Macular Neovascularization in a Case of Late-Onset Retinal Degeneration Treated with Aflibercept.

PURPOSE: To describe the outcomes from treatment of macular neovascularization (MNV) in a eye affected by Late Onset Retinal Degeneration (L-ORD). METHODS: A 72-year-old female patient presented with a history of decreased vision since several years. The patient was previously diagnosed with age-related macular degeneration and treated with anti-VEGFs. RESULTS: Clinical examination of the retina and ultra-widefield color fundus photographs showed extensive atrophy in both eyes. The left eye (OS) showed macular neovascularization (MNV) on fluorescein angiography (FA), subretinal fluid (SRF) on optical coherence tomography (OCT), and correspondent hemorrhages on the color fundus photography. Aflibercept anti-vascular endothelial factor treatment was used to treat the MNV in OS. CONCLUSION: We report a case of genetically confirmed L-ORD (heterozygous pathogenic mutation p.Ser163Arg in one C1QTN5 allele) with advanced degeneration of the retina complicated by MNV, which responded well to treatment with a single aflibercept injection.

Effect of statins on the age of onset of age-related macular degeneration.

BACKGROUND: This study evaluated the relationship between statin use and the age of onset of age-related macular degeneration (AMD). METHODS: Electronic Health Records from 52,840 patients evaluated at University of California Los Angeles (UCLA) Ophthalmology Clinics and 9,977 patients evaluated at University of California San Francisco (UCSF) Ophthalmology Clinics were screened. Survival analysis was performed using Cox proportional hazards regression models and visualized using Kaplan Meier survival curves, with the following covariates-sex, ethnicity, smoking history, fluoxetine use, obesity, diabetes mellitus, and hypertension. RESULTS: 5,498 of 52,840 patients at UCLA were diagnosed with AMD. Statin use was associated with a later AMD onset (HR = 0.8823, p < 0.0001), while female sex (HR = 1.0852, p= 00,035), obesity (HR = 1.4555, p < 0.0001), and fluoxetine (HR = 1.3797, p= 0.0003) were associated with an earlier AMD onset. Non-hispanic black (HR = 0.5687, p < 0.0001) and hispanic ethnicities (HR = 0.8269, p= 0.0028) were associated with a later AMD onset. When stratifying for ethnicity, statins, fluoxetine, sex, and obesity were significant only within non-hispanic white subjects. Statin use was significant among patients with dry AMD (HR = 0.8410, p= 0.0001) but not wet AMD (0.9188, p= 0.0351). In the replication cohort, 526 of 9,977 patients at UCSF had AMD. Associations between statins (HR = 0.7643, p= 0.0033), non-hispanic black ethnicity (HR = 0.5043, p= 0.0035), and obesity (HR = 1.9602, p < 0.0001) on AMD onset were confirmed. CONCLUSIONS: In both cohorts, statin use and non-hispanic black ethnicity are associated with a later AMD onset, while obesity with an earlier AMD onset.

Global metrics on ocular biometry: representative averages and standard deviations across ten countries from four continents.

BACKGROUND/OBJECTIVES: We provide global averages and standard deviations for ocular biometry-axial length (AL), corneal radius of curvature (CR), anterior chamber depth (ACD), lens thickness (LT), white to white (WTW), and central corneal thickness (CT). We hope a better understanding of normal and abnormal values will help clinicians gain further insight into their surgical outcomes, especially for off-target eyes. SUBJECTS/METHODS: We searched the MEDLINE database using keywords "axial length, corneal power, anterior chamber depth, lens thickness, white to white, and corneal thickness." We included studies that reported averages and standard deviations on eye biometry for at least 1300 eyes. Global weighted averages and standard deviations were calculated using the Cochrane method. RESULTS: Fourteen studies were included, originating from Asia (Japan, Singapore, Myanmar, Iran, South Korea, China), Europe (Germany, United Kingdom, Portugal), Australia, and North America (United States). Global ocular biometry metrics were: AL-23.49 mm ± 1.35 mm, CR-7.69 mm ± 0.28 mm, ACD-3.10 mm ± 0.47 mm, WTW-11.80 mm ± 0.42 mm, LT-4.37 mm ± 0.43 mm, and CT-544 µm ± 38 µm. Total eyes per value ranged from 19,538 to 90,814. CONCLUSIONS: We report global ocular biometry averages and standard deviations. No eyes were from studies in Africa or South America, highlighting the need to publish eye biometry data from these continents. We hope that promoting a deeper understanding of biometry values will help clinicians gain insight into surgical outcomes and drive innovations in lens calculations.

Netarsudil-Induced Corneal Flattening in a Child with Secondary Open-Angle Glaucoma.

