Vira J, Marchese A, Singh RB, Agarwal A. Swept-source optical coherence tomography imaging of the retinochoroid and beyond. Expert Rev Med Devices 2020;17(5):413-426.Abstract
: Swept-source optical coherence tomography (SS-OCT) imaging has ushered in an era of rapid and high-resolution imaging of the retinochoroid that provides detailed patho-anatomy of various layers.: In this detailed review, the technology of swept-source imaging including its principles and working has been discussed. The applications of SS-OCT in various conditions including age-related macular degeneration, diabetic retinopathy, pachychoroid spectrum of diseases, and inflammatory vitreoretinal conditions have been elaborated. For each disease, a brief review of literature along with the utility of SS-OCT and optical coherence tomography angiography has been provided with supporting figures. The advantages of SS-OCT over spectral-domain have been discussed if there is sufficient evidence in the literature. Finally, the review summarizes the technological advantages in this field of retinal imaging.: The introduction of SS-OCT in our clinics has added newer devices in our armamentarium that can provide high-quality images of the deep retina and choroid. These advances in medical devices can help in improving our knowledge relating to the pathophysiology of diseases and their evolution. In the near future, rapid and high-resolution imaging may provide real-time volumetric information of the whole retina and the choroid that can be readily used for patient care.
Dohlman JC, Habib LA, Cunnane ME, Yoon MK. Subperiosteal Masqueraders as Compared to Subperiosteal Abscess: Contrasting Clinical Presentation and Radiographic Densities. Ophthalmic Plast Reconstr Surg 2020;36(6):596-600.Abstract
PURPOSE: Subperiosteal orbital lesions are most commonly abscesses secondary to sinusitis but, in rare cases, may represent other processes. Here, the authors compare the clinical and radiographic presentation of subperiosteal abscesses and alternate subperiosteal processes ("masqueraders") in an effort to establish distinguishing preoperative diagnostic criteria. METHODS: A retrospective chart review of cases of subperiosteal orbital lesions that underwent surgical intervention over a 3-year period was performed. The medical records of 6 cases of subperiosteal masqueraders and 6 cases of abscesses were reviewed for the clinical course, imaging (including radiographic density of lesions), and pathology. Clinical and radiographic features of the 2 groups were compared. RESULTS: All cases presented with orbital signs on exam. Fever and leukocytosis were absent in the masquerader group and present in 3 patients from the abscess group. Common radiographic findings in both groups included a rim-enhancing convex mass along the orbital wall and adjacent sinus opacification, often with bony dehiscence. Of the masqueraders, the final diagnosis was hematoma in 3 cases, mucocele in 1, and malignancy in 2. The difference between the mean radiodensity of the subperiosteal abscesses, 38 ± 5 Hounsfield units (95% CI, 34-42), as compared with the average radiodensity of the masqueraders, 71 ± 5 Hounsfield units (95% CI, 67-75), was significant (p = 0.042). Comparing radiodensity of the orbital lesion to adjacent sinus lesions and metastatic lesions elsewhere was also informative in establishing the diagnosis. CONCLUSIONS: Radiographic features, particularly radiodensity, may help distinguish subperiosteal abscesses from other lesions and aid in preoperative diagnosis and management.
McColgan NM, Feeley MN, Woodward AM, Guindolet D, Argüeso P. The O-GlcNAc modification promotes terminal differentiation of human corneal epithelial cells. Glycobiology 2020;30(11):872-880.Abstract
Dynamic modification of nuclear and cytoplasmic proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) plays an important role in orchestrating the transcriptional activity of eukaryotic cells. Here, we report that the O-GlcNAc modification contributes to maintaining ocular surface epithelial homeostasis by promoting mucin biosynthesis and barrier function. We found that induction of human corneal epithelial cell differentiation stimulated the global transfer of O-GlcNAc to both nuclear and cytosolic proteins. Inflammatory conditions, on the other hand, were associated with a reduction in the expression of O-GlcNAc transferase at the ocular surface epithelia. Loss- and gain-of-function studies using small interfering RNA targeting O-GlcNAc transferase, or Thiamet G, a selective inhibitor of O-GlcNAc hydrolase, respectively, revealed that the presence of O-GlcNAc was necessary to promote glycocalyx barrier function. Moreover, we found that Thiamet G triggered a correlative increase in both surface expression of MUC16 and apical epithelial cell area while reducing paracellular permeability. Collectively, these results identify intracellular protein O-glycosylation as a novel pathway responsible for promoting the terminal differentiation of human corneal epithelial cells.
