Quality of Life (QoL) in Non-Acute Vogt-Koyanagi-Harada Disease (VKHD) at Two Time Points 24 Months Apart.

AIMS: To investigate the changes in quality-of-life (QoL) metrics at a 24-month interval in non-acute VKHD patients and their association with inflammation, treatment, and visual function. METHODS: SF-36 and VFQ-25 questionnaires were administered at two 24-month-apart moments to 22 non-acute VKHD patients followed for ≥12 months since acute disease onset. "Improvement," "unchanged," or "worsening" in questionnaires scores (difference >5-point) between M1 and M2 and their associations were sought. RESULTS: Absence of systemic treatment or optic disc hyperfluorescence was associated with improved general health (SF-36). Improvement in binocular contrast sensitivity resulted in better ocular pain score; absence of anterior uveitis relapse, stable fundus findings, no use of cyclosporine or no intravitreal injections resulted in unchanged/better dependency score; no intravitreal injections resulted in unchanged/better mental health score (VFQ-25). CONCLUSION: Stability/improvement in QoL scores was associated with controlled inflammation, better visual function, and no need for treatment. Subclinical inflammatory signs did not impact QoL scores.

Fingerprint sign in Vogt-Koyanagi-Harada disease: a case series.

BACKGROUND: The tomographic finding, which has been called the "fingerprint sign" in en face reconstructions, seems to be the result of a variety of processes that cause distension of the outer plexiform layer (OPL) and the Henle fiber layer (HFL). The aim of this paper is to describe the appearance of concentric rings at the OPL/HFL interface visualized using en face reconstructions of cross-sectional optical coherence tomography images of patients with Vogt-Koyanagi-Harada disease. METHODS: Retrospective analysis of images of six eyes of three patients obtained by cross-sectional OCT imaging and en face reconstruction at the level of the OPL/HFL interface. RESULTS: All eyes presented with a dentate or saw-tooth pattern of the OPL/HFL interface on cross-sectional OCT with corresponding concentric rings on en face OCT reconstruction, consistent with the recently published "fingerprint sign". Initial OPL/HFL interface changes were observed between the first and fourth months after treatment and resolution of VKHD associated serous retinal detachments. These OPL/HFL interface changes have persisted for many years following the resolution of the active inflammation. CONCLUSIONS: Changes in the OPL/HFL interface can be identified following successful treatment of VKHD. These included both a dentate or saw-tooth pattern on cross-sectional imaging and concentric rings or the "fingerprint sign" on en face reconstructions. These changes persisted for many years despite disease quiescence.

Ocular Adverse Events following Yellow Fever Vaccination: A Case Series.

PURPOSE: To describe four cases of ocular adverse events resembling intraocular inflammatory and non-inflammatory conditions following yellow fever vaccination (YFV) during a recent yellow fever (YF) outbreak in Brazil. METHODS: Charts of patients diagnosed with ocular adverse events after YFV between January 2017 and January 2019 at two tertiary referral centers in Brazil. RESULTS: Four patients (two adults and two children) are reported. Case 1 presented with typical findings of central serous chorioretinopathy which resolved spontaneously; case 2 was diagnosed with acute Vogt-Koyanagi-Harada disease; cases 3 and 4 had bilateral diffuse retinal vasculitis. In the absence of infectious and noninfectious disorders, the temporal association between stand-alone YFV and onset of ocular symptoms within 15 days was interpreted as evidence of causation. CONCLUSIONS: Clinicians should be aware of the wide spectrum of possible ocular adverse reactions to stand-alone YFV.

Detection of coronavirus-2 by real-time reverse transcription polymerase chain reaction in conjunctival swabs from patients with severe form of Coronavirus disease 2019 in São Paulo, Brazil.

