PURPOSE: To compare measurements of corneal epithelial thickness using optical coherence tomography (OCT) and very high-frequency digital ultrasound (VHFDU). METHODS: Retrospective analysis of 189 virgin corneas and 175 post-laser refractive surgery (LRS) corneas that had corneal epithelial thickness measurement with RTVue Fourier-domain OCT (Optovue, Inc., Fremont, CA) (tear film included) and Artemis VHFDU (ArcScan Inc., Morrison, CO) (tear film excluded). Averages were calculated for the central 2-mm diameter zone and for two further concentric annuli of 1.5- and 0.5-mm width, each divided into eight sectors. Agreement was analyzed by mean difference (OCT – VHFDU), 95% limits of agreement (LoA) (1.96 standard deviation of the difference), and Bland–Altman analysis. RESULTS: In virgin epithelium, mean central thickness was 53.4 ± 3.20 µ m (range: 46 to 62 µ m) with OCT and 54.1 ± 2.96 µ m (range: 48 to 61 µ m) with VHFDU; OCT measured thinnest in 70% with a mean difference of −0.71 µ m (95% LoA of ±3.94 µ m, P < .001). In post-LRS epithelium, mean central thickness was 57.9 ± 6.08 µ m (range: 42 to 77 µ m) with OCT and 60.5 ± 6.47 µ m (range: 42 to 79 µ m) with VHFDU; OCT measured thinnest in 88%, with a mean difference of −2.48 µ m (95% LoA of ±5.33 µ m, P < .001). A larger difference between methods was more common with thicker epithelium. CONCLUSIONS: Corneal epithelial thickness measurements using OCT were found to be slightly thinner than for VHFDU. In contrast to VHFDU, OCT measurement includes the tear film, so the true difference is probably approximately 4 µ m more than reported. The difference was greatest inferiorly and higher for post-LRS eyes and in thicker epithelium. [ J Refract Surg. 2015;31(7):438–445.]

Coenzyme Q10 (CoQ10) is a ubiquitous cofactor in the body, operating in the inner mitochondrial membrane, where it plays a vital role in the generation of adenosine triphosphate (ATP) through the electron transport chain (ETC). In addition to this, CoQ10 serves as an antioxidant, protecting the cell from oxidative stress by reactive oxygen species (ROS) as well as maintaining a proton (H⁺) gradient across lysosome membranes to facilitate the breakdown of cellular waste products. Through the process of ageing, the body becomes deficient in CoQ10, resulting in several systemic manifestations. On a cellular level, one of the consequences of CoQ10 deficiency is apoptosis, which can be visualised in tissues of the central nervous system (CNS). Diseases affecting the retina and brain such as age-related macular degeneration (AMD), glaucoma, Alzheimer’s disease (AD) and Parkinson’s disease (PD) have shown defects in cellular biochemical reactions attributed to reduced levels of CoQ10. Through further research into the pathogenesis of such conditions, the effects of CoQ10 deficiency can be counteracted through supplementation, early detection and intervention.

Considering the retina as an extension of the brain provides a platform from which to study diseases of the nervous system. Taking advantage of the clear optical media of the eye and ever-increasing resolution of modern imaging techniques, retinal morphology can now be visualized at a cellular level in vivo. This has provided a multitude of possible biomarkers and investigative surrogates that may be used to identify, monitor and study diseases until now limited to the brain. In many neurodegenerative conditions, early diagnosis is often very challenging due to the lack of tests with high sensitivity and specificity, but, once made, opens the door to patients accessing the correct treatment that can potentially improve functional outcomes. Using retinal biomarkers in vivo as an additional diagnostic tool may help overcome the need for invasive tests and histological specimens, and offers the opportunity to longitudinally monitor individuals over time. This review aims to summarise retinal biomarkers associated with a range of neurological conditions including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and prion diseases from a clinical perspective. By comparing their similarities and differences according to primary pathological processes, we hope to show how retinal correlates can aid clinical decisions, and accelerate the study of this rapidly developing area of research.

To measure and compare the interobserver reproducibility of manifest refraction according to a standardized protocol for normal preoperative patients in a refractive surgery practice. Private clinic, London, United Kingdom. Retrospective case series. This retrospective study comprised patients attending 2 preoperative refractions before laser vision correction. The first manifest refraction was performed by 1 of 7 optometrists and the second manifest refraction by 1 of 2 surgeons, all trained using a standard manifest refraction protocol. Spherocylindrical data were converted into power vectors for analysis. The dioptric power differences between observers were calculated and analyzed. One thousand nine hundred twenty-two consecutive eyes were stratified into a myopia group and a hyperopia group and then further stratified by each surgeon-optometrist combination. The mean surgeon-optometrist dioptric power difference was 0.21 diopter (D) (range 0.15 to 0.32 D). The mean difference in spherical equivalent refraction was 0.03 D, with 95% of all refractions within ±0.44 D for all optometrist-surgeon combinations. The severity of myopic or hyperopic ametropia did not affect the interobserver reproducibility of the manifest refraction. There was close agreement in refraction between surgeons and optometrists using a standard manifest refraction protocol of less than 0.25 D. This degree of interobserver repeatability is similar to that in intraobserver repeatability studies published to date and may represent the value of training and the use of a standard manifest refraction protocol between refraction observers in a refractive surgery practice involving co-management between surgeons and optometrists.

Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells) project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.

Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma.