Corneal neovascularization.

The optical clarity of the cornea is essential for maintaining good visual acuity. Corneal neovascularization, which is a major cause of vision loss worldwide, leads to corneal opacification and often contributes to a cycle of chronic inflammation. While numerous factors prevent angiogenesis within the cornea, infection, inflammation, hypoxia, trauma, corneal degeneration, and corneal transplantation can all disrupt these homeostatic safeguards to promote neovascularization. Here, we summarize its etiopathogenesis and discuss the molecular biology of angiogenesis within the cornea. We then review the clinical assessment and diagnostic evaluation of corneal neovascularization. Finally, we describe current and emerging therapies.

Computational Biomechanical Analysis of Asymmetric Ectasia Risk in Unilateral Post-LASIK Ectasia.

PURPOSE: To develop a computational approach to corneal biomechanical risk analysis in refractive surgery and to investigate its utility in an enigmatic case of unilateral ectasia after bilateral LASIK. METHODS: Preoperative corneal elevation datasets from both eyes of a patient who developed unilateral post-LASIK ectasia were used to construct geometrically patient-specific, microstructurally motivated finite element models. Models were assessed before and after implementation of case-specific treatment parameters for interocular differences in corneal geometry and strain behavior under physiological loading conditions. RESULTS: Standard clinical predictors of post-LASIK ectasia risk were similar for the affected and contralateral eyes, and no risk factor asymmetry was identified in tomographic screening that included posterior corneal elevation analysis. However, differences in the magnitude and distribution of strain and stress were observed that are consistent with greater predisposition to biomechanical instability in the affected eye. Load testing with simulated intraocular pressure increases provoked opposite trends in curvature change in the preoperative models representing affected and unaffected eyes, with steepening in the ectatic eye and flattening in the clinically stable eye. CONCLUSIONS: Patient-specific computational analyses revealed differences in intrinsic biomechanical behaviors that may predispose a cornea to instability after refractive surgery. Strain and stress analyses elucidated differential risk not ascertained with current refractive surgery screening paradigms. This pilot study illustrates a risk analysis approach that implicitly considers the entire corneal three-dimensional geometry and can be performed a priori in a screening setting. [J Refract Surg. 2016;32(12):811-820.].

Advances in Refractive Surgery: May 2013 to June 2014.

PURPOSE: The field of refractive surgery is changing quickly in the areas of screening, treatment, and postoperative management. The objective of this study was to review advances in the field of refractive surgery as reported in the peer-reviewed literature during the previous year. DESIGN: This was a literature review. METHODS: In this article, we highlight the progression in the field from May 2013 to the end of June 2014. This article is organized as preoperative, intraoperative, and postoperative considerations. RESULTS: The growing use of newer modalities of treatment, such as small-incision lenticule extraction (SmILE) and phakic intraocular lenses, and their safety and efficacy add to the armamentarium in treating refractive error. This past year has seen many studies, which show these procedures to be safe and effective. Also, structurally, SmILE may result in a more biomechanically stable cornea, so that we may be able to safely treat higher refractive errors. CONCLUSIONS: While laser-assisted in situ keratomileusis is the predominant surgical procedure, photorefractive keratectomy is still an appropriate choice in certain scenarios (higher risk for ectasia postrefractive surgery and patient choice) with safe, predictable results, and patient satisfaction. Many of the new developments in laser-assisted in situ keratomileusis have focused on flap creation with femtosecond lasers. Histopathology and in vivo optical coherence tomography studies have shown that the stromal bed is smoother, the side cuts are vertical, and the flap has predictable thickness. New surgical modalities, such as femtosecond lenticule extraction and SmILE, are increasingly being used.

Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities.

