Omega-3 fatty acids supplements for dry eye - Are they effective or ineffective?

Purpose: To evaluate effectiveness of omega-3 fatty acid supplements in relieving dry eye symptoms and signs in symptomatic visual display terminal users (VDT). Methods: A randomized controlled study was done; eyes of 470 VDT users were randomized to receive four capsules twice daily for 6 months (O3FAgroup), each containing 180 mg of eicosapentaenoic acid and 120 mg docosahexaenoic acid. The O3FA group was compared with another group (n = 480) who received four capsules of a placebo (olive oil) twice daily. Patients were evaluated at baseline, 1, 3, and 6 months, respectively. The primary outcome was improvement in omega-3 index (a measure of EPA and DHA ratio in RBC membrane). Secondary outcomes were improvement dry eye symptoms, Nelson grade on conjunctival impression cytology, Schirmer test values, tear film breakup time (TBUT), and tear film osmolarity. Means of groups (pre-treatment, 1, 3, and 6-months) were compared with repeated measure analysis of variance. Results: At baseline, 81% patients had low omega-3 index. In the O3FA group, a significant increase in omega-3 index, improvement in symptoms, reduction in tear film osmolarity, and increase in Schirmer, TBUT, and goblet cell density was observed. These changes were not significant in the placebo group. Improvement in test parameters was significantly (P < 0.001) better in patients with low omega3 index (<4%) subgroup. Conclusion: Dietary omega-3 fatty acids are effective for dry eye in VDT users; omega-3 index appears to be the predictor to identify potential dry eye patients who are likely to benefit from oral omega-3 dietary intervention.

Awareness Regarding Eye Donation among Doctors, Students, and Paramedics at a Tertiary Care Teaching Hospital.

INTRODUCTION: In the sub-continent, there is a huge discrepancy between the cornea collected and the ever-increasing demand. Lack of awareness, faulty perceptions, and unwillingness to donate corneas are the major hurdles. OBJECTIVES: To assess the level of awareness among doctors, students, and paramedics in a teaching hospital. MATERIALS AND METHODS: An analytical cross-sectional, pre-tested, study design assessed the awareness, knowledge, and attitude among health care workers (medical students, nurses, doctors, and paramedics) in the context of eye donation through a administered self-administered semi-structured questionnaire. RESULTS: In our study, 692 (57.7%) of the respondents were aware that the ideal time for donation was within six hours of death. Our study revealed that 875 (72.9) of the respondents were willing to donate their eyes; out of these 305 (25.4%) were MBBS students and 223 (18.6%) were nursing students, (Chi-square tests, p <0.001). Six-hundred and twenty-five (52.1%) respondents knew that the nearest eye bank should be contacted if they or any of their family members wished to donate their eyes. However, only 90 (7.5%) of the respondents' family/ relatives had donated his/her eyes. A significant association between knowledge of eye donation and the age, gender, religion, or marital status and knowledge of eye donation of participants was observed. CONCLUSION: The study highlights the need for creating awareness about eye donation among doctors, medical students, and paramedics, who can be an effective channel for planning, educating, and motivating the public to pledge for eye donation.

The Discriminatory Ability of Ganglion Cell Inner Plexiform Layer Complex Thickness in Patients with Preperimetric Glaucoma.

Purpose: To evaluate diagnostic performance of ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) parameters measured with Cirrus high-definition optical coherence tomography (OCT) in patients with preperimetric glaucoma. Methods: In this multicenter cross-sectional study, 150 eyes of 83 patients with preperimetric glaucoma were compared with 200 eyes of age and sex matched healthy subjects. All patients had visual field testing and OCT scanning of GCIPL and RNFL in all quadrants. The independent Samples t-test was used to determine if a difference exists between the means of two independent groups on a continuous dependent variable. The area under the receiver operating characteristic (ROC) curve (AUC) of each parameter was calculated for discriminatory ability between normal controls and preperimetric glaucoma. The sensitivity and specificity were estimated by point coordinates on ROC curve. Results: The best parameters for distinguishing preperimetric glaucoma from healthy eyes were the combined average GCIPL + average RNFL, followed by average RNFL + GCIPL (inferotemporal), and average RNFL + GCIPL (minimum). The GCIPL parameters with the highest to lowest AUC (in decreasing order) were inferotemporal, followed by average, minimum, superior, inferior, superonasal, inferonasal, superotemporal, and quadrants. The RNFL parameters with the highest to lowest AUC (in decreasing order) were average, followed by nasal, temporal, superior, and inferior quadrants. The sensitivity of combined GCIPL + RNFL parameters ranged 85%-88% and the specificity ranged 76%-88%. The sensitivity for RNFL parameters ranged 80%-90% and the specificity ranged 64%-88%. Conclusion: GCIPL and RNFL have good discriminatory ability; the sensitivity and specificity increase when both parameters are combined for early detection of glaucoma.

Long-term outcomes of small-incision cataract surgery in patients with uveitis.

