Purpose: To report a case of toxoplasma retinochoroiditis reactivation in an immunocompetent patient under atovaquone therapy. Methods: Case report. Results: A healthy woman with a history of ...bilateral toxoplasma retinochoroiditis since childhood presented with a reactivation of toxoplasma retinochoroiditis. Because earlier treatment regimens had either produced intolerable side effects and/or were deemed ineffective for the prevention of reactivation, the patient was started on atovaquone suspension (750 mg three times a day). After initial regression of the lesion and still under atovaquone therapy, the patient presented again five weeks later with worsened best-corrected visual acuity. Examination showed that the lesion had expanded again and more cells were present in the vitreous. Conclusions: To our knowledge, this is the first report of a reactivation of toxoplasma retinochoroiditis in an immunocompetent patient under atovaquone therapy, possibly indicating tachyzoite resistance to atovaquone.
There is much evidence that pigment-epithelium-derived factor (PEDF) is a potent antiangiogenic cytokine which inhibits retinal and choroidal neovascularization by inducing apoptosis in activated ...vascular endothelial cells. Furthermore, the regulation of PEDF appears to be linked to the regulation of vascular endothelial growth factor (VEGF), one of the most potent inducers of intraocular neovascularization. Previous studies have established that thermal photocoagulation, the mainstay in the therapy of various neovascular diseases of the posterior segment, results in a decrease in intraocular concentrations of VEGF and other angiogenic growth factors, thereby inhibiting active retinal neovascularization. In the current study, we sought to determine whether thermal photocoagulation has the potential to regulate the expression of PEDF in human retinal pigment epithelial (RPE) cells. Cultures of RPE cells were photocoagulated with a 532-nm diode laser. Subsequently, RNA was isolated for RT-PCR, and whole-cell extracts and precipitated cell culture supernatant were subjected to Western blot analysis. According to our results, PEDF mRNA and protein are significantly upregulated after photocoagulation. Moreover, PEDF protein was found to be secreted in the cell culture medium.
Resistance to activated protein C (APC) is among the coagulation disorders that have been implicated in retinal vein occlusion. However, since retinal vascular occlusions may be due to a combination ...of several mechanisms, the question of whether thrombophilic anomalies are pathogenic for this disorder remains controversial. In the current study, we investigated the prevalence of APC resistance in patients with retinal vein occlusion with reference to age and various cardiovascular risk factors. A cohort of 142 consecutive patients with retinal vein occlusion and a control group of 128 subjects matched for age, sex and several risk factors were screened for resistance to APC. Both cohorts were divided into two subgroups, according to the patient's age (< or =45 or >45 years) at the time of the retinal vein occlusion or a previous thromboembolic event. The proportion of individuals with resistance to APC was higher in the patient group (13 of 142; 9.1%) when compared to controls (6 of 128; 4.7%). Moreover, patient age < or =45 years by the time of the retinal vein occlusion or a previous thromboembolic event was significantly associated with a high prevalence of APC resistance (17%). By contrast, resistance to APC was present in 5 of 95 cases (5.3%) in the patient group >45 years and in 4 of 83 (4.8%) young controls. Our results indicate that APC resistance is highly prevalent in patients with retinal vein occlusion at age < or =45 years and/or with a history of thrombosis at this age. By contrast, the prevalence of APC resistance in patients who suffered a retinal vein occlusion when they were older than 45 years and had no history of thromboembolism appears to be similar to that seen in healthy control subjects or in the normal population. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects.
There is some evidence to suggest that thrombolysis has a beneficial effect in retinal vessel occlusion. However, there is concern that this therapeutic approach carries the risk of hemorrhage. ...Retrograde cannulation of the supraorbital arteries followed by irrigation with fibrinolytic agents may have the potential to minimize the risk of major complications. The study was conducted to investigate the anatomic and sonographic features of the supraorbital arteries.
This cadaver dissection study was performed on the orbits of 12 cadaveric specimens. In each orbit, the supraorbital region was dissected, followed by cannulation of the supraorbital vessels and injection of ink. In six orbits, the orbital vessels and the distribution of the injected ink were investigated. Continuous-wave Doppler sonographic analysis of the supratrochlear and the supraorbital artery was performed in 40 orbits of 20 volunteers to measure the distance between the arteries and the midline.
