Use of Whole-body FDG PET-CT to Aid in the Diagnosis of Occult Sarcoidosis

Purpose: To report a case where combined whole-body Fluorine-18 fluorodeoxyglucose (FDG) PET-CT scanning was used to aid in the diagnosis of a patient with occult sarcoidosis. Design: Case report. Methods: FDG PET-CT scanning was performed in a patient who presented with persistent bilateral panuveitis after cataract surgery and had undergone an extensive negative workup. Results: FDG PET-CT scanning demonstrated extensive mediastinal adenopathy. Biopsy showed a non-caseating granuloma with associated giant cell formation consistent with a diagnosis of sarcoidosis. Conclusions: FDG PET-CT scanning generates tomographic scans with excellent sensitivity, spatial resolution, and anatomical landmark identification and may be useful in the workup of idiopathic uveitis.     

Whole-body fluorine-18 fluordeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in staging of advanced uveal melanoma

Fluorine-18 fluordeoxyglucose positron emission tomography (FDG-PET) is an useful tool in diagnosing and monitoring of malignant cutaneous melanoma. However, the feasibility and usefulness of FDG-PET in uveal melanoma is not yet established. We present a patient with suspected advanced uveal melanoma who underwent combined FDG-PET/computed tomography (CT) for staging. FDG-PET/CT images demonstrated vital intraocular tumor. Anatomical assignment of the malignancy to the choroid was possible by means of the coregistered computed tomography. Furthermore, PET revealed an unknown otherwise undetected vital liver metastasis. We conclude that combined FDG-PET/CT has potential to further improve staging and therapy planning in patients with advanced uveal melanoma.     

Lacrimal Gland Uptake of 67Ga-gallium Citrate Correlates with Biopsy Results in Patients with Suspected Sarcoidosis

Abstract

Purpose: To investigate whether lacrimal gland uptake on ⁶⁷Ga-gallium citrate scintigraphy correlates with histopathologic evidence of sarcoidosis.

Methods: A retrospective, pilot study of 31 patients with suspected sarcoidosis who underwent gallium scintigraphy and lacrimal gland biopsy. Lacrimal gland gallium uptake was assessed by subjective visual scoring (SVS) and lacrimal uptake ratio (LUR).

Results: Eleven (36%) patients had lacrimal gland biopsies containing noncaseating granulomas. A statistically significant correlation was found between lacrimal gland gallium uptake and biopsy positivity using SVS (p?=?0.03) or LUR (p?=?0.01). Using SVS, biopsy positivity rate increased from 0 to 50% in patients with mild to intense uptake. Using LUR, biopsy positivity rate increased linearly as the ratio increased from 13% (LUR?<?4) to 100% (LUR?>?8).

Conclusions: Lacrimal biopsy positivity rate significantly correlated with gallium uptake on scintigraphy. Both SVS and LUR methods appear to correlate with histologic results and may potentially aid in patient selection for biopsy.     

Effect of lodoxamide on tear leukotriene levels in giant papillary conjunctivitis associated with ocular prosthesis

Leukotrienes have been shown to play a role in the patho-genesis of ocular inflammatory and allergic reactions like vernal kerato-conjunctivitis and contact lens-associated giant papillary conjunctivitis. This study was designed to determine leukotriene B4 (LTB4) and leukotriene C4 (LTC4) levels in the tears of patients with ocular prosthesis-associated giant papillary conjunctivitis (OP-GPC) and to evaluate the effects of lodoxamide 0.1% on tear LTB4 and LTC4 levels of OP-GPC patients. Tear LTB4 and LTC4 levels were determined by an ELISA technique in the tears of ten OP-GPC patients before and after treatment with lodoxamide 0.1% for one month. The results were compared with that of ten healthy control subjects. The mean tear LTB4 and LTC4 levels of the OP-GPC patients were significantly higher than those of the control group. After treatment with lodoxamide 0.1%, tear LTB4 and LTC4 levels of the OP-GPC patients decreased significantly. This is the first report of elevated LTB4 and LTC4 levels in tears of OP-GPC patients and it points to the possible role of leukotrienes in the immunopathogenesis of OP-GPC. The results also indicate that lodoxamide 0.1%, a mast cell membrane stabilizer, is effective in significantly reducing tear LTB4 and LTC4 levels in OP-GPC patients.     

自身免疫性干眼调节T细胞及细胞因子的表达

目的：探究调节性T细胞在自身免疫性干眼发病中的作用,并对泪液系统内调节性T细胞及相关细胞因子的表达做出分析,为自身免疫性干眼病的治疗提供更加有效的治疗方案。

方法：单独培养提纯分离出的兔泪腺上皮细胞一段时间后,将其与分离出的外周血淋巴细胞以1：1的比例混合进行培养,并用5-脱氧尿嘧啶核苷(5-Bromo-2-deoxyUridine,BrdU)检测外周血淋巴细胞的增殖情况,将已激活的自体外周血淋巴细胞通过耳缘静脉回输供体兔体内,回输细胞后的供体兔将作为兔自身免疫性干眼模型组,未诱导发病的正常兔个体为对照组,观察实验前后兔角膜染色和2、4、6、8wk的泪膜破裂时间、泪液的分泌等情况,回输细胞4wk后处死,收集双侧上下泪腺和结膜,并进行病理HE染色,然后提取泪腺组织中的总RNA,检测IL-17、TNF-α、IL-6、TGF-γ的表达。

结果：BrdU检测出的外周血淋巴细胞增值比率为3.72,激活的外周血淋巴细胞回输体内会诱导产生兔自身免疫性干眼,与正常组比较,泪膜破裂时间减少,且差异具有统计学意义(P<0.05); 模型组较对照组泪液分泌显著减少,且差异具有统计学意义(P<0.05); HE染色显示在回输细胞4wk后,结膜组织和泪腺均有淋巴细胞浸润,检测发现模型组IL-17、TNF-α、IL-6、TGF-γ的表达较对照组均有所增加,但IL-10、TGF-β的表达较对照组有所降低,且差异具有统计学意义(P<0.05); 流式细胞术检测表明,在对照组中,泪腺组织和脾脏中CD4⁺CD25⁺Treg细胞比例较高,模型组CD4⁺CD25⁺Treg细胞比例有所降低,且差异具有统计学意义(P<0.05)。

结论：兔干眼模型发病时,CD4⁺CD25⁺Treg细胞免疫抑制作用下降,IL-17、TNF-α、IL-6、TGF-γ等细胞因子在泪腺的炎症反应中都发挥着重要作用。     

Development and Characterization of a Rabbit Corneal Endothelial Cell Line

Purpose To develop a rabbit corneal endothelial cell line by transducing human papilloma virus (HPV) type 16 E6 and E7 oncogenes, and to characterize the inherent biological properties of the established cell line.Methods Primary rabbit corneal endothelial cells were infected with a recombinant retrovirus harboring HPV E6 and E7, and the transformed cells were clonally selected by G418.Results Among the total of eight independent clones, one cell line (Clone no. A3) cultured over 40 passages was chosen to further characterize its inherent biological properties. Typical cell doubling time for these cells was 51h, and the mean cell density of a flask culture was 1140 cells/mm². The various genes that are important for corneal endothelial functions were expressed at a level comparable to that of their normal counterparts. Furthermore, Na⁺/K⁺ ATPase activity was maintained throughout an extended period, and the measured value at passage 30 was about 10nmol inorganic phosphate/mg protein per minute.Conclusions These results suggest that the rabbit corneal endothelial cell lines obtained here maintain normal corneal endothelial characteristics, and could be used not only for biological studies on corneal endothelial cells but also for such applications as the reconstruction of the ocular surface with an artificial cornea. Jpn J Ophthalmol 2004;48:454–459 © Japanese Ophthalmological Society 2004     

Species variation in biology and physiology of the ciliary epithelium: Similarities and differences

Glaucoma is a leading cause of irreversible blindness worldwide. Lowering intraocular pressure (IOP) is the only strategy documented to delay the appearance and retard the progression of vision loss. One major approach for lowering IOP is to slow the rate of aqueous humor formation by the ciliary epithelium. As discussed in the present review, the transport basis for this secretion is largely understood. However, several substantive issues are yet to be resolved, including the integrated regulation of secretion, the functional topography of the ciliary epithelium, and the degree and significance of species variation in aqueous humor inflow. This review discusses species differences in net secretion, particularly of Cl⁻ and HCO₃⁻ secretion. Identifying animal models most accurately mimicking aqueous humor formation in the human will facilitate development of future novel initiatives to lower IOP.     

Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor l-NAME

In birds, the choroid plays a role in the visual regulation of eye growth, thickening in response to myopic defocus, and thinning in response to hyperopic defocus, in both cases moving the retina towards the image plane. This response is rapid, occurring within hours of the defocus stimulus. These changes are consistently associated with slower changes in the sclera, that result in the appropriate changes in axial elongation, decreasing growth in response to myopic defocus and increasing it in response to hyperopic defocus. The molecular mechanisms underlying the scleral response involve changes in the synthesis of extracellular matrix molecules, however, those underlying the changes in choroidal thickness are not known. However, evidence suggests that it may involve the gaseous signal molecule nitric oxide, as nitric oxide is a potent smooth muscle relaxant, and injections of the non-specific nitric oxide synthase inhibitor l-NAME transiently inhibits the thickening response. Interestingly, it also dis-inhibits ocular growth, in accordance with a mechanistic link between the two responses. If nitric oxide is part of the signal cascade underlying the visual regulation of eye growth, it would be important to ascertain the source of the molecule. As a first step towards doing so, we used various more specific NOS inhibitors and studied their effects on the choroidal and growth responses. Birds (7-12 days old) were fitted with +10 D lenses on one eye. On that day, single intravitreal injections (30 μl) of the following inhibitors were used: nNOS inhibitor N^ω-propyl-l-arginine (n = 12), iNOS inhibitor l-NIL (n = 16), eNOS/iNOS inhibitor l-NIO (n = 15), non-specific inhibitor l-NMMA (n = 30) or physiological saline (n = 18). Ocular dimensions were measured using high-frequency A-scan ultrasonography at the start of the experiment, and at 7, 24 and 48 h after. We found that the nNOS inhibitor N^ω-propyl-l-arginine had the same inhibitory effects on the choroidal response, and dis-inhibition of the growth response, as did l-NAME; neither of the other inhibitors had any effect except l-NMMA. We conclude that the choroidal compensatory response is influenced by nNOS, possibly from the intrinsic choroidal neurons, or the parasympathetic innervation from the ciliary and/or pterygopalatine ganglia.     

Opticin Ameliorates Hypoxia-Induced Retinal Angiogenesis by Suppression of Integrin α2-I Domain–Collagen Complex Formation and RhoA/ROCK1 Signaling

PurposeIt was previously demonstrated that opticin (OPTC) inhibits the collagen-induced promotion of bioactivities of human retinal vascular endothelial cells (hRVECs). The present in vivo study aimed to further investigate the regulatory role of opticin in vitreous collagen-mediated retinal neovascularization and to elucidate its regulatory mechanisms with regard to integrin α2-I domain–GXXGER complex formation and RhoA/ROCK1 signal change. The regulatory role of Mg²⁺ on integrin α2-I domain–GXXGER complex formation in the above process was also investigated.MethodsThe zebrafish model of hypoxia-induced retinopathy was established, and OPTC-overexpressing plasmids were intravitreally injected to assess the antiangiogenesis effect of opticin. The regulatory role of opticin in integrin α2-I domain–GXXGER complex formation in vivo was analyzed by mass spectrometry. The mRNA and protein expression of RhoA/ROCK1 were examined. The concentration of Mg²⁺ as an activator of the integrin α2-I domain–GXXGER complex was measured. Solid-phase binding assays were performed to investigate the interference of opticin in integrin α2 collagen binding and the regulatory role of Mg²⁺ in that process.ResultsOpticin and OPTC-overexpressing plasmid injection reduced retinal neovascularization in the zebrafish model of hypoxia-induced retinopathy. Mass spectrometry revealed that opticin could inhibit integrin α2-I domain–GXXGER complex formation. The Mg²⁺ concentration was also decreased by opticin, which was another indication of the complex activation. Injection of OPTC-overexpressing plasmids inhibited mRNA and the protein expression of RhoA/ROCK1 in the zebrafish model of hypoxia-induced retinopathy. The solid-phase binding assay revealed that opticin could block integrin α2–collagen I binding in the presence of Mg²⁺.ConclusionsOpticin exerts its antiangiogenesis effect by interfering in the Mg²⁺-modulated integrin α2-I domain–collagen complex formation and suppressing the downstream RhoA/ ROCK1 signaling pathway.     

Bimatoprost 0.01% vs bimatoprost 0.03%: a 12-month prospective trial of clinical and in vivo confocal microscopy in glaucoma patients

Purpose

To evaluate the safety of two commercially available formulations of bimatoprost eye drops: 0.03 and 0.01% ophthalmic solutions.

Methods

This was a randomized, prospective, parallel-group, open-label, cohort study. A total of 60 glaucoma patients (60 eyes) under bimatoprost 0.03% monotherapy since at least 1 year were enrolled. Selected patients were randomized to receive a single drop of bimatoprost 0.01% (n=30) or bimatoprost 0.03% (n=30) ophthalmic solutions for 12 months. Statistical analysis was performed using paired t-test and repeated measures ANOVA test.

Results

Global clinical score (the sum of pruritus, stinging/burning, blurred vision, sticky eye sensation, eye dryness sensation, and foreign body sensation) significantly decreased in the bimatoprost 0.01% group from baseline 4.7±3.8 to 2.9±2.3 (P<0.001) and 2.5±2.0 (P<0.001) at 6-month and 12-month follow-ups, respectively. Comparison between groups showed differences at both follow-up visits (P=0.003 and P<0.001, respectively). In vivo confocal microscopy revealed a significant increase in goblet cell density in the bimatoprost 0.01% group compared with the bimatoprost 0.03% group (P<0.001 at both follow-up visits). All functional parameters and conjunctival hyperemia improved in the bimatoprost 0.01% group at each follow-up visit (P<0.05) and in comparison with bimatoprost 0.03% (P<0.05).

Conclusion

The results of this trial suggest that bimatoprost 0.01% eye drops seem to decrease the ocular discomfort with respect to bimatoprost 0.03% eye drops.