Pneumatic displacement of submacular haemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

BACKGROUND: To compare the visual and anatomical outcomes of pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (VEGF) therapy versus anti-VEGF monotherapy in treatment-naive eyes with submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: In a retrospective comparative interventional study of 57 eyes, the changes in logMAR visual acuity (VA), and SMH height and area at baseline at months 1, 3 and 12 were compared between the PD and non-PD groups. RESULTS: There was no significant difference in mean VA in the PD versus non-PD group at month 12 (1.1 versus 0.7, p = 0.09). At baseline, the PD group, compared to the non-PD group, had significantly larger SMH area (35.9 versus 26.9 mm2, p = 0.04) and SMH height at the fovea (733.7 versus 503.6 µm, p < 0.01). The greatest reduction in SMH height and area occurred between baseline and month 1 in the PD group, which was faster than between month 1 and month 3 in the non-PD group, with similar findings in the matched pair analysis matched for SMH height and area. In the multivariable analysis, only baseline VA was associated with VA outcomes (month 1: ß = -0.46, 95% [confidence interval] CI = -0.78 to -0.14, p = 0.006; month 3: ß = -0.52, 95% CI = -0.86 to -0.18, p = 0.004; and month 12: ß = -0.78, 95% CI = -1.16 to -0.39, p < 0.001). CONCLUSIONS: The visual outcome of SMH at month 12 in nAMD and PCV is poor regardless of whether PD is performed in addition to anti-VEGF therapy, although a more rapid resolution of SMH can be expected.

Orthopaedic Personal Statement Thematic Review: Does Topic Matter?

Introduction: In the process of applying into medical residency, the Electronic Residency Application Service (ERAS) requires critical documents including a personal statement. Utility of personal statements are questioned based on suspected congruity of the content within personal statements among those who apply into orthopaedic surgery. The goal of this study was to identify and categorize the thematic elements found within the 2021 to 2022 personal statements of orthopaedic surgery applicants at a single institution and assess a correlation to interview invitation. Methods: Deidentified personal statements among 2021 to 2022 ERAS applicants were reviewed by the research staff and categorized into one of the proposed themes. Three hundred ninty-four applications passed initial screening filters, and 49 applicants were granted an interview. Proposed themes that were collected included: family of physician, working with hands, history of injury/disease, prior professional setting, immigration/travel, athlete/sports, reapplication, previous clinical experience, and other. χ2 test was used to analyze categorical themes and additional univariate group-to-group comparisons. Multivariate principal component analysis was performed to determine which themes were associated with interview invitation. Results: There was a significant difference in theme selection for an applicant's personal statement (χ2 = 209.5, p < 0.001), but no statistical difference was observed between each individual categorical themes and interview selection. Univariate group-to-group comparison demonstrated greater interview rates between immigration/travel compared with reapplicant and family of physician compared with working with hands. Multivariate principal component analysis demonstrated immigration/travel as the theme with a positive correlation toward an interview invitation. Conclusion: Despite a significant focus of the application process into orthopaedic surgery residencies, our single-institution study did observe specific themes that were more prevalent. There was an increased interview rate between applicant's themes for immigration/travel and family of physician when comparing groups. Immigration/travel was also identified as the only significant theme associated with interview invitation which may be due to the recent emphasis on promoting diversity within orthopaedic surgery.

Cataract Surgery and Cognitive Benefits in the Older Person: A Systematic Review and Meta-analysis.

