Short-Term Outcomes of Modified Boston Type-II Keratoprosthesis Implantation With Autologous Auricular Cartilage Reinforcement.

PURPOSE: To report the short-term visual outcomes and complications of a modified Boston Type-II keratoprosthesis (Kpro) procedure. DESIGN: Retrospective case series. METHODS: Thirty-seven eyes of 37 patients who had an implantation of autologous auricular cartilage-reinforced (AACR) Boston Type-II Kpro (BK2) were included in the current study. Preoperative and postoperative data were recorded and analyzed for each eye. Main outcome measures included best-corrected visual acuity, symptoms as assessed by questionnaires, complications associated with implantation, and retention of the implanted BK2 device. RESULTS: A total of 37 eyes, consisting of 19 with severe autoimmune dry eye (ADE) and 18 with burn injury, completed ≥12 months of follow-up. The median (interquartile range) best-corrected visual acuity at baseline, 1 month, 3 months, 6 months, 1 year, and 2 years of follow-up was hand motion (HM) 20/60 (20/100-20/40), 20/60 (20/200-20/40), 20/60 (20/200-20/40), 20/100 (20/200-20/40), and 20/100 (20/400-20/40), respectively. All eyes retained the initial device (37/37, 100%). Common postoperative complications included retroprosthetic membrane (n = 21), de novo glaucoma (n = 7), endophthalmitis (n = 1), and conjunctival erosion (n = 4). No ear complications were discovered during follow-up assessments. The ocular surface disease index score improved from baseline to a 2-year follow-up (median 57.5 vs 21.43). CONCLUSION: The modified AACR-BK2 procedure could be considered to restore vision in patients with end-stage corneal blindness.

Indoor air pollution and human ocular diseases: Associated contaminants and underlying pathological mechanisms.

People spend a long time indoors, especially young children. The risk of indoor pollution on human health is one of the current hotspots in environmental and public health. The human ocular surface is highly susceptible to indoor environment quality. Epidemiological data have linked human ophthalmological disorders with exposure to indoor pollution. In this review, we summarized the adverse impacts of indoor pollution on the human ocular surface. Several studies demonstrated that indoor contaminants including particulate matter, volatile/semi-volatile organic compounds, heavy metals, and fuel combustion and cigarette smoke exposure were associated with the incidence of human dry eye, conjunctivitis, glaucoma, cataracts, age-related macular degeneration, and keratitis. In addition, toxicological investigations revealed that indoor pollution-induced induced chronic inflammation, oxidative damage, and disruption of tight junctions are the main underlying pathological mechanisms for ocular surface diseases. Taken together, this review may expand the understanding of pollution-induced eye disorder and highlight the importance of reducing associated contaminants to decrease their detrimental effects on human eyes.

Effects of Nickel at Environmentally Relevant Concentrations on Human Corneal Epithelial Cells: Oxidative Damage and Cellular Apoptosis.

Nickel (Ni) is ubiquitous in the environment and evidence has suggested that Ni can cause ocular surface inflammation, especially in fine particulate matter and personal products. Continuous daily exposure to Ni-containing dust may adversely impact the human cornea, whereas the underlying mechanism of this phenomenon remains not fully understood. Here, human corneal epithelial cells (HCEC) were employed to analyze the toxicity of Ni via detections of cell morphology, cell viability, reactive oxygen species production, cell apoptosis rate, and apoptotic gene expression levels after exposure for 24 h to uncover the damage of Ni to the cornea. A concentration-dependent inhibition of HCECs' viability and growth was observed. In particular, Ni at 100 µM significantly decreased cell viability to 76%, and many cells displayed an abnormal shape and even induced oxidative damage of HCEC by increasing ROS to 1.2 times, and further led to higher apoptosis (24%), evidenced by up-regulation of apoptotic genes Caspase-8, Caspase-9, NF-κB, IL-1ß, and Caspase-3, posing a risk of dry eye. Our study suggested that Ni induces apoptosis of HCEC through oxidative damage. Therefore, Ni pollution should be comprehensively considered in health risks or toxic effects on the ocular surface.

Stand-Alone CuFeSe2 (Eskebornite) Nanosheets for Photothermal Cancer Therapy.

Two-dimensional CuFeSe2 nanosheets have been successfully obtained via solution-phase synthesis using a sacrificial template method. The high purity was confirmed by X-ray diffraction and the two-dimensional morphology was validated by transmission electron microscopy. The intense absorption in the 400-1400 nm region has been the basis for the CuFeSe2 nanosheets' photothermal capabilities testing. The colloidal CuFeSe2 (CFS) nanosheets capped with S2- short ligands (CFS-S) exhibit excellent biocompatibility in cell culture studies and strong photothermal effects upon 808 nm laser irradiation. The nanosheets were further loaded with the cancer drug doxorubicin and exposed to laser irradiation, which accelerated the release of doxorubicin, achieving synergy in the therapeutic effect.

Baseline characteristics associated with early visual acuity gains after ranibizumab treatment for retinal vein occlusion.

BACKGROUND: To identify baseline patient characteristics associated with early clinically significant visual acuity (VA) improvements within 3 months of treatment initiation in ranibizumab-treated patients with retinal vein occlusion (RVO) in the SHORE study. METHODS: Post hoc analysis of baseline patient characteristics in the randomized, open-label, vision examiner-masked SHORE phase 4 study that compared monthly versus pro re nata dosing of ranibizumab in patients with branch and central RVO. Patients who enrolled in SHORE fulfilled eligibility criteria per protocol (N = 202). SHORE data were retrospectively analyzed to identify baseline patient characteristics associated with early clinically significant improvements in VA, defined as improvement to a Snellen equivalent of 20/40 or better vision (≥ 69 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) or an increase in best-corrected VA (BCVA) of 15 or more ETDRS letters from baseline within 3 months of treatment initiation. Main outcome measures were BCVA gain of 15 or more ETDRS letters from baseline, Snellen equivalent of 20/40 or better vision, and baseline factors associated with early clinically significant improvement in BCVA. RESULTS: The median time for patients to achieve a BCVA of 20/40 or better was 59 days and the median time for patients to gain 15 or more ETDRS letters was 63 days. Better baseline BCVA (> 50 ETDRS letters/Snellen equivalent ≥ 20/100), greater baseline total macular volume (> 9.99 mm3), and presence of subretinal fluid at baseline were all associated with early improvement to 20/40 or better vision (ETDRS equivalent ≥ 69 letters; P < .0001, P = .02, and P = .03, respectively). CONCLUSIONS: This retrospective analysis found that better BCVA, greater total macular volume, and presence of subretinal fluid at baseline were associated with more rapid vision gains. Clinicians may find these helpful when considering the likelihood of achieving early clinically significant VA improvements with ranibizumab in patients with RVO. TRIAL REGISTRATION: ClinicalTrials.gov NCT01277302 .

Application of data mining methods to improve screening for the risk of early gastric cancer.

BACKGROUND: Although gastric cancer is a malignancy with high morbidity and mortality in China, the survival rate of patients with early gastric cancer (EGC) is high after surgical resection. To strengthen diagnosing and screening is the key to improve the survival and life quality of patients with EGC. This study applied data mining methods to improve screening for the risk of EGC on the basis of noninvasive factors, and displayed important influence factors for the risk of EGC. METHODS: The dataset was derived from a project of the First Hospital Affiliated Guangdong Pharmaceutical University. A series of questionnaire surveys, serological examinations and endoscopy plus pathology biopsy were conducted in 618 patients with gastric diseases. Their risk of EGC was categorized into low and high risk of EGC by the results of endoscopy plus pathology biopsy. The synthetic minority oversampling technique (SMOTE) was used to solve imbalance categories of the risk of EGC. Four classification models of the risk of EGC was established, including logistic regression (LR) and three data mining algorithms. RESULTS: The three data mining models had higher accuracy than the LR model. Gain curves of the three data mining models were convexes more closer to ideal curves by contrast with that of the LR model. AUC of the three data mining models were larger than that of the LR model as well. The three data mining models predicted the risk of EGC more effectively in comparison with the LR model. Moreover, this study found 16 important influence factors for the risk of EGC, such as occupations, helicobacter pylori infection, drinking hot water and so on. CONCLUSIONS: The three data mining models have optimal predictive behaviors over the LR model, therefore can effectively evaluate the risk of EGC and assist clinicians in improving the diagnosis and screening of EGC. Sixteen important influence factors for the risk of EGC were illustrated, which may helpfully assess gastric carcinogenesis, and remind to early prevention and early detection of gastric cancer. This study may also be conducive to clinical researchers in selecting and conducting the optimal predictive models.

