Phase I/II randomized, double-masked, placebo-controlled study of processed amniotic fluid drops after PRK.

PURPOSE: To evaluate the safety and efficacy of processed amniotic fluid (pAF) used postoperatively after photorefractive keratectomy (PRK). SETTING: University of Utah, Moran Eye Center, Salt Lake City, Utah. DESIGN: Randomized, double-masked, placebo-controlled prospective study. METHODS: 61 participants were randomized to receive either placebo or pAF drops, which were instilled 4 times per day for 1 week after PRK along with routine postoperative medications. The primary outcome measure was time to full re-epithelialization in days. Secondary measures included visual acuity at 30 days and postoperative pain scores during the first week. RESULTS: There was no significant difference in time to re-epithelialization, with a median of 5 days for both groups. There were no difference in pain indicator scores during the first week and no difference in corneal staining scores at day 30 between the 2 groups. There were no adverse events. CONCLUSIONS: This pilot study evaluating the safety and efficacy of pAF as an additional postoperative topical medication for PRK demonstrated that pAF did not improve the rate of epithelial healing after PRK. pAF may be safely studied in other ocular conditions to determine its effect on epithelial healing.

Suture-needle snare for scleral fixation.

Current scleral suture fixation techniques pose challenges for highly complex eyes. A scleral suture fixation technique using a snare that is fashioned out of a 27-gauge needle and 8-0 nylon suture is described. This technique is well-suited for scleral suture fixation in complex eyes because it reduces risk factors for intraoperative and postoperative complications, simplifies intraocular maneuvers, minimizes surgical trauma, and does not require specialized microinstrumentation.

Targeted Lens Pitting to Treat Negative Dysphotopsia.

PURPOSE: To describe a patient with negative dysphotopsia who underwent a novel non-invasive technique that uses the Nd:YAG laser to induce nasal light scattering through targeted lens pitting. METHODS: Case report. RESULTS: Symptoms of negative dysphotopsia resolved after targeted lens pitting. CONCLUSIONS: Targeted lens pitting with Nd:YAG laser is a potential technique that may help treat negative dysphotopsia in a manner that preserves intraocular anatomy. Further study is warranted to explore targeted lens pitting in both patients with and without prior retinal surgery as a treatment for negative dysphotopsia. [J Refract Surg. 2021;37(3):212-214.].

Epithelial Plaque Formation Secondary to Recombinant Human Nerve Growth Factor.

PURPOSE: To report a case of corneal epithelial plaque formation associated with recombinant human nerve growth factor (cenegermin 0.002%; Oxervate, Dompe[Combining Acute Accent] US Inc., Boston, MA), an as-yet unreported adverse event. METHODS: A case report and review of literature. RESULTS: A 45-year-old woman presented with a nonhealing 3.25- × 4.25-mm corneal epithelial defect secondary to multifactorial neurotrophic keratitis in the right eye. The epithelial defect was resistant to maximal medical therapy, and so cenegermin 0.002% was initiated, resulting in resolution of the corneal epithelial defect. After 6.5 weeks of treatment, she developed an unusual corneal epithelial plaque, decreased visual acuity, and eye pain. Cenegermin was ceased, after which the lesion resolved, visual acuity improved, and eye pain resolved. CONCLUSIONS: Cenegermin 0.002% has emerged as a promising treatment for neurotrophic keratitis. Reported adverse events with this agent have been minor and typically not vision threatening. Here, we describe corneal epithelial plaque formation as a visually significant adverse event that resolved with cessation of cenegermin 0.002%. Although the underlying mechanism is unknown, clinicians should be alerted to the possibility of epithelial plaque formation in patients being treated with recombinant human nerve growth factor for neurotrophic keratitis.

TWO CASES OF ACUTE RETINAL NECROSIS DUE TO VARICELLA ZOSTER DESPITE PRIOR SHINGLES VACCINATION.

PURPOSE: To review two cases of acute retinal necrosis in adults due to varicella zoster virus despite prior shingles vaccination. METHODS: Retrospective chart review. PATIENTS: A 62-year-old man and a 64-year-old man with unilateral acute retinal necrosis who had shingles vaccinations 16 and 7 months before their ocular symptoms. RESULTS: Polymerase chain reaction confirmation of varicella zoster virus in the anterior chambers of both patients. Both patients had good responses to oral antiviral therapy and topical and/or oral steroids. DISCUSSION: These two cases demonstrate that singles vaccination is not an absolute protection against varicella zoster virus-related acute retinal necrosis. However, such vaccination may reduce the severity of the acute retinal necrosis.

Use of Topical Insulin to Treat Refractory Neurotrophic Corneal Ulcers.

PURPOSE: To report the clinical course of 6 patients with refractory neurotrophic corneal ulcers that were treated with topical insulin drops. METHODS: Retrospective chart review of patients who had neurotrophic corneal ulcers or epithelial defects refractory to standard medical and surgical treatment. Insulin drops, prepared by mixing regular insulin in artificial tears with a polyethylene glycol and propylene glycol base at a concentration of 1 unit per milliliter, were prescribed 2 to 3 times daily. RESULTS: Six patients, aged 2 to 73 years, developed neurotrophic corneal ulcers refractory to a range of medical and surgical treatments, including bandage contact lens, amniotic membrane grafting, and permanent tarsorrhaphy. Each patient was administered topical insulin drops with complete corneal reepithelialization within 7 to 25 days. CONCLUSIONS: Topical insulin may be a simple and effective treatment for refractory neurotrophic corneal ulcers. Further study is required to determine the clinical efficacy and side effect profile of insulin drops.

Dysadherin specific drug conjugates for the treatment of thyroid cancers with aggressive phenotypes.

BACKGROUND: EDC1 is a novel type of antibody-drug conjugate which binds and inhibits the Na,K-ATPase on the surface of cancer cells expressing dysadherin. The purpose of this study was to determine the expression of dysadherin in different types of thyroid carcinoma, and evaluate the therapeutic potential of EDC1 for thyroid carcinomas. METHODS: Thyroid tissues from 158 patients were examined for dysadherin expression and correlation with clinicopathological features. Thyroid cancer cell lines were examined for the expression of dysadherin and effective dose range of EDC1. RESULTS: One in 53 benign thyroid tissues and 62% of thyroid cancers expressed dysadherin. All anaplastic and a majority of papillary thyroid cancers overexpressed dysadherin, while 25% of follicular thyroid cancers was found to be positive for dysadherin. Dysadherin expression significantly correlated with extrathyroidal extension and lymph node metastases in papillary thyroid cancer. Five of six human thyroid cancer cell lines analyzed expressed high levels of dysadherin. Of those cells lines sensitive to EDC1, half maximal effective concentrations (EC50) were observed to be between 0.125 nM and 1 nM. CONCLUSIONS: EDC1 showed selective inhibition of growth in thyroid cancer cells with moderate to high expression of dysadherin, thus could be a specific and effective treatment.

Comparing Nonrandomized Observational Studies With Randomized Controlled Trials in Cervical Disc Arthroplasty: A Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare the treatment effects of observational studies versus randomized controlled trials (RCTs) in cervical disc arthroplasty. SUMMARY OF BACKGROUND DATA: RCTs can be logistically challenging and sometimes insufficiently generalizable; well-designed observational studies have been suggested as an alternative. We hypothesized that treatment effects of observational studies in cervical disc arthroplasty are similar to those of RCTs. METHODS: We searched electronic database from 2000 to 2014. The Neck Disability Index (NDI) was the primary outcome from which the standardized pre-and-post mean difference (Hedges's g) was determined. Meta-analysis was performed to compare Hedges's g from observational studies to that of RCTs. Potential moderator variables including study quality, age, gender, industry sponsorship, location by continent, and disc types were also collected and analyzed. Observational studies were further stratified into prospective and retrospective, and they were compared to each other as well as to RCTs. RESULTS: We identified nine RCTs, 28 observational studies, and one hybrid study for meta-analysis. NDI Hedges's g was 2.15 for RCTs and 2.03 for observational studies, which was not significant (P = 0.416). No significant difference was found in secondary outcomes. However, after further stratification, prospective observational studies had less treatment effect in Visual Analog Scale neck compared with that of RCTs (1.60 vs. 2.11, P = 0.006). RCTs recruited younger patients (44.1 vs. 45.6, P = 0.008) with worse NDI at baseline (54.30 vs. 46.92, P < 0.001). Patients treated with ProDisc-C showed less standardized improvement on the NDI compared with the patients treated with Prestige (1.41 vs. 2.48, P = 0.026). CONCLUSION: Prospective observational studies that utilize the same features of RCTs such as inclusion and exclusion criteria validated clinical outcomes, and statistical methods can provide valuable information about the treatment effects on a generalizable population. LEVEL OF EVIDENCE: 4.

Radioguided parathyroidectomy for tertiary hyperparathyroidism.

BACKGROUND: Tertiary hyperparathyroidism (3HPT) is defined as the persistent hyperproduction of parathyroid hormone and resulting hypercalcemia after renal transplantation. Here, we examine the utility of radioguided parathyroidectomy (RGP) in patients with 3HPT. MATERIALS AND METHODS: We reviewed a prospective surgery database containing 80 3HPT patients who underwent RGP from January 2001-July 2014 at our institution. We evaluated patient demographics, operative management, radioguided neoprobe utilization, and operative outcomes. Data are reported as mean ± standard error of the mean. RESULTS: The mean age of the patients was 52 ± 1 y, and 46% were male. A total of 69 patients had hyperplasia and received subtotal parathyroidectomy, whereas 5 patients had double adenomas and 6 patients had single adenomas. The average calcium level among 3HPT patients was 10.8 ± 0.1 mg/dL preoperatively and 8.7 ± 0.1 mg/dL postoperatively. In vivo radioguided counts normalized to background counts averaged 145 ± 4%, whereas ex vivo counts normalized to background counts averaged 69 ± 5%. All but one ex vivo count was >20%. Ectopically located glands were successfully localized in 38 patients using the gamma probe. Ex vivo percentage did not correlate with parathyroid gland weight, preoperative parathyroid hormone, or preoperative calcium. Our radioguided approach achieved normocalcemia in 96% of 3HPT patients undergoing RGP; two patients developed recurrent disease. CONCLUSIONS: In this series, all enlarged parathyroid glands were localized and resected using the gamma probe. Thus, RGP reliably localizes adenomatous, hyperplastic, and ectopically located glands in patients with 3HPT, resulting in high cure rate after resection.

The effect of cinacalcet on intraoperative findings in tertiary hyperparathyroidism patients undergoing parathyroidectomy.

INTRODUCTION: Tertiary hyperparathyroidism (3HPTH) patients who undergo parathyroidectomy (PTX) are often managed with calcium lowering medications such as cinacalcet (Sensipar) before surgery. Here, we assess how cinacalcet treatment influences intraoperative parathyroid hormone (IOPTH) kinetics and surgical findings in 3HPTH patients undergoing PTX. METHODS: We reviewed retrospectively 113 patients 3HPTH who underwent PTX, 14 of whom were taking cinacalcet and 112 who were not taking the drug. IOPTH levels fitted to linear curves versus time were used to evaluate the role of cinacalcet. RESULTS: Cinacalcet did not correlate with rates of cure (P = .41) or recurrence (P = .54). Patients taking cinacalcet experienced a steeper decrease in IOPTH compared with those not taking the medication (P = .005). Cinacalcet treatment was associated with an increase in rate of hungry bones (P = .04). Weights of the heaviest glands resected (P = .02) and preoperative PTH levels (P = .0004) were greater among patients taking cinacalcet. CONCLUSION: Perioperative cinacalcet treatment in patients with 3HPTH alters IOPTH kinetics by causing a steeper decrease in IOPTH, but does not require modification of the standard IOPTH protocol. Although cinacalcet use does not adversely affect cure rates, it is associated with greater preoperative PTH and an increased incidence of hungry bones, hence serving as an indicator of more severe disease. Cinacalcet does not need to be held before operation.

The novel histone deacetylase inhibitor thailandepsin A inhibits anaplastic thyroid cancer growth.

BACKGROUND: Anaplastic thyroid cancer (ATC) remains refractory to available surgical and medical interventions. Histone deacetylase (HDAC) inhibitors are an emerging targeted therapy with antiproliferative activity in a variety of thyroid cancer cell lines. Thailandepsin A (TDP-A) is a novel class I HDAC inhibitor whose efficacy remains largely unknown in ATC. Therefore, we aimed to characterize the effect of TDP-A on ATC. METHODS: Human-derived ATC cells were treated with TDP-A. IC50 was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) rapid colorimetric assay, and cell proliferation was measured by viable cell count. Molecular mechanisms of cell growth inhibition were investigated by Western blot analysis of canonical apoptosis markers, intrinsic and extrinsic apoptosis regulators, and cell cycle regulatory proteins. Cell cycle staging was determined with propidium iodide flow cytometry. RESULTS: TDP-A dose- and time-dependently reduced cell proliferation. Increased cleavage of the apoptosis markers Caspase-9, Caspase-3, and poly adenosine diphosphate ribose polymerase were observed with TDP-A treatment. Levels of the intrinsic apoptosis pathway proteins BAD, Bcl-XL, and BAX remained unchanged. Importantly, the extrinsic apoptosis activator cleaved Caspase-8 increased dose-dependently, and the antiapoptotic proteins Survivin and Bcl-2 decreased. Among the cell cycle regulatory proteins, levels of CDK inhibitors p21/WAF1 and p27/KIP increased. Flow cytometry showed that ATC cells were arrested in G2/M phase with diminished S phase after TDP-A treatment. CONCLUSIONS: TDP-A induces a notable dose- and time-dependent antiproliferative effect on ATC, which is mainly attributed to extrinsic apoptosis with concomitant cell cycle arrest. TDP-A therefore warrants further preclinical and clinical investigations.