Purpose: To evaluate the long-term outcomes of manual small-incision cataract surgery (MSICS) in eyes with uveitis. Methods: Patients who underwent MSICS for uveitic cataract from 2009 to 2019 were retrospectively evaluated. Visually significant cataract and presence of less than five cells per high-power field in the anterior chamber for a minimum of 3 months were the prerequisites for surgery. Patients with follow-up less than 9 months were excluded. Results: After exclusion, 283 eyes of 264 patients were evaluated. The mean age of patients was 44.3 ± 11.3 years. The mean follow-up duration was 22 ± 11.5 months. The mean surgical time was 11.2 ± 3.2 min. One hundred and seventy-two eyes (60.8%) had anterior uveitis, 78 (27.5%) had posterior uveitis, and 33 (11.7%) had panuveitis. At the final follow-up, 253 eyes (88.4%) had corrected distance visual acuity (CDVA) better than 0.6 log of minimum angle of resolution (LogMAR) unit. The final endothelial cell counts were significantly (analysis of variance [ANOVA], P = 0.001) lower in eyes with human leukocyte antigen (HLA)-B27-associated uveitis and in eyes with idiopathic anterior uveitis. Patients on systemic corticosteroids had significantly better (P = 0.031) final visual acuity than those without preoperative corticosteroids. Recurrent uveitis (43.8%), Posterior capsule opacification (PCO) (19.4%), glaucoma (8.5%), cystoid macular edema (CME; 13.5%), and Epiretinal membrane (ERM) (5.6%) were the frequent complications. A significantly worse (ANOVA, P = 0.001) visual prognosis was seen in patients with Vogt-Koyanagi-Harada disease (VKH), sarcoidosis, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and serpiginous choroiditis. Conclusion: MSICS is safe in most cataracts due to uveitis and results in improvement in CDVA at 9 months. Posterior capsule opacification, macular edema, persistent uveitis, etiology of uveitis, and use of preoperative steroids significantly influenced the visual outcome.

Phytochemical-loaded liposomes for anticancer therapy: an updated review.

The major obstacles observed in current chemotherapy are severe adverse effects, narrow therapeutic indexes and multidrug resistance. Anticancer phytochemicals are extracted and purified from natural plants, providing alternative therapeutic approaches with recognized biomedical benefits. However, poor bioavailability, high dose requirements and non-specific targeting have made those molecules less effective. To tackle those issues, liposomal nanovesicles for phytochemical delivery are taken into consideration for improving the therapeutic effectiveness by increasing transportation across cell barriers and conferring attractive cancer-specific targeting capabilities. In the present review, the liposomal approaches of anticancer phytochemicals are discussed, and recent advances in these formulations applied to cancer phytotherapy are further reviewed by an informed approach.

This review describes the application of liposomal phyto-chemotherapy as a promising therapeutic and technological intervention against cancer that has the potential to enhance the effectiveness of cancer therapy, reduce the associated side effects and improve the clinical outcomes of cancer patients.

Response of a concentrated monoclonal antibody formulation to high shear.

There is concern that shear could cause protein unfolding or aggregation during commercial biopharmaceutical production. In this work we exposed two concentrated immunoglobulin-G1 (IgG1) monoclonal antibody (mAb, at >100 mg/mL) formulations to shear rates between 20,000 and 250,000 s(-1) for between 5 min and 30 ms using a parallel-plate and capillary rheometer, respectively. The maximum shear and force exposures were far in excess of those expected during normal processing operations (20,000 s(-1) and 0.06 pN, respectively). We used multiple characterization techniques to determine if there was any detectable aggregation. We found that shear alone did not cause aggregation, but that prolonged exposure to shear in the stainless steel parallel-plate rheometer caused a very minor reversible aggregation (<0.3%). Additionally, shear did not alter aggregate populations in formulations containing 17% preformed heat-induced aggregates of a mAb. We calculate that the forces applied to a protein by production shear exposures (<0.06 pN) are small when compared with the 140 pN force expected at the air-water interface or the 20-150 pN forces required to mechanically unfold proteins described in the atomic force microscope (AFM) literature. Therefore, we suggest that in many cases, air-bubble entrainment, adsorption to solid surfaces (with possible shear synergy), contamination by particulates, or pump cavitation stresses could be much more important causes of aggregation than shear exposure during production.

Characterization of arachnoidal cells cultured on three-dimensional nonwoven PET matrix.

PURPOSE: To culture physiologically functional primary arachnoidal cells on a suitable polymer substrate for an in-vitro model of the cerebrospinal fluid outflow pathway. METHODS: Primary cultures of arachnoidal cells were prepared within 24 hours post-mortem from brain tissue obtained from human cadavers at autopsy. Arachnoidal cells were characterized using immunocytochemistry and seeded onto needle punched non-woven poly(ethylene terephthalate)(PET) scaffolds. Metabolic rate, cell growth rate in log phase, morphologic assessment, immunocytochemistry, and protein analysis were used to characterize the cultures in both 2-D and 3-D-culture. Functional outflow assessment was performed using the Lucifer Yellow (LY) permeability assay and hydraulic conductivity (Lp) determination. RESULTS: Cells cultured on PET scaffold grew slightly slower than cells grown in 2-D-culture as measured by metabolic rate and growth rate, however, they often formed sheets that bridged between the adjacent scaffold filaments forming many junctional protein connections. LY permeability coefficients of 2-D cells were compared with cells from scaffolds, and were not significantly different (p > 0.05) for both culture conditions. Average Lp of cells from 2-D-culture and 3-D-scaffolds were compared and shown not to be significantly different. CONCLUSION: Based on the biochemical and functional analysis, it has been shown that cells cultured on 3D-PET scaffolds retained the same properties as cells from 2D-culture plates.

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue.

BACKGROUND: The arachnoid granulations (AGs) are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF) to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. METHODS: Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7-10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7-10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144) and their expression was quantified using flow cytometry analysis. RESULTS: Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. CONCLUSION: To our knowledge, this is the first report of the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow.