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ImportanceThe association of proliferative diabetic retinopathy (PDR) interventions of panretinal photocoagulation (PRP) and intravitreal injections (IVIs) with tractional retinal detachment (TRD) is unclear.ObjectivesTo determine whether different treatment types or a 6-month or longer period of loss to follow-up (LTFU) is associated with TRD.Design, Setting, and ParticipantsThis nested case-control study included data from January 1, 2000, to June 30, 2021, of patients with PDR. Those who progressed to TRD were matched to non-TRD controls up to a 5:1 ratio. Exclusion criteria included 2 or fewer years in the plan, history of nondiabetic retinopathy, vitreous hemorrhage, previous RD, or any other surgically indicated diagnosis. Patient data were obtained from a deidentified commercial and Medicare Advantage medical claims database. Statistical analysis was performed from January to May 2022.ExposuresPrimary exposures of interest were prior treatment (PRP, IVI, both) and any period of 6 months or longer in which the patient received no eye care.Main Outcomes and MeasuresOdds ratios (ORs) of IVI only compared with PRP and 6-month or longer LTFU on development of TRD.ResultsAfter application of inclusion and exclusion criteria, a total of 214 patients (mean [SD] age, 55.6 [12.4] years; 115 female [53.7%]) with PDR and TRD were matched to 978 controls (mean [SD] age, 65.6 [11.3] years; 507 female [51.8%]) with only PDR. Among patients with TRD, 69 (32.2%) were treated with laser only, 17 (7.9%) were treated with injection only, 39 (18.2%) were treated with both, and 89 (41.6%) had no prior treatment. Among patients in the PDR-only group, 207 (21.2%) received laser only, 83 (8.5%) received injection only, 57 (5.8%) received both, and 631 (64.5%) received no treatment. After adjusted analysis, no difference in odds of TRD for patients who received injection only compared with patients who received laser only was found (adjusted OR [aOR], 0.56; 95% CI, 0.27-1.14). Patients who received both treatments had higher odds of TRD compared with those who received laser only (aOR, 2.33; 95% CI, 1.21-4.48), and patients who had no treatment had lower odds of TRD (aOR, 0.46; 95% CI, 0.29-0.71; P P = .11).Conclusions and RelevanceResults of this case-control analysis suggest that there is no increased risk of TRD associated with IVI-only treatment or with 6-month or longer periods of LTFU, which supports the findings of other investigations. Nonetheless, LTFU rates continue to remain high in patients with PDR, which can contribute to substantial vision loss regardless of treatment regimen.

Manzar Ashtari,1– 3 Mikhail Lipin,1,2 Michelle Duong,4 Gui-Shuang Ying,5 Yinxi Yu,5 Albert Maguire,1,2 Jean Bennett1,2 1Department of Ophthalmology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 2Department of Ophthalmology, Center for Advanced Retinal & Ocular Therapeutics (CAROT) at the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 3Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 4Emergency Department, Mainline Health, Bryn Mawr, PA, USA; 5Department of Ophthalmology, Center for Preventative Ophthalmology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USACorrespondence: Manzar Ashtari, University of Pennsylvania, Perelman School of Medicine, Room 201 Anatomy/Chemistry Building, Philadelphia, PA, 19102, USA, Tel +1 215– 746-8259, Email ashtari@pennmedicine.upenn.eduIntroduction: Previous works on experience-dependent brain plasticity have been limited to the cortical structures, overlooking subcortical visual structures such as the lateral geniculate nucleus (LGN). Animal studies have shown substantial experience dependent plasticity and using fMRI, human studies have demonstrated similar properties in patients with cataract surgery. However, in neither animal nor human studies LGN has not been directly assessed, mainly due to its small size, tissue heterogeneity, low contrast/noise ratio, and low spatial resolution.Methods: Utilizing a new algorithm that markedly improves the LGN visibility, LGN was evaluated in a group of low vision patients before and after retinal intervention to reinstate vision and normal sighted matched controls.Results: Between and within groups comparisons showed that patients had significantly smaller left (p< 0.0001) and right (p < 0.00002) LGN volumes at baseline as compared to the one-year follow-up volumes. The same baseline and one year comparison in controls was not significant. Significant positive correlations were observed between the incremental volume increase after gene therapy of the left LGN and the incremental increase in the right (r = 0.71, p < 0.02) and left (r = 0.72, p = 0.018) visual fields. Incremental volume increase of the right LGN also showed a similar positive slope but did not reach significance.Discussion: These results show that despite significantly less volume at baseline, retinal gene therapy promotes robust expansion and increase in LGN volume. Reinstating vision may have facilitated the establishment of new connections between the retina and the LGN and/or unmasking of the dormant connections. The exact trajectory of the structural changes taking place in LGN is unclear but our data shows that even after years of low vision, the LGN in RPE65 patients has the potential for plasticity and expansion to a nearly normal volume one year after gene therapy administration.Keywords: brain plasticity, retinal gene therapy, lateral geniculate nucleus, image processing, brain morphometry

To evaluate the effect of postoperative topical prednisolone acetate and difluprednate on surgical outcomes of Ahmed glaucoma valve (AGV) implantation.Retrospective, comparative case series.The study population consisted of 102 eyes of 90 patients, including 52 eyes that received 1% prednisolone acetate (Pred Forte [PF]; Allergan Inc) and 50 eyes that received 0.05% difluprednate (Durezol [DZ]; Novartis Inc).The medical records of consecutive patients who underwent AGV implantation at the University of California, San Francisco, were retrospectively reviewed. Patients in the PF group received 1% prednisolone acetate 6 to 8 times per day tapered over 5 to 6 months postoperatively, and patients in the DZ group received 0.05% difluprednate 4 times daily tapered over 4 months postoperatively.Intraocular pressure (IOP), number of glaucoma medications, visual acuity (VA), postoperative complications, and the rate of treatment success.At 1 year, the IOPs (mean ± standard deviation) were 12.4 ± 3.7 mmHg in the DZ group and 13.0 ± 4.0 mmHg in the PF group (P = 0.49). The numbers of glaucoma medications were 0.72 ± 0.71 in the DZ group and 1.09 ± 0.91 in the PF group (P = 0.04), with reductions from baseline of 2.5 ± 1.0 glaucoma medications in the DZ group and 1.8 ± 1.6 glaucoma medications in the PF group (P = 0.01). The logarithm of the minimum angle of resolution VAs (mean ± standard deviation) were 0.55 ± 0.80 in the DZ group and 0.59 ± 0.65 in the PF group after 1 year of follow-up (P = 0.81). The cumulative probabilities of success were 95.8% in the DZ group and 93.5% in the PF group at 1 year (P = 0.61). Postoperative complications occurred in 4 eyes (7.7%) in the DZ group and 6 eyes (12%) in the PF group (P = 0.52).After 1 year, postoperative treatment with 0.05% difluprednate after AGV implantation resulted in a similar IOP, with the use of fewer glaucoma medications, compared with postoperative treatment with 1% prednisolone acetate. The rates of treatment success and surgical complications were comparable between the 2 groups during the first year of follow-up.

To determine the associations of presence and types of cardiovascular diseases (CVDs) with development of retinopathy of prematurity (ROP) in premature infants undergoing ROP examinations.We performed secondary analyses of data from the multi-center Postnatal Growth and ROP Validation Study (GROP-2). CVD was categorized based on pulmonary blood flow (PBF), systemic blood flow (SBF), pulmonary hypertension (PPHN), or dysrhythmia. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated from multivariable logistic regression models that included any ROP or severe ROP as outcome variable and any CVD or type of CVD as independent variable, with adjustment of covariates including birth weight (BW), gestational age (GA), and days on supplemental oxygen in the first month of postnatal life.Among 3980 infants, 528 (13.3%) had CVD (304 had increased PBF, 101 had decreased PBF, and 49 had PPHN), 1643 (40.4%) developed ROP, and 503 (12.6%) developed severe ROP. In multivariable analyses, presence of CVD was not significantly associated with increased risk of any ROP (aOR = 1.15, 95% CI: 0.90-1.46,CVD with increased PBF likely increases the risk of ROP. PPHN likely increases the risk of severe ROP.

To assess systemic associations of angioid streaks (AS) using a large US healthcare database.A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV).One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p 0.001), connective tissue disease (1.0% vs 0.3%, p 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis.In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation.

PURPOSE: This study aims to assess the effect of statins on progression from non-proliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). METHODS: Two cohort studies using a US medical claims database from 2002–2019 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 non-statin users. Of these, 27,325(18.2%) progressed to VTDR, 4,086(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.

Purpose To evaluate the diagnostic performance of swept-source anterior segment optical coherence tomography (SS-OCT) in differentiating eyes with primary angle closure disease (PACD) from eyes of control subjects, as well as eyes with PAC and PAC glaucoma (PACG) from eyes with PAC suspect (PACS) disease. Design Multicenter cross-sectional study. Methods Chinese patients were classified into control, PACS, and PAC/PACG groups. The area under the receiving operating characteristic curve (AUC) from logistic regression models was used to evaluate discriminating ability. Sensitivity and specificity were calculated, and performance of the models was validated using an independent dataset. Results A total of 2928 SS-OCT images from 366 eyes of 260 patients were recruited to develop diagnostic models. The validation dataset included 1176 SS-OCT images from 147 eyes of 143 patients. For distinguishing PACD from control eyes, average anterior chamber depth had the highest AUC (0.94). With a cutoff of 2.2 mm for average anterior chamber depth, the sensitivity and specificity were 90.2% and 85.2% in the training set. For distinguishing PAC/PACG from PACS, a multivariate model had an AUC of 0.83, with sensitivity and specificity of 82.0% and 62.8% in the training set. The validation set confirmed the findings. Conclusions SS-OCT of the anterior segment showed excellent diagnostic performance distinguishing PACD from normal eyes and moderate diagnostic ability distinguishing eyes with PAC/PACG from eyes with PACS. ACD alone may provide a simple and effective way to diagnose PACD from control subjects. As ACD can be obtained using other more available modalities, this has implications for the early diagnosis of PACD.

