m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma. However, the role of BACE2 in ocular melanoma remains unclear. In this study, we showed that BACE2 was significantly upregulated in ocular melanoma, and inhibition of BACE2 significantly impaired tumor progression both in vitro and in vivo. Notably, we identified that transmembrane protein 38B (TMEM38B), whose expression was highly dependent on BACE2, modulated calcium release from endoplasmic reticulum (ER). Inhibition of the BACE2/TMEM38B axis could trigger exhaustion of intracellular calcium release and inhibit tumor progression. We further demonstrated that BACE2 presented an increased level of N6-methyladenosine (m6A) RNA methylation, which led to the upregulation of BACE2 mRNA. To our knowledge, this study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression, and our findings suggest that m6A/BACE2/TMEM38b could be a potential therapeutic axis for ocular melanoma.

Evaluation of changes in choroidal thickness after implantable collamer lens surgery in high myopia patients with graves' Ophthalmopathy (inactive phase).

BACKGROUND: To evaluate the safety and effectiveness of the Visian Implantable Collamer Lens (ICL) implantation in high myopic patients with inactive Graves' ophthalmopathy (GO) by observing the changes of choroidal thickness (CT). METHODS: Eight patients (16 eyes) with high myopia accompanied with inactive GO were selected as the experimental group (group A) and 18 high myopic patients (36 eyes) without GO were selected as a control group (group B). The outcomes of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), safety index, efficacy index, intraocular pressure (IOP), vault, corneal endothelial count, and choroidal thickness (CT) were observed. The values of CT were measured using swept-source optical coherence tomography (SS-OCT) scans. RESULTS: The UCVA and BCVA in all operated eyes were better than that before surgery. The postoperative safety index and efficacy index were 1.23 and 1.19 in the group A, respectively, and 1.26 and 1.21 in the group B, respectively. In both groups, foveal CT increased significantly in high myopic patients at 2 h and at 3 months after surgery, compared to preoperative values. The same tendencies were observed in the inner nasal and outer nasal regions. Compared with patients without GO, the increase of CT was more obvious in GO patients, 2 h postoperatively (P = 0.006) and 3 months postoperatively (P = 0.011). CONCLUSIONS: The ICL implantation is safe and effective in high myopic patients with inactive GO. Subfoveal and nasal CT may be useful parameters for monitoring the activity of GO patients.

Conjunctival Melanoma Metastasis to the Contralateral Orbit.

BACKGROUND: Malignant melanoma predominantly occurs in whites, and is potentially fatal. Distant metastases often occur in lung, liver, brain, and could occur without prior regional disease. Conjunctival melanoma metastasis to contralateral orbit has never been reported. PATIENT PRESENTATION: A 60-year-old man who underwent a left primary conjunctival neoplasm resection 11 months ago presented for the evaluation of a conjunctival dark-colored mass with a bulging left lower eyelid that directly invaded the orbits bilaterally. A histopathologic examination and immunohistochemistry confirmed metastases from conjunctival melanoma. In addition, the contralateral orbit had metastases without local recurrence after surgery within the authors' department. The patient was given adjuvant therapy (vincristine + nedaplatin + dacarbazine) for 5 cycles, but he died 8 months after surgery. CONCLUSION: Malignant conjunctival melanoma may metastasize to the contralateral orbit. A histopathologic evaluation should be mandatory in patients with medical histories of malignancy to differentiate new primary tumors, metastases, and benign tumors.

Comprehensive Evaluation of Visual Function in Patients With Orbital Fracture by Visual Electrophysiology and Visual Field Examination.

