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Purpose: This work assesses bilateral ganglion cell layer-inner plexiform layer (GCL-IPL) thickness changes in patients with unilateral neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti-VEGF)., Methods: In this single-center, retrospective, cohort study, the medical records of patients with unilateral nAMD treated with anti-VEGF were reviewed. The treated group included eyes with newly diagnosed nAMD that subsequently underwent treatment with intravitreal anti-VEGF injections. The control group was the fellow eye with dry AMD. Eyes receiving at least 10 intravitreal injections were included. Measurement of GCL-IPL thickness was performed at different time points using spectral domain-optical coherence tomography., Results: A total of 216 eyes of 108 patients met the inclusion criteria. The mean age ± SD was 80.1 ± 10.7 years. Eyes in the treated group underwent a mean ± SD of 20.2 ± 7.2 injections in 21.3 ± 6.8 months. At baseline, average mean ± SD of GCL-IPL thickness was 73.71 ± 8.81 µm and 73.84 ± 8.26 µm in the treated and fellow eye, respectively ( P = .795). After 10 injections the average thickness was 65.41 ± 14.08 µm and 68.77 ± 13.24 µm in the treated and fellow eye, respectively ( P = .007). The absolute decrease in thickness was significantly greater in the treated eye than the fellow eye (mean ± SD, 8.31 ± 11.19 µm vs 5.07 ± 10.83 µm, respectively; P = .002)., Conclusions: GCL-IPL thickness decreased significantly in the treated group more than in the control group after 10 anti-VEGF injections. The mechanism and clinical significance of this observation warrants further study., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose: To evaluate the efficacy of intravitreal aflibercept as a second-line therapy in eyes with persistent diabetic macular oedema (DMO) despite receiving initial bevacizumab treatment., Methods: A prospective multicentre study was conducted in nine academic clinics in Israel. Starting from the first follow-up visit, a treat-and-extend regimen was applied in which the treatment intervals were extended by 2 weeks based on macular thickness using SD-OCT. The primary outcome was central subfield thickness (CST) at week 52., Results: Forty-four patients (n = 48 eyes) were recruited to the study, and 43 eyes completed 52 weeks of follow-up. Patients received a mean (±SD) of 7.9 ± 3.5 bevacizumab injections before enrolment. The mean (±SD) CST under aflibercept therapy decreased from 468 ± 131 μm at baseline to 303 ± 67 μm at 52 weeks (p = 0.002), and best corrected visual acuity improved from 64 ± 15 ETDRS letters at baseline to 75 ± 8 letters at week 52 (p = 0.001). Twenty (46%) eyes met the treat-and-extend criteria and received a mean (±SD) of 10.9 ± 2 aflibercept injections., Conclusions: Eyes with persistent DMO following initial bevacizumab therapy had a marked reduction in macular thickness and improved visual acuity following 1 year of treatment with intravitreal aflibercept. Less than half of the patients met eligibility criteria for extension of the treatment interval; for these patients, the treat-and-extend regimen resulted in a maximum treatment interval of 10 weeks during the first year.

Purpose: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES)., Methods: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H ( CFH ) p.Y402H; and age related maculopathy susceptibility 2 (ARMS2) p.A69S; and rare variants complement factor-I ( CFI) p.V412M; and hemicentin1 (HMCN1) c.4163delC identified previously in our population. Four families, whose initial screening for the aforementioned variants was negative, underwent WES (phase-2). Bioinformatics filtering was based on functionality (from a panel of 234 genes with proven or presumed association to AMD); predicted severity; and frequency (rare variants with minor allele frequency <1%). When applicable, further screening for specific rare variants was carried out on additional cases of similar ethnicities and phenotypes (phase-3)., Results: Phase-1 identified three families carrying CFI p.V412M mutation. WES analysis detected probable disease-related variants in three out of the remaining families. These included: a family with a variant in PLEKHA1 gene p.S177N; a family with previously reported variant p.R1210C in CFH gene; and two families with the C3 p.R735W variant., Conclusions: Rare, high-penetrance variants have a profound contribution to early-AMD pathogenesis. Utilization of WES in genetic research of multifactorial diseases as AMD, allows a thorough comprehensive analysis with the identification of previously unreported rare variants., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Purpose: To determine the characteristics of ocular injuries treated by Israel Defense Forces (IDF) field hospital following three natural disasters: the 2010 earthquake in Haiti, the 2013 typhoon in the Philippines, and the 2015 earthquake and avalanche in Nepal. The purpose was to provide data, which would assist allocation of ocular resources for future disasters., Design: Retrospective database study., Methods: Ocular clinical data collected from the IDF database. Time postdisaster was divided into three periods: 4-8, 9-12, and 13-16 days. Diagnoses were categorized as disaster-related (DRD), defined as directly resulting from the disaster (mostly ocular trauma), and nondisaster-related (NDRD), defined as preexisting conditions or results of postevent living conditions problems., Results: The field hospitals began functioning 3-8 days after the disaster and continued for 10.3 ± 1.5 days. Ocular conditions were treated in 265 (4.9%) of the total 5356 patients. Sixty-five cases were DRD and 200 were NDRD. Around day 9 postdisaster the predominant ocular referral changed from DRD to NDRD., Conclusions: Deployment of a field hospital to a natural disaster area should take into account the type and geographic location of the disaster as well as the high number of nontraumatic ocular conditions.

