Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor. Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we ...report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated. In vitro analyses of mesenchymal stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A-mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension.
To investigate whether cataract surgery by phacoemulsification induces progression of early age-related macular degeneration (AMD) to neovascular AMD.
Retrospective case-control study. Included were ...consecutive patients who had undergone phacoemulsification from January 2000 to February 2006 at the Recklinghausen Eye Centre, who had a preexisting diagnosis of early AMD and who were followed up for at least 1 year after surgery (n = 1152 eyes of 696 patients). The control group comprised phakic patients diagnosed with early AMD from January 2000 to February 2006, who did not undergo eye surgery and were followed up for at least 1 year (n = 334 eyes of 202 patients).
At baseline, control eyes had significantly better visual acuity than those of patients who were going to have cataract surgery (0.30/0.35 +/- 0.34 vs. 0.40/0.49 +/- 0.34, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). After 1 year, visual acuity in the control group was worse than in surgical eyes (0.30/0.39 +/- 0.38 vs. 0.20/0.26 +/- 0.30, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). In the cataract surgery group, neovascular AMD developed in 28 (2.43%) of 1152 eyes in the first postoperative year. In the control group, it developed in 6 (1.74%) of 344 eyes within 1 year. There was no significant difference between the groups in the incidence of neovascular AMD (P = 0.57, odds ratio 1.30, 95% CI 0.52-3.24, logistic regression analysis, adjusted for age and baseline visual acuity).
The results indicate that cataract surgery in eyes with early AMD is not a causative factor in neovascular AMD.
The authors report their surgical experience after sustained-release ganciclovir treatment, as well as replacing empty ganciclovir implants in patients with acquired immune deficiency syndrome (AIDS) ...and cytomegalovirus (CMV) retinitis.
Between November 1995 and August 1998, 79 eyes of 49 patients received 99 intravitreal ganciclovir implants. Patients were examined monthly after implant surgery. Follow-up periods ranged from 6 to 128 weeks.
At the first 3-week postoperative visit, 73 eyes (97.2%) of 46 patients exhibited stable conditions. In 6 eyes (3.8%) of 3 patients, further progression was noted due to resistance to ganciclovir. The most common early complication (within 6 weeks after implantation) was cystoid macular edema, observed in 7 eyes receiving implants. Retinal detachment was the most common late complication (over 6 weeks after implantation) in 11 eyes. In almost all eyes with CMV retinitis and retinal detachment, involvement of more than 25% of the retina was observed. Additional severe complications included extrusion of the first pellet in 2 eyes and cataract as a late complication in 5 eyes. A total of 28 eyes (35.4%) of 16 patients receiving a second implant did not experience significant three-line loss by the end of the follow-up period.
In the treatment of CMV retinitis, sustained-release ganciclovir implantation seems to be an alternative to intravenous ganciclovir. Early implantation and additional replacement of the device has the potential to decrease the risk of developing retinal detachment. We would recommend additional systemic antiviral CMV therapy to avoid infection of the fellow eye and CMV disease.
Zusammenfassung
Hintergrund
Umfrage der „Kommission Sektorenübergreifende Augenheilkunde“ als gemeinsame Kommission der Deutschen Ophthalmologischen Gesellschaft (DOG) und des Berufsverbandes der ...Augenärzte Deutschlands (BVA) zu den Auswirkungen der SARS-CoV-2-Pandemie auf die ophthalmologische Versorgung in Deutschland.
Methoden
Online-basierte Umfrage.