OBJECTIVE: At present, the effect of the visual electrophysiology and vision field examination in patients with orbital blowout fracture is rarely studied. So, the authors investigate the value of visual electrophysiology and vision field examination in the diagnosis of ocular contusion. METHODS: The position and range of fracture of 81 patients were determined by computed tomography (CT) scanning. Visual evoked potential (VEP), electroretinogram (ERG), and mfERG were vision field examination detected in 81 patients and the results were compared with those of contralateral healthy eyes. In addition, visual electrophysiology and vision field examination in diagnosis of eye contusion was analyzed and the correlation of the VEP, ERG, mfERG injury duration, and visual acuity was further analyzed. RESULTS: The visual acuity of orbital fractures was significantly decreased compared with that in the uninjured eyes (t = 2.181, P = 0.032). Compared injured eyes and normal eyes in 54 patients, b wave of Max-ERG and Cone-ERG implied value extension (t = -2.426, P = 0.025; t = -2.942, P = 0.014), P-VEP P100 Peak duration and amplitude significantly extended (t = 3.162, P = 0.007; t = 9.314, P = 0.000), and F-VEP P1 amplitude decreased significantly (t = 3.362, P = 0.004). mfERG showed that the injured eye central reaction was significantly decreased (t = 8.727, P = 0.000). There was a significant correlation between P-VEP P100 amplitude and visual acuity (r = 0.067, P = 0.000). But there was no significant correlation between the P100 peak value, amplitude of P-VEP, mfERG central reaction, and injured days, respectively. There was significant difference between 2 groups with average visual acuity and mean defect value (t = 3.253, 3.461, P = 0.006, 0.003). There was statistical means the difference in P-VEP abnormal group, visual field abnormal group, and combined detection abnormal groups, the abnormal rate increased significantly (χ = 3.931, P < 0.01). CONCLUSION: Orbital floor fracture can lead to optic nerve damage and also may be associated with decreased macular function. The combination analysis of visual electrophysiology and vision field examination is beneficial to early diagnosis of ocular trauma and can improve the positive rate in clinic practice.

Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A Retrospective Study.

BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 µm) between the tamponades. However, in the severe group (foveoschisis height >400 µm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 µm, but C3F8 is more effective for patients with a foveoschisis height >400 µm.

Choroidal thickness in patients with thyroid-associated ophthalmopathy, as determined by swept-source optical coherence tomography.

AIM: This study used swept-source optical coherence tomography (SS-OCT) to investigate subfoveal choroidal thickness (SFCT) in patients with thyroid-associated ophthalmopathy (TAO) who displayed different levels of disease activity and severity. METHODS: Thirty patients with TAO (60 eyes) and 38 healthy controls (67 eyes) in Shanghai, China, were recruited for this study. Disease activity and severity were graded using European Group on Graves' Orbitopathy standardised criteria. SFCT values were determined by SS-OCT. RESULTS: In total, 129 eyes were included in the final analysis. The mean SFCT was significantly thicker among patients with active disease (276.23±84.01 µm) than among patients with inactive disease (224.68±111.61 µm; p=0.049) or healthy controls (223.56±78.69 µm; p=0.01). There were no differences in SFCT among patients with moderate-to-severe disease, patients with severe disease and healthy controls (p>0.05). Changes in SFCT demonstrated strong predictive ability to distinguish active TAO from inactive TAO (area under the curve=0.659, 95% CI 0.496 to 0.822). CONCLUSIONS: SFCT was strongly associated with Clinical Activity Score in patients with TAO. Choroidal thickening was observed during active TAO. SS-OCT offers a non-invasive method for follow-up assessment.

Orbital Growth is Associated with Eyeball Size: A Study Using CT-based Three-dimensional Techniques.

AIM OF THE STUDY: This study was aimed to investigate the growth patterns and the relationship of the eyeball and the orbit using computed tomography (CT)-based three-dimensional (3D) techniques. MATERIALS AND METHODS: A total of 175 Chinese patients who had undergone craniofacial or orbital CT scans were enrolled. This study only included data from the unaffected eye and orbit. Images were processed using 3D reconstruction to obtain the eyeball and the orbit parameters. RESULTS: In early postnatal years, the sizes of eyeball and orbit increased significantly with age (p < 0.001) and reached a turning point at a critical age (8.967 and 12.800 years for the eyeball and orbit volume, respectively). The orbital index and orbital depth index, showing the shape of the orbital aperture and walls, decreased significantly with age (p < 0.001). In all ages, the orbit size was correlated with eyeball size (p < 0.001). The eye-orbit index, equivalent to the ratio of eye volume to orbital volume, declined steadily with age (p < 0.001). CONCLUSIONS: The eyeball and orbit developed rapidly in early postnatal years, and then matured at a critical age. The eyeball size significantly contributed to the orbital growth; this contribution may be reduced as the eye-orbit index decreased with age. To the best of our knowledge, this is the first report on the growth and interrelation of the eyeball and the orbit using CT-based 3D techniques.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

LACTB suppresses melanoma progression by attenuating PP1A and YAP interaction.

