Even-number measurement bias with Goldmann applanation tonometry in patients with glaucoma and glaucoma suspects.

CLINICAL RELEVANCE: Goldmann applanation tonometry is widely used for the diagnosis and management of glaucoma and its use is considered standard of care. However, the precision of this method may be reduced by a clinician tendency to round to even numbers. BACKGROUND: Studies have previously demonstrated an even-number measurement bias with Goldmann applanation tonometry during examination of a general patient population. Since it has not been determined whether this bias persists among glaucoma suspects and patients with glaucoma, further investigation was conducted. METHODS: A retrospective analysis was conducted on a random sample from a large dataset of >69,000 patients seen during a six-year period at an urban, academic primary eye care service. Patients without suspicion of glaucoma, patients with a suspicion of glaucoma, and patients with glaucoma were selected who had Goldmann tonometry performed. Chart reviews were performed to confirm status, and even/odd-numbered Goldmann tonometry measurement frequencies were compared. RESULTS: The analysis included 961 controls, 506 glaucoma suspects, 159 ocular hypertensives not taking medication, and 314 patients taking medications who carried a diagnosis of glaucoma or ocular hypertension. Among controls the Goldmann tonometry even/odd digit proportions were 62.8%/37.2% (N = 961, p < 0.0001), and the even-number bias persisted among the other groups with specific even/odd distributions being 61.9%/38.1% (N = 506, p < 0.0001) for glaucoma suspects not taking medications, 66.0%/34.0% (N = 159, p < 0.0001) for ocular hypertensives not taking medications, and 64.3%/35.7% (N = 314, p < 0.0001) for glaucoma/ocular hypertension patients taking medications. CONCLUSION: An even-number measurement bias with Goldmann tonometry may be prevalent even when the examiner is aware of there being greater importance for intraocular pressure measurement accuracy.

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.

Even-number Measurement Bias With Goldmann Applanation Tonometry.

While working with a large data set of Goldmann applanation tonometry (GAT) intraocular pressure (IOP) measurements for a separate investigation, we observed that the IOP distribution favored even-numbered values. Study of this phenomenon has been limited, and this larger data set enabled inquiry that showed new insight concerning the manner in which this bias may vary according to IOP level. This analysis of 69,537 right eyes measured via GAT demonstrated that even-number preference was essentially absent in the 21 to 24 mm Hg range, but then the bias gradually strengthened as it moved away from this range in a lower or higher IOP direction. These data suggest that there is an examiner proclivity to measure and/or record GAT readings as even-numbered values, but that this tendency varies depending on IOP level.

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.

Morphologic Patterns Formed by the Anomalous Fibers Occurring Along the Anterior Capsule of the Crystalline Lens in People With the Long Anterior Zonule Trait.

People with the long anterior zonule (LAZ) trait, which may have prevalence near 2%, have zonular fibers that extend more central than usual along the anterior capsule of the crystalline lens. The anomalous fibers can be observed in vivo with clinical slit lamp biomicroscopy after pharmacologic pupil dilation, and although minimally studied, the LAZ trait may have importance to glaucoma, retinal degeneration, and cataract surgery. To further characterize LAZ morphology, a custom computer program was used to trace LAZ fibers seen on retro-illumination photos acquired during previous study at an academic, urban eye care facility in Chicago, IL. There were 59 African-Americans (54 female; median age = 70 years, 53-91 years) included in the analysis. After initial review of the zonule tracings, we identified three basic LAZ patterns. We called one pattern (47% of right eyes) a "non-segmental LAZ pattern," which was predominated by fibers that could be visually traced to the dilated pupil border where they became obscured by the iris. Another pattern (35% of right eyes), the "segmental LAZ pattern," was predominated by fibers that appeared to terminate abruptly without detectable extension to the pupil border. The third pattern (18% of right eyes), the "mixed LAZ pattern," had a more equivalent mixture of the other two fiber morphologies. Compared to the "non-segmental" group, the "segmental" LAZ eyes had smaller central zonule-free zones (P < 0.0001), and they tended to exhibit fewer LAZ fibers (P = 0.07). These data improve understanding of LAZ clinical anatomy and may be helpful to future investigation. Anat Rec, 300:1336-1347, 2017. © 2017 Wiley Periodicals, Inc.

Anterior Chamber Depth, Lens Thickness, and Related Measures in African American Females With Long Anterior Zonules: A Matched Study With Control for Refractive Error.

