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Zeba A Syed,1 Gustavo Rosa Gameiro,1 Marco Ruggeri,1 Amr Elsawy,1,2 Ibrahim Sayed-Ahmed,1 Vatookarn Roongpoovapatr,1 Mohamed Abdel-Mottaleb,2 Mohamed Abou Shousha11Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Electrical and Computer Engineering, University of Miami College of Engineering, Coral Gables, FL, USAObjective: We present a novel method for screening eye bank donor corneas using high definition optical coherence tomography (HD-OCT). This technology allows for the quantification of endothelial/Descemet membrane (En/DM) complex thickness ex vivo.Design: Prospective interventional study.Participants: Fifty-two corneal grafts from 27 donors were included in this study. Twenty additional control eyes and 11 eyes with Fuchs’ endothelial corneal dystrophy were also evaluated for comparison.Methods: A custom built, high speed HD-OCT device (Envisu R2210, Bioptigen, Buffalo Grove, IL, USA) was used to obtain images, and custom-made graph-based segmentation software was used to automatically deconstruct corneal images into micro-layers. HD-OCT imaging was used to scan through the sealed sterile case of donor corneas stored in McCarey-Kaufman medium to image their En/DM complex through the center of the cornea.Results: This technology allowed for quantification of En/DM complex thickness in all donor corneas through the sealed sterile container used to transport graft tissue. Mean En/DM complex thickness of donor corneas was 17±4 μm. The difference between donor cornea En/DM thickness and that of control subjects (16±2 μm) was not statistically significant (p=0.3), suggesting that the transport container and media do not affect measurements. There was a significant difference between En/DM thickness of Fuchs’ endothelial corneal dystrophy eyes (25±5 μm) and both donor corneas (p

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Purpose: The aim of this study was to examine the impact of an 8-week high-speed circuit resistance training program (HSCT) on choriocapillaris density (CCD) in healthy older adults., Methods: Eighteen cognitively normal older adults were enrolled and randomly assigned to either the HSCT or the control group (CON). The HSCT group was comprised of 11 participants who trained three times a week for eight weeks, while the CON group consisted of 7 participants who did not engage in formal training. Optical coherence tomography angiography (OCTA) was employed to image both eyes of each subject at baseline and at the 8-week follow-up. The choriocapillaris density (CCD) of 2.5 mm in diameter centered on the fovea was measured., Results: The average age of the HSCT group was 70.3 ± 5.7 years, which was not different from the CON group (average age: 71.6 ± 5.2 years, p  = 0.62). There were no significant changes in CCD between baseline and the 8-week follow-up in either the HSCT or the CON group-specifically, the baseline CCD in the HSCT group was 63.3% ± 5% (Mean ± SD), which did not differ significantly from the 8-week follow-up after HSCT training (64.7% ± 4%, p  = 0.19). Likewise, there was no significant difference in CCD between baseline and the 8-week follow-up in the CON group (63.3% ± 3% and 62.7% ± 5%, respectively, p  = 0.66)., Conclusion: CCD appeared to remain stable after 8 weeks of HSCT in healthy older individuals, possibly due to autoregulation. Further research with extended training may be necessary to verify these findings.

Purpose: The purpose of this study was to validate the performance of a portable and remotely controlled slit lamp imaging adaptor., Methods: Twenty patients with anterior eye segment conditions participated in a randomized masked clinical trial. Imaging was performed using a Haag-Streit AG, BX 900 slit lamp biomicroscope and a new slit lamp prototype. Three ophthalmologists independently reviewed masked and randomized 2D images from both instruments and conducted physical eye examinations based on these images. Inter- and intra-grader reliability were assessed using kappa statistics, and sensitivity and specificity were determined with reference to the clinical eye examinations performed during the patients' visits., Results: The sensitivity and specificity of the evaluations with the prototype were 47.8% and 64.1%. Similarly, the evaluations from the conventional system obtained a sensitivity and specificity of 49.5% and 66.2%. The differences in the sensitivity and specificity between imaging modalities were not statistically significant (P > 0.05). The intra-grader reliability showed moderate to substantial agreement between the systems (κ = 0.522-0.708). The inter-grader reliability also indicated moderate agreement for the evaluations with the conventional system (κ = 0.552) and the prototype (κ = 0.474)., Conclusions: This study presents a new prototype that exhibits diagnostic accuracy on par with conventional slit lamps and moderate reliability. Further studies with larger sample sizes are required to characterize the prototype's performance. However, its remote functionality and accessibility suggest the potential to extend eye care., Translational Relevance: The development of portable and remotely controlled eye imaging systems will enhance teleophthalmology services and broaden access to eye care at the primary care level.

Objective: The objective of this study was to investigate the newly graduated physicians' attitudes and perceptions regarding the medical relationship with the pharmaceutical industry and identify the sociodemographic patterns related to such thinking., Methods: A structured questionnaire was administered to 4,601 participants selected from a pool of 16,323 physicians who were registered with one of the 27 Regional Medical Councils of Brazil in 2015. Answers were analyzed using two stratification variables: type of medical school (public vs. private) and the sex of the respondents., Results: Out of the participants, 61.8% believed that industry funding could support medical conferences and education, and 48.4% felt that small gifts and conference travel funding were acceptable. Conversely, 64.7% disagreed with industry-sponsored social events. Views on whether pharmaceutical representatives' visits influenced prescriptions were divided. Statistically significant differences were observed between genders and medical school types, with men and private school graduates being more accepting of certain industry interactions., Conclusion: The study highlights the nuanced attitudes of new doctors toward industry relationships, indicating the need for clearer ethical guidelines and education in medical schools to align practice with evolving societal values.

Purpose: To determine the changes in retinal microvascular density after a 24-week high-speed circuit resistance training program (HSCT) in healthy older adults., Methods: Thirty healthy older adults were recruited and randomly assigned to either a training group (HSCT) or a non-training (CON) group. Fifteen subjects (age 73.3 ± 7.76 yrs) in the HSCT group exercised three times per week on non-consecutive days for 24 weeks. Fifteen subjects in the CON group (age 72.2 ± 6.04 yrs) did not have formal physical training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at the 24-week follow-up. The vessel densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured., Results: There were no demographic differences between the study groups. There were significant decreases in the retinal vessel densities of RVN, SVP and DVP in the HSCT group (P < 0.05). However, there were no significant changes in all three vascular measurements in the CON group (P > 0.05), although the changes showed a decreasing trend. The decreased vessel densities were doubled in the HSCT group in comparison to the CON group. However, the differences between groups did not reach a significant level (P > 0.05)., Conclusions: This is the first study to reveal the decreased retinal vessel densities as a possible imaging marker for the beneficial effects of the 24-week HSCT program in older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and significance of intrinsically disordered proteins (IDPs) within the vitreous, utilizing a dataset of 1240 vitreous proteins previously discovered in the vitreous proteome by Murthy et al.in five healthy subjects. The results indicate that 26.9 % of vitreous proteins are highly disordered, 68.8 % possess moderate disorder, and only 4.3 % are highly ordered. A complex interaction network among these proteins suggests their biological importance, and approximately 25 % may undergo liquid-liquid phase separation (LLPS). These findings offer new perspectives on the vitreous' molecular composition and behavior, potentially impacting our understanding of eye-related diseases, physiological changes such as vitreous syneresis. Further research is needed to translate these insights into clinical applications, although the intrinsic protein disorder and its association with LLPS appears to play a role in vitreous proteome function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To objectively demonstrate eyelid spasms relief in hemifacial spasm (HFS) patients using a smartphone and a custom-made software., Methods: Nineteen patients with HFS had standardized videos recorded with a smartphone (iPhone 6S, Apple) camera before and 15 days after receiving onabotulinumtoxinA injections. Nineteen age-matched control subjects were also assessed. The Eye Aspect Ratio (EAR) is an algorithm previously described to determine whether the eye is opened or closed. When the eye is closed, EAR tends to be closer to zero. Analogously, if the eye is wide open, values are greater. A custom-made software using the EAR concept was developed and pre- and post-treatment EARs were analyzed to assess HFS patients., Results: Botulinum toxin (BoNT) injections led to a significant increase in the average EAR of the affected side: + 10.4% (p = 0.0175) of HFS patients, compared to baseline. Mean EAR before BoNT applications were significantly lower (16.2%) on the affected side (0.25 ± 0.05) of HFS patients when compared to controls (0.30 ± 0.05, p = 0.004). After BoNT injections, no statistically significant difference was observed for the average EAR between the affected side of HFS patients (0.27 ± 0.04) and controls (p = 0.20)., Conclusions: Use of a smartphone and custom-made software objectively demonstrated eyelid spasm relief in patients with HFS. Additional refinement of this system could permit more accurate assessments of treatment response rates for each patient, making it possible to be used in clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Little is known regarding changes induced by botulinum toxin injections on blinking parameters in blepharospasm (BSP) and hemifacial spasm (HFS) patients. The purpose of this study was to investigate objective changes induced by botulinum toxin (BoNT) injections on blinking parameters in BSP and HFS patients., Methods: Thirty-seven patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinumtoxinA injections. Twelve age-matched control subjects were also assessed. Pretreatment and post-treatment parameters were assessed and compared with normal controls. A high-speed camera and microlight-emitting diodes were used to register the blinking in patients and control groups. Outcomes were blinking frequency, amplitude, and maximum velocity of eyelid closure., Results: BoNT injections led to a significant reduction in all parameters, compared with baseline, in BSP and on the affected side in HFS, respectively: 22% ( P < 0.001) and 20% ( P = 0.015) in amplitude; 21% ( P = 0.04) and 39% in frequency ( P = 0.002); and 41% ( P < 0.001) and 26% ( P = 0.005) in maximum closing velocity. Blinking amplitude ( P = 0.017 and P = 0.019) and velocity ( P < 0.001 for both groups) were significantly lower at 30 days on BSP and on the affected HFS side, when compared with controls. BSP and HFS patients presented a significantly lower velocity of eyelid closure, even before BoNT, compared with controls ( P = 0.004. and P < 0.001, respectively)., Conclusions: Although blinking frequency became close to normal, amplitude and velocity after BoNT applications were significantly lower in BSP and on the affected side of HFS patients when compared with age-matched normal controls, demonstrating that blinking parameters do not normalize after treatment. The velocity of eyelid closure was shown to be significantly lower, even before BoNT treatment, when compared with control subjects., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Purpose: Information is scarce regarding the comprehensive profile of patients with essential blepharospasm and hemifacial spasm in Brazil. The present study aimed to assess the clinical features of patients with these conditions, followed up in two reference centers in Brazil., Methods: The study included patients with essential blepharospasm and hemifacial spasm, followed up at the Departments of Ophthalmology at Universidade Federal de São Paulo and Universidade de São Paulo. Apart from demographic and clinical features, past stressful events related to the first symptoms (triggering event), aggravating factors, sensory tricks, and other ameliorating factors for the eyelid spasms were assessed., Results: A total of 102 patients were included in this study. Most patients were female (67.7%). Essential blepharospasm was the most frequent movement disorder [51/102 patients (50%)], followed by hemifacial spasm (45%) and Meige's syndrome (5%). In 63.5% of the patients, the onset of the disorder was associated with a past stressful event. Ameliorating factors were reported by 76.5% of patients; 47% of patients reported sensory tricks. In addition, 87% of the patients reported the presence of an aggravating factor for the spasms; stress (51%) was the most frequent., Conclusion: Our study provides information regarding the clinical features of patients treated in the two largest ophthalmology reference centers in Brazil.

