Pathogenesis, Clinical Features, and Treatment of Patients with Myelin Oligodendrocyte Glycoprotein (MOG) Autoantibody-Associated Disorders Focusing on Optic Neuritis with Consideration of Autoantibody-Binding Sites: A Review.

Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.

Changes in Density of Peripapillary and Intrapapillary Capillaries on OCT Angiography in Acute Retinal Necrosis Treated by Pharmacotherapy Alone without Surgery.

PURPOSE: To analyze radial peripapillary capillaris (RPC) and intra-papillary capillaris (IPC) using optical coherence tomography angiography (OCTA) in acute retinal necrosis (ARN) with good outcome. METHODS: RPC and IPC were analyzed by OCTA in patients diagnosed with ARN and treated with pharmacotherapy alone without surgery at the Tokyo Medical University Hospital. RESULTS: A total of 13 patients were studied. Ophthalmoscopic examination showed no abnormality in the optic disc in 12 of the 13 patients. However, OCTA findings of the affected eye compared with the unaffected fellow eye revealed morphological abnormalities in RPC in nine cases (69%) and decrease in capillary network in RPC or IPC in eight cases (62%). CONCLUSION: In ARN, RPC and IPC were impaired even in eyes that were healed with medical treatment only without requiring surgical intervention and had no abnormal findings on ophthalmoscopic examination. This result suggests the presence of some degrees of optic neuropathy even in mild cases with good visual prognosis.

Anti-TNF-α Therapy for Refractory Uveitis Associated with Behçet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients.

PURPOSE: The efficacy of infliximab (IFX) and adalimumab (ADA) for treating Behçet's syndrome (BS) and sarcoidosis has not been compared adequately. METHODS: We reviewed the medical records of patients with uveitis diagnosed at Tokyo Medical University Hospital and compared the efficacy of IFX and ADA for BS and the efficacy of ADA for sarcoidosis and BS. RESULTS: 68 patients in IFX group and 63 patients in ADA group were analyzed. In BS patients, IFX and ADA were both effective in improving uveitic macular edema (UME). ADA improved UME in BS but not in sarcoidosis patients. The efficacy of ADA in reducing doses of corticosteroids and glaucoma medications was better in sarcoidosis than in the BS group. CONCLUSION: Both IFX and ADA are efficacious in improving UME in BS patients. The reason that ADA improves UME better in BS than in sarcoidosis may be due to the difference in pathogenesis between these diseases.

Clinical Characteristics, Management, and Factors Associated with Poor Visual Prognosis of Acute Retinal Necrosis.

Purpose: To identify the clinical characteristics of acute retinal necrosis (ARN) and clarify factors associated with poor visual prognosis.Methods: a nationwide multi-center retrospective chart review study was performed in Japan using data from the medical records of 149 consecutive ARN patients. Demographics, ocular signs, virologic testing of intraocular fluids, and treatment were examined. Factors associated with poor visual prognosis were investigated by regression analysis.Results: At initial presentation, anterior chamber cells or mutton-fat keratic precipitates (97%), unilaterality (93%), and yellow-white retinal lesions (86%) were recognized. In the clinical course, rapid circumferential expansion of retinal lesions (39%), development of retinal break or retinal detachment (55%), and optic atrophy (43%) were recorded. Four variables were identified as associated with poor visual prognosis.Conclusions: The present study identified clinical characteristics and factors associated with poor visual prognosis of ARN.

Intraocular surgery under adalimumab therapy in patients with refractory uveitis: a single center study of 23 eyes.

PURPOSE: We assessed the efficacy and safety of performing intraocular surgery for refractory uveitis under adalimumab (ADA) therapy. STUDY DESIGN: Single-center cohort study between 2016 and 2019. METHODS: In uveitis patients undergoing intraocular surgery under ADA treatment, we collected clinical data before surgery, and at the first visit, 6 months and last visit after surgery (follow-up 19.3 ± 8.1 months). Primary outcomes were visual acuity (VA) improvement in patients after cataract surgery, intraocular pressure (IOP) in patients after trabeculectomy and intraocular inflammation in all patients. Secondary outcomes were activated inflammation, vitreous opacity (OCV), uveitic macula edema (UME) and infection. RESULTS: Of 81 patients (161 eyes) initiated ADA therapy for uveitis, 19 patients (23 eyes) underwent intraocular surgery and were analyzed. Twelve of 18 eyes (66.6%) that underwent cataract surgery or vitrectomy with/without cataract surgery had improved VA at the last visit compared to before surgery. All 5 eyes that underwent trabeculectomy showed controlled IOP 6 months after surgery. Intraocular inflammation was resolved in 22 of 23 eyes at the first postoperative visit. Postoperative intraocular inflammation recurred in 3 eyes; 2 with UME, 1 with OCV. No eyes developed infection postoperatively. Preoperative ADA therapy duration was unrelated to relapse of intraocular inflammation. CONCLUSION: Surgery for refractory uveitis under ADA treatment is safe and achieves good visual outcome and uveitis control if inflammation exists before surgery. ADA does not increase the risk of infections. Intraoperative findings of UME at surgery requires attention for postoperative relapse.

Intravenous immunoglobulin treatment for steroid-resistant optic neuritis: a multicenter, double-blind, randomized, controlled phase III study.

PURPOSE: To evaluate the efficacy and safety of intravenous "freeze-dried sulfonated human normal immunoglobulin (GGS)" in patients with steroid-resistant optic neuritis (ON). STUDY DESIGN: Multicenter, prospective, double-blind, parallel-group, randomized controlled trial. METHODS: Patients with steroid-resistant acute ON were randomly assigned to receive either intravenous GGS (GGS group) or intravenous methylprednisolone (steroid pulse [SP] group). Visual acuity (logarithm of the minimum angle of resolution [logMAR]), mean deviation (MD) value of the Humphrey Field Analyzer, and critical flicker fusion frequency were measured as efficacy endpoints; adverse events (AEs) were assessed as the safety endpoint. RESULTS: Thirty-two patients (16 patients/group) received the study drugs. The primary endpoint, change in logMAR at week 2 compared to baseline, showed no statistically significant intergroup difference. However, compared with the SP group, change in the GGS group was increasingly indicative of visual improvement, with least squares mean difference of > 0.3 logMAR. On post-hoc analyses, the percentage of patients in the GGS and SP groups with improvement by ≥ 0.3 logMAR at week 2 were 75.0% and 31.3%, respectively. Changes in MD values at week 2 compared to baseline were 9.258  ±  8.296 (mean ± standard deviation) dB and 3.175  ±  6.167 dB in the GGS and SP groups, respectively. These results showed statistically significant intergroup differences (visual acuity improvement, P = 0.032; change in MD values, P = 0.030). No clinically significant AEs were observed. CONCLUSION: Our results suggest that intravenous immunoglobulin could be a safe and efficacious therapeutic option for prompt treatment of steroid-resistant acute ON. TRIAL REGISTRATION: JapicCTI-132080.

Changes in Etiology of Uveitis in a Single Center in Japan.

Purpose: We investigated the changes in etiology of uveitis at the Uveitis Clinic of Tokyo Medical University Hospital in recent years.Methods: Medical records of patients with uveitis diagnosed between 2011 and 2017 (Group A) and between 2001 and 2007 (Group B) were reviewed.Results: 1,587 patients in group A and 1,507 patients in group B were analyzed. For noninfectious uveitis, frequencies of Vogt-Koyanagi-Harada disease, intraocular lymphoma (IOL) and iridocyclitis in young girls increased, while those of sarcoidosis and Behçet's disease decreased in the recent era. For infectious uveitis, herpetic iridocyclitis, ocular toxoplasmosis, ocular syphilis, and bacterial endophthalmitis increased, while acute retinal necrosis and ocular toxocariasis decreased. Unclassified uveitis decreased, whereas infectious uveitis and IOL increased due to the availability of new diagnostic tests.Conclusion: Etiologies of uveitis have changed over the years. Further development of novel tests and diagnostic criteria would increase definitive diagnosis for unclassified uveitis. (147/150 words).

Characteristics of Japanese patients with Leber's hereditary optic neuropathy and idebenone trial: a prospective, interventional, non-comparative study.

PURPOSE: Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. STUDY DESIGN: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. METHODS: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. RESULTS: Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). CONCLUSION: Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.

Epidemiologic and Clinical Characteristics of Optic Neuritis in Japan.

