Immune Checkpoint Inhibitor (ICI) Induced Sinonasal Disease: Review of Literature and FDA Database.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of oncologic therapies whose mechanism of action can result in unique immune-related adverse events (irAEs) not seen in other cancer therapeutics. The objective of this study was to determine the presence of sinonasal irAEs with these medications. METHODS: A case report of chronic rhinosinusitis with nasal polyps (CRSwNP) caused by an ICI is presented and was the impetus for this review. Review of the literature using Pubmed and Cochrane Database of Systematic Reviews was performed. Additionally, we searched the FDA adverse event reporting system (FAERS) database for sinonasal AEs in the 7 FDA-approved ICIs. RESULTS: We demonstrate an emerging scientific literature describing cases of CRS associated with multiple ICIs with a particular predilection toward TH2 driven phenotypes. Review of the FAERS also demonstrates a small percentage of patients who report sinonasal complaints after initiating ICI therapy. CONCLUSION: Sinonasal symptoms and the development of CRS, in particular, are not currently well recognized as potential irAEs for ICIs. Increased awareness and further study may help to elucidate if these are more common than currently reported and if irAE-related CRS is a unique phenotype.

Enhancing Health Literacy: Evaluating the Readability of Patient Handouts Revised by ChatGPT's Large Language Model.

OBJECTIVE: To use an artificial intelligence (AI)-powered large language model (LLM) to improve readability of patient handouts. STUDY DESIGN: Review of online material modified by AI. SETTING: Academic center. METHODS: Five handout materials obtained from the American Rhinologic Society (ARS) and the American Academy of Facial Plastic and Reconstructive Surgery websites were assessed using validated readability metrics. The handouts were inputted into OpenAI's ChatGPT-4 after prompting: "Rewrite the following at a 6th-grade reading level." The understandability and actionability of both native and LLM-revised versions were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results were compared using Wilcoxon rank-sum tests. RESULTS: The mean readability scores of the standard (ARS, American Academy of Facial Plastic and Reconstructive Surgery) materials corresponded to "difficult," with reading categories ranging between high school and university grade levels. Conversely, the LLM-revised handouts had an average seventh-grade reading level. LLM-revised handouts had better readability in nearly all metrics tested: Flesch-Kincaid Reading Ease (70.8 vs 43.9; P < .05), Gunning Fog Score (10.2 vs 14.42; P < .05), Simple Measure of Gobbledygook (9.9 vs 13.1; P < .05), Coleman-Liau (8.8 vs 12.6; P < .05), and Automated Readability Index (8.2 vs 10.7; P = .06). PEMAT scores were significantly higher in the LLM-revised handouts for understandability (91 vs 74%; P < .05) with similar actionability (42 vs 34%; P = .15) when compared to the standard materials. CONCLUSION: Patient-facing handouts can be augmented by ChatGPT with simple prompting to tailor information with improved readability. This study demonstrates the utility of LLMs to aid in rewriting patient handouts and may serve as a tool to help optimize education materials. LEVEL OF EVIDENCE: Level VI.

Histopathologic evaluation of Asian-American patients with chronic rhinosinusitis with nasal polyps.

KEY POINTS: Asian-American (AA) patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have comparable rates of tissue eosinophilia compared to Caucasians when defined as >10 eosinophils/high-powered field (HPF). AA patients with CRSwNP have significantly higher incidence of mixed inflammation defined as >10 eosinophils/HPF and >10 neutrophils/HPF.

Current otolaryngologic applications of the novel self-assembling RADA-16 peptide matrix.

A novel bioresorbable agent on the market is PuraGel® (3-D Matrix, Tokyo, Japan), a RADA-16 product that acts as a synthetic hemostatic and space-filling gel that promotes wound healing and prevents adhesion formation. Given the reported benefits of accelerated wound healing and scar tissue prevention, there are multiple otolaryngologic applications where RADA-16 might improve outcomes. Our study highlights current utilization and associated post-operative complications with this product.

LONG-TERM NATURAL HISTORY OF PRESUMPTIVE DIVERTICULAR HEMORRHAGE.

OBJECTIVES: The natural history of patients with well-documented presumptive diverticular hemorrhage (TICH) is unknown. Our aims are to report: 1) rebleeding rates and clinical outcomes of presumptive TICH patients with and without rebleeding, 2) conversion to definitive TICH during long-term follow-up (F/U), and 3) risk factors for presumptive TIC rebleeding. METHODS: This was a retrospective cohort study of prospectively collected results of presumptive TICH patients from 1994 to 2023. Presumptive TICH was diagnosed for patients with TIC's without stigmata of recent hemorrhage and no other cause of bleeding found on anoscopy, enteroscopy, capsule endoscopy, computerized tomography angiography, or tagged red blood cell scan. Patients with ≤ 6 months of F/U were excluded. RESULTS: Of 139 patients with presumptive TICH, 104 were males and 35 females. Median age was 76 years. There were no significant differences in baseline demographics of rebleeders and non-rebleeders. During long-term median F/U of 73 months, 24.5% (34/139) rebled. 56% (19/34) of rebleeders were diagnosed as definitive TICH and they had significantly higher rates of readmission (p<0.001), reintervention (p<0.001), and surgery (p<0.001). During F/U, there were significantly higher rates of newly diagnosed hypertension (HTN) and/or atherosclerotic cardiovascular disease (ASCVD) in rebleeders (p = 0.033 from logistic model). All-cause mortality was 42.8%, but none was from TICH. CONCLUSIONS: For presumptive TICH during long-term F/U: 1) 75.5% did not rebleed and 24.5% rebled. 2) 56% of rebleeders were diagnosed as definitive TICH. 3) New development of HTN and ASCVD were risk factors for TIC rebleeding.

Features of Importance in Nasal Endoscopy: Deriving a Meaningful Framework.

OBJECTIVE: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies. STUDY DESIGN: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations. SETTING: An online questionnaire was distributed in July 2023. METHODS: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1. RESULTS: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case. CONCLUSION: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy.

Skeletal effects of sleeve gastrectomy, by sex and menopausal status and in comparison to Roux-en-Y gastric bypass surgery.

Context: Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. Data are lacking on the skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure. Objective: We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB. Design Setting Participants: Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center. Main Outcome Measures: Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively. Results: Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural parameters were smaller, while other changes were not. Conclusions: Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG.

Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes.

Functionality of the blood-brain barrier (BBB) relies on the interaction between endothelial cells (ECs), pericytes, and astrocytes to regulate molecule transport within the central nervous system. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, we explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC) model. Self-organized microvascular networks were formed by combining hiPSC-derived ECs, human brain vascular pericytes, and hiPSC-derived astrocytes within a fibrin hydrogel. The hiPSC-ECs and pericytes showed close interactions, but, somewhat unexpectedly, addition of astrocytes disrupted microvascular network formation. However, continuous fluid perfusion or activation of cyclic AMP (cAMP) signaling rescued the vascular organization and decreased vascular permeability. Nevertheless, astrocytes did not affect the expression of proteins related to junction formation, transport, or extracellular matrix, indicating that, despite other claims, hiPSC-derived ECs do not entirely acquire a BBB-like identity in the 3D VoC model.

Ameripathidae, a new family of antipatharian corals (Cnidaria, Anthozoa, Hexacorallia, Antipatharia).

A new family of antipatharian corals, Ameripathidae (Cnidaria: Anthozoa: Antipatharia), is established for Ameripathespseudomyriophylla Opresko & Horowitz, gen. et sp. nov. The new family resembles Myriopathidae and Stylopathidae in terms of the morphology of the polyps and tentacles and the pinnulate branching of the corallum. Phylogenetic analysis using a genomic data set of 741 conserved element loci indicates that the new family is sister to a clade containing the Myriopathidae, Stylopathidae, Antipathidae, and Aphanipathidae.

Multi-Institutional Analysis of Insurance Denial Patterns Within Rhinology.