Purpose: The purpose of this study was to assess blepharospasm patients regarding the effect of botulinum toxin in ocular surface parameters., Methods: A prospective study was performed in blepharospasm patients treated with onabotulinumtoxinA. A smartphone (iPhone 6S, Apple) and custom-made software were used to record the eyelid movements for 3 minutes in a standardized manner. Optical coherence tomography of the tear meniscus was used to assess the tear meniscus area. Tear break-up time and the Ocular Surface Disease Index questionnaire were also evaluated. Patients were assessed before and 15 days after botulinum toxin injections., Results: Forty eyes of 20 patients were evaluated. The frequency of the spontaneous eyelid movements was significantly reduced after treatment (23.18 ± 12.85 movements/min vs. 9.29 ± 6.87 movements/min; p < 0.0001). Significant increases in the tear meniscus area (0.020 ± 0.015 mm 2 vs. 0.057 ± 0.104 mm 2 ; p = 0.01) and in break-up time (4.2 ± 1.2 seconds vs. 5.1 ± 1.3 seconds; p = 0.03) were observed 15 days after treatment. A significant reduction in the Ocular Surface Disease Index (59.05 ± 19.04 vs. 21.2 ± 19.5; p < 0.0001) was also observed., Conclusion: Significant changes in the tear meniscus area, break-up time, and Ocular Surface Disease Index after treatment reflect the effect of botulinum toxin on the lacrimal pump and in the improvement of dry eye symptoms. Reduction of eyelid spasms after treatment in blepharospasm patients was demonstrated using a smartphone and custom-made software. Thus, beyond relieving eyelid spasms, botulinum toxin injections were associated with subjective and objective improvement of dry eye parameters in patients with blepharospasm., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: Subtle morphological alterations have been reported even in the nonaffected side of the orbicularis oculi muscle in patients with hemifacial spasm. However, no previous study assessed immunohistochemical, metabolic, and morphometric alterations in orbicularis oculi muscle fibers in affected and nonaffected sides in patients with this condition, compared with samples obtained from healthy subjects. The purpose of this study is to objectively assess and compare orbicularis oculi muscle (OOM) samples of hemifacial spasm affected and nonaffected sides and healthy subjects., Methods: Orbicularis oculi samples from 8 patients with hemifacial spasm who had not been previously treated and 6 healthy subjects were prepared using hematoxylin and eosin, nicotinamide adenine dinucleotide tetrazolium reductase, cytochrome oxidase, succinate dehydrogenase, Gomori staining, and monoclonal antibodies against myosin slow and myosin fast. A digital image analysis software was used for objective analysis., Results: OOM fiber area was significantly greater in both affected ( P = 0.0379) and nonaffected sides ( P = 0.0012) of HFS samples when compared with control subjects' fibers. A significantly greater number of oxidative fibers were observed in both affected and nonaffected sides of patients with HFS when compared with control subjects ( P < 0.001 for both). A significantly greater percentage of slow fibers was observed in the affected side of HFS patients ( P = 0.0012) compared with control subjects., Conclusions: This study's findings suggest that repeated contractions might lead to OOM fiber hypertrophy, increased mitochondrial metabolism, and possible conversion of fast-twitch orbicularis oculi muscle fibers into slow-twitch fibers in patients with HFS. Alterations were observed in affected and nonaffected sides, confirming initial findings that the nonaffected side is not normal in this unique condition., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by North American Neuro-Ophthalmology Society.)

Objective: The objective of this study was to evaluate fresh medical graduates' perceptions regarding the general aspects of ethics teaching in Brazilian medical schools., Methods: A structured questionnaire was applied to 4,601 participants among the 16,323 physicians who registered in one of the 27 Regional Medical Councils of Brazil in 2015. Answers to four questions regarding general aspects of ethics education in medical school were analyzed. Sampling procedures involved two stratification variables: legal nature (public vs. private) of medical schools and monthly household income higher than 10 minimum wages., Results: A large percentage of the participants had witnessed unethical behaviors during contact with patients (62.0%), toward coworkers (51.5%), and in relationships with patients' families (34.4%) over the course of their medical training. Even though most of the responders (72.0%) totally agreed that patient-physician relationship and humanities education were part of their medical school curriculum, important topics such as conflicts of interest and end-of-life education were not satisfactorily addressed in the participants' medical training. Statistically significant differences were found between the answers of public and private school graduates., Conclusion: Despite great efforts to improve medical ethics education, our findings suggest the persistence of deficits and inadequacies in the ethics training currently given in medical schools in Brazil. Further modifications in ethics training must be made to address the deficiencies shown in this study. This process should be accompanied by continuous evaluation.

Background and Purpose: It is challenging to assess essential blepharospasm (EB) patients objectively because they exhibit chaotic patterns of abnormal eyelid movements. Previously employed objective approaches used systems with low levels of accuracy systems or were too complex to be applied in routine clinical practice. We aimed to develop a practical tool using a smartphone camera and custom-made software to objectively assess the therapeutic effects of botulinum toxin in blepharospasm patients., Methods: Thirty-four patients with EB were evaluated before and 15 days after receiving onabotulinumtoxinA injections. The control group was composed of 19 age-matched healthy individuals. A smartphone (iPhone 6 S; Apple) was used to record spontaneous eyelid movements for 3 min, after which eyelid movement frequency was analysed using custom-made software., Results: Before treatment, eyelid movement frequency was significantly higher in the EB group (21.55 ± 13.30 movements/min) compared to the control group (8.26 ± 8.89 eyelid movements/min; p < 0.001). The frequency of spontaneous eyelid movements was significantly reduced after treatment in the EB patients (8.46 ± 6.32 eyelid movements/min; p < 0.001). After treatment, no statistically significant difference in eyelid movement rate was observed between the EB patients and the control group (p = 0.32)., Conclusions: Assessment of the spontaneous eyelid movements obtained with the smartphone camera and analysed with the custom-made software enabled us to objectively measure the therapeutic effects of botulinum toxin in patients with blepharospasm. Further refinement of this system could enable customized and fine adjustments to botulinum toxin doses based on each patient's needs., (© 2023 European Academy of Neurology.)