PURPOSE: To elucidate the clinical and epidemiologic characteristics of optic neuritis in Japan. DESIGN: Multicenter cross-sectional, observational cohort study. PARTICIPANTS: A total of 531 cases of unilateral or bilateral noninfectious optic neuritis identified in 33 institutions nationwide in Japan. METHODS: Serum samples from patients with optic neuritis were tested for anti-aquaporin-4 antibodies (AQP4-Abs) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) using a cell-based assay and were correlated with the clinical findings. MAIN OUTCOME MEASURES: Antibody positivity, clinical and radiologic characteristics, and visual outcome. RESULTS: Among 531 cases of optic neuritis, 12% were AQP4-Ab positive, 10% were MOG-Ab positive, 77% were negative for both antibodies (double-negative), and 1 case was positive for both antibodies. Pretreatment visual acuity (VA) worsened to more than a median 1.0 logarithm of the minimum angle of resolution (logMAR) in all groups. After steroid pulse therapy (combined with plasmapheresis in 32% of patients in AQP4-Ab-positive group), median VA improved to 0.4 logMAR in the AQP4-Ab-positive group, 0 logMAR in the MOG-Ab-positive group, and 0.1 logMAR in the double-negative group. The AQP4-Ab-positive group showed a high proportion of females, exhibited diverse visual field abnormalities, and demonstrated concurrent spinal cord lesions on magnetic resonance imaging (MRI) in 22% of the patients. In the MOG-Ab-positive group, although posttreatment visual outcome was good, the rates of optic disc swelling and pain with eye movement were significantly higher than those in the AQP4-Ab-positive and double-negative groups. However, most cases showed isolated optic neuritis lesions on MRI. In the double-negative group, 4% of the patients had multiple sclerosis. Multivariate logistic regression analysis of all participants identified age and presence of antibodies (MOG-Ab and AQP4-Ab) as significant factors affecting visual outcome. CONCLUSIONS: The present large-scale cohort study revealed the clinicoepidemiologic features of noninfectious optic neuritis in Japan. Anti-aquaporin-4 antibody-positive optic neuritis has poor visual outcome. In contrast, MOG-Ab positive cases manifested severe clinical findings of optic neuritis before treatment, but few showed concurrent lesions in sites other than the optic nerve and generally showed good treatment response with favorable visual outcome. These findings indicate that autoantibody measurement is useful for prompt diagnosis and proper management of optic neuritis that tends to become refractory.

Clinical features of anterior uveitis caused by three different herpes viruses.

PURPOSE: To compare the clinical findings in patients with anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). METHODS: We retrospectively analyzed the clinical profiles of HSV-AU (14 patients), VZV sine herpete (ZSH-AU: 21 patients), and CMV-AU (17 patients) diagnosed by the detection of corresponding viral DNA in aqueous humor samples by polymerase chain reaction. Further, five patients with Posner-Schlossman (P-S) syndrome were selected as controls for CMV-AU. RESULTS: Patients with CMV-AU were predominately male or older in age, and all cases were unilateral except for three patients with CMV-AU. Mutton-fat keratic precipitates (KPs) were found mostly in patients with HSV-AU and ZSH-AU. Severities of AU and viral load were the highest in ZSH-AU, followed by HSV-AU and CMV-AU. Iris atrophy was observed in HSV-AU (50%) and ZSH-AU (76%), with typical morphology of round type and sector type, respectively. In patients with CMV-AU, a ring-shaped KP was found in 53% patients, 76% of whom showed a decreased number of corneal endothelial cells. CMV was not detected in the aqueous humor of patients with typical P-S syndrome. CONCLUSION: Clinical findings of HSV-AU and VZV-AU were similar; however, more inflammatory findings were observed in VZV-AU. Iris atrophy morphologically differed in HSV-AU and VZV-AU. Inflammatory findings in CMV-AU were mild, and clinical features of iritis differed from those of the two former groups. A difference in the etiology between CMV-AU and P-S syndrome was observed.

Evaluation of efficacy of infliximab for retinal vasculitis and extraocular symptoms in Behçet disease.

PURPOSE: We evaluated ocular symptoms and activity of retinal vasculitis of Behçet disease before and after infliximab therapy, using Behçet disease ocular attack score 24 (BOS24) and fluorescein angiography (FA) score. We also analyzed the efficacy of infliximab for ocular and extraocular symptoms. STUDY DESIGN: Retrospective study. SUBJECT AND METHODS: Using medical records, we analyzed FA and BOS24 to evaluate the association between the efficacy of infliximab therapy and FA as well as BOS24 scores. Further, we evaluated the association between FA scores and extraocular symptoms. RESULTS: After 2 years of infliximab therapy, 6-month BOS24 was significantly reduced compared to that before treatment (PreBOS24-6M). After 4 years of infliximab therapy, 6-month BOS24 was also significantly reduced compared to preBOS24-6M. After 2 years of infliximab therapy, FA score median (interquartile range) decreased significantly compared to that before treatment [FA-2Y vs. preFA: 0 (0-0) vs.15.5 (12-24); P < 0.0001; n = 38]. The FA-4Y score in subjects followed for at least 4 years was also significantly lower than the preFA score [0 (0-0) vs.16.5 (12-24.5); P < 0.0001; n = 28]. Among 38 patients, extraocular symptoms were resolved following treatment in 29 cases (76.3%). No significant correlation was observed between the improvement in FA-2Y and FA-4Y scores and the occurrence and persistence of extraocular symptoms (P = 0.33; n = 38 or P = 0.4; n = 28). CONCLUSION: Infliximab therapy is effective for the treatment of ocular and extraocular involvement of Behçet disease. BOS24 and FA scores are useful for evaluating the efficacy of infliximab therapy.

