Myopic Shift Over Five Years Following Pediatric Lensectomy with Primary Intraocular Lens Implantation.

OBJECTIVE: To report the change in refractive error over 5 years following primary intraocular lens (IOL) placement by age at surgery, and to identify factors associated with the change in refractive error after 5 years. DESIGN: Prospective observational study at 61 pediatric eye care practices. PARTICIPANTS: 186 eyes of 152 children undergoing primary IOL implantation before 13 years of age for non-traumatic cataract. INTERVENTIONS: Cataract surgery with primary IOL placement MAIN OUTCOME MEASURES: Five-year change in refractive error (spherical equivalent) by age at surgery (<1 year; 1 to <2.5 years; 2.5 to <4 years; 4 to <7 years; 7 to <13 years). Five-year myopic shift in children 4 to <13 years with immediate postoperative myopia vs emmetropia or hyperopia. RESULTS: Mean spherical equivalent myopic shift (95% confidence interval [CI]) was -5.99 D (-7.64 to -4.34) when surgery was performed at 0 to <1 year of age (n=13), -3.53 D (-4.57 to -2.48) at 1 to <2.5 years (n=28), -1.91 D (-2.55 to -1.26) at 2.5 to <4 years (n=36), -2.04 D (-2.60 to -1.49) at 4 to <7 years (n=60), and -0.83 D (-1.27 to -0.40) at 7 to <13 years (n=49) (P<.01 for each comparison with the oldest group). Variability of myopic shift also decreased with increasing age (P<.01). In eyes of children 4 to <13 years (small sample size precluded analysis of children <4 years), there was significantly less mean change [95% CI] in refractive error over 5 years in eyes with myopia immediately after surgery (-0.69, 95% CI -1.48 to +0.10) than eyes with emmetropia/hyperopia immediately after surgery (-1.70, 95% CI -2.10 to -1.31) (difference = -1.01 D, 95% CI -1.89 to -0.14 D, P=.03). CONCLUSIONS: In this large, prospective cohort study of children younger than 13 years of age undergoing cataract surgery with primary IOL placement, there was greater and more variable myopic shift in children undergoing surgery at a younger age. Our finding of less myopic shift over 5 years in eyes with unintended immediate postoperative myopia deserves further study to more accurately guide IOL power selection.

Hippocampal-Sparing Radiation Therapy in Primary Sinonasal and Cutaneous Tumors of the Head and Neck.

Purpose: Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful radiation dose to their hippocampi, but this not a classic avoidance structure in radiation planning. We aimed to characterize the feasibility and tradeoffs of hippocampal-sparing radiation therapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. Methods and Materials: We retrospectively selected patients who were treated definitively for primary sinonasal or cutaneous malignancies of the H&N at an academic medical center. All received (chemo)radiation alone or adjuvantly and substantial radiation dose to 1 or both hippocampi. We created new HSRT plans for each patient with intensity modulated radiation therapy using the original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines and reviewed by a neuroradiologist. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTVs), and OARs were recorded and compared. Results: There were 18 sinonasal and 12 cutaneous H&N primary tumors (30 patients in total). Median prescription dose was 6600 cGy (range, 5000-7440 cGy), and 14 of the 30 patients received 120 cGy/fraction twice daily, 13 of the 30 patients received 200 cGy/fraction once daily, whereas others received 180-275 cGy/fraction once daily. The relative decrease in ipsilateral hippocampal Dmax and D100% using HSRT was 44% (median, 2009 cGy from 3586 cGy) and 65% (median 434 cGy from 1257 cGy), respectively. There were no statistically significant or clinically meaningful differences in PTV V100%, PTV D1%, or radiation dose to other OARs between HSRT and non-HSRT plans. Conclusions: HSRT is feasible and results in meaningful dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. We suggest target hippocampal constraints of Dmax < 1600 cGy and D100% < 500 cGy when feasible (without compromising PTV coverage or impacting other critical OARs). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Special Commentary: Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery.

Minimally invasive glaucoma surgery (MIGS) refers to a group of procedures generally characterized by an ab interno approach, minimal trauma to ocular tissue, moderate efficacy, an excellent safety profile, and rapid recovery. The number of MIGS procedures continues to increase, and their use has become widespread among glaucoma and cataract specialists. Standardization of the methodology and reporting of clinical endpoints in MIGS investigations enhances interpretation and comparison across different studies. The assessment of surgical interventions not only should consider statistical significance, but also whether the outcome is meaningful to patients. Minimal clinically important difference (MCID) is defined as the smallest change in a treatment outcome that is considered beneficial for an individual patient and prompts a change in their clinical management. Expert consensus is an accepted approach to determine the MCID. The American Academy of Ophthalmology's Glaucoma Preferred Practice Pattern® Committee is an expert panel that develops guidelines identifying characteristics and components of quality eye care. The Committee recommends that the cumulative probability of surgical success at 2 years with Kaplan-Meier survival analysis be used as the primary efficacy endpoint in MIGS studies. The Committee suggests that surgical success for standalone MIGS be defined as intraocular pressure (IOP) of 21 mmHg or less and reduced by 20% or more from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The proposed MCID for the cumulative probability of success of standalone MIGS at 2 years is 50%. The panel recommends that surgical success for MIGS combined with cataract extraction with intraocular lens implantation (CE-IOL) be defined as a decrease in glaucoma medical therapy of 1 medication or more from baseline without an increase in IOP or IOP of 21 mmHg or less and reduced by 20% or more from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The suggested MCID for the cumulative probability of success for MIGS combined with CE-IOL at 2 years is 65%. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Factors Influencing Patient Decision-Making in the Treatment of Muscle-Invasive Bladder Cancer.

BACKGROUND: In 2023, an estimated 82,290 individuals were diagnosed with bladder cancer in the United States. For muscle-invasive bladder cancer (MIBC), the American Urological Association recommends offering radical cystectomy with cisplatin-based neoadjuvant chemotherapy. However, patients are increasingly requesting alternative treatments. OBJECTIVE: To describe factors influencing selection of radical cystectomy with cisplatin-based neoadjuvant chemotherapy (NAC + RC), radical cystectomy monotherapy (RC), or tri-modality therapy (TMT) among patients with MIBC. METHODS: Individual, semi-structured phone interviews were conducted with 18 adults who underwent MIBC treatment at the University of North Carolina, recruiting six patients each from three treatment groups: 1) NAC + RC, 2) RC, and 3) TMT. Interview transcriptions were qualitatively analyzed using QSR NVivo, with major themes and sub-themes extracted. Patients also completed the Shared Decision-Making Questionnaire (SDM-Q-9; range 0-100). RESULTS: Concern for survival and risks, quality of life, and varied patient preferences for involvement influenced the decision-making process. Concern surrounding sexual function, bladder preservation, and urostomy bags drove patients towards TMT. High levels of shared decision-making were observed overall, with a median SDM-Q-9 score of 95 (IQR 89-100). Patients undergoing TMT reported the highest median SDM-Q-9 score (97, IQR 94-100), while those receiving radical cystectomy alone had the lowest (66, IQR 37-96). CONCLUSIONS: Patients with MIBC described a multifaceted treatment decision-making process, highlighting key influences, concerns, and unmet needs. Understanding this process can help address misconceptions and align treatment choices with patient goals. Physicians can use these insights to engage in shared decision-making, ultimately improving patient experiences and outcomes.

Poor Prognosis among Radiation-Associated Bladder Cancer Is Defined by Clinicogenomic Features.

Radiotherapy (RT) for prostate cancer has been associated with an increased risk for the development of bladder cancer. We aimed to integrate clinical and genomic data to better understand the development of RT-associated bladder cancer. A retrospective analysis was performed to identify control patients (CTRL; n = 41) and patients with RT-associated bladder cancer (n = 41). RT- and CTRL-specific features were then identified through integration and analysis of the genomic sequencing data and clinical variables. RT-associated bladder tumors were significantly enriched for alterations in KDM6A and ATM, whereas CTRL tumors were enriched for CDKN2A mutation. Globally, there were an increased number of variants within RT tumors, albeit at a lower variant allele frequency. Mutational signature analysis revealed three predominate motif patterns, with similarity to SBS2/13 (APOBEC3A), SBS5 (ERCC2/smoking), and SBS6/15 (MMR). Poor prognostic factors in the RT cohort include a short tumor latency, smoking status, the presence of the smoking and X-ray therapy mutational signatures, and CDKN2A copy number loss. Based on the clinical and genomic findings, we suggest at least two potential pathways leading to RT-associated bladder cancer: The first occurs in the setting of field cancerization related to smoking or preexisting genetic alterations and leads to the development of more aggressive bladder tumors, and the second involves RT initiating the oncogenic process in otherwise healthy urothelium, leading to a longer latency and less aggressive disease. SIGNIFICANCE: Clinicogenomic analysis of radiation-associated bladder cancer uncovered mutational signatures that, in addition to a short tumor latency, smoking, and CDKN2A loss, are associated with a poor outcome. These clinical and genomic features provide a potential method to identify patients with prostate cancer who are at an increased risk for the development of aggressive bladder cancer following prostate RT.

Complications, Visual Acuity, and Refractive Error 3 Years after Secondary Intraocular Lens Implantation for Pediatric Aphakia.

PURPOSE: To report the cumulative incidence of complications and to describe refractive error and visual acuity (VA) outcomes in children undergoing secondary intraocular lens (IOL) implantation after previous surgery for nontraumatic cataract. DESIGN: Pediatric cataract registry. PARTICIPANTS: Eighty children (108 eyes: 60 bilateral, 48 unilateral) undergoing lensectomy at younger than 13 years of age. METHODS: Annual data collection from medical record review through 5 years after lensectomy. MAIN OUTCOME MEASURES: Cumulative incidence of newly emergent complications after secondary IOL implantation; refractive error and VA by 5 years after lensectomy. RESULTS: Median follow-up after secondary IOL implantation was 2.7 years (interquartile range [IQR], 0.8-3.3 years; range, 0.6-5.0 years) for bilateral and 2.1 years (range, 0.5-6.4 years) for unilateral cases. A common complication after secondary IOL implantation was a glaucoma-related adverse event (GRAE; glaucoma or glaucoma suspect); the cumulative incidence was 17% (95% confidence interval [CI], 3%-29%) in bilateral cases and 12% (95% CI, 0%-23%) in unilateral cases. The cumulative incidence of surgery for visual axis opacification was 2% (95% CI, 0%-7%) for bilateral cases and 4% (95% CI, 0%-10%) for unilateral cases. The median prediction error within 90 days of implantation was 0.88 diopter (D; IQR, -0.50 to +3.00 D) less hyperopic than intended among 21 eyes for bilateral cases and 1.50 D (IQR, -0.25 to +2.38 D) less among 19 unilateral cases. The median spherical equivalent refractive error at 5 years (at a median of 5.1 years of age) in eyes receiving a secondary IOL was +0.50 D (IQR, -2.38 to +2.94 D) for 48 bilateral cases and +0.06 D (IQR, -2.25 to +0.75 D) for 22 unilateral cases. Median monocular VA at 5 years was 20/63 (IQR, 20/50-20/100) for bilateral cases (n = 42) and 20/400 (IQR, 20/160-20/800) for unilateral cases (n = 33). CONCLUSIONS: Eyes with secondary IOL implantation have a risk of developing new GRAEs. Five years after lensectomy (approximately 2.5 years after secondary IOL implantation), the average refractive error was less hyperopic than desired given the anticipated further myopic shift before refraction stabilizes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Isolated ectopia lentis with partial anterior dislocation and pupillary block: a case report.

BACKGROUND: Ectopia lentis is the dislocation of the natural crystalline lens and usually presents in the setting of trauma or other systemic diseases. Herein, we describe a case of an otherwise healthy four-year-old boy with isolated ectopia lentis whose partial lens dislocation was captured on a smartphone by the patient's father several days prior. CASE PRESENTATION: A four-year-old boy with no past medical, developmental, or trauma history presented with bilateral partial anterior lens dislocation with pupillary block. Initial ophthalmic evaluation two months prior was notable for uncorrected visual acuity at 20/100 OD, 20/250 OS, bilateral iridodenesis, and partially dislocated lenses inferonasally OD and inferiorly OS on slit lamp. Genetic testing found no abnormalities. Ten months later, the patient developed sudden onset of left eye pain. A dislocated lens and temporarily dilated left pupil were captured on a smartphone by the patient's father. He was evaluated 3 days later after a second episode and found to have hand motion vision OS, a fixed 8 mm left pupil with the crystalline lens subluxed into the pupil space and accompanying intraocular pressure OS of 40 mmHg. The lens was surgically removed with a limited anterior vitrectomy. Four and a half years after surgery, visual acuity was 20/125 OS with aphakic correction. The right eye eventually underwent prophylactic lensectomy and was 20/30 in aphakic correction. CONCLUSIONS: This report presents a unique presentation of isolated ectopia lentis with anterior lens dislocation and pupillary block and illustrates the role of smartphone photography in assisting in the triage of eye emergencies.

