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Medicine & Pharmacology, Ophthalmology; Keywords: amniotic membrane; epithelialization; inflammation; ocular surface disorders; anti-fibrotic action, amniotic membrane eye drop, amniotic membrane graft transplantation.
Online: 15 October 2018 (14:06:21 CEST)
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Abstract: The aim of this study is to emphasize on the clinical uses of amniotic membrane (AM) in multiple ocular disorders. AM possesses many properties including promotion of epithelialization, anti-fibrotic, anti-apoptotic, anti-angiogenic properties. Epithelial wound healing on the eye surface is promoted due to several epidermal and keratocyte growth factors as well as by its anti-inflammatory and anti-scarring effects due to interleukin-10, interleukin-1 receptor antagonists and inhibition of transforming growth factor- beta (TGF-β) signal transduction by AM in the corneal and conjunctival fibroblasts respectively. It plays a crucial role by functioning as a substitute of basement membrane (BM) and as a temporary graft material. It is not only being used as an eye graft but also its extract can be used as an eye drop for corneal and external eye diseases. So its proper preparation, preservation and clinical application can bring a revolutionary change in the treatment of different ocular disorders.
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Medicine & Pharmacology, Ophthalmology; Gene therapy, gene editing, CRISPR/Cas9, Cas12a, dual AAV, triple AAV, clinical trials, retina, hereditary retinal dystrophies
Online: 1 October 2018 (15:52:23 CEST)
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Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.
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Medicine & Pharmacology, Ophthalmology; choroidal neovascularization; neovascular age-related macular degeneration; calreticulin anti-angiogenic domain
Online: 18 September 2018 (08:27:47 CEST)
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Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.
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Medicine & Pharmacology, Ophthalmology; Glucosamine, intraocular pressure, glaucoma, osteoarthritis, medication side effects.
Online: 23 August 2018 (12:20:47 CEST)
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Glucosamine is the most common nutrition supplement used in the United States. It is promoted not only as a pain reliever but also a therapy to slow osteoarthritis. Although studies with 3,800 patients with osteoarthritis of the knee or hip found that glucosamine was no better than placebo, it continues to be used for these two indications due to its perceived safety. However, reports of an increased intraocular pressure are alarming, especially in glaucoma. Glycosaminoglycans play a key role in the physiology of the cornea, conventional outflow of aqueous humor and the retina. In theory, long-term treatment with glucosamine could reach a concentration that impacts the morphology and function of ocular tissues. We recommend ophthalmologists counsel glaucoma patients about the potential risks of glucosamine and encourage cessation in uncontrolled intraocular pressure.
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Andric Christopher Perez-Ortiz,
Alexandra Luna-Angulo,
Juan Carlos Zenteno,
Alvaro Rendon,
Liliana Guadalupe Cortes-Ballinas,
David Jimenez-Collado,
Bani Antonio-Aguirre,
Martha Janneth Peralta-Ildefonso,
Israel Ramirez,
Stefany Jacob-Kuttothara,
Francisco Javier Estrada-Mena
Medicine & Pharmacology, Ophthalmology; SGCD; delta-sarcoglycan; candidate-gene approach; AMD
Online: 7 August 2018 (10:04:52 CEST)
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1) Background: CFH and HTRA1 genes are traditional markers of increased risk of AMD across populations. Recent findings suggest that additional genes, for instance, in the dystrophin-associated protein complex might be promising markers for AMD. 2) Methods: Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of 134 cases with 134 unpaired controls. Cases were 60 years or older (CARMS grade 4-5, as assessed by experienced ophthalmologists following the AAO guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or RPE changes on fundus exam and negative family history of AMD. We examined SNPs in the SGCD gene: rs931798, rs140617, rs140616, and rs970476 by sequencing and RT-PCR. Genotyping quality check and univariate analyses were performed with PLINK v.1.9. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. 3) Results: After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% (1.81, 95%CI 1.06-3.14, p=0.031), especially the geographic atrophy phenotype (1.82, 95%CI 1.03-3.21, p=0.038) compared to the G/G homozygous. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (Adjusted OR 0.13, 95%CI 0.02-0.91, p=0.041). 4) Conclusions: SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted.
