Kung-Hung Lin

Acute Vision Loss after Intravitreal Injection of Bevacizumab (Avastin) Associated with Ocular Ischemic Syndrome

Aim: To report a patient with diabetic rubeosis who suffered from acute retinal ischemic change and stroke after intravitreal injection of bevacizumab. Methods: A 55-year-old man had diabetes with unilateral rubeosis and macular edema. Three days after receiving intravitreal injection of bevacizumab (1.25 mg in 0.1 ml), he developed acute vision loss and change of consciousness. A complete ocular examination, fluorescein angiography, carotid artery Doppler sonography and brain magnetic resonance imaging were performed. Results: Best corrected visual acuity before injection was 6/60 in the left eye. He had underlying left carotid artery stenosis combined with bilateral preproliferative diabetic retinopathy. Three days after intravitreal injection of bevacizumab, acute ocular ischemic syndrome occurred. He also suffered from acute stroke, and brain magnetic resonance angiography showed total left internal carotid artery occlusion. The final visual acuity was no light perception in the left eye and 3/6 in the right eye. Conclusions: Patients receiving intravitreal injections of bevacizumab should be evaluated for potential systemic risk factors such as carotid insufficiency, coagulopathy and poorly controlled diabetes mellitus. Acute ocular ischemic change may be associated with intravitreal injection of bevacizumab in patients with vascular compromised diabetic retinopathy and/or underlying stenosis of the carotid artery.

Efficacy of Intravitreal Injections of Antivascular Endothelial Growth Factor Agents in a Rat Model of Anterior Ischemic Optic Neuropathy.

PURPOSE We investigated the efficacy of intravitreal injections of anti-VEGF agents in a rat model of anterior ischemic optic neuropathy. METHODS We applied laser-induced photoactivation on the optic nerve head after intravenously administered rose bengal (RB). The rats immediately received an intravitreal injection of either ranibizumab or PBS. The density of retinal ganglion cells (RGCs) was calculated using retrograde FluoroGold labeling. Visual function was assessed by flash visual-evoked potentials (FVEP). We investigated TUNEL assays of the retinal sections and ED1 staining of the optic nerve. RESULTS After treatment, the RGC densities in the anti-VEGF-treated rats were not statistically significant different from those of the PBS-treated rats (57.0% vs. 40.0% in the central retinas; 39.8% vs. 33.6% in midperipheral retinas, both P > 0.05). Measurements of FVEP showed no statistically significant differences in preserved latency or amplitude of the P1 wave between anti-VEGF and PBS groups (latency 131 ± 15 ms versus 142 ± 14 ms, P = 0.157; amplitude 34 ± 12 μv versus 41 ± 13 μv, P = 0.423). Assays of TUNEL showed that there was no statistical difference in the number of apoptotic cells in the RGC layers between anti-VEGF and PBS groups (7.0 ± 0.8 cells/high-power field [HPF] versus 7.8 ± 1.3 cells/HPF; P = 0.275). In the optic nerves, we did not observe statistically significant differences in ED1-positive cells/HPF between anti-VEGF and PBS groups (P = 0.675). CONCLUSIONS Intravitreal injections of anti-VEGF did not have a protective effect in the rat model of anterior ischemic optic neuropathy.

Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model.

Factors influencing the retrograde labeling of retinal ganglion cells with fluorogold in an animal optic nerve crush model.

Purpose: To investigate whether different crush durations or a different fluorogold (FG) injection timing can affect the efficiency of FG retrograde labeling of retinal ganglion cells (RGCs) in the optic nerve (ON) crush model. Methods: We performed the ON crush in rats with a clip at different durations or a jewel forceps to compare the effects of different crush methods with FG staining. RGC density was compared between the FG injection 1 week before the sacrifice of the animals (group A) and the injection before the crush experiment (group B). Double staining with CD11b and FG in the retinal sections was conducted to investigate the relationship between the overcounting of RGCs and microglia. Results: The FG-stained particles were significantly decreased at the distal part of the crush site compared to the proximal site of the ON with a crush duration of over 30 s or when crushed with the jewel forceps. Two weeks after ON crush, the RGC count was higher both in the central and mid-peripheral retinas in group B. The percentage of CD11b-stained cells among the FG-stained cells in the RGC layer of retinas in group B was higher than that of group A (34% in group B vs. 4% in group A, p = 0.0001). Overcounting of RGC density in group B was due to additional microglia with FG engulfing. Conclusions: Our results suggest that each laboratory should test its setting conditions to avoid factors influencing the RGC density measurement before conducting ON crush experiments.

Efficacy of Intravitreal Injections of Triamcinolone Acetonide in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy.

