OUTCOMES OF INFECTIOUS PANUVEITIS ASSOCIATED WITH SIMULTANEOUS MULTI-POSITIVE OCULAR FLUID POLYMERASE CHAIN REACTION.

PURPOSE: To evaluate features of infectious panuveitis associated with multiple pathogens detected by ocular fluid sampling. METHODS: Single-center, retrospective, consecutive case series of patients with aqueous/vitreous polymerase chain reaction testing with >1 positive result in a single sample from 2001 to 2021. RESULTS: Of 1,588 polymerase chain reaction samples, 28 (1.76%) were positive for two pathogens. Most common pathogens were cytomegalovirus (n = 16, 57.1%) and Epstein-Barr virus (n = 13, 46.4%), followed by varicella zoster virus (n = 8, 28.6%), Toxoplasma gondii (n = 6, 21.4%), herpes simplex virus 2 (n = 6, 21.4%), herpes simplex virus 1 (n = 6, 21.4%), and Toxocara (n = 1, 3.6%). Mean initial and final visual acuity (logarithm of the minimum angle of resolution) were 1.3 ± 0.9 (Snellen ∼20/400) and 1.3 ± 1.1 (Snellen ∼20/400), respectively. Cytomegalovirus-positive eyes (n = 16, 61.5%) had a mean final visual acuity of 0.94 ± 1.1 (Snellen ∼20/175), whereas cytomegalovirus-negative eyes (n = 10, 38%) had a final visual acuity of 1.82 ± 1.0 (Snellen ∼20/1,320) ( P < 0.05). Main clinical features included intraocular inflammation (100%), retinal whitening (84.6%), immunosuppression (65.4%), retinal hemorrhage (38.5%), and retinal detachment (34.6%). CONCLUSION: Cytomegalovirus or Epstein-Barr virus were common unique pathogens identified in multi-PCR-positive samples. Most patients with co-infection were immunosuppressed with a high rate of retinal detachment and poor final visual acuity. Cytomegalovirus-positive eyes had better visual outcomes compared with cytomegalovirus-negative eyes.

An Unusual Manifestation of Brucella-Associated Uveitis in a Young Male Patient.

This is a unique case of retinoschisis as an ocular manifestation of brucellosis. A 38-year-old male presented with recurrent episodes of bilateral eye redness, predominately in his left eye. His visual acuity was not affected, and he did not report any other symptoms. On slit lamp examination, binocular Koeppe nodules of the iris and cells in the left anterior chamber were observed. Fundoscopy followed by meticulous multimodal imaging confirmed left inferior retinoschisis. The patient was diagnosed with panuveitis, and a series of laboratory examinations revealed positive anti-IgM Brucella antibodies. Ocular brucellosis can cause variable, atypical, and serious presentations, hence, early diagnosis is paramount to avoid complications.

Long-term clinical outcomes of patients with sympathetic ophthalmia.

PURPOSE: To present the long-term clinical outcomes of patients with sympathetic ophthalmia (SO). METHODS: Retrospective review of patients' medical files between 2002 and 2022. RESULTS: Included were seven patients (four males). The mean ± SD age at presentation was 37.9 ± 22.5 years. Four patients had co-morbidities: three had diabetes mellitus type 2 and one had Turner Syndrome. Trauma was the inciting event in six patients and postoperative endophthalmitis in one patient. Decreased visual acuity (VA) was the leading symptom in the sympathizing eye and all of the patients presented with panuveitis. The mean ± SD interval between the triggering incident and the onset of SO in six cases was 4.3 ± 4.2 months. One case presented 30 years following the eye injury. Five patients underwent enucleation/evisceration of the exciting eye. The mean ± SD presenting LogMAR BCVA in the sympathizing eye was 0.57 ± 0.82, and the final LogMAR BCVA was 0.61 ± 0.95. Inflammation was completely controlled in 5 patients at a mean ± SD of 8.55 ± 9.21 months following the institution of immunomodulatory therapy, and it was partially controlled in 2 patients. VA deteriorated in all 3 diabetic patients and improved or remained stable in the 4 young and healthy patients. The mean ± SD follow-up period after achieving drug-free remission was 28 ± 22.8 months. The mean ± SD follow-up time was 6.8 ± 5.6 years. CONCLUSIONS: SO is one of the most sight-threatening conditions, affecting the healthy eye. In this cohort, the favorable visual outcome was especially seen in young and healthy individuals. Visual prognosis is directly related to prompt diagnosis and treatment.

Corticosteroid implants for chronic non-infectious uveitis.

BACKGROUND: Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. OBJECTIVES: To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. Considering improvement in visual acuity, we assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.15 logMAR, 95% CI 0.06 to 0.24; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on improving BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence). Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence). AUTHORS' CONCLUSIONS: Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time. To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.

Corticosteroid implants for chronic non-infectious uveitis.

BACKGROUND: Uveitis is a term used to describe a group of intraocular inflammatory diseases. Uveitis is the fifth most common cause of vision loss in high-income countries, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of treatment for all subtypes of non-infectious uveitis. They can be administered orally, topically with drops, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. OBJECTIVES: To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE Ovid, Embase, PubMed, LILACS, and three trials registries to November 2021.  SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone (DEX) intravitreal implants with standard-of-care therapy or sham procedures, with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages, who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. MAIN RESULTS: We included data from four trials (683 participants, 907 eyes) that compared corticosteroid implants with either sham or standard-of-care therapy. Study characteristics and risk of bias Of the two trials that compared corticosteroid implants with sham procedure, one examined a 0.18 mg FA implant, and the other, a 0.7 mg DEX implant. The other two trials compared a 0.59 mg FA implant with standard-of-care therapy, which included systemic corticosteroids and immunosuppressive medications, if needed. We assessed the four trials to be at either low risk, or with some concerns of risk of bias across all domains. Findings Using sham procedure as control, combined results at the six-month primary time point suggested that corticosteroid implants may decrease the risk of uveitis recurrence by 60% (relative risk [RR] 0.40, 95% confidence interval [CI] 0.30 to 0.54; 2 trials, 282 participants; low-certainty evidence); and lead to a greater improvement in best-corrected visual acuity (BCVA; mean difference [MD] 0.22 logMAR, 95% CI 0.13 to 0.31; 1 trial, 153 participants; low-certainty evidence). Evidence based on a single-study report (146 participants) suggested that steroid implants may have no effects on visual functioning quality of life, measured on the National Eye Institute 25-Item Visual Function Questionnaire (MD 2.85, 95%CI -3.64 to 9.34; 1 trial, 146 participants; moderate-certainty evidence). Using standard-of care therapy as control, combined estimates at the 24-month primary time point suggested that corticosteroid implants were likely to decrease the risk of recurrence of uveitis by 54% (RR 0.46, 95% CI 0.35 to 0.60; 2 trials, 619 eyes). Combined estimates at 24 months also suggested that steroid implants may have little to no effects on BCVA (MD 0.05 logMAR, 95% CI -0.02 to 0.12; 2 trials, 619 eyes; low-certainty evidence). Evidence based on a single-study report (232 participants) suggested that steroid implants may have minimal clinical effects on visual functioning (MD 4.64, 95% CI 0.13 to 9.15; 1 trial, 232 participants; moderate-certainty evidence); physical functioning (SF-36 physical subscale MD 2.95, 95% CI 0.55 to 5.35; 1 trial, 232 participants; moderate-certainty evidence); or mental health (SF-36 mental subscale MD 3.65, 95% CI 0.52 to 6.78; 1 trial, 232 participants; moderate-certainty evidence); but not on EuroQoL (MD 6.17, 95% CI 1.87 to 10.47; 1 trial, 232 participants; moderate-certainty evidence); or EuroQoL-5D scale (MD 0.02, 95% CI -0.04 to 0.08; 1 trial, 232 participants; moderate-certainty evidence). Adverse effects Compared with sham procedures, corticosteroid implants may slightly increase the risk of cataract formation (RR 2.69, 95% CI 1.17 to 6.18; 1 trial, 90 eyes; low-certainty evidence), but not the risk of cataract progression (RR 2.00, 95% CI 0.65 to 6.12; 1 trial, 117 eyes; low-certainty evidence); or the need for surgery (RR 2.98, 95% CI 0.82 to 10.81; 1 trial, 180 eyes; low-certainty evidence), during up to 12 months of follow-up. These implants may increase the risk of elevated intraocular pressure ([IOP] RR 2.81, 95% CI 1.42 to 5.56; 2 trials, 282 participants; moderate-certainty evidence); and the need for IOP-lowering eyedrops (RR 1.85, 95% CI 1.05 to 3.25; 2 trials, 282 participants; moderate-certainty evidence); but not the need for IOP-lowering surgery (RR 0.72, 95% CI 0.13 to 4.17; 2 trials, 282 participants; moderate-certainty evidence).  Evidence comparing the 0.59 mg FA implant with standard-of-care suggested that the implant may increase the risk of cataract progression (RR 2.71, 95% CI 2.06 to 3.56; 2 trials, 210 eyes; low-certainty evidence); and the need for surgery (RR 2.98, 95% CI 2.33 to 3.79; 2 trials, 371 eyes; low-certainty evidence); along with the risk of elevated IOP (RR 3.64, 95% CI 2.71 to 4.87; 2 trials, 605 eyes; moderate-certainty evidence); and the need for medical (RR 3.04, 95% CI 2.36 to 3.91; 2 trials, 544 eyes; moderate-certainty evidence); or surgical interventions (RR 5.43, 95% CI 3.12 to 9.45; 2 trials, 599 eyes; moderate-certainty evidence). In either comparison, these implants did not increase the risk for endophthalmitis, retinal tear, or retinal detachment (moderate-certainty evidence).  AUTHORS' CONCLUSIONS: Our confidence is limited that local corticosteroid implants are superior to sham therapy or standard-of-care therapy in reducing the risk of uveitis recurrence. We demonstrated different effectiveness on BCVA relative to comparators in people with non-infectious uveitis. Nevertheless, the evidence suggests that these implants may increase the risk of cataract progression and IOP elevation, which will require interventions over time.  To better understand the efficacy and safety profiles of corticosteroid implants, we need future trials that examine implants of different doses, used for different durations. The trials should measure core standard outcomes that are universally defined, and measured at comparable follow-up time points.

TACROLIMUS FOR IMMUNOSUPPRESSION IN PATIENTS WITH NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIDES.

PURPOSE: To evaluate the effectiveness of tacrolimus in patients with noninfectious intermediate, posterior, or panuveitis needing a two-immunosuppressive-agent regimen. METHODS: Design: Retrospective cohort study. Setting: Two tertiary-care uveitis practices at academic medical centers. Patient population: Thirty-two patients with noninfectious intermediate, posterior, or panuveitides in whom single-agent immunosuppression was inadequate to effect successful corticosteroid sparing. Intervention: tacrolimus, added as the second immunosuppressive agent. Main outcome measure: successful corticosteroid sparing, defined as inactive uveitis at a dose of prednisone ≤7.5 mg/day. RESULTS: Active uveitis was present in 65.6% of patients at initiation of tacrolimus, and the median time to inactive uveitis was 1.5 months (95% confidence interval 1.2, 4.08). The median time to successful corticosteroid sparing was 3.9 months (95% confidence interval 1.41, 6.67), and by 6 months of follow-up successful corticosteroid sparing was achieved in 75% of patients. Tacrolimus was discontinued for side effects in five patients, three for tremor, and two for hyperglycemia. All side effects were reversible with tacrolimus discontinuation. CONCLUSION: Tacrolimus seems to have efficacy as a second immunosuppressive agent in two-immunosuppressive drug regimens, when a single agent does not permit successful corticosteroid sparing. Side effects were reversible with tacrolimus discontinuation.

A case of APMPPE-like panuveitis presenting with extensive outer retinal layer impairment following COVID-19 vaccination.

BACKGROUND: Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of new onset uveitis after vaccination have been reported. We report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy-like (AMPPE-like) panuveitis after COVID-19 vaccination in which the patient's pathological condition was evaluated using multimodal imaging. CASE PRESENTATION: A 31-year-old woman experienced bilateral hyperemia and blurred vision starting 6 days after her second inoculation of the COVID-19 vaccination. At her first visit, her visual acuity was decreased bilaterally, and severe bilateral anterior chamber inflammation and bilateral scattering of cream-white placoid lesions on the fundus were detected. Optical coherence tomography (OCT) showed serous retinal detachment (SRD) and choroidal thickening in both eyes (OU). Fluorescein angiography (FA) revealed hypofluorescence in the early phase and hyperfluorescence in the late phase corresponding to the placoid legions. Indocyanine green angiography (ICGA) showed sharply marginated hypofluorescent dots of various sizes throughout the mid-venous and late phases OU. The patient was diagnosed with APMPPE and was observed without any medications. Three days later, her SRD disappeared spontaneously. However, her anterior chamber inflammation continued, and oral prednisolone (PSL) was given to her. Seven days after the patient's first visit, the hyperfluorescent lesions on FA and hypofluorescent dots on ICGA partially improved; however, the patient's best corrected visual acuity (BCVA) recovered only to 0.7 OD and 0.6 OS, and the impairment of the outer retinal layer was broadly detected as hyperautofluorescent lesions on fundus autofluorescence (FAF) examination and as irregularity in or disappearance of the ellipsoid and interdigitation zones on OCT, which were quite atypical for the findings of APMPPE. Steroid pulse therapy was performed. Five days later, the hyperfluorescence on FAF had disappeared, and the outer retinal layer improved on OCT. Moreover, the patient's BCVA recovered to 1.0 OU. Twelve months after the end of treatment, the patient did not show any recurrences. CONCLUSIONS: We observed a case of APMPPE-like panuveitis after COVID-19 vaccination featuring some atypical findings for APMPPE. COVID-19 vaccination may induce not only known uveitis but also atypical uveitis, and appropriate treatment is required for each case.

