Amniotic membrane transplantation: structural and biological properties, tissue preparation, application and clinical indications.

The amniotic membrane is a single epithelial layer of the placenta. It has anti-inflammatory, anti-scarring, anti-angiogenic and possibly bactericidal properties. The basement membrane of the amniotic membrane acts as a substrate to encourage healing and re-epithelialisation. It has been used in many ocular surface diseases including persistent epithelial defects (corneal or conjunctival), chemical or thermal burns, limbal stem cell deficiency, cicatrising conjunctivitis, ocular graft versus host disease, microbial keratitis, corneal perforation, bullous keratopathy, dry eye disease, corneal haze following refractive surgery and cross-linking, band keratopathy, ocular surface neoplasia, pterygium surgery, and ligneous conjunctivitis. This review provides an up-to-date overview of amniotic membrane transplantation including the structural and biological properties, preparation and application, clinical indications, and commercially available products.

Treatment of Diabetic Macular Edema or Macular Edema Following Retinal Vein Occlusion Based on Repeated Injection of the Dexamethasone Intravitreal Implant: A Retrospective Real-World Analysis.

Purpose: To assess the "real world" utility of repeated injection with the dexamethasone intravitreal implant (DEX) in routine practice. Methods: This was a retrospective, single-center analysis of consecutive patients with diabetic macular edema, or macular edema following retinal vein occlusion, treated with DEX. None had received prior intravitreal steroid treatment. DEX was implanted as per the manufacturer's instructions. Results: Seventy-eight individuals (95 eyes) were included (50.0% female; mean age: 68.1 ± 12.4 years; mean duration of macular edema: 13.2 ± 12.9 months). Thirty-three eyes (34.7%) had received previous treatment with an anti-vascular endothelial growth factor (anti-VEGF) and/or laser. Thirty eyes (31.6%) underwent one round of DEX implantation; the remainder received 2-5 cycles (total: 225 cycles). Initial DEX treatment led to significant increases in visual acuity (VA) at 6 weeks (mean change: 4.6 letters; P=0.004). Greater VA improvements during the first treatment cycle were associated with inferior baseline VA (P=0.02), borderline associated with baseline central macular thickness (CMT; P=0.06), and independent of prior anti-VEGF treatment (P=0.39). In an analysis of all DEX injections, VA improvements were robust across cycles 1 and 2 but reduced in cycle 3 (P=0.03). CMT improvements did not differ based on injection number (P=0.20). Increases in intraocular pressure (IOP) were largest over the first 6 weeks (but rebounded towards baseline more rapidly) in cycle 1 versus cycles 2 and 3 (P<0.001). IOP rises were typically manageable with topical medications. Conclusion: This analysis confirms the broad utility of DEX and may inform decision-making in routine practice.

Comparison of Two Main Orthokeratology Lens Designs in Efficacy and Safety for Myopia Control.

Purpose: This study aimed to compare the efficacy and safety of corneal refractive therapy (CRT) lenses and vision shaping treatment (VST) lenses for myopia control in children. Methods: Medical records of 1,001 children (2,002 eyes) who had been fitted with orthokeratology lenses for over 1.5 years were retrospectively reviewed. We collected the clinical data of four types of orthokeratology (OK) lenses available: one CRT lens (brand: CRT) and three VST lenses (brands: Euclid, Alpha, and Hiline) over 1.5 years. Results were compared and analyzed using a one-way ANOVA and Pearson's chi-square test. Results: Axial length elongation in the CRT lens group was 0.13 ± 0.02 mm faster than that in the Euclid lens, 0.1 ± 0.02 mm faster in the Alpha lens, and 0.08 ± 0.02 mm faster in the Hiline lens over the 1.5-year period (all P < 0.05). Among the subjects, 37.3% of them using the CRT lens experienced more than 1 D of refractive growth, compared with 20.2-30.8% of subjects wearing the three groups of VST lenses (all P < 0.05). A lower incidence of total adverse events was found with the CRT lenses compared with the VST lenses (P < 0.05), especially corneal staining. No difference was found in axial length elongation, refraction growth, and incidence of adverse events among the three types of VST lenses (all P > 0.05). Conclusions: Compared with the VST lenses, CRT lenses demonstrated a weaker effect on myopia control but with a better safety profile. Different types of VST lenses had similar efficacy and safety in the context of controlling myopia progression.

Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle.

The endoplasmic reticulum (ER) regulates cellular protein and lipid biosynthesis. ER dysfunction leads to protein misfolding and the unfolded protein response (UPR), which limits protein synthesis to prevent cytotoxicity. Chronic ER stress in skeletal muscle is a unifying mechanism linking lipotoxicity to metabolic disease. Unidentified signals from cells undergoing ER stress propagate paracrine and systemic UPR activation. Here, we induce ER stress and lipotoxicity in myotubes. We observe ER stress-inducing lipid cell non-autonomous signal(s). Lipidomics identifies that palmitate-induced cell stress induces long-chain ceramide 40:1 and 42:1 secretion. Ceramide synthesis through the ceramide synthase 2 de novo pathway is regulated by UPR kinase Perk. Inactivation of CerS2 in mice reduces systemic and muscle ceramide signals and muscle UPR activation. The ceramides are packaged into extracellular vesicles, secreted and induce UPR activation in naïve myotubes through dihydroceramide accumulation. This study furthers our understanding of ER stress by identifying UPR-inducing cell non-autonomous signals.

Rhabdomyolysis caused by carnitine palmitoyltransferase 2 deficiency: A case report and systematic review of the literature.

Carnitine palmitoyltransferase 2 deficiency is an inherited metabolic disorder involving a deficiency in a mitochondrial enzyme necessary for long chain fatty acid oxidation, and therefore decreased utilisation of fatty acids. The adult form of this condition leads to recurrent rhabdomyolysis triggered by exercise, fasting and infection. It is a very rare condition with only a few hundred reported cases worldwide. Here we present a case of severe rhabdomyolysis in the context of carnitine palmitoyltransferase 2 deficiency in which major organ involvement was avoided, and organ support was not needed. This prompted us to perform a systematic review of the existing case reports in the literature to ascertain the most frequent patterns of organ involvement and assess the outcomes that are seen in these patients. Our findings suggest that these patients most frequently develop isolated renal failure, often requiring renal replacement therapy; however, the outcomes following this are very good, supporting the early involvement of intensive care teams.

A matched case-control study of the clinical, economic, and patient-reported outcomes of cystoid macular edema complicating phacoemulsification surgery.

PURPOSE: To assess the visual outcomes of pseudophakic cystoid macular edema (CME) as compared with age- and copathology-matched control subjects, the costs of treatment and follow-up, and the patient-reported outcomes using the new Cat-patient-reported outcome measures (PROM) 5 questionnaire. SETTING: West Suffolk Hospital NHS Foundation Trust, United Kingdom. DESIGN: Matched case-control study. METHODS: Fifty-two eyes of 49 patients developed CME over an 18-month period. Age- and copathology-matched patients were identified from clinical records over the same time period in a 2:1 ratio (90 eyes). Postoperative clinical outcomes were recorded including treatments received, costs of treatments, and patient-reported outcome measures using the Cat-PROM5. RESULTS: Patients with CME reported a significantly worse outcome from surgery than control subjects. Furthermore, patients with CME had significantly worse visual acuity postoperatively than control subjects (CME: logarithm of the minimum angle of resolution 0.40 ± 0.33, n = 37; control subjects: 0.30 ± 0.33; P < .05) despite there being no difference in preoperative visual acuity. In patients with epiretinal membrane (ERM), notably those with CME had worse patient-reported outcomes than control subjects with ERM, and only 18% received prophylactic corticosteroid injection at surgery compared with 63.6% of control subjects. CME resulted in an excess of 266 outpatient appointments, with 388 weeks of topical therapy, 18 orbital floor injections, 6 intravitreal steroid injections, 5 intravitreal antivascular endothelial growth factor injections, and 1 intravitreal dexamethasone implant with an excess expenditure of £216.81 per case. CONCLUSIONS: Patients developing CME after cataract surgery had reduced visual acuity at 4 to 6 weeks, patient-reported visual outcomes, and increased number of hospital appointments, treatments, and costs.

The use of pan-retinal photocoagulation to treat recurrent vitreous haemorrhage with neovascularisation in the context of Epstein syndrome: an MYH9-related disorder.

A female patient presented with stable chronic thrombocytopaenia with large platelets, sensorineuronal deafness and renal impairment. Her treatment was refractory to intravenous immunoglobulins (IVIG) and steroids for a putative diagnosis of immune thrombocytopaenic purpura (ITP). She underwent genetic testing which revealed a MYH9 mutation in-keeping with a diagnosis of Epstein Syndrome. Subsequently to this she developed globally constricted fields on Goldmann visual field testing. MRI pituitary was unremarkable but she was diagnosed with a pituitary microprolactinoma secondary to raised prolactin in the blood responsive to carbegoline therapy. She subsequently developed retinal haemorrhages and recurrent vitreous haemorrhages due to neovascularisation. Fluorescein angiography revealed the extent of the neovascularisation and microvascular ischaemia. She underwent pan-retinal photocoagulation (PRP) to treat the ischaemic stimulus which resulted in regression of the new vessels and cessation of vitreous haemorrhages. There are no previous reported cases of microvascular retinal disease in the literature in the context of Epstein Syndrome, and this is the first report of successful treatment with PRP.

Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption.

BACKGROUND: Diet is a major contributor to metabolic disease risk, but there is controversy as to whether increased incidences of diseases such as non-alcoholic fatty liver disease arise from consumption of saturated fats or free sugars. Here, we investigate whether a sub-set of triacylglycerols (TAGs) were associated with hepatic steatosis and whether they arise from de novo lipogenesis (DNL) from the consumption of carbohydrates. RESULTS: We conduct direct infusion mass spectrometry of lipids in plasma to study the association between specific TAGs and hepatic steatosis assessed by ultrasound and fatty liver index in volunteers from the UK-based Fenland Study and evaluate clustering of TAGs in the National Survey of Health and Development UK cohort. We find that TAGs containing saturated and monounsaturated fatty acids with 16-18 carbons are specifically associated with hepatic steatosis. These TAGs are additionally associated with higher consumption of carbohydrate and saturated fat, hepatic steatosis, and variations in the gene for protein phosphatase 1, regulatory subunit 3b (PPP1R3B), which in part regulates glycogen synthesis. DNL is measured in hyperphagic ob/ob mice, mice on a western diet (high in fat and free sugar) and in healthy humans using stable isotope techniques following high carbohydrate meals, demonstrating the rate of DNL correlates with increased synthesis of this cluster of TAGs. Furthermore, these TAGs are increased in plasma from patients with biopsy-confirmed steatosis. CONCLUSION: A subset of TAGs is associated with hepatic steatosis, even when correcting for common confounding factors. We suggest that hepatic steatosis risk in western populations is in part driven by increased DNL following carbohydrate rich meals in addition to the consumption of saturated fat.

Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) can progress from simple steatosis (i.e., nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. Currently, the driver for this progression is not fully understood; in particular, it is not known how NAFLD and its early progression affects the distribution of lipids in the liver, producing lipotoxicity and inflammation. In this study, we used dietary and genetic mouse models of NAFL and NASH and translated the results to humans by correlating the spatial distribution of lipids in liver tissue with disease progression using advanced mass spectrometry imaging technology. We identified several lipids with distinct zonal distributions in control and NAFL samples and observed partial to complete loss of lipid zonation in NASH. In addition, we found increased hepatic expression of genes associated with remodeling the phospholipid membrane, release of arachidonic acid (AA) from the membrane, and production of eicosanoid species that promote inflammation and cell injury. The results of our immunohistochemistry analyses suggest that the zonal location of remodeling enzyme LPCAT2 plays a role in the change in spatial distribution for AA-containing lipids. This results in a cycle of AA-enrichment in pericentral hepatocytes, membrane release of AA, and generation of proinflammatory eicosanoids and may account for increased oxidative damage in pericentral regions in NASH. CONCLUSION: NAFLD is associated not only with lipid enrichment, but also with zonal changes of specific lipids and their associated metabolic pathways. This may play a role in the heterogeneous development of NAFLD. (Hepatology 2017;65:1165-1180).