Focus on reuse: reducing waste associated with topical preoperative antiseptics.

PURPOSE: To outline the environmental and financial costs associated with single-use topical antiseptic (5% povidone-iodine [PVI] solution) in the ophthalmology theatre setting and explore potential methods of repurposing topical antiseptics. SETTING: Large tertiary referral center (Flinders Medical Centre, Adelaide, Australia). DESIGN: Single-center prospective observational study. METHODS: Dedicated containers placed in the ophthalmology theatre of the participating institution were used to collect the number of disposed PVI bottles over the 3-week study period. Descriptive statistics were employed to determine the associated packaging bottle weight, mean unused quantity (mL) and cost of the single-use topical PVI solution and costs of unused antiseptic. RESULTS: The total amount of waste generated from the use of single-use PVI bottles during the surveillance period was 10.823 kg, of which 21.9% was preventable; 72% of unused PVI by weight were discarded during the study period, equating to approximately $21 857.60 in wasted pharmaceutical content per year. 100% of the discarded PVI was successfully redirected and reused at a local wildlife rescue organisation and diverted from landfill. CONCLUSIONS: This study has demonstrated that the utilization of single-use topical preoperative PVI preparations is associated with significant financial, pharmaceutical and environmental waste. Future studies examining the recyclability of single-use PVI bottles and investigating systematic strategies to recycle and repurpose this waste are required.

TUBERCULOUS CHORIORETINITIS: A CHALLENGING CASE OF AN OPHTHALMIC MIMIC.

PURPOSE: To report a challenging case of tuberculous chorioretinitis. METHODS: Case report of a 51-year-old woman from the Middle East, who was referred from an optometrist with a suspicious retinal lesion in her right eye. RESULTS: Clinical examination showed multifocal, pale, elevated lesions temporal to the right macula with no vasculitis or hemorrhages. Infective and inflammatory workup showed unremarkable results. B-scan ultrasound confirmed an 8 mm × 3 mm × 10 mm right focal chorioretinal thickening. Computed tomography scanning showed calcified lung hilar nodes supporting a prior granulomatous process, along with an enhancing nodule in the right globe. Magnetic resonance imaging of the brain and obits showed retinal thickening of the temporal surface of the right globe with subtle enhancement without retrobulbar extension or evidence for cerebral vasculitis. Subretinal lesion biopsy showed mononuclear inflammatory cells with granulomatous inflammation, including multinucleated giant cells but no neoplastic features. Interferon-gamma release assay testing for tuberculosis showed negative result, but a high index of suspicion lead to tuberculin skin testing and subsequent treatment for tuberculous chorioretinitis. CONCLUSION: Ocular tuberculosis presents in a variety of ways, making it a challenging diagnosis. Herein, we describe such case of tuberculous chorioretinitis.

Salvageable waste associated with intravitreal injections: A local medical waste management approach.

BACKGROUND: Healthcare waste management is a globally challenging issue with an increased prevalence of disposable, single-use materials in developed countries and a rapidly ageing population continuing to drive an increase in the use of medical resources. One manifestation of this within ophthalmology is the increasing number of intravitreal injections given for conditions such as age-related macular degeneration and diabetic macular oedema. METHODS: A prospective controlled cohort study was performed over 5 weeks in 2021 during which two sites were selected to compare different approaches to sorting the waste generated by intravitreal injections. At Site A all waste associated with these injections was placed in standard hospital waste bins. Site B was the intervention arm where a real-time sorting of waste occurred. The number of injections given and waste amounts were recorded. RESULTS: 116 and 286 injections were given at Sites A and B, respectively over the study period. Site A generated an average of 470.7 g of waste per injection compared with 175.1 g at our intervention site. This represents a 62.8% reduction (p < 0.001). At Site B, where waste was sorted, a total of 50.1 kg of medical waste was generated from these injections during the study period of which 33.8 kg (67.5%) was salvageable. CONCLUSIONS: This is the first quantification of the medical waste associated with intravitreal injections, a burgeoning treatment for macular degeneration and diabetic retinopathy among other conditions. This study demonstrates a significant reduction in the amount of medical waste produced using an easily implementable real-world methodology.

Pallid Disc Oedema in a Young Patient: Clinical and Diagnostic Challenge.

A mid-thirties male with end-stage renal failure receiving haemodialysis on a background of four failed renal transplants, post-transplant lymphoproliferative disorder,and autonomic dysfunction presented with acute vision change in his left eye. Over days his vision in that eye deteriorated from 20/25 to no light perception. Given his complex medical background he was extensively investigated for infective, inflammatory, infiltrative and vasculitic aetiologies to explain acute vision loss with pallid disc swelling. A final diagnosis of non-arteritic anterior ischaemic optic neuropathy secondary to refractive hypotension and haemodialysis was reached.

Suprachoroidal Gas: A Rare Complication of Intravitreal Injection of Perfluoropropane.

This is a case report of a 75-year-old pseudophakic male, who presented with a massive submacular hemorrhage on a background of neovascular age-related macular degeneration. Intravitreal perfluoropropane was used to attempt pneumatic displacement of the submacular hemorrhage. The next day, subconjunctival gas was observed, with no gas seen in the vitreous cavity. Fundal examination showed suprachoroidal detachment. CT images confirmed gas entrapment, with no choroidal hemorrhage identified. The following case report describes suprachoroidal gas as a complication of intravitreal injection of perfluoropropane for pneumatic displacement of submacular hemorrhage. To our knowledge, this is the first such case in the literature. We describe the approach in differentiating suprachoroidal gas from hemorrhage and comment on a plausible mechanism for this complication. This report also serves as a review of the current state of knowledge in the area of suprachoroidal gas as a complication of pneumatic retinopexy and sutureless vitrectomy.

Breast cancer metastasis to gynaecological organs: a clinico-pathological and molecular profiling study.

Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathological and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy-number profiling, and targeted sequencing of 386 cancer-related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46.5 versus 60 years; p < 0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8 years (range 0-20 years), and survival following a diagnosis of metastasis was 1.95 years (range 0-18 years). Patients had an average of five involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver, or brain. Invasive lobular histology and luminal A-like phenotype were over-represented in this group (42.8 and 87.5%, respectively) and most patients had involved axillary lymph nodes (p < 0.001). Primary tumours frequently co-expressed oestrogen receptor cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24, and 11q13. In terms of phenotype conversion, oestrogen receptor status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor, androgen receptor, and GATA3 decreased. ESR1 and novel AR mutations were identified. Metastasis to gynaecological organs is a complication frequently affecting young women with invasive lobular carcinoma and luminal A-like breast cancer, and hence may be driven by sustained hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.

Riboflavin uptake transporter Slc52a2 (RFVT2) is upregulated in the mouse mammary gland during lactation.

While it is well recognized that riboflavin accumulates in breast milk as an essential vitamin for neonates, transport mechanisms for its milk excretion are not well characterized. The multidrug efflux transporter ABCG2 in the apical membrane of milk-producing mammary epithelial cells (MECs) is involved with riboflavin excretion. However, it is not clear whether MECs possess other riboflavin transport systems, which may facilitate its basolateral uptake into MECs. We report here that transcripts encoding the second (SLC52A2) and third (SLC52A3) member of the recently discovered family of SLC52A riboflavin uptake transporters are expressed in milk fat globules from human breast milk. Furthermore, Slc52a2 and Slc52a3 mRNA are upregulated in the mouse mammary gland during lactation. Importantly, the induction ofSlc52a2, which was the major Slc52a riboflavin transporter in the lactating mammary gland, was also observed at the protein level. Subcellular localization studies showed that green fluorescent protein-tagged mouse SLC52A2 mainly localized to the cell membrane, with no preferential distribution to the apical or basolateral membrane in polarized kidney MDCK cells. These results strongly implicate a potential role for SLC52A2 in riboflavin uptake by milk-producing MECs, a critical step in the transfer of riboflavin into breast milk.

Rescuing hepatocytes from iron-catalyzed oxidative stress using vitamins B1 and B6.

