Correlation of Adenoviral Titers with Severity of Adenoviral Conjunctivitis and Time to Viral Clearance for 21 Days.

SIGNIFICANCE: This investigation reports the correlation of conjunctival viral titers in adenoviral conjunctivitis with patient-reported symptoms and clinician-graded signs for 21 days of follow-up. PURPOSE: Adenoviral conjunctivitis is a highly contagious viral eye infection with significant morbidity and economic impact. This study investigates whether severity of signs and symptoms and time to viral clearance are correlated with conjunctival viral titers at baseline and during 21 days of follow-up. METHODS: The Reducing Adenoviral Patient Infected Days study was a pilot study of the efficacy of a single in-office administration of ophthalmic 5% povidone-iodine. This article outlines longitudinal analyses after the primary outcome report. Of 212 participants screened, 28 participants with quantitative polymerase chain reaction-confirmed adenoviral conjunctivitis were randomized and had follow-up visits on days 1, 2, 4, 7, 14, and 21. At each visit, clinician-graded signs, participant-reported symptoms, and a conjunctival swab for quantitative polymerase chain reaction analysis were obtained. The correlation of viral titers with symptoms and signs was calculated: (1) cross-sectionally at each visit and (2) longitudinally for 21 days using a repeated-measures mixed-effects model. RESULTS: Twenty-five of 28 participants had sufficient data for this report. Higher viral titers for 21 days were correlated with greater severity of symptoms (tearing, matting, and redness, r ≥ 0.70; P < .02) and greater severity of clinical signs (bulbar redness and serous discharge, r ≥ 0.60; P < .01). Eyes with highest baseline viral titers required longer time to viral clearance ( r = 0.59, P = .008). Signs and symptoms persisted in approximately half of the eyes even after viral clearance. CONCLUSIONS: Higher conjunctival viral titers across 21 days were strongly correlated with more severe signs and symptoms and longer time to viral clearance. Our results also indicate that symptoms and signs can persist after viral clearance.

Eyebrow Position Before and After Enucleation.

PURPOSE: The presence of eyebrow elevation in anophthalmic patients has been used as evidence to support a proprioceptive stimulus for frontalis innervation. In this study, we examined the frequency of brow elevation before and after enucleation and reviewed additional clinical findings to determine if any were associated with eyebrow position. METHODS: A retrospective study was performed on 134 anophthalmic patients. Demographics, measurements, and photographs were reviewed. Reference photographs were used to subjectively grade brow position and sulcus depth. RESULTS: Preoperative eyebrow elevation was present in 56.2% of patients without blepharospasm from a painful eye, of who 62% had chronic visual loss. Ipsilateral ptosis (p = 0.008), deep superior sulcus (p < 0.001), and right-sided pathology (p = 0.045) were more common in patients with brow elevation. Symmetrically elevated brows were more frequent before right than left enucleation (p = 0.05). Brow position remained stable after 61.9% of procedures. While often mild, postoperative brow elevation was seen in 31.0% of patients without preoperative elevation. Deepening of the superior sulcus was more common in patients with new relative brow elevation (p = 0.031). Anophthalmic ptosis and right-left surgical side were not associated with new postoperative brow elevation. CONCLUSIONS: Eyebrow elevation was often present prior to enucleation and associated with an increased occurrence of ptosis, superior sulcus deepening, and right-sided pathology. Intact vision was not needed to maintain an elevated brow. Superior sulcus deepening, but not ptosis, was more common in patients developing new postoperative brow elevation. The findings support both proprioceptive and compensatory mechanisms for eyebrow elevation.

Success of Masking 5% Povidone-Iodine Treatment: The Reducing Adenoviral Patient Infected Days Study.

