Vandenberghe L. COVID-19: Gene Transfer to the Rescue?. Hum Gene Ther. 2020;31(11-12):605–607.
Publications
2020
Xiao S, Gaier E, Mazow M, Stout A, Travers D, Angjeli E, Wu H, Binenbaum G, Hunter D. Improved adherence and treatment outcomes with an engaging, personalized digital therapeutic in amblyopia. Sci Rep. 2020;10(1):8328.
Given the prevalence of poor adherence to therapy and the biases of self-reporting across healthcare, we hypothesized that an engaging, personalized therapy may improve adherence and treatment outcomes in the home. We tested this hypothesis in the initial indication of amblyopia, a neurodevelopmental disorder for which available treatments are limited by low adherence. We designed a novel digital therapeutic that modifies patient-selected cinematic content in real-time into therapeutic visual input, while objectively monitoring adherence. The therapeutic design integrated a custom-designed headset that delivers precise visual input to each eye, computational algorithms that apply real-time therapeutic modifications to source content, a cloud-based content management system that enables treatment in the home, and a broad library of licensed content. In a proof-of-concept human study on the therapeutic, we found that amblyopic eye vision improved significantly after 12 weeks of treatment, with higher adherence than that of available treatments. These initial results support the utility of personalized therapy in amblyopia and may have broader relevance for improving treatment outcomes in additional indications.
E JY, Mihailovic A, Kuo PL, West S, Friedman D, Gitlin L, Li T, Schrack J, Ramulu P. Characterizing the Impact of Fear of Falling on Activity and Falls in Older Adults with Glaucoma. J Am Geriatr Soc. 2020;68(8):1847–1851.
OBJECTIVE: Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN: Prospective observational cohort study. SETTING: Hospital-based single-center recruitment. PARTICIPANTS: Individuals with glaucoma or suspected glaucoma. MEASUREMENTS: FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF≤0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF > 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95% CI = -743 to -71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.
Maleki A, Ueberroth J, Walsh M, Foster F, Chang P, Anesi S, Foster CS. Combination of Intravenous Methotrexate and Methylprednisolone Therapy in the Treatment of Severe Ocular Inflammatory Diseases. Ocul Immunol Inflamm. 2020;:1–5.
: To evaluate the efficacy of intravenous methotrexate and methylprednisolone in severe, sight-threatening ocular inflammatory conditions.: This was a retrospective observational case series. Patients who had received intravenous methotrexate for ocular inflammation with at least 24 months of follow-up were included in the study.: Ten patients (20 eyes) were included in this study. Mean age of the patients was 47.2 ± 17.7 (range:19-74). At 1-month follow-up visit, nine patients showed improvement and one patient failed treatment. At 12-month follow-up visit, all patients were in remission. Two patients were only on intravenous methotrexate infusions. At twenty-four-month follow-up visit, only one patient, in remission, was on intravenous methotrexate therapy. Leukopenia was the only adverse effect observed.: Intravenous methotrexate and methylprednisolone infusions can be an effective method of treatment in patients with severe, sight-threatening ocular inflammatory conditions.
Fan NW, Dohlman T, Foulsham W, McSoley M, Singh RB, Chen Y, Dana R. The role of Th17 immunity in chronic ocular surface disorders. Ocul Surf. 2020;
Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.
Dagi L, Rogers G, Proctor M, Meara J. Age at Craniosynostosis Surgery and Its Impact on Ophthalmologic Diagnoses: A Single-Center Retrospective Review. Plast Reconstr Surg. 2020;146(3):375e-376e.
Anchouche S, Yin J. Severe vernal keratoconjunctivitis complicated by anaesthetic abuse. Can J Ophthalmol. 2020;
Ozulken K, Ilhan C, Yuksel E, Mumcuoglu T. Preliminary effects of treating the half of high latent hyperopia on refractive and visual results of femtosecond laser-assisted in situ keratomileusis in subjects with hyperopia. Int Ophthalmol. 2020;40(9):2361–2369.
BACKGROUND: To evaluate the preliminary effects of treating the half of high latent hyperopia on refractive and visual outcomes of femtosecond laser-assisted in situ keratomileusis (LASIK) in young subjects with hyperopia. METHODS: This non-randomized comparative study includes 120 eyes of 60 subjects who underwent femtosecond LASIK to correct hyperopia. Group 1 (n = 60) includes subjects with ≤ 1D algebraic difference (DRSE) between cycloplegic (CRSE) and manifest (MRSE) refraction spherical equivalents and was treated by entering manifest refraction values. Group 2 includes subjects with > 1D DRSE and was treated by entering the mean manifest and cycloplegic refraction values. Refractive and subjective outcomes obtained at the 1-, 3-, and 6-month postoperative visits were compared. RESULTS: The mean age of the subjects was 26.2 ± 3.5 and 26.2 ± 5.2 years for Group 1 and Group 2, respectively. The male-to-female ratios were 10/10 in both groups. Demographic values of the groups were similar (p > 0.05). Preoperative MRSE values were similar (p = 0.924), while CRSE and DRSE values were significantly higher in Group 2 (p < 0.001). At the 1- and 3-month postoperative visits, MRSE was higher and uncorrected distance visual acuity (UDVA) was lower in Group 2 (p < 0.001). Subjective visual parameters and quality of vision scores were also worse in Group 2 during these visits (p < 0.001); however, at the 6-month visit, all outcomes for Group 2 improved, and MRSE, UDVA, some subjective visual parameters, and quality of vision scores became similar between groups (p > 0.05). CONCLUSION: At the 6-month visit after treating the half of > 1D latent hyperopia with femtosecond LASIK, refractive and visual outcomes like MRSE, UDVA, subjective visual parameters, and quality of vision scores become similar to those obtained in ≤ 1D latent hyperopia.
Koulouri I, Hellwinkel O, Altenähr S, Spitzer M, Fritz S, Feuerstacke J, Filev F. A new storage solution for the hypothermic preservation of corneal grafts: an experimental study. Cell Tissue Bank. 2020;21(3):507–521.
In this experimental study we used for the first time Tiprotec as a solution for corneal preservation and cold storage. We compared the resultant endothelial cell morphology and viability with this obtained after preservation of the ex-vivo corneas with both usual standard techniques: conventional cold storage (using Eusol-C) and organ culture. This prospective, in vitro, 3-armed parallel study was performed with the use of 90 porcine corneas (examined for their endothelial quality and transparency) randomly selected for preservation in three storage methods (each 30 corneas): organ culture, standard cold storage (Eusol-C) and experimental cold storage (Tiprotec) Endothelium cell quantity and quality as well as corneal opacification were assessed. The degree of endothelial transparency was significantly reduced over time with all preservation media, without any significant difference among the three groups at any point of time. A reduction in endothelial cell density was also observed with all three preservation media after 30 days of storage without statistically significant differences between groups. The number of hexagonal and pentagonal endothelium cells was significantly reduced overtime in all media with significantly more hexagonal and pentagonal in the organ culture group compared to the cold storage groups. We could show that the cryopreservation medium Tiprotec, used until now for the preservation of vascular grafts, was of similar quality compared to the medium Eusol-C for the hypothermic storage of corneal tissue for an extended period of time up to 30 days. In comparison to organic culture with culture medium KII, both Tiprotec and Eusol-C were found less effective in preserving endothelial cell quality, as assessed by the morphometric analysis, and viability, as assessed by the degree of vacuolization at least up to the 30th day of storage. However, both, Tiprotec- and Eusol-C-preserved corneas demonstrated a certain capacity to recover after their submission in organ culture.
Shoji M, Shishido S, Freitag S. The Use of Sirolimus for Treatment of Orbital Lymphatic Malformations: A Systematic Review. Ophthalmic Plast Reconstr Surg. 2020;36(3):215–221.
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.
