Emil Holmström

Anti-inflammatory medication following cataract surgery: a randomized trial between preservative-free dexamethasone, diclofenac and their combination

To examine the anti‐inflammatory efficacy and tolerance between preservative‐free dexamethasone (DEX) and diclofenac (DICL) eye drops, and their combination following cataract surgery.

Simvastatin pretreatment reduces caspase-9 and RIPK1 protein activity in rat cardiac allograft ischemia-reperfusion.

BACKGROUND In transplantation-associated ischemia/reperfusion injury (Tx-IRI), tumor necrosis factor alpha and damage-associated molecular patterns promote caspase-8 and -9 apoptotic and receptor-interacting protein kinase-1 and -3 (RIPK1/3) necroptotic pathway activation. The extent of cell death and the counterbalance between apoptosis and regulated necrosis eventually determine the immune response of the allograft. Although simvastatin prevents Tx-IRI, its role in apoptotic and necroptotic activity remains unsolved. METHODS Rat allograft donors and recipients were treated with a single-dose of simvastatin 2h prior to allograft procurement and reperfusion, respectively. Intragraft caspase-3, -8, and -9 and RIPK1 and -3 mRNA expression was analysed by quantitative RT-PCR and protein activity measured by immunohistochemistry and luminescent assays 6h after reperfusion. Lactate and lactate dehydrogenase (LDH) levels were analysed from allograft recipient and from hypoxic endothelial cell cultures having treated with activated simvastatin. RESULTS When compared to without cold ischemia, prolonged 4-hour cold ischemia significantly enhanced intragraft mRNA expression of caspase-3 and -9, and RIPK1 and -3, and elevated protein activity of caspase-9 and RIPK1 in the allografts. Simvastatin pretreatment decreased mRNA expression of caspase-3 and -9, and RIPK1 and -3 and protein activity of caspase-9 and RIPK1 in the allografts. Intragraft caspase-8 mRNA expression remained constant regardless of cold ischemia or simvastatin pretreatment. Simvastatin pretreatment attenuated lactate and LDH levels, both in the allograft recipients and in hypoxic endothelial cell cultures. CONCLUSIONS The beneficial effects of simvastatin pretreatment in cardiac allograft IRI may involve prevention of apoptosis and necroptosis.

The Impact of Deceased Donor Simvastatin Treatment on Kidney Transplant Outcomes - Results of a Double-Blinded, Randomized Controlled Trial

Background In heart transplantation (HTx), postoperative statin treatment has been shown to reduce cardiac allograft vasculopathy (CAV) and long-term mortality. We have previously shown that donor simvastatin treatment reduces ischemia-reperfusion injury and development of CAV in animal HTx models. Recently, we were also able to show that donor simvastatin decreases ischemia-reperfusion injury in clinical HTx (unpublished). However, HTx donors are multi-organ donors, and the effect of donor simvastatin treatment on kidney allograft remains unknown. Methods We randomized 84 HTx donors into equal groups to receive either 80 mg of simvastatin or nothing through nasogastric tube at the time of acceptance as a donor. All donors also donated one or both kidneys. We collected relevant clinical data and postoperative laboratory markers from both donors and kidney recipients. Kidney recipients were followed up for (currently) 1 year for rejections, mortality, plasma creatinine, acute kidney injury marker (NGAL), and kidney function. Results In total, 115 adult single kidney transplants were performed. Of these, 61 recipients received kidney from a simvastatin treated donor, and 54 from a control donor. There were three allografts that did not start at all due to thrombosis, two in simvastatin group and one in control group. The overall incidence of delayed graft function was 36%. The overall incidence of rejection in the first year was 16%. There were no significant differences in any of the measured follow-up parameters between donor treated allografts and controls. Conclusions Our results suggest that donor simvastatin treatment has little effect on kidney allograft outcome. More importantly, however, treating multi-organ donor with simvastatin in order to protect the heart is safe from the perspective of kidney allografts.

Macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome

Background: The purpose of the study was to identify macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome. The study was a post-hoc analysis of a randomized, double-blind, prospective single-center study. Patients were enrolled between January 2016 and October 2016 as per the national guidelines for the management of cataract in the Department of Ophthalmology, Kymenlaakso Central Hospital, Kotka, Finland. Methods: One hundred and fifty-six eyes of 149 patients undergoing routine cataract surgery. Postoperatively anti-inflammatory medication was either dexamethasone (N = 78) or diclofenac (N = 78). Spectral domain optical coherence tomography imaging and laser flare meter measurement of the anterior chamber were conducted before surgery and at the control visit 28 days postoperatively. Results: Baseline variables were comparable between eyes with pseudoexfoliation syndrome (N = 32) and those without (N = 124), except for intraocular pressure (P = 0.002) and glaucoma medication (P < 0.001). In patients having pseudoexfoliation syndrome, central retinal thickness increase (mean ± standard error of the mean) was 63.3 ± 35.5 μm for dexamethasone and 17.6 ± 5.8 μm for diclofenac, compared to 28.9 ± 8.0 μm (P = NS) and 6.9 ± 1.3 μm (P = 0.014) in eyes without pseudoexfoliation syndrome, respectively. Aqueous flare at 28 days was 25.8 ± 5.4 pu/ms for patients with pseudoexfoliation syndrome and 18.3 ± 1.8 pu/ms for those without (P = 0.030). Best corrected visual acuity gain and best corrected visual acuity at 28 days were less in patients having pseudoexfoliation syndrome compared to those without (0.39 ± 0.07 vs 0.59 ± 0.03 decimals, P = 0.007; and 0.77 ± 0.06 vs 0.92 ± 0.03 decimals, P = 0.008, respectively). Conclusion: Eyes with pseudoexfoliation syndrome may be predisposed to an increased aqueous flare and macular edema after cataract surgery. This study outlines the need to determine the optimal anti-inflammatory medication after cataract surgery in patients with pseudoexfoliation syndrome.