Marcus L Turner,1 Abu M Taha,1 Sean Yonamine,1 Yinxi Yu,2 Murtaza Saifee,1 Mike Yang,3 Gui-Shuang Ying,2 Ying Han,1 Julius T Oatts1 1Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA; 2Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 3Prism Eye Institute, Oakville, ON, CanadaCorrespondence: Julius T Oatts, Department of Ophthalmology, University of California, San Francisco, 490 Illinois Street, San Francisco, CA, 94158, USA, Tel +1 415 353 2800, Fax +1 415 353 2468, Email julius.oatts@ucsf.eduPurpose: To determine the change in Humphrey visual field and clinical parameters after minimally invasive glaucoma surgery combined with cataract surgery.Patients and Methods: Patients undergoing minimally invasive glaucoma surgery combined with cataract surgery in a multicenter retrospective case series between 2013 and 2021 with reliable preoperative and 12 to 18 month postoperative visual field measurements were included. Devices included iStent, XEN, and Hydrus. Clinical parameters were compared with a generalized linear model with generalized estimating equations between preoperative and postoperative visits including best corrected visual acuity, intraocular pressure, number of glaucoma medications and visual fields. Visual field metrics included mean deviation (MD), pattern standard deviation (PSD), visual field index (VFI), and Collaborative Initial Glaucoma Treatment Study (CIGTS) score of total deviation probability and pattern deviation probability.Results: Forty-four eyes from 39 patients were included. During the follow up period, visual acuity improved from 0.23± 0.17 to 0.10± 0.14 logMAR (mean ± standard deviation, p< 0.001), number of glaucoma medications was reduced from 2.68± 1.06 to 1.46± 1.32 (p< 0.001), and intraocular pressure decreased from 17.08± 4.23 mmHg to 14.92± 3.13 mmHg (p=0.003). Differences across devices were negligible. The only significant difference was a greater reduction in number of glaucoma medications in the XEN group (p< 0.001). There were no significant changes in the global parameters of VFI, MD, PSD, or CIGTS.Conclusion: Overall, minimally invasive glaucoma surgery combined with cataract surgery appears to be effective at stabilizing visual field function, reducing intraocular pressure, reducing number of glaucoma medications, and improving visual acuity over a 12 to 18 month follow-up period across MIGS devices.Keywords: glaucoma, MIGS, visual field, cataract

Author(s): Sutphin, John E; Ying, Gui-Shuang; Bunya, Vatinee Y; Yu, Yinxi; Lin, Meng C; McWilliams, Kathleen; Schmucker, Elizabeth; Kuklinski, Eric J; Asbell, Penny A; Maguire, Maureen G; Dry Eye Assessment and Management (DREAM) Study Research Group | Abstract: PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (rs); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation rs = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (rs = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (rs = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (rs from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

PURPOSE: To determine if metformin is associated with non-infectious uveitis (NIU). METHODS: Patients in an insurance claims database who initiated metformin (n=359,139) or other oral anti-diabetic medications (n=162,847) were followed for NIU development. Both cohort and case-control analyses were performed to assess differing exposure lengths using Cox and conditional logistic regression, respectively. RESULTS: The hazard ratio (HR) for incident NIU was not significantly different between the metformin and non-metformin cohorts [HR=1.19, 95% Confidence Interval (CI): 0.92-1.54, P=0.19]. The case-control analysis similarly showed no association between any metformin use 2 years before the outcome date and NIU [Odds ratio (OR)=0.64, 95% CI: 0.39-1.04, P=0.07]. However, there was a protective association between cumulative metformin duration [445-729 days adjusted OR (aOR)=0.49, 95% CI: 0.27-0.90, P=0.02) and dosage (>390,000 mg aOR=0.44, 95% CI: 0.25-0.78, P=0.001] compared with no metformin use. CONCLUSIONS: Our results suggest metformin use for longer durations may be protective of NIU onset.

Purpose To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED). Methods This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine). Results The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)]. Conclusions Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.

Purpose To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis. Design Retrospective cohort study. Participants Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan. Methods Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed. Main Outcome Measures Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code. Results There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83–1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04–1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05–1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03–1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20). Conclusions Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.

