Background: Anti-cancer drugs, particularly platins, have been showing ocular adverse events (OAEs) in patients undergoing chemotherapy.
Aim: To evaluate the potential association between the use of platins (cisplatin, carboplatin, and oxaliplatin) and the risk of OAEs by analyzing spontaneous reports and reviewing case reports.
Methods: A retrospective case/non-case study was conducted using spontaneous reports on OAEs by platins from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR) with χ2, Reporting Odds Ratio (ROR), and the Information Component (IC) to identify OAE signals for platins. In parallel, a review of case reports for OAEs from platins was conducted by a systematic literature search in PubMed and Google Scholar, published till 31st March 2024.
Results: A total of 4262 spontaneous reports of OAEs caused by platins were identified from the FAERS Database. Using disproportionality analysis, 69 signals were identified for platins and OAEs (carboplatin: 42, oxaliplatin: 16, cisplatin: 11). Choroidal infarction [PRR=215.1; χ2=4527.1; lower bound (LB) ROR=140.7; IC025=5.1] and orbital haemorrhage [PRR=120.0; χ2 =300.5; LB ROR=35.1; IC025=1.3] were the strong signals identified for carboplatin. Optic disc hyperaemia [PRR=208.2; χ2=742.5; LB ROR=74.1; IC025=2.2] and blindness cortical [PRR=23.7; χ2=382.5; LB ROR=14.8; IC025=3.1] were the signals identified for oxaliplatin and cisplatin, respectively. Of 69 signals, 52 disappeared, and 17 were retained after signal refinement analysis. A total of 32 case reports of OAEs associated with platins were identified through a systematic search in PubMed and Google Scholar, strengthening the association between platins and OAEs.
Conclusion: The study revealed a potential risk of OAEs when using platins as an anticancer medication. It is vital to update safety profiles for carboplatin and oxaliplatin in the prescribing information leaflet (PIL) due to insufficient data concerning ocular toxicity.

Introduction
Three different fixed-combination therapies with distinct pharmacological mechanisms, including Brimonidine/Timolol (FC-BT), Dorzolamide/Timolol (FC-DT), and Travoprost/Timolol (FC-TT), are approved for patients with glaucoma who respond poorly to topical beta-blockers. However, the comparative effectiveness of these therapies remains unclear.

Aims
To compare the treatment effects of three different combination therapies for glaucoma treatment in Taiwan.

Methods
We conducted a nationwide retrospective cohort study by analyzing Taiwan’s National Health Insurance Database. Adult patients who newly received topical fixed-combination therapies (FC-BT, FC-DT, and FC-TT) for glaucoma between 2010 and 2019 were included. The date of the first medication prescription was defined as the index date, and FC-DT was considered as the reference group for the comparison. We applied a propensity score overlapping weighting approach to ensure comparable baseline characteristics. The effectiveness outcomes included the incidence of curative procedures (i.e., incisional surgery or laser for glaucoma), blindness, and treatment persistence (i.e., the addition of other antiglaucoma medications and discontinuation of initial fixed-combination therapies).

Results
We identified a total of 59,535 patients receiving topical fixed-combination therapies for glaucoma (42.1% FC-BT, 52.7% FC-DT, and 5.83% FC-TT). In the comparison between FC-BT and FC-DT, the incidence rate for curative procedures was 35.03 (95% CI 33.38-36.74) and 38.56 (36.80-40.37) per 1,000 person-years, respectively, yielding an adjusted hazard ratio for curative procedures of 0.92 (0.86-0.98). In the comparison between FC-TT and FC-DT, the incidence rate for curative procedures was 31.10 (27.87-34.61) and 37.96 (34.33-41.88) per 1,000 person-years, respectively, yielding an adjusted hazard ratio for curative procedures of 0.83 (0.72-0.96). No significant differences were observed in other effectiveness outcomes, including blindness and treatment persistence, among these comparisons.

Conclusion
Our findings suggest that compared to FC-DT, both FC-BT and FC-TT as second-line treatments for glaucoma are associated with a lower rate of curative procedures.

Introduction: Topiramate, a second-generation anti-epileptic drug (AED), is FDA-approved for treating epilepsy, preventing migraines, and, when combined with phentermine, for weight loss in patients with a BMI over 30. Recommended dosages are 400 mg/day for epilepsy and 100 mg/day for migraines. Serious adverse effects, though rare, include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity.

Aims: To compare the risk of glaucoma associated with topiramate versus phenytoin in epilepsy patients.

Methods: Using the TriNetX platform, we conducted a comparative cohort study on newly diagnosed epilepsy patients treated with either phenytoin or topiramate, excluding those with a prior history of glaucoma from 2011 to 2023. Patients were matched by age and sex. A time-to-event analysis was performed, and data were censored at primary or secondary endpoints, last follow-up, medication changes, or new medications. The comparative risk of glaucoma was analyzed using the Cox proportional hazards model.

Results: We collected 80,193 phenytoin and 66,268 topiramate patients who were diagnosed as epilepsy. After matching, we had 41,505 patients in each cohort. After adjusting by age and sex, the comparative hazard ratio was 1.22 with 95% CI, 1.10-1.35, comparing to phenytoin.

Discussion/Conclusion: Topiramate was associated with a higher risk of glaucoma than phenytoin in epilepsy patients. Topiramate-induced myopic shift occurs due to ciliochoroidal effusion, leading to anterior rotation of the ciliary body and forward displacement of the lens-iris diaphragm, causing angle closure glaucoma. Prompt recognition and treatment are crucial to prevent permanent vision damage. Increased awareness among healthcare providers regarding topiramate's potential to cause acute angle closure glaucoma (AACG) is necessary. Patients should be informed about AACG symptoms and advised to seek immediate medical attention for visual disturbances to prevent long-term complications.

