A new class of chemotherapeutic agents, MEK inhibitors, has recently been developed and is proving to be an effective treatment for a number of cancers. A pattern of ocular adverse events has followed these drugs through clinical trials and their association with retinopathy is only just beginning to be recognized. We present two cases of MEK inhibitor-associated retinopathy followed by a review of the current literature on ocular toxicity associated with MEK inhibitors. Patients undergoing treatment with MEK inhibitors appear to have high rates of multifocal serous retinal detachments as well as retinal vein occlusions. We present the first report of cystoid macular edema associated with MEK inhibitor use. The mechanism of these adverse events is still unclear though they seem to be related to oxidative stress and blood retinal barrier breakdown. Management of the ocular toxicity can range from observation to topical treatments or intravitreal injections. Fortunately most ocular adverse events appear to be selflimited and do not require discontinuing the MEK inhibitor. Discontinuation or decreased dosing of MEK inhibitors may be reserved for cases of severe sight-threatening ocular toxicity.

Background: Many CpGs become hyper or hypo-methylated with age. Multiple methods have been developed by Horvath et al. to estimate DNA methylation (DNAm) age including Pan-tissue, Skin & Blood, PhenoAge, and GrimAge. Pan-tissue and Skin & Blood try to estimate chronological age in the normal population whereas PhenoAge and GrimAge use surrogate markers associated with mortality to estimate biological age and its departure from chronological age. Here, we applied Horvath's four methods to calculate and compare DNAm age in 499 subjects with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study using DNAm data measured by Illumina EPIC array in the whole blood. Association of the four DNAm ages with development of diabetic complications including cardiovascular diseases (CVD), nephropathy, retinopathy, and neuropathy, and their risk factors were investigated. Results: Pan-tissue and GrimAge were higher whereas Skin & Blood and PhenoAge were lower than chronological age (p < 0.0001). DNAm age was not associated with the risk of CVD or retinopathy over 18-20 years after DNAm measurement. However, higher PhenoAge (β = 0.023, p = 0.007) and GrimAge (β = 0.029, p = 0.002) were associated with higher albumin excretion rate (AER), an indicator of diabetic renal disease, measured over time. GrimAge was also associated with development of both diabetic peripheral neuropathy (OR = 1.07, p = 9.24E−3) and cardiovascular autonomic neuropathy (OR = 1.06, p = 0.011). Both HbA1c (β = 0.38, p = 0.026) and T1D duration (β = 0.01, p = 0.043) were associated with higher PhenoAge. Employment (β = − 1.99, p = 0.045) and leisure time (β = − 0.81, p = 0.022) physical activity were associated with lower Pan-tissue and Skin & Blood, respectively. BMI (β = 0.09, p = 0.048) and current smoking (β = 7.13, p = 9.03E−50) were positively associated with Skin & Blood and GrimAge, respectively. Blood pressure, lipid levels, pulse rate, and alcohol consumption were not associated with DNAm age regardless of the method used. Conclusions: Various methods of measuring DNAm age are sub-optimal in detecting people at higher risk of developing diabetic complications although some work better than the others.

OCT is essential in distinguishing between partial and full-thickness macular folds. The authors propose that partial-thickness folds should be termed "pseudo-folds," which represent a unique entity that has a favorable natural history. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:488-492.].

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