PURPOSE: To quantify the association between visit adherence and visual acuity (VA) in diabetic macular edema (DME). METHODS: This secondary analysis of the 2-year DRCRnet Protocol T study of 656 patients required one visit every 4 weeks in the first year, then at variable 4-16 week intervals in the second year. Visit adherence measured as: number of missed visits, average (avg days) and longest (max days) visit interval, average (avg missed days) and longest (max missed days) unintended visit interval, and visit constancy (percentage of 3-month periods with at least 1 visit). Avg and max missed days were categorized as on time(0 days), late(>0-60 days), and very late(>60 days). Primary outcome was change in ETDRS VA between baseline study visit and last attended visit, using multivariate linear regression models controlling for age, gender, race, ethnicity, treatment arm, baseline VA, hemoglobin A1c, insulin use and number of lasers and injections. RESULTS: Mean number of missed visits was 1.7. 616(94%) patients had 100% visit constancy. 331(51%) patients were on time, 171(26%) late, and 154(23%) very late in avg missed days. Max missed days ranged 0-696 days. Adjusted, each missed visit was associated with 0.3 letter decrease(95%CI: −0.6, −0.1, p=0.02); being very late in avg and max missed days saw −4.2 letters(95%CI: −6.4, −2.0, p4 days missed per attended visit saw 4.6 letters worse(95%CI:−7.3, −2.0, p

To determine the change in global and regional Humphrey visual fields (VF) after glaucoma drainage device (GDD) implantation over a 3-year follow-up period.Retrospective interventional case series.Patients undergoing GDD placement from between 2010 and 2015 with reliable preoperative and yearly postoperative VF measurements were included. Clinical parameters were compared between preoperative and follow-up visits, including visual acuity, intraocular pressure (IOP), number of glaucoma medications, global VF metrics (mean deviation [MD]), pattern standard deviation (PSD), CIGTS (Collaborative Initial Glaucoma Treatment Study) score of total deviation probability (CIGTS_TDP) and pattern deviation probability (CIGTS_PDP), and regional metrics (regional total deviation (TD), regional pattern deviation (PD), and regional CIGTS_TDP and CIGTS_PDP). Multivariate regression analyses were performed to determine risk factors for VF worsening after GDD surgery.A total of 106 eyes from 95 patients were included. Mean IOP ± SD was reduced from 23.1 ± 8.5 mm Hg to 12.7 ± 3.1 mm Hg at 3-year follow-up (P.001). MD, PSD, and global CIGTS_PDP showed no significant changes in follow-up, whereas global CIGTS_TDP showed mild progression from 10.7 to 12.8 at 3-year follow-up (P = .01). No regional metrics showed worsening at follow-up examinations. Defects in the superior hemifield were more common than in the inferior hemifield at baseline and follow-up examinations for all regional metrics. Pre-operative number of glaucoma medications was associated with worsening on CIGTS_TDP.Overall, GDD surgery is effective at stabilizing VF function over 3 years of follow-up. The superior hemifield is affected more than other regions. The number of pre-operative glaucoma medications is associated with mild VF progression, measured by CIGTS_TDP.

PURPOSE: To determine how kidney function identified by diagnosis codes compares to lab results-based kidney function for predicting risk of vision threatening diabetic retinopathy(VTDR). METHODS: A US medical claims database was used for this retrospective observational study. Adult patients enrolled from January 1, 2002 to December 31, 2016 with nonproliferative diabetic retinopathy(NPDR) were followed. Patients were excluded if they had any previous diagnosis or treatment of VTDR or VTDR diagnosed within 2 years of insurance plan entry. ICD9/10 Chronic kidney disease(CKD) diagnoses from outpatient claims were used to classify kidney disease with or without end stage renal disease(ESRD). Serum creatinine was used to calculate estimated glomerular filtration rates(eGFR). Multivariate Cox models with time-dependent covariates were used to assess the associations of kidney disease diagnosis and eGFR with progression to VTDR, controlling for demographics and time-dependent covariates(systemic health, laboratory results, insulin use). C-statistic(a measure of model discrimination), hazard ratio(HR) and their 95% confidence intervals(CI) were calculated from multivariate Cox models. RESULTS: Among 69,982 patients with NPDR, 12,770(18.2%) developed VTDR. C-statistic was identical(0.60, 95% CI: 0.59–0.60) for the multivariate model with eGFR and for the multivariate model with kidney diagnosis codes. eGFRs lower than 30mL/min/1.73m(2)(HR>1.14, p

To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study.Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines).No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (-36.6 vs. 24.5%, P =0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P =0.02, n=68); at 12 months, they did not differ ( P ≥0.18). No other differences between the treatment groups were detected.ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

