2021

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Abbasi B, Rizzo JF. Advances in Neuroscience, Not Devices, Will Determine the Effectiveness of Visual Prostheses. Semin Ophthalmol 2021;:1-8.Abstract
Innovations in engineering and neuroscience have enabled the development of sophisticated visual prosthetic devices. In clinical trials, these devices have provided visual acuities as high as 20/460, enabled coarse navigation, and even allowed for reading of short words. However, long-term commercial viability arguably rests on attaining even better vision and more definitive improvements in tasks of daily living and quality of life. Here we review technological and biological obstacles in the implementation of visual prosthetics. Research in the visual prosthetic field has tackled significant technical challenges, including biocompatibility, signal spread through neural tissue, and inadvertent activation of passing axons; however, significant gaps in knowledge remain in the realm of neuroscience, including the neural code of vision and visual plasticity. We assert that further optimization of prosthetic devices alone will not provide markedly improved visual outcomes without significant advances in our understanding of neuroscience.
Aboobakar IF, Friedman DS. Home Monitoring for Glaucoma: Current Applications and Future Directions. Semin Ophthalmol 2021;:1-5.Abstract
Technological advances provide a number of options for glaucoma monitoring outside the office setting, including home-based tonometry and perimetry. This has the potential to revolutionize management of this chronic disease, improve access to care, and enhance patient engagement. Here, we provide an overview of existing technologies for home-based glaucoma monitoring. We also discuss areas for future research and the potential applications of these technologies to telemedicine, which has been brought to the forefront during the ongoing COVID-19 pandemic.
Abu-El-Haija A, McGowan C, Vanderveen D, Bodamer O. Autosomal-dominant WFS1-related disorder-Report of a novel WFS1 variant and review of the phenotypic spectrum of autosomal recessive and dominant forms. Am J Med Genet A 2021;185(2):528-533.Abstract
Wolfram syndrome was initially reported as an autosomal recessive (AR), progressive neurodegenerative disorder that leads to diabetes insipidus, childhood onset diabetes mellitus (DM), optic atrophy, and deafness (D) also known as DIDMOAD. However, heterozygous dominant pathogenic variants in Wolfram syndrome type 1 (WFS1) may lead to distinct, allelic conditions, described as isolated sensorineural hearing loss (SNHL), syndromic SNHL, congenital cataracts, or early onset DM. We report a family with a novel dominant, likely pathogenic variant in WFS1 (NM_006005.3) c.2605_2616del12 (p.Ser869_His872del), resulting in cataracts, SNHL, and DM in a female and her mother. A maternal aunt had cataracts, DM, and SNHL but was not tested for the familial WFS1 mutation. Both the mother and maternal aunt had early menopause by age 43 years and infertility which may be a coincidental finding that has not been associated with autosomal dominant AD WFS1-related disorder to the best of our knowledge. Screening at risk individuals in families with the AR Wolfram syndrome, for DM, SNHL, and for cataracts is indicated.
Agrawal R, Testi I, Bodaghi B, Barisani-Asenbauer T, McCluskey P, Agarwal A, Kempen JH, Gupta A, Smith JR, De Smet MD, Yuen YS, Mahajan S, Kon OM, Nguyen QD, Pavesio C, Gupta V, Gupta V. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis. Ophthalmology 2021;128(2):277-287.Abstract
TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.
Agrawal R, Testi I, Mahajan S, Yuen YS, Agarwal A, Kon OM, Barisani-Asenbauer T, Kempen JH, Gupta A, Jabs DA, Smith JR, Nguyen QD, Pavesio C, Gupta V, Gupta V. Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis. Ophthalmology 2021;128(2):266-276.Abstract
TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.
Al-Lozi A, Cai S, Chen X, Perez VL, Venkateswaran N. Granulicatella Adiacens as an Unusual Cause of Microbial Keratitis and Endophthalmitis: A Case Series and Literature Review. Ocul Immunol Inflamm 2021;:1-5.Abstract
: To report two cases of microbial keratitis and/or endophthalmitis involving : Case series. : 24-year-old female with a history of Herpes simplex virus 1 (HSV-1) and keratitis presented with a geographic epithelial defect and infiltrate in the left eye. Cultures were positive for HSV-1 and . Keratitis resolved with topical vancomycin and oral valacyclovir. A 65-year-old female with a history of type II diabetes and failed therapeutic penetrating keratoplasty presented with inferior corneal graft haze and vitreous inflammation of the right eye. Therapeutic penetrating keratoplasty and pars plana vitrectomy were performed, and the corneal button returned positive for . The patient was treated with topical and intravitreal vancomycin as well as topical and systemic steroids. : These cases expand the literature on keratitis and endophthalmitis and corroborate the role of steroid use and prior surgery as paramount risk factors.
