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. These findings are in line with previous reports, though data on the efficacy of GDD surgery and macular edema in uveitic glaucoma is scarce.

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.

WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness.

Keratoconus is a degenerative eye condition which results from thinning of the cornea and causes vision distortion. Treatments such as ultraviolet (UV) cross-linking have proved effective for management of keratoconus when performed in early stages of the disease. The central corneal thickness (CCT) is a highly heritable endophenotype of keratoconus, and it is estimated that up to 95% of its phenotypic variance is due to genetics. Genome-wide association efforts of CCT have identified common variants (i.e. minor allele frequency (MAF) >5%). However, these studies typically ignore the large set of exonic variants whose MAF is usually low. In this study, we performed a CCT exome-wide association analysis in a sample of 1029 individuals from a population-based study in Western Australia. We identified a genome-wide significant exonic variant rs121908120 (P = 6.63 × 10(-10)) in WNT10A. This gene is 437 kb from a gene previously associated with CCT (USP37). We showed in a conditional analysis that the WNT10A variant completely accounts for the signal previously seen at USP37. We replicated our finding in independent samples from the Brisbane Adolescent Twin Study, Twin Eye Study in Tasmania and the Rotterdam Study. Further, we genotyped rs121908120 in 621 keratoconus cases and compared the frequency to a sample of 1680 unscreened controls from the Queensland Twin Registry. We found that rs121908120 increases the risk of keratoconus two times (odds ratio 2.03, P = 5.41 × 10(-5)).

ARHGEF12 influences the risk of glaucoma by increasing intraocular pressure.

Primary open-angle glaucoma (POAG) is a blinding disease. Two important risk factors for this disease are a positive family history and elevated intraocular pressure (IOP), which is also highly heritable. Genes found to date associated with IOP and POAG are ABCA1, CAV1/CAV2, GAS7 and TMCO1. However, these genes explain only a small part of the heritability of IOP and POAG. We performed a genome-wide association study of IOP in the population-based Rotterdam Study I and Rotterdam Study II using single nucleotide polymorphisms (SNPs) imputed to 1000 Genomes. In this discovery cohort (n = 8105), we identified a new locus associated with IOP. The most significantly associated SNP was rs58073046 (ß = 0.44, P-value = 1.87 × 10(-8), minor allele frequency = 0.12), within the gene ARHGEF12. Independent replication in five population-based studies (n = 7471) resulted in an effect size in the same direction that was significantly associated (ß = 0.16, P-value = 0.04). The SNP was also significantly associated with POAG in two independent case-control studies [n = 1225 cases and n = 4117 controls; odds ratio (OR) = 1.53, P-value = 1.99 × 10(-8)], especially with high-tension glaucoma (OR = 1.66, P-value = 2.81 × 10(-9); for normal-tension glaucoma OR = 1.29, P-value = 4.23 × 10(-2)). ARHGEF12 plays an important role in the RhoA/RhoA kinase pathway, which has been implicated in IOP regulation. Furthermore, it binds to ABCA1 and links the ABCA1, CAV1/CAV2 and GAS7 pathway to Mendelian POAG genes (MYOC, OPTN, WDR36). In conclusion, this study identified a novel association between IOP and ARHGEF12.

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium.

Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (-0.17 mmHg per 10 cm; 95 % CI -0.25, -0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.

Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p=1.4×10(-8)), and with rs7555523, located in TMCO1 at 1q24.1 (p=1.6×10(-8)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p=2.4×10(-2) for rs11656696 and p=9.1×10(-4) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

Common genetic variants associated with open-angle glaucoma.

Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), Southampton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.

A genome-wide association study of optic disc parameters.

The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p = 6.72x10(-19)) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p = 2.67x10(-33)) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p = 6.15x10(-11)) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p = 2.93x10(-10)) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N = 3,612), and the TwinsUK cohort (N = 843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin.

Nutrient intake and risk of open-angle glaucoma: the Rotterdam Study.

Open-angle glaucoma (OAG) is the commonest cause of irreversible blindness worldwide. Apart from an increased intraocular pressure (IOP), oxidative stress and an impaired ocular blood flow are supposed to contribute to OAG. The aim of this study was to determine whether the dietary intake of nutrients that either have anti-oxidative properties (carotenoids, vitamins, and flavonoids) or influence the blood flow (omega fatty acids and magnesium) is associated with incident OAG. We investigated this in a prospective population-based cohort, the Rotterdam Study. A total of 3502 participants aged 55 years and older for whom dietary data at baseline and ophthalmic data at baseline and follow-up were available and who did not have OAG at baseline were included. The ophthalmic examinations comprised measurements of the IOP and perimetry; dietary intake of nutrients was assessed by validated questionnaires and adjusted for energy intake. Cox proportional hazard regression analysis was applied to calculate hazard ratios of associations between the baseline intake of nutrients and incident OAG, adjusted for age, gender, IOP, IOP-lowering treatment, and body mass index. During an average follow-up of 9.7 years, 91 participants (2.6%) developed OAG. The hazard ratio for retinol equivalents (highest versus lowest tertile) was 0.45 (95% confidence interval 0.23-0.90), for vitamin B1 0.50 (0.25-0.98), and for magnesium 2.25 (1.16-4.38). The effects were stronger after the exclusion of participants taking supplements. Hence, a low intake of retinol equivalents and vitamin B1 (in line with hypothesis) and a high intake of magnesium (less unambiguous to interpret) appear to be associated with an increased risk of OAG.

Genetic architecture of open angle glaucoma and related determinants.

BACKGROUND: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG. METHODS: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean ± SD age: 64.6 ± 9.1 years). These risk scores were used to calculate the explained variance of VCDR and IOP in an independent cohort (Erasmus Rucphen Family study) consisting of 1646 participants (mean ± SD age: 46.8 ± 14.1 years) and the OAG risk in a subset of the Rotterdam Study cohorts. To evaluate false positive findings, we generated two new variables containing randomly sampled values to serve as a negative control. RESULTS: The explained variance of VCDR increased when increasing the number of SNPs included in the risk score, suggesting a polygenic model. We found no clear evidence for a similar model for IOP, suggesting that a small number of SNPs determine the susceptibility to IOP. The SNPs related to IOP in terms of p values contributed little to VCDR. The risk scores associated with VCDR were also associated significantly with OAG. This suggests a common polygenic background for VCDR and OAG CONCLUSIONS: We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model.

Efficacy and Safety of Micropulse Transscleral Cyclophotocoagulation.

Background: Early studies have shown that micropulse transscleral cyclophotocoagulation (MP-TSCPC) might be an effective and safe treatment option for lowering intraocular pressure (IOP). These studies were, however, somewhat limited, in particular by their retrospective nature and the length of follow-up. Therefore, we assessed the efficacy and safety of this novel treatment in a large cohort for up to 4 years. Methods: We performed a prospective cohort study, including all patients who were treated with MP-TSCPC since November 2017. The primary outcome was a reduction of IOP and the number of IOP-lowering medications. Results: The mean ± standard deviation baseline IOP and number of IOP-lowering medications were 26.6 ± 10.8 mmHg and 3.3 ± 1.3. IOP was reduced by 8.2 ± 7.9 (31.8% reduction), 6.9 ± 8.7 (28.1% reduction), and 7.1 ± 8.4 (30.2% reduction) mmHg after 6, 12, and 24 months, respectively (p < 0.001). The mean postoperative number of IOP-lowering medications was significantly reduced after 6 months by 0.6 ± 1.5 (p = 0.002) but was not significantly different after 12 or 24 months. Oral acetazolamide was significantly reduced from 28 (29%) eyes before treatment, to 9 (9%) at the last follow-up visit (p < 0.001). No major complications were observed after treatment. Conclusions: MP-TSCPC is a safe and effective treatment option for lowering IOP, but only reduced IOP-lowering medications in the first 6 months after treatment. However, MP-TSCPC is especially effective in getting patients off oral IOP-lowering drugs.

Efficacy of the PRESERFLO MicroShunt and a Meta-Analysis of the Literature.

Background: Recent studies on the PRESERFLO MicroShunt suggest that it may be effective in lowering intraocular pressure (IOP); however, the number of studies on this device remains limited. Therefore, we assessed the efficacy of the PRESERFLO MicroShunt in patients with glaucoma and performed a meta-analysis of published results. Methods: Prospective study including all patients that underwent PRESERFLO MicroShunt surgery from 2018 onwards. Sub-analyses were performed for cataract-combined procedures. To compare our results, we performed a systematic review and meta-analysis. IOP, IOP-lowering medication and surgical complications reported in the retrieved studies were assessed. Results: A total of 72 eyes underwent PRESERFLO-implant surgery (59 as standalone procedure and 13 as cataract-combined procedure). No significant differences were found in IOP and IOP-lowering medication between both groups. The mean ± standard deviation IOP and IOP-lowering medications of both groups taken together declined from 21.72 ± 8.35 to 15.92 ± 8.54 mmHg (p < 0.001, 26.7% reduction) and 3.40 to 0.93 (p < 0.001, 72.6% reduction) at 1 year follow-up, respectively. Secondary surgeries were required in 19.4% of eyes, the majority (71.4%) within 6 months. The meta-analysis including 14 studies (totaling 1213 PRESERFLO MicroShunt surgeries) from the systematic review showed a mean preoperative IOP and IOP-lowering medication of 22.28 ± 5.38 and 2.97 ± 1.07, respectively. The three-years postoperative pooled mean was (weighted mean difference, 95% CI) 11.07 (10.27 [8.23−12.32], p < 0.001) mmHg and 0.91 (1.77 [1.26−2.28], p < 0.001) for IOP and IOP-lowering medication, respectively. The most common reported complication was hypotony (2−39%). Conclusion: The PRESERFLO MicroShunt is effective and safe in lowering IOP and the number of IOP-lowering medications.

Clinical implications of old and new genes for open-angle glaucoma.

OBJECTIVE: Genome-wide association studies have revealed new insights into the genetic determinants of open-angle glaucoma (OAG). This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG. DESIGN: Population-based setting, family-based setting, and a case-control study. PARTICIPANTS: The Rotterdam Study I cohort (N = 5312; mean age±standard deviation [SD], 68.0±8.4 years). Findings were replicated in the Genetic Research in Isolated Populations combined with the Erasmus Rucphen Family study (N = 1750; mean age±SD, 48.3±15.2 years), and a cohort from Southampton (N = 702; mean age±SD, 72.5±10.7 years). METHODS: After identifying common variants associated with OAG within the established genes, the risk of OAG was analyzed using logistic regression. Discriminative accuracy was assessed by comparing the area under the receiver operator characteristic curve (AUC) for models, including the number of risk alleles, intraocular pressure, age, and gender, with the AUC for the same model but without the risk alleles. MAIN OUTCOME MEASURES: Odds ratios and AUCs of individual and combined risk alleles. RESULTS: No consistent significant associations for the established genes (MYOC, OPTN, and WDR36) with OAG were found. However, when comparing the load of risk variants between cases and controls, 2 of 3 studies showed a significant increased risk of OAG for participants carrying more risk alleles of the 3 established genes. When combining all 6 genes, participants carrying a high number of risk alleles (highest tertile) had a 2.29-fold to 3.19-fold increase in risk of OAG compared with those carrying only a few risk alleles. The addition of the newly identified genes to IOP, age, and gender resulted in a higher AUC compared with the AUC without the newly identified genes (P = 0.027). CONCLUSIONS: A significant contribution to the risk of OAG was found for the new common variants identified by recent genome-wide association studies, but not for variants within the established genes. Participants carrying a high number of risk alleles had an approximately 3-fold increase in the risk of OAG compared with those with a low number of risk alleles. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy of the XEN-Implant in Glaucoma and a Meta-Analysis of the Literature.

BACKGROUND: To assess the efficacy of XEN-implant surgery in patients with glaucoma, and to perform a meta-analysis of previously published results and compare these to our data. METHODS: Prospective case-control study, in which all eyes that underwent XEN-implant surgery were included from 2015 onwards. Sub-analyses were performed for eyes that underwent XEN-implant as standalone procedure and as cataract-combined procedure. To compare our results, a systematic review was performed using the Embase, PubMed, Web of Science, and Cochrane database. Meta-analyses were performed by combining data (intraocular pressure (IOP), IOP-lowering medication, and complications) from the retrieved studies. RESULTS: A total of 221 eyes underwent XEN-implant surgery (124 standalone and 97 cataract-combined). The mean ± standard deviation IOP declined from 18.8 ± 6.5 to 13.5 ± 4.3 mmHg at the last follow-up (p < 0.001; 28.9%). Postoperative, no significant differences in IOP or IOP-lowering medication were found between patients with and without combined procedure. Secondary surgeries were performed in 20.8% of eyes, most of them (63.0%) within six months. A meta-analysis of 19 studies retrieved from the systematic review showed a two-years postoperative pooled mean (weighted mean difference) of 14.5 (7.3) mmHg and 1.0 (1.6) for IOP and IOP-lowering medications, respectively (compared to 13.5 (5.3) mmHg and 3.2 (2.4) in the current study). CONCLUSION: XEN-implant surgery was effective and safe in lowering IOP and the number of IOP-lowering medications. There were no differences between standalone and combined procedures.

Incidence of glaucomatous visual field loss: a ten-year follow-up from the Rotterdam Study.

PURPOSE: To determine the 10-year incidence of glaucomatous visual field loss (GVFL) and to investigate the influence of risk factors for open-angle glaucoma on this incidence. DESIGN: Population-based cohort study. PARTICIPANTS: Participants aged > or =55 years from the Rotterdam Study. METHODS: Of the 7983 participants in the Rotterdam Study, 6806 underwent ophthalmic examinations at baseline (1990-1993). In 6723 of these 6806 participants (99%), both visual field screening and an assessment of the optic disc were performed. After exclusion of 93 participants with GVFL at baseline, 6630 participants at risk of developing GVFL remained. These participants underwent similar ophthalmic examinations during 2 follow-up visits (1997-1999 and 2002-2006). The incidence of GVFL was determined as an incidence rate and recalculated to a 10-year risk. Risk factors for open-angle glaucoma (age, gender, positive family history of glaucoma, baseline intraocular pressure (IOP), myopia, and baseline vertical cup-to-disc ratio [VCDR]) were assessed using Cox regression. The dependent variable was the development of GVFL. MAIN OUTCOME MEASURES: Ten-year risk and incidence rates of GVFL. Hazard ratios of the above-mentioned risk factors. RESULTS: Of 6630 participants, 3939 (59%) completed at least 1 follow-up examination and 2571 (39%) completed both; 108 participants developed GVFL. The overall incidence rate and 10-year risk of GVFL were 2.9 per 1000 person-years (95% confidence interval [CI], 2.4-3.5) and 2.8% (2.3-3.4), respectively. The 10-year risk increased from 1.9% at age 55 to 59 years to 6.4% at age > or =80 years (P<0.001). The incidence increased by 11% per millimeter of mercury increase in IOP (hazard ratio 1.11; 95% CI, 1.06-1.15). Male gender (1.62; 1.10-2.38), high myopia (spherical equivalent < or =-4 D myopic; 2.31; 1.19-4.49), and a baseline VCDR above the 97.5th percentile (4.64; 2.72-7.91) were associated with the development of GVFL. A positive family history was only significantly associated with the development of GVFL if IOP was removed from the model (2.0; 1.2-3.3; P = 0.012). CONCLUSIONS: These data provide an estimate of the incidence of GVFL in a white population. The development of GVFL was related to higher IOP, older age, high myopia, male gender, a positive family history of glaucoma, and a larger baseline VCDR.

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.

Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users.

BACKGROUND: Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their combinations in eye drops, and falls, dizziness and orthostatic hypotension in older patients. METHODS: All participants were long-term users of eye drops containing beta-blockers, prostaglandins or their combinations. They underwent a structured falls interview and blood pressure measurement for testing of orthostatic hypotension. The odds ratio for presence of orthostatic hypotension or a positive falls history according to use of beta-blocker eye drops was calculated with a binary logistic regression analysis. The main outcome measures were a positive falls history and the presence of orthostatic hypotension. RESULTS: In total, 148 of 286 subjects participated. After adjustment for age, gender, and use of fall-risk-increasing drugs other than beta-blocker eye drops, we found no significant difference in fall risk [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.268-1.327] between patients using ophthalmic beta-blockers or a combination of ophthalmic beta-blockers and prostaglandins, and patients using ophthalmic prostaglandins only. Although prevalence of orthostatic hypotension was higher in the beta-blocker group (OR: 1.67; 95% CI: 0.731-3.793) compared to the prostaglandin group, this was a non-significant difference. CONCLUSIONS: In our study, we did not find a significant association between long-term use of beta-blockers eye drops and falls, dizziness or orthostatic hypotension in older ophthalmic outpatients, compared to long-term use of prostaglandin eye drops.

Changes in intraocular pressure after intraocular eye surgery-the influence of measuring technique.

AIM: To investigate the changes in intraocular pressure (IOP) before and after intraocular surgery measured with Goldmann applanation tonometry (GAT) and pascal dynamic contour tonometry (PDCT), and assessed their agreement. METHODS: Patients who underwent trans pars plana vitrectomy (TPPV) with or without cataract extraction (CE) were included. The IOP was measured in both eyes with GAT and PDCT pre- and postoperatively, where the non-operated eyes functioned as control. RESULTS: Preoperatively, mean IOP measurements were 16.3±6.0 mm Hg for GAT and 12.0±2.8 mm Hg for PDCT for the operated eyes. Postoperatively, the mean IOP dropped to 14.3±5.6 mm Hg for GAT (P=0.011) and rose up to 12.7±2.6 mm Hg for PDCT (P=0.257). Bland-Altman analysis showed a poor agreement between GAT and PDCT with a mean difference of 2.9 mm Hg preoperatively and 95% limits of agreement ranging from -3.2 to 9.0 mm Hg. Postoperatively, the mean difference was 1.2 mm Hg with 95% limits of agreement ranging from -8.3 to 10.7 mm Hg. There were no significant differences between the TPPV and TPPV+CE group, except when measured with PDCT postoperatively (P=0.012). CONCLUSION: The IOP is reduced after surgery when measured with GAT and remained stable when measured with PDCT. However, the agreement between GAT and PDCT is poor. Although PDCT may be a more accurate predictor of the true IOP, it seems less suitable for daily use in the clinical practice.

Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age-related macular degeneration, glaucoma and cataract.

PURPOSE: To analyse intraocular cytokine levels and prevalence of intraocular antiretinal antibodies (ARAs) in patients with retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma and cataract, and correlate the results to clinical manifestations. METHODS: We collected intraocular fluid samples from patients with RP (n = 25), AMD (n = 12), glaucoma (n = 28) and cataract (n = 22), and serum samples paired with the intraocular fluids from patients with RP (N = 7) and cataract (n = 10). Interleukin (IL)-1ß, IL-1ra, IL-2, IL-6, IL-6rα, IL-7, IL-8, IL-10, IL-17A, IL-23, thymus- and activation-regulated chemokine (TARC), monocyte chemoattractant protein-1 (MCP-1), tumour necrosis factor-alpha (TNF-α), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) were measured using a multiplex assay. Antiretinal antibodies (ARA) detection was performed by indirect immunofluorescence. RESULTS: Increasing age was associated with increasing levels of IL-6, IL-8, TNF-α and VEGF. All patient groups exhibited distinct profiles of intraocular cytokines. Intraocular levels of IL-8 were highest in patients with AMD and glaucoma. Cataract patients exhibited high intraocular levels of IL-23. Intraocular levels of IL-2, IL-6, MCP-1 and PlGF in RP patients exceeded the levels of serum, indicating intraocular production. Intraocular ARAs were found in only one patient with AMD. CONCLUSION: Increased levels of inflammatory cytokines in intraocular fluid of patients with originally noninflammatory ocular diseases show that intraocular inflammation is involved in their pathogenesis of these entities. Moreover, we show that increasing age is associated with increasing levels of intraocular cytokines and conclude that future studies on intraocular mediators should be corrected for age of patients.