Time-of-Year Variation in Intraocular Pressure.

PRÉCIS: In this study conducted in Chicago, IL, intraocular pressure (IOP) level was found to have a subtle, but measurable, annual pattern. Reasonable evidence is presented for a time-of-year variation in IOP. Adequate numbers of subjects must be studied to detect this small variation. PURPOSE: The aim was to investigate the relationship between IOP and time of year. METHODS: During a separate investigation, patients from 2011 to 2018 (dataset A, N=3041) in an urban, academic facility in Chicago, IL received an examination that included Goldmann applanation tonometry. Regression analyses assessed the relationship between time of year and IOP. Two additional datasets, 1 collected in a similar manner during 1999 and 2002 (dataset B, N=3261) and another consisting of all first visits during 2012 and 2017 (dataset C, N=69,858), were used to confirm and further investigate trends. RESULTS: For dataset A, peak mean IOP occurred in December/January (15.7±3.7/15.7±3.8 mm Hg) and lowest in September (14.5±3.1 mm Hg). The analysis suggested conventional quarterly analysis (January to March, etc.) can conceal time-of-year relationships because of inadequate statistical power and timing of IOP variation. Multiple linear regression analysis, with a November-to-October reordering, detected an annual, downward IOP trend (P<0.0001). Analysis of dataset B confirmed this trend (P<0.001). Fourier analysis on datasets A and B combined supported a 12-month IOP cycle for right/left eyes (P=0.01/P=0.005) and dataset C provided stronger evidence for an annual periodicity (P<0.0001). Harmonics analysis of dataset C showed a repeating pattern where IOP trended downward around April, and then back upward around October. CONCLUSIONS: This analysis strongly supports a demonstrable annual, cyclical IOP pattern with a trough to peak variation of ≈1 mm Hg, which has a seasonal relationship.

Krukenberg's Spindles Strongly Suggest Long Anterior Zonule Associated Pigment Dispersion Mechanism in Older Patients.

Purpose: The purpose of this study was to further investigate factors associated with Krukenberg's spindle (KS) presence in a primary eye care setting. Methods: As part of a larger investigation, several practitioners in an academic eye care facility in Chicago, IL, USA evaluated patients for the long anterior zonule (LAZ) trait during 2011 to 2018, and data were collected on ocular/systemic health, lifestyle, and demographic variables, including the presence of a KS. Multivariate regression was used to assess relationships to KS presence. Results: Analysis included 3501 subjects with mean age of 51 ± 15 years (18-98 years; 65% women; and 84% African American). Among the right eyes, 57 (1.6%) had a KS, with this group having a mean age of 62 ± 13 years (25-86 years; 75% women; and 82% African American). There were 120 subjects (3.4%) with right eye LAZ, with mean age of 64 ± 11 years (36-91 years; 77% women; and 92% African American). There were 19 of 57 (33.3%) KS eyes that also had LAZ. Controlling for other factors, variables with the strongest relationship to KS presence were the LAZ trait (odds ratio [OR] = 12.2, 95% confidence interval [CI] = 6.5 to 22.8, P < 0.0001) and advancing age (OR = 1.3 per decade, 95% CI = 1.3 to 1.9, P < 0.0001). Conclusions: In the population studied, KS presence had its strongest relationship to the LAZ trait and advancing age. The KS-LAZ relationship may not be well-known, but these data strongly suggest that pigment dispersion signs, such as a KS, should prompt the clinician to consider the LAZ trait as a potential etiology, especially because LAZ is associated with higher IOP and possibly glaucoma.

Long Anterior Lens Zonules and Intraocular Pressure.

Purpose: To investigate the relation between intraocular pressure (IOP) and the idiopathic long anterior zonule (LAZ) trait. Methods: Patients presenting for primary eye care were examined for LAZ, identified as radially oriented zonular fibers with central extension >1.0 mm beyond the normal anterior lens insertion zone (estimated via slit lamp beam length). Ocular, systemic health, and lifestyle data were collected via comprehensive exam and questionnaire. Multivariate regression was used to assess the relationship between IOP (Goldmann) and LAZ. Results: There were 2169 non-LAZ and 129 LAZ subjects (mean age: 49.8 ± 15.0 vs. 62.6 ± 10.2 years; 63.6% vs. 76.0% female; 83.2% vs. 91.5% African American). Right eyes with >trace LAZ (n = 59 of 110) had higher unadjusted mean IOP than control eyes (16.4 ± 3.3 vs. 15.0 ± 3.3 mm Hg, P = 0.005), and with control for numerous factors, LAZ eyes had an average IOP of approximately 1.3 ± 0.4 mm Hg higher (P = 0.003) than non-LAZ eyes. Final model covariates included sex (P = 0.001); spherical-equivalent refractive error (D; P < 0.0001); body mass index (kg/m2; P < 0.001); presence of diabetes (P < 0.001); having >high school education (P < 0.001); systolic blood pressure (mm Hg; P < 0.0001); being an ever smoker (P = 0.006); and having history of any site cancer (P = 0.01). Conclusions: The LAZ trait, with potential prevalence near 2%, was associated with a higher IOP. This observation is consistent with the hypothesis that the trait is a marker for underlying mechanisms that elevate glaucoma risk.

Novel mutations in the cellular retinaldehyde-binding protein gene (RLBP1) associated with retinitis punctata albescens: evidence of interfamilial genetic heterogeneity and fundus changes in heterozygotes.

OBJECTIVE: To evaluate the molecular genetic defects associated with retinitis punctata albescens (RPA) in 5 patients from 3 families with this disease. METHODS: We examined 3 probands and 2 clinically affected relatives with RPA. Clinical examinations included best-corrected visual acuity, visual field testing, electroretinography, dilated fundus examination, and fundus photography. Leukocyte DNA was analyzed for mutations in the exons of the genes encoding cellular retinaldehyde-binding protein 1 (RLBP1), 11-cis-retinol dehydrogenase (RDH5), interphotoreceptor retinoid-binding protein (RBP3), and photoreceptor all-trans-retinol dehydrogenase (RDH8). Not all patients were evaluated for mutations in each gene. The exons were individually amplified and screened for mutations by single-stranded conformational polymorphism analysis or direct genomic sequencing. RESULTS: The 3 probands had similar clinical findings, including a history of poor night vision, the presence of punctate white deposits in the retina, and substantially reduced or absent rod responses on electroretinogram testing. One of the probands (patient 2:III:2) had 2 novel mutations in the RLBP1 gene (Arg151Trp and Gly31[2-base pair deletion], [GGA-->G-]). Segregation analysis showed that the 2 mutations were allelic and that the patient was a compound heterozygote. Both parents of the proband manifested round white deposits in the retina. The other 2 probands had no detected pathogenic mutations in RLBP1 or in the other 3 genes evaluated. CONCLUSIONS: The identification of novel RLBP1 mutations in 1 of our 3 probands, all with RPA, is further evidence of genetic (nonallelic) heterogeneity in this disease. The presence of round white deposits in the retina may be observed in those heterozygous for RLBP1. Clinical Relevance Patients with a clinical presentation of RPA can have genetically different mutations. Drusen-like lesions may be observed in heterozygotes in families with this disease and a mutation in RLBP1.