Publications

2013

Cruzat A, Tauber A, Shukla A, Paschalis E, Pineda R, Dohlman C. Low-cost and readily available tissue carriers for the Boston keratoprosthesis: a review of possibilities. J Ophthalmol. 2013;2013:686587.
The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual rehabilitation for eyes with severe corneal opacities not suitable for standard corneal transplantation. However, the B-KPro presently needs a corneal graft as a tissue carrier. Although corneal allograft tissue is readily available in the United States and other developed countries with established eye banks, the worldwide need vastly exceeds supply. Therefore, a simple, safe, and inexpensive alternative to corneal allografts is desirable for the developing world. We are currently exploring reasonable alternative options such as corneal autografts, xenografts, noncorneal autologous tissues, and laboratory-made tissue constructs, as well as modifications to corneal allografts, such as deep-freezing, glycerol-dehydration, gamma irradiation, and cross-linking. These alternative tissue carriers for the B-KPro are discussed with special regard to safety, practicality, and cost for the developing world.
PURPOSE: To compare the operating room performance of ophthalmology residents trained by traditional wet-lab versus surgical simulation on the continuous curvilinear capsulorhexis (CCC) portion of cataract surgery. SETTING: Academic tertiary referral center. DESIGN: Prospective randomized study. METHODS: Residents who chose to participate and provided informed consent were randomized to preoperative CCC training in the wet lab or on a simulator. Residents completed pre-practice demographic questionnaires including habits of daily living. After completion of their preoperative training (wet lab versus simulator), residents performed their first CCC of the clinical rotation under the direct supervision of an attending physician as part of their standard training at the facility. Residents then completed satisfaction questionnaires regarding their preoperative training. Two attending surgeons reviewed and graded each video of operating room performance. The mean score between the 2 attending physicians was used as the individual performance score for each of the 12 performance criteria. The overall score was calculated as the sum of these 12 individual performance scores (standardized). RESULTS: Ten residents trained in the wet lab and 11 on the simulator. There was no significant difference in overall score between the 2 groups (P=.608). There was no significant difference in any individual score except time (wet-lab group faster than simulator group) (P=.038). CONCLUSIONS: Preoperative simulator training prepared residents for the operating room as effectively as the wet lab. The time to pass the simulator curriculum was predictive of the time and overall performance in the operating room. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
Rahimi Darabad R, Suzuki T, Richards S, Jensen R, Jakobiec F, Zakka F, Liu S, Sullivan D. Influence of aromatase absence on the gene expression and histology of the mouse meibomian gland. Invest Ophthalmol Vis Sci. 2013;54(2):987–98.
PURPOSE: We hypothesize that aromatase, an enzyme that controls estrogen biosynthesis, plays a major role in the sex-related differences of the meibomian gland. To begin to test this hypothesis, we examined the influence of aromatase absence, which completely eliminates estrogen production, on glandular gene expression and histology in male and female mice. METHODS: Meibomian glands were obtained from adult, age-matched wild-type (WT) and aromatase knockout (ArKO) mice. Tissues were processed for histology or the isolation of total RNA, which was analyzed for differentially expressed mRNAs by using microarrays. RESULTS: Our results show that aromatase significantly influences the expression of more than a thousand genes in the meibomian gland. The nature of this effect is primarily sex-dependent. In addition, the influence of aromatase on sex-related differences in gene expression is predominantly genotype-specific. However, many of the sex-related variations in biological process, molecular function, and cellular component ontologies, as well as in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, are remarkably similar between WT and ArKO mice. The loss of aromatase activity has no obvious effect on the histology of meibomian glands in male or female mice. CONCLUSIONS: Our findings demonstrate that aromatase has a significant impact on gene expression in the meibomian gland. The nature of this influence is sex-dependent and genotype-specific; however, many of the sex-related variations in gene ontologies and KEGG pathways are similar between WT and ArKO mice. Consequently, it appears that aromatase, and by extension estrogen, do not play a major role in the sex-related differences of the mouse meibomian gland.
De Castro D, Santiago YM, Cunningham M, Gray S, Metson R, Fay A. A modified lacrimal sac implant for high-risk dacryocystorhinostomy. Ophthalmic Plast Reconstr Surg. 2013;29(5):367–72.
