Mercede Majdi

Notch Inhibition during Corneal Epithelial Wound Healing Promotes Migration

PURPOSE To determine the role of Notch signaling in corneal epithelial migration and wound healing. METHODS Immunolocalization of Notch1 was performed during epithelial wound healing in vivo in mouse corneal epithelial debridement wounds and in vitro in primary human corneal epithelial cells following a linear scratch wound. The effects of Notch inhibition, using the γ-secretase inhibitor N-(N-[3,5-difluorophenacetyl]-l-alanyl)-S-phenylglycine t-butyl ester (DAPT) or following stable transfection with Notch1-short hairpin RNA (shRNA), was evaluated in a scratch assay and transwell migration assay. Likewise, in vitro adhesion, proliferation and the actin cytoskeleton was examined. The DAPT effect was also evaluated in vivo in a mouse model of corneal epithelial wound healing. RESULTS The expression of Notch1 was reduced at the leading edge of a healing corneal epithelium both in vivo and in vitro. Notch inhibition using DAPT and using Notch1-shRNA both enhanced in vitro migration in scratch and transwell migration assays. Consistent with this increased migratory behavior, Notch inhibited cells demonstrated decreased cell-matrix adhesion and enhanced lamellipodia formation. Notch inhibition by DAPT was also found to accelerate corneal epithelial wound closure in an in vivo murine model without affecting proliferation. CONCLUSIONS The results highlight the role of Notch in regulating corneal epithelial migration and wound healing. In particular, Notch signaling appears to decrease in the early stages of wound healing which contributes to cytoskeletal changes with subsequent augmentation of migratory behavior.

The Use of Peer Optic Nerve Photographs for Teaching Direct Ophthalmoscopy

OBJECTIVE To use a novel teaching exercise to encourage students to practice ophthalmoscopy and to measure the learning effect both subjectively and objectively. DESIGN Comparative case series. PARTICIPANTS One hundred thirty-one fourth-year medical students on their 1-week ophthalmology rotations with 89 in the experimental group and 42 in the control group. METHODS Those in the experimental group had 1 eye dilated and their optic nerve photographed on the first day. The next day, these students received an unlabeled optic nerve photograph belonging to 1 of their peers (typically 8-10 per group) and were given 3 days to identify the student matching the photograph. The students in the control group were simply encouraged to practice ophthalmoscopy on each other without the use of photographs. MAIN OUTCOME MEASURES Both objective and subjective changes from the beginning to the end of the rotation were measured and compared between the 2 groups. RESULTS In the 89 students who used peer optic nerve photographs, 75 (84.3%) showed improvement in direct ophthalmoscopy skills over the course of the week. In contrast, only 12 (28.6%) of the 42 control students demonstrated an objective improvement (P<0.001). The subjective confidence levels likewise were more improved in the students who took part in the optic nerve photograph exercise. CONCLUSIONS These results suggest that the task of matching an unknown optic nerve photograph to the correct eye of a peer leads to increased self-confidence and more proficient use of the direct ophthalmoscope.

The Role of Demographic Characteristics in the Outcomes of Cataract Surgery and Gender Roles in the Uptake of Postoperative Eye Care: A Hospital-based Study

Purpose: To explore the effect of demographic characteristics on the outcomes of cataract surgery in terms of visual acuity and patient satisfaction, and gender role in the uptake of postoperative care. Methods: Comprehensive ocular examinations were performed on 478 subjects (558 eyes) over the age of 50 years who underwent surgery for age-related cataract at the largest eye hospital in Iran. Demographic characteristics were obtained and surgical records were reviewed. Results: Male subjects had significantly better outcomes in terms of uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) (mean difference 0.12 and 0.13 logMAR; p = 0.004 and p < 0.001, respectively). Women were significantly less satisfied than men (73.2% vs. 83.6%; p = 0.011). Postoperative UCVA and BSCVA were better in patients with higher levels of education (both p < 0.001). Age had an inverse association with UCVA (p = 0.004) and BSCVA (p < 0.001). Women were twice as likely to need capsulotomy (p = 0.002). Men’s uptake of postoperative refractive care was 4-fold that of women’s (31% vs. 7%). In multivariable analyses, age, sex, education, presence of ocular comorbidity and need for capsulotomy, spectacle prescription and other care were associated with postoperative UCVA (all p < 0.05; adjusted R2 = 0.256). Conclusion: Female patients were shown to be at a clear disadvantage in cataract surgery; outcomes of the procedure and postoperative care were both poorer. Older age, lower level of education, ocular comorbidity and unmet postoperative need were also associated with a poorer outcome.

Using artificial intelligence to predict the risk for posterior capsule opacification after phacoemulsification

PURPOSE: To apply artificial intelligence models to predict the occurrence of posterior capsule opacification (PCO) after phacoemulsification. SETTING: Farabi Eye Hospital, Tehran, Iran. DESIGN: Clinical‐based cross‐sectional study. METHODS: The posterior capsule status of eyes operated on for age‐related cataract and the need for laser capsulotomy were determined. After a literature review, data polishing, and expert consultation, 10 input variables were selected. The QUEST algorithm was used to develop a decision tree. Three back‐propagation artificial neural networks were constructed with 4, 20, and 40 neurons in 2 hidden layers and trained with the same transfer functions (log‐sigmoid and linear transfer) and training protocol with randomly selected eyes. They were then tested on the remaining eyes and the networks compared for their performance. Performance indices were used to compare resultant models with the results of logistic regression analysis. RESULTS: The models were trained using 282 randomly selected eyes and then tested using 70 eyes. Laser capsulotomy for clinically significant PCO was indicated or had been performed 2 years postoperatively in 40 eyes. A sample decision tree was produced with accuracy of 50% (likelihood ratio 0.8). The best artificial neural network, which showed 87% accuracy and a positive likelihood ratio of 8, was achieved with 40 neurons. The area under the receiver‐operating‐characteristic curve was 0.71. In comparison, logistic regression reached accuracy of 80%; however, the likelihood ratio was not measurable because the sensitivity was zero. CONCLUSION: A prototype artificial neural network was developed that predicted posterior capsule status (requiring capsulotomy) with reasonable accuracy. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Ultrasound biomicroscopy findings in fireworks- related blunt eye injuries

Purpose To present ultrasound biomicroscopic (UBM) findings and their clinical correlations in people with optically hazy media after injury at the Persian Wednesday Eve fireworks festival. Methods Ultrasound biomicroscopy was performed on a series of 32 eyes with severe closed-globe injuries by P40 ultrasound biomicroscope. Results The median age of the participants was 19 years, and 81.3% were male. All but one had gross hyphema. Seventy-five percent had an extension of the injury (at least) to Birmingham Eye Trauma Terminology zone II. Ultrasound biomicroscopy detected 3 more iridodialyses and 10 more cyclodialyses in addition to the respective 5 and 3 that were diagnosed clinically. Ten cases of angle recession were observed, and 5 were suggestive of subluxation of the crystalline lens. Two cases were suspected for anterior segment intraocular foreign body on clinical examination, but UBM and computed tomography scanning together ruled out such a diagnosis. Conclusions Our study showed the value of UBM in the assessment of severely contused eyes and hyphema. It made possible evaluation for dialyses and recessions at presentation. Ultrasound biomicroscopy illustrated diverse subclinical disruptions in clinically invisible anterior segment structures.

Corneal Limbal Stem Cell Niche

The cornea is not only essential for passing the light into the eye but also is responsible for more than two-thirds of the eye’s total refractive power. Corneal integrity and transparency is highly dependent on a healthy layer of continuously renewing stratified squamous epithelium located on its outer surface. The corneal epithelial stem/progenitor cells that replenish the corneal epithelium are located in a 1.5–2 mm wide area in between the cornea and sclera, known as the corneal scleral junction, or limbus. This stem cell niche has unique features that are critical to the function of the “limbal” stem cells. Understanding the biology of limbal stem cells has led to significant advancements in the treatment of patients with limbal stem cell deficiency, a group conditions in which the limbal stem cells and their niche are lost or damaged.