20 research outputs found
Epidemiologic and genetic insights into open-angle glaucoma
The eye is a very complex organ with a remarkable architecture (Figure 1). It is responsible
for one of the main senses of the human being, in that every living person can observe the
world through his/her eyes: âa mirror of lifeâ. Loosing this sense, and thus loss of sight, leads
to a significant reduction in quality of life. Therefore it is crucial to prevent or cure the eye from
sight-threatening disorders.
In the past centuries several sight-threatening disorders have been described. One
of the major eye disorders affecting the visual performance is glaucoma. A few centuries
ago the general thought was that glaucoma was a disease of the lens. The word glaucoma
means âopacity of the crystalline lensâ. Because a greenish color was observed in eyes with
glaucoma, the phenomenon has also been known as green cataract. However, extraction of
the deep sea-green colored lens in glaucomatous eyes did not result in restoration of vision,
but showed that the lens was often clear rather than opacified. Later on, when the difference
between glaucoma and cataract was discovered, the term glaucoma was used for several
eye disorders other than cataract. Nowadays we still do not exactly know what glaucoma is,
but we know that the optic nerve head is primarily affected instead of the lens. Nevertheless,
this does not indicate that the historical findings were all wrong. The greenish color of the
pupil has been ascribed to corneal haze and the presence of blood pigments in some forms of
glaucoma. Even today, in German the phrase âgrĂŒne Starâ means glaucoma
The Baerveldt Glaucoma Drainage Device: Efficacy, Safety, and Place in Therapy
Objective: This review summarizes published findings concerning the Baerveldt-350 glaucoma drainage device (GDD). Most studies focus on the comparison between different
treatments; in this review, the primary focus is efficacy, safety, and place in therapy for the
Baerveldt implant.
Methods: A systematic review was performed using the PubMed database for literature on
March 13th, 2020. Efficacy was estimated by performing multiple meta-analyses to calculate
the weighted mean difference in intraocular pressure (IOP) and IOP-lowering medication
after surgery. In order to get an indication of the safety of the Baerveldt implant, all recorded
peri- and postoperative complication were summarized.
Results: A total of 21 studies, including 12 randomized controlled trials, were included with
a follow-up up to 5 years, covering a mix of glaucoma types. At the last follow-up point, at 5
years postoperative, the mean (95% confidence interval) reduction in IOP was 15.57 mmHg
(14.43â16.71) and the mean (95% confidence interval) reduction in IOP-lowering medication
after surgery was 1.81 (1.61â2.01). Most frequently observed postoperative complications
were corneal edema (2â34%) and tube complications (4â33%). Rates of required re-intervention ranged from 0% to 51% across all included studies.
Conclusion: The efficacy of the Baerveldt implant is a significant reduction in IOP in the
long term. The safety profile of the Baerveldt implant in terms of complication incidence is
similar to those reported for other GDD's. For treatment of secondary glaucoma, we suggest
the Baerveldt (or any other similar GDD) as the choice of treatment in patients where highest
IOP reduction is desired
The effects of intravitreal injections on intraocular pressure and retinal nerve fiber layer: a systematic review and meta-analysis
The number of eye diseases treated with intravitreal injections is increasing. Obviously, an injection of fluid into the eye results in an increase of intraocular pressure (IOP), the main risk factor for glaucoma. However, the effect of these repeated IOP increases on the eye is unclear. Therefore, we performed a systematic review with meta-analyses. PubMed, Embase and Clinical Trials Registries were searched for articles investigating the relationship between intravitreal injections (anti-vascular endothelial growth factor [anti-VEGF] or steroids) and either IOP, retinal nerve fiber layer (RNFL)-thickness and glaucoma. Multiple meta-analyses were performed, combining data on intravitreal injection of anti-VEGF medication and dexamethasone implants. A total of 74 articles were eligible for meta-analyses. The short-term effect of an intravitreal injection of anti-VEGF showed a statistically significant increase in IOP. One day after injection of anti-VEGF, however, IOP was significantly lower than baseline. The long-term time-intervals showed no significant difference in IOP. After intravitreal injection of a dexamethasone implant, IOP was significantly higher than baseline 1Â month post-injection. RNFL-thickness was significantly reduced 6 and 12Â months post-injection of anti-VEGF, as well as at end of follow up. Caution is advised when using intravitreal medication, especially when treating patients with advanced glaucoma; in these cases, prophylactic IOP-lowering medication may be considered
The effect of multiple vitrectomies and its indications on intraocular pressure
Background: To assess the relationship between different indications for trans pars plana vitrectomies (PPV's) and the intraocular pressure (IOP), and the effect of multiple PPV's on the IOP. We also examined whether there were differences in the number of IOP-lowering medications or surgeries before and after PPV. Methods: A retrospective study including all patients that underwent at least one PPV in the period from 2001 till 2014 at our clinic. Medical records of all patients were reviewed and clinically relevant data were entered in a database. Generalized estimating equations models for repeated measurements were used to examine the effect of the number of PPV's on the IOP and on the risk of undergoing glaucoma surgery, for each of the indications for PPV. Results: Of 1072 PPV's 447 eyes fulfilled the inclusion criteria. The IOP increased with 3.0 mmHg after a PPV with indication retinal detachment (p < 0.001), but remained stable after PPV for epiretinal membrane (p = 0.555), macular hole (p = 0.695), and vitreous hemorrhage (p = 0.787). At the end of the follow-up period the number of IOP-lowering medications was significantly higher compared to baseline, except in the macular hole group (p = 0.103). Also, the number of eyes that underwent glaucoma surgery was significantly higher compared to the fellow (not-operated) eyes (p < 0.001). There was a significant association between the number of PPV's and the final IOP for the indication retinal detachment (p = 0.009), and between the number of PPV's and glaucoma surgery (odds ratio [95% confidence interval]: 2.60 [1.62-4.15]). Conclusions: The IOP rises significantly after PPV with indication retinal detachment. This association was not found for other indications for PPV. Also, the risk of IOP-lowering surgeries was higher after PPV, but not different between the PPV indications. The IOP should be monitored carefully after PPV, since there may be a higher risk of secondary glaucoma
Efficacy of glaucoma drainage devices in uveitic glaucoma and a meta-analysis of the literature
Purpose: To assess the efficacy of glaucoma drainage devices (GDD) in uveitic glaucoma and non-uveitic glaucoma, and to perform a meta-analysis of previously published results to compare with our data. Methods: Retrospective case-control study, in which all eyes that underwent GDD surgery were included from 2015 onwards. Cases were defined as patients with uveitic glaucoma. Patients with non-uveitic glaucoma served as controls. To compare our results, a review of the literature was performed using PubMed database. Results: A total of 99 eyes were included (38 with uveitic glaucoma). The preoperative IOP was 25.9 ± 7.7 mmHg and 27.9 ± 9.6 mmHg for patients with and without uveitis (p = 0.277). No significant differences were found between patients with and without uveitis in the final IOP or reduction in IOP (44.9% vs. 42.8%, respectively). Within the first year after surgery, 13.2% of cases developed macular edema (vs. 6.6%; p = 0.267) and 15.8% a transient hypotony (vs. 8.2%; p = 0.242). A meta-analysis of 24 studies showed a postoperative weighted mean difference of â 17.8 mmHg and 2.2 lower number of IOP-lowering medications in uveitic glaucoma (compared to â 13.2 mmHg and 3.5 in the current study, respectively). Conclusion: GDD surgery in patients with uveitis has a similar effect on IOP as in patients without uveitis. The risks of developing macular edema and hypotony were slightly higher in patients with uveitis, but the results were not statistically significant. The
Mapping mRNA Expression of Glaucoma Genes in the Healthy Mouse Eye
Purpose/Aim: Many genes have been associated with primary open-angle glaucoma (POAG). Knowing
exactly where they are expressed in the eye helps to unravel POAG pathology and to select optimal
targets for intervention. We investigated whether RNA in situ hybridization (RNA-ISH) is a convenient
technique to obtain detailed pan-ocular expression data of these genes. We tested this for four diverse
candidate POAG genes, selected because of unclear ocular distribution (F5 and Dusp1) and relevance for
potential new therapies (Tnf, TgfÎČr3). Optn, a POAG gene with well-known ocular expression pattern
served as control.
Methods: We made a list of candidate glaucoma genes reported in genetic studies. A table of their
ocular expression at the tissue level was compiled using publicly available microarray data (the ocular
tissue database). To add cellular detail we performed RNA-ISH for Optn, Tnf, TgfÎČr3, F5, and Dusp1 on
eyes of healthy, 2-month-old, pigmented, and albino mice.
Results: Expression of the Optn control matched with published immunohistochemistry data. Ocular
expression of Tnf was generally low, with patches of higher Tnf expression, superficially in the corneal
epithelium. F5 had a restricted expression pattern with high expression in the nonpigmented ciliary
body epithelium and moderate expression in the peripapillary region. TgfÎČr3 and Dusp1 showed
ubiquitous expression.
Conclusions: RNA-ISH is a suitable technique to determine the ocular expression pattern of POAG
genes, adding meaningful cellular detail to existing microarray expression data. For instance, the high
expression of F5 in the nonpigmented ciliary body epithelium suggests a role of this gene in aqueous
humor dynamics and intraocular pressure. In addition, the ubiquitous expression of TgfÎČr3 has implications for designing TGF-ÎČ-related glaucoma therapies, with respect to side effects. Creating pan-ocular
expression maps of POAG genes with RNA-ISH will help to identify POAG pathways in speci
Incidence of glaucomatous visual field loss after two decades of follow-up: the Rotterdam Study
To determine the incidence of glaucomatous visual field loss (GVFL) two decades after the start of the Rotterdam Study, and to compare known risk factors for open-angle glaucoma (OAG) between different clinical manifestations of OAG. Of 6806 participants aged 55 years and older from the population-based Rotterdam Study, 3939 underwent visual field testing at baseline and at least one follow-up round. The ophthalmic examinations included optic disc assessment and measurements of intraocular pressure (IOP), refractive error, diastolic blood pressure (DBP), and height and weight. The incidence rate of GVFL was calculated. Associations with the risk factors age, gender, baseline IOP, family history, myopia, DBP, and body-mass index [BMI] were assessed using Cox regression, with different clinical manifestations of OAG as outcome measure (glaucomatous optic neuropathy (GON), GVFL, GVFL and GON, GVFL without GON, and GON without GVFL). Median follow-up was 11.1 (IQR 6.8â17.2; range 5.0â20.3) years. The incidence rate of GVFL was 2.9 (95% confidence interval 2.4â3.4) per 1000 person years (140 cas
Aqueous humor proteome of primary open angle glaucoma: A combined dataset of mass spectrometry studies
Analysis of the proteins of the aqueous humor can help to
elucidate the complex pathogenesis of primary open angle
glaucoma. Thanks to advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) it is now possible to
identify hundreds of proteins in individual aqueous humor
samples without the need to pool samples. We performed
a systematic literature search to find publications that performed LC-MS/MS on aqueous humor samples of glaucoma
patients and of non-glaucomatous controls. Of the seven
publications that we found, we obtained the raw data of
three publications. These three studies used glaucoma patients that were clinically similar (i.e. undergoing glaucoma
filtration surgery) which prompted us to reanalyse and combine their data. Raw data of each study were analysed separately with the latest version of MaxQuant (version v1.6.11.0).
Outcome files were exported to Microsoft Excel. Samples belonging to the same patient were averaged to obtain peptide
expression values per individual. We compared the overlap of identified proteins using the VLOOKUP function of Excel
and a publicly available Venn diagram software. For the peptide sequences that can belong to multiple proteins (usually
of the same protein family), we initially included all possibly identified proteins. This ensured that we would not miss
a potential overlap between the studies due to differences in
identified peptide counts. Next, of those peptides of which
we compared multiple proteins, only one unique protein was
included in our analysis i.e. either the protein overlapping
bet
XENÂź Gel Stent compared to PRESERFLOâą MicroShunt implantation for primary open-angle glaucoma: two-year results
Purpose: To evaluate the long-term efficacy and safety of two minimally invasive glaucoma surgery implants with a subconjunctival drainage approach: the XEN45 Gel StentŸ (Xen) implant and the PRESERFLO⹠MicroShunt (MicroShunt). Methods: Retrospective comparative case series of primary open-angle glaucoma (POAG) patients with at least 6 months of follow-up after a MicroShunt or Xen implantation augmented with mitomycin C. Results: Forty-one eyes of 31 patients underwent Xen implantation, and 41 eyes of 33 patients, MicroShunt implantation. Baseline characteristics were similar, except for more combined surgeries with phacoemulsification in the Xen group (37% vs. 2%). Mean baseline IOP ± standard deviation dropped from 19.2 ± 4.4 to 13.8 ± 3.8 mmHg (n = 26) in the Xen group and from 20.1 ± 5.0 to 12.1 ± 3.5 (n = 14) in the MicroShunt group at 24 months of follow-up (p = 0.19, t-test). The number of IOP-lowering medications dropped from 2.5 ± 1.4 to 0.9 ± 1.2 in the Xen group and from 2.3 ± 1.5 to 0.7 ± 1.1 in the MicroShunt group. The probability of qualified success was 73% and 79% at 24 months of follow-up for the Xen and MicroShunt groups, respectively. Postoperative complications were usually mild and self-limiting. The number of bleb needling and secondary glaucoma surgery procedures was similar in both groups; however, in the Xen group more additional MicroPulseŸ transscleral cyclophotocoagulation procedures were performed. Conclusion: Xen Gel Stent and PreserFlo MicroShunt implantations achieved comparable results in POAG eyes in terms of IOP-lowering and surgical success, with a similar high safety profile
The aqueous humor proteome of primary open angle glaucoma: An extensive review
Background: We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG. Methods: We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio). Results: Out of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched. Conclusion: AH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression