Contrast Sensitivity Better Reflects Wide-Field Swept-Source Optical Coherence Tomography Angiography Vascular Metrics Among Healthy Eyes Compared to Visual Acuity.

BACKGROUND AND OBJECTIVE: To evaluate the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) and visual function in healthy eyes. PATIENTS AND METHODS: Fifty-seven eyes of 45 patients were evaluated with visual acuity (VA), contrast sensitivity (CS), and WF SS-OCTA (3 × 3, 6 × 6, and 12 × 12 mm images) on the same day. Mixed-effects multivariable regression analyses were performed. RESULTS: Contrast sensitivity metrics, including CS between 6 to 18 cycles per degree (cpd) and area under the logarithm CS function, were significantly associated with vessel density (VD) and vessel skeletonized density (VSD), whereas VA was not. The largest effect size was between CS at 18 cpd and VD (ß = 0.41, P = 0.007) and VSD (ß = 0.42, P = 0.006) on 12 × 12 mm images. CONCLUSIONS: Reduced VSD and VD on WF SSOCTA was significantly associated with decreased CS, whereas VA was not. These results suggest CS could serve as a screening tool for early stage retinal and neurologic disorders. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Epiretinal Membrane Formation following Rhegmatogenous Retinal Detachment Repair: A Retrospective Cohort Study.

INTRODUCTION: This study aimed to investigate the incidence of and risk factors for epiretinal membrane (ERM) formation following primary rhegmatogenous retinal detachment (RRD) repair. METHODS: This comparative, retrospective, single-center cohort study included eyes with primary RRD treated between 2011 and 2023 at Massachusetts Eye and Ear, Boston, Massachusetts, with pars plana vitrectomy (PPV), scleral buckle (SB), PPV+SB, or pneumatic retinopexy (PnR). Demographic, clinical, and surgical parameters were collected from medical records. The primary outcome was the risk of ERM formation, while the secondary outcome was the risk of ERM requiring surgery. Univariable and multivariable Cox regression were performed, and a hazard ratio (HR) and 95% confidence interval (95% CI) were reported. RESULTS: Overall, 394 eyes were included. The mean age was 58.49 ± 12.8 years, and most patients were male. There was a significantly lower risk of ERM formation following SB compared to PPV in the univariable analysis (HR = 0.2, 95% CI = 0.08-0.60, p = 0.003); however, there was no significant association between treatment modality and ERM formation on multivariable Cox regression controlling for confounding factors (p = 0.24). ERM formation was found more commonly in patients who were older (HR = 1.0 per 1 year increase in age, 95% CI = 1.01-1.04, p = 0.001), those with worse baseline visual acuity (HR = 1.3, 95% CI = 1.09-1.71, p = 0.008), and those with macula-off RRDs (HR = 2.1, 95% CI = 1.41-3.32, p < 0.001). CONCLUSION: Surgical modality does not have a significant impact on the risk of ERM following retinal detachment repair. However, age, baseline visual acuity, and macular status are important predictors of ERM formation after RRD repair.

Mohs surgery for squamoid eccrine ductal carcinoma.

Squamous eccrine ductal carcinoma is a rare cutaneous malignancy. It has the potential to locally recur and may occasionally metastasize. It presents a diagnostic challenge given its rare nature and overlapping histopathological features with other cutaneous carcinomas.

Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance. CONCLUSIONS: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessment of Microvascular Changes After Rhegmatogenous Retinal Detachment Repair Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: Our objective was to evaluate retinal microvascular changes and visual outcomes following rhegmatogenous retinal detachment (RRD) repair using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). PATIENTS AND METHODS: The study included 116 eyes of 111 patients with macula-off (n = 68) or macula-on (n = 48) RRD treated with a single successful procedure, 79 fellow eyes, and 183 eyes of control patients imaged with WF SS-OCTA (3 ×3, 6 ×6, and 12 ×12 mm images). Mixed-effects multiple linear regression models were used for statistical analysis. RESULTS: Vessel density (VD) and vessel skeletonized density (VSD) of the superficial capillary plexus (3 ×3 mm scans) and full-thickness retina (12 ×12 mm) were significantly reduced in RRD eyes compared to fellow and control eyes. Decreased VSD and VD in all layers (3 ×3 mm and 6 ×6 mm) were significantly associated with greater preoperative extent of retinal detachment (P < 0.05) and poorer postoperative best-corrected visual acuity (BCVA) in RRD eyes (P < 0.05). Macula-off status was associated with increased foveal avascular zone irregularity (12 ×12 mm, P = 0.02). CONCLUSIONS: Decreased VD on WF SS-OCTA is associated with poorer postoperative BCVA following RRD repair. [Ophthalmic Surg Lasers Imaging Retina 2024;55:310-317.].

Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion.

PURPOSE: To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). METHODS: We included 23 eyes with macular edema associated with non-ischemic CRVO from 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. RESULTS: Median CST decreased significantly from 369 µm (305-531) to 267 µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12 mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12 mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12 mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). CONCLUSION: Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.

Quantitative Contrast Sensitivity Function and the Effect of Aging in Healthy Adult Eyes: A Normative Database.

BACKGROUND AND OBJECTIVE: We sought to establish normative quantitative contrast sensitivity function (qCSF) values in healthy adult eyes and investigate the effect of age on qCSF. PATIENTS AND METHODS: Healthy eyes underwent qCSF testing (adaptive sensory technology) and Snellen's visual acuity (VA). Descriptive statistics and mixed-effects multivariable linear regressions were evaluated. RESULTS: A total of 334 eyes (290 patients) with median age 61 years (range 21 to 88) had qCSF values as follows: area under the log contrast sensitivity function curve: 1.18; contrast acuity: 1.32; contrast sensitivity (CS) at 1 cycle per degree (cpd): 1.32; CS at 1.5 cpd: 1.37; CS at 3 cpd: 1.38; CS at 6 cpd: 1.20; CS at 12 cpd: 0.69; CS at 18 cpd: 0.22. Linear reductions in qCSF values per decade of age ranged from -0.02 to -0.07 vs 0.01 for visual acuity (VA). Age had a greater effect on the majority of qCSF values than VA (beta standardized regression coefficient ranged from -0.309 to -0.141 for qCSF values vs 0.177 for VA). CONCLUSIONS: We herein establish a normative database for qCSF and quantify the effect of age on qCSF values, adding evidence towards the validation of qCSF as a clinical endpoint. [Ophthalmic Surg Lasers Imaging Retina 2024;55:212-219.].

Retrospective Analysis of Perioperative Dexmedetomidine Use in Retina Surgeries: Impact on Postanesthesia Care.

BACKGROUND AND OBJECTIVE: Dexmedetomidine (Precedex®) has been linked to depressive hemodynamic effects and increased length of stay in the post-anesthesia care unit (PACU) when used in ambulatory phacoemulsification procedures. We aimed to determine the prevalence and impact of dexmedetomidine use during ambulatory vitreoretinal procedures. PATIENTS AND METHODS: This retrospective cohort study involved 9,666 adult vitrectomies. Cases were divided into groups by anesthesia type: general anesthesia (GA) and monitored anesthesia care (MAC). For each group, various factors were compared between those who did and did not receive dexmedetomidine. Chi-squared and t tests were used for comparisons. RESULTS: Changes in mean arterial pressure in the MAC group were -1.69 ± 0.23 mmHg for no dexmedetomidine patients and -6.31 ± 0.39 mmHg for dexmedetomidine patients (P < 0.01). In the GA group, mean arterial pressure was -6.1 ± 0.35 mmHg for no dexmedetomidine patients and -11.18 ± 0.88 mmHg for dexmedetomidine patients (P < 0.01). PACU Phase II time in the MAC group was 36.93 ± 0.37 minutes and 40.67 ± 0.86 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). In the GA group, PACU Phase II time was 58.63 ± 0.95 minutes and 65.19 ± 2.38 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). CONCLUSIONS: Dexmedetomidine use in vitrectomies was associated with significant PACU delays. These delays may stem from adverse hemodynamic effects. [Ophthalmic Surg Lasers Imaging Retina 2024;55:86-91.].