Cannulation with retrograde injection of ink was successfully performed in both the supratrochlear and the supraorbital arteries. The supratrochlear artery exhibited a more superficial course and a larger diameter than the supraorbital artery (1.08 +/- 0.19 mm vs. 0.86 +/- 0.19 mm SD). Dissection to the orbital apex revealed a spread of ink into the ophthalmic and the central retinal arteries. The average distance between the exit of the supratrochlear artery and the midline was found to be 16.4 +/- 1.7 mm (range, 13-20). The average distance between the exit of the supraorbital artery and the midline measured 26.5 +/- 2.6 mm (range, 23-35).
The findings of this anatomic and sonographic study support the concept of percutaneous supraorbital vessel cannulation as a potential approach to thrombolysis in retinal vessel occlusion. The supratrochlear artery appears to provide the most reliable access route.
To report an association between spontaneous subhyaloidal hemorrhage and severe plasminogen activator inhibitor-1 (PAI-1) deficiency.
Case report.
A 29-year-old woman presented with sudden, painless ...visual loss to hand motion in her right eye. Ophthalmoscopy showed a massive subhyaloidal hemorrhage. The patients' medical history was negative for cardiovascular risk factors, trauma, infections or bleeding complications. Further investigation into possible causes revealed hyperfibrinolysis secondary to severe PAI-1 deficiency. The non-clearing subhyaloidal hemorrhage was successfully treated by pars plana vitrectomy, and her visual acuity improved to 20/20.
When ordering laboratory tests in patients with spontaneous subhyaloidal hemorrhage to rule out fibrinolytic disorders, severe PAI-1 deficiency should be considered in the differential diagnosis. Selective screening may be helpful in identifying ophthalmologic patients with hyperfibrinolysis, especially in young individuals with subhyaloidal hemorrhages in the absence of other recognized risk factors.
To report an association between retinal vein occlusion and increased plasma levels of histidine-rich glycoprotein.
Observational case report.
A 56-year-old woman presented with sudden and painless ...decrease of visual acuity of her right eye. Indirect ophthalmoscopy revealed retinal vein occlusion. She had experienced central retinal vein occlusion in this eye 6 years earlier.
The patient’s medical history was negative for cardiovascular risk factors. Further investigation into possible causes revealed increased values for histidine-rich glycoprotein.
When ordering laboratory tests in patients with retinal vein occlusion to rule out coagulation disorders, increased plasma levels of histidine-rich glycoprotein should be considered in the differential diagnosis. Selective screening may be helpful in identifying retinal vein occlusion patients with thrombophilic defects, especially in young individuals with recurrent retinal vein occlusion in the absence of recognized cardiovascular risk factors.
Vascular endothelial growth factor (VEGF) is among the cytokines which have been implicated in the pathogenesis of choroidal neovascularization secondary to age-related macular degeneration (ARMD). ...There is, however, evidence that intercellular signaling molecules, such as nitric oxide (NO), are involved in this process. NO is synthesized via the inducible isoform of NO synthase (iNOS), which is expressed after induction by cytokines. In the current study, we investigated whether VEGF and iNOS are coexpressed in choroidal neovascular membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and in spatial relation to vessel walls. As scored by light microscopy, we found a significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341) in vascular endothelial cells. Our study supports a significant role for iNOS in the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our findings suggest a possible relationship between NO and VEGF in the regulation of pathologic angiogenesis in this disease.
To evaluate the efficacy and safety of intracameral recombinant tissueplasminogen activator (rt-PA) application for fibrinolysis of fibrin formation after cataract surgery in children.
Johann ...Wolfgang Goethe-University, Department of Ophthalmology; Frankfurt am Main, Germany.
This study comprised 11 eyes of 10 patients aged 3 to 13 years (mean7.2 ± 3.68 SD) who developed severe fibrin formation after cataract surgery and IOL implantation despite intensive topical steroid therapy. Under general anesthesia, fibrinolysis was performed with 10 μg of rt-PA 7.18 ± 2.04 days after intraocular surgery. Follow-up included slitlamp examination, tonometry, visual acuity testing, and ophthalmoscopy. Anterior chamber flare measurements could be performed in 6 eyes.
Complete resolution of fibrin formations occurred in 90% of the patients. Inthese cases, no recurrent fibrinous reaction or adverse effects were noted. In 2 eyes of the same patient with a history of juvenile rheumatoid arthritis and chronic uveitis, fibrin clot dissolution was incomplete. A recurrent fibrinous formation could be observed after 2 and 4 weeks, respectively. A beginning band kenatopathy excluding the central and limbal cornea, was noted after 6 and 8 weeks, respectively.
Intraocular application of rt-PA 'appears to be a safe and efficacious therapeutic approach in the management of severe fibrinous reactions after pediatric cataract surgery.
The serine proteases tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) and their inhibitor, plasminogen activator inhibitor (PAI)-1, regulate a variety of processes ...involved in tissue morphogenesis and differentiation. There is much evidence that plasminogen activator-mediated extracellular matrix degradation is an important step in the development of ocular neovascular diseases. The authors investigated whether expression of t-PA, u-PA, and PAI-1 in human retinal glial cells (HRGCs) is influenced by exposure to transforming growth factor (TGF)-beta, a cytokine that regulates the proliferation and differentiation of cells.
The extracellular release of t-PA, u-PA, and PAI-1 was measured by enzyme-linked immunosorbent assay (ELISA) in the supernatant of HRGC cultures, under basal conditions and after stimulation with TGF-beta at various concentrations (2, 5, 10, or 20 ng/mL). Reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze mRNA levels. Smad2 phosphorylation was detected by Western blot analysis.
Under basal conditions, HRGCs secreted considerable amounts of t-PA and PAI-1. Stimulation with TGF-beta resulted in increased synthesis of t-PA and PAI-1 protein in a time- and dose-dependent manner. Moreover, an increased expression of t-PA and PAI-1 mRNA after supplementation with TGF-beta was observed, with maximum expression at 12 hours. In contrast, HRGCs did not respond to TGF-beta with any change of u-PA production, although there were detectable amounts of u-PA mRNA and protein. Phosphorylation of Smad2 was increased after addition of TGF-beta. This effect was partially reversible after treatment with interferon-gamma.
The production of plasminogen activators and PAI-1 by HRGCs reflects the potential role of these cells in the progression of neovascular ocular diseases. Furthermore, the finding that t-PA and PAI-1 synthesis by HRGCs is mediated by TGF-beta and its downstream effector Smad2 confirms the importance of the TGF-beta signaling pathway in the regulation of interactions between retinal cells and the extracellular matrix.
BACKGROUND A 60 member Turkish kindred with autosomal dominant hypertension, which cosegregates completely with brachydactyly and short stature, was studied. Affected people have severe hypertension ...and generally die of stroke by the age of 50. The hypertension closely resembles essential hypertension and, accordingly, the mechanisms of blood pressure elevation are unknown. The gene responsible was mapped to chromosome 12p. METHODS All 29 affected family members underwent a basic physical examination and funduscopy. Other than markedly elevated blood pressures and the residua of stroke in a few subjects, the apparent lack of end organ damage was striking, including the normal appearing fundi. Five affected individuals were studied in a clinical research unit study. All underwent a complete ophthalmological examination. Fluorescein angiograms were obtained in three subjects. RESULTS Systolic blood pressures ranged from 170 to 250 mm Hg, while diastolic blood pressures ranged from 100 to 150 mm Hg in affected individuals. In all affected subjects, the fundi were only minimally altered or clinically normal. All three fluorescein angiograms were normal. Despite severe hypertension since childhood the patients showed no signs of hypertensive retinopathy. CONCLUSIONS The absence of hypertensive retinopathy in this novel form of inherited hypertension is due to an altered structure of retinal arteriolar walls or some other protective mechanism. Since evidence of end organ damage is scarce in other organs as well, the protective mechanism appears to be generalised.
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