OBJECTIVES: To test conjunctival swabs from patients with laboratory-confirmed severe forms of coronavirus disease 2019 (COVID-19) for the presence of SARS-CoV-2 on real-time reverse-transcription polymerase chain reaction (rRT-PCR). METHODS: Fifty conjunctival swabs were collected from 50 in-patients with laboratory-confirmed severe forms of COVID-19 at the largest teaching hospital and referral center in Brazil (HCFMUSP, São Paulo, SP). The samples were tested for SARS-CoV-2 on rRT-PCR with the primers and probes described in the CDC protocol which amplify the region of the nucleocapsid N gene (2019_nCoV_N1 and 2019_nCoV_N2) of SARS-CoV-2 RNA and compared with naso/oropharyngeal swabs collected within 24 hours of the conjunctival swabs. RESULTS: Five conjunctival samples (10%) tested positive (amplification of the N1 and N2 primer/probe sets) while two conjunctival samples (4%) yielded inconclusive results (amplification of the N1 primer/probe set only). The naso/oropharyngeal swabs were positive for SARS-CoV-2 on rRT-PCR in 34 patients (68%), negative in 14 (28%) and inconclusive in 2 (4%). The 5 patients with positive conjunctival swabs had positive (n=2), negative (n=2) or inconclusive (n=1) naso/oropharyngeal swabs on rRT-PCR. Patients with negative or inconclusive naso/oropharyngeal swabs had the diagnosis of COVID-19 confirmed by previous positive rRT-PCR results or by serology. CONCLUSION: This is the first study to present conjunctival swab rRT-PCR results for SARS-CoV-2 in a Brazilian population. In our sample of 50 patients with severe forms of COVID-19, 10% had positive conjunctival swabs, most of which were correlated with positive naso/oropharyngeal rRT-PCR results.

Surveillance of post-cataract endophthalmitis at a tertiary referral center: a 10-year critical evaluation.

BACKGROUND: Acute post-cataract endophthalmitis (APE) is a rare complication potentially causing irreversible visual loss. A 10-year study of APE was conducted to determine its incidence, microbiological spectra and antibiotic resistance profile of APE-related pathogens at a major tertiary referral center in Brazil. METHODS: APE cases reported between January 2010 and December 2019 were included. Phacoemulsification and extracapsular cataract techniques were eligible; combined procedures, traumatic and congenital cataract were excluded. Vitreous samples were cultured and antimicrobial resistance was compared for the periods of 2010-2014 and 2015-2019. The results were analyzed with Fisher's exact test. RESULTS: Our sample consisted of 40,491 cataract surgeries and 51 (0.126%) APE cases. Culture was positive in 35 cases (71.4%), of which 31 (88.6%) Gram-positive, 3 (8.6%) Gram-negative, and 1 (2.9%) fungal. The most frequently isolated organism was Staphylococcus epidermidis (n = 17/35, 48.6%), followed by Staphylococcus aureus (n = 4/35, 11.4%). From 2010-2014 to 2015-2019, antimicrobial resistance increased against moxifloxacin (11.1-54.5%, p = 0.07), ciprofloxacin (54.5-72.7%, p = 0.659) and oxacillin (66.7-93.3%, p = 0.13). CONCLUSIONS: The observed incidence and microbial spectra were compatible with previous studies. A trend towards growing moxifloxacin and ciprofloxacin resistance was observed. Surveillance remains crucial to prevent treatment failure from antimicrobial resistance.

Impact of Inflammation and Treatment on Self-reported Quality of Life in Patients with Non-acute Vogt-Koyanagi-Harada Disease (VKHD).

Aims: To evaluate associations between vision-related (VR-) and health-related (HR-) QoL metrics and inflammation and treatment in non-acute VKHD patients.Methods: Cross-sectional study in a tertiary center in Sao Paulo, Brazil with 22 patients with non-acute VKHD followed prospectively for ≥12 months since acute disease onset, with systematic evaluation and predefined treatment protocols. VR- and HR-QoL aspects were assessed by VFQ-25 and SF-36 questionnaires, respectively. Associations between the questionnaire's subscale item scores with inflammation and systemic medical therapies were assessed.Results: After generalized linear model analysis, worse VA, severe fundus changes, fluctuation of VA and fluctuation of anterior chamber cells impacted negatively on VR-QoL items. Higher cumulative total dose of corticosteroids and use of immunosuppressive therapy impacted negatively on both questionnaires.Conclusion: Worse VA, clinical inflammation and systemic treatment have a significant impact on VR- and HR-QoL questionnaires. Subclinical choroidal inflammation did not seem to impact QoL.

Associations between functional and structural measurements in non-acute Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate associations between functional and structural measurements in patients with non-acute VKHD. METHODS: In this cross-sectional study, 16 non-acute VKHD patients (32 eyes; 14 female) were evaluated with multifocal electroretinogram (mfERG), standardized automated perimetry (SAP) and optical coherence tomography (OCT)examinations. All included patients had a minimum 12 months of follow-up from acute onset and were participants of an ongoing prospective study since acute phase with systematic clinical imaging evaluations and electroretinogram examinations within a predefined treatment. Age- and gender-matched controls were included. Main outcomes were functional and structural abnormalities and their correlation; secondary outcome was correlation of these findings with clinical characteristics, including fundus abnormalities. RESULTS: SAP and mfERG parameters were significantly worse in patients than in controls. Fourteen eyes (43.7%) had disrupted ellipsoid zone (EZ); visual acuity (VA) was similar between eyes with intact or disrupted EZ. Eyes with intact and disrupted EZ differed significantly concerning N1 and P1 amplitudes and N1 peak time values on mfERG and mean sensitivity (MS), central sensitivity (CS), foveal threshold, visual field index, mean deviation (MD) and pattern standard deviation values on SAP. The area under the curve on receiver operating curves for P1 amplitude was 0.81 (cut-off value = 34.7 nV/deg2 ) and for MD value was 0.84 (cut-off value = -5.2 dB). Central retinal thickness (CRT) significantly correlated with N1 and P1 amplitudes and P1 peak time values on mfERG (r = 0.354, r = 0.442 and r = -0.405, respectively) and MD, MS, CS and fovea threshold (log values) on SAP (r = 0.372, r = 0.406, r = 0.431 and r = 0.414, respectively). Statistically significant associations were found with the presence of peripapillary atrophy and recurrent anterior uveitis with a worse MD value (p = 0.004 and p < 0.001, respectively). CONCLUSION: In non-acute VKHD, disrupted EZ and reduced CRT were correlated with impaired mfERG and SAP parameters, even in patients with good VA.

Detection of coronavirus-2 by real-time reverse transcription polymerase chain reaction in conjunctival swabs from patients with severe form of Coronavirus disease 2019 in São Paulo, Brazil

OBJECTIVES: To test conjunctival swabs from patients with laboratory-confirmed severe forms of coronavirus disease 2019 (COVID-19) for the presence of SARS-CoV-2 on real-time reverse-transcription polymerase chain reaction (rRT-PCR). METHODS: Fifty conjunctival swabs were collected from 50 in-patients with laboratory-confirmed severe forms of COVID-19 at the largest teaching hospital and referral center in Brazil (HCFMUSP, São Paulo, SP). The samples were tested for SARS-CoV-2 on rRT-PCR with the primers and probes described in the CDC protocol which amplify the region of the nucleocapsid N gene (2019_nCoV_N1 and 2019_nCoV_N2) of SARS-CoV-2 RNA and compared with naso/oropharyngeal swabs collected within 24 hours of the conjunctival swabs. RESULTS: Five conjunctival samples (10%) tested positive (amplification of the N1 and N2 primer/probe sets) while two conjunctival samples (4%) yielded inconclusive results (amplification of the N1 primer/probe set only). The naso/oropharyngeal swabs were positive for SARS-CoV-2 on rRT-PCR in 34 patients (68%), negative in 14 (28%) and inconclusive in 2 (4%). The 5 patients with positive conjunctival swabs had positive (n=2), negative (n=2) or inconclusive (n=1) naso/oropharyngeal swabs on rRT-PCR. Patients with negative or inconclusive naso/oropharyngeal swabs had the diagnosis of COVID-19 confirmed by previous positive rRT-PCR results or by serology. CONCLUSION: This is the first study to present conjunctival swab rRT-PCR results for SARS-CoV-2 in a Brazilian population. In our sample of 50 patients with severe forms of COVID-19, 10% had positive conjunctival swabs, most of which were correlated with positive naso/oropharyngeal rRT-PCR results.

Usefulness of aqueous and vitreous humor analysis in infectious uveitis.

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Self-Reported Quality of Life in Patients with Long-Standing Vogt-Koyanagi-Harada Disease.

Purpose: To assess health-related (HR-) and vision-related (VR-) quality of life (QoL) in patients with long-standing Vogt-Koyanagi-Harada disease (VKHD).Methods: Cross-sectional study of 49 patients with disease duration ≥12 months followed at Uveitis Service, Universidade de São Paulo, BR, for at least 12 months. HR- and VR-QoL were evaluated using SF-36 and NEI VFQ-25 questionnaires, respectively. Demographic, clinical and visual function data were compared with questionnaire scores.Results: After generalized linear models, lower mensal household income was associated with lower scores in both questionnaires while unemployment was associated with SF-36 questionnaire only. Treatment with peri-/intraocular medications and ocular surgery were associated with higher scores on SF-36 questionnaire. Worse visual acuity (VA), ocular complications and no ocular surgery were related to lower scores on NEI VFQ-25 questionnaire.Conclusions: On HR- and VR-QoL questionnaires difficulties perceived by patients with long-standing VKHD were mainly associated with socio-economic aspects, VA, local treatment and ocular complications.

Usefulness of aqueous and vitreous humor analysis in infectious uveitis

OBJECTIVE: To evaluate the role of intraocular fluid analysis as a diagnostic aid for uveitis. METHODS: Twenty-eight samples (27 patients including 3 HIV-infected patients) with active (n=24) or non-active (n=4) uveitis were submitted to aqueous (AH; n=12) or vitreous humor (VH) analysis (n=16). All samples were analyzed by quantitative PCR for herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Toxoplasma gondii. RESULTS: The positivity of the PCR in AH was 41.7% (5/12), with 50% (2/4) in immunocompetent and 67% (2/3) in HIV+ patients. The positivity of the PCR in VH was 31.2% (5/16), with 13% (1/8) in immunocompetent and 50% (4/8) in immunosuppressed HIV negative patients. The analysis was a determinant in the diagnostic definition in 58% of HA and 50% of VH. CONCLUSION: Even in posterior uveitis, initial AH analysis may be helpful. A careful formulation of possible clinical diagnosis seems to increase the chance of intraocular sample analysis being meaningful.

Full-field electroretinogram behavior in Vogt-Koyanagi-Harada disease: a 24-month longitudinal study in patients from acute onset evaluated with multimodal analysis.

PURPOSE: To prospectively evaluate the dynamic changes of the full-field electroretinogram (ff-ERG) and its association with inflammatory signs in patients with Vogt-Koyanagi-Harada disease (VKHD) followed up after acute onset. METHODS: Twelve acute VKHD patients, who were followed up for at least 24 months, were enrolled at a tertiary center from June 2011 to January 2017. Treatment consisted of intravenous methylprednisolone followed by 1 mg/kg/day of oral prednisone with a slow tapering associated with late non-steroidal immunosuppressive therapy in previously defined cases. Inflammation was systematically evaluated with clinical and posterior segment imaging (PSI) exams (fluorescein angiography, FA, indocyanine green angiography, ICGA, enhanced depth imaging optical coherence tomography, EDI-OCT). A ff-ERG was performed upon enrollment as well as at predefined intervals. Scotopic ff-ERG parameters changes between the 12th and 24th months defined the ERG-stable or ERG-worsening groups. "Flare" was defined as an appearance or worsening of inflammatory signs (after the initial 6 months following disease onset) under the predefined treatment protocol. RESULTS: ff-ERG parameters initially improved in all eyes; in the evaluation between the 12th and 24th months, ff-ERG results were stable in 17 eyes (71 %) and worsened in 7 eyes (29 %). Subnormal ff-ERG results were observed in 15 eyes (62 %) at the 24th month. On the other hand, the flare was observed in 8 eyes (33 %) as cells in the anterior chamber and in 24 eyes (100 %) as any PSI inflammatory sign. The ERG-worsening group presented thicker subfoveal choroid at the first month (p = 0.001) and fluctuations in choroidal thickness more often during follow-up when compared to the ERG-stable group (p = 0.02). CONCLUSIONS: Scotopic ff-ERG parameters worsened between the 12th and 24th months in a quarter of the patients. Subclinical inflammation detected as an increase in CT seems to be related to worsening in visual function measured with ffERG.