Analysis of Uveal Melanoma 5-Year Survival Rates by Medicaid Status: A Nationwide Analysis.

PURPOSE: The survival outcomes of patients with primary uveal melanomas based on Medicaid status have not been previously discussed in the literature. METHODS: The Surveillance, Epidemiology, and End Results Medicaid database were utilized to identify patients with primary uveal melanomas diagnosed between 2006 and 2013. The Kaplan-Meier method was utilized to construct 5-year survival curves in adult, non-elderly patients. Log-rank testing was used to determine differences in survival rates, and multivariate Cox proportional hazards modeling was utilized to perform adjusted survival analysis. RESULTS: A total of 1,765 patients were included (Medicaid: 81, non-Medicaid: 1684). A total of 1683 (95.4%) were White. The average age was 51.75 years (SD = 9.5 years). Medicaid patients were more likely to be unmarried, live in a high poverty neighborhood, and live in a rural area (all p < .001). We observed no significant difference in 5-year survival rates between those enrolled in Medicaid (86.6%, 95% CI: 79.1%1-94.7%) and those not enrolled in Medicaid (85.5, 95% CI: 83.8%-87.2%) (p = .80). After controlling for socioeconomic and clinical factors, Medicaid enrollment was not associated with an increased risk of mortality compared to non-Medicaid enrollment. Age (aHR: 1.04, 95% CI: 1.02-1.06, p < .001) and tumor size >10 mm (aHR: 3.04, 95% CI: 1.49-6.21, p = .002) were associated with an increased risk of mortality. CONCLUSION: Medicaid enrollment was not associated with worse cancer-specific 5-year survival. Further research needs to be elicited to better understand the role of Medicaid enrollment in patients with primary uveal melanoma.

Mid-term and Long-term Outcomes After Total Cervical Disk Arthroplasty Compared With Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

STUDY DESIGN: A meta-analysis of randomized controlled trials (RCTs). OBJECTIVE: The aim of this study was to compare mid-term to long-term outcomes of cervical disk arthroplasty (CDA) with those of anterior cervical discectomy and fusion (ACDF) for the treatment of symptomatic cervical degenerative disk disease. SUMMARY OF BACKGROUND DATA: After ACDF to treat symptomatic cervical degenerative disk disease, the loss of motion at the index level due to fusion may accelerate adjacent-level disk degeneration. CDA was developed to preserve motion and reduce the risk of adjacent segment degeneration. Early-term to mid-term clinical outcomes from RCTs suggest noninferiority of CDA compared with ACDF, but it remains unclear whether CDA yields better mid-term to long-term outcomes than ACDF. MATERIALS AND METHODS: Two independent reviewers searched PubMed, Embase, and the Cochrane Library for RCTs with at least 60 months of follow-up. The risk ratio or standardized mean difference (and 95% CIs) were calculated for dichotomous or continuous variables, respectively. RESULTS: Eighteen reports of 14 RCTs published in 2014-2023 were included. The pooled analysis demonstrated that the CDA group had a significantly greater improvement in neurological success and Neck Disability Index than the ACDF group. The ACDF group exhibited a significantly better improvement in the Short Form-36 Health Survey Physical Component Summary than the CDA group. Radiographic adjacent segment degeneration was significantly lower in the CDA group at 60- and 84-month follow-ups; at 120-month follow-up, there was no significant difference between the 2 groups. Although the overall rate of secondary surgical procedures was significantly lower in the CDA group, we did not observe any significant difference at 60-month follow-up between the CDA and ACDF group and appreciated statistically significant lower rates of radiographic adjacent segment degeneration, and symptomatic adjacent-level disease requiring surgery at 84-month and 108- to 120-month follow-up. The rate of adverse events and the neck and arm pain scores in the CDA group were not significantly different from those of the ACDF group. CONCLUSIONS: In this meta-analysis of 14 RCTs with 5- to 10-year follow-up data, CDA resulted in significantly better neurological success and Neck Disability Index scores and lower rates of radiographic adjacent segment degeneration, secondary surgical procedures, and symptomatic adjacent-level disease requiring surgery than ACDF. ACDF resulted in improved Short Form-36 Health Survey Physical Component Summary scores. However, the CDA and ACDF groups did not exhibit significant differences in overall changes in neck and arm pain scores or rates of adverse events.

The Use of Additional Facedown Positioning with Silicone Oil Tamponade for the Treatment of Retinal Re-detachment.

PURPOSE: To highlight a potential alternative to additional surgery for management of retinal re-detachment through the use of additional facedown positioning with silicone oil tamponade. METHODS: Retrospective case-series of two patients evaluated with examination, multimodal imaging, including fundus photography, optical coherence tomography (OCT), and fluorescein angiography. RESULTS: In case 1, a 70-year-old female patient underwent surgery for a full-thickness macular hole with associated macula-off retinal detachment, but experienced a recurrent detachment and underwent a second surgery with silicone oil placement. Another recurrent detachment was found. The case was managed conservatively with face-down positioning, resulting in resolution of subretinal fluid and improvement in vision. At follow-up, the retina remained attached with stable vision. In case 2, a 25-year-old male patient underwent a surgical repair for PVR retinal detachment with a scleral buckle, cryotherapy, and external drainage. After multiple re-detachment surgeries with retinectomy and oil placement there was another tractional re-detachment of the fovea was noted. Management was with facedown positioning and follow-up evaluation showed resolution of the subretinal fluid and improvement in vision with stability for greater than 2 months. CONCLUSIONS: For recurrent retinal re-detachments with silicone oil in place, an additional week of facedown positioning can result in anatomic success and be a viable alternative or bridge to invasive surgical interventions. This approach may have greatest utility for patients who are poor surgical candidates without new peripheral pathology.

Dose-Dependent and Reversible Serous Retinal Detachments in Fibroblast Growth Factor Receptor Inhibitor-Associated Retinopathy.

We report two cases of fibroblast growth factor receptor (FGFR) inhibitor-associated retinopathy, including the first case of Debio 1347 associated retinopathy manifesting with bilateral serous retinal detachments along the superotemporal arcades and a case of erdafitinib associated retinopathy manifesting with classic foveal serous retinal detachments. Both cases demonstrate a clear dose-dependent and reversible class effect likely secondary to downstream effects of FGFR inhibition on the MEK pathway, resulting in retinal pigment epithelial cell dysfunction, and may also involve additional mechanisms of cellular injury through inhibition of the PI3K/AKT/mTOR pathway. FGFR inhibitor-associated retinopathy appears to manifest differently among patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:368-370.].

Divergent Metabolomic Signatures of TGFß2 and TNFα in the Induction of Retinal Epithelial-Mesenchymal Transition.

Epithelial-mesenchymal transition (EMT) is a dedifferentiation program in which polarized, differentiated epithelial cells lose their cell-cell adhesions and transform into matrix-producing mesenchymal cells. EMT of retinal pigment epithelial (RPE) cells plays a crucial role in many retinal diseases, including age-related macular degeneration, proliferative vitreoretinopathy, and diabetic retinopathy. This dynamic process requires complex metabolic reprogramming to accommodate the demands of this dramatic cellular transformation. Both transforming growth factor-beta 2 (TGFß2) and tumor necrosis factor-alpha (TNFα) have the capacity to induce EMT in RPE cells; however, little is known about their impact on the RPE metabolome. Untargeted metabolomics using high-resolution mass spectrometry was performed to reveal the metabolomic signatures of cellular and secreted metabolites of primary human fetal RPE cells treated with either TGFß2 or TNFα for 5 days. A total of 638 metabolites were detected in both samples; 188 were annotated as primary metabolites. Metabolomics profiling showed distinct metabolomic signatures associated with TGFß2 and TNFα treatment. Enrichment pathway network analysis revealed alterations in the pentose phosphate pathway, galactose metabolism, nucleotide and pyrimidine metabolism, purine metabolism, and arginine and proline metabolism in TNFα-treated cells compared to untreated control cells, whereas TGFß2 treatment induced perturbations in fatty acid biosynthesis metabolism, the linoleic acid pathway, and the Notch signaling pathway. These results provide a broad metabolic understanding of the bioenergetic rewiring processes governing TGFß2- and TNFα-dependent induction of EMT. Elucidating the contributions of TGFß2 and TNFα and their mechanistic differences in promoting EMT of RPE will enable the identification of novel biomarkers for diagnosis, management, and tailored drug development for retinal fibrotic diseases.

Sorting nexin 10 sustains PDGF receptor signaling in glioblastoma stem cells via endosomal protein sorting.

Glioblastoma is the most malignant primary brain tumor, the prognosis of which remains dismal even with aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs). We identified sorting nexin 10 (SNX10), an endosomal protein sorting factor, as selectively expressed in GSCs compared with NSCs and essential for GSC survival. Targeting SNX10 impaired GSC viability and proliferation, induced apoptosis, and reduced self-renewal capacity. Mechanistically, GSCs utilized endosomal protein sorting to promote platelet-derived growth factor receptor ß (PDGFRß) proliferative and stem cell signaling pathways through posttranscriptional regulation of the PDGFR tyrosine kinase. Targeting SNX10 expression extended survival of orthotopic xenograft-bearing mice, and high SNX10 expression correlated with poor glioblastoma patient prognosis, suggesting its potential clinical importance. Thus, our study reveals an essential connection between endosomal protein sorting and oncogenic receptor tyrosine kinase signaling and suggests that targeting endosomal sorting may represent a promising therapeutic approach for glioblastoma treatment.

Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry.

Metabolic dysfunction of retinal pigment epithelial cells (RPE) is a key pathogenic driver of retinal diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Since RPE are highly metabolically-active cells, alterations in their metabolic status reflect changes in their health and function. High-resolution respirometry allows for real-time kinetic analysis of the two major bioenergetic pathways, glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), through quantification of the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), respectively. The following is an optimized protocol for conducting high-resolution respirometry on primary human retinal pigment epithelial cells (H-RPE). This protocol provides a detailed description of the steps involved in producing bioenergetic profiles of RPE to define their basal and maximal OXPHOS and glycolytic capacities. Exposing H-RPE to different drug injections targeting the mitochondrial and glycolytic machinery results in defined bioenergetic profiles, from which key metabolic parameters can be calculated. This protocol highlights the enhanced response of BAM15 as an uncoupling agent compared to carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) to induce the maximal respiration capacity in RPE. This protocol can be utilized to study the bioenergetic status of RPE under different disease conditions and test the efficacy of novel drugs in restoring the basal metabolic status of RPE.

OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT REPAIR FOLLOWING INFECTIOUS ENDOPHTHALMITIS.

PURPOSE: To determine the incidence of and identify risk factors for redetachment in eyes that underwent rhegmatogenous retinal detachment (RRD) repair after infectious endophthalmitis. METHODS: Retrospective chart review of patients who had RRD surgery following a diagnosis of endophthalmitis from 2008 to 2021 at a tertiary referral center. Demographic and clinical characteristics as well as operative details were collected. Subjects with prior RRD, trauma, keratoprosthesis, or less than 3 months of postoperative follow-up were excluded. Univariate logistic regression analyses were performed. RESULTS: Thirty-four eyes of 34 patients were included. Most subjects were male with a mean age of 60.1 years. Exogenous (58.8%) was more common than endogenous (41.2%) sources of endophthalmitis. Seventeen of 34 eyes (50.0%) experienced redetachment. Significant risk factors were infection with virulent organisms, hypotony, and postoperative proliferative vitreoretinopathy. Initial management with vitreous tap or vitrectomy, exogenous versus endogenous source, and surgical procedure were not associated with recurrent RRD. At the final follow-up, 32 of 34 eyes (91.2%) were attached, although more than one third of these had silicone oil. CONCLUSION: Redetachment occurred in half of eyes that underwent surgical repair of RRD after endophthalmitis. Early vitrectomy, with or without prior vitreous tap, was not associated with a higher risk of redetachment and improved the likelihood of a positive culture result. Culture data can aid in risk stratification because organism virulence was a risk factor for recurrent RRD. Although visual outcomes were generally poor, most retinas remained attached at the final visit.

