Long-Term Effects of Adipose-Derived Stem Cells for the Treatment of Bilateral Limbal Stem Cell Deficiency.

PURPOSE: To determine the safety and feasibility of human autologous adipose tissue-derived adult mesenchymal stem cells (ASCs) for ocular surface regeneration in patients with bilateral limbal stem-cell deficiency (LSCD). METHODS: A phase IIa clinical trial was designed (https://Clinicaltrials.gov, NCT01808378) with 8 patients, 3 of whom had aniridia, 2 meibomian glands diseases, 2 multiple surgeries and 1 chronic chemical injury. The therapeutic protocol was as follows: 6-mm of central corneal epithelium was removed, 400,000 ASCs were injected into each limboconjunctival quadrant, 400,000 ASCs were suspended over the cornea for 20 min, and finally the cornea was covered with an amniotic membrane patch. RESULTS: No adverse events were detected after a mean of 86,5 months of follow-up. One year after surgery, 6 of the 8 transplants were scored as successful, five patients had improved uncorrected visual acuity (mean of 12 letters), two patients presented epithelial defects (also present at baseline) and the mean percentage of corneal neovascularization was of 28.75% (36.98%, at baseline). Re-examination 24 months after treatment disclosed preserved efficacy in 4 patients. At the last visit (after a mean of 86,5 months of follow up) epithelial defects were absent in all patients although improvement in all of the variables was only maintained in patient 3 (meibomian glands agenesia). CONCLUSION: ASCs are a feasible and conservative therapy for treating bilateral LSCD. The therapeutic effect differs between etiologies and diminishes over time.

SER recommendations for the treatment of uveitis.

OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.

Outcomes of Corneal Transplant in Childhood Glaucoma.

PRCIS: Childhood glaucoma produces alterations in the postnatal development and function of various ocular structures, including the cornea. Childhood glaucoma patients present lower corneal transplant survival rates. Our series shows outcomes of corneal transplant in childhood glaucoma with survival rates of 29% at 2 years. OBJECTIVE: To investigate the surgical outcome of different types of keratoplasty in eyes with childhood glaucoma. PATIENTS AND METHODS: A retrospective review was made of the medical records from 17 eyes of 15 patients who were diagnosed with childhood glaucoma and received a corneal transplantation between January 2010 and July 2020. Patient demographics, intraocular pressure, previous ocular surgery, comorbidities, corneal transplant surgery, and follow-up outcome were collected. The primary efficacy endpoint was graft survival (in months) until failure, the latter being considered as irreversible loss of corneal transparency. Secondary efficacy points were the need for an increase in topical hypotensive therapy and the need for additional surgery. RESULTS: Seventeen eyes of 15 patients were included, 11 eyes (10 patients) with primary congenital glaucoma and 6 with other types of childhood glaucoma. Corneal transplantation was performed at the mean age of 23.76 ± 14.86 years. At the time of the transplantation, the number of topical medications was 1.35 ± 1.27, intraocular pressure was 15.00 ± 8.34 mm Hg, and patients had received up to 7 glaucoma surgeries. Descemet stripping automated endothelial keratoplasty was performed in 13 eyes (76%) and penetrating keratoplasty in 4 (24%). After surgery, 7 (41%) eyes required increased topical treatment and 2 (12%) glaucoma surgery. Twelve eyes (71%) developed graft failure at 24 months, the mean time of survival being 13.88 ± 8.25 months. CONCLUSIONS: Management of corneal decompensation in childhood glaucoma poses a challenge. In this series of childhood glaucoma with corneal transplantations, the survival rate was 29% at 24 months.

Spontaneous Descemet Layer Dissection Without Pneumodissection in Femtosecond Laser-Assisted Mushroom-Type Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe a case of spontaneous Descemet layer dissection without pneumodissection in femtosecond laser-assisted mushroom-type deep anterior lamellar keratoplasty. METHODS: This study is a case report. RESULTS: A 46-year-old woman diagnosed with reticular dystrophy underwent, in her left eye, mushroom configuration femtosecond laser-assisted DALK (F-DALK). After laser trephination and removal of the superficial stroma using manual dissection, a type 2 BB formation was observed intraoperatively in the AS-OCT without signs of an associated microperforation. A deeper stromal removal was accomplished by layer-by-layer manual dissection, while the BB persisted. After stromal dissection, the donor cornea was secured with 8 interrupted 10-0 nylon sutures. The next day AS-OCT showed a detachment of DM. After 1 week, a spontaneous resolution of the DM detachment was observed. CONCLUSIONS: This unknown F-DALK intraoperative complication has been detected through intraoperative AS-OCT images which may improve our understanding of F-DALK surgery and possible complications associated with femtolaser-assisted procedures.

Anti-TNF vs tocilizumab in refractory uveitic cystoid macular edema due to Behcet's disease. Multicenter study of 49 patients.

OBJECTIVE: To compare the efficacy of TNF inhibitors (adalimumab (ADA) and infliximab (IFX)) vs tocilizumab (TCZ) in patients with refractory cystoid macular edema (CME) due to Behçet's disease (BD). METHODS: Multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. We analyzed the evolution of macular thickness (main outcome), best-corrected visual acuity (BCVA) and intraocular inflammation (Tyndall and vitritis) from baseline up to 4 years in the 3 groups mentioned. RESULTS: 49 patients and 72 eyes with CME were included. ADA was used in 25 patients (40 eyes), IFX in 15 (21 eyes) and TCZ in 9 (11 eyes). No statistically significant baseline differences were observed between the 3 groups except for a lower basal BCVA in TCZ group and a higher basal degree of intraocular inflammation in ADA group. Most patients from all groups had received several conventional immunosuppressive drugs. In addition, most patients in the group of TCZ had also received anti-TNF agents. Biological therapy was used in monotherapy (n=8) or combined with conventional immunosuppressive drugs (n=41). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory intraocular remission was achieved in all groups. CONCLUSION: Refractory CME associated with BD uveitis can be effectively treated either with ADA, IFX or TCZ. Furthermore, TCZ is effective in patients resistant to anti-TNF therapy.

Clinical outcomes of long-term corneas preserved frozen in Eusol-C used in emergency tectonic grafts.

To report the clinical results on the use of corneas frozen in Eusol-C as tectonic corneal grafts.Retrospective review of medical records of patients who received frozen corneas as emergency tectonic grafts from 2013 to 2020. Corneas had been stored in Eusol-C preservation media at - 78 °C for a mean time of 6.9 months. Diagnosis, transplant characteristics, microbial culture results, anatomic integrity, epithelial healing, neovascularization, transparency, infection and need for additional surgeries were registered. Fifty corneas were used in 40 patients (mean age 60.5 years, 20 males) with a median follow-up of 27.3 months after surgery. Need for tectonic graft was due to: perforation secondary to immune diseases (6, 12%), neurotrophic ulcer (11, 22%), trauma (3, 6%), corneal infection (11, 22%), chronic disorders of the ocular surface (9, 18%) and previous corneal graft failure (10, 22%). Mean size of grafts was 5.6 mm and 36 cases (72%) also received an amniotic membrane graft. Thirty-eight corneas achieved epithelization (76%), 25 (50%) were clear and 19 (38%) developed neovascularization. None of the corneas were rejected. Seventeen corneas (34%) failed: 7 (14%) due to reactivation of baseline disease and 10 (20%) due to primary graft failure. Four corneas (8%) had positive microbial cultures suggestive of contamination and 2 (4%) developed a cornea abscess non-related to a positive microbial culture. Long-term preservation of donor corneas in Eusol-C at - 78 °C is a viable technique to meet the needs of emergency grafts with minimal equipment.

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Changes in the total corneal refractive power after insertion of intrastromal rings in patients with keratoconus in short, medium and long term / Mudanças no poder refrativo total da córnea após a inserção de anéis intrastromais em pacientes com ceratocone a curto, médio e longo prazo

ABSTRACT Objective To analyze the short, medium and long-term efficacy and stability in 46 eyes with keratoconus, operated with Ferrara intrastromal corneal ring segments. Methods The primary endpoint was the mean keratometry of total corneal refractive power. We also studied the effects of age, degree of keratoconus and clinical phenotype on the results, as well as the following keratometry variations and aberrometry variations: flattest, most curved, mean, maximum, astigmatism, root mean square of primary coma aberration and root mean square of secondary coma aberration. Results The immediate postoperative reduction in mean keratometry of total corneal refractive power was 3.08±1.51 diopters (D) (p<0.001). At 4 years, the mean keratometry of total corneal refractive power increased to 0.57±0.96D (p=0.005). Between 4 and 7 years, there was no change in mean keratometry of total corneal refractive power (p=0.727). The degree of keratoconus was a factor affecting the efficacy of the intrastromal corneal ring segments, achieving a greater effect in those with a greater degree of keratoconus (p=0.012 between groups). The immediate postoperative reduction was 1.77±1.88D for the flattest, 3.91±2.30D for the most curved, 2.76±1.63D for the mean, 4.42±3.26D for the maximum, 2.15±2.68D for astigmatism, 1.03±0.83µm for root mean square of primary coma aberration and root mean square of secondary coma aberration (p<.001 in all cases). At 4 years, most curved increased by 0.42±0.78D (p=0.001), mean increased by 0.54±0.64 (p<0.001) and root mean square of primary coma aberration decreased 0.14±0.27µm (p=0.020). Conclusion Ferrara intrastromal corneal ring segment implantation is an effective and stable long-term treatment for patients with keratoconus. There is, however, partial regression in the medium term.

RESUMO Objetivo Analisar a eficácia e a estabilidade a curto, médio e longo prazo em 46 olhos com ceratocone, operados com segmentos de anel intrastromal corneano de Ferrara. Métodos A meta primária foi a ceratometria média de poder refrativo total da córnea. Também estudamos os efeitos da idade, grau de ceratocone e fenótipo clínico nos resultados, bem como as seguintes variações de ceratometria e variações de aberrometria: mais plana, mais curva, média, máxima, astigmatismo, raiz quadrada média da aberração comática primária e raiz quadrada média da aberração comática secundária. Resultados A redução pós-operatória imediata da ceratometria média do poder refrativo total da córnea foi de 3,08±1,51 dioptrias (D) (p<0,001). Aos 4 anos, a ceratometria média do poder refrativo total da córnea aumentou para 0,57±0,96D (p=0,005). Entre 4 e 7 anos, não houve mudança na ceratometria média da potência refrativa total da córnea (p=0,727). O grau de ceratocone foi um fator que afetou a eficácia dos segmentos do anel intrastromal da córnea, alcançando um efeito maior naqueles com maior grau de ceratocone (p=0,012 entre grupos). A redução pós-operatória imediata foi de 1,77±1,88D para a mais plana, 3,91±2,30D para a mais curva, 2,76±1,63D para a média, 4,42±3,26D para a máxima, 2,15±2,68D para o astigmatismo, 1,03±0,83µm para a raiz quadrada média da aberração comática primária e raiz quadrada média da aberração comática secundária (p<0,001 em todos os casos). Aos 4 anos, a maioria das curvas aumentou 0,42±0,78D (p=0,001), a média aumentou 0,54±0,64 (p<0,001) e a raiz quadrada média da aberração comática primária diminuiu 0,14±0,27µm (p=0,020). Conclusão O implante de anel intrastromal corneano Ferrara é um tratamento eficaz e estável a longo prazo para pacientes com ceratocone. Há, no entanto, uma regressão parcial a médio prazo.

Long-Term Results of Postoperative Rescuing of Inverted DMEK Grafts: Two Case Reports.

PURPOSE: The purpose of this study was to report the clinical outcomes of postoperative repositioning of 2 inverted Descemet membrane endothelial keratoplasty (DMEK) grafts in 2 patients with endothelial dysfunction. METHODS: Two patients underwent DMEK surgery in a tertiary referral corneal clinic. Initial surgery was performed by 2 different corneal surgeons, and a third surgeon repositioned both cases. In the early postoperative period, partial and subtotal detachments were observed at slitlamp and inverted graft orientation was confirmed by anterior segment optical coherence tomography. In both cases, uneventful reposition of the inverted graft was performed by an experienced DMEK surgeon on days 2 and 9 after initial DMEK surgery. RESULTS: Repositioning surgery was successful in both patients. The Moutsouris sign was used to confirm proper orientation. One patient had total graft adherence at day 1 postrepositioning. The second patient required a rebubbling procedure, despite the correct orientation confirmed by using anterior segment optical coherence tomography. Visual acuity and corneal thickness were stable in both cases (case 1: 20/30, 567 µm; case 2: 20/80, 543 µm). Both patients had clear corneas and functional cell counts 2 years after repositioning (451 cells/mm 2 and 1052 cells/mm 2 ). CONCLUSIONS: Postoperative repositioning of an inverted DMEK graft may be a viable procedure to delay or prevent regrafting.

Peripheral ulcerative keratitis as presenting manifestation of systemic microscopic polyangiitis: a case report / Ceratite ulcerativa periférica como manifestação de poliangiíte microscópica sistêmica: relato de caso

ABSTRACT Microscopic polyangiitis is a rare autoimmune disease of unknown etiology, characterized by inflammation and necrosis of blood vessels. It forms a part of the antineutrophil cytoplasmic antibody-associated vasculitides-a heterogeneous group of disorders characterized by vasculitis. It is a systemic disease affecting multiple organs. The patients may present with a wide variety of symptoms. Ocular manifestations may present as its initial clinical symptoms, necessitating a multidisciplinary approach for reducing the morbidity and mortality. Early diagnosis aids in the formulation of appropriate treatment and prevention of further complications. Aggressive treatment, including surgery, is often necessary to limit structural damage and preserve visual function. We present the case of an 82-year-old woman who initially presented with peripheral ulcerative keratitis that led to the diagnosis of microscopic polyangiitis.

RESUMO A poliangeíte microscópica é uma doença autoimune rara de etiologia desconhecida, caracterizada por inflamação e necrose dos vasos sanguíneos. Faz parte das vasculites associadas a anticorpos citoplasmáticos antineutrófilos - um grupo heterogêneo de doenças caracterizadas por vasculite. É uma doença sistêmica que afeta vários órgãos. Os pacientes podem apresentar uma grande variedade de sintomas. As manifestações oculares podem apresentar-se como seus sintomas clínicos iniciais, necessitando de abordagem multidisciplinar para redução da morbimortalidade. O diagnóstico precoce ajuda na formulação do tratamento adequado e na prevenção de complicações futuras. O tratamento agressivo, incluindo cirurgia, muitas vezes é necessário para limitar o dano estrutural e preservar a função visual. Apresentamos o caso de uma mulher de 82 anos que inicialmente apresentou ceratite ulcerativa periférica que levou ao diagnóstico de poliangite microscópica.

Peripheral ulcerative keratitis as presenting manifestation of systemic microscopic polyangiitis: a case report.

Microscopic polyangiitis is a rare autoimmune disease of unknown etiology, characterized by inflammation and necrosis of blood vessels. It forms a part of the antineutrophil cytoplasmic antibody-associated vasculitides-a heterogeneous group of disorders characterized by vasculitis. It is a systemic disease affecting multiple organs. The patients may present with a wide variety of symptoms. Ocular manifestations may present as its initial clinical symptoms, necessitating a multidisciplinary approach for reducing the morbidity and mortality. Early diagnosis aids in the formulation of appropriate treatment and prevention of further complications. Aggressive treatment, including surgery, is often necessary to limit structural damage and preserve visual function. We present the case of an 82-year-old woman who initially presented with peripheral ulcerative keratitis that led to the diagnosis of microscopic polyangiitis.

Preseptal cellulitis, intraocular inflammatory reaction and corneal persistent epithelial defect as side effects of avapritinib.

