Publications by authors named "Kamaljit Balaggan"
Article Synopsis
- The article DOI: 10.1371/journal.pone.0015730 has been corrected to address previous inaccuracies.
- The corrections made aim to enhance the clarity and reliability of the research findings.
- This serves to maintain the integrity of scientific publication and ensure accurate information dissemination.
Article Synopsis
- Cataract surgery is common, and this study compared Femtosecond Laser-Assisted Cataract Surgery (FLACS) with traditional Phacoemulsification Cataract Surgery (PCS) over a randomized trial involving 785 patients.
- The main focus was to assess visual acuity outcomes after 3 months, using uncorrected distance visual acuity as the primary measure, alongside other safety and patient-reported outcomes.
- Results showed similar visual acuity improvements in both FLACS and PCS groups, with slight variations, and included minimal complications like two posterior capsule tears in the PCS group.
Article Synopsis
- The study evaluated the 1-year outcomes of femtosecond laser-assisted cataract surgery (FLACS) compared to phacoemulsification cataract surgery (PCS) in a multicenter randomized trial.
- Out of 785 participants, both surgical methods showed similar uncorrected and corrected distance visual acuity, with no significant differences in overall outcomes except a slight advantage for binocular CDVA in the FLACS group.
- PCS was determined to be just as effective as FLACS concerning vision and safety, but FLACS had higher costs and was not found to be cost-effective.
Article Synopsis
- The study aimed to assess the effectiveness of femtosecond laser-assisted cataract surgery (FLACS) compared to traditional phacoemulsification cataract surgery (PCS) over a 3-month period in a randomized trial involving 785 patients.
- The trial, conducted across three UK hospitals, found no significant differences in unaided distance visual acuity and other outcomes between the two surgical methods, indicating that FLACS is comparable to PCS.
- Both surgical techniques showed similarly positive results in terms of visual acuity post-surgery, with low rates of complications, suggesting that FLACS is a viable alternative to PCS.
Article Synopsis
- The study aimed to assess how consistent SS-OCT measurements are for retinal and choroidal thickness in patients with neovascular age-related macular degeneration (nAMD).
- A total of 39 patients participated, receiving three scans each, with results indicating that measurement repeatability for retinal thickness varied between 13.2% to 28.7%.
- To detect real changes in thickness, the findings suggest that increases over 23.2% for retinal thickness and 57.2μm for choroidal thickness in the central macular area are necessary to ensure they are not just measurement errors.
Article Synopsis
- The study aimed to assess the reliability of spectral-domain optical coherence tomography (SDOCT) measurements of retinal and choroidal metrics in patients with neovascular age-related macular degeneration (nAMD).
- A total of 40 patients underwent multiple SDOCT scans, measuring retinal thickness across various macular subfields, and manual assessments of subfoveal choroidal thickness were also conducted.
- The findings indicate that a difference of over 31 μm in retinal thickness and over 35 μm in choroidal thickness is needed to signify actual clinical change in nAMD, with a refined threshold of 14 μm for specific measurements after excluding errors.
Background: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited.
Methods: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years.
Article Synopsis
- The study assessed the effectiveness of subconjunctival bevacizumab in treating corneal neovascularisation (CoNV) in 30 patients through a randomized, placebo-controlled trial.
- Patients received either bevacizumab or saline injections, with results showing a significant reduction in CoNV by 36% in the treatment group compared to a 90% increase in the placebo group.
- The findings suggest that bevacizumab injections are more effective than placebo for CoNV regression, but further research with larger sample sizes is recommended to confirm these results.
Article Synopsis
- - The study presents a unique case of a patient experiencing both hemiretinal vein occlusion and a delayed cilioretinal artery occlusion (CLRAO), highlighting the sequence of events leading to the CLRAO.
- - It includes detailed color fundus and fluorescein angiogram images to illustrate the conditions and the gradual development of the CLRAO.
- - The patient was found to have previously undiagnosed hypertension, received treatment, and, despite initial inferior visual field defects, improved to a vision of 20/40 six months later; the report also discusses the associated risk factors and possible causes.
Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration preferences might be distinct between these biological states. We performed integration site (IS) analyses on mouse dividing cells (fibroblasts and hematopoietic progenitor cells (HPCs)) transduced ex vivo and postmitotic cells (eye and brain) transduced in vivo.
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- Cell-cell adhesion plays a crucial role in the development and functioning of epithelial tissues by providing support and regulating cell growth and differentiation.
- The tight junction protein ZO-1 controls cell proliferation and gene expression by suppressing the Y-box transcription factor ZONAB, which has implications for retinal pigment epithelium (RPE) health.
- Experiments showed that both increasing ZONAB levels and reducing ZO-1 led to excessive RPE growth and structural changes resembling epithelial-mesenchymal transition, ultimately causing RPE dysfunction and highlighting the importance of ZO-1 and ZONAB in eye diseases.
Article Synopsis
- Müller cell gliosis is a response that occurs in various retinal diseases, making Müller cells potential targets for gene therapy due to their ability to align with injured areas in the retina.
- The study utilized AAV2/6 vectors to deliver a green fluorescent protein (GFP) gene specifically to Müller glial cells in mouse retinas, showing that the inner limiting membrane hindered transduction, but the GFAP promoter allowed for more specific targeting of these cells amidst others.
- Results confirm that using AAV2 vectors with the GFAP promoter effectively enables targeted gene expression in activated Müller cells, suggesting a new avenue for therapeutic strategies in retinal injuries.
Article Synopsis
- Retroviral vectors used in gene therapy can cause problems like clonal skewing or even leukemia, highlighting the need for thorough analyses of where these vectors integrate into the genome.
- Current techniques like LAM-PCR have limitations in identifying all genomic integrants due to reliance on specific restriction motifs, leading to incomplete understanding of their biological effects.
- A new nonrestrictive LAM-PCR method has been developed, which improves the retrieval of integration sites without being hindered by restriction motifs, offering a more comprehensive analysis for both preclinical and clinical samples.
Article Synopsis
- - The study investigates how the immune system in mice reacts to adeno-associated virus serotype 2 (AAV2) after being injected in the eye, focusing on its potential for treating eye diseases.
- - Researchers found that low doses of AAV2 resulted in minimal immune responses and continued transgene expression, while higher doses led to the development of neutralizing antibodies (NAbs) that could hinder effectiveness.
- - Overall, the results indicate that low-dose AAV2 is safe for repeat administration in the eye, but higher doses can trigger immune reactions that may reduce treatment success.
Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events.
View Article and Find Full Text PDFAqueous misdirection syndrome after pars plana vitrectomy for retinal detachment.
Retin Cases Brief Rep
November 2014
Article Synopsis
- - Aqueous misdirection syndrome (AMS) can occur unexpectedly after vitrectomy surgery, even in patients with no prior history of AMS or related eye conditions.
- - In a case report, a 72-year-old woman developed AMS after pars plana vitrectomy, which led to significantly elevated intraocular pressure (IOP) that didn't respond to medical treatments.
- - The patient underwent an emergency procedure to correct the issue and, after two years of follow-up, showed no recurrence of AMS and maintained normal IOP, highlighting the need to monitor for AMS post-vitrecomy.
Article Synopsis
- Zinc finger protein transcription factors (ZFP TFs) can regulate genes related to various diseases, and this study focused on using engineered ZFP TFs to boost expression of the Pedf gene to combat choroidal neovascularization (CNV).
- After injecting a viral vector containing the ZFP TF in mice, researchers found increased levels of Pedf mRNA and PEDF protein, alongside a notable reduction in CNV size six weeks post-injection.
- The effects were still present three months later, indicating that enhancing the body's anti-angiogenic defenses with ZFP TFs could be a promising new method for treating eye-related neovascular diseases.
Article Synopsis
- The study aimed to evaluate a surgical approach combining the removal of choroidal new vessels with the transplantation of retinal pigment epithelium to improve vision in patients with acute neovascular age-related macular degeneration (AMD).
- Twelve patients with recent vision loss due to AMD were involved in the trial, undergoing a specific surgical procedure where a graft from the retina was placed in the affected area.
- Six months post-surgery, 11 out of 12 patients had successful grafts, with some showing improved vision, although complications were noted in several patients, including retinal detachment.
Article Synopsis
- AAV- and lentivirus-mediated gene therapy shows structural benefits in retinal degeneration models but does not significantly slow photoreceptor cell loss.
- Neurotrophic factors like CNTF can extend photoreceptor survival but may also suppress retina function, indicating a need for careful dosing.
- In contrast, GDNF does not cause the same negative effects and can effectively slow cell death and improve retinal function when combined with gene therapy, demonstrating a potential more effective treatment strategy.
Article Synopsis
- Ciliary neurotrophic factor (CNTF) has demonstrated protective effects on retinal ganglion cells in models of acute ischemia combined with axoplasmic flow interruption, reflecting conditions seen in retinal diseases.
- In an experiment with rats, CNTF was delivered via an adeno-associated viral vector, leading to significantly higher survival rates of ganglion cells (12% survival in treated eyes vs 2% in control eyes) after induced retinal damage.
- While CNTF gene transfer showed potential for neuroprotection against acute ischemic injuries, it also resulted in a 50% reduction in retinal function, indicating a need to balance treatment effectiveness with maintaining retinal health.
Article Synopsis
- Retroviral and lentiviral vectors can pose a risk of insertional mutagenesis, potentially leading to health issues like cancer in mouse models and certain patients with severe genetic disorders.
- A significant challenge in using these vectors for gene therapy is ensuring stable gene expression while minimizing these risks.
- New studies have demonstrated that integration-deficient lentiviral vectors can effectively deliver genes in living rodents, providing long-lasting gene expression and offering potential treatments for conditions like retinal degeneration without integrating into the host's chromosomes.
Article Synopsis
- Ocular neovascularization linked to conditions like proliferative diabetic retinopathy and age-related macular degeneration is a major cause of severe vision loss in adults in developed nations.
- Research indicates that the Sonic hedgehog (Shh) signaling pathway is activated in the retina during neovascularization processes in animal models.
- Inhibiting the Shh pathway not only reduces abnormal blood vessel growth but also lowers levels of the growth factor VEGF, suggesting that targeting this pathway could be an effective treatment for ocular neovascular diseases.