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.

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital.

BACKGROUND: The aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients. METHODS: All patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis. RESULTS: During the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients. CONCLUSION: The COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Widefield optical coherence tomography angiography for early detection and objective evaluation of proliferative diabetic retinopathy.

PURPOSE: To evaluate the utility of widefield optical coherence tomography angiography (WF-OCTA) compared with clinical examination in grading diabetic retinopathy in patients diagnosed clinically with proliferative diabetic retinopathy (PDR) or severe non-proliferative diabetic retinopathy (NPDR). DESIGN: This retrospective observational case series included patients diagnosed clinically with PDR or severe NPDR. Patients underwent standard clinical examination and WF-OCTA imaging (PLEX Elite 9000, Carl Zeiss Meditec AG) using 12×12 montage scans between August 2018 and January 2019. Two trained graders identified neovascularisation at the disc (NVD) and neovascularisation elsewhere (NVE) on WF-OCTA which were compared with the clinical examination, and to ultra-widefield fluorescein angiography (UWFA) when available. RESULTS: Seventy-nine eyes of 46 patients were evaluated. Of those, 57 eyes were diagnosed clinically with PDR, and 22 with severe NPDR. NVD was detected on OCTA-B scan as preretinal hyperreflective material (PRHM) in 39 eyes (100%) with evident flow signals in 79.5% compared with 51.3% detected clinically. We further classified NVD on OCTA into four subtypes and found that subtypes 1 and 2 could not be seen on clinical examination alone. WF-OCTA detected NVE in 81% of the cases compared with 55.7% detected clinically. Using WF-OCTA resulted in a higher percentage of PDR grading (88.6%) than on clinical examination (72.2%). When available, UWFA confirmed the WF-OCTA diagnosis in the majority of cases. CONCLUSION: This study demonstrates that WF-OCTA has a higher detection rate of PDR than clinical examination. This suggests that this modality could be used non-invasively for the purpose of early detection and characterisation of neovascularisation.

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.

Scanning laser entoptic perimetry for the detection of age-related macular degeneration.

OBJECTIVE: To determine the sensitivity and specificity of scanning laser entoptic perimetry for detecting visual function damage due to age-related macular degeneration (ARMD). METHODS: We measured the presence or absence of visual field disturbances by entoptic perimetry and determined the severity of ARMD based on masked readings of fundus photographs. A prospective masked study comparing the findings of entoptic perimetry with fundus photographs was performed. We recruited 91 patients with ARMD and 24 patients without ARMD during ophthalmologic visits. An appropriate institutional review board approval was obtained for the project. The main outcome measure was the detection of visual scotomata. RESULTS: Scanning laser entoptic perimetry had an overall sensitivity of 82% and a specificity of 100% for the detection of ARMD. The sensitivity for early stages of the disease is greater than 70%, and increases to above 90% for moderate to late stages. CONCLUSION: Scanning laser entoptic perimetry is a specific and sensitive test for detecting ARMD, even at the earliest stages when patients are typically asymptomatic.

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.

Oral fluorescein angiography in patients with choroidal neovascularization and macular degeneration.

OBJECTIVE: To evaluate image quality of oral fluorescein angiography in patients with age-related macular degeneration and choroidal neovascularization. MATERIALS AND METHODS: Twenty four patients with proven choroidal neovascularization were examined in a prospective observational case series. Confocal oral and intravenous fluorescein angiography were performed using the Heidelberg Retina Angiograph. Oral and intravenous image quality were compared in a masked fashion. RESULTS: Choroidal neovascularization could be diagnosed in all patients using intravenous angiograms. Oral fluorescein angiography accurately detected the presence or absence of choroidal neovascularization in all patients and could determine the classification of choroidal neovascularization, location, and extent and borders in 20 (83.3%) of 24 patients. Early, mid, and late phases of oral angiograms occurred at 8, 15, and 26 minutes, respectively. CONCLUSION: Oral fluorescein angiography using the confocal Heidelberg Retina Angiograph allowed detection of choroidal neovascularization in all patients in this study. Visualization of extent and type of choroidal neovascularization was possible in most eyes with choroidal neovascularization. These findings suggest oral angiography is an excellent screening tool for choroidal neovascularization and allows guidance of treatment in the majority of cases.

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.

Human immunodeficiency virus type 2 (HIV-2) vector-mediated in vivo gene transfer into adult rabbit retina.

PURPOSE: To evaluate the potential usefulness of HIV-2 viral vector in in vivo retinal gene therapy. METHODS: An HIV-2 virus based viral vector was constructed and administered subretinally and intravitreally into rabbit eyes. After viral vector administration, the eyes were closely monitored for any adverse effects by slit lamp, indirect ophthalmoscopy, and fundus photography. Eyes were enucleated at specified times after injection, and reporter gene expression was identified within cell types and graded by the pattern and distribution of staining cells using fluorescent microscopy. RESULTS: The HIV-2 viral vector demonstrated efficient gene transfer into many types of retinal cells without apparent cytotoxicity. Notably with subretinal injection, the HIV-2 vector resulted in higher efficiency of transduction of photoreceptor cells than of the other cell types (p < 0.05). With the intravitreal administration of HIV-2 viral vectors, cellular transduction and transgene expression in the ganglion cell layer was the dominant finding. CONCLUSIONS: HIV-2 viral vector may be a useful gene delivery vehicle for retinal photoreceptor cells and ganglion cells. It deserves further exploration to investigate its potential merit in long term gene therapy protocols and in other animal species.

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.