In the following rescue experiments, iron-mediated hepatocyte oxidative stress cytotoxicity was found to be prevented if vitamin B1 or B6 was added 1h after treatment with iron. The role of iron in catalyzing Fenton-mediated oxidative damage has been implicated in iron overload genetic diseases, carcinogenesis (colon cancer), Alzheimer's disease and complications associated with the metabolic syndrome through the generation of reactive oxygen species (ROS). The objectives of this study were to interpret the cytotoxic mechanisms and intracellular targets of oxidative stress using "accelerated cytotoxicity mechanism screening" techniques (ACMS) and to evaluate the rescue strategies of vitamins B1 and B6. Significant cytoprotection by antioxidants or ROS scavengers indicated that iron-mediated cytotoxicity could be attributed to reactive oxygen species. Of the B6 vitamers, pyridoxal was best at rescuing hepatocytes from iron-catalyzed lipid peroxidation (LPO), protein oxidation, and DNA damage, while pyridoxamine manifested greatest protection against ROS-mediated damage. Thiamin (B1) decreased LPO, mitochondrial and protein damage and DNA oxidation. Together, these results indicate that added B1 and B6 vitamins protect against the multiple targets of iron-catalyzed oxidative damage in hepatocytes. This study provides insight into the search for multi-targeted natural therapies to slow or retard the progression of diseases associated with Fenton-mediated oxidative damage.

Metabolic mechanisms of methanol/formaldehyde in isolated rat hepatocytes: carbonyl-metabolizing enzymes versus oxidative stress.

Methanol (CH(3)OH), a common industrial solvent, is metabolized to toxic compounds by several enzymatic as well as free radical pathways. Identifying which process best enhances or prevents CH(3)OH-induced cytotoxicity could provide insight into the molecular basis for acute CH(3)OH-induced hepatoxicity. Metabolic pathways studied include those found in 1) an isolated hepatocyte system and 2) cell-free systems. Accelerated Cytotoxicity Mechanism Screening (ACMS) techniques demonstrated that CH(3)OH had little toxicity towards rat hepatocytes in 95% O(2), even at 2M concentration, whereas 50 mM was the estimated LC(50) (2h) in 1% O(2), estimated to be the physiological concentration in the centrilobular region of the liver and also the target region for ethanol toxicity. Cytotoxicity was attributed to increased NADH levels caused by CH(3)OH metabolism, catalyzed by ADH1, resulting in reductive stress, which reduced and released ferrous iron from Ferritin causing oxygen activation. A similar cytotoxic mechanism at 1% O(2) was previous found for ethanol. With 95% O(2), the addition of Fe(II)/H(2)O(2), at non-toxic concentrations were the most effective agents for increasing hepatocyte toxicity induced by 1M CH(3)OH, with a 3-fold increase in cytotoxicity and ROS formation. Iron chelators, desferoxamine, and NADH oxidizers and ATP generators, e.g. fructose, also protected hepatocytes and decreased ROS formation and cytotoxicity. Hepatocyte protein carbonylation induced by formaldehyde (HCHO) formation was also increased about 4-fold, when CH(3)OH was oxidized by the Fenton-like system, Fe(II)/H(2)O(2), and correlated with increased cytotoxicity. In a cell-free bovine serum albumin system, Fe(II)/H(2)O(2) also increased CH(3)OH oxidation as well as HCHO protein carbonylation. Nontoxic ferrous iron and a H(2)O(2) generating system increased HCHO-induced cytotoxicity and hepatocyte protein carbonylation. In addition, HCHO cytotoxicity was markedly increased by ADH1 and ALDH2 inhibitors or GSH-depleted hepatocytes. Increased HCHO concentration levels correlated with increased HCHO-induced protein carbonylation in hepatocytes. These results suggest that CH(3)OH at 1% O(2) involves activation of the Fenton system to form HCHO. However, at higher O(2) levels, radicals generated through Fe(II)/H(2)O(2) can oxidize CH(3)OH/HCHO to form pro-oxidant radicals and lead to increased oxidative stress through protein carbonylation and ROS formation which ultimately causes cell death.