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Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

PURPOSE: We report a case of advanced metastatic cutaneous melanoma with melanoma-associated retinopathy and pembrolizumab-related panuveitis and optic neuritis. METHODS: The patients condition was managed by systemic, topical, and intravitreal corticosteroids without discontinuing pembrolizumab. RESULTS: After initiation of systemic and topical steroid treatment, optic nerve edema improved. He developed chronic uveitis with cystoid macular edema with improvement in symptoms with intravitreal dexamethasone implants. The patient demonstrated a decrease in all metastatic lesions and improvement in melanoma-associated retinopathy. CONCLUSIONS: The new checkpoint inhibitor class including pembrolizumab shows promise as a therapy for advanced metastatic melanoma in patients resistant to all other forms of chemotherapy. In general, immune-related adverse effects are responsive to steroid therapy. The trend for treatment of posterior uveitis due to pembrolizumab is to discontinue pembrolizumab. Our case suggests that even severe cases of uveitis may be sufficiently ameliorated by concurrent systemic, intravitreal, and topical therapy to allow continuation of treatment.

Nous rapportons le cas d’un jeune homme de dix-sept ans présentant une baisse d’acuité visuelle bilatérale, une panuvéite, des décollements rétiniens exsudatifs et une infiltration choroïdienne diffuse. Le patient rapporte également des céphalées et otalgies. Sur base du fond d’œil, de la fluoangiographie, de l’angiographie au vert d’indocyanine et de la tomographie par cohérence optique, le diagnostic de maladie de Vogt Koyanagi Harada est posé. Le traitement par hautes doses de methylprednisolone et azathioprine montre une excellente réponse avec amélioration progressive de l’acuité visuelle et disparition du liquide sous-rétinien. Un mois après l’instauration du traitement, l’œil droit présente une vasculite rétinienne sectorielle avec subocclusion de la veine temporale inférieure et hémorragies sous-rétiniennes massives. Les tests de coagulation sanguine ainsi que les sérologies HIV et syphilis sont négatifs mais le QuantiFERON revient positif. Le pet-scan met en évidence des ganglions lymphatiques hyper métaboliques au niveau médiastinal et la biopsie confirme une tuberculose ganglionnaire active. Une thérapie antituberculeuse à base de rifampicine est initiée, entrainant une induction enzymatique du cytochrome p450 avec comme conséquence une baisse de l’efficacité des corticoïdes menant à une récidive de l’inflammation choroïdienne., [Vogt-Koyanagi-Harada disease in a young man, which was complicated by tuberculosis reactivation and occlusive retinal vasculitis] We report the case of a 17-year-old man presenting with bilateral visual loss, panuveitis, exudative retinal detachments, and diffuse choroidal infiltration. The patient also complained of headaches and ear pain. Based on the fundus image analysis, fluoangiography, indocyanine green angiography, and optical coherence tomography, Vogt-Koyagani-Harada disease was diagnosed. The patient received high-dose methylprednisolone along with azathioprine. He responded well to treatment with progressive visual improvement and subretinal fluid disappearance. One month later, his right eye exhibited a sectorial retinal vasculitis with inferotemporal vein branch occlusion and massive subretinal hemorrhages. Coagulation screening as well as HIV and syphilis serology were all negative; whereas QuantiFERON was positive. An 18F-FDG PET/CT revealed hypermetabolic mediastinal lymph nodes, and a biopsy confirmed active tuberculosis (TB) infection. Anti-TB quadritherapy was initiated, resulting in cytochrome P450 enzyme induction and lowered steroid treatment efficacy, with consecutive recurrence of choroidal inflammation.

PurposeTo evaluate the changes in quality of life in noninfectious uveitis patients treated with 2 of the most commonly prescribed antimetabolite treatments.DesignSecondary analysis of a multicenter, block-randomized clinical trial.MethodsEighty patients at Aravind Eye Hospitals in Madurai and Coimbatore, India, with noninfectious intermediate, posterior, or panuveitis were randomized to receive oral methotrexate, 25 mg weekly, or oral mycophenolate mofetil, 1 g twice daily, and were followed up monthly for 6 months. Best-corrected visual acuity, Indian Vision Function Questionnaire (IND-VFQ), and Medical Outcomes Study 36-item Short Form Survey (SF-36) were obtained at enrollment and at 6 months (or prior, in the event of early treatment failure).ResultsIND-VFQ scores, on average, increased by 9.2 points from trial enrollment to 6 months (95% confidence interval [CI]: 4.9, 13.5, P = .0001). Although the SF-36 physical component summary score did not significantly differ over the course of the trial, the mental component summary score decreased by 2.3 points (95% CI: -4.4, -0.1, P = .04) and the vitality subscale decreased by 3.5 points (95% CI: -5.6, -1.4, P = .001). Quality-of-life scores did not differ between treatment arms. Linear regression modeling showed a 3.2-point improvement in IND-VFQ score for every 5-letter improvement in visual acuity (95% CI: 1.9, 4.3; P < .001).ConclusionsAlthough uveitis treatment was associated with increased vision and vision-related quality of life, patient-reported physical health did not change after 6 months of treatment, and mental health decreased. Despite improved visual outcomes, uveitis patients receiving systemic immunosuppressive therapy may experience a deterioration in mental health-related quality of life.

PurposeTo report outcomes of Vogt-Koyanagi-Harada (VKH) disease from a clinical trial of antimetabolite therapies.DesignSubanalysis from an observer-masked randomized clinical trial for noninfectious intermediate, posterior, and panuveitis.Methodssetting: Clinical practice at Aravind Eye Hospitals, India.Patient populationForty-three of 80 patients enrolled (54%) diagnosed with VKH.InterventionPatients were randomized to either 25 mg oral methotrexate weekly or 1 g mycophenolate mofetil twice daily, with a corticosteroid taper.Main outcome measuresPrimary outcome was corticosteroid-sparing control of inflammation at 5 and 6 months. Secondary outcomes included visual acuity, central subfield thickness, and adverse events. Patients were categorized as acute (diagnosis ≤3 months prior to enrollment) or chronic (diagnosis >3 months prior to enrollment).ResultsTwenty-seven patients were randomized to methotrexate and 16 to mycophenolate mofetil; 30 had acute VKH. The odds of achieving corticosteroid-sparing control of inflammation with methotrexate were 2.5 times (95% CI: 0.6, 9.8; P = .20) the odds with mycophenolate mofetil, a difference that was not statistically significant. The average improvement in visual acuity was 12.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. On average, visual acuity for patients with acute VKH improved by 14 more ETDRS letters than those with chronic VKH (P < .001), but there was no difference in corticosteroid-sparing control of inflammation (P = .99). All 26 eyes with a serous retinal detachment at baseline resolved, and 88% achieved corticosteroid-sparing control of inflammation.ConclusionsThe majority of patients treated with antimetabolites and corticosteroids were able to achieve corticosteroid-sparing control of inflammation by 6 months. Although patients with acute VKH gained more visual improvement than those with chronic VKH, this did not correspond with a higher r

PurposeTo identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes.DesignCohort study using randomized controlled trial data.MethodsMulticenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA.ResultsBaseline factors significantly associated with reduced BCVA included age ≥50 vs <50 years; posterior vs intermediate uveitis; uveitis duration >10 vs <6 years; anterior chamber (AC) flare >grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening.ConclusionsIntermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation.

