3D X-ray computed tomography in the analyses of intraocular lenses explanted because of postoperative opacification.

PURPOSE: To use X-ray computed tomography (CT) -which describes the acquisition and reconstruction of 2-dimensional X-ray transmission images to create a 3D representation of a specimen -in the analyses of intraocular lenses (IOLs) explanted because of optical opacification occurring postoperatively. SETTING: John A. Moran Eye Center, and Utah Nanofab, University of Utah, Salt Lake City, Utah. DESIGN: Laboratory study. METHODS: A hydrophilic acrylic and a silicone lens (the latter from an eye with asteroid hyalosis) explanted because of postoperative calcification, as well as a poly(methyl methacrylate) (PMMA) lens explanted because of snowflake degeneration underwent analysis under gross and light microscopy. Then, they were attached to an appropriate support and scanned under a Zeiss Xradia Versa X-ray microscope. After data acquisition, data segmentation was performed with a commercially available program to separate image data into components. RESULTS: Morphology, size/volume, and specific location of calcified deposits on the surface or within the substance of explanted IOLs could be demonstrated by X-ray CT within the entire volume of each lens with high contrast and resolution. The PMMA lens showed multiple spaces/fissures in relation to Nd:YAG pitting of the optic, and what appeared to be sheets of delaminated PMMA material at different levels within the optic substance. CONCLUSIONS: The key benefit of X-ray CT is that it can be performed without physically sectioning the specimen. This preliminary study demonstrates that this technology can be potentially useful in the imaging and analyses of explanted, opacified lenses.

Implication of Corneal Refractive Surgery in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked disorder due to a dystrophin mutation and is the leading cause of muscular dystrophy. DMD presents with characteristic systemic effects, including severe muscular atrophy, cardiomyopathy, and ocular manifestations. Performing corneal refractive surgeries in patients with DMD raises concerns regarding patient positioning, risk of cataracts, and other comorbid conditions. Published reports of photorefractive keratectomy, laser-assisted in situ keratomileuses, and small incision lenticule extraction are lacking in this population. Here, we discuss a patient being evaluated for a corneal refractive surgery. This article also discusses the current understanding of DMD, known ocular manifestations, and factors to consider when evaluating a patient for potential corrective vision laser surgery.

Complications of foldable intraocular lenses requiring explantation or secondary intervention: 2022 survey with update of long-term trends.

PURPOSE: To assess the complications that resulted in the explantation or secondary intervention with foldable intraocular lenses (IOLs). SETTING: University setting, Salt Lake City, Utah. DESIGN: Survey study. METHODS: For the 25th consecutive year, surgeons were surveyed regarding complications associated with foldable IOLs requiring explantation or secondary intervention over the 2022 calendar year. These forms were made available online using the ASCRS and ESCRS websites and a fax-on-demand service. Surgeons completed 1 survey for each foldable IOL requiring explantation or secondary intervention. Further analysis determined complication trends related to specific IOL styles, materials, and types over the past 16 years (2007 to 2022). RESULTS: 103 completed surveys were returned in 2022 contributing to a total of 1627 tabulated surveys since 2007. In the 2022 survey, dislocation/decentration continued to be the most common complication overall. Glare/optical aberrations was a common complication associated with multifocal IOLs continuing a 16-year trend. In addition, hydrophilic acrylic IOLs as well as some silicone lenses in eyes with asteroid hyalosis demonstrated calcification as the most common complication necessitating explantation. CONCLUSIONS: Dislocation/decentration remains the leading cause of explantation in most IOL types. Glare/optical aberrations continue to be an associated complication of multifocal IOLs suggesting this ongoing issue has yet to be resolved with this type of IOL. In addition, calcification of hydrophilic acrylic lenses and silicone lenses is a rare event but continues to occur.

Rotational stability of a new hydrophobic acrylic intraocular lens platform.

PURPOSE: To evaluate rotational stability for ease of rotation of a new intraocular lens (IOL) platform with 4 haptics in an ex vivo model and compare it with a control single-piece lens with 2 open loops. SETTING: Intermountain Ocular Research Center, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Experimental study. METHODS: 10 human cadaver eyes were prepared as per the Miyake-Apple technique. After injection of the test or control lens, clockwise and counterclockwise rotations were attempted with a hook, with and without an ophthalmic viscosurgical device in place. Ease of rotation was scored as (1) very easy, (2) easy, (3) difficult, and (4) very difficult. Rotation of the entire eye containing test or control IOL was also performed with a multipurpose rotator (2 minutes; 220 revolutions per minute) to evaluate its effect on IOL alignment. RESULTS: There were statistically significant differences regarding ease of rotation between test and control lenses in all 4 scenarios, with rotation being more difficult with the test lens ( P < .05, Wilcoxon signed-rank test). No change in the alignment of test or control lenses was observed after eye rotation with the multipurpose rotator. CONCLUSIONS: The new IOL platform showed greater rotational stability than the control lens in this model, owing to design features such as 4 small arcs of contact between the haptics and the bag equator, a bulge at the distal end of each haptic, and arcuate haptics with curvatures oriented toward each other.