Avapritinib is a tyrosine kinase inhibitor currently being investigated on clinical trials for the treatment of unresectable or metastatic gastrointestinal stromal tumour (GIST). It has been recently approved by the Food and Drug Administration and the European Medicines Agency for the treatment of unresectable or metastatic GIST harbouring PDGFRa Exon 18 mutation and by the European Medicines Agency for the treatments of unresectable or metastatic GIST harbouring the PDGFRa D842V mutation. We report a clinical case of a 76-year-old female, diagnosed with a stage IV GIST, treated with avapritinib 300 mg once daily. through compassionate use who experienced an intraocular side effect not previously reported avapritinib. She developed preseptal cellulitis on her right eye following 2 months of treatment with avapritinib and, subsequently evolved to an intraocular inflammatory reaction and persistent corneal epithelial defect. The treatment with avapritinib was stopped and the patient received corticosteroid and corneal regenerating agents. The symptoms resolved within 1 month and the patient has remained on stable disease at two subsequent adjusted avapritinib doses (100 mg once daily) for over 1 year.

Topical insulin for refractory persistent corneal epithelial defects.

PURPOSE: To evaluate insulin eye drops for persistent epithelial defects (PEDs) that are refractory to usual treatment in clinical practice and to analyze how it may improve epithelization. METHODS: A prospective non-randomized hospital-based study was performed. Patients with PEDs that were refractory to conventional treatment were treated with insulin eye drops four times a day. Patients' demographics, PED etiology, concomitant treatments, and comorbidities were reviewed. The rate of PED closure and epithelial healing time were considered the primary outcome measures. RESULTS: 21 patients were treated with insulin drops (12 females and 9 males; mean age 72.2 years). Mean PED area before treatment was 17.6 ± 16.5 mm2 (median 13.2; range 3.9-70.6). PED comorbidities included seven eyes with infectious keratitis (33%), five eyes with calcium keratopathy (24%), ocular surgery on three eyes (14%), three eyes with lagophthalmos (14%), two eyes with bullous keratopathy (10%), and one patient with herpetic eye disease (5%). The eyes of 17 patients (81%) with refractory PEDs had reepithelized and four patients (19%) had still presented an epithelial defect by the end of the study follow-up period, although it had decreased in size. In patients where PED closure was achieved, mean time until reepithelization was 34.8 ± 29.9 days (median 23; range 7-114). In the remaining patients, a mean area reduction of 91.5% was achieved for the PEDs. CONCLUSION: Topical insulin can promote and accelerate corneal reepithelization of refractory PEDs. It also offers many other advantages, including excellent tolerance, availability, and cost-effectiveness.

Systemic Regulatory T Cells and IL-6 as Prognostic Factors for Anatomical Improvement of Uveitic Macular Edema.

Purpose: To investigate whether systemic immune mediators and circulating regulatory T cells (Tregs) could be prognostic factors for anatomic outcomes in macular edema secondary to non-infectious uveitis (UME). Methods: Multicenter, prospective, observational, 12-month follow-up study of 60 patients with UME. Macular edema was defined as central subfield thickness (CST) > 300 µm measured with spectral domain optical coherence tomography (SD-OCT). Serum samples and peripheral blood mononuclear cells (PBMC) were obtained from venous blood extraction at baseline. Serum levels of IL-1ß, IL-6, IL-8, IL-17, MCP-1, TNF-α, IL-10, and VEGF were determined by Luminex. Tregs population, defined as CD3+CD4+FoxP3+ in PBMC, was determined by flow cytometry. Main outcome measure was the predictive association between searched mediators and CST sustained improvement, defined as CST < 300 microns or a 20% CST decrease, at 6 months maintained until 12-months compared to baseline levels. Results: Multivariate logistic regression analysis showed an association between CST sustained improvement at 12 months follow-up and IL-6 and Tregs baseline levels. Higher IL-6 levels were associated with less events of UME improvement (OR: 0.67, 95% CI (0.45-1.00), P = 0.042), whereas higher levels of Tregs favored such improvement (OR: 1.25, 95% CI: 1.12-2.56, P = 0.049). Conclusions: Increased levels of Tregs and reduced levels of IL-6 in serum may be prognostic factors of sustained anatomical improvement in UME. These findings could enforce the opportunity to develop more efficient and personalized therapeutic approaches to improve long-term visual prognosis in patients with UME.

Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicenter study of 34 patients.

PURPOSE: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). DESIGN: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. SUBJECTS: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behçet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. METHODS: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. MAIN OUTCOME MEASURES: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. RESULTS: The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. CONCLUSIONS: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

Anti-IL6-Receptor Tocilizumab in Refractory and Noninfectious Uveitic Cystoid Macular Edema: Multicenter Study of 25 Patients.

PURPOSE: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 µm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 µm; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.

Predictors for functional and anatomic outcomes in macular edema secondary to non-infectious uveitis.

AIMS: We aimed to investigate predictive factors for visual and anatomic outcomes in patients with macular edema secondary to non-infectious uveitis. MATERIAL AND METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Participants included in the study were adults with non-infectious uveitic macular edema (UME), defined as central subfoveal thickness (CST) of >300 µm as measured by spectral domain optical coherence tomography (SD-OCT) and fluid in the macula. Demographic, clinical and tomographic data was recorded at baseline, 1, 3, 6 and 12 months. Foveal-centered SD-OCT exploration was set as the gold-standard determination of UME using a standard Macular Cube 512x128 A-scan, within a 6 x 6 mm2 area, and the Enhanced High Definition Single-Line Raster. To assess favorable prognosis, the main outcomes analyzed were the best-corrected visual acuity (BCVA) and the CST. Favorable prognosis was defined as sustained improvement of BCVA (2 lines of gain of the Snellen scale) and CST (decrease of 20% of the initial value or <300 µm) within a 12 month period. RESULTS: Fifty-six eyes were analyzed. The number of eyes with sustained improvement in the CST was 48 (86.2%), against 23 (41.1%) eyes with sustained improvement in BCVA. Favorable prognosis, as defined above, was observed in 18 (32.1%) eyes. UME prognosis was negatively correlated with baseline foveal thickening, alteration in the vitreo-macular interface and cystoid macular edema. In contrast, bilaterally, systemic disease and the presence of anterior chamber cells were predictive of favorable prognosis. CONCLUSION: Available treatment modalities in UME may avoid chronic UME and improve anatomic outcome. However, the proportion of functional amelioration observed during 12 months of follow-up is lower. Thicker CST, alteration in the vitreo-macular interface and cystoid macular edema may denote less favorable prognosis. Conversely, bilaterally, systemic disease and anterior chamber cells may be associated with favorable prognosis in UME.

Behavior of hyperreflective foci in non-infectious uveitic macular edema, a 12-month follow-up prospective study.

BACKGROUND: Hyperreflective foci have been described in OCT imaging of patients with retinal vascular diseases. It has been suggested that they may play a role as a prognostic factor of visual outcomes in these diseases. The purpose of this study is to describe the presence of hyperreflective foci in patients with non-infectious uveitic macular edema and evaluate their behavior after treatment. METHODS: We conducted a multicenter, prospective, observational, 12-month follow-up study. Inclusion criteria were age > 18 years and a diagnosis of non-infectious uveitic macular edema, defined as central macular thickness of > 300 µm as measured by OCT and fluid in the macula. Collected data included best corrected visual acuity, central macular thickness and the presence, number and distribution (inner or outer retinal layers) of hyperreflective foci. Evaluations were performed at baseline, and at 1, 3, 6, and 12 months after starting treatment. RESULTS: We included 24 eyes of 24 patients. The frequency of patients with ≥11 hyperreflective foci was 58.4% at baseline, falling to 20.8% at 12 months. Further, hyperreflective foci were observed in the outer retinal layers in 50% of patients at baseline and just 28.6% at 12 months. Mean LogMAR visual acuity improved from 0.55 (95% CI 0.4-0.71) at baseline to 0.22 (95% CI 0.08-0.35) at 12 months (p < 0.001). Mean central macular thickness decreased from 453.83 µm (95% CI 396.6-511) at baseline to 269.32 µm (95% CI 227.7-310.9) at 12 months (P < 0.001). Central macular thickness was associated with number (p = 0.017) and distribution (p = 0.004) of hyperreflective foci. CONCLUSIONS: We have observed hyperreflective foci in most of our patients with non-infectious uveitic macular edema. During follow-up and after treatment, the number of foci diminished and they tended to be located in the inner layers of the retina.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.