Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment.     

Gross and microscopic study of insertion of levator palpebrae superioris and its anatomical correlation in superior palpebral crease formation and its clinical relevance

Background

To study insertion of LPS and correlate anatomically the formation of superior palpebral crease and its clinical relevance in section of Indian population.

Methods

Twenty-five human eyelids from cadavers ranging from 15–80 years were studied by dissection and histology.

Results

The levator aponeurosis traverses through interfascicular space of orbicularis oculi with twenty four inserting into subcutaneous tissue. Low septo aponeurotic sling or preaponeurotic fat was not observed. Lower one third tarsal insertion seen in twenty four specimens. Fibres become denser as it reaches the connective tissue anterior to tarsal plate. The crease was at different levels in relation to the tarsal insertion.

Conclusion

The aponeurosis insertion is either to the skin, the subcutaneous tissue or into the interfascicular space of the orbicularis. The present study reaffirms the insertion of LPS to the subcutaneous tissue of the eyelid with an extension reaching lower one third of the tarsal plate. The tissues in the anterior tarsal plate are closely packed but to act as a single complex to form a dynamic crease has not been confirmed in the study. No gross or histological difference was observed in the skin of the eyelid in the vicinity of the crease. The pattern of insertion of LPS aponeurosis plays a direct role in the formation of superior palpebral crease an important role in surgeries for Ptosis. The eyelids studied were of Indian origin with crease, and further comparative studies needs to be done for the precise anatomical explanation of single fold eyelids.     

AIDS and heart disease: is cardiac surgery justified?

A compromised immune system, limited survival and increased risk to the anaesthetic and surgical team of acquiring HIV infection have been the major concerns in offering cardiac surgery to patients with AIDS. The current report presents a patient with AIDS who underwent successful, uncomplicated coronary artery surgery. He remains free of ischaemic and any infectioe symptoms 12 months postoperatively.     

Botulinum Toxin in the Treatment of Muscle Specific Oro-Facial Pain: A Literature Review

Facial pain associated with temporomandibular joint (TMJ) and surrounding structures has been a challenge to clinicians as far as diagnosis and management is concerned. Complexity of anatomical structures within a small area, function of teeth and surrounding periodontal ligament, action of muscles, pathologies, lack of diagnostic investigations, all these complicate specific diagnosis of TMJ disorders. Various classifications have been designed and studied to help diagnose and treat TMJ related disorders, of which the simplest one is pain from TMJ proper and surrounding muscles. Many treatment modalities to treat pain arising from muscles around TMJ like splints, mouth restriction exercises, injection of sclerosing agents etc. have been used with various degrees of success. Botulinum toxin has been shown to be effective in the treatment of oro-facial pain due to muscular disorders and the same is discussed in detail in this review literature.     

Development, sex steroid regulation, and phenotypic characterization of RFamide-related peptide (Rfrp) gene expression and RFamide receptors in the mouse hypothalamus

Arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3, encoded by the Rfrp gene) is the mammalian ortholog of gonadotropin-inhibiting hormone and can inhibit GnRH neuronal activity and LH release. However, the development and regulation of the RFRP-3 system in both sexes is poorly understood. Using in situ hybridization, we examined changes in Rfrp-expressing neurons in mice of both sexes during development and under different adulthood hormonal milieus. We found no sex differences in Rfrp expression or cell number in adult mice. Interestingly, we identified two interspersed subpopulations of Rfrp cells (high Rfrp-expressing, HE; low Rfrp-expressing, LE), which have unique developmental and steroidal regulation characteristics. The number of LE cells robustly decreases during postnatal development, whereas HE cell number increases significantly before puberty. Using Bax knockout mice, we determined that the dramatic developmental decrease in LE Rfrp cells is not due primarily to BAX-dependent apoptosis. In adults, we found that estradiol and testosterone moderately repress Rfrp expression in both HE and LE cells, whereas the nonaromatizable androgen dihydrotestosterone has no effect. Using double-label in situ hybridization, we determined that approximately 25% of Rfrp neurons coexpress estrogen receptor-α in each sex, whereas Rfrp cells do not readily express androgen receptor in either sex, regardless of hormonal milieu. Lastly, when we looked at RFRP-3 receptors, we detected some coexpression of Gpr147 but no coexpression of Gpr74 in GnRH neurons of both intact and gonadectomized males and females. Thus, RFRP-3 may exert its effects on reproduction either directly, via Gpr147 in a subset of GnRH neurons, and/or indirectly, via upstream regulators of GnRH.     

Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery

One of the promises of nanoparticle (NP) carriers is the reformulation of promising therapeutics that have failed clinical development due to pharmacologic challenges. However, current nanomedicine research has been focused on the delivery of established and novel therapeutics. Here we demonstrate proof of the principle of using NPs to revive the clinical potential of abandoned compounds using wortmannin (Wtmn) as a model drug. Wtmn is a potent inhibitor of phosphatidylinositol 3' kinase-related kinases but failed clinical translation due to drug-delivery challenges. We engineered a NP formulation of Wtmn and demonstrated that NP Wtmn has higher solubility and lower toxicity compared with Wtmn. To establish the clinical translation potential of NP Wtmn, we evaluated the therapeutic as a radiosensitizer in vitro and in vivo. NP Wtmn was found to be a potent radiosensitizer and was significantly more effective than the commonly used radiosensitizer cisplatin in vitro in three cancer cell lines. The mechanism of action of NP Wtmn radiosensitization was found to be through the inhibition of DNA-dependent protein kinase phosphorylation. Finally, NP Wtmn was shown to be an effective radiosensitizer in vivo using two murine xenograft models of cancer. Our results demonstrate that NP drug-delivery systems can promote the readoption of abandoned drugs such as Wtmn by overcoming drug-delivery challenges.     

Effect of early diagnosis and treatment with percutaneous lead extraction on survival in patients with cardiac device infections

Cardiac device infections (CDIs) represent a serious complication after the implantation of pacemakers and defibrillators. In addition to antimicrobials, complete hardware removal, mostly with percutaneous lead extraction (PLE), is necessary to limit recurrences. However, CDI diagnosis is often difficult and is sometimes delayed, and scarce data exist on how the timing of PLE may affect clinical outcomes. In this study, the in-hospital outcomes of 52 consecutive patients with CDIs who underwent PLE were retrospectively analyze. Co-morbidities such as diabetes mellitus, congestive heart failure, renal insufficiency, and end-stage renal disease were highly prevalent in the study cohort. Patients were divided into group A (bacteremia or device endocarditis) and group B (localized pocket infection). In-hospital mortality was 29% in group A and 5% in group B (p = 0.02) and was due mostly to sepsis. Hospital stays were shorter in group B patients (5.7 vs 21.7 days, p <0.001). Presentation with hypotension was more commonly observed in group A patients and was associated with higher in-hospital mortality, whereas pocket findings correlated with better survival. Postoperative courses after PLE were uneventful in most patients, and no fatal complications were observed. PLE was performed significantly earlier in group B patients (hospitalization day 1.3 vs 7.6, p <0.001). PLE performed within 3 hospitalization days was associated with lower in-hospital mortality (p = 0.01). In conclusion, PLE performed within 3 days from admission is associated with shorter hospitalization and better survival. A timely diagnosis is crucial, particularly in the absence of local findings, because early treatment with PLE is likely to prevent the catastrophic outcomes of unrelenting CDIs.