Background: Mild ptosis can be aesthetically displeasing for patients, especially in unilateral cases. However, some patients do not desire to undergo a surgical repair. Botulinum toxin injection might be an option in these cases., Objectives: The authors sought to objectively examine the effects of botulinum neurotoxin A (BoNT-A) injection into the orbicularis oculi muscle in the management of blepharoptosis., Methods: In this prospective study, 8 patients with mild to moderate ptosis received application of BoNT-A in the pretarsal orbicularis oculi muscle. Standardized photographs were obtained at baseline and 2, 4, and 24 weeks. Digital image analysis software (Image J) was employed for objective analysis. Primary outcomes were the margin reflex distance-1 and qualitative changes on a 4-point scale., Results: A significant increase in the margin reflex distance-1 on the treated side (baseline: 2.00 ± 1.13 mm; week 2: 2.52 ± 1.13 mm; P = 0.003) and a significant reduction (baseline: 3.23 ± 0.92 mm, week 2: 3.07 ± 0.96; P = 0.0268) on the contralateral eyelid were observed at week 2. After 24 weeks, the effect of BoNT-A diminished, and no significant difference from baseline was observed in either eyelid. Subjectively, 87.5% of patients reported improvement in their eyelid ptosis., Conclusions: Botulinum toxin injection in the pretarsal orbicularis oculi muscle can be an option to temporarily manage ptosis in patients who do not desire to undergo a surgical procedure. This alternative treatment can also be employed to manage temporary ptosis induced by botulinum toxin diffusion to the levator aponeurosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Given the aging of the population worldwide, to learn the underlying age-related biological phenomena is important to improve the understanding of the ageing process. Neurodegeneration is an age-associated progressive deterioration of the neuron. Retinal neurodegeneration during aging, such as the reduction in thickness of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) measured by optical coherence tomography (OCT), has been reported, but no studies have provided their specific alteration patterns with age. Therefore, this study is to provide visualization of the evolution of various tomographic intraretinal layer thicknesses during aging and to document age-related changes in focal thickness., Methods: A total 194 healthy subjects were included in this cross-sectional study. The subjects were divided into four age groups: G1, <35 years; G2, 35-49 years; G3, 50-64 years; and G4 ≥65 years. One eye of each subject was imaged using a custom-built ultrahigh-resolution optical coherence tomography (UHR-OCT). Volumetric data centered on the fovea were segmented to obtain the thickness maps of six intraretinal layers, including the macular retinal nerve fiber layer (mRNFL) and GCIPL., Results: There were alterations visualized in thickness maps in these intraretinal layers. The GCIPL showed a thickness reduction localized in the inner annulus in elder subjects (G4). Within the inner annulus, the most profound alteration in G4, an oval zone (length 0.76 mm and width 0.52 mm), appeared to be in the inferior sector about 0.61 mm below the fovea, named "A zone". The average thickness reduction of the A zone was 14.4 µm in the elderly group (G4). Age was significantly related to the GCIPL thickness of the inner annulus (ρ =-0.48; P<0.001) and of the A zone (ρ =-0.39, P<0.001)., Conclusions: This is the first study to apply UHR-OCT for visualizing the age-related alteration of intraretinal layers in a general population. The most profound change of the optic nerve fiber is an oval-like focal thinning in GCIPL, which occurred in the inferior sector within the inner annulus and was strongly related to increased age., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-860/coif). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: The water drinking test (WDT) is a well-known stress test that increases intraocular pressure (IOP) momentarily and can indicate risk of glaucoma progression. This study focuses on correlating changes in the retinal microvascular plexus with the WDT in young healthy subjects., Methods: A total of 20 eyes of 20 healthy young subjects (mean age 24.37 ± 2.17 years) were included in this study. In our protocol, WDT consisted of drinking 1 L of water within 5 min. Outcome measures in this prospective observational study were mean arterial pressure (MAP), heart rate (HR), IOP, and retinal vessel density of both superficial and deep macular retina using optical coherence tomography angiography (OCTA), which were assessed before water ingestion and four times after at 15-min intervals. OCTA images were later quantified by fractal analysis (box counting [ D box ]). One-way repeated measures analysis of variance (ANOVA) was used to assess the effects of WDT on each of the parameters., Results: The WDT resulted in significant peak changes of the following parameters compared to baseline: IOP: 15.63 ± 3.37 versus 18.38 ± 4.53 mmHg at 30 min, p  < 0.001; HR: 75.74 ± 12.23 versus 64.95 ± 11.37 bpm at 15 min, p  < 0.001; deep retinal vessel density 1.758 ± 0.14 versus 1.749 ± 0.16 at 15 min, p  = 0.040., Conclusions: Besides IOP elevation and systemic effects in HR, WDT is associated with temporary modifications of the deep vascular plexus in young healthy subjects.

Background: Considering evidence on competency-based curricula and the benefits of volunteering, this study highlights innovative ideas to improve medical education during the COVID-19 pandemic. We investigated the motivations and perceptions of competencies developed as leadership and management skills in medical students who joined the COVID-19 Volunteering Program in a Brazilian medical school., Methods: We performed a cross-sectional, qualitative study involving medical students from the University of São Paulo, Brazil. They were invited to participate in an institutional Volunteering Program during the pandemic and filled out online application forms, including sociodemographic fields and two open-ended questions about their motivation to volunteer and perceptions of their own competencies. At the end of the program, students who were involved in management-related activities were also invited to participate in focus group interviews to track their perceptions about volunteering in this area. Data were submitted to descriptive and content analysis methods. All participants provided informed consent with electronic signatures., Results: A total of 286 medical students subscribed to the Volunteering Program: 171 (60%) were men, 152 (53%) were enrolled in their 5th year of medical school, and 158 (55%) were 23-25 years old. One hundred and twelve (44%) students reported that they were motivated by altruistic reasons, 95 (37%) reported duty and 47 (19%) prioritized academic interests. Concerning CanMEDS competencies, 91 (36%) students' responses matched the Scholar component, followed by 51 (20%) with Collaborator, 49 (20%) with Professional, 32 (13%) with Communicator, 17 (7%) with Leader and 11 (4%) with Health Advocate. In focus groups, students reported the importance of management and leadership skills as a curricular component, motivations to volunteer, and acquired skills from volunteering in management and leadership-related activities, thereby indicating the development of resilient attitudes., Conclusions: Students who participated in the School of Medicine of University of Sao Paulo (FMUSP) Volunteering Program reported being motivated to help others (altruistic reasons) and to serve society as future health professionals (duty). Knowledge and work-related competencies prevailed over leadership or soft skills, emphasizing the importance of including such activities in the curriculum. Participating in management-related activities could help develop a more resilient attitude toward medical training. Volunteering programs offer students opportunities to develop competencies essential for their roles as future health professionals. Thus, we should think about including such activities in the curricular structure., (© 2022. The Author(s).)

