Transcription factor TFAP2B up-regulates human corneal endothelial cell-specific genes during corneal development and maintenance.

The corneal endothelium, which originates from the neural crest via the periocular mesenchyme (PM), is crucial for maintaining corneal transparency. The development of corneal endothelial cells (CECs) from the neural crest is accompanied by the expression of several transcription factors, but the contribution of some of these transcriptional regulators to CEC development is incompletely understood. Here, we focused on activating enhancer-binding protein 2 (TFAP2, AP-2), a neural crest-expressed transcription factor. Using semiquantitative/quantitative RT-PCR and reporter gene and biochemical assays, we found that, within the AP-2 family, the TFAP2B gene is the only one expressed in human CECs in vivo and that its expression is strongly localized to the peripheral region of the corneal endothelium. Furthermore, the TFAP2B protein was expressed both in vivo and in cultured CECs. During mouse development, TFAP2B expression began in the PM at embryonic day 11.5 and then in CECs during adulthood. siRNA-mediated knockdown of TFAP2B in CECs decreased the expression of the corneal endothelium-specific proteins type VIII collagen α2 (COL8A2) and zona pellucida glycoprotein 4 (ZP4) and suppressed cell proliferation. Of note, we also found that TFAP2B binds to the promoter of the COL8A2 and ZP4 genes. Furthermore, CECs that highly expressed ZP4 also highly expressed both TFAP2B and COL8A2 and showed high cell proliferation. These findings suggest that TFAP2B transcriptionally regulates CEC-specific genes and therefore may be an important transcriptional regulator of corneal endothelial development and homeostasis.

RETINAL MICROVASCULATURE AND VISUAL ACUITY AFTER INTRAVITREAL AFLIBERCEPT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION: An Optical Coherence Tomography Angiography Study.

PURPOSE: To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity. METHODS: Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined. RESULTS: After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm in the SCP and 3.25 ± 0.91 mm in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm in the SCP and 1.78 ± 1.73 mm in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P < 0.001) and with smaller SCP and DCP foveal avascular zone areas (both P < 0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P < 0.05) and ischemia (determined via pretreatment fluorescein angiography, P < 0.05), and positively correlated with photoreceptor integrity (P < 0.001). CONCLUSION: Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

Do Video Games Predict an Early Advanced Capacity to Learn Interventional Radiology Skills?

PURPOSE: To elucidate the relationship between video game (VG) play and interventional radiology (IR) technical skills in medical students. MATERIALS AND METHODS: Twenty medical students recruited at our institution's IR symposium completed a survey to ascertain demographics and prior VG experience, then participated in a 3-part trial of skills assessing IR and VG skill and visuospatial aptitude (VSA). IR skill was evaluated via an endovascular simulation task, VG skill by performance on three separate VGs, and VSA using the Cube Comparison test. Regression analysis was tested the strength of relationship between IR skill and VG experience, VG skill, and VSA, respectively, and participants were stratified by IR skill to top and bottom halves for survey-response comparison. RESULTS: There was no correlation between either VG skill or visuospatial aptitude and IR skill (r = -0.22, p = 0.35; and r = 0.14, p = 0.57). Greater number of years playing VGs correlated with superior IR skill (Spearman's rho=-0.45, p<0.05). Students who selected IR as their specialty of interest had extensive VG experience, playing for > 15 years (n = 4, 80%), at least 10 hours per week at their peak (n = 3, 60%), and reported being either "skilled" or "highly skilled" at VGs (n = 3, 60%). CONCLUSIONS: In our study, though limited by power, number of years playing VGs correlated positively with IR skills in medical students. Prior VG experience may predict an early advanced capacity to learn IR skills and an interest in the specialty.

Objective assessment of robotic suturing skills with a new computerized system: A step forward in the training of robotic surgeons.

INTRODUCTION: The purpose of this study was to assess robot-assisted suturing skills on a laparoscopic intestinal anastomosis model by using a novel computerized objective assessment system. METHODS: This study compared the suturing skills of 13 surgically naïve participants on an artificial intestinal anastomosis model that mimics real tissue. Each examinee sutured using da Vinci robot assistance under 2-D and 3-D visualization and with conventional laparoscopy (CL). Pressure-measuring and image-processing devices were employed to quantitatively evaluate suturing skills. Five unique criteria were used to evaluate the skills of participants. RESULTS: Suturing under 3-D visualization (P < 0.01) and with CL (P < 0.05) were significantly faster than under 2-D visualization. Sutures placed under 3-D (P < 0.05) and 2-D (P < 0.01) visualization had significantly better suture tension than those placed with CL, which did not meet acceptable values for suture tension. Sutures placed with CL had significantly better air pressure leakage than those placed under 2-D visualization (P < 0.05), which did not meet acceptable values for air pressure leakage and wound opening area. One participants failed to achieve full-thickness sutures with 2-D, two participants with CL, and one participant with 3-D. CONCLUSION: Using 3-D vision is necessary for complex maneuvering during robot-assisted minimally invasive surgery. Our quantitative assessment system is useful for evaluating the skill acquisition of surgeon-trainees undergoing robotic surgery training.