PURPOSE: To investigate anterior chamber depth (ACD), lens thickness (LT), vitreous body length (VBL), and axial length (AL) in African American females with long anterior zonules (LAZ) while controlling for refractive error. METHODS: The eyes of 50 African American females with LAZ were compared with 50 controls matched with age, race, sex, and refractive error. Central ACD, LT, VBL, and AL measurements were obtained in a masked manner using a-scan ultrasonography. RESULTS: LAZ cases had a mean age±SD of 67.1±7.6 years (range, 52 to 85 y) and a mean refractive error of +1.85±1.41 D (-1.75 to +4.75 D). Parameters were similar for controls. Mean ACD for cases was 2.45±0.34 mm and 2.57±0.38 mm for controls. Mean LT for cases was 4.94±0.43 mm and 4.83±0.45 mm for controls. Mean VBL for cases was 15.00±0.72 mm and 15.17±0.76 mm for controls. Mean AL for cases was 22.39±0.82 mm and 22.57±0.76 mm for controls. Using multiple logistic regression to control for any residual differences in age and refractive error, no significant differences were present between LAZ eyes and control eyes relative to the a-scan variables (P>0.1). CONCLUSIONS: When refractive error was controlled for, this group of African American females with LAZ did not exhibit clinically significant differences in ACD, LT, VBL, and AL as compared with controls.

Association of refractive error with optic nerve hypoplasia.

PURPOSE: To evaluate the association of refractive error with optic nerve hypoplasia (ONH). METHODS: A total of 30 ONH subjects were recruited and underwent comprehensive eye exams. Refractive error data from this group was compared to data from a group of 3232 non-ONH subjects from the same facility. Spherical equivalent was calculated to assess refractive error. Multiple logistic regression was used to evaluate the relationship between ONH and refractive error while controlling for age, race, and gender. RESULTS: The prevalence of hyperopia (≥+1.00 D), myopia (<-0.75 D), and anisometropia (≥1.00 D) was higher in ONH subjects than in controls. ONH subjects were 9.1 times more likely to be hyperopic than emmetropic (OR = 9.1, 95% CI = 2.9-28.4, p < 0.001) and 3.8 times more likely to be myopic than emmetropic (OR = 3.8, 95% CI = 1.2-11.5, p = 0.02). Unilateral ONH subjects were 10.0 times more likely to have anisometropia than controls (OR = 10.0, 95% CI = 3.9-25.6, p < 0.0001). Bilateral ONH subjects were 3.8 times more likely to have anisometropia than controls (OR = 3.8, 95% CI = 1.1-12.7, p = 0.03). CONCLUSIONS: Optic nerve hypoplasia subjects were more likely than control subjects to exhibit significant refractive errors, particularly hyperopia. Anisometropia tended to be more likely to occur in subjects with unilateral ONH than in bilateral ONH. Based on our findings, we recommend that clinicians perform a comprehensive eye examination on all patients with ONH and prescribe for existing refractive error when visual acuity or general visual function can realistically be improved.

Remnants of the anterior tunica vasculosa lentis and long anterior lens zonules.

PURPOSE: To investigate presence of remnants of the tunica vasculosa lentis, a possible indication of anterior segment dysgenesis, in subjects with the long anterior zonule (LAZ) trait. METHODS: Retroillumination photographs of the pupil region had been collected in earlier study of the LAZ trait in African Americans. Secondary image analysis was performed to assess the frequency of intact persistent pupillary membrane iris strands (PPMIS). RESULTS: The analysis included 148 subjects, comprised of 74 LAZ subjects (median age=70 y; range, 50 to 91 y; 64 females) and 74 controls (68 y; 50 to 83 y; 64 females). While controlling for age and sex, analysis showed that LAZ subjects were 3.1 times more likely than controls (odds ratio=3.1; 95% confidence interval, 1.4-6.7; P=0.004) to exhibit PPMIS in at least one of their eyes. CONCLUSION: The LAZ trait, which is being studied as a potential risk factor for glaucoma, was associated with presence of PPMIS in our study population.

Investigating ocular dimensions in African Americans with long anterior zonules.

