Veronese C, Pellegrini M, Maiolo C, Morara M, Armstrong GW, Ciardella AP. Multimodal ophthalmic imaging of staphylococcus aureus bacteremia associated with chorioretinitis, endocarditis, and multifocal brain abscesses. Am J Ophthalmol Case Rep 2020;17:100577.Abstract
Purpose: bacteriemia (SAB) as critical condition for the life and occasionally involves the eyes. The aim of this report is to describe the ocular involvement with multimodal imaging. Observations: A patient admitted for evaluation of acute onset of confusion, disorientation, and generalized malaise and found to have methicillin-resistant staphylococcus aureus (MRSA)-associated endocarditis and multifocal brain abscesses was evaluated by the ophthalmology service. The patient's visual acuity was 20/20 OU without relative afferent pupillary defect and normal intraocular pressures. Bedside anterior segment examination was normal. Posterior segment examination revealed intraretinal hemorrhages and Roth spots in the posterior pole of the right eye, and two deep well-defined focal white chorioretinal infiltrates and a hemorrhagic pigment epithelium detachment in the temporal quadrant of the left eye. Multimodal imaging was utilized to document these findings and ensure adequate antibiotic therapy. Conclusion: SAB has the potential for poor visual outcomes as well as significant morbidity and mortality. Multimodal imaging of SAB-related chorioretinitis allows for accurate diagnosis as well as assessment of response to antimicrobial therapy.
Veronese C, Maiolo C, Armstrong GW, Primavera L, Torrazza C, Della Mora L, Ciardella AP. New surgical approach for sutureless scleral fixation. Eur J Ophthalmol 2020;30(3):612-615.Abstract
PURPOSE: The aim of this article is to describe a novel surgical technique for sutureless scleral fixation of an intraocular lens using the newly developed FIL SSF Carlevale IOL (Soleko, Italy). METHODS: Four eyes of four patients with poor capsular support were recruited to our study, three resulting from intraocular lens subluxation and one case resulting from traumatic cataract. A novel sutureless sclera-fixated intraocular lens was implanted into the posterior chamber of each eye with sclerocorneal plugs fixating the lens to the wall of the eye. RESULTS: Mean age of patients was 52 ± 16 years, ranging from 35 to 70 years. Mean follow-up was 6.50 ± 1.29 months (range: 5-7 months). Mean preoperative best-corrected visual acuity was 0.50 ± 0.33 logMAR (range: 1-0.3 logMAR). Postoperative best-corrected visual acuity improved to 0.08 ± 0.08 logMAR (range: 0.2-0 logMAR). There was no significant change in the mean intraocular pressure and there were no postoperative complications, such as iatrogenic distortion or breakage of the intraocular lens haptic, intraocular lens decentration, endophthalmitis, or retinal detachment. DISCUSSION: To the best of our knowledge, this is the first report of outcomes using the novel sutureless sclera-fixated FIL SSF Carlevale IOL. This new surgical technique offers a simplified and effective approach for sutureless scleral intraocular lens fixation with good refractive outcomes.
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.
Vongsachang H, Friedman DS, Inns A, Kretz AM, Mukherjee MR, Callan J, Wahl M, Repka MX, Collins ME. Parent and Teacher Perspectives on Factors Decreasing Participation in School-Based Vision Programs. Ophthalmic Epidemiol 2020;27(3):226-236.Abstract
: To examine factors decreasing participation in school-based vision programs from parent and teacher perspectives.: We conducted 41 semi-structured focus groups (20 parent groups, 21 teacher/staff groups), at 10 Baltimore and 11 Chicago public elementary and middle schools offering school-based vision programs. School-based vision programs provided vision screening, eye exams, and eyeglasses if needed. Focus groups ranged in size from 2-9 participants (median = 5). Sessions were recorded, transcribed, and coded through an iterative process to develop themes using inductive analysis.: Ninety parents and 117 teachers/staff participated. Participants identified five major factors decreasing participation in school-based vision programs: (1) challenges with the consent form, including distribution, collection, and literacy and language barriers; (2) having existing eye care; (3) misunderstandings about the program, especially related to cost and insurance; (4) difficulty raising parental awareness of the program; and (5) certain attitudes towards vision, eye care, and school-based programs, including low prioritization of eye care, mistrust of the program, fear of sharing private information, not believing their child needs glasses, and reluctance accepting 'subsidized' services.: Parents and teachers identified important structural barriers to participation (i.e., consent form challenges and low parental awareness) and specific reasons for non-participation (i.e., attitudes, misunderstanding of the program, existing eye care) in school-based vision programs. Effective strategies are needed to facilitate return of consent forms and promote awareness of school-based vision programs among parents. Programs should also target services towards those currently without access to eye care and increase awareness about paediatric vision needs.
Vu THK, Chen H, Pan L, Cho K-S, Doesburg D, Thee EF, Wu N, Arlotti E, Jager MJ, Chen DF. CD4 T-Cell Responses Mediate Progressive Neurodegeneration in Experimental Ischemic Retinopathy. Am J Pathol 2020;190(8):1723-1734.Abstract
Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell-mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4 T-cell infiltration into the retina. Adoptive transfer of CD4 T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-γ-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.
Vujosevic S, Aldington SJ, Silva P, Hernández C, Scanlon P, Peto T, Simó R. Screening for diabetic retinopathy: new perspectives and challenges. Lancet Diabetes Endocrinol 2020;8(4):337-347.Abstract
Although the prevalence of all stages of diabetic retinopathy has been declining since 1980 in populations with improved diabetes control, the crude prevalence of visual impairment and blindness caused by diabetic retinopathy worldwide increased between 1990 and 2015, largely because of the increasing prevalence of type 2 diabetes, particularly in low-income and middle-income countries. Screening for diabetic retinopathy is essential to detect referable cases that need timely full ophthalmic examination and treatment to avoid permanent visual loss. In the past few years, personalised screening intervals that take into account several risk factors have been proposed, with good cost-effectiveness ratios. However, resources for nationwide screening programmes are scarce in many countries. New technologies, such as scanning confocal ophthalmology with ultrawide field imaging and handheld mobile devices, teleophthalmology for remote grading, and artificial intelligence for automated detection and classification of diabetic retinopathy, are changing screening strategies and improving cost-effectiveness. Additionally, emerging evidence suggests that retinal imaging could be useful for identifying individuals at risk of cardiovascular disease or cognitive impairment, which could expand the role of diabetic retinopathy screening beyond the prevention of sight-threatening disease.
Wallace DK, Kraker RT, Freedman SF, Crouch ER, Bhatt AR, Hartnett EM, Yang MB, Rogers DL, Hutchinson AK, VanderVeen DK, Haider KM, Siatkowski MR, Dean TW, Beck RW, Repka MX, Smith LE, Good WV, Kong L, Cotter SA, Holmes JM, Holmes JM. Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity. JAMA Ophthalmol 2020;Abstract
Importance: Intravitreous bevacizumab (0.25 mg to 0.625 mg) is commonly used to treat type 1 retinopathy of prematurity (ROP), but there are concerns about systemic toxicity, particularly the risk of neurodevelopmental delay. A much lower dose may be effective for ROP while reducing systemic risk. Previously, after testing doses of 0.25 mg to 0.031 mg, doses as low as 0.031 mg were found to be effective in small cohorts of infants. Objective: To find the lowest dose of intravitreous bevacizumab effective for severe ROP. Design, Setting, and Participants: Between April 2017 and May 2019, 59 premature infants with type 1 ROP in 1 or both eyes were enrolled in a masked, multicenter, dose de-escalation study. In cohorts of 10 to 14 infants, 1 eye per infant received 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreous bevacizumab. Diluted bevacizumab was prepared by individual research pharmacies and delivered using 300-µL syringes with 5/16-inch, 30-guage fixed needles. Analysis began July 2019. Interventions: Bevacizumab intravitreous injections at 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg. Main Outcomes and Measures: Success was defined as improvement by 4 days postinjection and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks. Results: Fifty-five of 59 enrolled infants had 4-week outcomes completed; the mean (SD) birth weight was 664 (258) g, and the mean (SD) gestational age was 24.8 (1.6) weeks. A successful 4-week outcome was achieved for 13 of 13 eyes (100%) receiving 0.016 mg, 9 of 9 eyes (100%) receiving 0.008 mg, 9 of 10 eyes (90%) receiving 0.004 mg, but only 17 of 23 eyes (74%) receiving 0.002 mg. Conclusions and Relevance: These data suggest that 0.004 mg may be the lowest dose of bevacizumab effective for ROP. Further investigation is warranted to confirm effectiveness of very low-dose intravitreous bevacizumab and its effect on plasma vascular endothelial growth factor levels and peripheral retinal vascularization.