Risk of uveitis in patients with psoriasis in Korea: A nationwide population-based cohort study.

BACKGROUND: Evidence for the association between psoriasis and uveitis according to the severity of psoriasis including psoriatic arthritis (PsA) and type of uveitis is lacking, and there are no data on the frequency or timing of recurrence of uveitis in patients with psoriasis. OBJECTIVES: We aimed to evaluate the risk of first occurrence and recurrence of uveitis in patients with psoriasis in the Korean population. We further evaluated the risk of uveitis according to the severity of psoriasis, comorbidity of PsA and location of uveitis. METHODS: In a nationwide retrospective cohort study, we compared 317,940 adult patients who had psoriasis with 635,880 matched controls. Incidence rates (IRs) and estimated IR ratios of the first occurrence and recurrence of uveitis were calculated using survival analysis and Poisson regression, respectively. RESULTS: The rate of uveitis incidence and uveitis recurrence in patients with psoriasis was 1.18 and 2.31 per 1000 person-years, respectively. Compared to the controls, the IR ratios of development and recurrence of uveitis in patients with psoriasis were 1.14 (95% CI 1.08, 1.2) and 1.16 (95% CI 1.12, 1.21), respectively. The recurrence rate of uveitis was highest within 3 years after the onset of psoriasis. The corresponding IR ratios for uveitis recurrence in patients with mild psoriasis, severe psoriasis and PsA were 1.11 (1.06, 1.16), 1.24 (1.16, 1.33) and 1.49 (1.31, 1.7), respectively. Patients with psoriasis had an increased risk of recurrence of anterior uveitis, and patients with both psoriasis and PsA had an increased risk of recurrence of both anterior-uveitis and panuveitis. CONCLUSIONS: Patients with psoriasis had a higher risk of both development and recurrence of uveitis, especially with severe psoriasis and PsA. The timing of uveitis recurrence was related to the onset of psoriasis, and patients who had psoriasis with PsA had an increased risk of vision-threatening panuveitis.

Protothecosis in four dogs in New Zealand.

CASE HISTORIES: Medical records of four dogs diagnosed with protothecosis in New Zealand were reviewed. The dogs were aged between 4 and 9 years and three of the four dogs were female. Breeds were one Labrador, one Miniature Schnauzer and two crossbreeds. The reasons for initial veterinary evaluation were a cough and opaque appearance of the right eye (Case 1), diarrhoea (Cases 2 and 3), and cutaneous disease (Case 4). CLINICAL FINDINGS: The ocular signs were characterised by panuveitis, retinal detachment and secondary glaucoma. Gastrointestinal signs included chronic haemorrhagic diarrhoea due to colitis. Three cases had disseminated infection and developed both bilateral, blinding, ocular disease and chronic gastrointestinal disease. Cutaneous signs consisted of draining fistulae over the olecranon, multifocal cutaneous nodules, and ulceration and tracts of the foot pads. Disseminated protothecosis was confirmed by histopathology of biopsied ocular tissues in Cases 1 and 2 and by gastrointestinal biopsies in Case 3. Prototheca spp. were also identified in cytological specimens from Cases 1 and 4 and recovered by culture in Cases 2 and 4. Cutaneous protothecosis was diagnosed in Case 4 initially by cytology and histopathology of skin lesions, and Prototheca zopfii was confirmed by PCR of cultured organisms. TREATMENT AND OUTCOME: Prior to diagnosis of protothecosis, a variety of treatments were prescribed to treat the gastrointestinal and ocular signs. After diagnosis, only Cases 2 and 4 received medication aimed at treating the protothecal infection, which was itraconazole in both cases. Following the progression of clinical signs and concerns about quality of life, all four dogs were euthanised. DIAGNOSIS: Disseminated protothecosis in three dogs, cutaneous protothecosis in one dog. CLINICAL RELEVANCE: Canine protothecosis is rarely reported, despite the ubiquity of the causal algae, and the disease usually carries an extremely grave prognosis when infection is generalised. In New Zealand, protothecosis should be considered as a differential diagnosis in dogs with panuveitis, chorioretinitis or retinal detachment, colitis, or nodular, ulcerative or fistulating cutaneous lesions.

Panuveitis of undetermined origin after diagnostic pars plana vitrectomy: clinical characterization and long-term outcome from a tertiary referral center.

PURPOSE: To identify the characteristics and outcome of panuveitis of undetermined origin (PUO) after diagnostic vitrectomy. METHODS: Retrospective analysis of all patients who underwent vitrectomy for diagnostic/therapeutic purposes from 2013 to 2020, whose vitreous biopsies turned out negative and final diagnoses were not clinically supported. RESULTS: Of 122 operated eyes, 36 eyes (29.5%) were defined as PUO (67.8 ± 14.9 years). The presenting clinical picture revealed a predominantly bilateral condition (70% of eyes) with significant posterior segment involvement: 3.1 ± 0.6 vitritis, 61.1% of eyes with retinal vasculitis, 44.4% with macular edema, and 30.6% with exudative retinal detachment. Presenting visual acuity was 1.2 ± 0.7 logMAR, and up to 90% remained stable or improved vision over a ~ 3.5 year observation period. None of the presenting clinical features turned out to be predictive of final visual outcome or survival. CONCLUSIONS: PUO is present in up to 30% of cases after diagnostic/therapeutic vitrectomy. This mainly bilateral condition shows chronic and overall stable long-term outcome, generally with retained steady visual function.

Ocular syphilis on the rise: a 10-year analysis from 2010 to 2020.

PURPOSE: The purpose of the study was to evaluate the incidence of ocular syphilis as well as diagnostic parameters, comorbidities, and visual outcomes over a 10-year time period in West Virginia. METHODS: A retrospective chart review included 25 eyes of 17 patients with ocular syphilis between 2010 and 2020. RESULTS: The incidence of systemic syphilis at a large tertiary referral center has increased from 27 cases in 2010 to 105 cases in 2020. Seventeen patients were identified with ocular syphilis. Bilaterality was present in 47.1% of cases. In this study, 70.6% of patients were male and 29.4% were female. The median age of presentation was 40.2 years (range 21-63). Panuveitis was the most common (60.0%) followed by isolated anterior uveitis (16.0%), chorioretinitis (12.0%), inner retinitis (4.0%), and papillitis (8.0%). Forty percent of patients had visual acuity worse than 20/400 on presentation. Post-treatment visual acuity improved in all patients. Rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TP-PA) tests were positive in 84.6% and 100% of cases, respectively. CSF venereal disease research laboratory (VDRL) was positive in 36.4%, CSF pleocytosis was present in 72.7%, and elevated CSF protein was observed in 81.8%. Human immunodeficiency virus (HIV) co-infection was present in 31.3%. A majority of patients experienced maculopapular rash and/or history of genital chancre. The anatomic classification of presenting uveitis (anterior, intermediate, posterior, and panuveitis) did not correlate with clinical variables including age, gender, HIV status, serologic test, presence of rash, or year of diagnosis (p > 0.05). CONCLUSION: Ocular syphilis is becoming increasingly prevalent and can present with a variety of ocular findings; therefore, it should be considered in the differential diagnosis for patients with ocular inflammation. Visual prognosis is excellent with timely diagnosis and treatment.

Tubulointerstitial nephritis and uveitis syndrome: a systematic review.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001. METHODS: We conducted a systematic review of the literature for cases of TINU syndrome. MEDLINE and Embase databases were screened. Full-length articles or letters reporting cases with both TIN and uveitis were selected. We investigated differences between males and females and paediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease (CKD) development. RESULTS: A total of 233 articles reporting 592 TINU cases were retained for the analysis. The median age of the included subjects was 17 years (interquartile range 13-46) with a female predominance (65%). Uveitis most frequently (52%) followed renal disease and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses, while they were slightly less likely than adults to suffer from acute kidney injury and to develop CKD. Adult age as well as posterior or panuveitis were associated with an increased risk of developing CKD. CONCLUSIONS: TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of CKD.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