BACKGROUND: Obtaining insurance approval is a necessary component of healthcare in the United States and denials of these claims have been estimated to result in a loss of 3% to 5% of revenue. OBJECTIVE: Examine the trends in insurance denials for rhinological procedures. METHODS: A retrospective review of deidentified financial data of patients who were treated by participating physicians across 3 institutions from January 1, 2021, to June 30, 2023. The data was queried for rhinological and non-rhinological procedures via CPT codes. Cumulative insurance denials were calculated and stratified by procedure and insurance type. Write-offs were dollar amounts associated with final denials. RESULTS: A sample of 102,984 procedures and visits revealed a final denial rate between 2.2% and 2.9% across institutions (p = .72). The top three rhinological procedures for final write-offs were: nasal endoscopy (16.24%, $111,836.87), nasal debridement or polypectomy (6.48%, $79,457.51), and destruction of intranasal lesion (2.11%, $56,932.20). The write-off percentage for each procedure was highest among commercial insurance payers as opposed to Medicare or Medicaid. CONCLUSION: Final denial rates of rhinology procedures ranged between 2% and 3%. Common procedures such as nasal endoscopy and nasal debridement are among the highest written-off procedures. Insurance denials can lead to notable revenue loss. Rhinology practices must continue to remain knowledgeable of the changes and effects of insurance reimbursement on their practice.

Sinonasal Tumors Masquerading as Invasive Fungal Sinusitis (IFS).

OBJECTIVES: Fungal tissue invasion in the setting of sinonasal malignancy has been rarely described in the literature. Only a handful of studies have discussed cases of suspected chronic and acute IFS (CIFS and AIFS, respectively), having an underlying undifferentiated sinonasal carcinoma, sinonasal teratocarcinosarcoma, and NK/T-cell lymphoma. METHODS: Here, we describe 3 cases of carcinoma mimicking IFS from a single institution. RESULTS: Each of our patients presented with sinonasal complaints as an outpatient in the setting of immunosuppression. Intranasal biopsies consistently were predominated by necrotic debris, with and without fungal elements, ultimately leading to a delay of oncologic care. The final pathologies included NK/T-cell lymphoma and SNEC. All patients were followed by radiation and chemotherapy, with 1 case of mortality. CONCLUSIONS: We aim to emphasize the importance of obtaining viable tissue as pathology specimens as the presence of necrosis with fungal elements may limit the diagnosis and ultimately delay the care of an underlying sinonasal carcinoma.

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy?

E-selectin, a cytoadhesive glycoprotein, is expressed on venular endothelial cells and mediates leukocyte localization to inflamed endothelium, the first step in inflammatory cell extravasation into tissue. Constitutive marrow endothelial E-selectin expression also supports bone marrow hematopoiesis via NF-κB-mediated signaling. Correspondingly, E-selectin interaction with E-selectin ligand (sialyl Lewisx) on acute myeloid leukemia (AML) cells leads to chemotherapy resistance in vivo. Uproleselan (GMI-1271) is a carbohydrate analog of sialyl Lewisx that blocks E-selectin binding. A Phase 2 trial of MEC chemotherapy combined with uproleselan for relapsed/refractory AML showed a median overall survival of 8.8 months and low (2%) rates of severe oral mucositis. Clinical trials seek to confirm activity in AML and mitigation of neutrophil-mediated adverse events (mucositis and diarrhea) after intensive chemotherapy. In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials.

Endoscopic Diagnosis and Treatment of Colonic Diverticular Bleeding.

This is a description and critical analysis of current diagnosis and treatment of diverticular hemorrhage. The focus is on colonoscopy for identification and treatment of stigmata of recent hemorrhage (SRH) in diverticula. A classification of definitive, presumptive, and incidental diverticular hemorrhage is reviewed and recommended. The approach to definitive diagnosis with urgent colonoscopy is put into perspective of other management strategies including angiography (of different types), nuclear medicine scans, surgery, and medical treatment. Advancements in diagnosis, risk stratification, and colonoscopic hemostasis are described including those that obliterate arterial blood flow underneath SRH and prevent diverticular rebleeding. Recent innovations are discussed.

Sinonasal Symptom Correlation With the Postoperative Polyp Scale (POPS).