Ambrosio L, Williams JS, Gutierrez A, Swanson EA, Munro RJ, Ferguson DR, Fulton AB, Akula JD. Carbonic anhydrase inhibition in X-linked retinoschisis: An eye on the photoreceptors. Exp Eye Res 2021;202:108344.Abstract
The retinoschisin protein is encoded on the short arm of the X-chromosome by RS1, is expressed abundantly in photoreceptor inner segments and in bipolar cells, and is secreted as an octamer that maintains the structural integrity of the retina. Mutations in RS1 lead to X-linked retinoschisis (XLRS), a disease characterized by the formation of cystic spaces between boys' retinal layers that frequently present in ophthalmoscopy as a "spoke-wheel" pattern on their maculae and by progressively worsening visual acuity (VA). There is no proven therapy for XLRS, but there is mixed evidence that carbonic anhydrase inhibitors (CAIs) produce multiple beneficial effects, including improved VA and decreased volume of cystic spaces. Consequently, linear mixed-effects (LME) models were used to evaluate the effects of CAI therapy on VA and central retinal thickness (CRT, a proxy for cystic cavity volume) in a review of 19 patients' records. The mechanism of action of action of CAIs is unclear but, given that misplaced retinoschisin might accumulate in the photoreceptors, it is possible-perhaps even likely-that CAIs act to benefit the function of photoreceptors and the neighboring retinal pigment epithelium by acidification of the extracellular milieu; patients on CAIs have among the most robust photoreceptor responses. Therefore, a small subset of five subjects were recruited for imaging on a custom multimodal adaptive optics retinal imager for inspection of their parafoveal cone photoreceptors. Those cones that were visible, which numbered far fewer than in controls, were enlarged, consistent with the retinoschisin accumulation hypothesis. Results of the LME modeling found that there is an initial benefit to both VA and CRT in CAI therapy, but these wane, in both cases, after roughly two years. That said, even a short beneficial effect of CAIs on the volume of the cystic spaces may give CAI therapy an important role as pretreatment before (or immediately following) administration of gene therapy.
Ambrosio L, Hansen RM, Moskowitz A, Oza A, Barrett D, Manganella J, Medina G, Kawai K, Fulton AB, Kenna M. Dark-adapted threshold and electroretinogram for diagnosis of Usher syndrome. Doc Ophthalmol 2021;Abstract
PURPOSE: To determine the utility of ophthalmology evaluation, dark-adapted threshold, and full-field electroretinogram for early detection of Usher syndrome in young patients with bilateral sensorineural hearing loss. METHODS: We identified 39 patients with secure genetic diagnoses of Usher Syndrome. Visual acuity, spherical equivalent, fundus appearance, dark-adapted threshold, and full-field electroretinogram results were summarized and compared to those in a group of healthy controls with normal hearing. In those Usher patients with repeated measures, regression analysis was done to evaluate for change in visual acuity and dark-adapted threshold with age. Spherical equivalent and full-field electroretinogram responses from dark- and light-adapted eyes were evaluated as a function of age. RESULTS: The majority of initial visual acuity and spherical equivalent results were within normal limits for age. Visual acuity and dark-adapted threshold worsened significantly with age in Usher type 1 but not in Usher type 2. At initial test, full-field electroretinogram responses from dark- and light-adapted eyes were abnormal in 53% of patients. Remarkably, nearly half of our patients (17% of Usher type 1 and 30% of Usher type 2) would have been missed by tests of retinal function alone if evaluated before age 10. CONCLUSIONS: Although there is an association of abnormal dark-adapted threshold and full-field electroretinogram at young ages in Usher patients, it appears that a small but important proportion of patients would not be detected by tests of retinal function alone. Thus, genetic testing is needed to secure a diagnosis of Usher syndrome.
André C, Durand ML, Buckley T, Cadorette J, Gilmore MS, Ciolino JB, Bispo PJM. A Cluster of Corneal Donor Rim Cultures Positive for Achromobacter Species Associated With Contaminated Eye Solution. Cornea 2021;40(2):223-227.Abstract
PURPOSE: To investigate a cluster of corneoscleral rim cultures positive for Achromobacter species over a 6-month period at Massachusetts Eye and Ear. METHODS: An increased rate of positive corneal donor rim cultures was noted at Massachusetts Eye and Ear between July and December 2017. Positive cultures were subjected to identification and antimicrobial susceptibility testing by phenotypic (MicroScan WalkAway) and genotypic (16S rDNA sequencing) methods. Samples of the eye wash solution (GeriCare) used in the eye bank were also evaluated. Antimicrobial activity of Optical-GS against Achromobacter spp. at 4°C and 37°C was assessed by time-kill kinetics assay. RESULTS: Of 99 donor rims cultured, 14 (14.1%) grew bacteria with 11 (78.6%) due to uncommon nonfermenting Gram-negative bacilli. These had been identified by standard automated methods as Achromobacter (n = 3), Alcaligenes (n = 3), Ralstonia (n = 2), Pseudomonas (n = 2), and Stenotrophomonas (n = 1). Eight of these 11 isolates were subsequently available for molecular identification, and all were identified as Achromobacter spp. Six bottles of eyewash solution were evaluated and were positive for abundant Achromobacter spp. (3.4 × 105 ± 1.1 CFU/mL). Optisol-GS had no bactericidal activity against Achromobacter spp. at 4°C after 24-hour incubation but was bactericidal at 37°C. None of the patients who had received the contaminated corneas developed postoperative infection. CONCLUSIONS: An eyewash solution arising from a single lot was implicated in the contamination of donor rims by Achromobacter spp. The isolates were able to survive in the Optisol-GS medium at the recommended storage temperature. This highlights the need to continue improving protocols for tissue preparation and storage.
Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nat Rev Endocrinol 2021;Abstract
Diabetes mellitus has profound effects on multiple organ systems; however, the loss of vision caused by diabetic retinopathy might be one of the most impactful in a patient's life. The retina is a highly metabolically active tissue that requires a complex interaction of cells, spanning light sensing photoreceptors to neurons that transfer the electrochemical signal to the brain with support by glia and vascular tissue. Neuronal function depends on a complex inter-dependency of retinal cells that includes the formation of a blood-retinal barrier. This dynamic system is negatively affected by diabetes mellitus, which alters normal cell-cell interactions and leads to profound vascular abnormalities, loss of the blood-retinal barrier and impaired neuronal function. Understanding the normal cell signalling interactions and how they are altered by diabetes mellitus has already led to novel therapies that have improved visual outcomes in many patients. Research highlighted in this Review has led to a new understanding of retinal pathophysiology during diabetes mellitus and has uncovered potential new therapeutic avenues to treat this debilitating disease.
Argüeso P. Galectins as Regulators of Corneal Inflammation. Curr Opin Physiol 2021;19:17-21.Abstract
The cornea is a transparent avascular tissue on the anterior segment of the eye responsible for providing refractive power and forming a protective barrier against the external environment. Infectious and inflammatory conditions can compromise the structure of the cornea, leading to visual impairment and blindness. Galectins are a group of β-galactoside-binding proteins expressed by immune and non-immune cells that play pivotal roles in innate and adaptive immunity. In this brief review, we discuss how different members of this family of proteins affect both pro-inflammatory and anti-inflammatory responses in the cornea, particularly in the context of infection, transplantation and wound healing. We further describe recent research showing beneficial effects of galectin-targeted therapy in corneal diseases.
Armstrong GW, Kalra G, De Arrigunaga S, Friedman DS, Lorch AC. Anterior Segment Imaging Devices in Ophthalmic Telemedicine. Semin Ophthalmol 2021;:1-8.Abstract
Obtaining a clear assessment of the anterior segment is critical for disease diagnosis and management in ophthalmic telemedicine. The anterior segment can be imaged with slit lamp cameras, robotic remote controlled slit lamps, cell phones, cell phone adapters, digital cameras, and webcams, all of which can enable remote care. The ability of these devices to identify various ophthalmic diseases has been studied, including cataracts, as well as abnormalities of the ocular adnexa, cornea, and anterior chamber. This article reviews the current state of anterior segment imaging for the purpose of ophthalmic telemedical care.