Wang J, Cui Y, Vingopoulos F, Kasetty M, Silverman RF, Katz R, Kim L, Miller JB. Disorganisation of retinal inner layers is associated with reduced contrast sensitivity in retinal vein occlusion. Br J Ophthalmol 2020;Abstract
BACKGROUND/AIMS: To determine if disorganisation of retinal inner layers (DRIL) is associated with reduced contrast sensitivity (CS) in patients with retinal vein occlusion (RVO) with a history of macular oedema (ME). METHODS: Prospective, observational cohort study. Patients with a history of ME secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) from October 2017 to July 2019 at a single institution were included. Patients underwent complete ophthalmic examination, spectral domain optical coherence tomography (SD-OCT) and CS testing using the quick contrast sensitivity function (qCSF) method. Eyes with coexisting macular disease were excluded. SD-OCT images were analysed for presence and extent of DRIL, intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective foci, epiretinal membrane (ERM), external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption, central macular thickness (CMT) and central foveal thickness (CFT). Multivariable mixed-effect linear regressions were performed for the area under the log contrast sensitivity function (AULCSF) using Stata (StataCorp). P values <0.05 were considered significant. RESULTS: 58 visits from 31 patients were included (1.9±1.2 visits per patient). 29 (50%) were for CRVO. The average age was 63.9±10.5 years. On multivariable analysis, DRIL extent (p<0.001), CMT (p=0.007), CFT (p=0.024) and moderate cataract (p=0.001) were significantly associated with worse AULCSF. CONCLUSIONS: DRIL extent is associated with reduced CS in eyes with ME secondary to RVO. DRIL is an imaging feature that has important implications for visual function.
Wang T, Tsirukis DI, Sun Y. Targeting Neuroinflammation in Neovascular Retinal Diseases. Front Pharmacol 2020;11:234.Abstract
Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation's effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.
Wang J, He X, Meng H, Li Y, Dmitriev P, Tian F, Page JC, Lu RQ, He Z. Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia. Neuron 2020;108(5):876-886.e4.Abstract
Myelination facilitates rapid axonal conduction, enabling efficient communication across different parts of the nervous system. Here we examined mechanisms controlling myelination after injury and during axon regeneration in the central nervous system (CNS). Previously, we discovered multiple molecular pathways and strategies that could promote robust axon regrowth after optic nerve injury. However, regenerated axons remain unmyelinated, and the underlying mechanisms are elusive. In this study, we found that, in injured optic nerves, oligodendrocyte precursor cells (OPCs) undergo transient proliferation but fail to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what is observed in human progressive multiple sclerosis. Mechanistically, we showed that OPC-intrinsic GPR17 signaling and sustained activation of microglia inhibit different stages of OPC differentiation. Importantly, co-manipulation of GPR17 and microglia led to extensive myelination of regenerated axons. The regulatory mechanisms of stage-dependent OPC differentiation uncovered here suggest a translatable strategy for efficient de novo myelination after CNS injury.
Wang J, Wang X, Gao Y, Lin Z, Chen J, Gigantelli J, Shapiro JI, Xie Z, Pierre SV. Stress Signal Regulation by Na/K-ATPase As a New Approach to Promote Physiological Revascularization in a Mouse Model of Ischemic Retinopathy. Invest Ophthalmol Vis Sci 2020;61(14):9.Abstract
Purpose: The identification of target pathways to block excessive angiogenesis while simultaneously restoring physiological vasculature is an unmet goal in the therapeutic management of ischemic retinopathies. pNaKtide, a cell-permeable peptide that we have designed by mapping the site of α1 Na/K-ATPase (NKA)/Src binding, blocks the formation of α1 NKA/Src/reactive oxygen species (ROS) amplification loops and restores physiological ROS signaling in a number of oxidative disease models. The aim of this study was to evaluate the importance of the NKA/Src/ROS amplification loop and the effect of pNaKtide in experimental ischemic retinopathy. Methods: Human retinal microvascular endothelial cells (HRMECs) and retinal pigment epithelium (ARPE-19) cells were used to evaluate the effect of pNaKtide on viability, proliferation, and angiogenesis. Retinal toxicity and distribution were assessed in those cells and in the mouse. Subsequently, the role and molecular mechanism of NKA/Src in ROS stress signaling were evaluated biochemically in the retinas of mice exposed to the well-established protocol of oxygen-induced retinopathy (OIR). Finally, pNaKtide efficacy was assessed in this model. Results: The results suggest a key role of α1 NKA in the regulation of ROS stress and the Nrf2 pathway in mouse OIR retinas. Inhibition of α1 NKA/Src by pNaKtide reduced pathologic ROS signaling and restored normal expression of hypoxia-inducible factor 1-α/vascular endothelial growth factor (VEGF). Unlike anti-VEGF agents, pNaKtide did promote retinal revascularization while inhibiting neovascularization and inflammation. Conclusions: Targeting α1 NKA represents a novel strategy to develop therapeutics that not only inhibit neovascularization but also promote physiological revascularization in ischemic eye diseases.
Wang J, Liu Y, Kam WR, Li Y, Sullivan DA. Toxicity of the cosmetic preservatives parabens, phenoxyethanol and chlorphenesin on human meibomian gland epithelial cells. Exp Eye Res 2020;196:108057.Abstract
Recently, we discovered that the cosmetic preservatives, benzalkonium chloride and formaldehyde, are especially toxic to human meibomian gland epithelial cells (HMGECs). Exposure to these agents, at concentrations approved for human use, leads within hours to cellular atrophy and death. We hypothesize that these effects are not unique, and that other cosmetic preservatives also exert adverse effects on HMGECs. Such compounds include parabens, phenoxyethanol and chlorphenesin, which have been reported to be toxic to corneal and conjunctival epithelial cells, the liver and kidney, as well as to irritate the eye. To test our hypothesis, we examined the influence of parabens, phenoxyethanol and chlorphenesin on the morphology, signaling, survival, proliferation and lipid expression of immortalized (I) HMGECs. These cells were cultured under proliferating or differentiating conditions with varying concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin for up to 5 days. We monitored the signaling ability, appearance, number and neutral lipid content of the IHMGECs, as well as their lysosome accumulation. Our findings show that a 30-min exposure of IHMGECs to these preservatives results in a significant reduction in the activity of the Akt pathway. This effect is dose-dependent and occurs at concentrations equal to (chlorphenesin) and less than (all others) those dosages approved for human use. Further, a 24-h treatment of the IHMGECs with concentrations of methylparaben, ethylparaben, phenoxyethanol and chlorphenesin close to, or at, the approved human dose induces cellular atrophy and death. At all concentrations tested, no preservative stimulated IHMGEC proliferation. Of particular interest, it was not possible to evaluate the influence of these preservatives, at close to human approved dosages, on IHMGEC differentiation, because the cells did not survive the treatment. In summary, our results support our hypothesis and show that methylparaben, ethylparaben, phenoxyethanol and chlorphenesin are toxic to IHMGECs.
