Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

Treatment discontinuation patterns of anti VEGF in retinal vein occlusion.

OBJECTIVE: The purpose of this research is to report on real-world anti-vascular endothelial growth factor (anti-VEGF) treatment patterns in retinal vein occlusions (RVO). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive RVO patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Medical records available until June 2022 were reviewed. Demographics, diagnosis, number of injections, treatment length, reason for discontinuation, and baseline and final data (e.g., date, age, best-corrected visual acuity [BCVA], and central subfield thickness) were recorded. Statistical analyses performed with STATA 17.0 assessed differences between baseline and final values, branch (BRVO) and central retinal vein occlusion (CRVO), and treatment-discontinuation subgroups. RESULTS: A total of 219 treatment-naive eyes were included (70.3 ± 13.2 years of age, 52.5% female), with 99 BRVOs and 120 CRVOs (2482 injections). The discontinuation rate was 76.7% (168 of 219), with 72.7% of patients (77 of 99) with BRVOs and 75.8% of patients (91 of 120) with CRVOs discontinuing injections. Reasons for discontinuation included stable off active therapy (98 eyes), severe comorbidity or death (17 eyes), switched to intraocular steroid (implant or injection) (12 eyes), lack of visual benefit (10 eyes), ocular comorbidity (5 eyes), patient decision (5 eyes), and patient transfer (5 eyes). Among the remaining 67 eyes, 16 (24%) were lost to follow-up. Reasons for discontinuation differed between BRVO and CRVO patients (p = 0.002). Eyes with CRVO presented with worse BCVA (p < 0.0001) and achieved worse final BCVA (p < 0.0001), but both groups experienced improvements (p < 0.0001). Younger age, better baseline BCVA, and a diagnosis of BRVO were independent predictors of better final visual acuity. CONCLUSION: Over 7.5 years, treatment was discontinued for three-quarters of RVOs. Stable disease was the most common reason for discontinuation, with nearly half (45%) of all RVOs in the cohort stable off active therapy. Better visual outcomes were achieved in BRVO than in CRVO, although both groups benefited from treatment.

Assessing the Performance of a Novel Bayesian Algorithm at Point of Care for Red Eye Complaints.

The current diagnostic aids for red eye are static flowcharts that do not provide dynamic, stepwise workups. The diagnostic accuracy of a novel dynamic Bayesian algorithm for red eye was tested. Fifty-seven patients with red eye were evaluated by an emergency medicine physician who completed a questionnaire about symptoms/findings (without requiring extensive slit lamp findings). An ophthalmologist then attributed an independent "gold-standard diagnosis". The algorithm used questionnaire data to suggest a differential diagnosis. The referrer's diagnostic accuracy was 70.2%, while the algorithm's accuracy was 68.4%, increasing to 75.4% with the algorithm's top two diagnoses included and 80.7% with the top three included. In urgent cases of red eye (n = 26), the referrer diagnostic accuracy was 76.9%, while the algorithm's top diagnosis was 73.1% accurate, increasing to 84.6% (top two included) and 88.5% (top three included). The algorithm's sensitivity for urgent cases was 76.9% (95% CI: 56-91%) using its top diagnosis, with a specificity of 93.6% (95% CI: 79-99%). This novel algorithm provides dynamic workups using clinical symptoms, and may be used as an adjunct to clinical judgement for triaging the urgency of ocular causes of red eye.

Quality of life and caregiver burden in pediatric glaucoma: A systematic review.

Pediatric conditions can lead to significant caregiver burden and poor quality of life (QoL). This systematic review describes research relating to caregiver burden and QoL of caregivers of pediatric glaucoma patients. A systematic database search of Embase, Medline, PsycINFO, CINAHL, Web of Science, and the three journals within the Association for Research in Vision and Ophthalmology (ARVO) was conducted in October 2021. Publications underwent abstract and full-text screening and were included if they reported pediatric caregivers' QoL using quantitative or qualitative methods. Review articles, publications not in English, and articles focusing on adult glaucoma patients were excluded. Studies then underwent risk of bias assessment and data extraction. Of the 105 publications identified, 8 publications with 667 participants were included in the review. Studies indicated significantly higher burden and poor QoL in caregivers. Female sex, lower education level, lower income, and working status of caregivers were associated with poorer QoL and greater burden. Additionally, more severe and longer duration of the child's disease negatively impacted these measures of caregiver wellbeing. Additionally, studies found significant improvement in caregiver QoL after patients underwent surgery with combined trabeculotomy-trabeculectomy. In conclusion, few studies have investigated the impact of pediatric glaucoma on caregivers. This review of the existing studies found poor QoL and high levels of caregiver burden within this population. Given the lifelong nature of pediatric glaucoma, there is a need for further longitudinal research focusing on the caregivers of these pediatric patients. Long-term follow-up would allow for a greater understanding of how caregiver QoL changes over the course of the disease.