SIGNIFICANCE: The effectiveness of masking is rarely evaluated or reported in single- or double-masked clinical trials. Knowledge of treatment assignment by participants and clinicians can bias the assessment of treatment efficacy. PURPOSE: This study aimed to evaluate the effectiveness of masking in a double-masked trial of 5% povidone-iodine for the treatment of adenoviral conjunctivitis. METHODS: The Reducing Adenoviral Patient Infected Days study is a double-masked, randomized trial comparing a one-time, in-office administration of 5% povidone-iodine with artificial tears for the treatment of adenoviral conjunctivitis. Masking was assessed by asking participants and masked clinicians at designated time points if they believed the treatment administered was povidone-iodine or artificial tears, or if they were unsure. Adequacy of masking was quantified using a modified Bang Blinding Index. RESULTS: Immediately after treatment, 34% of participants who received povidone-iodine and 69% of those who received artificial tears guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.31 and -0.38, respectively). On day 4, 38% of the povidone-iodine participants and 52% of the artificial tear participants guessed incorrectly or were unsure of their treatment (modified Bang Indices of 0.24 and -0.05, respectively), indicating adequate and ideal masking. On days 1, 4, 7, 14, and 21, masked clinicians guessed incorrectly or were unsure of treatment in 53%, 50%, 40%, 39%, and 42% among povidone-iodine participants compared with 44%, 35%, 38%, 35%, and 39% among artificial tears participants, respectively. The modified Bang Indices for clinician masking in the povidone-iodine group ranged from -0.05 to 0.25 and from 0.13 to 0.29 in the artificial tears group. CONCLUSIONS: Masking of participants and clinicians was adequate. Successful masking increases confidence that subjective measurements are not biased. We recommend quantitative assessment and reporting the effectiveness of masking in ophthalmic clinical trials.

Anophthalmic Ptosis and the Effects of Enucleation on Upper Eyelid Function.

PURPOSE: To describe the incidence of anophthalmic ptosis, identify clinical factors associated with its development, and evaluate the effects of enucleation on eyelid mechanics. METHODS: In this observational cohort study, measurements and photographs were reviewed in 139 patients who underwent enucleation between 2007 and 2016. Patient demographics, pre- and postoperative eyelid measurements, and exophthalmometry were used to assess the incidence of ptosis and effects of surgery on eyelid function. RESULTS: Preoperative ptosis was common and more often present in patients with enophthalmos (p = 0.0305) or reactive blepharospasm (p < 0.0001). The incidence of new-onset ptosis and improvement of preexisting ptosis following enucleation were similar (40%). Surgical repair was performed in 7% of patients with ptosis. Contralateral levator function declined with age and was positively correlated with exophthalmometry (p < 0.0001). Anophthalmic levator function was greater with increased anterior projection of the implant (p < 0.0001) and prosthesis (p < 0.0001). Patients with larger implants had improved levator function, with (p = 0.0065) and without (p = 0.0007) the prosthesis. Superior sulcus deepening was associated with decreased levator activity, but not margin-reflex distance. CONCLUSIONS: Preoperative ptosis was common, and often related to reactive blepharospasm or enophthalmos. Levator function declined with age, and correlated to greater anterior projection of the implant and prosthesis following enucleation. The surgeon can counsel patients regarding the similar likelihood (40%) of preoperative ptosis improving and new ptosis developing after enucleation. The primary factor the surgeon can modify to improve postoperative eyelid function is to maximize implant size, which is associated with greater levator activity.

Volumetric Versus Empirical Determination of Enucleation Implant Size.

