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Glaucoma is a neurodegenerative disease, which results in characteristic visual field defects. Intraocular pressure (IOP) remains the main risk factor for this leading cause of blindness. Recent studies suggest that disturbances in neurovascular coupling (NVC) may be associated with glaucoma. The resultant imbalance between vascular perfusion and neuronal stimulation in the eye may precede retinal ganglion cell (RGC) loss and increase the susceptibility of the eye to raised IOP and glaucomatous degeneration. Caveolin-1 (Cav-1) is an integral scaffolding membrane protein found abundantly in retinal glial and vascular tissues, with possible involvement in regulating the neurovascular coupling response. Mutations in Cav-1 have been identified as a major genetic risk factor for glaucoma. Therefore, we aim to evaluate the effects of Cav-1 depletion on neurovascular coupling, retinal vessel characteristics, RGC density and the positive scotopic threshold response (pSTR) in Cav-1 knockout (KO) versus wild type C57/Bl6 mice (WT). Following light flicker stimulation of the retina, Cav-1 KO mice showed a smaller increase in perfusion at the optic nerve head and peripapillary arteries, suggesting defective neurovascular coupling. Evaluation of the superficial capillary plexus in Cav-1 KO mice also revealed significant differences in vascular morphology with higher vessel density, junction density and decreased average vessel length. Cav-1 KO mice exhibited higher IOP and lower pSTR amplitude. However, there was no significant difference in RGC density between Cav-1 KO and wild type mice. These findings highlight the role of Cav-1 in regulating neurovascular coupling and IOP and suggest that the loss of Cav-1 may predispose to vascular dysfunction and decreased RGC signaling in the absence of structural loss. Current treatment for glaucoma relies heavily on IOP-lowering drugs, however, there is an immense potential for new therapeutic strategies that increase Cav-1 expression or augment its downstream signaling in order to avert vascular dysfunction and glaucomatous change.

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Breast-conserving surgery (BCS) followed by radiation therapy for breast cancer offers improved cosmetic results and comparable long-term survival rates as mastectomy. 1 However, BCS is associated with a higher risk for local recurrence, and published literature has reported re-excision rates as high as 20-70% due to positive resection margins of the tumour. The increased re-excision rates are associated with unfavourable consequences, including increased utilisation of healthcare resources and decreased patient satisfaction. 2 An important factor in reducing local recurrence rates in BCS is to achieve a microscopically clear margin absent of tumour cells. 3,4 Intraoperative assessment with frozen section (FS) analysis has been described as a popular method to reduce re-excision rates. 4 FS also offers significant cost savings to patients while improving efficiency in the utilisation of hospital resources through reduced re-operations. 5 On the other hand, opponents of routine use of intraoperative FS cite these reasons as barriers to adoption of the technique: longer operating times; little role for FS evaluation of resection margins that are grossly free of the tumour because of the fatty nature of the margins; diversion of pathologists' resources; and higher patient fees. [6][7][8] This study aims to audit the effect of intraoperative FS in BCS in a Singapore regional hospital.After approval from the ethics board, a retrospective study was conducted on consecutive breast cancer patients from Khoo Teck Puat Hospital (KTPH) in Singapore. We identified 186 patients who underwent BCS from January 2012 to February 2020. Eligible patients had either invasive or in situ carcinoma and were deemed to be candidates for BCS after clinical and radiographic evaluation. Patients who had metastases or a history of recurrent breast cancer were excluded. From 2017 onwards, our unit began to perform intraoperative FS routinely, with margins taken from the tumour cavity. Intraoperative ultrasound was also used as an adjunct to aid wide local excision in selected cases where the tumour was small and not well defined by clinical palpation.The following clinical factors were collected: patient's age, multifocality of the tumour, primary tumour size, staging of the tumour, histological type, and grade.