Nontraditional approaches to sedation for anterior segment surgery: a narrative review.

PURPOSE OF REVIEW: Surgical and anesthetic technological advancement have made both cataract and noncataract anterior segment surgery significantly less invasive and time-intensive, facilitating the transition of some of these procedures from the operating room under monitored anesthesia care (MAC) to the office-based setting without MAC. This transition has been aided by the popularization of nonintravenous approaches to achieving patient sedation for these procedures. In this review, we discuss the literature surrounding traditional and nontraditional methods of achieving patient sedation for anterior segment surgery. RECENT FINDINGS: Our survey of the literature suggests that nonintravenous (IV) approaches to sedation for these procedures may be just as safe, effective, and satisfactory to patients as traditional IV approaches. SUMMARY: As anterior segment surgery becomes less invasive and less time-intensive, providers considering transitioning their cataract and anterior segment surgery out of the operating room and into the office-based setting without MAC anesthesia should consider the non-IV sedation options outlined in this review to achieve adequate patient sedation and comfort.

Cost Drivers of Endothelial Keratoplasty: A Time-Driven Activity-Based Costing Analysis.

PURPOSE: To determine cost drivers of endothelial keratoplasty (EK) through evaluation of surgical costs and procedure length based on type of EK, use of preloaded grafts, and performance of simultaneous cataract surgery. DESIGN: This study was an economic analysis of EKs at a single academic institution using time-driven activity-based costing (TDABC) methodology. PARTICIPANTS: Endothelial keratoplasty surgical cases, including Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK), at the University of Michigan Kellogg Eye Center from 2016 to 2018 were included in the analysis. METHODS: Data and inputs were obtained via the electronic health record (EHR) and from prior literature. Simultaneous cataract surgeries were included and separately categorized for analysis. Endothelial keratoplasty expenses were determined with TDABC, a method for cost calculation that incorporates the time that key resources are used and each resource's associated cost rate. MAIN OUTCOME MEASURES: Main outcome measures included surgery length (in minutes) and day-of-surgery costs. RESULTS: There were 559 EKs included: 355 DMEKs and 204 DSAEKs. Fewer DSAEKs had simultaneous cataract extraction (47; 23%) than DMEK (169; 48%). Of the DMEKs, 196 (55%) used preloaded corneal grafts. Descemet membrane endothelial keratoplasty cost $392.31 less (95% confidence interval, $251.05-$533.57; P < 0.0001) than DSAEK and required 16.94 fewer minutes (14.16-19.73; P < 0.0001). Descemet membrane endothelial keratoplasty cases that used preloaded corneal grafts cost $460.19 less ($316.23-$604.14; P < 0.0001) and were 14.16 minutes shorter (11.39-16.93; P < 0.0001). In multivariate regression, preloaded graft use saved $457.19, DMEK (compared with DSAEK) saved $349.97, and simultaneous cataract surgery added $855.17 in day-of-surgery costs. CONCLUSIONS: Cost analysis of TDABC identified a day-of-surgery cost and surgical time reduction associated with the use of preloaded grafts for DMEK, DMEK compared with DSAEK, and isolated EK compared with EK combined with cataract surgery. This study provides an improved understanding of surgical cost drivers and margin incentivization, which may explain trends and indirectly influence patient care decisions in cornea surgery practices. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

DDX58(RIG-I)-related disease is associated with tissue-specific interferon pathway activation.

BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.

Impact of vaccination on keratoplasty.

PURPOSE OF REVIEW: Corneal graft rejection has been reported after coronavirus disease 2019 (COVID-19) vaccination. The purpose of this review is to evaluate the literature regarding corneal graft rejection after vaccination, including rejection rates and risk factors. We aim to create a framework to identify patients who are at higher risk for graft rejection and may warrant consideration of prophylactic interventions. RECENT FINDINGS: Graft rejection has been reported following administration of mRNA, viral vector, and inactivated whole-virion COVID-19 vaccines. Most cases had additional risk factors associated with rejection. Vaccination increases circulation of proinflammatory cytokines, CD4+ and CD8+ T-cell responses, and antispike neutralizing antibody, all of which may contribute to graft rejection. Two prospective studies have found no relationship between recent vaccination and rejection but 20% of cornea specialists report to have seen a vaccine-associated rejection and 22% recommend delaying vaccination in certain circumstances. Many specialists recommend prophylactic topical corticosteroids before and after vaccination to mitigate rejection risk but there is no evidence to support this practice on a wider scale. SUMMARY: Our framework identified 96.8% of penetrating keratoplasty patients with vaccine-associated rejection as higher risk. Further research is needed in order to develop evidence-based guidelines.