Armstrong GW, Kim LA, Vingopoulos F, Park J, Garg I, Kasetty M, Silverman RF, Zeng R, Douglas VP, Lopera F, Baena A, Giraldo M, Norton D, Cronin-Golomb A, Arboleda-Velasquez JF, Quiroz YT, Miller JB. Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms. JAMA Ophthalmol 2021;139(1):49-56.Abstract
Importance: Individuals with autosomal dominant mutations for Alzheimer disease are valuable in determining biomarkers present prior to the onset of cognitive decline, improving the ability to diagnose Alzheimer disease as early as possible. Optical coherence tomography (OCT) has surfaced as a potential noninvasive technique capable of analyzing central nervous system tissues for biomarkers of Alzheimer disease. Objective: To evaluate whether OCT can detect early retinal alterations in carriers of the presenilin 1 (PSEN1 [OMIM 104311]) E280A mutation who are cognitively unimpaired. Design, Setting, and Participants: A cross-sectional imaging study conducted from July 13, 2015, to September 16, 2020, included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired and 10 healthy noncarrier family members, all leveraged from a homogenous Colombian kindred. Statistical analysis was conducted from September 9, 2017, to September 16, 2020. Main Outcomes and Measures: Mixed-effects multiple linear regression was performed to compare the thickness values of the whole retina and individual retinal layers on OCT scans between mutation carriers and noncarriers. Simple linear-effects and mixed-effects multiple linear regression models were used to assess whether age was an effect modifier for PSEN1 mutation of amyloid β levels and retinal thickness, respectively. Fundus photographs were used to compare the number of arterial and venous branch points, arterial and venous tortuosity, and fractal dimension. Results: This study included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired (7 women [70%]; mean [SD] age, 36.3 [8.1] years) and 10 healthy noncarrier family members (7 women [70%]; mean [SD] age, 36.4 [8.2] years). Compared with noncarrier controls, PSEN1 mutation carriers who were cognitively unimpaired had a generalized decrease in thickness of the whole retina as well as individual layers detected on OCT scans, with the inner nuclear layer (outer superior quadrant, β = -3.06; P = .007; outer inferior quadrant, β = -2.60; P = .02), outer plexiform layer (outer superior quadrant, β = -3.44; P = .03), and outer nuclear layer (central quadrant, β = -8.61; P = .03; inner nasal quadrant, β = -8.39; P = .04; inner temporal quadrant, β = -9.39; P = .02) showing the greatest amount of statistically significant thinning. Age was a significant effect modifier for the association between PSEN1 mutation and amyloid β levels in cortical regions (β = 0.03; P = .001) but not for the association between PSEN1 mutation and retinal thickness. No statistical difference was detected in any of the vascular parameters studied. Conclusions and Relevance: These findings suggest that OCT can detect functional and morphologic changes in the retina of carriers of familial Alzheimer disease who are cognitively unimpaired several years before clinical onset, suggesting that OCT findings and retinal vascular parameters may be biomarkers prior to the onset of cognitive decline.
Arranz-Romera A, Hernandez M, Checa-Casalengua P, Garcia-Layana A, Molina-Martinez IT, Recalde S, Young MJ, Tucker BA, Herrero-Vanrell R, Fernandez-Robredo P, Bravo-Osuna I. A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies. Pharmaceuticals (Basel) 2021;14(1)Abstract
We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients' needs.
Arroyo JG, Seto B, Yamada K, Zeng K, Minturn R, Lemire CA. Rapid reduction of macular edema due to retinal vein occlusion with low-dose normobaric hyperoxia. Graefes Arch Clin Exp Ophthalmol 2021;Abstract
PURPOSE: We investigated the effects of a relatively inexpensive, non-invasive, short-term treatment with low-dose normobaric hyperoxia (NBH) on macular edema in patients with retinal vein occlusion (RVO). METHODS: Participants with macular edema associated with RVO were treated with 5 LPM of NBH via facemask (40% fraction of inspired oxygen, FIO2) for 3 h. Patients with non-fovea involving edema who elected to be observed returned for a second treatment 1 month later to test reproducibility. RESULTS: A 3-h session of NBH (n = 45) resulted in decreased maximum macular thickness (MMT) (mean 7.10%, t=9.63 P<.001) and central macular thickness (CMT) (mean 4.64%, t=6.90, P<.001) when compared to untreated eyes with RVO measured over the same period of time (n = 12) or their healthy fellow eye (n = 34; MMT:t=-9.60, P<.001;CMT: t=-6.72, P<.001). Patients who had a second NBH treatment 1 month later experienced a recurrence of their edema, but demonstrated a similar significant reduction in MMT and CMT after the second NBH treatment. CONCLUSIONS: Three-hour treatment with 40% FIO2 NBH results in a significant reduction in MMT and CMT. This study supports an ischemic mechanism for macular edema associated with retinal vein occlusion. TRANSLATIONAL RELEVANCE: Short-term low-dose normobaric hyperoxia is a simple, inexpensive, and ubiquitous treatment that may provide an alternate or adjunctive approach to treating macular edema in patients who are resistant to or cannot afford anti-VEGF medications.
