Novel Treatments for Diabetic Macular Edema and Proliferative Diabetic Retinopathy.

PURPOSE OF REVIEW: Diabetic retinopathy (DR), a common cause of vision loss, is projected to increase worldwide, and is associated with significant morbidity. The current standard-of-care treatments can preserve and significantly improve vision in many patients affected by DR. However, challenges such as heavy treatment burden and refractory disease remain. The purpose of this review is to highlight and discuss investigative agents in development for the treatment of DR. RECENT FINDINGS: There are several novel agents with unique mechanisms that may offer greater durability and efficacy compared to existing drugs. Some target new pathways, others leverage a slow-release delivery system, and some modify gene expression through a single-dose treatment. While unfavorable adverse events, such as intraocular inflammation, have been observed with longer-durability agents, many investigational products show excellent efficacy and safety profiles. The outcomes of ongoing and future trials may revolutionize the current treatment paradigm for DR.

Neoadjuvant versus adjuvant chemotherapy for muscle-invasive bladder cancer: a propensity matched analysis.

BACKGROUND: We compared survival outcomes among patients who received either NAC or AC and RC. METHODS: We identified patients in the National Cancer Data Base (NCDB) diagnosed with clinical T2-T4, N0, M0 urothelial carcinoma who underwent RC. Patients who received NAC were propensity matched by age, race, ethnicity, sex, insurance type, academic/research program, comorbidity, and clinical stage to patients receiving AC within 90 days of RC. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated from multivariable Cox regression models to compare overall survival (OS), downstaging to non-MIBC (NMIBC), and N upstaging. RESULTS: A total of 417 patients treated with NAC and 272 patients treated with AC were identified from 2004-2013. Patients who received NAC had better 5-year OS (46.2%, 95% CI: 39.2-53.0%) compared to patients who received AC (37.6%, 95% CI: 31.5-43.7%). NAC was a significant predictor of decreased mortality, decreased progression to node positivity, and downstaging to NMIBC (0.76, 0.60-0.96, P=0.023; 0.19, 0.13-0.28, P<0.001; 23.96, 8.91-64.42, P<0.001). CONCLUSIONS: The use of NAC+RC was associated with improved OS compared to RC+AC for patients diagnosed with T2-T4, N0, M0 bladder cancer. The increased survival benefit associated with NAC compared to AC among patients undergoing RC may be due to decreased progression to node positivity and pathological downstaging.

Timing of adjuvant chemotherapy and overall survival following radical cystectomy.

BACKGROUND: We investigated the relationship between timing of adjuvant chemotherapy on overall survival following radical cystectomy. METHODS: We retrospectively reviewed the National Cancer Data Base for patients with newly diagnosed pT2-T4, N0, M0 urothelial cell carcinoma who received no treatment prior to radical cystectomy. Patients who received no adjuvant chemotherapy or who received adjuvant chemotherapy more than 45 days after radical cystectomy were propensity matched to patients receiving adjuvant chemotherapy within 45 days of radical cystectomy. Selection bias was assessed by comparing the length of stay, readmission rate, and surgical approach between groups. Median survival was calculated using Kaplan-Meier analysis. Adjusted hazard ratios and 95% confidence intervals were calculated from a multivariable Cox regression model to examine factors affecting overall survival. RESULTS: From 2004 to 2014, 284 patients with muscle-invasive bladder cancer met inclusion criteria. Patients receiving chemotherapy within 45 days had the best 5-year overall survival (47.0%, 95%CI: 40.6%-53.2%) compared to those receiving chemotherapy after 45 days (37.5%, 95%CI: 31.4%-43.7%). Chemotherapy after 45 days and no adjuvant chemotherapy were significant predictors of worse overall survival compared to chemotherapy within 45 days (1.27, 1.02-1.59, P = 0.033 and 1.41, 1.12-1.78, P = 0.003). Receiving no adjuvant chemotherapy was not significantly different than chemotherapy after 45 days (1.11, 0.89-1.38, P = 0.348). Significant predictors of poorer overall survival were female sex (1.37, 1.04-1.81, P = 0.028), Medicare (1.37, 1.06-1.76, P = 0.016), pT3 stage (1.79, 1.35-2.38, P < 0.001), and pT4 stage (3.00, 2.20-4.01, P < 0.001). Significantly more patients with length of stay ≤7 days following RC received chemotherapy within 45 days (53.2%) compared to those who received adjuvant chemotherapy after 45 days after RC (44.0%) or no adjuvant chemotherapy (43.0%; P = 0.0369). CONCLUSIONS: Initiation of adjuvant chemotherapy within 45 days of radical cystectomy for patients with pT2-4 bladder cancer was associated with an overall survival benefit compared to patients who received adjuvant chemotherapy after 45 days or no adjuvant chemotherapy.

Photophobia and sensations of dryness in patients with migraine occur independent of baseline tear volume and improve following botulinum toxin A injections.

BACKGROUND: To evaluate the efficacy of botulinum toxin A (BoNT-A) in reducing photophobia and dry eye symptoms in individuals with chronic migraine. Additionally, we aimed to evaluate tear film volume as a potential contributor to symptoms in these patients. METHODS: Retrospective review of 76 patients who received BoNT-A for chronic migraine between 23 August 2017 and 13 December 2017 at the Miami Veterans Affairs Medical Center Neurotoxin Clinic. Demographic data and all comorbidities were queried via chart review. Standardised validated surveys were administered to assess symptoms prior to and after BoNT-A injection. Preinjection tear volumes were obtained using the phenol red thread (PRT) test. RESULTS: Preinjection migraine, photophobia and dry eye symptom scores were all significantly correlated, p<0.05, and none were associated with preinjection PRT results. After BoNT-A, improvements in migraine, photophobia and dry eye symptoms were also significantly correlated, p<0.05 and similarly did not associate with preinjection PRT results. Photophobia scores significantly improved following BoNT-A, while dry eye symptoms significantly improved in those with severe symptoms at baseline (DEQ-5 score ≥12), p=0.027. In logistic regression analysis of all individuals with dry eye symptoms (DEQ-5 ≥6), individuals with more severe dry eye symptoms were more likely improve, OR 1.27, 95% CI 1.06 to 1.51, p<0.01. CONCLUSIONS: BoNT-A significantly improved photophobia in patients being treated for migraine and also improved dry eye symptoms in patients with severe symptoms at baseline, independent of baseline tear film volume. These improvements may be due to modulation of shared trigeminal neural pathways.