Publications

2019

This article aimed to characterize, compare, and contrast the management of isolated orbital floor fractures among oculofacial and facial plastic surgeons in the United States. An anonymous 17-question multiple-choice web-based survey was distributed to all 590 members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) and all 1,300 members of the American Academy of Facial Plastic and Reconstructive Surgery (AAFPRS) using each society's email database from November 2016 to January 2017. Two-hundred twenty-five oculofacial and 135 facial plastic surgeons completed the survey. The most important indications for surgery among both oculofacial and facial plastic surgeons were motility restriction, enophthalmos, and diplopia at 2 weeks. The most common preferred time to surgical intervention was 8 to 14 days; however, facial plastic surgeons were more likely to operate after 4 to 7 days (  < 0.001). The most common choices of orbital implant material were porous polyethylene and porous polyethylene plus titanium for both oculofacial and facial plastic surgeons, nylon for oculofacial surgeons, and titanium for facial plastic surgeons. The majority rarely/never used intraoperative computed tomography imaging or navigation. Facial plastic surgeons were more likely to perform postoperative imaging (  < 0.001). We report results of the first survey of isolated orbital floor fracture management among oculofacial and facial plastic surgeons in the United States. This survey characterizes practice patterns and areas of similarities/differences among oculofacial and facial plastic surgeons in the management of isolated orbital floor fractures, which may help define the current standard of care.
Wirta D, Torkildsen G, Moreira H, Lonsdale J, Ciolino J, Jentsch G, Beckert M, Ousler G, Steven P, Krösser S. A Clinical Phase II Study to Assess Efficacy, Safety, and Tolerability of Waterfree Cyclosporine Formulation for Treatment of Dry Eye Disease. Ophthalmology. 2019;126(6):792–800.
PURPOSE: To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy. DESIGN: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator. PARTICIPANTS: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53). METHODS: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks. MAIN OUTCOME MEASURES: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups. CONCLUSIONS: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.
Liu CH, Wang Z, Huang S, Sun Y, Chen J. MicroRNA-145 Regulates Pathological Retinal Angiogenesis by Suppression of TMOD3. Mol Ther Nucleic Acids. 2019;16:335–347.
Pathological angiogenesis is a hallmark of various vascular diseases, including vascular eye disorders. Dysregulation of microRNAs (miRNAs), a group of small regulatory RNAs, has been implicated in the regulation of ocular neovascularization. This study investigated the specific role of microRNA-145 (miR-145) in regulating vascular endothelial cell (EC) function and pathological ocular angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). Expression of miR-145 was significantly upregulated in OIR mouse retinas compared with room air controls. Treatment with synthetic miR-145 inhibitors drastically decreased levels of pathological neovascularization in OIR, without substantially affecting normal developmental angiogenesis. In cultured human retinal ECs, treatment with miR-145 mimics significantly increased the EC angiogenic function, including proliferation, migration, and tubular formation, whereas miR-145 inhibitors attenuated in vitro angiogenesis. Tropomodulin3 (TMOD3), an actin-capping protein, is a direct miR-145 target and is downregulated in OIR retinas. Treatment with miR-145 mimic led to TMOD3 inhibition, altered actin cytoskeletal architecture, and elongation of ECs. Moreover, inhibition of TMOD3 promoted EC angiogenic function and pathological neovascularization in OIR and abolished the vascular effects of miR-145 inhibitors in vitro and in vivo. Overall, our findings indicate that miR-145 is a novel regulator of TMOD3-dependent cytoskeletal architecture and pathological angiogenesis and a potential target for development of treatments for neovascular eye disorders.
Werner A, Shen L. A Review of OCT Angiography in Glaucoma. Semin Ophthalmol. 2019;:1–8.
There is growing evidence that vascular dysfunction plays a role in the pathogenesis of glaucoma. The details of this relationship have remained elusive partially due to limitations in our ability to assess blood flow in the optic nerve. Optical coherence tomography angiography (OCTA) has emerged as a promising new technology well positioned to become the first clinically suitable test of optic nerve perfusion. OCTA uses the motion of red blood cells as an intrinsic contrast agent to create reproducible images of microvascular networks rapidly and non-invasively. A significant body of research regarding the use of OCTA in glaucoma has emerged in recent years. This review aims to provide an overview of the basic principles underlying OCTA technology, summarize the current literature regarding the application of OCTA in the management of glaucoma, and address the role of OCTA in explicating the vascular pathogenesis of glaucoma.
