SGLT2 inhibitors and diabetic retinopathy progression.

PURPOSE: To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. METHODS: A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. RESULTS: A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. CONCLUSION: Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.

INCIDENCE AND RISK FACTORS FOR EXUDATIVE RETINAL DETACHMENT FOLLOWING LASER PHOTOCOAGULATION FOR RETINOPATHY OF PREMATURITY.

PURPOSE: Exudative retinal detachment (ERD) may result from laser photocoagulation for retinopathy of prematurity. Although risk factors have been hypothesized from case reports, comparative studies have not been reported. We sought to evaluate risk factors for ERD following laser, comparing affected and unaffected infants. METHODS: Retrospective cohort study of infants undergoing retinopathy of prematurity laser at the Children's Hospital of Philadelphia over 6 years. All received near-confluent laser of avascular retina. Demographic, medical, and procedural risk factors for ERD were evaluated in univariate analysis because of the rarity of ERD. RESULTS: Among 149 lasered infants, 6 infants (4%, 95% confidence interval [CI] 1.5%-8.6%) developed ERD. Race was a significant risk factor ( P = 0.01). Among 71 African American or Hispanic infants, 6 (8.5%, 95% CI 3.2%-17.5%) developed ERD. Among 78 non-African American or Hispanic infants, 0 (0%, 95% CI 0%-4.6%) developed ERD. There were no significant differences in the other studied factors. CONCLUSION: Exudative retinal detachment was uncommon (4%) following retinopathy of prematurity laser. Despite so few cases, darker pigmented race with likely increased pigmented fundi was significantly associated with an increased ERD risk. Further study may reveal whether increased choroidal pigment causes greater laser tissue damage or makes it difficult to discern the ora, resulting in inadvertent lasering of the ciliary body, leading to ERD.

FACTORS ASSOCIATED WITH OUTCOMES OF SUPRACHOROIDAL HEMORRHAGE: An Individual Participant Data Systematic Review.

PURPOSE: To determine factors associated with visual and anatomic outcomes of suprachoroidal hemorrhage in studies published between 1990 and 2022. METHODS: Individual participant data systematic review. The protocol was prospectively registered on Open Science Framework ( https://osf.io/69v3q/ ). PubMed, EMBASE, Web of Science, and Google Scholar were searched for peer-reviewed studies of suprachoroidal hemorrhage with ≥3 patients published between January 1, 1990, and September 1, 2022. The primary outcome was the change in logarithm of the minimum angle of resolution visual acuity from the time of suprachoroidal hemorrhage diagnosis to last follow-up. RESULTS: Four hundred thirteen eyes from 49 studies were included, with mean (SD) age 60.8 (22.4) years and mean (SD) follow-up of 13.8 (12.6) months. Among 145 eyes with at least 6 months of follow-up, the mean (SD) gain in visual acuity was -0.98 (0.89) logarithm of the minimum angle of resolution. In multivariable regression, treatment with systemic steroids was associated with greater improvement in logarithm of the minimum angle of resolution visual acuity (adjusted mean [SE] -1.29 [0.09] vs. -0.16 [0.30] for no systemic steroids; P < 0.001) and greater odds of achieving anatomic success (adjusted OR 10.59, 95% confidence interval 2.59-43.3; P = 0.001). CONCLUSION: The use of systemic steroids was associated with better visual and anatomic outcomes for suprachoroidal hemorrhage.

Lacrimal Obstruction in Craniosynostosis: Anatomical and Genetic Risk Factors.

PURPOSE: To investigate whether patients with craniosynostosis exhibit higher rates of nasolacrimal duct obstruction (NLDO) and to explore potential risk factors. METHODS: Retrospective review including all craniosynostosis patients treated at both the Divisions of Ophthalmology and Plastic, Reconstructive, and Oral Surgery at The Children's Hospital of Philadelphia between 2009 and 2020 was conducted. Synostosis characteristics, lacrimal disorders, and genetic data were collected. Main outcome measures were the rate of NLDO and associations with anatomical and syndromic/genetic risk factors. RESULTS: The total of 767 participants had a mean age of 2.8 ± 3.8 years, 465 (60.6%) were males, 485 (63.2%) had no syndromic association; 631 (82.3%) had one major suture involved, 128 (17%) had involvement of 2 to 4 major sutures, and 429 (55.9%) underwent craniofacial surgery. Forty-eight (6.2%) patients had NLDO, which more prevalent in the genetic/syndromic group (11.0% vs. 3.5%, respectively, p < 0.001), with the highest prevalence observed in patients with Apert syndrome (n = 4, 30.8%). The genetic variants most associated with NLDO were EFNB1 (n = 1, 100%) and FGFR2 (n = 6, 19.4%). There was no association between NLDO and the number or types of sutures involved or a history of craniofacial surgery. CONCLUSIONS: Nasolacrimal duct obstruction is more common in patients with craniosynostosis compared to the general population. Having a putative syndrome or a putative genetic variant and female sex were risk factors for NLDO. Ophthalmic evaluations for all craniosynostosis patients and careful assessments of any symptoms of tearing are recommended.

Association of Surgical Necrotizing Enterocolitis and Its Timing with Retinopathy of Prematurity.

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 < 0.001) compared with infants without surgical NEC. Infants with early surgical NEC were at the highest risk of developing ROP and severe ROP (adjusted OR: 3.1 [95% CI: 2.1-4.8], and 3.3 [95% CI: 2.3-4.7] respectively, p < 0.001). Infants with late surgical NEC were also at increased risk of developing ROP and severe ROP (adjusted OR: 2.1 [95% CI: 1.3-3.4], and 1.9 [95% CI: 1.3-2.8] respectively, p < 0.001) compared with infants without surgical NEC. CONCLUSION: Infants with surgical NEC, especially early surgical NEC, are at higher risk of ROP and severe ROP. KEY POINTS: · Infants with surgical NEC are at higher risk of ROP and severe ROP than those without surgical NEC.. · Increased ROP risk is seen in infants with both early- or later onset surgical NEC.. · Early-onset surgical NEC is associated with a higher ROP risk compared with later onset surgical NEC..

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.

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study.

OBJECTIVES: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1ß, 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

Retinal Detachment after Treatment of Retinopathy of Prematurity with Laser versus Intravitreal Anti-Vascular Endothelial Growth Factor.

PURPOSE: 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. DESIGN: Nonrandomized, comparative cohort study. PARTICIPANTS: 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. METHODS: 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). MAIN OUTCOME MEASURES: 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. RESULTS: 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%]; P < 0.001). 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). CONCLUSIONS: 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.

Changes in Intraocular Pressure and Angle Structure after Dilation in Primary Angle-Closure Suspects with Visually Significant Cataract.

PURPOSE: To evaluate the safety of pupillary dilation in primary angle-closure suspects (PACS) with concurrent visually significant cataract (VSC), to identify risk factors associated with elevated intraocular pressure (IOP), and to describe changes in anterior segment anatomy after pupillary dilation. DESIGN: Prospective study. PARTICIPANTS: Patients with PACS and VSC and no prior laser or intraocular surgery were recruited. Visually significant cataract was defined as best-corrected visual acuity ≤ 20/40 due to cataract. METHODS: Subjects' eyes were dilated with 0.5% tropicamide and 0.5% phenylephrine hydrochloride. A standardized eye examination, biometry, and swept-source OCT (SS-OCT) were performed before dilation. Intraocular pressure and SS-OCT were repeated 1, 4, and 6 hours postdilation (PDH1, PDH4, and PDH6, respectively). All parameters were compared between time points before and after dilation using paired t test. Linear regression models were used to determine the risk factors associated with postdilation IOP changes. MAIN OUTCOME MEASURES: Change in IOP and SS-OCT parameters from baseline. RESULTS: Seventy-eight eyes from 78 patients were included, with 78, 66, and 12 patients completing the study at PDH1, PDH4, and PDH6, respectively. Mean IOP increased from 14.8 ± 2.6 mmHg at baseline to 15.5 ± 3.5 mmHg at PDH1 (P = 0.03) and decreased to 14.9 ± 3.1 mmHg at PDH4 (P = 0.09). Four patients (5.13%) and 3 patients (3.85%) had an increase in IOP ≥ 5 mmHg at PDH1 and PDH4, respectively. Two patients (2.56%) and 1 patient (1.28%) had an increase in IOP ≥ 8 mmHg at PDH1 and PDH4, respectively. None developed acute primary angle-closure during the observation period. Almost all anterior chamber parameters showed a significant increase after dilation at PDH1 and PDH4, except lens vault and iris volume, which decreased at PDH1 and PDH4 from baseline. Increase in anterior chamber depth was negatively associated with the level of IOP elevation after dilation (P < 0.01). CONCLUSIONS: Dilation of patients' eyes with PACS and VSC in this cohort appears to have a low risk for IOP spike. This may be associated with relaxation of the ciliary muscle leading to posterior displacement of the lens-iris diaphragm and deepening of the anterior chamber.

Visit adherence and visual acuity outcomes in patients with diabetic macular edema: a secondary analysis of DRCRnet Protocol T.

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. A total of 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, p < 0.001) and - 4.0 letters (95%CI - 6.1, - 1.9, p < 0.001), respectively, than on time. Those that averaged > 4 days missed per attended visit saw 4.6 letters worse (95%CI - 7.3, - 2.0, p < 0.001). CONCLUSIONS: Visit adherence is associated with visual acuity outcomes in DME patients.

Decreased risk of non-infectious anterior uveitis with statin therapy in a large healthcare claims database.

PURPOSE: The purpose of this study is to determine if statin therapy decreases the incidence of non-infectious uveitis (NIU) using a retrospective cohort study. METHODS: 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. RESULTS: 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). CONCLUSION: Our results suggest that statin therapy for > 150 days decreases the incidence of NIU.

Factors impacting cumulative dissipated energy levels and postoperative visual acuity outcome in cataract surgery.

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.

Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database.

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.

In-vivo longitudinal changes in thickness of the postnatal canine retina.

The objectives of the present work were to assess by spectral domain optical coherence tomography (OCT) the changes in thickness of the outer nuclear layer (ONL), the ONL + photoreceptor inner segment (IS), and the retinal thickness, as a function of age in the normal canine retina. OCT retinal scans extending from the edge of the optic nerve head (ONH) along the superior and inferior meridians were captured in both eyes of 17 normal dogs at age ranging from 4 to 119 weeks. The different parameters along the superior and the inferior regions were determined following manual segmentation using the Heidelberg Eye Explorer software. Changes in thickness with age were modeled using one-phase exponential decay models. In vivo OCT imaging results showed no interocular statistically significant differences in ONL, ONL + IS, and retinal thickness at any age. All three parameters were however found to be statistically significantly thicker in the superior vs inferior retina. A rapid thinning of the three layers occurs in both the superior and inferior retina between 4 and 12 weeks of age, before reaching a plateau at around 20 weeks of age. In conclusion, the ONL, ONL + IS, and retinal thickness of the normal canine retina decrease significantly during the first three postnatal months, and is likely attributed to an overall increase in the eye volume and tangential dispersion of the photoreceptor since early photoreceptor developmental cell death is very limited at that age. Establishment of the natural history of ONL, ONL + IS, and retinal thinning will allow a more accurate assessment of the progression of a retinal degenerative condition as well as facilitate the detection of positive rescue effect of novel retinal therapies evaluated in this large animal model.

Repeated intravitreal injections of antivascular endothelial growth factors and risk of intraocular pressure medication use.

PURPOSE: To determine the risk of initiating ocular hypertension and glaucoma treatment with repeated injections of antivascular endothelial growth factors (anti-VEGF). METHODS: A unique, retrospective cohort study was performed using a large national US medical claim database. The study population included patients who had 1 or more injections of an anti-VEGF agent. Exclusion occurred for any previous glaucoma, glaucoma suspect, glaucoma-related procedure, an ocular steroid injection, or not seeing an eye care provider at least once in each year of follow-up. Cohorts were divided into quartiles based on the number of injections performed over the follow-up period. Patients were observed for 2 and 3 years. The main outcome measure was defined as any new prescription for an ocular antihypertensive medication with a concurrent diagnosis of glaucoma, glaucoma suspect, or ocular hypertension. Multivariate logistic regression determined the odds of initiating glaucoma treatment in each injection quartile while controlling for numerous covariates. Sensitivity analysis assessed outcomes that included new medication only as well as a new medication plus diagnosis of glaucoma. RESULTS: In total, 17,113 and 9992 patients met 2- and 3-year observation end points, respectively. The multivariate odds ratio for initiating glaucoma treatment at 2 years was higher in the highest quartile (OR 1.96, 95% CI 1.39-2.76, p < 0.001) compared with the lowest. The 3-year comparison had similar results with increased odds in the highest quartile (OR 1.51, 95% CI 1.07-2.13, p = 0.006) compared with the lowest. Sensitivity analyses also showed similar results with more injections being associated with initiating treatment (p < 0.053 for all comparisons). CONCLUSIONS: Repeated anti-VEGF injections are associated with an increased odds of initiating treatment for ocular hypertension and glaucoma.

COMPARATIVE RISK OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION WITH BEVACIZUMAB, AFLIBERCEPT, AND RANIBIZUMAB.

PURPOSE: To determine whether sterile preloading of anti-vascular endothelial growth factor agents reduces the risk of postintravitreal injection endophthalmitis. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Association between Primary Open-Angle Glaucoma and Cognitive Impairment as Measured by the Montreal Cognitive Assessment.

BACKGROUND: It is currently unclear whether primary open-angle glaucoma (POAG) affects neurological functions outside of vision, such as cognition. OBJECTIVE: This study examined the association between POAG and cognitive impairment in African Americans. METHODS: Masked interviewers administered the Montreal Cognitive Assessment (MoCA) to patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study at the Scheie Eye Institute. Cases were further assessed for retinal nerve fiber layer (RNFL) thickness and visual field (VF) loss. Univariate and multivariate linear regression analyses were performed to compare mean MoCA score between cases and controls and to assess the association between POAG severity and MoCA score. RESULTS: A total of 137 patients completed the MoCA, including 70 cases and 67 controls. The mean age ± SD was 68.7 ± 11.2 years for cases and 65.7 ± 10.4 years for controls (p = 0.11). The mean MoCA total score (out of 30 points) was 20.3 among POAG cases and 21.3 among controls (mean difference = -1.03, 95% confidence interval, CI = -2.54 to 0.48, p = 0.18). After adjusting for age, gender, education level, diabetes, hypertension, and smoking status, the mean difference in the MoCA total score between cases and controls was -0.64 (95% CI = -1.72 to 0.45, p = 0.25). Among cases, more VF loss was associated with lower total MoCA score for mean deviation (adjusted linear trend p = 0.02) and VF index (adjusted linear trend p = 0.03). There was no significant association between average RNFL thickness and total MoCA score. CONCLUSIONS: POAG cases and controls had similar neurocognitive function as measured by the MoCA. Among POAG cases, worse VF loss was associated with lower MoCA. Future studies are needed to further elucidate the clinical effect of neuropathy in POAG.

Real-world socioeconomic determinants of corneal crosslinking in a national cohort.

PURPOSE: To characterize recent socioeconomic trends in patients with keratoconus/corneal ectasias undergoing corneal crosslinking (CXL). SETTING: A deidentified administrative medical claims database comprised commercial and Medicare Advantage health claims from across the United States. DESIGN: Population-based retrospective cohort study. METHODS: This study identified 552 patients with keratoconus/corneal ectasia who underwent CXL and 2723 matched controls who did not undergo CXL based on Current Procedural Terminology coding from a U.S. national insurance claims database from 2016 to 2020. For each patient, characteristics, including sex, race, age, household net worth, education level, insurance plan type, and geographic region, were extracted. Multivariate logistic regression was conducted to determine the odds of undergoing crosslinking. RESULTS: Age 30 years or older (odds ratio [OR], 0.34, P < .001) was associated with decreased likelihood of undergoing CXL. Sex, race, education, and patient income were not associated with odds of undergoing CXL. Patients with health maintenance organization insurance had lower odds of undergoing CXL (OR, 0.64, P = .047). Geographically, patients on the east coast (OR, 0.37, P < .001) and Lower Midwest (OR, 0.31, P < .001) had statistically lower odds of undergoing crosslinking. CONCLUSIONS: This is the first study to identify socioeconomic determinants of CXL, and it highlights that geographic location and insurance type may limit accessibility to patients.

Malignancy Risk Associated With the Use of Systemic Immunomodulatory Therapy in the Management of Noninfectious Uveitis.

PURPOSE: Patients with noninfectious uveitis (NIU) can require treatment with systemic immunomodulatory therapy (IMT), but it is unclear whether IMT drug categories increase the risk of malignancy in NIU patients. The purpose of this study is to determine if the use of systemic IMT in patients with NIU is associated with an increased risk of malignancy. DESIGN: Clinical cohort study. METHODS: Patients were identified from a US administrative medical claims database including some Medicare Advantage and commercial plans, from 2000 to 2022. About 318,498 NIU patients were identified. Enrollees were included in the analysis if they met the following criteria: continuous enrollment in the plan for at least 1 year, and at least 2 consecutive visit diagnoses of any type of NIU, after initiation of systemic IMT. We compared the rates of incident malignancy in NIU patients treated with IMT versus the rates among NIU patients not treated with IMT. Multivariable Cox regression models were used to predict the hazard of developing incident cancer. RESULTS: Of the 318,498 patients with NIU identified over a 15-year period, 318,006 did not develop malignancy, and 492 did develop malignancy. Of the patients that developed a malignancy, 280 (57%) were treated with systemic corticosteroids; 204 (41%) were treated with antimetabolites; 44 (9%) were treated with T cell inhibitors; 108 (22%) were treated with TNF alpha inhibitors; 2 (0.004%) were treated with interleukin-6 (IL-6) inhibitors; and 1 was treated with CD-20 antibodies. There were no malignancies reported in the group treated with alkylating agents. There was no association between any of the drug classes and incidence of malignancy. CONCLUSIONS: This study suggests that there is no increased risk of malignancy associated with the use of systemic IMT for patients with NIU.