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Background: Oxidative stress may play an important role in the etiology of primary open-angle glaucoma (POAG). The association between risk of POAG and lead exposure, which is an environmental source of oxidative stress, has not been fully investigated yet., Objective: Our objective was to determine the association between bone lead—a biomarker of cumulative lead dose (tibia lead) or an endogenous source of stored lead (patella lead)—and incident POAG., Methods: We examined a prospective cohort of 634 POAG-free men [mean baseline age=66.8 y of age (SD=6.7)] from the Normative Aging Study (NAS) who had tibia and patella K X-ray fluorescence lead measurements between 1 January 1991 and 31 December 1999. They also had standard ocular evaluations by NAS optometrists until 31 December 2014. POAG cases were identified by consistent reports of enlarged or asymmetric cup-to-disc ratio together with visual field defect or existence of disc hemorrhage. We used Cox proportional hazards regressions to estimate hazard ratios (HRs) of incident POAG and adjusted survival curves to examine changes in the risk of POAG during follow-up according to bone lead quartiles., Results: We identified 44 incident cases of POAG by the end of follow-up (incidence rate=74 per 10,000 person-years; median follow-up=10.6 y). In fully adjusted models, 10-fold increases in patella lead and tibia lead were associated with HRs of 5.06 (95% CI: 1.61, 15.88, p =0.005) and 3.07 (95% CI: 0.94, 10.0, p =0.06), respectively. The HRs comparing participants in the third and fourth quartiles with the lowest quartile were 3.41 (95% CI: 1.34, 8.66) and 3.24 (95% CI: 1.22, 8.62) for patella lead ( p -for-trend=0.01), and 3.84 (95% CI: 1.54, 9.55) and 2.61 (95% CI: 0.95, 7.21) for tibia lead ( p -for-trend=0.02)., Conclusions: Our study provides longitudinal evidence that bone lead may be an important risk factor for POAG in the U.S. population. https://doi.org/10.1289/EHP3442.

Aims: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG., Methods: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG., Results: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only., Discussion: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Background and Objective: Visual field loss is a complication of vitrectomy and a concern for patients with glaucoma. Our objective was to determine whether vitrectomy is associated with new field defects in patients with glaucoma., Patients and Methods: This retrospective case series involved 7 eyes of 7 patients, who had open-angle glaucoma and underwent vitrectomy for macular hole (2) or epiretinal membrane (5)., Results: Acuity improved by at least two lines in 5 eyes. Visual fields showed a change in mean deviation following vitrectomy (mean difference -1.50 dB, P=0.0006, paired Student's t-test). One eye had confirmed progression of a pre-existing visual field defect, but no new defects were apparent in the other eyes. Transient intraocular pressure rises requiring therapy occurred in 3 eyes. One eye developed macular edema, but no other operative complications occurred., Conclusions: The results of our small case series suggest that vitrectomy may be an acceptable intervention in eyes with glaucoma and co-existing macular problems.

Purpose: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC)., Methods: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites., Results: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%)., Conclusions: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.

Objective: To identify coexisting ocular diagnoses in a case series of eyes that developed cystoid macular edema (CME) associated with latanoprost therapy., Design: Retrospective observational case series., Participants: Seven eyes of seven patients who developed CME possibly associated with latanoprost treatment were studied., Intervention: When these patients, all of whom were treated with latanoprost in addition to other glaucoma medications, described blurred vision or eye irritation, ocular examination revealed CME, which was confirmed by fluorescein angiography. Latanoprost was discontinued, and in three cases topical corticosteroids and nonsteroidal anti-inflammatory agents were used to treat the CME., Main Outcome Measures: Visual acuity and intraocular pressure were determined before latanoprost use began, during therapy, and after latanoprost use ceased. In these cases, resolution of CME was documented clinically after discontinuing latanoprost., Results: Clinically significant CME developed after 1 to 11 months of latanoprost treatment, with an average decrease of 3 lines in Snellen visual acuity. Intraocular pressure decreased an average of 27.9% during treatment. Cystoid macular edema was confirmed in all cases by fluorescein angiography. In these seven patients, the following coexisting ocular conditions may have placed these eyes at risk for prostaglandin-mediated blood-retinal barrier vascular insufficiency: history of dipivefrin-associated CME, epiretinal membrane, complicated cataract surgery, history of macular edema associated with branch retinal vein occlusion, history of anterior uveitis, and diabetes mellitus. In all cases, the macular edema resolved following discontinuation of latanoprost, in some instances with concomitant use of steroidal and nonsteroidal anti-inflammatory agents., Conclusions: In this case series of pseudophakic, aphakic, or phakic eyes, the temporal relationships between the use of latanoprost and developing CME, and the resolution of CME following cessation of the drug, suggest an association between latanoprost and CME. In all cases, coexisting ocular conditions associated with an altered blood-retinal barrier were present.