Genetic associations with viral respiratory illnesses and asthma control in children.

BACKGROUND: Viral respiratory infections can cause acute wheezing illnesses in children and exacerbations of asthma. OBJECTIVE: We sought to identify variation in genes with known antiviral and pro-inflammatory functions to identify specific associations with more severe viral respiratory illnesses and the risk of virus-induced exacerbations during the peak fall season. METHODS: The associations between genetic variation at 326 SNPs in 63 candidate genes and 10 phenotypes related to viral respiratory infection and asthma control were examined in 226 children enrolled in the RhinoGen study. Replication of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment of small P values. Six of those genes (STAT4, JAK2, MX1, VDR, DDX58, and EIF2AK2) also showed significant associations with asthma exacerbations in the COPSAC study or with asthma or virus-induced wheezing phenotypes in the COAST study. CONCLUSIONS: We identified genetic factors contributing to individual differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma.

Posterior polar cataract: Minimizing risks.

BACKGROUND: Comparing surgical outcomes of management of posterior polar cataract, a congenital cataract, which is difficult to manage surgically and has been associated with poor surgical outcomes. METHODS: 46 eyes of 38 patients with posterior polar cataract underwent phacoemulsification and PCIOL implantation. RESULTS: In a prospective analytical study, 46 eyes of 38 patients with posterior polar cataracts underwent surgery at a zonal hospital of the armed forces. The posterior polar cataract incidence was 1.23 per 1000 with confidence interval (CI) of 0.0012. Of the 46 eyes operated, 6 had a posterior capsular rupture (PCR) (13.04%). The PCR incidence in normal cataracts is reported at approx. 1.1%, whereas, various studies have reported incidence of 6-36% in posterior polar cataracts. 41 eyes achieved a visual acuity of 6/12 or better (89.13%) and 39 eyes of 6/9 or better (84.78%). 4 patients had amblyopia (8.6%), Two patients developed macular edema (4.34%). Mean follow-up was 7 months (range 3-11 months). There was no case of nucleus drop or retinal detachment. CONCLUSION: Posterior polar cataracts are a surgical challenge. With controlled surgery, well defined techniques, a good surgical outcome can be achieved with reduced incidence of PCR.

A prospective interventional study of effect of accelerated orthokeratology on the corneal curvature and refraction among young adults with myopia.

BACKGROUND: Orthokeratology with reverse geometry contact lens is a non-surgical alternative to conventional contact lenses for correction of myopia. However, the strength of evidence for its efficacy and safety is limited to retrospective studies and only a few prospective studies. This prospective study, the first on Indian subjects, evaluated the outcome of orthokeratology among young myopes. METHODS: Fifty eyes of 25 young myopes (age 19-29 years) with myopia of -1 to 5.0 diopter underwent accelerated orthokeratology using the reverse geometry ortho K - LK lenses for correction of myopia. They were followed up prospectively with weekly vision, refraction, corneal topography, and pachymetry to assess the correction of myopia. RESULTS: The mean Log MAR vision corrected from 0.748 ± 0.225 at base line to 0.025 ± 0.0630 at 12 weeks with 86% achieving 6/6 unaided day time vision. This was associated with significant central corneal flattening and thinning. The lenses were well tolerated with no significant complications. CONCLUSION: Overnight accelerated orthokeratology effectively corrects moderate degree of myopia and provide excellent spectacle free day time vision without any significant adverse effects in the short term.

A clinical study to evaluate the efficacy of intravitreal Anti-VEGF therapy in treating macular edema due to retinal venous occlusions.

BACKGROUND: A non-randomized, interventional study was carried out various types of retinal venous occlusions with significant macular edema who required an Anti-VEGF injection. METHOD: One hundred and one consecutive patients diagnosed as a case of CRVO/HCRVO/BRVO were enrolled in the study provided they had significant macular edema. Atleast three intra-vitreal injections of Anti-VEGFs were given and both the pre and post injections BCVA and CMT on OCT were observed and analyzed. RESULTS: 87 patients (86.14%) showed a significant improvement of vision of atleast two lines on the Snellen's and mean BCVA improved from log MAR +1.084 to log MAR +0.455. CMT on OCT showed reduction in thickness after Anti-VEGF therapy in 99 patients out of 101 and mean CMT decreased from 586.30 µ at baseline to 329.50 µ. Both of these findings were statistically very significant. CONCLUSIONS: Anti-VEGF therapy had a marked improvement in BCVA along with a dramatic reduction in CMT in the vast majority of RVOs patients with no serious ocular or systemic side effects.

Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.

AIMS/HYPOTHESIS: Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (ß-alanyl-L-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. METHODS: We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry). RESULTS: Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (ß = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001). CONCLUSIONS/INTERPRETATION: These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.

