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A 30 year old woman with gradual vision loss OU
Digital Journal of Ophthalmology 2005
Volume 11, Number 15
August 15, 2005
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Darren J. Bell | University of Tennessee
Joseph Mastellone | University of Tennessee
Edward Chaum MD PhD | Univ. of Tennessee Memphis
Diagnosis and Discussion
Epidemiological studies of the progression of diabetic retinopathy by Klein et al. showed that only 10.5% of patients under the age of 30 with NPDR at baseline progress to proliferative retinopathy after a period of 4 years. Of those patients with preexisting PDR at the time of the initial examination, only 13.8% progressed to PDR with HRC after 4 years of follow up (2). However, patients with rapid progression of retinopathy were observed in the ETDRS studies (3). Development of PDR with HRC was seen at 1-year in 0.8% of patients with mild NPDR (level 35) at baseline and in 3.3% of patients with moderate NPDR (level 43, no IRMAs) at baseline as seen in this patient.
The progression to bilateral PDR with HRC in only 3 months; however, is striking in this case. Melberg et al. described a patient with acute lymphocytic leukemia who progressed from background diabetic retinopathy to severe proliferative diabetic retinopathy over a period of six months (4). The authors concluded that the accelerated course of progression was attributable to moderate anemia related to the leukemia and its treatment. In our patient, there was also severe retinal ischemia; however, we propose an alternative hypothesis and mechanism for the accelerated progression to proliferative disease.
Leukoembolization of the retina with resulting ischemia from infarction of the retinal capillary bed is seen in numerous conditions manifesting as Purtscher’s-like retinopathy (5). The mechanism of microvascular occlusion in these diseases is generally believed to be leukocyte aggregation resulting from activation of complement factor C5a. We suggest that the unusually rapid progression of her disease was exacerbated by a similar mechanism, i.e. granulocyte aggregation with secondary microvascular occlusion due to severe leukocytosis. Aggregation of stimulated granulocytes has been proposed as a mechanism of microvascular occlusion, as well as pressure-dependent plugging of vessels and endothelial cell damage by toxic leukocyte products (6). This aggregation hypothesis is supported by evidence of increased blood viscosity and leukostasis in the vasculature of brains of patients who have died from leukemia (7). The clinical presentation of severe peripheral retinal ischemia in our patient may have been due in part to unrecognized leukoembolization of the retinal vasculature prior to her diagnosis of CML. The progressive retinal ischemia may have exacerbated the secretion of angiogenic factors in the diseased retina and led to accelerated development of neovascular disease.
Interestingly, recent studies have found that systemic blood plasma concentrations of angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are significantly increased in patients with CML, compared to healthy controls (8,9). Extravascular leakage of circulating VEGF and bFGF from incompetent vessels into the compromised retina may also act to increase the local tissue levels of these angiogenic factors and accelerate the clinical course of proliferative disease. Increased amounts of circulating VEGF, produced independently of underlying retinal ischemia in patients with CML, could also provide a synergistic mechanism for the rapid development of PDR with high risk characteristics observed in our patient.
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