TOPIC: This systematic review and meta-analysis aims to clarify the association of cataract surgery with cognitive impairment and dementia. CLINICAL RELEVANCE: The association between vision impairment and cognitive decline is well-established. However, the cognitive benefits of cataract surgery are less clear. Given the lack of cure for dementia, identifying modifiable risk factors is key in caring for patients with cognitive deficits. METHODS: The study was conducted following Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. PubMed, Embase, and Cochrane Library were searched from inception through October 11, 2022, for studies reporting the effect of cataract surgery on cognitive impairment and dementia. We pooled maximally adjusted hazard ratios (HRs) for dichotomous outcomes and ratio of means (RoM) for continuous outcomes using a random-effects model. Heterogeneity was examined using sensitivity and subgroup analyses. The quality of evidence was evaluated using the Newcastle-Ottawa scale, Cochrane risk-of-bias tool for randomized trials, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: This review included 24 articles comprising 558 276 participants, of which 19 articles were analyzed qualitatively. The bias of studies ranged from low to moderate, and GRADE extended from very low to low. Cataract surgery was associated with a 25% reduced risk of long-term cognitive decline compared with those with uncorrected cataracts (HR, 0.75; 95% confidence interval [CI], 0.72-0.78). This cognitive benefit was seen across various cognitive outcomes and remained robust to sensitivity analyses. Participants who underwent cataract surgery showed a similar risk of long-term cognitive decline as healthy controls without cataracts (HR, 0.84; 95% CI, 0.66-1.06). Additionally, cataract surgery was associated with a 4% improvement in short-term cognitive test scores among participants with normal cognition (RoM, 0.96; 95% CI, 0.94-0.99), but no significant association was observed among participants with preexisting cognitive impairment. DISCUSSION: Cataract surgery may be associated with a lower risk of cognitive impairment and dementia, and cataract-associated vision impairment may be a modifiable risk factor for cognitive decline. Physicians should be aware of the cognitive sequelae of cataracts and the possible benefits of surgery. The cognitive benefits of cataract surgery should be investigated further in randomized trials. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Artificial Intelligence, Digital Imaging, and Robotics Technologies for Surgical Vitreoretinal Diseases.

OBJECTIVE: To review recent technological advancement in imaging, surgical visualization, robotics technology, and the use of artificial intelligence in surgical vitreoretinal (VR) diseases. BACKGROUND: Technological advancements in imaging enhance both preoperative and intraoperative management of surgical VR diseases. Widefield imaging in fundal photography and OCT can improve assessment of peripheral retinal disorders such as retinal detachments, degeneration, and tumors. OCT angiography provides a rapid and noninvasive imaging of the retinal and choroidal vasculature. Surgical visualization has also improved with intraoperative OCT providing a detailed real-time assessment of retinal layers to guide surgical decisions. Heads-up display and head-mounted display utilize 3-dimensional technology to provide surgeons with enhanced visual guidance and improved ergonomics during surgery. Intraocular robotics technology allows for greater surgical precision and is shown to be useful in retinal vein cannulation and subretinal drug delivery. In addition, deep learning techniques leverage on diverse data including widefield retinal photography and OCT for better predictive accuracy in classification, segmentation, and prognostication of many surgical VR diseases. CONCLUSION: This review article summarized the latest updates in these areas and highlights the importance of continuous innovation and improvement in technology within the field. These advancements have the potential to reshape management of surgical VR diseases in the very near future and to ultimately improve patient care. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of Smartphone-Based Telescreening for Retinopathy of Prematurity With and Without Artificial Intelligence in India.

Importance: Retinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting. Objective: To assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders. Design, Setting, and Participants: This prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded. Exposures: All participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)- and treatment requiring (TR)-ROP. Main Outcome and Measures: Sensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing. Results: A total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%. Conclusions and Relevance: In this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.

Trigger Wrist Caused by a Rheumatoid Nodule on the Flexor Pollicis Longus Tendon.

Background: Trigger wrist is a rare condition. Previously reported cases have involved nodules or ganglion cysts affecting flexor digitorum profundus tendons; however, we found no reported cases of trigger wrist caused by a rheumatoid nodule on the flexor pollicis longus tendon. Case Report: A 57-year-old female presented with the complaint of chronic triggering of the right thumb and numbness in her fingers consistent with carpal tunnel syndrome. Corticosteroid injection did not provide symptom relief, so the patient was scheduled for surgery. A 3 × 1.5-cm lesion was removed from the flexor pollicis longus tendon distal to the carpal tunnel. Histopathologic examination demonstrated that the lesion was a rheumatoid nodule. Conclusion: Patients with rheumatoid arthritis who present with trigger finger symptoms of the thumb with concomitant carpal tunnel symptoms require careful evaluation to rule out trigger wrist before the condition progresses to Mannerfelt lesion.