To determine the characteristics of children diagnosed with glaucoma suspect (GS) status, their clinical outcomes, and risk factors for progression to a diagnosis of glaucoma.This was a retrospective sequential cohort study of children18 years diagnosed as GS between 2013 and 2019, based on clinical (C-GS) and CGRN (CGRN-GS) criteria. Children with penetrating ocular trauma, steroid-response, treated ocular hypertension, and glaucoma at presentation were excluded. Outcomes included glaucoma, treated ocular hypertension, nonglaucomatous cupping (pseudoglaucomatous or physiologic), or persistent GS. Secondary outcomes were characteristics of children who progressed to glaucoma.A total of 887 children (mean age, 9.3 ± 4.7 years) were diagnosed as C-GS, because of optic nerve appearance (83%), family history (25%), ocular hypertension (15%), periocular lesion (4% [eg, Sturge-Weber]), blunt-trauma history (3%), ocular anomaly (2%), and systemic/genetic syndrome (1.5%). Outcomes among 487 children with one or more follow-up visits (mean, 1.7 ± 1.6 years) included 14 (3%) with glaucoma, 98 (20%) with physiologic cupping, 50 (10%) with prematurity-associated cupping, and 1 (0.2%) with treated ocular hypertension; 324 (67%) remained GS. Of children lost to follow-up, 116 (29%) were suspected physiologic or pseudoglaucomatous. Glaucoma diagnosis occurred at a mean age of 8.4 ± 5.5 years, based on elevated intraocular pressure (IOP; 79%), optical coherence tomography changes (43%), disk changes (21%), or field defects (14%). Risk factors for glaucoma were baseline IOP of ≥24 (P = 0.01) and periocular lesion (P = 0.008). Results from 773 children who met CGRN-GS criteria were similar.Risk of conversion to glaucoma diagnosis among children with glaucoma suspect status appears low. Baseline cup:disk ratio and family history of glaucoma were not predictive of glaucoma diagnosis. Baseline IOP24 and presence of a periocular lesion carry higher risk.

Background/aimsTo compare dry eye disease (DED) signs and symptoms between men and women, as well as between premenopausal and postmenopausal women, in the Dry Eye Assessment and Management (DREAM) study.Methods434 women and 101 men self-reported prior medical history and underwent a standardised DED assessment using the Ocular Surface Disease Index, Brief Pain Inventory, Tear Break-Up Time (TBUT)(s), Schirmer’s test 2 (mm/5 min), National Eye Institute-graded lissamine conjunctival staining, corneal staining, meibomian gland dysfunction evaluation and tear osmolarity (mOsms/L) at baseline, 6 months and 12 months. Multivariable linear regression models were used to compare these scores.ResultsWomen experienced significantly worse DED signs than men with lower Schirmer’s test scores (9.27 vs 12.16; pConclusionIn the DREAM study, women experienced more severe DED signs than men. Further, postmenopausal women presented with more severe DED signs than premenopausal women. Elucidating these differences may improve DED diagnosis and provide future direction in understanding sex-related differences in DED.Trial registration numberNCT02128763.

Anterior chamber depth (ACD) change after pupillary dilation is correlated with lens vault (LV) and anterior chamber width (ACW), as observed by swept-source optical coherence tomography (SS-OCT) at both horizontal and vertical scans in patients with primary angle closure suspect and cataract.The purpose of this study is to evaluate the association between ACD and other anterior chamber parameters after pharmacological dilation in patients with primary angle closure suspect and cataract.SS-OCT was performed for 78 patients at baseline and 1 hour after pharmacological dilation. Measurements were taken at 8 evenly spaced axes at 250, 500, and 750 μm from the scleral spur. Pearson correlation coefficient (ρ) was used to evaluate the relationship between averaged ACD change and other SS-OCT parameters. Multivariable regression analyses were performed to determine the parameters that predict ACD change.Across all 14 dimension and angle parameters, 12 parameters at the 270-degree axis and 10 parameters at the 0-degree axis yielded significant correlations with ACD change (ρ=0.24-0.55, P0.05). Angle parameters were most significantly correlated to ACD change 750 µm from the scleral spur. The prediction model for ACD change after pharmacological dilation at 0 degree included decreased LV, wider ACW, and increased trabecular iris space area (all P ≤0.001). The prediction model for ACD change at 270 degrees included: decreased LV, wider ACW, larger change in anterior chamber volume, larger baseline anterior chamber volume, and smaller baseline angle opening distance (all P ≤0.03).LV and ACW, as measured in both vertical and horizontal scans, were found to be determinants of the ACD change after pharmacological pupillary dilation. Examination of these parameters may help identify patients at higher risk of developing angle-closure disease.

Background/AimsA series at a single clinical centre recently demonstrated an association between the interstitial cystitis drug pentosan polysulfate sodium (PPS) and a vision-threatening pigmentary maculopathy. The aim of this study was to determine if an association exists between PPS use and macular disease in a large national cohort.MethodsA retrospective, matched cohort study using data from a large US medical claims database from 2002 to 2016 was performed. A total of 3012 and 1604 PPS users were compared with 15 060 and 8017 matched controls at 5 and 7 years, respectively. The primary outcome measures included (1) any new diagnosis of a hereditary or secondary pigmentary maculopathy (atypical maculopathy outcome), and (2) any new diagnosis of dry age-related macular degeneration (AMD) or drusen in addition to the aforementioned diagnoses (atypical maculopathy+AMD outcome).ResultsAt the 5-year and 7-year follow-up, 9 (0.3%) and 10 (0.6%) PPS patients progressed to the atypical maculopathy outcome compared with 32 (0.2%) and 25 (0.3%) control patients, respectively. 103 (3.4%) and 87 (5.4%) PPS patients developed the atypical maculopathy+AMD outcome compared with 440 (2.9%) and 328 (4.1%) control patients at 5 and 7 years, respectively. At 5 years, multivariate analysis showed no significant association (p>0.13). At 7 years, PPS users had significantly increased odds of having the atypical maculopathy+AMD outcome (OR=1.41, 95% CI 1.09 to 1.83, p=0.009).ConclusionsPPS exposure was associated with a new diagnosis of macular disease at the 7-year follow-up in a large national cohort.

BACKGROUND/AIMS: To determine if anaemia and oxygen delivery-related co-morbidities (ODCs) affect progression from non-proliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR). METHODS: This is a retrospective cohort study using medical claims data from a large US insurer. Cohorts were created from all NPDR patients between 2002 and 2016. Primary exclusion criteria consisted of any previous diagnosis of proliferative diabetic retinopathy (PDR), diabetic macular oedema (DME) or treatment used in the care of VTDR. The main outcome was a new diagnosis of VTDR (DME or PDR), PDR, or DME. A time-dependent, multivariate Cox proportional hazard regression was used to determine the association between anaemia and other ODCs with NPDR progression. RESULTS: Of the total 69,982 NPDR patients included for analysis, 12,270, 2,162, and 10,322 progressed to VTDR, PDR and DME, respectively. Both mild and moderate/severe (mod/sev) anaemia were associated with an increased hazard for progression to VTDR (mild HR:1.10, 95% CI:1.04–1.16, p 1.00, p

To determine whether sterile preloading of anti-vascular endothelial growth factor agents reduces the risk of postintravitreal injection endophthalmitis.This is a retrospective cohort study using medical claims data from a large, national US insurer. Cohorts were created using intravitreal injections of anti-vascular endothelial growth factor injections from 2005 to 2016. For inclusion, patients had to have at least 6 months of data before the injection and were excluded for any previous diagnosis of endophthalmitis, multiple injected drugs on the day of injection, or intraocular surgery within 15 days of the injection or between an injection and a diagnosis of endophthalmitis. The primary outcome was the odds of endophthalmitis after an intravitreal injection.A total of 706,725 bevacizumab, 210,849 ranibizumab, and 177,731 aflibercept injections were given to 130,327 patients. Multivariate analysis showed that ranibizumab and aflibercept together had an increased odds of endophthalmitis (odds ratio = 1.29, 95% confidence interval: 1.04-1.59, P = 0.02) compared with bevacizumab. Individually, ranibizumab (odds ratio = 1.25, 95% confidence interval: 0.97-1.61, P = 0.08) and aflibercept (odds ratio = 1.34, 95% confidence interval: 0.99-1.81, P = 0.06) each had higher odds of endophthalmitis, but neither result met significance. Also, when compared with male patients, female patients had a higher odds of getting endophthalmitis (odds ratio: 1.30, 95% confidence interval: 1.05-1.61, P = 0.02).The odds of endophthalmitis with aflibercept and ranibizumab combined were higher compared with the sterilely preloaded bevacizumab, arguing for a safety advantage of sterile preloading of anti-vascular endothelial growth factor injections.

Objective The study aimed to determine the association of surgical necrotizing enterocolitis (NEC) and its timing, with the development and timing of retinopathy of prematurity (ROP). Study Design This was a secondary data analysis of 7,483 preterm infants from the Postnatal Growth and Retinopathy of Prematurity Study. Associations between infants with surgical NEC, early-onset surgical NEC (8–28 days), and late-onset surgical NEC (over 28 days) with ROP were evaluated by using multivariable logistic regression models, controlling for birth weight, gestational age, small for gestational age status, chronic lung disease, intraventricular hemorrhage, hydrocephalus, patent ductus arteriosus, and periventricular leukomalacia. Results Three hundred fifty-six (4.8%) infants had surgical NEC, with 56% having early surgical NEC. Infants with surgical NEC had a higher risk of any ROP and severe ROP (adjusted odds ratio [OR]: 2.7; 95% CI: 1.9–3.7) and 2.5 (95% CI: 1.9–3.3), respectively; p Conclusion Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. Key Points

The purpose of this study is to determine if statin therapy decreases the incidence of non-infectious uveitis (NIU) using a retrospective cohort study. Patients enrolled in a national insurance plan who initiated statin (n = 711,734, statin cohort) or other lipid-lowering therapy (n = 148,044, non-statin cohort) were observed for NIU development. Incident NIU in the primary analysis was defined as a new diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Estimation of NIU incidence used multivariable Cox proportional hazards regression. The proportional hazards assumption was satisfied by creating two time periods of analysis, ≤ 150 and > 150 days. Subanalyses were performed by anatomic subtype. Overall, the primary outcome occurred 541 times over 690,465 person-years in the statin cohort and 103 times over 104,301 person-years in the non-statin cohort. No associations were seen in the ≤ 150-day analyses (p > 0.20 for all comparisons). However, after 150 days, the statin cohort was less likely to develop any uveitis [hazard ratio (HR) = 0.70, 95% confidence interval (CI): 0.51–0.97, P = 0.03] in the primary outcome analysis, but did not meet significance for the secondary outcome (HR = 0.85, 95% CI: 0.63–1.15, P = 0.30). Similarly, in the anatomic subtype analysis, after 150 days, the statin cohort was less likely to develop anterior uveitis (HR = 0.67, 95% CI: 0.47–0.97, P = 0.03) in the primary analysis, but the association did not reach significance for the secondary outcome (HR = 0.82, 95% CI: 0.56–1.20, P = 0.31). Our results suggest that statin therapy for > 150 days decreases the incidence of NIU.

The antiepileptic medication vigabatrin has been associated with ocular toxicity, and close ophthalmic monitoring has been recommended; however, there is no clear consensus regarding the value and feasibility of such monitoring in children. We describe ophthalmic assessments in children in a real-world clinical setting, the incidence of vigabatrin-related ocular toxicity, and the utility of regular screening or ancillary testing in children taking vigabatrin.The medical records of children taking vigabatrin with one or more ophthalmic assessments at Children's Hospital of Philadelphia or University of California, San Francisco, between May 2010 and May 2021, were reviewed retrospectively. Abnormalities on ophthalmic examination, visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT) were reviewed and categorized as attributable to vigabatrin, possibly attributable to vigabatrin, or not attributable to vigabatrin.A total of 1,281 assessments of 284 children (mean age, 2.09 years) were included. Of these, 283 (99.6%) had funduscopic examination(s), 37 (13.0%) had ERG, 19 (6.7%) had OCT, and 6 (2.1%) had formal VF. Rate of examinations and ERGs per child decreased over the 10-year study period. Two children (0.7%) had definite vigabatrin-related ocular toxicity, both identified on ERG. An additional 4 children (1.4%) had optic atrophy of unclear relation to vigabatrin, categorized as possible toxicity. The remaining 278 children did not have abnormal examination or testing findings attributable to vigabatrin.The incidence of vigabatrin-related ocular toxicity in children was low in our cohort. Ocular and neurologic comorbidities and limited examinations in children make identification of such toxicity challenging and the value of screening is unclear.

Compared with normal subjects with similar shallow anterior chamber depth (ACD), patients with primary angle closure disease (PACD) had narrower angle structures measured by swept-source optical coherence tomography (SS-OCT) at 250 μm from scleral spur (very root of iris), especially along oblique and vertical axis.To examine anterior segment structures in normal subjects whose ACD was shallow on slit-lamp examination but did not meet the diagnostic criteria of PACD, and to compare them with PACD patients with similar ACD.Patients were recruited from glaucoma clinic at Zhongshan Ophthalmic Center. A total of 40 eyes from 29 PACD patients and 40 eyes from 34 normal subjects received full ophthalmic examination and CASIA SS-1000 OCT tests. PACD eyes and control eyes were 1:1 matched for ACD at 0 degree of scan. Generalized linear model that accounted for inter-eye correlation was used to compare differences between the 2 groups for intraocular pressure and SS-OCT parameters. P-values were adjusted for multiple comparisons using the Bonferroni method.The PACD and control groups had similar age, but the PACD group had a significantly higher intraocular pressure (18.4 vs. 14.0 mm Hg, P=0.005). Angle parameters, representative of angle area, such as angle recess area and trabecular iris space area measured at 250 μm along axes of 90, 135, 225, and 315 degrees were significantly smaller in PACD group than those of control group (adjusted P0.05), while most of angle parameters at 500 and 750 μm, volume parameters, and anterior chamber parameters, were similar (adjusted P0.05).In PACD patients compared with normal subjects with similar anterior chamber shallowing, OCT findings measured at the iris root 250 μm from the scleral spur, especially in the oblique and vertical axes, including angle recess area and trabecular iris space area, may match gonioscopic findings more closely and provide further insight into mechanisms of PACD.

To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). Patients in a large healthcare claims database who initiated ACE-I (n = 695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n = 354,295). A second comparison was also made between patients who initiated ACE-I (n = 505,958) and those who initiated beta-blockers (BB, n = 538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR = 0.95, 95% Confidence Interval (CI): 0.85���1.07, P = .41] or secondary outcome [HR = 0.96, 95% CI: 0.86���1.07, P = .44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. Our results suggest there is no evidence that ACE-I have a protective effect on NIU.

Importance Oral contraceptives have been associated with cardiovascular disease, ischemic stroke, venous thromboembolic disease, and breast cancer. Retinal vascular occlusions share the same risk factors as cardiovascular and cerebrovascular disease. Objective To determine whether filling a prescription of female hormone therapy (FHT) is associated with an increased risk of retinal artery occlusion (RAO) or retinal vein occlusions (RVO). Design, Setting, and Participants A multiple-cohort study was conducted using an administrative claims insurance database comparing women who filled a prescription for FHT with matched control individuals. Exclusion occurred for those enrolled for less than 2 years in the plan, with no prior ophthalmologic examination, with a history of a RAO/RVO, with systemic diseases/medications that affected estrogen levels, or a disease associated with an increased risk for thromboembolism. Main Outcomes and Measures The primary outcome was the incidence of a new diagnosis of RAO or RVO. Cox proportional hazard regression modeling with inverse probability of treatment weight was used to assess the hazard ratio (HR) for a new diagnosis of RAO or RVO relative to filling prescription for FHT. Subanalyses were conducted to stratify by age, race/ethnicity, diabetes, and hypertension. Results A total of 205 304 women who filled a prescription for FHT were matched to 755 462 control individuals. After inverse probability of treatment weight, the study cohort was a mean age of 47.2 years, 71% were White, 7% were Black, 6% were Hispanic, 3% were Asian, and 3% were unknown. There were 41 cases (0.01%) of RAO and 68 cases of RVO (0.02%) in the FHT cohort. In comparison, there were 373 cases of RAO (0.05%) and 617 cases of RVO (0.08%) in the control cohort. After inverse probability of treatment weight, Cox regression analysis showed no difference in hazard for RAO, RVO, or combined outcomes in the FHT cohort relative to the control cohort (RAO HR, 1.17; 95% CI, 0.83-1.65;P = .36; RVO HR, 1.07; 95% CI, 0.82-1.39;P = .65; combined HR, 1.10; 95% CI, 0.89-1.36;P = .37). Subanalyses that stratified by age, diabetes, and hypertension similarly showed no significant associations between the FHT prescription cohort and all outcomes. Conclusions and Relevance These findings suggest that filling a prescription for FHT, and presumably taking FHT, does not increase the risk of RAO or RVO. Such history may not be relevant in the evaluation of an individual with an RAO or RVO nor do our results support stopping FHT in an individual who develops an RAO or RVO.

ObjectiveTo characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth.DesignRetrospective matched cohort study using data from the Postnatal Growth and Retinopathy of Prematurity study. Participants were born with birth weights of ResultsOf 4785 eligible infants, 813 (17%) developed sepsis and 693 (85%) were matched 1:1 to controls. Sepsis was associated with a greater decline in weight z-score (mean difference −0.09, 95% CI −0.14 to −0.03). Postnatal weight growth failure (decline in weight z- score>1) was present in 237 (34%) infants with sepsis and 179 (26%) controls (adjusted OR 1.49, 95% CI 1.12 to 1.97). Longitudinal growth trajectories showed similar initial changes in weight z-scores between infants with and without sepsis. By 3 weeks after sepsis onset, there was a greater decline in weight z-scores relative to birth values in those with sepsis than without sepsis (delta z-score −0.89 vs −0.77; mean difference −0.12, 95% CI −0.18 to −0.05). This significant difference persisted until 36 weeks or discharge.ConclusionInfants with sepsis had similar early weight growth trajectories as infants without sepsis but developed significant deficits in weight that were not apparent until several weeks after the onset of sepsis.

To compare rates of short-term retinal detachment (RD) of infants treated for type 1 retinopathy of prematurity (ROP) with intravitreal anti-vascular endothelial growth factor (VEGF) therapy with infants treated with laser therapy. The choice between these 2 treatments remains controversial. Comparative data are limited and describe re-treatment rates rather than retinal structural outcomes predictive of long-term vision. Anti-vascular endothelial growth factor acts faster than laser therapy, which may be beneficial for more aggressive ROP.Nonrandomized, comparative cohort study.The study included 1167 eyes of 640 infants treated for type 1 ROP. Among these, 164 eyes received anti-VEGF therapy and 1003 eyes received laser therapy.Pretreatment and posttreatment examinations and treatments were completed by ophthalmologists with expertise in ROP. The study was a secondary analysis of data from the retrospective Postnatal Growth and Retinopathy of Prematurity Study (G-ROP) 1 study (2006-2012) and the prospective G-ROP 2 study (2015-2017).Rate of RD (ROP stages 4A, 4B, or 5) within 8 weeks of initial treatment, an end point predictive of poor long-term vision. The results were stratified by postmenstrual age (PMA) at treatment as occurring before versus at or after 36 weeks and 0 days, because earlier disease may be considered more aggressive.Among 458 eyes treated before PMA 36 weeks and 0 days, the short-term RD rate was higher after laser therapy (29/368 eyes [7.9%]) than after anti-VEGF therapy (0/90 eyes [0%]; P0.001). Of 709 eyes treated at or after PMA 36 weeks and 0 days, short-term RD risk did not differ between groups (laser [20/635 eyes], 3.1%; anti-VEGF [1/74 eyes], 1.4%; P = 0.27).Anti-vascular endothelial growth factor therapy results in better short-term structural outcomes than laser therapy when type 1 ROP is treated before 36 weeks' PMA. After this age, both treatments have very low rates of short-term RD. The faster action of anti-VEGF agents likely is responsible for these findings.