Effect of Low-Fat Dietary Modification on Incident Open-Angle Glaucoma.

PURPOSE: We tested whether dietary modification (DM) altered the risk for incident primary open-angle glaucoma (POAG). DESIGN: Secondary analysis of a randomized intervention trial. PARTICIPANTS: We linked Medicare claims data to 45 203 women in the Women's Health Initiative Dietary Modification Trial, of which 23 776 participants were enrolled in fee-for-service Medicare Part B and had physician claims. METHODS: Women were randomized to follow either DM (a low-fat diet, with increased vegetable, fruit, and grain intake) or their usual diet without modification. Nine thousand three hundred forty women were randomized to the DM intervention, whereas 13 877 women were randomized to the control group. Our analyses were based on an intention-to-treat design, with a follow-up to the end of continuous Medicare coverage, death, or the last claims date (12/31/2018), whichever occurred first. Primary open-angle glaucoma was defined as the first claim with the International Classification of Diseases, Ninth or Tenth Revision, codes. Dietary data were assessed using a food frequency questionnaire. MAIN OUTCOME MEASURES: We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of POAG. Subgroup analyses were performed with P values for interaction. RESULTS: After exclusion of women with Medicare-derived glaucoma before randomization, the final analysis included 23 217 women (mean age, 64.4 ± 5.8 years). Baseline characteristics were balanced between the intervention and control groups. Primary open-angle glaucoma incidence was 11.1 per 1000 woman-years (mean follow-up, 11.6 ± 7.4 years; mean DM duration, 5.2 ± 3.2 years). We found no overall benefit of DM in reducing incident POAG (HR, 1.04; 95% CI, 0.96-1.12). Race and participant age did not modify this relation (P = 0.08 and P = 0.24 for interaction, respectively). In further analysis of baseline nutrient and food intake stratified by quartile groups, risk of open-angle glaucoma (OAG) in DM participants in the lowest quartile group for percentage calories (kilocalories) from total fat (33.8 or lower) was increased (HR, 1.22; 95% CI, 1.05-1.41; P = 0.007 for interaction). CONCLUSIONS: Analysis suggests that DM in participants in the lowest quartile group for percentage calories from total fat at baseline increased the risk of incident OAG among women regardless of age or race. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Newer advances in medical management of glaucoma.

The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited.

Refractive Outcomes for Combined Phacoemulsification and Glaucoma Drainage Procedure.

INTRODUCTION: To evaluate the refractive outcome of combined cataract extraction and glaucoma drainage device (GDD) surgery. METHODS: Patients who had undergone combined phacoemulsification with GDD surgery [Baerveldt, Abbott Medical, Abbott Park (IL) or Ahmed valve, New World Medical, Rancho Cucamonga (CA)] between June 2009 and August 2017 were included in the study. The main outcome measure evaluated was whether or not spherical equivalent (SE) between ± 1D from target refraction was achieved at 3-6 months postoperatively. RESULTS: The final analysis included 42 eyes of 38 patients who underwent combined phacoemulsification and GDD surgery. A refractive outcome of spherical equivalent (SE) between ± 1D of the target refraction was achieved in 30 of 42 eyes (71.43%) at 3-6 months after surgery. Mean preoperative axial length (AL) of eyes with postoperative SE outside ± 1D from target (SD = 0.98, p = 0.003) was noted to be 25.37 ± 0.98 mm (longer mean AL) and that of eyes with SE between ± 1D (SD = 0.89, p = 0.000) was found to be 23.34 ± 0.89 mm (average mean AL). Twelve (29%) eyes were noted to have a mean 0.52D (SD = 0.49; range 0.02-1.49) of corneal astigmatism induced by combined surgery. Age, central corneal thickness, preoperative anterior chamber depth, and pre- and postoperative intraocular pressure did not significantly affect refractive outcomes. CONCLUSION: Refractive outcomes within 1.00D of the target refraction were achieved in most patients undergoing a combined surgical approach. Longer AL was a risk factor among patients with refractive change > 1.00D from target.

ISAR Consensus Guidelines on Add-Ons Treatment in In vitro Fertilization.

STUDY QUESTION: What are the good practices for the use of ADD-ON Treatments in IVF cycles in INDIA? WHAT IS ALREADY KNOWN: Add on treatments in IVF are procedures and technologies which are offered to patients in hope of improving the success rates. A lot of add on treatments exist; most of them have limited evidence and data for the Indian patient population is miniscule. These interventions may have limited effects, so it is imperative that any new technology that is offered is evaluated properly and has enough evidence to suggest that it is safe and effective. STUDY DESIGN SIZE DURATION: This is the report of a 2-day consensus meeting where two moderators were assigned to a group of experts to collate information on Add on treatments in IVF in INDIA. This meeting utilised surveys, available scientific evidence and personal laboratory experience into various presentations by experts on pre-decided specific topics. PARTICIPANTS/MATERIALS SETTING METHODS: Expert professionals from ISAR representing clinical and embryology fields. MAIN RESULTS AND THE ROLE OF CHANCE: The report is divided in various components including the health of the Offspring, the various ADD ons available to an ART center, consensus points for each technology & qualifications and trainings for embryologists, the report and recommendations of the expert panel reflect the discussion on each of the topics and try to lay down good practice points for labs to follow. LIMITATIONS REASONS FOR CAUTION: The recommendations are solely based on expert opinion. Future availability of data may warrant an update of the same. WIDER IMPLICATIONS OF THE FINDINGS: These guidelines can help labs across the country to standardise their ART services and improve clinical outcomes, it will also motivate clinics to collect data and report the use of Add ons to the national registry. STUDY FUNDING/COMPETING INTERESTS: The consensus meeting and writing of the paper was supported by funds from CooperSurgical India.

Intraocular Lens Implantation In The Ciliary Sulcus: Challenges And Risks.

PURPOSE: This article reviews the current literature on the risks and challenges associated with intraocular lens (IOL) implantation in the ciliary sulcus. RECENT FINDINGS: The development of IOLs designed specifically for placement in the ciliary sulcus continues to be an area of interest for the ophthalmic industry. Currently the one-piece PMMA (polymethylmethacrylate) lens or a three-piece IOL are the best available options for IOL placement in the ciliary sulcus space. Single piece acrylic (SPA) IOLs are not designed for sulcus placement and there is growing evidence of chronic complications related to their use in the ciliary sulcus. Many of these eyes ultimately require surgical intervention, including lens exchange. Endoscopic imaging and ultrasound biomicroscopy (UBM) have enabled a better understanding of ciliary sulcus anatomy and measurements in the living eye. SUMMARY: When the capsular bag is compromised, IOL placement in the ciliary sulcus is a reasonable option. In these circumstances, appropriate choice of IOL, knowledge of the sulcus anatomy, and correct technique can improve results and reduce postoperative complications.

Wireless, Web-Based Interactive Control of Optical Coherence Tomography with Mobile Devices.

PURPOSE: Optical coherence tomography (OCT) is widely used in ophthalmology clinics and has potential for more general medical settings and remote diagnostics. In anticipation of remote applications, we developed wireless interactive control of an OCT system using mobile devices. METHODS: A web-based user interface (WebUI) was developed to interact with a handheld OCT system. The WebUI consisted of key OCT displays and controls ported to a webpage using HTML and JavaScript. Client-server relationships were created between the WebUI and the OCT system computer. The WebUI was accessed on a cellular phone mounted to the handheld OCT probe to wirelessly control the OCT system. Twenty subjects were imaged using the WebUI to assess the system. System latency was measured using different connection types (wireless 802.11n only, wireless to remote virtual private network [VPN], and cellular). RESULTS: Using a cellular phone, the WebUI was successfully used to capture posterior eye OCT images in all subjects. Simultaneous interactivity by a remote user on a laptop was also demonstrated. On average, use of the WebUI added only 58, 95, and 170 ms to the system latency using wireless only, wireless to VPN, and cellular connections, respectively. Qualitatively, operator usage was not affected. CONCLUSIONS: Using a WebUI, we demonstrated wireless and remote control of an OCT system with mobile devices. TRANSLATIONAL RELEVANCE: The web and open source software tools used in this project make it possible for any mobile device to potentially control an OCT system through a WebUI. This platform can be a basis for remote, teleophthalmology applications using OCT.

Efficacy of iron-supplement bars to reduce anemia in urban Indian women: a cluster-randomized controlled trial.

Background: India's high prevalence of iron-deficiency anemia has largely been attributed to the local diet consisting of nonheme iron, which has lower absorption than that of heme iron.Objective: We assessed the efficacy of the consumption of iron-supplement bars in raising hemoglobin concentrations and hematocrit percentages in anemic (hemoglobin concentration <12 g/dL) Indian women of reproductive age.Design: The Let's be Well Red study was a 90-d, pair-matched, cluster-randomized controlled trial. A total of 361 nonpregnant women (age 18-35 y) were recruited from 10 sites within Mumbai and Navi Mumbai, India. All participants received anemia education and a complete blood count (CBC). Random assignment of anemic participants to intervention and control arms occurred within 5 matched site-pairs. Intervention participants received 1 iron-supplement bar (containing 14 mg Fe)/d for 90 d, whereas control subjects received nothing. CBC tests were given at days 15, 45, and 90. Primary outcomes were 90-d changes from baseline in hemoglobin concentrations and hematocrit percentages. Linear mixed models and generalized estimating equations were used to model continuous and binary outcomes, respectively.Results: Of 179 anemic participants, 136 (76.0%) completed all follow-up assessments (65 intervention and 71 control participants). Baseline characteristics were comparable by arm. Mean hemoglobin and hematocrit increases after 90 d were greater for intervention than for control participants [1.4 g/dL (95% CI: 1.3, 1.6 g/dL) and 2.7% (95% CI: 2.2%, 3.2%), respectively]. The anemia prevalence at 90 d was lower for intervention (29.2%) than for control participants (98.6%) (OR: 0.007; 95% CI: 0.001, 0.04).Conclusions: The daily consumption of an iron-supplement bar leads to increased hemoglobin concentrations and hematocrit percentages and to a lower anemia prevalence in the target population with no reported side effects. This intervention is an attractive option to combat anemia in India. This trial was registered at clinicaltrials.gov as NCT02032615.

Wide field of view swept-source optical coherence tomography for peripheral retinal disease.

BACKGROUND/AIMS: To assess peripheral retinal lesions and the posterior pole in single widefield optical coherence tomography (OCT) volumes. METHODS: A wide field of view (FOV) swept-source OCT (WFOV SSOCT) system was developed using a commercial swept-source laser and a custom sample arm consisting of two indirect ophthalmic lenses. Twenty-seven subjects with peripheral lesions (choroidal melanomas, choroidal naevi, sclerochoroidal calcification, retinitis pigmentosa, diabetic retinopathy, retinoschisis and uveitis) were imaged with the WFOV SSOCT. Volumes were taken in primary gaze. Using the optic nerve to fovea distance as a reference measurement, comparisons were made between the lateral FOV of the WFOV SSOCT, current generation spectral-domain OCT (SDOCT) and widefield scanning laser ophthalmoscopy (SLO) of the same eyes. RESULTS: Peripheral pathologies were captured with WFOV SSOCT in 26 of the 27 subjects. The one not captured was in the far nasal periphery and was not seen in the primary gaze volume. Posterior pole associated pathologies were captured in all subjects. Current generation SDOCT had a mean lateral FOV of 2.08±0.21 optic nerve to fovea distance units, WFOV SSOCT had an FOV of 4.62±0.62 units and SLO had an FOV of 9.35±1.02 units. CONCLUSIONS: WFOV OCT can be used to examine both peripheral retinal pathology and the posterior pole within a single volume acquisition. SLO had the greatest FOV, but does not provide depth information. Future studies using widefield OCT systems will help further delineate the role of WFOV OCT to quantitatively assess and monitor peripheral retinal disease in three dimensions.

TAF4b promotes mouse primordial follicle assembly and oocyte survival.

Primary ovarian insufficiency (POI) affects 1% of women under the age of 40 and is associated with premature ovarian follicle depletion. TAF4b deficiency in adult female mouse models results in hallmarks of POI including stereotyped gonadotropin alterations indicative of early menopause, poor oocyte quality, and infertility. However, the precise developmental mechanisms underlying these adult deficits remain unknown. Here we show that TAF4b is required for the initial establishment of the primordial follicle reserve at birth. Ovaries derived from TAF4b-deficient mice at birth exhibit delayed germ cell cyst breakdown and a significant increase in Activated Caspase 3 staining compared to control ovaries. Culturing neonatal TAF4b-deficient ovaries with the pan-caspase inhibitor ZVAD-FMK suppresses the excessive loss of these oocytes around the time of birth. These data reveal a novel TAF4b function in orchestrating the correct timing of germ cell cyst breakdown and establishment of the primordial follicle reserve during a critical window of development.

Sourcing human embryos for embryonic stem cell lines: problems & perspectives.

The ability to successfully derive human embryonic stem cells (hESC) lines from human embryos following in vitro fertilization (IVF) opened up a plethora of potential applications of this technique. These cell lines could have been successfully used to increase our understanding of human developmental biology, transplantation medicine and the emerging science of regenerative medicine. The main source for human embryos has been 'discarded' or 'spare' fresh or frozen human embryos following IVF. It is a common practice to stimulate the ovaries of women undergoing any of the assisted reproductive technologies (ART) and retrieve multiple oocytes which subsequently lead to multiple embryos. Of these, only two or maximum of three embryos are transferred while the rest are cryopreserved as per the decision of the couple. in case a couple does not desire to 'cryopreserve' their embryos then all the embryos remaining following embryo transfer can be considered 'spare' or if a couple is no longer in need of the 'cryopreserved' embryos then these also can be considered as 'spare'. But, the question raised by the ethicists is, "what about 'slightly' over-stimulating a woman to get a few extra eggs and embryos? The decision becomes more difficult when it comes to 'discarded' embryos. As of today, the quality of the embryos is primarily assessed based on morphology and the rate of development mainly judged by single point assessment. Despite many criteria described in the literature, the quality assessment is purely subjective. The question that arises is on the decision of 'discarding' embryos. What would be the criteria for discarding embryos and the potential 'use' of ESC derived from the 'abnormal appearing' embryos? This paper discusses some of the newer methods to procure embryos for the derivation of embryonic stem cell lines which will respect the ethical concerns but still provide the source material.

Essential global role of CDC14 in DNA synthesis revealed by chromosome underreplication unrecognized by checkpoints in cdc14 mutants.

The CDC14 family of multifunctional evolutionarily conserved phosphatases includes major regulators of mitosis in eukaryotes and of DNA damage response in humans. The CDC14 function is also crucial for accurate chromosome segregation, which is exemplified by its absolute requirement in yeast for the anaphase segregation of nucleolar organizers; however the nature of this essential pathway is not understood. Upon investigation of the rDNA nondisjunction phenomenon, it was found that cdc14 mutants fail to complete replication of this locus. Moreover, other late-replicating genomic regions (10% of the genome) are also underreplicated in cdc14 mutants undergoing anaphase. This selective genome-wide replication defect is due to dosage insufficiency of replication factors in the nucleus, which stems from two defects, both contingent on the reduced CDC14 function in the preceding mitosis. First, a constitutive nuclear import defect results in a drastic dosage decrease for those replication proteins that are regulated by nuclear transport. Particularly, essential RPA subunits display both lower mRNA and protein levels, as well as abnormal cytoplasmic localization. Second, the reduced transcription of MBF and SBF-controlled genes in G1 leads to the reduction in protein levels of many proteins involved in DNA replication. The failure to complete replication of late replicons is the primary reason for chromosome nondisjunction upon CDC14 dysfunction. As the genome-wide slow-down of DNA replication does not trigger checkpoints [Lengronne A, Schwob E (2002) Mol Cell 9:1067-1078], CDC14 mutations pose an overwhelming challenge to genome stability, both generating chromosome damage and undermining the checkpoint control mechanisms.

Prevalences of oligozoospermia and azoospermia in male partners of infertile couples from different parts of India.

AIM: To determine whether there was any regional variation in the prevalence of azoospermia, oligozoospermia and mean sperm counts in male partners of infertile couples from different parts of India. METHODS: Data on 16,714 semen samples analyzed over the past five years from six different laboratories located in five cities of India were collated and evaluated. RESULTS: There was a regional variation in the prevalence of azoospermia. The prevalence of azoospermia was extremely high in Kurnool and Jodhpur (38.3% and 37.4%, respectively). There was also a regional variation in the prevalence of oligozoospermia (51%) in Kurnool. There was no significant difference in the mean sperm counts in normospermic men. CONCLUSION: There is a regional variation in the prevalence of azoospermia and oligozoospermia in the male partners of infertile couples from different regions of India. The prevalence of azoospermia in Kurnool and Jodhpur is higher than any other worldwide reported literature. Further studies need to be carried out to determine the cause of this.

Growth of human preimplantation embryos in vitro.

The human oocyte fertilizes and develops into embryos in the Fallopian tube and reaches the uterus only after compaction. However, for several years embryos that were developed following in-vitro fertilization (IVF) were transferred into the uterus on day 2 or 3 at the 4-8 cell stage in contrast to the in-vivo situation where they would be present in the Fallopian tube. Earlier attempts to grow embryos in vitro for 5 to 6 days were not always successful. Attempts were therefore made to understand the in-vivo environment of the Fallopian tube where the early embryonic development occurs. This article reviews the studies carried out to understand the composition of fluids in the Fallopian tube specifically with reference to the energy metabolites - lactate, pyruvate and glucose; it also covers how the formulation of culture media for human IVF and embryonic development were modified over the years based on some classical work done on embryo culture in laboratory animals.