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Medicine & Pharmacology, Ophthalmology; congenital cataract; consanguineous; circadian; mutation
Online: 6 August 2018 (12:04:11 CEST)
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In mice, mutations or targeted disruptions of the core circadian gene Bmal1 have been implicated in early onset of ocular pathologies, including premature/congenital cataract development. The aim of the present study was to analyze probands of consanguineous Pakistani cataract families to identify the novel pathogenic variants in the BMAL1 gene. We have studied 21 congenital cataract families. Ophthalmic examination was performed for the probands and available family members. Genomic DNA was isolated from peripheral blood. PCR and Sanger sequencing was performed for the entire coding region of the BMAL1 gene. Targeted Sanger sequencing of BMAL1 revealed a heterozygous variant c.41A>T; p.(Asp14Val) in one proband, but it did not co-segregate with the disease phenotype in the family. In addition, a nonsynonymous variant (rs2290037) was identified in five probands. Our study is the first one to analyze the role of BMAL1 gene mutations in humans for their association with congenital cataract. Although we were unable to find the variants associated with congenital cataract families from Pakistan, more studies from other populations will be informative to further prove the role of BMAL1 with the disease.
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Medicine & Pharmacology, Ophthalmology; retinal pigment epithelium (RPE); oxidative stress; mitochondria; apoptosis; 2-oxoglutarate carrier (OGC); dicarboxylate carrier (DIC); glutathione (GSH); mitochondrial GSH (mGSH)
Online: 19 July 2018 (08:15:58 CEST)
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Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.
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Medicine & Pharmacology, Ophthalmology; pigmentary glaucoma; ROCK kinase inhibitor; RKI-1447; trabecular meshwork; phagocytosis; cytoskeleton
Online: 9 July 2018 (13:27:28 CEST)
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Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.
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Medicine & Pharmacology, Ophthalmology; pigmentary glaucoma; trabecular meshwork; Goniotome; intraocular pressure; outflow facility
Online: 27 June 2018 (11:30:53 CEST)
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Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.
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Medicine & Pharmacology, Ophthalmology; Glaucoma; Intraocular Pressure(IOP) ; fundus images; early detection; Cup-to-Disk Ratio(CDR)
Online: 19 June 2018 (15:54:42 CEST)
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Glaucoma is a disease associated with retina of eye. Presently, millions of human being is suffering from this disease. Early detection of these diseases can save the people from blindness. Therefore, various methods have been developed for its detection. In this paper, we have studied the reported methods and summarized their performance in terms of accuracy of detection.
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Medicine & Pharmacology, Ophthalmology; short tunnel small flap; glaucoma drainage device implantation; tube exposure; STSF; Ahmed glaucoma valve; AGV
Online: 15 June 2018 (11:40:16 CEST)
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Purpose: To compare the efficacy and safety of graft-free short tunnel small flap (STSF) technique with that of scleral patch graft (SPG) in Ahmed glaucoma valve (AGV) implantation. Design: Randomized clinical trial. Participants: Eighty-eyes of eighty patients with medically uncontrolled glaucoma including 41 in STSF and 39 eyes in SPG. Methods: Patients were enrolled and assigned randomly to STSF or SPG. Main Outcome Measures: tube exposure, Intraocular pressure (IOP), number of glaucoma medications, best corrected visual acuity (BCVA), surgical complications, and success rate ( defined as intraocular pressure (IOP) >5 mmHg, ≤21 mmHg, and IOP reduction ≥20% from baseline at two consecutive visits after three months, no reoperation for glaucoma). Results: only one case in SPG developed tube exposure at 1-year follow-up. The cumulative probability of success during the first year of follow-up was 70% in the STSF and 65% in SPG (P = 0.36). IOP decreased significantly from 29.6 ± 8.6 mmHg at baseline to 16.4 ± 3.6 mmHg at the final follow-up in STSF (p = 0.001). The corresponding numbers for SPG were 30.9 ± 11.2 and 15.8 ± 4.7, respectively (p = 0.001). The final IOP was comparable between both groups (p = 0.65). Mean ± standard deviation of the number of glaucoma medications was 1.8 ± 0.9 in STSF and 1.6 ± 0.9 in SPG at final follow-up (P = 0.32). Postoperative complications developed in 8 patients (19%) in STSF and 9 patients (23%) in SPG (P = 0.81). Conclusions: STSF and SPG techniques had comparable complication rate at one-year follow-up. Both techniques were comparable in terms of success rate, postoperative IOP, and glaucoma medications.