Wang SK, Xue Y, Cepko CL. Microglia modulation by TGF-β1 protects cones in mouse models of retinal degeneration. J Clin Invest 2020;130(8):4360-4369.Abstract
Retinitis pigmentosa (RP) is a genetically heterogenous group of eye diseases in which initial degeneration of rods triggers secondary degeneration of cones, leading to significant loss of daylight, color, and high-acuity vision. Gene complementation with adeno-associated viral (AAV) vectors is one strategy to treat RP. Its implementation faces substantial challenges, however; for example, the tremendous number of loci with causal mutations. Gene therapy targeting secondary cone degeneration is an alternative approach that could provide a much-needed generic treatment for many patients with RP. Here, we show that microglia are required for the upregulation of potentially neurotoxic inflammatory factors during cone degeneration in RP, creating conditions that might contribute to cone dysfunction and death. To ameliorate the effects of such factors, we used AAV vectors to express isoforms of the antiinflammatory cytokine transforming growth factor beta (TGF-β). AAV-mediated delivery of TGF-β1 rescued degenerating cones in 3 mouse models of RP carrying different pathogenic mutations. Treatment with TGF-β1 protected vision, as measured by 2 behavioral assays, and could be pharmacologically disrupted by either depleting microglia or blocking the TGF-β receptors. Our results suggest that TGF-β1 may be broadly beneficial for patients with cone degeneration, and potentially other forms of neurodegeneration, through a pathway dependent upon microglia.
Wang J, Chen D, Sullivan DA, Xie H, Li Y, Liu Y. Expression of Lubricin in the Human Amniotic Membrane. Cornea 2020;39(1):118-121.Abstract
PURPOSE: Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis. METHODS: We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs. RESULTS: Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin. CONCLUSIONS: This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.
PURPOSE: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging. METHODS: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. RESULTS: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated. CONCLUSION: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.
Wang M, Tichelaar J, Pasquale LR, Shen LQ, Boland MV, Wellik SR, De Moraes CG, Myers JS, Ramulu P, Kwon MY, Saeedi OJ, Wang H, Baniasadi N, Li D, Bex PJ, Elze T. Characterization of Central Visual Field Loss in End-stage Glaucoma by Unsupervised Artificial Intelligence. JAMA Ophthalmol 2020;Abstract
Importance: Although the central visual field (VF) in end-stage glaucoma may substantially vary among patients, structure-function studies and quality-of-life assessments are impeded by the lack of appropriate characterization of end-stage VF loss. Objective: To provide a quantitative characterization and classification of central VF loss in end-stage glaucoma. Design, Setting, and Participants: This retrospective cohort study collected data from 5 US glaucoma services from June 1, 1999, through October 1, 2014. A total of 2912 reliable 10-2 VFs of 1103 eyes from 1010 patients measured after end-stage 24-2 VFs with a mean deviation (MD) of -22 dB or less were included in the analysis. Data were analyzed from March 28, 2018, through May 23, 2019. Main Outcomes and Measures: Central VF patterns were determined by an artificial intelligence algorithm termed archetypal analysis. Longitudinal analyses were performed to investigate whether the development of central VF defect mostly affects specific vulnerability zones. Results: Among the 1103 patients with the most recent VFs, mean (SD) age was 70.4 (14.3) years; mean (SD) 10-2 MD, -21.5 (5.6) dB. Fourteen central VF patterns were determined, including the most common temporal sparing patterns (304 [27.5%]), followed by mostly nasal loss (280 [25.4%]), hemifield loss (169 [15.3%]), central island (120 [10.9%]), total loss (91 [8.3%]), nearly intact field (56 [5.1%]), inferonasal quadrant sparing (42 [3.8%]), and nearly total loss (41 [3.7%]). Location-specific median total deviation analyses partitioned the central VF into a more vulnerable superonasal zone and a less vulnerable inferotemporal zone. At 1-year and 2-year follow-up, new defects mostly occurred in the more vulnerable zone. Initial encroachments on an intact central VF at follow-up were more likely to be from nasal loss (11 [18.4%]; P < .001). One of the nasal loss patterns had a substantial chance at 2-year follow-up (8 [11.0%]; P = .004) to shift to total loss, whereas others did not. Conclusions and Relevance: In this study, central VF loss in end-stage glaucoma was found to exhibit characteristic patterns that might be associated with different subtypes. Initial central VF loss is likely to be nasal loss, and 1 specific type of nasal loss is likely to develop into total loss.
Webb LM, Chen JJ, Aksamit AJ, Bhattacharyya S, Chwalisz BK, Balaban D, Manzano GS, Ali AS, Lord J, Clardy SL, Samudralwar RD, Mao-Draayer Y, Garrity JA, Bhatti TM, Turner LE, Flanagan EP. A multi-center case series of sarcoid optic neuropathy. J Neurol Sci 2020;:117282.Abstract
OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/μL; range: 1-643/μL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.
Whitman MC, Di Gioia SA, Chan W-M, Gelber A, Pratt BM, Bell JL, Collins TE, Knowles JA, Armoskus C, Pato M, Pato C, Shaaban S, Staffieri S, MacKinnon S, Maconachie GDE, Elder JE, Traboulsi EI, Gottlob I, Mackey DA, Hunter DG, Engle EC, Engle EC. Recurrent Rare Copy Number Variants Increase Risk for Esotropia. Invest Ophthalmol Vis Sci 2020;61(10):22.Abstract
Purpose: To determine whether rare copy number variants (CNVs) increase risk for comitant esotropia. Methods: CNVs were identified in 1614 Caucasian individuals with comitant esotropia and 3922 Caucasian controls from Illumina SNP genotyping using two Hidden Markov model (HMM) algorithms, PennCNV and QuantiSNP, which call CNVs based on logR ratio and B allele frequency. Deletions and duplications greater than 10 kb were included. Common CNVs were excluded. Association testing was performed with 1 million permutations in PLINK. Significant CNVs were confirmed with digital droplet polymerase chain reaction (ddPCR). Whole genome sequencing was performed to determine insertion location and breakpoints. Results: Esotropia patients have similar rates and proportions of CNVs compared with controls but greater total length and average size of both deletions and duplications. Three recurrent rare duplications significantly (P = 1 × 10-6) increase the risk of esotropia: chromosome 2p11.2 (hg19, 2:87428677-87965359), spanning one long noncoding RNA (lncRNA) and two microRNAs (OR 14.16; 95% confidence interval [CI] 5.4-38.1); chromosome 4p15.2 (hg19, 4:25554332-25577184), spanning one lncRNA (OR 11.1; 95% CI 4.6-25.2); chromosome 10q11.22 (hg19, 10:47049547-47703870) spanning seven protein-coding genes, one lncRNA, and four pseudogenes (OR 8.96; 95% CI 5.4-14.9). Overall, 114 cases (7%) and only 28 controls (0.7%) had one of the three rare duplications. No case nor control had more than one of these three duplications. Conclusions: Rare CNVs are a source of genetic variation that contribute to the genetic risk for comitant esotropia, which is likely polygenic. Future research into the functional consequences of these recurrent duplications may shed light on the pathophysiology of esotropia.
Wiegand I, Wolfe JM. Age doesn't matter much: hybrid visual and memory search is preserved in older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2020;27(2):220-253.Abstract
We tested younger and older observers' attention and long-term memory functions in a "hybrid search" task, in which observers look through visual displays for instances of any of several types of targets held in memory. Apart from a general slowing, search efficiency did not change with age. In both age groups, reaction times increased linearly with the visual set size and logarithmically with the memory set size, with similar relative costs of increasing load (Experiment 1). We replicated the finding and further showed that performance remained comparable between age groups when familiarity cues were made irrelevant (Experiment 2) and target-context associations were to be retrieved (Experiment 3). Our findings are at variance with theories of cognitive aging that propose age-specific deficits in attention and memory. As hybrid search resembles many real-world searches, our results might be relevant to improve the ecological validity of assessing age-related cognitive decline.
Williams PR, Benowitz LI, Goldberg JL, He Z. Axon Regeneration in the Mammalian Optic Nerve. Annu Rev Vis Sci 2020;6:195-213.Abstract
The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.