Simultaneous Occurrence of Buckle Infection and Migration: A Case Report.

Background: When scleral buckling is performed using a #240 encircling band anterior to the equator for rhegmatogenous retinal detachment, buckle migration may occur anteriorly, eroding the rectus muscle. There are few cases of buckle migration occurring simultaneously with buckle infection. Notably, most previous reports included inadequate data on the pathophysiology of buckle migration and did not include the Hess test and perioperative images. Case presentation: A 36-year-old man with a history of atopic dermatitis underwent scleral buckling for rhegmatogenous retinal detachment of the left eye with #287 and #240 encircling bands at Kagoshima University Hospital. Four years later, he developed discharge, redness, and diplopia of the left eye. He was then referred to our hospital because buckle infection was suspected. The buckle was partially visible on the lower nasal side. Optical coherence tomography of the anterior chamber revealed the buckle to be on the nasal side and overlying the medial rectus muscle. Buckle migration and infection in the left eye was diagnosed, and early buckle removal was recommended. Two weeks later, on the day before surgery, conjunctival melting progressed in the nasal and inferior areas, and the buckle was exposed to a greater extent. In the surgical video at the initial surgery, the silicone band was confirmed to pass under the four rectus muscles, specifically the inferior and medial rectus muscles. At the beginning of the second surgery, we confirmed that the buckles were over the inferior and medial rectus muscles. As far as could be observed after buckle removal, the inferior and medial rectus muscles were not present at the normal location. Postoperatively, ocular pain and discharge quickly resolved. The subjective symptoms of diplopia also improved, and the postoperative Hess chart showed an improved ocular movement in the upward and lateral directions. Conclusions: Buckle migration is a rare postoperative complication of scleral buckling; however, patients at risk of buckle migration, such as those with encircling scleral buckle anterior to the eyeball, should be monitored with caution. If a buckle infection develops, buckle migration may occur within a short period, and early buckle removal should be considered.

Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab.

BACKGROUND: To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory. METHODS: Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss' kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography. RESULTS: Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann-Whitney U test). The inter-rater agreement was high with a Fleiss' kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann-Whitney U test). CONCLUSIONS: Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy.

NSAIDs inhibit neovascularization of choroid through HO-1-dependent pathway.

Intraocular neovascularization is the leading cause of severe visual loss and anti-vascular endothelial growth factor (VEGF) therapy is currently performed for choroidal neovascularization (CNV). Despite its potent anti-angiogenic effect, there are concerns about its long-term safety. Non-steroidal anti-inflammatory drugs (NSAIDs) are common therapeutic agents used for treating inflammatory diseases, and their anti-stress effects are attracting attention now. We studied the effects of topical NSAIDs on CNV, focusing on anti-stress proteins. Cultured retinal pigment epithelium (RPE) cells were treated with NSAIDs: bromfenac, indomethacin, or vehicle control. Transcription factor NF-E2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase (HO)-1 were assessed using western blot and immunohistochemistry. As a result, NSAIDs induced translocation of Nrf2 into the nucleus and the robust expression of HO-1 in a dose- and time-dependent manner. Flow cytometric analysis revealed that bromfenac inhibited H(2)O(2)-induced apoptosis in cultured RPE cells. Next, we studied the effects of topical bromfenac on laser-induced CNV model in rat. The expressions of Nrf2 and HO-1, infiltrations of ED-1-positive macrophages at CNV lesions and size were analyzed. VEGF in the ocular fluid of these rats was also measured using enzyme-linked immunosorbent assay. Rats administered an inhibitor of HO-1 stannic mesoporphyrin (SnMP) were also studied. The results showed that topical bromfenac led to translocation of Nrf2 and induction of HO-1 in CNV lesions and that the number of infiltrating macrophages at the CNV lesion decreased. The sizes of CNV lesions were significantly smaller in bromfenac-treated rats than control CNV, and the effects were diminished by SnMP. VEGF increased in the ocular fluid after laser treatment and was inhibited by bromfenac and SnMP canceling these effects. NSAIDs inhibit CNV through the novel anti-stress protein HO-1-dependent pathway, indicating its potential therapeutic value for various intraocular angiogenic diseases including CNV.

1,5-Anhydro-D-fructose: A natural antibiotic that inhibits the growth of gram-positive bacteria and microbial biofilm formation to prevent nosocomial infection.

Nosocomial infections caused by microbial opportunistic infections or microbial biofilms may occur during hospitalization and increase patient morbidity, mortality and health care costs. Artificial antibiotic agents were initially used to prevent infection; however, the high prevalence of nosocomial infections has resulted in their excessive use, which has led to microbial resistance to these agents. The increase in microbial resistance to antibiotics and the development of antibiotic agents may be the cause of the production of other microbial resistance. Thus, natural compounds that have no adverse side effects would be a preferred treatment modality. Recently, the monosaccharide 1,5-anhydro-D-fructose (1,5-AF), a natural plant compound derived from starch, has been found to have multifunctional properties, including antioxidant, antiplatelet aggregation by thrombin and anti-inflammatory activities. The results of the present study demonstrate that 1,5-AF suppressed the growth of coagulase-negative staphylococci on the hands as well as the growth of Staphylococcus epidermidis, which is a cause of opportunistic infections. Furthermore, 1,5-AF suppressed biofilm formation by the methicillin-resistant Staphylococcus aureus. In conclusion, 1,5-AF is a natural compound that may be effective in preventing nosocomial infections, without causing adverse side effects.

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction.

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

Edaravone: a new therapeutic approach for the treatment of acute stroke.

Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS.

B cell-derived vascular endothelial growth factor A promotes lymphangiogenesis and high endothelial venule expansion in lymph nodes.

Vascular endothelial growth factor A (VEGF-A) is a prominent growth factor for both angiogenesis and lymphangiogenesis. Recent studies have shown the importance of VEGF-A in enhancing the growth of lymphatic endothelial cells in lymph nodes (LNs) and the migration of dendritic cells into LNs. VEGF-A is produced in inflamed tissues and/or in draining LNs, where B cells are a possible source of this growth factor. To study the effect of B cell-derived VEGF-A, we created transgenic mice (CD19(Cre)/hVEGF-A(fl)) that express human VEGF-A specifically in B cells. We found that the human VEGF-A produced by B cells not only induced lymphangiogenesis in LNs, but also induced the expansion of LNs and the development of high endothelial venules. Contrary to our expectation, we observed a significant decrease in the Ag-specific Ab production postimmunization with OVA and in the proinflammatory cytokine production postinoculation with LPS in these mice. Our findings suggest immunomodulatory effects of VEGF-A: B cell-derived VEGF-A promotes both lymphangiogenesis and angiogenesis within LNs, but then suppresses certain aspects of the ensuing immune responses.