2020

R
Rinaldi L, Ciricugno A, Merabet LB, Vecchi T, Cattaneo Z. The Effect of Blindness on Spatial Asymmetries. Brain Sci 2020;10(10)Abstract
The human cerebral cortex is asymmetrically organized with hemispheric lateralization pervading nearly all neural systems of the brain. Whether the lack of normal visual development affects hemispheric specialization subserving the deployment of visuospatial attention asymmetries is controversial. In principle, indeed, the lack of early visual experience may affect the lateralization of spatial functions, and the blind may rely on a different sensory input compared to the sighted. In this review article, we thus present a current state-of-the-art synthesis of empirical evidence concerning the effects of visual deprivation on the lateralization of various spatial processes (i.e., including line bisection, mirror symmetry, and localization tasks). Overall, the evidence reviewed indicates that spatial processes are supported by a right hemispheric network in the blind, hence, analogously to the sighted. Such a right-hemisphere dominance, however, seems more accentuated in the blind as compared to the sighted as indexed by the greater leftward bias shown in different spatial tasks. This is possibly the result of the more pronounced involvement of the right parietal cortex during spatial tasks in blind individuals compared to the sighted, as well as of the additional recruitment of the right occipital cortex, which would reflect the cross-modal plastic phenomena that largely characterize the blind brain.
Roh M, Miller JW, Jeng-Miller KW, Wang JC, Laíns I, Silverman RF, Loewenstein JI, Husain D, Vavvas DG, Miller JB. Subthreshold Exudative Choroidal Neovascularization Associated With Age-Related Macular Degeneration Identified by Optical Coherence Tomography Angiography. J Vitreoretin Dis 2020;4(5):377-385.Abstract
Purpose: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). Methods: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. Results: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of I to 10 years. Conclusions: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.
Rossato FA, Su Y, Mackey A, Ng YSE. Fibrotic Changes and Endothelial-to-Mesenchymal Transition Promoted by VEGFR2 Antagonism Alter the Therapeutic Effects of VEGFA Pathway Blockage in a Mouse Model of Choroidal Neovascularization. Cells 2020;9(9)Abstract
Many patients with wet age-related macular degeneration do not respond well to anti- vascular endothelial growth factor A (VEGFA) therapy for choroidal neovascularization (CNV), and the efficacy of anti-VEGFA decreases over time. We investigated the hypothesis that fibrotic changes, in particular via endothelial-to-mesenchymal transition (EndoMT), play a role in CNV and alter the therapeutic effects of VEGFA pathway blockage. Induction of EndoMT of primary human retinal endothelial cells led to a significantly reduced response to VEGFA at the level of gene expression, cellular proliferation, migration, and tube formation. Suppression of EndoMT restored cell responsiveness to VEGFA. In a mouse model of spontaneous CNV, fibrotic changes and EndoMT persisted as the CNV lesions became more established over time. VEGFA receptor-2 (VEGFR2) antagonism further induced fibrosis and EndoMT in the CNV. The combination of VEGFR2 antagonism and fibrosis/EndoMT inhibition was more effective than either individual treatment in reducing CNV. Our data indicate that fibrosis and EndoMT are involved in the progression of CNV, are exacerbated by VEGFR2 inhibition, and could provide an explanation for the reduced efficacy of anti-VEGFA treatment over time.
