The essential role of N6-methyladenosine RNA methylation in complex eye diseases.

There are many complex eye diseases which are the leading causes of blindness, however, the pathogenesis of the complex eye diseases is not fully understood, especially the underlying molecular mechanisms of N6-methyladenosine (m6A) RNA methylation in the eye diseases have not been extensive clarified. Our review summarizes the latest advances in the studies of m6A modification in the pathogenesis of the complex eye diseases, including cornea disease, cataract, diabetic retinopathy, age-related macular degeneration, proliferative vitreoretinopathy, Graves' disease, uveal melanoma, retinoblastoma, and traumatic optic neuropathy. We further discuss the possibility of developing m6A modification signatures as biomarkers for the diagnosis of the eye diseases, as well as potential therapeutic approaches.

The application and progression of CRISPR/Cas9 technology in ophthalmological diseases.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.

Detection of target DNA with a visual CRISPR-associated hyperbranched rolling circle amplification technique.

This paper presents a novel clustered regularly interspaced short palindromic repeat (CRISPR)-associated HRCA technique (CART). During the entire detection process of CART, the target DNA is first specifically recognized and cleaved by a pair of Cas9/sgRNA complexes; then, the cleaved product is ligated into circular DNA as the template of HRCA, and the circular DNA is efficiently amplified by HRCA. Therefore, CART has the advantages of Cas9/sgRNA (single-base mismatch specificity) and HRCA (isothermal reaction temperature and high sensitivity). This technique has been verified by detecting various human papillomavirus (HPV) genes with numerous subtypes. In summary, this study provides a new and effective method for the detection of nucleic acids.

Enhancing the Cellular Uptake of Macromolecules via Enzyme-Instructed Self-Assembly.

Poor solubility, low cellular uptake, and poor cell selectivity are the main obstacles hampering the therapeutic potential and clinic application of macromolecules. To overcome these limitations, here we propose a chemical modification strategy of macromolecules based on enzyme-instructed self-assembly (EISA). By using protoporphyrin IX (PpIX) and its metal complex Zn-PpIX as the modification objects, we demonstrated that the integration of enzymatic transformation and molecular self-assembly of macromolecules successfully improved the solubility of macromolecules, enhancing their intracellular uptake selectively against cancer cells. The proposed strategy is potentially applicable as a general tool for the development of macromolecule-based nanomedicine.

Reversed scleral tunnel technique for repair of iridodialysis after blunt force trauma: a retrospective clinical study.

BACKGROUND: To investigate the efficacy and safety of reversed scleral tunnel technique for repairing iridodialysis after blunt force trauma. METHODS: A total of 51 eyes of 51 patients with iridodialysis undergoing surgery were included in this study. Patients were divided into 2 groups: group A (the reversed scleral tunnel technique) and group B (the control group). Before the procedure and at 1, 3, and 6 months afterward, data on the patients' age, gender, treatments, diagnosis, mechanism of injury, best-corrected visual acuity (BCVA), intraocular pressure (IOP), degree of iridodialysis, lens status, concomitant ocular damage, number of sutures, complications, and follow-up time were collected and compared between the 2 groups. RESULTS: Iridodialysis was repaired and the pupil shape was restored to nearly round in all eyes. Standard phacoemulsification or lens removal was performed in all eyes. A final BCVA ≥20/60 was achieved in 13 eyes (48.1%) in Group A and 13 eyes (54.2%) in Group B. The IOP remained stable during the follow-up period in all eyes except 2 eyes (7.4%) in Group A and 3 eyes (12.5%) in Group B with angle recession. There were no statistically significant differences in BCVA and IOP between group A and group B. Intraoperatively, A significantly lower percentage of extensive subconjunctival hemorrhage occurred in Group A compared to Group B (1 eye versus 24 eyes, χ2 = 47.1, P = 0.00). Hyphema was observed in 2 eyes (7.4%) in Group A and 1 eye (4.2%) in Group B. Postoperatively, two eyes (7.4%) in Group A and 2 eyes (8.3%) in Group B developed retinal detachment. No other complications were noted during the follow-up period. CONCLUSIONS: The reversed scleral tunnel technique is a safe and effective approach for repairing iridodialysis after blunt force trauma with few complications, favorable cosmetic and visual outcomes.

Two high-fidelity variants: efSaCas9 and SaCas9-HF, which one is better?

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated endonuclease Cas9) nucleases have been widely applied for genome engineering. Staphylococcus aureus Cas9 (SaCas9) is compact, which can be packaged in AAV (adeno-associated virus) vector for in vivo gene editing. While, wild-type SaCas9 can induce unwanted off-target mutations and substantially limits the applications. So far, there are two reported SaCas9 variants with high-fidelity, including efSaCas9 from our previous study and SaCas9-HF. However, it remains unknown which one possessing the better fidelity and higher activity. Here, we performed a parallel comparison of efSaCas9 and SaCas9-HF in human cells through fluorescent reporter system and target deep sequencing, respectively. The results demonstrated that efSaCas9 possesses higher cleavage activity and fidelity than SaCas9-HF at the most endogenous sites in human cells. Collectively, our study provides insights for the rational selection of suitable SaCas9 for human genome editing.

Management of Vasoproliferative Tumors of the Retina with Macular Complications by Pars Plana Vitrectomy Combined with Episcleral Cryotherapy.

OBJECTIVE: To evaluate the efficacy of pars plana vitrectomy (PPV) combined with episcleral cryotherapy in treating vasoproliferative tumors of the retina (VPTR) with macular complications. METHODS: In this retrospective noncomparative interventional case-series analysis, we included 11 eyes of ten patients diagnosed with VPTR. All patients underwent comprehensive ophthalmic examinations and were treated with PPV combined with episcleral cryotherapy. Best-corrected visual acuity (BCVA), tumor activity, retinal morphological structure, and postoperative complications were evaluated. RESULTS: Macular complications included epimacular membrane (n = 10), macular hole (n = 3), and macular edema (n = 1). Tumors were treated with triple freeze-thaw episcleral cryotherapy during PPV. The mean logarithm of minimal angle of resolution (logMAR) BCVA dropped from 0.62 ± 0.58 to 0.39 ± 0.46. The difference between the mean values of logMAR BCVA before and after treatment was statistically significant (t = 2.48, P=0.033). The tumor activity was controlled effectively in nine cases. Compared with preoperative tumor activity, tumor activity after treatment was significantly lower (P < 0.01). The increase of central retinal thickness and the disruption of retinal layers were associated with macular holes, macular edema, and retinal proliferative membrane. After the treatment, visual acuity improved in 91% of the cases, and 73% had no long-term complications. CONCLUSION: PPV combined with episcleral cryotherapy promoted tumor regression, preserved retinal integrity, and improved visual acuity. Thus, the combination of PPV with episcleral cryotherapy can be considered effective and safe for the management of VPTR with macular complications.

RPE-derived exosomes rescue the photoreceptors during retina degeneration: an intraocular approach to deliver exosomes into the subretinal space.

Retinal degeneration (RD) refers to a group of blinding retinopathies leading to the progressive photoreceptor demise and vision loss. Treatments against this debilitating disease are urgently needed. Intraocular delivery of exosomes represents an innovative therapeutic strategy against RD. In this study, we aimed to determine whether the subretinal delivery of RPE-derived exosomes (RPE-Exos) can prevent the photoreceptor death in RD. RD was induced in C57BL6 mice by MNU administration. These MNU administered mice received a single subretinal injection of RPE-Exos. Two weeks later, the RPE-Exos induced effects were evaluated via functional, morphological, and behavior examinations. Subretinal delivery of RPE-Exos efficiently ameliorates the visual function impairments, and alleviated the structural damages in the retina of MNU administered mice. Moreover, RPE-Exos exert beneficial effects on the electrical response of the inner retinal circuits. Treatment with RPE-Exos suppressed the expression levels of inflammatory factors, and mitigated the oxidative damage, indicating that subretinal delivery of RPE-Exos constructed a cytoprotective microenvironment in the retina of MNU administered mice. Our data suggest that RPE-Exos have therapeutic effects against the visual impairments and photoreceptor death. These findings will enrich our knowledge of RPE-Exos, and highlight the discovery of a promising medication for RD.

Reoperation following vitrectomy for diabetic vitreous hemorrhage with versus without preoperative intravitreal bevacizumab.

BACKGROUND: To compare the reoperation rate in patients with vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) with or without preoperative intravitreal bevacizumab (IVB). METHODS: In this retrospective study, 280 patients (362 eyes) with diabetic VH were divided into a group that received preoperative IVB and a group that did not receive preoperative IVB. According to B-scan or color Doppler ultrasonography, the eyes were grouped as a VH group and a tractional retinal detachment (TRD) group. The reoperation rate, visual and anatomical outcomes of treatment were evaluated after 6 months. RESULTS: There were 17.4% of eyes in the VH group that did not receive preoperative IVB later required additional vitrectomy, while only 7.7% of the eyes in the VH group that received preoperative IVB required additional vitrectomy (P = 0.025). There were 45.5% of eyes in the TRD group that did not receive preoperative IVB had no reoperation, while only 21.4% of the eyes in the TRD group that received preoperative IVB had no reoperation (P = 0.004). The patients with one operation achieved better vision than those required reoperations in the VH group (P = 0.038) and TRD group (P = 0.019). CONCLUSIONS: Preoperative IVB significantly reduced the re-vitrectomy rate in patients with VH without TRD, but there was an increase in the reoperation rate in patients with VH combined with TRD.

Comparative Study on the Efficacy and Safety of Tumor Resection in Vitrectomy for Retinal Vasoproliferative Tumors.

PURPOSE: To investigate the efficacy and safety of combined vitrectomy with tumor resection in the treatment of retinal vasoproliferative tumors (RVPT). METHODS: Retrospective study. RVPT patients who underwent vitreous surgery at the Eye Hospital of Wenzhou Medical University from January 2011 to July 2017 were included. The main outcomes included treatment type, tumor activity, and best-corrected visual acuity (BCVA). RESULTS: Altogether, 16 patients with 17 eyes were enrolled with follow-up of no less than 6 months. Eight eyes were in the resection treatment group (Group R) and 9 eyes were in the conservative treatment group (Group C). Female (69%) were more common. The mean age was 50 (49.72 ± 12.92) years. Fifteen patients got unilateral onset and only one patient suffered bilaterally. The common symptoms were decreased visual acuity, floaters, and visual distortion. The preoperative BCVA ranged from hand movement to 20/20, with an average of 0.82 ± 0.75 LogMAR. Patients were all not high myopia, with a mean axial length of 23.27 ± 0.27 mm (21.61 mm to 24.67 mm). Of the retinal diseases, the epiretinal membrane was the most common, followed by vitreous hemorrhage, uveitis, subretinal fluid, and so on. Compared with the baseline BCVA, it improved more at postoperative 6 months and the last visit in Group R than in Group C (P=0.006 and P=0.033). The BCVA-improved 0.2 LogMAR or above in 6 months was 2 eyes in Group C and 7 eyes in Group R. All tumors in Group R were completely resected, whereas three in Group C (33.3%) had definite activity (P=0.008). In all samples, tumors were located on the inner side of the retina and had small vessel wall thickening and hyaline degeneration. The degree of astrocyte proliferation varies widely among different tumors. CONCLUSIONS: RVPT was more likely to occur in nonhigh myopia patients. Epiretinal membrane and vitreous hemorrhage were the main causes for vitreous surgery in RVPT patients. Compared with conservative treatment, surgical resection of the tumor is more beneficial to patients on visual acuity recovery and preventing tumor relapse. It is a safe and effective way to treat RVPT.

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

The novel chalcone analog L2H17 protects retinal ganglion cells from oxidative stress-induced apoptosis.

Chalcone is a plant metabolite widely found in fruits, vegetables, spices and tea, and has anti-tumor, anti-inflammation, immunomodulation, antibacterial and anti-oxidation activities, as well as many other pharmacological and biological effects. Our team has shown that its analogs have antioxidant activity, and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss. This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism. Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage. Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide. Only (E)-3,4-dihydroxy-2'-methylether ketone (L2H17), of the five chalcone analogs, markedly increased the survival rate of oxidatively injured RGC-5 cells. Thus, subsequent experiments only analyzed the results of the L2H17 intervention. Cell viability and apoptosis were measured. Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress. The mechanism of action by L2H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2. All results demonstrated that L2H17 could reduce the apoptosis of oxidatively injured cells, inhibit caspase-3 activity, increase Bcl-2 expression, decrease Bad expression, increase the activity of superoxide dismutase, inhibit the production of reactive oxygen species, increase Nrf2 immunoreactivity, and reduce the activating transcription factor 4, phospho-eukaryotic initiation factor 2 and CHOP expression. L2H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2, which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.

Photoreceptor Cell-Derived CAPN5 Regulates Retinal Pigment Epithelium Cell Proliferation Through Direct Regulation of SLIT2 Cleavage.

