Free-Floating Pigmented Vitreous Cysts: Clinical-Histopathologic Correlation.

Free-floating, pigmented vitreous cysts were documented in two patients. In a 15-year-old girl with intermittent symptoms, a 2.4-mm cyst was observed; origin was attributed to prior trauma, and clinical observation was pursued. In a 35-year-old woman with progressive symptoms, a 11.5-mm cyst was observed; origin was attributed to a history of multiple ocular surgical interventions, and surgical excision by pars plana vitrectomy was performed. [Ophthalmic Surg Lasers Imaging Retina 2024;55:55-58.].

Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography.

BACKGROUND: Automated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans. METHODS: In this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman's correlation was run to examine if the algorithm's probability score was associated with the severity stages of IFTMH. RESULTS: Six hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman's correlation coefficient of 0.15 was achieved between the algorithm's probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied. CONCLUSIONS: The DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm's probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Phage display uncovers a sequence motif that drives polypeptide binding to a conserved regulatory exosite of O-GlcNAc transferase.

The modification of nucleocytoplasmic proteins by O-linked N-acetylglucosamine (O-GlcNAc) is an important regulator of cell physiology. O-GlcNAc is installed on over a thousand proteins by just one enzyme, O-GlcNAc transferase (OGT). How OGT is regulated is therefore a topic of interest. To gain insight into these questions, we used OGT to perform phage display selection from an unbiased library of ~109 peptides of 15 amino acids in length. Following rounds of selection and deep mutational panning, we identified a high-fidelity peptide consensus sequence, [Y/F]-x-P-x-Y-x-[I/M/F], that drives peptide binding to OGT. Peptides containing this sequence bind to OGT in the high nanomolar to low micromolar range and inhibit OGT in a noncompetitive manner with low micromolar potencies. X-ray structural analyses of OGT in complex with a peptide containing this motif surprisingly revealed binding to an exosite proximal to the active site of OGT. This structure defines the detailed molecular basis driving peptide binding and explains the need for specific residues within the sequence motif. Analysis of the human proteome revealed this motif within 52 nuclear and cytoplasmic proteins. Collectively, these data suggest a mode of regulation of OGT by which polypeptides can bind to this exosite to cause allosteric inhibition of OGT through steric occlusion of its active site. We expect that these insights will drive improved understanding of the regulation of OGT within cells and enable the development of new chemical tools to exert fine control over OGT activity.

Demographic and Socioeconomic Factors in Prospective Retina-Focused Clinical Trial Screening and Enrollment.

Historically marginalized populations are disproportionately affected by many diseases that commonly affect the retina, yet they have been traditionally underrepresented in prospective clinical trials. This study explores whether this disparity affects the clinical trial enrollment process in the retina field and aims to inform future trial recruitment and enrollment. Age, gender, race, ethnicity, preferred language, insurance status, social security number (SSN) status, and median household income (estimated using street address and zip code) for patients referred to at least one prospective, retina-focused clinical trial at a large, urban, retina-based practice were retrospectively extracted using electronic medical records. Data were collected for the 12-month period from 1 January 2022, through 31 December 2022. Recruitment status was categorized as Enrolled, Declined, Communication (defined as patients who were not contacted, were contacted with no response, were waiting for a follow-up, or were scheduled for screening following a clinical trial referral.), and Did Not Qualify (DNQ). Univariable and multivariable analyses were used to determine significant relationships between the Enrolled and Declined groups. Among the 1477 patients, the mean age was 68.5 years old, 647 (43.9%) were male, 900 (61.7%) were White, 139 (9.5%) were Black, and 275 (18.7%) were Hispanic. The distribution of recruitment status was: 635 (43.0%) Enrolled, 232 (15.7%) Declined, 290 (19.6%) Communication, and 320 (21.7%) DNQ. In comparing socioeconomic factors between the Enrolled and Declined groups, significant odds ratios were observed for age (p < 0.02, odds ratio (OR) = 0.98, 95% confidence interval (CI) [0.97, 1.00]), and between patients who preferred English versus Spanish (p = 0.004, OR = 0.35, 95% CI [0.17, 0.72]. Significant differences between the Enrolled and Declined groups were also observed for age (p < 0.05), ethnicity (p = 0.01), preferred language (p < 0.05), insurance status (p = 0.001), and SSN status (p < 0.001). These factors may contribute to patient participation in retina-focused clinical trials. An awareness of these demographic and socioeconomic disparities may be valuable to consider when attempting to make clinical trial enrollment an equitable process for all patients, and strategies may be useful to help address these challenges.