S
Sadda SR, Nittala MG, Taweebanjongsin W, Verma A, Velaga SB, Alagorie AR, Sears CM, Silva PS, Aiello LP. Quantitative Assessment of the Severity of Diabetic Retinopathy. Am J Ophthalmol 2020;218:342-352.Abstract
PURPOSE: To determine whether a quantitative approach to assessment of the severity of diabetic retinopathy (DR) lesions on ultrawide field (UWF) images can provide new parameters to predict progression to proliferative diabetic retinopathy (PDR). METHODS: One hundred forty six eyes from 73 participants with DR and 4 years of follow-up data were included in this post hoc analysis, which was based on a cohort of 100 diabetic patients enrolled in a previously published prospective, comparative study of UWF imaging at the Joslin Diabetes Center. Diabetic Retinopathy Severity Score level was determined at baseline and 4-year follow-up visits using mydriatic 7-standard field Early Treatment Diabetic Retinopathy Study (ETDRS) photographs. All individual DR lesions (hemorrhage [H], microaneurysm [ma], cotton wool spot [CWS], intraretinal microvascular abnormality [IRMA]) were manually segmented on stereographic projected UWF. For each lesion type, the frequency/number, surface area, and distances from the optic nerve head (ONH) were computed. These quantitative parameters were compared between eyes that progressed to PDR in 4 years and eyes that did not progress. Univariable and multivariable logistic regression analyses were performed to identify parameters that were associated with an increased risk for progression to PDR. RESULTS: A total of 146 eyes of 73 subjects were included in the final analysis. The mean age of the study cohort was 53.1 years, and 42 (56.8%) subjects were female. The number and surface area of H/ma's and CWSs were significantly (P ≤ .05) higher in eyes that progressed to PDR compared with eyes that did not progress by 4 years. Similarly, H/ma's and CWSs were located further away from the ONH (ie, more peripheral) in eyes that progressed (P < .05). DR lesion parameters that conferred a statistically significant increased risk for proliferative diabetic retinopathy in the multivariate model included hemorrhage area (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.25-5.53), and greater distance of hemorrhages from the ONH (OR, 1.24; 95% CI, 0.97-1.59). CONCLUSIONS: Quantitative analysis of DR lesions on UWF images identifies new risk parameters for progression to PDR including the surface area of hemorrhages and the distance of hemorrhages from the ONH. Although these risk factors will need to be confirmed in larger, prospective studies, they highlight the potential for quantitative lesion analysis to inform the design of a more precise and complete staging system for diabetic retinopathy severity in the future. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
Saeed HN, Bouchard C, Shieh C, Phillips E, Chodosh J. Highlights from the 2nd Biennial Stevens Johnson syndrome symposium 2019: SJS/TEN from Science to Translation. Ocul Surf 2020;18(3):483-486.
Sahin A, Liu Y, Kam WR, Rahimi Darabad R, Sullivan DA. Dihydrotestosterone suppression of proinflammatory gene expression in human meibomian gland epithelial cells. Ocul Surf 2020;18(2):199-205.Abstract
PURPOSE: We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis. For comparison, we also examined whether DHT treatment elicits the same effect in immortalized human corneal (IHC) and conjunctival (IHConj) ECs. METHODS: Differentiated cells were cultured in media containing vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software. RESULTS: Our results demonstrate that DHT significantly suppressed the expression of numerous immune-related genes in HMGECs, such as those associated with antigen processing and presentation, innate and adaptive immune responses, chemotaxis, and cytokine production. DHT also enhanced the expression of genes for defensin β1, IL-1 receptor antagonist, and the anti-inflammatory serine peptidase inhibitor, Kazal type 5. In contrast, DHT had no effect on proinflammatory gene expression in HCECs, and significantly increased 33 gene ontologies linked to the immune system in HConjECs. CONCLUSIONS: Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.
Sakurada Y, Fragiotta S, Leong BCS, Parikh R, Hussnain AS, Freund BK. RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY. Retina 2020;40(4):657-662.Abstract
PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.
Sandhu HS, Hemmati HD, Dana R. Immune checkpoint inhibitors and corneal transplant rejection: a call for awareness. Immunotherapy 2020;12(13):947-949.
Savage SW, Zhang L, Swan G, Bowers AR. The effects of age on the contributions of head and eye movements to scanning behavior at intersections. Transp Res Part F Traffic Psychol Behav 2020;73:128-142.Abstract
The current study was aimed at evaluating the effects of age on the contributions of head and eye movements to scanning behavior at intersections. When approaching intersections, a wide area has to be scanned requiring large lateral head rotations as well as eye movements. Prior research suggests older drivers scan less extensively. However, due to the wide-ranging differences in methodologies and measures used in prior research, the extent to which age-related changes in eye or head movements contribute to these deficits is unclear. Eleven older (mean 67 years) and 18 younger (mean 27 years) current drivers drove in a simulator while their head and eye movements were tracked. Scans, analyzed for 15 four-way intersections in city drives, were split into two categories: (consisting only of eye movements) and (containing both head and eye movements). Older drivers made smaller scans than younger drivers (46.6° vs. 53°), as well as smaller scans (9.2° vs. 10.1°), resulting in overall smaller scans. For scans, older drivers had both a smaller head and a smaller eye movement component. Older drivers made more scans than younger drivers (7 vs. 6) but fewer scans (2.1 vs. 2.7). This resulted in no age effects when considering scans. Our results clarify the contributions of eye and head movements to age-related deficits in scanning at intersections, highlight the importance of analyzing both eye and head movements, and suggest the need for older driver training programs that emphasize the importance of making large scans before entering intersections.
Schoemaker D, Zuluaga Y, Viswanathan A, Shrimer M, Torrico-Teave H, Velilla L, Ospina C, Ospina GG, Lopera F, Arboleda-Velasquez JF, Quiroz YT. The INECO Frontal Screening for the Evaluation of Executive Dysfunction in Cerebral Small Vessel Disease: Evidence from Quantitative MRI in a CADASIL Cohort from Colombia. J Int Neuropsychol Soc 2020;26(10):1006-1018.Abstract
OBJECTIVES: Executive dysfunction is a predominant cognitive symptom in cerebral small vessel disease (SVD). The Institute of Cognitive Neurology Frontal Screening (IFS) is a well-validated screening tool allowing the rapid assessment of multiple components of executive function in Spanish-speaking individuals. In this study, we examined performance on the IFS in subjects with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an inherited condition leading to the early onset of SVD. We further explored associations between performance on the IFS and magnetic resonance imaging (MRI) markers of SVD. METHODS: We recruited 24 asymptomatic CADASIL subjects and 23 noncarriers from Colombia. All subjects underwent a research MRI and a neuropsychological evaluation, including the IFS. Structural MRI markers of SVD were quantified in each subject, together with an SVD Sum Score representing the overall burden of cerebrovascular alterations. General linear model, correlation, and receiver operating characteristic curve analyses were used to explore group differences on the IFS and relationships with MRI markers of SVD. RESULTS: CADASIL subjects had a significantly reduced performance on the IFS Total Score. Performance on the IFS correlated with all quantified markers of SVD, except for brain atrophy and perivascular spaces enlargement. Finally, while the IFS Total Score was not able to accurately discriminate between carriers and noncarriers, it showed adequate sensitivity and specificity in detecting the presence of multiple MRI markers of SVD. CONCLUSIONS: These results suggest that the IFS may be a useful screening tool to assess executive function and disease severity in the context of SVD.
Scott HA, Place EM, Ferenchak K, Zampaglione E, Wagner NE, Chao KR, DiTroia SP, Navarro-Gomez D, Mukai S, Huckfeldt RM, Pierce EA, Bujakowska KM. Expanding the phenotypic spectrum in RDH12-associated retinal disease. Cold Spring Harb Mol Case Stud 2020;6(1)Abstract
Retinol dehydrogenase 12, RDH12, plays a pivotal role in the visual cycle to ensure the maintenance of normal vision. Alterations in activity of this protein result in photoreceptor death and decreased vision beginning at an early age and progressing to substantial vision loss later in life. Here we describe 11 patients with retinal degeneration that underwent next-generation sequencing (NGS) with a targeted panel of all currently known inherited retinal degeneration (IRD) genes and whole-exome sequencing to identify the genetic causality of their retinal disease. These patients display a range of phenotypic severity prompting clinical diagnoses of macular dystrophy, cone-rod dystrophy, retinitis pigmentosa, and early-onset severe retinal dystrophy all attributed to biallelic recessive mutations in We report 15 causal alleles and expand the repertoire of known mutations with four novel variants: c.215A > G (p.Asp72Gly); c.362T > C (p.Ile121Thr); c.440A > C (p.Asn147Thr); and c.697G > A (p.Val233Ille). The broad phenotypic spectrum observed with biallelic mutations has been observed in other genetic forms of IRDs, but the diversity is particularly notable here given the prior association of primarily with severe early-onset disease. This breadth emphasizes the importance of broad genetic testing for inherited retinal disorders and extends the pool of individuals who may benefit from imminent gene-targeted therapies.