Pilocarpine 1.25% and the changing landscape of presbyopia treatment.

PURPOSE OF REVIEW: Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). RECENT FINDINGS: Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. SUMMARY: Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Clinical outcomes and visual prognostic factors in congenital aniridia.

BACKGROUND: Evaluate outcomes and identify prognostic factors in congenital aniridia. METHODS: Retrospective interventional case series of patients with congenital aniridia treated between 2012-2020. Ocular examination and surgical details were collected. Surgical failure was defined as disease progression or need for additional surgery for same/related indication. Kaplan-Meier survival curves, Wilcoxon test, and univariate and multivariate linear regression analyses were performed. RESULTS: Ninety-four patients with congenital aniridia presented at median 19.0 years. Two-thirds of patients underwent ≥ 1intraocular surgery, with average of 1.7 ± 2.3 surgeries/eye. At final follow-up (median 4.0 years), 45% of eyes had undergone lensectomy. Aphakic eyes showed worse visual acuity (VA) than phakic or pseudophakic eyes. Glaucoma affected 52% of eyes, of which half required IOP-lowering surgery. Glaucoma drainage devices showed the highest success rate (71%) at 14.2 ± 15.4 years of follow-up. Keratopathy affected 65% of eyes and one-third underwent corneal surgery. Keratoprosthesis had the longest survival rates at 10-years (64% with 95% CI [32,84]). LogMAR VA at presentation and final follow-up were not statistically different. Half of patients were legally blind at final follow-up. Final VA was associated with presenting VA, glaucoma diagnosis, and cataract or keratopathy at presentation. Penetrating keratoplasty and keratoprosthesis implantation correlated with worse BCVA. CONCLUSIONS: Most aniridic patients in this large US-based cohort underwent at least 1 intraocular surgery. Cataract, glaucoma, and keratopathy were associated with worse VA and are important prognostic factors to consider when managing congenital aniridia.

Updated safety precautions and guidance on eye banking procedures during the coronavirus disease 2019 pandemic.

PURPOSE OF REVIEW: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious coronavirus causing the COVID-19 pandemic. Although airborne spread through infectious respiratory droplets is the primary source of transmission, recent literature has suggested the ocular surface may be able to harbor viral particles. Here, we aim to discuss how SARS-CoV-2 affects the ocular surface and updated guidance on how SARS-CoV-2 transmission should be considered in the setting of eye banking and corneal transplantation procedures. RECENT FINDINGS: SARS-CoV-2 RNA can be found on the ocular surface, which may suggest the eye as a site of viral replication. However, there is poor correlation between PCR positivity on the ocular surface and ocular symptoms. To date, although viral particles can be found on the ocular surface, use of standard antiseptic procedures during corneal tissue procurement appears to sufficiently reduce viral load. In addition, preprocedure testing may further decrease the chances of transplanting an infected cornea without significantly impacting the overall accessibility to corneal tissue by decreasing the donor pool. SUMMARY: Corneal transplantation remains a well tolerated and highly successful procedure with no evidence of viral transmission with transplantation. Although the ocular surface has the required receptors to allow for viral replication, there is no clear evidence that the eye is a site for primary viral infection.

Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes.

Although squamous cell carcinomas (SCC) are the most frequent human solid tumor at many anatomic sites, the driving molecular alterations underlying their progression from precursor lesions are poorly understood, especially in the context of photodamage. Therefore, we used high-depth, targeted next-generation sequencing (NGS) of RNA and DNA from routine tissue samples to characterize the progression of both well- (cutaneous) and poorly (ocular) studied SCCs. We assessed 56 formalin-fixed paraffin-embedded (FFPE) cutaneous lesions (n = 8 actinic keratosis, n = 30 carcinoma in situ [CIS], n = 18 invasive) and 43 FFPE ocular surface lesions (n = 2 conjunctival/corneal intraepithelial neoplasia, n = 20 CIS, n = 21 invasive), from institutions in the US and Brazil. An additional seven cases of advanced cutaneous SCC were profiled by hybrid capture-based NGS of >1500 genes. The cutaneous and ocular squamous neoplasms displayed a predominance of UV-signature mutations. Precursor lesions had highly similar somatic genomic landscapes to SCCs, including chromosomal gains of 3q involving SOX2, and highly recurrent mutations and/or loss of heterozygosity events affecting tumor suppressors TP53 and CDKN2A. Additionally, we identify a novel molecular subclass of CIS with RB1 mutations. Among TP53 wild-type tumors, human papillomavirus transcript was detected in one matched pair of cutaneous CIS and SCC. Amplicon-based whole-transcriptome sequencing of select 20 cutaneous lesions demonstrated significant upregulation of pro-invasion genes in cutaneous SCCs relative to precursors, including MMP1, MMP3, MMP9, LAMC2, LGALS1, and TNFRSF12A. Together, ocular and cutaneous squamous neoplasms demonstrate similar alterations, supporting a common model for neoplasia in UV-exposed epithelia. Treatment modalities useful for cutaneous SCC may also be effective in ocular SCC given the genetic similarity between these tumor types. Importantly, in both systems, precursor lesions possess the full complement of major genetic changes seen in SCC, supporting non-genetic drivers of invasiveness.

Eye banking in the coronavirus disease 2019 era.

PURPOSE OF REVIEW: Coronavirus disease 2019, caused by novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly infectious; however, the different routes of transmission are not well understood. Transmission through tissue transplantation is possible and must be considered. This review will evaluate the current literature regarding routes of transmission, the likelihood of transmission through ocular tissue transplantation, and the guidelines in place to mitigate this risk. RECENT FINDINGS: Although respiratory droplets have been the primary route of SARS-CoV-2 transmission, there is evidence that transmission through blood donation and organ or tissue transplantation is possible. This includes corneal transplantation, as SARS-CoV-2 has been detected in conjunctival swabs of infected patients, and the ocular surface may play an important role in viral entry. Several tissue transplantation organizations have guidelines in place regarding the screening of donors and tissue procurement procedures, including clinical and/or PCR screening of donors. The Eye Bank Association of America (EBAA) is currently not recommending asymptomatic PCR screening. However, their antiseptic protocols may play an important role in viral inactivation. SUMMARY: Based on the current literature and guidelines, the risk of SARS-CoV-2 transmission through corneal transplantation is likely low. However, tissue screening guidelines need to be re-evaluated regularly as knowledge regarding the SARS-CoV-2 virus evolves.

Refractive approaches to visual rehabilitation in patients with keratoconus.

PURPOSE OF REVIEW: As keratoconus is a chronic disease affecting young people, vision-related quality of life is often significantly impaired in patients with this disease. However, successful management of keratoconus, including visual rehabilitation strategies, can improve quality of life in these patients. This review will describe clinical approaches that improve vision-related quality of life in patients with stable keratoconus. RECENT FINDINGS: Several types of contact lenses including scleral lenses have been used successfully to manage keratoconus. Eyes with severe keratoconus, even those in which fitting with other types of lenses is challenging, can be successfully fitted with scleral lenses. Although laser ablative procedures, such as photorefractive keratectomy (PRK) have been traditionally contraindicated in patients diagnosed with or suspected of having keratoconus, PRK has been attempted to partially correct refractive errors in keratoconus. Although phototherapeutic keratectomy and radial keratotomy have been reported to be used in eyes with keratoconus, effectiveness and safety results have varied. Implantation of phakic intraocular lenses and intraocular lenses, including toric intraocular lenses, which primarily correct regular astigmatism, with cataract extraction or refractive lens exchange can improve vision-related quality of life in patients with keratoconus by significantly reducing cylinder while improving uncorrected visual acuity. SUMMARY: Appropriate selection and application of treatment options based on consideration of multiple factors will help patients with keratoconus, improving their vision-related quality of life and delaying or avoiding keratoplasty.

Update on Descemet membrane endothelial keratoplasty.