Assessment of Cardiovascular Disease Among Predominantly Black Gout Patients.

INTRODUCTION: Although the association between gout and cardiovascular disease (CVD) has been extensively studied, scarce data are available for the Black population. We aimed to assess the association between gout and CVD in a predominantly Black urban population with gout. METHODS: A cross-sectional analysis was performed between a gout cohort and an age-/sex-matched control group. Clinical parameters and 2D echocardiograms were reviewed for the patients with gout and heart failure (HF). The primary outcome studied includes the prevalence and strength of association between gout and CVD. Secondary outcomes studied includes strength of association of gout and HF categorized by ejection fraction, mortality, and HF readmissions. RESULTS: Four hundred seventy-one patients with gout had a mean age of 63.7 ± 0.5 years; 89% were Black, 63% were men, and mean body mass index was 31.3 ± 0.4 kg/m 2 . Hypertension, diabetes mellitus, and dyslipidemia were present in 89%, 46%, and 52%, respectively. Compared with controls, patients with gout had significantly higher rates of angina, arrhythmia, coronary artery disease/stents, myocardial infarction, coronary artery bypass graft surgery, cerebrovascular accident, and peripheral vascular disease. The adjusted odds ratio for CVD was 2.9 (95% confidence interval, 1.9-4.5; p < 0.001). Gout patients had a higher prevalence of HF with 45% (n = 212) compared with controls with 9.4% (n = 44). Adjusted odds ratio for HF risk was 7.1 (95% confidence interval, 4.7-10.6; p < 0.01). CONCLUSIONS: Gout in a predominantly Black population confers 3 times the CVD risk and 7 times HF-specific risk compared with age- and sex-matched cohort. Further research is needed to confirm our findings and to develop interventions to reduce morbidity associated with gout.

Staphylococcus lugdunensis Endophthalmitis: Case Series and Literature Review.

Staphylococcus lugdunensis endophthalmitis is an uncommon intraocular infection with potentially visually devastating consequences. S. lugdunensis endophthalmitis have been reported following cataract surgery, trauma, intravitreal injections of anti-vascular endothelial growth factor agents and dexamethasone implant. We report four cases of postoperative S. lugdunensis endophthalmitis after cataract extraction (three patients) and combined pars plana vitrectomy and cataract extraction (one patient). The onset of presentation of endophthalmitis was acute (within 2 weeks) in two patients, subacute (2 to 6 weeks) in one patient, and chronic (more than 6 weeks) in one patient. All patients had presenting visual acuity (VA) of hand motions or worse and were treated with pars plana vitrectomy with intravitreal antibiotics. The final VA was 20/50 in two patients, 4/200 in one patient with pre-existing myopic maculopathy, and no light perception in one patient with retinal detachment. In antibiotic susceptibility testing, S. lugdunensis isolates were resistant to penicillin (3/4, 75%), but all were susceptible to vancomycin, oxacillin, teicoplanin, tigecycline, and sulfamethoxazole-trimethoprim. S. lugdunensis may be associated with acute or chronic endophthalmitis. Favorable visual outcomes can be achieved with prompt diagnosis and management.

Survey of Ophthalmology Training Experiences Among Young Ophthalmologists in the Asia-Pacific.