Purpose: To identify the causative gene and investigate the corresponding mechanisms for an autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) family. Methods: Clinical examination and genetic analysis were performed in a Chinese ADNIV family. To dissect the molecular consequence, we used gene targeting to knock-in a patient's specific mutation in the mouse genome. Immunostaining and immunoprecipitation were harnessed to analyze the colocalization and interaction of CAPN5 with SLIT2 in photoreceptors. The purified SLIT2-N, SLIT2-C fragments, and the conditioned medium from 661W cells with the overexpression of CAPN5 were treated on ARPE-19 cells. The viability of ARPE-19 cells was determined by MTT assays. The activation of protein kinase A (PKA) was analyzed by immunofluorescence and Western blotting in 661W and ARPE-19 cells as well as in frozen retina tissue from wildtype (WT) and knock-in mice. Results: We identified a novel CAPN5 mutation (p.R289W) in a Chinese family and generated the knock-in CAPN5R289W mouse. This mutation caused abnormal proliferative RPE in both humans and mice. CAPN5 directly cleaved WT SLIT2 in vitro, but not the mutant SLIT2 (p.R1113I). CAPN5 interacted with the SLIT2 in mouse retinal photoreceptors (661W cells) and increased cleavage and secretion of the SLIT2 fragments (SLIT2-N and SLIT2-C). Conditioned medium induced higher levels of secreted SLIT2 fragments, which promoted PKA activation and promoted proliferation of ARPE-19 cells. Conclusions: The novel CAPN5 mutation (p.R289W) is responsible for the present ADNIV family. The mutant CAPN5 stimulated secretion and cleavage of SLIT2 fragments that may act as a bystander to regulate abnormal RPE cell proliferation for ADNIV.

An anti-CAPN5 intracellular antibody acts as an inhibitor of CAPN5-mediated neuronal degeneration.

CAPN5 has been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Activation of CAPN5 may increase proteolysis and degradation of a wide range of substrates to induce degeneration in the retina and the nerve system. Thus, we developed an inhibitory intracellular single chain variable fragment (scFv) against CAPN5 as a potential way to rescue degeneration in ADNIV disease or in neuronal degeneration. We report that overexpression CAPN5 increases the levels of the auto-inflammatory factors toll like receptor 4 (TLR4), interleukin 1 alpha (IL1alpha), tumor necrosis factor alpha (TNFalpha) and activated caspase 3 in 661W photoreceptor-like cells and SHSY5Y neuronal-like cells. Both C4 and C8 scFvs specifically recognize human/mouse CAPN5 in 661W cells and SHSY5Y cells, moreover, both the C4 and C8 scFvs protected cells from CAPN5-induced apoptosis by reducing the levels of activated caspase 3 and caspase 9. The cellular expression C4 scFv reduced levels of the pro-inflammatory factor IL1-alpha activated caspase 3 in cells after CAPN5 overexpression. We suggest that CAPN5 expression has important functional consequences in auto-inflammatory processes, and apoptosis in photoreceptor like cells and neural-like cells. Importantly, the specific intracellular targeting of antibody fragments blocking activation of CAPN5 act as inhibitors of CAPN5 functions in neural like cells, thus, our data provides a novel potential tool for therapy in CAPN5-mediated ADNIV or neurodegenerative diseases.

A modified approach to actively remove high viscosity silicone oil through 23-gauge cannula.

AIM: To report a simple approach to actively remove high viscosity silicone oil through a 23-gauge cannula via pars plana. METHODS: Forty-eight eyes of 48 patients underwent silicone oil (5700 centistokes) removal (SOR) were enrolled. A section of blood transfusion set was prepared to connect a standard 23-gauge cannula and vitrectomy machine. Silicone oil was removed with suction of 500-mm Hg vacuum through the cannula. Main outcome measures were SOR duration, number of sutured sites, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications. RESULTS: Silicone oil was successfully removed in all cases. The mean SOR time was 5.70±0.85min. Nine eyes (18.75%) needed suture partial sclerotomies. No intraoperative complications were noted. Transient hypotony (≤8 mm Hg) was seen in 3 eyes (6.25%) on postoperative day 1, but all resolved within 1wk. Retinal reattachment was achieved in all cases and no other postoperative complications were noted during 3-month following-up. BCVA at the final visit improved or stabilized in all patients comparing to the preoperative level. CONCLUSION: Active removal of high viscosity silicone oil through a 23-gauge instrument cannula jointed with blood transfusion set is a practical and reliable technique when considering two sides of efficacy and safety.

Viscoat Assisted Inverted Internal Limiting Membrane Flap Technique for Large Macular Holes Associated with High Myopia.

Purpose. To investigate the surgical outcomes of Viscoat® assisted inverted internal limiting membrane (ILM) flap technique for large macular holes (MHs) associated with high myopia. Design. Prospective, interventional case series. Methods. Fifteen eyes of 15 patients with high myopia underwent vitrectomy and Viscoat assisted inverted ILM flap technique to treat MH without RD. Patients were followed up over 6 months. The main outcome measures were MH closure evaluated by optical coherence tomography (OCT) and best-corrected visual acuities (BCVAs). Result. MH closure was observed in all eyes (100%) following the initial surgery. Type 1 closure was observed in 13 eyes (86.7%); type 2 closure was observed in the remaining 2 eyes (13.3%). Compared to the preoperative baseline, the mean BCVA (logarithm of the minimum angle of resolution) improved significantly at 3 months and 6 months after surgery (P = 0.025, 0.019, resp.). The final BCVA improved in 10 eyes (66.7%), remained unchanged in 3 eyes (20.0%), and worsened in 2 eyes (13.3%). Conclusion. Vitrectomy combined with Viscoat assisted inverted ILM flap technique is an effective treatment for large MHs in highly myopic eyes. It may increase the success rate of the initial surgery and enhance the anatomical and functional outcomes.

Potential role of Cyr61 induced degeneration of human Müller cells in diabetic retinopathy.

The degeneration of Müller cells has been recognized to involve in the pathogenesis of diabetic retinopathy. However, the mechanism is not yet clear. This study is to explore the potential role of Cyr61, a secreted signaling protein in extracellular matrix, in inducing human Müller cell degeneration in diabetic retinopathy (DR). Twenty patients with proliferative diabetic retinopathy (PDR) and twelve non-diabetic patients were recruited for this study. Vitreous fluid was collected during vitrectomy surgery for Cyr61 ELISA. Human Müller cell line MIO-M1 were cultured to be subconfluent, and then treated with glucose (0-20 mM) or Cyr61 (0-300 ng/ml). Cyr61 expression induced by increasing concentrations of glucose was evaluated by RT-qPCR and Western blot. Effects of Cyr61 on Müller cells viability, migration and apoptosis were observed by MTT assay, Transwell assay, and TUNEL assay. Vitreous Cyr61 levels were observed to be 8-fold higher in patients with PDR (3576.92 ± 1574.58 pg/mL), compared with non-diabetic controls (436.14 ± 130.69 pg/mL). Interestingly, the active PDR group was significantly higher than the quiescent PDR group (P<0.01). In retinal Müller cells culture, high glucose significantly and dose-dependently elevated Cyr61 expression at both mRNA and protein levels. Cyr61 at high concentrations dose-dependently inhibited the viability and migration of Müller cells. TUNEL assay further revealed that high concentration of Cyr61 significantly promoted the cell apoptosis. In conclusion, these findings demonstrated for the first time that the expression of Cyr61 was elevated by high glucose in Müller cells, and Cyr61 inhibited cell viability and migration while induced apoptosis, suggesting the potential role of Cyr61 in Müller cell degeneration. The elevated Cyr61 levels in vitreous fluid of PDR patients further support its role in diabetic retinopathy (DR).

Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy.

PURPOSE: To determine the intravitreous levels of interleukin-18 (IL-18) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to ascertain their association with PDR activity. METHODS: Thirty eyes of 30 diabetic patients with PDR were divided into two groups (active PDR, n = 17; quiescent PDR, n = 13). Fifteen eyes of 15 non-diabetic patients (macular hole, n = 9; epiretinal membrane, n = 6) served as controls. All vitreous fluid samples were obtained during vitrectomy. IL-18 and VEGF were measured by enzyme-linked immunosorbent assay. Serum glycosylated hemoglobin as well as the basic demographic data was documented. RESULTS: Both IL-18 and VEGF levels were higher in patients with PDR than control (P < 0 .01 and P < 0 .01, respectively). Both IL-18 and VEGF in active PDR were higher than those in quiescent PDR (P = 0.048 and P = 0.03, respectively). A significant positive correlation (Spearman rank correlation coefficient (r s) = 0.502, P = 0.005) between IL-18 and VEGF was observed in all PDR patients but not in the control. The correlation between VEGF and IL-18 was even stronger in the subgroup of active PDR (r s = 0.684; P = 0.002), whereas no significant correlation was found in the subgroup of quiescent PDR (r s = 0.049; P = 0.873). CONCLUSIONS: Both intravitreous IL-18 and VEGF were elevated in patients with PDR, which were closely correlated in active PDR. IL-18 may contribute to retinal angiogenesis by acting together with or via VEGF, and become the potential therapeutic target for treatment of PDR.