Diagnostic value of pediatric blood culture bottles for acute postoperative endophthalmitis.

OBJECTIVE: To report our experience using conventional culture methods (CM) and pediatric blood culture bottles (PBCBs) for vitreous sample culture of acute postoperative endophthalmitis. METHODS: A retrospective study was conducted at the Department of Ophthalmology, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, BR, from January 2010 to December 2015, and it included 54 patients with clinically suspected acute postoperative endophthalmitis. Vitreous samples were obtained by vitreous tap or vitrectomy. Samples from January 2010 to December 2011 were cultivated in CM, whereas samples from January 2012 to December 2015 were inoculated in PBCBs. The measured outcome was the yield of positive cultures. RESULTS: Twenty cases were included in the CM group, and 34 cases were included in the PBCB group. The yield of positive cultures in PBCBs (64.7%) was significantly higher than that in conventional CM (35%, p=0.034). Staphylococcus epidermidis and Streptococcus viridans were the two most commonly found agents. CONCLUSION: PBCBs can be used successfully in clinically suspected endophthalmitis. The method showed a higher yield of positive cultures than the conventional method. This technique appears to have several advantages over the traditional method: it saves time, as only one medium needs to be inoculated; transportation to a laboratory is easier than in the traditional method, and there is no need to maintain a supply of fresh agar media. The use of PBCBs may be recommended as the primary method for microbiological diagnosis and is especially suitable for office settings and remote clinics.

Diagnostic value of pediatric blood culture bottles for acute postoperative endophthalmitis

OBJECTIVE: To report our experience using conventional culture methods (CM) and pediatric blood culture bottles (PBCBs) for vitreous sample culture of acute postoperative endophthalmitis. METHODS: A retrospective study was conducted at the Department of Ophthalmology, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, BR, from January 2010 to December 2015, and it included 54 patients with clinically suspected acute postoperative endophthalmitis. Vitreous samples were obtained by vitreous tap or vitrectomy. Samples from January 2010 to December 2011 were cultivated in CM, whereas samples from January 2012 to December 2015 were inoculated in PBCBs. The measured outcome was the yield of positive cultures. RESULTS: Twenty cases were included in the CM group, and 34 cases were included in the PBCB group. The yield of positive cultures in PBCBs (64.7%) was significantly higher than that in conventional CM (35%, p=0.034). Staphylococcus epidermidis and Streptococcus viridans were the two most commonly found agents. CONCLUSION: PBCBs can be used successfully in clinically suspected endophthalmitis. The method showed a higher yield of positive cultures than the conventional method. This technique appears to have several advantages over the traditional method: it saves time, as only one medium needs to be inoculated; transportation to a laboratory is easier than in the traditional method, and there is no need to maintain a supply of fresh agar media. The use of PBCBs may be recommended as the primary method for microbiological diagnosis and is especially suitable for office settings and remote clinics.

Clinical features of paediatric uveitis at a tertiary referral centre in São Paulo, SP, Brazil.