Ergebnisse
Insgesamt wurden 1190 Fragebögen (teilweise) beantwortet. Die Ambulanz- bzw. Sprechstundentätigkeit in der Zeit vom 15.03. bis 15.04.2020 gaben 69 (5,8 %) Teilnehmer mit „uneingeschränkt“, 756 (63,5 %) mit „reduziert“ und 330 (27,7 %) als „ausschließliche Notfallversorgung“ an, unabhängig von der Art der Einrichtung. Ambulante Operationen waren in 68,0 % der Hauptabteilungen, 42,0 % der Belegabteilungen, 45,0 % der operativen MVZ und Gemeinschaftspraxen und 33,0 % der operativen Einzelpraxen notfallchirurgischen Eingriffen vorbehalten. Stationäre Eingriffe waren in 75,0 % der Belegabteilungen und in 71,0 % der Hauptabteilungen auf die Versorgung von Notfällen beschränkt. Die Fallzahlen dringlicher Indikationen und Notfälle waren mit Ausnahme der Endophthalmitis (+8,2 %) rückläufig: Amotio retinae (−34,8 %), Bulbusperforation (−7,3 %), Glaukomanfall (−17,8 %), ZAV und AION (−31 %), Sonstige (−30,9 %), perforierende Keratoplastik und Amnionmembrantransplantation (−59,1 %). Institutionelle oder berufspolitische Vorgaben (76,0 %) sowie Terminabsagen durch Patienten (84,0 %) waren der häufigste Grund für eine Einschränkung der ophthalmologischen Versorgung.
Schlussfolgerung
Während der Pandemie kam es initial zu einer erheblichen Reduzierung nichtdringlicher konservativer und chirurgischer Behandlungen, von der alle Bereiche der Augenheilkunde betroffen waren. Aufgrund der für COVID-19-Patienten benötigten Intensivkapazitäten waren insbesondere stationäre Behandlungen weitgehend auf Notfälle beschränkt. Die Versorgung ophthalmologischer Patienten einschließlich Notfällen und dringlicher Behandlungen konnte sektorübergreifend aufrechterhalten werden, wobei für beide Gruppen ein (deutlicher) Rückgang der Fallzahlen beobachtet wurde.
To investigate the efficacy and safety of treating submacular hemorrhages secondary to age-related macular degeneration (ARMD) with intravitreous recombinant tissue plasminogen activator (rt-PA) and ...gas under various conditions.
Prospective, noncomparative case series.
Forty-three consecutive eyes of 42 patients with recent (range, 2–28 days) subfoveal hemorrhage secondary to ARMD were included in this study. The size of subretinal hemorrhage ranged from 0.25 to 30 disc areas.
All patients were treated with intravitreous injections of rt-PA (50 μg) and sulfur hexafluoride (0.5 ml). Postoperative prone positioning was maintained for 24 to 72 hours. Patient follow-up ranged from 4 to 18 months (mean, 6 months).
Best and final postoperative visual acuity in relation to size and onset of hemorrhage, displacement of subretinal blood, and surgical complications.
Best postoperative visual acuity compared with preoperative visual acuity was improved two or more Snellen lines in 19 eyes (44%) and stable in 24 eyes (56%). Final visual acuity was improved two or more lines in 13 eyes (30%), stable in 26 (61%), and two or more lines worse in 4 eyes (9%). Duration of hemorrhage ≤14 days was associated with a better gain of lines of vision (
P = 0.0058). Best postoperative acuity was maintained for an average of 4.2 months (range, 0.5–12 months). Overall, complete displacement of blood from under the fovea was achieved in 35 eyes (81%). Nine eyes (21%) developed recurrent hemorrhage, which required repeat treatment. In three patients (7%), a mild breakthrough vitreous hemorrhage was observed.
Our findings suggest that intravitreous injections of rt-PA and gas are of value for an improved and accelerated visual recovery in ARMD patients with submacular hemorrhage, although final visual outcome is often limited by the progression of the underlying ARMD. Patients with retinal hemorrhages of recent onset (≤14 days) seem to have the most favorable results. A rapid displacement of submacular blood may reveal discrete choroidal neovascular membranes amenable to further treatment. The complication rate of this minimally invasive technique seems to be low.