El síndrome de Vogt-Koyanagi-Harada (VKH) es una entidad clínica caracterizada por panuveítis granulomatosa bilateral difusa. Cursa con desprendimiento exudativo de la retina y puede acompañarse de alteraciones del sistema nervioso central, dermatológicas y auditivas. Aunque es de etiología desconocida, es considerada como una enfermedad autoinmune asociada a los haplotipos HLA-DR4. Se divide en tres fases: prodrómica, oftálmica y de convalecencia. El diagnóstico se realiza mediante la historia clínica y examen físico-oftalmológico completo, así como también por exámenes complementarios como la angiografía retinal fluoresceínica y punción lumbar. El tratamiento se basa en el uso de corticoides tópicos y sistémicos, siendo de gran importancia la dosis inicial y la duración del tratamiento. A continuación se presenta un caso clínico de un paciente de sexo masculino que consulta por disminución de la agudeza visual de ambos ojos y micropsia; mediante criterios clínicos y exámenes complementarios se llegó al diagnóstico de síndrome de Vogt-Koyanagi-Harada en su variante incompleta; él se manejó con corticoterapia tópica y sistémica. Al mismo tiempo este artículo revisa la literatura relacionada con esta patología.

Seasonal hyperacute panuveitis (SHAPU) is a potentially blinding ocular disease occurring in Nepal that principally affects young children. Random amplification of partially purified vitreous fluid (VF)-derived nucleic acid revealed the presence of human anelloviruses in VF of SHAPU patients. In a comparative study of patients with different ocular pathologies, SHAPU patients were at highest risk of harboring anelloviruses in their eyes. The majority of SHAPU patients had multiple anelloviruses in their VF. The ocular anellovirus load in SHAPU and non-SHAPU patients did not differ and no SHAPU-specific anellovirus variant was detected. Analysis of paired serum and VF samples from SHAPU and non-SHAPU patients showed that the anellovirus detected in VF samples most likely originated from the systemic viral pool during viremia, potentially through breakdown of the blood-ocular barrier. The detection of anelloviruses in VF samples of uveitis patients, profoundly so in SHAPU patients, is imperative and warrants elucidation of its clinical significance.

Seasonal hyperacute panuveitis (SHAPU) is a potentially blinding ocular disease occurring in Nepal that principally affects young children. Random amplification of partially purified vitreous fluid (VF)-derived nucleic acid revealed the presence of human anelloviruses in VF of SHAPU patients. In a comparative study of patients with different ocular pathologies, SHAPU patients were at highest risk of harboring anelloviruses in their eyes. The majority of SHAPU patients had multiple anelloviruses in their VF. The ocular anellovirus load in SHAPU and non-SHAPU patients did not differ and no SHAPU-specific anellovirus variant was detected. Analysis of paired serum and VF samples from SHAPU and non-SHAPU patients showed that the anellovirus detected in VF samples most likely originated from the systemic viral pool during viremia, potentially through breakdown of the blood-ocular barrier. The detection of anelloviruses in VF samples of uveitis patients, profoundly so in SHAPU patients, is imperative and warrants elucidation of its clinical significance.

A 64-year-old Mexican fisherman with a history of syphilis is diagnosed with panuveitis of the right eye after presenting with unilateral blurry vision, redness, and pain. A PPD was 35X30mm, and chest X-ray suggested tuberculosis. The patient’s pain and vision improved with 4-drug anti-tuberculous therapy, topical steroids, and cycloplegic eye drops.

A 64-year-old Mexican fisherman with a history of syphilis is diagnosed with panuveitis of the right eye after presenting with unilateral blurry vision, redness, and pain. A PPD was 35X30mm, and chest X-ray suggested tuberculosis. The patient’s pain and vision improved with 4-drug anti-tuberculous therapy, topical steroids, and cycloplegic eye drops.

The authors conducted a retrospective analysis of 201 patients with intermediate, posterior or panuveitis to determine the most frequent etiologies and collect some epidemiological data. A specific diagnosis was made in 70% of the cases: 35% were of infectious origin, 23% were associated with a systemic disease and 24% had a specific ocular condition. The most common entities included toxoplasmosis (24%), sarcoidosis (7.5%) and Behçet disease (5.5%). Birdshot retinochoroidopathy was the most frequent specific ocular disease (3.5%). The findings of this study are compared with those previously published in the literature.