Efeito colateral da pandemia de Covid-19 no Brasil sobre o número de procedimentos diagnósticos e de tratamento da sífilis / Side effect of the COVID-19 pandemic in Brazil on the number of diagnostic and treatment procedures for syphilis / Efecto secundario de la pandemia de Covid-19 en Brasil sobre el número de procedimientos de diagnóstico y tratamiento de la sífilis

A sífilis, uma infecção vertical e sexualmente transmissível, curável e prevenível, é um problema de saúde pública no Brasil. Métodos diagnósticos e tratamentos são importantes no controle da doença. A pandemia de Covid-19 causou atrasos em diagnósticos e no tratamento na atenção primária em várias doenças e em diversos países, pois interrompeu padrões usuais de atendimento à saúde. O objetivo do estudo é identificar se houve menor número de procedimentos diagnósticos e de tratamento realizados para sífilis nos primeiros sete meses de 2020, comparativamente à média dos mesmos meses entre 2016 e 2019, no Brasil e nas unidades federativas. A redução no número de procedimentos seria um indicativo de atraso no diagnóstico, na detecção e no tratamento da sífilis em 2020. Foram utilizadas informações disponibilizadas no Sistema de Informações Ambulatoriais (SIA/SUS). Os achados para o Brasil indicaram queda de 1/3 nos procedimentos de diagnóstico e de tratamento referentes à sífilis nos sete primeiros meses do ano da pandemia, comparados com a média dos sete primeiros meses nos quatro anos anteriores (2016-2019). Indicadores mostram diferenças importantes por unidades da federação, apontando para maiores quedas proporcionais nos volumes de procedimentos no Norte e Nordeste, com ênfase nos estados do Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco e Amapá.

Syphilis, a vertical and sexually transmitted infection, curable and preventable, is a public health problem in Brazil. Diagnostic methods and treatments are important in controlling the disease. The COVID-19 pandemic caused delays in diagnosis and lack of treatment in primary care in several diseases and in several countries, as the pandemic disrupted usual health care standards. The aim of the study was to identify whether there were fewer diagnostic and treatment procedures performed for syphilis in the first seven months of 2020, compared to the average for the same months between 2016 and 2019, in Brazil and Federative Units. The reduction in the number of procedures would be indicative of a delay in the diagnosis, detection and treatment of syphilis in 2020. Information used came from the Outpatient Information System (SIA / SUS). The findings for Brazil indicated a 1/3 drop in diagnosis and treatment procedures for syphilis in the first seven months of the year of the COVID-19 pandemic, compared with the first seven months of the previous four years (2016-2019). Indicators showed important differences by Federation Units, pointing to greater proportional decrease in the volume of procedures in the North and Northeast, with an emphasis on Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco and Amapá.

La sífilis, una infección vertical y de transmisión sexual, curable y prevenible, es un problema de salud pública en Brasil. Los métodos de diagnóstico y los tratamientos son importantes para controlar la enfermedad. La pandemia de Covid-19 provocó retrasos en el diagnóstico y tratamiento en la atención primaria de variadas enfermedades en varios países, ya que interrumpió los estándares habituales de atención de la salud. El objetivo del estudio fue identificar si se realizaron menos procedimientos de diagnóstico y tratamiento de la sífilis en los primeros siete meses de 2020 en comparación con la media de los mismos meses entre 2016 y 2019, en Brasil y en sus unidades federativas. La reducción del número de procedimientos indicaría indicativo de un retraso en el diagnóstico, la detección temprana y el tratamiento de la sífilis en 2020. Para ello se utilizó la información disponible en el Sistema de Información Ambulatoria (SIA/SUS). Los hallazgos indicaron una caída de un tercio en los procedimientos de diagnóstico y tratamiento de la sífilis en los primeros siete meses del año de la pandemia de Covid-19 para Brasil, en comparación con los primeros siete meses de los cuatro años anteriores (2016-2019). Los indicadores mostraron diferencias importantes por unidades de la Federación, apuntando a mayores caídas proporcionales en el volumen de trámites en el Norte y Nordeste, con énfasis en Maranhão, Roraima, Pará, Bahia, Rio Grande do Norte, Amazonas, Pernambuco y Amapá.

A Dual-Platform Point-of-Care Test for Neurosyphilis Diagnosis.

BACKGROUND: The diagnosis of neurosyphilis relies on cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein) and CSF-Venereal Disease Research Laboratory (VDRL) test. In resource-limited settings, the CSF-VDRL test may not be widely available. METHODS: We optimized a commercial immunochromatographic strip test, the DPP Chembio syphilis assay, for performance with CSF and tested centrifuged CSF samples of 71 patients with syphilis (35 with neurosyphilis and 36 without neurosyphilis). A CSF dilution of 1:4 was chosen based on agreement with CSF pools with documented results from the CSF-VDRL test and fluorescent treponemal antibody absorption test on CSF. Using an electronic reader, we obtained unit values of treponemal and nontreponemal antibodies for all study samples and generated a receiver operating characteristic curve; using the Youden index, we established diagnostic cutoffs with optimal sensitivity and specificity. RESULTS: Diagnostic sensitivity of the nontreponemal test was 80% (95% confidence interval, 63%-92%) and specificity was 97% (95% confidence interval, 85%-100%) for neurosyphilis diagnosis using a reactive CSF-VDRL that improved after neurosyphilis therapy as a criterion standard. CONCLUSIONS: In this small study, the DPP Chembio test showed promising results for neurosyphilis diagnosis. Further studies are needed to assess its performance in resource-limited settings.

Sífilis, la gran simuladora / 8 SYPHILIS, THE GREAT SIMULATOR. Case report of a patient with syphilitic uveitis

La sífilis desde hace siglos desafía a la humanidad, es transmitida por vía sexual y verticalmente durante la gestación.9 Esta enfermedad se hizo conocida en Europa a finales del siglo XV,13 y su rápida propagación por todo el continente la transformó en una de las principales plagas mundiales.Era preocupante el crecimiento de la endemia sifilítica en el siglo XIX 13.1. En contrapartida la medicina se desarrollaba, y la síntesis de las primeras drogas se hacía realidad. El mayor impacto tal vez fue la introducción de la penicilina en 1946, la cual por su eficacia hizo a muchos pensar que la enfermedad estaba controlada. En un estudio de revisión de literatura se dice que a raíz de la introducción de la penicilina la incidencia de sífilis (y de uveítis sifilítica) fue disminuyendo constantemente hasta finales de los años 90.3 resultando en la disminución del interés por su estudio y control. Con la aparición del síndrome de inmunodeficiencia adquirida (SIDA).2 se incrementó dramáticamente la evolución de esta enfermedad.En la literatura oftalmológica se comenzaron a documentar cada vez más casos e incluso se ha llegado a hablar de la «nueva epidemia de sífilis ocular¼1 Se estima que, anualmente, unos 357 millones de personas contraen alguna de las cuatro infecciones de transmisión sexual (ITS) siguientes: clamidias, gonorrea, sífilis o tricomoniasis.7 En el mundo hay una incidencia anual de aproximadamente 12 millones de pacientes con sífilis el 90% ocurre en países en desarrollo (OMS).

Syphilis has defied humanity for centuries, is transmitted sexually and vertically during pregnancy. This disease became known in Europe at the end of the 15th century,13 and its rapid spread throughout the continent transformed it into one of the main world plagues. The growth of the syphilitic endemic in the 19th century was worrisome.13.1 In contrast, medicine developed, and the synthesis of the first drugs became a reality. Perhaps the biggest impact was the introduction of penicillin in 1946, which, due to its effectiveness, led many to believe that the disease was controlled. In a literature review study, it is said that following the introduction of penicillin the incidence of syphilis (and syphilitic uveitis) was steadily decreasing until the end of the 90s.3 resultando in the decrease of interest in its study and control. With the onset of acquired immunodeficiency syndrome (AIDS). the evolution of this disease increased dramatically. In the ophthalmological literature, more and more cases have been documented and there has even been talk of the "new epidemic of ocular syphilis".1.1 It is estimated that some 357 million people each year get one of the four sexually transmitted infections (STIs) following: chlamydia, gonorrhea, syphilis or trichomonas's. In the world there is an annual incidence of approximately 12 million patients with syphilis 90% occurs in developing countries (WHO)

Abbott ARCHITECT Syphilis TP Chemiluminescent Immunoassay Accurately Diagnoses Past or Current Syphilis in Pregnancy.

OBJECTIVE: We evaluate diagnostic accuracy of the ARCHITECT chemiluminescent immunoassay (CIA) screening test in pregnancy, and evaluate pregnancy outcomes among screen-positive women. STUDY DESIGN: Samples from routine prenatal rapid plasma reagin (RPR) tests were collected between June 22 and August 18, 2017 and frozen. Samples were batch-tested with the Abbott ARCHITECT syphilis TP immunoassay (CIA, index test). We calculated sensitivity, specificity, predictive value, and false positivity. We compared pregnancy and neonatal outcomes among screen-positive women. RESULTS: Of 1,602 specimens, 35 (2.2%) were RPR + ; of those, 24 (69%) were CIA +/Treponema pallidum particle agglutination assay (TPPA)+ and 11 (31%) were CIA-/TPPA-. Of 1,567 RPR- specimens, 14 (0.9%) were CIA + ; of those, 13 (93%) were TPPA + , and one (7%) had a false positive CIA test. Sensitivity of the CIA (95% CI) was 100% (90.5-100%), specificity 99.9% (99.6-100%), positive predictive value 97.4% (86.2-99.9%), and false positive rate 0.06% (0.002-0.4%) for current or past syphilis. Among 37 CIA +/TPPA+ women, seven (19%) had RPR-negative status (Group 1), 11 (30%) had previously treated syphilis (Group 2), and 19 (51%) had active infection (Group 3). One stillbirth occurred in a woman with early, active syphilis identified at delivery; no adverse perinatal outcomes occurred among women in Groups 1 or 2. CONCLUSION: The ARCHITECT syphilis TP immunoassay accurately diagnoses current or past syphilis in pregnancy. Clinical history and staging remain essential using a reverse algorithm.

Evaluating congenital syphilis in a reverse sequence testing environment.

OBJECTIVES: To examine the effect of maternal reverse-sequence (RS) syphilis screening on management of infants at risk for congenital syphilis (CS) using a standardized approach. STUDY DESIGN: A retrospective study from 2011 to 2014 at an academic medical center using RS testing, involving chemiluminescent immunoassay (CIA), rapid plasma  reagin (RPR), and fluorescent treponemal antibody-absorption (FTA-ABS) assays for syphilis. Clinical management and outcomes of infants born to mothers with discordant (CIA+/RPR-/FTA+) serology were compared with national or internal guidelines. RESULTS: Sixty-three infants were classified as discordant (n = 21), presumed false positive (CIA+/RPR-/FTA-; n = 16), or true positive (CIA+/RPR+; n = 26) based on maternal serology. Only 24% of cases in the discordant group underwent recommended full evaluation. None of the evaluated infants in the discordant group (n = 8) were diagnosed with CS. CONCLUSIONS: Management of infants with discordant maternal RS serology remained reliant on clinical judgment. In our high-risk population, RS testing did not identify additional cases of CS.

Neurosyphilis: Concordance between cerebrospinal fluid analysis and subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis.

INTRODUCTION: The confirmation or analysis and exclusion of a diagnosis of neurosyphilis has long presented a challenge for infectious diseases clinicians. The authors reviewed the concordance between cerebrospinal fluid (CSF) analysis and the subsequent antibiotic strategy for patients undergoing evaluation of a diagnosis of neurosyphilis. METHODS: All patients with positive serum syphilis serology referred for CSF analysis between January 2009 and May 2016 were included. Indications for CSF analysis were determined by review of the hospital electronic medical records. CSF parameters were determined from the hospital pathology database. Cases were defined as either 'confirmed', 'supportive' of, or 'not supportive' of a diagnosis of neurosyphilis based on existing definitions. Subsequent therapy was defined as for neurosyphilis, late latent primary syphilis or no therapy based on existing guidelines. RESULTS: Of 131 patients reviewed, 95.4% were male and HIV co-infected (74%). A confirmed diagnosis of neurosyphilis was met by fourteen patients (10.7%). All but two of these were treated with a neurosyphilis-directed regimen. Of the 58 patients treated with neurosyphilis antibiotics, 17.2% had no CSF findings suggestive of the diagnosis. Seventy-three patients were not treated for neurosyphilis; however 35 of these met the CSF criteria for a diagnosis supportive of neurosyphilis. CONCLUSIONS: The results of routine CSF analysis in patients with a possible diagnosis of neurosyphilis are inconsistently applied in the clinical setting, calling into question the value of routine CSF. Empirical neurosyphilis treatment should be considered up front in patients with high pre-test probability of the diagnosis.

Performance evaluation of nine different syphilis serological tests in comparison with the FTA-abs test.

BACKGROUND: Serological methods have great importance for the detection of Treponema pallidum antibodies in syphilis diagnosis. The goal of the present study is to evaluate various commercially available screening assays in comparison with the FTA-abs test. METHODS: A total of 363 serum samples were enrolled in the study. Following routine testing including RPR and TPHA tests, each sample was tested by treponemal immunoassays (Chorus Syphilis Screen Recombinant, Architect Syphilis TP, Syphilis Virclia Monotest, Siemens Advia Centaur Syphilis, Euroimmun Treponema pallidum Screen ELISA, Vircell Syphilis ELISA IgG + IgM, SD Bioline Syphilis). The result obtained from each test was compared with the confirmatory FTA-abs test. Kappa (κ) coefficients were used to compare the concordance of the tests. RESULTS: When the various tests were evaluated in comparison with the FTA-abs test, the sensitivity, specificity and percent agreement of each test were as follows: Architect Syphilis TP, 92.3%, 94.5%, 92.8%; Chorus Syphilis Screen Recombinant, 87.9%, 91.2%, 88.7%; Syphilis Virclia Monotest, 80.5%, 97.8%, 84.9%; Siemens Advia Centaur Syphilis, 87.5%, 89%, 87.9%; Euroimmun Treponema pallidum Screen ELISA, 87.5%, 85.7%, 87.1%; Vircell Syphilis ELISA IgG + IgM, 73.2%, 62.6%, 70.5%; TPHA, 89%, 63.7%, 82.6%; SD Bioline Syphilis, 58.1%, 94.5%, 67.2%; RPR test, 57.7%, 57.1%, 57.6%. CONCLUSION: The results of the present study show that Treponema pallidum specific immunoassays with a performance similar or better than TPHA test generally performed well with the confirmatory FTA-abs test and may be an alternative for screening total antibodies in syphilis infection.

Analysis of rabies diagnosis in dogs and cats in the state of São Paulo, Brazil

The genetic lineage of rabies virus (RABV) associated with dogs has not been found in the state of São Paulo since 1998, and all cases of rabies in domestic animals reported since then have involved the RABV lineage that circulates in bats. As there has been a change in the rabies transmission cycle in cats and dogs, we decided to analyze the tests used to diagnose rabies in these animals in the 15-year period from 2002 to 2016 in the state of São Paulo. During this period, 85,508 central nervous system (CNS) samples from dogs and cats were submitted to the Rabies Diagnosis Section at the Pasteur Institute of São Paulo for testing. All of the samples were tested by the fluorescent antibody test (FAT) and at least one of the following three tests: mouse inoculation test (MIT), rabies tissue culture infection test (RTCIT) and reverse transcription polymerase chain reaction (RT-PCR). Of all the samples tested, twenty were positive in at least one of these assays. Four other positive samples were identified at other institutions in the state of São Paulo. Of the twenty samples that tested positive at the Pasteur Institute of São Paulo, nine were tested by FAT, and the results were subsequently confirmed by other techniques; five gave inconclusive results, and therefore, other techniques had to be used as soon as possible in case the samples were positive; and six were negative by FAT and positive by one or more of the following tests:...

Seroprevalence of maternal HIV, hepatitis B, and syphilis in a major maternity hospital in North Kordofan, Sudan.

Routine infectious diseases screening of Sudanese pregnant women has been patchy due to scarcity of healthcare resources and social stigma. We sought to determine the seroprevalence of HIV, hepatitis B, and syphilis among pregnant women attending antenatal care (ANC) at El Obeid Maternity Hospital in western Sudan. We also explored the association between these infections and a set of socio-demographic and maternal variables. Unlinked anonymous testing for HIV-1/2 antibodies, hepatitis B surface antigen, and Treponema pallidum antibodies was performed on residual blood samples collected during routine ANC (August 2016-March 2017). Seroprevalence of HIV was 1.13% (5/444; 95% CI 0.37-2.61%), hepatitis B 2.93% (13/444; 95% CI 1.57-4.95%), and syphilis 7.43% (33/444; 95% CI 5.17-10.28%). On bivariate analysis, there were no statistically significant associations between hepatitis B, syphilis, or a composite outcome including any of the three infections and age, stage of pregnancy, gravidity, parity, previous mode of delivery, history of blood transfusion, or husband polygamy. Urgent action is needed to scale up routine maternal screening for HIV, hepatitis B, and syphilis on an opt-out basis. Further research into the socio-demographic and behavioural determinants of these infections as well as their clinical outcomes is needed.

Prognostic Factors in Syphilitic Uveitis.

PURPOSE: To identify predictors of treatment success in syphilitic uveitis (SU). DESIGN: Retrospective multicentric analysis of patients treated for SU. PARTICIPANTS: A total of 95 eyes (66 patients, mean [standard deviation] aged 49 [12.5] years, 31 [47%] of whom were human immunodeficiency virus [HIV]+) were analyzed. METHODS: Activity of SU was assessed at 1 week and 1 month after treatment onset, and at last follow-up. Improvement was defined by a ≥2-step decrease of both anterior chamber and vitreous haze inflammation levels, and by the size reduction in chorioretinal lesions. MAIN OUTCOME MEASURES: Recovery was defined as the resolution of inflammation in all anatomic structures at 1 month. RESULTS: Panuveitis and posterior uveitis were the most frequent findings. Inflammatory parameters were higher in HIV+ patients. Recovery was reported in 65% and 85% of eyes at 1 month and at last follow-up, respectively. In multivariate analysis, after adjusting for initial best-corrected visual acuity and the antimicrobial treatment regimen, clinical improvement at 1 week (corrected risk ratios [cRR], 3.5 [2.3-3.8]; P = 0.001) was predictive of recovery at 1 month, whereas the use of periocular dexamethasone injections (cRR, 0.05 [0.02-0.6]; P = 0.01) and methylprednisolone pulses negatively affected the outcomes of eyes. CONCLUSIONS: Early improvement is the strongest predictor of ophthalmological recovery in SU.

Serologic Response to Treatment in Human Immunodeficiency Virus-Negative Syphilis Patients Using Automated Serological Tests: Proposals for New Guidelines

BACKGROUND: Automated analyzer-based nontreponemal serological tests for syphilis (STS) have been used for several decades. OBJECTIVE: In this study, we evaluated serological responses to treatment and proposed clinical guidelines for automated STS. METHODS: This retrospective cohort study analyzed human immunodeficiency virus-negative syphilis patients who were diagnosed with automated rapid plasma reagin (auto RPR) tests as a nontreponemal STS, and who also received the fluorescent treponemal antibody-absorption test as a confirmatory test. The ratio of auto RPR values after treatment against those at baseline was defined as the auto RPR ratio for the analysis of the serological response to treatment. The cutoff value for reliable seroreversion prediction was assessed with receiver-operating-characteristic curves. RESULTS: Overall, 89.7% of participants (78/87) seroreverted and 10.3% of participants (9/87) remained serofast during the two-year follow-up period. We were unable to describe trends in the changes among auto RPR values within six months after treatment because of high variation. All of the patients who had an auto RPR ratio ≥1.0 after six months continuously had positive serologic results during their 24-month follow-up and were classified as a serofast group. The receiver-operating-characteristic curves revealed a 25% reduction in auto RPR values nine months after treatment and predicted seroreversion with a sensitivity of 96.2% and a specificity of 100%. CONCLUSION: The most important primary checkpoint for syphilis treatment response is an increase in automated nontreponemal STS six months after treatment. Thus, we recommend monitoring the treatment response with an auto RPR.

A Case of Acute Interstitial Keratitis in a Patient with Acquired Syphilis

PURPOSE: To report a case of acute interstitial keratitis as the first clinical sign in a patient with latent syphilis. CASE SUMMARY: A 23-year-old female presented with visual impairment and discomfort in her right eye that developed 3 days earlier. The visual acuity in the right eye was 20/200 and corrected to 20/100, and slit lamp examination showed round sub-epithelial opacification in the central cornea with stromal edema and neovascularization on the cornea of the right eye. Whole body tests including serological tests were performed. Under the suspicion of acute interstitial keratitis, topical antibiotics and steroids were applied 4 times a day initially. Serological tests were reactive for venereal disease research laboratory test (VDRL). Under the suspicion of acute interstitial keratitis due to syphilis, fluorescent treponemal antibody absorption test IgM/IgG (FTA-ABS IgM/IgG) was performed; a positive result for FTA-ABS IgG led to diagnosis of acute interstitial keratitis with latent syphilis. During treatment, systemic doxycycline 200 mg for 4 weeks with topical antibiotics and steroids were administered, the opacity and edema of the cornea regressed after 2 weeks of treatment, and visual acuity in the patient's right eye improved to 20/20. CONCLUSIONS: We report an unusual case of acute interstitial keratitis as the first clinical manifestation of latent syphilis in an immunocompetent patient.

[Clinical features of neurosyphilis with optic neuritis as an initial finding].

Objective: To study the characteristics of neurosyphilis with optic neuritis as an initial finding. Methods: Retrospective analysis of clinical data and laboratory testing results of 16 cases (27 eyes) with optic neuritis as an initial finding of neurosyphilis from October 2010 to March 2015 in General Hospital of People's Liberation Army was made. Results: Six-teen patients (12 males, 4 females) were collected, the median age of patients was 47 (range 33 to 65) years ,the mean age was (49.63±9.05) years. Treponema pallidum particle agglutination assay (TPPA) analysis was positive in all of the patients and rapid plasma reagin (RPR) test was positive in 14 patients (2 patients did not test). Lumbar puncture was requested and performed for all patients. Cerebrospinal fluid (CSF) TPPA analysis was positive in 16 patients and RPR test was positive in 12 patients. The CSF white blood cell counting increased in 9 (56.3%) patients and 10(62.5%)patients presented with increased CSF protein level. Both eyes were involved in 11 patients (68.8%). Relative afferent papillary defect was positive in 11 patients. Twenty-seven eyes were affected in 16 patients, and among them 7 eyes' pupil diameter were 2.5 mm or less. Incipient visual acuity was less than 0.1 in 22 eyes. The slit lamp examination showed vitreous opacity in 12 eyes and visible cells in 6 eyes among 27 eyes. Fundus examination found that 6 eyes had papillary edema and 15 eyes had pallordisc among 27eyes. Electro-retinogram (ERG) was tested in 24 eyes, and 18 eyes were abnormal. Visual evoked potential (VEP) were performed in 26 eyes (flash VEP in 22 eyes, pattern VEP in 4 eyes), and all were abnormal. Fourteen eyes were tested by 30-2 perimetry, and 6 eyes had diffuse visual field defect, 2 eyes had peripheral visual field defect, 4 eyes had quadrant defect and 2 eyes had center scotoma. Fundus fluorescence angiography was done in 16 eyes and choroidal hyper-fluorescent dots were found in posterior pole in 4 eyes. All patients were treated with antibiotic medicines, among them 10 cases in the General Hospital, and 6 cases in the other hospitals. During 15 months follow-up after discharge, visual acuity of 17 eyes recovered to 0.5 and above. Conclusion: Syphilitic optic neuritis is a condition that manifests with severe visual loss and tends to involve both eyes, Some patients have a smaller pupil diameter. Due to the particular infective routes of the disease, patients often conceal their sexual history. The manifestations of ocular syphilis are complicated and easy to misdiagnose or undiagnose. Clinical manifestations combining with the detailed history taking, serum and cerebrospinal fluid examination can guide to an accurate diagnosis and prevent from permanent vision loss. (Chin J Ophthalmol, 2016, 52: 898-904).

Visual loss resulting from immunosuppressive therapy in patients with syphilitic uveitis.

Permanent visual loss can be caused by improper use of immunosuppressive therapy in cases of uveitis without differential diagnosis of syphilitic uveitis. We present four cases of syphilitic uveitis that were incorrectly diagnosed as being secondary to rheumatic diseases and were subsequently treated with immunosuppressive therapy, leading to permanent visual loss. These cases highlight the importance of ruling out syphilis in the differential diagnosis of inflammatory ocular diseases before starting use of immunosuppressive therapy.