Max Villain

Free radicals in retinal ischemia.

1. Reactive oxygen species (ROS) can be generated in biological tissues, including the retina, in particular under or after ischemia. They can provoke cell necrosis by reacting with cell components or they can trigger programmed cell death by activating specific targets. 2. Experiments based on electroretinography and electron spin resonance spin trapping analysis show that ROS are produced in the rabbit retina during ischemic episodes themselves as well as reperfusion. ROS are also generated as a consequence of ischemia by overstimulation of glutamate ionotropic receptors and calcium-dependent activation of enzymes such as phospholipase A2 and nitric oxide synthase. 3. The targets of ROS that can be responsible for functional damage of the retina are numerous: Na+-K+-ATPase inhibition leads to ionic imbalance and electroretinogram alteration; inhibition of glutamate transporter contributes to excitotoxicity. In addition, ROS can be deleterious by inducing protein synthesis (e.g., apoptotic proteins, vascular endothelial growth factor/vascular permeability factor). 4. In this short review, we consider the various mechanisms of ROS generation in retinal ischemia and the different effects of ROS so as to suggest possible effects of neuroprotective agents.

Nutritional, lifestyle and environmental factors in ocular hypertension and primary open‐angle glaucoma: an exploratory case–control study

Purpose:  To evaluate known and potential risk factors, including nutritional, lifestyle and environmental factors, differentiating patients with high‐tension primary open‐angle glaucoma (POAG) from control subjects with ocular hypertension (OHT).

Treatment of hypertension with renin-angiotensin system inhibitors and renal dysfunction: a systematic review and meta-analysis.

BACKGROUND To determine whether inhibitors of the renin-angiotensin system (RAS) reduce the incidence of renal dysfunction when compared to other antihypertensive treatments in patients with essential hypertension and no pre-existent renal disease. METHODS The search strategy used the Cochrane Library, Medline, previous meta-analyses, and journal reviews. The selection criteria included randomized, controlled trials of antihypertensive drugs that compared a RAS inhibitor with another treatment in essential hypertension. Studies that specifically enrolled only patients with diabetes or renal disease were not included. The quality assessment and data extraction of studies were performed by two independent reviewers. Effects on dichotomous renal outcome (serum creatinine (SCreat) higher than a prespecified value, doubling of SCreat or end-stage renal disease) and secondary continuous marker of renal outcome (change in SCreat) were calculated using Petos method. RESULTS 33,240 patients met the inclusion criteria for studies with a dichotomous outcome and 10,634 patients for studies with a continuous outcome. The mean follow-up was 42 ± 13 months. Patients randomized to RAS inhibitors did not show a significant reduction in the risk of developing renal dysfunction as compared to other antihypertensive strategies (odds ratio = 1.05; 95% confidence interval (CI) 0.89-1.25; P = 0.54). There was no significant difference in change of SCreat between groups (mean difference = 0.0005 mg/dl; 95% CI -0.0068 to 0.0077 mg/dl; P = 0.91). CONCLUSION In patients with essential hypertension and no pre-existent renal disease, prevention of renal dysfunction is not significantly different with RAS inhibitors when compared to other antihypertensive agents.

Visual acuity thresholds associated with activity limitations in the elderly. The Pathologies Oculaires Liées à l'Age study

Activity limitations, which induce loss of autonomy in the elderly, are a major public health problem. We investigated the associations between objectively determined visual impairments and activity limitations and assessed the visual acuity thresholds associated with these restrictions.

Retinal vascular caliber is associated with cardiovascular biomarkers of oxidative stress and inflammation: the POLA study.

Purpose Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology. Patients and Methods Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid. Results In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01). Conclusion In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.

Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture.

IMPORTANCE Postoperative endophthalmitis (POE) often results in severe visual impairment. In clinical studies, an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE. Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased. OBJECTIVE To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities, public or private, and whose medical records were obtained from the national administrative database. Data analyses were performed between March and November 2015. MAIN OUTCOMES AND MEASURES The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema. RESULTS From January 2010 to October 2014, a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older (58.9% were women, and the mean [SD] age was 73.9 [9.5] years) underwent cataract surgery; 1941 patients (0.08%) developed POE during the 6 weeks after cataract surgery. The incidence of POE after cataract surgery decreased over the course of the study (0.11%, 0.09%, 0.08%, 0.06%, and 0.05% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]) as the use of cefuroxime prophylactic injections increased (11.1%, 14.4%, 32.8%, 64.8%, and 79.1% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]). After multivariate adjustment, the risk of POE was reduced with the use of cefuroxime (odds ratio, 0.61 [95% CI, 0.56-0.68]). The retinal safety of an injection of cefuroxime, which was assessed by multiadjusted odds of retinal cystoid macular edema, was not increased for patients receiving cefuroxime injections (odds ratio, 0.86 [95% CI, 0.71-1.05]). For patients with a perioperative capsular rupture of the lens (the major risk factor for POE), the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not (0.37% vs 0.51%, respectively [P = .001]), whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime (5.6% vs 7.3%, respectively [P = .12]). CONCLUSIONS AND RELEVANCE These data suggest that, in routine practice, the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture. While these data might be used to support the consideration of its routine use to prevent POE, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between the injection of cefuroxime and POE.

Incidence and Characteristics of Cataract Surgery in France from 2009 to 2012: A National Population Study.

PURPOSE To report age- and sex-specific incidence rates of cataract surgery in France and evaluate the trends of cataract surgery from 2009 to 2012. DESIGN Cohort study. SUBJECTS Data for all patients who underwent primary cataract surgery in France between January 2009 and December 2012 were collected from the national database. METHODS Annual incidence rates were calculated and adjusted to the corresponding-year national population data from the French National Institute of Statistics. Kaplan-Meier analysis was used to assess the time between surgeries for both eyes. MAIN OUTCOME MEASURES Age- and sex-specific incidence of cataract surgery. RESULTS Over the 4 years, 2 717 203 eyes in 1 817 865 patients (59.1% were women; mean age, 73.5±0.015 years) underwent cataract surgery. Between 2009 and 2012, the total number of operated eyes per year increased, from 634 070 to 723 172 (+14.0%), and the number of patients with 1 or both eyes undergoing cataract surgery decreased, from 475 301 to 449 318 (-5.5%). The incidence of cataract surgery increased from 9.86 to 11.08/1000 person-years and that of operated patients (1 or both eyes) decreased from 7.39 to 6.89/1000 person-years. The incidence of cataract surgery ranged from 1.06/1000 person-years for patients aged 40 to 49 years to 65.94/1000 person-years for those aged 80 to 89 years. Between 2009 and 2012, the probability of second-eye surgery 12 months after the first-eye surgery increased from 40.6% to 51.2% (P < 0.0001). The median interval for surgery between eyes was 29 (interquartile range, 14-86) days. The rate of posterior capsular tear was 0.20%, with a higher proportion from extracapsular extraction than phacoemulsification (7.9% vs. 0.15%; P < 0.0001). The proportion of patients who underwent cataract surgery with a history of high myopia, eye trauma, or retinal detachment was 0.49%, 0.21%, and 0.80%, respectively. CONCLUSIONS This study documented the incidence and trends in cataract surgery in the overall population in France. Between 2009 and 2012, the number of people undergoing cataract surgery slightly decreased, but the total number of operated eyes increased because the proportion of surgeries on the second eye increased.

Visual Acuity Outcome and Predictive Factors after Bevacizumab for Central Retinal Vein Occlusion

Purpose. To evaluate the 12-month outcome and predictive factors of visual acuity (VA) changes following bevacizumab therapy for central retinal vein occlusion (CRVO). Methods. A total of 50 eyes from 50 patients with CRVO were consecutively included in this prospective study. Predictive factors were assessed by comparing baseline characteristics of patients classified into 3 groups: those showing a decrease in VA; those displaying a change in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score between 0 and 15; and those in whom an increase in VA ≥15 letters was achieved. Baseline variables considered in the analyses of predictive factors were demographic and clinical characteristics. Results. Mean baseline ETDRS letter score was 20±12 and mean macular thickness was 575.1±152.7 µm. Mean final ETDRS letter score improved significantly, reaching 27±20, p=0.04, while mean macular thickness decreased significantly to 391.1±229.6 µm, p<0.001. The predictive factors associated with an increase in VA ≥15 ETDRS letters were younger age (p=0.002), shorter duration of symptoms before treatment initiation (p=0.001), and a higher visual acuity pretreatment (p=0.004). The frequency of ischemic CRVO and low vision at baseline was higher among nonresponsive patients (p=0.005). Conclusions. Intravitreal bevacizumab seems to be an effective primary treatment option for macular edema due to CRVO. Its main drawback is that multiple injections are often necessary to maintain visual improvement. Early injections of bevacizumab in young patients in whom VA is relatively preserved leads to a significant improvement in VA. Ischaemic CRVO and poor baseline VA are associated with nonresponse to such therapy.

Visual impairment, optical correction, and their impact on activity limitations in elderly persons: the POLA study.

The loss of autonomy among older persons is a major public health issue. In the disablement process model1 chronic and acute conditions lead to psychological and physical deficiencies and ultimately to difficulty performing activities of daily life. In elderly, visual impairment is one of the major deficiencies leading to activity limitations and can be caused by either eye trauma or ocular diseases (affecting the ability to receive or process visual information), or by refractive errors (a failure of the eye to focus images sharply on the retina). Refractive errors affect about a third of the US and Western European populations.2 We estimated the proportion of uncorrected refractive errors and the potential improvement in daily life functioning that could be brought about by optimal visual correction.

Neuroradiological findings expand the phenotype of OPA1-related mitochondrial dysfunction

OBJECTIVE OPA1 mutations are responsible for more than half of autosomal dominant optic atrophy (ADOA), a blinding disease affecting the retinal ganglion neurons. In most patients the clinical presentation is restricted to the optic nerve degeneration, albeit in 20% of them, additional neuro-sensorial symptoms might be associated to the loss of vision, as frequently encountered in mitochondrial diseases. This study describes clinical and neuroradiological features of OPA1 patients. METHODS Twenty two patients from 17 families with decreased visual acuity related to optic atrophy and carrying an OPA1 mutation were enrolled. Patients underwent neuro-ophthalmological examinations. Brain magnetic resonance imaging (T1, T2 and flair sequences) was performed on a 1.5-Tesla MR Unit. Twenty patients underwent 2-D proton spectroscopic imaging. RESULTS Brain imaging disclosed abnormalities in 12 patients. Cerebellar atrophy mainly involving the vermis was observed in almost a quarter of the patients; other abnormalities included unspecific white matter hypersignal, hemispheric cortical atrophy, and lactate peak. Neurological examination disclosed one patient with a transient right hand motor deficit and ENT examination revealed hearing impairment in 6 patients. Patients with abnormal MRI were characterized by: (i) an older age (ii) more severe visual impairment with chronic visual acuity deterioration, and (iii) more frequent associated deafness. CONCLUSIONS Our results demonstrate that brain imaging abnormalities are common in OPA1 patients, even in those with normal neurological examination. Lactate peak, cerebellar and cortical atrophies are consistent with the mitochondrial dysfunction related to OPA1 mutations and might result from widespread neuronal degeneration.