Health disparities in ocular oncology.

Social determinants of health (SDH) play a crucial role in shaping health outcomes. Few studies have explored the impact of SDH in ocular oncology, looking at differences in disease presentation, treatment choices, and outcomes based on race, ethnicity, socioeconomic status (SES), and insurance status. Retinoblastoma exhibits disparities in survival, with lower-income countries experiencing substantially lower rates compared to high-income countries. In the U.S., racial and SES disparities exist, impacting treatment choices and outcomes in children with retinoblastoma. Disparities in treatment modalities based on race and SES have been reported in uveal melanoma, with non-White and economically disadvantaged patients more likely to undergo primary enucleation. Ocular surface squamous neoplasia (OSSN) exhibits racial and socioeconomic disparities in treatment outcomes. Black patients with OSSN face higher mortality, independent of tumor size, eye laterality, or tumor behavior. Given the rarity, there is no data on disparities in vitreoretinal lymphoma management. When using primary central nervous system lymphoma as a surrogate, management and survival outcomes vary based on factors such as race, socioeconomic status, and insurance status. This article aims to review current literature on disparities in ocular oncology, highlighting the need for granular data to better understand existing gaps in care within ocular oncology.

Cytomegalovirus Retinitis in an Eye with Unilateral Retinoblastoma: A Case Report.

Introduction: Cytomegalovirus (CMV) retinitis in the setting of pediatric retinoblastoma is exceedingly unusual. Here, we present the first reported case of CMV retinitis in an enucleated eye with retinoblastoma after chemotherapy in the western hemisphere. Case Presentation: A 2-year-old Hispanic male without a family history of retinoblastoma presented with a 3-month history of right eye exotropia and squinting. Clinical examination revealed dense white vitreous opacities in the right eye. Ocular oncology evaluation unveiled an exudative retinal detachment with vitreous seeds, subretinal seeding, and a tumor emanating from the retina in the superonasal quadrant of the right eye. The patient was diagnosed with unilateral Group D retinoblastoma, and RB1 sequencing revealed a pathogenic variant with mosaicism. Treatment involved systemic chemotherapy, intravitreal chemotherapy, and cryotherapy. However, the patient developed a rhegmatogenous retinal detachment with diffuse vitreous hemorrhage and ultimately underwent right eye enucleation. Interestingly, histopathological analysis of the enucleated eye revealed concomitant CMV retinitis alongside retinoblastoma. After consultation with infectious disease, antiviral treatment was not initiated as the patient remained asymptomatic and maintained a recovered immune system. Repeat CMV PCR confirmed viral clearance. The patient received a prosthetic eye and continues to be monitored for retinoblastoma recurrence. Conclusion: Clinicians should be aware of the potential for CMV retinitis to develop in retinoblastoma patients receiving chemotherapy, which may complicate clinical decision-making and management. Timely identification of CMV retinitis in this setting may improve patient ocular outcomes and overall prognosis.

Bilateral Cytomegalovirus Retinitis After Chimeric Antigen Receptor T-cell Therapy for B-cell Lymphoma.

Cytomegalovirus (CMV) retinitis is commonly associated with immunosuppression and can cause irreversible vision loss. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective cancer treatment option but requires immunosuppression, thereby increasing the possibility of acquiring opportunistic infections such as CMV. We present the case of a 76-year-old female with a history of hypertension and type 2 diabetes mellitus who initially presented with shortness of breath and was diagnosed with the activated B-cell subset of diffuse large B-cell lymphoma (DLBCL). She received multiple cycles of chemotherapy and experienced relapses with cardiac involvement. The patient developed vision loss in the right eye and was diagnosed with bilateral posterior vitritis. She underwent various treatments, including radiotherapy, systemic chemotherapy, cataract extraction, and vitrectomy. After CAR-T therapy, she developed bilateral CMV retinitis, confirmed through polymerase chain reaction testing and managed by valganciclovir. Overall, this case report describes the first reported case of bilateral CMV retinitis following CAR-T therapy for DLBCL. It emphasizes the need for early recognition and treatment of CMV retinitis to prevent permanent vision loss. The report also underscores the importance of regular ocular screening and consideration of prophylactic measures in patients undergoing CAR-T therapy.

