Background/aims To explore and characterise the clinical phenotype of acute anterior uveitis flares with delayed severity in patients with human leucocyte antigen B27 (HLA-B27)-associated anterior uveitis.Methods Retrospective chart review of patients with HLA-B27-associated anterior uveitis. Demographic and clinical data were recorded, as well as the clinical characteristics of acute anterior uveitis flares. A flare was considered to have delayed severity if any of the following criteria were met within 3-21 days of symptomatic onset: a two-step increase in anterior chamber inflammation on consecutive exams; a new development of hypopyon or fibrinoid aqueous reaction on consecutive examinations or a significant worsening of symptoms.Results A total of 371 patient charts were identified, of which 137 were included. 321 acute anterior uveitis flares were documented, with 36 (11.2%) meeting the criteria for a delayed severity flare. The average time from symptomatic onset was 10.2 days, and patients presented with an average anterior chamber cell grade of 3.5 in delayed severity flares compared with 1.6 in non-delayed severity flares. No significant difference in frequency of delayed severity presentation was noted based on the presence or absence of systemically associated rheumatological disease, papillitis on initial presentation and retinal vasculitis on initial presentation. The frequency of topical steroid therapy after symptomatic onset was not significantly different between the two flare phenotypes.Conclusions Our study presents the novel characterisation of a delayed severity phenotype of HLA-B27-associated acute anterior uveitis flares.

Objective: The efficiency of B-cell depletion therapy for severe ocular cicatricial pemphigoid (OCP) highlights the key role of B lymphocytes in the immunopathogenesis of OCP. B-cell activating factor (BAFF) is a potent B-cell growth factor and costimulator of immunoglobulin production. Elevated serum BAFF is associated with systemic autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and bullous pemphigoid. We hypothesize that serum BAFF levels are also increased in patients with OCP. Methods: Sera were collected from 30 patients with new-onset active OCP, 9 with disease in remission, 10 with OCP relapse, and 15 healthy control individuals. An enzyme-linked immunosorbent assay was performed to measure the concentration of serum BAFF. Results: BAFF was significantly higher in patients with new-onset active OCP (700.8 +/- 181.8 pg/mL) than in healthy control individuals (564.1 +/- 133.2 pg/mL; p = 0.014). No significant difference was found between patients with OCP in remission (585.4 +/- 216.2 pg/mL) and healthy control individuals. Patients with disease relapse treated with rituximab had an extremely high concentration of BAFF (1721.9 +/- 790.8 pg/mL). Longitudinal analysis of serum BAFF from 6 patients showed that BAFF decreased as the disease went from new onset (895.0 +/- 240.8 pg/mL) to remission (625.4 +/- 199.8 pg/mL; p = 0.003). Conclusions: BAFF is involved in the active inflammation of OCP. Targeting BAFF with an antagonist may be therapeutically beneficial for patients with refractory OCP, especially those resistant to rituximab.

Purpose To report a case of acute macular neuroretinopathy (AMN) after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema secondary to birdshot chorioretinopathy. Method A case report. Patient A 62-year-old female. Results The patient presented with acutely decreased vision and a ring scotoma around her central vision three days after intravitreal triamcinolone acetonide (TRIESENCE®) injection for cystoid macular edema in her right eye (OD) secondary to birdshot chorioretinopathy. She had undergone pars plana vitrectomy, cataract extraction, and secondary intraocular lens implantation OD three months prior to the recent injection. Best-corrected visual acuity (BCVA) was 20/1000 OD and 20/50 OS. Intraocular pressure was 21 mmHg OD and 12 mmHg OS. Fluorescein angiography demonstrated a hypofluorescent area in the perifoveal zone OD. Optical coherence tomography OD depicted hyperreflective areas in the outer nuclear layer, outer plexiform layer, and retinal pigment epithelium. We diagnosed her with AMN OD and started her on brimonidine three times a day OD. She came back a week later with resolved scotoma and her vision improved to 20/60 OD. Five weeks later, BCVA was 20/40 and Intraocular pressures (IOP) was 12 mmHg OD. Conclusions and importance Intravitreal triamcinolone injection may be a cause of AMN with cystoid macular edema (CME) and borderline-high intraocular pressure. Brimonidine may be an effective treatment for these patients in the early course of the disease.

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy with phenotypical features of pericentral retinal degeneration (PRD) who responded to IV immunoglobulin therapy. Methods: A case report. A 27-year-old man presented with recent subacute progressive nyctalopia and photopsia. Results: Dilated fundoscopy demonstrated confluent yellow–white patches along the main temporal vascular arcades with sparing of the central island in the posterior pole. Color vision, fundus autofluorescence, fluorescein angiography, static visual field, and electroretinographic studies were inconclusive for retinal degeneration. Subsequent genetic testing for known mutations was negative. Workup for paraneoplastic autoimmune retinopathy was negative. Antiretinal antibodies were positive. The patient was diagnosed with nonparaneoplastic autoimmune retinopathy and was treated with IV immunoglobulin, which resulted in objective and subjective improvement on electroretinography, visual field, and optical coherence tomography of the retina. Conclusion: Nonparaneoplastic autoimmune retinopathy may present in a patient with the clinical phenotype of PRD. It is essential to rule out nonparaneoplastic autoimmune retinopathy in patients with subacute changes in the natural course of pericentral retinal degeneration because treatment with IV immunoglobulin may be helpful.

Purpose: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). Methods: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens–Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. Results: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. Conclusions: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.

Objective: To compare the demographic, clinical, ancillary testing, and multimodal imaging characteristics of birdshot chorioretinopathy (BSCR) patients with late recurrence and birdshot patients with durable remission. Patients and Methods: This was a retrospective observational case series. The above-mentioned parameters were studied in BSCR patients with late recurrence (group 1) and BSCR patients with durable remission (group 2). Results: Fifty-five patients were included in this study. The average age of patients was 62.1 +/- 11.1 years (range, 35-88 years). Groups 1 and 2 included 20 (36.4%) and 35 (63.6%) patients, respectively. In group 1, the average age of patients was 60.5 +/- 10.39 years (range, 35-79 years). The female-to-male ratio was 16:4. In group 2, the average age of patients was 63.1 +/- 11.6 years (range, 37-88 years). The female-to-male ratio was 22:13. None of the demographic, clinical, ancillary testing, and multimodal imaging parameters were statistically significantly different between the two groups. Using a receiver operating characteristics (ROC) curve, we found that the ideal duration of successful therapy to induce durable remission was 30 months with 70% sensitivity and 40% specificity (ideal point on the curve). A Kaplan-Meier survival curve demonstrated that late recurrence was seen within 30 months after stopping successful treatment of patients with BSCR. Conclusion: There are no demographic, clinical, ancillary testing, or multimodal imaging characteristics that can predict late recurrence in BSCR patients. However, we found that 30 months of successful treatment may be ideal and recommended.

Purpose To examine the diagnostic and prognostic roles of serum interleukin-6 levels in patients with uveitis. Methods This was a retrospective observational case series. Demographic and clinical characteristics were compared between Group One (sixty patients) with normal serum IL-6 levels and Group Two (twenty patients) with high serum interleukin-6 levels. Results Mean IL-6 level was 1.77 +/- 0.97 pg/ml and 10.2 +/- 9.7 pg/ml in Group One and Group Two respectively. Age, presence of systemic disease, and mean number of flare-ups were statistically significant (p= .015,p= .000,p= .03, respectively). Multivariate analysis was performed on variables that were statistically significant in univariate analysis and showed that three variables had significant correlation with IL-6 levels in both groups: systemic disease (OR = 10.83,p< .001), Age (OR = 0.95,p= .03) and number of flare-ups (OR = 2.9,p= .02). Conclusion Serum IL-6 levels can provide diagnostic and prognostic information in regard to the course of disease and its treatment.

ABSTRACT Purpose To determine the response to the second TNF-α inhibitor (adalimumab and infliximab) after failing the first agent in idiopathic inflammatory retinal vascular leakage. Materials and Methods This was a retrospective observational case series. Patients with the diagnosis of idiopathic inflammatory retinal vascular leakage who had received both infliximab and adalimumab were included in the study. Results Twelve and 15 patients received adalimumab (Group one) and infliximab (Group two) as the first treatment, respectively. The remission rates between Group one (58.3%) and Group two (66.7%) were not statistically significant. (P = .4) As the second agent, adalimumab was more effective in younger patients (27.5 ± 20.6) compared to older patients (48.75 ± 10.2). (P = .03). Moreover, patients with lower vision responded marginally better to infliximab as the second treatment (P = .06). Conclusion Either TNF-α inhibitor, adalimumab and infliximab, can be employed in the treatment of the patients with idiopathic inflammatory retinal vascular leakage who fail one of these agents.

Objective: To investigate the clinical features, treatment, and visual outcome of occlusive retinal vasculitis (ORV), with a focal analysis on prognostic factors associated with poor visual outcome. Methods: We conducted a retrospective cohort study in patients diagnosed with ORV with at least 6 months of follow-up. Demographic data, ocular features, best corrected visual acuity (BCVA), fluorescein angiography, therapy regimens, and outcomes were collected from the Massachusetts Eye Research and Surgery Institution database from 2006 to 2017. Multivariate logistic regression was performed to analyze the factors independently predicting poor visual outcome. Results: Fifty-two patients (69 eyes) were enrolled, 42 with noninfectious cause, 9 with infectious cause, and 1 with maslupus erythematosus, and Beh??cet???s disease comprised the causes of ORV. Forty of the 42 patients with noninfectious ORV received immunomodulatory therapy (IMT), and 35 patients (87.5%) were able to achieve steroid-free remission. Compared with the BCVA at the initial visit (0.66 [??0.11] logMAR), there was significant improvement at the most recent visit (0.37 [??0.07] logMAR, p = 0.001). A multivariate analysis demonstrated that optic nerve atrophy, macular ischemia, and poor BCVA at initial presentation were independently correlated with poor visual outcome. Conclusions: ORV could be caused by a wide spectrum of systemic inflammatory diseases. Aggressive IMT is preferred to achieve a steroid-free durable remission for noninfectious ORV. Optic nerve atrophy, macular ischemia, and poor BCVA at the initial visit predict a poor visual outcome.

PURPOSE:To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy.PATIENTS AND METHODS:This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy.RESULTS:One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p < .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups.CONCLUSION:.Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.

Aim To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis. Patients and Methods Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study. Results Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found. Conclusion RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.

•Serpiginous choroiditis may be recurrent or refractory to chlorambucil in conjunction with systemic corticosteroids.•The stability of WBC counts within lower limits of normal is an essential factor for the success of chlorambucil therapy.•This can be achieved with dexamethasone intravitreal implant or systemic immunomodulatory without systemic corticosteroid therapy.

Inflammation can involve several ocular structures, including the sclera, retina, and uvea, and cause vascular changes in these tissues. Although retinal vasculitis is the most common finding associated with uveitis involving the posterior segment, other vascular abnormalities may be seen in the retina. These include capillary nonperfusion and ischemia, vascular occlusions, preretinal neovascularization, microaneurysms and macroaneurysms, and telangiectasia. Moreover, vasoproliferative tumors and subsequent coat-like response can develop secondary to uveitis. Fluorescein angiography is ideal for the investigation of retinal vascular leakage and neovascularization, while optical coherence tomography angiography can provide depth resolved images from the superficial and deep capillary plexus and can demonstrate vascular remodeling. Choroidal vascular abnormalities primarily develop in the choriocapillaris or in the choroidal stroma and can appear as flow void in optical coherence tomography angiography and filling defect and vascular leakage in indocyanine green angiography. Extensive choriocapillaris nonperfusion in the presence of choroidal inflammation can increase the risk of choroidal neovascular membrane development. Iris vascular changes may manifest as dilation of vessels in stroma due to inflammation or rubeosis that is usually from ischemia in retinal periphery secondary to chronic inflammation. More severe forms of scleral inflammation, such as necrotizing scleritis, are associated with vascular occlusion in the deep episcleral plexus, which can lead to necrosis of sclera layer and uveal exposure.

The therapeutic use of the RPE-neuropeptide α-MSH suppresses experimental autoimmune uveitis (EAU). This suppression is partially through the α-MSH melanocortin 5 receptor (MC5r). Therefore, we examined the possible role of MC5r-expression in the recovery of RPE suppression of phagolysosome-activation in macrophages following α-MSH-treatment of EAU.The conditioned media of cultured in situ RPE-eyecup from α-MSH-treated EAU wild-type and MC5r(-/-) mice were used to treat macrophages to assay for phagolysosome activation.MC5r(-/-) mice treated with α-MSH recovered from EAU, but with greater retinal damage, and the RPE suppressed phagolysosome activation in wild type but not in MC5r(-/-) macrophages. In addition, α-MSH did not suppress phagolysosome activation in MC5r(-/-) macrophages, and resting-MC5r(-/-) macrophages had augmented phagocytic activity.α-MSH treatment of EAU mediates a MC5r-dependent recovery of RPE suppression of phagolysosome activation in macrophages possibly altering antigen processing and presentation. Also, MC5r-expression helps protect the retina from inflammatory damage. In addition, MC5r-expression is important in the homeostatic maintenance of phagosome-maturation within macrophages.

PURPOSE:To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS:This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS:Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION:The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

Purpose: To report two cases; bilateral arteritic anterior ischemic optic neuropathy (AAION) and bilateral acute zonal occult outer retinopathy (AZOOR) after COVID-19 mRNA vaccination. Case Reports: The first patient was a 79-year-old female was presented to us 35 days after a sudden bilateral loss of vision, which occurred two days after receiving the second recombinant mRNA vaccine (Pfizer) injection. Temporal artery biopsy was compatible with AAION. At presentation, the best-corrected visual acuity was 20/1250 and 20/40 in the right and left eyes on the Snellen acuity chart, respectively. There was 3+ afferent pupillary defect in the right eye. The anterior segment and posterior segment exams were normal except for pallor of the optic nerve head in both eyes. Intraocular pressure was normal in both eyes. She was diagnosed with bilateral AAION and Subcutaneous tocilizumab 162 mg weekly was recommended with monitoring her ESR, CRP, and IL-6. The second patient was a 33-year-old healthy female who was referred to us for a progressive nasal field defect in her left eye, and for flashes in both eyes. Her symptoms started 10 days after receiving the second recombinant mRNA vaccine (Moderna) injection. Complete bloodwork performed by a uveitis specialist demonstrated high ESR (25) and CRP (19) levels. As a result, she was diagnosed with unilateral AZOOR in her left eye and was subsequently treated with an intravitreal dexamethasone implant in the same eye. At presentation, vision was20/20 in both eyes. The anterior segment and posterior segment exams were completely normal except for the presence of abnormal white reflex in the temporal macula of her left eye. We diagnosed her with bilateral AZOOR. Since she was nursing, intravitreal dexamethasone implant was recommended for the right eye. Conclusion: There may be a correlation between ocular inflammatory diseases with autoimmune mechanism and the mRNA COVID-19 vaccination.

Vogt–Koyanagi–Harada (VKH) disease is an autoimmune inflammatory disorder that can present with ophthalmic, neurologic, auditory, and dermatologic manifestations.1Burkholder BM. Vogt–Koyanagi–Harada disease.Curr Opin Ophthalmol. 2015; 26: 506-511Crossref PubMed Scopus (23) Google Scholar In this study, we investigated possible factors that might subsequently result in poor visual function. This study was approved by the New England Institutional Review Board, which has issued a waiver of informed consent for the retrospective chart review analysis. Twenty-six patients were included in this retrospective case series. There were 2 patients (7.7%) diagnosed with complete, 11 patients (42.3%) with incomplete, and 13 patients (50%) with probable VKH disease. The average age of the patients in this study was 42.9 ± 13.7 years (range, 21–64 years). The average duration between the first symptoms and first treatment was 23.5 ± 38.8 weeks. There were 6 patients (23%) in acute phase and 20 patients (77%) in recurrent/chronic phase. The average logMAR best-corrected visual acuity (BCVA) was 0.66 ± 0.83 (20/60; range, –0.1 to 2.8). All patients, except for one, were started on immunomodulatory therapy (IMT). This patient underwent fluocinolone acetonide intravitreal implant (0.59 mg) implantation in both eyes. The IMT regimens are shown in Table 1. The average duration of the follow-up period was 8.1 ± 3.1 years (range, 2–16 years). Patients were divided into 2 groups defined at last visit as good visual outcome (BCVA ≥ 20/40; no significant scotoma: 17 patients [65.3%]) or poor visual outcome (BCVA < 20/40; significant scotoma on visual field 24 degrees: 9 patients [34.7%]).Table 1Immunomodulatory therapy (IMT) regimens in patients with Vogt–Koyanagi–Harada diseaseIMT regimensPatients, n (%)Remission on IMTRemission off IMTAzathioprine6 (23%)1 (3.8%)NoneMycophenolate mofetil9 (34.6%)——Methotrexate6 (23%)1 (3.8%)1 (3.8%)Cyclosporine3 (11.5%)——Chlorambucil3 (11.5%)——Cyclophosphamide1 (3.8%)——Adalimumab3 (11.5%)2 (7.6%)NoneInfliximab5 (19.2%)1 (3.8%)NoneTocilizumab1 (3.8%)——Rituximab1 (3.8%)——Azathioprine + cyclosporine3 (11.5%)3 (11.5%)2 (7.6%)Methotrexate + cyclosporine3 (11.5%)——Mycophenolate mofetil + cyclosporine14 (53.8%)2 (7.6%)1 (3.8%)Methotrexate + sirolimus1 (3.8%)1 (3.8%)NoneMycophenolate mofetil + adalimumab4 (15.3%)3 (11.5%)2 (7.6%)Infliximab + methotrexate3 (11.5%)1 (3.8%)NoneChlorambucil + cyclosporine1 (3.8%)——Mycophenolate mofetil + tacrolimus1 (3.8%)——Mycophenolate mofetil + infliximab1 (3.8%)1 (3.8%)1 (3.8%)The boldface signifies the IMT regimens that induced and maintained durable remission even after IMT discontinuation. Open table in a new tab The boldface signifies the IMT regimens that induced and maintained durable remission even after IMT discontinuation. Poor visual function was defined as uncorrectable BCVA less than 20/40, significant scotoma secondary to VKH disease, or VKH complications on visual field 24 degrees at last visit. Significant scotoma was defined as 3 or more significant (p < 0.05) contiguous points, with at least 1 at the p < 0.01 level on the same side as the horizontal meridian.2Maleki A Swan RT Silpa-Archa S Preble JM He Y Foster CS. Short-wavelength automated perimetry parameters at baseline and following remission in patients with birdshot retinochoroidopathy.Am J Ophthalmol. 2016; 163 (83–92.e6)Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Patients’ BCVA at the first visit was classified as BCVA ≥ 20/40 and BCVA < 20/40 for statistical analysis. The demographic and clinical variables were compared in these two groups (Table 2).Table 2Comparison of demographic and clinical features between poor and good visual outcome groupsDemographic and Clinical CharacteristicsPoor Visual Outcome, (9 [34.7%])Good Visual Outcome (17 [65.3%])p Value*Age, y41.33 ± 15.7343.76 ± 12.490.662Female sex9 (100%)14 (82.4%)0.066Other systems involvement66.7%57.1%0.691Duration between the first symptoms and first treatment (months)38.783 ± 51.6412.00 ± 18.180.077Systemic corticosteroid therapy before first visit62.5%50.0%0.564Immunomodulatory therapy before first visit37.5%37.5%1.000Duration between first treatment and first visit (months)90.13 ± 175.40123.62 ± 310.660.729Disease status at first visit (active/inactive)77.8%88.2%0.488LogMAR BCVA at first visit0.65 ± 0.650.68 ± 0.920.996BCVA < 20/40 at initial visit54.5%57.1%0.7Anterior chamber inflammation66.7%44.1%0.426Intraocular pressure (mmHg)13.13 ± 3.0715.12 ± 5.160.179Vitreous inflammation55.6%55.9%0.988All positive FFA findings75.0%65.6%0.548Disc leakage on FFA66.6%47.1%0.4Pinpoint leakage on FFA66.6%46.1%0.2All positive OCT findings66.7%70.0%0.952Cystoid macular edema (CME)37.5%54.5%1.0Subretinal fluid66.6%75%0.72Treatment ≤ 4 weeks50%46.1%1.0Oral corticosteroid > 6 months with first IMT44.4%41.6%0.66Number of IMT regimens tried4.22 ± 2.732.41 ± 1.480.016Number of IMT agents tried4.22 ± 1.923.17 ± 1.420.13Number of IMT agents per regimen1 ± 0.071.82 ± 0.890.011Duration of oral corticosteroid therapy with first IMT (months)7.89 ± 7.8416.59 ± 42.120.242Number of procedures2.44 ± 2.571.00 ± 1.560.055Procedure (yes/no)77.8%41.2%0.017Number of recurrences2.44 ± 2.280.41 ± 0.860.034Recurrence (yes/no)88.9%23.5%0.007Presence of complication (yes/no)88.9%52.9%0.093BCVA, best corrected visual acuity; FFA, fundus fluorescein angiography; OCT, optical coherence tomography; IMT, immunomodulatory therapy.The boldface numbers are the variables which were statistically significantly different between two groups.p value ≤ 0.05 were statistically significant. Open table in a new tab BCVA, best corrected visual acuity; FFA, fundus fluorescein angiography; OCT, optical coherence tomography; IMT, immunomodulatory therapy. The boldface numbers are the variables which were statistically significantly different between two groups. p value ≤ 0.05 were statistically significant. The presence and number of recurrences, number of IMT regimens tried, and presence of complications requiring procedures were correlated with poor prognosis in this case series. These parameters have been shown in previous studies,3Maruyama K Noguchi A Shimizu A Shiga Y Kunikata H Nakazawa T. Predictors of recurrence in Vogt-Koyanagi-Harada disease.Ophthalmol Retina. 