Vertebrate Animal Models of RP59: Current Status and Future Prospects.

Retinitis pigmentosa-59 (RP59) is a rare, recessive form of RP, caused by mutations in the gene encoding DHDDS (dehydrodolichyl diphosphate synthase). DHDDS forms a heterotetrameric complex with Nogo-B receptor (NgBR; gene NUS1) to form a cis-prenyltransferase (CPT) enzyme complex, which is required for the synthesis of dolichol, which in turn is required for protein N-glycosylation as well as other glycosylation reactions in eukaryotic cells. Herein, we review the published phenotypic characteristics of RP59 models extant, with an emphasis on their ocular phenotypes, based primarily upon knock-in of known RP59-associated DHDDS mutations as well as cell type- and tissue-specific knockout of DHDDS alleles in mice. We also briefly review findings in RP59 patients with retinal disease and other patients with DHDDS mutations causing epilepsy and other neurologic disease. We discuss these findings in the context of addressing "knowledge gaps" in our current understanding of the underlying pathobiology mechanism of RP59, as well as their potential utility for developing therapeutic interventions to block the onset or to dampen the severity or progression of RP59.

Second primary malignancies of eye and ocular adnexa after a first primary elsewhere in the body.

PURPOSE: The eye and its adnexal structures can give rise to first or consecutive primary malignancies or to encounter metastasis. Our aim was to define the characteristics of the second primary neoplasms affecting the eye and its adnexa and find the risk modifying factors for them after malignancies elsewhere in the body. METHODS: We have queried the Surveillance, Epidemiology and End-Results "SEER"-9 program of the National Cancer Institute for the malignancies of the eye and its adnexa that occurred between 1973 and 2015. The malignancies were ordered chronologically according to their incidence: first or second primary malignancies. The tumors were classified according to ICD-O-3 classification. Standardized incidence ratios (SIR) and survival probabilities were calculated for subgroups. RESULTS: Among 3,578,950 cancer patients, 1203 experienced a second malignancies of the eye and its adnexa. The first malignancy was diagnosed between 50 and 69 years of age in 58.94% of them. The eyelid showed 280 events, while 50 in lacrimal gland, 181 in the orbit, 21 in the overlapping lesions, 15 in optic nerve, 148 in the conjunctiva, 9 in the cornea, 6 in the Retina, 379 in the choroid, and 93 in the ciliary body. The SIR of a second malignancy after a prior non-Hodgkin lymphoma was 2.42, and in case of previous skin carcinomas it was 3.02, melanoma of skin, and 2.13 and 1.58 in oral cavity/pharynx malignancies. The second ocular and adnexal neoplasms increased steadily over the 5-year periods on contrary to first primary neoplasms. The survival of patients affected with first ocular and adnexal neoplasms was significantly higher than those with second ocular and adnexal neoplasms. On the other side, second primary ocular and adnexal tumors showed a better survival than second primary malignancies elsewhere. CONCLUSIONS: The epidemiological differences between first and second ocular and adnexal primaries suggest different underlying mechanisms. Careful ocular examination should be integrated in the long-term follow-up plan of cancer patients. Special attention should be given to patients with non-Hodgkin's lymphoma and melanoma as first primary.

Combined corneal cross-linking and 320° intrastromal corneal ring segments in progressive keratoconus: one-year results.

BACKGROUND: Intrastromal corneal ring segments (ICRS) attain regularization of corneal surface in keratoconus (KC), while collagen cross-linking (CXL) halts or slows its progression. The long-arc 320° rings combined with CXL may have a dual-benefit synergistic effect of surface regularity and progression halt. METHODS: This was a prospective case series study including eyes with progressive KC. Femto-assisted 320° ICRS implantation and epi-off CXL 8 weeks later were carried out in all cases. Uncorrected (UCVA) and corrected distance visual acuity (CDVA) were assessed using Snellen's chart, while corneal tomography was evaluated using Scheimpflug imaging. Follow-up was carried out 3, 6, and 12 months after the CXL. RESULTS: Thirty-two eyes of 32 patients with progressive KC were included, 18 males and 14 females, and the mean age was 23.1 years. According to the Amsler-Krumeich classification, four eyes had stage 1 KC, 20 had stage 2 KC, and eight had stage 3 KC, and UCVA and CDVA improved from 0.1 ± 0.15 and 0.2 ± 0.19 to 0.4 ± 0.2 (P>  0.01) and 0.5 ± 0.2 (P>  0.01) respectively at 12 months. Manifest refraction spherical equivalent was reduced from - 5.6 ± 2.3 to - 1.1 ± 1.3 D at 12 months after the procedure (P>  0.01). In addition, maximum keratometry was significantly reduced from 54.8 to 49.3 diopters (P>  0.01), while the asphericity index (Q value) has changed from - 1.4 to - 0.25 (P>  0.01) after 12 months. No significant differences were detected between central (n = 12) and eccentric (n = 20) KC in all outcomes. CONCLUSION: The 320° ICRS-CXL protocol has improved the visual and the tomographic outcomes at 1 year in our patients with progressive KC. No differences were detected between central and eccentric cases. Further larger studies could ensure the safety profile of the combined protocol.

Corneal biomechanics and intraocular pressure assessment after penetrating keratoplasty for non keratoconic patients, long term results.

BACKGROUND: To evaluate corneal biomechanical properties by the Ocular Response Analyzer (ORA) in non keratoconic patients underwent penetrating keratoplasty (PK). METHODS: Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann- correlated intraocular pressure (IOPg), cornea-compensated IOP (IOPcc) using the ORA, and central graft thickness (CGT) were measured in 30 eyes at least two years after penetrating keratoplasty for non keratoconic indications. IOP using the Goldmann applanation tonometer (GAT) was also obtained after compensation for graft thickness and astigmatism. RESULTS: The mean age of patients was 33.1 ± 10.13 years; indications for PK were herpetic corneal scar (53.3%), corneal stromal dystrophy (23.3%), traumatic corneal opacity (10%), chemical corneal opacity (6.7%), and Fuchs endothelial dystrophy (6.7%). Mean CH and CRF were 8.52 ± 1.81 mmHg, and 8.56 ± 1.59 mmHg, respectively. Mean CGT was 532.43 ± 30 µm. Mean IOP GAT, IOPg, and IOPcc were 11.88 ± 3.66, 14.64 ± 4.08, and 17.27 ± 4.60 mmHg, respectively (P < 0.001). No significant association was found between CGT and IOP readings obtained using either the ORA or GAT. There were significant negative association between CH with both IOP GAT and IOPcc, while CRF had significant positive association with IOPg. CONCLUSION: After penetrating keratoplasty for non keratoconic patients, graft biomechanics does not return to average values even 2 years after the operation; moreover, intraocular pressure measurement with ORA gives higher values than thickness compensated GAT.

Family Medicine in Egypt From Medical Students' Perspective: A Nationwide Survey.

UNLABELLED: PHENOMENON: Attitudes of medical students toward family medicine as a specialty choice can provide information on the future supply of family physicians. Due to the current worldwide shortage of family physicians, these attitudes, with their subsequent effects on the state and dynamics of the healthcare system, are important to investigate. APPROACH: A web-based questionnaire was sent to 600 medical students, selected by a systematic random sampling technique, in 7 Egyptian medical schools. Participants were surveyed to assess their perception of the family medicine specialty as a future career and explore the impact of different factors, including undergraduate family medicine clerkships, on their attitudes toward family medicine. FINDINGS: We had a response rate of 75.2% (n = 451). Although 90.7% of students believed in the vital role that family medicine can play in Egypt's healthcare system, only 4.7% showed an intention to choose it as a future career. Students choosing family medicine as a first-career choice were more likely to have a prior contact with family physicians as consumers. Exposure to an undergraduate family medicine curriculum was associated with increased knowledge about family medicine but not the intentions to pursue it as a career. INSIGHTS: Medical students in Egypt have a positive perception of family medicine as an important specialty but low interest in its choice as a future career.

Evaluation of the external validity of a joint structure-function model for monitoring glaucoma progression.

The dynamic structure-function (DSF) model was previously shown to have better prediction accuracy than ordinary least square linear regression (OLSLR) for short series of visits. The current study assessed the external validity of the DSF model by testing its performance in an independent dataset (Ocular Hypertension Treatment Study-Confocal Scanning Laser Ophthalmoscopy [OHTS-CSLO] ancillary study; N = 178 eyes), and also on different test parameters in a sample selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study (DIGS/ADAGES). Each model was used to predict structure-function paired data at visits 4-7. The resulting prediction errors for both models were compared using the Wilcoxon signed-rank test. In the independent dataset, the DSF model predicted rim area and mean sensitivity paired measurements more accurately than OLSLR by 1.8-5.5% (p ≤ 0.004) from visits 4-6. Using the DIGS/ADAGES dataset, the DSF model predicted retinal nerve fiber layer thickness and mean deviation paired measurements more accurately than OLSLR by 1.2-2.5% (p ≤ 0. 007). These results demonstrate the external validity of the DSF model and provide a strong basis to develop it into a useful clinical tool.

Evaluation of a Tangential Map-Based Nomogram for Intrastromal Corneal Ring Segments' Implantation in Keratoconus: One Year Results.

PURPOSE: To evaluate a new tangential map-based nomogram versus the axial map-based nomogram for ICRS in keratoconus. METHODS: A prospective case series study including 64 eyes of 64 patients who underwent ICRS implantation. Cone location was determined for each eye with two maps: the axial and the tangential. Appropriate ring selection was determined using two surgical nomograms: axial map-based and tangential map-based. Visual, refractive, and topographic outcomes were assessed before, as well as at 3, 6, and 12 months after ICRS implantation. RESULTS: The cone location, and consequently the ring selection, was significantly different in the two nomograms with a "centralization tendency" in the tangential map. In the axial group, UDVA and CDVA improved from 0.12 ± 0.04 and 0.24 ± 0.08 to 0.28 ± 0.08 and 0.4 ± 0.1, respectively. Similarly, MRSE substantially decreased from -6.7 ± 3.3 to -1.2 ± 1.1D at 12 months after the procedure. In the tangential group, UDVA and CDVA improved from 0.09 ± 0.06 and 0.2 ± 0.1 to 0.5 ± 0.2 and 0.7 ± 0.2, respectively. MRSE substantially decreased from -4.9 ± 1D at 12 months after the procedure. In the tangential group, UDVA and CDVA improved from 0.09 ± 0.06 and 0.2 ± 0.1 to 0.5 ± 0.2 and 0.7 ± 0.2, respectively. MRSE substantially decreased from -4.9 ± 1D at 12 months after the procedure. In the tangential group, UDVA and CDVA improved from 0.09 ± 0.06 and 0.2 ± 0.1 to 0.5 ± 0.2 and 0.7 ± 0.2, respectively. MRSE substantially decreased from -4.9 ± 1P=0.01 ∗ . Similarly, the gain in the CDVA was 0.4 and 0.15 in the tangential and axial groups, respectively, at 12 months, P=0.01 ∗ . Similarly, the gain in the CDVA was 0.4 and 0.15 in the tangential and axial groups, respectively, at 12 months. CONCLUSION: The tangential map-based nomogram attained better visual and refractive outcomes at 1 year. In addition, the cone location was significantly different between both maps with a centralization tendency in the tangential one.

Difluprednate versus Prednisolone Acetate after Cataract Surgery: a Systematic Review and Meta-Analysis.

OBJECTIVE: Topical steroids are the cornerstone in controlling the inflammation after cataract surgery. Prednisolone acetate and difluprednate are the two main products for this purpose. However, it is unclear which one should be used in terms of effectiveness and safety. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline via PubMed, Cochrane Central Register of Controlled Trials, Web of science and clinicaltrials.gov were searched through 10 January 2018, and updated on 20 July 2019, in addition to researching the references' lists of the relevant articles. ELIGIBILITY CRITERIA: Randomised-controlled trials (RCTs) comparing difluprednate and prednisolone acetate regardless of the dosing regimen used. DATA EXTRACTION AND SYNTHESIS: Two independent authors assessed the included RCTs regarding the risk of bias using the Cochrane tool. Relevant data were extracted, and meta-analysis was conducted using a random-effects model. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to appraise the evidence quality. RESULTS: We included six RCTs with 883 patients: 441 received difluprednate and 442 received prednisolone acetate. The evidence quality was graded as moderate for corneal oedema and intraocular pressure and low for anterior chamber (AC) clearance. After small incision cataract surgery, difluprednate was superior in clearing AC cells at 1 week (OR=2.5, p>0.00001) and at 2 weeks (OR=2.5, p=0.04), as well as clearing the AC flare at 2 weeks (OR=6.7, p=0.04). After phacoemulsification, difluprednate was superior in terms of corneal clarity at 1 day (OR=2.6, p=0.02) and 1 week after surgery (OR=1.96, p=0.0007). No statistically significant difference was detected between both agents at 1 month in effectiveness. Also, both agents were safe, evaluated by the ocular hypertension (OR=1.23, p=0.8). CONCLUSION: With low-to-moderate certainty, difluprednate and prednisolone acetate are safe agents for controlling the inflammation after cataract surgery. Difluprednate showed significant superiority in terms of AC cells and AC flare at 2 weeks postoperatively.

Ebola virus disease: Essential clinical knowledge.

Since its initial outbreak in 1976, Ebola virus disease (EVD) has affected thousands of people, causing severe illness with high mortality rates. In the absence of a vaccine or effective specific treatment, as well as the lack of early diagnostic and detective methods, the EVD outbreak has generated a significant worldwide health concern. Insufficient health-care system resources, deficient infection control measures, and the shortage of appropriate personal protective equipment acted as amplifiers of the outbreak extension, especially in poorly resourced and unprepared communities. Operating on the frontlines, health-care workers must be familiar, not only with the identification of the disease, but also with the ability to protect themselves and initiate the appropriate response. This review seeks to provide essential information required to identify and manage the disease, with an emphasis on pathogenesis, transmission, diagnosis, treatment, and prevention. We conducted a literature search in MEDLINE/PubMed and Google Scholar using the following keywords: "Ebola, Ebola virus disease, Hemorrhagic Fever, Outbreak." We included all types of publications. To augment our study, we searched the reference lists of identified reviews.