A randomized controlled trial to assess safety and efficacy between terminal chop, stop and chop, and direct chop.

PURPOSE: The goal in developing new techniques of cataract surgery is to provide a safer, more efficient surgical experience with the lowest complication rate and endothelial cell loss. We compared the efficiency and safety of stop-and-chop, direct chop, and the novel terminal chop techniques of nuclear fragmentation for cataracts grade II-V. METHODS: We conducted a prospective randomized clinical trial comparing three different techniques of phacoemulsification, namely, stop-and-chop, direct chop, and terminal chop to assess any differences between them and to establish whether any one method was superior to the others. The pre- and postoperative parameters studied, included central corneal thickness (CCT), ultrasonic time (UST), endothelial cell density (CD), cell loss and effective phacoemulsification time (EPT), average cumulative dissipative energy (CDE), and best-corrected visual acuity, among others. RESULTS: 307 eyes were recruited to the study, 102 were recruited to the stop-and-chop group, 103 to the direct chop group, and 102 to the terminal chop group. Statistical differences were found between the techniques with regard to postoperative CCT among NS II (P. 0001) and NS IV cataracts (P = .005) with the lowest values in the terminal chop group among NS II, NS III, and NS IV cataracts. Endothelial cell loss was minimum with a terminal chop in NS II (P = .018) and NS IV cataracts (P = .245). CDE was minimum in terminal chop across different cataract densities. CONCLUSION: Terminal chop showed improvement over the other two techniques in terms of CDE and was comparable to them with regard to other parameters.

Diabetes more than retinopathy, it's effect on the anterior segment of eye.

Diabetes mellitus (DM) is one of the chronic metabolic noncommunicable diseases that has attained worldwide epidemics. It threatens healthy life around the globe, with mild-to-severe secondary complications and leads to significant illness including nephropathy, neuropathy, retinopathy, and macrovascular abnormalities including peripheral vasculopathy, and ischaemic heart disease. Research into diabetic retinopathy (DR), which affects one-third of persons with diabetes, has made considerable strides in recent years. In addition, it can lead to several anterior segment complications such as glaucoma, cataract, cornea, conjunctiva, lacrimal glands and other ocular surface diseases. Uncontrolled DM also caused gradual damage to corneal nerves and epithelial cells, which raises the likelihood of anterior segment diseases including corneal ulcers, dry eye disease, and chronic epithelial abnormalities. Although DR and other associated ocular complications are well-known, the complexity of its aetiology and diagnosis makes therapeutic intervention challenging. Strict glycaemic control, early detection and regular screening, and meticulous management is the key to halting the progression of the disease. In this review manuscript, we aim to provide an in-depth understanding of the broad spectrum of diabetic complications in the anterior segment of the ocular tissues and illustrate the progression of diabetes and its pathophysiology, epidemiology, and prospective therapeutic targets. This first such review article will highlight the role of diagnosing and treating patients with a plethora of anterior segment diseases associated with diabetes, which are often neglected.

A clinical trial on phakic intraocular lens for the treatment of refractive amblyopia in children and adolescents.

Purpose: To analyze the demographics and clinical outcomes of posterior chamber phakic intraocular (IOL) implantation for refractive amblyopia in children and adolescents. Methods: A prospective interventional study was performed on children and adolescents with amblyopia at a tertiary eye care center from January 2021 to August 2022. Twenty-three eyes of 21 anisomyopic and isomyopic amblyopia patients operated for posterior chamber phakic IOL (Eyecryl phakic IOL) as a treatment for amblyopia were included in the study. Patient demographics, pre- and postoperative visual acuity, cycloplegic refraction, anterior and posterior segment examination, intraocular pressure, pachymetry, contrast sensitivity, endothelial count, and patient satisfaction scores were evaluated. Patients were followed up at day 1, 6 weeks, 3 months, and 1 year after surgery, and visual outcomes and complications were documented. Results: The mean age of patients was 14.16 ± 3.49 years (range: 10-19 years). The mean intraocular lens power was - 12.20 diopter spherical (DS) in 23 eyes and - 2.25 diopter cylindrical (DC) in four patients. The mean unaided distant visual acuity (UDVA) and best-corrected visual acuity (BCVA) were 1.39 ± 0.25 and 0.40 ± 0.21 preoperatively on the log of minimum angle of resolution (logMAR) chart. Postoperatively, the visual acuity improved by 2.6 lines in 3 months period and maintained till 1 year. Postsurgery, contrast sensitivity in the amblyopic eyes significantly improved, and the average endothelial loss recorded was 5.78% at 1 year, which was statistically insignificant. Patient satisfaction score was statistically significant, with 4.736/5 recorded on the Likert scale. Conclusion: Posterior chamber phakic IOL is a safe, effective, and alternative method for treating amblyopia patients who are noncompliant with glasses, contact lenses, and keratorefractive procedures.

Protective immunity to Mycobacterium tuberculosis infection by chemokine and cytokine conditioned CFP-10 differentiated dendritic cells.

BACKGROUND: Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs). METHODS AND FINDINGS: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment. CONCLUSIONS: These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection.

Mycobacterium tuberculosis and dendritic cells: recognition, activation and functional implications.

The highly complex nature of interactions of Mycobacterium tuberculosis with cells of the immune system has puzzled researchers the world-over in understanding the pathogenesis and immunology associated with tuberculosis (TB). This has contributed to the delay in development of effective vaccine(s) for TB. Several excellent studies have provided only a glimpse of the kind and degree of immune responses elicited following infection by mycobacteria. Preferred entry via respiratory route results in the capture of mycobacteria by alveolar macrophages that eventually become their long-term hosts. Since the pathogen is rarely cleared this has resulted in the human population serving as a large reservoir for mycobacteria. Owing to their unique ability to prime naïve and memory T cells, dendritic cells (DCs) play important and indispensable roles in the initiation and maintenance of protective immune responses following infection. The kind of immune response initiated by DCs with respect to mycobacteria determines the character of immune responses mounted by the host against the pathogen. The profile of cytokines and chemokines secreted as a result of infection of DCs by mycobacteria further plays an important role in defining the course of infection. This minireview attempts to highlight key interactions of mycobacteria with dendritic cells. We discus the uptake of mycobacteria by DCs followed by DC activation and the spectrum of immune responses initiated by infected/activated DCs, followed by numerous ways the pathogen has devised to subvert protective responses.

Impaired generation of reactive oxygen species during differentiation of dendritic cells (DCs) by Mycobacterium tuberculosis secretory antigen (MTSA) and subsequent activation of MTSA-DCs by mycobacteria results in increased intracellular survival.

We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC) differentiation by 10-kDa Mycobacterium tuberculosis secretory Ag (MTSA) and survival of mycobacteria therein. Compared with GM-CSF, MTSA induced lower ROS production during DC differentiation from precursors. This result correlated with higher superoxide dismutase 1 expression in MTSA stimulated precursors as compared with GM-CSF stimulation. Furthermore, a negative regulation of protein kinase C (PKC) activation by ROS was observed during DC differentiation. ROS inhibited the rapid and increased phosphorylation of PKCalpha observed during DC differentiation by MTSA. In contrast, ROS inhibition increased the weak and delayed PKCalpha phosphorylation by GM-CSF. Similar to DC differentiation, upon activation with either M. tuberculosis cell extract (CE) or live Mycobacterium bovis bacillus Calmette-Guérin (BCG), DCs differentiated with MTSA (MTSA-DCs) generated lower ROS levels when compared with DCs differentiated with GM-CSF (GM-CSF-DCs). Likewise, a negative regulation of PKCalpha phosphorylation by ROS was once again observed in DCs activated with either M. tuberculosis CE or live M. bovis BCG. However, a reciprocal positive regulation between ROS and calcium was observed. Compared with MTSA-DCs, stimulation of GM-CSF-DCs with M. tuberculosis CE induced a 2-fold higher ROS-dependent calcium influx. However, pretreatment of MTSA-DCs with H(2)O(2) increased calcium mobilization. Finally, lower ROS levels in MTSA-DCs correlated with increased intracellular survival of M. bovis BCG when compared with survival in GM-CSF-DCs. Although inhibiting ROS in GM-CSF-DCs increased M. bovis BCG survival, H(2)O(2) treatment of MTSA-DCs decreased survival of M. bovis BCG. Overall our results suggest that DCs differentiated with Ags such as MTSA may provide a niche for survival and/or growth of mycobacteria following sequestration of ROS.

Regulation of immune responses to Mycobacterium tuberculosis secretory antigens by dendritic cells.

Towards elucidating the immune responses induced by antigens from the Mycobacterium tuberculosis (M. tb) RD-1 region, we have been characterizing their interactions with dendritic cells (DCs) and their precursors. We have shown that incubation of bone marrow DC precursors with M. tb antigens induces the differentiation of DC precursors and also the maturation of various DC subsets. While MTSA differentiated DCs were immature, MTSA matured DCs were terminally mature. However, regardless of their maturation status M. tb secretory antigen-activated DCs down-regulated pro-inflammatory T helper cell responses to a subsequent challenge with M. tb cell extract (CE) while increasing regulatory responses. Investigations into the underlying mechanisms showed that stimulation with M. tb CE changed the polarization of antigen-activated DCs from DC1 to DC2. This resulted in secretion of high levels of IL-10 and TGF-beta together with increased surface expression of CD86. Blocking either IL-10 or TGF-beta or CD86 restored Th1 responses to CE antigens. Conversely, treatment of antigen-activated DCs with IL-12 and/or IFN-gamma fully restored Th1 responses of CE antigens. These results indicate that M. tb strategically secretes antigens from infected macrophages to down-regulate pro-inflammatory immune responses at sites of infection.

Dominance of CD86, transforming growth factor- beta 1, and interleukin-10 in Mycobacterium tuberculosis secretory antigen-activated dendritic cells regulates T helper 1 responses to mycobacterial antigens.

We report that stimulation of Mycobacterium tuberculosis (M. tuberculosis) secretory antigen (MTSA)-differentiated dendritic cells (DCs) and MTSA-matured DCs with M. tuberculosis cell extract (CE) down-regulated proinflammatory responses to CE-primed T (CE-T) cells by increasing surface expression of CD86 after CE stimulation. CE stimulation also decreased interleukin (IL)-12p40 and interferon (IFN)- gamma levels and increased IL-10 and transforming growth factor- beta 1 (TGF- beta 1) levels from these DCs. Blocking either CD86, IL-10, or TGF- beta with monoclonal antibodies before CE stimulation restored the attenuated T helper 1 (Th1) responses of CE-T cells. Conversely, treatment of these DCs with IL-12p70 and/or IFN- gamma completely restored Th1 responses from CE-T cells. These results indicate that M. tuberculosis secretory antigens down-regulate proinflammatory Th1 responses to mycobacteria by differentially modulating the cytokine profiles and surface densities of costimulatory molecules on DCs. Of importance, this down-regulation is independent of the maturation status of MTSA-activated DCs and can be rescued after treatment of DCs with IFN- gamma or IL-12.