Ten-year Results after Conventional Corneal Cross-linking in Korean Patients with Progressive Keratoconus

Purpose@#To evaluate the long-term effects of conventional corneal cross-linking in patients with progressive keratoconus. @*Methods@#A total of 18 eyes of 9 patients diagnosed with keratoconus were analyzed retrospectively. One eye was diagnosed with progressive keratoconus and conventional corneal crosslinking was performed. The other eye was classified as non-progressive and remained untreated. All patients were assessed with best corrected visual acuity (BCVA), maximum keratometry (Kmax), mean keratometry (Kmean), corneal astigmatism, and corneal thickness. Clinical data were collected before the procedure and at 1, 3, 6 months and 1 to 10 years after the procedure. @*Results@#The BCVA significantly improved from 0.63 ± 0.18 logarithm of the minimum angle of resolution (logMAR) to 0.46 ± 0.25 logMAR at 10 years after conventional corneal crosslinking (p = 0.027). The Kmax and Kmean decreased from 65.90 ± 9.43 D and 52.82 ± 5.16 D to 62.83 ± 8.16 D and 51.52 ± 5.18 D, respectively (p = 0.021, p = 0.028, respectively). Corneal astigmatism decreased from 6.97 ± 2.21 D to 5.53 ± 1.64 D (p = 0.008). The thinnest corneal thickness decreased from 435.11 ± 53.37 μm to 369.22 ± 64.00 μm 1 month after the procedure (p = 0.008), and gradually improved over time. At 10 years, the thinnest corneal thickness increased to 410.11 ± 61.32 μm (p = 0.097). In the untreated eyes, the mean keratometry significantly increased after 4 years of follow-up, but other factors did not change significantly. Although corneal opacity persisted for up to 10 years in 3 eyes of the treatment group, there was no significant difference of BCVA compared to the treated eyes without corneal opacity (p = 0.714). @*Conclusions@#In patients with progressive keratoconus, conventional corneal crosslinking is a safe and effective procedure that suppresses long-term progression.

Combination Therapy of the Active KRAS-Targeting Antibody inRas37 and a PI3K Inhibitor in Pancreatic Cancer

KRAS activating mutations, which are present in more than 90% of pancreatic cancers, drive tumor dependency on the RAS/ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Therefore, combined targeting of RAS/MAPK and PI3K/AKT signaling pathways may be required for optimal therapeutic effect in pancreatic cancer.However, the therapeutic efficacy of combined MAPK and PI3K/AKT signaling target inhibitors is unsatisfactory in pancreatic cancer treatment, because it is often accompanied by MAPK pathway reactivation by PI3K/AKT inhibitor. Therefore, we developed an inRas37 antibody, which directly targets the intra-cellularly activated GTP-bound form of oncogenic RAS mutation and investigated its synergistic effect in the presence of the PI3K inhibitor BEZ-235 in pancreatic cancer. In this study, inRas37 remarkably increased the drug response of BEZ-235 to pancreatic cancer cells by inhibiting MAPK reactivation. Moreover, the co-treatment synergistically inhibited cell proliferation, migration, and invasion and exhibited synergistic anticancer activity by inhibiting the MAPK and PI3K pathways. The combined administration of inRas37and BEZ-235 significantly inhibited tumor growth in mouse models. Our results demonstrated that inRas37 synergistically increased the antitumor activity of BEZ-235 by inhibiting MAPK reactivation, suggesting that inRas37 and BEZ-235 co-treatment could be a potential treatment approach for pancreatic cancer patients with KRAS mutations.

Comparison of Ranibizumab and Bevacizumab for Macular Edema Associated with Branch Retinal Vein Occlusion

PURPOSE: To assess the effectiveness and safety of intravitreal ranibizumab compared with bevacizumab for the treatment of macular edema associated with branch retinal vein occlusion (BRVO). METHODS: This was a retrospective study of 80 eyes with macular edema associated with BRVO. Patients received either 0.5 mg of ranibizumab (n = 24) or 1.25 mg of bevacizumab (n = 56) intravitreally. Both groups received three initial monthly injections followed by as-needed injections. The best-corrected visual acuity, central subfield thickness, mean number of injections, and retreatment rate were evaluated monthly for 6 months after the initial injection. RESULTS: The best-corrected visual acuity significantly improved from logarithm of the minimal angle of resolution (logMAR) 0.55 ± 0.26 at baseline to 0.24 ± 0.26 at 6 months in the ranibizumab group (p < 0.001) and from logMAR 0.58 ± 0.21 at baseline to 0.29 ± 0.25 at 6 months in the bevacizumab group (p < 0.001), which is not a statistically significant difference (p = 0.770). The mean reduction in central subfield thickness at 6 months was 236 ± 164 µm in the ranibizumab group (p < 0.001) and 219 ± 161 µm in the bevacizumab group (p < 0.001), which is not also a statistically significant difference (p = 0.698). The mean numbers of ranibizumab and bevacizumab injections were 3.25 ± 0.53 and 3.30 ± 0.53, respectively (p = 0.602). In addition, after the three initial monthly injections, the retreatment rates for ranibizumab and bevacizumab injections were 20.8% and 26.7%, respectively (p = 0.573). CONCLUSIONS: Both ranibizumab and bevacizumab were effective for the treatment of BRVO and produced similar visual and anatomic outcomes. In addition, the mean number of injections and the retreatment rates were not significantly different between the groups.

A Case of Conjunctival Lithiasis with Clinical Manifestations of Superior Limbic Keratoconjunctivitis

PURPOSE: To report a case of conjunctival lithiasis with clinical manifestations of superior limbic keratoconjunctivitis. CASE SUMMARY: A 40-year-old male complained of pain, foreign body sensation and injection in the left eye lasting 1 month. The slit-lamp examination revealed injection of the superior bulbar conjunctiva, linear corneal band opacity, fine punctate staining and epithelial defect in the superior cornea area. After eversion of the left upper eyelid, there were many various-sized conjunctional concretions and inflammation in the superior tarsal conjunctiva. Therefore, we considered conjunctival lithiasis-induced clinical manifestations of superior limbic keratoconjunctivitis and then removed the conjunctival concretions using a 30-gauge needle. After the procedures, artificial tears, antibiotic eye drops, steroid eye drops and a therapeutic contact lens were applied. After 1 week, all symptoms and signs improved and there was no recurrence for 4 months. CONCLUSIONS: Mechanical stimulation by severe conjunctival lithiasis can induce clinical manifestations of superior limbic keratoconjunctivitis. Therefore, in patients with clinical manifestations of superior limbic keratoconjunctivitis, conjunctival lithiasis should be considered by observing the superior tarsal conjunctiva more closely.

Effect of restoration type on the stress distribution of endodontically treated maxillary premolars; Three-dimensional finite element study / 대한치과보존학회지

The purpose of this study was to investigate the effects of four restorative materials under various occlusal loading conditions on the stress distribution at the CEJ of buccal, palatal surface and central groove of occlusal surface of endodontically treated maxillary second premolar, using a 3D finte element analysis. A 3D finite element model of human maxillary second premolar was endodontically treated. After endodontic treatment, access cavity was filled with Amalgam, resin, ceramic or gold of different mechanical properties. A static 500N forces were applied at the buccal (Load-1) and palatal cusp (Load-2) and a static 170N forces were applied at the mesial marginal ridge and palatal cusp simultaneously as centric occlusion (Load-3). Under 3-type Loading condition, the value of tensile stress was analyzed after 4-type restoration at the CEJ of buccal and palatal surface and central groove of occlusal surface. Excessive high tensile stresses were observed along the palatal CEJ in Load-1 case and buccal CEJ in Load-2 in all of the restorations. There was no difference in magnitude of stress in relation to the type of restorations. Heavy tensile stress concentrations were observed around the loading point and along the central groove of occlusal surface in all of the restorations. There was slight difference in magnitude of stress between different types of restorations. High tensile stress concentrations around the loading points were observed and there was no difference in magnitude of stress between different types of restorations in Load-3.

Stress distribution of endodontically treated maxillary second premolars restored with different methods: Three-dimensional finite element analysis / 대한치과보존학회지

The purpose of this study was to evaluate the influence of elastic modulus of restorative materials and the number of interfaces of post and core systems on the stress distribution of three differently restored endodontically treated maxillary second premolars using 3D FE analysis. Model 1, 2 was restored with a stainless steel or glass fiber post and direct composite resin. A PFG or a sintered alumina crown was considered. Model 3 was restored by EndoCrown. An oblique 500 N was applied on the buccal (Load A) and palatal (Load B) cusp. The von Mises stresses in the coronal and root structure of each model were analyzed using ANSYS. The elastic modulus of the definitive restorations rather than the type of post and core system was the primary factor that influenced the stress distribution of endodontically treated maxillary premolars. The stress concentration at the coronal structure could be lowered through the use of definitive restoration of high elastic modulus. The stress concentration at the root structure could be lowered through the use of definitive restoration of low elastic modulus.

Stress analysis of maxillary premolars with composite resin restoration of notch-shaped class V cavity and access cavity; Three-dimensional finite element study / 대한치과보존학회지

The purpose of this study was to investigate the distribution of tensile stress of canal obturated maxillary second premolar with access cavity and notch-shaped class V cavity restored with composite resin using a 3D finite element analysis. The tested groups were classified as 8 situations by only access cavity or access cavity with notch-shaped class VS cavity (S or N), loading condition (L1 or L2), and with or without glass ionomer cement base (R1 or R2). A static load of 500 N was applied at buccal and palatal cusps. Notch-shaped cavity and access cavity were filled microhybrid composite resin (Z100) with or without GIC base (Fuji II LC). The tensile stresses presented in the buccal cervical area, palatal cervical area and occlusal surface were analyzed using ANSYS. Tensile stress distributions were similar regardless of base. When the load was applied on the buccal cusp, excessive high tensile stress was concentrated around the loading point and along the central groove of occlusal surface. The tensile stress values of the tooth with class V cavity were slightly higher than that of the tooth without class V cavity. When the load was applied the palatal cusp, excessive high tensile stress was concentrated around the loading point and along the central groove of occlusal surface. The tensile stress values of the tooth without class V cavity were slightly higher than that of the tooth with class V cavity.

The influence of occlusal loads on stress distribution of cervical composite resin restorations: A three-dimensional finite element study / 대한치과보존학회지

The purpose of this study was to investigate the influence of various occlusal loading sites and directions on the stress distribution of the cervical composite resin restorations of maxillary second premolar, using 3 dimensional (3D) finite element (FE) analysis. Extracted maxillary second premolar was scanned serially with Micro-CT (SkyScan1072; SkyScan, Aartselaar, Belgium). The 3D images were processed by 3D-DOCTOR (Able Software Co., Lexington, MA, USA). HyperMesh (Altair Engineering, Inc., Troy, USA) and ANSYS (Swanson Analysis Systems, Inc., Houston, USA) was used to mesh and analyze 3D FE model. Notch shaped cavity was filled with hybrid (Z100, 3M Dental Products, St. Paul, MN, USA) or flowable resin (Tetric Flow, Vivadent Ets., FL-9494-Schaan, Liechtenstein) and each restoration was simulated with adhesive layer thickness (40 microm). A static load of 200 N was applied on the three points of the buccal incline of the palatal cusp and oriented in 20degrees increments, from vertical (long axis of the tooth) to oblique 40degrees direction towards the buccal. The maximum principal stresses in the occlusal and cervical cavosurface margin and vertical section of buccal surfaces of notch-shaped class V cavity were analyzed using ANSYS. As the angle of loading direction increased, tensile stress increased. Loading site had little effect on it. Under same loading condition, Tetric Flow showed relatively lower stress than Z100 overall, except both point angles. Loading direction and the elastic modulus of restorative material seem to be important factor on the cervical restoration.

The influence of composite resin restoration on the stress distribution of notch shaped noncarious cervical lesion; A three dimensional finite element analysis study / 대한치과보존학회지

The purpose of this study was to investigate the effects of composite resin restorations on the stress distribution of notch shaped noncarious cervical lesion using three-dimensional (3D) finite element analysis (FEA). Extracted maxillary second premolar was scanned serially with Micro-CT (SkyScan1072; SkyScan, Aartselaar, Belgium). The 3D images were processed by 3D-DOCTOR (Able Software Co., Lexington, MA, USA). ANSYS (Swanson Analysis Systems, Inc., Houston, USA) was used to mesh and analyze 3D FE model. Notch shaped cavity was filled with hybrid or flowable resin and each restoration was simulated with adhesive layer thickness (40 microM). A static load of 500 N was applied on a point load condition at buccal cusp (loading A) and palatal cusp (loading B). The principal stresses in the lesion apex (internal line angle of cavity) and middle vertical wall were analyzed using ANSYS. The results were as follows 1. Under loading A, compressive stress is created in the unrestored and restored cavity. Under loading B, tensile stress is created. And the peak stress concentration is seen at near mesial corner of the cavity under each load condition. 2. Compared to the unrestored cavity, the principal stresses at the cemeto-enamel junction (CEJ) and internal line angle of the cavity were more reduced in the restored cavity on both load conditions. 3. In teeth restored with hybrid composite, the principal stresses at the CEJ and internal line angle of the cavity were more reduced than flowable resin.

Effects of occlusal load on the stress distribution of four cavity configurations of noncarious cervical lesions: a three-dimensional finite element analysis study / 대한치과보존학회지

The objective of this study was to investigate the effect of excessive occlusal loading on stress distribution on four type of cervical lesion, using a three dimensional finite element analysis (3D FEA). The extracted maxillary second premolar was scanned serially with Micro-CT. The 3D images were processed by 3D-DOCTOR. ANSYS was used to mesh and analyze 3D FE model. Four different lesion configurations representative of the various types observed clinically for teeth were studied. A static point load of 500N was applied to the buccal and lingual cusp (Load A and B). The principal stresses in lesion apex, and vertical sectioned margin of cervical wall were analyzed. The results were as follows 1. The patterns of stress distribution were similar but the magnitude was different in four types of lesion. 2. The peak stress was observed at mesial corner and also stresses concentrated at lesion apex. 3. The compressive stress under load A and the tensile stress under load B were dominant stress. 4. Under the load, lesion can be increased and harmful to tooth structure unless restored.

Effects of occlusal load on the cervical stress distribution: A three-dimensional finite element study / 대한치과보존학회지

The objective of this study was to investigate the effects of various occlusal loads on the stress distribution of the buccal cervical region of a normal maxillary second premolar, using a three dimensional finite element analysis (3D FEA). After 3D FE modeling of maxillary second premolar, a static load of 500N of three load cases was applied. Stress analysis was performed using ANSYS (Swanson Analysis Systems, Inc., Houston, USA). The maximum principal stresses and minimum principal stresses were sampled at thirteen nodal points in the buccal cervical enamel for each four horizontal planes, 1.0 mm above CEJ, 0.5 mm above CEJ, CEJ, 0.5 mm under CEJ. The results were as follows 1. The peak stress was seen at the cervical enamel surface of the mesiobuccal line angle area, asymmetrically. 2. The values of compressive stresses were within the range of the failure stress of enamel. But the values of tensile stresses exceeded the range of the failure stress of enamel. 3. The tensile stresses from the perpendicular load at the buccal incline of palatal cusp may be shown to be the primary etiological factors of the NCCLs.