Eyes of Africa: The Genetics of Blindness: Study Design and Methodology.

BACKGROUND: This report describes the design and methodology of the "Eyes of Africa: The Genetics of Blindness," a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health. METHODS: This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing. DISCUSSION: A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society.

PURPOSE: Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED). METHODS: This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, CT was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, intraclass correlation coefficients [ICCs], Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using ICCs. RESULTS: Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37 mm (15.96-28.90 mm) right and 21.22 mm (15.87-28.70 mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18 mm and 25 mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948-0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47 mm (10.92-30.88 mm) right and 20.30 mm (8.61-28.72 mm) left. Intrareader and interreader agreement was ideal (ICC 0.991-0.989). All exophthalmometers' mean differences from CT ranged between -0.06 mm (±1.36 mm) and 0.54 mm (±1.61 mm); 95% confidence interval fell within 1 mm. Magnitude of AGP did not affect exophthalmometry validity. Oculus best estimated CT AGP but differences from other exophthalmometers were not clinically meaningful in upright measurements. Photographic AGP (right ICC = 0.575, left ICC = 0.355) and palpebral fissure do not agree with CT. CONCLUSIONS: Upright clinical exophthalmometry accurately estimates CT AGP in TED. AGP measurement was reliably reproduced by the same clinician and between clinicians at multiple institutions using the protocol in this study. These findings allow reliable measurement of AGP that will be of considerable value in future outcome studies.

Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma.

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. Using genome-wide association single-nucleotide polymorphism data from the Glaucoma Genes and Environment study and National Eye Institute Glaucoma Human Genetics Collaboration comprising 3,108 cases and 3,430 controls, we assessed biologic pathways as annotated in the KEGG database for association with risk of POAG. After correction for genic overlap among pathways, we found 4 pathways, butanoate metabolism (hsa00650), hematopoietic cell lineage (hsa04640), lysine degradation (hsa00310) and basal transcription factors (hsa03022) related to POAG with permuted p < 0.001. In addition, the human leukocyte antigen (HLA) gene family was significantly associated with POAG (p < 0.001). In the POAG subset with normal-pressure glaucoma (NPG), the butanoate metabolism pathway was also significantly associated (p < 0.001) as well as the MAPK and Hedgehog signaling pathways (hsa04010 and hsa04340), glycosaminoglycan biosynthesis-heparan sulfate pathway (hsa00534) and the phenylalanine, tyrosine and tryptophan biosynthesis pathway (hsa0400). The butanoate metabolism pathway overall, and specifically the aspects of the pathway that contribute to GABA and acetyl-CoA metabolism, was the only pathway significantly associated with both POAG and NPG. Collectively these results implicate GABA and acetyl-CoA metabolism in glaucoma pathogenesis, and suggest new potential therapeutic targets.

Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss.

PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. DESIGN: Case-control study. PARTICIPANTS: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. MAIN OUTCOME MEASURES: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. RESULTS: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CONCLUSIONS: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.

Calculated computed tomography volumes of lacrimal glands and comparison to clinical findings in patients with thyroid eye disease.

PURPOSE: To describe the range of lacrimal gland volumes on CT in Caucasian patients with thyroid eye disease (TED) and to correlate with clinical findings. METHODS: With institutional review board approval, 125 orbital CT scans for TED were reviewed. OsiriX software was used to calculate the volume of the lacrimal gland. Comparison of the volumes was made with previously published results of the normal population. Patient race, gender, smoking status, diplopia, tearing, exophthalmometry, superficial punctate keratitis (SPK), lagophthalmos, restriction in motility, and VISA score were collected. RESULTS: The mean volume of the lacrimal gland in patients with TED was 0.890 cm in right orbits (standard deviation [SD] 0.348), 0.851 cm in left orbits (SD 0.350), with no significant difference between right and left (p = 0.311). The mean volume was 0.811 cm in right male orbits (SD 0.386) and 0.911 cm in right female orbits (SD 0.335), with no significant difference between men and women (p = 0.774). These findings were confirmed in an analysis of left orbits. The volume of right and left orbits correlated well (r = 0.777, p < 0.0001). The lacrimal gland volume in patients with TED was greater compared with the normal population using a 2-sample t test (p < 0.0001). Exophthalmometry (right: r = 0.225, p = 0.0115; left: r = 0.267, p = 0.0026) and subjective tearing (right: r = 0.226, p = 0.0138; left: r = 0.197, p = 0.0322) correlated with lacrimal gland volume. CONCLUSIONS: This study is the first to report the volume of the lacrimal gland calculated on CT scan for patients with TED. The lacrimal gland is larger in patients with TED and correlates with subjective tearing and exophthalmometry.