We report a case of a child with secondary open-angle glaucoma who developed 6.5 diopters (D) of corneal flattening upon the addition of Rhopressa (0.02% netarsudil dimesylate solution) eye drops to a preexisting treatment regimen of timolol and latanoprost. This change in corneal power reversed after netarsudil, a rho-kinase inhibitor, was discontinued and replaced with Vyzulta (0.024% latanoprostene bunod ophthalmic solution). The 4-year-old female patient presented with bilateral secondary open-angle glaucoma from Paired Box 6 (PAX6)-related aniridia, aphakia, and persistent fetal vasculature. She was started on netarsudil to treat elevated intraocular pressure (IOP) in her right eye, which was not adequately controlled by latanoprost and timolol. Over 4 months, she developed 6.5D of corneal flattening in her right eye. Netarsudil was stopped and the corneal flattening reversed. There is evidence to support the ability of rho kinase inhibitors to increase the healing of the corneal endothelium in addition to their intended IOP-lowering effects. Rho kinase inhibitors may increase cell proliferation and adhesion within the corneal endothelium, hence decreasing apoptosis and promoting cell preservation. If there was an excess of cell proliferation; however, this might induce stromal cells to abnormally secrete enzymes or proteins, such as TGFß-induced proteins. This could result in corneal fibrosis, thereby flattening the cornea. Further investigation is required to explore this phenomenon and elucidate its mechanism of action. Corneal flattening may be considered as a potential side effect of the use of netarsudil, particularly in young pediatric patients.

Oocyte activation deficiency and assisted oocyte activation: mechanisms, obstacles and prospects for clinical application.

BACKGROUND: Oocyte activation deficiency (OAD) is attributed to the majority of cases underlying failure of ICSI cycles, the standard treatment for male factor infertility. Oocyte activation encompasses a series of concerted events, triggered by sperm-specific phospholipase C zeta (PLCζ), which elicits increases in free cytoplasmic calcium (Ca2+) in spatially and temporally specific oscillations. Defects in this specific pattern of Ca2+ release are directly attributable to most cases of OAD. Ca2+ release can be clinically mediated via assisted oocyte activation (AOA), a combination of mechanical, electrical and/or chemical stimuli which artificially promote an increase in the levels of intra-cytoplasmic Ca2+. However, concerns regarding safety and efficacy underlie potential risks that must be addressed before such methods can be safely widely used. OBJECTIVE AND RATIONALE: Recent advances in current AOA techniques warrant a review of the safety and efficacy of these practices, to determine the extent to which AOA may be implemented in the clinic. Importantly, the primary challenges to obtaining data on the safety and efficacy of AOA must be determined. Such questions require urgent attention before widespread clinical utilization of such protocols can be advocated. SEARCH METHODS: A literature review was performed using databases including PubMed, Web of Science, Medline, etc. using AOA, OAD, calcium ionophores, ICSI, PLCζ, oocyte activation, failed fertilization and fertilization failure as keywords. Relevant articles published until June 2019 were analysed and included in the review, with an emphasis on studies assessing large-scale efficacy and safety. OUTCOMES: Contradictory studies on the safety and efficacy of AOA do not yet allow for the establishment of AOA as standard practice in the clinic. Heterogeneity in study methodology, inconsistent sample inclusion criteria, non-standardized outcome assessments, restricted sample size and animal model limitations render AOA strictly experimental. The main scientific concern impeding AOA utilization in the clinic is the non-physiological method of Ca2+ release mediated by most AOA agents, coupled with a lack of holistic understanding regarding the physiological mechanism(s) underlying Ca2+ release at oocyte activation. LIMITATIONS REASONS FOR CAUTION: The number of studies with clinical relevance using AOA remains significantly low. A much wider range of studies examining outcomes using multiple AOA agents are required. WIDER IMPLICATIONS: In addition to addressing the five main challenges of studies assessing AOA safety and efficacy, more standardized, large-scale, multi-centre studies of AOA, as well as long-term follow-up studies of children born from AOA, would provide evidence for establishing AOA as a treatment for infertility. The delivery of an activating agent that can more accurately recapitulate physiological fertilization, such as recombinant PLCζ, is a promising prospect for the future of AOA. Further to PLCζ, many other avenues of physiological oocyte activation also require urgent investigation to assess other potential physiological avenues of AOA. STUDY FUNDING/COMPETING INTERESTS: D.G. was supported by Stanford University's Bing Overseas Study Program. J.K. was supported by a Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW), alongside a National Science, Technology, and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST). The authors have no competing interests to declare.

NUSAP1 promotes invasion and metastasis of prostate cancer.

We have previously identified nucleolar and spindle associated protein 1 (NUSAP1) as a prognostic biomarker in early stage prostate cancer. To better understand the role of NUSAP1 in prostate cancer progression, we tested the effects of increased and decreased NUSAP1 expression in cell lines, in vivo models, and patient samples. NUSAP1 promotes invasion, migration, and metastasis, possibly by modulating family with sequence similarity 101 member B (FAM101B), a transforming growth factor beta 1 (TGFß1) signaling effector involved in the epithelial to mesenchymal transition. Our findings provide insights into the importance of NUSAP1 in prostate cancer progression and provide a rationale for further study of NUSAP1 function, regulation, and clinical utility.