Differential Chemoproteomics Reveals MARK2/3 as Cell Migration-Relevant Targets of the ALK Inhibitor Brigatinib.

Metastasis poses a major challenge in cancer management, including EML4-ALK-rearranged non-small cell lung cancer (NSCLC). As cell migration is a critical step during metastasis, we assessed the anti-migratory activities of several clinical ALK inhibitors in NSCLC cells and observed differential anti-migratory capabilities despite similar ALK inhibition, with brigatinib displaying superior anti-migratory effects over other ALK inhibitors. Applying an unbiased in situ mass spectrometry-based chemoproteomics approach, we determined the proteome-wide target profile of brigatinib in EML4-ALK+ NSCLC cells. Dose-dependent and cross-competitive chemoproteomics suggested MARK2 and MARK3 as relevant brigatinib kinase targets. Functional validation showed that combined pharmacological inhibition or genetic modulation of MARK2/3 inhibited cell migration. Consistently, brigatinib treatment induced inhibitory YAP1 phosphorylation downstream of MARK2/3. Collectively, our data suggest that brigatinib exhibits unusual cross-phenotype polypharmacology as, despite similar efficacy for inhibiting EML4-ALK-dependent cell proliferation as other ALK inhibitors, it more effectively prevented migration of NSCLC cells due to co-targeting of MARK2/3.

Comparison of surgical stabilization of rib fractures vs epidural analgesia on in-hospital outcomes.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) improves functional outcomes compared to controls, partly due to reduction in pain. We investigated the impact of early SSRF on pulmonary complications, mortality, and length of stay compared to non-operative analgesia with epidural analgesia (EA). METHODS: Retrospective cohort study of the Trauma Quality Improvement Program (TQIP) 2017 dataset for adults with rib fractures, excluding those with traumatic brain injury or death within twenty-four hours. Early SSRF and EA occurred within 72 h, and we excluded those who received both or neither intervention. Our primary outcome was a composite of pulmonary complications including acute respiratory distress syndrome (ARDS) or ventilator-associated pneumonia (VAP). Additional outcomes included unplanned endotracheal intubation, in-hospital mortality, and hospital and intensive care unit (ICU) length of stay (LOS) for those surviving to discharge. Multiple logistic and linear regressions were controlled for variables including age, sex, flail chest (FC), injury severity, additional procedures, and medical comorbidities. RESULTS: We included 1,024 and 1,109 patients undergoing early SSRF and EA, respectively. SSRF patients were more severely injured with higher rates of FC (42.8 vs 13.3%, p<0.001), Injury Severity Score (ISS) > 16 (56.9 vs 36.1%, p<0.001), and Abbreviated Injury Scale (AIS) Thorax > 3 (33.3 vs 12.2%, p<0.001). Overall, 49 (2.3%) of patients developed ARDS or VAP, 111 (5.2%) required unplanned intubation, and 58 (2.7%) expired prior to discharge. On multivariable analysis, SSRF was not associated with the primary composite outcome (OR: 1.65, 95%CI: 0.85-3.21). Early SSRF significantly predicted decreased risk of unplanned intubation (OR:0.59, 95%CI: 0.38-0.92) compared with early EA alone, however, was not a significant predictor of in-hospital mortality (OR: 1.27, 95%CI: 0.68-2.39). SSRF was associated with significantly longer hospital (Exp(ß): 1.06, 95%CI: 1.00-1.12, p = 0.047) and ICU LOS (Exp(ß): 1.17, 95%CI: 1.08-1.27, p<0.001). CONCLUSIONS: Aside from unplanned intubation, we observed no statistically significant difference in the adjusted odds of in-hospital pulmonary morbidity or mortality for patients undergoing early SSRF compared with early EA. Chest wall injury patients may benefit from referral to trauma centers where both interventions are available and appropriate surgical candidates may receive timely intervention.

