Effective Treatment with Intravitreal Injection of Bevacizumab for Exudative Retinal Detachment Secondary to Choroidal Metastasis of Non-Small Cell Lung Carcinoma.

BACKGROUND: Visual disturbance caused by cancer metastasis from other organs is one of the largest challenges to cancer patients' quality of life (QOL). Lung cancer is the most frequent primary site of choroidal metastasis in men, but improvement of visual disturbance has not always been emphasized in lung cancers. Recently intravitreal bevacizumab is a newer modality being tried for local control of choroidal metastases. CASE REPORT: A 68-year-old man was admitted the hospital with complaint of visual disturbance in his left eye. He was diagnosed with lung adenocarcinoma cT2N0M1b (OSS, OTH) stage IV. The ophthalmologic evaluation showed exudative fluid, which caused retinal detachment under the retina. Fluorescence angiography showed granular hyperfluorescence with leakage consistent with a tumor. He received radiotherapy for bone metastasis and systematic chemotherapy with carboplatin, pemetrexed, and bevacizumab, as well as intravitreal injection of bevacizumab 1.25 mg to improve the visual disturbance. His visual symptom and retinal detachment improved until he died. An autopsy revealed that the metastatic lesion in his left eye was totally cured macroscopically and microscopically. CONCLUSIONS: We report a case of exudative retinal detachment secondary to a metastatic choroidal tumor from lung adenocarcinoma, which was treated with chemotherapy and intravitreal injection of bevacizumab. Although he finally died of lung cancer, he maintained his visual QOL and autopsy revealed complete cure of the choroidal metastasis.

GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance.

Efficient engulfment of apoptotic cells is critical for maintaining tissue homoeostasis. When phagocytes recognize 'eat me' signals presented on the surface of apoptotic cells, this subsequently induces cytoskeletal rearrangement of phagocytes for the engulfment through Rac1 activation. However, the intracellular signalling cascades that result in Rac1 activation remain largely unknown. Here we show that G-protein-coupled receptor kinase 6 (GRK6) is involved in apoptotic cell clearance. GRK6 cooperates with GIT1 to activate Rac1, which promotes apoptotic engulfment independently from the two known DOCK180/ELMO/Rac1 and GULP1/Rac1 engulfment pathways. As a consequence, GRK6-deficient mice develop an autoimmune disease. GRK6-deficient mice also have increased iron stores in splenic red pulp in which F4/80(+) macrophages are responsible for senescent red blood cell clearance. Our results reveal previously unrecognized roles for GRK6 in regulating apoptotic engulfment and its fundamental importance in immune and iron homoeostasis.

Focal macular electroretinograms after photodynamic therapy combined with intravitreal bevacizumab.

BACKGROUND: Retinal function is transiently depressed after photodynamic therapy (PDT) alone. One of the reasons for this functional impairment is a reduction of choroidal circulation caused by the PDT. The purpose of this study was to determine whether PDT combined with intravitreal bevacizumab (PDT+IVB) can reduce or prevent the transient impaired macular function. In addition, we examined whether a significant correlation existed between the changes in the focal macular electroretinograms (FMERGs), optical coherence tomography (OCT)-determined morphology, and changes in choroidal circulation. METHODS: Thirty-eight eyes that were treated by full fluence PDT+IVB were studied. FMERGs, OCT, and indocyanine green angiography (ICGA) were performed before and after the PDT. The intensity of the diffuse fluorescence within the PDT site was measured by densitometry (I/N ratio). RESULTS: The macula was significantly thinner 1 week after PDT+IVB (P < 0.01). The mean a- and b-wave amplitudes of the FMERGs were not significantly decreased 1 week after PDT+IVB. The mean b-wave amplitudes 3 months after PDT+IVB were significantly increased (P < 0.01). The I/N ratio of ICGA 3 months after PDT+IVB was 0.88 ± 0.1. The correlation between the FMERGs and I/N ratio was not significant. CONCLUSION: The use of IVB with PDT mitigates the reduction of the FMERGs and reduces the macular thickness soon after PDT, regardless of the degree of impairment of choroidal circulation caused by PDT. Finally, the macular retinal function 3 months after PDT+IVB were better than that before the treatment.

Effect of photodynamic therapy alone or combined with posterior subtenon triamcinolone acetonide or intravitreal bevacizumab on choroidal hypofluorescence by indocyanine green angiography.

PURPOSE: Choroidal hypofluorescence has been reported beneath the photodynamic therapy (PDT) site in clinical studies. We evaluated the choroidal hypofluorescence after combined PDT with posterior subtenon injection of triamcinolone acetonide or PDT with an intravitreal injection of bevacizumab for age-related macular degeneration. METHODS: Two hundred and forty-two eyes with a subfoveal choroidal neovascularization caused by age-related macular degeneration were studied. Ninety-two eyes underwent PDT alone, 90 eyes underwent PDT with sub-Tenon injection of triamcinolone acetonide, and 60 eyes underwent PDT with intravitreal injection of bevacizumab. Verteporfin-induced choroidal hypoperfusion was determined by indocyanine green angiograms. The intensity of the diffuse fluorescence within the PDT site away from the choroidal neovascularization lesion and from the normal retina just peripheral to the optic disk was measured by densitometry (Topcon IMAGEnet computer system, Topcon, Tokyo, Japan) in the indocyanine green angiogram images obtained at 10 minutes 3 months after the PDT. The ratio of the average brightness of the retina within the PDT area to that of the retina peripheral to the optic disk (irradiated/nonirradiated retinal brightness ratio) was calculated for each angiogram. RESULTS: The irradiated/nonirradiated retinal brightness ratio of the angiograms was 0.96 in the PDT-alone group, 0.85 in the sub-Tenon injection of triamcinolone acetonide-PDT group, and 0.89 in the intravitreal injection of bevacizumab-PDT group (Kruskal-Wallis H test, P < 0.05). CONCLUSION: The degree of choroidal hypofluorescence in the indocyanine green angiogram images 3 months after PDT in the sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab group was higher than that of PDT-alone group. Sub-Tenon injection of triamcinolone acetonide and intravitreal injection of bevacizumab can prolong the duration of the choroidal hypofluorescence after PDT.

Differences in macular morphology between polypoidal choroidal vasculopathy and exudative age-related macular degeneration detected by optical coherence tomography.

PURPOSE: To evaluate the differences in the optical coherence tomographically determined macular morphology in eyes with polypoidal choroidal vasculopathy (PCV) from eyes with exudative age-related macular degeneration (AMD) quantitatively. METHODS: The medical records of 208 eyes of 203 Japanese patients with PCV or exudative AMD who were newly treated for choroidal neovascularization were reviewed. The six linear, low-resolution, high-speed scans of 6 mm were analyzed using a manually assisted computer algorithm, which allowed us to manually draw spline lines arbitrarily on the images so that the subretinal fluid and neurosensory retina could be segmented. The thickness of the neurosensory retina and height of the serous retinal detachment (SRD) within the central 3-mm and 6-mm areas were calculated. RESULTS: SRDs were observed in 53% (63/119) of the eyes with exudative AMD and in 78% (69/89) of the eyes with PCV (P < 0.001). The height of the SRD was 21.9 +/- 3.7 microm (+/-SEMs) in eyes with exudative AMD and 56.3 +/- 7.4 microm in eyes with PCV (P < 0.001). The thickness of the neurosensory retina was 300.0 +/- 5.2 microm in eyes with exudative AMD and 275.8 +/- 4.7 microm in eyes with PCV (P < 0.001). CONCLUSION: Eyes with PCV are characterized by a higher incidence of SRDs, greater SRD height, and less intraretinal edema than eyes with exudative AMD.

Elevated C-reactive protein levels in patients with polypoidal choroidal vasculopathy and patients with neovascular age-related macular degeneration.

PURPOSE: To determine the relationship between systemic C-reactive protein (CRP) levels and polypoidal choroidal vasculopathy (PCV) and advanced neovascular age-related macular degeneration (AMD) in Japanese patients. DESIGN: Case-control study. PARTICIPANTS: Ninety-seven patients with PCV, 176 with advanced neovascular AMD, and 262 control subjects without any macular abnormality were studied. METHODS: Color fundus photographs of the macular area were taken from both eyes in all subjects. Indocyanine green angiography and fluorescein angiography were performed for diagnosis. The CRP level was measured by a high-sensitivity assay using a latex aggregation immunoassay, and the levels in patients with PCV and neovascular AMD were compared with that in the control group using the Kruskal-Wallis test. Associations between CRP and PCV or neovascular AMD were compared using logistic regression analysis by computing the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles. MAIN OUTCOME MEASURES: The CRP levels in patients with PCV, patients with neovascular AMD, and control subjects. Standard univariate and multivariate analyses between groups. RESULTS: Median CRP levels were significantly higher in cases with PCV (0.94 mg/l) or with advanced neovascular AMD (0.95 mg/l) than in control subjects (0.43 mg/l) (P<0.001 for Kruskal-Wallis test). After adjusting for baseline characteristics such as age, gender, smoking status, alcohol use, body mass index, history, and use of antiinflammatory drugs, the increase in risk was significant for the highest quartile of CRP for both PCV (OR, 3.53; 95% CI, 1.49-8.40) and neovascular AMD (OR, 4.08; 95% CI, 1.94-8.56), and for the third quartile of CRP for neovascular AMD (OR, 2.29; 95% CI, 1.07-4.91). The trends for an increase in risk of disease with increase in CRP were statistically significant for both PCV (P = 0.001) and neovascular AMD (P<0.001). CONCLUSIONS: The significant associations between elevated serum CRP levels and PCV or neovascular AMD in the Japanese strongly suggest that inflammatory processes are involved in the pathogenesis of PCV and neovascular AMD.