Shootin1 Regulates Retinal Ganglion Cell Neurite Development: Insights From an RGC Direct Somatic Cell Reprogramming Model.

Purpose: Retinal ganglion cells (RGCs) connect the retina to the brain. Proper development of the axons and dendrites of RGCs is the basis for these cells to function as projection neurons to deliver visual information to the brain. The purpose of this study was to investigate the function of Shtn1 (which encodes shootin1) in RGC neurite development. Methods: Immunofluorescence (IF) was used to characterize the expression pattern of marker genes. An in vitro direct somatic cell reprogramming system was used to generate RGC-like neurons (iRGCs), which was subsequently used to study the function of Shtn1. Short-hairpin RNAs (shRNAs) were used to knock down Shtn1, and the coding sequence (CDS) of Shtn1 was used to overexpress the gene. Lentiviruses were used to deliver shRNAs or CDSs into iRGCs. The patch clamp technique was used to measure the electrophysiological properties of the iRGCs. RNA sequencing (RNA-seq) was used to examine transcriptome expression. Results: Using IF, we demonstrated that shootin1 is distinctively expressed in RGCs during the period in which RGCs actively develop and adjust the connections of their neurites with upstream and downstream neurons. Using the iRGC system, we demonstrated that Shtn1 promotes the growth and complexity of neurites and thus the electrophysiological maturation, of iRGCs. RNA-seq analyses showed that Shtn1 may also regulate gene expression and neurogenesis in iRGCs. Conclusions: Shtn1 promotes RGC neurite development. These findings improve our understanding of the molecular machinery governing RGC neurite development and may help to optimize future RGC regeneration methods.

Retinal Ganglion Cell Fate Induction by Ngn-Family Transcription Factors.

Purpose: Retinal ganglion cells (RGCs) are the projection neurons of the retina. Loss of RGCs is the cellular basis for vision loss in patients with glaucoma. Finding ways to regenerate RGCs will aid in the development of regenerative therapies for patients with glaucoma. The aim of this study was to examine the ability of Ngn-family transcription factors (TFs) to induce RGC regeneration through reprogramming in vitro and in vivo. Methods: In vitro, lentiviruses were used to deliver Ngn-TFs into mouse embryonic fibroblasts (MEFs). In vivo, mouse pup retina electroporation was used to deliver Ngn-TFs into late-stage retinal progenitor cells (RPCs). Immunofluorescence staining and RNA sequencing were used to examine cell fate reprogramming; patch-clamp recording was used to examine neuronal electrophysiologic functions. Results: In vitro, all three Ngn-TFs, Ngn1, Ngn2, and Ngn3, were able to work alone to reprogram MEFs into RGC-like neurons that resembled RGCs at the transcriptome level, exhibited typical neuronal membrane electrophysiologic properties, and formed functional synaptic communications with retinal neurons. In vivo, Ngn-TFs reprogrammed the differentiation-competent state of late-stage RPCs to generate RGCs. Conclusions: Ngn-TFs are effective in inducing an RGC-like fate both in vitro and in vivo and might be explored further in the future for glaucoma translational applications.

Safety and efficacy in pediatric secondary intraocular lens implantation, in-the-bag versus sulcus implantation: a multicenter, single-blinded randomized controlled trial.