Chemoradiation to the submental muscles alters hyoid movement during swallowing in a rat model.

Hyolaryngeal dysfunction is a commonly reported swallowing problem after chemoradiation treatment for head and neck cancer. The displacement of the hyolaryngeal complex during swallowing protects the airway and assists in opening the upper esophageal sphincter. Activation of the submental muscles, specifically the mylohyoid and geniohyoid muscles, is thought to facilitate movement of the hyoid. The purpose of this study was to determine if targeted radiation to the submental muscles given concurrently with chemotherapy alters hyolaryngeal displacement 1 mo after treatment. We hypothesized that chemoradiation treatment would result in abnormal patterns of hyoid movement compared with controls. Furthermore, we propose that these changes are associated with alterations in bolus size and discoordination of the jaw during drinking. Eighteen rats underwent either chemoradiation, radiation, or no treatment. Radiation treatment was targeted to submental muscles using a clinical linear accelerator given in 12 fractions of 4 Gy (3 days per week). Cycles of 1 mg/kg of cisplatin were administered concurrently each week of radiation. One month posttreatment, videofluoroscopy swallow studies (VFSS) were performed in self-drinking rats using a fluoroscope customized with a high-speed camera. The hyoid, jaw, and hard palate were tracked during swallowing from VFSS. Hyoid kinematics were analyzed from the start to the end of hyoid movement, and parameters were compared with bolus size and jaw movement. Significant differences in hyoid retraction parameters were found postchemoradiation. Alterations in the trajectory of hyoid motion during swallowing were observed. The findings demonstrate early changes in hyoid motion during swallowing associated with chemoradiation treatment.NEW & NOTEWORTHY Chemoradiation treatment for head and neck cancer can cause functional impairments in swallowing, which can adversely affect quality of life. This study provides new evidence that chemoradiation targeted to the submental muscles provokes early adaptations in hyoid movement during swallowing, which correlate with changes in bolus size. We also demonstrate a method for tracking the hyoid during swallowing in a rat model of chemoradiation injury.

A Suspicious Pigmented Lesion of the Conjunctiva.

A 74-year-old woman with a history of breast cancer, now in remission, presented for evaluation of a conjunctival lesion of the right eye. What would you do next?

Physical Activity and Children's Episodic Memory: A Meta-Analysis.

PURPOSE: The purpose of this review was to evaluate the effects of physical activity on children's free recall, cued recall, and recognition episodic memory and to explore potential moderating factors. METHODS: The following databases were searched: PubMed, ERIC, APA Psych Info, CINHAL, SPORTDiscus, and Google Scholar. Studies were included if: (1) participants were aged 4-18 years, (2) participants were typically developed, (3) participants were randomized to groups, (4) interventions employed gross movements, (5) sedentary group was used for control, (6) memory tests were quantitative, and (7) employed acute or chronic intervention. RESULTS: 14 studies met inclusion criteria resulting in the analysis of data from 7 free recall, 7 cued recall, and 8 recognition memory tests. Physical activity was found to have a positive influence on tests free (g = 0.56), cued recall (g = 0.67), and no influence on tests of recognition (g = 0.06). While some moderator analyses were significant, the authors do not consider these results to be meaningful in application. CONCLUSIONS: The effects of acute and chronic physical activity enhance specific aspects of long-term episodic memory. These findings suggest physical activity interventions developed for children may be expected to benefit some, but not all, types of memory processing.

Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.

The effects of physical activity timing and complexity on episodic memory: A randomized controlled trial.

