Outcomes of amniotic membrane transplant for refractory macular hole - an optical coherence tomography and autofluorescence long-term study.

PURPOSE: To analyze anatomical and functional outcomes of cryopreserved human amniotic membrane (hAM) transplant in refractory macular hole (MH) surgery, present retinal layers structure after MH closure, identify visual acuity improvement determinants and complication rate. METHODS: Prospective and interventional case series including seventeen patients: 13 refractory and 4 chronic (8, 15, 18 and 30-years) MH. All patients underwent vitrectomy, hAM subretinal transplant, tamponade and positioning. Complete ophthalmological examination, axial length, best-corrected visual acuity, retinography, optical coherence tomography (OCT) and autofluorescence were recorded. RESULTS: Mean follow-up was 31 months (range 6-53). Mean LogMAR visual acuity (1.71 ± 0.42) improved significantly (1.13 ± 0.41) (P < 0.001). Patients with better baseline BCVA ended up with better final BCVA (P = 0.018). Mean MH minimum linear diameter was 831 ± 252 µm and base diameter was 1409 ± 358 µm. MH closed in all patients. Transitory ocular hypertension in one patient and transient vitreous cavity haemorrhage in another were the only postoperative complications. OCT matched scans showed plug integration and inner retinal layers rearrangement. MH size did not correlate with final BCVA. Autofluorescence showed no developing atrophy signs during long-term follow-up. CONCLUSION: Cryopreserved human amniotic membrane transplant may be a valuable approach to achieve macular hole closure and visual acuity improvement in refractory MH. KEY MESSAGES: What is known Human amniotic membrane transplantation is a recent surgical technique for refractory, chronic or extra-large macular holes. This surgical procedure has a shallow learning curve, high macular hole closure rate, does not require silicone oil tamponade and has very low complication rate. What is new Subretinal amniotic membrane transplant technique was successful at closing all patients' macular holes and improving visual acuity. Concerning final visual acuity predictors neither preoperative characteristics, namely the macular hole size or duration, etiology, lens status or axial length, nor surgical procedure modifications such as flap shape or tamponade lead to different outcomes. Our series included patients with refractory macular holes due to failed extended ILM peeling, failed inverted flap technique, failed autologous retinal transplant and failed epiretinal amniotic membrane transplant suggesting the technique's effectiveness in challenging refractory cases.

Complete blood count parameters as biomarkers of retinopathy of prematurity: a Portuguese multicenter study.

PURPOSE: To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP). METHODS: Multicenter, prospective, observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed. RESULTS: A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (p < 0.001), hemoglobin (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin concentration (p < 0.001), lymphocytes (p = 0.035), and platelets (p = 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (p = 0.044), red blood cell distribution width (RDW) (p < 0.001), erythroblasts (p < 0.001), neutrophils (p = 0.030), neutrophils-lymphocytes ratio (p = 0.028), and basophils (p = 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression. CONCLUSION: In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.

Genetic Modulation of the Erythrocyte Phenotype Associated with Retinopathy of Prematurity-A Multicenter Portuguese Cohort Study.

The development of retinopathy of prematurity (ROP) may be influenced by anemia or a low fetal/adult hemoglobin ratio. We aimed to analyze the association between DNA methyltransferase 3 ß (DNMT3B) (rs2424913), methylenetetrahydrofolate reductase (MTHFR) (rs1801133), and lysine-specific histone demethylase 1A (KDM1A) (rs7548692) polymorphisms, erythrocyte parameters during the first week of life, and ROP. In total, 396 infants (gestational age < 32 weeks or birth weight < 1500 g) were evaluated clinically and hematologically. Genotyping was performed using a MicroChip DNA on a platform employing iPlex MassARRAY®. Multivariate regression was performed after determining risk factors for ROP using univariate regression. In the group of infants who developed ROP red blood cell distribution width (RDW), erythroblasts, and mean corpuscular volume (MCV) were higher, while mean hemoglobin and mean corpuscular hemoglobin concentration (MCHC) were lower; higher RDW was associated with KDM1A (AA), MTHFR (CC and CC + TT), KDM1A (AA) + MTHFR (CC), and KDM1A (AA) + DNMT3B (allele C); KDM1A (AA) + MTHFR (CC) were associated with higher RDW, erythroblasts, MCV, and mean corpuscular hemoglobin (MCH); higher MCV and MCH were also associated with KDM1A (AA) + MTHFR (CC) + DNMT3B (allele C). We concluded that the polymorphisms studied may influence susceptibility to ROP by modulating erythropoiesis and gene expression of the fetal/adult hemoglobin ratio.

Retinopathy of prematurity: contribution of inflammatory and genetic factors.

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.

A Delphi study on the clinical management of age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. As achieving a dry macula is one of the main objectives in AMD management, the purpose of this work was to reach a consensus on the relevance of retinal fluid in function, disease activity control and treatment patterns. METHODS: Forty-seven Portuguese ophthalmologists specialized in AMD participated in a DELPHI panel. Two rounds of presential meetings were conducted and a cut-off of 80% or more of votes was defined to consider answers consensual. RESULTS: Consensus was reached for 11 out of 18 questions. These questions focused on the impact of anatomical results on visual acuity, standards exams and parameters to assess disease activity, frequency and factors which influence disease activity assessment, criteria to use non-fixed treatment regimens, usefulness of individualized regimens and conditions for treatment interruption. No consensus was obtained for relevance of the different fluid types in AMD prognosis, frequency of fluid presence assessment, factors commonly associated with progression to geographic atrophy, ideal conditions for a fixed treatment regimen, date of first disease activity assessment and parameters to monitor disease activity. CONCLUSIONS: Consensus was achieved for over half of the questions assessed through this Delphi study. The questions for which no consensus was reached concerned either subjects that need further investigation or monitoring times which are influenced by resource availability. Raising awareness for these issues will allow the improvement of AMD management and treatment.

INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUES AND OUTER RETINAL LAYER STRUCTURES.

PURPOSE: To examine the influence of the inverted flap (IF) internal limiting membrane (ILM) technique in macular hole (MH) closure on outer retinal layers after MH surgery. METHODS: Retrospective study. Postoperative position of ILM, recovery rate of external limiting membrane and ellipsoid zone, and best-corrected visual acuity were evaluated. The Inserted group, where the IF is placed inside the hole, was compared with the Cover group, where the IF completely covers the hole. RESULTS: Sixty-two eyes of 58 patients who underwent vitrectomy and ILM peeling with the IF technique for large MHs (>400 µm) with successful MH closure and a follow-up of 12 months were evaluated. In the 24 eyes of the Inserted group, there was no regeneration of external limiting membrane or ellipsoid zone after 12 months. In the 38 eyes of Cover group, external limiting membrane recovered in 55.3% of patients 1 month after surgery, and in 86.1% after 12 months. The elipsoid zone layer was present in 58% of the patients. CONCLUSION: Poorer anatomical and visual results were associated with the IF technique where ILM insertion occurs compared with ILM placed over the hole. These findings suggest that insertion of the ILM in the hole might prevent outer retinal layers realignment and visual recovery in MH surgery.

The Outcomes of Switching from Short- to Long-Term Intravitreal Corticosteroid Implant Therapy in Patients with Diabetic Macular Edema.

BACKGROUND: First-line treatment for diabetic macular edema (DME) is usually with antivascular endothelial growth factor agents, followed by intravitreal corticosteroids as a second-line treatment option. Long-term corticosteroids may offer quality of life and effectiveness benefits over short-term implants. OBJECTIVES: To evaluate outcomes of patients with persistent or recurrent DME who switched from a short-term (dexamethasone) to a long-term (fluocinolone acetonide, FAc) corticosteroid intravitreal implant in a real-world setting. METHODS: This is a retrospective study in 9 Portuguese centers. An FAc intravitreal implant was administered according to product labeling. Effectiveness outcomes were mean change in visual acuity (VA; ETDRS letters), central retinal thickness (CRT; µm), and macular volume (MV; mm3). The safety outcome was mean change in intraocular pressure (IOP; mm Hg). All were analyzed at months 1 and 3, and then quarterly until month 24 after implantation. RESULTS: Forty-four eyes from 36 patients were analyzed. Mean duration of DME was 3.3 ± 1.9 years, and mean follow-up was 8 months. From baseline following FAc implantation, VA increased significantly at months 1 and 6 (mean +6.82 and +13.02 letters, respectively; p = 0.005), and last observation carried forward (LOCF; mean +8.3 letters; p = 0.002). CRT improved significantly at months 1 and 6 (mean -71.81 and -170.77 µm, respectively; p = 0.001), and LOCF (mean -121.46 µm; p = 0.001). MV was consistently, but not significantly, decreased from baseline to LOCF (mean -0.69 mm3; p = 0.062). The mean change in IOP was -0.25 and +0.88 mm Hg at months 1 and 6, respectively (p = 0.268), and +1.86 mm Hg at LOCF (p = 0.036). Increases were controlled with topical medication in most cases. CONCLUSIONS: The FAc intravitreal implant is effective in patients previously treated with short-term corticosteroid implants. Thus, after a suboptimal response to antiangiogenics or a short-term corticosteroid, a single FAc implant may be considered an effective and tolerable treatment that can improve long-term outcomes for patients with sight-threatening DME.

Intra- and Inter-Rater Agreement of Anterior Lamina Cribrosa Depth Measurements Using Enhanced-Depth Imaging Optical Coherence Tomography.

PURPOSE: To determine intra- and inter-rater agreement of anterior lamina cribrosa depth (ALCD) manual measurements using enhanced-depth imaging optical coherence tomography (EDI-OCT). METHODS: Observational study. EDI-OCT of the optic nerve head was performed in healthy subjects. ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane opening and the anterior border of the lamina cribrosa (LC), at the maximum depth point. Two experienced operators performed manual ALCD measurements of the LC independently, and one of the observers performed the same measurements twice. Intra- and inter-rater agreement was evaluated using intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) for the right eye vertical (REV) and horizontal (REH) scans and left eye vertical (LEV) and horizontal (LEH) scans. RESULTS: 120 eyes of 61 subjects, with a mean age of 62.1 ± 15.0 years. The mean REV, REH, LEV and LEH ALCD were 456.2 ± 84.3, 444.5 ± 92.2, 436.7 ± 81.6, 427.6 ± 82.7 µm, respectively. ALCD intra- and inter-rater ICC and intra- and inter-rater CCC varied between 0.85-0.95, 0.84-0.93, 0.85-0.95 and 0.84-0.93, respectively. CONCLUSIONS: ALCD manual intra- and inter-rater measurements with EDI-OCT showed high agreement. EDI-OCT is a reliable tool for ALCD measurement, which can provide potentially useful information for integrated glaucoma management.

Cataract surgery and intraocular pressure.

Cataract surgery is one of the most performed surgeries in the developed world. In addition to its significant impact on visual acuity, phacoemulsification has been hailed as a potential intraocular pressure (IOP)-lowering procedure. While current evidence suggests an overall significant and sustained decrease in IOP to exist after cataract surgery, the specific ocular characteristics that could help predict which patients are likely to benefit from this IOP-lowering effect remain unclear. This definition is important in glaucoma patients if this surgery is to be used in the treatment for this disease. Our review aims to summarize the literature on the subject, depicting possible mechanisms behind this IOP decrease, which type of patients are more likely to benefit from this surgery for IOP-lowering purposes and ultimately help optimizing disease management for the increasing number of patients with concomitant glaucoma and cataract.

Review on Dynamic Contour Tonometry and Ocular Pulse Amplitude.

Intraocular pressure (IOP) measurement is the cornerstone of the management of glaucoma patients. The gold standard for assessing IOP is Goldmann applanation tonometry (GAT). Recently, the dynamic contour tonometer (DCT) has become available. While both devices provide reliable IOP measurements, the results are not interchangeable. DCT has the advantage of measuring an additional parameter: ocular pulse amplitude (OPA). OPA is defined as the difference between systolic and diastolic IOP and represents the pulsatile wave front produced by the varying amount of blood in the eye during the cardiac cycle. It has been shown to vary with ocular structural parameters, such as axial length, corneal thickness, and ocular rigidity, as well as with systemic variables like heart rate, blood pressure, and left ventricular ejection fraction. Although the existence of some of these associations is still controversial, the clinical relevance of OPA has been consistently suggested, especially in glaucoma. Further research on this intriguing parameter could not only provide insight into glaucoma pathophysiology but also help integrate this variable into clinical practice.

Higher optic nerve sheath diameters are associated with lower ocular blood flow velocities in glaucoma patients.

PURPOSE: To investigate the relationship between optic nerve sheath diameter (ONSD) and retrobulbar blood flow velocities, as measured by color Doppler imaging (CDI) in glaucoma patients. METHODS: We performed a prospective, randomized, observer-masked study involving a total of 197 subjects. Once enrolled, they were divided by three groups: healthy controls (n = 51), normal-tension glaucoma patients (NTG, n = 58), and primary, open-angle glaucoma patients (POAG, n = 88). All subjects underwent a general ophthalmological examination, an ultrasound-based assessment of the ONSD, and a hemodynamic study of the retrobulbar vascularization using CDI. Non-parametric tests, chi-square contingency tables, and the Deming correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: ONSD was not different between experimental groups (p = 0.28). ONSD correlated positively with the pulsatility index of the ophthalmic artery in healthy individuals (p = 0.007), but not in glaucoma patients (NTG: p = 0.41; POAG: p = 0.22). In NTG patients, higher ONSD values were associated with lower end-diastolic and mean flow velocities in the short ciliary arteries (p = 0.005 in both correlations). No such correlation was found in healthy nor POAG groups (p range between 0.15 to 0.96). ONSD was not associated with any CDI-related variable of the central retinal artery in any cohort. Venous outflow velocities were not associated with ONSD in any of the three groups. CONCLUSIONS: ONSD is negatively correlated with retrobulbar blood flow velocities in glaucoma patients, but not in healthy controls.

Development of a Smartphone-Based System for Intrinsically Photosensitive Retinal Ganglion Cells Targeted Chromatic Pupillometry.

Chromatic Pupillometry, used to assess Pupil Light Reflex (PLR) to a coloured light stimulus, has regained interest since the discovery of melanopsin in the intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). This technique has shown the potential to be used as a screening tool for neuro-ophthalmological diseases; however, most of the pupillometers available are expensive and not portable, making it harder for them to be used as a widespread screening tool. In this study, we developed a smartphone-based system for chromatic pupillometry that allows targeted stimulation of the ipRGCs. Using a smartphone, this system is portable and accessible and takes advantage of the location of the ipRGCs in the perifovea. The system incorporates a 3D-printed support for the smartphone and an illumination system. Preliminary tests were carried out on a single individual and then validated on eleven healthy individuals with two different LED intensities. The average Post-Illumination Pupil Light Response 6 s after the stimuli offsets (PIPR-6s) showed a difference between the blue and the red stimuli of 9.5% for both intensities, which aligns with the studies using full-field stimulators. The results validated this system for a targeted stimulation of the ipRGCs for chromatic pupillometry, with the potential to be a portable and accessible screening tool for neuro-ophthalmological diseases.