Wolfe JM. Visual Search: How Do We Find What We Are Looking For?. Annu Rev Vis Sci 2020;6:539-562.Abstract
In visual search tasks, observers look for targets among distractors. In the lab, this often takes the form of multiple searches for a simple shape that may or may not be present among other items scattered at random on a computer screen (e.g., Find a red T among other letters that are either black or red.). In the real world, observers may search for multiple classes of target in complex scenes that occur only once (e.g., As I emerge from the subway, can I find lunch, my friend, and a street sign in the scene before me?). This article reviews work on how search is guided intelligently. I ask how serial and parallel processes collaborate in visual search, describe the distinction between search templates in working memory and target templates in long-term memory, and consider how searches are terminated.
Cousins CC, Pan BX, Chou JC, Shen LQ, Gordon MO, Kass MA, Ritch R, Pasquale LR. Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study. Am J Ophthalmol 2020;217:10-19.Abstract
PURPOSE: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective cross-sectional study of prospectively collected images. METHODS: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. RESULTS: Mean (SD) ΔA and ΔV were -2.2 (8.7) and -11.4 (9.7) pixel intensity units, respectively (P < .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥ .92) or between DH events with and without POAG (P ≥ .26). CONCLUSIONS: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.
Hysi PG, Choquet H, Khawaja AP, Wojciechowski R, Tedja MS, Yin J, Simcoe MJ, Patasova K, Mahroo OA, Thai KK, Cumberland PM, Melles RB, Verhoeven VJM, Vitart V, Segre A, Stone RA, Wareham N, Hewitt AW, Mackey DA, Klaver CCW, Macgregor S, for and Myopia CRE, Khaw PT, Foster PJ, and Consortium UKEV, Guggenheim JA, Guggenheim JA, Rahi JS, Jorgenson E, Hammond CJ. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat Genet 2020;52(4):401-407.Abstract
Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future.
Hui P-C, Shtyrkova K, Zhou C, Chen X, Chodosh J, Dohlman CH, Paschalis EI. Implantable self-aligning fiber-optic optomechanical devices for in vivo intraocular pressure-sensing in artificial cornea. J Biophotonics 2020;13(7):e202000031.Abstract
Artificial cornea is an effective treatment of corneal blindness. Yet, intraocular pressure (IOP) measurements for glaucoma monitoring remain an urgent unmet need. Here, we present the integration of a fiber-optic Fabry-Perot pressure sensor with an FDA-approved keratoprosthesis for real-time IOP measurements using a novel strategy based on optical-path self-alignment with micromagnets. Additionally, an alternative noncontact sensor-interrogation approach is demonstrated using a bench-top optical coherence tomography system. We show stable pressure readings with low baseline drift (<2.8 mm Hg) for >4.5 years in vitro and efficacy in IOP interrogation in vivo using fiber-optic self-alignment, with good initial agreement with the actual IOP. Subsequently, IOP drift in vivo was due to retroprosthetic membrane (RPM) formation on the sensor secondary to surgical inflammation (more severe in the current pro-fibrotic rabbit model). This study paves the way for clinical adaptation of optical pressure sensors with ocular implants, highlighting the importance of controlling RPM in clinical adaptation.
Chang W-C, Abe R, Anderson P, Anderson W, Ardern-Jones MR, Beachkofsky TM, Bellón T, Biala AK, Bouchard C, Cavalleri GL, Chapman N, Chodosh J, Choi HK, Cibotti RR, Divito SJ, Dewar K, Dehaeck U, Etminan M, Forbes D, Fuchs E, Goldman JL, Holmes JH, Hope EA, Hung S-I, Hsieh C-L, Iovieno A, Jagdeo J, Kim MK, Koelle DM, Lacouture ME, Le Pallec S, Lehloenya RJ, Lim R, Lowe A, McCawley J, McCawley J, Micheletti RG, Mockenhaupt M, Niemeyer K, Norcross MA, Oboh D, Olteanu C, Pasieka HB, Peter J, Pirmohamed M, Rieder M, Saeed HN, Shear NH, Shieh C, Straus S, Sukasem C, Sung C, Trubiano JA, Tsou S-Y, Ueta M, Volpi S, Wan C, Wang H, Wang Z-Q, Weintraub J, Whale C, Wheatley LM, Whyte-Croasdaile S, Williams KB, Wright G, Yeung SN, Zhou L, Chung W-H, Phillips EJ, Carleton BC. SJS/TEN 2019: From science to translation. J Dermatol Sci 2020;Abstract
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.
Ung C, Gragoudas E. Checkpoint inhibitor-induced sarcoid choroidal granulomas. Am J Ophthalmol Case Rep 2020;18:100652.Abstract
Purpose: To present a novel case of sarcoid choroidal granulomas due to nivolumab therapy for metastatic cutaneous melanoma. Observations: A 55 year-old male with a history of stage III metastatic cutaneous melanoma treated by nivolumab presented with bilateral choroidal lesions. The ophthalmologic examination revealed bilateral creamy, yellow choroidal lesions with no ocular inflammation. The systemic workup revealed pulmonary sarcoidosis confirmed by biopsy. Conclusion: Nivolumab is an immune checkpoint inhibitor therapy used in the treatment of metastatic melanoma. With the increasing use of immune checkpoint inhibitors in patients with advanced melanoma, clinicians should be aware of this potential associated immune-related adverse event.
Marmamula S, Barrenkala NR, Challa R, Kumbam TR, Modepalli SB, Yellapragada R, Bhakki M, Khanna RC, Friedman DS. Uncorrected refractive errors for distance among the residents in 'homes for the aged' in South India-The Hyderabad Ocular Morbidity in Elderly Study (HOMES). Ophthalmic Physiol Opt 2020;40(3):343-349.Abstract
PURPOSE: To investigate the prevalence and risk factors of Uncorrected Refractive Errors (URE) for distance in elderly residents in 'homes for the aged' in Hyderabad, India. METHODS: Individuals aged ≥60 years and residing in 'homes for the aged' in Hyderabad, India for a minimum of 1 month and providing consent for participation were recruited. All participants underwent visual acuity assessment, refraction, slit lamp biomicroscopy, intraocular pressure measurement, fundus examination, and retinal imaging. Monocular presenting visual acuity was recorded using a logMAR chart. Objective and subjective refraction were performed, and best-corrected visual acuity was recorded. URE was defined as presenting visual acuity worse than 6/12 but improving to 6/12 or better with refraction. Univariable and multivariable logistic regression analyses were used to assess the risk factors associated with URE. RESULTS: In total, 1 513 elderly participants were enumerated from 41 homes of which 1 182 participants (78.1%) were examined. The mean age of participants was 75.0 years (standard deviation 8.8 years; range: 60-108 years). 35.4% of those examined were men and 20.3% had no formal education. The prevalence of URE was 13.5% (95% CI: 11.5-15.5; n = 159). On applying multiple logistic regression analysis, compared to those living in private homes, the odds of URE were significantly higher among the elderly living in the aided homes (OR: 1.65; 95% CI: 1.11-2.43) and free homes (OR: 1.67; 95% CI: 1.00-2.80). As compared to those who reported having an eye examination in the last 3 years, the odds of URE were higher among those who never had an eye examination in the last three years (OR: 1.51; 95% CI: 1.07-2.14). Similarly, those who had unilateral cataract surgery (OR: 1.80; 95% CI: 1.10-2.93) or bilateral cataract surgery (1.69; 95% CI: 1.10-2.56) had higher odds of URE compared to those elderly who were not operated for cataract. Gender, self-report of diabetes, and education were not associated with URE. CONCLUSIONS: A large burden of URE was found among the residents in the 'homes for the aged' in Hyderabad, India which could be addressed with a pair of glasses. Over 40% of the residents never had an eye examination in the last three years, which indicates poor utilisation of eye care services by the elderly. Regular eye examinations and provision of spectacles are needed to address needless URE for distance among the elderly in residential care in India.