PURPOSE: To describe ophthalmology training experiences across the Asia-Pacific (APAC). DESIGN: Survey study. METHODS: We utilized an anonymous online survey, which was previously validated and conducted in Europe, through Young Ophthalmologist leaders from the national member societies of the Asia-Pacific Academy of Ophthalmology (APAO) from September 2019 to July 2021. Responses were based on a 5-point Likert scale (where applicable) and data were analyzed using Microsoft Excel. Our main outcome measures were differences between regions, that is, Southeast Asia (SEA) and Western Pacific (WP); and seniority, that is, trainees/junior ophthalmologists and senior ophthalmologists. RESULTS: We collated 130 responses representing 20 regions in the APAC region. The year of completion of ophthalmic training ranged from 1999 to 2024. The mean duration of training was 3.7±1.0 years. Most (98/130, 75%) indicated an interest for a common training standard across the APAC. Comparing SEA and WP trainees, both regions had similar working environments, but those in SEA reported significantly lower remuneration than their counterparts in WP ($600 vs $3000, P <0.05). WP trainees performed more phacoemulsification surgeries (76 WP vs 19 SEA), while SEA trainees conducted more manual small incision cataract surgeries (157 WP vs 1.5 SEA per duration of training). Senior ophthalmologists performed more cataract surgeries (210.9 senior ophthalmologists vs 40.1 junior ophthalmologists). Trainees had less confidence in medical competency areas such as interpreting an electroretinogram/visual evoked potential/electrooculogram (SEA=1.8, WP=2.1) and conducting an angiography (SEA=2.8, WP=3.4). CONCLUSIONS: Our study highlighted heterogeneity among ophthalmology training experiences in the APAC region, with the majority indicating an interest in a common training standard.

Systematic Review of Ligament Reconstruction of Traumatic Isolated Thumb Carpometacarpal Joint Dislocation.

INTRODUCTION: Thumb carpometacarpal (CMC) joint dislocations are rare with minimal agreement on surgical management. The dorsoradial ligament (DRL) is the primary joint stabilizer but has not historically been reconstructed. We hypothesize that the reported reconstruction of first CMC joint dislocations primarily uses the flexor carpi radialis (FCR) without collective agreement on a surgical technique. METHODS: A systematic review of the PubMed database from 1996 to 2022 was done. Keywords were "thumb dislocation," "thumb carpometacarpal dislocation," and "carpometacarpal joint ligament repair." Inclusion criteria included isolated, unstable thumb CMC dislocations with reconstruction. The Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were used. RESULTS: Four hundred thirty-seven records were identified, and nine met inclusion criteria. Two articles were cohort studies, and seven were case reports. Thirty-seven patients were included, and 26 patients had reconstruction with tendonous autograft. Twenty-five (96.2%) used the FCR and 1 (3.9%) from the palmaris longus. Three patients had reconstruction with a suture anchor. Surgical techniques varied between studies. DISCUSSION: The recommendation of the authors recreates the DRL during autograft repair. Current repair techniques that recreate the DRL use the FCR, but quantitative comparisons of tendonous autografts or suture anchors have not been done.

Assessment and management of retinopathy of prematurity in the era of anti-vascular endothelial growth factor (VEGF).

The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1-12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy. Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.

Addressing the Third Epidemic of Retinopathy of Prematurity Through Telemedicine and Technology: A Systematic Review.

The rising prevalence of retinopathy of prematurity (ROP) in low- and middle-income countries has increased the need for screening at-risk infants. The purpose of this article was to review the impact of tele-medicine and technology on ROP screening programs. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed using PubMed, Pro-Quest, and Google Scholar bibliographic search engine. Terms searched included retinopathy of prematurity, telemedicine, and tele-ophthalmology. Data regarding internet access and gross domestic product per capita were obtained from the World Bank. Information was also obtained about internet access, speeds, and costs in low-income countries. There has been increasing integration of telemedicine and technology for ROP screening and management. Low-income countries are using available internet options and information and communications technology for ROP screening, which can aid in addressing the unique challenges faced by low-income countries. This provides a promising solution to the third epidemic of ROP by expanding and improving screening and management. Although telemedicine systems may serve as a cost-effective approach to facilitate delivery of health care, programs (especially in lowand middle-income countries) require national support to maintain its infrastructure. [J Pediatr Ophthalmol Strabismus. 2021;58(4):261-269.].

Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model.

BACKGROUND: Human pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in the delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells, and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined. METHODS: Cynomolgus monkeys were systemically immunosuppressed and implanted with a hESC-RPE monolayer on a permeable polyester-terephthalate (PET) scaffold. Microscope-integrated intraoperative optical coherence tomography (miOCT)-guided surgery, postoperative follow-up incorporated scanning laser ophthalmoscopy, spectral domain (SD-) OCT, and full-field electroretinography (ERG) were used as outcome measures. In addition, histology was performed after a 28-day follow-up. RESULTS: Intercontinental cell shipment, which took >30 h from the manufacturing to the transplantation site, did not alter the hESC-RPE quality. The submacular hESC-RPE xenotransplantation was performed in 11 macaques. The miOCT typically revealed foveal disruption. ERG showed amplitude and peak time preservation in cases with favorable surgical outcomes. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The immunosuppression protocol efficiently suppressed retinal T cell infiltration and microglia activation. CONCLUSION: These results suggest both structural and functional submacular integrations of hESC-RPE xenografts. It is anticipated that surgical technique refinement will further improve the engraftment of macular cell therapeutics with significant translational relevance to improve future clinical trials.

Mechanistic Insight into Orthodontic Tooth Movement Based on Animal Studies: A Critical Review.

Alveolar bone remodeling in orthodontic tooth movement (OTM) is a highly regulated process that coordinates bone resorption by osteoclasts and new bone formation by osteoblasts. Mechanisms involved in OTM include mechano-sensing, sterile inflammation-mediated osteoclastogenesis on the compression side and tensile force-induced osteogenesis on the tension side. Several intracellular signaling pathways and mechanosensors including the cilia and ion channels transduce mechanical force into biochemical signals that stimulate formation of osteoclasts or osteoblasts. To date, many studies were performed in vitro or using human gingival crevicular fluid samples. Thus, the use of transgenic animals is very helpful in examining a cause and effect relationship. Key cell types that participate in mediating the response to OTM include periodontal ligament fibroblasts, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Intercellular signals that stimulate cellular processes needed for orthodontic tooth movement include receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α (TNF-α), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), sclerostin, transforming growth factor beta (TGF-ß), and bone morphogenetic proteins (BMPs). In this review, we critically summarize the current OTM studies using transgenic animal models in order to provide mechanistic insight into the cellular events and the molecular regulation of OTM.

Imaging Features of a Retinal Detachment and Secondary Epiretinal Membrane Following Inadvertent Globe Penetration From Peribulbar Anesthesia.

Purpose: We present imaging features of retinal detachment (RD) and secondary epiretinal membrane in a case of an inadvertent globe penetration following preoperative peribulbar anesthesia. Methods: A 60-year-old woman was referred for a localized RD and epiretinal membrane following uneventful cataract surgery. Widefield fundus photography and optical coherence tomography were used to assess and record the pathology. The current literature was reviewed. Results: Full-thickness breaks were noted in the neurosensory retina extending into the scleral wall. Vertical tracks were noted in the inferotemporal quadrant of the eye. The patient underwent trans pars plana vitrectomy, membrane peel, and gas. Her 1-month postoperative visual acuity was 20/30. Conclusions: Globe penetration with RD is a rare but potentially sight-threatening complication of peribulbar anesthesia. Diagnosis can be challenging because of the infrequency of occurrence and delays in presentation. A high index of suspicion is key alongside consideration of other likely differentials.

Gene-Based Therapeutics for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber's congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.

Mesenteric venous thrombosis: A lethal complication of hyperglycemic crises.

PURPOSE: Although hyperglycemic crises can lead to a hypercoagulable state, few instances of associated mesenteric venous thrombosis (MVT) have been reported. Worsening abdominal pain in the context of shock requiring vasopressor support should prompt urgent further investigation. SUMMARY: A 44-year-old Hispanic male arrived at an emergency department with chief complaints of lethargy, polydipsia, and polyuria. His past medical history included type 2 diabetes, epilepsy, obesity, tobacco smoking, and noncompliance with his medications. On arrival the patient had a serum glucose concentration of >1,600 mg/dL, and hyperosmolar hyperglycemic syndrome (HHS) was diagnosed. The patient was admitted to the intensive care unit with respiratory failure and subsequently developed shock refractory to fluid resuscitation, necessitating vasopressor support. On hospital day 4, a computerized tomogram obtained for investigation of increasing abdominal tenderness revealed superior MVT and pneumatosis intestinalis. Despite an emergency laparotomy and enterectomy, the patient ultimately succumbed on hospital day 41 due to recurrent pneumonia complicated by acute respiratory distress syndrome and septic shock. CONCLUSION: Shock that is refractory to aggressive fluid resuscitation, necessitating pressor support, in the setting of HHS or diabetic ketoacidosis should prompt investigation for the underlying source of shock. Other etiologies, including hypovolemic, cardiogenic, and obstructive shock, should be considered; however, infection is the leading trigger of hyperglycemic crises. Although rarely reported, MVT should be considered in the diagnostic algorithm in the absence of an identified infectious source. Prompt investigation should include use of diagnostic modalities such as computed tomography to assess for MVT.

Impact of tocilizumab administration on mortality in severe COVID-19.

The novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to an aberrant inflammatory response or cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19. A single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality. A total of 274 patients meeting inclusion and exclusion criteria were identified and 132 patients were included in the matched dataset (tocilizumab = 66; no tocilizumab = 66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group (odds ratio, 1.0; 95% confidence interval, 0.465 - 2.151; p = 1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.

Intravitreal Injection with a Conjunctival Injection Device: A Single-Center Experience.

Purpose: To evaluate the clinical performance of the intravitreal injection assistant device (InVitria) compared with the conventional freehand technique for delivering intravitreal injections. Methods: Seventy patients were randomized to receive intravitreal injections via the conventional freehand technique while 70 received injections using the InVitria. Half of all procedures in each group were performed by junior surgeons, while the rest were performed by senior surgeons. Results: Mean injections times were 90.0 ± 23.3 seconds and 64.9 ± 26.8 seconds for conventional versus InVitria (P < 0.001). Mean injection times with the conventional technique were 85.5 ± 23.0 seconds vs. 94.2 ± 23.0 seconds for senior versus junior surgeons (P = 0.120). Mean injection times with the InVitria were 56.1 ± 26.1 seconds vs. 66.3 ± 26.9 seconds (P = 0.211) for senior versus junior surgeons. There were no significant differences in pain scores regardless of technique (conventional versus In Vitria: 2.03 ± 1.73 vs. 2.13 ± 2.20, P = 0.770). Conclusions: In our experience, the InVitria is a comparable alternative to the conventional freehand technique of delivering intravitreal injections, with the potential for faster injection times and without compromising on patient comfort. Translational Relevance: The study provides evidence to suggest that the InVitria may be deployed effectively in clinical practice.

Design, implementation, and evaluation of a nurse-led intravitreal injection programme for retinal diseases in Singapore.

BACKGROUND: To describe the design, implementation, and evaluation of a nurse-led intravitreal injection (NL-IVT) programme in a Singapore tertiary eye hospital. METHODS: Patients requiring anti-vascular endothelial growth factor (VEGF) IVT were recruited. Implementation and evaluation were done in the Singapore National Eye Centre, a tertiary centre. To assess safety, nurse injectors recorded details of procedures performed and complications for an 8-month period from February 2019. To evaluate patient experience, we used a modified patient questionnaire and recorded both patients' waiting time and IVT procedure duration. A retrospective audit of IVTs before and after the introduction of NL-IVT was performed from January 2017 to September 2019. Cost difference between NL-IVT and standard doctor-led (DL) IVT was evaluated. RESULTS: A total of 8599 NL-IVTs were performed. No cases of severe complication were detected in the follow-up. A total of 135 patients who received NL-IVT and DL-IVT were surveyed. General satisfaction, interpersonal manner, financial aspect, time spent with injector, and staff competence were higher in NL-IVTs than in DL-IVTs (p < 0.05). There were no differences in terms of technical quality and communication. For 934 patients, waiting time was significantly shorter in NL-IVT (3.6 ± 10.3 min) compared with DL-IVTs (35.3 ± 32.3 min); on average, 19.7 min were saved through NL-IVT (p < 0.01). The cost difference per IVT between NL-IVT and DL-IVT is estimated at 286 SGD (163 GBP). CONCLUSION: With a well-designed training programme, NL-IVT is a safe, acceptable, and cost savings procedure. With increasing demand for IVT, NL-IVT provides an alternative model of care for healthcare systems globally.