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PurposeTo report two cases of spontaneous closure of lamellar macular holes with epiretinal proliferation (ERP).MethodsObservational cases report.ResultsTwo patients affected with lamellar macular hole showed progressive and spontaneous closure of the hole associated with ERP development. At presentation, both patients presented with irregular foveal contour, and foveal cavitation with apparent loss of retinal tissue. In both cases, ERP, also called "lamellar hole-associated epiretinal proliferation", was present and increased in size over time. This proliferation progressively developed across the hole with apparent restoration of the foveal contour and preservation of visual acuity.ConclusionThis report describes two cases of lamellar macular hole in which ERP increased over time, resulting in lamellar macular hole closure. Such observations may suggest a spontaneous healing process driven by glial cell proliferation.

Some of the newly diagnosed NV-AMD patients could have converted from iAMD to NV-AMD since their last visit with the outside eye care provider. However, 33% of enrollees self-reported eAMD or iAMD but had other ocular pathology, mostly geographic atrophy (GA) or neovascular AMD (NV-AMD). The use of social and digital media to recruit patients with early and intermediate age-related macular degeneration. [Extracted from the article]

To examine gender differences in visual functioning using the National Eye Institute Visual Functioning Questionnaire-25 (VFQ-25) in a Colorado cohort of patients with age-related macular degeneration (AMD). A retrospective cohort study was conducted using a registry of AMD patients who attended the Sue Anschutz-Rodgers Eye Center (2014 to 2019). Demographic, clinical, and image data were collected, and AMD was categorized as Early/Intermediate AMD, or unilateral/bilateral neovascular (NV) AMD, geographic atrophy (GA), or Both Advanced using the Beckman Classification. Each patient completed the VFQ-25, which evaluates visual functioning, generating a composite score and subscale scores for vision-specific activities. Univariate and multivariable general linear models were used to estimate the associations between gender and VFQ-25 scores with parameter estimates (PE) and standard errors (SE). Among 739 patients with AMD, 294 (39.8%), 115 (15.6%), 168 (22.7%), and 162 (21.9%) were diagnosed with Early/Intermediate AMD, GA, NV AMD, and Both Advanced, respectively. Adjusted for AMD classification, age and habitual visual acuity in the better-seeing and worse-seeing eyes, female gender was not significantly associated with lower composite VFQ-25 scores (PE (SE): −1.2 (0.9), p =.193), and was significantly associated with reportedly worse ocular pain and driving subscale scores (PE (SE): −4.6 (1.0), p <.0001 and −9.1 (2.1), p <.0001, respectively). Gender plays a role in reported driving activities and ocular pain among patients with AMD. This may need to be accounted for in future research related to the use of VFQ-25 for AMD. [ABSTRACT FROM AUTHOR]

Sparse data exist regarding low vision (LV) services referral patterns. We retrospectively examined our institution's intermediate age-related macular degeneration (iAMD) patients to determine factors influencing referral. We compared visual acuity (VA) and Visual Function Questionnaire (VFQ-25) composite and subscale scores for referred and non-referred iAMD patients. VA was collected at time of referral or most recent visit, and VFQ-25 was taken upon enrollment into the registry. Thirty-six (15.5%) of the 232 iAMD patients were referred to LV. Referred patients were more likely to have older age, worse VA in both eyes, and lower VFQ-25 scores. Univariate analysis of VFQ-25 subscales demonstrated worse scores in general vision, near, distance, mental health, role limitations, dependency, and driving. Multivariable analysis revealed lower scores in general health, general vision, and driving. Forty-eight percent of non-referred patients had VA or VFQ-25 composite scores at least as poor as the median for referred patients. Two-thirds of patients who were not referred had no discernable obstacle to referral. Our institution refers patients with worse objective and functioning vision, but more patients may benefit from referral. Future studies should identify metrics to prompt referral and evaluate this approach. [ABSTRACT FROM AUTHOR]

Purpose: The MER proto-oncogene tyrosine kinase (MERTK) helps maintain the homeostasis of the retinal pigmented epithelium (RPE). Additionally, MERTK regulates the innate immune system. As such inhibition of MERTK has gained recent interest as a target for cancer therapeutics. Herein, we present on MERTK inhibitor associated retinal toxicity in a human., Methods: A 43-year-old male with past medical history of esophageal adenocarcinoma was enrolled in a trial studying the MERTK inhibitor PF-07265807. As part of the study protocol, the patient was seen every two to three weeks for dilated fundus exams and ancillary testing. Data on the patient's relevant past medical history, ophthalmic exam findings, and imaging performed at baseline and subsequent ophthalmology visits was obtained via retrospective chart review., Results: At the patient's baseline visit, his dilated exam and testing were normal. Seven months after starting the MERTK inhibitor the patient developed subtle but reproducible signs of retinal toxicity with disruption of the extrafoveal ellipsoid zone on optical coherence tomography and extrafoveal hyper-autofluorescence on short wavelength fundus autofluorescence. The patient's vision remained stable throughout the study; however, the medication was stopped due to the unknown ocular effects as well as progression of the patient's cancer., Discussion: Patients taking MERTK inhibitors should be monitored by an ophthalmologist while on the drug. If toxicity develops, discussion of whether to continue the medication should take place between the patient, ophthalmologist, and oncologist, with consideration of the risks of vision loss versus benefits of taking the medication from a cancer perspective., Competing Interests: Conflicts of Interest: The authors have no conflicts to declare.

Background and Objective: Investigate associations between systemic vascular endothelial growth factor (VEGF) and optical coherence tomography (OCT) biomarkers in eyes with complete retinal pigment epithelium and outer retina atrophy (cRORA) secondary to non-neovascular age-related macular degeneration., Patients and Methods: Cross-sectional study of patients with cRORA. OCT images and blood samples were collected at study enrollment. OCT images were evaluated for biomarkers. Systemic VEGF levels were measured using a standard multiplex assay., Results: Study included 187 eyes from 96 patients. Lower levels of systemic VEGF were significantly associated with retinal pseudocysts (RPs) and subretinal hyper-reflective material (SHRM), a median of 7.7 pg/mL and 6.1 pg/mL for patients with the imaging biomarkers compared to those without (10.3 pg/mL [ P = 0.004] and 9.3 pg/mL [ P = 0.02], respectively)., Conclusion: This novel study shows that lower systemic VEGF levels were associated with SHRM and RP, which was shown to correspond to an intermediate stage of the atrophic process in age-related macular degeneration. Systemic VEGF could be a useful biomarker and therapeutic target for eyes with cRORA. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.] .

Purpose: Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex., Methods: We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4., Results: There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex., Conclusions: These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development., Translational Relevance: The plasma biomarker IL-4 is significantly elevated in patients with GA.

Purpose: A previous study from our research group showed significantly lower levels of RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in patients with intermediate age-related macular degeneration (AMD) compared to control patients with no AMD. The primary aim of this study was to assess levels of RANTES in a cohort of patients with a more advanced form of the disease, geographic atrophy (GA), in comparison with controls., Methods: The study was conducted on a cohort of patients with GA recruited into a Colorado AMD registry. Cases and controls were defined with multimodal imaging. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction., Results: The plasma levels of RANTES were significantly higher in the control group in comparison to the GA AMD group (median [interquartile range]): 10,204 [5799-19,554] pg/mL vs. 5435 [3420-9177] pg/mL, respectively, P < 0.01). When moderated by sex, there was no statistical difference between the male and female GA AMD or the male and female controls., Conclusions: We found lower level of RANTES in patients with GA AMD compared with controls. This finding is consistent with the findings from our previous intermediate AMD study. However, in contrast to the results of our previous research, when moderated by sex there was no statistical difference between male and female GA patients., Translational Relevance: The biomarker RANTES is significantly lower in GA AMD patients compared to controls.

Purpose: To report two cases of spontaneous closure of lamellar macular holes with epiretinal proliferation (ERP)., Methods: Observational cases report., Results: Two patients affected with lamellar macular hole showed progressive and spontaneous closure of the hole associated with ERP development. At presentation, both patients presented with irregular foveal contour, and foveal cavitation with apparent loss of retinal tissue. In both cases, ERP, also called "lamellar hole-associated epiretinal proliferation", was present and increased in size over time. This proliferation progressively developed across the hole with apparent restoration of the foveal contour and preservation of visual acuity., Conclusion: This report describes two cases of lamellar macular hole in which ERP increased over time, resulting in lamellar macular hole closure. Such observations may suggest a spontaneous healing process driven by glial cell proliferation.

Purpose: Age-related macular degeneration (AMD) is an acquired degenerative disease of the retina classified into early, intermediate, and advanced AMD. A key factor in the pathogenesis of AMD is the complement system. The interaction of age and sex with the complement system may affect the risk of developing AMD. The purpose of this study was to determine if there were sex-specific differences in levels of complement factors among patients with the intermediate phenotype of AMD (iAMD) and explore the correlation between age and complement proteins., Methods: We studied complement factors in patients with iAMD and controls without AMD. Nonparametric, rank-based linear regressions including a sex by AMD interaction were used to compare levels for each analyte. Correlations between age and complement proteins were evaluated using the Spearman rank correlation coefficient., Results: We found significantly higher levels of factor B and factor I in females compared with males with iAMD, whereas no differences were seen in complement levels in male and female controls. The ratios of Ba/factor B, C3a/C3, C4b/C4, and C5a/C5 were not different in males and females with iAMD., Conclusions: We demonstrate disparities in a subset of systemic complement factors between females and males with iAMD, but apparent complement turnover as measured by ratios of activation fragments to intact molecules was not different between these groups. The results suggest that complement system levels, including complement regulator factor I, exhibits sex-related differences in patients with iAMD and highlights that stratification by sex might be helpful in the interpretation of clinical trials of anticomplement therapy.