Radiation Retinopathy: Case report and review

BACKGROUND: Ocular damage from radiation treatment is a well established phenomenon. Many factors are now known to influence the incidence of radiation retinopathy, including total dosage and daily fraction size. Patients who are diabetic, hypertensive or received previous chemotherapy are more susceptible to radiation retinopathy. CASE PRESENTATION: A 55 year old male was referred from the oncology department with epiphora. His medical history included Type 2 Insulin treated Diabetes Mellitus and hypertension. One year prior to presentation he had undergone a total rhinectomy with a 4 week course of post-operative radiotherapy for an aggressive sqaumous cell carcinoma of the nose. On examination the visual acuity was noted to be 6/36 left eye and 6/9 right eye. Posterior segment examination revealed marked retinal ischaemia present in the posterior pole and macular region of both eyes. The appearance was not thought to be typical of diabetic changes, radiation retinopathy being the more likely diagnosis especially in view of his history. Over the next four months the vision in both eyes rapidly deteriorated to 3/60 left eye and 1/60 right eye. Bilateral pan retinal photocoagulation was thought to be appropriate treatment at this point. CONCLUSION: This case highlights the importance for ophthalmologists and oncologists to be aware of the close relationship between diabetes and radiation treatment and the profound rapid impact this combination of factors may have on visual function. Radiation is being used with increasing frequency for ocular and orbital disease, because of this more cases of radiation retinopathy may become prevalent. Factors which may potentiate radiation retinopathy should be well known including, increased radiation dosage, increased fraction size, concomitant systemic vascular disease and use of chemotherapy. Counselling should be offered in all cases at risk of visual loss. As no effective treatment currently exists to restore visual function, monitoring of visual acuity in all cases and early referral to the ophthalmologist as appropriate is warranted

Role of the breast cancer resistance protein (ABCG2) in drug transport

The 72-kDa breast cancer resistance protein (BCRP) is the second member of the subfamily G of the human ATP binding cassette (ABC) transporter superfamily and thus also designated as ABCG2. Unlike P-glycoprotein and MRP1, which are arranged in 2 repeated halves, BCRP is a half-transporter consisting of only 1 nucleotide binding domain followed by 1 membrane-spanning domain. Current experimental evidence suggests that BCRP may function as a homodimer or homotetramer. Overexpression of BCRP is associated with high levels of resistance to a variety of anticancer agents, including anthracyclines, mitoxantrone, and the camptothecins, by enhancing drug efflux. BCRP expression has been detected in a large number of hematological malignancies and solid tumors, indicating that this transporter may play an important role in clinical drug resistance of cancers. In addition to its role to confer resistance against chemotherapeutic agents, BCRP actively transports structurally diverse organic molecules, conjugated or unconjugated, such as estrone-3-sulfate, 17β-estradiol 17-(β-D-glucuronide), and methotrexate. BCRP is highly expressed in the placental syncytiotrophoblasts, in the apical membrane of the epithelium in the small intestine, in the liver canalicular membrane, and at the luminal surface of the endothelial cells of human brain microvessels. This strategic and substantial tissue localization indicates that BCRP also plays an important role in absorption, distribution, and elimination of drugs that are BCRP substrates. This review summarizes current knowledge of BCRP and its relevance to multidrug resistance and drug disposition