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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.

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

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.

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.

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.

IMPORTANCE: Diabetic retinopathy (DR) may progress from nonproliferative DR (NPDR) to vision-threatening DR (VTDR). Studies have investigated fenofibrate use as a protective measure with conflicting results, and fenofibrate is not typically considered by ophthalmologists in the management of DR currently. OBJECTIVE: To assess the association between fenofibrate use and the progression from NPDR to VTDR, proliferative DR (PDR), or diabetic macular edema (DME). DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used medical claims data from a large US insurer. Cohorts were created from all patients with NPDR 18 years or older who had laboratory values from January 1, 2002, to June 30, 2019. Exclusion criteria consisted of any previous diagnosis of PDR, DME, proliferative vitreoretinopathy, or treatment used in the care of VTDR. Patients were also excluded if they had a diagnosis of VTDR within 2 years of insurance plan entry, regardless of when NPDR was first noted in the plan. EXPOSURES: Fenofibrate use. MAIN OUTCOMES AND MEASURES: The main outcomes were a new diagnosis of VTDR (a composite outcome of either PDR or DME) or DME and PDR individually. A time-updating model for all covariates was used in multivariate Cox proportional hazard regression to determine hazards of progressing to an outcome. Additional covariates included NPDR severity scale, systemic illnesses, demographics, kidney function (based on estimated glomerular filtration rate level), hemoglobin A(1c), hemoglobin, and insulin use. RESULTS: A total of 5835 fenofibrate users with NPDR at baseline (mean [SD] age, 65.3 [10.4] years; 3564 [61.1%] male; 3024 [51.8%] White) and 144 417 fenofibrate nonusers (mean [SD] age, 65.7 [12.3] years; 73 587 [51.0%] male; 67 023 [46.4%] White) were included for analysis. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After controlling for all covariates, Cox model results showed fenofibrates to be associated with a decreased risk of VTDR (hazard ratio, 0.92 [95% CI, 0.87-0.98]; P = .01) and PDR (hazard ratio, 0.76 [95% CI, 0.64-0.90]; P = .001) but not DME (hazard ratio, 0.96 [95% CI, 0.90-1.03]; P = .27). CONCLUSIONS AND RELEVANCE: In this study, fenofibrate use was associated with a decreased risk of PDR and VTDR but not DME alone. These findings support the rationale for additional clinical trials to determine if these associations may be representative of a causal relationship between fenofibrate use and reduced risk of PDR or VTDR.

To evaluate the effect of changes in institutional peripheral oxygen saturation (SpOThis study was a secondary analysis of data from 21 North American hospitals during the periods 2006-2012 and 2015-2017. Hospitals were categorized based on whether or not SpOA total of 8,142 infants underwent ROP examinations at 21 hospitals during the two study periods: 5,716 in 2006-2012 (mean BW, 1109 ± 369 g; GA, 28.0 ± 2.6; 11.6% severe ROP); 2,426 in 2015-2017 (mean BW, 1086 ± 347 g; GA, 28.0 ± 2.8; 12.8% severe ROP). Fourteen hospitals increased SpOIncreases in institutional SpO