Ganglion cell complex changes in wet AMD patients treated with anti-VEGF intravitreal injections according to a treat-and-extend protocol.

OBJECTIVE: To analyze changes in ganglion cell complex (GCC) thickness in wet age-related macular degeneration (AMD) patients receiving intravitreal injections. DESIGN: Retrospective cohort study involving 46 eyes at a single tertiary ophthalmology practice. PARTICIPANTS: The injection group consisted of wet AMD patients who received intravitreal injections for at least 3 years following a treat-and-extend protocol. Twenty-two patients received ranibizumab, and 1 patient received aflibercept. The control group consisted of dry AMD patients who were observed only and did not receive medical treatment over the same period. GCC thickness and visual acuity were recorded at baseline and at 1-, 2-, and 3-year follow-up visits. RESULTS: In the injection group, there was a nonsignificant trend toward reduction in GCC thickness over 3 years (-4.09 ± 8.47 µm; p = 0.09). Within the injection group, correlation analysis between the number of intravitreal injections and GCC thickness was nonsignificant but trended toward a direct relationship, with more injections correlated with a relatively thicker GCC at 3 years. There was no significant change in GCC thickness between baseline and year 3 for the control group. CONCLUSIONS: Study results suggest that that there is no significant GCC thinning in wet AMD patients following a treat-and-extend regimen over 3 years.

Protocol for a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence for grading of ophthalmology imaging modalities.

BACKGROUND: With the rise of artificial intelligence (AI) in ophthalmology, the need to define its diagnostic accuracy is increasingly important. The review aims to elucidate the diagnostic accuracy of AI algorithms in screening for all ophthalmic conditions in patient care settings that involve digital imaging modalities, using the reference standard of human graders. METHODS: This is a systematic review and meta-analysis. A literature search will be conducted on Ovid MEDLINE, Ovid EMBASE, and Wiley Cochrane CENTRAL from January 1, 2000, to December 20, 2021. Studies will be selected via screening the titles and abstracts, followed by full-text screening. Articles that compare the results of AI-graded ophthalmic images with results from human graders as a reference standard will be included; articles that do not will be excluded. The systematic review software DistillerSR will be used to automate part of the screening process as an adjunct to human reviewers. After the full-text screening, data will be extracted from each study via the categories of study characteristics, patient information, AI methods, intervention, and outcomes. Risk of bias will be scored using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) by two trained independent reviewers. Disagreements at any step will be addressed by a third adjudicator. The study results will include summary receiver operating characteristic (sROC) curve plots as well as pooled sensitivity and specificity of artificial intelligence for detection of any ophthalmic conditions based on imaging modalities compared to the reference standard. Statistics will be calculated in the R statistical software. DISCUSSION: This study will provide novel insights into the diagnostic accuracy of AI in new domains of ophthalmology that have not been previously studied. The protocol also outlines the use of an AI-based software to assist in article screening, which may serve as a reference for improving the efficiency and accuracy of future large systematic reviews. TRIAL REGISTRATION: PROSPERO, CRD42021274441.

Comparison of Infectious Complications after Surgical Fixation versus Epidural Analgesia for Acute Rib Fractures.