Siddiqui Y, Yin J. Anterior Segment Applications of Optical Coherence Tomography Angiography. Semin Ophthalmol. 2019;:1–6.
: To review the current literature regarding optical coherence tomography angiography (OCT-A) applications in the anterior segment. : A literature search was performed for terms including OCT-Angiography, anterior segment, cornea, conjunctiva, iris, applications and use in ophthalmology. : Fifteen studies were identified, 14 in human subjects. Studies with OCT-A of the conjunctiva, episclera, cornea, and iris were identified, some with normal eyes imaged and others with various pathologies. Most of these studies imaged corneal neovascularization. Three studies described protocols used for image acquisition, one of which was referenced by two later papers. : OCT-A is a noninvasive technology with recent applications in the anterior segment. Several pilot studies have been performed on various anterior segment structures and disease states however standardization of image acquisition techniques is still needed. Future imaging could allow noninvasive and serial monitoring of pathology as well as recurrence after therapeutic intervention.
Aronow M, Wiley H, Gaudric A, Krivosic V, Gorin M, Shields C, Shields J, Jonasch E, Singh A, Chew E. VON HIPPEL-LINDAU DISEASE: Update on Pathogenesis and Systemic Aspects. Retina. 2019;39(12):2243–2253.
PURPOSE: To provide an update summarizing the biologic pathways governing von Hippel-Lindau (VHL) disease pathogenesis and to provide an overview of systemic manifestations as well as screening recommendations. METHODS: A PubMed search of the English language literature was reviewed using the following search terms: von Hippel-Lindau, von Hippel-Lindau disease, and VHL. Of 6,696 publications, the most current and pertinent information related to the pathogenesis and systemic aspects of VHL disease were included in this review. RESULTS: von Hippel-Lindau disease is one of the most frequently occurring multisystem familial cancer syndromes. The disease results from germline mutation in the VHL tumor suppressor gene on the short arm of chromosome 3. Mutation in the VHL gene affects multiple cellular processes including transcriptional regulation, extracellular matrix formation, apoptosis, and, in particular, the cellular adaptive response to hypoxia. As a result, there is widespread development of vascular tumors affecting the retina, brain, and spine, as well as a spectrum of benign and malignant tumors and/or cysts in visceral organs. CONCLUSION: The ophthalmologist plays a key role in VHL disease diagnosis, as retinal hemangioblastoma is frequently the first disease manifestation. Screening guidelines for individuals with known VHL disease, and those at risk of VHL disease, help to ensure early detection of potentially vision-threatening and life-threatening disease.
Bagdonaite-Bejarano L, Hansen R, Fulton A. Microperimetry in Three Inherited Retinal Disorders. Semin Ophthalmol. 2019;:1–6.
Microperimetry (MP) is used to assess visual sensitivity mediated by the central retina. As such, MP performance is a candidate outcome measure for gene therapy trials. Herein, we review MP results in three inherited retinal disorders for which gene therapy trials have been initiated-choroideremia, Stargardt disease, and X-linked juvenile retinoschisis. Each of these disorders typically presents in childhood and each has distinct effects on the central retina. Our review indicates that microperimetry is feasible in each of these conditions. The MP sensitivity maps vary among conditions consistent with known effects of each of the three conditions. There is, however, within each of the three disorders considerable variability in fixation stability and in the pattern of sensitivity loss. Microperimetry is a valuable tool for monitoring functional aspects of central retina in an individual patient, especially in combination with other modalities such as OCT, autofluorescence, and acuity and thus may contribute to evaluating the efficacy of gene treatments. Variability of the MP parameters raises some cautions in application of MP as an outcome measure in treatment trials that may have small sample sizes. Nonetheless, we suspect that MP will continue to have a rightful place in future gene therapy trials.