Systemic use of calcium channel blockers associated with less increase in central retinal thickness after uncomplicated cataract surgery

To examine the role of systemic medication on the risk of pseudophakic cystoid macular edema (PCME) following uneventful cataract surgery.

Preoperative visual acuity does not correlate with patient satisfaction for cataract surgery

Editor, C ataract surgery is one of the most common elective surgical procedures in Western countries, and the number of operations is expected to increase considerably in the next decades (Kessel 2011). Yet, there is very little scientific evidence to help the clinician to choose the patients most likely to benefit from the procedure. In a recent article,Weingessel et al. reported interesting results on the maximum acceptable waiting time of cataract patients. Their results showed that the maximum waiting time accepted by the patients was not associated with their better eye best-corrected visual acuity (BCVA) on clinical testing. They also concluded that the VF-14 score reflecting subjective difficulty with vision was more predictive of the patients’ preoperative medical condition than visual acuity (VA) (Weingessel et al. 2018). The American Academy of Ophthalmology preferred practice patterns, the National Institute for Health and Care Excellence recommendations and the current Danish national guideline are in line with these results by recommending not to use preoperative VA as the sole criterion as indication for cataract surgery, but to also take into account the patients’ self-reported subjective symptoms (Sundhedsstyrelsen 2013). In Sweden, a clinical tool NIKE (Nationell Indikationsmodell for Kataraktextraktion) is widely used for prioritizing patients on waiting lists for cataract surgery. The tool takes into account the patient’s subjective problems in day-to-day life in addition to VA and it has proven to be able to predict the benefit from surgery (Lundstrom et al. 2006). In recent years, it has led to reduced waiting times for those with the greatest need for surgery (Ng & Lundstrom 2014). Here, we report data of a total of 619 eyes scheduled for unilateral cataract surgery between January 2016 and December 2017. The overall satisfaction of the patients (male: female distribution 38:62%) was recorded by a structured home questionnaire and an interview by the research technician at the 28-day ( 2 days) postoperative visit.The analysis did not distribute first and second eye operations nor laterality, or dominance of the operated eye. On a scale of 0–10, the overall patient satisfaction was 9.39 0.83 (range 4–10). Neither the baseline BCVA evaluated by the referring ophthalmologist nor the BCVA gain at 28 days recorded by the research technician correlated with the patient’s satisfaction for cataract surgery (Table 1). Moreover, phacoemulsification energy reflecting the density of the cataract did not correlate with the level of satisfaction (Table 1). In conclusion, preoperative VA as an independent factor has low predictive value for the patient’s satisfaction for the surgery. Our results encourage using a system for waiting list prioritization that does not put too much importance solely on preoperative visual acuity but instead takes the patients’ subjective symptoms into account.

Postoperative management in cataract surgery: nepafenac and preservative-free diclofenac compared

Current cataract surgery guidelines recommend routine use of topical nonsteroidal anti‐inflammatory drugs (NSAIDs) in preventing pseudophakic cystoid macular oedema (PCME). Here, we compare the clinical efficacy and tolerability of two potent NSAIDs, nepafenac and preservative‐free diclofenac following cataract surgery.

Simvastatin Treatment Upregulates Anti-Fibrotic Bone Morphogenetic Protein-7 Expression at Rat Cardiac Allograft Rejection

Background: Bone morphogenetic protein (BMP)-7 mediates ischemic tolerance and anti-fibrotic effects in various organs such as kidney and heart. Recently, reno- and podocyte-protective effects of a potent HMG-CoA reductase inhibitor, pitavastatin, were accompanied by BMP-7 upregulation. Methods: Here, we investigated the effect of simvastatin treatment on BMP-7 expression in major MHC-mismatched rat cardiac allografts subjected to ischemia-reperfusion injury and adaptive immune activation at 10 days. Results: We localized Smad2 activity and Reca-1+ fibroblast specific protein-1+ immunoreactivity, suggesting endothelial-to-mesenchymal transition, at fibrotic borderline of cardiac allografts at 10 days. Simvastatin donor and recipient combination treatment significantly upregulated cardiac allograft BMP-7 expression when compared to nontreated controls at 10 days. Conclusion: The beneficial effect of statin treatment on cardiac allograft may in part be mediated through the upregulation of BMP-7.