Hermann Gümbel

Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions

OBJECTIVE 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. DESIGN Prospective, noncomparative case series. PARTICIPANTS 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. METHODS All patients were treated with intravitreous injections of rt-PA (50 microg) 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). MAIN OUTCOME MEASURES Best and final postoperative visual acuity in relation to size and onset of hemorrhage, displacement of subretinal blood, and surgical complications. RESULTS 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 <or=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. CONCLUSIONS 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 (<or=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.

Vitreous concentrations of TPA and plasminogen activator inhibitor are associated with VEGF in proliferative diabetic vitreoretinopathy.

PURPOSE In angiogenesis, matrix degradation is an important step in endothelial cell migration and proliferation. There is evidence that serine proteases, such as tissue plasminogen activator (TPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor (PAI), are involved in this process. We hypothesized that in eyes in which neovascularization is active, such as in proliferative diabetic vitreoretinopathy (PDVR), vitreous levels of these proteases are increased. Furthermore, correlation was sought between intraocular concentrations of serine proteases and vascular endothelial growth factor (VEGF), a multifunctional cytokine that has been shown to play a major part in mediating active neovascularization in patients with ischemic retinal diseases. METHODS Undiluted samples of vitreous fluid were obtained from patients who underwent vitreoretinal surgery for PDVR or retinal detachment. Vitreous levels of VEGF, TPA, UPA, and PAI were determined by enzyme-linked immunosorbent assay. RESULTS We found a statistically significant correlation between levels of VEGF and TPA (P<0.01) and VEGF and PAI (P<0.026) in the vitreous fluid of patients with PDVR. Concentrations of VEGF (P<0.03), TPA (P<0.042), and PAI (P<0.0098) in diabetic eyes were significantly higher than in nondiabetic eyes. Of 14 eyes with PDVR, 6 contained detectable levels of UPA. CONCLUSIONS A correlation between increased levels of VEGF and TPA or PAI in the vitreous fluid of eyes with PDVR reflects the possible role of plasminogen activators in the progression of this disease. An understanding of the endogenous inhibition of matrix degradation in ocular angiogenesis may be useful in the development of new treatment strategies.

In vitro inhibition of human cytomegalovirus replication by desferrioxamine

Desferrioxamine (DFO) is commonly used in therapy as a chelator of ferric ion in disorders of iron overload. We found that DFO inhibits human cytomegalovirus (HCMV) replication in infected cultures of human foreskin fibroblasts (HFF) at concentrations that have been achieved in humans with no significant adverse effects. The concentrations of DFO required for 50 and 90% reduction in the production of a HCMV-late antigen ranged for several HCMV strains from 3.1 to 4.9 microM and from 14.2 to 17.3 microM, respectively. DFO concentration of 60 microM had no significant effect on the viability of HFF cells. Inhibitory effects of DFO on HCMV replication were completely prevented by co-incubation with stoichiometric amounts of Fe3+.

In vitro inhibition of human cytomegalovirus replication in human foreskin fibroblasts and endothelial cells by ascorbic acid 2-phosphate

Antiviral activity of L-ascorbic acid-2-phosphate (ASC-2P), a long-acting derivative of L-ascorbic acid, against several human cytomegalovirus (CMV) strains was examined in cultures of human foreskin fibroblasts (HFF) and endothelial cells (EC). ASC-2P at concentrations ranging from 0.2 to 2 mM had no effect on the number of cells expressing 72 kDa CMV immediate early antigen (IEA) while it inhibited expression of 68 kDa late antigen (LA) in infected cultures of both cell types (30% and 55% reduction for EC and HFF, respectively). In HFF cells, virus yield was reduced up to 4-fold, when ASC-2P was added after CMV infection. Antiviral effects were significantly increased in cultures pretreated with ASC-2P. In HFF and EC pretreated for three subcultures (18 days) with 0.2 mM ASC-2P, a significant reduction of cells expressing IEA (75% and 80% reduction in EC and HFF, respectively) and LA (92% and 90% reduction for EC and HFF, respectively) was observed. Pretreatment for three subcultures with ASC-2P inhibited virus yield 50- to 100-fold in EC and 100- to 1000-fold in HFF. The continuous presence of ASC-2P was not required for its antiviral activity. A significantly higher reduction of virus replication with ganciclovir and foscarnet was obtained in ASC-2P pretreated cells than in untreated controls. The results showed that ASC-2P provides L-ascorbic acid with long-lasting antiviral activity against CMV. ASC-2P may be of benefit for the adjunctive treatment of CMV infection.

Reactivation of Toxoplasma Retinochoroiditis Under Atovaquone Therapy in an Immunocompetent Patient

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.

Induction of myogenic differentiation in a human rhabdomyosarcoma cell line by phenylacetate.

Sodium phenylacetate (NaPA) at concentrations ranging from 2 to 10 mM promoted myogenic differentiation of the human alveolar rhabdomyosarcoma cell line KFR. These concentrations inhibited DNA synthesis of the cells in a dose-dependent manner without significant effect on cell viability. The morphological differentiation of small mononuclear elements to terminal, elongated multinuclear structures resembling myotubes was accompanied by the expression of skeletal muscle myosin. The proportion of differentiated myosin-positive cells which was around 0.8-1.7% in control cultures 12 days after seeding was increased by NaPA treatment up to 47%. In the cytoplasm of differentiated cells, features of sarcomerogenesis were observed. These results suggest that NaPA is an effective inducer of rhabdomyosarcoma cell differentiation at concentrations that have been achieved in humans with no significant adverse effects.

Role of human cytomegalovirus genotype polymorphisms in AIDS patients with cytomegalovirus retinitis.

Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.

The human eye (retina): a site of persistent HCMV infection?

BackgroundHuman cytomegalovirus (HCMV) retinitis frequently occurs in severely naturally and iatrogenically immunocompromised patients. It has been shown that the immune-privileged retina is a major site of HCMV infection in AIDS patients. It is conceivable either that during the immunosuppression HCMV infection reactivates in various other organs viremically affecting the retina or that HCMV persisting in the retina may locally reactivate and result in HCMV retinitis.MethodsAs there is still controversy about the sites of HCMV latency and persistence we investigated 75 eyes of HIV-seronegative patients undergoing enucleation due to a variety of malignant and non-viral benign ophthalmic disorders for the retinal presence of HCMV antigen and DNA.ResultsNone of the analyzed patients had symptoms of HCMV retinitis. Immunohistologic staining as well as TaqMan DNA PCR analysis showed all samples to be free of HCMV.ConclusionsOur data suggest that the human eye is rather unlikely to be a site of productive or latent HCMV persistence.

[Bilateral influenza-triggered panuveitis and subsequent therapy with amantadine and hyperimmunoglobulins].

BACKGROUND Influenza A is one type of influenza virus that commonly causes acute respiratory illness. Outbreaks of influenza occur every year. Major antigenic variations preclude permanent immunity in the population. Often signs of conjunctivitis or photophobia are common during acute infection. Posterior uveitis is very rare. PATIENT A young lady with a diagnosed anterior uveitis was sent for further evaluation to the eye department with a known history of flu. RESULTS This patient had a severe ocular manifestation of influenza A infection. There was bilateral panuveitis with keratic precipitates, cells and flare, and an impressive retinopathy in both eyes. Serology was positive for influenza A. CONCLUSION The course of an influenza A infection is usually uncomplicated. Severe affection of the choriocapillaris results in a complicated post-influenza retinal pigmentary degeneration. Treatment with amantadine and therapy with hyperimmunoglobulins seem to be useful.

Emergency Treatment of Ocular Trauma.

Injuries to the eye and its adnexa are common in head and neck trauma centers. An ophthalmologist experienced in ocular traumatology is not always available. Therefore, every emergency physician should be familiar with the basic evaluation, triage, and management of ocular trauma. Above all, the identification of a need for immediate treatment should be implemented in the algorithm of an emergency room, especially in a head and neck trauma center, to reduce the risk of a devastating loss of vision. This article formulates the different types of ocular trauma and their required first-line therapy.