PURPOSE: To compare the use of sizing implants versus intraoperative volume measurements for individualization of enucleation implant size, and to identify preoperative factors affecting the choice of implant. METHODS: In this retrospective observational cohort study, 2 implant sizing methods were compared using clinical records and photographs in 139 patients who underwent enucleation between 2007 and 2016. RESULTS: There was no difference in mean implant (p = 0.6562) or prosthetic (p = 0.1990) enophthalmos between the 2 methods, or when comparing patients with and without conjunctival-Tenons fibrosis. The incidence and severity of superior sulcus deformity was similar between the methods (p = 0.6394). Preoperative phthisis (p < 0.0001) and intraoperative conjunctival-Tenons fibrosis (p = 0.0010) were more common in the sizing implant group. Among all study patients, mean implant size was larger in males (21.3 mm, n = 80) than females (20.7 mm, n = 59) (p = 0.0027). Implants >20 mm were more frequently inserted in patients with a wider Hertel exophthalmometry base (80% of males >95 mm; 77% of females >97 mm). Approximately 21.0% of patients demonstrated ≥8 mm of implant enophthalmos, suggesting an undersized implant. The authors estimate that 11% of patients could have received a sphere larger than 22 mm. CONCLUSIONS: Individualization of enucleation implant size can reduce the incidence of anophthalmic socket syndrome. The empirical use of sizing implants provided similar results as intraoperative volumetric measurements, when evaluated by postoperative superior sulcus depth and prosthetic or implant enophthalmos. Preoperative exophthalmometry may facilitate selection of implant size. Preexisting conjunctival-Tenon fascial fibrosis often did not limit implant size and was not associated with a higher prevalence of wound breakdown or implant exposure.

Central Corneal Thickness in the Ocular Hypertension Treatment Study (OHTS).

OBJECTIVE: Central corneal thickness influences intraocular pressure (IOP) measurement. We examined the central corneal thickness of subjects in the Ocular Hypertension Treatment Study (OHTS) and determined if central corneal thickness is related to race. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand three hundred one OHTS subjects with central corneal thickness measurements. INTERVENTION: Central corneal thickness was determined with ultrasonic pachymeters of the same make and model at all clinical sites of the OHTS. MAIN OUTCOME MEASURES: Correlation of mean central corneal thickness with race, baseline IOP, refraction, age, gender, systemic hypertension, and diabetes. RESULTS: Mean central corneal thickness was 573.0 ± 39.0 µm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 µm. Mean central corneal thickness for African American subjects (555.7 ± 40.0 µm; n = 318) was 23 µm thinner than for white subjects (579.0 ± 37.0 µm; P < 0.0001). Other factors associated with greater mean central corneal thickness were younger age, female gender, and diabetes. CONCLUSIONS: OHTS subjects have thicker corneas than the general population. African American subjects have thinner corneas than white subjects in the study. The effect of central corneal thickness may influence the accuracy of applanation tonometry in the diagnosis, screening, and management of patients with glaucoma and ocular hypertension.

Factors Associated with Adherence to Screening Guidelines for Diabetic Retinopathy Among Low-Income Metropolitan Patients.

In this retrospective analysis of patients with diabetes in an academic primary care clinic in St. Louis, attendance at ophthalmic screening appointments was recorded over a two-year observation window. Factors associated with adherence were analyzed by multivariable regression. Among 974 total patients included, only 330 (33.9%) were adherent within a two-year period. Multivariate analyses identified older age, female gender, primary language other than English, and attendance at ancillary diabetes clinic visits as factors associated with improved diabetic retinopathy screening adherence. Factors not associated with adherence included race and insurance status.

Identifying Incidence of and Risk Factors for Fluoroscopy-Guided Lumbar Puncture and Subsequent Persistent Low-Pressure Syndrome in Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: To explore the incidence of and potential risk factors for developing persistent low-pressure syndrome after lumbar puncture (LP) in patients with idiopathic intracranial hypertension (IIH), as measured by use of blood patches. METHODS: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and LP, comparing them to patients with multiple sclerosis (MS) as controls who also received diagnostic LPs. Demographic, clinical, and radiological data were collected for each patient. The main outcome measure was the rate of post-LP blood patches in IIH patients compared with MS patients. Secondary outcome measures were the likelihood of undergoing an epidural blood patch related to age, body mass index, volume removed, opening pressure, the difference between opening and closing pressure, and the level of puncture within the IIH cohort. RESULTS: One hundred four IIH patients and 149 MS patients were included in the study. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086). Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch. CONCLUSIONS: The incidence of low-pressure syndrome, as measured by blood patches, is similar in IIH patients and MS controls. This suggests that having elevated intracranial pressure before an LP is not protective against developing postpuncture low-pressure syndrome, contrary to common assumptions.

Estimating correlation between multivariate longitudinal data in the presence of heterogeneity.

BACKGROUND: Estimating correlation coefficients among outcomes is one of the most important analytical tasks in epidemiological and clinical research. Availability of multivariate longitudinal data presents a unique opportunity to assess joint evolution of outcomes over time. Bivariate linear mixed model (BLMM) provides a versatile tool with regard to assessing correlation. However, BLMMs often assume that all individuals are drawn from a single homogenous population where the individual trajectories are distributed smoothly around population average. METHODS: Using longitudinal mean deviation (MD) and visual acuity (VA) from the Ocular Hypertension Treatment Study (OHTS), we demonstrated strategies to better understand the correlation between multivariate longitudinal data in the presence of potential heterogeneity. Conditional correlation (i.e., marginal correlation given random effects) was calculated to describe how the association between longitudinal outcomes evolved over time within specific subpopulation. The impact of heterogeneity on correlation was also assessed by simulated data. RESULTS: There was a significant positive correlation in both random intercepts (ρ = 0.278, 95% CI: 0.121-0.420) and random slopes (ρ = 0.579, 95% CI: 0.349-0.810) between longitudinal MD and VA, and the strength of correlation constantly increased over time. However, conditional correlation and simulation studies revealed that the correlation was induced primarily by participants with rapid deteriorating MD who only accounted for a small fraction of total samples. CONCLUSION: Conditional correlation given random effects provides a robust estimate to describe the correlation between multivariate longitudinal data in the presence of unobserved heterogeneity (NCT00000125).

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

PURPOSE: Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Comparative series. PARTICIPANTS: One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study. METHODS: Samples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox proportional hazards analyses. MAIN OUTCOME MEASURES: Association of POAG with known genetic factors. RESULTS: No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (P = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure). CONCLUSIONS: The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.

Neuroimaging Features of Idiopathic Intracranial Hypertension Persist After Resolution of Papilloedema.

Papilloedema is a key clinical finding in the diagnosis of idiopathic intracranial hypertension (IIH). However, newly proposed criteria allow diagnosis without papilloedema only if certain neuroimaging features are present. It is currently unclear if these findings persist upon resolution of papilloedema and IIH. A retrospective chart review identified three groups of patients (six per group) who had received orbital imaging within 4 weeks of fundoscopic examination: (1) IIH patients without active papilloedema, (2) IIH patients with active papilloedema, and (3) patients with no history of IIH or papilloedema. All magnetic resonance imaging (MRI) scans were graded by a neuroradiologist who was blinded to clinical status. Neuroimaging features were compared by using the Kruskal-Wallis one-way analysis of variance. Measurements of sellar and optic nerve configuration showed a statistical trend with papilloedema status. For the control group versus the active papilloedema group, the values were 0.0597 and 0.0621, respectively. For the control group versus the resolved papilloedema group, the values were 0.0485 and 0.0512, respectively. However, globe and sellar p values for the resolved papilloedema group versus the active papilloedema group were 1.000 and 0.6023, respectively, and not significant. Sellar and globe configuration suggest that a statistical trend for persistence after papilloedema has resolved and intracranial pressure (ICP) has normalised. Careful clinical correlation and fundus examination are essential because some of these neuroimaging features can be seen in normal patients and those with resolved IIH, and their presence on MRI may not necessarily indicate active disease or elevated ICP.

Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure.

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSß° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.

Silent cerebral infarction, income, and grade retention among students with sickle cell anemia.

Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia.

Correlation between papilledema grade and diffusion-weighted magnetic resonance imaging in idiopathic intracranial hypertension.

BACKGROUND: To explore the relationship between diffusion-weighted magnetic resonance imaging (DWI) hyperintensity of the optic nerve head (ONH) and papilledema grade in patients with idiopathic intracranial hypertension (IIH). METHODS: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and visual field (VF) analysis who underwent orbital magnetic resonance imaging (MRI) within 4 weeks of diagnosis. A neuroradiologist masked to the diagnosis assessed the results of DWI for each eye independently and graded the signal intensity of the ONH into none, mild, and prominent categories. DWI grading was compared with papilledema grade and visual field mean deviation (VFMD) by Spearman rank correlation analysis and t-tests. RESULTS: Forty-two patients were included in the study. A statistically significant difference (P = 0.0195) was found between papilledema grade and patients with prominent DWI findings (n = 16; mean papilledema grade 3.75 ± 1.25) vs mild or no ONH hyperintensity (n = 26; mean papilledema grade 2.79 ± 1.24) at the time of initial diagnosis. DWI hyperintensity of the ONH at diagnosis was also found to be significantly correlated with the degree of papilledema at follow-up (ρ = 0.39, P = 0.0183) but not with VFMD. CONCLUSIONS: We found a significant correlation between the severity of papilledema and ONH hyperintensity on DWI in patients with IIH but not with VF loss or other visual parameters. These findings may offer insight into the pathophysiology of papilledema in IIH and provide a surrogate marker for the presence and severity of papilledema.

Visual field progression patterns in the ocular hypertension treatment study correspond to vulnerability regions of the disc.

OBJECTIVES: To determine the locations on the 24-2 visual field (VF) testing grid that are most likely to progress in patients with ocular hypertension (OHTN). Based on a structural model of superior and inferior areas of relative vulnerability at the optic disc, we hypothesized that the nasal and paracentral regions are more prone to show a reduction in sensitivity. METHODS: Posthoc analysis of data collected in phases 1 and 2 of the Ocular Hypertension Treatment Study (OHTS). A pointwise analysis was applied to determine the progression patterns in the early and delayed treatment groups. Each group's progression rate and frequency were calculated for each of the 52 locations corresponding to the 24-2 VF strategy, using trend- and event-based analyses, respectively. RESULTS: For the event-based analysis, the events were most commonly found in the nasal and paracentral regions. The same regions, with some modest variation, were found to have the fastest rates of progression (ROP) measured with trend analysis. A similar pattern of progression was observed in both the early and delayed treatment groups. The difference in event rates and ROP between the early and delayed treatment groups was also greatest in the nasal and paracentral regions. CONCLUSIONS: Development of VF loss in ocular hypertensive eyes appears to be consistent with the vulnerability zones previously described in glaucomatous eyes with established VF loss. Ocular hypotensive treatment likely helps to slow the rate of progression in these regions. This suggests that careful monitoring of these locations may be useful.

Natural history of adenoviral conjunctivitis in a US-based population: Viral load, signs, and symptoms.

PURPOSE: To report the clinical signs, symptoms, and viral clearance in individuals in the United States with adenoviral conjunctivitis (Ad-Cs). METHODS: Individuals ≥ 18 years presenting within 4 days of symptoms of Ad-Cs who met eligibility criteria and tested positive with both point-of-care immunoassay antigen and quantitative polymerase chain reaction (qPCR) testing were enrolled. Patient-reported symptoms, clinician-graded signs, and qPCR viral titers were collected at baseline, days 1-2, 4 (days 3-5), 7 (days 6-10), 14 (days 11-17) and 21 (days 18-21). RESULTS: There was no detectable viral titers by the day 14 visit in 6/8 patients. By day 21, there was no detectable viral titers in the 7 participants who completed the visit; however, signs and symptoms persisted including: blurry vision (5/7), discomfort (2/7) or redness (1/7). Masked clinicians also noted conjunctival redness (4/7), follicular conjunctivitis (4/7) and bulbar edema (3/7). CONCLUSION: Many patient-reported symptoms and clinical signs persist after viral titers are no longer detectable by qPCR. Using clinical signs and symptoms to determine quarantine duration may result in patients being furloughed longer than the time that the patient is infectious.

Quality of Life and Primary Open-Angle Glaucoma in the Ocular Hypertension Treatment Study.

Importance: If preperimetric glaucoma reduces patient-reported vision-related quality of life (VRQoL), clinicians might consider earlier and more aggressive treatment of some patients with ocular hypertension and early glaucoma. Objective: To determine the impact of preperimetric glaucoma and early glaucomatous visual field (VF) loss on participants' VRQoL compared with participants who did not develop glaucoma in the Ocular Hypertension Treatment Study (OHTS). Design, Setting, and Participants: This cross-sectional study used data from participants enrolled in the OHTS from 1994 to 1996 who completed 20-year examination follow-up and VRQoL surveys from January 7, 2016, to November 19, 2019. Diagnosis of primary open-angle glaucoma (POAG) required reproducible changes in VFs or optic discs as determined by reading centers and attributed to glaucoma by a masked end point committee. Data analysis was performed from June 27, 2023 to March 7, 2024. Exposure: Ocular hypertension and glaucoma. Main Outcomes and Measures: Cross-sectional analysis of Rasch-calibrated total scores of the National Eye Institute Visual Function Questionnaire (VFQ) and the Glaucoma Quality of Life (GQL) survey was performed. Total scores were standardized from 0 (poor) to 100 (good). The main outcomes were differences in total VRQoL scores between participants who did not develop POAG (control) and 4 mutually exclusive POAG groups: unilateral or bilateral disc POAG with no glaucomatous VF loss in either eye and unilateral or bilateral VF POAG with or without disc changes. Differences in total VRQoL scores were analyzed using univariate and multivariate linear regression models. Results: Of 1636 participants originally enrolled in the OHTS, 679 (42%) completed the 20-year examination and VRQoL surveys. Of those participants completing 20-year follow-up, mean (SD) participant age at follow-up was 73.8 (7.7) years, and 412 of 679 participants (60.7%) self-reported as female. The mean (SD) Rasch-calibrated total VFQ scores were 72.5 (13.4) in the no POAG group (control) vs 72.7 (13.8) in the unilateral disc POAG group (difference, 0.17; 95% CI, -3.17 to 3.41; P = .92), 73.4 (14.0) in the bilateral disc POAG group (difference, 0.92; 95% CI, -2.93 to 4.77; P = .64), 69.2 (14.5) in the unilateral VF POAG group (difference, 3.33; 95% CI, -6.38 to -0.27; P = .03), and 58.5 (16.9) in the bilateral VF POAG group (difference, -13.96; 95% CI, -17.73 to -10.19; P<.001). Similar results were found for the GQL questionnaire. Conclusions and Relevance: In this cross-sectional study, among the surviving participants of OHTS who completed the 20-year follow-up examination, those participants who developed preperimetric POAG but no glaucomatous VF loss did not report lower VFQoL compared with participants who did not develop POAG. This finding should allow clinicians and patients the time to determine the frequency of examinations and whether the initiation of treatment is appropriate.

Seasonal changes in visual field sensitivity and intraocular pressure in the ocular hypertension treatment study.

PURPOSE: Longitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects. DESIGN: Comparative case series. PARTICIPANTS: A total of 33 873 visits by 1636 participants enrolled in the Ocular Hypertension Treatment Study. Participants were split into 6 geographic zones according to the prevailing climate in their location. TESTING: At each visit, standard automated perimetry was conducted on each eye, and IOP was measured. MAIN OUTCOME MEASURES: Mixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (ΔMD) and on IOP, both overall and within each zone. RESULTS: When all the data were included, a significant seasonal effect on ΔMD was found with magnitude 0.06 dB, peaking in February (P < 0.001). Five of the 6 geographic zones exhibited significant seasonal effects on ΔMD, peaking between January and April, with magnitudes ranging from 0.04 dB (P = 0.049) to 0.21 dB (P < 0.001). Zones with greater climactic variation showed larger seasonal effects on ΔMD. All 6 zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (P ≤ 0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the 2 seasonal effects. CONCLUSIONS: The mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations. The cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test-retest variability.

What is the Optimal Frequency of Visual Field Testing to Detect Rapid Progression Among Hypertensive Eyes?

PRCIS: We evaluated 16,351 visual field (VF) tests from Ocular Hypertension Treatment Study (OHTS) database and showed that more frequent testing resulted in a shorter time to detect glaucoma progression, with the best trade-off being the 6-month intervals for high-risk and 12 months for low-risk patients. PURPOSE: To investigate the effect of different testing intervals on time to detect visual field progression in eyes with ocular hypertension. METHODS: A total of 16,351 reliable 30-2 VF tests from 1575 eyes of the OHTS-1 observation arm with a mean (95% CI) follow-up of 4.8 (4.7-4.8) years were analyzed. Computer simulations (n = 10,000 eyes) based on mean deviation values and the residuals of risk groups (according to their baseline 5 y risk of developing primary open angle glaucoma: low, medium, and high risk) were performed to estimate time to detect progression with testing intervals of 4, 6, 12, and 24 months using linear regression. The time to detect VF progression ( P < 5%) at 80% power was calculated based on the mean deviation slope of -0.42 dB/year. We assessed the time to detect a -3 dB loss as an estimate of clinically meaningful perimetric loss. RESULTS: At 80% power, based on the progression of -0.42 dB/year, the best trade-off to detect significant rates of VF change to clinically meaningful perimetric loss in high, medium, and low-risk patients was 6, 6, and 12-month intervals, respectively. CONCLUSION: Given the importance of not missing the conversion to glaucoma, the frequency of testing used in OHTS (6 mo) was optimal for the detection of progression in high-risk patients. Low-risk patients could potentially be tested every 12 months to optimize resource utilization.

Adjusting intraocular pressure for central corneal thickness does not improve prediction models for primary open-angle glaucoma.

PURPOSE: To determine if the accuracy of the baseline prediction model for the development of primary open-angle glaucoma (POAG) in patients with ocular hypertension can be improved by correcting intraocular pressure (IOP) for central corneal thickness (CCT). DESIGN: Reanalysis of the baseline prediction model for the development of POAG from the Ocular Hypertension Treatment Study (OHTS) substituting IOP adjusted for CCT using 5 different correction formulae for unadjusted IOP. PARTICIPANTS: A total of 1433 of 1636 participants randomized to OHTS who had complete baseline data for factors in the prediction model: age, IOP, CCT, vertical cup-to-disc ratio (VCDR), and pattern standard deviation (PSD). METHODS: Reanalysis of the prediction model for the risk of developing POAG using the same baseline variables (age, IOP, CCT, VCDR, and PSD) except that IOP was adjusted for CCT using correction formulae. A separate Cox proportional hazards model was run using IOP adjusted for CCT by each of the 5 formulae published to date. Models were run including and excluding CCT. MAIN OUTCOME MEASURES: Predictive accuracy of each Cox proportional hazards model was assessed using the c-statistic and calibration chi-square. RESULTS: C-statistics for prediction models that used IOP adjusted for CCT by various formulas ranged from 0.75 to 0.77, no better than the original prediction model (0.77) that did not adjust IOP for CCT. Calibration chi-square was acceptable for all models. Baseline IOP, whether adjusted for CCT or not, was statistically significant in all models including those with CCT in the same model. The CCT was statistically significant in all models including those with IOP adjusted for CCT in the same model. CONCLUSIONS: The calculation of individual risk for developing POAG in ocular hypertensive individuals is simpler and equally accurate using IOP and CCT as measured, rather than applying an adjustment formula to correct IOP for CCT.