PURPOSE: To investigate ocular dimensions in African Americans with the long anterior zonule (LAZ) trait. METHODS: A total of 61 African American LAZ subjects and 61 age-matched, race-matched, and sex-matched controls were compared with respect to central corneal thickness, central corneal curvature, axial length (AL), and subjective refraction. RESULTS: LAZ right eyes had a mean SR=+1.75±1.82 D and were 1.58 D (95% confidence interval, 0.83-2.31 D, P<0.0001) more hyperopic on average when compared with the control right eyes. LAZ right eyes also had an AL that was 0.69 mm (95% confidence interval, 0.34-1.04 mm, P<0.001) shorter on average than control right eyes. Similar results were found for left eyes. No differences were found with respect to central corneal curvature and central corneal thickness (P>0.05). CONCLUSIONS: In this data set, LAZ eyes tended to be more hyperopic and had ALs that were shorter than control eyes, characteristics that are consistent with elevated risk for angle-closure glaucoma.

Quantification of pupil parameters in diseased and normal eyes with near infrared iris transillumination imaging.

BACKGROUND AND OBJECTIVE: To investigate near infrared iris transillumination (NIRit) imaging as a new method to quantify pupil shape, size, and position because the imaging modality can uniquely provide simultaneous information regarding iris structural details that influence pupil characteristics and because exploration of related techniques could promote discovery helpful to clinical research and care. PATIENTS AND METHODS: Digital NIRit images of normal and diseased eyes were used along with computer-assisted techniques to quantify four primary pupil parameters, including pupil roundness (PR), pupil ovalness (PO), pupil size (PS), and pupil eccentricity (PE). A combined measure of PR and PO was also developed (the pupil circularity index [PCI]). Repeatability of the measures was studied and example analyses were performed. RESULTS: Pupil measures could be calculated for right eyes of 307 subjects (164 normal, 143 other), with fewer than 0.5% exclusions due to image quality. Repeatability study did not show significant bias (P < .05) for any of the four primary measures. Example analyses could show age-associated differences in pupil shape (≥ 50 year olds had less regular pupils than < 50 year olds: median PCI = 0.009 vs 0.006; P < .01) and that a group of pigment dispersion syndrome subjects (n = 27) had less regular pupils than a group of matched controls (PO = 0.9966 vs 0.9990; P < .05). CONCLUSION: Digital NIRit imaging can provide novel, reliable, and informative methods to quantify pupil characteristics while providing simultaneous information about iris structure that may influence these parameters.

Multispectral diagnostic imaging of the iris in pigment dispersion syndrome.

PURPOSE: To determine if wavelength selection with near infrared iris imaging may enhance iris transillumination defects (ITDs) in pigment dispersion syndrome. METHODS: An experimental apparatus was used to acquire iris images in 6 African-American (AA) and 6 White patients with pigment dispersion syndrome. Light-emitting diode probes of 6 different spectral bands (700 to 950 nm) were used to project light into patients' eyes. Iris patterns were photographed, ITD regions of interest were outlined, and region of interest contrasts were calculated for each spectral band. RESULTS: Contrasts varied as a function of wavelength (P<0.0001) for both groups, but tended to be highest in the 700 to 800 nm range. Contrasts were higher in Whites than AAs at 700 nm but the opposite was found at 810 nm (P<0.001). CONCLUSIONS: Optimized near infrared iris imaging may be wavelength dependent. Ideal wavelength to image ITDs in more pigmented eyes may be slightly longer than for less pigmented eyes.

Novel observations and potential applications using digital infrared iris imaging.

Digital infrared iris photography using a modified digital camera system was performed on approximately 300 subjects seen during routine clinical care and research at one facility. Because this image database offered an opportunity to gain new insight into the potential utility of infrared iris imaging, it was surveyed for unique image patterns. Then, a selection of photographs was compiled that would illustrate the spectrum of this imaging experience. Potentially informative image patterns were observed in subjects with cataracts, diabetic retinopathy, Posner-Schlossman syndrome, iridociliary cysts, long anterior lens zonules, nevi, oculocutaneous albinism, pigment dispersion syndrome, pseudophakia, suspected vascular anomaly, and trauma. Image patterns were often unanticipated regardless of preexisting information and suggest that infrared iris imaging may have numerous potential clinical and research applications, some of which may still not be recognized. These observations suggest further development and study of this technology.

Possible association between long anterior lens zonules and plateau iris configuration.

PURPOSE: To report plateau iris configuration (PIC) in subjects who have the long anterior zonule (LAZ) clinical trait. METHODS: Two elderly African American males who exhibited LAZ and had partial appositional angle closure persisting after laser iridotomy were imaged with high-resolution ultrasonography to examine for PIC. A third elderly LAZ subject who had narrow angles without closure was also imaged for PIC. Each subject was tested for a serine 163 arginine mutation (S163R) C1q tumor necrosis factor-related protein 5 gene (C1QTNF5/CTRP5) mutation, which may be associated with the LAZ phenotype. RESULTS: All 3 LAZ subjects also had PIC, an unlikely association due to chance alone. None carried the S163R CTRP5 mutation. CONCLUSIONS: LAZ and PIC may have association and require study because LAZ might be a useful indicator for an increased likelihood of PIC and risk of angle closure. Mutation other than CTRP5 S163R should also be considered for the LAZ trait, which could be an important phenotypic marker in genetic studies.

Infrared imaging technique may help demonstrate iris transillumination defects in blacks who show other pigment dispersion syndrome clinical signs.

PURPOSE: Pigment dispersion syndrome (PDS) is considered to be rare among blacks, although the inability to detect iris transillumination defects (ITDs) among very darkly pigmented irides could diminish the clinician's commitment toward the PDS diagnosis due to uncertainty brought on by the lack of this clinical sign. The goal of this study was to investigate the potential utility of a new infrared (IR) imaging technique to demonstrate ITDs among a group of blacks whose initial PDS diagnosis had to be based on pigment dispersal signs other than iris transillumination. METHODS: A previously described digital camera system, modified to detect visible and IR light, was used to image the irides of 10 blacks (20 eyes, 8 females, 2 males; age range=51 to 67 y) considered to have PDS on the basis of the clinical signs not including the presence of ITDs as detected with traditional slit lamp examination. Only 1 eye of 2 different subjects had ITDs that were detected with slit lamp examination, but these consisted of a very small, isolated ITD of questionable importance in each of the eyes. Normal control eyes that were matched according to age, race, sex, and refractive error were also photographed, and 2 glaucoma specialists independently reviewed PDS/control eye pairs in a masked fashion. They were instructed to select the eye more likely to be the PDS eye without the benefit of clinical information other than the digital transillumination characteristics. RESULTS: Observer no. 1 correctly selected the PDS eye among 19 of 20 (95%) PDS-normal eye pairs, and observer no. 2 correctly selected the PDS eye among 15 of 20 (75%) matched pairs. On the basis of these results, it was unlikely that observer no. 1 (Fisher exact test, P<0.0001) or observer no. 2 (P=0.06) selected the PDS eye IR image due to chance alone. It was also unlikely that selection agreement between the 2 observers was due to chance alone (kappa coefficient=0.58). CONCLUSIONS: Digital IR iris photography may help demonstrate abnormal ITDs among the darkly pigmented irides of blacks who have signs of pigment dispersal but who do not have detectable ITDs with traditional slit lamp examination. Infrared iris examination with newer methods should be studied further relative to blacks and others because useful clinical and/or research oriented information could be gained.

Blood pressure control in an African American sample with diabetes mellitus in an urban eye clinic.

BACKGROUND: The adequate control of blood pressure in patients with diabetes mellitus (DM) is important to limit the ocular and systemic complications of the disease. Hypertension in African Americans is among the highest in the world. This cross-sectional study reports the level of blood pressure control in a small sample of African American patients with DM at an urban eye care facility using the criteria defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII). METHODS: Five attending faculty members of the Illinois College of Optometry identified 234 African American patients with a diagnosis of DM over a period of 16 months. Blood pressure readings were recorded once at the time of their visit and were classified as controlled or uncontrolled based on the JNC VII cutoff of blood pressure less than 130/80 mmHg. RESULTS: Among the 234 African American patients in this study, 174 (74.4%) reported having DM and hypertension, and 60 (25.6%) reported having DM without hypertension. Of the patients with DM and a self-reported diagnosis of hypertension, 13.2% were controlled. Of the patients with diabetes without a self-reported diagnosis of hypertension, 26.7% were found to be adequately controlled. For the pooled data of 234 patients with diabetes, 16.7% met the JNC VII guidelines. CONCLUSION: The inadequate control of blood pressure in the African American population with DM is associated with increased disability and death from cardiovascular and renal disease. The results of this small cross-sectional study are consistent with those of other studies that show poor control of blood pressure in African American patients who have DM. Preventable blindness secondary to accelerated diabetic retinopathy from uncontrolled hypertension is a concern to all eye care practitioners.