Systemic and Ocular Adverse Events with Intravitreal Anti-VEGF Therapy Used in the Treatment of Diabetic Retinopathy: a Review.

PURPOSE OF REVIEW: Intravitreal anti-vascular endothelial growth factor (VEGF) agents are used routinely in the management of neovascular conditions including proliferative diabetic retinopathy and diabetic macular edema. While the efficacy of anti-VEGF agents has been well-validated, their ocular and systemic adverse events should always be considered and discussed with patients. The aim of this review is to discuss the most recent literature reports regarding the various ocular and systemic adverse events associated with intravitreal anti-VEGF treatment in diabetic retinopathy. RECENT FINDINGS: The most frequently reported adverse ocular events include subconjunctival hemorrhage, vitreous hemorrhage, increased intraocular pressure, uveitis, endophthalmitis, ocular surface disease, and traumatic cataract. Subconjunctival hemorrhage and vitreous hemorrhage are the most common ocular adverse events reported with intravitreal anti-VEGF treatment. The most serious (though rare) ocular adverse events include endophthalmitis and rhegmatogenous retinal detachment. A consensus regarding the association of systemic adverse events (such as myocardial infarction, stroke, and death) with intravitreal anti-VEGF treatments has not been established. Intravitreal anti-VEGF therapy is used in the treatment of diabetic retinopathy, macular degeneration, and other diseases. These agents are associated with a variety of ocular and systemic adverse events that ophthalmologists should always consider.

Clinical Outcome of Amniotic Membrane Transplant in Ocular Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis at a Major Burn Unit.

PURPOSE: To analyze the clinical outcome of amniotic membrane transplantation in patients with ocular Stevens-Johnson syndrome/toxic epidermal necrolysis at a major burn unit. DESIGN: Retrospective, non-randomized interventional study. METHODS: A retrospective chart review from April 2014 to January 2022 of 43 patients (85 eyes) at a burn center who underwent amniotic membrane transplantation (AMT) for severe ocular Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN was performed. Data regarding the clinical course and outcome were obtained. A comparison between the use of cryopreserved AMT rings (cryoAMT) and dehydrated AMT (deAMT) was also assessed. RESULTS: A total of 85 eyes in 43 patients underwent AMT for severe ocular SJS/TEN. Of the eyes, 72 received deAMT with symblepharon ring, whereas 13 received cryoAMT over the cornea surface. All patients had deAMT placed over the eyelid margins and palpebral conjunctivae and tucked into the fornices. The average best-corrected visual acuity (BCVA) on last follow-up examination was 20/33, 20/30, and 20/34 in all eyes, the cryoAMT group, and the deAMT group, respectively (no significant difference between groups). The most common suspected inciting agent was lamotrigine (17% of all cases). The average long-term complication score was 1.4, with no significant difference between the cryoAMT group (1.6) and the deAMT group (1.4, P = .5). Symblepharon formation was seen more in the cryoAMT group compared to the deAMT group (P < .05). CONCLUSION: The use of AMTs in severe ocular SJS/TEN greatly mitigates long-term complications and improves visual outcome. The retrospective nature of this study limits substantial conclusions regarding any significant difference in outcome between AMT treatment methods. Nevertheless, the use of cryopreserved AMT rings has a similar outcome profile compared to use of dehydrated AMTs with symblepharon ring. Further research is needed to evaluate optimal AMT techniques.

Intraoperative optical pachymetry in photorefractive keratectomy.

PURPOSE: To study the effect of variables on the accuracy and reliability of the optical pachymeter built into the WaveLight EX500 excimer laser during photorefractive keratectomy (PRK). SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, USA. DESIGN: Retrospective case series. METHODS: A chart review of 352 eyes (181 patients) that had excimer laser PRK was performed. Programmed excimer laser residual stromal bed (RSB) measurements, optical pachymeter measurements after ablation, and Scheimpflug pachymetry measurements (Pentacam) at the 1-year follow-up were compared. Variables included ablation time, preoperative spherical equivalent (SE), 1-year SE, mitomycin-C use, operating room temperature and humidity, and programmed monovision. RESULTS: The mean programmed RSB was 27 µm greater than the optical pachymetry post-ablation measurement (P < .001). Of patients with a 1-year follow-up, the 1-year Scheimpflug pachymetry RSB was 24 µm greater than the optical pachymetry post-ablation RSB (P < .001). Comparison of the programmed RSB with the optical pachymetry post-ablation RSB showed that the preoperative SE and ablation time had a Pearson correlation coefficient of -0.36 and 0.30, respectively (P < .001). There was no correlation between operating room temperature, humidity, or programmed monovision with these differences. CONCLUSIONS: The RSB post-ablation values measured by optical pachymetry during PRK were significantly lower than the programmed excimer laser RSB value and 1-year Scheimpflug pachymetry RSB value. Intraoperative pachymetry during PRK underpredicted the actual long-term RSB thickness. The greater temporary drying effect associated with increased ablation time in higher myopic corrections might have caused this error.

Accuracy of Alcon WaveLight® EX500 optical pachymetry during LASIK.

PURPOSE: To study the accuracy and reliability of optical pachymetry using the Alcon WaveLight EX500 during laser-assisted in situ keratomileusis (LASIK). MATERIALS AND METHODS: This was a retrospective chart review of 90 eyes from 45 patients who had undergone LASIK (mean age 35.2±8.2 years; 19 males, 26 females). The WaveLight FS200 femtosecond laser was programmed to cut LASIK flaps at a desired depth of 120 µm. Optical low-coherence reflectometry (WaveLight EX500) was used to measure central corneal thickness prior to lifting the flap, and the residual stromal bed immediately after excimer ablation. Flap thickness (FT) was calculated using simple subtraction. Optical coherence tomography (OCT) was used to measure central corneal thickness, flap thickness, and residual stromal bed in the postoperative period and the results compared to intraoperative measurements. RESULTS: Mean programmed FS200 FT was 119 µm. Mean FT using EX500 optical pachymetry was 109 µm. The difference between FS200- programmed and EX500-measured FT was 9 µm (P<0.001). There was also a significant difference between the EX500 and OCT FT (109 µm vs 119 µm, respectively; P<0.001). CONCLUSION: FT values calculated using intraoperative EX500 optical pachymetry were significantly lower than programmed FS200 values or OCT measurements.

The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy.

Caffeine is a widely consumed stimulant with the potential to enhance physical performance through multiple mechanisms. However, recent in vitro findings have suggested that caffeine may block skeletal muscle anabolic signaling through AMP-activated protein kinase (AMPK)-mediated inhibition of mechanistic target of rapamycin (mTOR) signaling pathway. This could negatively affect protein synthesis and the capacity for muscle growth. The primary purpose of this study was to assess the effect of caffeine on in vivo AMPK and mTOR pathway signaling, protein synthesis, and muscle growth. In cultured C2C12 muscle cells, physiological levels of caffeine failed to impact mTOR activation or myoblast proliferation or differentiation. We found that caffeine administration to mice did not significantly enhance the phosphorylation of AMPK or inhibit signaling proteins downstream of mTOR (p70S6k, S6, or 4EBP1) or protein synthesis after a bout of electrically stimulated contractions. Skeletal muscle-specific knockout of LKB1, the primary AMPK activator in skeletal muscle, on the other hand, eliminated AMPK activation by contractions and enhanced S6k, S6, and 4EBP1 activation before and after contractions. In rats, the addition of caffeine did not affect plantaris hypertrophy induced by the tenotomy of the gastrocnemius and soleus muscles. In conclusion, caffeine administration does not impair skeletal muscle load-induced mTOR signaling, protein synthesis, or muscle hypertrophy.