Sakurada Y, Parikh R, Freund BK.
RESOLUTION OF A SUBFOVEAL CHOROIDAL CAVERN AFTER HALF-DOSE PHOTODYNAMIC THERAPY FOR CENTRAL SEROUS CHORIORETINOPATHY. Retin Cases Brief Rep 2021;15(6):673-675.
AbstractPURPOSE: To describe resolution of a subfoveal choroidal cavern after half-dose verteporfin photodynamic therapy for persistent central serous chorioretinopathy. METHODS: Case report. RESULTS: A 43-year-old man was referred for treatment of chorioretinopathy in his left eye. On presentation, swept-source optical coherence tomography demonstrated a serous retinal detachment and a 161-μm-thick subfoveal choroidal cavern showing a characteristic tail of hypertransmission extending posteriorly. Subfoveal choroidal thickness measured 456 μm in the affected eye. Complete resolution of subretinal fluid and the subfoveal choroidal cavern were observed 3 months after half-dose verteporfin photodynamic therapy. Twelve months after treatment, subfoveal choroidal thickness had decreased further to 276 μm, and visual acuity had improved to 20/15. CONCLUSION: After half-dose verteporfin photodynamic therapy for chorioretinopathy, resolution of subretinal fluid was accompanied by resolution of a subfoveal choroidal cavern at 3 months and a 39.5% reduction in subfoveal choroidal thickness at 1 year.
Schoemaker D, Arboleda-Velasquez JF.
Notch3 Signaling and Aggregation as Targets for the Treatment of CADASIL and Other NOTCH3-Associated Small-Vessel Diseases. Am J Pathol 2021;191(11):1856-1870.
AbstractMutations in the NOTCH3 gene can lead to small-vessel disease in humans, including the well-characterized cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a condition caused by NOTCH3 mutations altering the number of cysteine residues in the extracellular domain of Notch3. Growing evidence indicates that other types of mutations in NOTCH3, including cysteine-sparing missense mutations or frameshift and premature stop codons, can lead to small-vessel disease phenotypes of variable severity or penetrance. There are currently no disease-modifying therapies for small-vessel disease, including those associated with NOTCH3 mutations. A deeper understanding of underlying molecular mechanisms and clearly defined targets are needed to promote the development of therapies. This review discusses two key pathophysiological mechanisms believed to contribute to the emergence and progression of small-vessel disease associated with NOTCH3 mutations: abnormal Notch3 aggregation and aberrant Notch3 signaling. This review offers a summary of the literature supporting and challenging the relevance of these mechanisms, together with an overview of available preclinical experiments derived from these mechanisms. It highlights knowledge gaps and future research directions. In view of recent evidence demonstrating the relatively high frequency of NOTCH3 mutations in the population, and their potential role in promoting small-vessel disease, progress in the development of therapies for NOTCH3-associated small-vessel disease is urgently needed.
Sena DF, Kilian R, Liu S-H, Rizzo S, Virgili G.
Pneumatic retinopexy versus scleral buckle for repairing simple rhegmatogenous retinal detachments. Cochrane Database Syst Rev 2021;11:CD008350.
AbstractBACKGROUND: A rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium caused by a full-thickness break associated with vitreous traction. While pneumatic retinopexy (PR), scleral buckle (SB), and vitrectomy are all well-received surgical interventions for eyes with RRD, their relative effectiveness has remained controversial. OBJECTIVES: To assess the effectiveness and safety of PR versus SB or PR versus a combination treatment of SB and vitrectomy for people with RRD and to summarize any data on economic measures and quality of life. SEARCH METHODS: We searched CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 3); Ovid MEDLINE; Ovid Embase; and four other databases on 11 March 2021. We used no date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials comparing the effectiveness of PR versus SB (with or without vitrectomy) for eyes with RRD. DATA COLLECTION AND ANALYSIS: After screening for eligibility, two review authors independently extracted study characteristics, methods, and outcomes. We followed systematic review standards as set by Cochrane. MAIN RESULTS: In this update, we identified and included one new randomized controlled trial. Together with two trials from the 2015 version of the review, we included three trials (276 eyes of 274 participants) comparing the effectiveness of PR versus SB. None compared PR versus a combined treatment of SB and vitrectomy. Of the three trials, one was a small study (published in 1996) with 20 participants (20 eyes) enrolled in Ireland and followed for a mean of 16 months; the second (published in 1989) included 196 participants (198 eyes) in the US followed for at least six months, and the third (published in 2021) was conducted in Italy and enrolled 58 participants (58 eyes) with a follow-up of 12 months. Overall, poor reporting quality resulted in unclear or high risks of bias. We found low-certainty evidence that PR may achieve retinal reattachment slightly less often than SB (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.81 to 1.02; I2 = 0%; 3 studies, 276 eyes). Eyes undergoing PR may also display a higher risk of recurrent retinal detachment (low-certainty evidence), but the RR estimates were very imprecise (RR 1.70, 95% CI 0.97 to 2.98; I2 = 0%; 3 studies, 276 eyes). All three studies described the final visual acuity (VA) after the two procedures. However, the results were reported using different metrics and could not be combined. One study (196 participants) reported the proportion of eyes with a final VA of 20/40 or greater and favored PR (RR 1.31, 95% CI 1.04 to 1.65; low-certainty evidence), whereas in the 2021 study, both groups showed an improvement in final VA and there was no evidence of a difference between the two (mean difference [MD] -0.03, 95% CI -0.25 to 0.19; low-certainty evidence). No study reported data on quality of life or economic measures. Postoperative safety outcomes generally favored PR versus SB (low/very low-certainty evidence); however, there was considerable uncertainty regarding the risk of any operative ocular adverse events (RR 0.55 CI 0.28 to 1.11; 276 eyes), glaucoma (RR 0.31, 95% CI 0.01 to 7.46; 198 eyes), macular pucker (RR 0.65, 95% CI 0.20 to 2.11; 256 eyes), proliferative vitreoretinopathy (RR 0.94, 95% CI 0.30 to 2.96; 276 eyes), and persistent diplopia (RR 0.24, 95% CI 0.03 to 2.09; 256 eyes). Eyes undergoing PR experienced fewer postoperative cataract developments (RR 0.40, 95% CI 0.21 to 0.75; 153 eyes), choroidal detachments (RR 0.17, 95% CI 0.05 to 0.57; 198 eyes), and myopic shift (RR 0.03, 95% CI 0.01 to 0.10; 256 eyes). AUTHORS' CONCLUSIONS: The current update confirms the findings of the previous review. PR may result in lower rates of reattachment and higher rates of recurrence than SB, but carries a lower burden of postoperative complications. The effects of these two procedures on other functional outcomes and quality of life remain uncertain. The available evidence remains insufficient and of low quality.
Sharifi S, Islam MM, Sharifi H, Islam R, Koza D, Reyes-Ortega F, Alba-Molina D, Nilsson PH, Dohlman CH, Mollnes TE, Chodosh J, Gonzalez-Andrades M.
Tuning gelatin-based hydrogel towards bioadhesive ocular tissue engineering applications. Bioact Mater 2021;6(11):3947-3961.
AbstractGelatin based adhesives have been used in the last decades in different biomedical applications due to the excellent biocompatibility, easy processability, transparency, non-toxicity, and reasonable mechanical properties to mimic the extracellular matrix (ECM). Gelatin adhesives can be easily tuned to gain different viscoelastic and mechanical properties that facilitate its ocular application. We herein grafted glycidyl methacrylate on the gelatin backbone with a simple chemical modification of the precursor, utilizing epoxide ring-opening reactions and visible light-crosslinking. This chemical modification allows the obtaining of an elastic protein-based hydrogel (GELGYM) with excellent biomimetic properties, approaching those of the native tissue. GELGYM can be modulated to be stretched up to 4 times its initial length and withstand high tensile stresses up to 1.95 MPa with compressive strains as high as 80% compared to Gelatin-methacryloyl (GeIMA), the most studied derivative of gelatin used as a bioadhesive. GELGYM is also highly biocompatible and supports cellular adhesion, proliferation, and migration in both 2 and 3-dimensional cell-cultures. These characteristics along with its super adhesion to biological tissues such as cornea, aorta, heart, muscle, kidney, liver, and spleen suggest widespread applications of this hydrogel in many biomedical areas such as transplantation, tissue adhesive, wound dressing, bioprinting, and drug and cell delivery.
Susanna FN, Melchior B, Paula JS, Boland MV, Myers JS, Wellik SR, Elze T, Pasquale LR, Shen LQ, Ritch R, Susanna R, Hood DC, Liebmann JM, De Moraes CG.
Variability and Power to Detect Progression of Different Visual Field Patterns. Ophthalmol Glaucoma 2021;4(6):617-623.
AbstractPURPOSE: To compare the variability and ability to detect visual field (VF) progression of 24-2, central 12 locations of the 24-2 and 10-2 VF tests in eyes with abnormal VFs. DESIGN: Retrospective, multisite cohort. PARTICIPANTS: A total of 52 806 24-2 and 11 966 10-2 VF tests from 7307 eyes from the Glaucoma Research Network database were analyzed. Only eyes with ≥ 5 visits and ≥ 2 years of follow-up were included. METHODS: Linear regression models were used to calculate the rates of mean deviation (MD) change (slopes), whereas their residuals were used to assess variability across the entire MD range. Computer simulations (n = 10 000) based on real MD residuals of our sample were performed to estimate power to detect significant progression (P < 5%) at various rates of MD change. MAIN OUTCOME MEASURES: Time required to detect progression. RESULTS: For all 3 patterns, the MD variability was highest within the -5 to -20 decibel (dB) range and consistently lower with the 10-2 compared with 24-2 or central 24-2. Overall, time to detect confirmed significant progression at 80% power was the lowest with 10-2 VF, with a decrease of 14.6% to 18.5% when compared with 24-2 and a decrease of 22.9% to 26.5% when compared with central 24-2. CONCLUSIONS: Time to detect central VF progression was reduced with 10-2 MD compared with 24-2 and C24-2 MD in glaucoma eyes in this large dataset, in part because 10-2 tests had lower variability. These findings contribute to current evidence of the potential value of 10-2 testing in the clinical management of patients with glaucoma and in clinical trial design.