5-Fluoro-Uracil and Low Molecular Weight Heparin in the Management of Proliferative Vitreo-retinopathy.

BACKGROUND: Proliferative vitreo-retinopathy (PVR) is the most common cause of failed repair of a primary rhegmatogenous retinal detachment (RRD). The success rates for the surgery of complicated RRD has doubled with improved vitreous techniques from 35-40% to approximately 65-75% at six months. However, despite these advances, recurrent vitreo-retinal traction leads to re-detachment in more than one-fourths of the initially successful cases. The use of adjunctive treatments to prevent cellular proliferation holds promise for the prevention of PVR or recurrences after surgery. One focus has been on the use of intra-vitreal antimetabolites to prevent the occurrence of PVR. METHODS: Thirty patients of complicated retinal detachment associated with PVR, C1 or more were managed by vitreo-retinal (VR) surgery with the addition of 250 µg / ml of 5-fluorouracil (5FU) and 1 IU / ml of low molecular weight heparin (LMWH) to the vitreous infusion. The patients were examined for any evidence of PVR till 180 days as also for any systemic or other ophthalmic complication. RESULT: Out of the 30 cases in the study group, 25 (83.34%) cases had retinal settlement at the end of six weeks, which is similar to the outcomes of conventional VR surgery. There was no case of any serious complication. CONCLUSION: The addition of LMWH and 5FU did not enhance the outcome of VR surgery.

Evaluation of Vitreous Substitutes in Managing Complicated Vitreo-retinal Surgeries.

BACKGROUND: Vitreous substitutes presently in use for intraoperative tamponade are perfluorocarbon liquids (PFCL) and for post operative tamponade are silicon oil (SO), sulphur hexafluoride (SF6) and perfluorocarbon gas (PFC). Several factors are important for a thorough understanding of each of these vitreous substitutes. The absorption or necessity for removal, indications for use (including clinical studies and special surgical methods), additives and complications of use have to be considered. METHODS: Three port standard pars plana vitrectomy was performed in 60 consecutive cases requiring intra-vitreal intervention. PFCL was used intra-operatively in 30 cases (PFCL group and X group). The eyes were implanted with SO (silicon oil subgroup), PFC (C3F8 sub-group) and SF6 (SF6 sub-group) in twenty cases each. Apart from best corrected visual acuity (BCVA), the retinal status and the longevity of gas when used, changes and reaction in both the anterior and posterior segments were noted. RESULT: The difference of postoperative BCVA in the PFCL and non-PFCL groups was statistically significant with p < 0.001. In both the PFCL and non-PFCL groups the difference between preoperative and postoperative BCVA was statistically significant with p < 0.0001. All three vitreous substitutes studied are effective given the case where they had been utilised. CONCLUSION: PFCL is invaluable in the management of complicated retinal detachment (RD). Where a vitreous microsurgery is indicated, the visual outcome is good. SF6 is useful for short-term tamponade. Silicon oil and C3F8 are useful for longer tamponade.

Primary 360° Broad Buckling in Retinal Detachment.

BACKGROUND: Chronic rhegmatogenous retinal detachment behaves like proliferative vitreo-retinopathy (PVR) even without evidence of the same. Surgery could be done either with conventional buckling procedures where the extent of buckling is determined by the number and location of the breaks or by primary vitreous surgery. In this study these cases were managed with primary 360°encircling broad buckle without a vitreous procedure. METHODS: 210 eyes, with rhegmatogenous retinal detachment of more than six months duration and with PVR up to C3 (CP3 focal) were subjected to buckling surgery. Trans-scleral cryopexy of the breaks, 360°encircling buckle with a 276 - 279 tire and subretinal fluid drainage was performed. RESULT: Most (85.74%) of the eyes showed anatomical retinal re-attachment. CONCLUSION: Primary broad encircling buckling can be conducted successfully in cases of long standing retinal detachment.

Management of Nucleus and IOL Drop.

BACKGROUND: Thirty six cases of lenticular nucleus drop following phacoemulsification and 43 cases of posterior dislocation of intraocular lens (IOL) inclusive of two paediatric cases were managed by a modified vitrectomy procedure without using perfluorocarbon liquid (PFCL). METHODS: In these cases the incision was placed inferotemporally at pars plana. The limbal sites of the earlier cataract surgery were utilised as the other two ports. In either case adequate vitrectomy was performed first. In cases of nuclear drop, the nucleus was impaled (speared) with a micro vitreo retinal blade and brought into the anterior chamber from where it was delivered out. In cases of IOL drop the same was picked up by an intra-vitreal forceps. RESULT: Of the 77 adult cases treated 57 (74%) of the eyes had a visual recovery of 6/18 or more. CONCLUSION: Prompt surgical management in cases of nuclear drop or posterior dislocation of IOL yields good results.