Outcome of Primary Monocanalicular Stent Placement in Pediatric Down Syndrome Patients with Congenital Nasolacrimal Obstruction.

PURPOSE: Congenital Nasolacrimal duct obstruction (CNLDO) is a relatively common problem in children with Down syndrome (DS). Probing and irrigation (PI) with monocanalicular stent intubation may be less successful than in non-DS patients, thus raising some concerns regarding the preferred treatment in this population. We aimed to analyze the surgical outcome of PI along with monocanalicular stent intubation in children with DS compared with non-DS patients. METHODS: Retrospective cohort study. Thirty-five eyes of 19 children with DS and 1,472 eyes of 1,001 children without DS underwent PI-monocanalicular stent intubation as a primary treatment for CNLDO. All patients were operated on by a single surgeon at the Children's Hospital of Philadelphia between 2009 and 2020. The main outcome measure was a surgical success, defined as the resolution of symptoms after surgery. RESULTS: A total of 1,020 patients were included, 48% females; mean age of 1.9 ± 1.4 years. The mean follow-up time was 35.0 months. The DS patients group consisted of 19 patients. Higher rates of right nasolacrimal duct obstruction and bilateral obstructions were observed in the DS group (100% vs. 73.2%; p = 0.006, and 84.2% vs. 46.8%; p = 0.001, respectively). Patients with DS had a lower success rate (57.1% vs. 92.4%; p < 0 .0001). The median time to failure was 3.1 months in the DS group, and 5.2 months in the group of patients without DS. The hazard ratio comparing DS to the no-DS outcome was 6.6 (95% CI: 3.2-13.7; p < 0.001). CONCLUSIONS: CNLDO in DS is more likely to be bilateral and less likely to resolve after primary monocanalicular stent placement.

Statin use and the risk of progression to vision threatening diabetic retinopathy.

PURPOSE: This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). METHODS: Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. RESULTS: Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR = 1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR = 1.03, 95% CI: 0.99-1.07, p = 0.13), PDR (HR = 0.89, 95% CI: 0.79-1.02, p = 0.09), DME (HR = 0.94, 95% CI: 0.86-1.03, p = 0.21), VH (HR = 1.00, 95% CI: 0.86-1.16, p = 0.99), and TRD (HR = 1.11, 95% CI: 0.89-1.38, p = 0.36). CONCLUSION: Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

Primary Monocanalicular Stent Intubation for Children With Congenital Nasolacrimal Duct Obstruction: Surgical Outcome and Risk Factors.

PURPOSE: To determine the risk factors impacting the surgical success of primary monocanalicular stent intubation for congenital nasolacrimal duct obstruction (CNLDO). METHODS: This is a retrospective interventional case series of patients 18 years and younger treated more than a 12-year period with monocanalicular stent intubation with inferior turbinate fracture for CNLDO by a single surgeon. Patients with dacryocystoceles, dacryocystitis, Down syndrome and previous tear duct surgery were excluded. An intraoperative grading scale of tear duct stenosis, date of stent removal, stent length, and postoperative symptoms were recorded. Surgical success was defined as the complete resolution of symptoms. RESULTS: One thousand four hundred sixty-nine stents were placed in 1,001 pediatric participants (533 unilateral, 468 bilateral). The mean age at surgery was 1.86 years (0.1-18.07). The mean follow up was 34.99 months (0.43-134.3) with mean in-office stent removal at 3.41 months (0.63-36.9). Early stent loss occurred in 14.8% intubations (217/1,469). The overall success rate was 92.4% (1,357/1,469 eyes). Subjects less than the age of 4 years had a success rate of 92.8% (1,296/1,397) compared with 84.7% (61/72) in children more than 4. In multivariable analysis, bilateral surgery, severe tear duct stenosis, and early stent loss were significantly associated with higher risk of surgical failure. CONCLUSIONS: Severe tear duct stenosis, early stent loss, and bilateral surgery were significant risk factors for surgical failure. While the success rate stratified by age at surgery suggested a lower success after the age of 4. Primary monocanalicular stent intubation is an effective and safe treatment for CNLDO sparing a child the need for multiple staged surgeries.

SYSTEMIC MEDICATION USE AND THE INCIDENCE AND GROWTH OF GEOGRAPHIC ATROPHY IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS.

PURPOSE: To determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials. METHODS: Participants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models. RESULTS: In multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios ≤1.86, P ≥ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P = 0.02). CONCLUSION: None of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.

Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy.

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. METHODS: A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. RESULTS: A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92-1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95-1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58-1.12, p = 0.20). CONCLUSION: We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.

Outcomes of resident physician-performed cataract surgery in a diverse veterans affairs health system population.

Purpose: To evaluate visual acuity (VA) outcomes and complications from resident physician-performed cataract surgery in a diverse Veterans Affairs Hospital population. Methods: A retrospective chart review was conducted for patients who underwent cataract surgery performed by resident physicians from 01/01/2013 to 12/31/2015 at the Veterans Affairs Medical Center. Intraoperative and postoperative clinical information, best-corrected VA (BCVA) (1 day, months 1, 2-3, and 6), and surgery complications were extracted. Univariable and multivariable linear regression models were performed for risk factors of BCVA change. Results: This study included 1183 patients, with mean (SD) age of 70.8 (9.3) years. 1154 (97.5%) were males, 493 (41.7%) African-American, and 681 (57.6%) Caucasian. The mean (SD) VA in logMAR was 0.69 (0.74) at baseline, improved to 0.19 (0.36) at 1 month, 0.16 (0.34) at 2-3 months, and 0.14 (0.36) at 6 months. 1080 (91.3%) patients experienced VA improvement from baseline and 1023 (86.5%) patients achieved at least 20/40 BCVA at 1 month. There were 86 (7.3%) complications, most commonly including 47 (4.0%) posterior capsular tears and 64 (5.4%) vitreous loss. In multivariable analysis, younger age (P < 0.0001), worse baseline VA (P < 0.0001), and absence of iris prolapse (P < 0.001) were significantly associated with greater improvement in VA at 1 month. Conclusion: In a diverse VAMC, resident-performed cataract surgeries achieved significant improvement in VA with a cumulative complication rate lower than previously reported. Resident physician education may benefit from specific focus on prevention of iris prolapse and better incision construction during surgery as these intraoperative events often led to delayed stabilization of visual outcome beyond 1 month.

Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma.

BACKGROUND/AIMS: Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat type 2 diabetes mellitus. Recent work showed that treatment with the GLP-1R agonist NLY01 decreased retinal neuroinflammation and glial activation to rescue retinal ganglion cells in a mouse model of glaucoma. In this study, we used an insurance claims database (Clinformatics Data Mart) to examine whether GLP-1R agonist exposure impacts glaucoma risk. METHODS: A retrospective cohort of patients who initiated a new GLP-1R agonist was 1:3 age, gender, race, classes of active diabetes medications and year of index date matched to patients who initiated a different class of oral diabetic medication. Inverse probability of treatment weighting (IPTW) was used within a multivariable Cox proportional hazard regression model to test the association between GLP-1R agonist exposure and a new diagnosis of primary open-angle glaucoma, glaucoma suspect or low-tension glaucoma. RESULTS: Cohorts were comprised of 1961 new users of GLP-1R agonists matched to 4371 unexposed controls. After IPTW, all variables were balanced (standard mean deviation <|0.1|) between cohorts. Ten (0.51%) new diagnoses of glaucoma were present in the GLP-1R agonist cohort compared with 58 (1.33%) in the unexposed controls. After adjustment, GLP-1R exposure conferred a reduced hazard of 0.56 (95% CI: 0.36 to 0.89, p=0.01), suggesting that GLP-1R agonists decrease the risk for glaucoma. CONCLUSIONS: GLP-1R agonist use was associated with a statistically significant hazard reduction for a new diagnosis of glaucoma. Our findings support further investigations into the use of GLP-1R agonists in glaucoma prevention.

Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials.

OBJECTIVE: To predict 2-year visual acuity (VA) responses to anti-VEGF therapy, using early morphologic and functional responses in patients with neovascular age-related macular degeneration (nAMD). DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: A total of 1185 participants with untreated active nAMD and best-corrected visual acuity (BCVA) 20/25 to 20/320 at baseline. METHODS: Secondary analysis of data from participants randomized to either ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of 2-year BCVA responses with baseline morphologic and functional characteristics and their change from baseline at 3 months were assessed, using univariable and multivariable linear regression models for BCVA change and logistic regression models for ≥ 3-line BCVA gain from baseline. The performance of predictions for 2-year BCVA outcomes using these characteristics was assessed using R2 for BCVA change and area under the receiver operating characteristic curve (AUC) for ≥ 3-line BCVA gain. MAIN OUTCOME MEASURES: Best-corrected visual acuity change and ≥ 3-line gain from baseline at year 2. RESULTS: In multivariable analyses that included previously reported significant baseline predictors (baseline BCVA, baseline macular atrophy, baseline retinal pigment epithelium elevation [RPEE], and maximum width and early BCVA change from baseline at 3 months), new RPEE occurrence at 3 months was significantly associated with more BCVA gain at 2 years (10.2 letters vs. 3.5 letters for RPEE resolved, P < 0.001), and none of the other morphologic responses at 3 months were significantly associated with BCVA responses at 2 years. These significant predictors moderately predicted 2-year BCVA gain with an R2 = 0.36. Baseline BCVA and ≥ 3-line BCVA gain at 3 months predicted 2-year ≥ 3-line gain with AUC 0.83 (95% confidence interval, 0.81-0.86). CONCLUSIONS: Most structural responses on OCT at 3 months were not independently predictive of the 2-year BCVA responses, which were associated with baseline factors and the 3-month BCVA response to anti-VEGF therapy. A combination of baseline predictors, early BCVA, and morphologic responses at 3 months only moderately predicted the long-term BCVA responses. Future research is needed to better understand the factors contributing to the variation in long-term vision outcomes with anti-VEGF therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Thiazolidinedione use and retinal fluid in the comparison of age-related macular degeneration treatments trials.

BACKGROUND: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD). METHODS: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium fluid, and foveal thickness of retinal layers were evaluated at baseline and during 2-year follow-up. Comparisons of outcomes between thiazolidinedione usage groups were adjusted by macular neovascularisation lesion type in multivariable regression models. RESULTS: Patients taking thiazolidinedione (n=30) had lower adjusted mean VA score at baseline (difference -6.2 letters; p=0.02), greater proportion with intraretinal fluid (IRF) at year 2 (75% vs 50%, adjusted OR 2.8; p=0.04), greater mean decrease in subretinal tissue complex thickness from baseline at year 1 (difference -75.1 um; p=0.02) and greater mean decrease in subretinal thickness at year 1 (difference -41.9 um; p=0.001) and year 2 (difference -43.3 um; p=0.001). CONCLUSIONS: In this exploratory analysis, patients with diabetes taking thiazolidinediones and treated with bevacizumab or ranibizumab for nAMD had worse baseline mean VA, greater reductions in subretinal and subretinal tissue complex thickness from baseline, and greater proportions with IRF comparing to patients not taking thiazolidinediones. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00593450.

Recent Practice Patterns in Acute Retinal Artery Occlusions in the United States.

PURPOSE: To determine how to practice patterns for work-up of incident retinal artery occlusion (RAO) compare to the American Academy of Ophthalmology (AAO) guidelines. METHODS: In this cohort study, patients receiving a new diagnosis of RAO, either central (CRAO) or branch (BRAO), were identified between 2002 and 2020 from a large US medical claims database. Claims were reviewed for diagnostic tests specified by the AAO as essential components of an RAO work-up including carotid ultrasound, echocardiogram, magnetic resonance imaging (MRI) and emergency department (ED) referral. Outcomes included rates of and time to completion of work-up. RESULTS: 18697 new outpatient diagnoses of RAO (11348 BRAO, 7349 CRAO) were analyzed. 15.9% and 30.4% of patients received carotid ultrasounds within 7 and 30 days, respectively. 9.4% and 21.1% of patients received echocardiograms within 7 and 30 days, respectively. 4.9% and 8.1% of patients received a brain MRIs within 7 and 30 days, respectively. Only 4.1% of patients were referred to the ED within a day of diagnosis. Ophthalmologists diagnosed the majority (78.7%) of RAOs compared to neurologists (0.6%). Patients diagnosed by ophthalmologists were significantly more likely to have carotid ultrasound within 7 days, but those diagnosed by neurologists were more likely to have echocardiogram, MRI, and ED referral (p < .01 for all comparisons). The rates of adherence to the AAO care guidelines increased significantly between 2002 and 2020 (p < .01). CONCLUSIONS: The referral and work-up practices demonstrated in this new RAO diagnosis patient cohort have improved with time but are still far below the standard recommended by the AAO.

