Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials.

PURPOSE: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. DESIGN: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

INTRAVITREAL METHOTREXATE INJECTION FOR THE TREATMENT AND PREVENTION OF PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To report on our experience using intravitreal methotrexate (MTX) in patients with retinal detachment associated with proliferative vitreoretinopathy and/or open globe injury. METHODS: This study performed a retrospective chart review of a consecutive series of 21 eyes of 21 patients who underwent serial intravitreal MTX injection for treatment and/or prevention of proliferative vitreoretinopathy from December 2021 to January 2024. RESULTS: Twenty-one patients underwent pars plana vitrectomy, membrane peeling, laser photocoagulation, silicone oil infusion, and intravitreal MTX injection. Postoperatively, all eyes received a series of intravitreal MTX (400 µg/0.1 mL) injections. Optimally, injections were administered weekly for 8 weeks and every 2 weeks for four weeks for a total of 13 injections, beginning intraoperatively at the conclusion of retinal reattachment surgery. Mean baseline preoperative and postoperative visual acuity was logarithm of the minimum angle of resolution 3.2 (approximately hand motions vision) and 2.5 (between CF and hand motions vision), respectively, yielding an average improvement in visual acuity of 0.7 logarithm of the minimum angle of resolution units (0 ETDRS lines/letters). These 21 patients received an average of 10.5 injections. With a single operation, detachments in 19 (90%) of 21 eyes were successfully reattached. Corneal epithelial defects were noted in 7 (33%) of 21 patients. CONCLUSION: Serial intravitreal MTX injection was associated with 90% single operation retinal reattachment rate in the setting of retinal detachment with proliferative vitreoretinopathy or retinal detachment at high risk of proliferative vitreoretinopathy.

Factors Linked to Injection Interval Extension in Eyes with Wet Age-Related Macular Degeneration Switched to Brolucizumab.

PURPOSE: To evaluate factors associated with anti-vascular endothelial growth factor (VEGF) injection interval extension in patients with neovascular age-related macular degeneration (nAMD) switched to brolucizumab treatment. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who switched from another anti-VEGF agent to brolucizumab-only treatment for ≥ 12 months from October 8, 2019, through November 26, 2021. METHODS: Univariable and multivariable analyses examined associations of demographic and clinical characteristics with the likelihood of interval extension after switching to brolucizumab therapy. MAIN OUTCOME MEASURES: Eyes were classified as either extenders or nonextenders at 12 months. Extenders were eyes that achieved (1) an extension of ≥ 2 weeks in the brolucizumab injection interval at 12 months versus the interval before switching (time between the last known prior anti-VEGF injection and first [index] brolucizumab injection) and (2) stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) visual acuity (VA) at 12 months versus VA at index injection. RESULTS: Of 2015 eyes among 1890 patients who switched to brolucizumab treatment, 1186 (58.9%) were extenders. In univariable analyses, demographic and clinical characteristics were comparable between extenders and nonextenders, except that extenders had shorter intervals before switching versus nonextenders (mean, 5.9 ± 2.1 weeks vs. 10.1 ± 7.6 weeks, respectively). In multivariable logistic regression modeling, a shorter interval before switching was associated significantly and positively with interval extension with brolucizumab therapy (adjusted odds ratio, 5.6 for interval before switching of < 8 weeks versus ≥ 8 weeks; 95% confidence interval, 4.5-6.9; P < 0.001), and eyes with an index VA of 40 to 65 letters were significantly less likely to be extenders than eyes in the higher (better) index VA categories. CONCLUSIONS: Length of the treatment interval before switching was the characteristic associated most strongly with successful interval extension with brolucizumab. Treatment-experienced patients who required more frequent injections (i.e., shorter intervals before switching) showed the greatest extensions when switching to brolucizumab. With careful consideration of benefits and risks, brolucizumab may be a valuable option for patients with higher treatment burdens because of the need for frequent injections. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

One-Year Brolucizumab Outcomes in Neovascular Age-Related Macular Degeneration from a Large United States Cohort in the IRIS® Registry.

PURPOSE: To evaluate visual acuity (VA) and injection intervals in patients with neovascular age-related macular degeneration (nAMD) after 12 months of brolucizumab therapy in clinical practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who received brolucizumab exclusively for 12 months (2308 eyes of 2079 patients). METHODS: Observational study of eyes with a first injection of brolucizumab (index), followed by 2 or more brolucizumab injections over the following 12 months without switching to another anti-vascular endothelial growth factor (VEGF) agent. MAIN OUTCOME MEASURES: Primary outcomes were change in best recorded VA and, for eyes receiving prior anti-VEGF therapy (treatment-experienced eyes), the difference between the brolucizumab injection interval at 12 months and the anti-VEGF injection interval before switching. The interval before switching was defined as the time between the prior anti-VEGF and index brolucizumab injections; brolucizumab interval was the time between the closest injection to day 365 and the preceding injection. Secondary outcomes included incident adverse events. RESULTS: Overall VA at index was 61.6 ± 18.4 Early Treatment Diabetic Retinopathy Study letters; 83.7% of treatment-naive eyes (184/220) and 86.1% of treatment-experienced eyes (1797/2088) showed stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) VA at 12 months. Among treatment-experienced eyes receiving a prior anti-VEGF injection within 365 days before index, 29.5% (594/2015) showed an interval before switching of 8 weeks or more (mean, 7.6 ± 5.5 weeks), whereas 83.1% (1734/2015) showed a brolucizumab injection interval at 12 months of 8 weeks or more (mean, 10.3 ± 4.0 weeks). In all, 77.1% of treatment-experienced eyes (1554/2015) showed an interval extension of 1 week or more; of these, 55.4% (861/1554) showed an extension of 4 weeks or more. CONCLUSIONS: In this community-based study, at 12 months, brolucizumab treatment prolonged the interval between anti-VEGF injections for most treatment-experienced eyes, particularly those with shorter intervals before switching, while maintaining or improving VA. With careful balancing of the benefits and risks, switching to brolucizumab treatment may offer the advantage of extending the treatment interval for patients with a high anti-VEGF therapy burden. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Work-related ocular trauma in the United States: a National Trauma Databank study.

PURPOSE: This study aims to investigate trends and risk factors associated with work-related ocular injuries occurring in adults aged 19-64 using the National Trauma Databank (NTDB). METHODS: In this retrospective, cross-sectional study, the NTDB was used to collect all patients with an ICD-9 code of work-related ocular trauma from 2007 to 2014. Demographic data and risk factors collected included age, gender, race, setting, machinery, and mechanism. Descriptive statistics, univariate, and logistic regression multivariate analyses were conducted. RESULTS: Between 2007 and 2014, 234,983 cases of work-related trauma were identified, of which 11,097 (5.7%) cases involved ocular trauma. The mean age of patients was 40.7 years (SD = 12.2), and the majority of patients (93.7%) were male. Most injuries occurred in an industrial facility, and the most common injuries were orbital floor fractures (OFFs), ocular contusions, open wounds to the adnexa, and open globe injuries (OGIs). OFFs most commonly involved a concurrent fracture of another facial or skull bone. Male gender (RR = 1.22; CI 1.09-1.38), accidental falls (RR = 1.50; CI 1.41-1.60), trauma from falling objects (RR = 1.34; CI 1.21-1.48), involvement in an unarmed fight (RR = 1.63; CI 1.39-1.91), assault by a blunt object (RR = 1.59; CI 1.31-1.91), and injury caused by animals (RR = 1.63; CI 1.30-2.02) were risk factors for OFFs. Patients with OFFs were less likely to have a concurrent OGI (RR = 0.27; CI 0.23-0.32). On the other hand, injuries occurring in industrial facilities (RR = 1.29; CI 1.11-1.51) and injuries with a loose foreign body striking the eye or adnexa (RR = 1.54; CI 1.28-1.84) were risk factors for OGI. The most common causes of work-related ocular trauma were accidental falls, motor vehicle accidents, and accidentally being struck in the eye. The mean length of hospital stay was 6.56 days (SD = 10.82); 36.7% of patients required ICU admission, and the overall in-hospital mortality rate was 2.8%. CONCLUSION: The majority of work-related ocular trauma occurred in men, most commonly in industrial locations. Accidental falls were the most common identified cause of trauma. OFF was the most common ocular injury; 80% of OFF cases involved additional facial and skull fractures. Patients with OFFs were less likely to have a concurrent OGI compared with patients without OFFs.

Epidemiology of United States tennis-related ocular injuries from 2000 to 2019.

PURPOSE: To characterize trends in ocular tennis injuries over the last 20 years. METHODS: The National Electronic Injury Surveillance System was utilized to characterize tennis-related eye injuries in a nationally representative sample of emergency department visits. Data were divided into 5 age groups, and various demographic information was obtained. RESULTS: Approximately 16,000 tennis-related ocular injuries were identified with males being affected nearly 2:1 compared to females. The youngest age group (0-20) had the greatest proportion of injuries, with most injuries in boys 11-15 years old. Injuries occurred most often during the spring season. Most patients were treated and released from the ED. Of those patients who were hospitalized, one-third had an open globe injury. CONCLUSIONS: The overall number of injuries trended downward during the timespan of the study. Although most patients did not experience serious visual consequences, the greatest proportion of ocular tennis injuries occurred in the pediatric age group in whom the risk of amblyopia is high. Primary care providers and tennis regulatory bodies should consider recommending eye safety sports goggles in children to mitigate the potential for significant visual morbidity.

The Impact of Frailty Syndrome on Endogenous Endophthalmitis Development and Outcomes: A Population-Level Analysis.

PURPOSE: Characterize the impact of frailty on endogenous endophthalmitis (EE) development and clinical outcomes among septicemic patients. DESIGN: Population-level, retrospective cohort study. PARTICIPANTS: Adult inpatients within the National Inpatient Sample (years 2002-2014) diagnosed with bacterial septicemia. METHODS: Septicemic patients were classified as frail or nonfrail using the previously validated Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator, and diagnosis of EE was abstracted from International Classification of Diseases 9 codes. We used multivariable logistic regression to generate odds ratios (ORs) for rates of EE development and in-hospital mortality based on frailty status. We also examined the association between frailty and blood culture-proven organism class, inpatient length of stay, and total charges billed to insurance. MAIN OUTCOME MEASURES: Incidence of EE among septicemic patients; rates of EE development among frail and nonfrail patients; blood culture-proven microbe type, length of stay, and total charges billed to insurance. RESULTS: 9294 of 18 470 658 (0.05%) inpatients with bacteremia developed EE, 2102 (22.6%) of whom had at least 1 frailty-defining feature (predominantly malnutrition [68%]). Odds of developing EE were 16.7% higher for frail patients (OR, 1.167; 95% confidence interval, 1.108-1.229) when controlling for age, sex, race, concomitant human immunodeficiency virus/AIDS, pyogenic liver abscess, infectious endocarditis, cirrhosis, and diabetes with chronic complications. Frail EE patients had a 27.9% increased odds of in-hospital death, independent of age, sex, race, and Elixhauser comorbidity score (OR, 1.279; 95% confidence interval, 1.056-1.549). Higher rates of methicillin-resistant Staphylococcus aureus bacteremia (14.3% vs. 10.9%, P = 0.000016), gram-negative bacteremia (7.6% vs. 4.9%, P = 0.000003), and concomitant candidemia (10.4% vs. 7.0%, P = 0.0000004) were associated with frailty. Hospital stays were significantly longer (median, 14 days; interquartile range, 19 days; P < 0.00001) and total charges billed to insurance were significantly greater (median, $96 398; interquartile range, $154,682; P < 0.00001) among frail EE patients. CONCLUSIONS: Frailty syndrome is independently associated with development of EE in the setting of bacterial septicemia; frailty-associated EE may occur in patients with malnutrition and particular bacterial subtypes, and it predisposes to higher rates of in-hospital death and health care resource usage.

Enucleation in pediatric open globe injuries: demographics and risk factors.

PURPOSE: The purpose of this study is to report the demographics and risk factors for undergoing primary enucleation in the setting of acute open globe injury (OGI) in the pediatric population in the USA. METHODS: This retrospective, cross-sectional study of pediatric patients with OGIs in the USA between 2002 and 2014 was conducted utilizing data from the National Inpatient Sample Database. Descriptive statistics, chi-square testing, and univariate and multivariable analyses were performed. RESULTS: In the USA, 8944 cases of pediatric OGI were identified between 2002 and 2014 in the NIS Database, of which 344 underwent primary enucleation. Blacks and Asian/Pacific Islanders made up higher proportions of enucleated cases compared to non-enucleated cases. Older age, male sex, being Black or Asian/Pacific Islander, OGI with an intraocular foreign body, rupture type OGI, and concurrent endophthalmitis were identified as risk factors for undergoing enucleation. There was no significant difference in insurance status among enucleated versus non-enucleated cases. Mean length of hospital stay (in days) was almost 3 times higher in enucleated OGIs. By hospital's geographic location, the Midwest hospitals had a greater proportion of enucleated versus non-enucleated cases compared to other regions. CONCLUSION: Significant demographic differences were identified in OGI patients that underwent primary enucleation versus repair with regard to age, sex, race, the geographic location of hospital admission, mean length of hospital stay, type of ocular injury, and other ocular complications. Most pediatric traumatic enucleations between 2002 and 2014 were reported in teenagers (16-20 age group), in males, and in Blacks.

Epidemiologic trends in pediatric ocular injury in the USA from 2010 to 2019.

PURPOSE: Epidemiologic studies related to the demographics and trends of ocular injury in the pediatric cohort in the last decade are limited. This study describes epidemiologic trends in consumer product-related pediatric ocular injuries from 2010 to 2019. METHODS: This is a retrospective observational study utilizing data from the National Electronic Injury Surveillance System (NEISS). Inclusion criteria include pediatric patients ages 1-20 presenting to NEISS emergency departments with an ocular injury from January 1, 2010, to December 31, 2019. Outcome measures include prevalence of ocular injury related to consumer products stratified by age group, sex, and injury setting. RESULTS: There were an estimated 636,582 consumer product (CP)-related incidents of ocular injury in children ages 1-20 years with an average age of 9.7 years (SD = 5.92) between 2010 and 2019; 416,378 (65.4%) patients were males with a male-to-female ratio of 1.9:1. The annual incidence of CP-related ocular injury in males decreased from 2010 to 2019 while that in females remained unchanged. The greatest number of injuries occurred in the 1-5-year age group (31%) followed 6-10 group (25%), 16-20 (22%), and 11-15 (21%). Ocular contusion was the most common diagnosis. The most common setting of injury was home (63%). The majority (96%) of patients were treated and released from the ED suggesting a minor injury. Of the 1% of patients admitted to the hospital with ocular injuries, one-fourth were due to an open globe injury. Most ocular injuries occurred in the summer months, and presentation to the ED was more frequent on the weekend than a weekday. Over one-fourth (28%) of injuries were sports-related followed by detergents/chemicals (16%), toys (11%), home workshop equipment (8%), kitchenware (5.0%), and home furniture in (4.4%). CONCLUSIONS: The frequency and rate of pediatric ocular injuries in the USA decreased during the last decade. Sports and non-powder guns caused the greatest number of eye injuries in the older pediatric cohorts (11-15- and 16-20-year age groups), while detergents/chemicals accounted for nearly 1/3 of all injuries in younger children (1-5 years). Prophylactic measures targeted to specific age groups will be important in reducing eye injuries further.

Epidemiology of welding-associated ocular injuries.

PURPOSE: Currently, there exists a lack of recent epidemiological data concerning ocular injuries due to welding related activities. Our study analyzes trends in ocular injuries related to usage of welding equipment in the U.S. from 2010 to 2019. METHODS: Using the Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) Database, we queried data from January 1st 2010 to December 31st 2019 using the corresponding product code for welding equipment (896). Results were stratified by year, and standard descriptive statistical methods were applied to components including gender, age, diagnoses, and ED disposition. Circumstances leading up to the injuries were reviewed as well. RESULTS: Between 2010 and 2019 a total of 109,127 welding-associated ocular injuries occurred in the United States (95% CI, 86937-131,316). Estimates show a decreasing trend in cases from 13,415 (95% CI, 9979-16,851) in 2010 to 6944 (95% CI, 4868-9020) in 2019. A majority of cases occurred in men (98.2%) and in the 10-49 year age range (83.8%). 3.3% of cases involved spectators and 44% were bilateral. The top three ocular injury diagnoses were flash burns (62.1%), foreign body implantation (19.6%), and contusions/abrasions (11.1%). The number of radiation injuries trended down from 9286 in 2010 to 4023. With respect to a documented location, 38.9% occurred at home and 4.5% occurred in a school setting. Most patients (99.9%) were discharged from the ED; 0.1% were admitted to the hospital. CONCLUSIONS: The data suggests that number of ocular injuries related to welding has decreased significantly over the past 10 years. The most common injuries were radiation burns, foreign body disruption, and contusions/abrasions of the eye. Patients were predominantly men and between the ages of 10 and 49. Of note, almost half of all ocular injuries due to welding were bilateral, and 3% of ocular injuries were seen in spectators.

Epidemiology of ocular injuries associated with landscaping tools.

The purpose of this retrospective, cross-sectional study was to determine and analyze the trends in ocular injuries related to landscaping activities and equipment from 2010 to 2019. A total of 168,845 ocular injuries were associated with landscaping activities with the majority of cases occurring in men (80.4%) between the ages of 41-60 during the summer months of June, July, and August. The majority of ocular injuries did not require admission (97.8%) but of those that were admitted 42% had an open globe injury (n = 399). The results of this investigation provide useful information for emergency room physicians and ophthalmologists in understanding the prevalence of these landscaping-associated ocular injuries and further draw suspicion for the incidence of open globe injuries in this population.

Predictive factors of enucleation after open globe injuries.

BACKGROUND: Trauma is the leading cause of enucleations in the USA. Current information regarding open globe injuries (OGI) is based mainly on data from individual tertiary care centers across the country which might skew the findings towards the population served by these level-one trauma centers. The aim of this study is to evaluate the demographics, characteristics, and risk factors of traumatic enucleations in a large data sample. METHODS: Descriptive cross-sectional observational study using the National Inpatient Sample (NIS) Database from 2002 to 2013. Inpatients with traumatic enucleations were identified using ICD-9 codes. Chi-square and logistic regression analyses were used to identify differences between the enucleated and non-enucleated cohorts and to evaluate the predictive factors of enucleation in OGIs. RESULTS: Enucleations were performed in 3020 (6.2%) of 48,563 OGIs identified. The average age in the enucleated cohort for males vs. females was 44.7 vs. 62.2 years. In the USA, the highest number of traumatic enucleations occurred in the 21-40 group (41.8%) and the fewest in the 80+ age group (11.8%). The risk of enucleation decreased across the age groups significantly. Compared with the 21-40 age group, the risk of undergoing enucleation was 15% lower in patients 41 to 60 years of age, 35% in patients 61 to 80, and 40% lower in patients over 80. In total, 5.1% OGIs in women and 6.7% of OGIs in men were enucleated. The risk of enucleation was 29% higher in men than in women. The highest absolute number of enucleations was seen in Whites. Compared with Whites, Blacks had a 63% higher risk of enucleation following an OGI. OGIs with rupture-type injury, endophthalmitis, or phthisis were significantly higher odds to be enucleated. CONCLUSIONS: The risk of enucleation following traumatic OGI significantly increased for patients who were in the 21-40 age group, of Black race, or of male gender; the risk also increased if the injury was a rupture-type or associated with endophthalmitis or phthisis. The risk of depression was 75% higher in enucleated patients versus non-enucleated patients.

EARLY RETINAL MICROVASCULAR ABNORMALITIES IN YOUNG ADULTS WITH TYPE 1 DIABETES MELLITUS WITHOUT CLINICALLY EVIDENT DIABETIC RETINOPATHY.

PURPOSE: To characterize the early retinal microvascular changes in young adults (age: 22.69 ± 3.50 years) with Type 1 diabetes mellitus without clinically detectable diabetic retinopathy using optical coherence tomography angiography and investigate the associated factors. METHODS: A total of 36 participants with Type 1 diabetes mellitus (70 eyes) and 34 healthy controls (57 eyes) were retrospectively reviewed. The analyzed optical coherence tomography angiography indices included capillary vessel density, foveal avascular zone area/perimeter/acircularity index, and foveal vascular density, acquired in the 6 × 6-mm2 area centered on the fovea. The generalized estimation equations model was applied to compare the mean values and to study the associated factors. RESULTS: In subjects with diabetes, statistically significant decreases were observed in parafoveal vessel density in both superficial and deep capillary plexuses, foveal avascular zone area/perimeter, and foveal vascular density when compared with controls (all P < 0.05). Higher glycated hemoglobin level was independently associated with the decrease of parafoveal vessel density as well as the increase of foveal avascular zone area/perimeter (all P < 0.05). Prepubescent onset of diabetes mellitus was also independently associated with the decrease of superficial parafoveal vessel density, foveal avascular zone area/perimeter, and foveal vascular density (P = 0.015, 0.011, 0.015, and 0.001, respectively). CONCLUSION: In young adults with Type 1 diabetes mellitus lacking clinical signs of diabetic retinopathy, optical coherence tomography angiography revealed alterations in retinal microvasculature that were associated with glycated hemoglobin level and onset of diabetes mellitus related to puberty.

Endogenous endophthalmitis in patients with intravenous opioid use: demographics and associated comorbidities.

PURPOSE: To identify risk factors for endogenous endophthalmitis (EE) in hospitalized adults, under 65 years of age, with a history of intravenous opioid use and non-ocular infection. METHODS: The National Inpatient Sample Database was used to identify cases of EE with a recent history of intravenous opioid use disorder with associated non-ocular infection. Systemic and ocular comorbidities were identified using codes from the International Classification of Diseases, Ninth Revision (ICD-9). Descriptive and regression analyses were performed to evaluate the risk factors for EE using IBM SPSS 23. RESULTS: Of the 605,859 inpatients, 21-65 years age, who had a history of recent opioid-IVDU and an associated IVDU-associated systemic infection, 363 (0.1%) had EE. Systemic comorbidities such as diabetes mellitus, mitral valve disease, aortic valve disease, history of cardiac valve transplantation, chronic kidney disease/renal failure, cirrhosis, active or previous radiation therapy, and history of solid organ transplantation were significantly more prevalent in patients with EE. A significantly increased risk of EE in intravenous opioid users was noted if they were of male gender (OR = 1.84), Asian/Pacific Islander ethnicity (OR = 4.41), had history of cirrhosis (OR = 2.33), active or history of radiation therapy (OR = 14.74), history of solid organ transplantation (OR = 5.91), candidemia (OR = 15.22), and infectious endocarditis (OR = 4.83). Conversely, concurrent alcohol use disorder (OR = 0.35) decreased the risk of EE. CONCLUSION: Various demographic variables and systemic comorbidities increased the risk of developing EE in inpatients with a history of intravenous opioid use with associated non-ocular infection.

Improving outcomes in retinal detachment: the potential role of rho-kinase inhibitors.

PURPOSE OF REVIEW: Retinal detachment initiates a series of events that lead to degenerative changes in retinal synaptic architecture as well as the well-known phenomena of gliosis and photoreceptor apoptosis. Retinal reattachment does not always result in complete visual recovery, even if the fovea is not directly involved in the detachment. Rho-kinase (ROCK) inhibitors may mitigate some of these deleterious changes including disruption of synaptic architecture, photoreceptor apoptosis, and initiation of the epithelial-mesenchymal transition that characterizes proliferative vitreoretinopathy (PVR). This review focuses on the use of ROCK inhibitors to modulate synaptic disjunction. RECENT FINDINGS: ROCK inhibition prevents retinal detachment-induced photoreceptor synaptic terminal retraction (i.e., synaptic disjunction), thereby diminishing the damage of the first synapse in the visual pathway. ROCK inhibition also reduces retinal detachment-induced photoreceptor apoptosis and suppresses PVR progression in preclinical models. SUMMARY: Inhibition of ROCK may help to optimize visual recovery after retinal detachment surgery or iatrogenic detachments during cell transplantation or viral subretinal injection and might play a role in reducing the risk of PVR after retinal detachment surgery.

Assessing the risk of stroke development following retinal artery occlusion.

BACKGROUND: Retinal artery occlusion (RAO) can cause acute, painless, and irreversible loss of vision. Using a large sample population database, we investigated the possible impact of RAO and numerous other clinical and non-clinical factors on the risk of developing a subsequent cerebrovascular accident. METHODS: Cases of RAO were obtained from the National Inpatient Sample (NIS) database between 2002 and 2013 using ICD-9 codes. Associated morbidities and procedures were assessed in these cases with a primary hospital admitting diagnosis of stroke. Univariate and multivariate logistic regression analyses were carried out in RAO cases to determine risk factors for stroke. The Bonferroni correction method was applied. RESULTS: The RAO group consisted of 19,809 cases that were separated into stroke (n=1,157, 55% male, mean age: 69±0.4 years) and non-stroke (n=18,652, 55% male, mean age: 68±0.1) cohorts. Age groups associated with reduced risk of stroke with respect to were 20-39 (OR: 0.391), 40-59 (OR: 0.842), and 60-79 (OR: 0.837). No cases of stroke were present for ages < 20. Other factors associated with a reduced stroke risk were carotid stenosis (OR: 0.187), transient ischemic attack (OR: 0.064), coronary artery disease (OR: 0.788), cardiac catheterization (OR: 0.481), and septicemia (OR: 0.333). Factors associated with an increased risk of stroke included hypertension (OR: 1.418), tobacco use (OR: 1.568), valvular disease (OR: 1.359), hyperlipidemia (OR: 1.298), and non-stroke cerebrovascular disease (OR: 2.985). CONCLUSIONS: A large patient population was used to determine that RAO patients with a history of hypertension, hyperlipidemia, tobacco usage, valvular disease, or non-stroke cerebrovascular disease had an increased risk of stroke. Patients below the age of 40 had significantly reduced the odds of stroke. Carotid stenosis, coronary artery disease, transient ischemic attacks, cardiac catheterization, and septicemia were all independently associated with a decreased risk of stroke development in RAO patients.

Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches.

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has become the standard treatment for neovascular AMD, many patients do not respond adequately to this therapy or experience a slow loss of efficacy of anti-VEGF agents after repeated administration. Additionally, current treatment with intravitreal anti-VEGF agents is associated with a significant treatment burden for patients, caregivers, and physicians. New approaches have been proposed for treating neovascular AMD. Among them, designed ankyrin repeat proteins (DARPins) seem to be as effective as monthly ranibizumab, but with greater durability, which may enhance patient compliance with needed injections.

Simulating an Anti-Vascular Endothelial Growth Factor Switch in Neovascular Age-Related Macular Degeneration: A HARBOR Subanalysis.

PURPOSE: A simulated switching study assessed the effects of continuing the same anti-vascular endothelial growth factor (VEGF) treatment among patients who typically are considered for a therapy switch. Post hoc analysis of data from HARBOR was undertaken. Patients with neovascular age-related macular degeneration who demonstrated a suboptimal response after 3 or 6 months of ranibizumab treatment were identified as switching candidates. Rather than switching, however, patients continued on ranibizumab treatment, and visual and anatomic outcomes from the point of the hypothetical switch were examined. DESIGN: Post hoc analysis of the phase 3 HARBOR clinical trial. PARTICIPANTS: Patients were included in 3- and 6-month switcher analyses if they received 3 of 3 initial monthly ranibizumab doses and 5 of 6 initial monthly ranibizumab doses, respectively, and met all the following: 5-letter or fewer gain from baseline, best-corrected visual acuity (BCVA) 20/40 or worse, and intraretinal or subretinal fluid with central foveal thickness (CFT) equal to or greater than central subfield thickness. METHODS: Patient data were examined at months 3 and 6 to identify those who met predetermined switching criteria. Best-corrected visual acuity and CFT were examined from the point at which switching criteria were met through months 6, 12, 18, and 24 of HARBOR and compared with those who did not meet the criteria. MAIN OUTCOME MEASURES: Outcome measures included mean BCVA and CFT change over time from the point (month 3 or 6) at which switching criteria were met. RESULTS: By months 3 and 6, only 44 of 1059 patients (4.2%) and 37 of 769 patients (4.8%), respectively, met the inclusion criteria for hypothetical switching. Patients who met switching criteria at month 3 gained, on average, 5.3 letters from months 3 to 12 and 2.7 letters from months 3 to 24. Month 6 switchers gained, on average, 1.6 letters from months 6 to 12 and 1.8 letters from months 6 to 24. Both groups experienced significant CFT reductions over 24 months. CONCLUSIONS: Month 3 hypothetical switchers achieved vision and anatomic improvement while continuing their original ranibizumab treatment. Month 6 switcher outcomes replicated those commonly reported in published anti-VEGF switching studies: stable vision or nominal improvements in vision with continued substantial anatomic improvement.

POSTTRAUMATIC ENDOPHTHALMITIS: An 18-Year Case Series.

PURPOSE: To describe the demographics, characteristics, management, and visual outcomes of eyes diagnosed with endophthalmitis after open globe injury. METHODS: Retrospective cohort analysis of all patients diagnosed with endophthalmitis after open globe injury from 1997 to 2015 at University Hospital, Newark, NJ. RESULTS: Twenty-six eyes were identified (all male patients; mean age: 37 ± 15 years). Cultures were positive in 16 eyes (62%), with Staphylococcus species (7 eyes, 44%) being the most common organism. Twelve eyes (46%) presented with open globe injury and concurrent endophthalmitis; 14 eyes (54%) developed endophthalmitis a mean of 14 days after open globe repair (OGR; 1 outlier of 98 days excluded). All eyes were managed with systemic and intravitreal antibiotics. The presence of intraocular foreign body (P < 0.05) and delayed primary OGR (P < 0.03) were significantly more common with concurrent versus post-OGR endophthalmitis. Four (29%) eyes in the post-OGR endophthalmitis group had corneal wound leak after OGR. Four (15%) eyes with no light perception vision were enucleated. Ten (40%) of 25 eyes with documented best-corrected visual acuity had final best-corrected visual acuity ≥20/200; final best-corrected visual acuity ranged from no light perception to 20/20. CONCLUSION: The presence of intraocular foreign body and delayed presentation were significantly more common with concurrent endophthalmitis. Twenty-nine percent of eyes that presented with endophthalmitis after OGR had a wound leak. Final best-corrected visual acuity ≥20/200 was achieved in 40% of cases.