Diagnosis and treatment of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis.

Anti-myelin-oligodendrocyte glycoprotein (MOG) antibody positive optic neuritis has been established as a new subset of optic neuropathy. Anti-MOG antibodies are usually measured by cell-based assay. Patients with anti-MOG antibody positive optic neuritis respond well to steroid therapy, and, while visual acuity outcomes are favorable, significant visual field defects remain. Furthermore, patients who are anti-MOG antibody positive have higher rates of recurrence compared to antibody negative patients. Based on these findings, anti-MOG antibody positive patients with optic neuritis have the characteristics of good visual outcomes, residual visual field defects, and high risk of recurrence. Tests for anti-MOG antibody are useful for the diagnosis and treatment of optic neuritis.

Role of PU.1 Expression as an Inflammatory Marker in Experimental Autoimmune Uveoretinitis.

PURPOSE: PU.1 is an Ets family transcription factor, which is essential for the development of immune system through generation of myeloid and lymphoid lineages. In this study, we investigated PU.1 expression in the retina of mice with experimental autoimmune uveoretinitis (EAU) and the association between PU.1 expression level and inflammation in EAU. METHODS: IRBP 1-20 peptide-immunized mice were used. Quantitative PCR, ELISA analysis, cytometric bead array (CBA), assay and immunostaining were conducted using ocular tissues and lymph nodes. RESULTS: Quantitative PCR showed significant increases in mRNA levels of PU.1 in the retina at the peak of inflammation. Immunostaining of retina flat mounts revealed that most PU.1-positive cells were co-stained with anti-CD11c and anti-F4/80 antibodies. PU.1 knockdown in lymph node cells significantly suppressed IRBP-stimulated IFN-γ production measured by ELISA and IL-2 production measured by CBA. CONCLUSION: PU.1 may play crucial roles in the development and progression of inflammation in EAU.

Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors.

BACKGROUND: To examine the usefulness of measuring immune mediators in aqueous humor samples for differentiating malignant uveal melanoma from benign pigmented intraocular tumors. METHODS: Thirteen eyes of 13 patients with uveal melanoma were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors served as controls. Undiluted samples of aqueous humor were collected, and a cytometric bead array was used to determine the aqueous humor concentrations of 35 immune mediators comprising 14 interleukins (IL), interferon-γ, interferon-γ-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, MIP-1ß, regulated on activation normal T cell expressed and secreted, monokine induced by interferon-γ, basic fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon-inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, vascular endothelial growth factor, angiogenin, tumor necrosis factor-α, lymphotoxin-α, and CD40L. RESULTS: Aqueous humor levels of angiogenin, IL-8, and MCP-1 were significantly higher in eyes with malignant melanoma than in those with benign tumors (p < 0.05). CONCLUSIONS: Angiogenin, IL-8, and MCP-1 levels in aqueous humor may be potential markers for distinguishing malignant uveal melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and appropriate clinical management of malignant uveal melanoma.

Comprehensive polymerase chain reaction assay for detection of pathogenic DNA in lymphoproliferative disorders of the ocular adnexa.

Infectious agents have been identified as a major cause of specific types of human cancers worldwide. Several microorganisms have been identified as potential aggravators of ocular adnexal neoplasms; however, given the rarity of these neoplasms, large epidemiological studies are difficult to coordinate. This study aimed to conduct an exhaustive search for pathogenic DNA in lymphoproliferative disorders (LPD) of the ocular adnexa in a total of 70 patients who were diagnosed with LPD of the ocular adnexa between 2008 and 2013. Specimens were screened for bacterial, viral, fungal, and parasitic DNA by multiplex polymerase chain reaction (PCR) and quantitative real-time PCR. Among cases of conjunctival mucosa-associated lymphoid tissue lymphoma, human herpes virus (HHV)-6, HHV-7, chlamydia, Epstein-Barr virus (EBV) and bacterial 16S ribosomal DNA were detected. In cases of IgG4-related ocular disease, similar pathogens were detected but in a larger number of patients. Our PCR assays detected DNAs of various infectious agents in tumor specimens, especially HHV6, HHV7, and EBV, with different positive rates in various types of LPD. Chronic inflammatory stimulation or activation of oncogenes from these infectious agents might be involved in the pathogenesis of LPD of the ocular adnexa.

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Clinical Profile of Anti-Myelin Oligodendrocyte Glycoprotein Antibody Seropositive Cases of Optic Neuritis.

We have studied the clinical picture of anti-aquaporin antibody (AQP4-Ab)- and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive optic neuritis. However, optic neuritis associated with MOG-Abs has not been elucidated using new methods such as cell-based assay. Hence, we conducted a comprehensive investigation on its clinical profile. Serum samples from 70 patients (17 males and 53 females, mean age 43.1 years) with optic neuritis were tested for MOG-Abs by cell-based assay. In MOG-Ab seropositive patients, the disease type, recurrence status, and visual function outcome were analysed. Among 70 patients, 18 were MOG-Ab seropositive. The 18 patients comprised 2 with chronic relapsing inflammatory optic neuropathy, 2 with AQP4-Ab seropositive optic neuritis (neuromyelitis optica), 12 with idiopathic optic neuritis, and 2 with optic neuritis associated with multiple sclerosis. Excluding two cases that were also AQP4-Ab seropositive, MOG-Ab seropositive cases had relatively favourable visual acuity outcome (although not significantly different from seronegative cases) but had significant residual visual field deficit (p = 0.0015). Furthermore, the number of relapses of optic neuritis per year was significantly greater in MOG-Ab seropositive cases than in seronegative cases (0.82 vs. 0.40; p = 0.0005). MOG-Abs may contribute to the heterogeneous clinical picture of optic neuritis, and although visual acuity outcome is favourable, there is a tendency of residual visual field deficit and a possibility of repeated relapses.

Development and validation of new diagnostic criteria for acute retinal necrosis.

PURPOSE: The purposes of this study are to develop and validate new diagnostic criteria for acute retinal necrosis (ARN) based on the ocular findings, clinical course, and virologic testing of intraocular fluids. SUBJECTS AND METHODS: The Japanese ARN Study Group, comprising 8 uveitis specialists and 1 statistician, was formed to develop new diagnostic criteria for ARN. The criteria used a combination of clinical features consistent with ARN including 6 early-stage ocular findings ([1a] anterior chamber cells or mutton-fat keratic precipitates; [1b] yellow-white lesion(s) in the peripheral retina [granular or patchy in the early stage, then gradually merging]; [1c] retinal arteritis; [1d] hyperemia of the optic disc; [1e] inflammatory vitreous opacities; and [1f] elevated intraocular pressure), 5 clinical courses ([2a] rapid expansion of the retinal lesion(s) circumferentially, [2b] development of retinal breaks or retinal detachment, [2c] retinal vascular occlusion, [2d] optic atrophy, and [2e] response to antiviral agents), and the results of virologic testing of intraocular fluids by means of either polymerase chain reaction or the Goldmann-Witmer coefficient for herpes simplex virus or varicella zoster virus. Various combinations of findings were analyzed to maximize the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The criteria were then used to retrospectively analyze patients who had been diagnosed as having ARN or control uveitis. Patients were followed at 1 of 7 tertiary uveitis clinics between 2009 and 2011. RESULTS: Analysis of the data allowed delineation of 2 levels of diagnosis: "virus-confirmed ARN" (defined as the presence of both early-stage ocular findings 1a and 1b, the presence of any 1 of the 5 clinical courses, and a positive virologic test result) and "virus-unconfirmed ARN" (defined as the presence of 4 of 6 early-stage ocular findings including 1a and 1b, presence of any 2 of the 5 clinical courses, and a negative virologic test result, or when virologic testing had not been performed). The new diagnostic criteria were applied to 45 patients with ARN and 409 patients with control uveitis, resulting in a sensitivity of 0.89, a specificity of 1.00, a PPV of 1.00, and an NPV of 0.99. CONCLUSIONS: New diagnostic criteria for ARN were developed and found to achieve high statistical values.