Background: Surgical stabilization of rib fractures (SSRF) is associated with decreased mortality and respiratory complications. Patients who are not offered SSRF are often treated with epidural analgesia (EA) to reduce pain and improve pulmonary mechanics. We sought to compare infectious complications in patients undergoing either SSRF or EA. We hypothesized that infectious complications are equivalent between the two treatment groups. Patients and Methods: We performed a retrospective cohort study of adult trauma patients with acute rib fractures within the Trauma Quality Improvement Program (TQIP) 2017 dataset and used International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify patients who underwent SSRF or EA. We excluded patients who received both treatments in the same admission. Our primary outcome was the development of sepsis. Secondary outcomes were specific infections including ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (CAUTI), and central line-associated blood stream infections (CLABSI). Multiple logistic regression analyses were used to adjust for age, injury severity score (ISS), chest Abbreviated Injury Scale (AIS), flail chest, traumatic brain injury (TBI), and comorbidities. Results: We identified 2,252 and 1,299 patients who underwent SSRF and EA, respectively. Patients with SSRF were younger with higher ISS and longer length of stay (LOS). There was no difference in mortality, however, SSRF had higher rate of sepsis (1.6% vs. 0.5%; p = 0.001), VAP (5.1% vs. 0.9%; p < 0.001), CAUTI (1.7% vs. 0.5%; p = 0.001), and CLABSI (0.2% vs. 0%; p = 0.05). On multiple regression, SSRF was associated with higher odds of sepsis (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.04-6.63), CAUTI (OR, 2.96; 95% CI, 1.11-7.88), and VAP (OR, 3.24; 95% CI, 1.73-6.06). Among those who developed sepsis, there was no significant difference in mortality or LOS between groups. Conclusions: Despite no difference in mortality, SSRF was associated with increased risk of septic complications in patients with rib fractures compared to epidural analgesia. Identifying, and addressing, risk factors of sepsis in this patient population is a critical performance improvement process to optimize outcomes without increased adverse events.

Commercial and Instant Coffees Effectively Lower Aß1-40 and Aß1-42 in N2a/APPswe Cells.

Background: Alzheimer's disease (AD) is a multifactorial neurological disease with neurofibrillary tangles and neuritic plaques as histopathological markers. Due to this, although AD is the leading cause of dementia worldwide, clinical AD dementia cannot be certainly diagnosed until neuropathological post-mortem evaluation. Coffee has been reported to have neurologically protective factors, particularly against AD, but coffee brand and type have not been taken into consideration in previous studies. We examined the discrepancies among popular commercial and instant coffees in limiting the development and progression through Aß1-40 and Aß1-42 production, and hypothesized that coffee consumption, regardless of brand or type, is beneficial for stalling the progression and development of Aß-related AD. Methods: Coffee samples from four commercial coffee brands and four instant coffees were purchased or prepared following given instructions and filtered for the study. 5, 2.5, and 1.25% concentrations of each coffee were used to treat N2a/APPswe cell lines. MTT assay was used to assess cell viability for coffee concentrations, as well as pure caffeine concentrations. Sandwich ELISA assay was used to determine Aß concentration for Aß1-40 and Aß1-42 peptides of coffee-treated cells. Results: Caffeine concentrations were significantly varied among all coffees (DC vs. MDC, PC, SB, NIN, MIN p < 0.05). There was no correlation between caffeine concentration and cell toxicity among brands and types of coffee, with no toxicity at 0.5 mg/ml caffeine and lower. Most coffees were toxic to N2a/APPswe cells at 5% (p < 0.05), but not at 2.5%. Most coffees at a 2.5% concentration reduced Aß1-40 and Aß1-42 production, with comparable results between commercial and instant coffees. Conclusion: All coffees tested have beneficial health effects for AD through lowering Aß1-40 and Aß1-42 production, with Dunkin' Donuts® medium roast coffee demonstrating the most consistent and optimal cell survival rates and Aß concentration. On the other hand, Starbucks® coffee exhibited the highest cell toxicity rates among the tested coffees.

Developing an Effective Peptide-Based Vaccine for COVID-19: Preliminary Studies in Mice Models.

Coronavirus disease 2019 (COVID-19) has caused massive health and economic disasters worldwide. Although several vaccines have effectively slowed the spread of the virus, their long-term protection and effectiveness against viral variants are still uncertain. To address these potential shortcomings, this study proposes a peptide-based vaccine to prevent COVID-19. A total of 15 B cell epitopes of the wild-type severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein were selected, and their HLA affinities predicted in silico. Peptides were divided into two groups and tested in C57BL/6 mice with either QS21 or Al(OH)3 as the adjuvant. Our results demonstrated that the peptide-based vaccine stimulated high and durable antibody responses in mice, with the T and B cell responses differing based on the type of adjuvant employed. Using epitope mapping, we showed that our peptide-based vaccine produced antibody patterns similar to those in COVID-19 convalescent individuals. Moreover, plasma from vaccinated mice and recovered COVID-19 humans had the same neutralizing activity when tested with a pseudo particle assay. Our data indicate that this adjuvant peptide-based vaccine can generate sustainable and effective B and T cell responses. Thus, we believe that our peptide-based vaccine can be a safe and effective vaccine against COVID-19, particularly because of the flexibility of including new peptides to prevent emerging SARS-CoV-2 variants and avoiding unwanted autoimmune responses.

Use of conditional reprogramming cell, patient derived xenograft and organoid for drug screening for individualized prostate cancer therapy: Current and future perspectives (Review).

Prostate cancer mortality is ranked second among all cancer mortalities in men worldwide. There is a great need for a method of efficient drug screening for precision therapy, especially for patients with existing drug­resistant prostate cancer. Based on the concept of bacterial cell culture and drug sensitivity testing, the traditional approach of cancer drug screening is inadequate. The current and more innovative use of cancer cell culture and in vivo tumor models in drug screening for potential individualization of anti­cancer therapy is reviewed and discussed in the present review. An ideal screening model would have the ability to identify drug activity for the targeted cells resembling what would have occurred in the in vivo environment. Based on this principle, three available cell culture/tumor screening models for prostate cancer are reviewed and considered. The culture conditions, advantages and disadvantages for each model together with ideas to best utilize these models are discussed. The first screening model uses conditional reprogramed cells derived from patient cancer cells. Although these cells are convenient to grow and use, they are likely to have different markers and characteristics from original tumor cells and thus not likely to be informative. The second model employs patient derived xenograft (PDX) which resembles an in vivo approach, but its main disadvantages are that it cannot be easily genetically modified and it is not suitable for high­throughput drug screening. Finally, high­throughput screening is more feasible with tumor organoids grown from patient cancer cells. The last system still needs a large number of tumor cells. It lacks in situ blood vessels, immune cells and the extracellular matrix. Based on these current models, future establishment of an organoid data bank would allow the selection of a specific organoid resembling that of an individual's prostate cancer and used for screening of suitable anticancer drugs. This can be further confirmed using the PDX model. Thus, this combined organoid­PDX approach is expected to be able to provide the drug sensitivity testing approach for individualization of prostate cancer therapy in the near future.

BYPASS-OMA: Hypoglycemic Hyperinsulinemic Nesidioblastosis after Gastric Bypass Surgery-A Case Report and Review of the Literature.

This rare case vignette describes hypoglycemic, hyperinsulinemic nesidioblastosis in a female patient with prior Roux-en-Y gastric bypass. The patient presented with severe symptomatic hypoglycemia resistant to IV dextrose and diazoxide, requiring surgical resection. Traditional imaging found nonspecific findings, and biochemical analysis was inconsistent with insulinoma. A gallium-68 dotatate PET scan was utilized to successfully localize the tumor in the distal pancreas. She underwent laparoscopic resection of the distal pancreatic lesion with resolution of her symptoms and return to euglycemia. The histological evaluation confirmed the diagnosis of nesidioblastosis. Nesidioblastosis is a rare complication of bariatric surgery that may be more clinically relevant with rising prevalence of obesity. Diagnosis with conventional imaging modalities may be challenging; however, the dotatate PET scan may have high utility in detecting lesions. It is essential for clinicians to consider nesidioblastosis in the differential diagnosis of hyperinsulinemic hypoglycemic conditions and recognize there may be a link with increasing rates of bariatric surgery.

University of Toronto's redesigned ophthalmology curriculum and eye dissection lab.

OBJECTIVE: To present a multifaceted approach to ophthalmology undergraduate medical education and to assess the efficacy of an eye dissection laboratory in enhancing medical student learning. DESIGN: Curriculum review, validation, and student feedback evaluations. PARTICIPANTS: Year 2 medical students enrolled in the University of Toronto's Doctor of Medicine Program. METHODS: Student feedback evaluations were compiled from the University of Toronto undergraduate medical education student surveys before 2012-2016 and following introduction of the redesigned foundations ophthalmology curriculum at the University of Toronto (2017-2018). Students who participated in the Eye Dissection Lab as part of the newly designed curriculum completed the pre- and postsession satisfaction and overall interest in ophthalmology questionnaires and a knowledge-based test. RESULTS: Analysis of 1640 student evaluations demonstrated an increase in ophthalmology curriculum rating following the launch of the foundations ophthalmology curriculum (p = 0.015). Among the 335 students who completed the eye dissection lab, there was a significant increase in the average scores for the satisfaction questionnaire, knowledge-based test, and level of interest in the field of ophthalmology from before and after the session, with improvements in scores noted in 91%, 42%, and 36% of the educational parameters of the participants, respectively (p < 0.001). CONCLUSIONS: The newly designed foundations ophthalmology curriculum and the eye dissection lab at the University of Toronto serve as effective means for enhancing ophthalmology teaching in medical schools across Canada.

Sociodemographics Associated With Risk of Diabetic Retinopathy Detected by Tele-Ophthalmology: 5-Year Results of the Toronto Tele-Retinal Screening Program.

OBJECTIVES: Our aim in this study was to describe screening outcomes and sociodemographic characteristics of patients in an urban tele-ophthalmology screening program for diabetic retinopathy (DR). METHODS: A prospective cohort study was conducted on adults with diabetes type 1 or type 2 enrolled in the Toronto Tele-Retinal Screening Program between September 2013 and March 2019. RESULTS: A total of 1,374 screenings were completed, of which 344 (25%) detected DR. Of all participants, 17% did not have provincial health coverage and 21% had never had an eye exam. Of the 587 patients who completed sociodemographic questionnaires, the majority (84%) were born outside of Canada, and only 62% preferred English as their spoken language. Forty percent reported a household income of <$25,000, with these participants having an increased likelihood of detectable DR (odds ratio [OR], 1.83; p<0.01). CONCLUSIONS: Participants with low income are more likely to screen positive for DR. Tele-ophthalmologic screening can be effective in an urban, culturally diverse and socioeconomically disadvantaged population.

COVID-19 Vaccines: Current Conditions and Future Prospects.

It has been over a year since SARS-CoV-2 was first reported in December of 2019 in Wuhan, China. To curb the spread of the virus, many therapies and cures have been tested and developed, most notably mRNA and DNA vaccines. Federal health agencies (CDC, FDA) have approved emergency usage of these S gene-based vaccines with the intention of minimizing any further loss of lives and infections. It is crucial to assess which vaccines are the most efficacious by examining their effects on the immune system, and by providing considerations for new technological vaccine strategies in the future. This paper provides an overview of the current SARS-CoV-2 vaccines with their mechanisms of action, current technologies utilized in manufacturing of the vaccines, and limitations in this new field with emerging data. Although the most popular COVID-19 vaccines have been proven effective, time will be the main factor in dictating which vaccine will be able to best address mutations and future infection.

Surgical Management of Recurrent and Persistent Macular Holes: A Practical Approach.

Primary surgery for macular hole (MH) closure has a high success rate with current methods of pars plana vitrectomy and internal limiting membrane (ILM) peeling. When primary surgery fails, there are several options available for secondary repair, including extension of the ILM peel, creation of an ILM flap, pedunculated ILM flap, lens capsule flap transplantation, autologous retinal transplantation, use of a human amniotic membrane plug, adjuvant autologous platelet concentrate, induction of macular detachments with subretinal blebs, and creation of retinal incisions. In this review, we discuss the practical approach to each of these surgical techniques for the management of recurrent or persistent MHs.