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.

VARIX OF A VORTEX VEIN AMPULLA INDUCED BY NODULAR SCLERITIS.

PURPOSE: To describe a patient with a painful red-eye syndrome and a choroidal mass lesion that was diagnosed after multimodal imaging with a vortex vein ampulla varix induced by a nodular posterior scleritis. METHODS: Retrospective case report documented with fluorescein angiography, indocyanine green angiography, b-mode ultrasound, fundus imaging, and swept-source optical coherence tomography. RESULTS: A 24-year-old man presented with a painful red eye and sudden onset blurred vision. Fundus exam disclosed macular choroidal folds and a nonpigmented mass lesion at the inferior equator. Swept-source optical coherence tomography showed enlarged choroidal vessels with fluid in the suprachoroidal space under the central macula and a hyporeflective lobulated choroidal cavity in the inferior temporal retina. Multimodal imaging with contrast dyes showed a dilated vortex vein ampulla with early hyperfluorescence and a complete washout in late acquisitions on indocyanine green. The patient recovered uneventfully after a short-course administration of oral nonsteroidal anti-inflammatory drugs, disclosing irregular scleral nodules on swept-source optical coherence tomography that remained stable over a twelve-month follow-up. CONCLUSION: This report suggests that nodular posterior scleritis can induce a vortex vein ampulla varix and contributes to a better understanding of the pathophysiology of this entity. We further suggest that in a diagnostic puzzling scenario the inflammatory syndrome should be treated before attempting to perform a chorioretinal biopsy.

IMPLICATIONS OF THE MORPHOLOGIC PATTERNS OF TYPE 1 MACULAR NEOVASCULARIZATION ON MACULAR ATROPHY GROWTH ON PATIENTS UNDER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To evaluate the correspondence between macular atrophy (MA) progression and Type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration. METHODS: Retrospective review of consecutive patients with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral domain optical coherence tomography, en-face near infra-red imaging and fundus autofluorescence. Macular neovascularization blood flow morphology was evaluated by swept-source optical coherence tomography-angiography. Qualitative features were categorized per ETDRS sector as: immature, mature; and hypermature pattern. An automatic analysis was designed in MATLAB coding language to compute MA per ETDRS. Measurements were compared between the baseline and the last follow-up visit. RESULTS: Twenty eyes from 20 patients were included; the mean age was 85.4 (8.3) years. The median follow-up was 1.85 (1.0-2.4) years and the median anti-vascular endothelial growth factor injection rate during follow-up was 4.0 (2.0-5.0) injections/year. During follow-up, sectors with persistence of an immature blood flow pattern had a lower MA growth rate than sectors with mature macular neovascularization flow patterns (P = 0.001). CONCLUSION: The presence of an immature blood flow pattern on optical coherence tomography-angiography is associated with a lower progression rate of MA.

Quantitative Optical Coherence Tomography Angiography Biomarkers in a Treat-and-Extend Dosing Regimen in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the association between quantitative optical coherence tomography angiography (OCT-A) parameters and clinical outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with a treat-and-extend dosing regimen on a 12-month follow-up interval. Methods: Observational, prospective study of consecutive patients. The treatment protocol was based on a loading dose of three anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) followed by a treat-and-extend regimen. Eyes were evaluated by swept-source OCT-A at baseline, 1 month after the loading dose and at 12 months. A quantitative analysis was issued for fractal dimension (FD), lacunarity index (LAC), blood flow surface area (SA), and vessel density (VD). An association of these parameters with the anatomic response and functional responses, and IVI number at 12 months of follow-up was assessed. A level of significance α = 0.05 was considered. Results: Sixty-four patients were included, 52 of whom (81%) completed the 12-month study protocol. The median number of injections at 12 months was 7 (P25-P75: 6-12). FD and SA were reduced 1 month after the loading dose of anti-VEGF (P < 0.001). The generalized linear models using baseline FD and baseline SA achieved the best performance in discriminating a lower treatment burden (area under the curve [AUC] = 0.78; 95% confidence interval [CI]: 0.64-0.91 and AUC = 0.76; 95% CI: 0.63-0.90, respectively). Conclusions: Baseline OCT-A may provide useful biomarkers for the treatment burden in nAMD. Translational Relevance: The application of fractal dimension and automatic blood flow area algorithms to OCT-A data can distinguish patients with distinct treatment burdens in the first year of nAMD.

Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation.

Brain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor-independent mechanism by reversing the reaction catalysed by S-adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S-adenosylmethionine (SAM)-dependent methyltransferases. Astrocytes are essential in maintaining brain homeostasis but their pathological activation and uncontrolled proliferation plays a role in neurodegeneration and glioma. Adenosine can affect cell proliferation, but the effect of increased adenosine concentration on proliferation of astrocytes is not clarified and was addressed in present work. Human astrocytes (HA) were treated for 3 days with test drugs. Cell proliferation/viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay and by cell counting. Cell death was evaluated by assessing lactate dehydrogenase release and by western blot analysis of αII-Spectrin cleavage. 30 µM-Adenosine caused a 40% ± 3% (p < .05, n = 5) reduction in cell proliferation/viability, an effect reversed by 2U/ml-adenosine deaminase, but unchanged in the presence of antagonists of any of the adenosine receptors. Adenosine alone did not induce cell death. 100 µM-Homocysteine alone caused 16% ± 3% (p < .05) decrease in HA proliferation. Combined action of adenosine and homocysteine decreased HA proliferation by 76% ± 4%, an effect higher (p < .05) than the sum of the effects of adenosine and homocysteine alone (56% ± 5%). The inhibitory effect of adenosine on HA proliferation/viability was mimicked by two adenosine kinase inhibitors and attenuated in the presence of folate (100 µM) or SAM (50-100 µM). The results suggest that adenosine reduces HA proliferation by a receptor-independent mechanism probably involving reversal of SAH hydrolase-catalysed reaction.

Choroidal naevi complicated by choroidal neovascular membrane and outer retinal tubulation.

AIMS: To present the outcomes of a series of patients with choroidal neovascular membrane (CNV) secondary to a choroidal naevus and report the presence of outer retinal tubulation. METHODS: In this retrospective series, patients underwent a complete clinical and imaging assessment (fundus photo, fluorescein angiography and optical coherence tomography) and were observed or managed with intravitreal anti-VEGF injections dependent on whether visual acuity was affected. RESULTS: Seventeen patients were included in this study. Of this, 46% (8/17) had classic or predominantly classic CNV and 53% (9/17) had occult or minimally classic CNV. Active treatment with intravitreal anti-VEGF injections was required in 35% (6/17). Visual acuity improved in three eyes by 2-4 Snellen lines, remained stable in one eye and worsened in two eyes by 2 Snellen lines. CNV partially regressed in five cases. In the observation group (65%, 11/17), visual acuity did not change during follow-up period. Outer retinal tubulation was found in 18% (3/17). CONCLUSIONS: Anti-VEGF treatment is effective in the management of vision threatening CNV secondary to a choroidal naevus. Functional or anatomical improvement was obtained in 66% of treated eyes. Outer retinal tubulation, noted in 18%, showed the clinical importance of this sign in determining continuation of anti-VEGF treatment.