Very limited progress has been made in the management of advanced melanoma, especially melanoma of uveal origin. Lactamase ß (LACTB) is a novel tumor suppressor; however, its biological function in melanoma remains unknown. Herein we demonstrated markedly lower LACTB expression levels in melanoma tissues and cell lines. Overexpression of LACTB suppressed the proliferation, migration and invasion of melanoma cells in vitro. Mechanistically, LACTB inhibited the activity of yes-associated protein (YAP). We showed that the level of phospho-YAP (Serine 127) was increased upon LACTB overexpression, which prevented the translocation of YAP to the nucleus. Further, LACTB could directly bind to PP1A and attenuate the interaction between PP1A and YAP, resulting in decreased YAP dephosphorylation and inactivation in a LATS1-independent manner. Additionally, transfection of phosphorylation-defective YAP mutants reversed LACTB-induced tumor suppression. Upstream, we demonstrated that SOX10 binds to the LACTB promoter and negatively regulates its transcription. Overexpression of LACTB also suppressed the tumorigenicity and lung metastasis of MUM2B uveal melanoma cells in vivo. Taken together, our findings indicate a novel SOX10/LACTB/PP1A signaling cascade that renders YAP inactive and modulates melanoma progression, offering a new therapeutic target for melanoma treatment.

Implantable collamer lens with a central hole for residual refractive error correction after corneal refractive surgery.

The present study aimed to assess the visual and refractive outcomes of an implantable collamer lens with a central hole (ICL V4c) for residual refractive error correction after corneal refractive surgery in individuals with myopia. A total of 16 eyes of eight consecutive patients with myopia undergoing ICL V4c implantation after corneal refractive surgery were investigated. The uncorrected visual acuity (VA) and best-corrected VA were examined prior to surgery and at 1, 3 and 6 months after surgery. The post-operative values of the modulation transfer function (MTF) cutoff frequency, Strehl ratio (SR), objective scattering index (OSI) and Optical Quality Analysis System (OQAS) values (OVs) were quantitatively assessed using an OQAS. At 6 months after surgery, the mean uncorrected LogMAR VA was 0.06±0.10 and the values had improved in 100% of the eyes. The mean MTF cutoff frequency, SR, OSI, OV 100%, OV 20% and OV 9%, were 31.294±4.321 cycles/degree, 0.187±0.039, 1.399±0.274, 1.066±0.261, 0.748±0.287 and 0.509±0.229, respectively. In conclusion, ICL V4c implantation for the correction of residual refractive error after corneal refractive surgery appeared feasible and safe and also had an excellent optical performance. However, long-term changes in visual quality require further investigation.

Comparison of choroidal thickness in high myopic eyes after FS-LASIK versus implantable collamer lens implantation with swept-source optical coherence tomography.

AIM: To investigate the changes in choroidal thickness (CT) in high myopic eyes after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery or central hole implantable collamer lens (ICL V4c) implantation using swept-source optical coherence tomography (SS-OCT). METHODS: We examined the right eyes of 116 patients with high myopia who were candidates for FS-LASIK surgery and ICL implantation. Sixty eyes underwent ICL V4c implantation and 56 eyes were subjected to FS-LASIK surgery. The CT was measured with SS-OCT. All data were recorded preoperatively and 2h, 1wk, 1 and 3mo postoperatively. Other demographic information was collected, including age, sex, uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), spherical equivalent (SE), intraocular pressure (IOP) and axial length (AL). RESULTS: The UCVA improved in both groups and showed no significant differences between groups. There also were no significant differences between the two groups in postoperative BCVA and SE (P=0.581 and 0.203, respectively). The foveal CTs, inner nasal and outer nasal CTs were significantly thicker at 2h postoperatively in both groups (P<0.05) but returned to baseline levels in 1wk; after 1mo, no significant differences were found relative to the preoperative values. At 3mo in each group, nine regions showed variations in the CT as compared with preoperative thickening, but only the foveal and nasal area CTs preoperative differences were statistically significant (P<0.05). In addition, there was no significant difference in 9 regions of CT between the two groups at all follow-up times (P>0.05). CONCLUSION: The CTs after ICL implantation and FS-LASIK surgery are significantly thicker than those before operation, especially in the foveal and nasal areas, but there is no significant difference between the two methods.