Background: The steady-state pattern electroretinogram (PERG) is a sensitive measure of retinal ganglion cell (RGC) function that includes within-test progressive changes-adaptation-reflecting RGC autoregulatory dynamics. Comprehensive PERG assessment in patients with multiple sclerosis (MS) (with or without optic neuritis [ON]) may provide unique information about RGC dysfunction and its progression, as well as a comparison between functional loss and structural loss as measured by optical coherence tomography (OCT). The goal of this project was to measure steady-state PERG components and their associations with intraretinal layer thicknesses in MS., Methods: One hundred forty eyes of 70 patients with relapsing-remitting MS and 126 eyes of 63 age- and sex-matched healthy control subjects (HC) were investigated using a new-generation PERG method and ultrahigh-resolution OCT. Of MS eyes, there were 30 eyes with ON (MSON), 22 non-ON fellow eyes (MSFE), and 88 non-ON MS eyes (MSNON). PERG amplitude, phase (latency), and adaptation of amplitude and phase were measured and correlated with OCT-determined thicknesses of intraretinal layers., Results: The average PERG amplitude in MSON eyes was significantly lower than MSFE (P = 0.007), MSNON (P = 0.002), and HC (P < 0.001). The PERG amplitude in MSFE eyes was also significantly lower than HC (P = 0.039). The PERG latency in MSON eyes was significantly shorter than in MSFE (P = 0.001), MSNON (P = 0.002), and HC (P < 0.001). The PERG latency in MSFE (P = 0.007) and MSNON (P = 0.002) was significantly shorter than in HC. However, no significant differences were found between MSFE and MSNON (P > 0.05). PERG adaptation of amplitude in MSON was significantly lower than that in MSNON (P = 0.039) and HC (P = 0.037). Both the amplitude and latency in the MS eyes were significantly correlated with the thicknesses of the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL)., Conclusions: Shortened PERG latency and impaired autoregulatory dynamics occurred in MS, suggesting preferential dysfunction of small, slower RGC axons and decreased ability of RGC to autoregulate their gain in response to PERG stimulus. The established relations of PERG measurements with intraretinal thickness measurements suggested that PERG losses were primarily associated with GCIPL and mRNFL thinning., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

The current pandemic of COVID-19 caused thousands of deaths and healthcare professionals struggle to properly manage infected patients. This review summarizes information about SARS-CoV-2 receptor binding dynamics and intricacies, lung autopsy findings, immune response patterns, evidence-based explanations for the immune response, and COVID-19-associated hypercoagulability.

Purpose: There is anecdotal evidence that upper blepharoplasty might lead to raised intraocular pressure (IOP). If this association is confirmed, then patients with glaucoma and glaucoma suspects could be at risk if they underwent this procedure with no appropriate follow up. Here, the authors aimed to determine whether there are significant changes in IOP after upper blepharoplasty., Methods: This prospective study evaluated the IOP at baseline and 1, 2, and 6 weeks after an upper blepharoplasty in individuals with mild to moderate dermatochalasis. Upper blepharoplasty might change the pressure exerted by the upper eyelid into the cornea, and this could affect the corneal surface and the IOP; thus, the corneal topography was also recorded before and at 6 weeks., Results: The IOP of 40 eyes was evaluated. The mean (±SD) preoperative IOP was 14.19 ± 2.12 mm Hg. A statistically significant increase in IOP was observed at 1 (15.15 ± 2.27 mm Hg, p = 0.009), 2 (15.57 ± 2.29 mm Hg, p < 0.0001), and 6 weeks (15.21 ± 2.60 mm Hg, p = 0.001) postoperatively. A statistically significant increase in steep K (preoperative: 44.66 ± 2.06, 6 weeks: 44.78 ± 2.28, p = 0.007) and corneal astigmatism was also observed (preoperative: 0.78 ± 0.43, 6 weeks: 0.89 ± 0.45, p = 0.006) at 6 weeks., Conclusions: Upper blepharoplasty resulted in a mild and statistically significant increase in intraocular pressure postoperatively. The authors' results suggest that upper blepharoplasty should be carefully evaluated in glaucoma and glaucoma suspect patients.

Background: Although the nonaffected side appears to be clinically normal in hemifacial spasm (HFS), it is not known whether this side can be considered normal regarding histopathological findings. The purpose of this study was to objectively evaluate and compare orbicularis oculi samples of patients with HFS (not previously treated with botulinum toxin) and control patients undergoing cosmetic upper eyelid blepharoplasty., Methods: Orbicularis oculi samples from 22 eyelids were evaluated. There were 7 samples from the affected and 7 samples from the nonaffected sides of patients with HFS who had not been previously treated with botulinum toxin, and 8 samples from normal control patients. Muscle samples were prepared using hematoxylin and eosin staining, and a digital image analysis software was used for objective analyses., Results: When compared with normal controls, endomysial and perimysial connective tissue areas were significantly increased (P = 0.015) on the affected side in HFS, suggesting that this disorder is associated with chronic alterations that lead to muscle degeneration. Cell density was significantly reduced on the affected (P = 0.028) and also on the nonaffected sides in HFS (P = 0.003) compared with normal controls. This was observed, although, clinically, there were no signs or symptoms of increased muscular contraction on the nonaffected sides in any of the patients with HFS studied., Conclusions: Significant morphological differences in the orbicularis oculi muscle in patients with HFS were observed on both the affected and nonaffected sides. Our findings suggest a potential role for muscle homeostasis disturbances on both sides for patients with HFS. Affected sides in patients with HFS did, however, demonstrate muscle degeneration that was not present on the nonaffected sides.

Purpose: The goal of this study was to determine the volumetric vessel density (VVD) in the intraretinal layers and its relationship with visual function and disability in patients with multiple sclerosis (MS)., Design: Cross-sectional study., Methods: A total of 80 patients with relapsing-remitting MS and 99 age- and sex-matched healthy controls (HC) were recruited. The retinal microvascular network in the macular area was imaged using optical coherence tomography angiography in 123 eyes without a history of optic neuritis (ON) (MSNON) and 36 eyes with a history of ON (MSON). The VVD was calculated as the vessel densities in the retinal vascular network (RVN), superficial vascular plexus (SVP), or deep vascular plexus (DVP) of an annulus (0.6-2.5 mm in diameter), divided by the corresponding tissue volume of the intraretinal layers respectively., Results: The VVD of RVN and DVP in MSNON were significantly higher than in HC (P < .05). The VVD of RVN, SVP, and DVP in MSON were significantly higher than in MSNON and HC (P < .05). The VVD in both RVN and SVP were positively related to EDSS and disease duration, but negatively related to low-contrast letter acuity (P < .05). The VVD measurements were also negatively and strongly related to the corresponding tissue volumes (P < .05)., Conclusions: This is the first study to reveal increased retinal VVD in patients with relapsing-remitting MS. The measurements of VVD in the RVN and SVP were related to disability and visual function, which may be developed as image markers for tracking disease progression., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To assess spontaneous blinking and anomalous eyelid movements in patients with hemifacial spasm with an emphasis on interocular differences. Spontaneous eyelid movements were registered bilaterally for 3 min using a high-speed video camera in 28 patients with hemifacial spasm (HFS) who had not been treated with botulinum toxin injections for at least 5 months. The degree of blink conjugacy, maximum velocity, and amplitude of the closing phase of the blinks were determined for the affected and non-affected sides. Out of the 28 subjects, 23 (82%) presented with abnormal nonconjugate spasms that were similar to blinks, and in 17 (61%), high-frequency eyelid twitches were detected between blinks on the affected eye. The rate of nonconjugate blink-like spasms ranged from 0.3 to 24.7 movements/min. With regard for conjugate blinks, there was no significant interocular difference in amplitudes or eyelid closure velocities. The amplitude and velocity were significantly lower for nonconjugate movements than for spontaneous blinks. HFS is a unique condition in which complex patterns of eyelid movements, including both conjugate and nonconjugate movements, are present. Conjugate movements correspond to spontaneous blinking, and the same metrics were observed in affected and non-affected eyes. Nonconjugate movements correspond to anomalous nonconjugate blink-like spasms and high-frequency eyelid twitches in the affected eye, both of which were characterized by lower amplitudes and velocities than were observed in conjugate movements.

Purpose: The goal was to visualize topographic thickness maps of the intraretinal layers and evaluate their discrimination abilities and relationships with clinical manifestations in patients with multiple sclerosis (MS) and a history of optic neuritis (ON)., Methods: Thirty patients with relapsing-remitting MS (34 eyes with a history of ON [MSON] and 26 non-ON fellow eyes [MSFE]) were recruited together with 63 age- and sex-matched controls (HC). Ultrahigh resolution optical coherence tomography was used to image the macula and the volumetric data set was segmented to yield six intraretinal layers. Topographic thickness maps were aligned and averaged for the visualization. The thickness maps were partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) and related to Sloan low-contrast letter acuity (LCLA), Expanded Disability Status Scale (EDSS), and disease duration., Results: Focal thickness reduction occurred in the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL), with the most profound reduction occurring in MSON eyes (P < 0.05). A horseshoe-like thickness reduction pattern (U Zone) in the GCIPL appeared in MSON. The thickness of the U Zone had better discrimination power than the ETDRS partitions (area under the curve = 0.97) and differentiated 96% of MSON from HC. The thickness of the U Zone was positively correlated to 2.5% LCLA (r = 0.38, P < 0.05) and 1.25% LCLA (r = 0.57, P < 0.05)., Conclusions: The horseshoe-like thickness reduction of the GCIPL appeared to be an ON-specific focal thickness alteration with the highest discrimination power of prior ON.

Purpose : The goal of this work was to determine whether the retinal tissue perfusion (RTP) is impaired in patients with multiple sclerosis (MS). Methods : Seventy-four patients [66 relapsing-remitting MS (RRMS) and 8 clinically isolated syndrome (CIS)] and 74 age- and gender-matched healthy controls were recruited. RTP was calculated as the retinal blood flow (measured using retinal function imager) supplying the macular area divided by the corresponding tissue volume of the inner retina from the inner limiting membrane to the outer plexiform layer, as measured by ultrahigh-resolution optical coherence tomography. Results : The RTP in the MS group was 2.37 ± 0.59 nl/s/mm 3 (mean ± standard deviation), which was significantly lower than the control group (4.06 ± 0.89 nl/s/mm 3 , P < .001), reflecting a decrease of 42%. The blood flow volume was 2.50 ± 0.50 nl/s in MS, which was 45% lower than in the control group (4.56 ± 0.91 nl/s, P < .001). In addition, the tissue volume of the inner retina was significantly lower than in the control group (P < .05). The RTP in patients with MS was significantly correlated with the retinal blood flow volume (r = 0.84, P < .001) and retinal tissue volume (r = -0.56, P < .001). However, the retinal blood flow in patients with MS was not related to the tissue volume (r = -0.06, P = .59). Conclusions : Impaired retinal tissue perfusion occurred in patients with MS, which could be developed as a possible biomarker in monitoring disease progression in MS.

Background: The aim was to determine the relationship between bulbar conjunctival microcirculation and retinal microcirculation in a healthy population., Method: A functional slit-lamp biomicroscope (FSLB) was used to measure blood flow velocity (BFV) and blood flow rate (BFR) in the conjunctiva while a retinal function imager (RFI) was used to measure macular BFV and BFR in the retina. One eye of each subject of 58 self-reported healthy subjects was imaged in the same session on the same day., Results: The mean BFV in the venules of the conjunctiva was 0.49 ± 0.13 mm/s, which was significantly slower than that in the retinal arterioles (3.71 ± 0.78 mm/s, P  < 0.001) and retinal venules (2.98 ± 0.58 mm/s, P  < 0.001). The BFR in the conjunctiva (0.09 nl/s) was also significantly lower than that in the retina (arterioles = 0.81 nl/s, venules = 0.68 nl/s, all P  < 0.001). The BFVs and BFRs were not related between the conjunctiva and retina (r ranged from - 0.17 to - 0.05, all P  > 0.05)., Conclusion: The microcirculation in the retina appeared to be different from that in the conjunctiva., Competing Interests: All research methods are by the tenets of the Declaration of Helsinki and approved by the Human Subject Research Office (HSRO) at the University of Miami (ID: 20070492). All subjects were recruited voluntarily and were informed about the purposes, methods, and the potential risks of the study. A signed consent form was obtained from each volunteer.All study subjects gave informant consent.The authors declare that they have no competing interests.