Gene and cell therapy for age-related macular degeneration: A review.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss among the elderly in Western communities, with an estimated global prevalence of 10 - 20% in people older than 65 years. AMD leads to central vision loss due to degeneration of the photoreceptors, retinal pigment epithelium and the choriocapillaris. Beckman's classification for AMD, based upon color fundus photographs, divides the disease into early, intermediate, and late forms. The late, vision-threatening stage includes both neovascular AMD and geographic atrophy. Despite its high prevalence and impact on patients' quality of life, treatment options for AMD are limited. While neovascular AMD can be medically managed with anti-VEGF intravitreal injections, until very recently there has been no approved treatment options for atrophic AMD; however, in February 2023 the first treatment for geographic atrophy - pegcetacoplan - was approved by the US FDA. We describe the current landscape of potential gene and cell therapeutic strategies for late-stage AMD, with an emphasis on the therapeutic options that might become available in the next few years.

Retinopathy of prematurity: A review of pathophysiology and signaling pathways.

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is characterized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and nitrosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced retinal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about signaling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.

Long-Term Effect of Anti-Vascular Endothelial Growth Factor (Anti-VEGF) Injections in Choroidal Neovascularization Secondary to Angioid Streaks.

Purpose: This study aimed to evaluate the long-term effectiveness of intravitreal anti-vascular endothelial growth factor (VEGF) injections in the treatment of choroidal neovascularization (CNV) associated with angioid streaks. Methods: Multicenter retrospective cohort study, including eyes with CNV secondary to angioid streaks treated with anti-VEGF injections, were performed. Best-corrected visual acuity (BCVA) in ETDRS letters; qualitative and quantitative (foveal thickness) OCT parameters; anti-VEGF type; and number of injections were collected at baseline and at 3, 6, 12, 24, 36, 48, 60, and 72 months. Results: Thirty-nine eyes from 29 patients, 17 (58.6%) females, were included. The mean follow-up time was 69.4 ± 34.5 months. BCVA was 59.3 ± 23.3 letters at baseline and 63.7 ± 21.9 letters at 48 months. At 3 months, BCVA improved 6.9 ± 11.7 letters (P=0.003). Then, BCVA remained stable. The mean foveal thickness decreased from 343.3 ± 120.2 µm at baseline to 268.3 ± 65.4 at 48 months (P=0.021). The mean number of injections was 4.6 ± 2.1 at 12 months, decreasing to 1.7 ± 2.4 injections between 36 and 48 months (P=0.093). Conclusion: This real-world study suggests that the functional and morphologic response to anti-VEGF therapy for CNV related to angioid streaks is generally satisfactory and maintained in the long term.

Trabeculectomy with mitomycin C alone or coupled with intracamerular bevacizumab? A 2-year comparative study.

PURPOSE: To compare outcomes of primary trabeculectomy using either mitomycin C (MMC) alone versus MMC augmented with intracamerular bevacizumab in patients with open-angle glaucoma. METHODS: Retrospective, cohort, two-centre, comparative study. Patients' data were screened between October 2015 and March 2019, with inclusion requiring a minimum follow-up of 24 months. Primary outcome was intraocular pressure (IOP) lowering at 24 months, with surgical success defined with different maximum IOP targets (≤18, ≤16 and ≤14 mm Hg) and at least 30% reduction and higher than 5 mm Hg. Absolute success was achieved if no IOP-lowering medication was needed and a qualified success if otherwise. Safety outcomes were analysed. RESULTS: A total of 110 eyes underwent trabeculectomy with MMC, 51 of these combined with intracamerular bevacizumab. Both strategies were effective in terms of IOP lowering (baseline vs 2 years postoperatively: 24.4 (8.0) mm Hg vs 12.1 (5.3) mm Hg in the MMC group; 25.1 (8.7) vs 10.8 (3.8) mm Hg in the MMC+bevacizumab group; p<0.001 in both comparisons). The MMC+bevacizumab group had a significant difference towards higher efficacy on absolute success rates at all targets (IOP≤14 or ≤16 or ≤18 mm Hg; p=0.010, p=0.039 and p=0.007, respectively). The large majority (93%) of the MMC+bevacizumab group was drop-free at 24 months, and 41% had IOP below 10 mm Hg. Complication rates were low and similar between groups, with no systemic adverse events. CONCLUSIONS: Intracamerular bevacizumab in MMC-augmented primary trabeculectomy increases the chances of obtaining low IOP outcomes. This strategy may be useful when planning for surgeries aiming at target pressures in the low teens. TRIAL REGISTRATION NUMBER: ISRCTN93098069.