PURPOSE To investigate effects of intravitreal injections of triamcinolone acetonide (IVI-TA) at different times in a rodent model of nonarteritic anterior ischemic optic neuropathy (rAION). METHODS After inducing ischemic optic neuropathy, the rats received either IVI-TA (0.32 mg/2 μL) at 1 day (1d-TA), 1 week (7d-TA), 2 weeks (14d-TA), or PBS. The density of retinal ganglion cells (RGCs) was calculated using retrograde Fluorogold labeling. Electrophysiological visual function was assessed by flash visual evoked potentials (FVEPs). Apoptosis assays of the retinal sections and immunohistochemistry of ED1 staining of the optic nerves were performed. RESULTS Four weeks postinfarct, the 1d- and 7d-TA groups had significantly rescued RGCs in the central (2160 ± 250 mm(2), P = 0.004; 2050 ± 660, P = 0.008, respectively) and midperipheral retinas (1240 ± 130; 1250 ± 220, respectively, both P = 0.004) compared with those of the PBS-treated rats. Flash visual evoked potentials demonstrated improvements in P1 amplitude (μV) in the 1d- and 7d-TA groups (both P < 0.05). Assays of TUNEL showed a decrease in the number of apoptotic cells in the RGC layers of 1d- and 7d-TA-treated retinas compared with the PBS-treated group (both P = 0.004). Cells ED1-positive were significantly decreased in the optic nerve (ON) of the 1d- and 7d-TA groups compared with the PBS group (P = 0.004 and 0.02, respectively). CONCLUSIONS Within 1 week postinfarct of rAION, IVI-TA had neuroprotective effects on RGC survival with an increase in the electrophysiological amplitude of VEPs and a decrease in microglial infiltration in the ONs.

Protective effects of cerebrolysin in a rat model of optic nerve crush.

To investigate the effects of cerebrolysin (Cbl) on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model of ON crush. Rats received intravitreal injection of Cbl (n = 20), intra‐ON injection of Cbl (n = 20), intraperitoneal injection (IPI) of Cbl (n = 20), or phosphate buffered saline (PBS; n = 20) every day for 2 weeks after ON crush injury. At 3 weeks post‐trauma, RGC density was counted by retrograde labeling with FluoroGold and visual function was assessed by flash visual‐evoked potentials. Activities of microglia after insults were quantified by immunohistochemical analysis of the presence of ED1 in the optic nerve. At 3 weeks postcrush, the densities of RGCs in the Cbl‐IVI group (1125 ± 166/mm2) and in the Cbl‐IPI treatment group (1328 ± 119/mm2) were significantly higher than those in the PBS group (641 ± 214/mm2). The flash visual‐evoked potential measurements showed that latency of the P1 wave was significantly shorter in the Cbl‐IVI‐ and Cbl‐IPI‐treated groups (105 ± 4 ms and 118 ± 26 ms, respectively) than in the PBS‐treated group (170 ± 20 ms). However, only Cbl IPI treatment resulted in a significant decrease in the number of ED1‐positive cells at the lesion sites of the ON (5 ± 2 cells/vs. 30 ± 4 cells/high‐power field in control eyes). Treatment with intra‐ON injection of Cbl was harmful to the optic nerve in the crush model. Systemic administration of Cbl had neuroprotective effects on RGC survival and visual function in the optic nerve crush model.

Acute Ophthalmoplegia with Tonic Pupils

A 38-year-old female was diagnosed with atypical Miller Fisher syndrome (MFS) after she presented with bilateral ophthalmoplegia and bilateral tonic pupils without ataxia or areflexia following a flu-like infection. She had negative findings for a CSF examination, brain imaging and electrophysiological response; furthermore she was negative for serum ganglioside antibodies. We reported this interesting case and discuss the atypical presentation.

Treatment strategies for neuromyelitis optica

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease with pathogenic autoantibodies that act against the astrocyte water channel protein, i.e. aquaporin-4: the disease is associated with recurrent episodes of optic neuritis (ON) and transverse myelitis, often resulting in severe disability. The main goals in treatment of NMO include acute symptomatic therapy and long-term stabilization of symptoms by preventing relapse. In recent years, ongoing randomized controlled trials in NMO patients have studied evidence for treatment. Briefly, acute-stage management (with pulse therapy using corticosteroids and/or plasmapheresis) and maintenance therapy (including rituximab, mycophenolate mofetil, and azathioprine) have been recommended in some case series and retrospective studies. Because of the high prevalence of liver disease, all NMO patients in Taiwan should be screened for hepatitis B and C before treatment is initiated. Although immunosuppression and plasma exchange are the mainstays of therapy for NMO ON, several selective and potentially therapeutic strategies targeting specific steps in NMO pathogenesis including blockers of NMO-IgG binding and inhibitors of granulocyte function have been evaluated in recent years.

Contents Vol. 51, 2014

J. Alio, Alicante A.J. Augustin, Karlsruhe D. Balasubramanian, Hyderabad F. Bandello, Milano A. Bialasiewicz, Doha D. Borchman, Louisville, Ky. A. Bringmann, Leipzig T. Das, Hyderabad D. Goldblum, Basel G. Guarnaccia, Lugano K. Hegde, Baltimore, Md. J. Hua, Boston, Mass. N. Ibaraki, Shimotsuke-City T. Ishibashi, Fukuoka J. Jonas, Mannheim D. Lam, Guangzhou C. Meyer, Olten G.A. Moviglia, Buenos Aires N. Osborne, Oxford Y. Ozawa, Tokyo M. Rehak, Leipzig G. Richard, Hamburg K. Sasaki, Uchinada L. Schmetterer, Vienna J. Smith, Portland, Oreg. P. Söderberg, Uppsala J. Trevithick, London, Ont. K. Tsubota, Tokyo A. Wegener, Bonn J.O. Zárate, Buenos Aires Journal for Translational and Clinical Research