[The relationship between NLRP3 inflammsomes expression and liver damage after allogeneic hematopoietic stem cell transplantation in mice model].

OBJECTIVE: To explore the function of nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammsomes in liver damage after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The study presented a murine (BALB/c-based) model of allo-HSCT. Chimera rate was measured by flow cytometry. The hematoxylin-eosin, Masson's trichrome, immunohistochemistry staining were used to observe the pathology changes in liver, then measured the degree of liver damage. Inflammation cells and NLRP3 were measured by Western blot, cytokines IL-1ß, IL-18 and NLRP3 related genes were tested with real-time quantitative polymerase chain reaction (q-PCR). RESULTS: Hematopoietic stem cells had been successfully transplanted, the chimera rate was geater than 97% on the 10th day. Liver damage occurred after allo-HSCT and suffered infiltration of inflammation cells, which reached the peak on day 15, then moved to moderate; the cytokines IL-1ß, IL-18 had the similar trend with liver injury, and reached the highest level on day 15, their mRNA expressions increased by (1.19 ± 0.40) fold and (1.64 ± 0.76) fold, respectively; Meanwhile, caspase-1 had the similar trend, its mRNA expression increased by (3.51 ± 0.46) fold on day 15; the inflammasomes NLRP1, NLRP3, NLRC4 and NLRP5 expressed in liver on day 15 of post-allo-HSCT, and NLRP3 inflammasome expressed highest among them. The mRNA and protein level of NLRP3 inflammasomes were kept with the serious degree of the liver damage, its mRNA expression increased by (2.91 ± 0.41) fold on day 15. CONCLUSION: NLRP3 inflammsome expressed in liver injury during allo-HSCT in mice, and may be one of the important factors contributed to liver injury.

[Effect of endothelial progenitor cell on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation mouse model].

OBJECTIVE: To examine the effects of endothelial progenitor cell (EPC) on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation (allo-HSCT) mouse model. METHODS: Allo-HSCT mouse model was established with condition of BU/CY, in which C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donors and recipients respectively. Recipients were randomly divided into 4 groups: untreated group, BU/CY condition group, bone marrow transplantation (BMT) group and transplantation of BM cells combined with EPCs (combined transplantation) group. The pathological changes of BM cells following transplantation were dynamically observed. Changes of BM sinusoidal endothelium and angiogenesis were observed by MECA-32 antibody immunohistochemical staining. The proportion of intramedullary stem and progenitor cells and serum cytokines were analyzed by flow cytometry. The numbers of peripheral blood cells were also counted. RESULTS: (1) Injuries of BM hematopoietic tissue, sinusoidal endothelium and vascular were less severe in combined transplantation group than of BMT group. (2) EPC infusion significantly increased BM hematopoietic stem cells 21 days after transplantation. The percentage of BM hematopoietic stem cells in combined transplantation group peaked on day +14, which was higher than of BMT group (0.1743 vs 0.0787) (P<0.05). The continuously increased percentage of BM hematopoietic progenitor cells in combined transplantation group was significantly higher than in BMT group on day +21 (0.4550 vs 0.3905) (P<0.05). (3) The number of peripheral white blood cells in combined transplantation group was always higher than of BMT group, which reached the peak on day +14 (0.74×109/L to 0.47×109/L) (P<0.05). The peak number of peripheral blood platelets on day +14 in combined transplantation group was significantly higher than of group BMT (1228.9×109/L to 977.12×109/L) (P<0.05). CONCLUSION: Allo-HSCT combined with EPC infusion accelerated hematopoietic reconstitution compared with BMT alone in allo-HSCT mouse model.

Biotransformations of anticancer ruthenium(III) complexes: an X-ray absorption spectroscopic study.