Colonoscopy utilization and outcomes in older adults: Data from the New Hampshire Colonoscopy Registry.

BACKGROUND: Colonoscopy is frequently performed in older adults, yet data on current use, and clinical outcomes of and follow-up recommendations after colonoscopy in older adults are lacking. METHODS: This was an observational study using the New Hampshire Colonoscopy Registry of adults age ≥65 years undergoing colonoscopy for screening, surveillance of prior polyps, or evaluation of symptoms. The main outcomes were clinical findings of polyps and colorectal cancer and recommendations for future colonoscopy by age. RESULTS: Between 2009 and 2019, there were 42,611 colonoscopies, of which 17,527 (41%) were screening, 19,025 (45%) surveillance, and 6059 (14%) for the evaluation of symptoms. Mean age was 71.1 years (SD 5.0), and 49.3% were male. The finding of colorectal cancer was rare (0.71%), with the highest incidence among diagnostic examinations (2.4%). The incidence of advanced polyps increased with patient age from 65-69 to ≥85 years for screening (7.1% to 13.6%; p = 0.05) and surveillance (9.4% to 12.0%; p < 0.001). Recommendations for future colonoscopy decreased with age and varied by findings at current colonoscopy. In patients without any significant findings, 85% aged 70-74 years, 61.9% aged 75-79 years, 39.1% aged 80-84 years, and 27.4% aged ≥85 years (p < 0.001) were told to continue colonoscopy. Among patients with advanced polyps, 97.2% aged 70-74 years, 89.6% aged 75-79 years, 78.4% aged 80-84 years, and 66.7% aged ≥85 years were told to continue colonoscopy (p < 0.001). CONCLUSIONS: Within this comprehensive statewide registry, clinical findings during colonoscopy varied by indication and increased with age. Overall rates of finding advanced polyps and colorectal cancer are low. Older adults are frequently recommended to continue colonoscopy despite advanced age and insignificant clinical findings on current examination. These data inform the potential benefits of ongoing colonoscopy, which must be weighed with the low but known potential immediate and long-term harms of colonoscopy, including cost, psychological distress, and long lag time to benefit exceeding life expectancy.

Effect of Autologous Platelet-Rich Plasma Drops in the Treatment of Ocular Surface Disease.

Purpose: Platelet rich plasma (PRP) is an autologous preparation that concentrates platelets in a small volume of plasma. The purpose of this study was to determine if PRP eye drops improved the symptoms and signs of ocular surface disease. Patients and Methods: A retrospective case series was conducted of patients who were prescribed PRP eye drops. Subjects were excluded if they did not have follow-up, underwent intraocular surgery prior to follow-up, received nerve growth factor treatments, or did not have a baseline examination with photography. Symptoms were assessed using the Ocular Surface Disease Index (OSDI). Patients also underwent a slit lamp exam, ocular surface staining with fluorescein and lissamine green, and Schirmer testing. Results: The charts of 47 patients treated with PRP drops for ocular surface disease were reviewed. Sixty-four eyes of 32 patients were included in the study who had photographs of lissamine green staining taken at baseline and at follow-up. Thirteen patients (28%) had ocular graft-versus-host disease, 16 patients (34%) had Sjögren's syndrome, and 4 patients (8.5%) had rheumatoid arthritis. There was a statistically significant decrease in OSDI score from baseline to follow-up (39.5 vs 30.8 points, p = 0.02). Among the 64 eyes included, 9 (14%) had an improvement in conjunctival lissamine green staining, while 6 (9%) had an increase in staining at follow-up. Among the 20 eyes with Schirmer testing, there was a borderline significant increase in score from baseline to follow-up (5.9 vs 9.7, p = 0.06). Among the 44 eyes that had corneal fluorescein staining (CFS) reported, 8 (18.2%) had decreased staining and 2 (4.5%) had increased staining at follow-up. Conclusion: Treatment with PRP drops was associated with a significant improvement in symptoms in patients with ocular surface disease. Future larger prospective studies are needed to further evaluate the efficacy of PRP drops for treating ocular surface disease.

