Investigación en Uveítis y Retina

Background/objectives: Vogt-Koyanagi-Harada (VKH) disease has been historically associated with specific ethnic groups, suggesting an underlying susceptibility. Prior to this study, no meta-analysis had synthesized the global epidemiology of VKH, and therefore, information on its geographic distribution remained incomplete. The present study aims to determine the global distribution of VKH disease diagnosis in individuals presenting with uveitis.

Methods: A systematic review and meta-analysis of quantitative studies published between 2001 and 2025 in PubMed, SciELO, and LILACS was conducted following PRISMA-P guidelines. Case reports were excluded. Risk of bias was assessed using the Murad assessment tool for case series. A random-effects model was used to pool frequency estimates with 95% confidence intervals and prediction intervals.

Results: Of 7153 articles identified, 258 studies were analyzed, spanning six continents and 44 countries. The estimated frequency of VKH among uveitis cases was 5.11% (CI:4.31-5.90%; PI: 0.00-15.18%) overall, with predominance of females. When subgrouped into pediatric and adult populations, the estimated frequency was 2.43% (CI:1.83-3.02%; PI: 0.00-6.38%) and 6.15% (CI:4.06-8.24%; PI: 0.00-19.77%), respectively. Frequencies varied across regions, with higher rates reported in Southeast Asia, East Asia, and Africa, and lower rates in North America, Europe, and Oceania. Regarding the quality evaluation, most studies were considered as medium-high quality (162/169, 96%).

Conclusion: This systematic review and meta-analysis support the existence of geographical differences in VKH disease expression and the need for additional epidemiological research, particularly in underrepresented regions. These findings should be interpreted in the context of methodological heterogeneity and potential publication and geographic bias.

Publicado en Eye (London, England). Eye (Lond) 2026 Aug;40(12):1942-1955.

Aims: To characterise the incidence of bilateral involvement and choroidal neovascularisation (CNV) in punctate inner choroiditis (PIC).

Methods: Retrospective, single-centre case series of 52 patients with PIC evaluated at a tertiary referral centre in the USA. Patients meeting Standardization of Uveitis Nomenclature criteria were included. Records were reviewed for laterality, CNV, treatment and visual outcomes. Incidence rates were calculated using person-year and eye-year denominators with staggered entry anchored at PIC diagnosis. Kaplan-Meier methods were used for time-to-event analyses. Time-updated analysis assessed immunosuppression as a risk modifier for active CNV.

Results: At diagnosis, 31/52 patients (59.6%) had unilateral disease. During follow-up, 11 developed fellow-eye involvement (0.08/person-year; 95% CI 0.04 to 0.13), with the highest incidence within 5 years of diagnosis (0.20/person-year; 95% CI 0.09 to 0.36). None of the four unilateral patients treated with immunosuppression developed fellow-eye disease while receiving therapy. At diagnosis, CNV was present in 34/73 eyes (46.6%). During follow-up, 20 eyes developed incident CNV (0.06/eye-year; 95% CI 0.04 to 0.10), highest within 5 years of diagnosis (0.14/eye-year; 95% CI 0.08 to 0.22). In time-updated analysis controlling for prior CNV, immunosuppression was associated with reduced odds of active CNV (OR, 0.50; 95% CI 0.27 to 0.93). 10 eyes developed visual acuity worse than 20/40, all associated with CNV; 8 improved to better than 20/40 after anti-vascular endothelial growth factor therapy.

Conclusion: PIC frequently presents unilaterally but carries risk of bilateral progression. CNV is common at presentation and is a cause of vision loss. Immunosuppression is associated with reduced odds of active CNV.

Publicado en The British journal of ophthalmology. Br J Ophthalmol 2026 Jul.

Purpose: To report the clinical and histopathologic features of cicatrizing conjunctivitis associated with variegate porphyria (VP).

Methods: A comprehensive literature search was performed in PubMed and Google Scholar through September 2025 using terms related to porphyria and ocular involvement. All relevant case reports, series, reviews, original articles, and cited references were included.

Results: A 52-year-old woman with a history of seizures, dorsal hand skin lesions, and lower-extremity paresthesia presented with cicatrizing conjunctivitis and corneal opacification with neovascularization. A systemic evaluation demonstrated elevated urinary and fecal porphyrins. Molecular analysis revealed a novel heterozygous 3.49-Mb deletion encompassing the entire protoporphyrinogen oxidase gene. Conjunctival histopathology revealed subepithelial bullae with acanthotic epithelium, and direct immunofluorescence was negative for immune complex deposition.

Conclusions: Ocular manifestations in porphyria are rare and have primarily been described in porphyria cutanea tarda and congenital erythropoietic porphyria. A review of the English language literature summarizing reported cases of porphyria-associated cicatrizing conjunctivitis is presented. This report broadens the differential diagnosis of cicatrizing conjunctivitis to include VP.

Publicado en Cornea. Cornea 2026 Jun.

Purpose: Describe the demographic and clinical characteristics, treatment outcomes, and ocular complications in patients with tubulointerstitial nephritis and uveitis (TINU) syndrome.

Methods: Retrospective study of TINU patients seen at the Foster Center for Ocular Immunology (Duke University) and Wilmer Eye Institute (Johns Hopkins School of Medicine) between January 2014-December 2023. Patients were diagnosed using the 2021 SUN Working Group criteria.

Results: 27 TINU patients, 16 (59%) males, aged 20.4 ± 15.8 (range: 7-71) years were included. The mean follow-up time was 24.3 ± 16.5 (range: 7-75) months. All tested patients had an elevated urinary β2-microglobulin. Ten (37%) patients had positive renal biopsy. Thirteen (48%) patients presented with isolated anterior uveitis, and 14 (52%) had additional intermediate/posterior segment findings in at least one eye. At baseline, all patients were managed with topical corticosteroids (TCS), with 6 (27%) patients requiring oral prednisone (PRD) and 17 (63%) steroid-sparing immunosuppressive therapy (SS-IMT). Inflammatory control was achieved in 26 (96%) patients with TCS only (n = 4), TCS+PRD (n = 5), TCS+SS-IMT (n = 6), and TCS+PRD+SS-IMT (n = 11). Thirteen of 26 patients (50%) developed disease relapse at a mean time of 8.9 ± 18.9 (range: 1-71) months. One patient was lost to follow-up. Eighteen (67%) patients developed TINU-associated ocular complications. Five eyes from 4 patients had a median decrease in visual acuity of 2 Snellen lines (range: 1-4) during follow-up.

Conclusion: The demographic and clinical presentation of TINU is heterogeneous. Intermediate and posterior segment manifestations are common. Treatment with topical and systemic corticosteroids only may be insufficient to prevent disease relapse, with most patients requiring long-term immunosuppressive therapy.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2026 Apr;34(3):464-472.