Purpose: The purpose of this study was to visualize the topographic thickness patterns of the intraretinal layers and their associations with clinical manifestations in patients with multiple sclerosis (MS)., Methods: Ninety-four eyes of 47 relapsing-remitting MS patients without history of optic neuritis were imaged using optical coherence tomography and compared with 134 eyes of 67 healthy subjects. Volumetric data centered on the fovea were segmented to obtain the thickness maps of six intraretinal layers. The thickness measurements partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) partition were correlated to the Expanded Disability State Scale (EDSS) and Sloan low contrast visual acuity (LCVA). The receiver-operating characteristics (ROC) curves were calculated to obtain the area under the ROC curves (AUCs)., Results: The ganglion cell-inner plexiform layer (GCIPL) showed horseshoe-like thickness reduction profoundly at the nasal sector. The most profound thickness reduction zone (circular area, diameter = 1 mm) was located at 2 mm in the nasal sector and 0.4 mm inferior from the fovea, named the "M zone." The thickness reduction of the M zone was -7.3 μm in MS eyes, which was the most profound alteration, compared to any ETDRS sectors. The AUC of the M zone was 0.75. The relationship between the thickness of the M zone and EDSS (r = -0.59, P < 0.001) or 2.5% LCVA (r = 0.51, P < 0.001) were ranked as the strongest relation compared to any ETDRS sectors., Conclusions: This is the first study, to our knowledge, to visualize focal thickness alteration of GCIPL and reveal its relationship to visual function and disability in patients with MS without history of optic neuritis.

Background: The goal was to quantitatively analyze the bulbar conjunctival microvascular density using optical coherence tomography angiography (OCTA) and compare it to the vessel density using functional slit-lamp biomicroscopy (FSLB)., Methods: Temporal bulbar conjunctiva of 20 eyes (10 healthy subjects) was imaged using both OCTA and FSLB. Image processing was performed including equalization, de-noising, thresholding, and skeletonization. The vessel density was measured by fractal analysis (box counting, Dbox) and pixel counting (%)., Results: Vessel density (Dbox) of the bulbar conjunctiva obtained using OCTA was 1.28 ± 0.01 Dbox, which was significantly lower than the result (1.32 ± 0.01 Dbox, P  < 0.001) obtained using FSLB. Furthermore, the vessel density (%) obtained using OCTA was 3.31 ± 0.12%, which was also significantly lower than the result (3.69 ± 0.16%, P  < 0.001) obtained using FSLB. No significant correlations (r ranged from 0.21 to 0.32, P  > 0.05) between both instruments were found in both vessel density methods (Dbox and percentage). However, in each of the devices, vessel density in Dbox was significantly correlated with the vessel density in percentage ( r  = 1.0 for FSLB and r  = 0.98 for OCTA, both P  < 0.001)., Conclusion: This study demonstrated that the vessel density of the bulbar conjunctiva obtained using OCTA can be quantified, and the results were not compatible with that obtained using slit-lamp biomicroscopy photography., Competing Interests: All research methods were conducted following the tenets of the Declaration of Helsinki and approved by the ethics committee board of the University of Miami. All subjects were recruited voluntarily and were informed about the purposes, methods, and the potential risks of the study. A signed consent form was obtained from each volunteer.All study subjects gave informant consent.The authors declare that they have no competing interests.

Objective: To evaluate the impact of a complex-care-based medical school in the context of the Brazilian health care system on students' career choices., Methods: This was a retrospective cross-sectional study based on medical regulatory organization records. It included records for 7,419 physicians who graduated from FMUSP. Geographic data were analyzed using Kernel maps, and the statistical analysis was performed with SPSS® version 24.0. A p-value less than 0.05 was considered significant., Results: Of the 7,419 physicians, 68.6% (95% CI 67.5-69.7) were male, and 20.7% (95% CI 19.8%-21.7%) had no medical specialty, compared to 46.4% nationwide. Internal medicine and surgery-based specialties were more popular, accounting for 39.4% (95% CI 38.3%-40.5%) and 16.8% (95% CI 15.5%-17.6%) of our study group, compared to the Brazilian averages of 25.9% and 13.5%. Our graduates also had a higher probability of staying in São Paulo City, especially when born outside the city., Conclusion: We believe that FMUSP remains an interesting model for studying the impact of a highly specialized center on the education and career choices of medical students.

Objectives: The increasing demand for medical specialties with flexible working hours has been associated with the important role of quality of life as a determining factor when choosing a career in medicine, which might change the motivations for pursuing a career in ophthalmology. We aim to identify the main determinants of ophthalmology as a career choice as well as the reasons that motivated previous generations to follow this path., Methods: Responses to self-administered online questionnaires were analyzed., Results: A total of 225 responses were analyzed, including those of baby boomers (21), generation X (48), generation Y (131) and generation Z (25). Although the main reasons for choosing ophthalmology as a career are the same for all the generations in this study (flexible working hours, self-satisfaction from helping people improve their vision and the possibility of performing surgical procedures), some reasons for this career choice are more important to the younger generations (short-term results and short procedures), and some are more important to the older generations (the influence of an ophthalmologist in the family)., Conclusion: The main reasons for choosing ophthalmology as a career are essentially the same over time. The differences in secondary motivations could be explained by generational differences.

Health care has changed since the decline in mortality caused by infectious diseases as well as chronic and non-contagious diseases, with a direct impact on the cost of public health and individual health care. We must now transition from traditional reactive medicine based on symptoms, diagnosis and treatment to a system that targets the disease before it occurs and, if it cannot be avoided, treats the disease in a personalized manner. Precision Medicine is that new way of thinking about medicine. In this paper, we performed a thorough review of the literature to present an updated review on the subject, discussing the impact of the use of genetics and genomics in the care process as well as medical education, clinical research and ethical issues. The Precision Medicine model is expanded upon in this article to include its principles of prediction, prevention, personalization and participation. Finally, we discuss Precision Medicine in various specialty fields and how it has been implemented in developing countries and its effects on public health and medical education.