Intraocular Pharmacokinetics and Safety of Subretinal Injection Compared with Intravitreal Application of Conbercept in Vitrectomized Rabbit Eyes.

PURPOSE: To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. METHODS: The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. RESULTS: On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 µg/ml and 0.11 ± 0.07 µg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 . CONCLUSIONS: Our study indicates that applying conbercept by subretinal injection can reduce the drug clearance rate and sustain a long maintenance period in ocular tissue, which suggests that subretinal conbercept injection may be a potentially valuable treatment option.

Intraocular pharmacokinetics of anti-vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil-filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study.

PURPOSE: Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). METHODS: Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6 months postoperatively. RESULTS: The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 ± 6.11 µg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 ± 0.46 µg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT0-t ) by subretinal injection (11.57 ± 0.83 days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10 ± 1.00 days, p < 0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). CONCLUSIONS: The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.

Evaluation of changes in choroidal thickness after surgical implantation of collamer lens in patients with different degrees of high myopia.

The aim of the present study was to investigate the potential changes in the choroidal thickness (CT) after surgical implantation of collamer lens (ICL) and to determine whether the variations in CT were associated with the degree of myopia. In the study, 98 eyes from 98 myopia patients were divided into two groups according to the degree of myopia: High myopia and super-high myopia. All eyes were measured using the swept-source optical coherence tomography (SS-OCT) technique. CT and CT variations were also recorded. The foveal CT increased significantly in high-myopia patients at 2 h after surgery and 3 months after surgery; the same tendency was observed in the inner nasal CT and outer nasal CT at the same time-points. In patients with super-high myopia, the subfoveal CT increased significantly at 2 h and 3 months after surgery compared with the pre-operative values. No statistically significant differences were obtained in any of the nine different choroidal regions evaluated at post-operative week 1 and post-operative month one. Furthermore, the increase in the subfoveal CT in the super-myopia group was significantly higher than that in the high-myopia group at 2 h and at 3 months after ICL. The results of the present study indicated that the CT significantly increased 2 h after the surgery and then reached a peak at 3 months, particularly in the subfoveal and nasal areas. A higher degree of myopia was associated with greater subfoveal choroidal changes.

Tumor suppressor role of microRNA-545 in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the predominant histological type of oral cancer, and poses an important threat to human health. MicroRNA (miRNA) serves important functions in the pathogenesis of OSCC, and in that of other types of cancer. For example, miR-545 exhibits inhibitory functions in pancreatic ductal adenocarcinoma, lung cancer and hepatocellular carcinoma. In the present study, the function of miR-545 was assessed in OSCC. Obtained results indicated decreased levels of miR-545 in OSCC tissues when comparing with the adjacent normal tissues. Overexpression of miR-545 inhibited HSC4 cells proliferation and migration, and vice versa. Furthermore, miR-545 was identified to target the 3'-UTR of retinoic acid-inducible gene-I (RIG-I), and there was a negative association between RIG-I mRNA expression and miR-545 expression in the 20 OSCC tissues. In conclusion, the present data demonstrate the tumor suppressive role of miR-545 in OSCC.

Physiological response in the leaf and stolon of white clover under acid precipitation and freeze-thaw stress.

Freeze-thaw (FT) in northern China is a common event in spring and autumn, and the release of sulfur dioxide from coal-burning in winter is apt to trigger acid precipitation. Both these stresses can aggravate the wintering ability of white clover (Trifolium repens L.). Acid precipitation and FT simulation experiments were carried out in the field and an indoor alternation refrigerator, respectively. The contents of soluble protein, soluble sugar, malondialdehyde (MDA), proline and antioxidant activity were tested under acid precipitation and FT stress. The results showed that under acid precipitation stress, the content of MDA, peroxidase and superoxide dismutase increased in both leaves and stolons, whereas soluble protein and soluble sugar content declined compared with the control groups. During the freezing period, the content of antioxidant enzyme activity, soluble protein and proline increased at first and then dropped, whereas MDA and soluble sugar content both increased. As a conclusion, the stolon of white clover is more sensitive than the leaf to short-term stress, either as the single FT stress or the combined stress of FT and acid precipitation, suggesting that maintaining more leaves can contribute to the resistance of white clover to these stresses.

Assessment of Ocular Surface Damage during the Course of Type 2 Diabetes Mellitus.

PURPOSE: To investigate the impact of disease duration on the ocular surface during the course of type 2 diabetes mellitus compared with nondiabetic controls. METHODS: One hundred twenty diabetic patients were divided into three groups according to disease duration: less than 5 years, 5-10 years, and over 10 years. All eyes were imaged using a corneal topographer (Oculus Keratograph 5M). Tear film measurements and meibography were also recorded. Meibomian gland changes were scored from 0 to 6 (meiboscore). RESULTS: The noninvasive breakup time first (NIKBUT-1st) and noninvasive breakup time average (NIKBUT-avg) were significantly shorter in the over 10 years diabetic group compared with the control group (P=0.0056 and P=0.010, resp.). Tear meniscus height (TMH) was significantly lower in the over 10 years diabetic group compared with the control group (P=0.0016) and the 5 years group (P=0.0061). We also found that more patients in the over 10 years diabetic group showed bulbar and limbal hyperemia compared with the control group (bulbar hyperemia: P=0.049; limbal hyperemia: P=0.026). The meiboscore in the over 10 years diabetic group was significantly higher compared with the other three groups (P < 0.05). Bulbar hyperemia showed a significant negative correlation with NIKBUT-1st in the over 10 years diabetic group (r=-0.35 and P < 0.05). CONCLUSION: Ocular surface damage in long-term type 2 diabetes is more severe than that in patients with shorter disease duration.

Modified technique for intrascleral fixation of posterior chamber intraocular lens without scleral flaps.

We present a modified technique for intrascleral fixation of a posterior chamber intraocular lens (IOL) without scleral flaps and assess its long-term safety and efficacy. The haptics of the IOL are externalized with a 23-gauge forceps and fixated in a scleral tunnel. Two clockwise scleral incisions are made using a 23-gauge needle at an angle 30 degrees above the sclera. A 3-piece IOL is inserted into the anterior chamber with an injector through the cornea incision, and the trailing haptic is kept outside to prevent the IOL from falling into the vitreous cavity. The leading haptic is held wit a forceps and extracted from the eye through the scleral incisions. The trailing haptic is held with a forceps and both haptics externalized onto the sclera. The conjunctival incisions are closed with 8-0 absorbable sutures tied to fixate 1 haptic (2 o'clock) after 1 more bite on the scleral bed.

Evaluation of secondary surgery to enlarge the peeling of the internal limiting membrane following the failed surgery of idiopathic macular holes.

The aim of the present study was to evaluate the clinical results of pars plana vitrectomy (PPV) combined with the surgical enlargement of internal limiting membrane (ILM) peeling in patients who had previously undergone failed idiopathic macular hole (IMH) surgery. In the study, 134 eyes from 130 IMH patients who had received PPV combined with ILM peeling surgery (2 disk diameters) were analyzed. Within this cohort, 14 eyes had IMHs that were not closed, of which 13 eyes underwent a second surgery involving enlargement of the ILM peeling. The extent of the ILM peeling was increased to the vascular arcades of the posterior fundus in the secondary surgery. Of the 13 eyes that underwent secondary surgery, five were in stage III and nine were in stage IV. The second surgery successfully achieved IMH closure in 61.5% (8/13) of the eyes. The IMH was completely closed following surgery and the logMAR vision increased from 0.98 to 0.84 (P=0.013) in the 8 successfully treated cases. The surgical enlargement of ILM peeling closed the IMHs and improved vision in the majority of patients. In addition, the procedures were safe. Therefore, the results of the present study indicate that enlargement of ILM peeling may be an effective therapy for patients who have previously undergone the failed surgical correction of an IMH.

HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells.

HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications.