Differences in imaging biomarkers between patients with intermediate and advanced non-neovascular age-related macular degeneration (AMD) in the University of Colorado AMD registry.

PURPOSE: To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD). METHODS: Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000 um and 2000 um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant. RESULTS: 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p = 0.001), calcified drusen (4.3% vs. 40.0%, p < 0.0001), RPD (26.2% vs. 53.3%, p < 0.0001), ORT (0.5% vs. 46.9%, p < 0.0001), RP (1.1% vs. 46.3%, p < 0.0001), pigment migration (53.2% vs. 100%, p < 0.0001), and iRORA (17.9% vs. 80.2%, p < 0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188 µm (SD: 60) and 194 µm (SD: 69), compared to the advanced nnAMD with measurements of 153 µm (SD: 68), and 161 µm (SD: 76). This difference was statistically significant (p < 0.0001 and p = 0.0002). CONCLUSIONS: Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.

Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate.

PURPOSE: Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD). DESIGN: Prospective cohort study. METHODS: One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated. RESULTS: Average GA growth rate was 1.430 mm2/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate. CONCLUSIONS: Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.

Uveitis in the Setting of Co-Existing Systemic Sarcoidosis and Multiple Sclerosis.

We report a case of intermediate uveitis in the setting of both systemic sarcoidosis and multiple sclerosis. A 68-year-old female was diagnosed with bilateral granulomatous intermediate uveitis and cystoid macular edema. Initial systemic work-up was unrevealing. The uveitis was treated successfully with local corticosteroid injections. Eighteen months after presentation, the patient developed new systemic symptoms. Additional testing revealed systemic lymphadenopathy, with biopsy showing non-caseating granulomas, leading to a diagnosis of sarcoidosis. However, MRI of the brain and spinal cord along with cerebrospinal fluid analysis was consistent with MS. The management of the uveitis and systemic inflammation was co-managed by ophthalmology, neurology, and rheumatology, and eventually controlled with leflunomide and rituximab. Patients can rarely have co-existing systemic sarcoidosis and multiple sclerosis. Although challenging to diagnose, radiographic findings and cerebrospinal fluid analysis can be helpful to differentiate multiple sclerosis and neurosarcoidosis. Management of these patients requires coordination between multiple specialties.

Dyschromatopsia and contrast sensitivity changes in COVID-19 patients.

PURPOSE: To evaluate the alterations in the psycho-physical tests, contrast sensitivity (CS) and hue discrimination (total estimation score, TES) in COVID-19 patients. METHODS: A prospective case-control study was undertaken in 2021-22 to look at CS and TES among COVID-19 patients and RT-PCR negative normal subjects by a mobile app "smart optometry" and X-Rite's free online version of Farnsworth-Munsell 100 hue test. Strict visual acuity (minimum of 6/9 equivalent on Snellen) and other clinical parameters were used as exclusion criteria to filter potentially confounding pre-receptoral co-morbid conditions. The effect of mismatch in recruiting age and sex matched controls during the pandemic were analyzed by multivariate linear regression. RESULT: One-way ANOVA ruled out any influence of gender on CS and TES; however, there was significant difference in the TES on Mann Whitney U test (TES- 2.95 +/- 3.8 for cases; 0.30 +/- 1.1 for controls; p <0.001) and it persisted after accounting for age. Six controls with breakthrough infections had a significant deterioration in TES (Mean scores -3.0; 95% CI = -5.89 to -0.11; p = 0.04) on paired t test. Qualitative analysis showed that S-cone mediated deficiencies outnumber those affecting M-L cone mediated deficiencies. Among 53 subjects exhibiting three sensory features, anosmia, loss of taste and dyschromatopsia, nine (16.98%) had all features concurrently. CONCLUSION: The study demonstrates that COVID-19 infection leads to altered TES representing dyschromatopsia -an ocular counterpart of anosmia, with little difference on CS.

Age-Related Alterations of the Macular Choroid in Healthy Eyes Assessed by Swept-Source Optical Coherence Tomography Angiography.

OBJECTIVE: To analyze age-related changes in the choroid in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: This was a cross-sectional, prospective, observational study enrolling 222 eyes of 116 healthy participants. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec) with a 6 x 6 mm pattern centered on the fovea. Subfoveal choroidal thickness (CT) and choroidal volume (CV) were generated automatically through manufacturer tools available in the Advanced Retinal Imaging (ARI) hub network. Choroidal vascularity index (CVI) and choriocapillaris flow deficits (CCFD) were computed using ImageJ. RESULTS: CV was found to be significantly higher in women than men. Overall, there was a significant positive correlation between CVI and CCFD, and a significant negative correlation between CT and CV with age. The relationship, however, was more complex, as a decade-wise analysis showed that CT and CV increased until the second decade, followed by a decrease until the sixth decade, and then an increase again in the seventh and eighth decades. CVI was highest in the seventh decade. In contrast, CCFD increased consistently with age and in all the Early Treatment of Diabetic Retinopathy Study (ETDRS) rings. CONCLUSION: The choroidal blood flow and its thickness reduces as the age advances. While the choroidal flow deficits show a consistent increase with age and the distance from the foveal center, the relationship of other parameters with age is more complex. Having a normative database from healthy subjects is imperative for understanding the changes taking place in diseased states. Choroidal parameters can show significant variations with age. These differences are not uniform or consistent with age, highlighting the importance of a normative reference database to assess the significance of choroidal alterations associated with disease. [Ophthalmic Surg Lasers Imaging Retina 2023;54:526-534.].

Interleukin-4 Plasma Levels Stratified by Sex in Intermediate Age-Related Macular Degeneration and Geographic Atrophy.

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.

The relationship of diabetic retinopathy severity scales with frequency and surface area of diabetic retinopathy lesions.

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions' numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohen's Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions' number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.

Fractal analysis of the macular region in healthy eyes using swept-source optical coherence tomography angiography.

PURPOSE: This cross-sectional observational study evaluated the relationship between retinal vascular fractal dimension (FD) and age, as well as other vascular parameters in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: The study cohort consisted of 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured and analyzed using the Plex Elite 9000 and software tools available in the advanced retinal imaging (ARI) network hub. The retinal vascular layers were defined by the instrument's automatic retinal layer segmentation. The fractal analysis was performed on the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the whole retina. Grayscale OCTA images were standardized and binarized using ImageJ and fractal box-counting analyses were performed using Fractalyse software. Pearson's correlation was used to analyze the correlation between FD and retinal vascular parameters. RESULTS: The results showed that FD values were significantly higher in the 6 mm ring and the whole 6 × 6 scan region when compared to the 1 mm ETDRS central subfield. The correlation between age and FD was weak with a significant positive correlation between age and FD of the SCP in the 6 mm ring and between age and FD of the DCP in the 1 mm ring. Overall, differences in FD values in these healthy eyes were extremely small regardless of age or macular location. CONCLUSION: FD values in normal eyes show little variation with age and are relatively stable across the macula. This suggests that FD values may not need adjustment for age or location when evaluated in the context of retinal disease.

Age-related assessment of foveal avascular zone and surrounding capillary networks with swept source optical coherence tomography angiography in healthy eyes.

AIM: To assess the macular capillary networks and foveal avascular zone (FAZ) with swept-source optical coherence tomography angiography in healthy eyes. METHODS: This cross-sectional, prospective, observational study enrolled 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center. Vessel length density (VLD), perfusion density (PD), and FAZ parameters were analyzed using the manufacturer's automated software. RESULTS: A significant negative correlation was observed between age and average VLD in the superficial plexus, and average PD in both the superficial plexus and the whole retina. A significant positive correlation between age and foveal avascular zone perimeter and area was also noted. Age-wise comparisons showed a trend for an increase in VLD and PD until 40 years of age, with a subsequent decrease in the older age in the macular region. The central subfield showed a decrease in the vessel density measurements in the 21-40 age group. FAZ area and perimeter were the mirror inverse of the central subfield vessel density measurements with a numerically greater area and perimeter in the 21-40 age group compared to the 0-20 and 41-60 age groups. FAZ circularity was significantly reduced after 40 years of age. CONCLUSION: Age-related changes in the vessel density and FAZ parameters in the healthy macula are complex and vary with the macular location. These results carry significance when interpreting the data from diseased eyes.

Clinical Profile, Immediate- and Short-term Outcome of Patients with Intermediate-risk Acute Pulmonary Thromboembolism.

Background: Long-term outcomes of acute pulmonary thromboembolism (PTE) have been reported. However, the immediate- and short-term outcomes have not been reported adequately. Objectives: Primary objective was to determine the patient characteristics, and immediate- and short-term outcomes of intermediate-risk PTE, and the secondary objective was to evaluate the benefit of thrombolysis in normotensive PTE patients. Material and methods: This study included patients diagnosed with acute intermediate PTE. Patient's electrocardiography (ECG) parameters along with echocardiography (echo), etc., conducted at the time of admission, during their stay in hospital, at the time of discharge, and during follow-up were recorded. The patients were treated using thrombolysis or anticoagulants depending on hemodynamic decompensation. During follow-up, they were reassessed for echo parameters-right ventricular (RV) function and pulmonary arterial hypertension (PAH). Results: Among 55 patients, 29 (52.73%) were diagnosed with intermediate high-risk PTE and 26 (47.27%) with intermediate low-risk PTE. They were normotensive and most of them had a simplified pulmonary embolism severity index (sPESI) score <2. Typical ECG pattern S1Q3T3 along with echo patterns and elevated cardiac troponin levels were observed in most of the patients. Patients treated with thrombolytic agents showed a reduction in hemodynamic decompensation as opposed to patients treated with anticoagulants who had clinical signs of right heart failure (RHF) on follow-up after 3 months. Conclusion: This study contributes to the existing literature on outcomes of intermediate-risk PTE and the effect of thrombolysis on patients with hemodynamic stability. Thrombolysis reduced the incidence and progression of RHF in patients with hemodynamic instability. How to cite this article: Mathiyalagan P, Rajangam T, Bhargavi K, Gnanaraj R, Sundaram S. Clinical Profile, Immediate- and Short-term Outcome of Patients with Intermediate-risk Acute Pulmonary Thromboembolism. Indian J Crit Care Med 2022;26(11):1192-1197.