Outcomes of Resident Performed Hydrus, iStent, and Kahook Glaucoma Procedures in a Predominantly African American Population.

PRCIS: This retrospective study characterized the efficacy and safety of 3 different microinvasive glaucoma surgery (MIGS) procedures in a predominantly African American population at the Philadelphia Veterans Affairs Hospital (Hydrus, Kahook, iStent), demonstrating no significant difference in intraocular pressure (IOP) and medication reduction between the 3 at long-term follow-up. PURPOSE: To compare the efficacy and safety of 3 different MIGS procedures in a predominantly African American population. METHODS: Retrospective cohort study of patients undergoing cataract extraction combined with 1 of 3 MIGS procedures (Hydrus, iStent, Kahook) at the Philadelphia Veterans Affairs Medical Center between January 1, 2015 and November 1, 2020. Analysis of variance and regression models were used to compare reduction in IOP and medication use among 3 MIGS types. RESULTS: A total of 123 eyes of 112 patients were included, including 56 (45.5%) eyes for Hydrus, 40 (32.5%) eyes for iStent, and 27 (22.0%) eyes for Kahook. Adjusted mean IOP reduction was greater for Hydrus at postoperative day 1 (-4.49 vs. -1.76 for iStent and -1.69 for Kahook, P=0.05 and greater for Kahook at postoperative week 1 (-2.53 vs. +0.70 for iStent vs. -1.41 for Hydrus, P=0.02), but did not differ significantly between MIGS types at subsequent postoperative visits (all P>0.05). In multivariable analysis, MIGS type was not significantly associated with reduction in IOP or medication use at 9 to 12 months postoperatively. There were no significant differences in complication rates across MIGS types. CONCLUSION: In this study, the difference in IOP lowering and medication reduction postoperatively between the Hydrus, iStent, and Kahook was not statistically significant after postoperative day 1. More studies are needed to evaluate outcomes of MIGS surgeries in glaucoma populations of different disease severity.

Association of metformin and development of dry age-related macular degeneration in a U.S. insurance claims database.

PURPOSE: To assess whether metformin is associated with dry age-related macular degeneration (dAMD) development. METHODS: In this retrospective cohort study, patients enrolled in a nationwide U.S. medical insurance claims database from 2002 to 2016 were included if they had diabetes mellitus, were ⩾55 years old, and were enrolled for ⩾2 years without a prior AMD diagnosis. The primary exposure was metformin use analyzed as either active or prior use or cumulative metformin dosage over the study period. A time updating Cox proportional hazard regression was used to estimate the hazard ratio of dAMD incidence with metformin exposure. RESULTS: Among 1,007,226 diabetic enrollees, 53.3% were female and 66.4% were white with a mean hemoglobin A1c of 6.8%. Of eligible enrollees, 166,115 (16.5%) were taking metformin at the index date. Over the study period, 29,818 (3.0%) participants developed dAMD. In the active versus prior use of metformin model, active use conferred an increased hazard of developing dAMD (HR, 1.08; 95% CI, 1.04-1.12) while prior use had a decreased hazard (HR, 0.95; 95% CI 0.92-0.98). The cumulative metformin dosage model showed a significant trend toward increased hazard of dAMD incidence with increasing cumulative dosage (p < 0.001), with the lowest dosage quartile having decreased hazard of dAMD incidence (HR, 0.95; 95% CI, 0.91-0.99) and the highest having increased hazard (HR, 1.07; 95% CI, 1.01-1.13). CONCLUSIONS: Small, conflicting associations between metformin exposure and development of dAMD were observed depending on cumulative dosage and whether drug use was active, suggesting metformin did not substantially affect the development of dAMD.

Self-identified Black Race as a Risk Factor for Intraocular Pressure Elevation and Iritis Following Prophylactic Laser Peripheral Iridotomy.

PRCIS: In primary angle closure suspects (PACS), self-identified Black race was a risk factor for intraocular pressure (IOP) elevation and iritis following laser peripheral iridotomy (LPI). Laser type was not associated with either immediate post-LPI IOP elevation or iritis in multivariate analysis. PURPOSE: The aim was to determine the impact of laser type and patient characteristics on the incidence of IOP elevation and iritis after LPI in PACS. MATERIALS AND METHODS: The electronic medical records of 1485 PACS (2407 eyes) who underwent either neodymium-doped yttrium-aluminum-garnet or sequential argon and neodymium-doped yttrium-aluminum-garnet LPI at the University of Pennsylvania between 2010 and 2018 were retrospectively reviewed. Average IOP within 30 days before LPI (baseline IOP), post-LPI IOP within 1 hour, laser type, laser energy, and the incidence of new iritis within 30 days following the procedure were collected. Multivariate logistic regression accounting for intereye correlation was used to assess factors associated with incidence of post-LPI IOP elevation and iritis, adjusted by age, sex, surgeon, and histories of autoimmune disease, diabetes, and hypertension. RESULTS: The incidence of post-LPI IOP elevation and iritis were 9.3% (95% confidence interval: 8.1%-10.5%) and 2.6% (95% CI: 1.9%-3.2%), respectively. In multivariate analysis, self-identified Black race was a risk factor for both IOP elevation [odds ratio (OR): 2.08 compared with White; P=0.002] and iritis (OR: 5.07; P<0.001). Higher baseline IOP was associated with increased risk for post-LPI IOP elevation (OR: 1.19; P<0.001). Laser type and energy were not associated with either post-LPI IOP elevation or iritis (P>0.11 for all). CONCLUSIONS: The incidence of immediate IOP elevation and iritis following prophylactic LPI was higher in Black patients independent of laser type and energy. Heightened vigilance and increased medication management before and after the procedure are suggested to help mitigate these risks.

Predominantly Persistent Intraretinal Fluid in the Comparison of Age-related Macular Degeneration Treatments Trials.

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. MAIN OUTCOME MEASURES: Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year 2. RESULTS: Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P = 0.002), and was 65.0 and 67.4, respectively (P = 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P = 0.006) and change (4.3 vs. 8.1; P = 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P = 0.004) and changes (2.4 vs. 7.1; P = 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio = 1.49; P = 0.03). CONCLUSIONS: Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.

Appendectomy Should Be Performed During Minimally Invasive Surgery for Endometriosis.

OBJECTIVES: To determine the prevalence of appendiceal histopathology in patients with confirmed endometriosis following minimally invasive surgery (MIS) for endometriosis. To determine whether pre-operative symptoms, age, intra-operative appendiceal appearance, or endometrioma laterality were associated with appendix histopathology in patients with suspected endometriosis. METHODS: One hundred thirty-five patients ages 16-52 with suspected endometriosis undergoing MIS for endometriosis with concomitant appendectomy at two metropolitan academic hospitals from January 1, 2012 to June 30, 2017 were included in this retrospective chart-review study. Medical records were reviewed for pre-operative symptoms, age, intraoperative appendix appearance, appendix histopathology, histopathologically-confirmed endometriosis, and endometriomas. RESULTS: In patients with confirmed endometriosis, the prevalence of all appendiceal histopathology was 25%, which included appendiceal endometriosis (18%), appendiceal tumors (2%), and inflammation (5%). Dyspareunia was the only pre-operative symptom significantly associated with appendiceal histopathology (p = 0.04). The presence of a right endometrioma was associated with appendiceal histopathology (p = 0.009). Additionally, appendiceal histopathology was not significantly associated with age nor intra-operative appendiceal characteristics. CONCLUSION: This manuscript adds to the limited pool of studies regarding appendiceal histopathology and appendiceal tumors in patients with suspected and confirmed endometriosis. On the basis of the high rate of histopathological appendices found in this population; the lack of association with possible diagnostic factors such as age, most pre-operative symptoms, and intra-operative appendiceal characteristics; and the relatively low risks of concomitant appendectomy, we suggest that surgeons consider concomitant appendectomies at the time of MIS for endometriosis.

Efficacy of an Intranasal Tear Neurostimulator in Sjögren Syndrome Patients.

PURPOSE: To assess the efficacy and safety of an intranasal tear neurostimulator (ITN) device in Sjögren syndrome (SS) patients. METHODS: This was a two-visit prospective, randomized, controlled, same-day crossover study in participants with SS. Inclusion criteria were assessed at a baseline screening visit and included an Ocular Surface Disease Index (OSDI) score ≥13, and a Schirmer with anesthesia ≤10 mm/5 min (in at least one eye), with a cotton swab stimulation induced increase of ≥4 mm in the same eye. Participants returned for the application visit, where they received intranasal and extranasal applications of the ITN in random sequence, separated by at least 60 min. Schirmer scores were measured in both eyes after each application and compared to baseline values. Generalized linear models were performed to compare the change in Schirmer scores from baseline, and generalized estimating equations were used to account for correlations from repeated measurements in the same eye and measurements from two eyes of the same patient. RESULTS: Fifty-five participants were screened and 35 were enrolled (all female), ranging in age from 31 to 72 years (mean, 57 years). The baseline OSDI score ranged from 14 to 91 (mean, 50.5), and the baseline Schirmer score had a mean (SD) of 6.4 (3.5) ranging from 0 to 20 (mm/5min). Improvement in Schirmer scores was significantly greater for intranasal device application (13.5 mm/5min, 95% CI: 10.4, 16.5) compared to extranasal device application (0.8mm/5min, 95% CI: -0.9, 2.4) (p<0.0001). The effects of the intranasal device application were significant regardless of the participant's baseline Schirmer score and systemic SS medication usage (p<0.05). CONCLUSION: Intranasal application of the ITN device significantly increased tear production in a subset of SS patients compared to baseline and was more effective than extranasal application. While production of the ITN device was recently discontinued, our findings suggest that other therapies that neurostimulate the lacrimal function unit may be effective in a subset of SS patients.

Predominantly Persistent Subretinal Fluid in the Comparison of Age-Related Macular Degeneration Treatments Trials.

OBJECTIVE: To describe predominantly persistent subretinal fluid (SRF) in eyes receiving ranibizumab or bevacizumab for neovascular age-related macular degeneration and to compare visual acuity (VA) to eyes with nonpersistent SRF. DESIGN: Cohort within randomized clinical trial. PARTICIPANTS: Comparison of Age-related Macular Degeneration Treatments Trials patients assigned to pro re nata treatment. METHODS: Graders evaluated monthly OCT scans for SRF. Predominantly persistent SRF through week 12 was defined as SRF at baseline and weeks 4, 8, and 12. Predominantly persistent SRF through 1 or 2 years was defined as SRF in 80% or more of visits by years 1 or 2, respectively. Linear regression models including baseline predictors of VA and predominantly persistent intraretinal fluid (IRF) were used to evaluate mean differences in vision outcomes. PRIMARY OUTCOME MEASURES: Predominantly persistent SRF through year 1, adjusted VA score and VA change, and foveal SRF thickness. RESULTS: Among 406 eyes with baseline SRF, SRF persisted in 108 eyes (26.6%) through week 12, in 94 eyes (23.2%) through year 1, and in 77 eyes (19.0%) through year 2. Adjusted VA means at year 1 were similar between eyes with predominantly persistent versus non persistent SRF by week 12 (68.1 vs. 70.2 letters; P = 0.18), year 1 (67.6 vs. 70.2 letters; P = 0.11), and year 2 (71.4 vs. 70.9 letters; P = 0.78). Adjusted changes in mean VA at year 1 were similar between eyes with predominantly persistent versus nonpersistent SRF by week 12 (6.3 vs. 7.6 letters; P = 0.38), year 1 (5.5 vs. 7.8 letters; P = 0.14), and year 2 (8.1 vs. 7.7 letters; P = 0.78). Among eyes with predominantly persistent SRF through year 1, foveal SRF was absent in 46 eyes (48.9%), thickness was 1 to 200 µm in 48 eyes (50.0%) and more than 200 µm in 1 eye (1.1%) at year 1. CONCLUSIONS: Eyes with predominantly persistent and nonpersistent SRF through week 12, year 1, or year 2 showed similar VA outcomes after adjustment for baseline covariates and persistent IRF. At the foveal center, predominantly persistent SRF was most commonly absent or present in small quantities.