Evidence for the Hepato-Retinal Axis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Liver health has been reported to be associated with retinal pathology in various ways. These include deposition of retino-toxins, neovascular drive, and disruption of the blood-retina barrier. Extrahepatic synthesis of implicated molecules and hemodynamic changes in liver dysfunction are also considered. The objective was to review the current evidence for and against a hepato-retinal axis that may guide further areas of preclinical and clinical investigation. METHODS: This was a systematic review. PubMed and Cochrane were queried for English language studies examining the connection between hepatic dysfunction and retinal pathology. RESULTS: Fourteen studies were included and examined out of 604 candidate publications. The studies selected include preclinical studies as well as clinical case series and studies. CONCLUSIONS: Several liver pathologies may be linked to retinal pathology as mediated by hepatically synthesized molecules. The hepato-retinal axis may be present and further, targeted studies of the axis are warranted. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Incidence of ocular pathology following bariatric surgery for with morbid obesity across a large United States National Database.

BACKGROUND/OBJECTIVES: Bariatric surgery, as indicated for treatment of morbid obesity, has been studied in association with short term effects on ocular pathology. However, effects of surgery on postoperative disease incidence is largely unknown. SUBJECTS/METHODS: In this retrospective cohort study, the TriNetX United States Collaborative Network national database, was queried for patients with an ICD-10 code for morbid obesity and a procedural code for bariatric surgery. Patients were propensity score matched across baseline demographics at the time of surgery and compared to those presenting with an ICD10 code for morbid obesity with no records of a procedural code for bariatric surgery, identifying 42,408 patients per cohort. New diagnoses or procedural codes found after the surgical index date for diabetic retinopathy, age-related macular degeneration, glaucoma, low vision, and blindness along with pertinent treatment metrics were monitored. RESULTS: Bariatric surgery was found to be associated with reduced future risk of diabetic retinopathy (RR: 0.283; 95% CI: 0.252-0.319), macular edema (RR: 0.224; 95% CI: 0.170-0.297), vitreous hemorrhage (RR: 0.459; 95% CI: 0.323-0.653), ocular hypertension (RR: 0.387; 95% CI: 0.387-0.487), glaucoma (RR: 0.360; 95% CI: 0.326-0.399), use of ocular pressure lowering medications (RR: 0.565; 95% CI: 0.496-0.644), age-related macular degeneration (RR: 0.628; 95% CI: 0.447-0.882), cataract surgery (RR: 0.524; 95% CI: 0.448-0.612), and low vision and blindness (RR: 0.328; 95% CI: 0.294-0.365) compared to patients not surgically managed. CONCLUSIONS: The present analysis comprising a large US cohort of patients suggests that bariatric surgery is associated with a decreased risk of future ocular morbidity and mortality.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-Term Visual Outcomes in Patients With Idiopathic Epiretinal Membrane Surgery.

BACKGROUND AND OBJECTIVE: Our aim was to assess long-term outcomes following surgical repair of idiopathic epiretinal membrane (ERM) with pars plana vitrectomy (PPV) and membrane peel (MP). PATIENTS AND METHODS: A retrospective study evaluated patients with idiopathic ERM who underwent surgical repair at a single academic tertiary center with five to nine years of postoperative follow-up, assessing preoperative characteristics, surgical techniques, best visual acuity (BVA), and optical coherence tomography biomarkers at various time points. RESULTS: The study involved 67 patients (72 eyes) with an average postoperative follow-up of 82.8 ± 18.8 months. Patients with cone outer segment tips integrity at initial presentation and 1-year follow-up and patients with external limiting membrane and ellipsoid zone integrity at 1-year follow-up were noted to have significantly better long-term visual acuity than those without. More than 85% of patients achieved a BVA > 70 seven years after surgical repair. CONCLUSIONS: Vitreoretinal surgery for idiopathic ERM resulted in improved anatomical recovery and sustained visual acuity gain over long-term follow-up. [Ophthalmic Surg Lasers Imaging Retina 2024;55:70-77.].

Impact of Dyslipidemia Medications on the Prevalence of Diabetic Retinopathy Among a Large US Cohort.

BACKGROUND AND OBJECTIVE: Dyslipidemia medications such as statins and fibrates may be associated with a reduction in diabetic retinopathy (DR) progression, but real-world data is lacking. This study evaluates cholesterol-lowering medications and their association with the prevalence of DR and advanced DR complications. PATIENTS AND METHODS: Data was collected using codes from the International Classification of Diseases on TriNetX, a cross-sectional database of over 79 million Americans, between June and August 2022. Prevalence and prevalence odds ratios (POR) were calculated. RESULTS: Patients taking pitavastatin (OR 0.64, 95% CI 0.49, 0.84), fenofibrate (OR 0.83, CI 0.79, 0.87), or evolocumab (OR 0.80, CI 0.68, 0.95) had lower POR of proliferative DR compared to nonproliferative DR. Patients taking any cholesterol medication had a lower POR of vitreous hemorrhage. Patients taking fibrates also had lower POR of neovascular glaucoma. CONCLUSION: This exploratory study highlights positive associations between DR and dyslipidemia and medications that may have fewer worsening events in DR patients. [Ophthalmic Surg Lasers Imaging Retina 2023;54:626-633.].

Time to fellow eye involvement in patients with unilateral diabetic macular oedema.

OBJECTIVE: To examine the time to onset of disease in the fellow eye of patients with unilateral DMO in routine clinical practice and to identify risk factors for development of bilateral DMO. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred forty treatment-naive patients 18 years or older with unilateral DMO presenting to Cole Eye Institute between January 2012 and July 2021. METHODS: Records of patients with unilateral DMO were reviewed for development of DMO in the fellow eye. Demographic, diabetic, ocular, and systemic characteristics were collected at initial DMO diagnosis date. Bivariate and multivariate analyses were performed and significant factors were modelled using Kaplan-Meier curves. RESULTS: Fifty patients with conversion to bilateral DMO and 90 patients without conversion were identified. Average time to bilateral DMO was 15.0 ± 15.7 months. 64% of patients converted within 1 year and 90% converted within 3 years. HbA1c (p = 0.003), diabetic retinopathy duration (p = 0.029), and diabetic foot disease (DFD) (p = 0.002) were identified as significant risk factors for conversion. Patients with better visual acuity at time of initial diagnosis and history of panretinal photocoagulation (PRP) (p = 0.044) or focal laser (p = 0.035) in the primary eye were also more likely to convert. CONCLUSIONS: Participants were most likely to develop fellow eye DMO within the first year after initial DMO diagnosis. In routine clinical practice, poor glycaemic control and DFD were risk factors associated with bilateral eye involvement. Clinicians may consider screening the fellow eye of high-risk individuals at each appointment within the first year of diagnosis.

Functional Imaging of Mitochondria in Age-Related Macular Degeneration Using Flavoprotein Fluorescence.

PURPOSE: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. METHODS: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. RESULTS: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity (P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity (P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity (P = 0.018 and 0.024, respectively). CONCLUSIONS: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [Ophthalmic Surg Lasers Imaging Retina 2023;54:24-31.].

Interventions to reduce loss to follow up in common retinal pathology: A systematic review.

PURPOSE: Loss to follow-up or fragmented follow-up episodes (LTFU) may contribute to suboptimal clinical outcomes, especially when comparing real world data to clinical trials. This systemic review gathers available evidence around interventions meant to decrease the LTFU in AMD, RVO, and DME patients. PATIENTS AND METHODS: PubMed was queried using a literature search strategy and reviewed by the authors. Studies with interventions aimed at reducing lost to follow up were included. RESULTS: Ten studies were extracted from 89 candidate publications. DISCUSSION: Telephone interventions featuring assistance in scheduling in improving LTFU in urban, African American populations over 50 years old with diabetic retinopathy. The same interventions have shown promise in glaucoma, but remain understudied in AMD, RVO, and other geographic, ethnic, and socioeconomic demographics. CONCLUSION: No sole intervention with efficacy in improving LTFU has been developed. A standardized definition of LTFU, as well as testing interventions across broad age, geography, ethnic, racial, and socioeconomic lines. Longitudinal data would also add credence to the efficacy of purported interventions. OTHER: No sources of funding for this article.

Visual, Anatomic Outcomes, and Natural History of Retinal Nerve Fiber Layer Schisis in Patients Undergoing Epiretinal Membrane Surgery.

PURPOSE: To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERMs) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice. DESIGN: Retrospective case-control study. PARTICIPANTS: Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013 to 2021. METHODS: Patients were grouped by the presence or absence of sRNFL before surgery. Preoperative and postoperative data were collected regarding visual acuity (VA), changes in central subfield thickness (CST) over time, and presence of cystoid macular edema. MAIN OUTCOME MEASURES: Frequency of sRNFL in patients undergoing idiopathic ERM surgery. RESULTS: Overall, 48 (53.9%) of 89 patients presented with sRNFL. Schisis of the retinal nerve fiber layer patients presented with significantly decreased VA compared with those without (58.63 ± 12.48 vs. 67.68 ± 7.84 ETDRS letters, P < 0.001, respectively). At the final follow-up after ERM removal, there was no significant difference in final VA in patients with sRNFL compared with those without (71.16 ± 2.93 vs. 74.11 ± 2.76, P = 0.467). At presentation, patients with sRNFL had greater CST than those without (454 ± 10.01 vs. 436 ± 0.23, P = 0.23). This difference persisted at the 90-day follow-up after ERM removal (402 ± 8.08 vs. 375 ± 10.19 µm, P = 0.043). The resolution of sRNFL was reported at postoperative week 1 in 30 (96.7%) of 31 cases. CONCLUSIONS: Schisis of the retinal nerve fiber layer is a microstructural feature in > 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Impact of Travel Distance on Rhegmatogenous Retinal Detachment Presentation and Outcomes.

BACKGROUND AND OBJECTIVE: Rhegmatogenous retinal detachment (RRD) requires urgent surgical intervention. The effect of travel distance on RRD outcomes is unclear. PATIENTS AND METHODS: This retrospective cohort study included 642 patients who underwent RRD repair at Cole Eye Institute from 2012 to 2020. Google Maps was used to calculate the travel distance in miles from the residential zip code to the presenting and surgery location addresses. Multivariable logistic and bivariate linear regressions were used to compare macula-off status and best-corrected visual acuity (BCVA) in ETDRS letters at presentation and at 6-month follow-up, with patient travel distance divided into < 25 miles, 25 to 50 miles, and > 50 miles. RESULTS: Four hundred sixty-two patients were examined in the final cohort. The retinal reattachment rate was 94.3% for less than 25 miles, 96.3% for 25 to 50 miles, and 95.9% for greater than 50 miles (P = 0.63). In multivariable analysis, distance to presenting location was not associated with macula-off status (P = 0.69) or BCVA at follow-up (P = 0.27). Oneway analysis of distance and time from presentation to surgery in days revealed that distance to surgical site was associated with longer time to surgery (P = 0.003). Subset analysis of patients with income less than $25,520 (n = 18) revealed greater distance to presenting and surgical location was associated with longer time to surgery (P < .0001), but was not associated with BCVA at follow-up (P = 0.53). CONCLUSIONS: This data suggests that patients who live further from the hospital achieve equivalent outcomes from RRD repair, despite delays in surgery. [Ophthalmic Surg Lasers Imaging Retina 2022;53:666-672.].

Progression to Vision-Threatening Retinopathy Complications Following Panretinal Laser for Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To report the time in which patients with panretinal photocoagulation (PDR) progress to vision-threatening retinopathy (VTR) complications after receiving PRP, and risk factors in routine clinical practice. PATIENTS AND METHODS: Records of patients with complete PRP for PDR were retrospectively reviewed for up to 3.5 years after PRP. Two hundred twenty eyes were selected. RESULTS: Time from PRP to VTR was 1.25 ± 0.82 years. Age, Black race, neovascularization of the disc on examination, diabetic foot disease (DFD), and high-risk PDR characteristics on fluorescein angiography were identified as significant risk factors. Half of patients with DFD on examination developed a VTR within 1.5 years after PRP (P < .001). CONCLUSION: In clinical practice, providers may consider DFD and Black race as predictors of time to VTR event within 4 years after PRP in patients with PDR. [Ophthalmic Surg Lasers Imaging Retina. 2022;53(4):186-193.].