Israeli Air Force (IAF) pilots continue flying combat missions after the symptoms of natural near-vision deterioration, termed presbyopia, begin to be noticeable. Because modern pilots rely on the displays of the aircraft control and performance instruments, near visual acuity (VA) is essential in the cockpit. We aimed to apply a method previously shown to improve visual performance of presbyopes, and test whether presbyopic IAF pilots can overcome the limitation imposed by presbyopia. Participants were selected by the IAF aeromedical unit as having at least initial presbyopia and trained using a structured personalized perceptual learning method (GlassesOff application), based on detecting briefly presented low-contrast Gabor stimuli, under the conditions of spatial and temporal constraints, from a distance of 40 cm. Our results show that despite their initial visual advantage over age-matched peers, training resulted in robust improvements in various basic visual functions, including static and temporal VA, stereoacuity, spatial crowding, contrast sensitivity and contrast discrimination. Moreover, improvements generalized to higher-level tasks, such as sentence reading and aerial photography interpretation (specifically designed to reflect IAF pilots' expertise in analyzing noisy low-contrast input). In concert with earlier suggestions, gains in visual processing speed are plausible to account, at least partially, for the observed training-induced improvements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The tumor-suppressor gene p53 encodes a phosphoprotein involved in the control of cell growth. p53 expression and function have been documented in malignancy, apoptosis and the aging processes. Recently, p53 has been mapped and characterized in the normal cornea across different species. In the present study, high levels of cytoplasmic p53 protein were noted in normal primary corneal epithelium cultures by immunohistochemistry and western blot analysis. Following ultraviolet (UV) irradiation, the level of cytoplasmic p53 protein expression was increased beginning from 30 min and lasting until 6 h post-irradiation and then returned close to control levels by 24 h. Cytoplasmic p53 phosphorylation was detected from 30 min following UV treatment until 6 h post-irradiation. p53 protein became apparent in the nucleus in a fraction of these cultured cells beginning 30 min following UV irradiation and was still present 24 h later. We also found that p53 colocalized with mitochondria 2 h following UV irradiation in some of the cells and remained there up to 24 h. As the expression levels of p53 transcription following UV irradiation were not significantly altered, the increase in cytoplasmic p53 protein expression may be conditional only upon post-translational stabilization. We also observed that the apoptotic index increased following UV irradiation in the same time frame as the p53 nuclear transfer and was partially suppressed by pifithrin-α, which is a reversible inhibitor of p53-mediated apoptosis and p53-dependent gene transcription. The present study offers new evidence suggesting that cytoplasmic p53 in rodent corneal epithelium is functionally active.

Background: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease., Objectives: To describe the contemporary experience of splenic infarction., Methods: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003., Results: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic infarction brought a previously undiagnosed underlying disease to attention. Only half the subjects complained of localized left-sided abdominal pain, 36% had left-sided abdominal tenderness; 31% had no signs or symptoms localized to the splenic area, 36% had fever, 56% had leukocytosis and 71% had elevated lactate dehydrogenase levels. One splenectomy was performed and all patients survived to discharge. A post hoc analysis demonstrated that single infarcts were more likely to be associated with fever (20% vs. 63%, p < 0.05) and leukocytosis (75% vs. 33%, P = 0.06), Conclusions: The clinical presentation of splenic infarction in the modern era differs greatly from the classical teaching, regarding etiology, signs and symptoms. In patients with unexplained splenic infarction, investigation frequently uncovers a new underlying diagnosis.

Cytomegalovirus (CMV) colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-IgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment. We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients.

Purpose: The tumor-suppressor gene p53 encodes a phosphoprotein involved in the control of cell growth. Its expression and function have been documented in malignancy, apoptosis, and other abnormal cell proliferation processes. Recently, expression of p53 has been demonstrated in certain normal tissues, including whole eye. The purpose of the study was to map and to characterize expression of p53 in the normal murine eye., Methods: Eyes of adult C57BL/6 mice were enucleated after death by CO2 narcosis. Expression of p53 in frozen sections of whole cryoprotected eyes was mapped by indirect immunofluorescence microscopy using the anti-p53 monoclonal antibodies 248 and 421 and the polyclonal antibody FL-393. Additionally, eyes were freshly dissected to separate the various ocular tissues. In these ocular tissues, expression of p53 was quantitated with ELISA and Western blot analyses., Results: Strong expression of p53 was observed in various normal ocular tissues. The corneal and conjunctival epithelium exhibited very high cytoplasmic p53 protein levels. High nuclear p53 protein staining was seen in the lens epithelial cells of the central and pre-equatorial zones and in the lens fiber nuclear bow, situated posterior to the epithelial germinative zone. Cells of the actual lens germinative zone did not stain for p53 protein. Low levels of p53 protein were expressed in retinal tissue., Conclusions: High levels of p53 protein are found in various normal murine ocular tissues, especially the corneal and conjunctival structures and the lens epithelium. Each of these tissues demonstrate unique patterns of staining.