2018; 2: 343-350Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 4Chee SP Jap A Bacsal K. Prognostic factors of Vogt-Koyanagi-Harada disease in Singapore.Am J Ophthalmol. 2009; 147 (154–61.e1)Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 5Ohno S Minakawa R Matsuda H. Clinical studies of Vogt-Koyanagi-Harada's disease.Jpn J Ophthalmol. 1988; 32: 334-343PubMed Google Scholar, 6Read RW Rechodouni A Butani N et al.Complications and prognostic factors in Vogt-Koyanagi-Harada disease.Am J Ophthalmol. 2001; 131: 599-606Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 7Mondkar SV Biswas J Ganesh SK. Analysis of 87 cases with Vogt-Koyanagi-Harada disease.Jpn J Ophthalmol. 2000; 44: 296-301Crossref PubMed Scopus (52) Google Scholar, 8Al-Kharashi AS Aldibhi H Al-Fraykh H et al.Prognostic factors in Vogt-Koyanagi-Harada disease.Int Ophthalmol. 2007; 27: 201-210Crossref PubMed Scopus (63) Google Scholar, 9Sheu SJ Kou HK Chen JF. Significant prognostic factors for Vogt-Koyanagi-Harada disease in the early stage.Kaohsiung J Med Sci. 2004; 20: 97-105Crossref PubMed Google Scholar but number of IMT regimens tried is a new factor. This suggests that a more aggressive IMT regimen to induce faster remission and use of a fewer number of IMTs may be important for better prognosis in patients with VKH disease. It is important to note that IMT regimens are different from IMT agents. In this case series, poor visual outcome was correlated with more IMT regimens and fewer IMT agents in each regimen tried (Table 2). It was shown that a combination of conventional IMT (including azathioprine or mycophenolate mofetil) and a T-cell inhibitor (including cyclosporine or tacrolimus) or a combination of conventional IMT and tumor necrosis factor alpha inhibitors (including adalimumab or infliximab) was more effective than monotherapy using conventional or biologic response modifier agents (42.3% vs 25%; see Table 1). This case series did not show any correlation between the age of the patients and poor visual outcomes. This suggests that older patients may require more aggressive IMT therapy than younger patients because prognosis is poorer in older patients5Ohno S Minakawa R Matsuda H. Clinical studies of Vogt-Koyanagi-Harada's disease.Jpn J Ophthalmol. 1988; 32: 334-343PubMed Google Scholar,7Mondkar SV Biswas J Ganesh SK. Analysis of 87 cases with Vogt-Koyanagi-Harada disease.Jpn J Ophthalmol. 2000; 44: 296-301Crossref PubMed Scopus (52) Google Scholar and that IMT improves the visual prognosis in older patients with VKH disease. Fluocinolone acetonide intravitreal implants induced and maintained remission in all eyes (9 eyes), with no IMT employment, during the active period of the intravitreal implant. The main objections to this study were its retrospective nature and small sample size, unavailability of indocyanine green angiography and enhanced depth imaging optical coherence tomography for all patients, and selection bias from being a referral tertiary centre. The combination of conventional IMT or biologic response modifier agents, including tumor necrosis factor alpha inhibitors, with T-cell inhibitors may be a promising regimen in the treatment of patients with VKH disease, especially in chronic/recurrent cases. The sooner the disease is controlled and the fewer experimental IMT regimens tried, the lesser is the chance of poor visual function. C. Stephen Foster declares the following: Consultancies with Aldeyra Therapeutics (Lexington, Mass.), Allakos (Redwood City, Calif.), Bausch & Lomb Surgical, Inc (Rancho Cucamonga, Calif.), Eyegate Pharma (Waltham, Mass.), Genentech (South San Francisco, Calif.), Novartis (Cambridge, Mass.), and pSivida (Watertown, Mass.); grants or grants pending with Aciont (Salt Lake City, Utah), Alcon (Aliso Viejo, Calif.), Aldeyra Therapeutics (Lexington, Mass.), Bausch & Lomb (Rochester, NY), Clearside Biomedical (Alpharetta, Ga.), Dompé Pharmaceutical (Milan, Italy), Eyegate Pharma (Waltham, Mass.), Mallinckrodt Pharmaceuticals (Staines-upon-Thames, U.K.), Novartis Pharmaceuticals (Cambridge, Mass.), pSivida (Watertown, Mass.), and Santen (Osaka, Japan); and payments for lectures including service on speaking bureaus: Alcon (Aliso Viejo, Calif.), Allergan (Dublin, Ireland), and Mallinckrodt Pharmaceuticals (Staines-upon-Thames, UK). Stock or Stock. Stephen D. Anesi declares the following: consultancies with Santen (Osaka, Japan), Mallinckrodt Pharmaceuticals (Staines-upon-Thames, U.K.), Allakos (Redwood City, Calif.), Eyepoint (Watertown, Mass.), and Takeda (Tokyo, Japan); speakerships with AbbVie (Chicago, Ill.), Mallinckrodt Pharmaceuticals (Staines-upon-Thames, U.K.), and Eyepoint (Watertown, Mass.); and options: Eyegate Pharma (Waltham, Mass.) The other authors have nothing to declare. This study was approved by the New England Institutional Review Board, which has issued a waiver of informed consent for the retrospective chart review analysis. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. All participants provided consent for publication if any identifying information is included in the manuscript.

