Fluocinolone intravitreal implant (Iluvien) for macular edema secondary to immune recovery uveitis in patient with acute myeloid leukemia.

PURPOSE: To report the use of Fluocinolone intravitreal implant (Iluvien) for the treatment of persistent cystoid macular edema (CME) due to immune recovery uveitis syndrome in a patient with previous cytomegalovirus retinitis and acute myeloid leukemia. DESIGN: Case report. METHODS: The clinical history of a patient who received an Iluvien implant in one eye for the treatment of cystoid macular edema due to immune recovery uveitis syndrome, previously treated with peribulbar Triamcinolone and intravitreal Dexamethasone injections, was reviewed. RESULTS: A 48-year-old woman presented with cystoid macular edema due to immune recovery uveitis syndrome. The patient had a history of cytomegalovirus retinitis 3.5 years prior, secondary to immunosuppressive treatment for an acute myeloid leukemia. Three periocular triamcinolone injections and two dexamethasone intravitreal implants were performed, but the edema recurred, so fluocinolone intravitreal implant was used, achieving a sustained control of the condition at one year of follow-up. CONCLUSION: The Fluocinolone intravitreal implant may be an effective treatment for persistent CME in patients with immune recovery uveitis syndrome.

Episcleritis and periorbital edema secondary to VEXAS syndrome.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described autoinflammatory entity caused by a UBA-1 gene mutation. Among the most frequent symptoms it produces fever, cytopenias, polychondritis, pulmonary infiltrates and up to 40% ocular involvement such as periorbital edema, uveitis, episcleritis, scleritis and retinal vasculitis. Patients respond to high doses of corticosteroids, however, many end up being refractory to them and to the classic immunosuppressants. We described the case of a 77-year-old male patient with ocular involvement in the form of episcleritis and periorbital edema who was later diagnosed with VEXAS Syndrome. The patient, after failing treatment with immunosuppressants, is currently receiving treatment with oral steroids and tocilizumab. Ophthalmologist must be aware of the ophthalmological affectation of autoinflammatory diseases and especially of this new entity described as the VEXAS Syndrome.

The retinal bacillary layer detachment: Clinical features and outcomes in posterior uveitis.

PURPOSE: To describe the clinical characteristics, presentation and response to treatment in posterior uveitis patients with bacillary layer detachment (BLD) seen on optical coherence tomography (OCT). MATERIALS AND METHODS: Retrospective review of patients with posterior uveitis and SD-OCT scans consistent with BLD. Data collected included demographics, uveitic etiology, treatment and duration of follow-up. Outcome measures included macular volume, central subfoveal thickness and visual acuity. RESULTS: Sixteen patients (20 eyes) were included. Twelve were female (75%). The mean age was 43.68 ± 14.7 years. The most frequent etiology of the uveitis was Vogt-Koyanagi-Harada (VKH) disease (n=10), followed by sympathetic ophthalmia (n=2). BLD was bilateral in four patients. Eight patients were treated with intravenous methylprednisolone boluses. Immunosuppressive therapies were required in 8 patients. The mean follow-up was 70 months (range: 2.0-216.0). CONCLUSION: BLD was observed in a series of posterior uveitis cases of various etiologies, showing functional and structural resolution with treatment in most cases.

Hyper-Reflective Outer Nuclear Layer (HONL) in Vogt-Koyanagi-Harada Disease and Sympathetic Ophthalmia.

PURPOSE: To describe the optical coherence tomography (OCT) findings of hyper-reflective outer nuclear layer (HONL) in two cases of stromal choroiditis (Vogt-Koyanagi-Harada disease - VKH, and sympathetic ophthalmia - SO). METHODS: Case report. RESULTS: Clinical and imaging findings of two patients (37-year-old female with VKH and 34-year-old male with SO) have been described. Both patients showed typical features of the disease with subretinal fluid accumulation and choroidal thickening on OCT. However, OCT of both patients at the initial visit revealed HONL, which was unusual in these conditions. During follow-up, OCT scans revealed thinning and atrophy of the outer retinal layers, irregular thickening of the retinal pigment epithelium, and irregular autofluorescence pattern on autofluorescence imaging. CONCLUSIONS: The presence of HONL may serve as a poor prognostic factor in VKH and SO, resulting in thinning and atrophy of the outer retinal layers.

Guidance on brolucizumab management recommendations.

PURPOSE: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of IOI at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. METHODS: The recommendations made by the authors are based on their clinical experience, critical review of (i) the pivotal trials, the post-hoc analysis of the Safety Review Committee, (ii), and (iii) the published literature. RESULTS: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i) ruling out non-recommended patient profiles (prior history of ORI), (ii) screening the patient prior to each injection to rule out active ORI, (iii) monitoring the patient for early warning signs, and (iv) treating immediately should any adverse events develop. CONCLUSIONS: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision.

[Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: result of the COVID-19-GEAS patient survey]. / Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes.

INTRODUCTION: The objetive of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey. MATERIAL AND METHODS: Internal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population. RESULTS: A total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive. CONCLUSIONS: Both asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.

Impact of novel coronavirus infection in patients with uveitis associated with an autoimmune disease: Result of the COVID-19-GEAS patient survey.

INTRODUCTION: The objective of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey. MATERIAL AND METHODS: Internal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population. RESULTS: A total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive. CONCLUSIONS: Both asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.

Multidisciplinary care and units for uveitis in the internal medicine departments in Spain: Survey of the Systemic Autoimmune Diseases Group.

OBJECTIVE: To identify the multidisciplinary uveitis units in which internal medicine departments participate in collaboration with ophthalmology departments in Spain. MATERIAL AND METHODS: We conducted a multicentre, observational cross-sectional study that collected information using a structured survey sent by email to 1015 partners of the Systemic Autoimmune Diseases Workgroup of the Spanish Society of Internal Medicine (GEAS-SEMI) from the 1st to the 31st of March 2017. RESULTS: We identified a total of 21 support units/consultations for the ophthalmology departments. Seventeen (81%) of the units were specific internal medicine-ophthalmology consultations, and 5 (24%) units had been created in the past 5 years. A median of 460 patients were assessed per unit by the end of the year. CONCLUSIONS: This study shows, for the first time in Spain, the important and close collaboration between ophthalmologists and internists, especially in highly specialized national reference institutions.

Multidisciplinary care and units for uveitis in the internal medicine departments in Spain: Survey of the Systemic Autoimmune Diseases Group. / Unidades y asistencia multidisciplinar de uveítis en los servicios de medicina interna en España: encuesta del Grupo de Enfermedades Autoinmunes Sistémicas.

OBJECTIVE: To identify the multidisciplinary uveitis units in which internal medicine departments participate in collaboration with ophthalmology departments in Spain. MATERIAL AND METHODS: We conducted a multicentre, observational cross-sectional study that collected information using a structured survey sent by email to 1015 partners of the Systemic Autoimmune Diseases Workgroup of the Spanish Society of Internal Medicine (GEAS-SEMI) from the 1st to the 31st of March 2017. RESULTS: We identified a total of 21 support units/consultations for the ophthalmology departments. Seventeen (81%) of the units were specific internal medicine-ophthalmology consultations, and 5 (24%) units had been created in the past 5 years. A median of 460 patients were assessed per unit by the end of the year. CONCLUSIONS: This study shows, for the first time in Spain, the important and close collaboration between ophthalmologists and internists, especially in highly specialised national reference institutions.

Evolution of retinal changes measured by optical coherence tomography in the assessment of hydroxychloroquine ocular safety in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this report is to analyse retinal changes over a five-year period, assessed by spectral domain-optical coherence tomography (SD-OCT), in patients from the Lupus-Cruces cohort treated with hydroxychloroquine (HCQ). METHODS: SD-OCT screening was performed annually between 2012 and 2017. Average macular thickness (AMT), ganglion cell layer thickness (GCLT) and qualitative data of retinal pigment epithelium (RPE) and external retina (ExtR) were collected prospectively. We compared data from 2012 (first) and 2017 (second) SD-OCT. RESULTS: We studied 110 patients and 195 eyes. No cases of HCQ toxicity were detected. At the time of the second SD-OCT, 99% patients had taken a daily dose of HCQ ≤5 mg/kg/day. The median time on HCQ was 133 months. The mean AMT and GCLT were significantly lower in both eyes at the second SD-OCT; however, all the differences were clinically insignificant at less than 1%. Qualitative analysis of RPE and ExtR showed no significant changes. Similar results were found among patients with risk factors for retinopathy. The comparison of patients with and without risk factors showed no differences. CONCLUSIONS: This study shows clinically irrelevant retinal changes in an SLE cohort on HCQ treatment over a five-year follow-up. Our findings support the safety of long-term HCQ at doses ≤5 mg/kg/day.

Study of association of CTLA4 gene variants to non-anterior uveitis.

This study was undertaken to investigate the possible genetic association of functional CTLA4 polymorphisms with susceptibility to non-anterior uveitis. Four hundred and seventeen patients with endogenous non-anterior uveitis and 1517 healthy controls of Spanish Caucasian origin were genotyped for the CTLA4 polymorphisms rs733618, rs5742909 and rs231775, using predesigned TaqMan(©) allele discrimination assays. PLINK software was used for the statistical analyses. No significant associations between the CTLA4 polymorphisms and susceptibility to global non-anterior uveitis were found. It was also the case when the potential association of these genetic variants with the anatomical localization of the disease, such as intermediate, posterior or panuveitis, was assessed. Our results do not support a relevant role of these CTLA4 polymorphisms in the non-anterior uveitis genetic predisposition.

Anterior tuberculous scleritis: A diagnostic challenge.

CASE REPORT: We present the case of a 26 year-old Pakistani male, who after the presumptive diagnosis of anterior tuberculous scleritis (by an atypical clinical appearance and positive epidemiological link), was diagnosed with pulmonary tuberculosis. DISCUSSION: Nodular anterior scleritis is an uncommon presentation of tuberculosis (TB). It is considered a diagnostic challenge because of the difficulty to extract bacilli from the ocular tissue. However, a detailed medical history and eye examination can be the key to an accurate diagnosis and appropriate treatment of the TB.

Vitreous levels of somatostatin in patients with chronic uveitic macular oedema.

PURPOSE: Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. METHODS: Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. STATISTICS: χ(2)-square test, Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. RESULTS: Plasma SST concentrations were similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22-29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38 mg/ml vs 0.73±0.32 mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73 pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (ρ=0.191, P=0.57 and ρ=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (ρ=0.302, P=0.31 and ρ=0.45, P=0.13). CONCLUSIONS: Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.

[Uveitis: diagnostic approach]. / Aproximación diagnóstica a las uveítis.

A 32 year-old woman was referred from the Ophthalmology Department to rule out a possible systemic disease. Her only past medical history of relevance was a tuberculosis contact during childhood. She complained of floaters and progressive blurring of vision in both eyes for some months, as well as arthralgia and cough. Her visual acuity was 0.3 in the right eye and 0.4 in the left eye. Biomicroscopy showed bilateral anterior granulomatous uveitis (1+ cells). Funduscopy showed bilateral vitritis 3+, snow banking and peripheral phlebitis. Fluorescein angiography did not show central vasculitis, and optical coherence tomography showed bilateral cystoid macular oedema. Fundus autofluorescence was normal. How would you initially assess this patient in order to decide which systemic examination should be performed, bearing in mind the ophthalmological manifestations?

Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion.

PURPOSE: To investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs). DESIGN: Retrospective case-control study. PARTICIPANTS: Nineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group). METHODS: Macular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time of vitreoretinal surgery. IL-8 and MCP-1 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Variables were compared with the Mann-Whitney U-test, Wilcoxon's signed-ranked test, and the chi2-test, when appropriate. To examine correlations, Spearman's rank-order correlation coefficients were calculated. Statistical significance was set at P<0.05. RESULTS: The vitreous fluid levels of IL-8 (median: 63.5 pg/ml) and MCP-1 (median: 1522.4 pg/ml) were significantly higher in the patients with BRVO than in the control group (median: 5.1 and 746.5 pg/ml respectively; P<0.001 and <0.001 respectively). Vitreous IL-8 and MCP-1 were significantly correlated in patients with BRVO (P=0.009). CONCLUSIONS: Both IL-8 and MCP-1 were elevated in the vitreous fluid of patients with BRVO and macular oedema. Both chemokines may contribute to the pathogenesis of macular oedema in patients with BRVO.

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema.

OBJECTIVE: In a recent study, we found high levels of erythropoietin (EPO) in patients with diabetic macular oedema (DME), suggesting a role of EPO in the pathogenesis of this condition. To investigate a possible relationship between EPO and other diseases causing macular oedema, we determined vitreous levels of this peptide in patients with macular oedema secondary to retinal vein occlusion (RVO) and compared them with levels in patients with DME and control patients. METHODS: Vitreous and serum samples were obtained from patients with macular oedema secondary to RVO, DME, epiretinal membrane, and macular hole (controls). EPO was measured by radioimmunoassay. RESULTS: No differences were found in median vitreous EPO levels between patients with RVO and controls: RVO, 76 mU/ml (30-806) vs controls, 25 mU/ml (10-75) (P=0.105). Median EPO concentration was higher in DME patients than in patients with RVO or controls: DME, 430 mU/ml (41-3000) vs RVO, 76 mU/ml (30-806) (P<0.0001) vs controls, 25 mU/ml (10-75) (P<0.0001). CONCLUSIONS: EPO levels are not elevated in patients with macular oedema secondary to RVO. Patients with DME have high levels of EPO. These results suggest that EPO could be involved in the pathogenesis of diabetic retinopathy, but not in macular oedema secondary to RVO.

