal dystrophy.

AIM: To describe the complex, overlapping phenotype of four Chinese patients with inherited retinal dystrophies (IRDs) who harbored two pathogenic genes simultaneously. METHODS: This retrospective study included 4 patients affected with IRDs. Medical and ophthalmic histories were obtained, and clinical examinations were performed. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) based on exome capture technology was used for genetic screening. RESULTS: Four patients were identified to harbor disease-causing variants in two different genes. Patient retinitis pigmentosa (RP) 01-II:1 exhibited both classical ABCA4-induced Stargardt disease (STGD) 1 and USH2A-associated RP, patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP, patient RP03-II:1 exhibited both USH2A-induced autosomal recessive retinitis pigmentosa (arRP) syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa (adRP), and patient RP04-II:2 exhibited USH2A-induced arRP syndrome and EYS-induced arRP at the same time. CONCLUSION: Our study demonstrates that genotype-phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease.

Change of Vascular Endothelial Growth Factor Levels following Vitrectomy in Eyes with Proliferative Diabetic Retinopathy.

PURPOSE: To study the change of concentrations of vascular endothelial growth factor (VEGF) in vitreous cavity after vitrectomy in eyes with proliferative diabetic retinopathy (PDR). METHODS: In this retrospective study, intravitreal fluid samples were taken at baseline (beginning of the vitrectomy) and postoperatively (several days later after vitrectomy) at the time of prophylactic injection of bevacizumab in forty-eight eyes of forty-eight patients with PDR. Postvitrectomy fluid samples were divided into four groups according to the time interval between the vitrectomy and the injection (group 1, 3-5 days; group 2, 6-10 days; group 3, 11-15 days; group 4, 16-21 days; twelve eyes in each group). Postvitrectomy fluid sample was paired with baseline sample for each eye. VEGF concentrations in the samples were determined by enzyme-linked immunosorbent assay. Recurrent vitreous hemorrhage and neovascular glaucoma within six months postvitrectomy were also analyzed. RESULTS: Overall, the intravitreal VEGF level after vitrectomy (median, 36.95 pg/ml; range, 3.2-1,299.4 pg/ml) was significantly less than the VEGF level at baseline (median, 704.5 pg/ml; range, 30.6-1,981.1 pg/ml). Postoperative and baseline VEGF levels were significantly correlated (r = 0.499, p < 0.01). Both the absolute value of postoperative VEGF concentrations and the postop/baseline VEGF ratios declined with time and dramatically decreased in groups 3 and 4. In only two eyes, the postoperative VEGF level was even higher than the baseline VEGF level (postop/baseline VEGF ratio >1), and recurrent vitreous hemorrhage developed within six months in these two eyes. CONCLUSIONS: After vitrectomy for PDR, intravitreal VEGF levels decreased substantially in the majority of patients, while persistent high-VEGF level occurred in a few individuals. Postoperative VEGF levels and postop/baseline VEGF ratio declined with time. The postop/preop VEGF ratio may serve as a predictor for late complications.

YangXue QingNao Wan, a Compound Chinese Medicine, Attenuates Cerebrovascular Hyperpermeability and Neuron Injury in Spontaneously Hypertensive Rat: Effect and Mechanism.

OBJECTIVE: The purpose of the study was to explore the effect of YangXue QingNao Wan (YXQNW), a compound Chinese medicine, on cerebrovascular hyperpermeability, neuronal injury, and related mechanisms in spontaneously hypertensive rat (SHR). METHODS: Fourteen-week-old male SHR were used, with Wistar Kyoto (WKY) rats as control. YXQNW (0.5 g/kg/day), enalapril (EN, 8 mg/kg/day), and nifedipine (NF, 7.1 mg/kg/day) were administrated orally for 4 weeks. To assess the effects of the YXQNW on blood pressure, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured. After administering the drugs for 4 weeks, the cerebral blood flow (CBF), albumin leakage from microvessels in middle cerebral artery (MCA)-dominated area, and the number and morphology of microvessels were assessed in the hippocampus area and cortex. Neuronal damage and apoptosis were assessed by Nissl staining and TUNEL staining. To assess the mechanisms of cerebrovascular hyperpermeability, we performed immunofluorescence and Western blot to assess the expression and integrity of cerebral microvascular tight junction (TJ) and caveolin-1 (Cav-1) in cortex. Energy metabolism and Src-MLC-MLCK pathway in cortex were assessed then for elucidating the underlying mechanism of the observed effect of YXQNW. RESULTS: Spontaneously hypertensive rat exhibited higher blood pressure, Evans blue (EB) extravasation, albumin leakage, increased brain water content, decreased CBF, perivascular edema, and neuronal apoptosis in the hippocampus and cortex, all of which were attenuated by YXQNW treatment. YXQNW inhibited the downregulation of TJ proteins, mitochondrial Complex I, Complex II, and Complex V, and upregulation of caveolin-1, inhibiting Src/MLCK/MLC signaling in SHR. YXQNW combined with EN + NF revealed a better effect for some outcomes compared with either YXQNW or EN + NF alone. CONCLUSION: The overall result shows the potential of YXQNW to attenuate blood-brain barrier (BBB) breakdown in SHR, which involves regulation of energy metabolism and Src/MLCK/MLC signaling. This result provides evidence supporting the application of YXQNW as an adjuvant management for hypertensive patients to prevent hypertensive encephalopathy.