Azad AD, Chen EM, Hinkle J, Rayess N, Wu D, Eliott D, Mruthyunjaya P, Parikh R. Anti-Vascular Endothelial Growth Factor and Panretinal Photocoagulation Use after Protocol S for Proliferative Diabetic Retinopathy. Ophthalmol Retina 2021;5(2):151-159.Abstract
PURPOSE: To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S. DESIGN: A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN). PARTICIPANTS: Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents. METHODS: Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015). MAIN OUTCOME MEASURES: Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR. RESULTS: From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n = 6379) were anti-VEGF agents, and 36.4% (n = 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β = -32 vs. post-Protocol S: -77; P = 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β = -48 vs. 161, respectively; P = 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β = -9 vs. -58 respectively; P = 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β = -57 vs. 187; P = 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β = -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β = -48 vs. 140, respectively; P < 0.001). CONCLUSIONS: Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.
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Baker TL, Greiner JV, Vesonder M. SARS-CoV-2 safety: Guidelines for shielding frontline nurses. Nursing 2021;51(3):32-42.Abstract
ABSTRACT: Protecting nurses in healthcare facilities from SARS-CoV-2 infection is essential for maintaining an adequate nursing force. Foundational guidelines, consistently utilized, protect the nursing staff from infection. This article describes guidelines designed to reduce acute infection and associated morbidity and mortality among nursing staff and improve compliance with infection prevention protocols.
Ballios BG, Pierce EA, Huckfeldt RM. Gene editing technology: Towards precision medicine in inherited retinal diseases. Semin Ophthalmol 2021;:1-9.Abstract
To review preclinical and clinical advances in gene therapy, with a focus on gene editing technologies, and application to inherited retinal disease. A narrative overview of the literature, summarizing the state-of-the-art in clinical gene therapy for inherited retinal disease, as well as the science and application of new gene editing technology. The last three years has seen the first FDA approval of an in vivo gene replacement therapy for a hereditary blinding eye disease and, recently, the first clinical application of an in vivo gene editing technique. Limitations and challenges in this evolving field are highlighted, as well as new technologies developed to address the multitude of molecular mechanisms of disease. Genetic therapy for the treatment of inherited retinal disease is a rapidly expanding area of ophthalmology. New technologies have revolutionized the field of genome engineering and rekindled an interest in precision medicines for these conditions.
Baumal CR, Sarraf D, Bryant T, Gui W, Muakkassa N, Pichi F, Querques G, Choudhry N, Teke MY, Govetto A, Invernizzi A, Eliott D, Gaudric A, Cunha de Souza E, Naysan J, Lembo A, Lee GC, Freund BK. Henle fibre layer haemorrhage: clinical features and pathogenesis. Br J Ophthalmol 2021;105(3):374-380.Abstract
BACKGROUND: To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented. METHODS: This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented. RESULTS: Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up. CONCLUSION: The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.
Benedi-Garcia C, Vinas M, Dorronsoro C, Burns SA, Peli E, Marcos S. Vision is protected against blue defocus. Sci Rep 2021;11(1):352.Abstract
Due to chromatic aberration, blue images are defocused when the eye is focused to the middle of the visible spectrum, yet we normally are not aware of chromatic blur. The eye suffers from monochromatic aberrations which degrade the optical quality of all images projected on the retina. The combination of monochromatic and chromatic aberrations is not additive and these aberrations may interact to improve image quality. Using Adaptive Optics, we investigated the optical and visual effects of correcting monochromatic aberrations when viewing polychromatic grayscale, green, and blue images. Correcting the eye's monochromatic aberrations improved optical quality of the focused green images and degraded the optical quality of defocused blue images, particularly in eyes with higher amounts of monochromatic aberrations. Perceptual judgments of image quality tracked the optical findings, but the perceptual impact of the monochromatic aberrations correction was smaller than the optical predictions. The visual system appears to be adapted to the blur produced by the native monochromatic aberrations, and possibly to defocus in blue.

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