Endoresection in high posterior choroidal melanomas: long-term outcome.

BACKGROUND: Eyes with high posterior choroidal melanomas are frequently enucleated because of the potential complications of radiotherapy. The aim of this study was to evaluate the safety and efficacy of endoresection at long-term follow-up. METHODS: Retrospective, non-randomised, interventional case series. Thirty-eight patients underwent endoresection. For primary procedures, inclusion criteria were tumour thickness >or=8 mm, base <15 mm, tumours not exceeding the equatorial area. Endoresection was also undertaken as the salvage procedure in four patients. Main outcomes measured were metastatic disease, survival, local recurrences, visual acuity, enucleation rate, and surgical complications. RESULTS: Follow-up time ranged from 23 to 129 months (mean 70.63 months). Preoperative visual acuity ranged from "hand-movements" to 20/20 (mean, 20/60). In primary cases, mean tumour thickness was 10.1 mm and mean base diameter 9.9 mm. At the latest visit, 92.1% patients still retained the eye. Final visual acuity ranged from "no light perception" to 20/30 (mean 20/300). Two patients experienced local recurrence before 3 years of follow-up. Melanoma metastatic disease was found in two patients at 5 years of follow-up. Kaplan-Meier survival analysis for all causes was 88.2% at 5 years. Specific survival was 90.9% at 5 years. CONCLUSIONS: At long-term follow-up, the risk of metastasis or local recurrence, and survival rates were similar to other techniques, although comparisons are difficult because of the unusual presentation of this type of melanoma. Further studies and longer follow-up are needed.

Surgical embolus removal in retinal artery occlusion.

AIMS: To evaluate the anatomical outcomes, safety and functional effectiveness of surgical embolus removal in retinal artery occlusion (RAO). METHODS: Prospective study of seven patients with RAO of <36 h duration. All eyes underwent pars plana vitrectomy and a longitudinal incision of the anterior wall of the occluded arteriole in an attempt to remove the embolus. Outcome measures included visual acuity and arteriolar reperfusion, as evaluated with fluorescein angiography. RESULTS: Surgical removal of the embolus was achieved in six of the seven (87.5%) patients, visual acuity improved from a median of 20/400 (range: hand movements 20/25) to 20/40 (range: hand movements 20/25), and reperfusion of the occluded vessel was angiographically confirmed in four of the six patients in whom the embolus was successfully removed. CONCLUSION: Surgical removal of retinal arterial emboli seems to be an effective and safe treatment for RAO, but a randomised and controlled clinical trial will be necessary to establish an evidence base for the role, if any, of this intervention.

Interleukin-8, monocyte chemoattractant protein-1 and IL-10 in the vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: To determine the intra-vitreous levels of two pro-inflammatory cytokines [interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)] and the anti-inflammatory cytokine interleukin-10 (IL-10) in patients with proliferative diabetic retinopathy (PDR). In addition, the relationship between the profile of cytokines and PDR activity has also been evaluated. PATIENTS AND METHODS: The study included 22 consecutive diabetic patients with PDR (4 Type 1 and 18 Type 2) on whom a vitrectomy was performed. Sixteen age-matched non-diabetic patients with other conditions requiring vitrectomy, but in which the retina was not directly affected by neovascularization served as a control group. IL-8, MCP-1 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The vitreal levels of both IL-8 and MCP-1 were strikingly higher in diabetic patients with PDR in comparison with the control group [173.5 (64-1670) vs. 49 pg/ml (25-145), P < 0.001, and 2171 (388-6155) vs. 438 pg/ml (207-1344), P < 0.001, respectively]. In addition, the vitreous concentrations of IL-8 and MCP-1 were higher in patients with active PDR than in those patients with quiescent PDR [324.5 (80-1670) vs. 173.5 pg/ml (64-487), P = 0.06 and 3596 (1670-6155) vs. 1143 pg/ml (388-2500), P = 0.01, respectively]. However, vitreal levels of IL-10 in diabetic patients were similar to that obtained in the control group [2.89 (1.55-5.50) vs. 2.46 pg/ml (2.2-5.41), P = NS]. CONCLUSIONS: The pro-inflammatory cytokines IL-8 and MCP-1 are increased in the vitreous fluid of PDR patients without an increase in the anti-inflammatory cytokine IL-10. In addition, both IL-8 and MCP-1 intra-vitreous levels correlated with PDR activity, thus suggesting that these cytokines may be pathogenically important in PDR.