BACKGROUND: Non-infectious intermediate, posterior, and panuveitis (NIIPPU) represent a heterogenous collection of autoimmune and inflammatory disorders isolated to or concentrated in the posterior structures of the eye. Because NIIPPU is typically a chronic condition, people with NIIPPU frequently require treatment with steroid-sparing immunosuppressive therapy. Methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus are non-biologic, disease-modifying antirheumatic drugs (DMARDs) which have been used to treat people with NIIPPU. OBJECTIVES: To compare the effectiveness and safety of selected DMARDs (methotrexate, mycophenolate mofetil, tacrolimus, cyclosporine, and azathioprine) in the treatment of NIIPPU in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, the Latin American and Caribbean Health Sciences database, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform, most recently on 16 April 2021. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing selected DMARDs (methotrexate, mycophenolate, tacrolimus, cyclosporine, and azathioprine) with placebo, standard of care (topical steroids, with or without oral steroids), or with each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 11 RCTs with a total of 601 participants in this review. DMARDs versus control Two studies compared an experimental DMARD (cyclosporine A or enteric-coated mycophenolate [EC-MPS]) plus oral steroid with steroid monotherapy. We did not pool these results into a meta-analysis because the dose of cyclosporine used was much higher than that used in current clinical practice. The evidence is very uncertain about whether EC-MPS plus low-dose oral steroid results in a higher proportion of participants achieving control of inflammation over steroid monotherapy (risk ratio [RR] 2.81, 95% confidence interval [CI] 1.10 to 7.17; 1 study, 41 participants; very low-certainty evidence). The change in best-corrected visual acuity (BCVA) was reported separately for right and left eyes. The evidence for improvement (lower logarithm of the minimum angle of resolution (logMAR) indicates better vision) between the groups is very uncertain (mean difference [MD] -0.03 and -0.10, 95% CI -0.96 to 0.90 and -0.27 to 0.07 for right and left, respectively; 1 study, 82 eyes; very low-certainty evidence). No data were available for the following outcomes: proportion of participants achieving a 2-line improvement in visual acuity, with confirmed macular edema, or achieving steroid-sparing control. The evidence for the proportion of participants requiring cessation of medication in the DMARD versus control group is very uncertain (RR 2.61, 95% CI 0.11 to 60.51; 1 study, 41 participants; very low-certainty evidence). Methotrexate versus mycophenolate We were able to combine two studies into a meta-analysis comparing methotrexate versus mycophenolate mofetil. Methotrexate probably results in a slight increase in the proportion of participants achieving control of inflammation, including steroid-sparing control, compared to mycophenolate at six months (RR 1.23, 95% CI 1.01 to 1.50; 2 studies, 261 participants; moderate-certainty evidence). Change in BCVA was reported per eye and the treatments likely result in little to no difference in change in vision (MD 0.01 logMAR higher [worse] for methotrexate versus mycophenolate; 2 studies, 490 eyes; moderate-certainty evidence). No data were available for the proportion of participants achieving a 2-line improvement in visual acuity. The evidence is very uncertain regarding the proportion of participants with confirmed macular edema between methotrexate versus mycophenolate (RR 0.49, 95% CI 0.19 to 1.30; 2 studies, 35 eyes; very low-certainty). Methotrexate versus mycophenolate may result in little to no difference in the proportion of participants requiring cessation of medication (RR 0.99, 95% CI 0.43 to 2.27; 2 studies, 296 participants; low-certainty evidence). Steroids with or without azathioprine versus cyclosporine A Four studies compared steroids with or without azathioprine (oral steroids, intravenous [IV] steroids, or azathioprine) to cyclosporine A. We excluded two studies from the meta-analysis because the participants were treated with 8 mg to 15 mg/kg/day of cyclosporine A, a significantly higher dose than is utilized today because of concerns for nephrotoxicity. The remaining two studies were conducted in all Vogt-Koyanagi-Harada disease (VKH) populations and compared cyclosporine A to azathioprine or IV pulse-dose steroids. The evidence is very uncertain for whether the steroids with or without azathioprine or cyclosporine A influenced the proportion of participants achieving control of inflammation (RR 0.84, 95% CI 0.70 to 1.02; 2 studies, 112 participants; very low-certainty evidence), achieving steroid-sparing control (RR 0.64, 95% CI 0.33 to 1.25; 1 study, 21 participants; very low-certainty evidence), or requiring cessation of medication (RR 0.85, 95% 0.21 to 3.45; 2 studies, 91 participants; very low-certainty evidence). The evidence is uncertain for improvement in BCVA (MD 0.04 logMAR lower [better] with the steroids with or without azathioprine versus cyclosporine A; 2 studies, 91 eyes; very low-certainty evidence). There were no data available (with current cyclosporine A dosing) for the proportion of participants achieving a 2-line improvement in visual acuity or with confirmed macular edema. Studies not included in synthesis We were unable to include three studies in any of the comparisons (in addition to the aforementioned studies excluded based on historic doses of cyclosporine A). One was a dose-response study comparing cyclosporine A to cyclosporine G, a formulation which was never licensed and is not clinically available. We excluded another study from meta-analysis because it compared cyclosporine A and tacrolimus, considered to be of the same class (calcineurin inhibitors). We were unable to combine the third study, which examined tacrolimus monotherapy versus tacrolimus plus oral steroid, with any group. AUTHORS' CONCLUSIONS: There is a paucity of data regarding which DMARD is most effective or safe in NIIPPU. Studies in general were small, heterogenous in terms of their design and outcome measures, and often did not compare different classes of DMARD with each other. Methotrexate is probably slightly more efficacious than mycophenolate in achieving control of inflammation, including steroid-sparing control (moderate-certainty evidence), although there was insufficient evidence to prefer one medication over the other in the VKH subgroup (very low-certainty evidence). Methotrexate may result in little to no difference in safety outcomes compared to mycophenolate.

Clinical features and visual outcomes of ocular sarcoidosis at a tertiary referral center in Tokyo.

BACKGROUND: To analyze clinical features, treatment, complications, and visual outcomes of ocular sarcoidosis at a tertiary center in Tokyo. METHODS: Clinical records of 53 patients with ocular sarcoidosis ("definite" or "presumed") presenting between 2013 and 2018 to the Kyorin Eye Center were retrospectively reviewed. Diagnosis was based on the revised criteria of the International Workshop on Ocular Sarcoidosis. RESULTS: Definite (biopsy-proven) disease was present in 87% of patients and presumed disease in 13%. The mean age at presentation was 58 years (13-81 years) and 68% were women. The mean follow-up was 34 months (6-70 months). Forty-five patients (85%) had panuveitis, and the most common ocular clinical sign suggestive of ocular sarcoidosis was bilaterality (92%). Ocular complications were observed in 93 eyes (85%), most commonly cataract (73%), epiretinal membrane (24%), macular edema (24%) and glaucoma (19%). Thirty-one eyes (30%) underwent cataract surgery and 12 eyes (12%) underwent pars plana vitrectomy. Ten patients (19%) received systemic corticosteroid therapy and 33 eyes (32%) received periocular corticosteroid injections. The best-corrected visual acuity was 1.0 or better in 51% of eyes at presentation, 57% at 6 months, 50% at 12 months, and 58% at 36 months. CONCLUSIONS: The majority of ocular sarcoidosis patients were women, had bilateral disease and panuveitis involvement. Most eyes maintained good visual acuity, although surgical interventions for cataract and epiretinal membrane were common.

OPTICAL COHERENCE TOMOGRAPHY FEATURES IN IDIOPATHIC NONINFECTIOUS INTERMEDIATE, POSTERIOR, OR PANUVEITIS.

PURPOSE: To characterize optical coherence tomography features in patients with idiopathic intermediate, posterior, or panuveitis. METHODS: This is a retrospective case series of all consecutive cases of idiopathic intermediate, posterior, or panuveitis at four tertiary care centres between 2010 and 2021. RESULTS: A total of 94 eyes (55 patients) were followed for an average duration of 29.8 (SD 21) months. The median central macular thickness was 284 µ m at baseline and 267 µ m at last follow-up. At baseline and last follow-up, respectively, 24% and 20% of uveitic eyes had intraretinal fluid, 12% and 1% subretinal fluid, and 43% and 54% epiretinal membrane. In addition, ellipsoid zone abnormalities on en-face were noted in 34% and 19% of cases at baseline and last follow-up, respectively. The baseline median visual acuity was significantly lower among cases with ellipsoid zone en-face slab abnormalities compared with those without (0.2 logarithm of minimum angle of resolution [interquartile range: 0-0.6] vs. 0.1 logarithm of minimum angle of resolution [interquartile range: 0-0.3], P = 0.0051). CONCLUSION: With initiation of treatment, the central macular thickness, intraretinal fluid, subretinal fluid, and ellipsoid zone en-face abnormalities improved over time, whereas the number of cases with epiretinal membrane increased among eyes with idiopathic intermediate, posterior, and panuveitis. Presence of ellipsoid zone en-face abnormalities at presentation may be associated with worse visual acuity.

Reply to: differential diagnosis of pseudohypopyon and discussion of extranodal natural killer/T-cell lymphoma presenting as hypopyon panuveitis.

Extranodal natural killer/T-cell lymphoma rarely presents as intraocular masquerade syndrome. We thank Dr. Evereklioglu for bringing up the importance of a thorough ocular examination, differential diagnosis, and consideration of the characteristics of ocular masquerade syndrome.

Cooperation with rheumatologists on intensive systemic treatment for psoriatic arthritis-related panuveitis with retinal vasculitis: a case report.

BACKGROUND: Patients with psoriatic arthritis (PsA) may develop uveitis, a potentially serious ocular complication. PsA-related uveitis may result in significant morbidity and even vision loss if underdiagnosed or under-treated. We presented a case with long-standing recurrent uveitis and retinal vasculitis successfully managed by fortified systemic immunomodulators for systemic PsA. CASE PRESENTATION: A 47-year-old woman was referred under the impression of acute anterior uveitis in her right eye in recent one month. Ocular examinations showed panuveitis in both eyes with intense vitreous opacity in her right eye. Fundus fluorescence angiography revealed retinal vasculitis in both eyes. Systemic surveys excluded the possibility of infection but showed an elevated inflammation marker. With intensive immunosuppressive treatment, inflammation resolved and the vision improved. CONCLUSION: Our case highlights not only the importance of intensified systemic therapy in treating PsA-related uveitis but the importance of multidisciplinary collaboration. Recurrent uveitis may be an indicator of disease activity prior to other inflammatory markers.

Extranodal natural killer/T-cell lymphoma presenting as hypopyon panuveitis: a case report.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, generally affects the orbit by direct extension. It can even rarely present as severe intraocular inflammation mimicking endophthalmitis. Delayed diagnosis and treatment are frequently reported. CASE PRESENTATION: A 43-year-old woman presented with 2-month blurred vision in her left eye. Ocular examination revealed hypopyon panuveitis. She was initially diagnosed with endogenous endophthalmitis, which proved irresponsive to antimicrobial therapy. High-dose prednisolone was given afterward, but this failed to stop the development and continuous progression of ocular inflammation. The diagnosis of ENKTL was finally confirmed from the pathological findings of oral ulcers and cervical lymph nodes and chemotherapy was prescribed. After the first cycle of chemotherapy, the patient's ocular inflammation subsided. Unfortunately, her left eye became phthisis with progressive visual loss within 9 months following the diagnosis. CONCLUSIONS: The diagnosis of intraocular ENKTL is frequently delayed, which can lead to severe problems for treatment as the disease is aggressive with a poor prognosis. It can be found not only in elderly patients but also in a middle-aged individual. In patients with ocular inflammation, a thorough systemic evaluation and histopathological examination of the associated systemic findings is extremely helpful and may reveal the cause of the ocular inflammation, including revealing possible ENKTL.

An unusual case of eosinophilic uveitis in a cat.

An 8-year-old female spayed domestic short-haired cat was examined for recurrent unilateral anterior uveitis of 5 month's duration. No underlying cause was found on infectious disease screening. The cat also had a 4-year history of allergic or immune-mediated skin disease that was controlled with corticosteroid injections followed by long-term oral cyclosporine therapy. Medical management with frequent topical anti-inflammatory drugs (prednisolone acetate 1% suspension, diclofenac 0.1% solution) controlled the intraocular inflammation; however, the uveitis would relapse when therapy was discontinued. Eventually, secondary glaucoma developed OD and the eye was enucleated. At the time of surgery, a complete blood count showed a mild eosinophilia. Histopathology revealed a marked panuveitis characterized by an abundant accumulation of mixed inflammatory cells, with a predominantly eosinophilic infiltrate in the anterior chamber, iris, ciliary body, and choroid. No etiologic agents were found on serial sections, and there were no cellular criteria for malignancy noted. Nine months after enucleation, the chronic dermatitis appeared to be in remission despite no further medical management. This is the first known report of a primarily eosinophilic uveitis in a cat with chronic allergic skin disease and may be considered an ocular variant of feline eosinophilic granuloma complex.

Describing the Clinical and Laboratory Features and HLA-B Pattern of Adult-Onset Idiopathic Autoimmune Uveitis at a Tertiary Hospital in South India: A Cross-Sectional Study.

INTRODUCTION: There is a scarcity of information available on clinical and laboratory features of adult-onset idiopathic autoimmune uveitis. Therefore, we conducted a single centre descriptive cross-sectional study. Patients and Methods. A chart review of all patients with idiopathic autoimmune uveitis with onset after 18 years of age who were referred to the rheumatology department between January 2017 and December 2018 was performed. Their clinical features, demographic features, and HLA-B genotypes were documented and described. RESULTS: Out of 210 patients referred to rheumatology, 66 were found to have uveitis, and 16 of these had an adult-onset idiopathic autoimmune uveitis. Apart from a slight female preponderance (62.5%), our patients were characterized by a high proportion of panuveitis (4 out of 16, i.e., 25%). There was an increased frequency of occurrence of synechiae (5 out of 16, i.e., 31.3%), retinal vasculitis (4 out of 16, i.e., 25%), optic disc edema (3 out of 16, i.e., 18.8%), and cystoid macular edema (seen in 2 patients, i.e., 12.5%). These features correlated with the anatomical subtypes. Retinal vasculitis and optic disc edema present in three fourth of all panuveitis cases were the most prominent features. The odds of finding HLA-B∗35 in retinal vasculitis were 33 times higher than odds of finding it in idiopathic autoimmune uveitis patients not having retinal vasculitis (OR 33; 95% CI 1.6-698). CONCLUSION: Idiopathic autoimmune uveitis in our patients is characterized by a high frequency of panuveitis and retinal vasculitis, and complications with a probable association between HLA-B∗35 and retinal vasculitis.