PURPOSE:To evaluate the parameters of the Fixed-Luminance and Multi-Luminance flicker electroretinography protocol among patients with early active birdshot chorioretinopathy. METHODS:Fixed-Luminance magnitude, Fixed-Luminance phase, Multi-Luminance magnitude area under the curve, and Multi-Luminance phase area under the curve parameters were compared between early active birdshot chorioretinopathy patients and an age-matched control group. RESULTS:There was no statistically significant difference between the Fixed-Luminance flicker magnitude (P = .6), the Fixed-Luminance flicker phase (P = .9), and the Multi-Luminance flicker phase area under the curve (P = .55) when each was compared to the normal population; however, the difference between the mean Multi-Luminance flicker magnitude area under the curve in our patients and the healthy control group was statistically significant. (P = .003). CONCLUSIONS:Multi-Luminance flicker magnitude area under the curve has been shown to be significantly different from the normal population in the early active course of the disease. ABBREVIATIONS:BSCR: birdshot chorioretinopathy; cd: Cadmium; ERG: Electroretinography; FA: Fluorescein angiography; FL-: Fixed-luminance; HVF: Humphrey visual field; Hz: Hertz; ICG: Indocyanine green; m2: Square meter; ML-: Multi-luminance; ms: millisecond; SITA: Swedish interactive thresholding algorithm; SWAP: Short wave-length automated perimetry.