Levonorgestrel intrauterine device use and incident idiopathic intracranial hypertension among commercially insured women.

OBJECTIVES: To estimate the hazard of incident idiopathic intracranial hypertension, a potentially blinding condition, among women using levonorgestrel intrauterine devices (LNG-IUD) compared to copper IUD, as conflicting associations have been reported. STUDY DESIGN: This retrospective, longitudinal cohort study identified women ages 18-45 years in a large care network (January 1, 2001, to December 31, 2015) using LNG-IUD, subcutaneous etonogestrel implant, copper IUD, tubal device/surgery, or hysterectomy. Incident idiopathic intracranial hypertension was defined as the first diagnosis code for after 1 year without any codes and following brain imaging or lumbar puncture. Kaplan-Meier analysis estimated time-dependent probabilities of idiopathic intracranial hypertension at 1 and 5 years after incident contraception use, stratified by type. Cox regression estimated the hazard of idiopathic intracranial hypertension associated with LNG-IUD use compared to copper IUD (primary comparison) after adjusting for sociodemographics and factors associated with idiopathic intracranial hypertension (e.g., obesity) or contraception selection. A sensitivity analysis with propensity score-adjusted models was performed. RESULTS: Of 268,280 women, 78,175 (29%) used LNG-IUD, 8715 (3%) etonogestrel implant, 20,275 (8%) copper IUD, 108,216 (40%) hysterectomy, 52,899 (20%) tubal device/surgery, and 208 (0.08%) developed idiopathic intracranial hypertension over a mean follow-up of 2.4 ± 2.4 years. Also, 1-/5-year Kaplan-Meier idiopathic intracranial hypertension probabilities were 0.0004/0.0021 for LNG-IUD and 0.0005/0.0006 for copper IUD users. LNG-IUD use did not show significantly different hazard of idiopathic intracranial hypertension compared to copper IUD (adjusted hazard ratio 1.84 [95% CI 0.88, 3.85]). Sensitivity analyses were similar. CONCLUSIONS: We did not observe a significantly increased hazard of idiopathic intracranial hypertension among women using LNG-IUD compared to copper IUDs. IMPLICATIONS: The lack of an association between LNG-IUD use and idiopathic intracranial hypertension in this large observational study provides reassurance to women considering initiation or continued use of this highly effective contraceptive method.

Social Risk Factor Associations With Presenting Visual Acuity in Patients With Microbial Keratitis.

Importance: Neighborhood-level social risk factors may contribute to health disparities in microbial keratitis (MK) disease presentation. Understanding neighborhood-level factors may identify areas for revised health policies to address inequities that impact eye health. Objective: To investigate if social risk factors were associated with presenting best-corrected visual acuity (BCVA) for patients with MK. Design, Setting, and Participants: This was a cross-sectional study of patients with a diagnosis of MK. Patients presenting to the University of Michigan with a diagnosis of MK between August 1, 2012, and February 28, 2021, were included in the study. Patient data were obtained from the University of Michigan electronic health record. Main Outcomes and Measures: Individual-level characteristics (age, self-reported sex, self-reported race and ethnicity), presenting log of the minimum angle of resolution (logMAR) BCVA, and neighborhood-level factors, including measures on deprivation, inequity, housing burden, and transportation at the census block group, were obtained. Univariate associations of presenting BCVA (< 20/40 vs ≥20/40) with individual-level characteristics were assessed with 2-sample t, Wilcoxon, and χ2 tests. Logistic regression was used to test associations of neighborhood-level characteristics with the probability of presenting BCVA worse than 20/40 after adjustment for patient demographics. Results: A total of 2990 patients with MK were identified and included in the study. Patients had a mean (SD) age of 48.6 (21.3) years, and 1723 were female (57.6%). Patients self-identified with the following race and ethnicity categories: 132 Asian (4.5%), 228 Black (7.8%), 99 Hispanic (3.5%), 2763 non-Hispanic (96.5%), 2463 White (84.4%), and 95 other (3.3%; included any race not previously listed). Presenting BCVA had a median (IQR) value of 0.40 (0.10-1.48) logMAR units (Snellen equivalent, 20/50 [20/25-20/600]), and 1508 of 2798 patients (53.9%) presented with BCVA worse than 20/40. Patients presenting with logMAR BCVA less than 20/40 were older than those who presented with 20/40 or higher (mean difference, 14.7 years; 95% CI, 13.3-16.1; P < .001). Furthermore, a larger percentage of male vs female sex patients presented with logMAR BCVA less than 20/40 (difference, 5.2%; 95% CI, 1.5-8.9; P = .04), as well as Black race (difference, 25.7%; 95% CI, 15.0%-36.5%;P < .001) and White race (difference, 22.6%; 95% CI, 13.9%-31.3%; P < .001) vs Asian race, and non-Hispanic vs Hispanic ethnicity (difference, 14.6%; 95% CI, 4.5%-24.8%; P = .04). After adjusting for age, self-reported sex, and self-reported race and ethnicity, worse Area Deprivation Index (odds ratio [OR], 1.30 per 10-unit increase; 95% CI, 1.25-1.35; P < .001), increased segregation (OR, 1.44 per 0.1-unit increase in Theil H index; 95% CI, 1.30-1.61; P < .001), higher percentage of households with no car (OR, 1.25 per 1 percentage point increase; 95% CI, 1.12-1.40; P = .001), and lower average number of cars per household (OR, 1.56 per 1 less car; 95% CI, 1.21-2.02; P = .003) were associated with increased odds of presenting BCVA worse than 20/40. Conclusion and Relevance: Findings of this cross-sectional study suggest that in a sample of patients with MK, patient characteristics and where they live were associated with disease severity at presentation. These findings may inform future research on social risk factors and patients with MK.

Glaucoma Medication Adherence 1 Year after the Support, Educate, Empower Personalized Glaucoma Coaching Program.

PURPOSE: To assess the efficacy of the Support, Educate, Empower (SEE) glaucoma coaching program on medication adherence among poorly adherent patients with glaucoma for 12 months after cessation of the intervention. DESIGN: Uncontrolled intervention study with a pre-post design. PARTICIPANTS: The SEE cohort was recruited from the University of Michigan and included patients with glaucoma aged ≥ 40 years, taking ≥ 1 medication, who self-reported poor adherence. Electronic medication monitoring of those who completed the program continued for up to 1 year after the coaching intervention. METHODS: Adherence was monitored electronically (AdhereTech) during the 7-month program and 12-month follow-up period. Adherence was the percentage of doses taken on time. Participants were censored for surgery, change in glaucoma medications, or adherence monitor disuse. The SEE program included automated medication reminders, 3 in-person motivational interviewing-based counseling sessions with a glaucoma coach, and 5 phone calls with the coach for between-session support. There was no contact between the study team and participants during the 12-month follow-up after program cessation. Baseline participant characteristics were summarized with descriptive statistics. Paired t tests and Wilcoxon signed rank tests were used to investigate significant changes in monthly adherence during follow-up. MAIN OUTCOME MEASURES: Change in electronically monitored medication adherence over the 12 months following the conclusion of the SEE program. RESULTS: Of 48 participants, 39 (81%) completed the SEE program and continued electronic medication monitoring for up to 1 year after program cessation. The mean age of the participants was 64 years (standard deviation [SD], 10); of the 39 participants, 56% were male, 49% were Black, and 44% were White. The mean length of follow-up was 284 days (SD, 110; range, 41-365 days). Censoring occurred in 18 (56%) participants. The mean adherence during the follow-up period was 67% (SD, 22%). This was significantly lower than the adherence during the SEE program (mean, 81%; SD, 18%; P < 0.0001) but significantly higher than the baseline preprogram adherence (mean, 60%; SD, 18%; P = 0.0393). The largest monthly losses occurred at months 1 (mean, 7%; P = 0.0001) and 4 (mean, 6%; P = 0.0077). CONCLUSIONS: Glaucoma medication adherence decreased significantly in the year after cessation of the SEE coaching program but remained significantly higher than baseline adherence. To maintain excellent long-term medication adherence, intermittent reinforcement sessions may be necessary.

The Association between Medication Adherence and Visual Field Progression in the Collaborative Initial Glaucoma Treatment Study.

PURPOSE: To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN: The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma. PARTICIPANTS: Three hundred seven participants randomized to the medication arm of the CIGTS. METHODS: Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, "Did you happen to miss any dose of your medication yesterday?" The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported. MAIN OUTCOME MEASURE: Mean deviation over time. RESULTS: Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17-1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86-1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19-3.26; P < 0.0001). CONCLUSIONS: This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss.

A Glaucoma-Specific Brief Motivational Interviewing Training Program for Ophthalmology Para-professionals: Assessment of Feasibility and Initial Patient Impact.

Our objective was to test the feasibility of, fidelity to, and initial impact of a brief, glaucoma-specific motivational interviewing (MI) training program for ophthalmic para-professionals. This prospective, mixed-methods study had two components, one for staff and one for patients. Staff fidelity to MI principles was graded through audio-recorded encounters after initial and final training sessions. After training, patients graded staff for adherence to autonomy supportive care. Semi-structured interviews with para-professionals elicited feedback about the training and about their ability to implement MI in the clinic. The impact on patient satisfaction with staff communication, eye drop instillation self-efficacy, and overall health activation was assessed using a survey pre- and post-training. Para-professionals met two of three program goals for MI skills and improved in their overall scores for MI fidelity. Para-professionals noted lack of time in the clinic as a significant barrier to implementing counseling. Patient satisfaction with staff communication increased after the training (p = 0.04) among patients who rated their staff above the mean for providing autonomy supportive care. The intervention did not improve patients' eye drop instillation self-efficacy or overall health activation. Training para-professional staff in brief, glaucoma-specific MI techniques is feasible and may improve patient satisfaction, though dedicated time in clinic is needed to implement MI counseling into glaucoma practice.

Association of Limiting Opioid Prescriptions With Use of Opioids After Corneal Surgery.

Importance: Opioids, which carry a high risk for addiction and overdose, are commonly prescribed after corneal surgery. Data are lacking describing opioid prescribing practices and opioid needs by patients after ophthalmic surgery. Objectives: To quantify opioid use and to assess the association of decreasing the number of opioid tablets prescribed after corneal surgery with postsurgical use. Design, Setting, and Participants: This prospective cohort study investigated opioid use after corneal surgery using direct interviews of 2 adult patient cohorts separated by an updated opioid prescribing guideline. The first cohort survey assessed the quantity of opioid tablets used after surgery. The cornea division of a tertiary care academic medical center reviewed the use needs and decreased the number of tablets prescribed after routine cases. Simultaneously, a statewide opioid monitoring program began that provided patients with opioid information. A second unique cohort received a more detailed survey to assess use, opioid disposal, and pain control. Data for the first cohort were collected from December 1, 2017, through January 19, 2018; for the second cohort, from June 1 to September 15, 2018. Data were analyzed from October 24, 2018, through September 24, 2019. Exposure: Corneal surgery. Main Outcomes and Measures: Differences in use of opioid tablets used by both patient cohorts, assessed using the 2-sample t test. Results: Of 112 eligible, contacted patients, 82 consented to participate (42 men [51%]; mean [SD] age, 42.5 [17.8] years) and were included in the analysis; 38 of 42 participated in the first cohort and 44 of 70 participated in the second cohort. Of those receiving opioid prescriptions, the first cohort was prescribed significantly more tablets than the second cohort (mean [SD], 18.8 [4.2] vs 6.6 [3.1]; difference, 12.2 [95% CI, 10.4-14.0]; P < .001). The first cohort used significantly more tablets than the second cohort (mean [SD], 8.3 [7.0] vs 4.0 [3.2]; difference, 4.3 [95% CI, 1.4-7.2]; P = .005) and had significantly more leftover tablets (mean [SD], 10.3 [6.9] vs 2.9 [2.7]; difference, 7.5 [95% CI, 4.7-10.2]; P < .001). In the detailed survey for the second cohort, 19 of 27 patients reported pain control as adequate (70% [95% CI, 50%-86%]); 6 of 27, as more than needed (22% [95% CI, 9%-42%]). Twenty of 28 participants (71% [95% CI, 55%-88%]) had leftover tablets; 17 of these (85% [95% CI, 62%-97%]) did not dispose of leftovers, and 3 (15% [95% CI, 3%-38%]) threw away or flushed leftovers. Conclusions and Relevance: After an assessment of opioid needs, physicians prescribed fewer opioid pills. However, patients who underwent cornea surgery and received fewer tablets continued to have adequate pain control and used even fewer tablets compared with the initial cohort. Patients with unused opioid tablets did not dispose of them properly.

Trends in and Predictors of Depression Among Participants in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

PURPOSE: To characterize longitudinal trends and factors predictive of depressive symptoms following glaucoma diagnosis in Collaborative Initial Glaucoma Treatment Study (CIGTS) participants. DESIGN: Cohort study using follow-up data from a clinical trial. METHODS: A total of 607 participants with newly diagnosed open-angle glaucoma were enrolled at 14 clinical centers in the United States from October 1993 through April 1997, randomized to treatment with medication or surgery, and followed every 6 months through 2004. The 8-item Center for Epidemiologic Studies Depression Scale (CES-D) was administered at baseline and follow-up visits. Three outcome measures were investigated: overall CES-D depression score, presence of mild or worse depression (CES-D score ≥ 7), and number of depressive symptoms endorsed. RESULTS: The average baseline CES-D score was 2.4 (SD = 3.8), 12.5% of subjects reported symptoms associated with mild or worse depression, and 55.3% reported at least 1 depressive symptom. By 1 year posttreatment, depression measures decreased (1.5, 6.7%, and 38.4%, respectively), with modest decreases thereafter. Baseline factors predictive of mild or worse depression included worse vision-related quality of life (VRQOL) (odds ratio [OR] = 2.41), female sex (OR = 1.42), younger age (OR per 10 years younger = 1.24), and less than high school education (OR = 2.93); other outcomes showed similar results. CONCLUSIONS: Depressive symptoms decreased considerably during the first year after treatment initiation, but were elevated in those with impaired VRQOL. Given the potential of depression to reduce treatment adherence and thus increase the risk of glaucoma progression, eye care providers should ask patients about depressive symptoms, provide reassurance when appropriate, and make referrals as necessary.

Do Largest Basal Tumor Diameter and the American Joint Committee on Cancer's Cancer Staging Influence Prognostication by Gene Expression Profiling in Choroidal Melanoma.

PURPOSE: To evaluate the prognostication of choroidal melanoma (CM) by the gene expression profiling (GEP) test. DESIGN: Cohort study. METHODS: Retrospective review of 293 CM patients from 2 centers. RESULTS: Of 293 patients, 132 (45%) were class 1A by GEP, 63 (22%) were class 1B, and 98 (33%) were class 2. Class 2 tumors had more ciliary body involvement and greater largest basal dimension (LBD), and were thicker. GEP results and increasing LBD were independently predictive of time to metastasis. Kaplan-Meier survival analysis estimated the probability of 3-year metastasis-free survival (MFS) of 0.99 in class 1A, 0.90 in class 1B, and 0.60 in class 2. The probability of 3-year MFS was 0.49 in class 2 patients with LBD ≥ 12 mm vs 1.00 in those with LBD < 12 mm, 0.89 in class 1B with LBD ≥ 12 mm vs 0.93 in those with LBD < 12 mm, and 0.99 in class 1A with LBD ≥ 12 mm vs 1.00 in those with LBD < 12 mm. In American Joint Committee on Cancer (AJCC) stage I CMs, the probability of 3-year MFS was 1.0 for class 1A and 1B, and 0.79 for class 2. In stage II CMs, the probability of 3-year MFS was 0.99 for class 1A, 0.89 for class 1B, and 0.61 for class 2. In stage III CM, the probability of 3-year MFS was 1.0 for class 1A, 0.60 for class 1B, and 0.41 for class 2. CONCLUSIONS: GEP testing provided significant prognostic information for CM. Class 2 tumors with LBD ≥ 12 mm and class 2 and 1B tumors with AJCC stage III showed significantly worse prognosis.

Teleophthalmic Approach for Detection of Corneal Diseases: Accuracy and Reliability.

PURPOSE: Corneal and anterior segment diseases cause most of the urgent visits to eye care professionals. We evaluated the diagnostic accuracy of detecting corneal diseases using external photographs from 2 portable cameras for telemedicine purposes. METHODS: This is a prospective study of adults with a clinical diagnosis of corneal pathology including corneal abrasions, ulcers, scars, and pterygia. A cornea specialist provided the gold standard diagnosis by slit-lamp examination. Images of both eyes were obtained using iTouch 5S and Nidek VersaCam cameras in multiple gazes and interpreted by 3 cornea specialists for the presence of pathology. Accuracy to detect disease was compared with gold standard diagnosis, stratified by the camera and grader. Reliability was evaluated with weighted kappa statistics. Graders assessed image quality on a Likert scale from 1 (poor) to 9 (optimal). RESULTS: A total of 198 eyes (110 subjects) were photographed. By gold standard diagnosis, 59 eyes (30%) had corneal scars, 34 (17%) had ulcers, 13 (7%) had abrasions, 10 (5%) had pterygia, and 82 (41%) were normal. Sensitivity to detect AS pathology ranged from 54% to 71% for the iTouch and 66% to 75% for the Nidek, across graders; specificity ranged from 82% to 96% for the iTouch and 91% to 98% for the Nidek. The intergrader reliability was moderate to strong (kappa ranges: 0.54-0.71 for the iTouch; 0.75-0.76 for the Nidek). Quality ratings were variable between graders. CONCLUSIONS: External photographs taken by standard, nonenhanced portable cameras and interpreted remotely by ophthalmologist graders yielded sensitivity values that are not yet suitable for telemedicine applications. Additional work is needed to improve the ability to detect AS pathology remotely.

Glaucoma Screening in Nepal: Cup-to-Disc Estimate With Standard Mydriatic Fundus Camera Compared to Portable Nonmydriatic Camera.

PURPOSE: To compare cup-to-disc ratio (CDR) measurements from images taken with a portable, 45-degree nonmydriatic fundus camera to images from a traditional tabletop mydriatic fundus camera. DESIGN: Prospective, cross-sectional, comparative instrument validation study. METHODS: Setting: Clinic-based. STUDY POPULATION: A total of 422 eyes of 211 subjects were recruited from the Tilganga Institute of Ophthalmology (Kathmandu, Nepal). Two masked readers measured CDR and noted possible evidence of glaucoma (CDR ≥ 0.7 or the presence of a notch or disc hemorrhage) from fundus photographs taken with a nonmydriatic portable camera and a mydriatic standard camera. Each image was graded twice. MAIN OUTCOME MEASURES: Effect of camera modality on CDR measurement; inter- and intraobserver agreement for each camera for the diagnosis of glaucoma. RESULTS: A total of 196 eyes (46.5%) were diagnosed with glaucoma by chart review; 41.2%-59.0% of eyes were remotely diagnosed with glaucoma over grader, repeat measurement, and camera modality. There was no significant difference in CDR measurement between cameras after adjusting for grader and measurement order (estimate = 0.004, 95% confidence interval [CI], 0.003-0.011, P = .24). There was moderate interobserver reliability for the diagnosis of glaucoma (Pictor: κ = 0.54, CI, 0.46-0.61; Topcon: κ = 0.63, CI, 0.55-0.70) and moderate intraobserver agreement upon repeat grading (Pictor: κ = 0.63 and 0.64, for graders 1 and 2, respectively; Topcon: κ = 0.72 and 0.80, for graders 1 and 2, respectively). CONCLUSIONS: A portable, nonmydriatic, fundus camera can facilitate remote evaluation of disc images on par with standard mydriatic fundus photography.

Predictors of Photographic Quality with a Handheld Nonmydriatic Fundus Camera Used for Screening of Vision-Threatening Diabetic Retinopathy.

PURPOSE: To analyze predictors of image quality for a handheld nonmydriatic fundus camera used for screening of vision-threatening diabetic retinopathy. METHODS: An ophthalmic photographer at an Aravind Eye Hospital obtained nonmydriatic and mydriatic fundus images from 3 fields in 275 eyes of 155 participants over 13 months using a Smartscope camera (Optomed, Oulu, Finland) and a Topcon tabletop fundus camera (Topcon, Tokyo, Japan). Two fellowship-trained retina specialists graded the images. Repeated-measures logistic regression assessed predictors of the main outcome measure: gradability of the fundus images. RESULTS: Of 2,475 images, 76.2% of the Smartscope nonmydriatic images, 90.1% of the Smartscope mydriatic images, and 92.0% of the Topcon mydriatic images were gradable. Eyes with vitreous hemorrhage (OR = 0.24, p < 0.0001) or advanced cataract (OR = 0.08, p < 0.0001) had decreased odds of image gradability. Excluding eyes with cataract or vitreous hemorrhage, nonmydriatic macular image gradability improved from 68.4% in the first set of 55 eyes to 94.6% in the final set of 55 eyes. CONCLUSION: With sufficient training, paraprofessional health care staff can obtain high-quality images with a portable nonmydriatic fundus camera, particularly in patients with clear lenses and clear ocular media.

Comparison of prednisolone acetate 1.0% and difluprednate ophthalmic emulsion 0.05% after cataract surgery: Incidence of postoperative steroid-induced ocular hypertension.

PURPOSE: To compare intraocular pressure (IOP) outcomes between 2 common, commercially available corticosteroid drops: difluprednate ophthalmic emulsion 0.05% and prednisolone acetate 1.0%. SETTING: TLC Eyecare and Laser Centers, Jackson, Michigan, USA. DESIGN: Retrospective chart review. METHODS: The outcomes of consecutive patients who had uneventful cataract surgery from April 2013 to September 2013 and used prednisolone acetate postoperatively were compared with the outcomes of consecutive patients who had uneventful cataract surgery from June 2014 to October 2014 and used difluprednate postoperatively. RESULTS: The study included 224 eyes treated with prednisolone acetate 4 times daily for 30 days and 225 eyes treated with difluprednate 2 times daily for 30 days. There was no significant difference between the 2 groups in age, sex, or race. In addition, the mean IOP did not differ significantly between the prednisolone acetate group and the difluprednate group at the preoperative measurement or 1 month after surgery, nor was there a difference in the 1-month change in IOP between groups. No association was found between the incidence of a 6 mm Hg or higher increase in IOP 1 month after surgery and steroid treatment. One month postoperatively, 4 eyes in the prednisolone acetate group and 5 eyes in the difluprednate group had an IOP higher than 21 mm Hg. CONCLUSIONS: There was no significant difference in the mean IOP or percentages showing IOP elevation between eyes treated with difluprednate and eyes treated with prednisolone acetate after cataract surgery. This was likely the result of low-frequency dosing and short duration of steroid use.

Binocular Measures of Visual Acuity and Visual Field versus Binocular Approximations.

PURPOSE: To assess the relationship of binocular visual function tests with binocular approximations using data from the Collaborative Initial Glaucoma Treatment Study (CIGTS). DESIGN: Case series based on existing data from a clinical trial. PARTICIPANTS: Six hundred seven patients with newly diagnosed open-angle glaucoma from the CIGTS. METHODS: Monocular visual field (VF) and visual acuity (VA) tests were performed at baseline and every 6 months thereafter. Binocular tests of visual function (Esterman VF score, binocular VA) were added to the CIGTS protocol 3 years into the study. The binocular approximations of binocular visual function were better or worse eye, average eye, better or worse location, and binocular summation or pointwise binocular summation. Associations between binocular tests and binocular approximations to represent binocular visual function were assessed with Pearson's correlations (r), as was the relationship between vision-related quality of life (VR QOL; Visual Activities Questionnaire [VAQ] and the 25-item National Eye Institute Visual Function Questionnaire [NEI VFQ-25]) and binocular tests or binocular approximations of visual function. MAIN OUTCOME MEASURES: Binocular visual function (VF and VA) and VR QOL. RESULTS: Five hundred seventy-five patients underwent at least 1 binocular visual function test. The Esterman score was correlated significantly with all binocular approximations of VF, with r values ranging from 0.31 (worse-eye mean deviation [MD]) to 0.42 (better-eye MD; P < 0.0001 for all). Binocular VA showed stronger correlations with binocular approximations, with r values ranging from 0.65 (worse-eye VA) to 0.80 (binocular summation; P < 0.0001 for all). Correlations between the VAQ and Esterman score were stronger in 7 of 9 subscales (r = -0.14 to -0.25; P < 0.05 for all) than correlations with all 7 binocular approximations. In contrast, correlations between the VAQ and binocular VA (r = -0.07 to -0.21) were weaker in all subscales than those with better-eye, average-eye, and binocular summation of VA (r = -0.12 to -0.25), but not different from worse-eye values. These trends also were found in relevant subscales of the NEI VFQ-25. CONCLUSIONS: We found limited benefit in binocular testing of VA in the clinical setting as a means of approximating a patient's reported visual functioning. In contrast, we found some benefit in performing binocular VF testing, because the results correlated more closely with reported functioning than binocular approximations.

Thyroid-Related Orbital Decompression Surgery: A Multivariate Analysis of Risk Factors and Outcomes.

PURPOSE: Despite the number of publications on orbital decompression surgery for thyroid eye disease, there are few comparative studies and most studies are underpowered. The goal of the study is to use multivariable analysis to identify independent patient and disease-related predictors of response to decompression surgery and of need for secondary decompressions. METHODS: The authors retrospectively reviewed all patients who underwent transorbital thyroid-related orbital decompression surgery at the Kellogg Eye Center of the University of Michigan between 1999 and 2014. Demographic, medical, and surgical covariates were collected. Decompression techniques included medial, lateral, and balanced decompressions, with or without orbital fat removal. Main outcomes included proptosis reduction and secondary decompressions, both analyzed at the orbital level. Univariate and multivariable analyses (with adjustment for interorbit correlation) were conducted to determine predictors of the outcomes of interest. RESULTS: Mean proptosis reduction was 3.8 ± 2.4 mm (mean ± standard deviation, N = 420 orbits). The secondary decompression rate was 13.8% (82/594). On multivariable mixed linear regression, larger preoperative proptosis (p < 0.0001), balanced decompression (p = 0.0002), thyroid eye disease duration < 4 years (p = 0.0093), and history of orbital radiation (p = 0.0111) were all predictive of greater proptosis reduction. On multivariable survival modeling, factors associated with increased hazard for secondary decompression include younger age (p = 0.0434), larger preoperative proptosis (p = 0.0001), unilateral decompression (p = 0.0272), preoperative steroid treatment (p = 0.0200), and normal thyroid function (p = 0.0148). Factors associated with decreased hazard include adjunctive fat decompression (p = 0.0004), balanced decompression (vs. lateral, p = 0.0039), and African-American ethnicity (p = 0.0076). CONCLUSIONS: Despite a diverse study cohort, the authors have identified factors associated with clinically relevant outcomes of decompression surgery for thyroid eye disease, including proptosis reduction and incidence of secondary decompression. Randomized controlled trials of different treatment algorithms for TED are needed to devise optimized guidelines for individualizing surgical care.

Elevated Serum Tetrac in Graves Disease: Potential Pathogenic Role in Thyroid-Associated Ophthalmopathy.

Context: The sources and biological impact of 3,3',5,5' tetraiodothyroacetic acid (TA4) are uncertain. CD34+ fibrocytes express several proteins involved in the production of thyroid hormones. They infiltrate the orbit in Graves disease (GD), an autoimmune process known as thyroid-associated ophthalmopathy. It appears that the thyrotropin receptor plays an important role in the pathogenesis of thyroid-associated ophthalmopathy. Objective: To quantify levels of TA4 in healthy participants and those with GD, determine whether fibrocytes generate this thyroid hormone analogue, and determine whether TA4 influences the actions of thyroid-stimulating hormone and thyroid-stimulating immunoglobulins in orbital fibroblasts. Design/Setting/Participants: Patients with GD and healthy donors in an academic medical center clinical practice were recruited. Main Outcome Measures: Liquid chromatography-tandem mass spectrometry, autoradiography, real-time polymerase chain reaction, hyaluronan immunoassay. Results: Serum levels of TA4 are elevated in GD. TA4 levels are positively correlated with those of thyroxine and negatively correlated with serum levels of triiodothyronine. Several cell types in culture generate TA4 from ambient thyroxine, including fibrocytes, HELA cells, human Müller stem cells, and retinal pigmented epithelial cells. Propylthiouracil inhibits TA4 generation. TA4 enhances the induction by thyrotropin and thyroid-stimulating immunoglobulins of several participants in the pathogenesis of thyroid-associated ophthalmopathy, including interleukin 6, hyaluronan synthase 1, prostaglandin endoperoxide H synthase 2, and haluronan production. Conclusion: TA4 may be ubiquitously generated in many tissues and enhances the biological impact of thyrotropin and thyroid-stimulating immunoglobulins in orbital connective tissue. These findings may identify a physiologically important determinant of extrathyroidal thyroid-stimulating hormone action.

The effect of humidity and temperature on visual outcomes after myopic corneal laser refractive surgery.

OBJECTIVE: To determine whether procedure room environmental conditions are associated with outcomes after myopic laser in situ keratomileusis (LASIK) or laser-assisted keratomileusis (LASEK). DESIGN: Retrospective chart review. PARTICIPANTS: Eight hundred sixty-three eyes of 458 consecutive patients at a university-based academic practice. METHODS: We reviewed the medical records of consecutive patients who underwent LASIK or LASEK over a 3-year period. Linear mixed regression models were used to investigate the association of laser room temperature and humidity with the outcomes of visual acuity and postoperative manifest spherical equivalent refraction. Repeated measures logistic regression models were used for the outcomes of diffuse lamellar keratitis (DLK) and need for enhancement surgery. RESULTS: Subjects were on an average 38.6 years old at the time of surgery (standard deviation [SD] =10.3) and the average spherical equivalent refraction of eyes was 3.8 diopters (SD =2.03). Regression models did not reveal a significant association between temperature and uncorrected distance visual acuity (UDVA) or corrected distance visual acuity (CDVA), or between humidity and UDVA (P>0.05 for all). However, increased humidity was associated with a small but statistically significant improvement in CDVA after LASIK at 1 day, 1 month, 3 months, and 1 year postoperatively (P<0.05 for all). There was no significant association between temperature and humidity and the need for enhancement, the incidence of DLK, or postoperative manifest refraction. CONCLUSION: While increased laser room humidity was consistently associated with small improvements in CDVA after myopic LASIK over time, variations in room temperature and humidity were not associated with UDVA, the need for enhancement, the incidence of DLK, or refraction after myopic LASIK or LASEK.

Safety and Feasibility of Quantitative Multiplexed Cytokine Analysis From Office-Based Vitreous Aspiration.

PURPOSE: The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. METHODS: Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. RESULTS: An adequate volume of vitreous fluid (100-200 µL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42-926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. CONCLUSIONS: Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.

Refusal of Trabeculectomy for the Fellow Eye in Collaborative Initial Glaucoma Treatment Study (CIGTS) Participants.

PURPOSE: To understand the reasons for refusal of fellow eye surgical treatment for glaucoma after first eye trabeculectomy. DESIGN: Post hoc analysis of data collected in a multicenter, randomized clinical trial. METHODS: Data from participants in the Collaborative Initial Glaucoma Treatment Study (CIGTS) who were randomized to and underwent initial trabeculectomy on their study eye, and whose fellow eye was eligible for surgical treatment, were analyzed. Participant demographic data and characteristics, surgical data from the study eye, and quality-of-life survey results were compared between groups that received or refused trabeculectomy in their fellow eye. The main outcome measure was patient refusal of fellow eye surgery for glaucoma. RESULTS: Of 159 participants who were randomized to and underwent trabeculectomy on their study eye and had a fellow eye that was eligible for surgery, 30 (19%) refused fellow eye surgery. Eligible patients who refused fellow eye trabeculectomy did not differ significantly in visual function or local eye symptoms from those that underwent fellow eye trabeculectomy (all P > .05). In a multivariable analysis of data, increased fellow eye preoperative intraocular pressure (IOP) was associated with decreased odds (OR = 0.89, P = .0188), study eye hypotony at 3 months postoperatively was associated with increased odds (OR = 7.24, P = .0125), and argon suture lysis procedure was associated with decreased odds (OR = 0.38, P = .0385) of surgery refusal. CONCLUSIONS: Refusal of fellow eye surgery was not uncommonly encountered in the CIGTS. Those who refused fellow eye surgery had lower fellow eye IOP and were more likely to have had hypotony after study eye trabeculectomy.

Prospective Randomized Trial Comparing Efficacy of Topical Loteprednol Etabonate 0.5% Versus Cyclosporine-A 0.05% for Treatment of Dry Eye Syndrome Following Hematopoietic Stem Cell Transplantation.

PURPOSE: To evaluate the safety and efficacy of topical loteprednol etabonate (LE) 0.5% compared with cyclosporine A (CsA) 0.05% for the prophylaxis and treatment of dry eye syndrome (DES) after hematopoietic stem cell transplantation (HSCT). METHODS: Seventy-five patients were randomized to LE (n = 76 eyes of 38 patients) or CsA (n = 74 eyes of 37 patients) pre-HSCT. Lissamine green and fluorescein staining, tear break-up time, tear osmolarity (Osm), Schirmer score (Sch), intraocular pressure, visual acuity, and Ocular Surface Disease Index were assessed pre-HSCT, 3, 6, 9, and 12 months post-HSCT. RESULTS: There were no differences in DES incidence (P = 0.22; log-rank test) or progression (P = 0.41; log-rank test) between the 2 treatment arms during the course of the study. Among eyes with no DES at enrollment, the Kaplan-Meier analysis yielded a 90% rate of DES development in cyclosporine-treated eyes and a 79% rate of DES development in LE-treated eyes by 12 months post-HSCT. The Kaplan-Meier analysis of eyes with DES at enrollment demonstrated a 38% rate of disease progression among cyclosporine-treated eyes and a 26% rate of disease progression among loteprednol-treated eyes by 12 months. No patient in either group had an elevation of 10 mm Hg or greater from baseline at any study visit, and no patients had their treatment discontinued for elevation in intraocular pressure. CONCLUSIONS: Pre-HSCT initiation of LE 0.5% appears to be safe and may be as effective as CsA 0.5% for the treatment and prophylaxis of DES following HSCT.

Regression rate of posterior uveal melanomas following iodine-125 plaque radiotherapy.

AIM: To characterize the regression rate of posterior uveal melanoma following radioactive iodine-125 (I-125) plaque. MATERIALS AND METHODS: We retrospectively analyzed 95 patients with posterior uveal melanoma who were treated with only radioactive I-125 plaque and had more than 3 years follow-up. All patients were treated with plaque radiotherapy using tumor dose of 85 Gy at the tumor apex, following COMS protocol. Regression rate was assessed with standardized A-scan ultrasonography. Associations with tumor regression were evaluated by means of mixed linear regression modeling. RESULTS: Mean decrease in the tumor thickness (% original thickness) at 12, 24, and 36 months after radiotherapy for melanomas < 3 mm in thickness was 29%, 38%, and 45%, for melanoma 3-8 mm in thickness was 32%, 44%, and 59%, and for melanoma more than 8 mm in thickness was 52%, 62%, and 68%, respectively. With a doubling of follow-up time (0.5-1 year, or 1-2 years of follow-up from treatment), tumors < 3 mm in thickness at treatment showed a 0.5 mm decrease in tumor thickness, whereas melanomas 3-8 mm showed a 1 mm decrease, and melanomas >8 mm showed a 1.7 mm decrease. Uveal melanomas that developed systemic metastasis showed an additional 0.4 mm decrease with a doubling of follow-up time from treatment, compared with those that did not develop metastasis (P = 0.050). CONCLUSIONS: Posterior uveal melanomas with higher initial thickness show steeper and more reduction in tumor thickness following radioactive I-125 plaque. After the initial phases, the regression curve became similar for tumors with different thicknesses.