ABSTRACT
Purpose: Our primary aim was to evaluate intraocular cytokines (IC) before and after dexamethasone in diabetic macular edema (DME). Our secondary aim was to study the early and late effects of single dexamethasone implant in DME. Methods: This before and after comparative study was conducted at the Department of Ophthalmology and Centre for Nanosciences at a quaternary referral center in Kerala, India, from September 2016 to September 2018. Patients underwent complete ophthalmological examination and cytokine analysis before and after dexamethasone implant. Levels of cytokines at baseline and repeat sample were studied. Results: Twenty?seven eyes (21 patients) were divided into two groups depending on time from baseline to second injection. Group 1 included patients with <3 months between the two samples – 12 (44.4%). Group 2 included patients with >3 months between the two samples –15 (55.6%). Best corrected visual acuity (BCVA) and central macular thickness (CMT) improved significantly post?dexamethasone in group 1, but not in group 2. Interleukin (IL)?4, IL?6, IL?10, vascular endothelial growth factor (VEGF), IL?1?, interferon?gamma inducible protein?10 (IP?10), monocyte chemoattractant protein?1 (MCP?1), and IL?2 decreased post?injection in group 1. But cytokines increased post?dexamethasone in group 2, except IL?10. When compared to baseline, IL?6 reduced to half in group 1 (P?value 0.814) and it tripled in group 2 ( P?value 0.009). The level of VEGF in the first and second samples was not different in either group. Conclusion: Our study suggests that dexamethasone acts more on IC than VEGF in DME. This is significant in the first 3 months with a rebound effect on IL?6 after 3 months. Our study also suggests that repeat injection of DEX in DME should be done at 3 months to prevent deterioration of visual acuity (VA) and worsening of CMT.
ABSTRACT
Maple syrup urine disease (MSUD) is predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which encode for the E1α, E1β and E2 subunits of the branched-chain α-keto acid dehydrogenase complex, respectively. Because disease causing mutations play a major role in the development of the disease, prenatal diagnosis at gestational level may have significance in making decisions by parents. Thus, this study was aimed to screen South Indian MSUD patients for mutations and assess the genotype-phenotype correlation. Thirteen patients diagnosed with MSUD by conventional biochemical screening such as urine analysis by DNPH test, thin layer chromatography for amino acids and blood amino acid quantification by HPLC were selected for mutation analysis. The entire coding regions of the BCKDHA, BCKDHB and DBT genes were analyzed for mutations by PCR-based direct DNA sequencing. BCKDHA and BCKDHB mutations were seen in 43% of the total ten patients, while disease-causing DBT gene mutation was observed only in 14%. Three patients displayed no mutations. Novel mutations were c.130C>T in BCKDHA gene, c. 599C>T and c.121_122delAC in BCKDHB gene and c.190G>A in DBT gene. Notably, patients harbouring these mutations were non-responsive to thiamine supplementation and other treatment regimens and might have a worse prognosis as compared to the patients not having such mutations. Thus, identification of these mutations may have a crucial role in the treatment as well as understanding the molecular mechanisms in MSUD.