Precise prediction of size of a foldable capsular vitreous body via computerized three-dimensional ocular reconstruction in severe retinal detachment.

BACKGROUND: This study aimed to precisely predict the size and silicone oil injection of a foldable capsular vitreous body (FCVB) via computerized three-dimensional (3D) ocular reconstruction in the treatment of severe retinal detachment in China. METHODS: The 3D software Unigraphics NX was applied to determine the volume of the inner cavity with 16-30 mm axial length, assigning the anterior and posterior chambers, the FCVB sizes, and the silicone oil injection volume, and modeling the data between the axial length and the FCVB size. In clinical practice, IOL Master was applied to accurately measure the axial length of the contralateral healthy eye to anchor the anterior-posterior and horizontal diameters of the operated eye in horizontal position CT, and compared with the model to recommend the FCVB size and silicone oil amount, and the clinical effect was validated in cases across five hospitals in China. RESULTS: For the axial length of 16-30 mm, the volume of the inner cavity is 1.2 ml-8.4 ml. FCVB size and silicone oil volume were recommended based on this volume of the inner cavity. Of 253 cases, we noted 11 cases implanted with AV-10P and 1.05 ± 0.21 ml of silicone oil, 41 with AV-12P and 1.58 ± 0.18 ml of silicone oil, 163 with AV-13.5P and 2.48 ± 0.29 ml of silicone oil, 31 with AV-15P and 3.57 ± 0.39 ml of silicone oil, and 7 with AV-17P and 5.71 ± 0.81 ml of silicone oil. There was no significant difference in postoperative visual acuity scores compared with preoperative (P = 0.097), postoperative IOP(10.29 ± 0.57mmHg)was slightly higher than preoperative IOP (9.76 ± 0.48 mmHg), but there was still no statistically significant difference between the two comparisons (P = 0.405). CONCLUSION: Three-dimensional reconstruction prediction is a good solution for eyeballs with obvious individualized changes in severe retinal detachment, and this method helps doctors standardize FCVB size selection and the silicone oil amount for patients.

Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6.

Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Intravitreal chemotherapy achieves favorable clinical outcomes in controlling RB vitreous seeds, which are a common reason for treatment failure. Thus, a novel, effective and safe intravitreal chemotherapeutic drug is urgently required. The malaria drug artesunate (ART) recently demonstrated remarkable anticancer effects with mild side effects. The purpose of this study is to investigate the anti-RB efficacy, the underlying mechanism and the intraocular safety of ART. Herein, we verified that ART inhibits RB cell viability and induces cell apoptosis in a dose- and time-dependent manner. Microarray analysis revealed that Kruppel-like factor 6 (KLF6) was upregulated after ART treatment, and this was further confirmed by real-time PCR and western blot assays. Silencing of KLF6 expression significantly reversed ART-induced RB cell growth inhibition and apoptosis. Furthermore, ART activated mitochondria-mediated apoptosis of RB cells, while silencing KLF6 expression significantly inhibited this effect. In murine xenotransplantation models of RB, we further confirmed that ART inhibits RB tumor growth, induces tumor cell apoptosis and upregulates KLF6 expression. In addition, KLF6 silencing attenuates ART-mediated inhibition of tumor growth in vivo. Furthermore, we proved that intravitreal injection of ART in Sprague-Dawley (SD) rats is safe, with no obvious retinal function damage or structural disorders observed by electrophysiology (ERG), fundal photographs, fundus fluorescein angiography (FFA) or optical coherence tomography (OCT) examinations. Collectively, our study revealed that ART induces mitochondrial apoptosis of RB cells via upregulating KLF6, and our results may extend the application of ART to the clinic as an effective and safe intravitreal chemotherapeutic drug to treat RB, especially RB with vitreous seeds.

Influence of super-hydrophobic silicone rubber substrate on the growth and differentiation of human lens epithelial cells.

Materials with low cell adhesion are advantageous for production of replacement intraocular lens (IOL) to prevent posterior capsular opacification (PCO). We evaluated the feasibility of compression molding for manufacture of silicone rubber with super-hydrophobic surface and low cell infiltrative characteristics compared to ordinary hydrophobic silicone rubber. Silicone specimens with complex surface topology (super-hydrophobic) or smooth surfaces (hydrophobic) were manufactured by vacuum deforming and molding. Contact angle, microscopic surface structure, and transparency were evaluated. Super-hydrophobic and smooth samples were compared for effects on proliferation, adhesion, and morphology of human lens epithelial cells (hLECs). Epithelial-mesenchymal transition (EMT) was examined by immunofluorescence expression of fibronectin (Fn), Alpha-smooth muscle actin (α-SMA), and vimentin. The surface contact angle of super-hydrophobic silicone was greater than that of smooth silicone (153.8° vs. 116°). The super-hydrophobic surface exhibited a micron-scale palisade structure under scanning electron microscopy (unit length, width, and height of 80, 25, and 25 µm, respectively). However, cell number per 50 × microscopic field on super-hydrophobic surfaces was markedly reduced 24 and 72 h post-seeding compared to smooth surfaces (p < 0.01). Cells were cuboidal or spherical after 72h on super-hydrophobic surfaces, and exhibited numerous surface microvilli with fluff-base polarity, while cells on smooth surfaces exhibited morphological characteristics of EMT. Expression levels of the α-SMA and vimentin were reduced on super-hydrophobic surfaces compared to smooth surfaces. Super-hydrophobic silicon inhibits proliferation, adhesion, and EMT of hLECs, properties that may prevent fibrosis following cataract surgery.

Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

PURPOSE: This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. METHODS: Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. RESULTS: Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p < 0.001) and significantly lower body weights (p < 0.001). Colour photography and FFA did not reveal any vessel abnormalities in the diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2+ pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. CONCLUSIONS: Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

RISK OF SILICONE OIL AS VITREOUS TAMPONADE IN PARS PLANA VITRECTOMY: A Systematic Review and Meta-Analysis.

PURPOSE: The authors examined the differences between silicone oil and other vitreous tamponades or placebo in performing pars plana vitrectomy. METHODS: This review and meta-analysis was conducted in accordance with the PRISMA guidelines. Seven databases and the reference lists of the retrieved randomized controlled trial articles were searched to identify eligible studies. The primary outcomes were the rate of redetachment after endotamponade removal, the rate of reoperation, and poor visual acuity. The secondary outcomes were adverse events and quality of life related to postoperative position. RESULTS: Ten articles (12 trials) were included. There were no significant differences between silicone oil and other agents in most of the primary and second outcomes. Only the risk of hypotony was found to be significantly lower when filling with silicone oil, compared with other agents. No trial reported the quality of life related to postoperative position. CONCLUSION: Based on the available studies, the authors conclude that there is no significant difference in the risk of poor outcomes between pars plana vitrectomy with silicone oil and that with other vitreous tamponades with different surgical histories.

Assessing oxygen saturation in retinal vessels in high myopia patients pre- and post-implantable collamer lens implantation surgery.

PURPOSE: To determine whether posterior chamber phakic implantable collamer lens (ICL) surgery in high myopia patients impedes oxygen saturation of retinal vessels. METHODS: Mean oxygen saturation and diameter in retinal blood vessels were measured before and after ICL implantation surgery to correct high myopia refractive errors (i.e. -6.00 to -20.25 dioptres [D]), using an Oxymap T1 retinal oximeter. RESULTS: In 17 eyes of 17 patients, the Oxymap T1 retinal oximeter detected a small but significant decrease in oxygen saturation of retinal venules, 1-week postoperatively (compared to preoperative measurements). Moreover, at 1 week after ICL implantation, the diameter of patient retinal vessels had consistently contracted, compared to preoperative measurements. By 1 month after ICL surgery, however, both the oxygen saturation and retinal vessel diameter had returned to preoperative levels. Otherwise, no statistically significant difference in oxygen saturation and diameter of retinal arterioles was found when comparing their measurements before and 1 week after implantation. CONCLUSION: Stable levels of oxygen saturation in retinal vessels, as detected by the Oxymap T1 oximeter, show ICL implantation would not leave lasting impact or adverse effects to retina oxygen saturation in high myopia patients.

Preoperative and postoperative measurements of retinal vessel oxygen saturation in patients with different grades of cataracts.

PURPOSE: To assess the retinal vessel blood oxygen saturation preoperatively and postoperatively in patients with different grades of cataracts. METHODS: This study included 40 eyes from 40 patients with senile cataracts ranging from grade 1 to 3. All 40 eyes received standard phacoemulsification and intraocular lens implantation. The mean retinal arterial and venular oxygen saturation (SO2 ) levels were measured using the Oxymap system prior to, immediately after and 3 months after cataract surgery. The arterial-venular difference (AVD) was calculated as the difference between the arterial and venular saturations. Linear regression analysis was performed to identify the relationship between the lens density grades and changes in the measured retina vessel SO2 . RESULTS: The mean age of the subjects was 64.1 ± 7.8 years, and 14 (35%) were male. The mean SO2 level increased in the retinal arterioles from 90.5 ± 7.8% to 95.0 ± 6.7% immediately postoperatively and to 98.3 ± 5.3% at 3 months after surgery (p < 0.001). The mean venular saturation levels were 43.4 ± 9.7%, 58.0 ± 8.5% and 61.9 ± 6.5% at baseline, immediately after and at 3 months postoperatively, respectively, with a statistically significant increase after surgery (p < 0.001). The mean AVD significantly decreased from 47.1 ± 8.9% before surgery to 37.1 ± 7.3% immediately after and 36.4 ± 6.4% 3 months after surgery (p < 0.02). A linear regression model indicated that denser lens opacity was significantly associated with a larger amplitude of the venular SO2 level and the AVD after cataract surgery: change of venous SO2  = 5.934-0.191 × Age + 13.534 × Lens Grade (age: p = 0.586; lens grade: p < 0.001); change in AVD = -7.438-0.037 × Age + 7.744 × Lens Grade (age: p = 0.917; lens grade: p = 0.031). CONCLUSIONS: Retinal arterial and venular oxygen saturation levels are significantly increased after cataract surgery, and increase rates vary with the preoperative grading of lens density.

Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα, and PDGFR Targets.

Ocular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20-30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα, and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 µg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets.

The efficacy and safety of a novel posterior scleral reinforcement device in rabbits.

PURPOSE: To evaluate the efficacy and safety of posterior scleral reinforcement (PSR) device for myopia suppression in rabbits' eyes. METHODS: PSR surgery was performed on the normal 12 8-week-old New Zealand white rabbits' right eyes. To determine efficacy of the device, ophthalmic examination would be taken at pre-operation and post-operation (1 week, 1 month, 3 months, 6 months, and 1 year), such as A-ultrasound, diopter and B-ultrasound. Evaluation of safety were based on the following indicators: intraocular pressure (IOP), slit lamp, fundus photography, fundus fluorescein angiography and pathological examination after surgery. The efficacy and safety of PSR device were evaluated by comparison (treated eyes and contralateral eyes) of pre and post-operation. RESULTS: The novel PSR device could significantly shorten axial length (preoperative axial length: 16.36 ± 0.14 mm, postoperative 1 week, 1 month, 3 months, 6 months and 1 year axial lengths: 15.03 ± 0.28 mm, 15.23 ± 0.32 mm, 15.39 ± 0.31 mm, 15.45 ± 0.22 mm and 15.45 ± 0.22 mm; P=0.00037<0.001) in the treated eyes (right eyes) after surgery. At different postoperative time points, the B-ultrasound images showed that the PSR located in appropriate position and supported the posterior sclera very well. At the same time, IOP of treated eyes kept a relatively stable level (preoperative IOP: 12.56 ± 2.01 mmHg, postoperative IOP: ranging from 11.33 ± 1.23 mmHg to 13.44 ± 2.19 mmHg, P>0.05) post-operation 1 year. During observation period, there was no significant inflammatory reaction and complications such as anterior chamber flare, empyema, endophthalmitis, vitreous hemorrhage, retina detachment and retinal choroid neovascularization by slit lamp, fundus photography and fundus fluorescein angiography. In addition, there were no pathologic changes be found by comparison treated eyes group and contralateral group eyes based on pathological examinations. CONCLUSIONS: In vivo study, effectively and safely, the novel PSR device can inhibit rabbits' axial length elongation during postoperative 1 year. This study demonstrates that this novel PSR could be a potential treatment approach for myopia.

MACULAR BUCKLING USING A THREE-ARMED SILICONE CAPSULE FOR FOVEOSCHISIS ASSOCIATED WITH HIGH MYOPIA.

PURPOSE: To investigate the safety and efficacy of a novel macular buckling technique on foveoschisis in highly myopic eyes. METHODS: Highly myopic eyes with foveoschisis, posterior staphyloma, and axial length greater than 26.5 mm, but without a full-thickness macular hole, were included. Macular buckling was performed in the included eyes using a three-armed adjustable silicon capsule. RESULTS: Eight eyes from eight patients (five women) were enrolled in this study. The mean follow-up period was 11.6 (range 9-14) months. After surgery, the best-corrected visual acuity was improved in 7/8 (87.5%) eyes, optical coherence tomography imaging showed gradual anatomic improvement of macula over time. The final best-corrected visual acuity gained 21.5 early treatment diabetes retinopathy study letters from baseline on average (P = 0.014). Postoperatively, the most common complications were transiently elevated intraocular pressure (62.5%) and asymptomatic abduction limitation (100%), and the most serious complication was hemorrhagic choroidal detachment (25%). CONCLUSION: Macular buckling with a three-armed adjustable silicone capsule resulted in anatomic and visual improvement in eyes with myopic foveoschisis.