PURPOSE OF REVIEW: To provide an update on new perspectives on Descemet membrane endothelial keratoplasty (DMEK). RECENT FINDINGS: Preloaded DMEK grafts allow optimization of DMEK surgery time and reduce costs of the procedure, which is allowing the procedure to become more easily performed as reflected in the increasing number of cases. The surgical technique in the United States differs from the technique in Europe, but outcomes have been similar. Hemi-DMEK and quarter-DMEK have shown similar outcomes to conventional DMEK with respect to corneal transparency and visual acuity. Three-year follow-up of hemi-DMEK has also shown stability in endothelial cell count while maintaining corneal transparency. SUMMARY: DMEK is becoming more accepted as the procedure of choice for treating endothelial failure. However, challenges with the surgical technique have limited wider implementation of this lamellar corneal transplantation. Preloaded DMEK provides one solution for the surgical challenges associated with the procedure while also reducing costs. Variations in the surgical technique for DMEK, including hemi-DMEK and quarter-DMEK, allow for central corneal clarity similar to traditional DMEK, but both result in lower endothelial cell density (ECD).

Adenoviral keratitis: a review of the epidemiology, pathophysiology, clinical features, diagnosis, and management.

PURPOSE OF REVIEW: Adenoviral keratitis is a common and bothersome ocular infection that produces a lot of burden on healthcare systems and patients. The goal of this article is to provide a review of the topic, with an emphasis on current attempts at advancing strategies in diagnosis and management. RECENT FINDINGS: Sixty-eight articles and one textbook published on adenoviral keratitis were reviewed. The findings on the epidemiology, pathophysiology, clinical features, diagnosis, and management were summarized. Any contradicting opinions for which the literature was unclear were either omitted or recorded as lacking strong evidence. SUMMARY: Although significant effort has been made to develop new methods for diagnosis and management, adenoviral keratitis is predominantly diagnosed clinically with prevention being the mainstay of management. The use of newer DNA analysis techniques and topical anti-inflammatory agents for treatment of corneal infiltrates show promising results, but a better understanding of the pathogenesis and clinical features can lead to more targeted methods of diagnosis and therapy.

Donor cornea tissue in cases of drowning or water submersion: eye banks practice patterns and tissue outcomes.

Surgical use of donor corneal tissue from victims of water submersion (drowning or submersion secondary to death) remains controversial due to limited evidence about the quality of these tissues. To assess the safety of donor corneal tissue from victims of water submersion, an investigation of eye banks' practice patterns and tissue outcomes was conducted. All 79 Eye Bank Association of America accredited eye banks were contacted for a phone interview of practices regarding tissue from victims of water submersion. A retrospective review of corneal tissues from 2014 to 2016 from a large eye bank network was performed to identify all donors submerged in water. Corneal epithelial integrity, endothelial cell density (ECD), rim cultures, and adverse events were analyzed for associations with water submersion characteristics. 49 eye banks (62% response) participated in the survey. 55% of these eye banks had specific, written protocol for tissue eligibility from donors submerged in water. With or without specific protocol, eye banks reported considering water type (84%) and length of time submerged (92%) to determine eligibility. 22% of eye banks reported medical director involvement when eligibility determination was unclear. 79 tissues from 40 donors who were submerged were identified in 2014-2016 eye bank data. No donor tissues had pre-processing corneal infiltrates, positive rim cultures, or adverse events post-keratoplasty. Corneal epithelial integrity and ECD were not associated with water type or length of time submerged. In conclusion, data from a large eye bank network showed no adverse events or outcomes, indicating these tissues may be safe.

Recurrent Corneal Erosions in Corneal Dystrophies: a Review of the Pathogenesis, Differential Diagnosis, and Therapy.

INTRODUCTION: Recurrent corneal erosions in corneal dystrophies are visually significant and bothersome to patients. The goal of this article is to review the pathogenesis, differential diagnosis, and management of recurrent corneal erosions in corneal dystrophies. PATIENTS AND METHODS: Forty-eight articles and 1 textbook recently published on corneal erosions in corneal dystrophies were reviewed. The findings on the pathogenesis and clinical characteristics of erosions in each dystrophy were summarized. Any contradicting opinions for which the literature was unclear were either omitted or recorded as lacking strong evidence. RESULTS AND CONCLUSIONS: The epithelial-stromal complex plays an important role in the pathogenesis of erosions in corneal dystrophies. The clinical features of each corneal dystrophy guide their diagnosis and management. A better understanding of the pathogenesis and clinical features of erosions in corneal dystrophies can lead to better clinical outcomes.