Anthony T. W. Cheung

Periodic blood exchange transfusion is a treatment modality commonly used to manage pediatric sickle cell anemia at the University of California Davis Medical Center. The goal of exchange transfusion therapy is to ameliorate vasoocclusion and improve tissue perfusion by removing sickled red blood cells and introducing normal red blood cells. Using computer-assisted intravital microscopy, pretransfusion and posttransfusion microvascular characteristics were analyzed. In this study, the bulbar conjunctiva exhibited a "blanched" avascular appearance in all 6 pediatric sickle cell anemia patients before transfusion, indicative of tissue hypoperfusion and ischemia. Immediately after transfusion, substantial improvement in vascularization and tissue perfusion resulted, reflected by the enhanced appearance of capillaries and arterioles. In addition, a decrease in red cell velocity was observed. These observations provide evidence that exchange transfusion therapy is beneficial in ameliorating vasoocclusion and improving tissue perfusion. However, with the paradoxical posttransfusion decrease in red cell velocity presumably due to induced hyperviscosity from the large transfusion volume, blood flow is still impaired. This decreased velocity may thwart efforts to improve oxygen delivery through transfusion and may, to some extent, promote vasoocclusion instead. This paradoxical result warrants further investigation on the effects of transfusion volume and viscosity in the exchange transfusion process.

Soft contact lenses are commonly used to improve vision acuity or in cosmetic enhancement. We hypothesize that contact lens use can cause inadvertent damage to either the conjunctival microcirculation via direct vasoocclusion when the lens physically interacts with or damages the underlying vessels, or to the bulbar conjunctiva itself when the lens rests unevenly on the surface of the bulbar conjunctiva. Computer-assisted intravital microscopy was utilized to document (via video recording) and objectively quantify (via image analysis) real-time microvascular abnormalities resulting from changes and vessel remodeling in the conjunctival microcirculation in long-term (>2 yrs) contact lens users (n = 102), with non-users serving as control subjects (n = 29). A severity index (SI) – computed as the arithmetic sum of the abnormalities found in the conjunctival microcirculation in each contact lens user – was established for objective comparison with control subjects and critical interpretation. Contact lens user SI was significantly higher than control SI (user = 6.21 ± 1.26; control = 2.31 ± 1.49; p < 0.05), indicative of severe vasculopathy arising from contact lens use. The users also had significantly wider conjunctival vessel diameter (user = 71.25 ± 12.09 μm; control = 52.20 ± 5.10 μm; p < 0.05). Additional abnormalities, including damaged vessels, hemosiderin deposits (from damaged vessels or injury to the surface of the bulbar conjunctiva), vessel sludging, intermittent blood flow, and vessel tortuosity were commonly found in or adjacent to locations where the contact lens physically rested on the underlying conjunctival vessels. These results strongly suggest that microvascular abnormalities and remodeling changes occurred as a result of the inadvertent physical interaction of the lenses with either the underlying conjunctival vessels or the surface of the bulbar conjunctiva in contact lens users.

The conjunctival microcirculation in 14 pediatric and eight adult sickle cell anemia (SCA) patients was studied using computer‐assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric [vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits] and dynamic [vessel sludging/sludged flow, boxcar blood (trickled) flow, and abnormal flow velocity] abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs. 6.6 ± 2.4; P = 0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down, or prevent progressive microvascular deterioration. Am. J. Hematol., 2010.

Context: The etiology of Alzheimer’s disease (AD) is inconclusive. Treatments targeting amyloid have largely been unsuccessful. There is increasing evidence that vasculopathy may play an important pathogenic role in AD. Objective: Longitudinal measur

We hypothesize that real-time in vivo microvascular abnormalities should correlate with biochemical markers of inflammation/endothelial dysfunction in T1DM. Real-time quantification of T1DM and healthy non-diabetic control microcirculation was conducted utilizing computer-assisted intravital microscopy. Selected biochemical markers (high sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecules (sVCAM), soluble intercellular adhesion molecules (sICAM), soluble E-selectin (sE-selectin), nitrotyrosine, superoxide anion (O2-), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha)) were used for correlation. The severity of microvascular abnormalities, as reflected by the arithmetic severity index (SI), was significantly increased in T1DM vs. controls (5.89 +/- 1.47 vs. 2.34 +/- 1.48; P<0.001). In addition several of the specific microvascular abnormalities (related to flow and morphometry) were significantly more prevalent in the T1DM patients. Finally, the following significant positive correlations existed between the inflammatory/endothelial dysfunction markers and specific microvascular abnormalities: sVCAM and abnormal vessel diameter (P=0.004, OR =1.033, 95% CI for OR =(1.01, 1.056)), superoxide (O2-) release and abnormal vessel distribution (P=0.032, OR =1.798, 95% CI for OR =(1.051, 3.075)), and sE-selectin and abnormal vessel distribution (P=0.036, OR =1.118, 95% CI for OR =(1.007, 1.241)). In view of such significant correlations, we conclude that these specific microvascular abnormalities can serve as unique physiologic markers of endothelial dysfunction to correlate with the biochemical markers of inflammatory/endothelial dysfunction in disease progression and therapeutic efficacy studies.