BACKGROUND: Treatment of pediatric cataract remains challenging because of the extremely high incidence of postoperative adverse events (AEs), especially the AEs related to the locations of secondary implanted intraocular lens (IOL). There are two common locations for secondary IOL implantation in pediatric aphakic eyes: ciliary sulcus or in-the-bag implantation. However, there are currently no large, prospective studies comparing complication rates and visual prognosis of in-the-bag versus ciliarysulcus secondary IOL implantation in pediatric patients. Whether or how much secondary in-the-bag IOL implantation benefits the pediatric patients more than sulcus implantation and deserves to be performed routinely by surgeons remains to be elucidated. Here, we describe the protocol of a randomized controlled trial (RCT) designed to evaluate the safety and efficacy of two approaches of IOL implantation in pediatric aphakia. METHODS: The study is a multicenter, single-blinded RCT with 10 years of follow-up. Overall, a minimum of 286 eyes (approximately 228 participants assuming 75% have two study eyes) will be recruited. This study will be carried out in four eye clinics across China. Consecutive eligible patients are randomized to undergo either secondary in-the-bag IOL implantation or secondary sulcus IOL implantation. Participants with two eyes eligible will receive the same treatment. The primary outcomes are IOL decentration and the incidence of glaucoma-related AEs. The secondary outcomes include the incidence of other AEs, IOL tilt, visual acuity, and ocular refractive power. Analysis of the primary and secondary outcomes is to be based on the intention-to-treat and per-protocol analysis. Statistical analyses will include the χ2 test or Fisher's exact test for the primary outcome, mixed model and generalized estimated equation (GEE) model for the secondary outcome, Kaplan-Meier survival curves for the cumulative probability of glaucoma-related AEs over time in each group. DISCUSSION: To the best of our knowledge, this study is the first RCT to evaluate the safety and efficacy of secondary IOL implantation in pediatric aphakia. The results will provide high-quality evidence for the clinical guidelines for the treatment of pediatric aphakia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05136950. Registered on 1 November 2021.

The impact of preloaded intraocular lens implantation system (TECNIS iTec®) in routine cataract surgery in China: a time-motion analysis.

OBJECTIVE: To evaluate the impact on surgical efficiency and labor time cost of preloaded intraocular lens (IOL) implantation system compared with manual IOL implantation system in age-related cataract surgery in China. METHODS: This study was an observational, multicenter, prospective time-motion analysis. IOL preparation time, operation time, cleaning time, number and cost of cataract surgeries in eight participating hospitals were collected. The linear mixed model was used to explore factors associated with the difference in operation time between the preloaded IOL implantation system and the manual IOL implantation system. A time-motion model was constructed to convert the operation time cost saved by using preloaded IOL into economic benefits from hospital and social perspective, respectively. RESULTS: There were 2,591 cases included in the study (preloaded IOL: 1,591 cases; manual IOL: 1,000 cases). The preloaded IOL implantation system was significant time-saving in both preparation time and operation time compared to the manual IOL implantation system (25.48s vs. 47.04s, P < 0.001 and 353.84s vs. 367.46s, P = 0.004, respectively). An average total of 35.18s can be saved by using preloaded IOL per procedure. The results of linear mixed model showed that the type of IOL was the main factor leading to the difference in preparation time between preloaded IOL and manual IOL implantation system. By switching from manual IOL to preloaded IOL, the model projected additional 392 surgeries can be performed each year and an increase in revenue of $565,282 per hospital, a 9% increase from hospital perspective. And the annual productivity loss saved by using preloaded IOL was $3,006 in eight hospitals from perspective of society. CONCLUSION: Compared with manual IOL implantation system, the preloaded IOL implantation system reduces lens preparation time and operation time, which increases potential surgical volume and revenue, and reduces the loss of work productivity. This study provides real-world evidence to support the advantages of the preloaded IOL implantation system in improving efficiency of ophthalmic surgery in China.

Identification of a New Mutation p.P88L in Connexin 50 Associated with Dominant Congenital Cataract.

Congenital hereditary cataract is genetically heterogeneous and the leading cause of visual impairment in children. Identification of hereditary causes is critical to genetic counselling and family planning. Here, we examined a four-generation Chinese pedigree with congenital dominant cataract and identified a new mutation in GJA8 via targeted exome sequencing. A heterozygous missense mutation c.263C > T, leading to a proline-to-Leucine conversion at the conserved residue 88 in the second transmembrane domain of human connexin 50 (Cx50), was identified in all patients but not in unaffected family members. Functional analyses of the mutation revealed that it disrupted the stability of Cx50 and had a deleterious effect on protein function. Indeed, the mutation compromised normal membrane permeability and gating of ions, and impeded cell migration when overexpressed. Together, our results expand the pathogenic mutation spectrum of Cx50 underlying congenital cataract and lend more support to clinical diagnosis and genetic counseling.

Effectiveness of intraoperative intraocular lens use on improving surgical safety for dense cataract phacoemulsification: a randomized controlled trial.

We designed this study to assess if surgical safety can be improved by intraoperative use of intraocular lens (IOL) for cataract phacoemulsification. We performed phacoemulsification cataract removal on 401 patients. We randomly assigned these patients into three groups: the standard setting (Group I, n = 134), with reduced vacuum and flow rate (Group II, n = 137), and with IOL insertion before the last quadrant was emulsified with standard setting (Group III, n = 130). The primary outcomes included the risk of posterior capsular rupture (PCR), ultrasound time, energy, and complications. The secondary outcomes included central corneal thickness (CCT), CCT changes, endothelial cells (ETC) counting, ETC loss, and the best corrected distance visual acuity (BCVA) measured on day 1, day 7 and day 30. If PCR occurred, we emulsified the residual lens materials after insertion of IOL and clean of the prolapsed vitreous. We found that the risk of PCR in Group III (0/130) was lower than Group I (9/134, corrected relative risk (RR) = 18.44, 95% CI: 1.08-313.56) and Group II (3/137, corrected RR = 6.64, 95% CI: 0.35-27.41). Group III showed better BCVA on day 1 and 7, less ECC loss on day 7 and 30, and less CCT increase on day 1 and 7. No cases converted to extracapsular cataract extraction. No residual lens materials misdirected into vitreous cavity. Intraoperative use of IOL can improve surgical safety for dense cataract phacoemulsification.

A Novel Mutation p.S93R in CRYBB1 Associated with Dominant Congenital Cataract and Microphthalmia.

Purpose: To identify the pathogenetic mutations in a four-generation Chinese family with dominant congenital cataracts and microphthalmia.Methods: A four-generation Chinese family with dominant congenital cataracts were recruited. Genomic DNAs were collected from their peripheral blood leukocytes and subjected to whole exome sequencing. The genetic mutations were identified by bioinformatic analyses and verified by Sanger sequencing.Results: Whole exome sequencing revealed a c.279C>G point mutation in the CRYBB1 gene which was further verified by Sanger sequencing. The nucleotide replacement results in a novel mutation p.S93R in a conserved residue of ßB1 crystallin which is predicted to disrupt normal ßB1 structure and function.Conclusions: We identified a novel missense mutation p.S93R in CRYBB1 in a Chinese family with autosomal dominant congenital cataracts and microphthalmia. This serine residue is extremely conserved evolutionarily in more than 50 ßγ-crystallins of many species. These data will be very helpful to further understand the structural and functional features of crystallins.

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization.

Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 h that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch's membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 h that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch's membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 min and was detectable for 6-12 h. Administration of 0.5% drops to the cornea twice a day significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases. KEY MESSAGE: Acriflavine, an inhibitor of HIF-1, suppresses retinal and choroidal neovascularization. HIF-1 plays a critical role in ocular neovascularization. Acriflavine's fluorescence provides a mean to track its entry and exit from the retina. Acriflavine has therapeutic potential for the treatment of ocular neovascularization.

Eosinophilic Granulomatosis with Polyangiitis Presenting with Skin Rashes, Eosinophilic Cholecystitis, and Retinal Vasculitis.

BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome (CSS), is a rare vasculitis of unknown etiology. Most of the patients have a long history of asthma and then develop autoimmune inflammation of small and medium-sized blood vessels, with consequent reduction of blood flow to various organs and tissues. EGPA can cause disorders in multiple systems; the most seriously affected organs are the retina, kidney, brain, cardiovascular system, and skin. CASE REPORT The patient was hospitalized for high fever and skin rashes and then developed right upper abdominal pain, decreased visual acuity, coma, and convulsions. Laboratory investigations showed marked eosinophilia (9412/mm3). Following cholecystectomy, histopathological examination revealed a marked inflammatory cell infiltrate composed mainly of eosinophils. Retinal vasculitis and medium and peripheral vascular closure were confirmed by fundus fluorescence angiography (FFA). The coma and convulsions were controlled successfully by high-dose methylprednisolone. After gradual tapering of the methylprednisolone, the patient's blood count recovered to a normal level, and the other systematic disorders disappeared; however, she was left with irreversible blindness. CONCLUSIONS EGPA can cause eosinophilic cholecystitis, retinal vasculitis, and neuropathy in the short term and calls for effective treatments in order to avoid binocular blindness.

Vascular cell-adhesion molecule-1 plays a central role in the proangiogenic effects of oxidative stress.

Oxidative stress exacerbates neovascularization (NV) in many disease processes. In this study we investigated the mechanism of that effect. Mice deficient in superoxide dismutase 1 (Sod1(-/-) mice) have increased oxidative stress and show severe ocular NV that is reduced to baseline by antioxidants. Compared with wild-type mice with ischemic retinopathy, Sod1(-/-) mice with ischemic retinopathy had increased expression of several NF-κB-responsive genes, but expression of vascular cell-adhesion molecule-1 (Vcam1) was particularly high. Intraocular injection of anti-VCAM-1 antibody eliminated the excessive ischemia-induced retinal NV. Elements that contributed to oxidative stress-induced worsening of retinal NV that were abrogated by blockade of VCAM-1 included increases in leukostasis, influx of bone marrow-derived cells, and capillary closure. Compared with ischemia alone, ischemia plus oxidative stress resulted in increased expression of several HIF-1-responsive genes caused in part by VCAM-1-induced worsening of nonperfusion and, hence, ischemia, because anti-VCAM-1 significantly reduced the increased expression of all but one of the genes. These data explain why oxidative stress worsens ischemia-induced retinal NV and may be relevant to other neovascular diseases in which oxidative stress has been implicated. The data also suggest that antagonism of VCAM-1 provides a potential therapy to combat worsening of neovascular diseases by oxidative stress.

The influence of phacoemulsification on corneal endothelial cells at varying blood glucose levels.

PURPOSE: To investigate the influence of phacoemulsification on corneal endothelial cells in diabetes patients and normal controls. METHODS: Phacoemulsification and intraocular lens implantation were performed on 75 patients with diabetic cataract (126 eyes) who were divided into two groups: Experimental group 1 (Glu ≤ 6mmol/L); Experimental group 2 (Glu 6-10 mmol/L) and 65 non-diabetic controls (112 eyes). The density and percentage of hexagonal cells and coefficient of variation of the corneal endothelia were measured before surgery and 1 day, 1 month and 3 months postoperatively. RESULTS: There was no statistical difference in the density and percentage of hexagonal cells and coefficient of variation of the corneal endothelia prior to phacoemulsification (P>0. 05) between the three groups. The density and percentage of hexagonal cells of the corneal endothelia decreased significantly after surgery in all three group (P<0.05), while the Coefficient of variation increased in all groups (P< 0.05). The rate of loss of corneal endothelial cells in the diabetic groups was significantly higher than for the control group (P<0.05), the percentage of hexagonal cells in the diabetic groups was significantly lower than for the control group (P<0.05), and the coefficient of variation in the diabetic groups was significantly higher than for the control group (P<0.05) at 1 day, 1 month and 3 months post-operatively. There was no statistical difference between the two diabetic groups in terms of these post-operative measurements. CONCLUSION: The corneal endothelium of diabetic patients is more prone to damage from phacoemulsification. It is advisable to evaluate the corneal endothelium routinely prior to phacoemulsification, particularly in diabetic persons.

Torsional ultrasound efficiency under different vacuum levels in different degrees of nuclear cataract.

PURPOSE: To evaluate the efficiency of torsional ultrasound (US) under different vacuum levels in eyes with cataract with different degrees of nuclear density. SETTING: Cataract Service, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. METHODS: In this prospective randomized series, eyes with age-related cataract were divided into 3 groups based on nuclear density. Eyes in each group were randomly assigned to 1 of 3 subgroups and treated with phacoemulsification under vacuum of 250 mm Hg (subgroup 1), 450 mm Hg (subgroup 2), or 600 mm Hg (subgroup 3). Data included preoperative and postoperative corrected distance visual acuity (CDVA), endothelial cell density, and central corneal thickness (CCT) and intraoperative US time and cumulative dissipated energy (CDE). RESULTS: The study evaluated 998 patients (1073 eyes). In each group, there was a statistically significant decrease in US time, CDE, and postoperative endothelial cell loss with increased vacuum (P<.05). At 1 day and 7 days, the CDVA was statistically significantly better in subgroups 2 and 3 (P<.05) and the CCT was thinner when vacuum was higher. There was no statistically significant difference in CDVA and CCT between subgroups 30 days postoperatively (P>.05). CONCLUSIONS: Torsional US with a high vacuum level was safe for cataract extraction. With less US energy and endothelial cell loss, torsional US was more efficient than with higher vacuum levels with lower levels.

A comparative study of non-chopping rotation and axial rotation versus quick chop phacoemulsification techniques.

BACKGROUND AND OBJECTIVE: The authors describe the non-chopping rotation and axial rotation phacoemulsification techniques and compare them with the quick chop technique in terms of efficacy and safety. PATIENTS AND METHODS: A prospective, randomized, comparative study of 654 eyes of patients with cataracts who underwent phacoemulsification and intraocular lens implantation was conducted. Patients were randomly assigned to three groups according to phacoemulsification technique and were subdivided into four groups according to nuclear density. RESULTS: For grade 1 and 2 nuclei, non-chopping rotation and axial rotation techniques outperformed the quick chop technique in ultrasound time, cumulative dissipated energy, best-corrected visual acuity, central corneal thickness, and endothelial cell loss. For grade 3 nuclei, the axial rotation technique did best according to the same terms. For grade 4 nuclei, the two rotation techniques were less efficient for lens removal. CONCLUSION: The non-chopping rotation and axial rotation phacoemulsification techniques are advisable for removal of soft to medium-hard nuclei. For hard nuclei, chopping techniques are more successful.

Early changes in clear cornea incision after phacoemulsification: an anterior segment optical coherence tomography study.

PURPOSE: We aimed to investigate the ultrastructures of clear corneal incisions 24 hours after phacoemulsification using anterior segment optical coherence tomography (AS-OCT). METHODS: Sixty eyes of 60 patients scheduled for cataract surgery were randomly selected. All eyes underwent the same phacoemulsification procedure carried out by one experienced surgeon. Two-plane temporal clear corneal tunnel incisions were performed. The same types of intraocular lens and implant system were used in all patients. Images of the ultrastructures of the corneal incisions were taken using AS-OCT before and 1 day after surgery. RESULTS: Corneal thickness increased at the incision site after surgery in all eyes (p < 0.001). Epithelial bulla in the incision region was seen in two eyes (3%). Gaping at the internal aspect of the corneal wound was seen in 42 eyes (70%). Eyes with gaping had thicker localized cornea (p = 0.002). Descemet's membrane detachment was seen in 49 eyes (82%); this seemed to be associated with lower preoperative intraocular pressure (p = 0.01). CONCLUSIONS: Anterior segment OCT provides sensitive and detailed measurements of the ultrastructures in clear corneal incision.

[Comparative studies of wavefront aberration and contrast sensitivity after phacoemulsification and intraocular lens implantation].

OBJECTIVE: To study the difference of the contrast sensitivity and wavefront aberration of two eyes who undergone phacoemulsification and intraocular transplantation respectively. METHODS: Sixty-three patients with cataract were included in the study. With the consent of the patients, one eye was implanted SA60AT intraocular lens and another eye was implanted Tennis Z9001 intraocular lens after phacoemulsification. One and three months post-surgery, the best corrected visual acuity was recorded by computer and comprehensive optometry. Contrast sensitivity was analyzed by CSV-1000. The corneal aberration was measured by Option Keratron Scout. The whole ocular aberration was evaluated by Allegretto Waver Analyzer at pupillary diameter 4 mm and 6 mm. RESULTS: The best corrected visual acuity and the corneal spherical aberration, corneal coma aberration and RMS had no significant difference between the two groups. After one and three months, the contrast sensitivity of 3, 6, 12, 18c/d had statistic significance between the eye with and without glare through univariate split-plot analysis. The Z9001 contrast sensitivity value was much higher than the SA60AT groups. The results of Zernike polynomials C12, RMS4 and RMSh had statistic significance between the two groups through T-test. The Z9001 group value was much lower than the SA60AT groups. CONCLUSIONS: The Z9001 intraocular lens transplantation can reduce total ocular aberration, special the spherical aberration and improve visual acuity.

Aberration and contrast sensitivity comparison of aspherical and monofocal and multifocal intraocular lens eyes.

BACKGROUND: Higher-order aberrations and contrast sensitivity were evaluated in patients who underwent phacoemulsification cataract extraction followed by implantation of aspherical, monofocal or multifocal intraocular lens (IOL) replacements. METHODS: In this comparative trial, 124 patients with an average age of 66.8+/-5.2 years and their 124 eyes were randomly divided into three surgical implantation groups to receive one of three types of IOLs in replacement of cataract lenses. The patients of group 1 were given an aspherical IOL Z9001 (AMO, Santa Ana, CA, USA) replacement, and group 2 was implanted a monofocal IOL SA60AT (Alcon, Fort Worth, TX, USA) and group 3 the multifocal IOL SA40N (AMO). Post-surgical best-corrected visual acuity, corneal aberrations, total ocular aberrations, pupil diameters, capsulorhexsis sizes and contrast sensitivity were measured and compared. RESULTS: There was no statistical difference for mean best-corrected visual acuity, pupil diameter, curvilinear capsulorhexis size and corneal aberration among the three groups. For the spherical aberration, fourth-order higher-order aberration and total ocular higher-order aberration, the SA40N group was higher than the SA60AT group and the SA60AT group was higher than the Z9001 group, and the differences between the three groups were statistically significant for these measurements. Contrast sensitivity was higher for the Z9001 group than the SA60AT group and the SA60AT group was higher than the SA40N group, and the difference was statistically significant in all the spatial frequencies of 3, 6, 12 and 18. CONCLUSIONS: Although the multifocal IOL can provide near vision, it can increase higher-order aberration and negatively influence contrast sensitivity. However, the aspherical IOL can reduce aberration and improve contrast sensitivity as compared with the monofocal IOL.

Torsional mode versus conventional ultrasound mode phacoemulsification: randomized comparative clinical study.

PURPOSE: To compare the intraoperative and short-term postoperative outcomes of cataract surgery performed with torsional mode and conventional ultrasound mode using the Infiniti Vision System (Alcon Laboratories). SETTING: Cataract Service, Zhongshan Ophthalmic Center, Sun-Yat-Sen University, Guangzhou, China. METHODS: In this randomized comparative study, 525 eyes were assigned to phacoemulsification by torsional mode or conventional ultrasound (US) mode. The surgery was performed by an experienced surgeon, and the outcomes were evaluated by an examiner who was masked to treatment assignments. Primary outcome measures were US time (UST), cumulative dissipated energy (CDE), and surgical complications. Patients were seen 1, 7, and 30 days after surgery. Postoperative outcome measures were the final best corrected visual acuity (BCVA) and the change in corneal clarity, central corneal thickness (CCT), and endothelial cell count. RESULTS: The US group had 262 eyes and the torsional group, 263 eyes. All patients completed the follow-up visits. In the eyes with nucleus density grades of 1, 2, 3, and 4, the mean UST was 10.25 seconds +/- 7.4 (SD), 25.14 +/- 5.5 seconds, 36.45 +/- 8.3 seconds, and 61.44 +/- 17.8, respectively, in the US group and 8.32 +/- 6.8 seconds, 18.45 +/- 7.2 seconds, 29.48 +/- 12.4 seconds, and 48.39 +/- 20.3 seconds, respectively, in the torsional group (P<.001); the mean CDE was 1.25 +/- 0.5, 4.18 +/- 1.2, 8.59 +/- 6.5, and 16.51 +/- 9.6, respectively, in the US group and 0.94 +/- 0.3, 3.13 +/- 2.7, 7.47 +/- 12.6, and 14.08 +/- 8.3, respectively, in the torsional group (P<.001). At 1 day and 7 days, the mean BCVA was 0.23 +/- 0.12 logMAR and 0.00 +/- 0.10 logMAR, respectively, in the US group and 0.18 +/- 0.11 logMAR and -0.08 +/- 0.05 logMAR, respectively, in the torsional group (P<.001). At 30 days, the mean BCVA was -0.10 +/- 0.07 logMAR and -0.12 +/- 0.06 logMAR in the US group and the torsional group, respectively (P>.01). At 1 day and 7 days, the mean CCT was 625 +/- 80 microm and 568 +/- 37 microm, respectively, in the US group and 601 +/- 35 microm and 559 +/- 40 microm, respectively, in the torsional group (P<.001). At 30 days, the mean CCT was 531 +/- 30 microm in the US group and 529 +/- 39 microm in the torsional group (P>.01). At 7 days and 30 days, the mean central corneal endothelial cell count was 2135 +/- 858 cells/mm(2) and 2084 +/- 527 cells/mm(2), respectively, in the US group and 2004 +/- 656 cells/mm(2) and 1953 +/- 615 cells/mm(2), respectively, in the torsional group (P<.001). CONCLUSION: The torsional mode may provide more effective lens removal with a lower level of phacoemulsification time and energy.

Protection of retinal ganglion cells against glaucomatous neuropathy by neurotrophin-producing, genetically modified neural progenitor cells in a rat model.

OBJECTIVE: To investigate in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by sub-retinal space or vitreous cavity injection of brain-derived neural factor (BDNF) produced by genetically modified neural progenitor cells (NPCs). METHODS: Adult Sprague-Dawley (SD) rat RGCs were labeled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-obitally crushed with a 40 g power forceps to partially block ON axoplasmic flow. Animals were randomized to three groups. The left eye of each rat received a sham injection, NPCs injection or an injection of genetically modified neural progenitors producing BDNF (BDNF-NPCs). Seven, 15 and 30 days after ON crush, retinas were examined under a fluorescence microscope. By calculating and comparing the average RGCs densities and RGC apoptosis density, RGC survival was estimated and the neuro-protective effect of transplanted cells was evaluated. RESULTS: Seven, 15 and 30 days after crush, in the intra-vitreous injection group, mean RGC densities had decreased to 1885 +/- 68, 1562 +/- 20, 1380 +/- 7 and 1837 +/- 46, 1561 +/- 58, 1370 +/- 16, respectively with sham injection or neural progenitors injection. However, RGCs density in the groups treated with intra-vitreous injection of BDNF-NPC was 2101 +/- 15, 1809 +/- 19 and 1625 +/- 34. Similar results were found in groups after sub-retinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences among groups through nonparametric tests followed by the Mann-Whitely test. RGC apoptosis density in BDNF-NPC at each follow-up time was less than in other groups. CONCLUSIONS: A continuous supply of neurotrophic factors by the injection of genetically modified neural progenitors presents a highly effective approach to counteract optic neuropathy and RGC degeneration after partial ON axoplasmic flow blockage.

[Analysis of intra-operative and early post-operative complications and safety in non-penetrating trabecular surgery].

OBJECTIVE: To evaluate the safety, effectiveness and complications of non-penetrating trabecular surgery (NPTS). METHODS A total of 168 patients ( 258 eyes) of primary open angle glaucoma were divided into 2 groups randomly, and they were matched according to the age, sex and severity of disease. NPTS with reticulated hyaluronic acid implant was taken in one group, and traditional trabeculectomy was taken in the other. Pre-a2operative mean intraocular pressure (IOP) in the NPTS group and trabeculectomy group was (31.85 +/- 4.83) and (32.59 +/- 4.62) mm Hg (1a(c)mm Hg = 0.133 kPa), respectively. The post-operative IOP and complications in these 2 groups were compared. RESULTS: (1) IOP: The mean IOP on post-operative 7th, 14th day, 1st, 3rd and 6th month was (6.67 +/- 2.43), (11.42 +/- 2.89), (12.59 +/- 2.24), (15.45 +/- 1.82), and (17.99 +/- 1.80) mm Hg respectively in the NPTS group, while that in the trabeculectomy group for the same time a(c)series was (4.87 +/- 1.65), (10.48 +/- 2.38), (12.01 +/- 2.83), (15.01 +/- 2.66), an.d (17.48 +/- 2.97) mm Hg respectively. Statistically significant differences between these 2 groups were found on the post-operative 7th day and 14th day (t = 7.03, 2.89; P < 0.000 1, P = 0.004). However, significant difference was not noted for pre-operative and other post-operative IOP in the follow-up (t = 1.28, 1.78, 1.55, 1.60; P = 0.202, 0.077, 0.124, 0.112). (2) Visual acuity: There were no statistical differences of visual acuity between the 2 groups (kappa(2) = 0.135, 0.151, 0.024, 0.076; P = 0.935, 0.927, 0.988, 0.963). (3) COMPLICATIONS: I and II degree shallow anterior chamber was encountered in 57 eyes in the NPTS group, while that in the trabeculectomy group was 70. Twelve eyes with III degree shallow anterior chamber were found exclusively in the trabeculectomy group. Ciliary body or choroidal detachment was found in 66 and 70 eyes respectively in the NPTS and trabeculectomy group. Hypotony was encountered in 5 eyes exclusively in the trabeculectomy group. COMPLICATIONS were found to be statistically different in 2 groups (kappa(2) = 9.95, 15.27, 4.60, 6.19; P < 0.05). Hyphema was found in 2 and 6 eyes respectively in the NPTS and trabeculectomy group. Light anterior uveitis was found in 5 and 9 eyes respectively in the NPTS and trabeculectomy group. Vitreous extrusion was experienced in 1 eye of trabeculectomy group. Some complications (16.2%) related to operative skill were also experienced in the NPTS group. CONCLUSIONS: Over-filtration and surgical injury related complications are significantly reduced in the NPTS group compared to those in the trabeculectomy group. NPTS is safer than traditional trabeculectomy. Mastering surgical skills is required for reducing complications of NPTS.

[Alteration of lateral geniculate body cells after partial injury].

OBJECTIVE: To investigate the damage of the cells of the lateral geniculate bodies (LGB) of Sprague-Dawley (SD) rats after partial optic nerve injury. METHODS: The optic nerve was pressed by a forceps (40 g) for 30 seconds to set up the animal model with optic nerve injury. LGB was chopped in serial coronal slices (10 microm thickness) by a cryomicrotome. The apoptosis of LGB cells was detected with terminal deoxynucleotidyl transferase (TDT)-mediated dUTP nick end-labeling (TUNEL) technique after one week. After retrograde labeling with Granular Blue (GB) through injecting GB into optic center, the average density of the LGB cells was counted under the fluorescent microscope. Using monoclonal rabbit anti-rat neurofilament (NF) antibody, the neurons of LGB were detected by immunochemistry stains, and the standard avidin-biotin complex immunoperoxidase technique was used for immunostaining. RESULTS: The results of TUNEL analysis showed that the mechanism of the LGB cells pathogenesis was apoptosis. The LGB cells appeared clear striation in the control group, and the cells in experimental group decreased obviously after immunohistrochemical staining. The average density of LGB cells was (5 172 +/- 248) cells/mm(2) in control group, and (4 144 +/- 61) cells/mm(2) in experimental group. CONCLUSION: After partial optic nerve injury, the LGB cells are obviously damaged, which may be related to apoptosis of LGB cells.