Background: Mucous membrane pemphigoid with ocular involvement (oMMP) is an autoimmune disease that results in chronic conjunctivitis, conjunctival scarring, and if left untreated, permanent vision loss. oMMP is quite rare with incidence rates between one in 12,000 to one in 60,000, but there is a lack of large population-based studies that focus solely on oMMP. Thus, we sought to examine the cumulative and annual incidence and prevalence of oMMP in the TriNetX database and compared these findings to the US population for greater generalizability.

Methods: This was a retrospective study utilised International Classification of Disease, 10th edition (ICD-10) codes to determine the yearly and cumulative incidence and prevalence, demographics, ocular complications, and immunosuppressant treatments prescribed for oMMP from 2013 to 2023. TriNetX software was used to analyze the data.

Results: A total of 4052 patients were diagnosed with oMMP with a mean age of 73 years (SD = 14; range 18-90). The majority of patients were female (n = 2604 64.26%) and non-Hispanic, white (n = 3098, 76.46%). Prednisone was the most common systemic medication prescribed to 40% of patients. The most used immunosuppressive drug was mycophenolate mofetil (21%). Glaucoma was the most common ocular complication (n = 375, 9.25%). Between 2013 and 2023, there was a continuous rise in the cumulative incidence and prevalence rates. The 11-year cumulative incidence and prevalence were 1.41per 100,000 persons and 6.72 per 100,000 persons, respectively.

Conclusions: Compared to current literature, the TriNetX population with oMMP had similar demographics and immunosuppressant use, but showed a higher incidence and an overall increasing prevalence.

Publicado en Eye (London, England). Eye (Lond) 2025 Dec;39(18):3257-3261.

Purpose: Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis globally, with a significant risk of visual impairment. However, the lack of standardized data collection hinders meaningful comparisons across studies. This study aimed to develop a consensus-based set of Common Data Elements (CDEs) for observational studies in OT using a Delphi approach.

Design: A set of CDEs was developed through a combination of a comprehensive literature review, a hybrid workshop, and a Delphi consensus process. This effort was led by an international panel of experts in OT to define a standardized CDE set for research and clinical purposes.

Methods: A multidisciplinary steering committee identified an initial list of candidate CDEs through a targeted literature review. A panel of 30 international experts participated in a structured, one-round Delphi process to evaluate and refine these CDEs. Consensus was determined based on predefined thresholds for inclusion, exclusion, and modification.

Results: A total of 139 CDEs were categorized across nine domains: Demographic and Background Information, Medical and Ocular History, Clinical Presentation, Clinical Findings, Lesion Characteristics, Diagnostics, Imaging Findings, Treatment and Interventions, and Outcomes. All 139 CDEs met the inclusion criteria, with 79.8% rated as "very important". The consensus underscores the importance of a comprehensive, standardized dataset for OT research.

Conclusions: This study establishes the first expert-derived standardized dataset requested for reporting OT outcomes, providing a framework to standardize data collection for future observational studies. Adopting these CDEs will enhance data comparability, improve meta-analyses, and strengthen the evidence base for clinical decision-making in OT. Future work will focus on real-world validation and refinement of this dataset.

Publicado en Journal of ophthalmic inflammation and infection. J Ophthalmic Inflamm Infect 2025 Sep;15(1):68.

Publicado en Eye (London, England). Eye (Lond) 2025 Aug;39(12):2334-2336.

Background: The uveitides are a group of intraocular inflammatory diseases which can lead to blindness without treatment. It has been shown that socioeconomic status, health literacy, and access to healthcare play a pivotal role in the prevalence, severity, and treatment outcomes in ophthalmic conditions. We review the current literature on the impact of social determinants of health (SDoH) in patients with uveitis.

Methods: A systematic literature search was conducted utilizing PubMed, Google Scholar, and Embase databases in July 2024. Inclusion criteria included studies written in English, focusing on SDoH in patients with uveitis using the following keywords: "uveitis," "social determinants of health," "socioeconomic status," "education," "access to healthcare," "health literacy," "health disparities," "race/ethnicity," "gender," and "environmental factors." Case reports were excluded.

Results: Fifty two articles were included. Among these, 31 addressed healthcare access (e.g. limited specialist availability, cost/insurance barriers, urban-rural gaps), 23 highlighted economic stability (e.g. low income, out-of-pocket costs, poor medication adherence), 19 discussed environment and community (e.g. higher infectious uveitis rates in resource-limited areas, lack of social support), 18 focused on racial and ethnic disparities (e.g. advanced disease at presentation, worse outcomes for African American, Hispanic, and Indigenous populations), and 15 addressed education and awareness (e.g. low health literacy, inadequate patient education materials). Nine papers examined two domains, and 10 incorporated three or more. Across domains, limited resources and knowledge were associated with delayed diagnosis, suboptimal adherence, and poorer visual outcomes.

Conclusion: The current literature shows a correlation between SDoH and an increased incidence and poorer disease outcomes in patients with uveitis. Further research is needed to mitigate disparities in care for patients with uveitis.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2025 Aug;33(6):1013-1022.

PurposeTo report the case of a patient with ocular West Nile virus infection (WNVI) and to describe the demographics, eye characteristics, and treatment of patients with WNVI reported in the literature.MethodsSystematic literature search using the PubMed MEDLINE database searching for all cases of ocular WNVI published from inception until October 14, 2023. Inclusion criteria were patients with serologic and/or cerebrospinal fluid diagnosis of WNVI with ocular involvement.ResultsA total of 60 patients (111 eyes), including the present case, were included. Most patients were males (57%), diagnosed in the United States (77%), and with a mean age at presentation of 54 years. The median time elapsed between the viral prodrome, and eye symptoms was 7 days. Neurologic involvement was present in 47 (78%) patients. Diabetes mellitus was the most frequent systemic comorbidity (45%). Posterior segment findings were present in 107 (96%) eyes. Multifocal chorioretinal lesions (86%), vitreous inflammation (51%), intraretinal hemorrhages (43%), and retinal vasculitis (21%) were the most frequent findings. Fluorescein angiography was performed in 88 (79%) eyes. Fifty-seven (51%) eyes did not receive treatment. Topical and systemic steroids were prescribed to 35% and 28% of eyes, respectively.ConclusionWNVI should be considered as a potential diagnosis in older patients who exhibit posterior uveitis, especially if they have recently experienced flu-like symptoms and have been exposed to mosquitoes. A comprehensive ocular assessment, which includes a dilated fundus examination and ocular imaging studies, can help raise suspicion for this condition even before serological confirmation is obtained.

Publicado en European journal of ophthalmology. Eur J Ophthalmol 2025 May;35(3):844-855.

Purpose: To evaluate clinical and treatment outcomes in patients with peripheral ulcerative keratitis (PUK).

Design: Retrospective, case series SUBJECTS: Patients diagnosed with PUK at the Wilmer Eye Institute between January 2003 and October 2022.

Methods: Data collected included demographics, presence of systemic disease, disease laterality, duration of disease, PUK activity, presence of corneal perforation, and treatments. Outcomes of interest included: disease control, corticosteroid-sparing success, corticosteroid-discontinuation success, sustained drug-free remission, disease reactivation, occurrence of perforation, and need for surgery.

Results: Fifty-seven patients with PUK were identified. The median age was 53 years, with 46% of patients being Black. Most patients (56%) had an associated systemic diagnosis. The median duration of symptoms prior to presentation was 3 months and 42% of patients presented with bilateral disease. Of the 81 affected eyes, 7 had perforated prior to presentation. During a median follow-up of 3 years, 76% of patients received oral prednisone and 80% received at least 1 immunosuppressive drug. Disease control was achieved in all patients within a median of 1.3 months. The rates of corticosteroid-sparing success and corticosteroid discontinuation were 0.44 per patient-year (/PY) and 0.27/PY, respectively. Sustained drug-free remission was achieved in only 6% of patients. During follow-up, the rate of corneal perforation was 0.009/EY. The rate of disease reactivation was 0.07/EY, with a median time to reactivation of ∼2 years.

Conclusions: Over a moderate amount of follow-up, systemic therapy achieved disease control, corticosteroid-sparing and corticosteroid discontinuation. However, sustained drug-free remission was infrequent in our cohort.

Publicado en American journal of ophthalmology. Am J Ophthalmol 2025 Apr;272:98-105.

Background: Non-infectious uveitis is a diverse group of inflammatory conditions that collectively account for substantial blindness worldwide. Expert guidelines and results of clinical trials guide treatment, but real-world clinical care is impacted by additional factors. In 2023, an international group of uveitis-specialised ophthalmologists formed the International Study Group for Systemic Immunomodulatory Drug Treatment of Non-Infectious Uveitis to report current practice.

Methods: 221 study group members from 53 countries completed a 30-item questionnaire on their management of non-infectious uveitis including: indications for and investigations prior to initiating systemic immunomodulatory drugs, use of conventional and biological drugs, and follow-up of treated patients.

Results: Major indications to initiate systemic immunomodulatory drugs were: uveitis not controlled with oral prednis(ol)one (n=208, 94.1%), specific uveitis diagnosis (n=197, 89.1%), and patient intolerance of oral prednis(ol)one (n=186, 84.2%). All members (n=221, 100%) performed pretreatment screens including: blood chemistry (n=217, 98.2%), blood examination (n=207, 93.7%), and Quantiferon assay (n=196, 88.7%). Eight conventional and 14 biological drugs were prescribed: methotrexate was the preferred conventional drug overall (n=126, 57.0%) and for 9 of 11 uveitides, and adalimumab was the preferred biological drug overall (n=216, 97.7%) and for 11 of 11 uveitides. When drugs were combined, methotrexate plus adalimumab was most popular (n=158 of 188 members, 84.0%). Patients with inactive uveitis were typically evaluated and screened for drug toxicity every 6-12 weeks (n=161, 72.9%, and 165, 74.7%, respectively).

Conclusion: Our report describes practice patterns of a large international group of uveitis specialists treating non-infectious uveitis with systemic immunomodulatory drugs.

Publicado en The British journal of ophthalmology. Br J Ophthalmol 2025 Mar;109(4):482-489.

Purpose: To analyze the incidence of ocular inflammatory diseases and related ocular complications in patients with and without a history of cigarette, cannabis, vaping, and chewing tobacco use or exposure to tobacco smoke.

Methods: Patients aged 18 years and older with and without a history of cigarette, vape, cannabis, or chewing tobacco use, patients with and without a history of exposure to second-hand smoke, and patients with a diagnosis of an ocular inflammatory disease were included in our study. Odds ratios (ORs) were calculated to analyze the proportion of individuals who developed uveitis, scleritis, ocular mucous membrane pemphigoid (oMMP), and each ocular complication after cigarette, cannabis, vaping, and chewing tobacco use and exposure to tobacco smoke, compared to nonusers or those not exposed to tobacco smoke.

Results: Compared to nonsmokers, the OR for developing uveitis was 1.459 times higher for cannabis users (P = 0.016, 95% confidence interval [CI]: 1.072-1.985) and 1.712 times higher for those exposed to tobacco smoke (P < 0.001, 95% CI: 1.366-2.146). The odds of developing scleritis were 2.596 times higher for cannabis users (P = 0.002, 95% CI: 1.389-4.853), 1.667 times higher for vape users (P = 0.008, 95% CI: 1.14-2.438), and 1.612 times higher for chewing tobacco users (P = 0.013, 95% CI: 1.102-2.357). The odds of developing oMMP were 1.923 times higher for cigarette users (P = 0.042, 95% CI: 1.011-3.657). The odds of developing glaucoma were 1.551 times higher for cigarette users (P < 0.001, 95% CI: 1.234-1.95), 1.547 times higher for vape users (P < 0.002, 95% CI: 1.223-1.956), 1.574 times higher for chewing tobacco users (P < 0.001, 95% CI: 1.25-1.982), and 1.707 times higher for those exposed to tobacco smoke (P = 0.001, 95% CI: 1.229-2.37). Finally, the odds of developing cataracts were 2.513 times higher for cigarette users (P < 0.001, 95% CI: 1.821-3.469), 1.923 times higher for cannabis users (P = 0.005, 95% CI: 1.204-3.069), 2.151 times higher for vape users (P < 0.001, 95% CI: 1.509-3.064), 2.162 times higher for chewing tobacco users (P < 0.001, 95% CI: 1.525-3.064), and 4.205 times higher for those exposed to tobacco smoke (P < 0.001, 95% CI: 2.89-6.068).

Conclusions: History of cannabis use and exposure to second-hand smoke are significantly associated with an increased risk of uveitis, whereas a history of chewing tobacco, vape, and cannabis use is significantly associated with an increased risk of scleritis. Cigarette use is also associated with a significantly increased risk of oMMP.

Publicado en Journal of current ophthalmology. J Curr Ophthalmol 2025;37(4):421-429.

Introduction. To describe two cases of crystalline lens dislocation as a presenting feature of invasive group A Streptococcus (GAS) infection and its management. Case presentation. We report on a 58-year-old woman and a 36-year-old man who presented in 2024 with acute vision loss and severe ocular and systemic symptoms. Both patients were found to have lens dislocation and were diagnosed with invasive GAS infection. The 58-year-old woman had a complicated clinical course leading to enucleation, while the 36-year-old man responded favourably to early and aggressive treatment with systemic and intravitreal antibiotics. The responsible GAS strains were sequence type (ST) 28 and ST433, respectively. Conclusion. These cases highlight the importance of recognizing crystalline lens dislocation as a potential sign of ocular GAS infection. Two specific strain types of GAS associated with these findings, ST28 and ST433, are reported. In patients with GAS sepsis presenting with corneal oedema and zonular loss, clinicians should immediately initiate treatment, including intravitreal antibiotic injections and systemic therapy. Prompt and aggressive management can be crucial in preserving ocular structures.

Publicado en Access microbiology. Access Microbiol 2025;7(5).