An anti-metastatic drug, NAMI-A ((ImH)[Ru(III) Cl4 (Im)(dmso)]; Im=imidazole, dmso=S-bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru(III) Cl4 (Ind)2 ]; Ind=indazole), are two Ru-based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solutions or gels (e.g, albumin, transferrin and collagen), undiluted blood serum, cell-culture medium and human liver (HepG2) cancer cells, were studied by Ru K-edge X-ray absorption spectroscopy (XAS). These XAS data were fitted from linear combinations of spectra of well-characterised Ru compounds. The absence of XAS data from the parent drugs in these fits points to profound changes in the coordination environments of Ru(III) . The fits point to the presence of Ru(IV/III) clusters and binding of Ru(III) to S-donor groups, amine/imine and carboxylato groups of proteins. Cellular uptake of KP1019 is approximately 20-fold higher than that of NAMI-A under the same conditions, but it diminishes drastically after the decomposition of KP1019 in cell-culture media, which indicate that the parent complex is taken in by cells through passive diffusion.

Comparison of fresh corneal tissue versus glycerin-cryopreserved corneal tissue in deep anterior lamellar keratoplasty.

PURPOSE: To compare the microstructural differences in fresh corneal tissue (FCT) with glycerin-cryopreserved corneal tissue (GCCT) used during deep anterior lamellar keratoplasty (DALK). METHODS: The medical records of 48 consecutive patients who underwent DALK for stromal opacity without endothelial abnormalities were retrospectively reviewed. Patients were divided into two groups: an FCT group (n = 22) and a GCCT group (n = 26), according to the corneal tissue used. The best corrected visual acuity (BCVA), slit lamp, corneal topography, pachymetry, and laser scanning in vivo confocal microscopy examinations at 2 weeks and 1, 3, 6, 12, and 24 months after surgery were analyzed. RESULTS: No graft rejection developed in the GCCT group, whereas stromal rejection developed in one eye in the FCT group. There were no significant differences in spherical equivalent (P = 0.37), astigmatism (P = 0.26), BCVA (P = 0.64), central corneal thickness (P = 0.73), or endothelial cell density (P = 0.49) between the two groups at 24 months. Confocal microscopy showed that GCCT was acellular, whereas dendritelike cells and keratocytes were found in the FCT group 2 weeks after surgery. The keratocyte density improved significantly in the GCCT group at 3 months after surgery, whereas it decreased significantly after surgery in the FCT group during follow-up. No significant difference in regeneration of nerve fibers was found in the subbasal layer and anterior stroma between the two groups at 24 months. CONCLUSIONS: DALK using GCCT provides clinical results comparable to FCT. GCCT can be used safely and effectively for DALK and may minimize stromal rejection after surgery.

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.

Corneoscleral necrosis after episcleral Au-198 brachytherapy of uveal melanoma.

PURPOSE: To describe the risk factors for the development of corneoscleral necrosis (CSN) and its management in patients with primary choroidal or ciliochoroidal melanoma who underwent episcleral Au-198 brachytherapy. METHODS: Clinical records of patients with symptoms of dry eye, foreign body sensation, pain, and evidence of CSN after Au-198 brachytherapy for uveal melanoma treated over a 22-year period were reviewed retrospectively. Risk factors for the development of CSN were identified and various methods of management were evaluated. The data were analyzed using multivariant analysis. A P < 0.05 was taken as a level of statistical significance. RESULTS: Of the 202 eyes of 202 patients treated with Au-198 radioactive plaque, 15 (7.4%) patients with symptomatic complaints of dry eye and pain showed evidence of CSN. First signs were noted as early as 1 month to as late as 5 years (median time 5 months) after the treatment. Risk factors for the development of CSN included tumor thickness greater than 6 mm and ciliary body involvement (P < 0.05). Associated risk factor included intraocular pressure greater than 21 mmHg. Four patients required conservative management, 11 patients required scleral patch and/or conjunctival flaps, and 6 eyes eventually required enucleation. Eyes which developed CSN were more likely to undergo enucleation compared with eyes having no evidence of CSN (P < 0.05). None of the eyes with CSN, which required enucleation because of the failed treatment, had histopathologic evidence of recurrent tumor or tumor invading sclera. CONCLUSION: Corneoscleral necrosis may occur soon or several years after Au-198 brachytherapy for uveal melanoma. Risk factors for CSN include tumor thickness greater than 6 mm, ciliary body involvement, and intraocular pressure >21 mmHg. Closer follow-up, early recognition, and timely intervention may avert serious consequences.