Over the past years, there has been a dramatic increase in the number of identifiable causes of thrombophilia. However, to date, there are no large, prospective studies to assess an optimal, ...cost-effective approach with regard to screening and case finding for thrombophilic risk factors in patients presenting with retinal vessel occlusion. Two hundred twenty-eight patients with retinal vein occlusion (RVO) and 130 age-matched healthy controls were prospectively screened for thrombophilic risk factors. Both cohorts were divided into three subgroups, depending on the patients' age at the time of the RVO or a previous thromboembolic event. Patient age < or =45 years was associated with a high prevalence of coagulation disorders (p<0.0001). Among patients < or =45 years and >45 to < or =60 years, a family history of thromboembolism was strongly associated with the presence of thrombophilic disorders. The absence of cardiovascular risk factors was found to be a strong predictor for the presence of coagulation disorders in all patient groups (< or =45 years, p=0.003; >45 to < or =60 years, p=0.0008; >60 years, p=0.001). Multivariate analysis revealed the presence of resistance to activated protein C (p=0.014), antiphospholipid antibodies (p=0.022), and deficiency of the anticoagulant proteins (p=0.05) as independent risk factors for the development of RVO among patients < or =45 years. Our results indicate that thrombophilic disorders are associated with the development of retinal vein occlusion in patients < or =45 years by the time of the RVO or a previous thromboembolic event, in patients with a family history of thromboembolism, or in patients without cardiovascular risk factors.
Factor XII deficiency is among the coagulation disorders that have been implicated in major thromboembolic events. However, little is known about an association of this coagulation disorder and ...retinal vessel occlusion. In the current study, we investigated the prevalence of factor XII deficiency in patients with retinal vein occlusion (RVO) with reference to age and cardiovascular risk factors.
Cross-sectional study.
A cohort of 150 consecutive patients with central or branch retinal vein occlusion and 135 subjects matched for age and gender were prospectively screened for factor XII deficiency. Both cohorts were divided into two subgroups (≤45 or >45 years), depending on the patients' age at the time of the RVO or a previous thromboembolic event.
Overall, factor XII deficiency was found to be present in 14 (9.3%) of 150 patients and in 1 (0.7%) of 135 controls (P = .0009). Patient age ≤45 years at the time of the RVO or a previous thromboembolic event was associated with a high prevalence of factor XII deficiency (18%). By contrast, only 5 (5%) of 100 patients >45 years (P = .016) and none of the young controls (P = .0001) tested positive for factor XII deficiency. The prevalence among patients >45 years was similar to that found in age-matched controls (2%; P = .66).
Our results indicate that factor XII deficiency is highly prevalent in RVO patients ≤45 years of age. By contrast, the prevalence of factor XII deficiency in RVO patients older than 45 years appears to be similar to that seen in healthy individuals.
Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data ...is lacking to address this question.
REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO.
Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial.
Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted.
Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm.
By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology.
ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.
Nitric oxide (NO) is an important signal-transduction molecule that plays a significant role in the regulation of cardiovascular functions. In the L-arginine-NO pathway, NO synthase (NOS) converts ...L-arginine (L-Arg), the only known biologic substrate for NO formation, to NO and L-citrulline (L-Cit). Excessive NO production mediated by the inducible isoform of NOS has been implicated in the pathogenesis of various diseases. In the present study it was hypothesized that in vitreoretinal disorders such as diabetic retinopathy the production of L-Arg-NO pathway-related metabolites may be upregulated as a result of increased NO generation.
From 20 eyes of nondiabetic subjects and 22 eyes of diabetic patients with (n = 14) and without (n = 8) diabetic retinopathy, undiluted samples of aqueous humor were drawn before cataract surgery. Levels of L-Arg, L-Cit, and the specific NOS by-product N(G)-hydroxy-L-arginine (HOArg) were measured by high-performance liquid chromatography.
L-Arg, L-Cit, and HOArg were detected in all aqueous humor samples from diabetic and nondiabetic patients (n = 42). Comparison of HOArg levels in nondiabetic and diabetic subjects showed significantly higher levels in diabetic patients (P = 0.002). Concentrations of HOArg were higher in samples from patients with (P = 0.005) and without diabetic retinopathy (P = 0.033) than in control subjects. No statistically significant differences were observed in L-Arg or L-Cit levels.
Elevated levels of HOArg in the aqueous humor of diabetic patients reflect the possible role of NO as a significant factor in the regulation of retinal vascular functions and intraocular proliferative changes in diabetes mellitus in vivo. The control of intraocular NO production may constitute a potential therapeutic approach in diabetic retinopathy.
PDF
