Longitudinal changes in pigment epithelial detachment composition indices (PEDCI): new biomarkers in neovascular age-related macular degeneration.

PURPOSE: To evaluate novel, automated biomarkers, pigment epithelial detachment composition indices (PEDCI) in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy through 24 months. METHODS: Retrospective analysis of 37 eyes (34 patients) with PED associated with nAMD receiving as-needed anti-VEGF treatment was performed. Best-corrected visual acuity (BCVA) and optical coherence tomography images were acquired at a treatment-naïve baseline and 3-, 6-, 12-, 18-, and 24-month visits. Previously validated automated imaging biomarkers, PEDCI-S (serous), PEDCI-N (neovascular), and PEDCI-F (fibrous) within PEDs were measured. ANOVA analysis and Spearman correlation were performed. RESULTS: Mean BCVA (in logMAR) was 0.60 ± 0.47, 0.45 ± 0.41, 0.49 ± 0.49, 0.61 ± 0.54, 0.59 ± 0.56, and 0.67 ± 0.57 at baseline, 3, 6, 12, 18, and 24 months respectively. Overall, BCVA showed minimal worsening of 0.07 ± 0.54 logMAR (p = 0.07). 13.38 ± 3.77 anti-VEGF injections were given through 24 months. PEDCI-F showed an increase of 0.116, 0.122, 0.036, and 0.006 at months 3, 6, 12, and 18 respectively and a decrease of 0.004 at month 24 (p = 0.03); PEDCI-S showed a decrease of 0.064, 0.130, 0.091, 0.092, and 0.095 at months 3, 6, 12, 18, and 24 respectively (p = 0.16); PEDCI-N showed a decrease of 0.052 at month 3 and an increase of 0.008, 0.055, 0.086, and 0.099 at months 6, 12, 18, and 24 respectively (p = 0.06). BCVA was negatively correlated with PEDCI-F (r = -0.28, p < 0.01), and positively correlated with PEDCI-N (r = 0.28, p < 0.01) and PEDCI-S (r = 0.15, p = 0.03). CONCLUSION: Longitudinal analysis of PEDCI supports their utility as biomarkers that characterize treatment related effects by quantifying the relative composition of PEDs.

The Complement System as a Therapeutic Target in Retinal Disease.

The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.

Ten-year follow-up and sequential evaluation of multifocal retinal pigment epithelium abnormalities in central serous chorioretinopathy.

PURPOSE: The study aims to analyze the 10-year outcomes in "simple" and "complex" central serous chorioretinopathy (CSCR) and to evaluate the longitudinal changes in multifocal retinal pigment epithelium (RPE) alterations. METHODS: This was a retrospective, multicentric, longitudinal, observational study in patients with a diagnosis of CSCR. Visual acuity outcomes and recurrence characteristics of simple and complex were analyzed. Changes in number of foci of RPE alterations from baseline to last visit were evaluated. RESULTS: Out of 235 eyes screened, the study included 67 eyes of 39 patients (32 males and 7 females) with CSCR (12 simple and 55 complex CSCR). A total of 17 (29.9%) eyes had a unifocal RPE alteration, while the remaining 50 had multifocal RPE alterations at baseline. In eyes with complex CSCR, the 10-year visual acuity was significantly worse (p < 0.001), more number of eyes required treatment (p = 0.03), higher number of RPE alterations were present at baseline and last follow-up (p < 0.001 for both), and number of recurrences were higher (p < 0.001), than simple CSCR. Focal collections of RPE alterations and leakage site corresponded to mid-phase hyper-fluorescent plaques (MPHP) in all eyes. On multivariate regression analysis, a larger area of RPE alteration was associated with a worser 10-year visual acuity (p = 0.004) and complex CSCR was associated with higher number of recurrence (p = 0.005). CONCLUSION: A different course of disease progression was seen in simple and complex CSCR. An evolution in foci of RPE alterations was seen, from a simple area of MPHP, to focal RPE alterations and finally to leakage.

Regression patterns of central serous chorioretinopathy using en face optical coherence tomography.

PURPOSE: To study the regression patterns of subretinal fluid (SRF) in central serous chorioretinopathy (CSCR) on sequential en face optical coherence tomography (OCT) and its relationship to leak locations. METHODS: Retrospective study on patients with acute CSCR. Inclusion criteria were (i) availability of data, sequential OCT and OCT angiography (B scan and en face OCT) every 2 weeks until resolution of SRF or 6 months, whichever is earlier; (ii) single active leak. Exclusion criteria were (i) presence of macular neovascularization or atypical CSCR, (ii) diffuse pigment epitheliopathy, (iii) multiple leaks. Serial en face OCT scans were evaluated and the area of SRF was measured using ImageJ software. Correlation coefficient was calculated for the regression rate of SRF area and central retinal thickness (CRT) over the first month of follow-up and the time of complete SRF resolution. RESULTS: Out of the 25 eyes, 20 eyes demonstrated a centripetal regression, and 5 eyes demonstrated a centrifugal regression. In eyes with a leakage point <1000µ from the fovea, 86% resolved in a centripetal fashion, and in eyes with leak site ≥1000µ away from fovea, 70% eyes resolved centripetally. There was a correlation (r=-0.47, p=0.018) of the rate regression of SRF area during the first month and timing of resolution. In contrast, this correlation was absent (r=-0.16, p=0.44) for CRT regression. CONCLUSION: Our en face-based analysis of sequential OCTs of regressing CSCR demonstrated a tendency for the subfoveal SRF to resolve towards the end or a centripetal pattern of regression. Prediction of resolution of SRF at 1 month is better with en face area of SRF in comparison to CRT.

Geographical Trends in Global Ophthalmology Research from 2002-2022.

PURPOSE: Characterize geographical trends in ophthalmology research between 2002-2022 and explore associations between study locations, designs, and funding sources DESIGN: Trend study METHODS: Analysis of 4199 publications from American Journal of Ophthalmology, British Journal of Ophthalmology, Investigative Ophthalmology and Visual Science, JAMA Ophthalmology, and Ophthalmology. All original full-length publications from 2002, 2012, and 2022 were included. Exclusion criteria were meta-analyses, literature reviews, and case reports. Main outcome measures were publication years, locations, study designs, and funding sources. RESULTS: Publications from North America (45.8%), Europe (30.7%), and Asia (28.9%) were the most common, whereas Africa (0.8%) and South America (1.4%) were least represented. North American research decreased by 10.6% (p < 0.001), whereas Asian research increased by 25.4% (p < 0.001). The USA contributed 42.3% of research but experienced a 11.3% decline from 2002-2022 (p < 0.001). USA publications received 5.8% more industry funding from 2002-2022 (p = 0.006). China's research grew by 17.0% and had the highest proportion of government (83.1%) or intramural (24.2%) funding (p < 0.001), with government-funded studies increasing by 46.7% (p < 0.001). Japan was less associated with all funding types (p ≤ 0.001). Singapore, Iceland, and Switzerland were top performers when adjusted for population size. CONCLUSIONS: Within the examined journals, the USA remains the primary research contributor, with China witnessing rapid growth and Japan facing stagnation. Despite the USA's declining research proportion, North America and Europe continue to maintain a disproportionately high presence in prestigious academic journals. Publications from Africa and South America are limited.

Pigment epithelial detachment composition indices in central serous chorioretinopathy as a biomarker for disease activity: A computational methodology and 1 year outcomes.

PURPOSE: Investigation of pigment epithelial detachment (PED) characteristics in central serous chorioretinopathy (CSCR) is underrepresented in the literature. We present a novel computational approach to quantify PED composition indices (PEDCI) in CSCR and track changes over time. METHODS: 34 eyes with active CSCR were analyzed quarterly over a 1-year period. Cases were categorized into acute and chronic CSCR depending on a symptom duration of less than 3 months or more than 3 months respectively. PED, retinal and choroidal dimensions were manually measured, and interval changes were compared using repeated measures of variance ANOVA. PED composition analysis involved manual segmentation followed by automated sub segmentation of PED areas to identify serous, neovascular and fibrous tissues. PEDCI for each component was compared among cases of acute and chronic CSCR. RESULTS: CMT and NSD-h decreased by 65.2 µm (p = 0.01), and 86.5 µm (p < 0.01) respectively at 12 months. At baseline, 7/17 acute CSCR eyes and 8/15 chronic CSCR eyes had a concomitant PED; acute cases had both serous and neovascular components (PEDCI-S: 16.95%, PEDCI-N: 40.3%), whereas chronic cases only had a neovascular component (PEDCI-S: 0%, PEDCI-N: 30.5%). At 12-month follow-up, 6/7 of acute CSCR group and 6/8 chronic CSCR group had a concomitant PED; PEDCI-S was largest for acute CSCR (53.4%) and PEDCI-N was largest for chronic CSCR (46.7%). CONCLUSION: We identify a novel biomarker PEDCI to differentiate acute and chronic CSCR with higher PEDCI-S in acute CSCR, and higher PEDCI-N in chronic CSCR.

Artificial intelligence in chorioretinal pathology through fundoscopy: a comprehensive review.

BACKGROUND: Applications for artificial intelligence (AI) in ophthalmology are continually evolving. Fundoscopy is one of the oldest ocular imaging techniques but remains a mainstay in posterior segment imaging due to its prevalence, ease of use, and ongoing technological advancement. AI has been leveraged for fundoscopy to accomplish core tasks including segmentation, classification, and prediction. MAIN BODY: In this article we provide a review of AI in fundoscopy applied to representative chorioretinal pathologies, including diabetic retinopathy and age-related macular degeneration, among others. We conclude with a discussion of future directions and current limitations. SHORT CONCLUSION: As AI evolves, it will become increasingly essential for the modern ophthalmologist to understand its applications and limitations to improve patient outcomes and continue to innovate.

Gender differences in central serous chorioretinopathy based on the new multimodal imaging classification.

PURPOSE: To analyse the gender-specific differences in central serous chorioretinopathy (CSCR) based on a new multimodal imaging classification system. METHOD: This was a retrospective, multicentric, longitudinal, observational study in patients with a diagnosis of unilateral or bilateral CSCR. Visual acuity outcomes and differences based on 'Simple' and 'Complex' CSCR were analysed. The occurrence of choroidal neovascularization (CNVM) and number of recurrences were also compared. Regression analysis was used to evaluate baseline predictors of final visual acuity. RESULTS: The study included 109 eyes of 58 patients (55 eyes of 28 female patients and 54 eyes of 30 male patients). Simple CSCR was seen in 8 (14.8%) eyes and 21 (38.2%) eyes in male and female groups respectively, while complex CSCR was seen in 46 (85.2%) eyes and 34 (61.8%) eyes in male and female groups respectively (p = 0.005). Recurrence was more commonly seen in males (34 eyes) than in females (23 eyes) (p = 0.03). Males (96.7%) were also significantly more likely to have a bilateral presentation (78.6% in females) (p = 0.03). Conversely, CNVM was more commonly seen in female eyes (8 eyes) than male eyes (4 eyes) (p = 0.23). On multivariable regression analysis, factors affecting reduced need for treatment were history of steroid use, good visual acuity at baseline, and simple CSCR. Factors affecting good final visual acuity were history of steroid use, good visual acuity at baseline, and younger age. CONCLUSION: Males tended to have complex CSCR and recurrence compared to the female sub-group, while females exhibited CNVM more commonly than males.

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months. METHODS: This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F). RESULTS: A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = - 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = - 0.53; p < 0.001 and PCV, r = - 0.09; p = 0.58). CONCLUSION: PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Capabilities and Limitations of Student-Led Free Vision Screening Programs in the United States.

Purpose: The Consortium of Student-Led Eye Clinics (CSLEC), founded in 2021, administered a comprehensive survey to document the types of services, most common diagnoses, and follow-up care protocols offered by student-led free vision screening programs (SLFVSP) in the United States. Methods: An 81-question institutional review board (IRB)-approved survey was administered to student-led vision screening eye clinics from October 1, 2022 to February 24, 2023. Results: Sixteen SLFVSPs were included in the final analysis, of which 81% (n = 13) conducted variations of fundoscopic examinations and 75% (n = 12) measured intraocular pressure. Cataracts and diabetic retinopathy were reported as the most frequent diagnoses by the majority of SLFVSPs (n = 9, 56%); non-mobile SLFVSPs more commonly reported cataract as a frequent diagnosis (P < 0.05). Most patients screened at participating programs were uninsured or met federal poverty guidelines. Prescription glasses were offered by 56% of the programs (n = 9). SLFVSPs that directly scheduled follow-up appointments reported higher attendance rates (66.5%) than those that only sent referrals (20%). Transportation was the most cited barrier for follow-up appointment attendance. Conclusions: SLFVSPs, one community vision screening initiative subtype, vary significantly in scope and capabilities of identifying vision threatening disease. The follow-up infrastructure is not uniformly robust and represents a key target for improving care delivery to at-risk populations. Translational Relevance: The CSLEC aims to develop a consensus-based standardization for the scope of screening services, offer guidelines for diagnostic criteria, promote real-time data stewardship, and identify means to improve follow-up care mechanisms in member communities.

Three-dimensional choroidal contour mapping in healthy population.

Purpose was to study 3-dimensional choroidal contour at choroidal inner boundary (CIB) and choroidal outer boundary (COB) in healthy eyes. Healthy eyes imaged on wide field swept-source optical coherence tomography were included. Delineation of CIB and COB was done based on our previously reported methods. Quantitative analysis of the surfaces of CIB and COB was based on analyzing best fit spherical radius (R) (overall and sectoral). One hundred and seven eyes of 74 subjects with a mean age of 46.4 ± 19.3 years were evaluated. Overall, R COB (mean ± SD: 22.5 ± 4.8 mm) < R CIB (32.4 ± 9.4 mm). Central sector had the least R at COB (7.2 ± 5.9 mm) as well as CIB (25.1 ± 14.3 mm) across all age groups. Regression analysis between R (CIB) and age (r = -0.31, r2 = 0.09) showed negative correlation (P < 0.001) and that between R (COB) and age was positive (r = 0.26, r2 = 0.07) (P = 0.01). To conclude, central sector is the steepest sector in comparison to all the other sectors. This is indicative of a prolate shape of choroidal contour at CIB and COB. Outer boundary of choroid is steeper than inner boundary across all age groups. However, with ageing, outer boundary becomes flatter and inner boundary becomes steeper.

Longitudinal structural changes in central serous chorioretinopathy: A multimodal imaging-based study.

PURPOSE: To analyse the longitudinal changes in imaging parameters in eyes with acute or chronic central serous chorioretinopathy (CSCR). METHODS: This was a multicentric, retrospective, longitudinal, observational study in patients with a diagnosis of CSCR and having at least 4 years of follow-up. Trend in choroidal thickness (CT), area of double layer sign (DLS), area of retinal pigment epithelium (RPE) alterations, and area of hyper-autofluorescence were analysed. RESULTS: A total of 175 eyes of 146 patients with a mean age of 52.9 ± 12.5 years were included. Fifty-two eyes had acute and 123 had chronic CSCR at baseline. There was an overall decreasing trend of CT values during follow up (from 354.4 ± 74.8 at baseline to 343.2 ± 109.4 at final visit). There was a steady rise in DLS width and RPE alteration in the overall cohort (from 811.7 ± 760.6 microns and 3.5 ± 3.3 disc areas respectively at baseline to 1209.1 ± 1113.18 microns, 4.1 ± 3.6 disc areas at final visit). An initial rise in hyper-autofluorescent area followed by steady fall was seen in chronic CSCR. A significant positive correlation (r = 0.54, p = 0.004) was seen between change in DLS width and change in area of hyper-autofluorescence. On linear regression analysis, lower CMT and absence of intraretinal fluid at baseline were associated with greater increase in RPE abnormalities. CONCLUSION: Acute and chronic CSCR had different pattern of change in imaging parameters with area of RPE alterations in acute CSCR not reaching values close to that of chronic CSCR eyes even after long follow up.

Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration.

Optical coherence tomography has revolutionized the diagnosis and management of neovascular age-related macular degeneration. OCT-derived biomarkers have the potential to further guide therapeutic advancements with anti-vascular endothelial growth factor; however, the clinical convergence between these two tools remains suboptimal. Therefore, the aim of this review of literature was to examine the current data on OCT biomarkers and their prognostic value. Thirteen biomarkers were analyzed, and retinal fluid had the strongest-reported impact on clinical outcomes, including visual acuity, clinic visits, and anti-VEGF treatment regimens. In particular, intra-retinal fluid was shown to be associated with poor visual outcomes. Consistencies in the literature with regard to these OCT prognostic biomarkers can lead to patient-specific clinical decision making, such as early-initiated treatment and proactive monitoring. An integrated analysis of all OCT components in combination with new efforts toward automated analysis with artificial intelligence has the potential to further improve the role of OCT in nAMD therapy.

Radiomics-Based Prediction of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration With Pigment Epithelial Detachment.

Purpose: Machine learning models based on radiomic feature extraction from clinical imaging data provide effective and interpretable means for clinical decision making. This pilot study evaluated whether radiomics features in baseline optical coherence tomography (OCT) images of eyes with pigment epithelial detachment (PED) associated with neovascular age-related macular degeneration (nAMD) can predict treatment response to as-needed anti-vascular endothelial growth factor (VEGF) therapy. Methods: Thirty-nine eyes of patients with PED undergoing anti-VEGF therapy were included. All eyes underwent a loading dose followed by as-needed therapy. OCT images at baseline, month 3, and month 6 were analyzed. Images were manually separated into non-responding, recurring, and responding eyes based on the presence or absence of subretinal fluid at month 6. PED radiomics features were then extracted from each image and images were classified as responding or recurring using a machine learning classifier applied to the radiomics features. Results: Linear discriminant analysis classification of baseline features as responsive versus recurring resulted in classification performance of 64.0% (95% confidence interval [CI] = 0.63-0.65), area under the curve (AUC = 0.78, 95% CI = 0.72-0.82), sensitivity 0.79 (95% CI = 0.63-0.87), and specificity 0.58 (95% CI = 0.50-0.67). Further analysis of features in recurring eyes identified a significant shift toward non-responding mean feature values over 6 months. Conclusions: Our results demonstrate the use of radiomics features as predictors for treatment response to as-needed anti-VEGF therapy. Our study demonstrates the potential for radiomics feature in clinical decision support for personalizing anti-VEGF therapy. Translational Relevance: The ability to use PED texture features to predict treatment response facilitates personalized clinical decision making.

Pigment epithelial detachment composition indices (PEDCI) in neovascular age-related macular degeneration.

We provide an automated analysis of the pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) and estimate areas of serous, neovascular, and fibrous tissues within PEDs. A retrospective analysis of high-definition spectral-domain OCT B-scans from 43 eyes of 37 patients with nAMD with presence of fibrovascular PED was done. PEDs were manually segmented and then filtered using 2D kernels to classify pixels within the PED as serous, neovascular, or fibrous. A set of PED composition indices were calculated on a per-image basis using relative PED area of serous (PEDCI-S), neovascular (PEDCI-N), and fibrous (PEDCI-F) tissue. Accuracy of segmentation and classification within the PED were graded in masked fashion. Mean overall intra-observer repeatability and inter-observer reproducibility were 0.86 ± 0.07 and 0.86 ± 0.03 respectively using intraclass correlations. The mean graded scores were 96.99 ± 8.18, 92.12 ± 7.97, 91.48 ± 8.93, and 92.29 ± 8.97 for segmentation, serous, neovascular, and fibrous respectively. Mean (range) PEDCI-S, PEDCI-N, and PEDCI-F were 0.253 (0-0.952), 0.554 (0-1), and 0.193 (0-0.693). A kernel-based image processing approach demonstrates potential for approximating PED composition. Evaluating follow up changes during nAMD treatment with respect to PEDCI would be useful for further clinical applications.

Longitudinal follow-up and outcome analysis in central serous chorioretinopathy.

OBJECTIVES: To analyse the longitudinal changes in visual acuity and risk factors for recurrence or development of choroidal neovascularisation (CNV) in eyes with acute or chronic central serous chorioretinopathy (CSCR). METHODS: This was a retrospective, multicentric, longitudinal, observational study done in patients with a diagnosis of unilateral or bilateral CSCR and having at least 4 years of follow-up between the years 1999 and 2020. Kaplan-Meier curves were used for assessing cumulative risks. Multivariate logistic, linear and cox regression models were used for risk factor analyses. The trend in visual acuity, cumulative risks of recurrence and CNV formation was analysed. RESULTS: A total of 117 out of 175 eyes (66.8%) had stable or improvement in vision at last follow-up, while 24 eyes had more than/equal to 3 line loss of vision. Four eyes (7.7%) with acute CSCR at initial presentation developed features of chronic CSCR at the final presentation. Thirty-seven eyes had recurrence during the follow-up with a 10-year cumulative recurrence rate of around 30%. On Cox proportional hazard regression analysis, history of previous treatment and male gender (p = 0.03) were associated with a lower risk of recurrence. Twenty-four developed de novo CNV by the end of follow-up and higher age (p = 0.001) and a higher number of recurrences (p = 0.05) were associated with a higher risk of early de novo CNV formation. The cumulative 10-year CNV development rate was 17.4%. CONCLUSION: A non-temporal relationship between acute and chronic CSCR was seen. Previous treatment, smoking and baseline RPE abnormality affected recurrence of SRF or CNV formation.