BACKGROUND: Commonly used endoscopic nasal polyp grading scales have been shown to correlate poorly with symptom scores and quality of life metrics. The recently described Postoperative Polyp Scale (POPS) is a grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities by describing incremental recurrence in relation to the surgically opened sinus cavities. OBJECTIVE: The objective of this study was to determine if the POPS correlated with sinonasal symptoms. METHODS: CRSwNP patients were prospectively administered SNOT-22 questionnaires and graded according to the POPS starting at their 1-month postoperative appointments. Total POPS scores (sum of each side) and Max POPS score (larger value of left and right) were correlated with SNOT-22 total scores and subdomains using Kendall correlation testing. RESULTS: A total of 127 patients were enrolled in the study. Both Total POPS or Max POPS were significantly correlated to the SNOT-22 total score (P < .001, P < .001), Rhinologic (P < .001, P < .001), Extra-Nasal Rhinologic (P < .001, P < .001), Ear/Facial (P < .001, P < .001), and Psychologic (P = .028, P = .017) subdomains. Kendall's tau indicated strong correlation (≥0.3) with Rhinologic subdomain, moderate correlation (.21-.29) with Extra-Nasal Rhinologic and Ear/Facial subdomains, and weak correlation (.1-.19) with Psychologic subdomain. CONCLUSION: Previous endoscopic nasal polyp grading scales poorly correlate with symptoms and patient reported outcome measures. The new POPS moderately correlates with the total SNOT-22 score and strongly correlates with the Rhinologic subdomain, indicating that it may have good potential as a tool to evaluate postoperative CRSwNP patients.

Sex Disparities in Academic Productivity and Rank Among Abdominal Transplant Faculty in the United States.

BACKGROUND: The aim of this study was to examine sex differences in academic rank and productivity among members of the American Society of Transplant Surgeons in the United States. METHODS: Cross-sectional, focusing on current board-certified abdominal transplant surgeons in the United States. Demographic factors such as sex, region, and faculty rank were collected from institutional websites. Academic metrics, including H-index, total publications, and relative citation ratio, were collected from Scopus and iCite. RESULTS: We identified 536 surgeon members of the American Society of Transplant Surgeons with an academic institution. The majority were men (83%). Men were in practice longer than women (17.9 ± 11 vs 11.7 ± 9 years, P < .0001) and had higher academic metrics, including H-index (25.6 ± 20 vs16.4 ± 14, P < .0001) and total publications (110 ± 145 vs 58.8 ± 69, P < .0001). There was a significant difference in faculty appointments by sex (P < .05), with men showing evidence of increased academic advancement. After adjusting for academic rank, PhD status, and location of medical school and residency, women remained associated with a lower H-index on multivariate analysis (P < .01). CONCLUSION: Sex disparities in academic rank and achievement are present among transplant surgical faculty in the United States, and future efforts are needed to promote sex equity in transplant surgery academia.

Improved waitlist and comparable post-transplant outcomes in simultaneous heart-kidney transplantation under the 2018 heart allocation system.

OBJECTIVE: This study aimed to investigate the clinical trends and the impact of the 2018 heart allocation policy change on both waitlist and post-transplant outcomes in simultaneous heart-kidney transplantation in the United States. METHODS: The United Network for Organ Sharing registry was queried to compare adult patients before and after the allocation policy change. This study included 2 separate analyses evaluating the waitlist and post-transplant outcomes. Multivariable analyses were performed to determine the 2018 allocation system's risk-adjusted hazards for 1-year waitlist and post-transplant mortality. RESULTS: The initial analysis investigating the waitlist outcomes included 1779 patients listed for simultaneous heart-kidney transplantation. Of these, 1075 patients (60.4%) were listed after the 2018 allocation policy change. After the policy change, the waitlist outcomes significantly improved with a shorter waitlist time, lower likelihood of de-listing, and higher likelihood of transplantation. In the subsequent analysis investigating the post-transplant outcomes, 1130 simultaneous heart-kidney transplant recipients were included, where 738 patients (65.3%) underwent simultaneous heart-kidney transplantation after the policy change. The 90-day, 6-month, and 1-year post-transplant survival and complication rates were comparable before and after the policy change. Multivariable analyses demonstrated that the 2018 allocation system positively impacted risk-adjusted 1-year waitlist mortality (sub-hazard ratio, 0.66, 95% CI, 0.51-0.85, P < .001), but it did not significantly impact risk-adjusted 1-year post-transplant mortality (hazard ratio, 1.03; 95% CI, 0.72-1.47, P = .876). CONCLUSIONS: This study demonstrates increased rates of simultaneous heart-kidney transplantation with a shorter waitlist time after the 2018 allocation policy change. Furthermore, there were improved waitlist outcomes and comparable early post-transplant survival after simultaneous heart-kidney transplantation under the 2018 allocation system.

Patient Outcomes of Definitive Diverticular Hemorrhage After Colonoscopic, Medical, Surgical, or Embolization Treatment.