High intensity focused ultrasound for glaucoma: 1-year results from a prospective pragmatic study.

BACKGROUND: Ciclo plasty using high-intensity focused ultrasound (HIFU) technology acts through the selective coagulation of the ciliary body. Our aim was to evaluate the safety and efficacy profiles of 8-s probe HIFU cyclocoagulation using the EyeOP1 device. METHODS: Prospective pragmatic trial. INCLUSION CRITERIA: adult glaucoma patients with uncontrolled IOP despite optimised medical therapy, and/or intolerant to medical therapy required to achieve target IOP. PRIMARY OUTCOME: surgical success defined as IOP reduction from baseline >20% with final IOP ≤21 mmHg, without adding any IOP-lowering drugs, and without loss of light perception; or decreased use of IOP-lowering drugs with stable/decreased IOP, without loss of light perception. SECONDARY OUTCOMES: mean IOP, intra and postoperative complications, best-corrected visual acuity (BCVA) and number of IOP-lowering drugs at each visit. Outcome data were collected preoperatively and at postoperative day 1, and months 1, 3, 6 and 12. RESULTS: Forty-nine eyes of forty-nine patients (28 male) with a mean age of 70 ± 14 years were enroled. Pre-operative IOP was 26.9 ± 7.4 mmHg under 2.8 ± 0.9 topical medications, decreasing to 17.8 ± 6.4 mmHg under 2.3 ± 1 drugs at 12 months (p < 0.01). One-year surgical success was achieved in 71.4% of patients (IOP-reduction criteria: 59.2%; decreased use of IOP-lowering drugs: 38.8%). Eight patients were ultimately submitted to other glaucoma surgical interventions. Five patients experienced serious adverse events (loss of light perception n = 5; hypotony n = 1). CONCLUSIONS: This innovative non-invasive technology seems to be effective in decreasing IOP and/or the number of administered drops in patients with refractory glaucoma. It seems a valuable tool to delay or preclude the need for filtering procedures in the majority of the patients.

Guidelines for the Management of Center-Involving Diabetic Macular Edema: Treatment Options and Patient Monitorization.

Diabetic macular edema (DME) is the main cause of visual impairment associated with diabetic retinopathy (DR) and macular laser, during approximately three decades, and was the single treatment option. More recently, intravitreous injections of anti-angiogenics and corticosteroids modified the treatment paradigm associated with significant vision improvements. Nevertheless, not all patients respond satisfactorily to anti-VEGF or corticosteroid injections, so an adequate treatment choice and a prompt switch in therapeutic class is recommended. Several algorithms and guidelines have been proposed for treating center involving DME to improve patients' vision and quality of life. However, in Portugal, such guidelines are lacking. The present review aimed to provide guidelines for the treatment options and patient monitorization in the management of center-involving DME. We recommend anti-vascular endothelial growth factor (VEGF) as first-line therapy after a clinical evaluation accompanied by a rigorous metabolic control. Depending on the response obtained after 3-6 monthly intravitreal injections we suggest switching outside the class in case of a non-responder, maintaining the anti-VEGF-therapy in responders to anti-angiogenics. The treatment regimen for Dexamethasone intravitreal implant (DEXii) should be pro-re-nata with bi-monthly or quarterly monitoring visits (with a scheduled visit at 6-8 weeks after DEXii for intraocular pressure control). If a patient does not respond to DEXii, switch again to anti-VEGF therapy, combine therapies, or re-evaluate patients diagnose. There is a resilient need to understand the disease, its treatments, regimens available, and convenience for all involved to propose an adequate algorithm for the treatment of diabetic retinopathy (DR) and DME in an individualized regimen. Further understanding of the contributing factors to the development and progression of DR should bring new drug discoveries for more effective and better-tolerated treatments.

A Non-Infectious Uveitis Multidisciplinary Clinic in a Tertiary Referral Center: Clinical Impact and Added Value.

Non-infectious uveitis (NIU) is a group of sight-threatening diseases that generates significant burden for the healthcare systems due to its adverse outcomes, irreversible structural complications in the eye with loss of visual function, limited clinical expertise and low-grade evidence for best practice. The usefulness of multidisciplinary care, specifically close collaboration between Rheumatologists and Ophthalmologists in NIU, has been emphasized in the literature. In this paper, the assessment tools and protocols used in our clinic are depicted and an overview of our activity with a brief description of the patients included in our registry, between 2018 and 2020 is provided. The cohort of 290 patients assessed in our NIU clinic, their demographics, sources of referral, details about immunosuppression treatment, and internal and external collaborations is described. This experience-based manuscript aims to describe the general functioning of our multidisciplinary NIU clinic, highlighting the benefits and drawbacks of multidisciplinary team management in patients with NIU, ultimately initiating a dialogue on what an NIU clinic should be and providing information for newly NIU clinics start-up. In conclusion, establishing a standardized and multidisciplinary clinic in NIU allows to systematically observe and follow-up this infrequent disease at a tertiary hospital level, thus improving quality of care delivery and research avenues.

Amlodipine effects on vasomotion in rabbit external ophthalmic artery.

BACKGROUND: In order to understand the role of ocular blood flow in normal and pathological conditions, knowledge of the pharmacological control mechanisms involved in the ocular vascular bed is essential. The present study was designed to investigate the reactivity of the rabbit external ophthalmic artery and its collaterals to amlodipine, in order to answer two questions: (1) What are amlodipine effects upon perfusion pressure and spontaneous oscillations in the in situ perfused rabbit eyes? (2) Can intraarterial amlodipine counteract ET-1 induced vasoconstriction? METHODS: Rabbit external ophthalmic arteries (n = 12) in a head-mounted preparation were cannulated and perfused with warmed tyrode. Vasomotor response curves to intraarterial injections of amlodipine 3 mg/ml followed by phenylephrine 250 microg (group A, n = 6) and to amlodipine 3 mg/ml after an intraarterial injection of endothelin-1 (ET-1) 27 microg/ml (group B, n = 6) were obtained. For statistical analysis, the paired t-test and Fourier analysis of frequency spectrums of spontaneous oscillations were used. RESULTS: Before any drug administration, spontaneous oscillations were observed in the 12 rabbit models. In group A, amlodipine elicited vasodilation and a decrease in frequency and amplitude of the oscillations. In group B, ET-1 induced an increase in vasoconstrictor tone and vasomotion became more evident. With amlodipine after ET-1, we obtained vasodilation and abolition of the vasospasm. CONCLUSIONS: Our study has two main conclusions: (1) amlodipine, an L-type calcium channel blocker, caused intense vasodilation and decreased both frequency and amplitude of the spontaneous oscillations observed in the rabbit external ophthalmic artery and its collaterals, and (2) when we applied amlodipine in arteries previously contracted by the administration of ET-1, vascular resistance greatly decreased and spontaneous oscillations were abolished. Since ET-1 levels are increased in several ischemic ocular diseases, amlodipine might be beneficial in these patients, allowing a protective action against vasospasm.