Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Clinical Characteristics of the Charles Bonnet Syndrome in Patients with Neovascular Age-Related Macular Degeneration: The Importance of Early Detection.

PURPOSE: We investigated the characteristics, prognosis, and clinical outcome of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD). METHODS: Five hundred psychiatrically healthy patients with neovascular AMD were screened for CBS. The individuals that fulfilled the inclusion criteria were systematically interviewed using a structured questionnaire that covered the impact, prognosis, risk factors, phenomenology, symptoms, and knowledge about the syndrome. A control group of 45 patients was used for comparison. Demographic data, current medication, and ocular risk factors were collected in all patients. RESULTS: Forty-five patients with CBS were identified. The majority of patients reported images that consisted of colored (62%) animals (44%) or faces (42%) that lasted for seconds (53%). Most patients reported a self-limited disease with a median duration of symptoms between 9 and 11.5 months, with only 7% knowing about CBS at symptom onset. The degree of visual deficit did not predict the characteristics, complexity, frequency, duration, or impact of visual hallucinations. One-third of patients reported negative outcome, which was associated with shorter duration of CBS (p = 0.023), fear-inducing images (p < 0.001), and impact on daily activities (p = 0.015). CONCLUSION: The prevalence of CBS in neovascular AMD patients is high and clinically relevant. Patients with recent onset of visual hallucinations and describing fear-inducing images are at greater risk for negative outcome. Periodic screening may minimize the negative consequences of this disease.

Long-Term Effect of Anti-VEGF Agents on Intraocular Pressure in Age-Related Macular Degeneration.

PURPOSE: To analyze the effect of anti-vascular endothelial growth factor (VEGF) agents on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (AMD). Materials andMethods: This is a retrospective study that included 72 patients treated unilaterally with anti-VEGF agents according to a pro re nata regimen. Fellow noninjected eyes (n = 72) were used as controls. IOP variation and the development of sustained ocular hypertension (OHT) were assessed both in the injected and in the fellow eyes. RESULTS: While the final IOP was not significantly different between the 2 groups, sustained OHT developed in 4.2% of the injected eyes and 1.4% of the controls. In the study group, no significant IOP variation was noted during follow-up in patients receiving ≤20 injections, but there was a significant increase in IOP with time in more frequently treated patients (p = 0.041). Comparison of both subgroups demonstrated that patients receiving >20 injections suffered significantly greater IOP variation (p = 0.034) during follow-up, and that these patients tended to require IOP-lowering treatment more frequently (p = 0.090). CONCLUSION: Multiple anti-VEGF injections lead to an increase in IOP, although this variation is not sufficient to cause development of OHT in the majority of patients.

Sonographic measurement of cervical length as a predictor of preterm delivery: a systematic review.

AIM: To evaluate if transvaginal cervical length measurement in the second-trimester scan is an effective screening test for preterm delivery. METHODS: We performed a search in Medline and, for each selected article, information was extracted regarding the performance of the test in terms of sensitivity, specificity, positive, and negative likelihood ratios, in low-risk, high-risk, and multiple gestations. We also evaluated the performance of the combined test (more than one sonographic marker). RESULTS: A positive relationship was established between short cervix and preterm delivery in all articles. The majority of studies presented high specificity and positive likelihood ratio, while sensitivity and negative likelihood ratio were variable and globally poor. Better values of accuracy were found in high-risk and multiple gestations and, in all studied subgroups, for preterm delivery at lower gestational ages. CONCLUSIONS: We conclude that a short cervix is predictive of preterm delivery and can identify women that may benefit from preventive and therapeutic measures, however, a negative result is not always reassuring.

The 2021 Portuguese Society of Ophthalmology joint guidelines with Paediatric Rheumatology on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis.

AIM: To develop the first Ophthalmology joint guidelines with Paediatric Rheumatology with recommendations on the screening, monitoring and medical treatment of juvenile idiopathic arthritis-associated uveitis (JIA-U), endorsed by the Portuguese Society of Ophthalmology (SPO). METHODS: A systematic literature review was conducted to include publications up to July 14th 2020, with no language restrictions, in order to include all the international position papers/guidelines concerning the medical management of JIA-U and randomised clinical trials assessing the efficacy and safety of medical treatment in this field. We searched through MEDLINE (PubMed), Scopus, Web of Science and Cochrane Library. The Delphi modified technique to generate consensus was used. Preliminary evidence statements were subject to an anonymous agreement assessment and discussion process using an online survey, followed by further discussion and update at a national meeting. A draft of the manuscript with all recommendations was then circulated among all participants and suggestions were incorporated. The final version was again circulated before publication. RESULTS: Twenty-six recommendations were developed focusing on the following topics: general management (3), screening and follow-up of uveitis (4), treatment (17) and health education in JIA-U among patients and families (2). CONCLUSION: These guidelines were designed to support the shared medical management of patients with JIA-U and emphasize the need for a multidisciplinary approach between Ophthalmology and Paediatric Rheumatology regarding the comprehensive care of JIA-U. We acknowledge that updating these recommendations will be warranted in the future, as more evidence becomes available. KEY-WORDS: juvenile idiopathic arthritis, uveitis, biological treatment, conventional immunosuppressive treatment, multidisciplinary management, guidelines, consensus, review, Delphi Technique.

Screening for pre-eclampsia: a systematic review of tests combining uterine artery Doppler with other markers.

AIMS: To perform a systematic review of screening for pre-eclampsia (PE) with the combination of uterine artery Doppler (UAD), maternal history, mean arterial pressure and/or maternal serum markers. METHODS: We identified eligible studies through a search of Medline, and, for each included study, we assessed the risk of bias and extracted relevant data. We reported the performance of screening tests according to the target population (low- or high-risk), the trimester of screening (first and/or second) and the subset of PE screened for (early and late). RESULTS: Several tests provided moderate or convincing prediction of early PE, but screening for late PE was poor. Although UAD is more accurate in the second trimester, we found encouraging results for first-trimester screening when it was combined with other markers. Performance of screening was consistently lower in populations with risk factors for PE in the maternal history. CONCLUSIONS: We present encouraging results for the prediction of early PE, even in the first trimester of pregnancy. The different performance of tests in screening for early vs. late PE, and of low- vs. high-risk populations, supports the concept that PE is a heterogeneous disease.

Nocardia Subretinal Abscess: A Rare and Challenging Case Report.

PURPOSE: To describe a positive clinical response of a patient with submacular Nocardia abscess due to a rapid and efficient treatment. Case report. We describe a case of a 50-year-old man with a painless visual decline of the left eye. Four years later, he had been diagnosed with systemic nocardiosis. Examination of the left eye revealed a submacular white mass with fluffy borders and another smaller white lesion, with well-defined borders, in the inferior temporal vascular arch. A systemic antibiotic treatment with SMX-TMP and intravenous imipenem and a single intravitreal injection of bevacizumab was performed. CONCLUSION: Prompt diagnosis and treatment ensured an expeditious resolution of the abscess and significant improvement of visual acuity. The diagnostic approach of a high index of suspicion coupled with directed treatment is required when dealing with subretinal inflammatory lesions.

Covid-19 Impact on Macular Neovascularization and Retinal Vein Occlusion Treatment: Single-Center Experience.

PURPOSE: The aim of this study was to evaluate whether the coronavirus disease 19 (COVID-19) pandemic resulted in undertreatment and subsequent loss of visual acuity (VA) in patients with macular neovascularization (MNV) or retinal vein occlusion (RVO) regularly treated with intravitreal antivascular endothelial growth factor injections. METHODS: Single-center, retrospective study of patients scheduled for treatment between March 19 and June 1, 2020, the national mandatory quarantine period. Patients' demographics, VA, and scheduled treatment during this period were reviewed via medical records. All patients were analyzed regarding treatment attendance rates. The visual impact of COVID-19 was assessed in patients who had been treated and presented a stable VA for >6 months before the beginning of the quarantine. RESULTS: This study included 927 eyes from 769 patients. The attendance rate increased throughout the study timeframe (p < 0.001) and correlated negatively with higher patient's age (r = -0.142; p = 0.005). Patients with age-related macular degeneration (67.6%) had lower attendance rates (p = 0.007) and were older (p < 0.001). The visual impact analysis included 400 eyes from 325 patients. The average VA variation throughout this period was -1.7 ± 8.4 ETDRS letters and was similar in different retinal pathologies (p = 0.334). VA variation did not correlate with the number of missed treatments per patient (r = 0.100; p = 0.150). The prevalence of subretinal fluid and intraretinal fluid, as well as central retinal thickness decreased significantly throughout the study period (p values of <0.001, <0.001, and 0.032, respectively). CONCLUSION: The COVID-19 pandemic had a significant impact on the attendance rate of patients with MNV or RVO to their scheduled treatments, which was higher in the first week of mandatory quarantine. Nevertheless, VA did not decrease significantly during this period, with a limited VA variation regardless of primary retinal disorder and morphological parameters even improved in the eyes included in the visual impact analysis.

Bilateral Angle Narrowing and Acute Myopia Induced by Indapamide: A Case Report.

