Drug-Induced Liver Injury During a Glaucoma Neuroprotection Clinical Trial.

There are several ongoing, worldwide clinical trials with a cumulative target enrollment of over 1300 participants on the role of nicotinamide (a specific form of vitamin B3) as a therapeutic neuroprotective treatment for glaucoma. We describe a serious adverse event of drug-induced liver injury (DILI) likely related to the use of 3 grams/day nicotinamide in a glaucoma clinical trial (clinicaltrials.gov identifier: NCT05695027) based in the United States. This report is important to share with the medical community, as other participants in glaucoma nicotinamide trials globally may have similar adverse events and many patients are using nicotinamide as a health supplement without medical supervision. We recommend that investigators, physicians, and patients remain vigilant about DILI as they seek novel vision-preserving neuroprotective therapies.

Detecting Established Glaucoma Using OCT Alone: Utilizing an OCT Reading Center in a Real-World Clinical Setting.

Purpose: We evaluated the ability of an optical coherence tomography (OCT)-based reading center for glaucoma (ORG) to detect established glaucoma using OCT alone. Methods: This study included eyes from 70 consecutive patients with established glaucoma (i.e. moderate or severe glaucoma according to the International Classification of Diseases [ICD]-10 guidelines) and 20 consecutive healthy subjects, who had no evidence of glaucomatous optic neuropathy (GON) or visual field (VF) loss in either eye. Using a standardized ORG quality assessment, 33 eyes were excluded due to media opacity (12), poor image quality (13), or epiretinal membrane (8). Of the remaining 147 eyes, 86 had established glaucoma and 36 were from healthy controls (total n = 122). Based on the OCT report alone and applying a previously described evaluation method, the presence of GON in each eye was determined by two masked ORG graders. The main outcome measures were sensitivity and specificity for detection of eyes with established glaucoma. Results: Of the 86 eyes with established glaucoma (average mean deviation [MD] = -10.9 ± 7.7 dB, range = -0.5 to -31.5 dB), only one eye (MD = -0.46) was missed (sensitivity = 98.8%). However, the other eye of this patient was correctly classified as GON. Therefore, at a patient level, sensitivity was 100%. None of the 36 healthy eyes was classified as GON by the ORG (specificity = 100%). Conclusions: An OCT-based reading center is able to identify eyes with established glaucoma using OCT alone with high sensitivity and specificity. Translational Relevance: Our study validates the use of a systematic OCT-based approach for glaucoma detection in a real-world setting.

Identifying Rapid Glaucoma Progression Using Hemifield Rates of Progression.

PRCIS: Hemifield rates of progression are more sensitive to focal progression (or faster progression) than global rates. This can aid in tailoring management and treatment decisions. PURPOSE: To determine if the rate of progression (ROP) of each hemifield of the 24-2 visual field (VF) aids in the detection of rapidly progressing eyes. METHODS: In this retrospective longitudinal study, we evaluated 1658 eyes of 1658 consecutive glaucoma patients with global mean deviation (MD) VF loss between -3 and -15 dB at baseline and ≥8 reliable VF tests (Swedish Interactive Thresholding Algorithm 24-2) with over ≥3 years of follow-up. The ROP (dB/year) based on global MD, superior hemifield MD, and inferior hemifield MD was calculated. The worst hemifield ROP (ROPworst) and hemifield ROP absolute difference (ROPdiff) were determined for each eye. Eyes were categorized based on the ROP from each metric as slow (-0.5 dB/year or better), rapid (worse than -0.5 dB/year), very rapid (worse than -1.0 dB/year), and catastrophic (worse than -2.0 dB/year) progression. The rate of significant asymmetric hemifield progression rate (ROPdiff ≥0.5 dB/year) was also evaluated. RESULTS: On average, ROPworst was faster than ROPglobal by 0.25±0.3 dB/year ( P <0.001). Based on ROPworst, 422 eyes (25%) were classified as progressing more rapidly than the ROPglobal classification. Over 40% (153/339) of the eyes classified as rapid progressors by ROPglobal were classified as very rapid or catastrophic progressors based on ROPworst. Eyes that progressed more rapidly based on ROPworst also had a higher rate of asymmetric progression. CONCLUSION: Hemifield ROPs are more sensitive to focal progression (or faster progression) than global rates and can aid in tailoring management and treatment decisions.

Improving glaucoma staging in clinical practice by combining the ICD-10 glaucoma severity classification system and optical coherence tomography.

OBJECTIVE: The International Classification of Disease, 10th revision (ICD-10) codes used for glaucoma severity classification are based on the 24-2 visual-field (VF) test. This study aim was to assess the added value of providing clinicians with optical coherence tomography (OCT) data, in addition to functional data, for glaucoma staging in clinical practice. EXPOSURE: Disease classification was determined for 54 glaucoma eyes, according to the principles of the ICD-10 guidelines. Eyes were independently graded in a masked fashion using the 24-2 VF test and 10-2 VF test, with and without OCT information. The reference standard (RS) for severity was determined using a previously published automated structure-function topographic agreement for glaucomatous damage using all available information. RESULTS: The RS classified eyes as mild, moderate and advanced in 3, 16 and 35 cases, respectively. Individual and combined 24-2 and 10-2 based gradings were significantly different from the RS (all P < 0.005), with Kappa agreements of 0.26, 0.45 and 0.42 respectively (P < 0.001). Classifications using OCT combined with either of the VF were not-significantly different from the RS (P > 0.3) with Kappa agreements of 0.56 and 0.57 respectively (P < 0.001). Combining 24-2 with OCT had less severity overestimations while 10-2 with OCT had fewer underestimations. CONCLUSION: Combining OCT and VF data provides better staging of glaucoma severity than VF data alone. The 24-2 and OCT combination seems most appropriate given the high concordance with the RS and less overestimation of severity. Incorporating structural information into disease stages allows clinicians to set more appropriate severity-based treatment targets for individual patients.

Effect of Phacoemulsification on Intraocular Pressure in Eyes with Functioning Tube Shunts.

Purpose: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in eyes with functioning tube shunts. Methods: This was a retrospective chart review of primary open-angle glaucoma (POAG) patients with a functioning tube who underwent phacoemulsification and had ≥24 months of follow-up. The primary end point was defined as surgical failure (IOP > 21 mmHg) at month 24, progression to no light perception (NLP) vision, glaucoma reoperation, or implant removal. Surgical failure defined as IOP >18 and >15 mmHg, changes in visual acuity (VA), IOP, and number of medications were assessed. Results: Twenty-seven eyes of 27 patients with moderate or severe POAG were included. The mean age of the patients was 64.2 ± 10.8 years. The interval between the tube shunt and phacoemulsification was 28.8 ± 25.0 months. At the end of the study, four (14.8%) eyes met the failure criteria; the average time to failure was 9.3 ± 3.8 months. The causes of failure were high IOP in two (50.0%) and glaucoma reoperation in two (50.0%) eyes; however, no eyes progressed to NLP vision. Surgical failure defined as IOP >18 and >15 mmHg showed an increasing failure rate (18.5% and 48.5%, respectively).Themean IOP and medications number remained stable at month 24 compared to baseline (P = 0.131 and P = 0.302, respectively). Initially, VA showed improvement, with the greatest improvement at 6 months (P = 0.001), but at 24 months the improvement was no longer significant (P = 0.430). Conclusion: Phacoemulsification in patients with functioning tubes did not change the mean IOP in most of the patients (86.2%); the number of medications also did not increase.

Hemorrhagic Complications Following Trabecular Bypass Microstent Surgery in the Setting of Antithrombotic Therapy.

PRCIS: In this retrospective study, the use of chronic antithrombotic therapy (ATT) did not increase the risk of hemorrhagic complications after trabecular bypass microstent surgery and phacoemulsification. Stent type and female sex were associated with hyphema. PURPOSE: To report the incidence of hemorrhagic complications after trabecular bypass microstent surgery and phacoemulsification with and without (ATT). METHODS: Retrospective case series on glaucoma patients on chronic ATT who underwent trabecular bypass microstent surgery (iStent, iStent inject, and Hydrus) combined with phacoemulsification between 2013 and 2019 with ≥3-month follow-up. The primary outcome measure was the incidence of hemorrhagic complications within a 3-month postoperative period. Generalized estimating equations were created to account for inter-eye correlation and logistic regression analysis was performed to identify factors predictive of hemorrhagic complications. RESULTS: Of 333 patients (435 eyes), 161 patients (211 eyes) were on ATT and 172 patients (224 eyes) were not on ATT; both groups were similar in age and baseline ocular characteristics. The only hemorrhagic complication was hyphema, which occurred in 84 (19.3%) eyes (41 ATT, 43 non-ATT eyes; P = 1.00). Onset was at postoperative day 1 in 98.8% of eyes, with a duration of 1 week in 73.8% of eyes, without difference between ATT and non-ATT groups. Hyphema was most common with Hydrus microstent (36.4%) versus iStent (19.9%) and iStent inject (8.5%) ( P = 0.003). In the multivariate model, the female sex was a predictor of hyphema [hazard ratio (HR) = 2.062; P = 0.009], iStent inject was protective against hyphema (HR = 0.379; P = 0.033), whereas Hydrus did not reach statistical significance (HR = 2.007; P = 0.081). Age, systemic comorbidities, ATT use, and baseline ocular characteristics were not significant predictors. CONCLUSIONS: Hemorrhagic complications after trabecular bypass microstent surgery were limited to transient hyphema and were not associated with chronic ATT use. Stent type and female sex were associated with hyphema.

Female Editorial Authorship Trends in High-Impact Ophthalmology Journals.

IMPORTANCE: Individuals with perceived experience and expertise are invited by editorial boards to provide commentary through editorials. Female representation among editorialists is not yet defined. OBJECTIVE: To determine female representation as editorial authors in 3 high-impact general ophthalmology journals. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study investigates the proportion of female authorship in editorials published between 2005 to 2009 and 2015 to 2019 in 3 journals: Ophthalmology, JAMA Ophthalmology, and American Journal of Ophthalmology. Data were collected from April to June 2020. MAIN OUTCOMES AND MEASURES: Proportions of female first and senior (last or solo) authors between 2005 to 2009 compared with 2015 to 2019. Secondary outcome measures include representation by sex across degree types and subspecialties. Comparisons were made for all editorialists and ophthalmologist editorialists. RESULTS: Of 814 editorial articles, there were 1179 (first and senior) authors identified. Women held 301 (25.5%) of these authorships, including 116 of 365 first authorships (32.9%) and 185 of 814 senior authorships (23.9%). Overall, female first and senior authorships grew by 68.0% between 2005 to 2009 and 2015 to 2019 (85 of 469 [18.1%] vs 216 of 710 [30.4%]; difference, 12.3%; 95% CI, 7.4-317.2; P < .001). Between 2005 to 2009 and 2015 to 2019, first and senior authorships by women increased (first: 33 of 133 [24.8%] vs 83 of 232 [35.8%]; difference, 11.0%; 95% CI, 1.4-320.6; P = .03; senior: 52 of 336 [15.5%] vs 133 of 478 [27.8%]; difference, 12.3%; 95% CI, 6.8-317.9; P < .001). JAMA Ophthalmology most substantially contributed to the increase in female first and senior authorships (13.8% and 16%), although the test for homogeneity among the 3 journals was not significant. The proportion of female ophthalmologist first authors was greater than the proportion of American Board of Ophthalmology-certified female ophthalmologists (81 of 281 [28.9%] vs 123 of 672 [18.3%]; difference, 10.6%; 95% CI, 5.3-315.9; P < .001). CONCLUSIONS AND RELEVANCE: The proportion of female senior authors increased by 68.0% between 2005 to 2009 and 2015 to 2019, but female authors represented only 25.5% of editorialists. Compared with male ophthalmologists, female ophthalmologists were more commonly first than senior authors. Additionally, female authors were more likely to be nonophthalmologists or to hold nonmedical, non-PhD degrees. While the swelling rank of female editorialists has paralleled the rising proportion of female ophthalmologists over time, parity by sex has yet to be attained. Greater awareness of disparities and strategies to mitigate them may help equalize representation.

Gender Compensation Gap for Ophthalmologists in the First Year of Clinical Practice.

PURPOSE: To identify the role of gender and other factors in influencing ophthalmologists' compensation. DESIGN: Cross-sectional study. PARTICIPANTS: U.S. practicing ophthalmologists. METHODS: Between January and March 2020, an anonymous survey was sent to U.S. residency program directors and practicing ophthalmologists who recently completed residency training. Respondents who completed residency ≤ 10 years ago and responded to questions about gender, fellowship training, state of practice, and salary were included. Propensity score match (PSM) analysis was performed with age, academic residency, top residency, fellowship, state median wage, practice type, ethnicity, and number of workdays. Multivariate linear regression (MLR) analysis controlled for additional factors along with the aforementioned variables. MAIN OUTCOME MEASURES: Base starting salary with bonus (SWB) received in the first year of clinical position was the main outcome measure. A multiplier of 1.2 (20%) was added to the base salary to account for bonus. RESULTS: Of 684 respondents, 384 (56% were female, 44% were male) from 68 programs were included. Female ophthalmologists received a mean initial SWB that was $33 139.80 less than that of their male colleagues (12.5%, P = 0.00). The PSM analysis showed an SWB difference of -$27 273.89 (10.3% gap, P = 0.0015). Additionally, SWB differences were calculated with the number of workdays substituted by operating room (OR) days (-$27 793.67 [10.5% gap, P = 0.0013]) and clinic days (-$23 597.57 [8.90% gap, P = 0.0064]) in separate PSM analyses. The SWB differences between genders were significant using MLR analyses, which also controlled for work, clinic, and OR days separately (-$22 261.49, $-18 604.65, and $-16 191.26, respectively; P = 0.017, P = 0.015, P = 0.002, respectively). Gender independently predicted income in all 3 analyses (P < 0.05). Although an association between gender and the attempt to negotiate was not detected, a greater portion of men subjectively reported success in negotiation (P = 0.03). CONCLUSIONS: Female ophthalmologists earn significantly less than their male colleagues in the first year of clinical practice. Salary differences persist after controlling for demographic, educational, and practice type variables with MLR and PSM analyses. These income differences may lead to a substantial loss of accumulated earnings over an individual's career.