Evaluating the Diagnostic Accuracy of a Novel Bayesian Decision-Making Algorithm for Vision Loss.

The current diagnostic aids for acute vision loss are static flowcharts that do not provide dynamic, stepwise workups. We tested the diagnostic accuracy of a novel dynamic Bayesian algorithm for acute vision loss. Seventy-nine "participants" with acute vision loss in Windsor, Canada were assessed by an emergency medicine or primary care provider who completed a questionnaire about ocular symptoms/findings (without requiring fundoscopy). An ophthalmologist then attributed an independent "gold-standard diagnosis". The algorithm employed questionnaire data to produce a differential diagnosis. The referrer diagnostic accuracy was 30.4%, while the algorithm's accuracy was 70.9%, increasing to 86.1% with the algorithm's top two diagnoses included and 88.6% with the top three included. In urgent cases of vision loss (n = 54), the referrer diagnostic accuracy was 38.9%, while the algorithm's top diagnosis was correct in 72.2% of cases, increasing to 85.2% (top two included) and 87.0% (top three included). The algorithm's sensitivity for urgent cases using the top diagnosis was 94.4% (95% CI: 85-99%), with a specificity of 76.0% (95% CI: 55-91%). This novel algorithm adjusts its workup at each step using clinical symptoms. In doing so, it successfully improves diagnostic accuracy for vision loss using clinical data collected by non-ophthalmologists.

Lacrimal Gland Hypoplasia and Corneal Anesthesia in MIRAGE Syndrome: A Case Report and Literature Review.

PURPOSE: The purpose of this report was to describe the ocular findings in Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital problems, and Enteropathy (MIRAGE) syndrome, a multisystem congenital disorder. METHODS: This was a case report and literature review. RESULTS: An infant with MIRAGE syndrome (combined immunodeficiency with recurrent infections, growth restriction, adrenal insufficiency, 46,XY karyotype with hypovirilization, dysphagia, gastroesophageal reflux disease, and dysautonomia) underwent ophthalmological evaluation because of persistent conjunctivitis during his 8-month admission in the neonatal intensive care unit. His parents noted absence of tears when crying since birth. Bilateral broad corneal epithelial defects were noted, and treatment was initiated with frequent lubricating ointment. At 9 months, his vision was estimated at 20/380 in both eyes using Teller Acuity Cards. There were persistent bilateral epithelial defects, confluent punctate epithelial erosions, low Schirmer strip wetting (right eye 3 mm and left eye 2 mm), and decreased corneal sensation. Brain magnetic resonance imaging images demonstrated hypoplastic lacrimal glands bilaterally. More aggressive lubrication and installation of punctal plugs in all 4 lids were successful at preventing further epithelial defects. CONCLUSIONS: This case presents deficient lacrimation as a manifestation of MIRAGE syndrome and is the first to identify lacrimal gland hypoplasia and corneal anesthesia. Autonomic and neurologic dysfunction have been proposed to play a role in the pathophysiology of hypolacrimation in similar syndromes and likely contributed to the poor ocular surface in this case. Patients with MIRAGE should undergo ophthalmic assessment as soon as possible after birth because early intervention is essential to preventing irreversible corneal damage.

Dry eye disease and psychiatric disorders: A systematic review and meta-analysis.

The association between dry eye disease (DED) and psychiatric conditions is a highly researched topic. This work reviews the literature on this relationship, examining the prevalence and correlations of depression and anxiety with dry eye signs and symptoms. A comprehensive literature search of MEDLINE, EMBASE, PsycINFO, and gray literature was conducted, with keywords for dry eye and mood disorders, depression, anxiety, and suicide. Eligible studies underwent quality assessment using the Newcastle-Ottawa Scale. Meta-analysis was performed using STATA 15.0. Fixed- and random-effects models were computed based on the presence of heterogeneity. Thirty-two studies were included, with 31 reporting on depression and 19 on anxiety. Meta-analysis results found a depression prevalence of 40% (CI: [0.29, 0.52]) in DED patients, with 1.81 times higher odds of prevalence compared to controls (CI: [1.61, 2.02]). Prevalence of anxiety was 39% (CI: [0.15, 0.64]), with 2.32 times higher odds of prevalence compared to controls (CI: [1.67, 3.23]). Depression scores were significantly higher in patients with DED in all studies. Anxiety scores were significantly higher in DED patients in studies using all scales except the Hospital Anxiety and Depression Scale-Anxiety Subscale. DED symptom scores were significantly associated with depression (ES = 0.43; CI: [0.31, 0.55]) and anxiety (ES = 0.41; CI: [0.32, 0.50]) scores. In conclusion, depression and anxiety are more prevalent and severe in DED patients and are correlated with dry eye symptoms but not signs. These findings highlight the interrelationship between these disorders and have important implications for providing appropriate care to these patients.

Cyclin-like proteins tip regenerative balance in the liver to favour cancer formation.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. A variety of factors can contribute to the onset of this disease, including viral infection, obesity, alcohol abuse and non-alcoholic fatty liver disease (NAFLD). These stressors predominantly introduce chronic inflammation leading to liver cirrhosis and finally the onset of HCC; however, approximately 20% of HCC cases arise in the absence of cirrhosis via a poorly defined mechanism. The atypical cyclin-like protein Spy1 is capable of overriding cell cycle checkpoints, promoting proliferation and has been implicated in HCC. We hypothesize that Spy1 promotes sustained proliferation making the liver more susceptible to accumulation of deleterious mutations, leading to the development of non-cirrhotic HCC. We report for the first time that elevation of Spy1 within the liver of a transgenic mouse model leads to enhanced spontaneous liver tumourigenesis. We show that the abundance of Spy1 enhanced fat deposition within the liver and decreased the inflammatory response. Interestingly, Spy1 transgenic mice have a significant reduction in fibrosis and sustained rates of hepatocyte proliferation, and endogenous levels of Spy1 are downregulated during the normal fibrotic response. Our results provide support that abnormal regulation of Spy1 protein drives liver tumorigenesis in the absence of elevated fibrosis and, hence, may represent a potential mechanism behind non-cirrhotic HCC. This work may implicate Spy1 as a prognostic indicator and/or potential target in the treatment of diseases of the liver, such as HCC. The cyclin-like protein Spy1 enhances lipid deposition and reduces fibrosis in the liver. Spy1 also promotes increased hepatocyte proliferation and onset of non-cirrhotic hepatocellular carcinoma (HCC). Thus, Spy1 may be used as a potential target in the treatment of HCC.

Trends in low vision care provided by ophthalmologists in Ontario between 2009 and 2015.

OBJECTIVE: Little is known about how low vision services by ophthalmologists are being provided. Here, we analyze the patterns of provision and utilization of vision rehabilitation services in Ontario, Canada. DESIGN: Retrospective population-based study between 2009 and 2015. PARTICIPANTS: Ophthalmologists (n = 92) who billed for vision rehabilitation services through the Ontario Health Insurance Plan in Ontario and the patients (n = 8949) who received these services. METHODS: Billing data for low vision services (2009-2015) was received from Ontario Health Insurance Plan. Data were analyzed to describe patient demographics (age, sex, geographic distribution, number, and type of visits) and service provider information (geographic location, number of years providing services, and number of services per year). RESULTS: It is estimated that ≤ 5% of patients with low vision in Ontario accessed these vision rehabilitation services by ophthalmologists. The majority of these patients were females (61%) and > 60 years old (79%). While patient and provider geographic distributions overlapped in the areas with largest patient populations, many regions lacked services. The majority of patients (71%) made only one vision rehabilitation visit. Nine providers practiced low vision for 7 years, while 43 provided services for only 1 year. In 2015, the most common diagnostic service provided to low vision patients was Optical Coherence Tomography of the retina and the most common therapeutic service was intravitreal for wet age-related macular degeneration. CONCLUSION: Although low vision services increased between 2009 and 2015, there were differences in ability to access care based on age, sex, and geographic location.