[Vitrectomy without internal limiting membrane peeling associated with gas tamponade for treatment of foveoschisis in pathologic myopia].

OBJECTIVE: To evaluate the efficacy of vitrectomy without internal limiting membrane (ILM) peeling associated with gas tamponade in eyes with myopic foveoschisis. METHODS: A prospective study was conducted, in which 49 pathological myopia patients (52 eyes) with myopic foveoschisis were enrolled and divided into three groups according to the different therapeutic procedures: 22 patients (24 eyes) underwent vitrectomy without internal limiting membrane (non-gas tamponade group), 15 patients (16 eyes) received vitrectomy without internal limiting membrane peeling but combined with gas tamponade (gas tamponade group) and 12 patients (12 eyes) did not receive surgical treatments (control group). SAS 9.13 was used for the statistic analysis. Best-corrected visual acuity (BCVA) and optical coherence tomographic (OCT) findings of the foveal thickness before and after the operation (the 3rd, 6th, and 9th month postoperatively) were obtained and compared by the Wilcoxon Rank-Sum test. Non-parameters Wilcoxon symbols test was used to compare the BCVA, the central foveal thickness (CFT) and maximum foveal thickness (MxFT) of each group before and after the surgery. RESULTS: Postoperative visual acuity was significantly increased in the two operation groups (t = 2.57, P < 0.05; t = 3.58, P < 0.05) but not increased in the control group (t = 1.84; P > 0.05). The difference of BCVA between these three groups was not significant (χ(2) = 0.24, P > 0.05). OCT showed the mean foveal thickness was significantly decreased postoperatively. Vitrectomy without peeling of the ILM significantly promoted the retinal reattachment in eyes with myopic foveoschisis. No retinal reattachment was found in the control group while 16 and 13 retinal reattachment were found in the non-gas tamponade (66.7%) and gas tamponade group (81.3%), the difference between these two operation groups and the control was statistically significant (χ(2) = 20.50, P < 0.05). During the follow-up, two eyes in the control group developed a macular hole and both developed retinal detachment (RD) in the 6 and 8 month, respectively. The remaining 10 eyes did not develop any complications, although the thickness of the macula increased significantly. A transient increase of intraocular pressure occurred in three eyes and had been cured by medications within 2 weeks after gas tamponade. A macular hole was recognized in one eye 2 months after surgery and the retina was reattached at the fovea 1 month after reoperation. CONCLUSIONS: Vitrectomy without ILM peeling could be a safe and effective surgical approach for the treatment of foveoschisis in pathologic myopia. In addition, gas tamponade can improve the success rate of the operation.

Proposed classification of lens capsule defects.

BACKGROUND: Capsule defects are common during or after intraocular surgery of various kinds. The purpose of this work is to establish a classification system of lens capsule defects to provide uniform description of these defects for ophthalmic research and IOL implantation. METHODS: A retrospective study of 128 patients (156 eyes) with lens capsule injury after ocular trauma and intraocular surgery was performed. The patients were divided into two groups. Capsule defects were defined and classified according to the location, size, shape and tension of the capsule and its effect on posterior chamber IOL implantation. RESULTS: Lens capsule defects were classified into four types: Type I - complete capsule; Type II - incomplete capsule, but has enough area and tension to support two IOL haptics; Type III - incomplete capsule, is able to support only one IOL haptic and the other haptic needs a suture; Type IV - no capsule, both IOL haptics need suture fixation. Type I and Type II were each divided into three subtypes. Type III was divided into two subtypes. The shape of the capsule defects included fissure-like, triangle, round, irregular and fan-like. All eyes with capsule defects can be sorted into one of these types, and it is easy to guide IOL implantation according to the classification. Type II was the most common among the two groups in this study. CONCLUSION: The classification of lens capsule defects is feasible and favorable for uniform clinical description, clinical research and IOL implantation.