PURPOSE: The reported 5% of patients with nasolacrimal duct obstruction who fail dacryocystorhinostomy likely include patients with severe mucosal disease or anatomical anomalies. The technique described herein avoids mucosal anastomosis and minimizes mucosal manipulation by inserting a permanent silicone conduit from the lacrimal sac into the nasal cavity. METHODS: This retrospective review of 9 surgical cases was performed with institutional review board approval. Six patients underwent 9 surgeries (3 sequentially bilateral) for dacryocystitis. Two patients had Wegener granulomatosis, 1 had pemphigoid, 1 sarcoidosis, 1 Rosai-Dorfman disease, and 1 congenital choanal atresia with chronic neonatal dacryocystitis. In each case, a modified Rains sinus stent was inserted through an external lacrimal sac incision with the draining end positioned in the nasal cavity. Two patients underwent concurrent canalicular intubation with Guibor silicone stents to prevent internal punctum obstruction by the lacrimal sac implant. Recurrence of symptoms, patient comfort, and modified Rains stent stability and patency were evaluated. RESULTS: Mean follow up was 30 months (range 7-59 months). The modified Rains stent remained stable and patent in 7 of 9 cases, and symptoms resolved in 8 of 9 cases. In 1 patient with sarcoidosis, the modified Rains stent became repeatedly obstructed with nasal secretions and ultimately dislodged after intranasal manipulation by a physician unfamiliar with the surgery. In no other case did the patient experience recurrent infection, and in those cases, epiphora resolved entirely. In the patient with pemphigoid, one of the modified Rains stents extruded 6 months postoperatively, but his symptoms remained controlled. No adverse reaction to the implant material was seen. CONCLUSIONS: A Rains silicone frontal sinus stent can be modified for implantation into the lacrimal sac and can safely and effectively drain the lacrimal sac into the nose in patients with severe mucosal disease or anatomical anomalies. Additional study and a stent specifically designed for this application will likely improve outcomes.
De Castro D, Fay A, Wladis E, Nguyen J, Osaki T, Metson R, Curry W. Self-irrigating piezoelectric device in orbital surgery. Ophthalmic Plast Reconstr Surg. 2013;29(2):118–22.
PURPOSE: Orbital osteotomy risks injury to the eyeball and orbit soft tissues. Used extensively in oral and maxillofacial surgery, piezoelectric technology offers a greater margin of safety than traditional bone cutting instruments. The authors describe the novel use of this system in a variety of orbital surgeries. METHODS: This interventional case series was performed in accordance with institutional review board regulations. The medical records of all patients who had undergone orbital surgery using the piezoelectric blade at 3 institutions were reviewed. Indication for surgery, gender, age, duration of follow up, intraoperative complications, surgical result, and postoperative course was recorded. RESULTS: Sixteen patients underwent surgery on 18 orbits using the piezoelectric system between August 2011 and June 2012. Surgeries performed included orbital decompression (8), lateral orbitotomy (5), cranio-orbitotomy (4), and external dacryocystorhinostomy (1). Eight were female and 8 were male patients. Mean age was 55 years old (standard deviation 15 years). Mean follow up was 82 days. The osteotomy created by the blade was narrow and smooth in every case. The surgeons uniformly appreciated the precision and safety of the instrument compared with traditional electric saw blades. There were no soft tissue lacerations or intraoperative complications and reconstructions were uniformly uneventful. Postoperative healing was rapid with no unexpected inflammation, and no palpable bony defects were appreciated in the reconstructed cases. CONCLUSIONS: Because it does not cut soft tissue and cuts a narrow trough, the self-irrigating piezoelectric saw blade appears safer and more precise than traditional electric saw blades in and around the orbit.
Ding J, Kam W, Dieckow J, Sullivan D. The influence of 13-cis retinoic acid on human meibomian gland epithelial cells. Invest Ophthalmol Vis Sci. 2013;54(6):4341–50.
PURPOSE: Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells. METHODS: To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated. RESULTS: We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9. CONCLUSIONS: Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA-related induction of MGD.
Ding J, Sackmann-Sala L, Kopchick J. Mouse models of growth hormone action and aging: a proteomic perspective. Proteomics. 2013;13(3-4):674–85.
Growth hormone (GH) is a protein secreted by the anterior pituitary and circulates throughout the body to exert important actions on growth and metabolism. GH stimulates the secretion of insulin-like growth factor-I (IGF-I) that mediates some of the growth promoting actions of GH. The GH/IGF-I axis has recently been recognized as important in terms of longevity in organisms ranging from Caenorhabditis elegans to mice. For example, GH transgenic mice possess short lifespans while GH receptor null (GHR-/-) mice have extended longevity. Thus, the actions of GH (or IGF-I) or lack thereof impact the aging process. In this review, we summarize the proteomic analyses of plasma and white adipose tissue in these two mouse models of GH action, i.e. GH transgenic and GHR-/- mice. At the protein level, we wanted to establish novel plasma biomarkers of GH action as a function of age and to determine differences in adipose tissue depots. We have shown that these proteomic approaches have not only confirmed several known physiological actions of GH, but also resulted in novel protein biomarkers and targets that may be indicative of the aging process and/or new functions of GH. These results may generate new directions for GH and/or aging research.