AIMS: To analyse the clinical features, systemic associations, treatment and visual outcomes of uveitis in children from a referral centre in São Paulo, Brazil. METHODS: Clinical records of patients under 16 years old who attended the Uveitis Service, Hospital das Clinicas, Faculdadede Medicina, Universidade de São PauloFMUSP, between April and September 2017, were reviewed retrospectively. Patients with incomplete medical records, previous ocular trauma, or less than six6 months of follow-up were excluded. RESULTS: Thirty-nine children (25 female/14 male) were included. There was predominance of bilateral (89.7%), asymptomatic (56.4%) and recurrent/chronic cases (84.6%). The mean age at study inclusion was 10.7±3.4 years (range 3-16 years). Improvement or preservation of visual acuity (VA) was observed in 27 patients (84%); VA was not informed in 8 patients. Patients were referred early to tertiary centre (55% within 6 months of uveitis diagnosis). Anterior uveitis was the most common involvement (46%), followed by intermediate uveitis (26%). Juvenile idiopathic arthritis (JIA)-associated uveitis (41%) and immune-mediated intermediate uveitis (25.6%) were the principal non-infectious conditions; ocular toxoplasmosis (7.7%) and toxocariasis (5.1%) were the most common infectious conditions. Ocular complications were observed at first visit in 46% of patients and in 90% during final evaluation. Oral prednisone, immunosuppressive therapy (IMT) and/or biologic agents were used in all non-infectious conditions (32 children, 82%); IMT and/or biologic agents were used in all patients with JIA-associated uveitis and in 50% of patients with immune-mediated intermediate uveitis. CONCLUSION: Paediatric patients with uveitis are referred early to this centre and, although severe, adequate management with systemic IMT may preserve VA.

Outcomes of phacoemulsification in patients with uveitis at a tertiary center in São Paulo, Brazil: a review of cases from 2007 to 2012.

PURPOSE:: To evaluate the outcomes of phacoemulsification with intraocular lens (IOL) implantation in eyes with uveitis. METHODS:: Consecutive patients with uveitis and cataracts who had phacoemulsification and acrylic IOL implantation during 2007-2012 were evaluated for visual outcomes, etiology, and complications. Inflammation was controlled for at least 3 months before surgery, and oral prednisone (0.5 mg/kg/day) was administered to patients with non-infectious uveitis. RESULTS:: This study investigated 45 eyes in 38 patients with a mean age of 52 ± 12.5 years. The most common etiologies among non-infectious causes (n=32; 73.3%) were Vogt-Koyanagi-Harada disease (n=9), Fuchs heterochromic iridocyclitis (n=4), and sympathetic ophthalmia (n=3). Four cases were idiopathic. Among infectious cases (n=13; 28.9%), the most common causes were toxoplasmosis (n=6) and presumed ocular tuberculosis (n=4). An acrylic IOL was implanted in-the-bag in all cases. After 1-year follow-up, an improvement in visual acuity of two or more lines was observed in 38 eyes (84.4%), and 28 eyes (62.2%) achieved a postoperative visual acuity of ≥0.5. Posterior capsule opacification was observed in 10 eyes (22.2%). Persistent postoperative inflammation (of >6 months) was observed in seven eyes (15.5%) and recurrence occurred in four eyes (8.8%). IOL was explanted in one eye. Intraocular hypertension was observed in six eyes (13.3%). CONCLUSIONS:: Phacoemulsification with IOL implantation improved vision in most patients with coexisting cataracts and uveitis. Good preoperative and postoperative control of inflammation plays an important role in achieving favorable visual outcomes. Furthermore, the final visual outcome depends on the posterior segment status.

Bactec™ blood culture bottles allied to MALDI-TOF mass spectrometry: rapid etiologic diagnosis of bacterial endophthalmitis.

Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has been used for direct identification of pathogens from blood-inoculated blood culture bottles (BCBs). We showed that MALDI-TOF MS is an useful technique for rapid identification of the causative agents of endophthalmitis from vitreous humor-inoculated BCBs with a simple protocol.