Target Delineation in Postoperative Radiation Therapy for Head and Neck Cancer After Flap Reconstruction.

Delineation of the clinical target volume (CTV) after resection of head and neck cancer can be challenging, especially after flap reconstruction. The main area of contention is whether the entire flap should be included in the CTV. Several case series have reported marginal misses and intraflap failures when the entire flap was not routinely included in the CTV. On the other hand, available data have not convincingly demonstrated a detriment to long-term outcomes using intensity modulated radiotherapy after flap reconstruction. On the contrary, postoperative radiation can facilitate epilation and mucosalization of the flap tissue, reduce flap bulk, and improve long-term esthetic and functional outcomes. Therefore, our standard practice is to include the entire flap in the CTV. In certain scenarios, we may allow for a lower dose to part of flap distant from the resection bed than the flap-tumor bed junction, where recurrences are most likely. We provide three case vignettes describing such scenarios where sparing part of the flap, and more importantly, the nearby uninvolved native tissue, from high-dose radiation may be justified.

Prognostic utility of biopsy-based PTEN and ERG status on biochemical progression and overall survival after SBRT for localized prostate cancer.

Introduction/background: Phosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer. Methods/materials: Patients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p <0.05 was considered statistically significant. Results: Ninety-nine consecutive patients were included in the analysis with a median follow-up of 72 months. A statistically significant improvement in bPFS (p = 0.018) was observed for wild type ERG patients with an estimated 5-year bPFS of 94.1% vs. 72.4%. Regarding PTEN mutational status, significant improvements in were observed in both bPFS (p = 0.006) and OS (p < 0.001), with estimated 5-year bPFS rates of 91.0% vs. 67.9% and 5-year OS rates of 96.4% vs. 79.4%. When including both ERG and PTEN mutational status in the analysis, there were statistically significant differences in both bPFS (p = 0.011) and OS (p < 0.001). The estimated 5-year bPFS rates were 100%, 76.6%, 72.9%, and 63.8% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. The estimated 5-year OS rates were 93.9%, 100%, 80.0%, and 78.7% for patients with ERG+/PTEN+, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- phenotypes respectively. Conclusion: ERG rearrangements and PTEN deletions detected on biopsy samples are associated with poorer oncologic outcomes in prostate cancer patients treated with SBRT and merit further study in a dedicated prospective trial.

High-risk prostate cancer treated with a stereotactic body radiation therapy boost following pelvic nodal irradiation.

Purpose: Modern literature has demonstrated improvements in long-term biochemical outcomes with the use of prophylactic pelvic nodal irradiation followed by a brachytherapy boost in the management of high-risk prostate cancer. However, this comes at the cost of increased treatment-related toxicity. In this study, we explore the outcomes of the largest cohort to date, which uses a stereotactic body radiation therapy (SBRT) boost following pelvic nodal radiation for exclusively high-risk prostate cancer. Methods and materials: A large institutional database was interrogated to identify all patients with high-risk clinical node-negative prostate cancer treated with conventionally fractionated radiotherapy to the pelvis followed by a robotic SBRT boost to the prostate and seminal vesicles. The boost was uniformly delivered over three fractions. Toxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Oncologic outcomes were assessed using the Kaplan-Meier method. Cox proportional hazard models were created to evaluate associations between pretreatment characteristics and clinical outcomes. Results: A total of 440 patients with a median age of 71 years were treated, the majority of whom were diagnosed with a grade group 4 or 5 disease. Pelvic nodal irradiation was delivered at a total dose of 4,500 cGy in 25 fractions, followed by a three-fraction SBRT boost. With an early median follow-up of 2.5 years, the crude incidence of grade 2+ genitourinary (GU) and gastrointestinal (GI) toxicity was 13% and 11%, respectively. Multivariate analysis revealed grade 2+ GU toxicity was associated with older age and a higher American Joint Committee on Cancer (AJCC) stage. Multivariate analysis revealed overall survival was associated with patient age and posttreatment prostate-specific antigen (PSA) nadir. Conclusion: Utilization of an SBRT boost following pelvic nodal irradiation in the treatment of high-risk prostate cancer is oncologically effective with early follow-up and yields minimal high-grade toxicity. We demonstrate a 5-year freedom from biochemical recurrence (FFBCR) of over 83% with correspondingly limited grade 3+ GU and GI toxicity measured at 3.6% and 1.6%, respectively. Long-term follow-up is required to evaluate oncologic outcomes and late toxicity.

Assessing Abuse-Deterrent formulations utilizing Ion-Exchange resin complexation processed via Twin-Screw granulation for improved safety and effectiveness.

Opioid misuse is a public health crisis in the United States. In response, the FDA has approved drug products with abuse-deterrent features to reduce the risk of prescription opioid abuse. Abuse-deterrent formulations (ADFs) typically employ physical or chemical barriers or incorporate agonist-antagonist combinations as mechanisms to deter misuse. This study aims to assess the impact of abuse-deterrent properties, specifically ion-exchange resin complexation as a chemical barrier, on a model drug, promethazine hydrochloride (PMZ) tablets. Various formulations were developed through twin-screw wet granulation (TSWG) followed by twin-screw melt granulation (TSMG). In the TSWG process, the drug interacts with the resin through an exchange reaction, forming a drug-resin complex. Additionally, the study explored factors influencing the complex formation between the drug and resin, using the drug loading status as an indicator. DSC and ATR studies were carried out to confirm the formation of the drug-resin complex. Subsequently, hot melt granulation was employed to create a matrix tablet incorporating Kollidon® SR and Kollicoat® MAE 100P, thereby enabling sustained release properties. The drug-resin complex embedded in the matrix effectively deters abuse through methods like smoking, snorting, or parenteral injection, unless the drug can be extracted. In order to assess this, solvent extraction studies were conducted using an FDA-recommended solvents, determining the potential for abuse. Further investigations involved dissolution tests in change-over media, confirming the extended-release properties of the formulation. Results from dissolution studies comparing the ground and intact tablets provided positive evidence of the formulation's effectiveness in deterring abuse. Finally, alcohol-induced dose-dumping studies were conducted in compliance with FDA guidelines, concluding that the formulation successfully mitigates dose dumping in the presence of alcohol.

Outcomes and Complications 5 Years After Surgery for Pediatric Cataract Associated With Persistent Fetal Vasculature.

PURPOSE: To report 5-year outcomes after surgery for cataract associated with persistent fetal vasculature (PFV). DESIGN: Clinical cohort study using pediatric cataract registry data collected annually from medical records. METHODS: This study included 64 children <13 years of age who were undergoing surgery for unilateral, nontraumatic cataract associated with PFV. Proportions with age-normal visual acuity (VA) and VA better than 20/200 at 5 years' follow-up were estimated. Cumulative incidences of complications and additional surgeries by 5 years were calculated. Outcomes were compared between eyes with unilateral PFV and eyes with unilateral non-PFV cataract from our registry. RESULTS: Forty-eight of 64 eyes were aphakic postoperatively (median age at surgery 2 months [range 1-13 months]) and 16 were pseudophakic (29 months [range 2-92 months]). Overall, 4 of 42 eyes (10% [95% confidence interval {CI} 3%-23%]) achieved age-normal VA. VA better than 20/200 was achieved in 17 (59% [95% CI 39%-76%]) unilateral aphakic PFV eyes and 44 (43% [95% CI 32%-54%]) unilateral non-PFV aphakic eyes (age-adjusted odds ratio = 1.90 [95% CI 0.81-4.50]; P = .14). The most common complication in aphakic PFV eyes was glaucoma-related adverse events (cumulative incidence 24% [95% CI 9%-37%]). There was no significant difference in glaucoma-related adverse events between PFV and non-PFV eyes in aphakic participants ≤1 year of age at lensectomy (age-adjusted hazard ratio = 1.20 [95% CI 0.54-2.64], P = .66). CONCLUSIONS: A wide range of visual outcomes for PFV cataract were observed with a 10% probability of achieving age-normal VA. There was an ongoing risk for the development of glaucoma-related adverse events in PFV eyes.

Pediatric Optic Pathway Gliomas Resource Utilization and Prevalence in the OptumLabs Data Warehouse.

BACKGROUND: Although significant progress has been made in improving the rate of survival for pediatric optic pathway gliomas (OPGs), data describing the methods of diagnosis and treatment for OPGs are limited in the modern era. This retrospective study aims to provide an epidemiological overview in the pediatric population and an update on eye care resource utilization in OPG patients using big data analysis. METHODS: Using the OptumLabs Data Warehouse, 9-11 million children from 2016 to 2021 assessed the presence of an OPG claim. This data set was analyzed for demographic distribution data and clinical data including average ages for computed tomography (CT), MRI, strabismus, and related treatment (surgery, chemotherapy, and radiation), as well as yearly rates for optical coherence tomography (OCT) and visual field (VF) examinations. RESULTS: Five hundred fifty-one unique patients ranging in age from 0 to 17 years had an OPG claim, with an estimated prevalence of 4.6-6.1 per 100k. Among the 476 OPG patients with at least 6 months of follow-up, 88.9% had at least one MRI and 15.3% had at least one CT. Annual rates for OCT and VF testing were similar (1.26 vs 1.35 per year), although OCT was ordered for younger patients (mean age = 9.2 vs 11.7 years, respectively). During the study period, 14.1% of OPG patients had chemotherapy, 6.1% had either surgery or radiation, and 81.7% had no treatment. CONCLUSIONS: This study updates OPG demographics for the modern era and characterizes the burden of the treatment course for pediatric OPG patients using big data analysis of a commercial claims database. OPGs had a prevalence of about 0.005% occurring equally in boys and girls. Most did not receive treatment, and the average child had at least one claim for OCT or VF per year for clinical monitoring. This study is limited to only commercially insured children, who represent approximately half of the general child population.

Use and Cost of Sustained-Release Corticosteroids for Cataract Surgery Under the Medicare Pass-Through Program.

Importance: Sustained-release corticosteroids offer the potential of improved compliance and greater patient convenience for anti-inflammatory treatment after cataract surgery. However, they are substantially more expensive than postoperative corticosteroid eye drops, which have historically been standard care. Objective: To examine the use and cost of sustained-release corticosteroids in patients with Medicare who underwent cataract surgery in the US during the temporary pass-through reimbursement program period. Design, Setting, and Participants: This cross-sectional study examined Medicare fee-for-service (FFS) claims from beneficiaries with at least 12 continuous months of Medicare enrollment who underwent at least 1 cataract surgery from March 2019 through December 2021. Patients younger than 65 years, those with missing demographic information, those who had more than 1 cataract surgery on each eye, and those who received more than 1 corticosteroid on the day of surgery were excluded. Cataract surgeries with concurrent use of dexamethasone intraocular suspension 9% or dexamethasone ophthalmic insert were identified. Information on surgeon demographic characteristics and costs of surgery and drugs were extracted. Data were analyzed from June 15 to December 4, 2022. Exposure: Use of dexamethasone intraocular suspension 9% or dexamethasone ophthalmic insert during cataract surgery. Main Outcome Measures: Utilization rate and cost of dexamethasone intraocular suspension 9% and dexamethasone ophthalmic insert among Medicare FFS beneficiaries who underwent cataract surgery. Results: A total of 4 252 532 cataract surgeries in Medicare FFS beneficiaries (mean [SD] age, 74.8 [5.8] years; 1 730 811 male [40.7%] and 2 521 721 female [59.3%]) were performed by 12 284 ophthalmologists (8876 male [72.3%], 2877 female [23.4%], and 531 sex unknown [4.3%]). In all, 34 627 beneficiaries (0.8%) received dexamethasone intraocular suspension 9% and 73 430 (1.7%) received a dexamethasone ophthalmic insert; the use of both drugs increased over the study period. The mean (SD) Medicare allowed charges for dexamethasone intraocular suspension 9% and dexamethasone ophthalmic insert were $531.47 ($141.52) and $538.49 ($63.79), respectively. Conclusions and Relevance: Despite offering the potential of improved compliance and greater patient convenience, findings of this study suggest that sustained-release corticosteroid use during cataract surgery was low and associated with cost increases to the health care system vs conventional postoperative eye drops. As these new products must be priced high enough to qualify for the Medicare pass-through program, unreasonable cost may have been a deterrent to their use, suggesting that the current Medicare reimbursement rules may not be appropriate for sustained-release postoperative corticosteroids in cataract surgery.

Complications Occurring Through 5 Years Following Primary Intraocular Lens Implantation for Pediatric Cataract.

Importance: Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective: To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants: This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures: Lensectomy with primary IOL implantation. Main Outcome and Measures: Five-year cumulative incidence of complications by age at surgery (<2 years, 2 to <4 years, 4 to <7 years, and 7 to <13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results: The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P < .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (<2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to <4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to <7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance: In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.

Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure.

Introduction: Brain metastases are the most common intracranial tumor diagnosed in adults. In patients treated with stereotactic radiosurgery, the incidence of post-treatment radionecrosis appears to be rising, which has been attributed to improved patient survival as well as novel systemic treatments. The impacts of concomitant immunotherapy and the interval between diagnosis and treatment on patient outcomes are unclear. Methods: This single institution, retrospective study consisted of patients who received single or multi-fraction stereotactic radiosurgery for intact brain metastases. Exclusion criteria included neurosurgical resection prior to treatment and treatment of non-malignant histologies or primary central nervous system malignancies. A univariate screen was implemented to determine which factors were associated with radionecrosis. The chi-square test or Fisher's exact test was used to compare the two groups for categorical variables, and the two-sample t-test or Mann-Whitney test was used for continuous data. Those factors that appeared to be associated with radionecrosis on univariate analyses were included in a multivariable model. Univariable and multivariable Cox proportional hazards models were used to assess potential predictors of time to local failure and time to regional failure. Results: A total of 107 evaluable patients with a total of 256 individual brain metastases were identified. The majority of metastases were non-small cell lung cancer (58.98%), followed by breast cancer (16.02%). Multivariable analyses demonstrated increased risk of radionecrosis with increasing MRI maximum axial dimension (OR 1.10, p=0.0123) and a history of previous whole brain radiation therapy (OR 3.48, p=0.0243). Receipt of stereotactic radiosurgery with concurrent immunotherapy was associated with a decreased risk of local failure (HR 0.31, p=0.0159). Time interval between diagnostic MRI and first treatment, time interval between CT simulation and first treatment, and concurrent immunotherapy had no impact on incidence of radionecrosis or regional failure. Discussion: An optimal time interval between diagnosis and treatment for intact brain metastases that minimizes radionecrosis and maximizes local and regional control could not be identified. Concurrent immunotherapy does not appear to increase the risk of radionecrosis and may improve local control. These data further support the safety and synergistic efficacy of stereotactic radiosurgery with concurrent immunotherapy.

Corrigendum: Time interval from diagnosis to treatment of brain metastases with stereotactic radiosurgery is not associated with radionecrosis or local failure.

[This corrects the article DOI: 10.3389/fonc.2023.1132777.].

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

INTRODUCTION: SBRT is an increasingly popular treatment for localized prostate cancer, though considerable variation in technical approach is common and optimal dose constraints are uncertain. In this study, we sought to identify dosimetric and patient-related predictors of acute rectal toxicity. METHODS: Patients included in this study were treated with prostate SBRT on a prospective institutional protocol. Physician-graded toxicity and patient-reported outcomes were captured at one week, one month, and three months following SBRT. DVH data were extracted and converted into relative volume differential DVHs for NTCP modeling. Patient- and disease-related covariates along with NTCP model predictions were independently tested for significant association with physician-graded toxicity or a decline in bowel-related QoL. A multivariate model was constructed using forward selection, and significant parameter cutoff values were obtained with Fischer's exact test to group patients by risk of developing physician-graded toxicity or detriments in patient-reported QoL. RESULTS: One hundred and three patients treated for localized prostate cancer with SBRT were included in our analysis. 52% of patients experienced a clinically significant decline in bowel-related QOL within 1 week of completion of treatment, while only 27.5% of patients developed grade 2+ physician-graded rectal toxicity. Sequential feature selection multivariate logistic regression identified rectal V22.5 Gy (p = 0.001) and D19% (p = 0.001) as independent predictors of clinically significant toxicity, while rectal V20Gy (p = 0.004) and D25.3% (p = 0.007) were independently correlated with physician-graded toxicity. Global multivariate step-wise logistic regression identified only D19% (p = 0.001) and V20Gy (p = 0.004) as independent predictors of acute bowel bother or physician-graded rectal toxicity respectively. CONCLUSIONS: Moderate doses to large rectal volumes, D19% and V20Gy, were associated with an increased incidence of a clinically significant decrease in patient-reported bowel QOL and physician-scored grade 2+ rectal toxicity, respectively. These dosimetric parameters may help practitioners mitigate acute toxicity in patients treated with prostate SBRT.

Development and Characterization of Different Dosage Forms of Nifedipine/Indomethacin Fixed-Dose Combinations.

Studies have shown that 40 individuals out of 100,000 are diagnosed with rheumatoid arthritis (RA) yearly, with a total of 1.3 million in the United States. Furthermore, the impact of RA in some cases can extend to cardiovascular diseases (CVD), as the studies showed that 84% of RA patients are at risk of developing hypertension. This study aims to design and develop different dosage forms (capsule-in-capsule and three-dimensional (3D) printed tablet) of nifedipine/indomethacin fixed-dose combination (FDC). The hot-melt extrusion (HME) was utilized alone and with fused deposition modeling (FDM) techniques The developed dosage forms were intended to provide delayed-extended and immediate release profiles for indomethacin and nifedipine, respectively. FDC dosage forms were successfully developed and characterized. Nifedipine formulations showed significant improvement in release profiles, having 94% of the drug release at 30 minutes compared with pure nifedipine, which had a percent release of 2%. Furthermore, the release of indomethacin was successfully delayed at a pH of 1.2 and extended at a pH of 6.8. Differential scanning calorimetry results showed endothermic crystalline peaks at 165 °C and 176 °C for indomethacin and nifedipine, respectively. Moreover, the thermal analysis of all formulations showed the absence of the endothermic peaks indicating complete solubilization of indomethacin and nifedipine in the polymeric carriers. All formulations had post-processing drug content in the range of 95% to 98%. Moreover, results from the stability study showed that all formulations were able to remain chemically and physically stable with no signs of recrystallization or degradation. The designed FDC dosage forms could improve the quality of life by enhancing patient compliance and preventing the need for polypharmacy.

Disulfiram 3D printed film produced via hot-melt extrusion techniques as a potential anticervical cancer candidate.

Cervical cancer is known globally as one of the most common health problems in women. Indeed, one of the most convenient approaches for its treatment is an appropriate bioadhesive vaginal film. This approach provides a local treatment modality, which inevitably decreases dosing frequency and improves patient compliance. Recently, disulfiram (DSF) has been investigated and demonstrated to possess anticervical cancer activity; therefore, it is employed in this work. The current study aimed to produce a novel, personalized three-dimensional (3D) printed DSF extended-release film using the hot-melt extrusion (HME) and 3D printing technologies. The optimization of the formulation composition and the HME and 3D printing processing temperatures was an important factor for overcoming the DSF heat-sensitivity issue. In addition, the 3D printing speed was specifically the most crucial parameter for alleviating heat-sensitivity concerns, which led to the production of films (F1 and F2) with an acceptable DSF content and good mechanical properties. The bioadhesion film study using sheep cervical tissue indicated a reasonable adhesive peak force (N) of 0.24 ± 0.08 for F1 and 0.40 ± 0.09 for F2, while the work of adhesion (N.mm) for F1 and F2 was 0.28 ± 0.14 and 0.54 ± 0.14, respectively. Moreover, the cumulative in vitro release data indicated that the printed films released DSF for up to 24 h. HME-coupled 3D printing successfully produced a patient-centric and personalized DSF extended-release vaginal film with a reduced dose and longer dosing interval.