PURPOSE. A growing body of evidence points to complement dysregulation in diabetes. Early studies have indicated the presence of complement components inside the eye in patients with diabetic retinopathy, but these data have been confounded by leakage of proteins from the systemic circulation into the vitreous cavity. METHODS. We took samples of plasma and vitreous from patients with and without proliferative diabetic retinopathy (PDR) and measured levels of 16 complement components as well as albumin. We employed a normalized ratio using local and systemic complement and albumin levels to control for vascular leakage into the vitreous cavity. RESULTS. Before normalizing, we found significantly higher levels of 16 complement components we measured in PDR eyes compared to controls. After normalizing, levels of C4, factor B, and C5 were decreased compared to controls, while C3a and Ba levels were elevated compared to controls. We also found higher ratios of C3a/C3, C5a/C5, and Ba/factor B in PDR eyes compared to controls. CONCLUSIONS. We found evidence of local, intraocular activation of C3, C5, and factor B. The normalized data suggest involvement of the alternative complement pathway. By showing activation of specific complement components in PDR, this study identifies targets for diagnostic and therapeutic potential.
Purpose A growing body of evidence suggests complement dysregulation is present in the vitreous of patients with diabetic eye disease. Further translational study could be simplified if aqueous—as opposed to vitreous—were used to sample the intraocular complement environment. Here, we analyze aqueous samples and assess whether a correlation exists between aqueous and vitreous complement levels. Methods We collected aqueous, vitreous, and plasma samples from patients with and without proliferative diabetic retinopathy (PDR) undergoing vitrectomy. We assessed correlation between complement levels in aqueous and vitreous samples after using a normalizing ratio to correct for vascular leakage. Spearman correlation coefficients were used to assess the correlation between complement levels in the aqueous and vitreous. Results Aqueous samples were obtained from 17 cases with PDR and 28 controls. In all patients, aqueous Ba, C3a, and albumin levels were strongly correlated with vitreous levels (Spearman correlation coefficient of 0.8 for Ba and C3a and 0.7 for albumin; all P values < 0.0001). In PDR eyes only, aqueous and vitreous C3a levels were significantly correlated (Spearman correlation coefficient 0.7; P = 0.002), whereas in control eyes, both Ba and C3a (Spearman correlation coefficients of 0.7; P < 0.0001) were significantly correlated. Conclusions A strong correlation exists between aqueous and vitreous complement levels in diabetic eye disease. Translational Relevance The results establish that accurate sampling of the intraocular complement can be done by analyzing aqueous specimens, allowing for the rapid and safe measurement of experimental complement targets and treatment response.
Primary nasolacrimal duct malignacy is rare. Only a few tumours have been reported originating from this location including lymphoma, 1 Kaposi's sarcoma, 2 adenocarcinoma, 3 angiofibroma, 4 and squamous cell carcinoma. 5 Mucosal melanoma represents 1-2% of all melanomas, 6 with 25-50% in the head and neck-that is, upper respiratory tract, oral cavity, and pharynx. Other sites include urinary, female genital, and ano-rectal tracts. These tumours are uncommon, present in the fifth to eighth decades, have slight male preponderance and are more common in darker skinned individuals. Cutaneous melanoma presents two decades earlier and is more common in white people and is associated with sun exposure.
Simultaneous spatiotemporal focusing (SSTF) is applied to lens tissue and compared directly with standard femtosecond micromachining of the tissue at the same numerical aperture. Third harmonic generation imaging is used for spatio-temporal characterization of the processing conditions obtained with both a standard and SSTF focus. Simultaneous spatiotemporal focusing with application to micromachiningSimultaneous spatiotemporal focusing [1-2] enables the precise delivery of energetic pulses as a result of the effective suppression of nonlinear processes such as self-focusing [3][4]. Figure 1 illustrates the dramatic difference between a standard focus (left) and a SSTF focus (right) as function of pulse energy. In figure 1, the plasma breakdown created at focus is imaged as a function of increasing pulse energy. In the standard case (left column), as the pulse energy is increased the focal spot shifts away from the paraxial image plane and moves toward the focusing optic. Once the energy is increased by ~3.5 times, the focal spot has shifted by ~200 µm and is visibly distorted. In contrast, the SSTF focus remains at the paraxial focal plane and is undistorted even when the pulse energy is increased by ~9 times. This localization makes SSTF much more amenable to large scale tissue manipulation where energetic pulse delivery is desirable as a result of the broad range of tissue conditions and the necessity to maintain precise delivery as a result of having to ablate close to sensitive membranes. Lens tissueThis localized behavior is immediately realized as applied to tissue ablation. In figure 2, histological slices of porcine lens tissue ablated with a standard focus and an SSTF focus are compared. In each instance, a 35 µm focal spot was directed at the surface of a porcine lens. The pulse duration was ~75 fs, the pulse repetition rate is 1 KHz, the average laser power is 90 mW, and the sample translation speed was kept constant in all cases. Identical ablation conditions results in significantly different damage morphology. The damage with the standard focus extends for 100's of µm into the sample, while the SSTF ablation zone is limited to the targeted surface of the lens.
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