BACKGROUND: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH). AIMS: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment. METHODS: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan-Meier analysis was for time-to-first diverticular rebleed. RESULTS: 162 patients with DDH were stratified based on their final treatment before discharge-104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow-Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications. CONCLUSIONS: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments.

Structures, functions and adaptations of the human LINE-1 ORF2 protein.

The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one-third of the human genome through a 'copy and paste' mechanism catalysed by its multifunctional enzyme, open reading frame 2 protein (ORF2p)1. ORF2p reverse transcriptase (RT) and endonuclease activities have been implicated in the pathophysiology of cancer2,3, autoimmunity4,5 and ageing6,7, making ORF2p a potential therapeutic target. However, a lack of structural and mechanistic knowledge has hampered efforts to rationally exploit it. We report structures of the human ORF2p 'core' (residues 238-1061, including the RT domain) by X-ray crystallography and cryo-electron microscopy in several conformational states. Our analyses identified two previously undescribed folded domains, extensive contacts to RNA templates and associated adaptations that contribute to unique aspects of the L1 replication cycle. Computed integrative structural models of full-length ORF2p show a dynamic closed-ring conformation that appears to open during retrotransposition. We characterize ORF2p RT inhibition and reveal its underlying structural basis. Imaging and biochemistry show that non-canonical cytosolic ORF2p RT activity can produce RNA:DNA hybrids, activating innate immune signalling through cGAS/STING and resulting in interferon production6-8. In contrast to retroviral RTs, L1 RT is efficiently primed by short RNAs and hairpins, which probably explains cytosolic priming. Other biochemical activities including processivity, DNA-directed polymerization, non-templated base addition and template switching together allow us to propose a revised L1 insertion model. Finally, our evolutionary analysis demonstrates structural conservation between ORF2p and other RNA- and DNA-dependent polymerases. We therefore provide key mechanistic insights into L1 polymerization and insertion, shed light on the evolutionary history of L1 and enable rational drug development targeting L1.

Gender-Specific Differences in Preoperative Concerns in Patients Undergoing Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

OBJECTIVES: Among patients with chronic rhinosinusitis (CRS), gender differences in epidemiology as well as quality of life have been reported. However, whether gender differences in endoscopic sinus surgery (ESS) preoperative concerns exist is unclear. METHODS: CRS patients undergoing ESS at 3 tertiary care centers in Los Angeles completed the validated Western Surgical Concern Inventory - ESS assessing ESS preoperative concerns. RESULTS: Of the 75 patients included, female patients expressed greater concern than male patients in regard to nasal packing, undergoing anesthesia, impact of surgery on daily activities, and pain and discomfort following surgery. CONCLUSION: This study suggests there are gender differences in ESS preoperative concerns and otolaryngologists should be aware of these possible concerns during preoperative discussions.

Volumetric Reconstruction of a Human Retinal Pigment Epithelial Cell Reveals Specialized Membranes and Polarized Distribution of Organelles.

Purpose: Despite the centrality of the retinal pigment epithelium (RPE) in vision and retinopathy our picture of RPE morphology is incomplete. With a volumetric reconstruction of human RPE ultrastructure, we aim to characterize major membranous features including apical processes and their interactions with photoreceptor outer segments, basolateral infoldings, and the distribution of intracellular organelles. Methods: A parafoveal retinal sample was acquired from a 21-year-old male organ donor. With serial block-face scanning electron microscopy, a tissue volume from the inner-outer segment junction to basal RPE was captured. Surface membranes and complete internal ultrastructure of an individual RPE cell were achieved with a combination of manual and automated segmentation methods. Results: In one RPE cell, apical processes constitute 69% of the total cell surface area, through a dense network of over 3000 terminal branches. Single processes contact several photoreceptors. Basolateral infoldings facing the choriocapillaris resemble elongated filopodia and comprise 22% of the cell surface area. Membranous tubules and sacs of endoplasmic reticulum represent 20% of the cell body volume. A dense basal layer of mitochondria extends apically to partly overlap electron-dense pigment granules. Pores in the nuclear envelope form a distinct pattern of rows aligned with chromatin. Conclusions: Specialized membranes at the apical and basal side of the RPE cell body involved in intercellular uptake and transport represent over 90% of the total surface area. Together with the polarized distribution of organelles within the cell body, these findings are relevant for retinal clinical imaging, therapeutic approaches, and disease pathomechanisms.