Metastatic Prostate Cancer to the Optic Canal: A Large-Cohort Analysis.

Prostate cancer (PCa) can present with metastases in rare cases, including those to the optic canal. Currently, no guidelines exist for managing PCa metastases in this patient population. This article aims to examine optic canal metastases through a large-cohort analysis. It involves a systematic review of the literature through a pooled analysis of published cases of PCa with optic canal or orbital metastasis, including one case previously reported from our institution. A subgroup analysis was employed to compare cases with optic metastases as their initial PCa presentation, hormone-naive (HN), versus those with optic metastases after PCa diagnosis, hormone-refractory (HR).  A total of 45 patients with ocular metastasis from PCa were included in this study. The mean age at diagnosis overall was 66.8 years (range: 45-85 years). Moreover, 16 cases (50%) had deceased, with a median time-to-death of 22 (range: 2-84) months. Regarding subgroup analysis, the mean age at diagnosis was 69.5 years (53-85 years) in the HN group and 64.5 years (45-83 years) in the HR group. With regard to reported survival, 10 (62.5%) cases belonged to the HN subset with a median follow-up duration of 12 (range: 1.5-36) months. In terms of reported mortality, 10 (62.5%) were from the HR subset with a median time-to-death of 32.5 (range 0.5-84) months. Our study constitutes the largest and most comprehensive examination of patients with optic canal metastases due to PCa so far. While optic canal metastases are a rare manifestation of PCa, they are linked with a poor prognosis. We also observed significant differences between HR and HN cohorts, which may indicate a difference in clinical presentations.

Herpes endotheliitis following laser-assisted in situ keratomileusis and photorefractive keratectomy.

Herpes endotheliitis is a less common manifestation of herpes keratitis, and characteristic examination findings include corneal edema and the presence of keratic precipitates. Infection may be primary or secondary to herpes virus reactivation following exposure to a potential trigger such as physiologic stress or environmental factors. Ocular surgery, including laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK), can trigger reactivation in patients with or without a documented history of previous herpes infection. We present two patients with visually insignificant stromal scarring who denied a previous history of herpetic disease and developed herpes endotheliitis following LASIK and PRK. We demonstrate the importance of an appropriately thorough preoperative evaluation and further workup of any corneal abnormalities, even if such findings initially appear inconsequential.

The Impact of Antiviral Resistance on Herpetic Keratitis.

ABSTRACT: Herpes simplex keratitis resistance to antiviral treatment presents a growing concern. The herpes simplex virus has many different mechanisms of resistance to antiviral treatment, which have been well described. Resistance to acyclovir occurs because of mutations in the viral thymidylate kinase and DNA polymerase that decrease this enzyme's affinity for its substrate. This article discusses factors that explain the prevalence of this resistance, the ability for recurrences in immunocompromised populations, current treatments for acyclovir-resistant herpes simplex keratitis, and novel therapies for this growing concern.

Visual Outcomes of Photorefractive Keratectomy Enhancement After Primary LASIK.

PURPOSE: To evaluate the safety, efficacy, and predictability of photorefractive keratectomy (PRK) at least 4 years after primary laser in situ keratomileusis (LASIK) and compare it to the United States Food and Drug Administration (FDA) criteria. METHODS: This retrospective, single-site study compared patients who underwent PRK enhancement from 2014 to 2019 after primary LASIK to those who only underwent primary LASIK without re-treatment from the same time period. Patient demographics and clinical information were compared between the two groups. Visual outcomes and postoperative complications were evaluated in the enhancement group. RESULTS: A total of 374 eyes with PRK enhancement were compared to 472 without re-treatment. Age, sex, surgical eye, and preoperative sphere, and spherical equivalent (SE) were significantly different between the enhancement and control groups (P < .05). At 12 months post-enhancement, 67% had uncorrected distance visual acuity (UDVA) of 20/20 or better, 98% had UDVA of 20/40 or better, and 0.4% of eyes lost at least two lines of corrected distance visual acuity (CDVA). A total of 83% and 98% of eyes were within ±0.50 and ±1.00 diopters of the target, respectively. Post-enhancement complications (n = 66) included dryness (6.1%), epithelial ingrowth (2.7%), and haze (2.7%). CONCLUSIONS: Older age at the time of the primary LASIK, female sex, right surgical eye, and more myopic sphere and SE were risk factors for enhancement. Although PRK enhancements are considered off-label procedures, they produce favorable outcomes at 3 and 12 months postoperatively while meeting FDA benchmarks for safety, efficacy, and predictability. [J Refract Surg. 2022;38(11):733-740.].

Pharmacological management of cancer pain: Novel therapeutics.

Patients diagnosed with cancer often experience pain during their treatment course, making it difficult to care for themselves and continue with their activities of daily living. When cancer is found at later stages, the pain can become severe and constant; reducing their quality of life and significantly affecting mental and physical well-being. Despite opioids being known to provide adequate analgesia for higher pain levels, they are often the reason for under-dosing because of their adverse effects and concern for addiction. There are also patients who do not respond well to opioids because of genetic anomalies or personal preference. Therefore, there is a need for novel non-opioid cancer pain treatments. There are many new cancer pain treatments that are emerging. This manuscript discusses cancer pain, risk factors, epidemiology, guidelines for the treatment of cancer pain, personalization of cancer pain therapy, breakthrough pain, cancer-induced peripheral neuropathy, established cancer pain treatment options, and novel emerging cancer pain treatment options.

Assessing Patients with Alpha-1 Antitrypsin Deficiency for Corneal Refractive Surgery: A Review and Clinical Experience.

Alpha-1 Antitrypsin Deficiency (AATD) is an autosomal inheritable disorder that impairs the protease inhibitor alpha-1 antitrypsin. This disorder presents with various systemic effects, including liver cirrhosis, centrilobular emphysema, and ocular manifestations. Performing corneal refractive surgery in patients with AATD raises concerns regarding the increased rates of corneal erosions, corneal ulcerations, potential developing descemetoceles, and other ocular manifestations. Patient outcomes for laser-assisted in situ keratomileuses (LASIK), photorefractive keratectomy (PRK), small incision lenticule extraction (SMILE), and other ocular corrective surgeries are lacking in this population. This article provides experiences performing corneal refractive surgery, discusses the current understanding of AATD, including its ocular manifestations, and explores factors to consider when evaluating patients for corneal procedures. The aim of this paper is to address the manifestations of AATD prior to performing corrective vision surgery.

Antipsychotic Use in Pregnancy: Patient Mental Health Challenges, Teratogenicity, Pregnancy Complications, and Postnatal Risks.

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs.

Association of Tumor Lysis Syndrome and Metastatic Melanoma.

Background Tumor lysis syndrome (TLS) is a known oncologic emergency characterized by severe metabolic derangements. TLS has been well documented in patients with hematologic malignancies, but rarely with metastatic melanoma. The objective of this study was to investigate the clinical characteristics and outcomes of TLS with metastatic melanoma.  Methods Retrospective literature review and analysis. Results Eighteen cases of TLS were identified with metastatic melanoma from published literature. The median age of patients was 63 years (36-79 years). All patients have stage IV disease. Seven cases (39%) of TLS were associated with multiple treatment regimes, including nivolumab (22%), ipilimumab (16%), and dacarbazine (22%). The time from treatment to diagnosis was 3.5 days (8 hours-21 days) in treatment-related TLS. Three cases (17%) were due to spontaneous TLS. The majority of cases have a high tumor burden (77.5%) and liver metastasis (83%). Seven cases were treated with rasburicase (39%). The mortality rate was 100% for the patients with spontaneous TLS and 73% for patients with treatment-related TLS. Three cases utilized traditional chemotherapy and the six most recent cases of treatment-associated TLS utilized immunotherapy and targeted therapy. Conclusion TLS in metastatic melanoma, due to either spontaneous or treatment-related causes, is associated with a very high mortality rate. This study highlights the importance of awareness, early intervention, and risk assessment of this underdiagnosed emergency.

A machine-learning approach for accurate detection of copy number variants from exome sequencing.

Copy number variants (CNVs) are a major cause of several genetic disorders, making their detection an essential component of genetic analysis pipelines. Current methods for detecting CNVs from exome-sequencing data are limited by high false-positive rates and low concordance because of inherent biases of individual algorithms. To overcome these issues, calls generated by two or more algorithms are often intersected using Venn diagram approaches to identify "high-confidence" CNVs. However, this approach is inadequate, because it misses potentially true calls that do not have consensus from multiple callers. Here, we present CN-Learn, a machine-learning framework that integrates calls from multiple CNV detection algorithms and learns to accurately identify true CNVs using caller-specific and genomic features from a small subset of validated CNVs. Using CNVs predicted by four exome-based CNV callers (CANOES, CODEX, XHMM, and CLAMMS) from 503 samples, we demonstrate that CN-Learn identifies true CNVs at higher precision (∼90%) and recall (∼85%) rates while maintaining robust performance even when trained with minimal data (∼30 samples). CN-Learn recovers twice as many CNVs compared to individual callers or Venn diagram-based approaches, with features such as exome capture probe count, caller concordance, and GC content providing the most discriminatory power. In fact, ∼58% of all true CNVs recovered by CN-Learn were either singletons or calls that lacked support from at least one caller. Our study underscores the limitations of current approaches for CNV identification and provides an effective method that yields high-quality CNVs for application in clinical diagnostics.