Retinal Microvasculature and Visual Acuity after Intravitreal Aflibercept in Diabetic Macular Edema: An Optical Coherence Tomography Angiography Study.

We investigated changes in retinal vascular area and the foveal avascular zone (FAZ) after intravitreal aflibercept in diabetic macular edema (DME) and the association of these changes with visual outcomes. The retinal vascular area in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) and the FAZ area were measured using optical coherence tomography angiography (OCTA) in 23 eyes of 23 patients with DME, before and after intravitreal aflibercept. Overall, there was no significant change in retinal vascular area or FAZ. Better BCVA after treatment was significantly associated with larger retinal vascular area in the SCP and the DCP, both at baseline (R2 = 0.512, P < 0.001 and R2 = 0.361, P = 0.002, respectively) and after intravitreal aflibercept (R2 = 0.717, P < 0.001 and R2 = 0.618, P < 0.001, respectively). MAs were observed in the DCP in 20 eyes (87%), but only detected in four eyes (17%) in the SCP before treatment. The number of eyes with MAs in the DCP significantly decreased to 13 (57%) after treatment (P = 0.049). The persistence of DME was associated with persistent MAs (P = 0.019) and less visual gain (P = 0.031) following treatment. Thus, preserving retinal perfusion and the resolution of MAs are associated with better vision and resolution of the DME after intravitreal aflibercept.

Noninvasive assessment of corneal alterations associated with monoclonal gammopathy.

Aggregation of monoclonal immunoglobulin can lead to organ damage. However, the necessity of invasive examination such as biopsy has hampered better understanding of the pathophysiology. Corneal crystalline deposition is a rarely reported but known ocular manifestation of multiple myeloma. It is unclear whether the cornea is a common target of monoclonal immunoglobulin deposition. We conducted a prospective clinical case-control study to objectively quantify monoclonal gammopathy-associated corneal changes as well as any therapeutic response. Using an ophthalmic Scheimpflug camera imaging for noninvasive corneal assessments, we quantified densitometry values in 30 patients. Although none had crystalline keratopathy, corneal transparency in monoclonal gammopathy patients was significantly impaired compared to that in age-matched controls, based on noninvasive Scheimpflug camera imaging. Furthermore, treatment for multiple myeloma seemed to eradicate the diffuse aggregation of monoclonal proteins. Our results indicate that exposure to monoclonal immunoglobulin may induce the accumulation of monoclonal immunoglobulin in the cornea, and ophthalmic examinations such as corneal densitometry measurements with a Scheimpflug camera may be useful for noninvasive evaluation of monoclonal immunoglobulin deposition diseases.

Corneal infiltration and xanthoma formation in mycosis fungoides.

PURPOSE: To report a case of corneal infiltration and xanthoma formation in mycosis fungoides (cutaneous T-cell lymphoma). OBSERVATIONS: A middle aged Japanese man with mycosis fungoides (MF) involving the face was referred to Ophthalmology for evaluation of unilateral, painless conjunctival injection. Biopsy of the conjunctiva revealed a malignant T cell population consistent with MF tumor invasion. Years later, he returned following several episodes of infectious keratitis with a painless, yellow, rapidly forming mass in the left eye over two weeks. Corneal biopsy showed foamy histiocytes and positive staining for CD68, and a diagnosis of corneal xanthoma was made. CONCLUSIONS AND IMPORTANCE: Severe ocular surface disease can rarely occur in MF by direct invasion of tumor cells. Corneal infiltration and xanthoma development may be avoidable by careful monitoring for infectious keratitis in patients with conjunctival involvement, as in our case.

Changes in Retinal Microvasculature and Visual Acuity After Antivascular Endothelial Growth Factor Therapy in Retinal Vein Occlusion.

Purpose: To investigate the changes in the retinal microvasculature during the course of anti-VEGF therapy in eyes with macular edema due to retinal vein occlusion (RVO) and their association with visual outcomes. Methods: The vessel density (VD) and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively measured by optical coherence tomography angiography (OCTA) in 48 consecutive eyes with RVO before and 1, 3, 6, 9, and 12 months after anti-VEGF therapy. Anti-VEGF therapy was performed either with ranibizumab or aflibercept following a pro re nata (PRN) regimen. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA were assessed. Results: The BCVA improved significantly at 12 months (P < 0.001). Better BCVA at 12 months was significantly associated with a better VD in the SCP and DCP both at baseline (R2 = 0.524, P < 0.001 and R2 = 0.457, P < 0.001, respectively) and at 12 months (R2 = 0.521, P < 0.001 and R2 = 0.662, P < 0.001, respectively). Overall, both VD and FAZ did not change significantly during the 12 months. However, the progression of nonperfusion was observed in the SCP in 6 (13%) eyes and in the DCP in 10 (21%) eyes. The number of macular edema recurrence was significantly associated with a decrease in the VD (P = 0.006 [SCP] and P < 0.001 [DCP]) and less visual gain (P = 0.02) after treatment. Conclusions: Anti-VEGF therapy maintains retinal perfusion in most patients with RVO. Preserving retinal perfusion is crucial for better visual outcomes.