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: “a mirror of life”. 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 “opacity of the crystalline lens”. 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 “grüne Star” means glaucoma

Worldwide Incidence of Ocular Melanoma and Correlation With Pigmentation-Related Risk Factors

Purpose: The worldwide incidence of ocular melanoma (OM), uveal melanoma (UM), and conjunctival melanoma has last been reported on 15 years ago. Recently, light iris color and four specific single-nucleotide-polymorphisms (SNPs) have been identified as a UM-risk factor. Furthermore, six iris color predicting SNPs have been discovered (IrisPlex). Interestingly, two of these (rs129138329 and rs12203592) are also UM-risk factors. We collected worldwide incidence data of OM and investigated its correlations with iris color, IrisPlex SNPs, and UM-risk SNPs. Methods: Cases of OM, as defined by the International Classification of Diseases Oncology C69 (eye), 8720/3 to 8790/3 (malignant melanoma), and 8000 to 8005 (malignant neoplasm), between 1988 and 2012, were extracted from the Cancer Incidence in Five Continents. Incidence rates were age-standardized and their trends were analyzed with joinpoint regression and age period cohort modeling. Frequencies for each country of iris color, IrisPlex SNPs, and UM-risk SNPs were collected from the literature. Results:Incidence rates were generally ≥8.0 cases per million person-years in Northern Europe, Western Europe, and Oceania; 2.0 to 7.9 in North America, Eastern Europe, and Southern Europe; and &lt;2.0 in South America, Asia, and Africa. OM incidence correlated with latitude (r = 0.77, P ≤ 0.001) and is expressed as a north-to-south decreasing gradient in Europe. SNP rs12913832 correlated with OM incidence (r = 0.83, P ≤ 0.001), blue iris color (r = 0.56, P ≤ 0.05), green iris color (r = 0.51, P ≤ 0.05), and brown iris color (r = -0.64, P ≤ 0.01). Trends were stable for most countries (28/35). Conclusions: OM incidence is highest in populations of European ancestry and lowest in populations of Asian and African ancestry. Overall, trends are stable, and the spatial correlation among OM incidence, iris color, and rs12913832 may support the role of pigmentation-related risk factors in OM development.</p

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 (14.43–16.71) and the mean (95% confidence interval) reduction in IOP-lowering medication after surgery was 1.81 (1.61–2.01). Most frequently observed postoperative complications were corneal edema (2–34%) and tube complications (4–33%). 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 1 month post-injection. RNFL-thickness was significantly reduced 6 and 12 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

Dietary nitrate intake is associated with decreased incidence of open-angle Glaucoma: The Rotterdam study

Previous studies suggest that nitric oxide is involved in the regulation of the intraocular pressure (IOP) and in the pathophysiology of open-angle glaucoma (OAG). However, prospective studies investigating the association between dietary nitrate intake, a source of nitric oxide, and incident (i)OAG risk are limited. We aimed to determine the association between dietary nitrate intake and iOAG, and to evaluate the association between dietary nitrate intake and IOP. From 1991 onwards, participants were followed each five years for iOAG in the Rotterdam Study. A total of 173 participants developed iOAG during follow-up. Cases and controls were matched on age (mean ± standard deviation: 65.7 ± 6.9) and sex (%female: 53.2) in a case:control ratio of 1:5. After adjustment for potential confounders, total dietary nitrate intake was associated with a lower iOAG risk (odds ratio (OR) with corresponding 95% confidence interval (95% CI): 0.95 (0.91–0.98) for each 10 mg/day higher intake). Both nitrate intake from vegetables (OR (95% CI): 0.95 (0.91–0.98) for each 10 mg/day higher intake) and nitrate intake from non-vegetable food sources (OR (95% CI): 0.63 (0.41–0.96) for each 10 mg/day higher intake) were associated with a lower iOAG risk. Dietary nitrate intake was not associated with IOP. In conclusion, dietary nitrate intake was associated with a reduced risk of iOAG. IOP-independent mechanisms may underlie the association with OAG

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 6.8–17.2; range 5.0–20.3) years. The incidence rate of GVFL was 2.9 (95% confidence interval 2.4–3.4) per 1000 person years (140 cas

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 − 17.8 mmHg and 2.2 lower number of IOP-lowering medications in uveitic glaucoma (compared to − 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