Corneal Microaneurysm-A Vascular Feature of Conjunctival Squamous Intraepithelial Neoplasia.

PURPOSE: The diagnosis of conjunctival squamous intraepithelial neoplasia (CSIN) can be difficult because of the heterogeneous appearance. Despite established risk factors and diagnostic support by high-resolution optical coherence tomography (hrOCT) and indocyanine green angiography (ICGA), the only reliable diagnostic method is a histological work-up. This case report is the first to describe corneal microaneurysms in CSIN as a vascular feature for conjunctival tumor angiogenesis. METHODS: An 84-year-old male patient was referred with a suspected diagnosis of pterygium. Biomicroscopic examination revealed a whitish epithelial lesion of conjunctival origin with centripetal corneal growth and extension over 5 limbal hours. Intralesional vascularization showed highly altered morphology with aneurysmal changes. After imaging with hrOCT and ICGA, excision was performed in a "no-touch double-freeze and thaw" technique, followed by histological and immunohistochemical work-up. RESULTS: hrOCT showed an epithelial, hyperreflective lesion with a maximum thickness of 272 µm and sharp central border. ICGA confirmed active perfusion and partial thrombosis of the aneurysmal terminal vascular buds dilated to 405 µm with early dye leakage within the first minute. Histological examination confirmed the clinical diagnosis of CSIN with focal high-grade dysplasia. Postoperatively, there was no recurrence during the observation period of 5 months. CONCLUSIONS: Intralesional terminal microaneurysms are a feature of tumor angiogenesis in CSIN. The relevance and frequency of this potential new risk factor for malignancy should be investigated in further studies.

The Impact of the COVID-19 Pandemic on the Quality of Care of Treatment-Naïve Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept. / Die Auswirkungen der COVID-19-Pandemie auf die Versorgungsqualität von therapienaiven PatientInnen mit neovaskulärer altersbedingter Makuladegeneration unter intravitrealer Aflibercept-Therapie.

OBJECTIVE: The aim of this study was to compare the quality of care received by treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept therapy before the coronavirus disease 2019 (COVID-19) pandemic with patients who received the same therapy during the pandemic. METHODS: Data, including best corrected visual acuity (BCVA) as the logarithm of the minimum angle of resolution (logMAR) and anatomical outcomes at diagnosis and at each follow-up, was collected on 297 treatment-naïve patients who received intravitreal aflibercept. Therapy-naïve patients who started therapy at least 24 months prior to the first pandemic-related lockdown and were thus treated exclusively prior to the pandemic (n = 123) were compared with patients who started therapy within 12 months prior to the first lockdown and were thus treated during the pandemic (n = 174). Both groups were followed over a two-year period. RESULTS: In patients treated before the COVID-19 pandemic, VA remained stable (0.58 ± 0.41 logMAR) compared to baseline (0.54 ± 0.34 logMAR; p = 0.228) until the end of the observation period. In patients treated during the COVID-19 pandemic, BCVA dropped below the baseline (0.56 ± 0.35 logMAR) within 24-month of follow-up (0.79 ± 0.43 logMAR; p = 0.010). Compared to the patients treated prior to the COVID-19 pandemic, the latter group showed a significantly worse VA at the 6-month (p = 0.041), 12-month (p = 0.040), 18-month (p = 0.024), 21-month (p = 0.035), and 24-month (p = 0.004) follow-up. Additionally, the group treated during the COVID-19 pandemic received significantly fewer aflibercept injections (3,94 ± 1,9 vs. 3,30 ± 1,6; p = 0,007) and fewer follow-up examinations (2,71 ± 1,2 vs. 2,16 ± 0,9; p < 0,001) in the second year compared to the group that was treated before the COVID-19 pandemic. CONCLUSION: We confirmed significantly worse VA outcomes in the group of nAMD patients treated during the COVID-19 pandemic. Impeded access to care could be attributed to the restrictions imposed owing to the COVID-19 pandemic.

Long-term persistence with aflibercept therapy among treatment-naïve patients with exudative age-related macular degeneration in a universal health care system: a retrospective study.

BACKGROUND: This study aimed to analyse the persistence rates of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) who received intravitreal aflibercept therapy in a universal health care system. METHODS: In this single-centre retrospective cohort study, we audited data of 918 treatment-naïve patients who received exclusively intravitreal aflibercept therapy for nAMD between September 2015 and May 2021. The primary outcome measures were the rates of treatment nonpersistence (gap in ophthalmological care > 6 months) and long-term nonpersistence (> 12 months). RESULTS: The rates of nonpersistence and long-term nonpersistence were 12.3% and 3.4% after one year; 22.4% and 9.5% after two years; and 38.3% and 19.3% after five years, respectively. Logistic regression analysis revealed that older age (p = 0.045), male sex (p = 0.039), requirement for caretakers or ambulance (p = 0.001), and low visual acuity of the study eye (p = 0.010) or fellow eye (p = 0.029) were independent risk factors for long-term nonpersistence. Patients aged > 80 and > 85 years (p = 0.013 and p = 0.022, respectively) had more than twice the risk for being nonpersistent to therapy within two years of follow-up compared with younger patients. Male patients (p = 0.033), patients requiring a caretaker (p = 0.038), and patients living > 60 km from the clinic (p = 0.029) had a 2 × higher risk of being persistently nonpersistent to therapy. CONCLUSIONS: Patients with nAMD who were treated with aflibercept had lower nonpersistence rates than those reported in current literature. Multiple independent risk factors were correlated with long-term nonpersistence, early nonpersistence, or complete loss to follow-up. Considering the possible consequences of reduced compliance, further strategies are urgently needed for patients at risk of nonpersistence to therapy.

Intravitreal Aflibercept Therapy and Treatment Outcomes of Eyes with Neovascular Age-Related Macular Degeneration in a Real-Life Setting: A Five-Year Follow-Up Investigation.

INTRODUCTION: We aimed to evaluate visual and anatomical outcomes among eyes with neovascular age-related macular degeneration (nAMD) that were persistent to intravitreal aflibercept therapy compared to those that were nonpersistent to therapy. METHODS: We audited 648 treatment-naïve eyes of 559 patients regarding visual acuity (VA) given as the logarithm of the minimum angle of resolution (logMAR) and anatomic outcomes at baseline and at each subsequent follow-up visit for up to 5 years. Nonpersistence was defined as a visit-free interval of > 6 months. RESULTS: Among the enrolled eyes, 405 were persistent to the therapy and 243 (37%) were nonpersistent, of which 161 (66%) eyes returned for further therapy after a gap of clinical care. In the nonpersistent group, we observed a decline from 0.58 ± 0.35 to 0.92 ± 0.57 logMAR (p = 0.01) after 60 months. Compared with the persistent group, the nonpersistent group had worse visual outcomes at their 33-month (p = 0.03), 42-month (p = 0.01), 51-month (p = 0.001) and 60-month (p = 0.01) visits. Additionally, 5/405 (1.2%) eyes in the persistent group and 8/161 (5.0%) eyes in the nonpersistent group developed an end-stage disease with a subfoveal fibrosis during the observational period (p = 0.013). CONCLUSION: We found that eyes with nAMD that were nonpersistent to intravitreal aflibercept therapy experienced statistically significantly worse VA compared to eyes persistent to therapy within 3 years. Moreover, eyes in the nonpersistent group had a four-fold higher risk of developing a fovea-involving fibrosis. Considering the potential irreversible deterioration with respect to best-corrected VA within nAMD, strategies need to be developed for patients at risk of nonpersistence to therapy.

Two Cases of Acute Macular Neuroretinopathy Associated with the Adenovirus-based COVID-19 Vaccine Vaxzevria (Astrazeneca).

PURPOSE: To report two cases of acute macular neuroretinopathy (AMN) in young female patients following the administration of the adenovirus-based coronavirus disease 2019 (COVID-19) vaccine Vaxzevria (AstraZeneca). METHODS: Spectral-domain optical coherence tomography and infrared imaging were used to confirm the diagnosis of AMN. RESULTS: Both patients showed a parafoveal hyperreflective band in the outer nuclear layer, disruption of the ellipsoid and interdigitation zones of the photoreceptor layers, and correlating hyporeflective areas on the near-infrared images. Both patients presented with flu-like fever and sudden onset of fortifications within 48 hours of vaccination. One patient showed altered flow in the deep capillary plexus and highly elevated thrombotic parameters. CONCLUSION: We report a possible association between immune-mediated AMN and the administration of adenovirus-based COVID-19 vaccine Vaxzevria.

Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders.

PURPOSE: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy. METHODS: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features. RESULTS: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness. CONCLUSIONS: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.

High expression of mTOR signaling in granulomatous lesions is not predictive for the clinical course of sarcoidosis.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker. MATERIAL AND METHODS: This is a retrospective analysis of 58 patients with histologically confirmed sarcoidosis. Immunohistochemical staining of granulomas from tissue samples was evaluated for the expression of activated mTORC1 signaling, including phosphorylated mTOR, its downstream effectors S6K1, 4EBP1 and the proliferation marker Ki-67. Patients were categorized according to different clinical phenotypes, serum biomarkers, and immunomodulatory therapy. RESULTS: All patients showed activated mTORC1 signaling in granulomas, which correlated with its downstream effectors S6K1 and 4EBP1 but was not related to Ki-67 expression. The mTORC1 activity revealed an association neither to disease severity nor the necessity of treatment; however, p-mTOR inversely correlated with cumulative corticosteroid dosage. CONCLUSION: Our data confirm activation of the mTORC1 pathway in sarcoidosis, supporting the hypothesis that mTOR is a significant driver in granuloma formation. However, we could not find a relationship between the degree of mTOR activation and disease severity or the need for therapy.