Seminario-Vidal L, Kroshinsky D, Malachowski SJ, Sun J, Markova A, Beachkofsky TM, Kaffenberger BH, Ergen EN, Mauskar M, Bridges A, Calhoun C, Cardones AR, Chen ST, Chodosh J, Cotliar J, Davis MDP, DeNiro KL, Dominguez AR, Eljure-Téllez J, Femia A, Fox LP, Guda A, Mitchell C, Mostaghimi A, Ortega-Loayza AG, Owen C, Pasieka H, Rahnama-Moghadam S, Saeed HN, Saunderson RB, Shanbhag S, Sharon VR, Strowd L, Venkatesh S, Wanat KA, Wetter DA, Worswick S, Micheletti RG. Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. J Am Acad Dermatol 2020;82(6):1553-1567.Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.
Shah DN, Al-Moujahed A, Newcomb CW, Kaçmaz OR, Daniel E, Thorne JE, Foster SC, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Rosenbaum JT, Sen NH, Suhler EB, Bhatt NP, Kempen JH, for Group SITEDR. Exudative Retinal Detachment in Ocular Inflammatory Diseases: Risk and Predictive Factors. Am J Ophthalmol 2020;218:279-287.Abstract
PURPOSE: This study evaluated the risk and risk factors for exudative retinal detachment (ERD) in ocular inflammatory diseases. DESIGN: Retrospective cohort study. METHODS: Patients with noninfectious ocular inflammation had been followed longitudinally between 1978 and 2007 at 4 US subspecialty uveitis centers. The main outcome measurements were occurrences of ERD and predictive factors. RESULTS: A total of 176 of 14,612 eyes with ocular inflammation presented with ERD. Among uveitis cases, Vogt-Koyanagi-Harada syndrome (VKH) (odds ratio [OR] = 109), undifferentiated choroiditis (OR = 9.18), sympathetic ophthalmia (OR = 8.43), primary or secondary panuveitis (OR = 7.09), multifocal choroiditis with panuveitis (OR = 4.51), and "other" forms of posterior uveitis (OR = 16.9) were associated with a higher prevalence of ERD. Among the 9,209 uveitic or scleritic eyes initially free of ERD and followed, 137 incident ERD cases were observed over 28,949 eye-years at risk (incidence rate = 0.47% [0.40%-0.56%/eye-year]). VKH (HR = 13.2), sympathetic ophthalmia (HR = 5.82), undifferentiated choroiditis (HR = 6.03), primary or secondary panuveitis (HR = 4.21), and rheumatoid arthritis (HR = 3.30) were significantly associated with incident ERD. A significant dose-response relationship with the prevalence and incidence of ERD were observed for AC cells and vitreous cell activity. African Americans had significantly higher prevalence and incidence of ERD. CONCLUSIONS: Other ocular inflammatory conditions in addition to VKH syndrome and posterior scleritis were associated with increased risk of ERD, indicating that ERD does not necessarily dictate a diagnosis of VKH or posterior scleritis. In addition, the relationship between ERD and inflammatory severity factors implies that inflammation is a key predictive factor associated with developing ERD and requires early and vigorous control.
Shakhmantsir I, Dooley SJ, Kishore S, Chen D, Pierce E, Bennett J, Sehgal A. RNA Splicing Factor Mutations That Cause Retinitis Pigmentosa Result in Circadian Dysregulation. J Biol Rhythms 2020;35(1):72-83.Abstract
Circadian clocks regulate multiple physiological processes in the eye, but their requirement for retinal health remains unclear. We previously showed that Drosophila homologs of spliceosome proteins implicated in human retinitis pigmentosa (RP), the most common genetically inherited cause of blindness, have a role in the brain circadian clock. In this study, we report circadian phenotypes in murine models of RP. We found that mice carrying a homozygous H2309P mutation in () display a lengthened period of the circadian wheel-running activity rhythm. We show also that the daily cycling of circadian gene expression is dampened in the retina of H2309P mice. Surprisingly, molecular rhythms are intact in the eye cup, which includes the retinal pigment epithelium (RPE), even though the RPE is thought to be the primary tissue affected in this form of RP. Downregulation of , another RNA splicing factor implicated in RP, leads to period lengthening in a human cell culture model. The period of circadian bioluminescence in primary fibroblasts of human RP patients is not significantly altered. Together, these studies link a prominent retinal disorder to circadian deficits, which could contribute to disease pathology.
Shanbhag SS, Hall L, Chodosh J, Saeed HN. Long-term outcomes of amniotic membrane treatment in acute Stevens-Johnson syndrome/toxic epidermal necrolysis. Ocul Surf 2020;18(3):517-522.Abstract
PURPOSE: To report the long-term outcomes of amniotic membrane (AM) use in the form of transplantation (AMT) and self-retained amniotic membrane (ProKera® device, PD) in acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Electronic records of all patients with a diagnosis of SJS/TEN at Massachusetts Eye and Ear between January 2008 and January 2018 were reviewed. Patients who received AM in acute SJS/TEN were selected. Only patients with follow-up ≥ 3 months after discharge were included. RESULTS: Data of 55 eyes of 29 patients were analyzed. All 55 eyes received the first AM at a median interval of 5 days (inter-quartile range (IQR): 3-7 days) after onset of skin rash. Fifty-six percent of eyes (31/55) received AMT while 44% (24/55) received PD. Forty percent of eyes (22/55) required a repeat AMT or PD. Median follow-up after initial AM was 2.5 years (IQR: 1.2-3.6 years). At last follow-up, the best-corrected visual acuity was ≥20/40 in 87% of eyes (48/55). The most common complications in the chronic phase were meibomian gland disease and dry eye, seen in 78% of eyes (43/55) and 58% of eyes (32/55) respectively. CONCLUSIONS: Long-term results show that early use of AM in the acute phase of SJS/TEN may be effective in mitigating severe vision loss after SJS/TEN. However, eyelid-related complications and dry eye remain a common problem even with the use of AM.
Shi C, Pundlik S, Luo G. Without low spatial frequencies, high resolution vision would be detrimental to motion perception. J Vis 2020;20(8):29.Abstract
A normally sighted person can see a grating of 30 cycles per degree or higher, but spatial frequencies needed for motion perception are much lower than that. It is unknown for natural images with a wide spectrum how all the visible spatial frequencies contribute to motion speed perception. In this work, we studied the effect of spatial frequency content on motion speed estimation for sequences of natural and stochastic pixel images by simulating different visual conditions, including normal vision, low vision (low-pass filtering), and complementary vision (high-pass filtering at the same cutoff frequencies of the corresponding low-vision conditions) conditions. Speed was computed using a biological motion energy-based computational model. In natural sequences, there was no difference in speed estimation error between normal vision and low vision conditions, but it was significantly higher for complementary vision conditions (containing only high-frequency components) at higher speeds. In stochastic sequences that had a flat frequency distribution, the error in normal vision condition was significantly larger compared with low vision conditions at high speeds. On the contrary, such a detrimental effect on speed estimation accuracy was not found for low spatial frequencies. The simulation results were consistent with the motion direction detection task performed by human observers viewing stochastic sequences. Together, these results (i) reiterate the importance of low frequencies in motion perception, and (ii) indicate that high frequencies may be detrimental for speed estimation when low frequency content is weak or not present.
Shire DB, Gingerich MD, Wong PI, Skvarla M, Cogan SF, Chen J, Wang W, Rizzo JF. Micro-Fabrication of Components for a High-Density Sub-Retinal Visual Prosthesis. Micromachines (Basel) 2020;11(10)Abstract
We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School's teaching hospital, the Massachusetts Eye and Ear-and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches.
