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.

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.

Fluocinolone acetonide 0.2 µg/day intravitreal implant in non-infectious uveitis affecting the posterior segment: EU expert user panel consensus-based clinical recommendations.

BACKGROUND: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. METHODS: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. RESULTS: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. CONCLUSIONS: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes.

Design and Development of a Web-Based Prospective Nationwide Registry for Ocular Inflammatory Diseases: UVEITE.PT - The Portuguese Ocular Inflammation Registry.

Uveitis is a heterogeneous collection of infrequent diseases, which poses significant challenges to cost-effective research in the field. Medical registries are being increasingly recognized as crucial tools to provide high-quality data, thus enabling prospective clinical research. This paper describes the design and technical structure development of an innovative countrywide electronic medical record for uveitis, Uveite.pt, and gives an overview of the cohort registered since its foundation, March 2020.Uveite.pt is an electronic medical record platform developed by the Portuguese Ocular Inflammation Group (POIG), a scientific committee of the Portuguese Ophthalmology Society. This is a nationwide customized web-based platform for uveitis patients useful for both clinical practice and real-world-based research, working as a central repository and reporting tool for uveitis. This paper describes the technical principles, the design and the development of a web-based interoperable registry for uveitis in Portugal and provides an overview of more than 400 patients registered in the first 18 months since inception.In infrequent diseases, the existence of registries enables to gather evidence and increase research possibilities to clinicians. The adoption of this platform enables standardization and improvement of clinical practice in uveitis. It is useful to apprehend the repercussion of medical and surgical treatments in uveitis and scleritis, supporting clinicians in the strict monitoring of drug adverse reactions and surgical outcomes.

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.

Deep Capillary Plexus Features in Acute Macular Neuroretinopathy: Novel Insights Based on the Anatomy of Henle Fiber Layer.

Purpose: The purpose of this study was to identify a precise location of deep capillary plexus (DCP) injury in acute macular neuroretinopathy (AMN) lesions using multimodal imaging. Methods: En face structural optical coherence tomography (OCT) images were manually segmented to delineate outer retinal AMN lesions involving the ellipsoid zone and interdigitation zone. AMN lesion centroid was calculated, and image distortion was applied to correct for Henle fiber layer (HFL) length and orientation. The resulting image was registered with the corresponding en face OCT angiography (OCTA) image segmented at the DCP and structural OCT volume before grading for vascular and structural features, respectively. Results: Thirty-nine AMN lesions from 16 eyes (11 female patients, mean age 34 ± 4 years) were analyzed. After correcting for HFL anatomy, in 62% of AMN lesions, the centroid co-localized with a capillary vortex (pattern 1); flow defects were detected in 33% of lesions (pattern 2); and in 5% of lesions no specific pattern could be identified (pattern 3). The detection of a specific pattern increased after correcting the projection of AMN lesion for HFL anatomy (28% vs. 5%, P = 0.04). Outer nuclear layer thickness was lower in the centroid area in 10 (29%) AMN lesions from 6 patients, all corresponding to lesions fitting pattern 2 (r = 0.78, P < 0.001). Conclusions: AMN lesions might be a result of DCP impairment at the level of the capillary vortex or draining venule. In eyes with AMN, the location of outer retinal changes associated with DCP ischemia appears to be influenced by the length and orientation of HFL.

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.

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.

Severe acute syphilitic posterior placoid chorioretinitis with complete spontaneous resolution: The natural course.

PURPOSE: We report on a case of unilateral acute syphilitic posterior placoid chorioretinitis (ASPPC) with spontaneous resolution of the lesions, and discuss the role of an altered versus adequate immune response as the major pathogenic factor. METHODS: We describe a case of acute loss of visual acuity (VA) in the left eye (LE) in a 55-year-old healthy man. RESULTS: The patient presented with VA of 20/20 in the right eye (RE) and hand movements in the LE. Fundoscopy revealed a large yellowish placoid macular lesion with subretinal fluid in the LE, with no abnormalities detected in the RE. Fluorescein angiography showed early hypofluorescence with late staining in the affected area. The clinical findings progressed fast during the first week, with extension of the initial lesion outside the temporal retinal vascular arcades and the appearance of new lesions in the same eye. The patient abandoned the clinic for two weeks with no treatment. When observed again, VA of the LE had recovered to 20/20 and the lesions had completely resolved. Venereal disease research laboratory (VDRL) and fluorescent treponemal antibody absorption (FTA-ABS) tests results were positive and HIV antibody test titers negative. The diagnosis of ASPPC in the left eye was made. The patient accepted treatment with penicillin G only 45 days after the initial presentation. AV remained stable at 20/20 both eyes and no relapses of the lesions were observed during this period without therapy. The patient was followed for 3 months after treatment. He remained asymptomatic and the ophthalmic examination was unremarkable. CONCLUSIONS: The pathogenesis of ASPPC is still not understood. Our case showed a sequential pattern of the chorioretinal lesions, with initial aggravation and complete posterior spontaneous resolution, showing the natural course of the disease. These findings suggest the presence of an adequate ocular immune response in patients with ASPPC, not supporting the initially proposed hypothesis of the importance of a modified immune response as the major pathogenic factor.

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.