In the last decades, personalized medicine has been increasing its presence in different fields of medicine, including ophthalmology. A new factor that can help us direct medicine towards the challenge of personalized treatments is the microbiome. The gut microbiome plays an important role in controlling immune response, and dysbiosis has been associated with immune-mediated diseases such as non-infectious uveitis (NIU). In this review, we gather the published evidence, both in the pre-clinical and clinical studies, that support the possible role of intestinal dysbiosis in the pathogenesis of NIU, as well as the modulation of the gut microbiota as a new possible therapeutic target. We describe the different mechanisms that have been proposed to involve dysbiosis in the causality of NIU, as well as the potential pharmacological tools that could be used to modify the microbiome (dietary supplementation, antibiotics, fecal microbiota transplantation, immunomodulators, or biologic drugs) and, consequently, in the control of the NIU. Furthermore, there is increasing scientific evidence suggesting that the treatment with anti-TNF not only restores the composition of the gut microbiota but also that the study of the composition of the gut microbiome will help predict the response of each patient to anti-TNF treatment.
Biological drugs, especially those targeting anti-tumour necrosis factor α (TNFα) molecule, have revolutionized the treatment of patients with non-infectious uveitis (NIU), a sight-threatening condition characterized by ocular inflammation that can lead to severe vision threatening and blindness. Adalimumab (ADA) and infliximab (IFX), the most widely used anti-TNFα drugs, have led to greater clinical benefits, but a significant fraction of patients with NIU do not respond to these drugs. The therapeutic outcome is closely related to systemic drug levels, which are influenced by several factors such as immunogenicity, concomitant treatment with immunomodulators, and genetic factors. Therapeutic drug monitoring (TDM) of drug and anti-drug antibody (ADAbs) levels is emerging as a resource to optimise biologic therapy by personalising treatment to bring and maintain drug concentration within the therapeutic range, especially in those patients where a clinical response is less than expected. Furthermore, some studies have described different genetic polymorphisms that may act as predictors of response to treatment with anti-TNFα agents in immune-mediated diseases and could be useful in personalising biologic treatment selection. This review is a compilation of the published evidence in NIU and in other immune-mediated diseases that support the usefulness of TDM and pharmacogenetics as a tool to guide clinicians’ treatment decisions leading to better clinical outcomes. In addition, findings from preclinical and clinical studies, assessing the safety and efficacy of intravitreal administration of anti-TNFα agents in NIU are discussed.
The aim of this study was to evaluate the efficacy of a treat-and-extend (T&E) regimen of ranibizumab as the first-choice treatment in macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). We conducted a retrospective study of 20 patients who developed MO due to BRVO treated with intravitreal ranibizumab in a T&E regimen between 2016 and 2017 with a minimum follow-up of two years. Patients were classified as complete responders if treated with ranibizumab alone or incomplete responders if salvage treatment with other medications or laser was needed. Data on best corrected visual acuity (BCVA) and central macular thickness (CMT) every 6 months were recorded. The mean BCVA (logMAR) improved from 0.60 ± 0.36 to 0.29 ± 0.44 and the CMT decreased from 559.85 ± 198.61 to 305.85 ± 11.78 μm. We found statistically significant differences between complete and incomplete responders on the average number of injections during the second year (2.46 ± 2.18 compared to 5.43 ± 1.27; p = 0.007) and change of the BCVA and CMT between both groups (p < 0.001) at 6, 12, 18 and 24 months. T&E seems to be effective in MO secondary to BRVO, improving visual function and decreasing CMT, with less need for injections.
Objectives: The aim of this study was to establish the concordance between conventional 20 Mhz ultrasonography and an ultrawide-field (UWF) imaging system (Optos® California) in the measurement of basal diameters of melanocytic choroidal tumors. Methods: A retrospective study comparing diagnostic tests was conducted in patients with untreated melanocytic choroidal lesions (either nevus or melanoma) who had undergone both UWF imaging and ultrasonography. Only cases with a clear visualization of tumor borders in both imaging modalities were included. Longitudinal and transversal base diameters of the melanocytic tumors were measured by 20 MHz US (one observer) and UWF fundus photography (two observers). Interobserver agreement was assessed for UWF imaging first to validate the technique. Then, UWF imaging measurements were compared with 20 MHz US results. Results: In total, 106 patient images were reviewed, of which 61 were excluded due to unclear visualization of tumor margins. We found excellent concordance (from ICC and defined Bland–Altman plots) for interobserver and inter-technique agreement in estimating basal diameters when using pseudocolor composite and red laser images by comparing them with 20 MHz US results. Conclusions: UWF fundus imaging, when complete visualization of the tumor margins is possible, could be as reliable as ultrasonography in the measurement of the basal diameters of choroidal melanocytic tumors.
Background: The declaration of the first state of alarm for COVID-19 in March 2020 provoked changes in ophthalmological care. The objective of this study was to assess its impact on reorganising care activities, the mental health of ophthalmologists and the training of residents. Methods: We sent an anonymous online questionnaire between August and October 2020 to consultant ophthalmologists and residents who were active during the state of alarm in Spain. We used Google Forms® software for data collection. We analysed responses according to the degree of regional impact. Results: We received a total of 328 responses from the 17 Autonomous Communities. We saw that 99.4% of respondents changed their work activities with 50% reductions in surgery (94.5%) and consultations (93.0%). Furthermore, 58.8% of respondents reported increased anxiety, and 29.9% transferred to support other services, with this number reaching 49.6% in the hardest-hit regions. Training programs were greatly reduced in external consultations (90.7%), and surgical training was completely cancelled (100%). Additionally, 56.5% of trainees wanted to prolong their residence periods. Conclusions: The first wave of the pandemic produced significant changes in ophthalmology services, and these changes were more pronounced in the most affected regions. It caused a negative psychological impact on a high rate of respondents and an interruption of the training of ophthalmology residents. Predictably, the negative consequences of this delay in ophthalmological care on patients will be uneven between regions.
The prognosis of uveal melanoma is significantly influenced by the risk of metastasis, which varies according to clinical and genetic features. Driver mutations can predict the likelihood of disease progression and survival, although the data in the literature are inconsistent. This meta-analysis aimed to evaluate the prognostic significance of driver mutations, including GNAQ, GNA11, BAP1, and SF3B1, in the advancement of uveal melanoma. A comprehensive search of databases yielded relevant studies, and data from 13 studies (848 eyes) were synthesized to assess the impact of these mutations on metastasis-free survival. The BAP1 mutation and negative immunohistochemistry were associated with a higher risk of metastasis (logHR = 1.44, 95% CI 1.05–1.83). GNAQ, GNA11, and SF3B1 mutations did not show a significant increase in risk. In summary, BAP1 has proven to reliably predict the likelihood of disease progression in uveal melanoma, while further studies are needed to establish the significance of other driver mutations.