PURPOSE: To describe a clinical case of indapamide induced bilateral angle narrowing and acute myopia. MATERIALS AND METHODS: Clinical case report. RESULTS: A 37-year-old Caucasian emmetropic man presented to the Emergency Department with complaints of acute-onset bilateral blurry vision, nine days after starting treatment for arterial hypertension with a combination of indapamide and amlodipine. Clinical examination revealed the presence of myopia and appositional closure of the anterior chamber angle. Ultrasound biomicroscopy and mode B ultrasonography disclosed bilateral ciliochoroidal effusion with anterior rotation of the ciliary body and iridocorneal angle narrowing. After intraocular pressure control with brimonidine and timolol, and replacement of indapamide/amlodipine by amlodipine only, the patient was discharged. Complete resolution of the clinical manifestations was observed after three weeks, with no sequelae. CONCLUSIONS: Indapamide may cause acute myopia and angle closure secondary to ciliochoroidal effusion that are fully reversible after drug withdrawal, as long as timely diagnosis is established. Therefore, indapamide, as well as other sulfonamide-derived drugs, must always be considered in the differential diagnosis of acute myopia and angle closure.

Treatment of Neovascular Age-Related Macular Degeneration with Anti-VEGF Agents: Predictive Factors of Long-Term Visual Outcomes.

PURPOSE: To evaluate the predictive factors of long-term visual outcomes in neovascular age-related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti-VEGF) agents. METHODS: Unicentric retrospective review of patients with nAMD treated with anti-VEGF agents. Visual outcomes, 12 and 60 months after diagnosis, were evaluated. In an attempt to identify predictive factors of visual outcomes, multiple variables (demographic and epidemiological characteristics, angiographic and tomographic features) were analyzed, at baseline and during follow-up. RESULTS: One hundred and seventeen patients were included. In multivariate analysis, baseline best-corrected visual acuity was associated with all visual endpoints at 12 and 60 months. Additionally, age, gender, number of injections, and development of subretinal fibrosis during follow-up were also significant predictors of visual outcomes at 60 months. CONCLUSIONS: Several factors can be useful in clinical practice as predictors of visual outcomes in response to anti-VEGF treatment of nAMD.

The Charles Bonnet Syndrome in Patients With Neovascular Age-Related Macular Degeneration: Association With Proton Pump Inhibitors.

Purpose: We investigate the prevalence of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD) and analyze the role of oral proton pump inhibitors (PPIs) and other potential risk factors. Methods: A total of 510 consecutive patients with neovascular-AMD followed at a single tertiary center in Portugal were screened for CBS. Using a structured questionnaire, psychiatrically healthy individuals were interviewed systematically and divided into a CBS group and a non-CBS group. Demographic data, current medication, and ocular risk factors were collected and compared between the two groups. Results: A total of 500 patients met the inclusion criteria and 471 with complete data were included in the final analysis. The prevalence of CBS was 9.0% (45/500). Using a binary logistic regression model, correlations were found between older age (P = 0.002), PPI intake (P = 0.022), poor visual acuity (P = 0.004), and development of CBS. PPIs doubled the risk of CBS from 7% (20/304) to 15% (25/167), with an odds ratio of 2.154. The increased risk for visual hallucinations caused by PPIs was independent of age (P = 0.598) and visual acuity (P = 0.739). Conclusions: The prevalence of CBS in neovascular-AMD patients is high and mainly affects older individuals with poor visual acuity. PPIs seem to increase the risk of development of hallucinations independently of the degree of visual loss.

Switch to Aflibercept in the Treatment of Neovascular AMD: Long-Term Results.

PURPOSE: To report the long-term clinical outcomes after switching from intravitreal bevacizumab or ranibizumab to aflibercept therapy in eyes with AMD. METHODS: Retrospective analysis of changes in BCVA, SD-OCT image, and frequency of injections after 1, 2, and 3 years of follow-up. RESULTS: 164 eyes were analyzed, 101 eyes switched from bevacizumab (group 1) and 63 from ranibizumab (group 2). One year after the switch, there was an overall nonsignificant mean decrease of 2 ETDRS letters in BCVA. Three years after, there was an overall mean decrease of 7 ETDRS letters, which was statistically significant. A significant improvement in the mean CRT was found at 1, 2, and 3 years. There was a significant decrease in the mean number of injections per year (7.8 to 6.5, p < 0.005) between the first and third year. CONCLUSION: Aflibercept can be useful in the management of refractory neovascular AMD, with a good morphological response. However, in the long-term, BCVA stabilization was not achieved.

Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes.

PURPOSE: To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD) with anti-VEGF agents. MATERIALS AND METHODS: We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes. RESULTS: A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71%) maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (-96.6 µm), and 56% of patients maintained dry retinas. CONCLUSION: Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients.