Long-Term Outcomes in Early versus Limited Response to Anti-VEGF Treatment for Retinal Vein Occlusion.

OBJECTIVE: Macular edema secondary to retinal vein occlusion (RVO) is a sight-threatening condition. Previous studies showed that early responders (ERs) who respond well to anti-VEGF injections within 3 months of treatment have better outcomes, as measured by best visual acuity (BVA) and central subfield thickness (CST) at 12 months postinjection initiation compared with limited early responders (LERs). This study analyzed whether ER eyes continue to respond better than LER eyes over longer periods. This study also aimed to identify baseline comorbidities associated with response status. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients aged > 18 years with RVO-related macular edema treated with anti-VEGF injections. METHODS: Patients were categorized as ERs or LERs. Limited early responder eyes were defined as having CST reduction < 10%, BVA gain < 5 ETDRS letters, or both at 3 months after anti-VEGF initiation. Best visual acuity and CST changes over the 24- and 36-month period after the first anti-VEGF treatment were compared between ERs and LERs. Patient characteristics and systemic comorbidities were identified by chart review. Statistical analysis involved the Levene test, Welch t test, and Welch analysis of variance. MAIN OUTCOME MEASURES: Best visual acuity and CST changes over the initial 24-month and 36-month periods after treatment. RESULTS: The 24-month cohort included 68 ERs and 39 LERs, and the 36-month cohort included 58 ERs and 33 LERs. At the 24-month time point, there were significant differences in BVA and CST gains between ERs (+19.8 letters, -221.2 um) and LERs (-2.4 letters, -90.1 um; P < 0.001, P < 0.01). Similarly, at 36 months, there were significant differences in BVA and CST gains between ERs (+17.7 letters, -229.3 um) and LERs (+1.3 letters, -128 um; P < 0.001, P < 0.05). After controlling for differences in baseline BVA and CST, only the 24-month change in BVA remained significant (P < 0.001). There were no significant associations between response status and cardiopulmonary, endocrine, and oncologic comorbidities. CONCLUSIONS: Early responder eyes with branched retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) have better functional responses to anti-VEGF injections at 24 months compared with LER eyes, even after controlling for baseline differences. Early identification of eyes as ERs or LERs in BRVO and CRVO may predict long-term functional prognoses. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characterizing and Predicting Limited Early Response in Eyes With Retinal Vein Occlusion Using Machine Learning in Routine Clinical Practice.

OBJECTIVE: To characterize and predict limited early responders (LER) in eyes with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (anti-VEGF). PATIENTS AND METHODS: This retrospective cohort study of 116 eyes with edema secondary to RVO characterized early responders (ER) and LER 3 months after initiating anti-VEGF treatment. Baseline characteristics and 12-month outcomes were compared. A machine learning (ML) algorithm was developed to predict LER. RESULTS: At baseline, LER had higher best-corrected visual acuity (BCVA) than ER (P< 0.0001) and lower central subfield thickness (CST) than ER (P< 0.01). At 12 months, change in BCVA was + 0.8 and + 21.4 letters, and change in CST was -104.4 and -187.1 µm for LER and ER, respectively (P < 0.0001, P < 0.05). The ML algorithm achieved area under the receiver operating characteristic curve = 0.73. CONCLUSION: ER eyes experienced greater functional and anatomical improvements at 12 months in routine clinical practice than LER. The ML algorithm achieved moderately high performance predicting LER. [Ophthalmic Surg Lasers Imaging Retina 2023;54:231-237.].

Baseline factors and reason for cancellation of elective ophthalmic surgery.

OBJECTIVES: To determine the baseline risk factors for elective ophthalmic surgery cancellations and characterise the reasons for cancellation. METHODS: This is a retrospective, non-randomised study performed at a large tertiary ophthalmic centre. It included a consecutive sample of patients above the age of 18 who had an ophthalmic surgery scheduled at Cole Eye Institute, Cleveland Clinic, OH between January 2012 and December 2019. An automated search pull identified 75,908 scheduled surgeries (63,987 completed and 11,921 cancelled surgeries). Statistical analysis was performed using R (version 3.5.1). Main outcome measures were baseline factors that impact risk for surgery cancellation and reasons for surgery cancellation. RESULTS: Analysis was performed on 69,963 scheduled surgeries (57.37% Female, 42.63% Male; Mean age of 62.72 years; 59,959 completed and 10,004 cancelled surgeries). Of the 2384 cancelled surgeries with reasons provided, the most common causes of cancellation were patient refusal (38.42%), patient health condition (18.79%), and rescheduling of surgery (15.27%). Female sex, black race, patient age less than 50 years, non-cataract surgeries, regional mean household income greater than $82,900, Medicare insurance, and geographical distance of less than 10 miles from home to the surgery site were each associated with a significantly increased risk of surgery cancellation (p < 0.01). CONCLUSIONS: This study successfully identified several baseline factors predicting elective ophthalmic surgery cancellation. The clinical insights gained from these lines of enquiry may be used to construct models that not only identify patients at greater risk for cancellation but also highlight which interventions have greatest efficacy in preventing ophthalmic surgery cancellations.

Glial cell line-derived neurotrophic factor-induced mice liver defatting: A novel strategy to enable transplantation of steatotic livers.

Moderate macrovesicular steatosis (>30%), which is present in almost 50% of livers considered for transplantation, increases the risk of primary graft dysfunction. Our previously published data showed that glial cell line-derived neurotrophic factor (GDNF) is protective against high-fat diet (HFD)-induced hepatic steatosis in mice. Hence, we hypothesized that perfusion of steatotic livers with GDNF may reduce liver fat content before transplantation. Livers from 8 weeks of regular diet (RD) and of HFD-fed mice were perfused ex vivo for 4 hours with either vehicle, GDNF, or a previously described defatting cocktail. The liver's residual fat was quantified colorimetrically using a triglyceride (TG) assay kit and by Oil Red O (ORO) and Nile red/Hoechst staining. Liver tissue injury was assessed by using a lactate dehydrogenase (LDH) activity assay. In vitro induction of lipolysis in HepG2 cells was assessed by measuring glycerol and free fatty acid release. ORO staining showed significantly more steatosis in livers from HFD-fed mice compared with RD-fed mice (P < 0.001). HFD livers perfused with GDNF had significantly less steatosis than those not perfused (P = 0.001) or perfused with vehicle (P < 0.05). GDNF is equally effective in steatotic liver defatting compared to the defatting cocktail; however, GDNF induces less liver damage than the defatting cocktail. These observations were consistent with data obtained from assessment of liver TG content. Assessment of liver injury revealed significant hepatocyte injury in livers perfused with the control defatting cocktail but no evidence of injury in livers perfused with either GDNF or vehicle. In vitro, GDNF reduced TG accumulation in HepG2 cells and stimulated increased TG lipolysis. In conclusion, GDNF can decrease mice liver fat content to an acceptable range and could be a potential defatting agent before liver transplantation.