"Test-Retest Reliability of Intraocular Pressure Measurements with Office-Based versus Home-Based Rebound Tonometers".

PRCIS: Intraocular pressure (IOP) measurements obtained with the HOME2 rebound tonometer are interchangeable with measurements obtained using the office-based IC100 and IC200 rebound tonometers, making characterization of circadian IOP achievable with no inter-device sources of variability. PURPOSE: To evaluate test-retest reliability between intraocular pressure (IOP) measurements obtained with a home rebound tonometer operated by patients and those obtained with office rebound tonometers operated by experienced clinical staff. METHODS: Following training and practice with a home rebound tonometer (iCare HOME2) in a randomly selected eye, patients with established or suspected open-angle glaucoma underwent IOP measurement in the fellow eye as follows in randomized order: 3 good quality measurements with the iCare IC100 operated by experienced clinical staff, 3 good quality measurements with the iCare IC200 operated by experienced clinical staff, and 3 good quality measurements with the HOME2 operated by the subject. The Shrout-Fleisch intraclass correlation coefficient ICC (2,1) was the measure of reliability utilized based on the model using two-way random effects, absolute agreement, and single measurement. RESULTS: Thirty eyes of 30 patients were evaluated. The Pearson correlation coefficient (r) for IOP measurements taken with the IC100 and HOME2 was 0.97, with the IC200 and HOME2 was 0.96, and with the IC100 and IC200 was 0.97. Test-retest reliability between HOME2 and IC100 (ICC 0.90), HOME2 and IC200 (ICC 0.92), and IC100 and IC200 (ICC 0.94) all reflected excellent test-retest reliability. CONCLUSION: The test-retest reliability of IOP measurements taken by patients using the iCare HOME2 self-tonometer compared with IOP measurements taken by trained operators using the iCare IC100 and IC200 tonometers was uniformly excellent (ICCs all ≥0.9). These findings indicate that these three devices should be considered interchangeable for the clinical assessment of circadian IOP.

Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United States.

PURPOSE: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender. METHODS: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women. RESULTS: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01). CONCLUSIONS: The estrogen SNP pathway was associated with POAG among women.

Calculated CT volumes of lacrimal glands in normal Caucasian orbits.

INTRODUCTION: The objective was to describe the range of normal volumes for the lacrimal gland calculated from CT. METHODS: A retrospective review with institutional review board approval of 293 CT scans of 586 orbits was performed. Patients were included if they were Caucasian and aged 18 years or older. Orbits were excluded if there was a disease or trauma. OsiriX software was used to outline the lacrimal gland in consecutive axial slices and to calculate the volume. Inter-rater agreement was assessed in a subset of 30 randomly selected orbits by observers of different levels of training using the intraclass correlation coefficient (ICC). RESULTS: Two hundred sixty orbits of 187 patients were included. The mean volume of the lacrimal gland was 0.696 cm2 in right orbits (SD = 0.261) and 0.649 cm2 in left orbits (SD = 0.231), with no significant difference between right and left (p= 0.125). The mean volume was 0.680 cm2 in men (SD = 0.241) and 0.662 cm2 in women (SD = 0.260), with no significant difference between men and women (p = 0.564). There was an inverse relationship between gland volume and age (Pearson r= -0.428 right orbits and -0.469 left orbits). Of the 73 bilateral patients, right and left orbits correlated well (Pearson r = 0.712). Agreement was good among the observers (ICC = 0.727). CONCLUSIONS: This is the first study to report the range of normal volume for Caucasian lacrimal glands measured on CT scans. The volume of the lacrimal gland decreases with age, and there is no gender or laterality difference.

Glaucoma Treatment Patterns in Sub-Saharan Africa.

PRCIS: Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma. Laser therapy was underutilized where they were available. Physicians were more likely to recommend surgery in severe glaucoma, laser therapy in mild glaucoma, while recommendation of medical therapy did not depend on glaucoma severity. PURPOSE: To characterize treatment patterns for newly diagnosed glaucoma in sub-Saharan Africa (SSA). METHODS: This was a multicenter cross-sectional study of adults newly diagnosed with glaucoma at 27 eye care centers in 10 African countries. In addition to demographic and clinical data, physician treatment recommendations (medication, laser, surgery, or no treatment) were recorded. Statistical analyses were performed using STATA version 14.0. RESULTS: Data from 1201 patients were analyzed. Physicians were most likely to recommend primary medical therapy upon diagnosis of glaucoma (69.4%), with laser (13.2%), surgery (14.9%), and no treatment (2.5%) recommended to the remaining patients. All sites had medical therapy available and most (25/27, 92.6%) could provide surgical treatment; only 16/27 (59.3%) sites offered laser, and at these sites, 30.8% of eyes were recommended to undergo primary laser procedures. As glaucoma severity increased, the laser was recommended less, surgery more, and medications unchanged. Patient acceptance of medical therapy was 99.1%, laser 88.3%, and surgery 69.3%. CONCLUSIONS: Medical therapy for first-line glaucoma management is preferred by most physicians in SSA (69%). Laser therapy may be underutilized at centers where it is available. These findings underscore the need for comparative studies of glaucoma treatments in SSA to inform the development of evidence-based treatment guidelines and of programs to reduce glaucoma blindness in SSA. Strategic approaches to glaucoma therapy in SSA must address the question of whether medical therapy is the most optimal first-line approach in this setting.

CT dimensions of the lacrimal gland in Graves orbitopathy.

PURPOSE: To determine if lacrimal dimensions are enlarged in Graves orbitopathy on CT and to correlate size with clinical data. METHODS: One hundred and twenty-eight adult Caucasian patients with Graves orbitopathy who had CT at initial presentation to the authors' clinic were identified. The lacrimal gland width and length were measured on axial and coronal scans using the OsiriX software according to an established protocol. Comparison of dimensions with a published normal population was made. Clinical data near the time of CT were collected, including gender, age, smoking, subjective diplopia, exophthalmometry, intraocular pressure, corneal staining, and the VISA activity score for correlation with gland size. RESULTS: The lacrimal glands in Graves orbitopathy were significantly larger in all measured dimensions (p = 0.0001 for each dimension). There were no differences between the genders (p values ranged between 0.3855 and 0.8699). Exophthalmometry showed weak correlation with gland size in all dimensions (p value range, 0.0058 to <0.0001; r value range, -0.2616 to 0.4181). Smoking correlated significantly with gland enlargement in right coronal and axial width dimensions (p = 0.0150 and p = 0.0232, respectively). VISA inflammatory score was borderline correlated with right axial width. Lacrimal gland size did not correlate with diplopia, intraocular pressure, or corneal staining. CONCLUSIONS: The lacrimal gland is statistically significantly enlarged in Graves orbitopathy. Only weak correlation was found between gland enlargement and smoking, proptosis, and inflammatory activity. Future research will address the causal changes of enlargement and their effect on lacrimal function.

Clinical outcomes following selective laser trabeculoplasty in Afro-Caribbean patients with glaucoma at high risk for progression.

AIM: To characterise clinical outcomes following selective laser trabeculoplasty (SLT) in eyes of Afro-Caribbean patients with open-angle glaucoma (OAG) at high risk for progression. METHODS: In a prospective interventional case series, patients meeting high-risk criteria (advanced disease, unilateral glaucoma blindness, inadequate intraocular pressure (IOP) on >2 medications, recent progression on medications, inability to administer, afford or tolerate medications) underwent bilateral 360° SLT and managed based on their subsequent clinical course. Patient-specific indications for SLT-IOP reduction (IOP group) or reduced reliance on medical therapy (MED group)-were recorded before treatment. IOP and medication use were recorded every 3-4 months through up to 24 months of follow-up. Outcomes were analysed separately in the IOP and MED groups. RESULTS: Among 33 right eyes (left eye outcomes were similar) in the IOP group, mean (SD) IOP was significantly reduced from 21.7 (7.5) mm Hg to 16.2-17.1 mm Hg over follow-up (p<0.0177); medication use remained unchanged (p>0.05) at all time points. Among 36 right eyes in the MED group, mean medication use was 1.9 (0.9) at baseline and ranged from 1.2 to 1.4 medications per eye through follow-up (p<0.0033), and mean IOP was significantly reduced at months 1-6 (to 13.1 (2.3) mm Hg, p=0.0013), months 13-18 (to 14.3 (2.8), p=0.0136) and unchanged at other time points. No vision-threatening adverse events occurred. CONCLUSIONS: Afro-Caribbean patients with OAG at risk for progression can achieve clinically and statistically significant reductions in IOP or medications through up to 24 months following a single 360° SLT treatment. TRIAL REGISTRATION NUMBER: NCT02375009.

The social construction of genomics and genetic analysis in ocular diseases in Ibadan, South-western Nigeria.

Genomics, an emerging field to improve public health practice, has potential benefits to understanding ocular diseases. This study explored the social construction of genomics in ocular diseases in the blind community in Ibadan, Nigeria, through two focus group discussions and twelve in-depth interview sessions conducted among people living with ocular disorders. The data were thematic and content-analysed. Although the participants had limited knowledge about ocular diseases, genomics, and their nexus, they maintained a positive attitude toward its potential benefits. This informed their willingness to participate in genomics testing for ocular diseases. The participants preferred saliva-based sample collection over blood-based, and expressed concern for the procedure and accrued benefits of genomics studies. Thus, public sensitisation about ocular diseases and client-centred genomics testing procedures should be engendered.

Clinical Characteristics and Stage at Presentation of Glaucoma Patients in Sub-Saharan Africa.

PRCIS: The initial presentation of glaucoma varies meaningfully across SSA. A comprehensive strategy with regional customization based on local differences is needed to reduce glaucoma blindness in SSA. PURPOSE: To explore regional variations in the presentation of newly diagnosed glaucoma in Sub Saharan Africa (SSA). METHODOLOGY: This was a multicenter, cross-sectional study in which newly diagnosed, consecutive, glaucoma patients aged older than or equal to 18 years were recruited from 27 eye clinics in 10 countries throughout SSA. Demographic and ophthalmic examination data were collected. Glaucoma severity was based on optic nerve head and visual field assessment. Statistical analyses were performed using STATA version 14.0. RESULTS: Among 1214 enrolled patients with newly diagnosed glaucoma from Western, Eastern, and Southern Africa, the overall mean (SD) age was 59.9 (17.1) years. More than half of all patients (716/1178; 60.8%) presented with severe glaucoma in the worse eye, and one-third (36.9%) had severe glaucoma in both eyes. Primary open angle glaucoma was the commonest form of glaucoma in all regions (77.4%). A family history of blindness (260/1204, 21.6%) was common. Patients from Western Africa had lower mean presenting intraocular pressure (26.4 [11.1] mm Hg, P <0.001), but had worse glaucoma in the better eye based on mean cup-disc ratio (0.8; P <0.001) and mean visual field mean deviation [10.4 (8.4)] dB, P =0.016) compared with other regions. Exfoliation glaucoma was more common in Eastern Africa (30/170=17.7%, P <0.001) compared with other regions. CONCLUSION: The initial presentation of glaucoma varies meaningfully across SSA. A comprehensive strategy with regional customization based on local differences is needed to reduce glaucoma blindness in SSA.

Short-term repeatability of diurnal intraocular pressure patterns in glaucomatous individuals.

PURPOSE: To evaluate the short-term repeatability of diurnal intraocular pressure (IOP) patterns in eyes with primary open-angle glaucoma (POAG). DESIGN: Observational cohort study. PARTICIPANTS: Forty-seven subjects with treated POAG. METHODS: Subjects underwent assessment of IOP using Goldmann tonometry every 2 hours from 0800 to 2000 on 2 visits 1 week apart. Intervisit agreement of IOP by time point and of IOP change between time points was assessed using intraclass correlation coefficients (ICCs). MAIN OUTCOME MEASURES: Diurnal IOP patterns. RESULTS: Between-visit agreement of IOP values at each time point was generally fair to good, with ICCs ranging from 0.45 to 0.71 in right eyes and from 0.51 to 0.71 in left eyes. Between-visit agreement of IOP change over time periods between time points was uniformly poor, with ICCs ranging from -0.08 to 0.38 in right eyes and from -0.11 to 0.36 in left eyes. CONCLUSIONS: Treated POAG patients do not manifest a repeatable diurnal IOP pattern from day to day when measured by Goldmann tonometry. Measurement of single-day IOP variation poorly characterized short-term IOP variation.

Asymmetry of 24-hour intraocular pressure reduction by topical ocular hypotensive medications in fellow eyes.

PURPOSE: A core assumption for the 1-eye therapeutic trial of ocular hypotensive medications is the symmetrical reduction of intraocular pressure (IOP) in paired eyes. This assumption was evaluated for 24-hour IOP reduction in patients who underwent monotherapy or adjunctive therapy. DESIGN: Database study. PARTICIPANTS: Patients 41 to 79 years of age with primary open-angle glaucoma or ocular hypertension. METHODS: Twenty-four-hour IOP data from the paired eyes of patients undergoing bilateral monotherapy (n = 66) of latanoprost, travoprost, timolol, or brimonidine or bilateral adjunctive therapy (n = 52) with brinzolamide or timolol added to latanoprost monotherapy were analyzed retrospectively. Measurements of IOP were obtained every 2 hours in a sleep laboratory before and after at least 4-week drug treatments. Strengths of association for single-pair IOP reductions and average IOP reductions in the paired eyes during the office-hour, diurnal, nocturnal, and 24-hour periods and in different body positions were analyzed. MAIN OUTCOME MEASURES: Variance for the difference, percentage distribution of large absolute difference, and coefficient of determination (r(2)) in the paired IOP reductions. RESULTS: The standard deviations for the differences in single-pair IOP reductions from the means were larger than 2.5 mmHg for all periods and body positions under monotherapy and adjunctive therapy. Absolute differences in single-pair IOP reductions of the cutoff thresholds of 3 and 2 mmHg or more occurred in more than 20% and 36% cases, respectively. Corresponding coefficients of determination were 0.240 to 0.374 with monotherapy and 0.215 to 0.381 with adjunctive therapy. When the average differences in the paired IOP reductions were analyzed for a specific period and posture, the standard deviations for the differences in the paired IOP reductions and the percentage distributions of large absolute differences were reduced, and most coefficients of determination were improved. CONCLUSIONS: There is only a weak association between the right- and left-eye responses to IOP-lowering monotherapy or adjunctive therapy during a 24-hour period when single-pair IOP data are considered. Considering the averages of multiple paired IOP responses can improve the strength of the association. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A history of glaucoma pharmacology.

The history of glaucoma pharmacology begins in 1862 with the isolation of physostigmine from the calabar bean. The discovery of epinephrine's intraocular pressure lowering capacity came along some 40 years later. During the 20th century, drug discovery and development accelerated, with the introduction of carbonic anhydrase inhibitors, beta blockers, and prostaglandin analogs. This survey of the history of glaucoma medications reviews some of the pivotal stories behind the development of the drugs that we use daily to manage our patients with glaucoma. In addition, some unmet needs that persist in glaucoma pharmacology are discussed.

Computed tomography dimensions of the lacrimal gland in normal Caucasian orbits.

INTRODUCTION: CT is frequently used to assess the lacrimal gland, yet no published reports exist of normal dimensions using this modality. We retrospectively evaluated CT data from normal orbits and measured the lacrimal gland dimensions. METHODS: Two-hundred ninety-three consecutive orbital CT scans (586 orbits) of 282 patients were identified. Caucasian patients aged 18 years and older without known orbital disease were included. Traumatized orbits were excluded. All repeated scans were excluded. Length and width of the lacrimal gland were measured in axial and coronal sections with GE Centricity Software. The primary outcome was a descriptive analysis of the distribution of dimensions in normal orbits. A random subset of patient scans was measured independently by observers at different levels of training, and intraclass correlation coefficients (ICCs) were established. RESULTS: Three hundred orbits (150 right orbits and 150 left orbits) of 282 patients were included. Normal distributions occurred with axial and coronal length measurements. Mean (10th and 90th percentiles) lacrimal gland axial length in right orbits was 14.7 mm (10.9 mm and 18.3 mm) and 14.5 mm in left orbits (10.3 mm and 18.3 mm). Coronal length averaged 17.7 mm in right eyes (13.9 mm and 21.8 mm) and 16.9 mm in left eyes (12.8 mm and 20.8 mm). Axial and coronal width showed non-normal distributions. No statistically significant difference in dimensions was found between genders, and a significant inverse linear relation occurred between gland size and age. Agreement was significant among the observers (ICC >0.7). CONCLUSION: This study presents a normal range of Caucasian lacrimal gland dimensions seen on CT. Lacrimal gland size decreases with age, and no gender difference exists. This range can aid in differentiating diseased and nondiseased lacrimal glands, especially when correlated with physical examination. This may be useful in clinical trials that involve lacrimal gland size.

Low-energy Selective Laser Trabeculoplasty Repeated Annually: Rationale for the COAST Trial.

The recent Laser in Glaucoma and Ocular Hypertension Trial provided the evidentiary basis for a paradigm shift away from the historical medication-first approach to glaucoma--which has numerous limitations, the most important of which is poor adherence to therapy --and toward a laser-first approach. Now 20 years after its commercialization, selective laser trabeculoplasty (SLT) is routinely performed consistently with its initial description, with energy titrated to the appearance of fine, champagne-like cavitation bubbles. A recent data set suggested that lower energy SLT, applied as primary therapy and repeated annually irrespective of intraocular pressure--rather than pro re nata when its effect wanes and irrespective of intraocular pressure rises --yields longer medication-free survival than standard energy SLT repeated pro re nata. A new study--Clarifying the Optimal Application of SLT Therapy --has been initiated to explore this preliminary finding in a pair of consecutive randomized trials. Herein, we provide an evidence-based rationale for the use of low-energy SLT repeated annually as primary therapy for mild to moderate primary open-angle glaucoma or high-risk ocular hypertension.

Long-Term Outcomes of Selective Laser Trabeculoplasty for Open-Angle Glaucoma in the Caribbean.

PURPOSE: To characterize long-term clinical outcomes of monotherapy selective laser trabeculoplasty (SLT) in Afro-Caribbean patients with open-angle glaucoma (OAG). DESIGN: This was a post hoc analysis of nearly 8 years (median, 3.2; interquartile range, 2.1-7.1) of pooled data from the West Indies Glaucoma Laser Study and its preliminary study. METHODS: Setting: Three eye care practices in Saint Lucia and Dominica. PARTICIPANTS: Afro-Caribbean adults with mild-moderate OAG treated with ≤2 medications (61 in preliminary study, 72 in West Indies Glaucoma Laser Study). INTERVENTION: Participants underwent medication washout, baseline intraocular pressure (IOP) determination, and bilateral 360-degree SLT. Participants were followed for up to 94 months. Repeat SLT was performed according to prespecified criteria. MAIN OUTCOME MEASURES: The primary outcome was mean IOP reduction from baseline. The secondary outcome was medication-free survival with SLT repeated as needed. RESULTS: The pooled data set included 265 eyes of 133 Afro-Caribbean participants. The mean (standard deviation) baseline IOP was 21.2 (3.4) and 21.2 (3.9) mmHg in right and left eyes, respectively. Over 8 years, the mean IOP ranged from 12.8 to 15.7 mm Hg and from 13.1 to 15.8 mm Hg, respectively (P < .0001 for every comparison with baseline). The median medication-free survival time for initial SLT was 85.4 months in both eyes. The 94-month medication-free survival of SLT repeated as needed was 71.2% and 71.7%, respectively. CONCLUSIONS: Monotherapy SLT, repeated as needed, safely provides significant IOP reductions in most Afro-Caribbean adults with primary OAG through nearly 8 years of follow-up and has significant potential to delay or prevent glaucoma-related vision loss in black patients in low-resource regions.