ABSTRACT
Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive ectopic mineralization disorder, characterized by skin, eye and cardiovascular symptoms. The most devastating ocular complication is choroidal neovascularization, which is thought to be mediated by vascular endothelial growth factor (VEGF) signaling, a molecule encoded by the VEGFA gene. As early detection and treatment is essential to preserve vision, prioritization of patients at risk is crucial, but impossible because of wide phenotypic variability and a lack of genotype-phenotype correlations for PXE. This study aimed to validate the previously suggested association of five single nucleotide VEGFA variants (rs13207351, rs833061, rs699947, rs25648 and rs1413711) with a severe PXE retinopathy in an independent cohort. Direct Sanger sequencing was performed in 100 PXE patients, with a mild (56) or severe (44) PXE retinopathy. The inclusion criteria for severe retinopathy were a unilateral best-corrected visual acuity of <5/10 and/or the need for anti-angiogenic treatment. We found a significant association of three of five variants and borderline missed significance for one. These data further suggest the VEGFA gene to be a modifier gene for the PXE retinopathy. Hereby, we provide the necessary evidence to implement these variants in ocular risk stratification and individualized patient follow-up.
Subject(s)
Genetic Markers/genetics , Polymorphism, Single Nucleotide/genetics , Pseudoxanthoma Elasticum/genetics , Retinal Diseases/genetics , Vascular Endothelial Growth Factor A/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Choroidal Neovascularization/genetics , Cohort Studies , Female , Genetic Association Studies/methods , Humans , Male , Middle Aged , Prognosis , Skin/pathology , Young AdultABSTRACT
PURPOSE: To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. METHODS: A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. RESULTS: Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. CONCLUSIONS: In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.
Subject(s)
Choroidal Neovascularization/drug therapy , Pseudoxanthoma Elasticum/complications , Ranibizumab/administration & dosage , Visual Acuity , Angiogenesis Inhibitors/administration & dosage , Choroid/pathology , Choroidal Neovascularization/diagnosis , Choroidal Neovascularization/etiology , Female , Follow-Up Studies , France , Humans , Intravitreal Injections , Male , Middle Aged , Prospective Studies , Pseudoxanthoma Elasticum/diagnosis , Pseudoxanthoma Elasticum/drug therapy , Retrospective Studies , Tomography, Optical Coherence , Treatment OutcomeABSTRACT
The purpose of the study was to determine if implantation of blue-filtering intraocular lenses (IOLs) affects post-operative mood, inducing more depression, compared to patients undergoing implantation with conventional IOLs. The study was conducted at the Angers University Hospital, France. This was a prospective with a lowercase pilot study, including consecutive patients planned to undergo cataract surgery in both eyes within 1 week. The same type of IOL was used in both eyes of each patient. The choice of IOL was not randomized but driven by the habits and experience of each participating surgeon. Cognitively healthy patients (an MMSE score higher than 25) were assessed before and after surgery, using the 30-item geriatric depression scale (GDS) to seek symptoms of depression. Univariate and multiple logistic regressions were used to examine the association between the type of IOL and the 30-item GDS score improvement during the 3 months after lens implantation, while adjusting for participants' characteristics (age, visual acuity). Blue-filtering IOLs were used in 16 patients (mean ± standard deviation, 75.6 ± 7.5 years; 75 % female), and untinted IOLs in 18 patients (77.3 ± 6.9 years; 77.8 %female). Pre-operatively visual acuity and GDS scores were comparable in the two groups. The post-operative GDS score was improved by 1.91 ± 3.10 points in the whole sample (P = 0.002), as well as in each subgroup of patients. Three months after surgery, the mean change in GDS score did not differ between groups (P = 0.365), nor did the mean visual acuity (P = 0.198).
Subject(s)
Cataract Extraction , Depression/etiology , Filtration/instrumentation , Lens Implantation, Intraocular/instrumentation , Lenses, Intraocular/adverse effects , Light , Aged , Aged, 80 and over , Cataract Extraction/methods , Color Vision , Depression/diagnosis , Female , Humans , Lens Implantation, Intraocular/methods , Logistic Models , Male , Middle Aged , Pilot Projects , Postoperative Period , Prospective Studies , Psychiatric Status Rating Scales , Visual AcuityABSTRACT
INTRODUCTION: Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. CASE REPORT: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. CONCLUSION: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.