Intravitreal triamcinolone acetonide for diabetic macular edema.

PURPOSE: Intravitreal injection of triamcinolone acetonide has been advocated to treat exudative diabetic macular edema. The purpose of the study was to evaluate the clinical outcome of an intravitreal injection of triamcinolone acetonide as treatment for diffuse diabetic macular edema. METHODS: This study was a retrospective, interventional, clinical case series examining 210 eyes of 174 patients who received an intravitreal injection of 1 or 4 mg of triamcinolone acetonide for treatment of diffuse diabetic macular edema. Inclusion criteria were clinically significant macular edema, visual acuity loss, and leakage shown by fluorescein angiography. Main outcome measures were visual acuity and intraocular pressure. Mean follow-up time +/- SD was 6.6 +/- 3.1 months. RESULTS: In the study group, visual acuity improved significantly (P < 0.001) from a median of 20/200 (mean logMAR, 0.92) at baseline to 20/80 (mean logMAR, 0.82) at 6 months. Mean intraocular pressure +/- SD increased from 15.4 +/- 3.4 mmHg (median, 16 mmHg; range, 6-26 mmHg) to a maximal value of 20.4 +/- 6.2 mmHg (median, 19 mmHg; range, 12-51 mmHg) during the follow-up period. Complications included culture-negative sterile endophthalmitis in six cases and cataract extraction in five eyes. CONCLUSIONS: Intravitreal injection of 1 to 4 mg of triamcinolone acetonide may benefit patients by improving visual acuity in eyes with clinically significant diabetic macular edema. This study did not provide significant evidence to justify its routine use in clinical practice for all patients with diabetic macular edema. A randomized clinical trial on this issue would provide more conclusive evidence and help identify those patients most likely to benefit from intravitreal triamcinolone acetonide.

A review of treatments for macular degeneration: a synopsis of currently approved treatments and ongoing clinical trials.

PURPOSE OF REVIEW: The purpose of this report is to review recent literature and ongoing clinical trials of the treatment of neovascular age-related macular degeneration. RECENT FINDINGS: Advances in the understanding of the pathogenesis of age-related macular degeneration and choroidal neovascularization have resulted in the emergence of pharmacotherapies targeting various aspects of angiogenesis. Preliminary results with the new agents have been encouraging. Moreover, longer follow-up and subgroup analyses of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy studies have suggested new potential indications for photodynamic therapy. SUMMARY: Currently a patient with wet macular degeneration may have multiple investigational options that were unavailable several years ago. Ongoing clinical trials are aimed at determining the long-term safety and efficacy of these new pharmacologic and combination therapy modalities.

Kayser-Fleischer ring as the presenting sign of Wilson disease.

PURPOSE: To describe a case in which the recognition by the ophthalmologist of Kayser-Fleischer rings played a crucial role in the diagnosis of Wilson disease (hepatolenticular degeneration). DESIGN: Interventional case report. METHODS: An 18-year-old woman was found to have bilateral peripheral golden brown pigment deposits at the level of the Descemet membrane consistent with Kayser-Fleischer rings. She initially denied systemic symptoms. RESULTS: The serum cerumoplasmin level of the patient was normal. Liver function tests were also normal. Further evaluations with 24-hour urine copper assay and liver biopsy were positive for Wilson disease. She underwent anticopper therapy and, 6 months later, reported improved concentration and balance. No appreciable change occurred in the Kayser-Fleischer rings. CONCLUSION: Wilson disease occurs when a defective copper-transporting enzyme in the liver results in toxic copper accumulation in multiple organs. Because of the insidious nature of the disease, patients may not seek medical attention until severe irreversible damage has occurred. By diagnosis of Kayser-Fleischer rings, ophthalmologists may play a critical role in the early recognition and proper evaluation of such patients.