Purpose: To describe the frequency of delayed and missed visits for Juvenile idiopathic arthritis (JIA)-uveitis patients and explore the demographic factors associated with delay in clinical follow-up.

Methods: This was a retrospective chart review of patients with > 2 appointments for JIA-associated uveitis between August 1984 and October 2022. Patient visits were classified as adherent, delayed, or missed if they followed up within the recommended follow-up time, outside the recommended follow-up time window, or more than 3 years after their last visit or never.

Results: There were 106 patients with a mean age of 15.5 years (range, 1.6-50.4). A total of 3169 visits over a cumulative follow-up time of 899.4 years (mean: 8.6 years of follow-up) occurred with 71 visits (2.2%) missed and 424 visits (13.4%) delayed. Sixty-nine patients (65.1%) had at least one delayed visit. Demographic and uveitis disease characteristics were all nonsignificant factors for a delayed or missed visit. Although having military-sponsored insurance was significant (P < 0.01), all other insurance types were not significantly associated with having a delayed visit.

Conclusions: Overall, the proportion of delayed and missed visits was quite low, even during the severe acute respiratory syndrome coronavirus 2 pandemic. Although patients with military insurance appear to be at increased risk for delayed follow-up visits, other insurances, distance to clinic, and demographic characteristics did not appear to be associated with delayed or missed follow-ups.

Publicado en Journal of current ophthalmology. J Curr Ophthalmol 2025;37(1):69-72.

Purpose: To assess the accuracy and completeness of ChatGPT-generated answers regarding uveitis description, prevention, treatment, and prognosis.

Methods: Thirty-two uveitis-related questions were generated by a uveitis specialist and inputted into ChatGPT 3.5. Answers were compiled into a survey and were reviewed by five uveitis specialists using standardized Likert scales of accuracy and completeness.

Results: In total, the median accuracy score for all the uveitis questions (n = 32) was 4.00 (between "more correct than incorrect" and "nearly all correct"), and the median completeness score was 2.00 ("adequate, addresses all aspects of the question and provides the minimum amount of information required to be considered complete"). The interrater variability assessment had a total kappa value of 0.0278 for accuracy and 0.0847 for completeness.

Conclusion: ChatGPT can provide relatively high accuracy responses for various questions related to uveitis; however, the answers it provides are incomplete, with some inaccuracies. Its utility in providing medical information requires further validation and development prior to serving as a source of uveitis information for patients.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2024 Nov;32(9):2052-2055.

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2024 Oct;32(8):1819-1831.

Purpose: To describe the clinical course and evaluate treatment of ocular surface changes in patients receiving immune checkpoint inhibitor (ICI) therapy.

Methods: Multiple markers of ocular surface dryness were evaluated in 16 patients on ICI therapy. The Wilcoxon rank-sum test was used to determine the significant change in the initial and final ocular surface indices.

Results: Fifty percent of the eyes demonstrated worsening Schirmer I scores; 29% showed an increase in lissamine green staining. During follow-up, 43% of patients experienced a decline in OSDI scores. Treatments included preservative-free artificial tears (88%), cyclosporine (25%), topical corticosteroids (31%), warm compresses (25%); punctal plugs (13%). Median follow-up time was 3.4 months (range:0-79 ); median ICI treatment duration was 7 months (range:1-40). Four patients died during the observation period.

Conclusion: A significant proportion of patients experience changes in ocular surface markers while treated with ICIs. Medical intervention can lead to stabilization of ocular surface disease.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2024 Oct;32(8):1522-1525.

Objectives: To report patients with systemic lymphoma and cytomegalovirus (CMV) retinitis, treated with a combination of oral and intravitreal antiviral agents on an outpatient basis.

Methods: Retrospective cases series. Information was gathered from the database of the Uveitis clinics at Moorfields Eye Hospital, United Kingdom from December 2014 to December 2018. The inclusion criteria comprised the diagnosis of systemic lymphoma, associated with a diagnosis of CMV retinitis. Exclusion criteria were alternative ocular diagnosis, human immunodeficiency virus (HIV), primary intraocular lymphoma, or other causes of immunosuppression.

Results: All seven subjects had been under oncologist care for systemic lymphoma. CMV retinitis presented with a median of 61 months after the systemic lymphoma diagnosis. Five patients underwent a vitreous biopsy, and four of them returned PCR positive for CMV and the fifth patient had PCR positive in a blood sample. All patients were treated with oral Valganciclovir, with an induction dose of 900 mg every 12 h for up to 3 weeks until disease resolution and a maintenance dose thereafter. All but one received additional intravitreal Foscarnet injections, with a dose of 2.4 mg /0.1 ml.

Conclusions: The management of patients with systemic lymphoma and CMV retinitis with oral and intravitreal antiviral agents, resulted in effective disease control.

Publicado en Eye (London, England). Eye (Lond) 2023 Jun;37(9):1895-1903.

Introducción: El tratamiento de la tuberculosis (TB) ocular es un tema que genera controversia en el mundo. Para el correcto manejo de estos pacientes, es necesario el desarrollo de guías que consideren la epidemiología de la TB ocular en cada nación. El objetivo de este consenso fue discutir de forma interdisciplinaria la epidemiología, fisiopatología, clínica, diagnóstico, estudio y tratamiento de los pacientes con TB ocular, para establecer un algoritmo de tratamiento y proponer qué pacientes deben ser tratados en Chile y con qué tratamiento. Además, se establecieron acuerdos para efectuar quimioprofilaxis de los pacientes con TB latente que tienen indicación de tratamiento inmunosupresor por enfermedades inflamatorias oculares.

Publicado en Revista chilena de infectología. Rev Chil Infectol. 2023 jun;40(3):270-283.

Purpose: To study the types of uveitis examined in a hospital serving indigent populations in need of low-cost care.

Methods: A retrospective chart review examined the electronic medical records of all patients with uveitis-related at Drexel Eye Physicians. Data collected included demographics, anatomic location of the uveitis, systemic disease associations, treatment modalities and insurance. Statistical analysis was performed using χ² or Fischer exact tests.

Results: 270 patients (366 eyes) were included for analysis, 67% of patients identified as African American. Most eyes (95.3%, N = 349) were treated with topical corticosteroid drops, and only 6 (1.6%) received an intravitreal implant. Immunosuppressive medications were started in 24 patients (8.9%). Nearly 80% depended to some extent on Medicare or Medicaid Assistance for treatment coverage. There was no association between insurance type and use of biologics or difluprednate.

Conclusion: We found no association between insurance type and the prescription of medications for uveitis that should be used at home. There was a minimal number of patients prescribed medications for implantation in the office. The adherence of use of medications at home should be investigated.

Publicado en BMC ophthalmology. BMC Ophthalmol 2023 Apr;23(1):140.

Aim: To evaluate if there is a difference in the clinical course of primary vitreoretinal lymphoma (PVRL) in vitrectomized versus non-vitrectomized eyes.

Methods: Observational multicenter retrospective case series of patients diagnosed with PVRL between 2007 and 2019, at three tertiary centers. The main outcomes were relapse rates, inflammatory parameters, and best-corrected visual acuities (BCVA). Statistical methods used were an adjusted generalized estimating equation model, and a proportional Cox model.

Results: Eighty patients (150 eyes) were followed for a median of 1.7 years. At presentation, there were no clinical differences between the groups. The relapse rate was 0.091/eye-year (EY) for vitrectomized eyes and 0.087/EY for non-vitrectomized eyes (p = .35). Vitrectomized eyes had better BCVA than non-vitrectomized eyes (p < .001).

Conclusions: Vitrectomy had no effect on the relapse rate in eyes with PVRL. However, the decrease in vitreous cell and debris led to vitrectomized eyes having better visual acuity than non-vitrectomized eyes.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2023 Apr;31(3):496-500.

Publicado en Revista medica de Chile. Rev Med Chil 2023 Mar;151(3):306-312.

Background: The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection.

Purpose: The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A.

Methods: A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted.

Results: Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified.

Conclusion: To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

Publicado en Diagnostics (Basel, Switzerland). Diagnostics (Basel) 2023 Feb;13(4).

Background: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide.

Methods and findings: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836).

Results: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%-58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%-48%) and blindness in 20% (95% CI 13%-30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72-8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59-6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment.

Conclusion: Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy.

Publicado en PloS one. PLoS One 2023;18(4):e0283845.

Background: Appraisals of Vogt-Koyanagi-Harada disease (VKH) have become progressively more complete, since its first description in 1906. The availability of new investigational methods has improved our knowledge of the immunopathology, clinicopathology, diagnosis, and management of VKH disease. This review aimed to describe some of the steps that led to better characterization of VKH as a clinical entity.

Methods: We searched on PubMed for articles that described the history of VKH disease and analyzed the progress in disease appraisal with new investigational and imaging methods. In particular, we searched for articles that investigated the clinicopathology, diagnosis, and management of VKH.

Findings: The following developments were considered essential for improving the appraisal and understanding of VKH: (1) the history of the disease, (2) immunopathological mechanisms, (3) clinicopathology, (4) the importance of distinguishing initial-onset from chronic disease, (5) relevant imaging modalities, among which indocyanine green angiography is crucial, (6) diagnostic criteria that facilitate early diagnosis, and (7) the need for early, prolonged, aggressive treatment that combines steroidal and non-steroidal immunosuppression.

Conclusion: Based on these findings, the definition of VKH has improved. VKH disease starts in the choroidal stroma and later involves other structures when it is not diagnosed and treated early. Indocyanine green angiography and enhanced depth imaging optical coherence tomography facilitate early diagnosis and precise monitoring of choroidal inflammation. ICGA is clearly the gold standard for appraisals and follow-ups in VKH disease, however EDI-OCT should be especially considered in those areas where ICGA is not fully available. These modalities have contributed substantially to a "cure" for VKH, when treatment is introduced within the therapeutic window of opportunity.

Publicado en Journal of ophthalmic inflammation and infection. J Ophthalmic Inflamm Infect 2022 May;12(1):17.

Purpose: To describe the effectiveness and side effect profile of difluprednate therapy in a series of patients with anterior scleritis.

Design: Retrospective, interventional case series.

Methods: Data collected from all patients with anterior scleritis who used difluprednate as a single treatment agent from January 1, 2018, to January 1, 2020, including demographics, scleritis type, presence of nodules or necrosis, changes in scleritis activity, intraocular pressure (IOP), number of difluprednate drops used, best-corrected visual acuity (BCVA), and lens status. The primary outcome was clinical resolution of scleritis. Secondary outcomes included BCVA loss ≥2 lines, change in lens status or cataract surgery, and IOP ≥24 mm Hg.

Results: Twenty-five patients (35 eyes) were analyzed. The median age was 60 years (range 13-78); 60% were female; 64% were White. Forty percent had bilateral disease, and 44% of patients had an associated systemic disease. The majority of eyes (66%) had diffuse anterior scleritis. Eighty-three percent of eyes achieved resolution of scleritis, with a median time of resolution of 6 weeks. Eyes treated with an initial dose of ≥4 times daily were more likely to achieve disease resolution (hazard ratio [HR] = 3.43, 95% confidence interval [CI] 1.19, 9.88, P = .02). Nine eyes had IOP elevation. Four eyes lost ≥2 lines of BCVA, and 1 due to cataract progression. One eye underwent cataract surgery.

Conclusions: Difluprednate alone may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Publicado en American journal of ophthalmology. Am J Ophthalmol 2022 Mar;235:172-177.

Acquired hemophilia A (AHA) is a rare condition that may be drug-induced. In this case report, we describe a patient who presented with extensive subcutaneous bleeding three years after beginning treatment with adalimumab for necrotizing scleritis. His workup was compatible with drug-induced AHA. He was treated with high-dose corticosteroids, cyclophosphamide, and rituximab. Adalimumab was discontinued. We present this case as an example of a rare, but potentially life-threatening, complication of adalimumab.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2022 Feb;30(2):294-296.

Publicado en International ophthalmology. Int Ophthalmol 2022 Jan;42(1):1-6.

Purpose: To evaluate the different definition of refractoriness in uveitis in the literature.

Methods: We systematically searched the literature in order to identify definitions of refractory noninfectious uveitis in adult patients. A search strategy in the databases of MEDLINE and Scopus was used to find articles published between January 2005 and October 2018.

Results: Definitions of corticosteroids-refractoriness were related to two main concepts: persistence of inflammation despite the use of corticosteroid and recurrences above a dosage threshold. In terms of immunomodulatory therapy and biologic agents, we observed a great variety of definitions: persistence of inflammation, number of attacks, side effects or complications, symptoms, and best-corrected visual acuity.

Conclusions: The results of this systematic review demonstrate the current lack of consensus on the definition for refractory uveitis, regardless of the treatment being used and revealed a new terminology based on a comprehensive and operational definition for each specific category of refractoriness.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2022 Jan;30(1):174-179.

Vogt-Koyanagi-Harada (VKH) disease is a primary autoimmune stromal choroiditis. This review aimed to provide a novel perspective of the disease. We took into account recent developments in the understanding of the disease and crucial progress in investigational modalities of the choroid, which has led to new, simpler diagnostic criteria. We analysed recent novel notions in the literature and new diagnostic tools for VKH. We identified the following updates for VKH disease: (1) A crucial differentiation between the acute initial-onset and the chronic forms of the disease; (2) the integration of new, precise imaging methods to assess choroidal inflammation; (3) the promotion of simplified, more reliable diagnostic criteria for acute initial-onset of the disease, based on the sine qua non presence of diffuse choroiditis, detected with indocyanine green angiography (ICGA) and/or Enhanced Depth Imaging OCT (EDI-OCT); and (4) treatment optimisation through early, vigorous, sustained corticosteroid and nonsteroidal immunosuppression, as the first line of treatment for initial-onset VKH disease, and monitoring subclinical choroidal inflammation during follow-ups. Several studies have shown that most patients could discontinue treatment without an inflammation relapse. ICGA and EDI-OCT represented the methods of choice for precisely monitoring disease evolution. Simplified, precise, new diagnostic criteria allow early diagnosis of VKH. In VKH disease, inflammation exclusively originates in the choroidal stroma. Therefore, in many cases, early, sustained treatment, with dual corticosteroid and nonsteroidal immunosuppressive therapy can result in full "healing", which obviates chronic, uncontrolled, subclinical choroidal inflammation.

Publicado en Eye (London, England). Eye (Lond) 2022 Jan;36(1):29-43.

Purpose: To report the outcomes of the escalation of adalimumab (ADA) dose for refractory ocular inflammatory diseases.Methods: A retrospective case series of 15 patients (29 eyes) diagnosed with ocular inflammatory disease, including uveitis and scleritis, which was not adequately controlled with standard, every other week ADA dosing, leading to an escalation to weekly dosing.Results: Ten of fifteen patients escalated to weekly ADA achieved control of their inflammation; neither of the two patients increased for control of cystoid macular edema (CME) had resolution and required regional corticosteroids. One patient discontinued weekly ADA due to serious infection. The median length of follow up was 12 months.Conclusion: Our series suggests that the escalation of ADA can be a useful strategy for treating recalcitrant ocular inflammation, but may not be adequate to treat refractory CME.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2021 Nov;29(7-8):1564-1568.

miRNAs, one of the members of the noncoding RNA family, are regulators of gene expression in inflammatory and autoimmune diseases. Changes in miRNA pool expression have been associated with differentiation of CD4+ T cells toward an inflammatory phenotype and with loss of self-tolerance in autoimmune diseases. Vogt-Koyanagi-Harada (VKH) disease is a chronic multisystemic pathology, affecting the uvea, inner ear, central nervous system, and skin. Several lines of evidence support an autoimmune etiology for VKH, with loss of tolerance against retinal pigmented epithelium-related self-antigens. This deleterious reaction is characterized by exacerbated inflammation, due to an aberrant T H 1 and T H 17 polarization and secretion of their proinflammatory hallmark cytokines interleukin 6 (IL-6), IL-17, interferon γ, and tumor necrosis factor α, and an impaired CD4+ CD25 high FoxP3+ regulatory T cell function. To restrain inflammation, VKH is pharmacologically treated with corticosteroids and immunosuppressive drugs as first and second line of therapy, respectively. Changes in the expression of miRNAs related to immunoregulatory pathways have been associated with VKH development, whereas some genetic variants of miRNAs have been found to be risk modifiers of VKH. Furthermore, the drugs commonly used in VKH treatment have great influence on miRNA expression, including those miRNAs associated to VKH disease. This relationship between response to therapy and miRNA regulation suggests that these small noncoding molecules might be therapeutic targets for the development of more effective and specific pharmacological therapy for VKH. In this review, we discuss the latest evidence regarding regulation and alteration of miRNA associated with VKH disease and its treatment.

Publicado en Frontiers in cell and developmental biology. Front Cell Dev Biol 2021;9:658514.

Purpose: To describe distinctive stages of Vogt-Koyanagi-Harada (VKH) disease: initial-onset acute versus chronic recurrent disease.

Methods: A comprehensive literature review regarding stages and clinical presentations of VKH disease was conducted.

Results: Despite a list of signs that has been described as characteristic features of early or late phases of VKH disease, the current classification -developed by an international committee and published in 2001- does not consider a distinction regarding the time from onset of disease symptoms, and specific findings observed at certain time point from the symptoms presentation and outcomes related to the stage of VKH disease. In that sense, chronic recurrent VKH disease is more refractory to treatment and is associated with a higher rate of complications. Accordingly, this subset of VKH patients has poorer functional and anatomical outcomes than patients with an initial-onset acute disease.

Conclusions: An early clear distinction of VKH phenotype [Initial-onset acute versus chronic recurrent disease] should be considered in each clinical scenario, evaluating the delay in diagnosis and the clinical presentation, since it may help clinicians to perform a correct disease prognosis categorization and thus to make treatment decisions in terms of potential refractoriness or expected clinical outcomes.

Publicado en Journal of ophthalmic inflammation and infection. J Ophthalmic Inflamm Infect 2020 Sep;10(1):23.

Publicado en JAMA ophthalmology. JAMA Ophthalmol 2020 Jul;138(7):e194120.

Purpose: To report the occurrence of conjunctivitis associated with the use of dupilumab in patients with atopic dermatitis.

Methods: A retrospective small case series.

Results: The first case was a 56-year-old man who developed conjunctivitis 2 weeks after starting dupilumab. The second case was a 19-year-old man who developed blepharoconjunctivitis 3 months after staring dupilumab. The ocular inflammation in both cases resolved rapidly and remained controlled with topical steroid drops without necessitating the discontinuation of dupilumab. However, the second patient had already developed conjunctival cicatrization in 1 eye at the time of presentation.

Conclusions: The pathophysiology and the risk factors for the development of conjunctivitis in patients who take dupilumab for atopic dermatitis are not completely understood. However, topical steroid treatment halts the inflammation effectively without discontinuation of dupilumab therapy.

Publicado en Cornea. Cornea 2020 Jun;39(6):784-786.

Non-infectious uveitis (NIU) is a group of disorders characterized by intraocular inflammation at different levels of the eye. NIU is a leading cause of irreversible blindness in working-age population in the developed world. The goal of uveitis treatment is to control inflammation, prevent recurrences, and preserve vision, as well as minimize the adverse effects of medications. Currently, the standard of care for NIU includes the administration of corticosteroids (CS) as first-line agents, but in some cases a more aggressive therapy is required. This includes synthetic immunosuppressants, such as antimetabolites (methotrexate, mycophenolate mofetil, and azathioprine), calcineurinic inhibitors (cyclosporine, tacrolimus), and alkylating agents (cyclophosphamide, chlorambucil). In those patients who become intolerant or refractory to CS and conventional immunosuppressive treatment, biologic agents have arisen as an effective therapy. Among the most evaluated treatments, TNF-α inhibitors, IL blockers, and anti-CD20 therapy have emerged. In this regard, anti-TNF agents (infliximab and adalimumab) have shown the strongest results in terms of favorable outcomes. In this review, we discuss latest evidence concerning to the effectiveness of biologic therapy, and present new therapeutic approaches directed against immune components as potential novel therapies for NIU.

Publicado en Frontiers in Pharmacology, mayo 2020.

Purpose: To investigate the potential of utilizing the expression of genes for glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase-1 (MKP-1) as biomarkers of corticosteroid (CS) refractoriness and disease activity in patients with Vogt-Koyanagi-Harada (VKH) disease.

Design: Prospective cohort study.

Methods: Twenty VKH patients receiving their first cycle of CS treatment in the absence of additional systemic immunosuppressive therapy and a control group of fifteen healthy volunteers were recruited from the University of Chile (Santiago, Chile) and US National Institutes of Health (Bethesda, United States). Intraocular inflammation was clinically quantified at enrolment and all follow-up visits. CS refractoriness was defined as an ocular reactivation of VKH upon CS withdrawal at a daily oral prednisone dose of 10 mg or more. Quantitative Reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure the mRNA levels of the alpha (α) and beta (β) isoforms of GR and MKP-1 in peripheral blood mononuclear cells (PBMC) after in vitro stimulation with either anti-CD3/anti-CD28 antibodies, lipopolysaccharide (LPS), or phytohemagglutinin (PHA), in the presence or absence of dexamethasone (Dex).

Results: After 6 hours of stimulation in the presence of Dex, PBMC from CS-refractory VKH patients had an impaired elevation in GRα expression (P = .03). Furthermore, inactive patients showed a significant Dex-induced upregulation of MKP-1 (P = .005).

Conclusions: In this pilot study, the expression of GR isoforms and MKP-1 corresponded with patients’ clinical response to systemic CS treatment and disease activity, respectively. Hence, these candidate biomarkers have potential clinical utility in the early identification of CS refractoriness and subclinical inflammation in patients with VKH disease.

Publicado en American Journal of Ophthalmology. Am J Ophthalmol. 2019 Nov;207:319-325.

Purpose: Parinaud’s oculo-glandular syndrome (POGS) is the most frequent manifestation of ocular bartonellosis, and usually presents with local lymphadenopathies and systemic symptoms. We present a case of isolated conjunctival granuloma as the sole manifestation of ocular bartonellosis.

Observations: A 67-year-old female presented to the authors’ eye clinic with complaints of a 2-week history of unilateral red eye and chemosis. Slit lamp examination revealed an isolated bulbar conjunctival granuloma. The remainder of the eye examination was unremarkable. Topical treatment with gatifloxacin and prednisolone acetate was started. Etiological work-up was performed. General laboratory tests revealed only a mild leukocytosis, and interferon gamma-release assay and chest computed tomography were normal. Serological testing for Bartonella henselae was positive at titers of 1:1024. Three weeks after initial symptoms, lymphadenopathies, malaise, and fever appeared. Systemic azithromycin was added, which resulted in complete regression of the disease.

Conclusion and importance: Conjunctival granulomas present a wide range of differential diagnoses to the practitioner. Ocular bartonellosis is a relevant cause of conjunctival granuloma. POGS should be suspected in cases of conjunctival granulomata non-responsive to local therapy. It is important to consider that other agents to treat POGS have been described and are available, and that appropriate serological tests should be performed.

Publicado en American Journal of Ophthalmology Case Reports.  Am J Ophthalmol Case Rep. 2019 Feb 23;14:58-60.

Purpose: To describe clinical features of patients with diabetes mellitus-associated uveitis (DMAU).

Methods: Retrospective analysis of clinical records of patients with uveitis and diabetes mellitus (DM) presented in an uveitis referral centre in Chile. Demographic data, comorbidities, complete ophthalmic examination, and treatments were analyzed.

Results: We found 72 patients with uveitis and DM: 16 with DMAU and poorly regulated DM (22%), 15 with DMAU and well-controlled DM (21%), and 41 with uveitis due to established other causes than DM (57%). Patients with DMAU in poorly regulated diabetes, presented inflammation of 3-4+ cells in 33%, a fibrinous reaction in 28%, hypopyon in 17% and posterior synechiae in 83%, compared with 5%, 0%, 0%, and 50% in the group with well-controlled DM, respectively (p < 0.05). Most DMAU patients responded well to topical or periocular steroids.

Conclusion: Patients with DMAU with poorly regulated DM present a more severe inflammation compared with patients with DMAU with well-controlled DM.

Publicado en Ocular Immunology and Inflammation. Ocul Immunol Inflamm. 2019 Feb 27;1-4

Propósito: Describir el cuadro clínico y evolución de uveítis secundarias drogas para el tratamiento de melanoma cutáneo metastásico (MCM)

Método: Descripción de 5 casos, evaluados en 2 centros.

Resultados: Primer caso, paciente varón de 45 años que consulta por dolor y baja visión bilateral. Usuario de Vemurafenib durante los últimos 16 meses. Al examen destaca una agudeza visual (AV) de 1.0 OU, celularidad moderada en cámara anterior, snowballs y envainamiento vascular retina periférico. El estudio etiológico fue negativo.

Segundo caso: Mujer de 34 años que consulta por cuadro de inflamación intensa en cámara anterior, asociado a lesiones redondas e hipopigmentadas retinales. Su AV era de OD:0,3 y OI: 0,5. Además con vitíligo en tronco y abdomen. En tratamiento actual de Vemurafenib y previo de Ipilimumab y Nivolumab por melanoma de piel.

Tercer caso: Varón de 52 años que consulta por baja de visión bilateral y ojo rojo, en tratamiento con Dabrafenib y Trametinib desde hace 5 meses por un MCM. Al examen físico destacaba una AV de 1.0 bilateral y solo celularidad anterior, con un fondo de ojos normal.

Cuarto caso: Mujer de 61 años con MCM en tratamiento con Trametinib y Dabrafenib, derivada por pérdida visual bilateral. Su examen arroja una paunuveitis bilateral, papilitis, desprendimientos serosos extensos de retina y AV de cuenta dedos OU. Un completo estudio etiológico fue también negativo.

Quinto caso: Varón de 52 años con diagnóstico de MCM que consultó por baja abrupta de visión bilateral. Tratado con Vemurafenib por 4 meses y posteriormente con Dabrafenib y Trametinib por 3 meses hasta el momento de la consulta. Al examen, su AV era de OD: 0,9 y OI 1,0. El segmento anterior estaba sano, pero al fondo de ojos presentaba un desprendimiento de retina bilateral, con líquido intraretinal, asociado a lesiones hipopigmentadas en forma de gusanos a nivel retinal.

Los 3 primeros casos, recibieron corticoides tópicos con buena respuesta, sin suspender su tratamiento de base. El 4º caso requirió metilprednisolona y Micofenolato para el control de la inflamación. El último paciente, no continuó en seguimiento por el pésimo pronóstico vital.

Conclusiones: Las uveítis asociadas al tratamiento del MCM son una nueva entidad reconocida recientemente. El oftalmólogo debe tenerlas presentes al momento del diagnóstico diferencial.

Presentado en el XXVI Congreso Chileno de Oftalmología. Viña del Mar, Chile. 2018.

Purpose: To describe the use of biologic therapy in a group of Chilean patients with non-infectious uveitis or scleritis, focusing on inflammation, visual acuity, adverse effects and associated therapies.

Methods: Retrospective, cross sectional, observational study. Medical records of patients with non-infectious uveitis and/or scleritis and biologic therapy were reviewed at 2 medical centres. Demographic data, degree of inflammation during follow-up, drugs used and complications were recorded in an Excel database and analysed using Stata®12 software.

Results: We found 41 patients with uveitis or scleritis and biologic treatment. The average age was 15 years at diagnosis (1.5-64). The most frequent aetiology of the inflammation was JIA-associated anterior uveitis. Adalimumab was the main drug used. In the subgroup of patients with ophthalmic indication of biologic therapy and a minimum follow-up of 1 year (1 to 5.6 years, 25 patients), we found a complete control of the inflammation in 72%, 84% and 92% at 3, 6 and 12 months, respectively. 44% had flares-up during follow-up (average 2.8 reactivations per-patient). In 6 patients the treatment was discontinued after 25 months (14-34) of quiescence, occurring reactivations in all but one.

Severe complications seen during treatment were one Varicella Zoster infection, one patient with Leukoencephalopathy, one with pustular psoriasis and one with a non-Hodgkin lymphoma.

Conclusions: Biologic treatment is effective in treating uveitis and scleritis in patients where conventional immunosuppressive drugs have failed. However, despite this high effectiveness, the withdrawal of treatment usually entails a reactivation of the disease and it is not exempted from complications.

Presentado en el 14th Congress of the International Ocular Inflammation Society (IOIS) and the 4th International Assembly of Ocular Inflammation Societies . Laussane, Switzerland. 18-21 october, 2017

Purpose: To determine the performance of T-SPOT.TB, an interferon gamma release assay test, in patients with ocular tuberculosis (TB) in a BCG-vaccinated, non-endemic population.

Methods: We employed a nested case-control design. In total, 45 subjects were enrolled (23 patients with ocular tuberculosis and 22 patients with other causes of uveitis). A blood sample was collected from each subject, and T-SPOT.TB was executed. Laboratory professionals were blinded to the disease status of each subject.

Results: Five patients were excluded because of indeterminate results. The calculated sensitivity and specificity were 0.80 and 0.85, respectively. The positive likelihood ratio was 5.33 and the negative likelihood ratio was 0.23. The overall accuracy of the test was 0.83.

Conclusions: T-SPOT.TB adequately diagnosed ocular TB. This technique is particularly useful in populations where BCG vaccinations are still mandatory.

cataracts. Therefore, efforts should be made to avoid a delay in the diagnosis of ocular TB and to identify prognostic factors for visual outcomes and complications.

Publicado en Ocular Immunology and Inflammation. Ocul Immunol Inflamm. 2017 Aug;25(4):455-459.

Purpose: To characterize the clinical features in patients with presumed ocular tuberculosis (TB) and determine prognostic factors of visual outcomes and complications in this disease.

Material and methods: Retrospective case series of 35 patients (29 females, 6 males) with presumed ocular TB from referral centers in Chile and Spain between 2002 and 2012. Medical records were reviewed, and data regarding clinical features, complications, best-corrected visual acuity (BCVA), duration of disease, extraocular manifestations, and therapy were retrieved. Prognostic factors for low vision (BCVA 20/50 or less), legal blindness (BCVA 20/200 or less), and complications (cataract, glaucoma, and macular lesion) were evaluated. To calculate correlations, we used Spearman’s rank correlation test. To determine clinical predictors, we used the binary logistic regression test.

Results: Anterior and non-granulomatous uveitis was the most common types of inflammation. Only 2 (5.7%) patients had respiratory symptoms, and 6 (17.1%) patients had an abnormal chest X-ray at diagnosis. All patients received combined antitubercular therapy with a mean duration of 6.9 ± 2.3 months. A longer duration of symptoms at diagnosis was associated with both low vision and legal blindness. Older patients had a higher risk of legal blindness. A longer duration of symptoms as well as anterior inflammation demonstrated an increased risk for cataract formation. The duration of the symptoms and baseline BCVA had a positive correlation with the final BCVA. Prognostic factors of macular lesions were not found.

Conclusions: The diagnosis of ocular TB can be difficult due to the lack of extraocular manifestations and the broad spectrum of ocular features. A longer duration of symptoms at diagnosis was associated with poorer visual outcomes and cataracts. Therefore, efforts should be made to avoid a delay in the diagnosis of ocular TB and to identify prognostic factors for visual outcomes and complications.

Publicado en Current Eye Research. Curr Eye Res. 2017 Jul;42(7):1029-1034.

Purpose: To describe the pattern of uveitis in a tertiary center in Santiago, Chile.

Methods: We reviewed all of the case records with a presumptive diagnosis of uveitis from patients referred to the Uveitis Department of Hospital del Salvador between 2002 and 2012. Initial assessment was standardized. We tested for association among causes, gender, and age groups.

Results: Anterior uveitis was the leading anatomical location of the inflammation (40.4%). A specific etiology was demonstrated in 59% of cases (28.7% infectious). Vogt-Koyanagi-Harada syndrome (VKH) was the most frequent cause of uveitis (17.2%). We found association between idiopathic intermediate uveitis, toxocariasis, juvenile idiopathic arthritis, VKH, toxoplasmosis, diabetes mellitus (DM)-associated uveitis, tuberculosis, and idiopathic anterior uveitis and age groups. VKH, DM-associated uveitis, and syphilis-associated uveitis were associated with gender.

Conclusions: Our sample shows a distribution of causes of uveitis similar to those in developed countries. The prevalence of VKH is higher than expected.

Publicado en Ocular immunology and inflammation. Ocul Immunol Inflamm 2015 Aug;23(4):339-345.

Purpose: To evaluate clinical outcomes of first-line immunomodulatory therapy (IMT) and prednisone alone or late IMT in Vogt-Koyanagi-Harada disease.

Methods: Retrospective cohort study of 152 patients with Vogt-Koyanagi-Harada disease evaluated in a referral uveitis clinic in Chile from 1985 to 2011. Medical records of these patients were reviewed. Demographic data, clinical evaluation, type of treatment, functional outcomes, glucocorticoid (GC) dose and complications were recorded. Multivariate logistic regression was used to identify prognostic factors of poor response to GC.

Results: There were no significant differences between first-line IMT group and prednisone alone/late IMT group in terms of visual acuity (VA) improvement, complications and GC sparing effect. There was a trend for a higher frequency of systemic adverse effects leading to discontinuation of treatment in patients receiving IMT than in those receiving prednisone (14.6% and 6.5%, respectively). The subgroup of patients with poor response to GC who showed functional improvement had a significantly earlier time to IMT initiation than the patients who had no improvement. We identified following prognostic factors of poor response to GC: VA ≤ 20/200, fundus depigmentation, chronic disease and tinnitus at diagnosis. Patients with a prognostic factor (excluding tinnitus) and VA improvement had an earlier IMT initiation than those who had worse functional outcome.

Conclusion: There were no differences in outcomes between first-line IMT and prednisone alone/late IMT in the entire VKH group. However, in a subset of patients, there was a significant better functional outcome with earlier IMT initiation.

Publicado en Acta Ophthalmologica. Acta Ophthalmol. 2015: 93: e475–e480.