Introduction: Glaucoma is treated primarily with medication such as topical prostaglandins and β-blockers. Although the side effects include asthma attacks, the quantitative risk has not been sufficiently assessed.
Aim: To assess topical prostaglandins and β-blockers at risk factors for asthma attacks compared with other glaucoma medications using a population-based cohort study with a target trial emulation framework.
Methods: We used a Japanese administrative claims database, to construct a cohort of patients aged ≥20 years who were newly prescribed prostaglandins, β-blockers, or other glaucoma medications from April 2012 to March 2021. We estimated the intention-to-treat (ITT)-hazard ratio (HR) for asthma attacks using inverse probability of treatment (IPT)-weighted Cox models. The IPT weight was computed with a generalized logistic model conditioned on the patient’s sex, age, medical history, medication history, body mass index, smoking history, and occurrence of outcome up to 1 year before the index date. We also estimated the per-protocol (PP)-HR using IPT- and inverse probability of censoring (IPC)-weighted Cox models with adjustment for nonrandom treatment changes. The IPC weight was calculated using pooled logistic models conditioned on the variables employed to compute the IPT weight plus 60-day time points.
Result: We extracted 28,362 patients (males: 19,369 [68.3%]; mean age [standard deviation]: 53.8 [8.9] years), 16,201 patients (10,209 [63.0%]; 52.6 [9.4] years), and 13,472 patients (7,793 [57.9%]; 54.5 [9.5] years) treated with prostaglandins, β-blockers, and other glaucoma medications, respectively. Compared with other glaucoma medications, the crude HR, ITT-HR, PP-HR (95% confidence interval) for prostaglandins were 0.89 (0.71–1.13), 1.00 (0.78–1.27), and 0.91 (0.69–1.20), respectively. For β-blockers, the respective values were 0.67 (0.50–0.89), 0.72 (0.54–0.97), and 0.58 (0.40–0.83).
Conclusion: Prostaglandins and β-blockers do not increase the risk of asthma attacks compared with other glaucoma medications, regardless of treatment changes.

Introduction:
Blood glucose instability can lead to organ damage through various mechanisms. Intraoperative glycemic fluctuations are known risk factors for postoperative acute kidney injury (AKI). However, no previous research has specifically investigated the relationship between postoperative glycemic variability (GV) and acute kidney disease (AKD) or long-term renal dysfunction.

Aims:
To investigate the association between postoperative GV, calculated using five methods, and the risk of AKD in patients undergoing cardiac surgery involving cardiopulmonary bypass.

Methods:
We conducted a multicenter retrospective study involving 8,090 adult patients from three academic medical centers in Eastern China between 2015 and 2023. Seven-day postoperative GV was calculated using the standard deviation (SD), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), average daily risk range (ADRR), and time out of target range (TOR). The primary focus was on the occurrence of AKD between 8 and 90 days post-surgery, categorized into persistent AKD and delayed AKD based on AKI status in the first 7 days.

Results:
During the 8-90 day postoperative period, AKD occurred in 522 of 8,090 (6.5%) patients. Postoperative GV was significantly higher in the AKD group (p<0.001 for each metric). After adjusting for relevant covariates, each GV metric was significantly associated with elevated AKD risk (standardized hazard ratio (SHR) from 1.20 (95% CI: 1.12-1.27, for SD) to 1.30 (95% CI: 1.20-1.40, for TOR). When categorizing kidney disease subtypes, GV was correlated with persistent AKD but not with delayed AKD.

Discussion:
Our study highlights the association between GV and increased AKD risk in adults undergoing cardiac surgery, especially in patients with prolonged kidney injury. These findings underscore the importance of stabilizing blood glucose levels in the postoperative period to mitigate AKD risk and highlight the need for prospective studies to explore causal relationships and identify potential clinical interventions.

Introduction:
The Kidney Failure Risk Equation (KFRE) was developed to predict the risk of progression to end-stage kidney disease (ESKD). Although validated in multinational cohorts, the KFRE's applicability to the Asian population remains uncertain due to under-representation in these studies.

Aims:
This study aimed to validate the KFRE equation using data from the Tianjin CKD Cohort to verify its applicability to the Asian population.

Methods:
National cohort data from Tianjin Inspur Healthcare Big Data was utilized. Between January 2018 and June 2023, a total of 127,916 adult patients were enrolled, including 60,668 patients with G3 to G5 chronic renal failure. Using the original KFRE (4-variable, 6-variable, and 8-variable equations), we predicted the 2- and 5-year risk of ESKD progression. Renal failure was defined as ESKD requiring kidney replacement therapy (KRT) within 2 or 5 years. The predictive performance, discrimination, and calibration of these models were assessed using the area under the receiver operating characteristic curve (ROC-AUC), Harrell’s C-index, and calibration curves.

Results:
The cohort included 60,668 patients, with 28,923 treated continuously for 2 years and 11,832 for 5 years. Among them, 6,500 and 2,867 progressed to renal replacement therapy, respectively. The KFRE model discriminated poorly for 2-year (C-statistics of 0.52, 95% CI 0.51 to 0.53; 0.54, 95% CI 0.53 to 0.55; and 0.54, 95% CI 0.53 to 0.55) and 5-year (C-statistics of 0.52, 95% CI 0.51 to 0.53; 0.53, 95% CI 0.51 to 0.55; and 0.54, 95% CI 0.53 to 0.55) ESRD predictions. The poorly calibrated Brier scores (0.5, 0.46, and 0.49 at 2 years and 0.56, 0.52, and 0.55 at 5 years) indicate that predictions were less accurate than observations.

Discussion:
This external validation study demonstrates that the KFRE performs poorly in predicting ESKD progression in Asian populations.