Shoji MK, Shishido S, Freitag SK. The Use of Sirolimus for Treatment of Orbital Lymphatic Malformations: A Systematic Review. Ophthalmic Plast Reconstr Surg 2020;36(3):215-221.Abstract
PURPOSE: Orbital lymphatic malformations are rare congenital choristomas associated with pain, proptosis, exposure keratopathy, and vision loss. Current treatments of surgery, drainage, and sclerotherapy may have adverse effects including risk of damage to surrounding structures, swelling, and malformation persistence or recrudescence. Sirolimus, which inhibits mammalian target of rapamycin, a regulator of cell growth and vascular endothelial growth factor expression, has successfully treated systemic vascular malformations. However, its efficacy and safety have not yet been well established for orbital lymphatic malformations. METHODS: Systematic review and analysis of relevant published literature were performed. PubMed, Embase, and World of Science searches were conducted for studies involving sirolimus treatment of orbital lymphatic malformations through July 2019. RESULTS: Nine case series and reports with 10 total patients who received sirolimus for treatment of orbital lymphatic malformations were included. The age at sirolimus initiation ranged from 1 week to 23 years. The malformation was lymphatic in 6 patients, lymphaticovenous in 3 patients, and lymphatic-arteriovenous in 1 patient. Six patients underwent ineffective prior therapy including sclerotherapy, surgery, or medical therapy. Initial sirolimus dosage ranged from 0.05 mg/kg twice a day to 1 mg twice a day, and duration ranged from 6 months to 53 months. Seven patients had partial response, and 3 patients, all of whom had a microcystic malformation component, experienced complete response. Adverse effects included mild reversible leukopenia, hypertriglyceridemia, hypercholesterolemia, and transaminitis with adverse effects denied or not specified for 6 patients. CONCLUSIONS: Sirolimus may be a safe and effective treatment for orbital lymphatic malformations, especially microcystic malformations.
Shoshany TN, Michalak S, Staffa SJ, Chinn RN, Bishop K, Hunter DG. Effect of Primary Occlusion Therapy in Asymmetric, Bilateral Amblyopia. Am J Ophthalmol 2020;211:87-93.Abstract
PURPOSE: Many bilateral amblyopia patients have asymmetric visual acuity (VA). There is no standard treatment for these patients, and outcomes have not been well described. Our goal is to compare VA outcomes in this group based on timing of occlusion therapy. DESIGN: Retrospective interventional comparative case series. METHODS: Setting: Institutional practice. PatientPopulation: Patients diagnosed with amblyopia at Boston Children's Hospital between 2010 and 2014. InclusionCriteria: VA ≥ 0.3 logMAR bilaterally by objective optotype-based measures, interocular difference (IOD) ≥ 0.18 logMAR, age 2-12 years. ExclusionCriteria: Loss to follow-up, managed surgically, deprivation amblyopia. Patients had either primary or secondary occlusion (primary = initiated when VA ≥ 0.3 logMAR bilaterally; secondary = initiated to correct residual IOD once VA improved to ≤0.18 logMAR in the stronger eye). ObservationProcedure: Patient demographics, VA, IOD, and stereopsis were compared between groups. OutcomeMeasures: VA improvement at 12-18 months and at last visits. RESULTS: Of 2,200 patients reviewed, 167 (7.6%) had asymmetric, bilateral amblyopia; 98 met inclusion and exclusion criteria. Patients were equally divided between primary (n = 50) and secondary (n = 48) occlusion groups. There were no differences in demographics, baseline VA, or IOD between groups (P ≥ .22), although the primary occlusion group had a higher proportion of strabismic amblyopia (P = .007). VA in both eyes, IOD, and stereopsis improved similarly between groups, even after stratifying by amblyopia subtype (P ≥ .48). The secondary occlusion group was more likely to achieve 20/30 bilaterally and IOD ≤ 1 line at 12-18 months (P ≤ .4), although this equalized by the last visit. CONCLUSION: In patients with asymmetric, bilateral amblyopia, VA improved by 4 lines in the weaker eye and 2 lines in the stronger eye, while IOD improved by 2 lines, irrespective of occlusion status. Primary occlusion thus provided no further benefit over spectacle correction alone.
Shoshany TN, Michalak SM, Chinn RN, Staffa SJ, Hunter DG. Evaluating Amblyopia Treatment Success Using the American Academy of Ophthalmology IRIS50 Measures. Ophthalmology 2020;127(6):836-838.

Pages