Background: It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer's disease. The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer's disease (CAD)., Methods: Twenty-four CAD patients and 19 cognitively normal (CN) age-matched controls were recruited. A retinal function imager (RFI, Optical Imaging Ltd., Rehovot, Israel) was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the fovea. Blood flow volumes of arterioles (entering the macular region) and venules (exiting the macular region) of the supplied area were calculated. Macular blood flow was calculated as the average of arteriolar and venular flow volumes. Custom ultra-high-resolution optical coherence tomography (UHR-OCT) was used to calculate macular tissue volume. Automated segmentation software (Orion, Voxeleron LLC, Pleasanton, CA) was used to segment six intra-retinal layers in the 2.5 mm (diameter) area centered on the fovea. The inner retina (containing vessel network), including retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer (INL) and outer plexiform layer (OPL), was segmented and tissue volume was calculated. Perfusion was calculated as the flow divided by the tissue volume., Results: The tissue perfusion in CAD patients was 2.58 ± 0.79 nl/s/mm 3 (mean ± standard deviation) and was significantly lower than in CN subjects (3.62 ± 0.44 nl/s/mm 3 , P  <  0.01), reflecting a decrease of 29%. The flow volume was 2.82 ± 0.92 nl/s in CAD patients, which was 31% lower than in CN subjects (4.09 ± 0.46 nl/s, P <  0.01). GCIPL tissue volume was 0.47 ± 0.04 mm 3 in CAD patients and 6% lower than CN subjects (0.50 ± 0.05 mm 3 , P  < 0.05). No other significant alterations were found in the intra-retinal layers between CAD and CN participants., Conclusions: This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer's disease., Competing Interests: All research methods are in accordance with the tenets of the Declaration of Helsinki and approved by the ethics committee board of the University of Miami, FL. All subjects were recruited voluntarily and informed of the purposes, methods, and the potential risks of the study. A signed consent form was obtained from each volunteer.All study subjects gave informed consent.The authors declare that they have no competing interests.

Introduction: The anterior commissure is an area of glottic cancer infiltration, even in early stages., Objective: To evaluate the invasion by tumors into the anterior commissure cartilage in surgical specimens of frontolateral laryngectomy., Methods: Forty-eight patients who had undergone frontolateral laryngectomy for T1b/T2 squamous cell carcinoma were included. Epidemiological and clinical aspects as well as morphological histopathological analysis were evaluated., Results: Of the 48 patients, 42 (87.5%) had T1b lesions and 6 (12.5%) had T2. Thirty-four cases (70.8%) showed healthy tissue between the tumor and the thyroid cartilage, 10 cases (20.8%) had a tumor in close proximity to the cartilage, and in 4 cases (8.3%) there was cartilage invasion. There was no major risk of adverse outcome in the groups with infiltration or tumor adjacent to the cartilage. Level of differentiation, mitotic index, nuclear irregularity, and the presence of nucleolus and tumor necrosis were not related to cartilage invasion., Conclusion: The infiltration of thyroid cartilage occurred in 8.3% of tumors and did not change the outcome in patients submitted to frontolateral laryngectomy. The morphological characteristics did not present any statistical significance., (© 2018 S. Karger AG, Basel.)

Background: A detailed analysis of the tomographic thickness of intraretinal layers may provide more information on neurodegeneration in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Objective: The goal was to analyze tomographic thickness patterns of intraretinal layers in patients with AD andMCI., Method: Forty-nine patients (25 AD and 24 MCI) and 21 cognitively normal (CN) controls were imaged using ultra-high-resolution optical coherence tomography to obtain volumetric data centered on the fovea. The segmented intraretinal layers were retinal nerve fiber layer (RNFL), ganglion cell- inner plexiform layer (GCIPL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL), and retinal photoreceptor (PR), in addition to the total retinal thickness(TRT)., Results: The thickness differences were negative (thinning) mainly in TRT, RNFL, and GCIPL in both AD and MCI groups in comparison to CN, while the thickness differences were positive (thickening) mainly in ONL and PR in AD. GCIPL of AD and MCI was thinner in superior, nasal superior, and temporal superior quadrants, compared to CN (p < 0.05). GCIPL of the inner superior, inner nasal superior, inner temporal superior, and outer nasal superior sectors was significantly thinner in AD than CN (p < 0.05). GCIPL of the outer superior, inner temporal superior, outer nasal, and temporal superior sectors was significantly thinner in MCI than CN (p < 0.05)., Conclusion: Focal thinning of the GCIPL was visualized and quantified by detailed partitions in AD and MCI, which provides specific information about neurodegeneration in MCI and AD.

Purpose: To disclose, using an ex vivo study, the histopathological mechanism behind in vivo thickening of the endothelium/Descemet membrane complex (En/DM) observed in rejected corneal grafts (RCGs)., Methods: Descemet membrane (DM), endothelium, and retrocorneal membranes make up the total En/DM thickness. These layers are not differentiable by high-definition optical coherence tomography; therefore, the source of thickening is unclear from an in vivo perspective. A retrospective ex vivo study (from September 2015 to December 2015) was conducted to measure the thicknesses of DM, endothelium, and retrocorneal membrane in 54 corneal specimens (31 RCGs and 23 controls) using light microscopy. Controls were globes with posterior melanoma without corneal involvement., Results: There were 54 corneas examined ex vivo with mean age 58.1 ± 12.2 in controls and 51.7 ± 27.9 years in RCGs. The ex vivo study uncovered the histopathological mechanism of En/DM thickening to be secondary to significant thickening (P < 0.001) of DM (6.5 ± 2.4 μm) in RCGs compared with controls (3.9 ± 1.5 μm)., Conclusions: Our ex vivo study shows that DM is responsible for thickening of the En/DM in RCGs observed in vivo by high-definition optical coherence tomography and not the endothelium or retrocorneal membrane.