PURPOSE: Photoreceptor neuronal degenerations are common, incurable causes of human blindness affecting 1 in 2000 patients worldwide. Only half of all patients are associated with known mutations in over 250 disease genes, prompting our research program to identify the remaining new genes. Most retinal degenerations are restricted to the retina, but photoreceptor degenerations can also be found in a wide variety of systemic diseases. We identified an X-linked family from Sri Lanka with a severe choroidal degeneration and postulated a new disease entity. Because of phenotypic overlaps with Bietti's crystalline dystrophy, which was recently found to have systemic features, we hypothesized that a systemic disease may be present in this new disease as well. METHODS: For phenotyping, we performed detailed eye exams with in vivo retinal imaging by optical coherence tomography. For genotyping, we performed whole exome sequencing, followed by Sanger sequencing confirmations and cosegregation. Systemic investigations included electron microscopy studies of peripheral blood cells in patients and in normal controls and detailed fatty acid profiles (both plasma and red blood cell [RBC] membranes). Fatty acid levels were compared to normal controls, and only values two standard deviations above or below normal controls were further evaluated. RESULTS: The family segregated a REP1 mutation, suggesting choroideremia (CHM). We then found crystals in peripheral blood lymphocytes and discovered significant plasma fatty acid abnormalities and RBC membrane abnormalities (i.e., elevated plasmalogens). To replicate our discoveries, we expanded the cohort to nine CHM patients, genotyped them for REP1 mutations, and found the same abnormalities (crystals and fatty acid abnormalities) in all patients. CONCLUSIONS: Previously, CHM was thought to be restricted to the retina. We show, to our knowledge for the first time, that CHM is a systemic condition with prominent crystals in lymphocytes and significant fatty acid abnormalities.

A Review of Secondary Photoreceptor Degenerations in Systemic Disease.

Photoreceptor neuronal degenerations are common and incurable causes of human blindness with one in 2000 affected. Approximately, half of all patients are associated with known mutations in more than 200 disease genes. Most retinal degenerations are restricted to the retina (primary retinal degeneration) but photoreceptor degeneration can also be found in a wide variety of systemic and syndromic diseases. These are called secondary retinal degenerations. We review several well-known systemic diseases with retinal degenerations (RD). We discuss RD with hearing loss, RD with brain disease, and RD with musculoskeletal disease. We then postulate which retinal degenerations may also have previously undetected systemic features. Emerging new and exciting evidence is showing that ubiquitously expressed genes associated with multitissue syndromic disorders may also harbor mutations that cause isolated primary retinal degeneration. Examples are RPGR, CEP290, CLN3, MFSD5, and HK1 mutations that cause a wide variety of primary retinal degenerations with intact systems.

Systematically assessing the situational relevance of electronic knowledge resources: a mixed methods study.

UNLABELLED: Electronic Knowledge Resources (EKRs) are increasingly used by physicians, but their situational relevance has not been systematically examined. OBJECTIVE: Systematically scrutinize the situational relevance of EKR-derived information items in and outside clinical settings. BACKGROUND: Physicians use EKRs to accomplish four cognitive objectives (C1-4), and three organizational objectives (O1-3): (C1) Answer questions/solve problems/support decision-making in a clinical context; (C2) fulfill educational-research objectives; (C3) search for personal interest or curiosity; (C4) overcome limits of human memory; (O1) share information with patients, families, or caregivers; (O2) exchange information with other health professionals; (O3) plan-manage-monitor tasks with other health professionals. METHODS: Longitudinal mixed methods multiple case study: Cases were 17 residents' critical searches for information, using a commercial EKR, during a 2-month block of family practice. Usage data were automatically recorded. Each "opened" item of information was linked to an impact assessment questionnaire, and 1,981 evaluations of items were documented. Interviews with residents were guided by log files, which tracked use and impact of EKR-derived information items. Thematic analysis identified 156 critical searches linked to 877 information items. For each case, qualitative data were assigned to one of the seven proposed objectives. RESULTS: Residents achieved their search objectives in 85.9% of cases (situational relevance). Additional sources of information were sought in 52.6% of cases. Results support the seven proposed objectives, levels of comparative relevance (less, equally, more), and levels of stimulation of learning and knowledge (individual, organizational). CONCLUSION: Our method of systematic assessment may contribute to user-based evaluation of EKRs.