Marco Marques

Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

Purpose: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). Methods: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. Results: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. Conclusions: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects.

Human plasma metabolomics in age-related macular degeneration (AMD) using nuclear magnetic resonance spectroscopy

Purpose To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. Methods Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. Results Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. Conclusion For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

Efficacy and safety of postvitrectomy intravitreal triamcinolone therapy for diabetic macular edema.

Purpose After vitrectomy, diffusion and clearance rates of numerous drugs are increased, leading to a shorter intravitreal half-life. This raises doubts about the efficacy of intravitreal therapies, as retina specialists generally believe that a shorter half-life compromises the drugs’ therapeutic effect. We conducted a study to evaluate the functional and anatomical effect of intravitreal triamcinolone acetonide therapy (IVTA) in previously vitrectomized eyes with diabetic macular edema (DME). Methods In this retrospective, multicenter case series study including vitrectomized patients with DME who underwent IVTA injections, central macular thickness (CMT) measured with spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters were evaluated after each procedure. All relevant medical data were collected, including previous ophthalmologic treatments and comorbidities. Results Twenty vitrectomized eyes of 20 patients, mean age 58.1 years (range 40-72 years), were enrolled in the study. All patients presented DME and received at least one IVTA injection. Mean time between pars plana vitrectomy and IVTA was 12.9 ± 8.7 months. Mean pretreatment and posttreatment CMT was 438.8 ± 90.8 μm and 301.2 ± 76.2 μm, respectively, a difference that reached statistical significance (p<0.001). Mean gain in BCVA letter score was 7.83 ± 14.9 letters after treatment (p = 0.039). Mean intraocular pressure was significantly increased after IVTA (17.2 ± 1.9 mm Hg at baseline vs 21.2 ± 4.59 mm Hg after IVTA, p = 0.002). Conclusions A positive anatomical and functional effect was observed in our cohort. Our results suggest that, despite prior vitrectomy, triamcinolone remains a valid therapeutic approach for eyes with persistent DME. Further prospective randomized studies with larger patient samples are needed to validate this conclusion.

Automated Brightness and Contrast Adjustment of Color Fundus Photographs for the Grading of Age-Related Macular Degeneration

Purpose The purpose of this study was to develop an algorithm to automatically standardize the brightness, contrast, and color balance of digital color fundus photographs used to grade AMD and to validate this algorithm by determining the effects of the standardization on image quality and disease grading. Methods Seven-field color photographs of patients (>50 years) with any stage of AMD and a control group were acquired at two study sites, with either the Topcon TRC-50DX or Zeiss FF-450 Plus cameras. Field 2 photographs were analyzed. Pixel brightness values in the red, green, and blue (RGB) color channels were adjusted in custom-built software to make the mean brightness and contrast of the images equal to optimal values determined by the Age-Related Eye Disease Study (AREDS) 2 group. Results Color photographs of 370 eyes were analyzed. We found a wide range of brightness and contrast values in the images at baseline, even for those taken with the same camera. After processing, image brightness variability (brightest image–dimmest image in a color channel) was reduced 69-fold, 62-fold, and 96-fold for the RGB channels. Contrast variability was reduced 6-fold, 8-fold, and 13-fold, respectively, after adjustment. Of the 23% images considered nongradable before adjustment, only 5.7% remained nongradable. Conclusions This automated software enables rapid and accurate standardization of color photographs for AMD grading. Translational Relevance This work offers the potential to be the future of assessing and grading AMD from photos for clinical research and teleimaging.

Long-Term Management of RAP Lesions in Clinical Practice: Treatment Efficacy and Predictors of Functional Improvement.

Purpose: To evaluate the long-term efficacy of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) and to identify predictors of functional outcome. Methods: Retrospective case series comprised 79 eyes of 68 consecutive patients with RAP followed up ≥36 months. Primary end-points were best-corrected visual acuity (BCVA) and central macular thickness (CMT) variation at 36 months and at the last visit. Results: Mean follow-up time was 59.8 ± 16.0 months. All eyes were treated with pro re nata ranibizumab, with (n = 33) or without (n = 46) photodynamic therapy (PDT). Stabilization or improvement in BCVA was observed in 50.6% of the patients at 36 months, and in 40.5% at the end of the follow-up, where 20.3% preserved reading vision. A significant decrease in CMT was observed at 36 months (p < 0.001), but not at the end of the follow-up. Geographic atrophy (GA) was present in 59.5% of the eyes at the final visit. Baseline subretinal fluid was associated with better visual outcomes (p = 0.001). Results of combination treatment with intravitreal ranibizumab and PDT did not significantly differ from ranibizumab monotherapy. Conclusion: Modest functional outcomes can be expected from the long-term treatment of RAP lesions in clinical practice, most likely due to the advent of GA. Baseline subretinal fluid positively correlated with final BCVA.

Endogenous endophthalmitis secondary to erysipelas.

A 64-year-old woman with chronic right arm lymphoedema presented with progressive and painful vision loss in the right eye following diagnosis of erysipelas in the ipsilateral arm. Visual acuity was light perception. Biomicroscopy revealed marked conjunctival injection, decreased corneal transparency and an inflammatory mass in the anterior chamber, which precluded fundoscopy. The ocular ultrasonography features were consistent with acute endophthalmitis, and the patient was admitted to the hospital. A systemic evaluation, including complete physical examination, echocardiography and blood tests, ruled out other sources of infection besides the cutaneous site. Blood cultures were positive for group A Streptococcus. A diagnosis of unilateral acute endophthalmitis due to group A Streptococcus bacteraemia secondary to erysipelas was made and successfully treated with optimal medical care, including prompt intravitreal and systemic antibiotic administration. Despite resolution of the infectious process, visual acuity did not improve.

Epiretinal Proliferations Associated with Lamellar Macular Holes: Clinical and Surgical Implications

Objectives: To describe the prevalence of lamellar hole-associated epiretinal proliferation (LHEP) and to correlate this finding with lamellar macular hole (LMH) morphology and prognosis after a surgical or conservative approach. Methods: This is a retrospective multicenter case series comprising consecutive LMH patients followed for ≥6 months. Serial spectral-domain optical coherence tomographies were evaluated for the presence of epiretinal membrane (ERM) and LHEP, diameter of the LMH aperture, base, and floor thickness. Pars plana vitrectomy with ERM and internal limiting membrane peeling was performed in the surgical cases. Results: A total of 62 eyes from 57 consecutive patients were included. Mean follow-up time was 27.1 ± 19.8 months. LHEP was observed in 33 (53.2%) eyes. Patients with LMH and LHEP presented a larger external diameter (p = 0.001) and thinner floors (p = 0.018). Twenty-seven (81.8%) of the patients with LMH and LHEP presented a degenerative intraretinal cavitation, compared to 23.3% in the non-LHEP group (p = 0.001). No differences were observed in visual performance or closure rate between the 2 groups after surgery or in the subset of patients followed conservatively. Conclusions: LHEP was correlated with the anatomical conformation of the LMH, yielding thinner floors and larger external diameters. However, it did not correlate with the anatomical or functional results, both in the patients who underwent surgery and in those managed conservatively.

Extraocular Muscles Involvement as the Initial Presentation in Metastatic Breast Cancer

Orbital metastasis is a rare event, and metastatic disease affecting the extraocular muscles is an even less frequent complication of solid tumors. Herein, we report an unusual case of ptosis as the initial presentation of an invasive breast cancer. A 68-year-old woman presented with III and VI partial nerve paresis, secondary to a compressive retrobulbar mass. Magnetic resonance imaging revealed an infiltrative lesion involving the extraocular muscles. Tissue biopsy yielded a result compatible with metastasis to the orbit, with immunohistochemistry analysis suggesting breast as the primary organ. Mammography identified an area of architectural distortion; stereotactic wire-guided biopsy confirmed the result of the previous orbital biopsy. A positron emission tomography scan demonstrated disseminated disease. Palliative chemotherapy with bone-modulating agents and subsequent hormonal therapy was proposed. Unfortunately, the patient did not respond to therapy and died 38 months after diagnosis.

Multimodal Evaluation of the Fellow Eye of Patients with Retinal Angiomatous Proliferation

Introduction: We conducted a multimodal, cross-sectional evaluation. Methods: Eyes were divided into 4 study groups: controls, early/intermediate age-related macular degeneration (AMD), fellow eyes of retinal angiomatous proliferation (RAP), and RAP eyes. Patients were evaluated with spectral-domain optical coherence tomography (OCT), enhanced depth imaging-OCT, and OCT angiography (OCTA). OCTA images were processed to generate maps of the vessel density and perfusion density of the superficial and deep retinal layers (SRL and DRL) and the choriocapillaris level (CL). The thickness of the outer nuclear layer and choroid was manually assessed. Results: We included 135 eyes of 100 patients (51 controls, 30 AMD, 42 RAP, and 12 fellow eyes). The fellow eyes showed a significantly lower vascular perfusion of the SRL, DRL, and CL (p < 0.02) than the early/intermediate AMD and control eyes did. Similarly, RAP eyes presented a lower vascular perfusion of the DRL and CL (p < 0.05). Besides, structural analyses of the fellow eyes and RAP eyes revealed a significantly higher prevalence of macular pigmentary changes, atrophy of the retinal pigment epithelium, hyperreflective “clumps” above flat drusen, amongst others, than early/intermediate AMD and control eyes (p < 0.05). Conclusion: We present the first report on the OCTA analysis of the fellow eye of patients with RAP. The reduced perfusion density and vessel density observed contributes, in association with clearly defined structural changes, to a wider characterization of RAP as a distinctive phenotype.