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Medicine & Pharmacology, Ophthalmology; neovascular AMD; new therapies; anti-VEGFs; AMD signalling
Online: 12 June 2018 (08:26:56 CEST)
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Neovascular age-related macular degeneration (nAMD) accounts for one of the leading causes of blindness among the aging population. The current treatment options for nAMD include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). However, standardised frequent administration of anti-VEGF injections only improves the vision in approximately 30%-40% of nAMD patients. Current therapies targeting nAMD pose a significant risk of retinal fibrosis and geographic atrophy (GA) development in nAMD patients. A need exists to develop new therapies to treat nAMD with effective and long-term anti-angiogenic effects. Recent research on nAMD has discovered novel therapeutic targets and angiogenic signalling mechanisms involved in its pathogenesis. For example, tissue factor, human intravenous immune globulin, interferon-β signalling, cyclooxygenase-2 (COX-2) and cytochrome P450 monooxygenase lipid metabolites have been identified as key players in the development of angiogenesis in AMD disease models. Furthermore, novel therapies such as NLRP3 inflammasome inhibition, targeted intraceptor nanoparticle therapy, inhibitors of integrins and tissue factor are currently being tested at the level of clinical trials to treat nAMD. The aim of this review is to discuss the scope for alternative therapies proposed to anti-VEGFs for the treatment of nAMD.
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Medicine & Pharmacology, Ophthalmology; Marfan syndrome; ophthalmology; ectopis lentis; ocular complication; management
Online: 9 May 2018 (08:37:24 CEST)
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Marfan syndrome is an autosomal dominant genetic connective tissue disorder that results from mutations in the fibrillin-1 gene located on chromosome band 15q 15–21. Fibrillin, a glycoprotein, is widely expressed throughout the body and contribute to elasticity and force-bearing capacity of connective tissue. In the eye, fibrillin is a key constituent of the ciliary zonules, which suspend the crystalline lens in place. The zonular defect leads to ectopia lentis that is hallmark of Marfan ocular abnormalities and occurs in 60 to 80% of cases. Other less common ocular features of Marfan syndrome are increased axial length, astigmatism, and flat cornea. Visual function in Marfan syndrome could be affected in several ways: ectopia lentis, refractive error, amblyopia, retinal detachment, cataract, and glaucoma. Management of subluxated lens starts with correction of refractive error with eyeglasses in mild cases. In more severe cases, especially when lens bisects the pupil, complete correction of refractive error is impossible without removing subluxated lens. The best method for visual rehabilitation after lens extraction is still debated. Aphakic Artisan implantation at the time of subluxated lens removal results in good visual outcomes with acceptable safety profile. Studies with longer term follow up and larger sample populations are needed to evaluate the safety of this procedure in patients with Marfan syndrome.
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Medicine & Pharmacology, Ophthalmology; primary open angle glaucoma; dorzolamide/timolol fixed combination; drug efficacy; safety
Online: 24 April 2018 (10:36:58 CEST)
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Purpose: To compare the therapeutic efficacy and safety of dorzolamide/timolol fixed-combination in newly diagnosed primary open angle glaucoma patients. Methods: In this prospective, interventional case series, newly diagnosed primary open angle glaucoma (POAG) patients that had not been treated for glaucoma were included. Patients were started on Cosopt twice a day (BID) for 1 month and then switched to three times a day (TDS) for additional 1 month. Patients underwent comprehensive ophthalmic examination, diurnal intraocular pressure (IOP), blood pressure (BP) and 24-hours heart rate (HR) measurements at baseline, month 1( BID), and month 2( TDS). IOP, systolic and diastolic pressures were measured at 8:00 AM,12:00 AM, 4:00 PM, 8:00 PM and 12:00 PM. Throughout the study, all adverse events were recorded and monitored by the investigators. Results: In 31 POAG patients that completed the study ,mean baseline IOP was 23.1±3.15 mmHg . IOP was decreased significantly 16.5 ± 2.21 at 1 month (P < 0.0001) and 13.9 ± 2.23 mmHg at 1 and 2 month follow up. (P < 0.0001) IOP was significantly lower in month 2 compared to month 1 (P = 0.0004). While Cosopt BID significantly reduced the mean 24-hour systolic BP and mean 24-hour HR from baseline (P < 0.0001), the mean 24-hour systolic BP and HR remained unchanged 2ith Cosopt TDS compared to BID (P = 0.62). Conclusions: Cosopt TDS has a superior IOP-lowering effect than Cosopt BID in POAG patients with comparable safety profile.
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Medicine & Pharmacology, Ophthalmology; Ab interno trabeculectomy; Trabectome surgery; long-term outcomes; microinvasive glaucoma surgeries; MIGS
Online: 19 April 2018 (11:41:02 CEST)
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Purpose: To analyze the five-year results of Trabectome ab interno trabeculectomy of a single glaucoma center. Method: In this retrospective interventional single-center case series, data of 93 patients undergoing ab interno trabeculotomy between September 2010, and December 2012 were included. Kaplan-Meier analysis was performed using success criteria defined as postoperative intraocular pressure (IOP) ≤21 mm Hg, or >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio (HR). Results: The retention rate for five years follow-up was 66%. The cumulative probability of success at 1, 2, 3, 4 and 5 years was 82.6%, 76.7%, 73.9%, 72.3%, and 67.5%. Risk factors for failure were lower baseline IOP (HR=0.27, P=0.001), younger age (HR=0.25, P=0.02), and higher central corneal thickness (HR=0.18, P= 0.01). Pseudoexfoliation was associated with a higher success rate (HR= 0.39, P=0.02). IOP was decreased significantly from 20.0±5.6 mmHg at baseline to 15.6±4.6 mmHg at 5-year follow-up (P=0.001). The baseline number of glaucoma medications was 1.8±1.2, which decreased to 1.0±1.2 medications at 5 years. Conclusion: Trabectome surgery was associated with a good long-term efficacy and safety profile in this single-center case series with a high retention rate. A higher baseline IOP, older age, thinner cornea, and pseudoexfoliation glaucoma were associated with a higher success rate.
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Medicine & Pharmacology, Ophthalmology; Methanol exposure; toxic effects; subcontractor manufacturing; dispatched workers; visual defect; neurobehavioral function
Online: 3 April 2018 (18:11:15 CEST)
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An outbreak of occupational methanol poisoning occurred in small-scale 3rd tier factories of large-scale smartphone manufacturer, in the Republic of Korea, in 2016. To investigate the working environment and the health effect of the methanol exposure among co-workers of the methanol poisoning cases, we performed a cross sectional study on 155 workers at the five aluminum CNC cutting factories. Air and urinary methanol concentration were measured by gas chromatography, and health examination included symptoms, ophthalmological examinations and neurobehavioral tests. Multiple logistic regression analyses controlled for age and sex were conducted for revealing association of employment duration with symptoms. Air concentrations of methanol in factory A and E were ranged from 228.5 to 2220.0 ppm. Mean urinary methanol concentrations of the workers in each factory were from 3.5 mg/L up to 91.2 mg/L. The odds ratios for symptom of deteriorating vision and CNS increased, according to the employment duration, after adjusting for age and sex. Four cases with injured optic nerve and two cases with decreased neurobehavioral function were founded among co-workers of the victims. This study showed that the methanol exposure under poor environmental control not only produce eye and CNS symptoms but also affect neurobehavioral function and optic nerve.
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Medicine & Pharmacology, Ophthalmology; pigment dispersion syndrome; pigmentary glaucoma; trabecular meshwork; phagocytosis; migration; contraction; cytoskeleton; gene microarray; Rho signaling pathway
Online: 2 April 2018 (09:00:45 CEST)
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Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.
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Medicine & Pharmacology, Ophthalmology; pigmentary glaucoma; pigment dispersion; intraocular pressure; trabecular meshwork; cytoskeleton; phagocytosis; gene expression microarray; signal pathway
Online: 27 March 2018 (07:22:15 CEST)
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Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.
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Medicine & Pharmacology, Ophthalmology; ab interno trabeculectomy; intraocular pressure; outflow facility; canalogram; trabecular meshwork
Online: 27 March 2018 (07:13:49 CEST)
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Purpose: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.
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Medicine & Pharmacology, Ophthalmology; glaucoma; lamina cribrosa; optic nerve head; optical coherence tomography; corneal hysteresis; visual field; trabeculectomy
Online: 24 February 2018 (12:06:05 CET)
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Purpose: To investigate the relationship of lamina cribrosa displacement to corneal biomechanical properties and visual function after mitomycin C-augmented trabeculectomy. Method: Eighty-one primary open angle eyes were imaged before and after trabeculectomy using an enhanced depth spectral-domain optical coherence tomography (SDOCT). Corneal biomechanical properties were measured with the Ocular Response Analyser before the surgery. The anterior lamina cribrosa (LC) was marked at several points in each of six radial scans to evaluate LC displacement in response to Intraocular pressure (IOP) reduction. A Humphrey visual field test (HVF) was performed before the surgery as well as three and six months postoperatively. Results: Factors associated with a deeper baseline anterior lamina cribrosa depth (ALD) were cup-disc ratio (P=0.04), baseline IOP (P= 0.01), corneal hysteresis (P= 0.001), and corneal resistance factor (P= 0.001). After the surgery, the position of LC became more anterior (negative), posterior (positive) or remained unchanged. The mean LC displacement was -42 μm (P= 0.001) and was positively correlated with the magnitude of IOP reduction (regression coefficient: 0.251, P=0.02), and negatively correlated with age (regression coefficient: - 0.224, P= 0.04) as well as baseline cup-disk ratio (Regression coefficient: -0.212,P= 0.05) Eyes with a larger negative LC displacement were more likely to experience an HVF improvement of more than 3 dB gain in mean deviation (P= 0.002). Conclusion: A lower SDOCT cup-disc ratio, younger age, and a larger IOP reduction were correlated with a larger negative LC displacement and improving HVF. Corneal biomechanics did not predict LC displacement.
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Medicine & Pharmacology, Ophthalmology; eye, cataract, epidemiology, public health
Online: 19 February 2018 (17:37:16 CET)
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Background: To assess the incidence and characteristic of cataract surgery in Poland from 2010 to 2015 and to interpret these findings. Patients and methods: Data from all patients who underwent cataract surgery alone or in combined procedures in Poland between January 2010 and December 2015 were evaluated. Patient data were from the national database of hospitalizations maintained by National Health Fund, data on the population of Poland were obtained from Central Statistical Office of Poland. Results: In total 1,218,777 cataract extractions (alone or combined with other procedures) were performed in 1,081,345 patients during 2010 -2015. Overall, the incidence of cataract surgery increased from 5.22/1000 person-years in year 2010 to 6.17/1000 person-years in year 2015. Phacoemulsification was performed in 97.46% of cataract extractions, and 3.02% of cataract extractions were combined procedures. The rate of one-day procedures increased from 28.3% in year 2010 to 43.1% in year 2015. The probability of second-eye surgery 12 months after the first-eye surgery increased from 44% in 2010 to 73% in 2015 (log-rank test p<0.0001). Conclusion: In Poland, from 2010 to 2015 the total incidence of cataract surgery, the number of people who underwent surgery, and the numbers of one-day and combined cataract surgeries, increased significantly.
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Medicine & Pharmacology, Ophthalmology; pig eye perfusion model; pigmentary glaucoma; ocular hypertension; ocular hypotension; phagocytosis; rho-kinase inhibitor
Online: 5 February 2018 (04:39:57 CET)
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Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67 × 107 pigment particles/mL) for 48 hours before being subjected to the RKI-1447 (n = 16) or the vehicle control (n = 12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas.
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Medicine & Pharmacology, Ophthalmology; Ahmed glaucoma valve; trabectome surgery; hypertensive phase; glaucoma surgery
Online: 5 February 2018 (04:10:08 CET)
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Purpose: To evaluate the efficacy and survival rates of same session ab interno trabeculectomy with the trabectome and Ahmed glaucoma valve implant (AT) in comparison to the Ahmed glaucoma valve alone (A). Method: A total of 107 eyes undergoing primary glaucoma surgery were enrolled in this retrospective comparative case series, including 48 eyes which underwent AT and 59 eyes which received A alone. Participants were identified using the procedural terminology codes, and their medical records were reviewed. The primary outcome measure was surgical success, defined as intraocular pressure (IOP) > 5 mmHg, ≤ 21 mmHg, and IOP reduction ≥ 20% from baseline at two consecutive visits after three months, no reoperation for glaucoma. Secondary outcome measures were IOP, the number of glaucoma medications, incidence of a hypertensive phase, and best corrected visual acuity (BCVA). Results: The cumulative probability of success at one year was 70% in AT, and 65% in A (p=0.85). IOP decreased significantly from 26.6 ± 10.1 mmHg at baseline to 14.7 ± 3.3 mmHg at the final follow-up in AT (p= 0.001). The corresponding numbers for A were 28.8 ± 10.2 and 16.7 ± 4.9, respectively (p= 0.001). The final IOP was significantly lower in AT (p= 0.022). The number of medications at baseline was comparable in both groups (2.6 ± 1.2 in AT and 2.5 ± 1.3 in A, p=0.851). Corresponding number at 1 year visit was 1.2±2 in AT and 2.8±1.8 in A (p=0.001). The incidence of a hypertensive phase was 18.7% in AT and 35.5% in A (p=0.05). HP resolved in only 30% of eyes. The criteria for HP resolution were fulfilled in 9 eyes (30%). There was no difference in the rate of resolution of the hypertensive phase between AT and A (33.3% and 28.5%, respectively, p=0.67). Conclusion: Ahmed glaucoma valve implant with same session trabectome surgery significantly decreased the rate of the hypertensive phase and postoperative IOP as well as the number of glaucoma medications.
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Medicine & Pharmacology, Ophthalmology; Retinal Pigment Epithelium (RPE); endosomes; phagosomes; lysosomes, autophagy; RPE cultures; Age-related Macular Degeneration (AMD)
Online: 29 January 2018 (09:07:19 CET)
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Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.
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Medicine & Pharmacology, Ophthalmology; primary open-angle glaucoma; minimally invasive glaucoma surgery; ab interno trabeculectomy; intraocular pressure; success rate
Online: 11 January 2018 (05:01:57 CET)
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To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P<0.05). The number of glaucoma medications also decreased from a baseline of 2.0±0.9 to 1.2± 0.21 at 2 years (P=0.04). The overall success was 78%, with patients undergoing combined surgery having a higher success than those with Trabectome surgery alone (100% vs. 76%). No major complications were seen. The Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.
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Medicine & Pharmacology, Ophthalmology; myopia, hyperopia, anisometropia
Online: 21 November 2017 (04:28:01 CET)
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Background: To investigate the distribution of refractive errors and their characteristics in older adults. Methods: The study design was cross-sectional study. A total of 1107 men and women were interviewed and underwent detailed ophthalmic examinations, 998 subjects underwent refraction. Myopia was defined as spherical equivalent (SER) refraction ≤ −0.5 dioptres (D) and hyperopia was defined as SER ≥ +0.5 dioptres (D). Results: Among those who were refracted the distribution of myopia and hyperopia was 24.1% (95% CI 21.4–26.7) and 37.5% (95% CI 34.5–40.5), respectively. Myopia decreased from 28.7% in subjects aged 35-59 years to 19.3% in those aged 60 years or older and hyperopia increased from 21.8% at 35–59 years of age to 53.3% in subjects aged ≥60 years. Multiple regression analysis showed decreasing age (OR 0.98, 95% CI 0.96–1.00), female gender (OR 1.87, 95% CI 1.18–2.95) and presence of cataract (OR 2.40 , 95% CI 1.24–4.63) were independent risk factors associated with myopia. Conclusions: The distribution of refractive errors found in our study is similar to those reported in other Caucasian populations and differs from Asian populations. Myopia was positively associated with younger age, female gender and presence of cataract.
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Medicine & Pharmacology, Ophthalmology; dry eye; lacrimal gland; lipids and lipidomics; Meibomian gland; ocular surface disorders; proteins and proteomics; tear film
Online: 22 May 2017 (09:54:47 CEST)
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The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome, because the tear film represents the interface between the eye and the environment. Despite having a multifactorial origin, the main risk factors for the emergence of the ocular disease are female gender and advanced age. Likewise, morphological changes in several glands and in chemical composition of their secretions such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors to maintain a condition of good health of the ocular anterior segment. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic infiammation that reflex on the ocular surface. However, it is one of the most commonly encountered disease in clinical practice and many other causes related to daily life and to lengthen the average life will contribute to the beginning. This review will consider how and what disorders of the ocular surface are responsible for a widespread pathology so. In the end, the most appropriate and new therapies will be briefly exposed according to the specific pathology.