Correlation of Asymmetric Dimethyl Arginine Level to Sickle Retinopathy in Children With Sickle Cell Disease.

Asymmetric dimethyl arginine (ADMA) is a competitive inhibitor of nitric oxide synthetase especially in L-arginine deficiency, which is the case in sickle cell disease (SCD). we aimed to assess the level of ADMA in children with sickle retinopathy and to correlate it to the degree of retinopathy. In this cross-sectional study 40 children with SCD were included, 20 of them with sickle cell retinopathy (SCR) (group I), 20 with normal fundus examination (group II), and another 20 healthy children served as controls (group III). We measured ADMA level by ELISA and performed fundus examination. Seventeen of the 20 children included in group I had Grade I retinopathy (85%), 2 children had Grade II retinopathy (10%), and 1 child had Grade III retinopathy (5%). ADMA was significantly higher in SCD than controls ( P -value <0.001), and it was even higher in patients with SCR compared those without retinopathy ( P -value <0.002), and there was positive linear correlation between ADMA and the grade of retinopathy. The type of retinopathy detect in the studied patients was the nonproliferative type. In conclusion, ADMA is elevated in children with SCD, and its level is even higher in those who develop SCR.

Vascular endothelial growth factor gene polymorphism prevalence in patients with diabetic macular oedema and its correlation with anti-vascular endothelial growth factor treatment outcomes.

BACKGROUND: To study the possible association between vascular endothelial growth factor gene polymorphism and diabetic macular oedema, and its correlation to the outcomes of anti-vascular endothelial growth factor treatment. DESIGN: Prospective study. PARTICIPANTS: 392 diabetic patients were included; 180 patients of them had no retinopathy, 212 patients had diabetic retinopathy. Diabetic retinopathy patients were classified into four groups as defined by the absence or presence of macular oedema or proliferative retinopathy. METHODS: In all subjects, polymerase chain reaction-restriction fragment length polymorphism was conducted to detect the vascular endothelial growth factor gene C-634G polymorphism. Serum levels of vascular endothelial growth factor were estimated. Changes of visual acuity and central macular thickness after bevacizumab treatment in diabetic macular oedema patients of different genotypes were monitored for 9-12 months. MAIN OUTCOME MEASURES: Vascular endothelial growth factor C-634G genotypes distribution in different groups; correlation between genotypes, and changes in visual acuity and central macular thickness after intravitreal bevacizumab treatment. RESULTS: CC genotype was significantly prevalent among diabetic macular oedema patients (P = 0.019). Significant higher serum levels of vascular endothelial growth factor were detected in diabetic retinopathy and diabetic macular oedema patients with CC genotype (P = 0.02, 0.016). After bevacizumab treatment, individuals with genotypes CG and GG have a decreased chance of positive treatment outcomes compared t with CC genotype (P < 0.001). CONCLUSIONS: Vascular endothelial growth factor C-634G polymorphism (CC genotype) is a genetic risk factor for diabetic macular oedema, and its presence provides significantly better visual outcome following bevacizumab treatment.

The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinase, on a new animal model of epiretinal membrane.

PURPOSE: To develop a simple epiretinal membrane (ERM) animal model and evaluate the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase. METHODS: This experiment was carried out on 18 eyes of nine Brown Norway rats. Preretinal hemorrhage was induced bilaterally using diode laser focused deeply on choroidal blood vessels. One day later, AG3340 was injected intravitreally in the right eyes while the left eyes received equal amounts of vehicle. The developed epiretinal membrane was measured in disk areas and compared between groups. RESULTS: Clinically, preretinal hemorrhage showed a slow clearance persisting for 8 to 10 weeks. ERM was well established around 12 weeks. Histologically, ERMs consist of fibroblast and glial cells embedded in collagen-rich extracellular matrix infiltrated by macrophages. Seventy-five percent of the hemorrhagic laser burns in the control group developed ERM, whereas only 25% of the hemorrhagic laser burns in treated group developed ERM (P = 0.01). The total surface area of developed ERM was 3.66 DD in treated eyes versus 25.45 DD in control eyes (P = 0.049). The mean surface area of ERM per eye was 0.52 disk areas +/- 1.05 in treated eyes versus 3.18 +/- 3.07 in control eyes. CONCLUSION: We demonstrated that ERM can be induced on rat retina by simple hemorrhagic retinal laser coagulation. This new animal model could be used for future evaluation of different medical treatment modalities for proliferating ERM. Furthermore, AG3340 demonstrated an inhibitory effect on ERM formation in this new rat model.

Long-term results of treatment of macular complications in eyes with immune recovery uveitis using a graded treatment approach.

PURPOSE: To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis. METHODS: A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol. RESULTS: Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery. CONCLUSION: Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration.

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment. DESIGN: Randomized controlled clinical trial. METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes. RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes. CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.

Effects of preoperative and postoperative epiretinal membranes on macular hole closure and visual restoration.

OBJECTIVE: To investigate the effects of epiretinal membranes (ERMs) on macular hole surgical results and postoperative visual restoration. DESIGN: A subgroup analysis arising from a multicenter, controlled, randomized clinical trial. PARTICIPANTS: Ninety-one phakic eyes with an idiopathic macular hole that underwent standard vitrectomy for macular hole repair with or without ERM peeling. METHODS: Preoperative, intraoperative, and postoperative data of macular status, ERM status, and visual function status were recorded, and their relationships were analyzed. MAIN OUTCOME MEASURES: Visual acuity and clinical features of macular hole and ERM on baseline examination and scheduled follow-ups. RESULTS: ERM peeling was associated with greater anatomic hole closure success rates (67% of the ERM peeled vs. 35% of nonpeeled, P = 0.03) but not associated with visual improvement in eyes with anatomic hole closure (2.9 lines improvement vs. 3.6 lines improvement, P > 0.5). Macular hole reopening was associated with excessive ERM growth (P = 0.005). Postoperative ERMs were more common in the eyes that underwent cataract surgery after vitrectomy (77% in aphakic and 36% in phakic eyes, P = 0.02). Macular hole edge approximation or hole appearance after initial vitrectomy for hole repair was stable over the average 18-month period in 89% of the eyes; only approximately 10% of the eyes underwent changes in their hole appearance. The hole edge approximation or hole appearance was associated with preoperative hole size and postoperative visual acuity. Preoperative hole size was found to be the major predictor of postoperative visual acuity (P < 0.005). CONCLUSIONS: Surgical ERM peeling increases the anatomic hole closure rate. The presence of postoperative ERMs was not associated with postoperative visual acuity; however, excessive ERM growth contributed to hole reopening. Preoperative hole size was the most sensitive predictor for postoperative visual acuity. Surgical intervention during the early stages of macular hole before ERM formation is strongly recommended.