The Effect of Sample Medication Use on Subsequent Anti-VEGF Agent Selection for Neovascular Age-Related Macular Degeneration.

PURPOSE: Medication samples of anti-VEGF agents can represent a good option for retina specialists to provide timely treatment for newly converted neovascular age-related macular degeneration (nvAMD) while prior-authorizations (PA) are pending. Our study examines the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in nvAMD. DESIGN: Retrospective cohort study. PARTICIPANTS: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. METHODS: Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. The utilization of different anti-VEGF agents in each group was compared at various time points using chi-square tests for independence of proportions. MAIN OUTCOME MEASURES: Anti-VEGF agent selection for the first four injections and at one year were examined. RESULTS: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in sample (96.2%, 95.9%, 91.9%, 93.4%, respectively), and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p < .001), third (3.1% vs. 41.3%, p < .001), fourth injections (4.7% vs. 40.4%, p < .001), and at 1 year (0% vs. 33.8%, p < .001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p < .001), third (76.3% vs. 41.5%, p < .001), and fourth injections (76.7% vs. 43.4%, p < .001), and at 1 year (77.0% vs. 52.7%, p < .001). CONCLUSIONS: Sample medications in nvAMD may be initiated for many reasons, including awaiting PA approval. Our study found that eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment. Given the persistent use of more expensive medications at subsequent injections for patients who were initiated on samples, insurance payors may consider waiving PA requirements for bevacizumab to avoid a paradoxical increase in health-care costs.

Dimethyl Fumarate Blocks Tumor Necrosis Factor-Alpha-Driven Inflammation and Metabolic Rewiring in the Retinal Pigment Epithelium.

The retinal pigment epithelium (RPE) acts as a metabolic gatekeeper between photoreceptors and the choroidal vasculature to maintain retinal function. RPE dysfunction is a key feature of age-related macular degeneration (AMD), the leading cause of blindness in developed countries. Inflammation is a key pathogenic mechanism in AMD and tumor necrosis factor-alpha (TNFα) has been implicated as a pro-inflammatory cytokine involved in AMD. While mitochondrial dysfunction has been implicated in AMD pathogenesis, the interplay between inflammation and cellular metabolism remains elusive. The present study explores how the pro-inflammatory cytokine, TNFα, impacts mitochondrial morphology and metabolic function in RPE. Matured human primary RPE (H-RPE) were treated with TNFα (10 ng/ml) for up to 5 days. TNFα-induced upregulation of IL-6 secretion and inflammatory genes (IL-6, IL-8, MCP-1) was accompanied by increased oxidative phosphorylation (OXPHOS) and reduced glycolysis, leading to an increase in cellular adenosine triphosphate (ATP) content. Transmission electron microscopy (TEM) revealed defects in mitochondrial morphology with engorged mitochondria and loss of cristae integrity following TNFα treatment. Pre-treatment with the anti-inflammatory drug, 80 µM dimethyl fumarate (DMFu), blocked TNFα-induced inflammatory activation of RPE (IL-6, IL-8, MCP-1, CFH, CFB, C3) and normalized their bioenergetic profile to control levels by regulating PFKFB3 and PKM2 gene expression. Furthermore, DMFu prevented TNFα-induced mitochondrial dysfunction and morphological anomalies. Thus, our results indicate that DMFu serves as a novel therapeutic avenue for combating inflammatory activation and metabolic dysfunction of RPE in AMD.

Hypopyon and White Cataract Due to an Intraocular Helminth.

We describe a case of a 29-year-old man with a history of intravenous drug use and vague history of eye trauma who presented with a hypopyon and white cataract in the right eye. He underwent pars plana vitrectomy and lensectomy; his anterior chamber aspirate revealed a single helminth on calcofluor stain. We suspect that his helminth infection may be secondary to unsanitary eating and drinking practices. As overall hygiene and dietary habits have improved during the years, parasitic helminth infections are relatively rare in nonendemic areas, especially in the nonpediatric population. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:168-171.].