The role of two types of acute physical activity (PA) bouts were assessed on young adults' free-recall and recognition memory in two experiments, which differed in the temporal relation of PA and word encoding. Before or following training on the Rey Auditory Verbal Learning Task, participants performed a simple two-step dance, a complex four-step dance, or remained seated. Hypotheses proposed that PA prior to encoding and complex PA would enhance PA's mnemonic benefits. Memory assessed post-PA, 24 h, and 7 days after training indicated that timing and complexity of PA did not impact free-recall or recognition memory. Findings differ from a previous study showing complex PA benefited motor learning more than simple PA (Tomporowski & Pendleton, 2018). The inconsistency may be due to different working memory processes underlying consolidation and retrieval of procedural or episodic information. Theory-based explanations regarding memory storage and retrieval are proposed to elucidate this selective process.

An unusual case of rapid resolution of bilateral vitelliform deposits after discontinuation of pentosan polysulfate sodium.

Purpose: To report the structural and functional changes in a 67-year-old male with pentosan polysulfate sodium (PPS) maculopathy with a progressive resolution of bilateral vitelliform lesions after PPS cessation. Observations: The patient was initially seen after taking daily PPS for over 26 years. Three months after discontinuing PPS, the bilateral vitelliform lesions identified on spectral-domain optical coherence tomography (SD-OCT) at initial consultation had completely resolved. Bilateral resolution of vitelliform lesions was associated with a decline in best-corrected visual acuity, and ellipsoid zone disruption on SD-OCT. Conclusions and importance: Several PPS maculopathy phenotypes have been previously described including vitelliform lesions. Our case highlights that discontinuing PPS may lead to rapid resolution of vitelliform lesions in PPS maculopathy and may be associated with a rapid reduction in vision.

The Sensitivity of Ultra-Widefield Fundus Photography Versus Scleral Depressed Examination for Detection of Retinal Horseshoe Tears.

PURPOSE: Ultra-widefield (UWF) imaging is commonly used in ophthalmology in tandem with scleral depressed examinations (SDE) to evaluate peripheral retinal disease. Because of the increased reliance on this technology in tele-ophthalmology, it is critical to evaluate its efficacy for detecting the peripheral retina when performed in isolation. Therefore, we sought to evaluate UWF imaging sensitivity in detecting retinal horseshoe tears (HSTs). STUDY DESIGN: Retrospective clinical validity and reliability study. METHODS: A single-institutional retrospective analysis was performed on patients at the Shiley Eye Institute, University of California, San Diego. Patients with HSTs seen on SDE who underwent treatment with laser were included in the study. A total of 140 patients with HSTs in the right and/or left eyes met the inclusion criteria. Those with concomitant ruptured globes, retinal detachments, and vitreous hemorrhages were excluded. A total of 123 patients with 135 HSTs were included in the final analysis. The primary outcome was the number of HSTs detected by UWF imaging. A secondary outcome was HST location. Sensitivity was measured with respect to HST location, and statistical significance was calculated by Fisher exact testing. RESULTS: A total of 69 (51.1%) HSTs were visualized on UWF images and 66 (48.9%) were not visualized. The sensitivity of UWF imaging in capturing HSTs was 7 of 41 (17.1%), 8 of 25 (32.0%), 7 of 14 (50.0%), and 47 of 55 (85.5%) for the superior, inferior, nasal, and temporal quadrants, respectively. Sensitivities between HST visibility and location were statistically significant (P < .001). CONCLUSIONS: Nearly half of HSTs were missed by UWF imaging. This study demonstrates that UWF imaging alone is not sufficiently sensitive to exclude the presence of HSTs.

Improved Visual Outcomes after Severe Open-Globe Injuries Associated with Perioperative Vitreoretinal Evaluation.

PURPOSE: To investigate the impact of perioperative evaluation by a vitreoretinal surgeon on outcomes after severe open-globe injury (OGI). DESIGN: Retrospective, comparative study. SUBJECTS: Open-globe injury cohorts from 2 academic United States ophthalmology departments with disparate OGI management protocols and vitreoretinal referral patterns. METHODS: Patients with severe OGI (presenting visual acuity [VA] of counting fingers or worse) from the University of Iowa Hospitals and Clinics (UIHC) were compared with patients with severe OGI from the Bascom Palmer Eye Institute (BPEI). At UIHC, almost all cases of OGI were repaired by anterior segment surgeons, with postoperative vitreoretinal referral at the surgeon's discretion. In contrast, at BPEI, all OGIs were both repaired and managed postoperatively by a vitreoretinal surgeon. MAIN OUTCOME MEASURES: Rate of vitreoretinal surgeon evaluation, rate of pars plana vitrectomy (PPV) (either primary or secondary), and VA at the last follow-up. RESULTS: Overall, 74 subjects from UIHC and 72 subjects from BPEI met the inclusion criteria. There were no differences in preoperative VA or rates of vitreoretinal pathology. The rate of vitreoretinal surgeon evaluation was 100% at BPEI and 65% at UIHC (P < 0.001), and the rate of PPV was 71% at BPEI and 40% at UIHC (P < 0.001). Median VA at the last follow-up in the BPEI cohort was 1.35 logarithm of the minimum angle of resolution (logMAR) (interquartile range [IQR], 0.53-2.30, corresponding to a Snellen VA of ∼ 20/500) compared with a median VA of 2.70 logMAR (IQR, 0.93-2.92, corresponding to a Snellen VA of light perception) in the UIHC cohort (P = 0.031). Overall, 68% of patients in the BPEI cohort had an improvement in VA from presentation to last follow-up versus 43% in the UIHC cohort (P = 0.004). CONCLUSIONS: Automatic perioperative evaluation by a vitreoretinal surgeon was associated with a higher rate of PPV and improved visual outcomes. Prompt evaluation by a vitreoretinal surgeon, either preoperatively or in the early postoperative period, should be considered, when logistically feasible, in severe OGIs because PPV is frequently indicated and may result in significant visual improvement. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A simplified procedure for isolation of primary murine microglia.

There are various approaches in which one can isolate microglia from murine brains, such as immunomagnetic, density gradient, FACS and differential adhesive methods. In this procedure a modified flask-tapping approach was used due to its simplicity and reproducibility. Our protocol requires only a single step to isolate the microglia from the mixed cell population. Once the microglia were isolated, we characterized cell purity, microglial morphology and phagocytic activity. The single-step protocol, without the need for additional astrocyte or oligodendrocyte separation, allows microglial cells to be used immediately for experimental purposes. The protocol is low-cost and can be performed in any lab with standard cell-culture equipment.

Surgical Outcomes of Acute Retinal Necrosis-Related Retinal Detachment in Polymerase Chain Reaction-Positive Patients: A Single-Center Experience.

PURPOSE: To evaluate the clinical features, operative techniques, and surgical outcomes of patients who underwent surgery for acute retinal necrosis (ARN)-related retinal detachment (RD). DESIGN: Retrospective, longitudinal, consecutive case series. PARTICIPANTS: Patients with polymerase chain reaction-positive ARN presenting from 2011 to 2021 who underwent vitreoretinal surgery for ARN-related RD at our institution. METHODS: Univariate, multivariate, and survival analyses were used to determine predictors of anatomic and functional outcomes. MAIN OUTCOME MEASURES: Single-surgery anatomic success rate, recurrent RD, and visual acuity (VA) at 1 year. RESULTS: Thirty-four eyes of 34 patients (32.4% women, mean age, 45.1 ± 20.4 years) were included for analysis with a median follow-up of 2.5 years (interquartile range [IQR], 0.8-5.5 years). Presenting VA was 1.1 ± 0.8 logarithm of the minimum angle of resolution (LogMAR) (Snellen ∼20/250). The median time from presentation to RD surgery was 1.7 months (IQR, 0.8-4.1 months), and the mean preoperative VA was 1.6 ± 0.8 LogMAR (Snellen ∼20/800). Small-gauge pars plana vitrectomy (PPV) with or without a scleral buckle (SB) was performed for all eyes with an overall single-surgery success rate of 63.6%, with no statistically significant differences in visual/anatomic outcomes between PPV and PPV/SB cases. Silicone oil was used for tamponade in 33 (97.1%) cases and was removed in 10 (30.3%) with good anatomic and final functional outcomes (Snellen âˆ¼20/80). Independent predictors of recurrent RD included the female sex (hazard ratio, 8.38; 95% confidence interval, 2.03-34.68; P < 0.01) and zone 1 retinitis involvement at presentation (hazard ratio, 10.95; 95% confidence interval, 2.12-56.48; P < 0.01). The mean VA at 1 year (VA1year) and at the final follow-up both had a Snellen equivalent of 20/640 (P > 0.05 for both compared with preoperative VA, respectively). Eyes that achieved single-surgery success had VA1year of 20/200 versus hand movements in those with single-surgery failure (P < 0.01). On multivariate linear regression, younger age (P = 0.04) and better presenting VA (P < 0.01) were both associated with better VA1year. CONCLUSIONS: Moderate single-surgery anatomic success can be achieved with modern vitreoretinal surgical techniques for ARN-related RD, although visual outcomes remain poor. Further studies investigating interventions for increasing single-surgery success rates, for the inflammatory complications of ARN, and for preventing ARN-related RD are needed.

Endophthalmitis Associated with a Retained Cilium in the Clear Corneal Wound after Cataract Surgery.

We report a case of endophthalmitis occurring secondary to a retained cilium in a clear corneal wound after cataract surgery. A 67-year-old female presented to an ophthalmology emergency room with light perception vision in the right eye 5 days after routine cataract surgery. Examination of the right eye demonstrated decreased vision, conjunctival injection, a corneal endoplaque, and anterior chamber fibrin. Additionally, a cilium was visible in the clear corneal incision. A vitreous aspiration and injection of antibiotics and steroid were performed, and the patient underwent a vitrectomy the next day. Intraoperative cultures and culture of the cilium grew Staphylococcus epidermidis. One year after vitrectomy, the patient's vision recovered to 20/25 in the operated eye. In conclusion, a retained cilium in a clear corneal wound related to cataract surgery, though rare, may result in endophthalmitis. The surgical field should be cleared of cilia on the ocular surface prior to surgery. Proper draping and use of povidone-iodine antisepsis are essential in reducing the risk of endophthalmitis.

Sensitizing drug-resistant cancer cells from blood using microfluidic electroporator.

Direct assessment of patient samples holds unprecedented potential in the treatment of cancer. Circulating tumor cells (CTCs) in liquid biopsies are a rapidly evolving source of primary cells in the clinic and are ideal candidates for functional assays to uncover real-time tumor information in real-time. However, a lack of routines allowing direct and active interrogation of CTCs directly from liquid biopsy samples represents a bottleneck for the translational use of liquid biopsies in clinical settings. To address this, we present a workflow for using a microfluidic vortex-assisted electroporation system designed for the functional assessment of CTCs purified from blood. Validation of this approach was assessed through drug response assays on wild-type (HCC827 wt) and gefitinib-resistant (HCC827 GR6) non-small cell lung cancer (NSCLC) cells. HCC827 cells trapped within microscale vortices were electroporated to sequentially deliver drug agents into the cytosol. Electroporation conditions facilitating multi-agent delivery were characterized for both cell lines using an automatic single-cell image fluorescence intensity algorithm. HCC827 GR6 cells spiked into the blood to emulate drug-resistant CTCs were able to be collected with high purity, demonstrating the ability of the device to minimize background cell impact for downstream sensitive cell assays. Using our proposed workflow, drug agent combinations to restore gefitinib sensitivity reflected the anticipated cytotoxic response. Taken together, these results represent a microfluidics multi-drug screening panel workflow that can enable functional interrogation of patient CTCs in situ, thereby accelerating the clinical standardization of liquid biopsies.

Case report: Vitreous hemorrhage as the presenting sign of retinal cavernous hemangioma in a newborn.

PURPOSE: To report a case of vitreous hemorrhage as the presenting sign of retinal cavernous hemangioma (RCH) in a newborn. OBSERVATIONS: A five-week-old full-term male with a history of seizures and birth trauma underwent ophthalmology screening. Initial eye examination revealed vitreous hemorrhage. Subsequent examination under anesthesia with multi-modal imaging revealed vitreous hemorrhage and an intra-retinal mass with numerous sac-like aneurysmal dilatations, consistent with RCH. CONCLUSIONS AND IMPORTANCE: Vitreous hemorrhage in a neonate is an atypical presentation of RCH. Clinicians should be aware that birth trauma may lead to vitreous hemorrhage from RCH. This is the first description of RCH, a rare retinal vascular tumor, in a newborn.

WIDE-FIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF DIABETIC TRACTIONAL RETINAL DETACHMENTS BEFORE AND AFTER SURGICAL REPAIR.

PURPOSE: Wide-field (WF) swept-source (SS) optical coherence tomography angiography (SS-OCTA) was used to image diabetic tractional retinal detachments (TRDs) before and after pars plana vitrectomy. The clinical utility of SS-OCTA was assessed. METHODS: Patients with diabetic TRDs were imaged prospectively with SS-OCTA. Ultrawide-field imaging was obtained when possible. Postoperative WF SS-OCTA imaging was performed. RESULTS: From January 2018 through December 2019, 31 eyes of 21 patients with diabetic TRDs were imaged. Wide-field SS-OCTA en-face images captured all areas of TRD and fibrovascular proliferation within the posterior pole that were visualized on ultrawide-field imaging. Optical coherence tomography angiography B-scans revealed the vascularity of preretinal membranes and identified areas of vitreoretinal traction and posterior vitreous detachment. Ten eyes underwent pars plana vitrectomy. Postoperative SS-OCTA imaging demonstrated removal of fibrovascular membranes, relief of traction, and resolution of TRDs. Retinal ischemia before and after surgical repair appeared similar. CONCLUSION: All clinically relevant features of diabetic TRDs were identified at baseline and assessed longitudinally after pars plana vitrectomy using WF SS-OCTA, which showed resolution of vitreoretinal traction and no apparent change in the status of retinal perfusion after surgery. If the media are clear and fixation is adequate, WF SS-OCTA is likely the only imaging modality needed for the diagnosis and longitudinal evaluation of diabetic TRDs.

NNC 26-9100 increases Aß1-42 phagocytosis, inhibits nitric oxide production and decreases calcium in BV2 microglia cells.

Microglia are the resident immune cell of the brain involved in the development and progression of Alzheimer's disease (AD). Modulation of microglia activity represents a potential mechanism for treating AD. Herein, the compound NNC 26-9100 (NNC) was evaluated in toxicity, nitric oxide release, Aß1-42 uptake and cytosolic calcium assays during lipopolysaccharide (LPS)-activated conditions using mouse BV2 microglia cells. After 24 hours, LPS increased cell toxicity in the alamar blue and lactate dehydrogenase assays, increased nitrite release, and increase cytoplasmic calcium. Addition of NNC decreased the LPS-induce lactate dehydrogenase release, had no effect in the alamar blue assay, decreased nitrite release and decreased cytosolic calcium. In the absence of LPS, NNC increased uptake of FITC-tagged Aß1-42. These data demonstrate that NNC treatment decreases nitrosative stress and microglia cell damage during LPS-induced activation and enhances phagocytosis of Aß1-42 during non-inflammatory conditions. Thus, NNC 26-9100 may have beneficial effects in AD and in inflammatory diseases of the brain through enhancement of microglial Aß clearance, and cell protective effects through prevention of elevated cytosolic calcium and inhibition of nitric oxide release.