Parikh R, Palmer V, Kumar A, Simon JW. Surgical Confusions in Ophthalmology: Description, Analysis, and Prevention of Errors from 2006 through 2017. Ophthalmology 2020;127(3):296-302.Abstract
PURPOSE: To characterize surgical confusions in ophthalmology to determine their incidence, root causes, and impact on patients and physicians. DESIGN: Retrospective cohort study of errors in ophthalmic surgical procedures between January 1, 2006, and December 31, 2017. PARTICIPANTS: One hundred forty-three cases involving surgical confusions. METHODS: Cases were identified by the Ophthalmic Mutual Insurance Company from closed case files and by the New York State Health Department from the New York Patient Occurrence Reporting and Tracking program that identified the surgical confusions. MAIN OUTCOME MEASURES: Incidence and impact by intended surgery, error type, and root cause as well as preventability by the Universal Protocol. RESULTS: Of the 143 cases of surgical confusions identified, 92 cases (64.3%) were deemed preventable by the Universal Protocol. Approximately two thirds, 95 cases (66.4%), were cases of incorrect implants being used during cataract surgery (cataract extraction and intraocular lens implantation), of which 33 cases (34.7%) were not preventable by the Universal Protocol. Wrong eye blocks or anesthesia accounted for 20 cases (14.0%), incorrect eye procedures accounted for 10 cases (7.00%), incorrect refractive surgery measurements accounted for 6 cases (4.20%), incorrect patient or procedure accounted for 5 cases (3.50%), incorrect intraocular gas concentration accounted for 4 cases (2.80%), and incorrect medication in surgery accounted for 3 cases (2.10%). The most common root cause of confusion was an inadequately performed time out, which was responsible for nearly one third of all surgical confusions, 46 cases (32.2%). Incorrect lens orders or calculations before surgery (so-called upstream errors) were the second most common cause of surgical confusion, involving 31 cases (21.7%). The average legal indemnity for incorrect implant during cataract surgery was $57 514 (United States dollars). The average indemnity for incorrect refractive surgery measurement was $123 125, that for incorrect eye procedure was $50 000, and that for incorrect gas concentration was $220 844. CONCLUSIONS: Most surgical confusions could have been prevented by following the Universal Protocol properly. However, upstream errors, originating in the clinic or office before surgery, and ineffective communication during time outs suggest a need for modification of the Universal Protocol.
Gise RA, Heidary G. Update on Pediatric Optic Neuritis. Curr Neurol Neurosci Rep 2020;20(3):4.Abstract
PURPOSE OF REVIEW: The purpose of this review is to provide an update on advances in the understanding of pediatric demyelinating optic neuritis. RECENT FINDINGS: In the past decade, the disease phenotypes for demyelinating syndromes in children have been more clearly defined. Pediatric optic neuritis may present as a clinically isolated syndrome or in the setting of underlying neurologic disease. In addition to optic neuritis associated with multiple sclerosis or neuromyelitis optica, recent work has identified antibodies to the myelin oligodendrocyte glycoprotein (MOG IgG) as a unique demyelinating cause with distinct features regarding treatment and prognosis. The disease phenotypes for demyelinating pediatric optic neuritis have expanded. Treatment strategies vary and are not universally effective for each cause of demyelinating disease. Accurately distinguishing among these unique clinical syndromes is therefore critical for initiation of appropriate treatment to prevent disability, to maximize visual outcomes, and to provide insight into long-term prognosis.