Combined central retinal artery and medial posterior ciliary artery occlusion: Localizing the lesion.

Purpose: To report a rare case of a combined central retinal artery (CRA) and medial posterior ciliary artery (MPCA) occlusion due to an atherosclerotic lesion in the common trunk supplying both arteries. Observations: A 75-year-old man presented with acute vision loss associated with elevated intraocular pressure in the right eye. Multi-modal imaging revealed a combined retinal and choroidal infarction in the distribution of the CRA and MPCA, localizing the lesion to the common trunk of the ophthalmic artery supplying both the CRA and MPCA. Neurovascular imaging provided supportive evidence for the diagnosis. Conclusions and importance: A simultaneous retinal and choroidal vascular occlusion is an uncommon presentation. Familiarity with the anatomy of the ophthalmic arteries and its branches facilitates localizing the lesion.

Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion.

PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) biomarkers associated with ranibizumab injection frequency after 7 monthly doses in the prospective, multicenter SHORE study for macular edema due to retinal vein occlusion (RVO). DESIGN: Prospective phase IV clinical trial data. METHODS: Post hoc analysis of 95 patients who received 7 monthly doses of ranibizumab followed by either pro re nata (PRN) or nonrandomized monthly injections from months 7-15 in eyes with macular edema secondary to RVO. Baseline SD-OCT biomarkers assessed include central subfield thickness (CST), epiretinal membrane presence, intraretinal and subretinal fluid, hyperreflective foci, disorganization of retinal inner layers (DRIL), and disruption of the external limiting membrane, ellipsoid zone, or interdigitation zone. Univariate and multivariable regression analyses evaluated the association between SD-OCT biomarkers and ranibizumab injection frequency. RESULTS: Mean age of patients was 65.3 (SD, 12.7) years. Overall, 57.9% had BRVO/HRVO and 42.1% of eyes had CRVO. Mean BCVA improved (+17.5 [SD, 1.2] Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) during the 7-month fixed dosing period, remaining stable from baseline (+20.1 [SD, 1.5] ETDRS letters) during the PRN phase from months 7-15. The mean number of PRN injections was 4.32 (SD, 2.35). On multivariate regression, greater baseline DRIL (ß = 0.021, P = .0275) and higher CST at month 3 (ß = 0.01, P < .001) were associated with a higher total number of PRN injections. CONCLUSION: Greater baseline DRIL and higher CST at 3 months after starting ranibizumab treatment are associated with more frequent ranibizumab injections in PRN-treated patients with macular edema due to RVO.

PREVALENCE, CHARACTERISTICS, AND OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN EYES WITH TRABECULECTOMY OR GLAUCOMA DRAINAGE DEVICES.

PURPOSE: To describe the prevalence, management, and outcomes of rhegmatogenous retinal detachment (RRD) after incisional glaucoma filtering surgery. METHODS: All patients with a history of trabeculectomy or glaucoma drainage device surgery who were subsequently diagnosed with an RRD from January 1, 2016, to January 1, 2021, at the Wills Eye Hospital were identified. RESULTS: Forty-six eyes met the inclusion criteria. The mean age was 60.7 ± 19.6 years, and 15 patients (32.6%) were female. Of all eyes, 34 (73.9%) were diagnosed with primary open-angle glaucoma. The mean time from most recent incisional glaucoma surgery to RRD diagnosis was 1,133 ± 1,644 days. There were 19 eyes (41.3%) with preoperative proliferative vitreoretinopathy (9 eyes [19.6%] with Grade C proliferative vitreoretinopathy) and 35 eyes (76.1%) had macula-off RRD at the time of presentation. At RRD presentation, 4 eyes (8.7%) had concomitant endophthalmitis, 5 (10.9%) had concurrent choroidal detachment, and 2 (4.7%) had concurrent vitreous hemorrhage. Primary vitrectomy was performed in most (91.3%) cases. Silicone oil tamponade was often required (71.1%). The single surgery success rate was 65.2% (30 of 46). The mean preoperative logarithm of the minimum angle of resolution visual acuity was 1.72 ± 0.78 (Snellen acuity 20/1,050), and the mean final postoperative logarithm of the minimum angle of resolution was 1.59 ± 0.89 (20/778, P = 0.2853). Of glaucoma surgeries performed, the 5-year prevalence of RRD was 0.71% (26 of 3,664, 95% Poisson confidence interval 0.48%-1.04%). CONCLUSION: The 5-year prevalence of RRDs after trabeculectomy or glaucoma drainage device was 0.71%. Most patients presented with macula-involving detachments, often with proliferative vitreoretinopathy. Anatomical and visual outcomes were poor.

Factors Associated With Good Visual Acuity Outcomes After Retinectomy in Eyes With Proliferative Vitreoretinopathy.

PURPOSE: To investigate factors associated with good visual acuity (VA) following repair of rhegmatogenous retinal detachments (RD) with proliferative vitreoretinopathy (PVR) undergoing retinectomy. DESIGN: Interventional, retrospective, case-control study. METHODS: This single-institution study evaluated patients who underwent retinectomy during repair of RD with PVR from January 1, 2015 to December 31, 2019. A good VA cohort was identified based on a final VA ≥20/70. A 2:1 age-matched and gender-matched poor VA cohort with VA <20/70 was subsequently identified. Metrics compared between the two cohorts included time from primary and recurrent RD diagnosis to surgery, lens status, initial RD size, macula involvement, PVR grade, and size of retinectomy. RESULTS: A total of 5355 eyes were diagnosed with primary RD during the study period, of which 345 had PVR and underwent retinectomy. The good VA cohort included 62 eyes with a mean final logMAR VA of 0.32 [Snellen 20/42], while the poor VA cohort included 119 eyes with a mean final logMAR VA of 1.54 [Snellen 20/693; P < .0001]. On multivariate analysis, smaller initial RD size (P = .0090), fewer surgeries (P = .0002), shorter time between recurrent RD diagnosis and subsequent surgeries (P = .0006), better preoperative VA (P = .0276), and pseudophakia at final visit (P = .0049) remained significant predictors of good vision. CONCLUSION: Eyes undergoing retinectomy during repair of RD with PVR can achieve good VA outcomes. The primary modifiable factor associated with better VA was shorter delay between redetachment diagnosis and surgery, particularly in the absence of silicone oil tamponade.

FACTORS AFFECTING RETINAL REDETACHMENT AFTER SILICONE OIL REMOVAL FOR RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To report factors affecting the retinal redetachment rate after silicone oil removal (SOR) following rhegmatogenous retinal detachment (RRD) repair. METHODS: Retrospective cohort study from December 1, 2014, to March 1, 2020, of 205 consecutive patients treated for RRD with silicone oil (SO) tamponade and subsequent SOR with at least 6-month follow-up. Primary outcome measure was the rate of retinal redetachment after SOR. RESULTS: The retinal redetachment rate after SOR was 18.5%. Preoperative macula and lens status, proliferative vitreoretinopathy, previous retinectomy, retinal detachment size, concomitant phacoemulsification, previous scleral buckling, and endolaser during SOR did not affect the redetachment rate after SOR. Previous SO exchange was associated with increased redetachment (OR 2.53, 95% CI [1.11-5.80], P = 0.0278). Twelve months of SO tamponade had lower redetachment rates compared with 3 months (OR 0.25, 95% CI [0.04-0.09], P = 0.048). Shorter SO tamponade (3 vs. 12 months) had better final visual outcomes after SOR (0.80 ± 0.61 vs. 1.41 ± 0.66, P < 0.0001). CONCLUSION: No preoperative or intraoperative factors in this analysis influenced the risk of redetachment after SOR except duration of SO tamponade and previous SO exchange. Although longer SO tamponade duration may be associated with lower rates of redetachment, visual outcomes may be worse.

Clinical Characteristics and Management Outcomes of Rhegmatogenous Retinal Detachments Due to Retinal Dialysis.

Purpose: This work assesses the clinical characteristics and outcomes of various treatment methods in managing rhegmatogenous retinal detachments secondary to retinal dialysis. Methods: In this retrospective, consecutive case series, patients presenting to a tertiary referral vitreoretinal service from 2015 to 2020 were chosen. The primary outcome measure was the single-surgery anatomic success (SSAS) rate in the first 90 days after surgery and overall SSAS rate until the last visit. Results: Eighty-six eyes of 84 patients were included. Mean (SD) age was 30 (14.8) years (range, 7-71 years). Fifty-nine (70%) patients were men and 55 eyes (64%) had a history of trauma. Dialysis occurred in the inferotemporal quadrant in 50 eyes (58%) of the entire cohort and 25 of 55 eyes (45%) with prior trauma. Fifty-one eyes (59.3%) were managed by scleral buckle (SB), 25 eyes (29.2%) with laser retinopexy, and 10 eyes (11.6%) with pars plana vitrectomy (PPV). The SSAS rate in the first 90 days after surgery was 94.1% (81 of 86 eyes), including 90.1% of eyes with SB, 100% of eyes with laser retinopexy, and 100% of eyes with PPV (P = .07). The overall SSAS rate, however, was 89.5% (77 of 86) eyes, including 90.1% of eyes with SB, 84% of eyes with laser retinopexy, and 100% of eyes with PPV (P = .4). Final attachment rate was 100% in the entire cohort. Conclusions: With careful consideration of underlying pathology, all 3 treatment modalities can provide high rates of anatomic and functional success.

Application of Forcing Functions to Electronic Health Records Is Associated With Improved Pain Control for Patients Undergoing Radiation Therapy for Bone Metastases.

Pain is a common problem for patients undergoing radiation therapy, exacerbated by inconsistent pain documentation. Free-form templates, pain score prompts, and forcing functions are a hierarchy of constraint systems that can be applied to data entry. This study assessed the impact of incorporating these models into electronic health records on pain documentation rates during 450 on-treatment visits and pain severity of 258 patients with bone metastases and breast and thoracic cancer during radiation therapy. Pain documentation is associated with more robust constraint systems: free form (0.11, 95% CI [0.07, 0.18]), pain score prompts (0.87, 95% CI [0.81, 0.92]), and forcing functions (0.97, 95% CI [0.93, 0.99]). Forcing functions also were associated with improved pain control over the course of radiation treatment for bone metastases compared with pain score prompts (P = .026, nonparametric Kruskal-Wallis). Use of forcing functions correlates with increased pain documentation rates, which contributes to improved pain management.

3D printed temporal bone as a tool for otologic surgery simulation.

PURPOSE: In this face validity study, we discuss the fabrication and utility of an affordable, computed tomography (CT)-based, anatomy-accurate, 3-dimensional (3D) printed temporal bone models for junior otolaryngology resident training. MATERIALS AND METHODS: After IRB exemption, patient CT scans were anonymized and downloaded as Digital Imaging and Communications in Medicine (DICOM) files to prepare for conversion. These files were converted to stereolithography format for 3D printing. Important soft tissue structures were identified and labeled to be printed in a separate color than bone. Models were printed using a desktop 3D printer (Ultimaker 3 Extended, Ultimaker BV, Netherlands) and polylactic acid (PLA) filament. 10 junior residents with no previous drilling experience participated in the study. Each resident was asked to drill a simple mastoidectomy on both a cadaveric and 3D printed temporal bone. Following their experience, they were asked to complete a Likert questionnaire. RESULTS: The final result was an anatomically accurate (XYZ accuracy = 12.5, 12.5, 5 µm) 3D model of a temporal bone that was deemed to be appropriate in tactile feedback using the surgical drill. The total cost of the material required to fabricate the model was approximately $1.50. Participants found the 3D models overall to be similar to cadaveric temporal bones, particularly in overall value and safety. CONCLUSIONS: 3D printed temporal bone models can be used as an affordable and inexhaustible alternative, or supplement, to traditional cadaveric surgical simulation.

Cardiogenic Shock Requiring Extracorporeal Membrane Oxygenation Support in a Patient with Panhypopituitarism: A Case Report.

We present a 58-year-old female with a past history of a pituitary adenoma resected two years prior to admission who developed polymorphic ventricular tachycardia and cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We noted that the patient had stopped taking all of her medications six months prior to presentation. An extensive workup revealed acute panhypopituitarism with secondary hypothyroidism, secondary adrenal insufficiency, and central diabetes insipidus. She was immediately initiated on thyroid and adrenal hormone replacement therapy as well as fluid replacement. Within five days of her medical treatment, the patient's cardiac function improved and she was successfully weaned from VA-ECMO and subsequently discharged home with appropriate hormone replacement therapy.

Parasex Generates Phenotypic Diversity de Novo and Impacts Drug Resistance and Virulence in Candida albicans.

Candida albicans is a diploid fungus that is a frequent cause of mucosal and systemic infections in humans. This species exhibits an unusual parasexual cycle in which mating produces tetraploid cells that undergo a nonmeiotic program of concerted chromosome loss to return to a diploid or aneuploid state. In this work, we used a multipronged approach to examine the capacity of parasex to generate diversity in C. albicans First, we compared the phenotypic properties of 32 genotyped progeny and observed wide-ranging differences in fitness, filamentation, biofilm formation, and virulence. Strikingly, one parasexual isolate displayed increased virulence relative to parental strains using a Galleria mellonella model of infection, establishing that parasex has the potential to enhance pathogenic traits. Next, we examined parasexual progeny derived from homothallic, same-sex mating events, and reveal that parasex can generate diversity de novo from identical parental strains. Finally, we generated pools of parasexual progeny and examined resistance of these pools to environmental stresses. Parasexual progeny were generally less fit than control strains across most test conditions, but showed an increased ability to grow in the presence of the antifungal drug fluconazole (FL). FL-resistant progeny were aneuploid isolates, often being diploid strains trisomic for both Chr3 and Chr6. Passaging of these aneuploid strains frequently led to loss of the supernumerary chromosomes and a concomitant decrease in drug resistance. These experiments establish that parasex generates extensive phenotypic diversity de novo, and that this process has important consequences for both virulence and drug resistance in C. albicans populations.

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues.

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming.